NATIONAL ASTHMA EDUCATION AND PREVENTION PROGRAM

Quick Reference from the 

Working Group Report on

Managing Asthma 

During Pregnancy:

Recommendations 

for Pharmacologic 

Treatment

Update 2004*

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

National Heart, Lung, and Blood Institute

* This Quick Reference summarizes the findings of the NAEPP 

Working Group Report on Managing Asthma During Pregnancy:

Recommendations for Pharmacologic Treatment—Update 

2004 (NIH Publication No. 05-3279), which is available at

http://www.nhlbi.nih.gov/health/prof/lung/asthma/astpreg.htm. 
2 NAEPP Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment

Maintaining adequate control of asthma

during pregnancy is important for the

health and well-being of both the mother and her baby. Asthma has been

reported to affect 3.7 to 8.4 percent of

pregnant women,1 making it potentially

the most common serious medical 

problem to complicate pregnancy. The

largest and most recent studies suggest

that maternal asthma increases the risk

of perinatal mortality, preeclampsia,

preterm birth, and low birth weight

infants. More severe asthma is associated with increased risks,2, 3 while bettercontrolled asthma is associated with

decreased risks.4

In 1993, the National Asthma Education

and Prevention Program (NAEPP) published the Report of the Working Group

on Asthma and Pregnancy (Asthma 

and Pregnancy Report 1993),5 which

presented recommendations for the management of asthma during pregnancy.

Since then, there have been revisions to 

the general asthma treatment guidelines,

Guidelines for the Diagnosis and

Management of Asthma—Expert Panel

Report 2 (EPR-2 1997),6 and Expert

Panel Report: Guidelines for the

Diagnosis and Management of Asthma

—Update on Selected Topics 2002

(EPR—Update 2002);7 release of new

asthma medications; and publication 

of new gestational safety data.

Managing Asthma During Pregnancy:

Recommendations for Pharmacologic

Treatment—Update 2004 (Asthma and

Pregnancy—Update 2004)8 reflects the

NAEPP’s commitment to keep recommendations for clinical practice up to

date and based on systematic reviews of

the evidence. Asthma and Pregnancy—

Update 2004 was developed through the

collective expertise of an expert panel 

on asthma and pregnancy (Working

Group). The NAEPP Science Base

Committee and NAEPP Coordinating

Committee members provided review

and comment. The recommendations

made in Asthma and Pregnancy—Update

2004 are intended to assist clinical decisionmaking; the clinician and patient still

need to develop individual treatment

plans that are tailored to the specific

needs and circumstances of the patient.

The scope of the current systematic

review is pharmacologic treatment 

of asthma in women during their 

pregnancy; however, highlights from

EPR-2 1997 and EPR—Update 2002 

relative to other aspects of asthma care

are also presented because they should

enhance the overall success and safety 

of managing asthma in pregnancy.

Systematic Review of the Evidence

A systematic review of the evidence on

the safety of asthma medications during

pregnancy was conducted by drug class.

Of 226 articles retrieved in the search 

of literature published in peer-reviewed

journals from January 1990 through

May 2003, 42 met criteria for inclusion

in the evidence review; 2 additional 

articles published after May 2003 were

included, for a total of 44 articles.

A summary of the findings from the 

evidence, arranged by medication 

category, follows.

Beta2-Agonists

One experimental animal study9 and six

human studies were included. The six

human studies consisted of one case

report10 and five clinical studies11–15

that included a total of 6,667 pregnant

women, of whom 1,929 had asthma and

1,599 had taken beta2-agonists. The

data were reassuring regarding the safety

of beta2-agonists during pregnancy.

More data were available for albuterol.

Two long-acting inhaled beta2-agonists

have become available since 1993—

salmeterol and formoterol. Limited 

data are available on their use during 

pregnancy. The pharmacologic and 

toxicologic profiles of these two drugs

are similar to the short-acting inhaled

beta2-agonists, with the exception of

their prolonged retention in the lungs.

Theophylline

Seven experimental animal studies16–22

and eight human studies were included.

The experimental animal studies

confirm the association of high-dose

theophylline and adverse pregnancy 

outcomes in animals. The eight human

studies, consisting of two case reports23, 24

and six clinical studies11, 13, 25–28 (of

which two were randomized controlled

trials), included a total of 57,163 pregnant women, of whom 3,616 had asthma and 660 had taken theophylline.

Studies and clinical experience confirm

the safety of theophylline at recommended doses (to serum concentration of

5–12 mcg/mL) during pregnancy. In a

randomized controlled trial, there were

no differences in asthma exacerbations

or maternal or perinatal outcomes in the

theophylline versus the beclomethasone

dipropionate treatment groups.

However, in the theophylline treatment

group, there were higher levels of reported side effects and discontinuation of the

medication and an increase in the proportion of women with forced expiratory volume in 1 second (FEV1) at less

than 80 percent of that predicted.25

Anticholinergics

No data on anticholinergics were available for the current evidence review.

Inhaled corticosteroids

Three experimental animal studies29–31

and 10 human studies were included.

