National Asthma Education Program







Report of the Working Group on
Asthma and Pregnancy




MANAGEMENT OF ASTHMA DURING PREGNANACY

















NATIONAL INSTITUTES OF HEALTH
National Heart, Lung, and Blood Institute


Report of the Working Group on
Asthma and Pregnancy




Management of 
Asthma 
During 
Pregnancy







NATIONAL INSTITUTES OF HEALTH
National Heart, Lung, and Blood Institute
National Asthma Education Program

Public Health Service
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

NIH Publication No. 93-3279
September 1993


TABLE OF CONTENTS

National Asthma Education Program Coordinating 
Committee vi
Working Group on Asthma and Pregnancy vii
FOREWORD ix 
EXECUTIVE SUMMARY 1 
CHAPTER 1: OVERVIEW AND INTRODUCTION 5 
CHAPTER 2: DEFINITION, PATHOGENESIS, AND DIAGNOSIS OF 
ASTHMA 7 
 Definition 7 
 Pathogenesis 7 
 Airway Inflammation 7
 Epithelial Injury 7
 Neural Mechanisms 7
 Intrinsic Smooth Muscle Abnormalities 7
 Airway Geometry 7
 Pathophysiology of Exacerbations of Asthma 7 
 Diagnosis 8 
CHAPTER 3: PHYSIOLOGY OF PREGNANCY AND INTERACTIONS 
WITH ASTHMA 11 
 Maternal Physiology and Impact on Fetal Oxygenation 11 
 Respiratory System Changes 11
 Cardiovascular System Changes 12
 Circulatory System Changes 13 
 Fetal Response to Maternal Critical Illness 13 
 Fetal Management 13 
 The Effect of Asthma on Mother and Fetus 14 
 Epidemiologic Studies 14
 Mechanisms 14 
 Effects of Pregnancy on Asthma 14 
 Epidemiology 14
 Other Clinical Observations 14
 Mechanisms 15
CHAPTER 4: ASTHMA DRUGS IN PREGNANCY AND LACTATION 17 
 Physiologic Changes in Pregnancy Affecting Drug 
Distribution 17 
 Breast Feeding 18 
 How Drug Therapies Are Evaluated 18 
 Animal Data 18
 Human Data 18
 The FDA Categories 18 
 Asthma Drugs: Summaries of Findings 18 
 Anti-Inflammatory Agents 18
 Bronchodilators 19
 Antihistamines 20
 Decongestants 20
 Immunotherapy/Environmental Agents 20 
 Asthma Drugs: Human and Animal Data 21 
 Anti-Inflammatory Agent: Corticosteroids 21
 Anti-Inflammatory Agent: Cromolyn Sodium 21
 Anti-Inflammatory Agent: Nedocromil Sodium 22
 Bronchodilator: Beta-Adrenergic Agonists
(Beta2-Agonists) 22
 Bronchodilator: Nonselective Beta-Agonists 22
 Bronchodilator: Theophylline 23
 Bronchodilator: Anticholinergics 23
 Antihistamines 23
 Decongestants 24 
CHAPTER 5: FOUR COMPONENTS OF THE MANAGEMENT OF 
ASTHMA DURING 
PREGNANCY AND LACTATION 25 
 Introduction 25 
 Goals of Therapy for Pregnant Women 25
 Principles of Therapy for Pregnant Women 25 
 Component 1: Objective Measures for Assessment and 
Monitoring 25 
 Maternal Lung Function 25
 Fetal Monitoring 26 
 Component 2: Measures To Avoid or Control Asthma 
Triggers 27 
 Environmental Control 27
 Immunotherapy 28
 Vaccines 28 
 Component 3: Pharmacologic Therapy 28 
 General Principles of Pharmacologic Management 28
 Preferred Medications and Selection Criteria for
Pregnant 
Women With Asthma 29
 Step-Care Pharmacologic Management of Asthma During 
Pregnancy 29
 Management of Exercise-Induced Asthma 33
 Management of Exacerbations of Asthma During Pregnancy 
35
 Component 4: Patient Education 46 
 Building a Partnership 46
 The Content of Teaching 46
 Psychological Support 47 
CHAPTER 6: SPECIAL CONSIDERATIONS 49 
 Hypertension 49
 Diabetes 49
 Rhinitis 49 
 Diagnosis 49
 Treatment 49 
 Sinusitis 50 
 Diagnosis 50
 Treatment 50 
 Anaphylaxis 50 
 Treatment 50 
REFERENCES 51
APPENDIX: PATIENT HANDOUTS 59

LIST OF TABLES 

Table 1. Characteristic Asthma Symptoms 8
Table 2. Common Triggers of Asthma 8
Table 3. Central Hemodynamic Changes 12
Table 4. Data Supporting a Relationship Between Poor Asthma 
Control and Perinatal Mortality/Morbidity 15
Table 5. Physiologic Changes During Pregnancy That May Affect 
the Course of Asthma 16
Table 6. Potential Fetal/Neonatal Adverse Effects of Asthma 
Drugs 19
Table 7. Drugs and Dosages for Asthma and Associated 
Conditions Preferred for Use During Pregnancy 29
Table 8. Drugs for Asthma and Associated Conditions That 
Generally Should Be Avoided During Pregnancy 30
Table 9. Dosages of Drugs in Acute Exacerbations of Asthma 
During Pregnancy 41

LIST OF FIGURES 

Figure 1. Respiratory Changes During Pregnancy 11 

LIST OF CHARTS 

Chart 1. Management of Asthma During Pregnancy: Chronic Mild 
Asthma 31
Chart 2. Management of Asthma During Pregnancy: Chronic 
Moderate Asthma 32
Chart 3. Management of Asthma During Pregnancy: Chronic 
Severe Asthma 34
Chart 4. Acute Exacerbations of Asthma During Pregnancy: 
Home Management 36
Chart 5. Acute Exacerbations of Asthma During Pregnancy: 
Emergency Department Management 38
Chart 6. Acute Exacerbations of Asthma During Pregnancy: 
Hospital Management 39
Chart 7. Management of Asthma During Labor 44
Chart 8. Management of Asthma During Delivery 45

COORDINATING COMMITTEE

Claude Lenfant, M.D., Chairman
National Heart, Lung, and Blood Institute

Lynn A. Bosco, M.D., M.P.H.
Agency for Health Care Policy and Research

Nancy Sander
Allergy and Asthma Network/Mothers of Asthmatics

Albert L. Sheffer, M.D.
American Academy of Allergy and Immunology

Marc L. Rivo, M.D., M.P.H.
American Academy of Family Physicians

Gary Rachelefsky, M.D.
American Academy of Pediatrics

Sheila Fitzgerald, R.N., Ph.D.
American Association of Occupational Health Nurses

Thomas Kallstrom, R.R.T.
American Association for Respiratory Care

Allan T. Luskin, M.D.
American College of Allergy and Immunology

Robert A. Barbee, M.D., F.C.C.P.
American College of Chest Physicians

Robert Rothstein, M.D.
American College of Emergency Physicians

Sandra Klima
American Hospital Association

Noreen Clark, Ph.D.
American Lung Association

Paul Williams, M.D.
American Medical Association

Barbara Santamaria, R.N., M.P.H.
American Nurses' Association, Inc.

Dennis Williams, Pharm.D.
American Pharmaceutical Association

Pamela Luna, Dr.P.H.
American Public Health Association

Lani Majer, M.D.
American School Health Association

Leslie Hendeles, Pharm.D., F.C.C.P.
American Society of Hospital Pharmacists

A. Sonia Buist, M.D.
American Thoracic Society

Barbara Hager, M.P.H., R.H.Ed., C.H.E.S.

Association of State and Territorial Directors of Public 
Health Education

Mary Worstell, M.P.H.
Asthma and Allergy Foundation of America

Benedict I. Truman, M.D., M.P.H.
Centers for Disease Control

Vivian Haines, R.N., M.S., S.N.P.
National Association of School Nurses

Sadako Holmes, R.N.
National Black Nurses' Association, Inc.

Marsha Davenport, M.D., M.P.H.
National Center for Health Statistics

Ruth I. Quartey, M.A., R.R.T.
NHLBI Ad Hoc Committee on Minority Populations 

Lawrence Prograis, Jr., M.D.
National Institute of Allergy and Infectious Diseases

Sheila A. Newton, Ph.D.
National Institute of Environmental Health Sciences

Floyd Malveaux, M.D., Ph.D.
National Medical Association

L. Kay Bartholomew, Ed.D., M.P.H.
Society for Public Health Education

Joe Caliguro
U.S. Department of Education 

Maria Segarra, M.D.
U.S. Public Health Service




WORKING GROUP ON ASTHMA AND PREGNANCY OF THE NATIONAL ASTHMA 
EDUCATION PROGRAM

Allan T. Luskin, M.D., Chair
Associate Professor of Medicine and Immunology/Microbiology
Department of Immunology and Microbiology
Rush Medical Center
Chicago, Illinois

Steven Clark, M.D.
Professor of Obstetrics and Gynecology
University of Utah
Director, Intermountain Health Care Perinatal Centers
Salt Lake City, Utah

Marilyn Frederiksen, M.D.
Associate Professor
Department of Obstetrics and Gynecology
Associate in Clinical Pharmacology
Northwestern University Medical School
Chicago, Illinois 

Mark Jacobs, M.D.
Director, Perinatal Services
Marin General Hospital
Assistant Clinical Professor
Department of Obstetrics, Gynecology, and Reproductive 
Sciences
University of California San Francisco
San Francisco, California 

Ralph Kaufman, M.D.
Professor of Pediatrics and Pharmacology
Wayne State University School of Medicine
Director, Division of Clinical
 Pharmacology and Toxicology
Children's Hospital of Michigan
Detroit, Michigan

Debra Myers, M.D.
Assistant Clinical Professor of Medicine
Department of Medicine, Division of
 Pulmonary and Critical Care
Indiana University School of Medicine
Indianapolis, Indiana

Harold S. Nelson, M.D.
Senior Staff Physician
Department of Medicine
National Jewish Center for Immunology and Respiratory 
Medicine
Denver, Colorado

Michael Schatz, M.D.
Associate Clinical Professor of Medicine and Pediatrics
University of California San Diego
 School of Medicine
Department of Allergy
Kaiser-Permanente Medical Center
San Diego, California 

Anthony Scialli, M.D.
Associate Professor of Obstetrics and Gynecology
Georgetown University Medical Center
Director, Reproductive Toxicology Center
Columbia Hospital for Women
Washington, D.C.

Robert A. Wise, M.D.
Associate Professor of Medicine
Johns Hopkins University 
 School of Medicine
Johns Hopkins Asthma and Allergy Center
Baltimore, Maryland



FEDERAL 
LIAISON REPRESENTATIVES

Donald McNellis, M.D.
Special Assistant for Obstetrics
Pregnancy and Perinatology Branch
Center for Mothers and Children
National Center for Child Health and Human Development
Bethesda, Maryland 

Lawrence Prograis, Jr., M.D.
Deputy Director
Division of Allergy, Immunology, and Transplantation
National Institute of Allergy and Infectious Diseases
Bethesda, Maryland



NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STAFF

Sydney R. Parker, Ph.D.
Chief, Prevention, Education, and Research Training Branch
Division of Lung Diseases

Virginia Silver Taggart, M.P.H.
Health Program Specialist
Division of Lung Diseases

Robinson Fulwood, M.S.P.H.
Coordinator, National Asthma Education Program
Office of Prevention, Education, and Control

Suzanne Hurd, Ph.D.
Director
Division of Lung Diseases

SUPPORT STAFF

Ted Buxton, M.P.H.
University Research Corporation

Lisa Harris
University Research Corporation

Lucy Blanton
Consultant, Editor



The Working Group would like to thank the following 
consultants for their review of a draft of this report:

Thomas Benedetti, M.D.
Eugene R. Bleecker, M.D.
Paul Greenberger, M.D.
Myron Lipkowitz, M.D.
Julie Graves Moy, M.D.
Robert M. Ward, M.D.
Nathan Wasserstrum, M.D., Ph.D.

FOREWORD

The many questions and uncertainties concerning the 
treatment of asthma during pregnancy are addressed in this 
report by the Working Group on Asthma and Pregnancy of the 
National Asthma Education Program (NAEP). The working group 
was made up of 12 physicians experienced in treating pregnant 
women with asthma and included obstetricians/gynecologists, a 
reproductive toxicologist, pediatric and adult 
pharmacologists, as well as allergists and pulmonologists. 
The working group met three times in the course of 18 months. 

This report focuses on ensuring the safety of mothers and 
fetuses. The working group emphasizes that the risks of 
uncontrolled asthma are far more dangerous to the pregnant 
patient with asthma and her fetus than are the risks from the 
medications used to control asthma. The report is designed 
to enable clinicians to use therapy appropriately for chronic 
control as well as for symptomatic relief of asthma in 
pregnant women. It draws heavily on the comprehensive 
guidelines for detecting and treating asthma that are 
contained in the NAEP Expert Panel Report: Guidelines for 
the Diagnosis and Management of Asthma (1991). Treatment 
recommendations conform to those of the expert panel report 
but are adapted specifically for pregnant women with asthma. 
Topics specific to pregnant women, such as fetal monitoring, 
the safety of asthma drugs to the fetus, and treating asthma 
during labor and delivery are addressed in detail.

During the development of this report, the working group 
recognized that the amount of empirical data available on the 
treatment of pregnant women with asthma is limited. The data 
are nevertheless sufficient to estimate the risks and 
benefits and to make reasonable recommendations for care. 
Animal data, therapeutic principles, and the expert judgment 
and experience of the working group were used to form the 
recommendations where data with human subjects were not 
available. 

The working group emphasizes that the recommendations in 
this report are general guidelines developed to assist 
clinician and patient decisions about appropriate asthma 
care. Specific therapeutic regimens must be tailored to 
individual needs and circumstances. Because the 
recommendations are based upon review of the scientific 
literature, the expert panel report of the NAEP, the expert 
judgment and opinion of the working group, and review and 
approval by all members of the NAEP Coordinating Committee, 
they represent a broad consensus. However, these 
recommendations are not to be construed either as an official 
regulatory document or as a document that has been endorsed 
by the U.S. Food and Drug Administration. 

This report is designed principally to provide all 
clinicians who care for pregnant women with new insights into 
asthma management. It is hoped that the report will promote 
the best possible asthma care for pregnant women, improve 
maternal health and well-being, and ensure healthy pregnancy 
outcomes. 

On behalf of the NAEP Coordinating Committee and the 
National Heart, Lung, and Blood Institute, I would like to 
acknowledge the excellent efforts of the working group and 
the leadership of its chair, Dr. Allan T. Luskin. 
Dedication, thoroughness, and a commitment to improving the 
care of pregnant women with asthma have characterized the 
development of this report. 




Claude Lenfant, M.D., Director
National Heart, Lung, and Blood Institute
Chairman, National Asthma Education Program Coordinating 
Committee

EXECUTIVE SUMMARY

Asthma is one of the most common illnesses that complicate 
pregnancy. Asthma may occur for the first time during 
pregnancy, or it may change during pregnancy; about one-third 
of pregnant women with asthma experience worse asthma during 
pregnancy, one-third remain the same, and one- third improve. 
In any case, pregnant women with asthma need treatment to 
control their asthma and thus protect their health and the 
health of their fetus. Asthma is a chronic, persistent 
disease of the airways characterized by exacerbations of 
coughing, wheezing, chest tightness, and difficult breathing 
that are usually reversible, but that can be severe and 
sometimes fatal. Recent studies demonstrated that 
inflammation is a critical factor in the pathogenesis of 
asthma, and therefore asthma therapy is predicated on 
medications to reverse and prevent this abnormality. 

Pregnant women with asthma require long-term management to 
maintain lung function and blood oxygenation to ensure the 
oxygen supply to the fetus. Uncontrolled asthma during 
pregnancy can produce serious maternal and fetal 
complications. Maternal complications include preeclampsia, 
gestational hypertension, hyperemesis gravidarum, vaginal 
hemorrhage, toxemia, and induced and complicated labors. 
Fetal complications include increased risk of perinatal 
mortality, intrauterine growth retardation, preterm birth, 
low birth weight, and neonatal hypoxia. When asthma is 
properly controlled, however, pregnant women with asthma can 
maintain a normal pregnancy with little or no increased risk 
to themselves or their fetuses. 

The goals of therapy for pregnant women with asthma are to 
control symptoms, including nocturnal symptoms; maintain 
normal or near-normal pulmonary function; maintain normal 
activity levels, including exercise; prevent acute 
exacerbations of asthma; avoid any adverse effects from 
asthma medications; and deliver a healthy infant. To achieve 
these goals, the Working Group on Asthma and Pregnancy 
strongly recommends that asthma be as aggressively treated in 
pregnant women as it is in nonpregnant women. 
Underestimation of asthma severity and undertreatment of 
exacerbations are two common errors that may lead to adverse 
maternal and fetal outcomes. 

Asthma care should be integrated with obstetric care. 
Effective management of asthma includes ongoing management to 
prevent asthma exacerbations and control chronic symptoms, 
and early intervention to relieve acute exacerbations. There 
are four integral components of effective asthma management: 

1. Use objective measures for assessment and 
monitoring. 

Maternal lung function. Objective measures of lung 
volumes or flow rates are essential for assessing and 
monitoring the severity of asthma in order to make 
appropriate therapeutic recommendations. Using an office 
spirometer in the initial assessment of all pregnant patients 
being evaluated for asthma, and periodically thereafter as 
appropriate, is recommended. The single best measure of 
pulmonary function for assessing severity is forced 
expiratory volume in 1 second (FEV1). 

Peak expiratory flow rate (PEFR), which can be measured 
reliably with inexpensive portable peak flow meters, 
correlates well with FEV1. Home peak expiratory flow 
monitoring should be considered for patients who take 
medications daily. Regular monitoring can help detect early 
signs of deterioration, indicate when asthma therapy might be 
changed, and assess response to therapy. Women with asthma 
may have minimal symptoms but still have abnormal pulmonary 
function tests and potentially impaired fetal oxygenation. 
Peak flow measurement will also help differentiate asthma 
from other causes of dyspnea during pregnancy. 

Fetal monitoring. Fetal evaluation is based on objective 
measurements made by different techniques used according to 
gestational age and risk factors. Early (12 to 20 weeks) 
sonography provides a benchmark for progressive fetal growth. 
Sequential sonographic evaluations of fetal growth are 
indicated in second and third trimesters if asthma is 
moderate or severe or if growth retardation is suspected. 
Electronic fetal heart rate monitoring and ultrasonic 
determinations of fetal behavior in the third trimester 
should be used as needed to ensure fetal well-being. For 
many third-trimester patients weekly fetal assessment is 
sufficient, but frequency should increase if fetal problems 
are suspected. Daily maternal recording of fetal activity, 
or "kick counts," should be encouraged. 

Immediate antepartum fetal assessment is indicated in asthma 
exacerbations with an incomplete or poor response to therapy 
or with significant maternal hypoxemia. One reasonable 
approach to antepartum fetal assessment is continuous 
electronic fetal heart rate monitoring. 

When women with asthma are admitted in labor, careful fetal 
monitoring is essential. Intensive fetal monitoring (either 
continuous electronic tent auscultation) is recommended for 
those patients who enter labor with uncontrolled or severe 
asthma and with a nonreassuring admission test of fetal 
assessment or other risk factors. 

2. Avoid or control asthma triggers.

The identification and control of triggers--factors that 
induce airway inflammation or precipitate asthma 
exacerbations--are important in controlling asthma during 
pregnancy. Avoiding exposure to identified allergens and 
irritants can reduce asthma symptoms, airway 
hyperresponsiveness, and the need for medication. In 
addition, eliminating all exposure to tobacco smoke is 
important for pregnant women with asthma. Although 
immunotherapy should not be started during pregnancy, ongoing 
immunotherapy may be continued to reduce the response to a 
specifically identified allergen. 

3. Establish medication plans for chronic management 
of asthma and for managing exacerbations using 
preferred medications. 

Chronic management of asthma. Asthma is a disease that 
varies among patients, and the degree of severity may change 
for individual patients from 1 month or season to the next or 
during pregnancy. Therefore, specific therapeutic regimens 
must be tailored to individual needs and circumstances. A 
stepwise approach to pharmacological therapy, in which the 
number and frequency of medications are increased with 
increasing asthma severity, permits this flexibility. Once 
control of asthma is sustained for several weeks or months, a 
reduction in therapy--a step down--can be carefully considered 
because the aim of pharmacotherapy is to use the least 
medication to maintain control. The stepwise approach 
presented with detailed recommendations in this report 
emphasizes that anything more than mild occasional asthma 
requires daily therapy with inhaled anti-inflammatory agents, 
either cromolyn sodium or beclomethasone. Further, all 
patients must have inhaled beta2-agonists to relieve 
symptoms, but it is essential that patients should not rely 
on frequent use of bronchodilator agents to control their 
asthma. An increased need for inhaled beta2-agonist is an 
indication that the asthma is deteriorating and anti-
inflammatory therapy should be instituted or increased. 

An extensive review (discussed in the report) of the animal 
and human studies on the effects of asthma medications found 
few risks of adverse effects to the fetus. The known risks 
of uncontrolled asthma are far greater than the known risks 
to the mother or fetus from asthma medications. 

Managing exacerbations. Anticipatory or early 
intervention is important in treating acute exacerbations. 
This reduces the likelihood of an episode progressing to 
severe airway obstruction with impaired maternal/fetal 
oxygenation. Every patient needs to have a written action 
plan for recognizing and responding early to signs of 
worsening asthma. The action plan indicates how to increase 
medications in response to decreased PEFR or increased 
symptoms and how to obtain medical advice at any time. 

Patients should not delay seeking medical help in the 
emergency department or hospital if any of the following 
occur: therapy does not provide rapid improvement, the 
improvement is not sustained, there is further deterioration, 
the asthma exacerbation is severe, or the fetal kick count 
decreases. 

Treatment in the emergency department or hospital emphasizes 
intensified administration of inhaled beta2-agonists, oxygen 
supplementation, and the early introduction of systemic 
corticosteroids. 

Monitoring is essential because, in the presence of a 
moderate to severe exacerbation, deterioration can be rapid 
and a decrease in maternal PaO2 (especially below 60 mmHg) 
and fetal PaO2 can result in profoundly decreased fetal 
oxygen saturation and fetal hypoxia. Furthermore, fetal 
distress can occur even in the absence of maternal 
hypotension or hypoxia. Aggressive monitoring of fetal well-
being is essential during critical maternal illness. 

Managing asthma during labor and delivery. The 
patient's regularly scheduled asthma medications should be 
continued during labor and delivery. The patient's PEFR 
should be taken upon admission to labor and delivery and, 
subsequently, every 12 hours. Asthma is often quiescent 
during labor and delivery. However, if asthma symptoms 
develop, PEFR should be monitored after asthma treatments. 
The patients should be kept well hydrated and be provided 
adequate analgesia to limit the risk of bronchospasm. 
Patients who have required chronic systemic corticosteroids 
during pregnancy should be given hydrocortisone to treat for 
possible adrenal suppression. 

Narcotic analgesics that cause histamine release should be 
avoided; fentanyl is a preferred agent. Lumbar epidural 
analgesia reduces oxygen consumption and minute ventilation 
during first and second stages of labor, which offers 
patients with asthma considerable benefit. If a general 
anesthetic is necessary, preanesthetic use of atropine and 
glycopyrrolate may provide bronchodilatory effect. For 
induction of anesthesia, ketamine is the agent of choice. 
Low concentrations of halogenated anesthetics can provide 
bronchodilation to the patient with asthma. 

For labor induction, oxytocin is the drug of choice. Prior 
to term, the use of 15 methyl prostaglandin F2-alpha should 
be avoided because it may cause bronchospasm; use of 
prostaglandin E2 suppositories or gel has not been reported 
to cause bronchospasm. 

For postpartum hemorrhage, oxytocin is the recommended agent. 
If additional agents are required, methylergonovine as well 
as ergonovine should be avoided if possible because they may 
cause bronchospasm. If their use is unavoidable, 
pretreatment with methylprednisolone is recommended. If 
prostaglandin treatment is necessary, the safest analog is 
E2, which is less likely to cause bronchospasm. 

The treatment of preterm labor in a patient already receiving 
asthma medication creates the risk of dangerous drug 
interactions. During an asthma exacerbation, uterine 
contractions are common and usually do not progress to 
preterm labor. Successful treatment of the exacerbation will 
usually abate the contractions. If tocolytic therapy is 
necessary, care should be taken to avoid the use of more than 
one type of beta2-agonist. Magnesium sulfate is recommended 
to treat uterine contractions if the patient is already 
taking a systemic beta2-agonist for her asthma. 

4. Educate pregnant patients to develop a partnership 
in asthma management. 

It is of the greatest importance for pregnant women with 
asthma to understand that they are "breathing for two." 
These women need information on how to properly control and 
manage their asthma during pregnancy to reduce the risk to 
the fetus. Concerns of pregnant women need to be elicited 
and addressed. Open communication, joint development of a 
treatment plan by the clinician and patient, and 
encouragement of the family's efforts to improve prevention 
and treatment of the patient's symptoms will assist in 
promoting maternal and fetal safety and well-being. 
Providing support to pregnant women with asthma during this 
potentially anxious time is important.

This report elaborates on these four components of effective 
asthma management for pregnant patients. It provides more 
detailed recommendations with supporting documentation from 
the scientific literature.



1
OVERVIEW AND INTRODUCTION 

Asthma is one of the most common illnesses that complicate 
pregnancy. Recent studies have shown that approximately 4 
percent of pregnancies are complicated by bronchial asthma. 
The true prevalence may be even higher; at least 10 percent 
of the population appears to have nonspecific airway 
hyperreactivity, a hallmark of asthma. Furthermore, during 
the 1980's, the prevalence, morbidity, and mortality of 
asthma increased; specifically, from 1980 to 1989, the 
prevalence of asthma increased by 60 percent. This major 
national health problem stimulated the launching of the 
National Asthma Education Program; this report is one of its 
endeavors to alter these trends and to help persons with 
asthma live normal lives. 

Uncontrolled asthma has serious maternal and fetal 
complications. With uncontrolled asthma there is an 
increased risk of perinatal mortality, premature and/or low 
birth weight infants, and preeclampsia. Asthma may begin or 
be exacerbated during pregnancy, and pregnancy may adversely 
affect the course of asthma in about one-third of the 
pregnant women with asthma. Therapy for medical conditions 
complicating pregnancy may affect the control of asthma, and 
therapy for asthma may influence the pregnancy or 
complicating conditions such as diabetes and hypertension. 

Nevertheless, most pregnant women with asthma can 
successfully control their asthma and have a healthy baby. 
Proper control of asthma should allow a woman with asthma to 
maintain a normal pregnancy with little or no increased risk 
to herself or her fetus. 

A number of myths have complicated the delivery of 
appropriate asthma care during pregnancy. On one hand are 
notions that asthma is uncommon, mild, or only a minimally 
inconvenient illness, or that asthma is a psychological 
problem. On the other hand are beliefs that asthma 
necessitates severe limitations on activities or that asthma 
requires potentially dangerous medicine for control. There 
is a perception among the lay population that all medicine is 
harmful during pregnancy. However, concerns about 
pharmacotherapy must be balanced by an understanding of the 
significant adverse effects of uncontrolled asthma. Women 
with asthma may have minimal symptoms but still have abnormal 
pulmonary function tests and potentially impaired fetal 
oxygenation. Patients will often be more receptive to taking 
appropriate medication if they understand the importance of 
maintaining fetal oxygenation--that the pregnant woman is 
"breathing for two." 

Traditionally, asthma therapy was characterized by reliance 
on symptomatic therapy with bronchodilators. This reflects 
the view of asthma as an intermittent acute illness that is 
primarily a bronchospastic event. However, recent 
pathophysiological insights more clearly define the dominant 
role of chronic airway inflammation in contributing to 
bronchial hyperreactivity and exacerbations of reversible 
airway obstruction. Thus asthma is now viewed as a chronic 
disease characterized by acute exacerbations. Therapy should 
focus on treating the underlying chronic inflammation with 
specific anti-inflammatory therapy. Control of inflammation 
should minimize or eliminate the acute exacerbations and 
dramatically decrease the morbidity and mortality of the 
illness. 

Patients with asthma who are pregnant need asthma treatment. 
Therefore, pregnant women and women attempting to become 
pregnant should receive pharmacologic and nonpharmacologic 
treatments to safely treat asthma and help them reach 
realistic goals for their health and the health of their 
children. 

Asthma therapy for pregnant women has clear-cut goals. These 
include control of symptoms, with no nocturnal awakenings due 
to asthma, no limitation of activities including exercise, 
normal or near-normal maternal pulmonary function tests and 
oxygenation, prevention of exacerbations of asthma, no 
emergency department visits or hospitalizations, and use of 
convenient therapy with minimum side effects for mother and 
fetus. 

This report emphasizes the importance of a good working 
relationship among the patient, her family, and her 
clinician(s). It also provides assistance to the clinician 
in providing the necessary education to the mother so that 
she will understand the goals of therapy, appropriately 
monitor her condition, and optimally use the various 
therapeutic options. 

The National Asthma Education Program has previously 
published a comprehensive Expert Panel Report: Guidelines 
for Diagnosis and Management of Asthma. The report of the 
Working Group on Asthma and Pregnancy draws heavily on this 
original report. More detailed information and references 
concerning many aspects of the pathophysiology, diagnosis, 
and treatment of asthma may be found in the expert panel 
report. 

The report of the Working Group on Asthma and Pregnancy is 
designed to enable the clinician to use therapy appropriately 
for chronic control of asthma as well as symptomatic 
improvement. The report discusses the pathophysiology of 
asthma that underlies the therapeutic recommendations. 
Monitoring of pulmonary function and appropriate prenatal 
care will assist in assessing severity of asthma and response 
to therapy, predicting impending exacerbations, and detecting 
a fetus at risk. 

During the development of this report on asthma and 
pregnancy, the working group recognized that there is a 
limited amount of empirical data available on the treatment 
of pregnant women with asthma. However, there are sufficient 
data to assess risks and benefits and to make reasonable 
recommendations for care. Where empirical human data were 
not available, animal data, therapeutic principles, and the 
expert judgment and experience of the working group were used 
to form the recommendations. Treatment recommendations in 
general conform to those of the Expert Panel on the 
Management of Asthma, as adapted for pregnant women. 

The Working Group on Asthma and Pregnancy believes that the 
implementation of the recommendations in this report will 
increase maternal health and well-being and significantly 
diminish perinatal morbidity and mortality.



2
DEFINITION, PATHOGENESIS, AND DIAGNOSIS OF ASTHMA

DEFINITION

Although the typical clinical syndrome of asthma--episodic 
cough, wheezing, and dyspnea with reversible airflow 
obstruction--is not difficult to recognize, asthma may present 
with atypical symptoms such as isolated cough, chest 
discomfort, or exertional dyspnea. A widely accepted 
definition remains elusive (American Thoracic Society, 1987). 
The definition of asthma may overlap other related disorders 
such as asthmatic bronchitis and infectious bronchitis. One 
generally agreed-upon, working definition of asthma is as 
follows: 

Asthma is a lung disease with the following 
characteristics: (1) airway obstruction that is 
partially or completely reversible either spontaneously or 
with treatment; (2) airway inflammation; and (3) 
increased airway responsiveness to a variety of stimuli. 

PATHOGENESIS 

Asthma is characterized by airway hyperresponsiveness with 
exaggerated bronchoconstriction in response to many physical, 
chemical, and pharmacologic agents. Airflow obstruction with 
wheezing can occur after exposure to allergens, environmental 
irritants, viral respiratory infections, cold air, or 
exercise. Virtually all people with asthma have airway 
hyperresponsiveness, which often correlates with the clinical 
severity of the disease. Many individuals without overt 
symptoms of asthma can exhibit airway hyperresponsiveness, 
but they usually show less response to provoking agents. 

Several mechanisms have been proposed to explain airway 
hyperresponsiveness in asthma, including airway inflammation, 
abnormalities in bronchial epithelial integrity, alterations 
in autonomic neural control of airways, changes in intrinsic 
bronchial smooth muscle function, alterations in the volume 
and composition of the airway liquid lining layer, defects in 
control of bronchial blood flow, and abnormal airway geometry 
(Widdicombe, 1991). 

Airway Inflammation 

Airway inflammation is thought to be a key factor in airway 
hyperresponsiveness, given the evidence suggesting the 
presence of airway inflammation in individuals with even mild 
asthma. Cellular infiltrates of eosinophils, neutrophils, 
lymphocytes, mast cells, and macrophages are present. The 
release of inflammatory mediators is thought to lead to the 
migration and activation of more inflammatory cells, 
destruction of the epithelial cell layer integrity, 
abnormalities of autonomic neural control of airway tone, 
changes in mucociliary function, and increased airway smooth 
muscle responsiveness.

Epithelial Injury 

Desquamation of epithelial cells and alteration of their 
barrier function as a consequence of the airway inflammatory 
process can lead to increased permeability to inhaled 
allergens and other provoking agents, impaired mucociliary 
clearance, impaired metabolism of peptide hormones, impaired 
regulation of the bronchial fluid lining layer, and increased 
response to cholinergic stimulation. 

Neural Mechanisms 

People with asthma have increased airway responsiveness to 
cholinergic stimulation. Nonspecific irritants induce 
bronchospasm, at least in part through stimulation of vagal 
pathways. It has also been postulated that there is abnormal 
local release of neuropeptides that leads to defective smooth 
muscle relaxation, mucosal vascular congestion, and edema. 

Intrinsic Smooth Muscle Abnormalities 

Although airway smooth muscle is clearly hypertrophied in 
asthma, in vitro studies have failed to show increased 
constriction to pharmacologic stimulation. There may, 
however, be impaired relaxation characteristics of the airway 
smooth muscle or failure of normal control mechanisms in 
vivo.

Airway Geometry 

Narrowing of the airway lumen by bronchial mucosal edema, 
inflammatory cellular infiltrates, excess mucus and fluid, 
and smooth muscle hypertrophy or constriction may contribute 
to airway hyperresponsiveness. The tendency for the airway 
to close and to increase airway resistance with shortening of 
the surrounding smooth muscle is enhanced by the narrowed 
airway lumen. 

Normally, inflation of the lung leads to forces that tend to 
open airways through peribronchial attachments to alveolar 
septa. Peribronchial edema and inflammatory infiltration 
reduce the effectiveness of these alveolar septal attachments 
to maintain airway patency. 

Pathophysiology of Exacerbations of Asthma 

Exacerbations of asthma are acute or subacute episodes of 
progressively worsening shortness of breath, cough, wheezing, 
chest tightness, or some combination of these symptoms. 
Exacerbations are characterized by decreases in expiratory 
airflow. 

Airway smooth muscle contraction that results in airway 
obstruction is a primary abnormality in asthma. Other 
physiological changes also contribute to the clinical 
findings characteristic of asthma exacerbations. 

 Airways narrow because of bronchospasm, mucosal edema, and 
mucus plugging. Air is trapped behind peripheral small 
airways that become closed. 

 Functional residual capacity rises because of airway 
closure and tonic contraction of inspiratory muscles. 
Hyperinflation helps keep airways open, but breathing 
requires more effort. 

 Accessory muscles of respiration are used to maintain 
ventilation. 

 Hypoxemia occurs during severe exacerbations because of 
mismatching of ventilation and perfusion. 

 Hypercapnia may occur during life-threatening exacerbations 
because of respiratory muscle failure. Respiratory muscle 
failure is the consequence of increased work of breathing 
and the impaired mechanical advantage of the respiratory 
muscles in the hyperinflated condition. 

 Pulmonary vascular resistance may increase due to hypoxemia 
and hyperinflation. 

 Negative pleural pressures become more negative as lung 
hyperinflation occurs; this is manifested by pulsus 
paradoxus. 

DIAGNOSIS

Asthma may present for the first time during pregnancy, and 
the diagnosis may be confused with the physiologic dyspnea of 
pregnancy. The diagnosis of asthma is based on a compatible 
medical history, physical examination, and laboratory test 
results. Other disorders with similar clinical presentations 
may need to be excluded when the diagnosis is in question. 
Diagnosis of asthma focuses on establishing episodic airway 
obstruction and the reversibility of the obstruction. 

People with asthma typically have a history of episodic 
cough, chest tightness, wheezing, and dyspnea. Asthma may 
also present with atypical symptoms such as an isolated 
cough, chest pain, recurrent bronchitis, or exertional 
dyspnea. Characteristic chest symptoms that support the 
diagnosis of asthma are listed in table 1. Common triggers 
of asthma symptoms are listed in table 2. The history is 
frequently also positive for rhinitis, sinusitis, or flexural 
eczema. Often there is a family member with asthma or 
allergies. 

During an acute exacerbation, the physical examination may 
reveal hyperinflation, prolonged duration of expiration, 
wheezing, and use of accessory respiratory muscles. The 
physical examination may be normal between exacerbations. 

Diagnostic pulmonary function findings include airflow 
obstruction on spirometry that is reversible. The failure to 
respond immediately to an inhaled bronchodilator does not 
exclude the diagnosis. Repeat spirometry after several weeks 
of treatment may show improvement. Home measurement of peak 
expiratory airflow (see Component 1: Objective Measures for 
Assessment and Monitoring in chapter 5) may show increased 
variability or decreased peak flow in association with 
symptoms. Methacholine challenge testing can establish the 
presence of airway hyperreactivity but is rarely needed to 
establish the diagnosis of asthma. When performed with 
proper monitoring, methacholine challenge testing poses no 
excess risk to pregnant patients. 

Additional studies may also be considered. No one test is 
appropriate for every patient. Procedures to consider are: 

 Complete blood count (CBC). 

 Chest x-ray. (This can rule out other causes of airway 
obstruction.) 

 Sputum examination and stain for eosinophilia. (Sputum 
eosinophilia is highly characteristic of asthma; 
neutrophils predominate in bronchitic sputum.) 

 Nasal secretion stain for eosinophils. (Neutrophilic nasal 
discharge is characteristic of sinusitis.) 

 Complete pulmonary function studies, including inspiratory 
and expiratory flow volume curve. (These may reveal upper 
airway problems that simulate asthma.) 

 In certain circumstances, selected skin (in vivo) or in 
vitro tests to determine specific IgE antibodies to common 
inhalant allergens (useful for establishing the role of 
allergy in a pregnant patient's asthma and for guiding 
advice on specific environmental control measures). 

 Rhinoscopy. 

 Sinus x-rays. 

 Monitoring of esophageal pH for gastroesophageal reflux. 

Although recurrent episodes of cough and wheezing are almost 
always due to asthma, the clinician needs to be aware of 
other causes of airway obstruction leading to wheezing. 
These include: 

 Upper airway mechanical obstruction

 Laryngeal dysfunction

 Chronic bronchitis

 Emphysema

 Pulmonary edema (cardiac or noncardiac)

 Pulmonary infiltrates with eosinophilia

 Infectious bronchitis and bronchiectasis

 Cystic fibrosis

 Antibody deficiency obstruction. 

In addition, there are such conditions as pulmonary embolism, 
hyperventilation syndrome, and physiologic dyspnea of 
pregnancy that may mimic symptoms of asthma. When the 
diagnosis of asthma is in question, it is appropriate to 
refer the patient to a specialist in asthma care (usually an 
allergist or pulmonologist).



3
PHYSIOLOGY OF PREGNANCY AND INTERACTIONS WITH ASTHMA

This chapter focuses on the impact of maternal physiology on 
fetal oxygenation, on the effect of asthma on mother and 
fetus, and, finally, on the effect of pregnancy on asthma. 

Maternal Physiology and Impact on Fetal Oxygenation 

Changes in maternal respiratory, cardiovascular, and 
circulatory systems during pregnancy influence fetal 
oxygenation and acid base status. This section looks at 
these physiological alterations and their clinical 
implications. 

Respiratory System Changes 

A relative hyperventilation during pregnancy is seen 
beginning in the first trimester, with minute ventilation 
increasing up to 48 percent by term. This change is due to 
an increase in tidal volume; respiratory rate is relatively 
unchanged during pregnancy, so tachypnea in pregnancy 
(respirations more than 20 per minute) is an abnormal finding 
that must be investigated. Increased tidal volume change is 
due principally to increased placental progesterone 
production, which also accounts for a sensation of shortness 
of breath ("dyspnea of pregnancy") that is common in 
pregnancy. The hyperventilation of pregnancy is associated 
with significant changes in arterial blood gas with a resting 
arterial carbon dioxide tension (PCO2) below 35 mmHg. This 
chronic respiratory alkalosis is partially compensated for by 
increased renal bicarbonate excretion. Total oxygen 
consumption and basal metabolic rate also increase by 20 
percent and 15 percent, respectively, accounting for 
increased maternal oxygen tension, which is also common in 
normal pregnancy. Normal values of PO2 range from 106 to 108 
mmHg during the first trimester and decrease slightly in the 
third trimester (Prowse & Gaensler, 1965; Templeton & Kelman, 
1976). Oxygenization is significantly influenced by postural 
effects. Twenty-five percent of pregnant women experience 
arterial oxygen tensions of less than 90 mmHg in the supine 
position, and there is also an increased likelihood of 
developing increased alveolar-arterial oxygen gradients in 
the supine, compared to the upright, position. 

In terms of pulmonary function, the following are seen by 
term: a decrease in residual volume, functional residual 
capacity, expiratory reserve volume, and total lung capacity; 
an increase in inspiratory capacity; and no change in vital 
capacity or forced expiratory volume in 1 second (FEV1) 
(Bonica, 1972; see figure 1). All the changes just discussed 
have the potential for profound impact upon the clinical 
interpretation of pulmonary function studies and blood gas 
measurements in the pregnant woman with asthma and must be 
clearly kept in mind in the clinical interpretation of such 
data. In general, however, those measurements of pulmonary 
function in common clinical use (such as respiratory rate or 
FEV1) do not change with pregnancy, so any changes in these 
measures should be considered abnormalities and treated as 
such. 

Recent information suggests that during painful labor there 
is relative hypoventilation between contractions resulting in 
decreased maternal PO2. 

With normal pulmonary function, the fetal implications of 
this phenomenon are negligible. However, this information 
forms a rationale for the liberal use of oxygen in laboring 
patients with any degree of respiratory impairment. Maternal 
oxygen saturation must remain greater than 95 percent to 
assure adequate fetal oxygenation (Clark, 1990). 

Cardiovascular System Changes 

During normal pregnancy, resting cardiac output is 
significantly increased by 6 weeks gestation, peaking at 30 
to 50 percent over nonpregnant values by the early part of 
the third trimester (Clark et al., 1989). This increase is a 
result of increases in both heart rate and stroke volume and 
is sustained throughout the pregnancy (see table 3). In the 
third trimester, cardiac output is significantly decreased in 
either the supine or standing positions. Up to 10 percent of 
women may experience the "supine hypotensive syndrome," a 
marked drop in blood pressure resulting from venacaval 
occlusion in the supine position (Holmes, 1960). Supine 
hypotension can have important maternal hemodynamic 
consequences and, because of decreased uterine perfusion, may 
result in fetal hypoxia and bradycardia. Thus recumbent 
pregnant women should avoid the supine position and favor the 
lateral decubitus or lateral tilt position. 

Further significant increases in cardiac output are seen in 
the peripartum period. Labor is associated with an 
additional 1 to 2 liters per minute by the second stage 
(Ueland & Hansen, 1969). This increase may be minimized by 
having the patient labor in the lateral recumbent position 
with epidural anesthesia (Clark et al., 1991). In the 
immediate postpartum period, cardiac output is increased 
further, by up to 40 to 50 percent (Ueland et al., 1969), as 
a result of the "autotransfusion" phenomenon--the release of 
venacaval obstruction and expulsion of blood from the 
utero/placental bed into the central circulation. Thus the 
period of maximum risk for patients with compromised 
cardiovascular function is during the peripartum period. 
Cesarean section does not appear to reduce this risk. 

Circulatory System Changes 

Blood volume. Blood volume increases markedly in 
pregnancy, with an increase in plasma volume at term 
averaging 40 to 50 percent over nonpregnant values (Clark et 
al., 1989). This increase, due to estrogen stimulation of 
aldosterone, begins as early as 4 to 6 weeks gestation, 
plateaus at approximately 32 to 34 weeks gestation, and then 
remains unchanged until delivery. There is a concomitant 
increase in red cell mass, erythropoiesis being stimulated by 
chorionic somatomammotrophin, progesterone, and possibly 
prolactin. Because red cell mass is increased 20 to 25 
percent as opposed to the greater increase in plasma volume, 
a "physiologic anemia" of pregnancy may be produced. In 
absolute terms, it is estimated that blood volume in single 
pregnancies is increased 1,600 cc, with an average 2,000-cc 
increase observed by 32 weeks in twin gestations. 

Blood pressure. Systolic and diastolic arterial blood 
pressure decrease until midpregnancy and gradually return to 
nonpregnant values by term (Wilson et al., 1980). These 
changes appear to be secondary to hormonally mediated 
decreases in systemic vascular resistance. Thus blood 
pressures that might be considered frankly hypotensive in the 
adult male may be normal in the pregnant female, especially 
during the second trimester of pregnancy. In evaluating 
blood pressure in the seriously ill pregnant patient with 
asthma, a comparison of prenatal blood pressure records is 
important. 

Other hemodynamic changes. Systemic vascular resistance 
falls by the second trimester, rising toward normal by late 
third trimester. However, even in the late third trimester, 
systemic vascular resistance is decreased by 20 percent 
compared to nonpregnant controls (Clark et al., 1989). 
Similarly, pulmonary vascular resistance falls 35 percent by 
late pregnancy compared to nonpregnant values. Left 
ventricular stroke work index, pulmonary capillary wedge 
pressure, and central venous pressure all remain unchanged. 
The pulmonary-capillary-wedge pressure/colloid-oncotic 
pressure gradient decreases significantly, however, by the 
third trimester of pregnancy. This predisposes the pregnant 
woman to pulmonary edema, either because of increased 
intravascular pressure (i.e., increased fluid overload) or 
increased pulmonary capillary permeability. 

Fetal Response to Maternal Critical Illness

In the presence of maternal critical illness, such as an 
acute exacerbation of asthma, the maternal arterial PO2 may 
fall from its normal value of near 106 mmHg. Because the 
fetus operates on the steep portion of the oxygen 
dissociation curve (normal fetal venous PO2 is close to 33 
mmHg), decreases in maternal and fetal PaO2 (especially below 
60 mmHg) can result in profoundly decreased fetal oxygen 
saturation and fetal hypoxia. Administration of oxygen to 
the mother produces only small increases in fetal PaO2. For 
example, as the maternal PaO2 increases from 91 to 583 mmHg, 
fetal PaO2 rises only from 11 to 16 mmHg. However, because 
the fetus is on the steep portion of the hemoglobin oxygen 
dissociation curve, a small change in fetal PaO2 produces 
significantly increased fetal oxygen saturation and may be of 
benefit to the marginally hypoxic fetus (Motoyama et al., 
1967; Sobrevilla et al., 1971). This may be especially true 
if there are problems with fetal-placental function such as 
intrauterine growth retardation. Thus, aggressive monitoring 
of fetal well-being is essential during critical maternal 
illness. 

Adequacy of uterine blood flow is another important 
consideration for the fetus of a seriously ill mother. Near 
term, uterine blood flow approaches 500 cc per minute, 
accounting for approximately 10 percent of total maternal 
cardiac output. Circulation to the placental cotyledons 
accounts for 85 to 90 percent of uterine blood flow at term. 
The uterine arteries exhibit remarkably little capacity for 
autoregulation. Thus as systemic arterial pressure falls, so 
does uterine and placental blood flow. In addition, maternal 
hyperventilation and hypocarbia may cause uterine vasospasm, 
decreasing uterine blood flow. In the hypotensive or hypoxic 
mother, compensatory vasodilation aimed at maintaining 
circulation to vital organs such as the heart and brain will 
decrease uterine blood flow even further. It is therefore 
not surprising that maternal hypotension or significant 
hypoxia of any etiology may be first brought to the 
clinician's attention by an abnormal fetal heart rate pattern 
indicating fetal distress. Because maternal compensatory 
mechanisms will tend to maintain systemic arterial pressure 
and oxygenation of vital maternal organs at the expense of 
uterine blood flow, fetal distress can occur even in the 
absence of maternal hypotension or hypoxia. Thus the fetus 
acts as a built-in oximeter; in the absence of fetal heart 
rate abnormalities, clinically significant maternal hypoxia 
or hypotension are highly unlikely (Clark, 1990). 

Aggressive monitoring of fetal well-being is essential during 
critical maternal illness. Although abrupt and profound 
maternal cardiopulmonary decompensation, manifested as fetal 
bradycardia, should be readily apparent, more subtle 
deterioration of maternal condition may produce only 
diminished beat-to-beat fetal heart rate variability and/or 
subtle hypoxic decelerations. Thus even in a medical or 
surgical intensive care unit setting, continuous electronic 
monitoring of the fetal heart rate, along with appropriate 
interpretation, is important after the beginning of the third 
trimester. 

Fetal Management 

Intrauterine growth retardation and adverse perinatal outcome 
have been associated with asthma during pregnancy. For this 
reason, all patients with moderate or severe asthma or 
uncontrolled asthma during pregnancy should have serial 
ultrasound assessment of fetal growth as well as antepartum 
fetal heart rate assessment during the late third trimester 
of pregnancy. 


The Effect of Asthma on Mother and Fetus 

Epidemiologic Studies 

Two large epidemiologic studies published in the early 1970's 
most clearly define the potential adverse effects of maternal 
asthma on pregnancy and the infant. One study (Bahna & 
Bjerkedal, 1972) described pregnancy outcomes in 381 women 
with asthma compared to a control population of 112,530 
pregnant women with no medical illness. There was a 
statistically significant increase in preterm births and low 
birth weight infants, decreased mean birth weight, increased 
neonatal mortality, and increased neonatal hypoxia in the 
pregnancies of women with asthma compared to control 
pregnancies. The study also found a statistically 
significant increase in hyperemesis gravidarum, vaginal 
hemorrhage, and toxemia as well as a significant increase in 
induced and complicated labors in pregnant women with asthma 
versus control pregnant women. The study did not find an 
increased incidence of congenital malformations. 

The second study (Gordon et al., 1970) compared the pregnancy 
outcome of 277 women with asthma to the pregnancy outcome of 
the entire cohort population of 30,861 women. This study 
found a statistically significant increase in perinatal 
mortality in pregnant women with asthma versus pregnant women 
without asthma. Neonatal mortality was not specifically 
reported in this series. Maternal "chronic hypertensive 
disease" was present in three of the eight cases of fetal 
death. The data also suggested that pregnant women with 
severe asthma were at particularly high risk. 

Subsequent controlled studies have reported increases in low 
birth weight infants (Lao & Huengsburg, 1990), chronic 
hypertension (Dombrowski et al., 1986), and preeclampsia 
(Stenius-Aamiala et al., 1988) in pregnant women with asthma 
compared to pregnant women without asthma. In addition to 
fetal morbidity and mortality, severe asthma during pregnancy 
may be a cause of maternal mortality (Gordon et al., 1970; 
Schaefer & Silverman, 1961; Williams, 1967). These 
epidemiological studies have found that pregnant women with 
asthma have increased risk of perinatal mortality, 
prematurity, intrauterine growth retardation, gestational 
hypertension, and other adverse effects. These studies, 
however, do not define the mechanisms of the increased risk. 

Mechanisms 

Definition of the mechanisms of asthma's adverse effects on 
pregnancy would allow institution of optimal intervention 
strategy. Potential explanations for the adverse effects of 
maternal asthma on pregnancy and the neonate include: (1) 
poor asthma control, (2) asthma medications (see chapter 4), 
(3) increased prevalence of cigarette smoking among pregnant 
women with asthma versus pregnant women without asthma 
(Dombrowski et al., 1986), (4) extrapulmonary autonomic 
nervous system abnormalities, such as uterine muscle 
hyperreactivity (Bertrand et al., 1985), and (5) an increased 
proportion of African Americans among asthma patients 
(Centers for Disease Control, 1990a) with associated excess 
perinatal morbidity (Centers for Disease Control, 1990b). 
The published data do not fully define the mechanism(s) of 
maternal asthma's potential adverse effects on pregnancy and 
the infant. However, available information does suggest that 
poor asthma control may be the most important factor (see 
table 4). The information available also supports the 
important generalization that adequate asthma control during 
pregnancy is important in improving maternal/fetal outcome. 


Effects of Pregnancy on Asthma 

Epidemiology 

A number of studies suggest that the course of asthma may 
change during pregnancy. In a combined series of 1,087 
patients from the literature, the course of asthma was 
reported to improve in 36 percent, worsen in 23 percent, and 
remain unchanged in 41 percent (Gluck & Gluck, 1976). 
However, individual studies differed substantially in their 
results (Gluck & Gluck, 1976). This pattern is maintained in 
recent studies (Gluck & Gluck, 1976; Juniper et al., 1989; 
Schatz et al., 1988a; Stenius-Aamiala et al., 1988; White et 
al., 1989), in which 18 to 69 percent of patients improved 
while 6 to 42 percent worsened. There are at least two 
reasons for this variability: (1) the method by which the 
course of asthma was assessed and (2) the asthma severity of 
the population studied. Review of the data suggests that 
women with severe asthma prior to pregnancy are more likely 
to deteriorate during pregnancy (Gluck & Gluck, 1976; White 
et al., 1989). The variable effect of pregnancy on the 
course of asthma appears to be more than random fluctuations 
in the natural history of the disease because the changes 
generally revert toward the prepregnancy level of severity 
within 3 months postpartum (Schatz et al., 1988a). It is 
also of interest that asthma severity is often consistent 
among successive pregnancies in individual women (Schatz et 
al., 1988a; Williams, 1967). 

Other Clinical Observations 

A study that prospectively evaluated methacholine sensitivity 
in 16 pregnant women with asthma (Juniper et al., 1989) found 
a twofold improvement (decrease) in airway responsiveness 
during pregnancy compared to preconception and postpartum. 
An associated improvement in clinical asthma severity, as 
indicated by a reduction in minimum medication requirements, 
was also observed. Individually, 11 of 16 subjects 
demonstrated improved airway responsiveness. Change in 
responsiveness was not closely related to serum 
concentrations of progesterone or estriol. 

Additional observations have identified factors contributing 
to worsening asthma during pregnancy. Upper respiratory 
tract infections appear to be the most common precipitants of 
asthma exacerbations during pregnancy (Williams, 1967). 
Patient noncompliance with medical regimens may also be 
associated with poor asthma control during pregnancy, 
especially among adolescents (Apter et al., 1989). The peak 
incidence of exacerbations appears to be between the 24th and 
36th weeks of gestation (Gluck & Gluck, 1976), particularly 
in women whose asthma worsens with pregnancy (Schatz et al., 
1988a). In contrast, women with asthma, in general, tend to 
experience fewer symptoms during weeks 37 to 40 of pregnancy 
than during any prior 4-week gestational period (Schatz et 
al., 1988a). Finally, asthma generally remains quiescent 
during labor and delivery. Ninety percent of 360 women with 
asthma in one study had no symptoms of asthma at all during 
labor and delivery (Schatz et al., 1988a). Of those who did, 
approximately half required no acute treatment, some used 
inhaled bronchodilators, and only two required intravenous 
aminophylline. 

Mechanisms 

The mechanisms responsible for the altered course of asthma 
during pregnancy are unknown and represent a fertile area for 
additional research. There are multiple biochemical, 
physiological, and psychological factors that could 
potentially ameliorate or exacerbate asthma during pregnancy 
(see table 5). It seems probable that the importance of 
individual factors varies from individual to individual, and 
presumably a combination of these factors determines what 
effect, if any, pregnancy will have on the course of asthma.





4
Asthma Drugs in Pregnancy and Lactation

The effects of drugs used for asthma on fetal development and 
on infants who are breast fed are discussed in this chapter. 

When considering the possible effects of drugs and disease on 
pregnancy, it is important to keep in mind the background 
incidence of adverse pregnancy outcome in the general 
population. For example, congenital anomalies are recognized 
in 3 to 8 percent of live-born infants, miscarriage occurs in 
20 to 25 percent of clinically diagnosed pregnancies, and 
severe mental retardation occurs in 1 to 2 percent of births. 
In addition, although birth defects are the most dramatic 
evidence of embryogenesis gone amiss, other endpoints of 
abnormal development are equally significant. These include 
spontaneous abortion (miscarriage), fetal death (stillbirth), 
and functional abnormalities such as impairments in the 
nervous or immune systems. Growth retardation, preterm 
labor, and other obstetric complications are also 
developmental problems of clinical importance. The challenge 
is to determine whether a drug or disease exposure increases 
the incidence of adverse outcome over the background 
incidence. 

It is also important to remember that drug-induced birth 
defects are unusual: Of the 3 to 8 percent of newborns with 
congenital anomalies, only 1 percent or fewer of these are 
attributable to drug exposures (Czeizel & Racz, 1990). 


PHYSIOLOGIC CHANGES IN PREGNANCY AFFECTING DRUG DISTRIBUTION

With the profound physiologic changes that occur during 
pregnancy, it is reasonable to suppose that these changes 
affect the manner in which drugs are handled by the body. 
Pharmacokinetics is the study of drug absorption, 
distribution, metabolism, and elimination in the body. 
Although few therapeutic agents have been completely studied 
as to the effect of pregnancy on the drug's pharmacokinetics, 
the following changes have been shown to occur during 
pregnancy and are clinically relevant: 

 Reduction in plasma proteins. This is largely caused 
by a decrease in serum albumin concentration (Dean et al., 
1980). During pregnancy, drugs bound to serum albumin show a 
reduction in protein binding and a corresponding increase in 
the available free fraction of the drug (Connelly et al., 
1990; Frederiksen et al., 1986; Gardner et al., 1987). This 
change in protein binding implies that for certain drugs 
plasma concentrations should be reduced or kept at the lower 
end of the therapeutic range during pregnancy (Connelly et 
al., 1990). For example, the protein binding of theophylline 
decreases by 10 to 15 percent during pregnancy; therefore, 
the therapeutic range for theophylline needs to be modified 
to account for the corresponding increase in the free 
fraction of theophylline. During pregnancy, theophylline 
plasma concentrations between 8 and 12 g/mL are 
therapeutically equivalent to concentrations of 10 to 15 
 g/mL in the nonpregnant patient. 

 Increased total body water and plasma volume. 
Several studies, however, have shown that this change does 
not affect the volume of distribution for drugs if the weight 
of the patient is taken into consideration (Aldridge et al., 
1981; Frederiksen et al., 1986; Gardner et al., 1987; 
Philipson, 1977; Philipson & Stiernstedt, 1982). Therefore, 
to achieve the therapeutic drug concentration usually 
recommended, the mg/kg dose should be calculated using the 
actual weight of the patient. For example, to calculate a 
loading dose of aminophylline or theophylline for a pregnant 
patient not previously receiving a methylxanthine, use the 
recommended 6-mg/kg regimen and the actual weight of the 
patient at the time therapy is instituted. 

 Decreased gastrointestinal motility. This change 
does not affect the overall absorption of even poorly 
absorbed drugs, such as ampicillin (Philipson, 1977); 
however, the time to peak drug concentration is prolonged, 
and the peak concentration is lower (Philipson, 1977). This 
may in part explain the observation that an oral dose of 500 
mg of ampicillin during pregnancy gives a plasma peak 
concentration 40 percent lower than in a nonpregnant patient, 
and the peak concentration occurs approximately 1 hour later. 

 Altered drug elimination. Pregnancy can alter the 
manner in which drugs are eliminated from the body, with the 
greatest effect occurring in the last trimester of pregnancy. 
Renal elimination of drugs may increase for such drugs as 
theophylline, ampicillin, and cefuroxime due to the increase 
in glomerular filtration rate that occurs during pregnancy 
(Frederiksen et al., 1986; Philipson, 1977; Philipson & 
Stiernstedt, 1982). Metabolic elimination of drugs is less 
predictable; some drugs, such as methadone, have an increase 
in metabolic clearance (Pond et al., 1985) and others, 
including theophylline, have a decrease in metabolic 
clearance (Frederiksen et al., 1986; Gardner et al., 1987). 
Therefore, the elimination route and characteristics of each 
drug must be considered, and frequent use of therapeutic drug 
monitoring is indicated. Thus, because the overall 
elimination rate of intravenous methylxanthine decreases by 
30 percent in the last trimester of pregnancy, the 
recommended dose for intravenously administered 
methylxanthine is a continuous infusion rate of 0.4 mg/kg/hr 
theophylline (or 0.5 mg/kg/hr aminophylline) in order to 
maintain serum theophylline concentrations within the range 
of 8-12 g/mL. 

As a general rule most medications administered to pregnant 
women will cross the placenta and can be detected in fetal 
blood. However, extremely large molecular weight drugs, or 
highly polar compounds, such as heparin, do not effectively 
cross the placenta in measurable amounts. 

Breast Feeding 

Nearly all medications enter breast milk by diffusion from 
plasma. Milk concentrations are typically very low, and it 
is unusual for infants to receive a dose sufficient to 
produce toxic effects. Recommendations concerning drugs and 
breast feeding have been made by the American Academy of 
Pediatrics Committee on Drugs (1989) and by the World Health 
Organization (Bennett, 1988).


HOW DRUG THERAPIES ARE EVALUATED

Animal Data 

Experimental animals differ from humans in a number of ways, 
including drug handling, sensitivities to drug effects, and 
embryonic timetables. These differences notwithstanding, 
animal teratology experiments can be useful in evaluating 
human drug risks. 

Animal studies are designed to maximize the response of the 
system to potential toxic effects of test agents. This is 
accomplished by using large doses; the highest dose 
customarily chosen is one that induces maternal toxicity. 

It is believed that positive results in a testing scheme 
using appropriate doses in at least two species, one of which 
is not a rodent, is sufficient to raise suspicion of human 
developmental risk. There are no known human developmental 
toxicants that would not be identified by this scheme. It 
follows that if an agent is appropriately tested in 
animals and found not to be a developmental toxicant, its 
potential for developmental toxicity in humans is low. 
Thalidomide is often given as an example for which animal 
testing was inadequate to identify human developmental risk. 
In fact, thalidomide was tested before the development of 
modern protocols and is not a reflection on the adequacy of 
current testing methods, which would have detected 
thalidomide's risk. 

Positive data in animal studies are not completely 
informative because it may not be possible to know whether 
the high doses used, maternal toxicity, or species 
differences were responsible for the effects on the 
offspring. 

Human Data 

Case reports, in which an exposure and an outcome are 
presented, are the most common human data available, but they 
cannot be used to imply cause and effect. Controlled human 
studies include two general designs: the cohort, in which 
exposed and nonexposed populations are evaluated 
prospectively to determine outcome, and the case control, in 
which affected and nonaffected subjects are evaluated 
retrospectively for whether or not they were exposed. Cohort 
studies require large numbers of exposed women to detect 
unusual outcomes and are often impractical and expensive. 
Case control studies identify outcomes of interest; however, 
accurate ascertainment of exposure may be difficult. With 
both cohort and case control studies, controlling for 
confounding factors, such as other exposures, ethnicity, and 
socioeconomic factors, is important. 

Human reports, when available, can be reassuring supplements 
to negative animal data. By themselves, human studies rarely 
include sufficient numbers of exposed individuals to rule out 
a low order increase in adverse pregnancy outcome. 

One of the largest human cohort drug studies during pregnancy 
was the National Collaborative Perinatal Project (Heinonen et 
al., 1977). In this investigation, women were enrolled as 
early as possible during pregnancy. Histories were taken for 
exposure to medications and other agents. As the pregnancies 
progressed, exposure histories were updated. The outcomes 
for more than 50,000 children were evaluated, and 
associations between exposures and birth defects were 
identified. As the investigators of this study noted, the 
large number of different exposures and the large number of 
different adverse outcomes made it likely that some exposures 
and outcomes would be associated by chance alone. Therefore, 
all data suggesting impact of drugs on pregnancy outcome from 
the National Collaborative Perinatal Project should be viewed 
as preliminary until independently confirmed. 

The FDA Categories 

In an effort to summarize the availability of animal and/or 
human developmental data on a drug, the Food and Drug 
Administration (FDA) uses a letter-based code (A, B, C, D, or 
X). A large amount of information of varying quality may not 
be adequately represented by a single letter designation, and 
the FDA category scheme is not considered very useful for 
making specific therapeutic decisions. 


ASTHMA DRUGS: SUMMARIES OF FINDINGS

This section and table 6 contain summaries of the findings of 
studies evaluating the various asthma drugs. Information 
about the specific studies on which these summaries are based 
may be found in the subsequent section, Asthma Drugs: Human 
and Animal Data. 

Anti-Inflammatory Agents 

Corticosteroids. Among the most effective anti-
inflammatory drugs for the treatment of asthma are 
corticosteroids. The primary mechanisms of action are 
interference with arachidonic acid metabolism and synthesis 
of leukotrienes and prostaglandins, prevention of directed 
migration and activation of inflammatory cells, and increased 
responsiveness of beta-
receptors of airway smooth muscle. Corticosteroids can be 
administered parenterally (e.g., methylprednisolone, 
hydrocortisone), orally (e.g., prednisone, prednisolone, 
methylprednisolone), or as aerosols (beclomethasone, 
flunisolide, and triamcinolone). 

Chronic maternal administration of oral or parenteral 
(systemic) corticosteroids have been associated with 
decreased birth weight. Animal studies show palatal clefting 
in species very sensitive to this anomaly, but no increase in 
birth defects has appeared in humans. Three agents are 
available for inhalation: beclomethasone, triamcinolone, and 
flunisolide. Of these, the largest experience in pregnancy 
is with beclomethasone. Triamcinolone and flunisolide use 
during pregnancy has not been studied. Because of its 
reassuring clinical experience, beclomethasone is the 
preferred inhaled corticosteroid during pregnancy. Although 
systemic absorption of inhaled corticosteroids can occur, the 
low plasma levels achieved by inhalation make it unlikely 
that fetal effects will be seen. Neither systemic nor 
inhaled corticosteroid use by the mother is a 
contraindication to breast feeding. 

Cromolyn sodium. This drug is a nonsteroidal anti-
inflammatory agent for the chronic management of asthma. 
Administered prophylactically, cromolyn sodium inhibits 
early- and late-phase allergen-induced airway narrowing as 
well as acute airway narrowing after exercise and after 
exposure to cold dry air and sulfur dioxide. Its mechanism 
of action is not fully understood, but it is thought that 
cromolyn sodium stabilizes and prevents mediator release from 
mast cells. 

Acceptable animal studies and human experience suggest little 
potential for fetal harm from cromolyn sodium.

Nedocromil sodium. This is a new anti-inflammatory 
pyranoquinalone that appears similar in action to cromolyn 
sodium. Although preclinical animal data are reassuring, 
there is no reported experience with this agent during human 
pregnancy. 

Bronchodilators 

Beta2-adrenergic agonists (beta2-agonists). Beta2-
agonists relax airway smooth muscle and may modulate mediator 
release from mast cells and basophils. Inhaled beta2-
agonists are the medications of choice for initial treatment 
of acute exacerbations of asthma and for the prevention of 
exercise-induced asthma. Beta2-agonists have also been used 
chronically to aid in the control of persistent airway 
narrowing, although recent reports suggest that regularly 
scheduled use of beta2-agonists (as opposed to as-needed or 
prn use) is associated with diminished control of asthma 
(Sears et al., 1990). Because well-controlled asthma 
requires minimal use of inhaled beta2-agonist, increased use 
is an indication of deteriorating control. Metaproterenol 
(orciprenaline), albuterol (salbutamol), pirbuterol, 
bitolterol, and terbutaline are commonly used selective 
beta2-agonists. 

Animal studies with beta2-agonists are generally negative, 
although some of these agents produce anomalies at high 
doses. Human experience is extensive, but generally 
restricted to the latter part of pregnancy. There is no 
evidence of fetal injury from the use of these drugs 
systemically or by inhalation, and there is no 
contraindication to the use of these agents during lactation. 

Nonselective beta-agonists. Beta-agonists that activate 
both beta1 and beta2 receptors include epinephrine 
(adrenaline) and its isopropyl analog, isoproterenol. 
Epinephrine given subcutaneously in severe acute 
exacerbations may be considered, although other therapies are 
initiated first. Epinephrine is also present in some over-
the-counter asthma inhalers, although its use in this manner 
is not recommended. Concern has been raised about uterine 
vasoconstriction due to the alpha-adrenergic effects of 
epinephrine (Briggs et al., 1990). 

The effects of nonselective beta2-agonists on experimental 
animals may be of concern; however, the occasional, episodic 
use of epinephrine for severe acute exacerbations is unlikely 
to produce chronic hemodynamic changes such as were seen in 
the animal studies. The positive findings of the National 
Collaborative Perinatal Project require confirmation before 
they can be considered sufficient evidence of epinephrine 
toxicity. 

Theophylline. Theophylline is the principal methylxanthine 
used in asthma 

therapy. Although its precise mechanism is not known, 
theophylline serves as a mild-to-moderate bronchodilator, 
depending upon serum concentration. When given in a 
sustained-release preparation, it has long duration of action 
and is thus particularly useful in the control of nocturnal 
asthma. When used in combination with usual doses of inhaled 
beta2-agonists, theophylline may produce additional 
bronchodilation. In addition, theophylline may also reduce 
respiratory muscle fatigue and possess some degree of anti-
inflammatory activity. 

Theophylline use during pregnancy has been extensive and 
without evidence of adverse effects to the neonate when doses 
are guided by appropriate serum levels (not exceeding 12 
 g/mL). Approximately 1 percent or less of the maternal 
theophylline dose reaches the nursing infant; this is usually 
not clinically significant. 

Anticholinergics. Inhaled anticholinergic agents produce 
bronchodilation by reducing intrinsic vagal tone to the 
airways. Such agents also block reflex bronchoconstriction 
caused by inhaled irritants. Atropine, a belladonna 
alkaloid, is the prototype anticholinergic, but it has local 
and systemic adverse effects for the patient with asthma. 
Ipratropium, a quaternary derivative given by inhalation, 
lacks atropine's adverse effects. It has been shown to be 
effective in treating acute exacerbations when used in 
nebulized form. The role of ipratropium in day-to-day 
management of asthma has not been established. 

Anticholinergic agents have been used during pregnancy 
without adverse effects. Ipratropium produces less systemic 
effect than atropine and is not contraindicated in pregnancy, 
although it is generally not used except for patients with 
severe asthma. 

Antihistamines 

Antihistamines are used to block the action of histamine 
released during a mast cell activation in response to an 
allergen or other stimulus. Antihistamines are present in 
many over-the-counter cold and allergy remedies. Newer H1-
blockers such as terfenadine and astemizole have 
significantly less sedative properties than older "first 
generation" medications. 

Antihistamines have not been shown to be harmful during early 
pregnancy, and the animal and human experience suggest 
little, if any, potential for human teratogenicity. It seems 
reasonable to choose older antihistamines for which 
reassuring human data exist for use during pregnancy. 
Although concerns have been raised about antihistamine 
effects on young children, there are no data establishing 
adverse effects due to late pregnancy or lactational use of 
these drugs. Antihistamines are considered compatible with 
breast feeding (American Academy of Pediatrics Committee on 
Drugs, 1989). 

Decongestants 

Decongestants are alpha-adrenergic drugs used to constrict 
blood vessels in the nasal mucosa. Agents in this class 
include oxymetazoline, phenylephrine, phenylpropanolamine, 
ephedrine, and pseudoephedrine. Because these drugs have 
alpha-adrenergic activity, there is concern about their 
potential to constrict the vascular supply involved in 
maternal-fetal gas and nutrient exchange (Smith & Corbascio, 
1970); however, pseudoephedrine appears not to produce this 
effect at therapeutic doses. Human experience with 
decongestants has not produced a consistent picture of birth 
defects, although the National Collaborative Perinatal 
Project has raised questions about phenylephrine and 
phenylpronolomine. 

Immunotherapy/Environmental Agents 

A number of reports have appeared describing immunotherapy 
without apparent adverse effect on human pregnancy (Chester, 
1950; Derbes & Sodeman, 1946; Heinonen et al., 1977; Jensen, 
1953; Maietta, 1955; Metzger et al., 1978; Schaefer & 
Silverman, 1961). Anaphylaxis following immunotherapy is a 
potential risk to mother and fetus. Patients already 
receiving immunotherapy may be maintained at their current or 
somewhat reduced dose during pregnancy; however, it is 
generally advisable not to begin immunotherapy during 
pregnancy. 

The influenza vaccine is a killed virus vaccine. There have 
been two reports that together include 245 women vaccinated 
just before or during pregnancy. No adverse outcomes were 
attributable to the vaccine (Deinard & Ogburn, 1981; Sumaya & 
Gibbs, 1979). 

Tannic acid may be used to denature environmental cat or dust 
mite antigen. There are no published studies on exposure to 
this agent during pregnancy. 

Benzyl benzoate is an ascaricide used to clear dust mites 
from an environment. Teratogenicity tests have been negative 
in rats (Morita et al., 1981) and mice (Eibs et al., 1982). 

Boric acid is useful as an insecticide in eliminating 
cockroaches. Feeding boric acid to pregnant rats does not 
increase the incidence of adverse pregnancy outcome (Weir & 
Fisher, 1972). An evaluation of 253 pregnancies with early 
exposure to boric acid was unable to identify a significant 
increase in the incidence of birth defects in the offspring 
(Heinonen et al., 1977). 


ASTHMA DRUGS: HUMAN AND ANIMAL DATA

Anti-Inflammatory Agent: Corticosteroids 

Developmental Toxicity--
Animal Data 

High doses of corticosteroids characteristically cause cleft 
palate in developing mice, rats, and rabbits, although not 
all steroids produce this effect in all species (Pinsky & 
DiGeorge, 1965; Walker, 1967, 1971). The developmental 
toxicity of beclomethasone in mice and rabbits is similar to 
that associated with other corticosteroids, consisting of 
increased fetal resorptions and cleft lip/palate (Esaki et 
al., 1976; Ohguro et al., 1970). High-dose inhalation 
studies in pregnant monkeys and feeding studies in rats 
demonstrate that a decrease in fetal survival and weight is 
associated with the maternal toxicity of this agent, but 
without an observable increase in fetal malformations in 
these species (Furuhashi et al., 1979; Hasegawa et al., 1979; 
Sumaya & Gibbs, 1979; Tanioka, 1976). 

Triamcinolone has been associated with cleft palate in 
offspring when given to pregnant mice, rats, rabbits, and 
hamsters (Shah & Kilistoff, 1976; Walker, 1965, 1967, 1969). 
It also caused central nervous system, craniofacial, and 
other abnormalities in the offspring of three different 
nonhuman primates (Hendricks et al., 1975, 1980; Jerome & 
Hendricks, 1988; Parker & Hendricks, 1983; Tarara et al., 
1988). It has been noted that triamcinolone is 200 times 
more potent in producing palatal clefts in mice than is 
cortisone (Walker, 1965). In avian experiments, 
triamcinolone produces inhibition of scale and feather 
development, as do other corticosteroids; however, 
triamcinolone is 10,000 times more potent a teratogen in this 
model than is hydrocortisone (Fischer & Sawyer, 1986). 

Developmental Toxicity--
Human Data 

A large experience with humans has failed to suggest any 
increase in facial clefts or other birth defects from the use 
of corticosteriods (Bongiovanni & McPadden, 1960; Briggs et 
al., 1990; Serment & Ruf, 1968). 

Clinical observations suggest prenatal exposure to systemic 
corticosteroids is associated with a 300- to 400-gram 
decrease in birth weight and a small increase in "small-for-
dates" babies (Pirson et al., 1985; Reinisch et al., 1978; 
Scott, 1977). This effect on growth has been seen in women, 
without other known causes of fetal growth impairment, who 
took 10 mg of prednisone throughout their pregnancies 
(Reinisch et al., 1978). Severe fetal growth retardation has 
been described in a single case in which a woman used 
extremely high doses of topical (not inhaled) triamcinolone 
in the middle trimester of pregnancy (Katz et al., 1990). 

There have also been concerns that some of the toxicity 
associated with corticosteroids in adults may be seen in 
offspring. Cataracts are occasionally observed in adults 
receiving corticosteroids, and congenital cataracts were 
reported in one infant exposed to prednisone throughout 
pregnancy (Kraus, 1975). 

Suppression of the immune system may be seen with high-dose 
corticosteroids. Although immunosuppression lasting 15 weeks 
after birth was observed in one infant born of a woman 
receiving high doses of prednisone and azathioprine (Cote et 
al., 1974), lymphopenia and reduced immunoglobin levels have 
not been commonly observed in similarly exposed infants 
(Cederqvist et al., 1977). 

Two clinical studies have investigated the outcome of 101 
pregnancies in which women received beclomethasone and/or 
prednisone for severe asthma (Fitzsimmons et al., 1986; 
Greenberger & Patterson, 1983). The prevalence of congenital 
malformations in this population was within the normal range 
for all births, although the incidence of premature 
deliveries and low birth weight infants was slightly 
increased (Fitzsimmons et al., 1986). 

In general, nonhalogenated corticosteroids do not cross the 
placenta well, and there is no reason to believe that fetal 
or neonatal adrenal suppression will occur with maternal 
therapy. High-dose systemic corticosteroids have been used 
to accelerate lung maturity in pregnancies at risk for 
premature delivery. Although a number of reports raised 
concerns about effects of such therapy on brain development, 
followup of treated human pregnancies has shown no adverse 
effects of steroid treatment on neurodevelopmental testing at 
age 5 (Doyle et al., 1989). 

Breast Feeding 

Small amounts of prednisone and its active metabolite, 
prednisolone, will enter breast milk (Katz & Duncan, 1975; 
McKenzie et al., 1975; Ost et al., 1985). Even at 80 mg per 
day, however, the amount secreted in breast milk would be 
equivalent to less than 10 percent of a nursing infant's 
endogenous cortisol production, and it is unlikely that such 
a dose could produce clinically significant effects (Ost et 
al., 1985). Prednisone and prednisolone are considered 
compatible with breast feeding (American Academy of 
Pediatrics Committee on Drugs, 1989). 

Anti-Inflammatory Agent: Cromolyn Sodium 

Developmental Toxicity--Animal Data 

Intravenous and subcutaneous injections of cromolyn or 
closely related compounds did not produce fetal malformations 
in mice, rats, or rabbits (Cox et al., 1970). 

Developmental Toxicity--Human Data 

A report on 296 pregnancies during which cromolyn was used 
did not suggest an increase in fetal abnormalities associated 
with this drug (Wilson, 1982). 

Anti-Inflammatory Agent: Nedocromil Sodium 

Developmental Toxicity--
Animal Data 

Adverse reproductive effects were not seen in preclinical 
reproductive studies in rats and rabbits using 800 times the 
human therapeutic dose (Clark et al., 1986). Insufficient 
detail was presented in the report to evaluate the 
teratologic methods used. 

Developmental Toxicity--
Human Data 

None available. 

Bronchodilator: Beta-Adrenergic Agonists (Beta2-
Agonists) 

Developmental Toxicity--
Animal Data 

Experiments using mice, rats, rabbits, and rhesus monkeys 
have not associated metaproterenol with teratogenic activity 
(Banerjee & Woodard, 1971; Hollingsworth et al., 1971; Matsuo 
et al., 1982). 

In a preliminary study published in abstract, albuterol 
(salbutamol) produced an increase in cleft palate in mice but 
no increase in anomalies in rats and rabbits (Szabo et al., 
1975). Unpublished reports from the manufacturer also show 
cleft palate induction in mice, which are very susceptible to 
this defect, and cranioschisis in rabbits. The latter effect 
was produced with 78 times the maximum human dose. 
Pirbuterol, an analog of albuterol, did not result in 
increased congenital anomalies in the offspring of rats and 
rabbits treated during pregnancy (Sakai et al., 1989). 

Unpublished studies by the manufacturer reported no adverse 
pregnancy effects in mice, rats, or rabbits given up to 1,500 
times the recommended human dose of terbutaline. Similar 
reports for pirbuterol noted no adverse effects at very high 
doses (300 mg/kg) in rats. In rabbits, this high dose 
produced abortion and fetal mortality. No information was 
given on maternal toxicity, a possible contributor to fetal 
death at such high doses. 

Developmental Toxicity--
Human Data 

Experience with beta2-adrenergic agonists as tocolytics has 
shown that these drugs can produce tachycardia, hypoglycemia, 
and tremor in prenatally exposed neonates (Baillie et al., 
1970; Zilianti & Aller, 1971). The effects are treatable and 
reversible and do not constitute contraindications to the use 
of these medications. Terbutaline treatment of pregnant 
women has been shown to produce either no change or an 
increase in uterine blood flow (Akerlund et al., 1975; 
Cskny et al., 1982; Soares de Moura, 1981). Inhaled beta2-
agonist therapy did not produce an increase in adverse 
pregnancy outcome in 259 women, 180 of whom used these agents 
during the first trimester (Schatz et al., 1988b). 

Breast Feeding 

Terbutaline is considered compatible based on the very low 
levels appearing in milk (Bennett, 1988). Presumably, the 
same considerations apply to other agents in this group. 

Bronchodilator: 
Nonselective Beta-Agonists 

Developmental Toxicity--
Animal Data 

Anomalies have been produced by direct epinephrine injection 
of rat and rabbit fetuses (Jost, 1953; Jost et al., 1969). 
The injection of pregnant mice with epinephrine produced a 
14-percent frequency of cleft palate (Loevy & Roth, 1968). 
Epinephrine-induced malformations are also produced in the 
chick embryo (Hodach et al., 1974). Epinephrine impairs 
uteroplacental perfusion in sheep and monkeys (Adamsons et 
al., 1971; Misenheimer et al., 1972; Rosenfeld et al., 1976). 

Data on isoproterenol are instructive in isolating the role 
of hemodynamic changes in producing developmental toxicity. 
Injection of isoproterenol into incubating chick eggs results 
in abnormalities in the embryo (Cheung et al., 1977; Dusek & 
Ostadal, 1985; Janatova et al., 1986; Kuhlmann et al., 1983; 
Ostadal et al., 1987). The developmental toxicity of 
isoproterenol in the chick can be antagonized by pretreatment 
with beta-blocking agents (Janatova et al., 1986; Kuhlmann et 
al., 1983; Ostadal et al., 1987). It is believed that 
catecholamine-induced alterations in blood flow in the 
embryonic cardiovascular system are responsible for 
isoproterenol-associated toxicity (Cheung et al., 1977; Clark 
et al., 1985). This agent has also been found to cause 
hepatotoxicity (Dusek & Ostadal, 1984) and limb malformations 
in a small percentage of chick embryos (Bruyere et al., 
1983). Teratogenic effects have also been noted after 
administration of isoproterenol to mice (Robson et al., 1965) 
and hamsters (Geber, 1969). Experiments in rats (Jones-Price 
et al., 1983; Vogin et al., 1970) and rabbits (Hollingsworth 
et al., 1971; Vogin et al., 1970) have not shown teratogenic 
effects, although hemodynamic effects of the drug are evident 
in a number of experimental animals (Macdonald et al., 1984; 
Robkin et al., 1976; Tweed et al., 1987; van de Walle & 
Martin, 1985). 

Developmental Toxicity--
Human Data 

There is only one report that suggests epinephrine might be 
associated with human teratogenesis. The National 
Collaborative Perinatal Project found an association between 
first trimester exposure to epinephrine and an increased risk 
of major and minor malformations as a group (Heinonen et al., 
1977). Inguinal hernia was the only specific anomaly that 
was associated with epinephrine both after first trimester 
exposures or anytime during pregnancy. 

The National Collaborative Perinatal Project included 31 
women who used isoproterenol during the first trimester. No 
increase in birth defects was shown (Heinonen et al., 1977). 

Bronchodilator: Theophylline 

Developmental Toxicity--
Animal Data 

Theophylline administration to pregnant mice at up to 600 
mg/kg produced cleft palate and digit defects (Tucci & 
Skalko, 1978). Teratogenic effects were not observed, 
however, in rat experiments (Fujii et al., 1972; Maren & 
Ellison, 1972). 

Developmental Toxicity--
Human Data 

The National Collaborative Perinatal Project included 193 
pregnant women with exposure to theophylline or to 
aminophylline, a complex of theophylline and ethylenediamine. 
No increase in adverse pregnancy outcome was identified. In 
addition, there is a large experience with the use of 
theophylline in pregnant women, with the consequent 
impression that this agent does not pose risks to development 
(Greenberger & Patterson, 1978). Case reports have appeared 
of children with heart defects born after maternal 
theophylline use; however, a large collaborative case-control 
study did not associate congenital heart disease with use of 
theophylline during pregnancy (Rubin et al., 1991). 

Theophylline crosses the placenta easily, and theophylline 
concentrations in the fetus are likely to be equal to or 
slightly higher than those in the mother. Newborns who were 
exposed to theophylline in utero have shown signs of 
theophylline intoxication, including jitteriness, 
tachycardia, and vomiting (Arwood et al., 1979; Yeh & Pildes, 
1977). Generally, these symptoms have been observed in 
neonates with blood theophylline levels of more than 12 g/mL 
(Horowitz et al., 1982; Ron et al., 1984). Because 
therapeutic levels in the pregnant woman should not exceed 12 
 g/mL, appropriate dosing should not result in toxicity in 
the newborn. 

Breast Feeding 

Theophylline is excreted into breast milk, and a milk-to-
plasma ratio of 0.73 has been reported (Berlin, 1981). 
Although less than 1 percent of the maternal dose of 
theophylline may be transferred to the neonate (Stec et al., 
1980; Yurchak & Jusko, 1976), increased sensitivity to this 
drug may produce toxic effects in the newborn, including 
vomiting, feeding difficulties, jitteriness, and cardiac 
arrhythmias. 

Bronchodilator: Anticholinergics 

Developmental Toxicity--
Animal Data 

Relatively high doses of atropine 
did not cause developmental abnormalities in rats, chicks, or 
dogs (Back et al., 1961; Bueker & Platner, 1956; Maeda & 
Yasuda, 1979). Skeletal abnormalities detected after 
atropine was administered to pregnant mice may have resulted 
from the maternal toxicity of the atropine, and not from 
selective teratogenic effects (Arcuri & Gautieri, 1973). The 
adverse findings in mice could not be reproduced (Zellers, 
1979). Teratology studies on ipratropium have been negative 
in rats and rabbits (Niggeschulze & Palmer, 1976; Nishimura 
et al., 1978). When tested in mice and rats, glycopyrrolate 
was not associated with an increased incidence of birth 
defects (Kagiwada et al., 1983). 

Developmental Toxicity--
Human Data 

Although atropine readily crosses the human placenta (Kanto 
et al., 1981; Kivalo & Saarikoski, 1977) and may alter fetal 
heart rate (Onnen et al., 1979) or inhibit fetal breathing 
(Roodenburg et al., 1979), fetal exposure to this drug has 
not been associated with adverse developmental effects or 
significant fetotoxicity, whether exposure occurred early in 
pregnancy (Heinonen et al., 1977; Mellin, 1964) or shortly 
before delivery (Abboud et al., 1983; Diaz et al., 1980; Janz 
& Fuchs, 1964). Glycopyrrolate use in pregnant women near 
term has not been associated with adverse effects (Abboud et 
al., 1981, 1983). 

Breast Feeding 

Although the elimination of atropine is reduced in children 
below 2 years of age, atropine exposures through breast milk 
have not been widely associated with neonatal toxicity 
(Stewart, 1981). Atropine is considered compatible with 
breast feeding (American Academy of Pediatrics Committee on 
Drugs, 1989). 

Antihistamines 

Developmental Toxicity--Animal Data 

Teratogenicity testing in rats, mice, and rabbits has not 
suggested an association between diphenhydramine and 
congenital malformations (Naranjo & de Naranjo, 1968; 
Schardein et al., 1971). Astemizole was not teratogenic in 
rats and rabbits at 200 times the recommended human dose in 
unpublished premarketing studies by the manufacturer. 
Embryolethality was seen at maternally toxic doses in the 
rats in this study. Terfenadine was reported by its 
manufacturer to produce a decrease in pup survival in rats 
given 63 times the human dose during pregnancy. 

Developmental Toxicity--Human Data 

The National Collaborative Perinatal Project suggested a 
possible association between the use of brompheniramine and 
chlorpheniramine during pregnancy and an increase in the 
incidence of birth defects (Heinonen et al., 1977). Because 
of the small numbers of affected children and the 
miscellaneous nature of the defects, these findings cannot be 
accepted as showing causation. Confirmation of these 
associations has not appeared in spite of the widespread use 
of these agents. 

Antihistamines are not considered to be teratogenic (Aselton 
et al., 1985; Greenberger & Patterson, 1978), although some 
antihistamines have been associated with birth defects in 
retrospective studies. For example, one study (Saxen, 1974) 
found that first trimester use of diphenhydramine was more 
common among 599 children born with oral clefts (20 
exposures) than among 590 controls without clefts (6 
exposures). The manufacturer of astemizole has on record 63 
exposed pregnancies through February 1988 with no birth 
defects. Since that time, four reports of congenital 
anomalies have been brought to the manufacturer's attention; 
however, there is no indication whether this exceeds the 
number to be expected by chance alone. 

The most convincing data set for an antihistamine is that 
concerning doxylamine, a drug once used as an antinauseant 
during pregnancy and now used in over-the-counter sleep aids. 
A number of human studies have confirmed the lack of 
teratogenicity of this agent, confirmed by a meta-analysis 
(Einarson et al., 1988). 

Third trimester use of antihistamines has rarely been 
described in association with a withdrawal syndrome in the 
neonate. The reports do not permit conclusion of a cause-
and-effect relationship. 

Breast Feeding 

Antihistamines are said to inhibit lactation, although this 
effect appears largely to be a theoretical concern. These 
drugs are often withheld during nursing; however, milk 
concentrations of these agents are extremely low, and there 
are no data establishing adverse effects on the neonate. 

Decongestants 

Developmental Toxicity--
Animal Data 

A dose of phenylephrine equivalent to the content of one 
"cold" tablet has been shown to decrease uterine blood flow 
by 40 percent in pregnant sheep (Cottle et al., 1982). 
Another investigation, also performed on pregnant sheep, 
indicated that the uterine vascular bed is substantially more 
responsive to the vasoconstrictive effects of alpha-
adrenergic agonists than is the systemic vasculature (Magness 
& Rosenfeld, 1986). Ephedrine was associated with 
cardiovascular anomalies in the chick, even when very small 
doses were used (Nishikawa et al., 1985). 

Developmental Toxicity--
Human Data 

Pseudoephedrine normally will not produce hypertensive 
effects until more than four times its therapeutic dose is 
consumed (Pentel, 1984). Because of its favorable 
therapeutic index, pseudoephedrine appears to be the 
preferred decongestant for use during pregnancy. When 
ingested by healthy pregnant subjects in the third trimester, 
a single 60-mg dose of pseudoephedrine did not significantly 
alter blood pressure or blood flow velocities in the uterine 
or fetal circulation (Smith et al., 1990). 

The National Collaborative Perinatal Project included more 
than 4,000 women exposed to phenylephrine during pregnancy, 
1,249 of whom were exposed during the first 4 lunar months 
(Heinonen et al., 1977). Possible associations were found 
between first trimester exposure and ear and eye defects, 
syndactyly, and clubfoot, and between pregnancy use in 
general and hip dislocation, musculoskeletal deformities, and 
umbilical hernia. It is important to recognize, however, 
that these associations are based on the appearance of small 
numbers of children with malformations. For example, for 
abnormalities associated with first trimester exposure to 
phenylephrine, the largest group consisted of eight children 
with eye and ear defects. Critical statistical analysis of 
these data has not been performed, and it is not currently 
known whether, in fact, phenylephrine increases the incidence 
of any birth defect. 

The National Collaborative Perinatal Project also found a 
possible association between use of phenylpropanolamine 
during the first 4 months of pregnancy and hypospadias, eye 
and ear malformations, polydactyly, and pectus excavatum 
(Heinonen et al., 1977). The number of malformations in this 
study was small (seven cases in the largest of the groups), 
and the observational design does not permit the conclusion 
that phenylpropanolamine was the causative agent in these 
abnormalities. 

The National Collaborative Perinatal Project was unable to 
identify an association between ephedrine exposure in the 
first trimester and an increase in any kind of birth defect 
(Heinonen et al., 1977). This report included 373 exposed 
pregnancies. Near term, ephedrine may be given to treat or 
avoid hypotension associated with epidural analgesia or with 
anaphylactic reactions. No adverse effects of such therapy 
have been documented, and ephedrine has been found not to 
alter intervillous blood flow (Hollmen et al., 1984). 

When studied in 12 uncomplicated pregnancies, a single dose 
of a 0.05-percent oxymetazoline nasal spray did not 
significantly alter blood flow velocity in the uterine 
arcuate artery, fetal aorta, or umbilical artery (Rayburn et 
al., 1990). A single dose such as this may not be 
representative of usual patterns of use. In one case report, 
the excessive use of an oxymetazoline nasal spray by a woman 
in her 41st week of pregnancy was associated with a 
nonreactive nonstress test and late decelerations in fetal 
heart rate, suggesting that uterine perfusion may have been 
impaired (Baxi et al., 1985). 

Breast Feeding 

Pseudoephedrine is excreted in breast milk. The reported 
milk-to-plasma ratio for this agent was approximately 3.0. A 
nursing neonate may ingest about 0.6 percent of the maternal 
dose (Findlay et al., 1984). The use of this drug during 
lactation has not been associated with adverse effects in 
exposed newborns, and it is categorized as compatible with 
breast feeding (American Academy of Pediatrics Committee on 
Drugs, 1989).






5
FOUR COMPONENTS OF THE MANAGEMENT OF ASTHMA DURING PREGNANCY 
AND LACTATION*

Introduction

Effective management of asthma for pregnant women relies on 
four integral components: 

 Objective measures for assessing and monitoring 
maternal lung function and fetal well-being in 
order to make appropriate therapeutic 
recommendations 

 Measures to avoid or control 
asthma triggers in the patient's environment 

 Pharmacologic therapy 

 Patient education. 


Goals of Therapy for Pregnant Women 

Goals for the management of asthma in pregnant women--as for 
all asthma patients--are: 

 Maintain (near) normal pulmonary function rates 
 Control symptoms, including nocturnal symptoms
 Maintain normal activity levels, including exercise
 Prevent acute exacerbations of asthma
 Avoid adverse effects from asthma medications. 

An important additional goal for the management of asthma in 
pregnant women is: 

 Give birth to a healthy baby. 


Principles of Therapy for Pregnant Women 

Asthma is a chronic condition with acute 
exacerbations. Continuing attention is required to control 
symptoms, prevent exacerbations, and reduce chronic airway 
inflammation. 

Prevention of exacerbations is particularly important. 
This includes avoidance of triggers, and for allergic 
patients the avoidance of allergens, especially in the indoor 
environment. It also includes regular (daily) and aggressive 
use of anti-inflammatory medication for many patients. 

Anticipatory or early intervention in treating acute 
exacerbations of asthma reduces the likelihood of the 
episode progressing to severe airway obstruction and 
impaired maternal/fetal oxygenation. 

Both nonpharmacologic and pharmacologic therapies 
should be considered. Optimal use of nonpharmacologic 
measures is important because they may reduce the requirement 
for medication. Therefore, patients, if allergic, should 
avoid exposure to house-dust mites, animal dander, pollen, 
and mold spores. Patients should avoid irritant triggers, 
especially active and passive exposure to tobacco smoke. 

Using as few medications as possible is generally 
desirable. Inhaled medications are preferred; however, 
systemic drugs should be employed when inhaled medications 
are not sufficient to control symptoms and normalize 
pulmonary function. 

Although some not yet fully defined risk may be associated 
with the use of asthma medications during pregnancy, it is 
well recognized that the greater risk to the fetus is 
uncontrolled asthma. The Working Group on Asthma and 
Pregnancy strongly recommends that asthma should be 
aggressively treated in pregnant women just as it should be 
in nonpregnant patients. Studies to date have identified few 
risks to the fetus from drugs employed in treating asthma. 
The known risk of uncontrolled asthma, which causes morbidity 
in the mother and hypoxemia in the fetus, is far greater than 
any known risks to the mother or fetus from asthma 
medications. 

Striving to maintain the mother's normal lung function 
and blood oxygenation is essential to ensure normal 
oxygen supply to the fetus. 

Treating associated conditions is an important adjunct 
to asthma therapy. Such conditions as sinusitis, rhinitis, 
and gastroesophageal reflux can aggravate asthma; treatment 
can lead to more effective asthma control. (See chapter 6, 
Special Considerations.) 


Component 1: Objective Measures for Assessment and 
Monitoring;

Maternal Lung Function 

Pulmonary function tests are essential for assessing the 
severity of asthma in order to make appropriate therapeutic 
recommendations. Asthma is characterized by variable airflow 
obstruction that is often at its worst at night or on 
arising. Measurements of pulmonary function performed during 
the day in the physician's office may offer incomplete 
insight into the course of the asthma throughout the 24-hour 
day. Home measurement of pulmonary function is important for 
assessing circadian variation in pulmonary function and for 
documenting that asthma is the cause of nocturnal awakening. 
Patients' and physicians' perceptions of the severity of 
asthma are often insensitive, making a quantitaive assessment 
of airflow obstruction highly desirable. Further, it can be 
extremely difficult for the patient and her physician to 
differentiate breathlessness associated with pregnancy, 
anxiety, or asthma without objective measures of lung 
function. 

Pulmonary function has traditionally been assessed by 
spirometry. FEV1 (the volume of air expired in 1 second from 
maximum inspiration) is the single best measure of pulmonary 
function for assessing severity. Therefore, it is 
recommended that office spirometry be conducted in the 
initial assessment of all pregnant patients being evaluated 
for asthma, and periodically thereafter as appropriate. 

The peak expiratory flow rate (PEFR) is the greatest flow 
velocity that can be obtained during a forced expiration 
starting with fully inflated lungs, and it correlates well 
with FEV1. PEFR can be measured reliably with inexpensive, 
portable peak flow meters. Because PEFR only measures large 
airway function, however, PEFR is not the most sensitive 
measurement of airflow obstruction. Thus PEFR measurements 
may not be sufficient to make a diagnosis or to fully 
evaluate the physiologic impairment associated with asthma. 
Nevertheless, home PEFR monitoring is extremely useful in 
assessing circadian variation in pulmonary function (an 
indication of airway hyperresponsiveness) and in following 
both the course of asthma and a patient's response to 
therapy. PEFR measurements can also help differentiate 
asthma from other causes of dyspnea during pregnancy. 

Use PEFR to assess symptoms and predict exacerbations 
of asthma. It is recommended that PEFR be used as the 
objective parameter to follow in assessing symptoms and 
making therapeutic recommendations when such recommendations 
depend on the severity of airflow obstruction. PEFR 
monitoring is especially valuable for detecting deterioration 
of asthma, predicting acute exacerbations, and assessing 
response to therapy. Availability of PEFR measurements not 
only allows formulation of a management plan with criteria 
for both intensification of therapy and recourse to medical 
assistance but also facilitates telephone communication with 
health care providers. Maintenance of as near normal 
pulmonary function as possible is desirable during pregnancy; 
patients for whom there is any concern in this regard should 
be supplied with a home peak flow meter device. In general 
this includes all women with moderate to severe asthma. 
These patients should record PEFR in the morning, upon 
arising, and approximately 12 hours later, and should bring 
PEFR records to each prenatal visit. 

Use PEFR to adjust asthma therapy. Predicted values of 
PEFR are in the range of 380 to 550 liters per minute for 
women and do not change during the course of pregnancy. 
Rather than employing the predicted value, it is often better 
to establish a personal best PEFR for each patient at a time 
when asthma is well controlled. Recommendations for changes 
in asthma therapy may then be based on deviations from this 
personal best level. For more complete discussion, see the 
National Asthma Education Program's Expert Panel Report: 
Guidelines for the Diagnosis and Management of Asthma. 


Fetal Monitoring 

The goal of managing the pregnant woman with asthma is to 
optimize maternal pulmonary function and to identify those 
fetuses at risk for intrauterine growth retardation and 
adverse outcome. In the absence of maternal or fetal 
decompensation, an additional goal should be to provide a 
normal family-centered birthing experience. Prevention of 
adverse fetal outcome is complicated. Ill-informed concern 
about adverse fetal outcomes associated with medications used 
early in pregnancy may defer appropriate drug therapy (see 
chapter 4). Further, in the third trimester, monitoring of 
the fetus is sometimes overlooked during an asthma 
exacerbation. Finally, there are multiple methods available 
for fetal evaluation; more research is needed to determine 
which method correlates best with good fetal outcome. 

Therefore, principles for management of the fetus during a 
pregnancy complicated by asthma are: 

 There is little additional risk from mild or well-
controlled asthma. 

 Other coexistent conditions such as hypertension or 
diabetes increase risk. 

 Patients with severe or uncontrolled asthma warrant 
increased surveillance. 

 Consultation with a perinatologist is recommended when 
serious fetal problems are suspected. 

 The most common errors leading to adverse outcome are 
underestimation of asthma severity and undertreatment of 
exacerbations. 

Fetal evaluation during the pregnancy of a woman with asthma 
is longitudinal and uses different techniques according to 
gestational age and risk factors. Because accurate 
determination of gestational age is crucial in making 
obstetric decisions, early (12 to 20 weeks) sonography should 
be performed for most patients, especially when accurate 
clinical dating is not possible or if asthma is moderate or 
severe. Early obstetric sonography will provide a benchmark 
against which fetal growth can be measured. Monitoring of 
pregnant patients with asthma starts with an evaluation of 
progressive fetal growth. Growth during the second and third 
trimesters is determined by careful serial measurements of 
fundal height. Confirmation with sequential sonographic 
evaluations of fetal growth is indicated if the patient's 
asthma is uncontrolled or if growth retardation is suspected. 
In the third trimester electronic fetal heart rate monitoring 
(nonstress test or contraction stress test) and ultrasonic 
determinations of fetal behavior (biophysical assessment) 
should be used, if needed, to assure fetal well-being. 
Indications for antepartum fetal assessment include growth 
retardation, moderate to severe asthma, asthma exacerbation, 
and decreased fetal movements. The type of monitoring chosen 
and its frequency depend on many factors. For many third 
trimester patients, weekly fetal assessment is sufficient; if 
fetal problems are suspected the frequency increases. Daily 
maternal recording of fetal activity, or "kick counts," 
should be encouraged. Several methods are used and appear to 
improve perinatal outcome in both low- and high-risk 
pregnancies. 

If there is serious maternal illness, as in an acute 
exacerbation of asthma with an incomplete or poor response to 
therapy or with significant maternal hypoxemia, previous 
fetal monitoring is irrelevant, and intensive fetal 
monitoring should begin and continue until maternal status is 
stable. One reasonable approach to antepartum fetal 
assessment is continuous electronic fetal heart rate 
monitoring. It is rarely necessary to deliver a fetus by 
emergency cesarean section for acute asthma complicated by 
respiratory failure. In most cases, fetal distress can be 
successfully treated by aggressive ventilation and medical 
management. 

When women with asthma are admitted in labor, careful fetal 
monitoring is essential. In low-risk patients, continuous 
electronic fetal monitoring may not be necessary. Fetal 
assessment can be accomplished by 20 minutes of electronic 
monitoring--the so-called admission test. Subsequently, for 
patients with mild or moderate asthma that is well controlled 
and with a reassuring admission test, intermittent 
auscultation, peak expiratory flow rate measurements, or 
electronic fetal heart rate monitoring may be sufficient. 
Intensive fetal monitoring is recommended for those patients 
who enter labor with uncontrolled or severe asthma and have a 
nonreassuring admission test or other risk factors. This may 
be performed by either continuous electronic fetal heart rate 
monitoring or intermittent auscultation (every 15 minutes in 
the first stage of labor; every 5 minutes in the second stage 
of labor). During the course of labor, intensive fetal 
monitoring may be considered to guide appropriate obstetrical 
and asthma management decisions. (See charts 7 and 8.) 


COMPONENT 2: MEASURES TO AVOID OR CONTROL ASTHMA TRIGGERS

Environmental Control 

Eliminating adverse environmental exposures is critically 
important in controlling asthma during pregnancy. Irritants 
and allergens that provoke acute symptoms may also increase 
airway hyperresponsiveness, which in turn may increase 
vulnerability to further irritant or allergen exposure. 
Nonspecific irritants include tobacco smoke, dusts, strong 
odors, and environmental air pollutants. Certainly if the 
patient herself is smoking she should be strongly encouraged 
to quit and referred to an appropriate smoking cessation 
program. 

If allergy plays a role in an individual patient's asthma, 
environmental control measures to avoid these specific 
allergens are paramount. All warm-blooded pets, including 
small rodents and birds, produce dander, urine, and saliva 
that can cause allergic reactions. To eliminate exposure to 
animal dander, the animal should be removed from the house. 
Removal of the pet may not afford immediate relief even when 
followed by vigorous cleaning because dander has been shown 
to remain in the home for many months. Recent studies 
indicate that the residual allergen can be rendered 
nonallergenic by application of a 3-percent tannic acid 
spray, which is commercially available. If the pet cannot be 
removed from the house, it should at the very least be kept 
out of the pregnant woman's bedroom at all times. If there 
is forced-air heating in a home where a pet resides, the air 
ducts into the bedroom should be sealed. An electric 
baseboard heater can be used if necessary. Weekly washing of 
the pet may reduce exposure somewhat by decreasing the amount 
of dander and dried saliva deposited on carpets and 
furnishings. 

House-dust mites appear to play a major role in the causation 
of allergic asthma. Because they are dependent for survival 
on moisture from the atmosphere, they occur in environments 
where the relative humidity is usually greater than 50 
percent. Mite allergen is found throughout the home: in 
mattresses, pillows, carpets, upholstered furniture, bed 
covers, clothes, and soft toys. Mite antigen is easily found 
in the air during house cleaning, but it is present in only 
very small amounts in undisturbed air. Mite antigen control 
involves encasing mattresses in airtight, plastic covers; 
either encasing pillows or washing them weekly; and washing 
bedding weekly in water that is 130 F. If allergic to 
house-dust mites, a pregnant woman should not vacuum and 
should remain away from home for about 1 hour following house 
cleaning. If this is not possible, wearing a mask while 
vacuuming may be helpful. Additional measures that may be 
indicated include use of an acaracide (mite killer) on the 
carpets and avoidance of lying on upholstered furniture. In 
areas of very high humidity, she should consider using a 
dehumidifier or air conditioner. The use of humidifiers is 
discouraged because they provide moisture that may encourage 
mite growth. Home humidity levels should be maintained at 
less than 50 percent. 

Indoor exposure to mold and cockroach allergens may be 
important in homes with specific problems with dampness 
(molds) or infestation (cockroaches). Outdoor allergen 
exposure can be reduced by avoiding outdoor activities during 
the warmer months from midmorning until dusk, the period of 
highest prevalence for pollens and some mold spores. The use 
of an air conditioner during these same months will allow the 
woman to keep her doors and windows closed, effectively 
preventing outdoor pollen and mold spores from entering the 
home. 


Immunotherapy 

Immunotherapy may prevent allergic inflammation and has been 
shown to reduce asthma symptoms provoked by such allergens as 
house-dust mites, cat dander, grass pollen, and Alternaria. 
Immunotherapy may be considered for patients when avoiding 
allergens and irritants is not possible and when appropriate 
medication fails to control asthma symptoms. 

The principal concern with the use of immunotherapy during 
pregnancy has been the occurrence of systemic reactions 
(anaphylaxis). Induction of uterine contractions following 
anaphylaxis and resulting in abortion has been reported, 
although rarely. Patients at increased risk of anaphylaxis 
include those who are receiving increasing doses of antigen, 
have extreme sensitivity, and/or are exposed to high levels 
of ambient allergens. Accordingly, the general 
recommendation is that immunotherapy should not be started 
during pregnancy, but that ongoing immunotherapy may be 
continued at the current dose. Exceptions would be if 
immunotherapy has only recently been started or if the 
patient is experiencing frequent reactions that have 
prevented her from reaching an effective dose. Further, 
patients who have demonstrated a tendency to have systemic 
reactions should have their treatment discontinued. Extra 
caution is required during the patient's pollen season, when 
she may be at greater risk of experiencing a systemic 
reaction; therefore a reduction in dose during this period 
should be considered. 


Vaccines 

It is generally recommended that an influenza vaccine be 
given each year to patients with moderate and severe asthma. 
Influenza is a killed vaccine, and there is no evidence 
suggesting that it is associated with any maternal or fetal 
risk, although it has been recommended that it should be 
given after the first trimester as an extra precaution. 


Component 3: Pharmacologic Therapy

Discussion of this component opens with a statement of the 
general principles of pharmacologic management and a listing 
of preferred medications and selection criteria for pregnant 
women with asthma. Following are the protocols for managing 
asthma during pregnancy, the exacerbations of asthma during 
pregnancy, and asthma during labor and delivery. There are 
no randomized prospective human studies of asthma 
pharmacotherapy during pregnancy. The following 
recommendations are based on the published safety and 
efficacy data and the experience of the working group 
members. 


General Principles of Pharmacologic Management 

 Tailor general therapy guidelines to individual 
patient needs. Asthma is a disease that varies among 
patients. Further, the degree of severity for any woman 
may change from one month or season to the next or during 
pregnancy. Therefore, specific pharmacologic regimens 
must be tailored to individual needs and circumstances 
and integrated with recommendations for nonpharmacologic 
management strategies. 

 Integrate asthma care with obstetrics care. The 
obstetrical care provider must be involved in asthma 
care. Consultation with an asthma specialist is 
appropriate as indicated for evaluation of the role of 
allergy and irritants, complete pulmonary function 
studies, or evaluation of the medication plan if there 
are complications in achieving the goals of therapy. A 
team approach is required if there is more than one 
clinician managing the asthma and the pregnancy. 

 Obtain information on asthma status during 
prenatal visits. Collect the following information: 

 1. Day and nighttime symptoms

 2. Peak flow measures or spirometry reading

 3. Medication usage. 

 Use step-care pharmacologic therapy. An aim of 
therapy is to use the minimum medication needed to maintain 
control with the least risk of adverse effects. The step-
care approach in which the number of medications and 
frequency of administration are increased as necessary to 
establish control (step up) and reduced when possible to 
maintain control (step down) is used to achieve this aim. 

 - In general, every asthma patient must have an inhaled 
beta2-agonist available for rescue treatment of acute 
symptoms. This rescue treatment also has a step-care 
pattern. Medications are added as necessary to control 
symptoms. The increase is often temporary and depends 
on the severity and duration of the asthma exacerbation 
as well as the patient's response. (Note, however, 
that increasing use of rescue treatment by the patient 
is an indication to review the medication plan and 
possibly to increase preventive therapy.) 

 - Maintenance therapy, or chronic management of asthma, 
also uses a step-care approach and is based on the 
severity of disease: mild, moderate, or severe. 

 Monitor continually. Continual monitoring, which 
includes objective measures of lung function, is necessary to 
ensure that therapeutic goals are met. 

 - While the patient is achieving control of asthma, PEFR 
variability greater than 10 to 20 percent and continued 
presence of chronic symptoms indicate a need to 
reevaluate the patient's technique in using medication, 
any environmental aggravators and the patient's efforts 
to control them, the pressure of concomitant upper 
respiratory disease, and finally, the possibility that 
medications need to be increased. 

 - Once asthma control is established, regular followup 
visits in conjunction with prenatal visits continue to 
be essential. Clinicians need to monitor and review 
the treatment plans, the medications, and the patient's 
management techniques (i.e., for using medicines and 
peak flow meters, for controlling the environment). 


Preferred Medications and Selection Criteria for 
Pregnant Women With Asthma 

The choice of a specific medication plan during pregnancy is 
based on the following considerations: 

1. Available animal and human gestational data (see chapter 
4). 

2. Efficacy. 

3. Preference for drugs administered by inhalation. (Asthma 
is a disease of the airways and therefore treatment by 
inhalation is generally preferable to systemic therapy. 
Aerosolized medications for asthma deliver the drug 
directly to the airways in higher concentrations and 
systemic effects are usually avoided.) 

4. Preference for older medications with a long history of 
use during pregnancy and documented clinical 
investigation. 

Based on these considerations, the specific drugs listed in 
table 7 are currently preferred by the Working Group on 
Asthma and Pregnancy for the management of asthma and 
associated conditions during pregnancy. However, it should 
be noted that lack of inclusion of a specific medication on 
this list does not necessarily imply that it is inappropriate 
for use during pregnancy. Table 8 lists drugs for asthma and 
associated conditions that generally should be avoided during 
pregnancy. 


Step-Care Pharmacologic Management of Asthma During 
Pregnancy 

Treatment plans for asthma during pregnancy are based on the 
goals of therapy, the general principles for managing asthma, 
and information on the use of medications during pregnancy. 
This section and its accompanying charts present application 
of these principles to the development of treatment protocols 
based on the severity of disease. Specific therapeutic 
regimens must be tailored to the needs and circumstances of 
the individual patient. The step-care approach recommends 
increasing the number and frequency of medications with 
increasing asthma severity. Once control of asthma is 
established and sustained for several weeks, a reduction in 
therapy, or step down, is carefully considered in order to 
identify the minimum therapy required to maintain control. 


Chronic Mild Asthma (Chart 1) 

Inhaled beta2-agonists by themselves are usually sufficient 
therapy for mild, intermittent asthma. If symptoms disappear 
and pulmonary function normalizes with inhaled beta2-
agonists, they can be used indefinitely on an as-needed 
basis. However, their use on a daily basis, or even more 
often than three times a week, usually indicates a need for 
anti-inflammatory therapy (see chronic moderate asthma). 

Oral theophylline does not usually give prompt 
bronchodilation and therefore is not recommended for episodic 
asthma. 


Chronic Moderate Asthma (Chart 2) 

The category of moderate asthma includes those patients who 
have symptoms that are not controlled or that are poorly 
regulated by episodic administration of a beta2-agonist. 
Some patients have frequent (more than twice a week) 
symptomatic exacerbations of asthma. Other patients do not 
have acute exacerbations and can regulate symptoms by 
moderating their lifestyles, but their pulmonary functions 
(FEV1 or PEFR 60 to 80 percent of predicted range) indicate 
potential compromises in airway function or maternal-fetal 
oxygenation. These patients have very fragile control of 
their asthma. Many asthma specialists think that all 
patients with moderate asthma should receive inhaled anti-
inflammatory medication to diminish airway inflammation and 
airway hyperresponsiveness. 

 Anti-inflammatory agents are the primary therapy in 
moderate asthma. 

 - Cromolyn sodium is virtually devoid of side effects and

is the most effective nonsteroidal anti-inflammatory 
drug for asthma currently available. Its efficacy is 
less predictable than that of inhaled corticosteroids 
and a 4- to 6-week trial may be necessary to determine 
the benefit for individual patients. 

 - Inhaled corticosteroids provide effective asthma 
control with minimal side effects at recommended doses. 
Immediate benefit may not be evident, however, because 
suppression of symptoms and PEFR improvement are often 
not maximal until after 2 to 4 weeks of treatment. A 
spacer should be considered not only to reduce 
oropharyn- geal candidiasis but also to improve 
respiratory tract penetration and to reduce the 
possibility of systemic effects. 

 - A burst, or short tapering course, of oral 
corticosteroids is indicated when asthma is not 
controllable by any combination of bronchodilators, 
cromolyn sodium, or inhaled corticosteroids, even at 
increased doses. Such deterioration of asthma is 
characterized by gradual reductions in PEFR 
(approximately 20 percent) that fail to have a 
sustained response to inhaled bronchodilators, by 
greater intolerance of activities or exercise, and by 
the development of nocturnal symptoms. A short course 
of, for example, 40 mg of prednisone per day (single or 
divided dosing) for up to 1 week followed by up to 7 to 
14 days of tapering doses may be effective. At the end 
of this therapeutic deescalation, oral corticosteroids 
can be stopped; if asthma symptoms do not occur and 
pulmonary functions remain normal, no additional oral 
steroid therapy is necessary. However, if the burst of 
prednisone does not control symptoms, is effective for 
less than 10 to 24 days, or is repeated frequently, the 
patient has severe asthma and obviously needs 
additional therapy. 

 - Nedocromil sodium has properties similar to cromolyn, 
but because it is a newer drug, there is less 
documented clinical experience with it during 
pregnancy. 

 Bronchodilators. The physician has several choices: 

 - As-needed (prn) inhaled beta2-agonist must be available

for treatment of acute exacerbations. 

 - Regular administration of inhaled beta2-agonists may be

effective. However, as noted earlier, some studies 
have raised questions about the effectiveness and 
safety of regularly scheduled use of inhaled beta2-
agonists. It is recommended that regularly scheduled 
inhaled beta2-agonist treatment should be kept to a 
minimum. Because well-controlled asthma requires 
minimal use of inhaled beta2-agonists, an increased 
use--or even a daily use--generally indicates the need to 
institute or intensify regular anti-inflammatory 
therapy. 

 - Sustained-release theophylline or long-acting oral 
beta2-agonist taken once a day in the evening may be 
helpful for the patient with primarily nocturnal 
symptoms because the currently available inhaled beta2-
agonists have a limited duration of action--4 to 6 
hours. However, when patients who use sustained-
release theophylline (or oral beta2-agonist) to control 
nocturnal symptoms also take anti-inflammatory 
medication, they may be able to discontinue the 
bronchodilator usage after 4 to 6 weeks. 

If theophylline is the primary bronchodilator, beta2-agonist 
therapy can be administered episodically on an as-needed 
basis. 


Chronic Severe Asthma (Chart 3) 

Patients with severe asthma should be evaluated by an asthma 
specialist. 

Patients whose asthma is not controlled with maximal doses of 
bronchodilators and inhaled anti-inflammatory agents may need 
systemic corticosteroids on a routine basis. In such cases, 
the physician will use long-term oral corticosteroids. 

Anti-inflammatory medication. Daily anti-inflammatory 
medication is recommended to suppress and prevent airway 
inflammation and airway responsiveness. 

 Inhaled corticosteroids in higher doses (336-840 g a day 
or more) are recommended as the primary inhaled anti-
inflammatory therapy. Use of a spacer device will reduce 
oropharyngeal candidiasis, improve delivery of the 
medication, and reduce the possibility of systemic 
effects. 

 Two puffs of cromolyn sodium, four times a day may be 
given in addition to inhaled corticosteroids. 

 The use of oral corticosteroids on a long-term basis is 
often required. In this case, the lowest possible dose 
(alternate day or single daily dose) should be used and 
administered under the supervision of an asthma 
specialist. Patients must be monitored closely for the 
adverse side effects of corticosteroids. Prolonged use 
of oral corticosteroids may be associated with increased 
risk of gestational diabetes, preeclampsia, and 
intrauterine growth retardation. The evaluation of these 
possibilities may be most appropriately managed in 
consultation with an obstetrician specializing in high-
risk pregnancy care. Attempts should be made to reduce 
oral corticosteroids with persistent administration of 
high doses of inhaled corticosteroids (e.g., 800 g or 
more per day). Monitoring for clinical signs of adrenal 
insufficiency is important when a patient is being 
transferred from oral to inhaled corticosteroids. 


Bronchodilator medication. 

 Inhaled beta2-agonists must be available as needed (prn 
for treatment of asthma symptoms and acute 
exacerbations). 

 Sustained-release theophylline and/or a long-acting oral 
beta2-agonist may be given, especially to control 
nocturnal symptoms. 

 Regular administration of inhaled beta2-agonists may be 
effective, although it is recommended that their use be 
kept to a minimum. 


Management of Exercise-Induced Asthma 

Exercise-induced asthma (EIA)--which, if left untreated, can 
limit and disrupt normal lives--is the term for airway 
narrowing that occurs minutes after the onset of vigorous 
activity. 

EIA should be anticipated in all asthma patients; most have 
the airway hyperirritability that leads to this condition. 


Diagnosis of EIA 

A good history is the most important diagnostic tool. 
Symptoms of asthma should not interfere with the pregnant 
patient's usual activities or exercise. If indicated, an 
exercise challenge can be used to establish the diagnosis. 
It can be conducted in a formal laboratory setting. It can 
also consist of measurements of PEFR or FEV1 before and after 
the patient undertakes whatever task caused the symptoms. A 
15-percent decrease in PEFR or FEV1 at 5 to 10 minutes after 
exercise is compatible with EIA. 

EIA is caused mainly by smooth muscle constriction. 
Exercise-induced asthma generally reaches its peak 5 to 10 
minutes after stopping the vigorous activity and usually 
resolves in another 20 to 30 minutes. 


Management Strategies for EIA 

The goal of management is to enable patients to participate 
in any activity they choose without experiencing asthma 
symptoms. Patients who are taking regularly scheduled anti-
inflammatory therapy may have sufficient control of asthma 
such that it is not provoked by exercise. EIA can be 
prevented with inhalation of beta2-agonist 5 to 60 minutes 
before exercise; the pretreatment is helpful for up to 
several hours. Cromolyn is also acceptable. If the patient 
still experiences symptoms with exercise, two puffs of 
inhaled beta2-agonist should relieve the symptoms, and the 
dose should be increased for future exercise pretreatment. 
Combined beta2-agonists and cromolyn pretreatment may be 
effective when neither one suffices. 


Management of Exacerbations of Asthma During Pregnancy 

Exacerbations of asthma are acute or subacute episodes of 
progressively worsening shortness of breath, cough, wheezing, 
or chest tightness, or a combination of these symptoms. 
Respiratory distress is common. Exacerbations are 
characterized by decreases in expiratory airflow that can be 
documented and quantified by measurement of lung function 
(PEFR or spirometry). 

This section looks first at general considerations and 
treatment goals for exacerbations of asthma during pregnancy 
and then presents, in general terms and with accompanying 
charts, methods for managing asthma exacerbations in home, 
emergency department, and hospital settings. 


General Considerations 

 Prevention and early treatment to reverse symptoms 
are the best strategies for the management of asthma 
exacerbations. Important elements of this early 
treatment to prevent deterioration and abort 
exacerbations include: 

 - Written action plans, prearranged with the physician, 
to help the patient to manage asthma exacerbations at 
home 

 - Recognition of early indicators of an exacerbation, 
including worsening PEFR or FEV1 

 - Prompt communication between patient and health care 
provider about any serious deterioration and its 
treatment 

 - Appropriate intensification of antiasthma medications, 
including in many cases a short course of systemic 
corticosteroids 

 - Removal of or withdrawal from any allergic or irritant 
trigger in the environment because treatment is less 
effective if there is continued exposure. 

 Pregnant patients with potentially fatal asthma include 
those patients with a history of: 

 - Prior intubation for asthma 

 - Two or more hospitalizations for asthma in the past 
year 

 - Three or more emergency care visits for asthma in the 
past year 

 - Hospitalization or an emergency care visit for asthma 
within the past month 

 - Current use of systemic corticosteroids or recent 
withdrawal from systemic corticosteroids 

 - Past history of syncope or hypoxic seizure due to 
asthma 

 - Prior admission for asthma to a hospital-based 
intensive care unit 

 - Serious psychiatric disease or psychosocial problems. 

Individuals with one or more of these risk factors require 
particularly intensive patient education, close monitoring, 
and prompt care. They should be counseled to seek medical 
care early during an exacerbation and instructed about the 
availability and appropriate use of ambulance services. 


Treatment Goals 

The principal goals of treatment in exacerbations of asthma 
are: 

 Rapid reversal of airflow obstruction, thereby 
relieving respiratory distress. 

 - Repetitive administration of inhaled beta2-agonists 
best achieves this rapid reversal of airflow 
obstruction (Brenner, 1983b; McFadden, 1989). 

 - Early addition of systemic corticosteroids speeds the 
rate of improvement among patients who fail to respond 
or respond incompletely to inhaled beta2-agonists 
(Fanta et al., 1983). 

 Prevention of potential fetal hypoxemia by 
administering supplemental oxygen to maintain maternal 
arterial oxygen saturation greater than or equal to 95 
percent. In rare instances, severe alveolar 
hypoventilation requires mechanically assisted 
ventilation. Be alert to the reverse of expected 
hypocarbia (PCO2 increased to 35 mmHg indicates serious 
hypoventilation during pregnancy). Fetal monitoring is 
essential because significant fetal hypoxemia may occur 
in the absence of maternal hypoxemia (see chapter 3). 

 Reduction of the rate of recurrent severe asthma 
symptoms by intensifying the patient's asthma medication 
regimen upon discharge from the emergency department. 
Often a short course of oral corticosteroids is useful. 

Crucial to successful achievement of these treatment goals is 
close monitoring of the patient's condition and response to 
treatment with serial measurements of lung function. These 
measurements quantify the severity of the asthma exacerbation 
and the extent of improvement with treatment. The ranges for 
PEFR and FEV1 in the protocols are general guidelines, not 
precise criteria. PEFR and FEV1 results should be seen as 
aids in a monitoring and decision making process that also 
takes into account such other factors as the patient's 
history, current symptoms, and physical findings. 


Home Management of Acute Exacerbations of Asthma 
During Pregnancy (Chart 4) 

Successful management of exacerbations of asthma requires 
early initiation of asthma therapy. When pregnant patients 
are able to initiate treatment at home, they not only avoid 
delays in treatment but also add to their sense of control 
over their asthma and their lives. The degree of care 
provided in the home depends on the physician's and the 
patient's experience and the availability of emergency care. 
(For example, patients who live in rural settings may, by 
necessity, have to manage asthma exacerbations at home.) 
Many patients who have moderately severe to severe asthma 
will have at home the equipment and medications necessary for 
treating and monitoring an asthma exacerbation. 

For an individual patient, the optimal management strategy 
evolves out of patient and physician experience with what 
"works" and what does not work in treating acute 
exacerbations. General guidelines applicable to most 
patients are presented in chart 4. 

 Home PEFR determinations are an integral part of home 
management strategies. They make it possible for the 
patient to obtain information, which can then be shared 
with the clinician, regarding the severity of the 
exacerbation and the response to treatment. 

 Patients are encouraged to use inhaled beta2-agonist 
medications with increased frequency during an 
exacerbation and, under certain circumstances, begin or 
increase the dose of systemic corticosteroids. 

 Patients should not delay seeking medical help if the 
asthma exacerbation is severe, if therapy does not give 
rapid improvement, if sustained improvement is not 
achieved, if there is further deterioration, or if the 
fetal kick count decreases. Furthermore, severe 
exacerbations in the third trimester of pregnancy are 
best managed with concurrent intensive fetal monitoring. 

 Recovery from an acute exacerbation is often gradual. 
Medications for acute therapy may need to be continued 
for several days to sustain relief of symptoms and 
improvement in PEFR. However, patients should seek 
medical care rather than rely on bronchodilator therapy 
in excessive doses or for prolonged periods of time. 

 Pursed-lips breathing and other forms of controlled 
breathing may help to maintain calm during a period of 
respiratory distress, but they do not bring about any 
improvement in lung function. 

 NOT recommended are the following home management 
techniques: 

 - Drinking large volumes of liquids or breathing warm, 
moist air (e.g., the mist from a hot shower) 

 - Rebreathing into a bag held tightly at the nose and 
mouth 

 - Using over-the-counter antihistamines, or asthma and 
cold remedies. 


Hospital-Based Emergency Department Management and 
Hospital Management of Acute Exacerbations of Asthma 
During Pregnancy (Charts 5 and 6) 

Severe exacerbations of asthma are potentially life 
threatening. Care must be expeditious. Emergency care for 
pregnant patients may occur in labor and delivery units based 
on individual hospital policies. However, for simplicity, 
emergency care will be said to occur in the emergency 
department in this report. 

Effective therapies may be available in a physician's office. 
However, serious maternal exacerbations require close 
observation; repetitive, intensified treatment, and 
repetitive measurements of maternal lung function and fetal 
monitoring in the third trimester. Most moderate and severe 
exacerbations of asthma during pregnancy require prompt 
transfer to and a complete course of therapy in an emergency 
department or hospital (Brenner, 1983a). 

Assessment. In the emergency department, a brief history 
and physical examination pertinent to the exacerbation are 
appropriate prior to treatment. A more detailed history and 
complete physical examination should be performed once 
therapy has been started. 

 Important questions to ask in obtaining a brief 
history concern: 

 - Time of onset and cause of present exacerbation of 
asthma 
 - Severity of symptoms, including exercise limitation and

sleep disturbance 
 - All current medications 
 - Prior hospitalizations and emergency department visits 
for asthma, particularly within the past year 
 - Prior episodes of respiratory insufficiency due to 
asthma (loss of consciousness or intubation and 
mechanical ventilation) 
 - Significant prior cardiopulmonary disease 
 - Expected date of delivery for the infant 
 - Obstetrical problems or risk factors 
 - Presence or absence of fetal activity. 

 Objectives of the physical examination include: 

 - Assessment of the severity of the exacerbation. 
Predictors of severe airflow obstruction include pulsus 
paradoxus (greater than or equal to 12 mmHg fall in 
systolic blood pressure during inspiration), use of 
accessory muscles of respiration, diaphoresis, and 
inability to recline with head elevated less than 30 
degrees. 

 - Identification of complications (e.g., pneumonia, 
atelectasis, pneumothorax, or pneumomediastinum). 

 - Assessment of overall patient status, including level 
of alertness, fluid status, and presence of cyanosis, 
respiratory distress, and wheezing. (Wheezing can be 
an unreliable indicator of obstruction; in rare cases, 
extremely severe obstruction may be accompanied by a 
"silent chest" [Shim & Williams, 1980].) 

 - Assessment of fetus. 

 Functional assessments: 

 - In the emergency department, assessment of PEFR or FEV1

at least hourly. In the hospital, measurements should 
optimally be made before and after bronchodilator 
therapy at least twice daily. 

 - In both the emergency department and hospital, 
measurements of arterial oxygen saturation should be 
made by pulse oximetry (where available). 

 - In both the emergency department and hospital, 
intensive monitoring should be instituted and continued 
until the exacerbation is controlled (see Fetal 
Monitoring in Objective Measures for Assessment and 
Monitoring). 

 Laboratory studies: 

 - In the emergency department, such laboratory studies as

complete blood count, chest x-ray (with appropriate 
shielding), and serum theophylline concentration are 
rarely needed for initial assessment, and their 
performance should not be permitted to delay initiation 
of treatment. 

 - After initial treatment in the emergency department: 

 ~ A complete blood count (CBC) is appropriate in 
patients with fever or purulent sputum.

 ~ Chest x-ray should be obtained for patients 
suspected of a complicating cardiopulmonary process. 
Appropriate shielding should be used.

 ~ Serum theophylline concentration should be measured 
in patients taking theophylline prior to 
presentation. 

 - Arterial blood gas (ABG) measurements should be 
performed to evaluate arterial PCO2 in patients with 
obvious hypoventilation, cyanosis, or severe distress 
after initial treatment, especially if PEFR is less 
than 200 liters per minute or FEV1 is less than or 
equal to 40 percent of predicted. Patients with 
arterial PCO2 greater than or equal to 30 mmHg will 
require repeated ABG measurements to monitor their 
response to treatment. 

 - Oximetry can be used to follow oxygen saturation. 
Measures of arterial blood gases are required if oxygen 
saturation remains below 95 percent when the patient is 
on supplemental oxygen. 

 Characteristics identifying patients at particular 
risk for life-threatening deterioration include: 

 - Less than 10-percent improvement in PEFR or FEV1 in the

emergency department 
 - Prior history of life-threatening exacerbations 
 - PEFR less than 100 liters per minute or FEV1 less than 
25 percent of predicted 
 - PCO2 greater than or equal to 35 mmHg. 


Treatment. In the emergency department and hospital, the 
primary therapies are repeated administration of inhaled 
beta2-agonist bronchodilators and systemic corticosteroids. 
Supplemental oxygen should be given to patients with 
significant hypoxemia and to all patients when arterial 
oxygen monitoring is not available and if fetal heart rate 
abnormalities are detected. Other treatment may include 
methylxanthines and antibiotics. 

 Beta2-agonists (for recommended doses, see table 9): 

 - Reversal of airflow obstruction is most effectively 
achieved by the repetitive administration of inhaled 
beta2-agonist bronchodilators. 

 - Inhalation of a beta2-agonist solution aerosolized by a

nebulizer is favored, although some studies raise the 
possibility that supervised delivery by metered-dose 
inhaler (MDI) with a spacer device may be equally 
effective. 

 - Onset of action for inhaled beta2-agonist is less than 
5 minutes; repetitive administration produces 
incremental bronchodilation. 

 - Duration of action in severe asthma is not precisely 
known. 

 - Three doses spaced every 20 to 30 minutes can safely be

given as initial therapy to patients without comorbid 
cardiovascular disease. Thereafter, the frequency of 
administration varies according to the severity of the 
patient's symptoms and occurrence of adverse side 
effects. In patients without underlying cardiovascular 
disease, administration as frequently as every 1 to 2 
hours is safe for periods of severe airflow 
obstruction. 

 Systemic corticosteroids (for recommended doses, see 
table 9): 

 - In the emergency department: Immediate administration 
of systemic corticosteroids is warranted for patients 
with severe exacerbations of asthma and in whom no 
improvement is observed after the initial dose of 
beta2-agonist, or in those patients who develop an 
exacerbation despite the regular use of oral 
corticosteroids (Harris et al., 1987; Harrison et al., 
1986; Littenberg & Gluck, 1986; McFadden, 1989). 
Patients with severe airflow obstruction (PEFR less 
than 200 liters per minute or FEV1 less than or equal 
to 40 percent of predicted) after the initial hour of 
treatment should be given systemic corticosteroids. 

 - In the hospital: Systemic corticosteroids speed the 
resolution of severe asthma exacerbations refractory to 
bronchodilator therapy and should be given to all 
patients admitted to the hospital for severe asthma. 

 Oxygen. Supplemental oxygen should be administered to 
the pregnant patient to achieve an arterial oxygen 
saturation of greater than or equal to 95 percent. In 
the absence of available continuous oxygen saturation 
monitoring, supplemental oxygen should be administered to 
all patients. 

 Methylxanthines (see table 9 for recommended doses): 

 - In the emergency department: Intravenous aminophylline

is not recommended. It has been demonstrated that in 
the first 4 hours of treatment aminophylline provides 
no additional benefit to optimal inhaled beta2-agonist 
therapy (Fanta et al., 1986; Rossing et al., 1980; 
Siegel et al., 1985). When used in combination with 
repetitively administered beta2-agonist 
bronchodilators, intravenous aminophylline causes 
increased adverse side effects without effecting 
additive bronchodilation (Fanta et al., 1982; Josephson 
et al., 1979; Siegel et al., 1985). 

 - In patients currently taking a theophylline-containing 
preparation, serum theophylline concentration should be 
determined. Maintenance theophylline may be considered 
if the patient is hospitalized. Monitoring 
theophylline levels is imperative. In the last 
trimester of pregnancy, theophylline clearance is 
reduced, and dosages need to be decreased accordingly. 
The theophylline level should be maintained between 8 
and 12 g/mL to reduce adverse effects that may result 
from changes in drug disposition in the pregnant 
patient. 

 Antibiotics. The use of antibiotics is generally 
reserved for those patients with purulent sputum 
(discolored because of polymorphonuclear leukocytes, not 
eosinophils), especially when combined with fever. The 
presence of bacterial sinusitis should be treated with 
antibiotics if suspected (see Chapter 6, Special 
Considerations). 

 Some treatments--anticholinergics, hydration, and chest 
physical therapy--are generally not beneficial; others--
mucolytics and sedation--should be avoided. 

 Anticholinergics. Ipratropium bromide in MDI form does 
not appear to benefit patients receiving intensive 
bronchodilator therapy with beta2-agonists. In contrast, 
ipratropium bromide nebulizer solution may be of some 
benefit to patients with severe exacerbations, but it is 
not currently available in the United States. 

 Hydration. Among adults intravenous or oral 
administration of large volumes of fluids does NOT play a 
role in the management of severe asthma. However, 
pregnant patients may become dehydrated as a result of 
increased respiratory rate and decreased oral intake. 
Dehydration may cause uterine contractions. Assessment 
of fluid status should be made (urine output, urine 
specific gravity, mucous membrane moisture, 
electrolytes), and appropriate corrections provided. 

 Chest physical therapy. In general, among patients 
with normal respiratory muscle strength and effective 
cough, chest physical therapy is not beneficial and may 
be unnecessarily stressful for the severely breathless 
patient. However, in selected patients who manifest 
severe mucus hypersecretion or atelectasis as part of 
their asthma exacerbation, postural drainage, chest 
vibration and percussion, and other techniques of chest 
physical therapy may be beneficial. 

 Mucolytics. Administration of mucolytic agents (e.g., 
acetylcysteine, potassium iodide) in severe exacerbations 
of asthma may worsen cough or airflow obstruction and 
should be avoided. 

 Sedation. Because of their respiratory depressant 
effect, anxiolytic, hypnotic, and narcotic drugs should 
be strictly avoided in severely ill asthma patients. 

 With intensive therapy, unpleasant side effects (e.g., 
palpitations, tremulousness, sense of inner raciness, 
headache) may occur, but injurious adverse reactions 
(e.g., significant cardiac arrhythmias or myocardial 
ischemia) are rare. 

 Impending respiratory failure (pregnant patients with 
severe asthma and an arterial PCO2 greater than or equal 
to 35 mmHg after intensive therapy) should be treated in 
an intensive care unit. In general, if there is steady 
deterioration in clinical signs and symptoms despite 
intensive therapy for asthma, the pregnant patient should 
be intubated and mechanically ventilated when the PCO2 is 
greater than or equal to 45 mmHg and rising. It is 
rarely necessary to deliver a fetus by emergency cesarean 
section for acute asthma complicated by respiratory 
failure. In most cases, fetal distress can be 
successfully treated by aggressive ventilation and 
medical management.

 An arterial line should be placed for continuous blood 
pressure, heart rate, and blood gas monitoring. 
Ventilation of an asthma patient is difficult and always 
requires the assistance of a qualified specialist. 

 All pregnant patients admitted to intensive care units 
should have consultation with an asthma specialist. 
Consultation should also be considered for patients with 
multiple hospital admissions. 


Patient discharge. 

 From the emergency department: 

 - Release of the pregnant patient from the emergency 
department depends on the patient's response to 
treatment. 

 - In general, consider pregnant patients for 
hospitalization if their FEV1 remains 40 percent or 
less of predicted (PEFR is less than 200 liters per 
minute) or if their FEV1 is greater than 40 percent but 
less than 70 percent (PEFR is between 200 and 300) when 
the following factors pertain: persistent symptoms; 
evidence of pneumonia; past history of severe asthma; 
prolonged increase in asthma symptoms prior to the 
emergency department visit; use of multiple antiasthma 
medications, especially of systemic corticosteroids, at 
the time of the exacerbation; nonreassuring fetal 
assessment; uterine irritability; inadequate access to 
medications and medical care; poor home situation; 
comorbid psychiatric illness. 

 - Avoid prolonged (more than 2 to 4 hours) detention in 
the emergency department of pregnant asthma patients 
awaiting a good response to treatment. Extended 
treatment in a holding area or overnight unit with 
sufficient monitoring and nursing care may be 
appropriate. 

 - For patients with a rapid response, require a 30- to 
60-minute period of observation after the last dose of 
bronchodilator to ensure stability of response before 
discharging them from the hospital. 

 - Prescribe at least 3 to 5 days of treatment to be 
continued after discharge. Most regimens should 
include a course of oral corticosteroids to reduce the 
rate of recurrent severe asthma symptoms and to treat 
the underlying pathology of the exacerbation (Woolcock, 
1989). 

 - Emphasize the need for continuous, regular care in an 
outpatient setting. A followup medical appointment is 
necessary within 7 days to ensure complete resolution 
of the exacerbation and to review the long-term 
medication plan. 

 - Consider issuing a peak flow meter and providing 
patient education on how to make and record daily PEFR 
measurements. 

 - Review discharge medications and inhaler technique. 
Where appropriate, provide patient education on 
avoidance of asthma triggers. 

 - Notify the physicians managing the patient's asthma and

pregnancy, by telephone if possible. 

 From the hospital: 

 - Prior to discharge, the pregnant patient's medication 
must be adjusted to an oral and/or inhaled regimen. 
The optimal timing of this transition is not precisely 
established, but the general approach is to wait until 
the patient is minimally symptomatic with no or minimal 
wheezing corresponding to a PEFR or FEV1 value between 
60 and 70 percent of predicted. 

 - During the first 24 hours after this medication 
adjustment, closely observe patients for possible 
deterioration. Because changing from intravenous to 
oral corticosteroids usually involves a significant 
dose reduction, relapse may occur. 

 - Discharge most patients with a beta2-agonist 
bronchodilator by MDI, dry powder inhaler, or 
compressor-driven nebulizer, to be used no more than 
every 3 or 4 hours. 

 - Confirm the patient's ability to maintain good lung 
function with near normal PEFR. 

 - Prior to discharge of patients who receive supplemental

oxygen during their hospitalization, confirm the 
adequacy of their arterial oxygen saturation while they 
are breathing room air. The preferred method of 
measurement is pulse oximetry. 

 - Initiate inhaled corticosteroids at the first followup 
visit during the prednisone taper. Alternatively, 
begin inhaled corticosteroids along with the oral 
corticosteroid therapy prior to discharge from the 
hospital; this approach may enhance patient adherence. 

 - If theophylline is used, base the oral dose of 
theophylline on the dose required to achieve serum 
concentration levels between 8 to 12 g/mL and initiate 
careful monitoring to keep the theophylline level 
between 8 to 12 g/mL. 

 - Schedule a followup appointment for 3 to 7 days 
following discharge. 

 - Provide patient education: 

 ~ Educate patients about their discharge medications 
and the importance of a followup medical visit in an 
outpatient regular-care setting. 

 ~ Educate patients in the use of peak flow meters to 
monitor their lung function at home.

 ~ Review inhaler technique. 

 ~ Recommend fetal kick count recording during 
exacerbations in the third trimester. 


Management of Asthma During Labor and Delivery (Charts 
7 and 8) 

General considerations. To manage the patient with 
asthma during labor and delivery, it is recommended that the 
patient's regularly scheduled asthma medications (inhaled 
cromolyn, beclomethasone, and/or oral theophylline) be 
continued during labor and delivery. The patient's PEFR 
should be measured upon admission to labor or delivery, and 
subsequently every 12 hours. If asthma symptoms develop, 
PEFR should be measured after asthma treatments (see 
Management of Exacerbations of Asthma During Pregnancy). The 
patient should be kept well hydrated and be provided adequate 
analgesia to limit the risk of bronchospasm. Patients who 
have required chronic systemic corticosteroids or several 
short courses of systemic corticosteroids during pregnancy 
should be given 100 mg hydrocortisone every 8 hours until 24 
hours postpartum to treat for possible adrenal suppression. 

When women with asthma are admitted in labor, careful fetal 
monitoring is essential. In low-risk patients, continuous 
electronic fetal monitoring may not be necessary. Fetal 
assessment can be accomplished by 20 minutes of electronic 
monitoring--the so-called admission test. Subsequently, for 
patients with mild or moderate asthma that is well controlled 
and with a reassuring admission test, intermittent 
auscultation, peak expiratory flow rate measurements, or 
electronic fetal heart rate monitoring may be sufficient. 
Intensive fetal monitoring is recommended for those patients 
who enter labor with uncontrolled or severe asthma and have a 
nonreassuring admission test or other risk factors. This may 
be performed by either continuous electronic fetal heart rate 
monitoring or intermittent auscultation (every 15 minutes in 
the first stage of labor; every 5 minutes in the second stage 
of labor). During the course of labor, intensive fetal 
monitoring may be considered to guide appropriate obstetrical 
and asthma management decisions. (See charts 7 and 8.) 

For labor induction, oxytocin is the drug of choice. The use 
of 15-methyl prostaglandin F2-alpha should be avoided because 
it is a synthetic analog of prostaglandin F2-alpha that has 
been reported to cause bronchospasm in patients with asthma 
(Fishburne et al., 1972). Use of prostaglandin E2 has been 
reported to cause bronchospasm (Fraser & Brash, 1974); 
however, a recent report has shown that it can safely be used 
in the patient with asthma for therapeutic abortion or labor 
induction with a dead fetus (Towers et al., 1991). Use of 
intravaginal or intracervical prostaglandin E2 gel for 
cervical ripening prior to labor induction has not been 
reported to cause bronchospasm (Lao & Huengsburg, 1990; 
Rayburn, 1989). 

Analgesic and anesthetic considerations. When choosing 
a narcotic analgesic to use in the patient with asthma, 
consideration must be given to the propensity of that agent 
to cause histamine release that may precipitate bronchospasm. 
Morphine and meperidine should therefore be avoided, and a 
preferred agent may be fentanyl. Narcotic analgesics do 
cause respiratory depression and should be not used if there 
is an acute asthma exacerbation. 

Lumbar epidural analgesia reduces oxygen consumption and 
minute ventilation during the first and second stages of 
labor, which offers patients with asthma considerable benefit 
(Hagerdal et al., 1983). Dilute concentrations of local 
anesthetics and narcotics administered by continuous epidural 
infusion technique offer consistent analgesia and minimize 
motor blockade for labor and delivery (Chestnut et al., 
1989). In the patient with an asthma exacerbation, epidural 
analgesia has been reported to enhance the response to 
bronchodilator therapy (Younker et al., 1987). However, 
bronchospasm has been reported in approximately 2 percent of 
patients with asthma receiving regional anesthesia (Fung, 
1985). 

If a general anesthetic is necessary, preanesthetic use of 
atropine and glycopyrrolate may provide a bronchodilatory 
effect (Gal & Suratt, 1981). For induction of anesthesia, 
ketamine is the agent of choice because it decreases airway 
resistance (Corssen et al., 1972) and can prevent 
bronchospasm (Hirshman et al., 1979). Low concentrations of 
halogenated anesthetics can provide the patient with asthma 
with bronchodilatation, allowing high inspired concentrations 
of oxygen and avoiding maternal awareness of the surgery, and 
does not appear to contribute to postpartum hemorrhage. 

Postpartum hemorrhage. The pharmacologic treatment of 
postpartum hemorrhage in a patient with asthma is different 
because many of the commonly used oxytocic drugs for 
treatment of uterine atony may worsen bronchospasm. Oxytocin 
is the drug of choice for postpartum hemorrhage. However, if 
additional agents are required, methylergonovine, as well as 
ergonovine, should be avoided because they may cause 
bronchospasm (Crawford, 1980). If their use is unavoidable, 
pretreatment with methylprednisolone is recommended. The use 
of 15-methyl prostaglandin F2-alpha should also be avoided 
because it is a synthetic analog of prostaglandin F2-alpha, 
which is a bronchoconstrictor and may worsen asthma 
(Fishburne et al., 1972). If prostaglandin treatment is 
necessary, the safest analog is E2, which is less likely to 
cause bronchospasm. If there is severe uterine hemorrhage, a 
20 mg prostaglandin E2 suppository can be administered 
rectally, thereby avoiding the "washout" effect caused by 
continued vaginal bleeding. 

Preterm labor. The treatment of preterm labor in a patient 
already receiving asthma medication creates the risk of 
dangerous drug interactions. During an asthma exacerbation, 
uterine contractions are common and usually do not progress 
to preterm labor. Usually, with successful treatment of the 
acute asthma exacerbation, uterine contractions abate without 
additional therapy. However, if progressive cervical change 
occurs before term, tocolytic therapy should be instituted, 
taking care to avoid the use of more than one kind of beta2-
agonist. If a patient is already taking a systemic beta2-
agonist for her asthma, the alternative tocolytic agent, 
magnesium sulfate, is recommended for uterine contractions. 
Magnesium sulfate may be safer than the beta2-agonists as 
tocolytic therapy, and it may provide some bronchodilation. 
There are no theoretical contraindications to the use of 
calcium channel blockers, such as nifedipine; however, there 
are no reports of concurrent use to treat women with asthma 
with preterm labor. The use of indomethacin is relatively 
contraindicated in the patient with asthma. However, because 
aspirin intolerance occurs in only a few patients with 
asthma, for those patients who have previously demonstrated 
ability to tolerate aspirin and other nonsteroidal anti-
inflammatory agents, indomethacin can be considered. 
Consultation with an asthma specialist may be helpful for 
those asthma patients who also have rhinosinusitis, given the 
association between aspirin sensitivity and nasal polyps. 


COMPONENT 4: PATIENT EDUCATION

Patient education is a powerful tool for helping patients 
gain the motivation, skill, and confidence to control their 
asthma (Feldman et al., 1987; Mellins, 1989). Patient 
education should begin at the time of diagnosis and be 
integrated with continuing care. All members of the health 
care team should participate in the process. 

Building a Partnership 

Much of the day-to-day responsibility for managing asthma 
falls on the patient and her family. Active participation by 
the clinician, the patient, and the family in a partnership 
can improve adherence to the treatment plan and stimulate 
improvements in asthma management (Schulman, 1979; Clark, 
1989). This partnership concept includes open communication, 
joint development of a treatment plan by the clinician and 
patient, and encouragement of the family's efforts to improve 
prevention and treatment of the patient's symptoms. An 
important step in building the partnership is to ask 
questions early at each visit to identify the patient's main 
concerns about and expectations for treatment. Patients can 
focus fully on the clinician's recommendations only after 
these have been addressed (Korsch et al., 1968). 

The medicolegal implications of pharmacologic management of 
asthma during pregnancy warrant specific consideration. It 
is recommended that, through patient education, the clinician 
should: 

 Acknowledge that, although relatively few medications 
have been proven harmful during pregnancy, no medication 
for asthma, allergy--or any condition--can be considered 
absolutely safe 

 Discuss the potential direct and indirect consequences 
for the mother and for the baby of inadequately 
controlled asthma, emphasizing that the recommended 
medications are safe enough to be preferable to the 
uncontrolled asthma that would result if the medications 
are not used 

 Discuss the medication choices available and the 
rationale for the selection of a particular treatment 
plan 

 Document the discussion in the patient's record and that 
informed consent for the treatment plan was obtained. 


The Content of Teaching 

Patient education involves helping patients understand 
asthma, helping patients learn and practice the skills 
necessary to manage asthma, and supporting patients as they 
adopt appropriate asthma management behaviors and adhere to 
their treatment plans. Providing information will not 
accomplish these objectives by itself. Developing the 
patient's asthma management skills and confidence that she 
can control asthma is also required. 

Sample patient education handouts on the following topics are 
in the appendix: "How To Control Asthma Triggers," "How To 
Use a Peak Flow Meter," "How To Use a Metered-Dose Inhaler," 
and "Good News and Great Tips for Pregnant Women With 
Asthma." Areas and topics to be considered in patient 
education for asthma include: 

 Definition of asthma (with an emphasis on the chronic 
nature of asthma and the goals of therapy). 

 Key points about the signs and symptoms of asthma 
(the main symptoms of acute asthma episodes, the 
variability of symptoms among patients, the need to 
recognize and treat even mild symptoms, the importance of 
PEFR measurements in detecting early symptoms). 

 Characteristic changes in the airways of asthma 
patients and the role of medications (inflammation, 
bronchospasm, and excessive, thick mucus; inhaled 
steroids, cromolyn, and bronchodilators). 

 Asthma triggers and how to avoid or control them 
(allergens and irritants, viral respiratory tract 
infections, and exercise). 

 Treatment (the need for individualized continuing care, 
adverse effects and how to reduce them, the need for 
preventive treatment, the importance of early treatment 
of acute episodes). 

 Patient fears concerning medication. (Responses to 
common fears include the following: inhaled 
corticosteroids are safe and efficacious; toxicity 
effects can be minimized by reducing the dosage; asthma 
medications are not addictive; continuous use does not 
reduce effectiveness.) 

 Use of written guidelines (including medication plans 
for maintenance therapy and managing exacerbations as 
well as criteria for detecting onset of symptoms, 
initiating treatment for acute episodes, seeking 
emergency care, and recognizing when long-term treatment 
is less than optimal). 

 Use of written diaries (to record asthma triggers, 
symptoms, actions taken, and PEFR in order to see 
patterns and report to the clinician). 

 Correct use of inhalers. 

 Criteria for premedicating to prevent onset of 
symptoms (before exercise; before exposure to allergens, 
cold air, or irritants). 

 Optimal use of home peak expiratory flow rate 
monitoring (to help decide when to initiate or terminate 
treatment, when to seek emergency care, or when to 
consider additional chronic treatment because of, for 
example, high variability in PEFR readings or evening 
dips below morning PEFR levels). 

 Evaluation of results of treatment plan. (Review 
whether the goals of therapy are being achieved; identify 
any adherence problems in order to overcome barriers or 
to negotiate changes in the treatment plan. Adherence to 
the treatment plan is enhanced when the plan is 
simplified as much as possible and when the plan 
considers both the patient's ability to afford the 
medications and the payment method.) 

 Fears and misconceptions. (Asthma is not caused by 
psychological factors; most deaths are related to 
undertreatment, and death is rare in children; people 
with asthma should live full and active lives; with 
proper treatment asthma does not lead to permanent lung 
disability.) 

 Family understanding and support (need for family 
education about asthma, need for help in managing an 
acute exacerbation). 

 Feelings about asthma (need for acknowledging negative 
feelings and their validity; possible need for obtaining 
referrals to self-management programs, counseling, and 
social services). 


Psychological Support 

Pregnancy is a time of psychological stress due to changes in 
body image, the physical symptoms accompanying pregnancy, and 
fears regarding the pregnancy, labor, delivery, and the 
developing fetus. Many pregnant women experience emotional 
lability and ambivalence regarding the pregnancy. In the 
patient who has asthma there are additional concerns. The 
stress associated with normal pregnancy may aggravate asthma 
in some predisposed women. Furthermore, the morbidity of 
asthma may compound the stresses of pregnancy. There may 
also be additional fears regarding the effect of the asthma 
or the medications taken for the asthma on the developing 
infant. 

Suggestions for psychological management for the patient with 
asthma during pregnancy include: 

 Discussion. Allow the patient ample opportunity to 
express her fears and concerns. 

 Education. Factual information should be given to the 
patient regarding: 

 - The lack of adverse effects of properly managed asthma 
on pregnancy 

 - The possible effects of pregnancy on the course of 
asthma 

 - What is known regarding the effects of the medication 
taken for asthma on the developing infant 

 - The anticipated course of labor and delivery 

 - The patterns of inheritance of asthma and allergic 
diseases 

 - Possible strategies to reduce the risk for the infant. 

 Support. Support and reassurance can be provided by the 
physician through frequent scheduled appointments and 
easy accessibility at other times.


6
SPECIAL CONSIDERATIONS

HYPERTENSION

When a pregnant woman with asthma either has hypertension or 
develops hypertension, the pharmacologic management of the 
hypertension is best achieved by avoiding the use of beta-
adrenergic antagonists (beta-blockers) because they may 
exacerbate the asthma. 


DIABETES

If diabetes, either insulin-dependent or gestational, and 
asthma coexist during pregnancy, the overall management may 
be complicated because asthma medication may impair 
carbohydrate tolerance and worsen diabetes. Specifically, 
systemic beta2-agonists and systemic corticosteroids may 
cause hyperglycemia, which necessitates close monitoring of 
blood sugars and may increase the patient's insulin 
requirements. Although it would be best to avoid the use of 
these agents during the pregnancy of a woman with diabetes, 
asthma exacerbations may require systemic beta2-agonists 
and/or systemic steroids. Close communication among the 
physicians managing the asthma, the diabetes, and the 
pregnancy is necessary. 


RHINITIS

Significant nasal symptoms occur in approximately 35 percent 
of randomly selected women (Mabry, 1980, 1986). Few data 
exist regarding the interrelationships between rhinitis and 
pregnancy. In one survey, preexisting rhinitis worsened 
during pregnancy in 34 percent of the women, improved in 15 
percent, remained unchanged in 45 percent, and could not be 
evaluated in 6 percent (Schatz & Zeiger, 1991). It seems 
unlikely that gestational rhinitis would have any direct 
adverse effect on the course of pregnancy, but severe 
rhinitis can interfere with sleeping, eating, or emotional 
well-being. In addition, uncontrolled rhinitis or sinusitis 
during pregnancy may exacerbate coexisting asthma. 


Diagnosis 

Essentially, any of the recognized forms of rhinitis may 
occur during pregnancy, but the most common types appear to 
be allergic rhinitis, rhinitis medicamentosa, vasomotor 
rhinitis, and bacterial rhinosinusitis. 

Allergic rhinitis is caused by an intranasal IgE-mediated 
reaction to inhaled allergens such as pollen, house-dust 
mites, mold spores, or animal dander. Prominent symptoms 
include sneezing, runny nose, nasal itching, and eye itching 
that may be exacerbated seasonably or by exposure to 
allergens (grass, house-dust mites, animal dander). 

Rhinitis medicamentosa is the syndrome of rebound nasal 
congestion resulting from the overuse of topical 
vasoconstricting nose sprays. It may complicate another 
underlying cause of chronic rhinitis or a viral upper 
respiratory infection. 

Vasomotor rhinitis of pregnancy is a syndrome of nasal 
congestion and vasomotor instability limited to the 
gestational period. Symptoms in these women with this 
condition tend to be most prominent in the second half of 
pregnancy (Bende et al., 1989; Mohun, 1943) and usually 
disappear within 5 days postpartum (Mohun, 1943). 


Treatment 

Many women will be able to tolerate their nasal symptoms 
during pregnancy with little or no pharmacologic therapy. 
Although this may be desirable, especially during the first 
trimester, substantially bothersome symptoms warrant 
treatment. 

For patients with allergic rhinitis, as with allergic 
asthma, environmental control measures are important to 
reduce antigen exposure. Pharmacotherapy is reasonable if 
environmental control measures do not provide sufficient 
control. Intranasal cromolyn may be considered first, based 
on its topical effects and reassuring gestational animal and 
human data (see chapter 4). For patients with allergic 
rhinitis inadequately controlled by intranasal cromolyn, 
antihistamine therapy (tripelennamine or chlorpheniramine) 
should be considered. Many patients with eosinophilic 
rhinitis will respond better to a combination of an 
antihistamine and pseudoephedrine than to either drug alone. 

An alternative to oral therapy for allergic rhinitis during 
pregnancy is intranasal corticosteroid therapy. Although 
there is no published experience on the use of these 
medications intranasally during pregnancy, some authors 
consider these medications to be preferable to oral 
medications for allergic rhinitis during pregnancy due to 
their topical application (Norman, 1983). Intranasal 
beclomethasone is recommended, beginning with two sprays in 
each nostril twice daily and then tapering to the lowest 
effective dose. 

Although discontinuation of the topical vasoconstrictor is 
the most important treatment of rhinitis medicamentosa, 
intolerable congestion frequently results. Addition of 
intranasal beclomethasone (two sprays in each nostril twice 
daily) usually allows comfortable discontinuation of the 
offending vasoconstricting spray. 

Two nonpharmacologic approaches may be useful for patients 
with vasomotor rhinitis during pregnancy. A buffered 
saline nose spray may be helpful for the nasal dryness, nasal 
bleeding, and vascular congestion associated with pregnancy. 
Exercise (commensurate with the pregnancy) may also be useful 
because exercise leads to physiologic nasal vasoconstriction. 
When pharmacologic therapy is required, pseudoephedrine is 
recommended. 


SINUSITIS

Bacterial rhinosinusitis may complicate another underlying 
cause of rhinitis or may follow a viral upper respiratory 
infection. The incidence of sinusitis in pregnancy has been 
reported to be 1.5 percent, an apparent sixfold increased 
incidence over the nonpregnant population (Sorri et al., 
1980). 


Diagnosis 

The diagnosis of sinusitis during pregnancy is often made 
empirically based on clinical findings of posterior nasal 
drainage, sinus distribution pain, and purulent discharge 
lasting more than 5 to 7 days. A high index of suspicion 
must be maintained for bacterial sinusitis during pregnancy 
because as many as half of pregnant women with documented 
sinusitis may lack the classic clinical findings (Sorri et 
al., 1980). Sinus radiographs should be used during 
pregnancy when indicated, such as when a clinically diagnosed 
sinus infection is not responding to antibiotic therapy or 
when a probable clinical diagnosis cannot be made without 
radiologic confirmation. 


Treatment 

Cultures of sinus aspirates obtained during pregnancy have 
shown the most common sinus pathogens to be Hemophilus 
influenza and Streptococcus pneumonae (Sorri et al., 1980). 
Data on the use of antibiotics during pregnancy have been 
reviewed (Hamod & Khouzomi, 1988). Amoxicillin is the 
initial antibiotic of choice in the management of sinusitis 
during pregnancy in women who are not allergic to penicillin. 
Erythromycin is recommended for the penicillin-allergic 
patient with gestational sinusitis, and the addition of 
sulfisoxazole may be considered in early or midpregnancy if 
the patient is not responding in 5 to 7 days. Experience 
suggests that 3 weeks of therapy is superior to a 10- to 14-
day course with regard to preventing the development of 
recurrent sinusitis during pregnancy. Oxymetazoline nose 
spray or drops (for up to 5 days) and pseudoephedrine may 
also be helpful as adjunctive and symptomatic therapy of 
gestational bacterial rhinosinusitis. Medications that 
generally should be avoided are listed in table 8. 

An appropriate cephalosporin, amoxicillin/beta-lactamase 
inhibitor, erythromycin, or erythromycin plus sulfisoxazole 
(in early or midpregnancy) may be considered for women with 
unequivocal clinical sinusitis who do not respond to 
amoxicillin. If improvement does not occur, sinus films 
should be obtained, and sinus irrigation may be necessary as 
both a diagnostic and therapeutic modality. 


ANAPHYLAXIS

Any agent that can cause anaphylaxis in the nonpregnant state 
could potentially lead to anaphylaxis in the susceptible or 
sensitized pregnant patient. Maternal hypoxemia and 
hypotension caused by anaphylaxis may be catastrophic to the 
mother and the fetus (Entman & Moise, 1984; Erasmus et al., 
1982). Thus management of anaphylaxis during pregnancy must 
be aggressive and expeditious, and all anaphylactic reactions 
should be considered potentially severe or life threatening 
until resolved. 


Treatment 

Because of the altered circulatory and respiratory physiology 
during pregnancy, adequate intravascular volume repletion and 
oxygenation are particularly important in the management of 
anaphylaxis during pregnancy to prevent both maternal and 
fetal complications. Epinephrine (0.3 cc of 1:1000 
intramuscularly [IM]) is the initial pharmacologic treatment 
of choice and may be repeated every 10 to 15 minutes. If the 
reaction is due to a cutaneous injection or sting, a 
tourniquet should be placed above the site, 0.1 cc 
epinephrine should be injected at the site of the injection 
or sting, and 0.3 cc epinephrine should be injected into the 
opposite arm. Unless the reaction resolves promptly after 
the first epinephrine injection, diphenhydramine 50 mg IM 
(i.v. with hypotension) should be administered. For 
persistent symptoms, cimetidine 300 mg i.v. should be given. 
For persistent wheezing, nebulized beta2-agonists (see table 
9) may be administered, and for recalcitrant hypotension, 
plasma expanders are indicated. In cases of extreme 
hypotension where tissue perfusion may be inadequate, 
intravenous epinephrine (1:10,000) may be considered. A more 
detailed protocol for the management of anaphylaxis during 
pregnancy is described elsewhere (Schatz & Zeiger, 1991).




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APPENDIX: 
PATIENT HANDOUTS 

 GOOD NEWS AND GREAT TIPS FOR PREGNANT WOMEN WITH ASTHMA 

 HOW TO CONTROL ASTHMA TRIGGERS 

 HOW TO USE A METERED-DOSE INHALER 

 HOW TO USE A PEAK FLOW METER 

 MY WEEKLY ASTHMA SYMPTOM AND PEAK FLOW DIARY 

 ASTHMA CONTROL PLAN






GOOD NEWS AND GREAT TIPS FOR PREGNANT WOMEN WITH ASTHMA 
ASTHMA CAN BE CONTROLLED DURING PREGNANCY 

Congratulations! Your pregnancy is an exciting event, and 
your visit to the doctor shows you care about staying 
healthy. You are breathing for two now, and you need 
to keep your asthma under control. By taking the steps 
listed in this handout, you can control your asthma and 
protect your baby. 

If you do not take these steps, you could lose control of 
your asthma. Asthma symptoms such as coughing, chest 
tightness, wheezing, and shortness of breath can keep your 
baby from getting enough oxygen to grow well. Your baby 
could be less healthy and smaller when born, or could even be 
born too early. But these things do not need to happen! 
Asthma can be controlled so you can have a normal pregnancy, 
labor, and delivery and a healthy baby! 

Here are the steps you can take to control your asthma and 
protect your baby: 

1. Work with your doctor and other health care 
providers. 

 Keep your appointments. 

 Ask all the questions you have. Writing them down before 
each visit is a good idea. It helps you remember them 
all. 

 Tell your doctor about any wheezing, coughing, or 
shortness of breath that you have.

 Tell your doctor if you notice any changes in your 
asthma. 

 Tell your doctor any concerns you have about your 
medicines or the other parts of your treatment plan. 

 Make sure you know what your doctor wants you to do 
before you leave the office. 

2. Take your medicines. 

 Follow directions exactly about when to take your asthma 
medicines and how much medicine to take. 

 Don't stop taking your asthma medicines unless your 
doctor directs you. 

 Get your doctor's okay before you take ANY new medicines 
or over-the-counter drugs (drugs you choose yourself at 
the store, such as headache, cough, or cold medicine). 

Remember: Using asthma medicine during pregnancy is much 
safer than letting your asthma get out of control. Such 
asthma medicines as inhaled beta-agonists, cromolyn, and 
inhaled steroids are safe for pregnant women when you take 
them as directed by your doctor. So, take your medicines and 
control your asthma!

3. Watch your asthma and treat symptoms fast. 

Pregnancy is a time of change. Your asthma can change too 
and can get worse, better, or stay the same. If this is your 
first pregnancy, there is no way to predict what will happen 
with your asthma. If you have been pregnant before, your 
asthma is most likely to change--or not change--the same way it 
did with your last pregnancy. It is very important for you 
to watch your asthma closely. 

 Use a peak flow meter each day so you can find any 
changes in your asthma and act early. 

 Know how to tell if your asthma is getting worse. Make a 
list with your doctor of the ways you can tell if your 
asthma is getting worse. 

 Make a plan with your doctor for dealing with any sign 
that your asthma is getting worse. Use it. 


4. Stay away from your asthma triggers. 

Your asthma triggers are those things that you know make your 
asthma worse. House dust mites or damp places, animals, 
tobacco smoke, and very cold air are some examples of asthma 
triggers. You can stay away from some triggers. For other 
triggers, you can take action to keep them from bothering 
your asthma. See the "How to Control Asthma Triggers" 
handout for more information. 

5. Do not smoke or stay around people who smoke. 

 Cigarette smoke makes it more likely that you will have 
asthma episodes. 

 Smoking during your pregnancy makes it more likely that 
your baby will be born too early and too small. Your 
baby is more likely to be sick more often, too. 

 If babies breathe in other people's smoke, the babies' 
lungs will not grow and work as well as they should. The 
baby is likely to have more colds and earaches. 

 When babies live with people who smoke, they have a 
greater chance of developing asthma. 

 If you smoke, now is the time to stop! Your doctor or 
nurse will help you. Ask them. 


ANSWERS TO SOME COMMON QUESTIONS 

 Are asthma medicines safe for pregnant women? Yes, 
asthma medicines are safe when you take them as directed 
by your doctor. It is very important for your baby's 
health that you keep your asthma under good control! 

 Can I exercise? Yes! You can exercise. Exercise is 
important and you should be able to be physically active 
without having asthma symptoms. Talk to your doctor 
about this. 

 Can I take allergy shots? Yes. Allergy shots can be 
continued if you were getting them before you were 
pregnant. But allergy shots should not be started for 
the first time while you are pregnant. 

 Should I get flu shots? You can get flu shots. These 
are made from dead viruses that will not harm you or your 
baby. Flu shots are often recommended for people who 
have asthma. Ask your doctor. 

 What happens if I get an asthma episode (or 
"attack") during labor or delivery? Asthma episodes 
usually do not occur during labor and delivery. If 
asthma symptoms do occur, you will receive prompt 
treatment and you and your baby will be watched 
carefully. Your asthma will be controlled so you can 
have a normal labor and delivery. 

 Will my breast milk be safe for my baby? Yes. Very 
little asthma medicine will get to your baby through your 
breast milk. The small amount in breast milk will not 
harm your baby. 

 Will my baby have asthma? Perhaps. A child is more 
likely to have asthma when one or both parents have 
asthma or allergies.


How To Control Asthma Triggers*

Because you have asthma, your airways are very sensitive. 
They may react to things called triggers--these are things 
that can make asthma symptoms start. When you are near an 
asthma trigger your airways may become swollen, tighten up, 
and produce too much mucus. You may start to wheeze, cough, 
have congestion, itchy eyes, or a runny nose. It's important 
to find out what your asthma triggers are and figure out ways 
to control them. 

Each person has different triggers. Here are common triggers 
and actions you can take to control them. Controlling your 
triggers will help you have fewer asthma symptoms and it will 
make your asthma treatment work better! 

 Ask your doctor and other health care providers to help 
you find out what your asthma triggers are. You may need 
to keep a written record of your activities. For 
example, you write down what you were doing, and where, 
whenever you have symptoms. This will help you notice if 
your symptoms are caused by being near certain things. 
For example, if your symptoms are worse when you make 
your bed or vacuum, dust mites may be a trigger. 

 Ask your doctor for help in deciding which actions will 
help the most to reduce your asthma symptoms. 

 Number each action item in order of importance. Carry 
out the actions at the top of the list first. Once you 
have completed these actions, move on to actions that are 
of lesser importance. 

 Discuss the results of these efforts with your doctor. 


Pollens and Molds (Outdoor) 

o Use air conditioning, if possible, during seasons when 
pollen and mold are highest. 

o Keep windows closed during seasons when pollen and mold 
are highest. 

o Avoid handling wet leaves or garden debris. 

o Consider staying indoors during the middle of the day and 
afternoon when the pollen count is highest. 

o If you are outside when the pollen count is high, it 
might help if you wash your hair before you go to bed. 


House Dust Mites 

These are actions you should take to gain control of 
dust mites: 

o Put your mattress in an airtight, or plastic, cover. 

o Put your pillow in an airtight cover or wash it once a 
week, every week, in hot water (130 F). 

o Avoid sleeping or lying on upholstered furniture. 

o Remove carpets that are laid on concrete. 

o Wash your bed covers and clothes once a week every week 
in hot water (130 F). 

Some additional actions include: 

o Reduce indoor humidity to less than 50 percent. Use a 
dehumidifier if needed. 

o Remove carpets from your bedroom. 

o Use chemical agents to kill mites or to change mite 
antigens in the house. 

o Avoid using a vacuum or being in a room while it is being 
vacuumed. 

o If you must vacuum, one or more of the following things 
can be done to reduce the amount of dust you breathe 
in. 

  Use a dust mask. 

  Use a central vacuum cleaner with the collecting bag 
out side the home. 

  Use a vacuum cleaner that has powerful suction. 


Animal Allergy 

All warm-blooded pets, including dogs, cats, birds, and 
rodents, can make your asthma worse. The flakes or scales 
from the skin, hair, or feathers of these animals and dried 
saliva or urine can make people start coughing, wheezing, or 
get itchy, watery eyes. This is called an allergy. The 
shortness of a pet's hair does not matter. There is no such 
thing as an allergy-free dog or cat. 

o Remove the animal from the house. 

o If you must have a pet with fur or feathers, keep the pet 
out of your bedroom at all times. 

o If there is forced-air heating in the home and you have a 
pet, close the air ducts in your bedroom. 

o Wash the pet once a week, every week. 

o Avoid visits to friends or relatives who have pets with 
fur or feathers. 

o Take asthma medicine (cromolyn or beta2-agonist; cromolyn 
is often preferred) before visiting homes or sites 
where animals with fur or feathers are present. 

o Choose a pet without fur or feathers. 

o Avoid products made with feathers, for example, pillows 
and comforters. Also avoid pillows, bedding, and 
furniture stuffed with kapok (silky fibers from the 
seed pods of the silk-cotton tree). 


Cockroach Allergy 

o Use insect sprays; but have someone else spray when you 
are outside of your home. 

o Air out your home for a few hours after spraying. 

o Use roach traps. 


Indoor Molds 

o Keep bathrooms, kitchens, and basements well aired. 

o Clean bathrooms, kitchens, and basements regularly. 

o Do not use humidifiers. 

o Use dehumidifiers for damp basement areas, with humidity 
level set for less than 50 percent but above 25 
percent. Empty and clean the dehumidifier water tray 
regularly. 


Tobacco Smoke 

o Do not smoke. 

o Do not allow smoking in your home. 

o Have household members smoke outside. 

o Do not allow any smoking in your bedroom. Encourage 
family members to quit smoking. Ask your doctor for 
help on how to quit. 

o Cigarette smoke can also harm your infant and young 
children. Studies show that children who breathe their 
mother's smoke have more lung diseases, such as asthma. 
Children with asthma who are around smoke have reduced 
lung function. They need more medicine and emergency 
room visits than children who are not around smoke. 


Wood Smoke 

o Avoid using a wood-burning stove to heat your home. 

o Avoid using kerosene heaters. 


Strong Odors and Sprays 

o Do not stay in your home when it is being painted. Allow 
enough time for the paint to dry. 

o Avoid perfume and perfumed cosmetics such as talcum 
powder and hairspray. 

o Do not use room deodorizers. 

o Use nonperfumed household cleaning products whenever 
possible. 

o Reduce strong cooking odors (especially frying) by using 
a fan and opening windows. 



Colds and Infections 

o Wash your hands frequently if people around you have a 
cold or flu. 

o Be sure to get the right amount of rest, exercise, and 
nutritious food. 

o Talk to your doctor about flu shots. 

o Do not take over-the-counter cold remedies, such as 
antihistamines and cough syrup, unless you speak to 
your doctor first. 


Exercise 

Exercise can make some people's asthma worse. But don't 
avoid exercise, it is important for your health! These 
things will help you exercise without bothering your asthma. 

o Work out a medicine plan with your doctor that helps you 
to exercise comfortably. 

o Take inhaled beta2-agonist or cromolyn medicine before 
you start to exercise, if needed. 

o Warm up before exercising and cool down afterwards. 


Weather 

o Wear a scarf over your mouth and nose in cold weather. 

o Pull a turtleneck over your nose on windy or cold days. 

o Dress warmly in the winter or on windy days. 

Remember: Following these suggestions will help keep asthma 
episodes from starting. It will help your asthma medicine 
work better! A plan to control your asthma triggers is an 
important part of controlling asthma!! 





HOW TO USE A METERED-DOSE INHALER* 

Using a metered-dose inhaler is a good way to take asthma 
medicines. There are few side effects because the medicine 
goes right to the airways inside the lungs. It takes only 5 
to 10 minutes for the medicine to have an effect compared to 
liquid asthma medicines, which can take 1 to 3 hours. A 
spacer or holding chamber attached to the inhaler can help 
make your inhaler easier to use. For patients taking inhaled 
steroids, a spacer may help prevent irritation to the mouth. 


USING THE INHALER 

1. Remove the cap and hold the inhaler upright. 

2. Shake the inhaler. 

3. Tilt your head back slightly and breathe out. 

4. Use the inhaler in any one of these ways. (A is the best 
way. B is useful for all patients. C is okay if you are 
having trouble with A or B.)

 A. Open mouth with inhaler 1 to 2 inches away

 B. Use spacer

 C. In the mouth 

5. Press down on the inhaler to release the medicine as you 
start to breathe in slowly. 

6. Breathe in slowly for 3 to 5 seconds. 

7. Hold your breath for 10 seconds to allow the medicine to 
reach deep into your lungs. 

8. Repeat puffs as prescribed. Waiting 1 minute between 
puffs may permit the second puff to go deeper into the 
lungs. 

Note: Dry powder capsules are used differently. To use a 
dry powder inhaler, close your mouth tightly around the 
mouthpiece and inhale very fast. 


CLEANING 

The inhaler should be cleaned often to prevent buildup that 
will clog the inhaler. 

1. Once a day, clean the inhaler and cap by rinsing them in 
warm running water. Let them dry before you use it 
again. 

2. Twice a week wash the plastic mouthpiece with mild 
dishwashing soap and warm water. Rinse and dry it well 
before putting it back. 


CHECKING HOW MUCH MEDICINE IS LEFT IN THE CANISTER 

1. If the canister is new, it is full. 

2. An easy way to check the amount of medicine left in your 
metered-dose inhaler is to place the canister in a 
container of water and observe the position it takes in 
the water. 





HOW TO USE A PEAK FLOW METER* 

It is very important during pregnancy to keep your lung 
function close to normal--that is, to make sure that your 
lungs are working as well as possible. Normal lung function 
is needed to provide enough oxygen to your growing baby! 

A peak flow meter is a device that measures your lung 
function, that is, how well your lungs are working. This 
information will help you and your doctor to better control 
your asthma. For example, during an asthma episode the 
airways of the lungs get narrow and blocked. The peak flow 
meter can measure how much the airways are blocked hours--even 
days--before you feel any chest tightness, coughing, or 
wheezing. By taking your medicine as soon as the peak flow 
measure changes, you may be able to stop the episode quickly 
and avoid a severe episode of asthma. 

The peak flow meter can also be used to help you and your 
doctor: 

 Decide if your medicine plan is working well. 

 Decide when to add, reduce, or stop medicine. 

 Decide when to seek emergency care. 

 Identify triggers--that is, what causes your asthma to get 
worse. 

Peak flow meters are used to check your asthma the way that 
blood pressure cuffs are used to check high blood pressure. 


HOW TO USE A PEAK FLOW METER: 

1. Place the arrow at the base of the numbered scale. 

2. Stand up. 

3. Take a deep breath. 

4. Place the meter in your mouth and close your lips around 
the mouth piece. Do not put your tongue inside the hole. 
Do not bend your neck. 

5. Blow out as hard and fast as you can. 

6. Write down the number you get. 

7. Repeat steps 1 through 6 two more times. 

8. Write down the highest of the three numbers achieved. 


FIND YOUR PERSONAL BEST PEAK FLOW NUMBER 

Your personal best peak flow number is the highest peak flow 
number you can achieve over a 2-week period when your asthma 
is under good control--that is, when you feel good and do not 
have any coughing, wheezing, shortness of breath, or chest 
tightness. 

Each patient's asthma is different, and your best peak flow 
number may be higher or lower than the average number for 
someone of your height, weight, and sex. This means that it 
is important for you and your doctor or nurse to find your 
own personal best peak flow number. Your own medicine plan 
needs to be based on your own personal best peak flow number. 

To find out your personal best peak flow number, you will 
need to do these things: 

 Use the peak flow meter every day for 2 weeks. 

 Use the peak flow meter mornings and evenings (when you 
wake up and about 10 to 12 hours later). 

 Use the peak flow meter before and after taking inhaled 
bronchodilator, if you take one. 

 Write down the peak flow numbers on "My Weekly Asthma 
Symptom and Peak Flow Diary." 

 Review the information in your diary with your doctor. 


DISCUSS WITH YOUR DOCTOR WHAT TO DO WHEN YOUR PEAK FLOW 
NUMBERS CHANGE 

The most important thing about measuring your peak flow 
number every day is to see how much it changes from your 
personal best number and from one reading to another. Your 
doctor will give you an "asthma control plan" that tells you 
what actions to take when there is a change in your peak flow 
numbers. For example, a fall in your peak flow of 20 to 30 
percent of your personal best number may mean the start of an 
asthma episode. You need to follow your asthma control plan! 


USE THE PEAK FLOW ZONE SYSTEM TO MANAGE YOUR ASTHMA 

Peak flow zones are set up like traffic lights to help you 
know what to do when your peak flow number changes. Once you 
know your personal best peak flow number, your doctor will 
give you the numbers that tell you what to do in each zone. 
You or your doctor can write these on your Asthma Control 
Plan and "My Weekly Asthma Symptom and Peak Flow Diary." For 
example: 

Green zone (80 to 100 percent of your personal best number) 
signals all clear. No asthma symptoms are present, and you 
may take your medicines as usual. 

Yellow zone (50 to 80 percent of your personal best number) 
signals caution. An episode of asthma may be starting and 
you will need to take extra medicine for a while according to 
your doctor's directions. Or, your overall asthma may not be 
under good control, and the doctor may need to change your 
daily medicine plan. 

Red zone (below 50 percent of your personal best number) 
signals a medical alert. You must take an inhaled beta2-
agonist right away, and call your doctor if your peak flow 
number does not return quickly to the yellow or green zone 
and stay in that zone. 

Record your personal best peak flow number and peak flow 
zones on the upper left-hand corner of "My Weekly Asthma 
Symptom and Peak Flow Diary." 

USE THE DIARY TO KEEP TRACK OF YOUR PEAK FLOW 

Write down your peak flow number on "My Weekly Asthma Symptom 
and Peak Flow Diary" every day, or as instructed by your 
doctor. 





MY WEEKLY ASTHMA SYMPTOM AND PEAK FLOW DIARY*

___ My predicted peak flow number
___ My personal best peak flow number
___ My green zone (OK) 80-100% of personal best 
___ My yellow zone (Caution) 50-80% of personal best
___ My red zone (Danger) less than 50% of personal best 

Date 
 
m pm 
m pm am 
m am 
m am pm 
m pm 
m pm
Peak flow reading 
 
No asthma symptoms 
 
Mild asthma symptoms 
 
Moderate asthma
symptoms 
 
Serious asthma
symptoms 
 
Medicine used to
stop symptoms 
 
Urgent visit to the
doctor 
 

1. Take your peak flow reading every morning (am) when you 
wake up and every night (pm) at bedtime. Try to take 
your peak flow readings at the same time each day. If 
you take an inhaled beta2-agonist medicine, take your 
peak flow reading before you take that medicine. Write 
down the highest reading of three tries in the box that 
says peak flow reading.

2. Look at the upper left corner of this sheet to see 
whether your number is in the green, yellow, or red zone.

3. In the space below the date and time, put an "X" in the 
box that matches the symptoms you have when you record 
your peak flow reading.

4. Look at your "Asthma Control Plan" for what to do when 
your number is in one of the zones and you have asthma 
symptoms.

5. Put an "X" in the box beside "medicine used" if you took 
extra asthma medicine to stop your symptoms.

6. If you made any visit to your doctor's office, emergency 
department, or hospital for treatment of an asthma 
episode, put an "X" in the box marked "urgent visit." 
Tell your doctor if you went to the emergency department 
or hospital.

No symptoms = No symptoms (wheeze, cough, chest 
tightness, or shortness of breath) even 
with normal physical activity.

Mild symptoms = Symptoms during physical activity, but not 
at rest Asthma symptoms do not keep you 
from sleeping or being active.

Moderate symptoms = Symptoms while at rest; symptoms may 
keep you from sleeping or being active.

Severe symptoms = Severe symptoms at rest (wheeze may be 
absent); symptoms cause problems.

walking or talking; muscles in neck or between ribs are 
pulled in when breathing.

* Adapted from National Asthma Education Program Teaching 
Your Patients About Asthma: A Clinician's Guide 
Washington, DC: US Department of Health and Human 
Services, 1992.

 Your doctor can also provide you with the average peak flow 
number for someone of your sex, height, and usual weight .







ASTHMA CONTROL PLAN

FOR (NAME OF PATIENT) ______________________________________

PREPARED BY (NAME OF CLINICIAN) 
__________________________


This plan will help you control your asthma and know what to 
do if you have an asthma episode. Keeping your asthma under 
control will help you: 

 Be active without having asthma symptoms. This includes 
being active in exercise and sports. 

 Sleep through the night without having asthma symptoms. 

 Prevent asthma episodes (attacks). 

 Have the best possible peak flow number--lungs that work 
well. (See "How To Use a Peak Flow Meter" handout.) 

 Avoid side effects from medicines. 


Here are three ways to control your asthma: 

 Follow your medicine plan 

 -- Follow your green zone plan every day to keep most 
asthma symptoms from starting. 

 -- Recognize your symptoms of an asthma episode. Act 
quickly to stop them. 

 -- Follow the yellow zone plan to stop asthma symptoms 
and to keep an asthma episode from getting serious. 

 -- Follow the red zone plan to take care of a serious 
episode. This is an emergency plan! 

 Whenever possible, stay away from things that bring on 
your asthma symptoms. Follow your asthma trigger control 
plan to reduce the number of things in your home, 
workplace, or classroom that bother your asthma. 

 See your doctor regularly. Talk about this plan with your 
doctor. Your doctor will mark (check) on the plan what 
you should do. 



IMPORTANT INFORMATION: 

Doctor ______________________________________________

Telephone Number _____________________________________

Address ______________________________________________


Hospital ____________________________________________

Telephone Number _____________________________________

Address ______________________________________________


Ambulance ___________________________________________

Telephone Number _____________________________________


Friend/Relative To Call __________________________

Telephone Number _____________________________________


Taxi ________________________________________________

Telephone Number _____________________________________




Follow the symptoms and action steps in these three zones to 
help you control your asthma.

GREEN ZONE: ALL CLEAR
This is where you should be every day.

Peak flow _____________________________________
 (80-100 percent of 
personal best)*

No symptoms of an asthma episode. You are able to do your 
usual activities and sleep without having symptoms.

o Take these medicines.

Name of Medicine How much to take When to take it
______________ ______________ ____________
______________ ______________ ____________

o Follow your asthma trigger control plan (Worksheet No. 20) 
to avoid things that bring on your asthma.

o Take ______________________ before exercise.
 (Name of medicine)


YELLOW ZONE: CAUTION
This is not where you should be every day. Take action to 
get your asthma under control.

Peak flow between __________________________________
 (50-80 percent of personal best)*

Symptoms of an asthma episode may be mild or moderate. You 
may be coughing, wheezing, feel short of breath, or feel like 
your chest is tight. These symptoms may keep you from your 
usual activities or keep you from sleeping.

o First, take this medicine.

Name of Medicine How much to take When to take it
______________ ______________ _____________

o Next, if you feel better in 20 to 60 minutes or your peak 
flow is over ______________________________, take the 
medicatine listed below.
 (70 percent of personal best)

Name of Medicine How much to take When to take it
______________ ______________ _____________

o Keep taking your green zone medicine(s).

But, if you DO NOT feel better in 20 to 60 minutes or your 
peak flow is under ______________________________, Follow 
the Red Zone Plan.
(70 percent of personal best)

Let the doctor know if you keep going into the Yellow Zone. 
Your Green Zone medicine may need to be changed to keep other 
episodes from starting.


RED ZONE: MEDICAL ALERT
This is an emergency! Get help. Your asthma symptoms are 
serious.

Peak flow under _________________________________
 (50 percent of personal best)

You may be coughing, very short of breath, and/or the skin 
between your ribs and your neck may be pulled in tight. You 
may have trouble walking or talking. You may not be wheezing 
because air cannot move out of your airways.

o First, take this medicine:

Name of Medicine How much to take When to take it
______________ ______________ _____________

o Next, call the doctor to talk about what you should do 
next. Tell him/her this is an emergency.

But, see the doctor RIGHT AWAY or go to the hospital if any 
of these things are happening:

 Lips or fingernails are blue

 You are struggling to breathe

 You do not feel any better 20 to 30 minutes after taking 
the extra medicine and your peak flow is still under 
_______________________
 (50 percent of personal best)

 Six hours after you take the extra medicine, if you still 
need inhaled beta2-agonist medicine every 1 to 3 hours 
and your peak flow is under _______________________
 (70 percent of personal best)

* This is a general guideline only. Some people have 
asthma that gets worse very fast. They may need to have 
a Yellow Zone start at 90 percent of their personal best.











Discrimination Prohibited: Under provisions of applicable 
public laws enacted by Congress since 1964, no person in the 
United States shall, on the grounds of race, color, national 
origin, handicap, or age, be excluded from participation in, 
be denied the benefits of, or be subjected to discrimination 
under any program or activity (or, on the basis of sex, with 
respect to any education program or activity) receiving 
Federal financial assistance. In addition, Executive Order 
11141 prohibits discrimination on the basis of age by 
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contracts, and Executive Order 11246 states that no federally 
funded contractor may discriminate against any employee or 
applicant for employment because of race, color, religion, 
sex, or national origin. Therefore, the National Heart, 
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these laws and Executive Orders.







U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Public Health Service
National Instututes of Health

NIH Publication No. 93-3279
September 1993