The human studies included eight 

studies of pregnant women. Of the eight

studies, five were cohort studies;11, 13, 32–34

one was a controlled trial;35 and two

were randomized controlled trials.25, 28

These eight studies included a total of

21,072 pregnant women, of whom

16,900 had asthma and 6,113 had taken

inhaled corticosteroids. Also included

were two studies of newborns from the

Swedish Birth Registry—one compared

the rate of abnormalities among 2,014

newborns whose mothers had taken

budesonide to the rate of abnormalities

in the total newborn population,

although the number in that population

was not reported;36 the other study compared 2,900 newborns whose mothers

had taken budesonide to the total newborn population of 293,948;37 there may

be some overlap in the populations of

these two studies. There are three major

conclusions from the evidence review:

(1) the risk of asthma exacerbations

associated with pregnancy can be

reduced and lung function (FEV1)

improved with the use of inhaled corticosteroid therapy;25, 28, 34 (2) no studies

Update 2004

Quick Reference from the 

Working Group Report on

Managing Asthma 

During Pregnancy:

Recommendations 

for Pharmacologic 

Treatment

NATIONAL ASTHMA EDUCATION AND

PREVENTION PROGRAM
Quick Reference 3

to date, including studies of large birth

registries, have related inhaled corticosteroid use to any increases in congenital malformations or other adverse

perinatal outcomes; and (3) the 

preponderance of data on inhaled 

corticosteroids during pregnancy is

with budesonide. Few or no studies are

available on the other inhaled corticosteroid formulations during pregnancy.

Oral (systemic) corticosteroids

Nine experimental animal studies38–46

and eight human studies were included. The animal studies do not change

the previous understanding (Asthma

and Pregnancy Report 1993)5 of the

steroid-mediated clefting or decreases

in fetal growth in animals. The eight

human studies in the current evidence

review included one report of two

meta-analyses:47 one meta-analysis

used six cohort studies that included

51,380 pregnant women, of whom

535 had taken oral corticosteroids; the

other meta-analysis used four casecontrol studies,48–51 each of which was

also eligible to be included in the evidence review. These four case-control

studies included 52,038 pregnant

women, of whom 25 had taken oral

corticosteroids. The remaining three

human studies included one casecontrol study52 and two prospective

cohort studies11, 13 that included a total

of 4,321 pregnant women, of whom

1,998 had asthma and 213 had taken

oral corticosteroids. The findings 

from the current evidence review are

conflicting. Oral corticosteroid use,

especially during the first trimester 

of pregnancy, is associated with an

increased risk for isolated cleft lip with

or without cleft palate (the risk in the

general population is 0.1 percent; the

risk in women on oral corticosteroids

is 0.3 percent).47 However, very few

pregnant women who had oral

steroid-dependent asthma were included in the studies, and the length, 

timing, and dose of exposure to the

drug were not well described. Oral

corticosteroid use during pregnancy 

in patients who have asthma is associated with an increased incidence of

preeclampsia and the delivery of 

both preterm and low birth weight

infants.13, 47, 52 However, the available

data make it difficult to separate the

effects of the oral corticosteroids on

these outcomes from the effects of

severe or uncontrolled asthma, which

has been associated with maternal

and/or fetal mortality.

Cromolyn

No experimental animal studies and

two human studies were included in

the current review. The two human

studies consisted of prospective cohort

studies11, 13 that included 4,110 pregnant women, of whom 1,917 had

asthma and 318 had taken cromolyn.

The safety of using cromolyn during

pregnancy is supported by the current

review of evidence.

Leukotriene modifiers

Leukotriene modifiers include two

compounds available as oral tablets

(the receptor antagonists montelukast

and zafirlukast) and 5-lipoxygenase

pathway inhibitors (e.g., zileuton). No

animal studies and one human study

were available for review. The human

study was an observational study of

2,205 pregnant women, 873 with

asthma, of whom 9 took leukotriene

modifiers, but the specific agent was

not identified.11 The conclusion is that

minimal data are currently available

on the use of leukotriene modifiers

during pregnancy. Reassuring animal

studies have been submitted to the

Food and Drug Administration (FDA)

for leukotriene receptor antagonists

but not for the leukotriene lipoxygenase inhibitor.

Recommendations for Managing Asthma

During Pregnancy

The Working Group recommends 

the following principles and stepwise

approach to pharmacologic therapy

for managing asthma during pregnancy. (See figures 1–6.) The principles

and approach are based on the

Working Group’s interpretation of 

the current scientific review of the 

evidence on the safety of asthma 

medications during pregnancy and

consideration of previous NAEPP

reports: the Asthma and Pregnancy

Report 1993, the EPR-2 1997, and 

the EPR—Update 2002.

General principles

• The treatment goal for the pregnant

asthma patient is to provide optimal

therapy to maintain control of asthma for maternal health and quality

of life as well as for normal fetal

maturation. Asthma control is

defined as:

- Minimal or no chronic symptoms 

day or night

- Minimal or no exacerbations

- No limitations on activities

- Maintenance of (near) normal 

pulmonary function

- Minimal use of short-acting 

inhaled beta2-agonist

- Minimal or no adverse effects 

from medications

• It is safer for pregnant women with

asthma to be treated with asthma 

medications than for them to have 

asthma symptoms and exacerbations.

Monitoring and making appropriate

adjustments in therapy may be required

to maintain lung function and, hence,

blood oxygenation that ensures oxygen supply to the fetus. Inadequate

control of asthma is a greater risk to

the fetus than asthma medications

are. Proper control of asthma should

enable a woman with asthma to

maintain a normal pregnancy with little or no risk to her or her fetus.

• The obstetrical care provider should

be involved in asthma care, including monitoring of asthma status during prenatal visits. A team approach

is helpful if more than one clinician

is managing a pregnant woman with

asthma.

• Asthma treatment is organized around

four components of management:

- Assessment and monitoring of 

asthma, including objective measures of pulmonary function. 

Because the course of asthma 

changes for about two-thirds of 

women during pregnancy,53

monthly evaluations of asthma 

history and pulmonary function 

are recommended. Spirometry 

tests are recommended at the time 

of initial assessment. For routine 

monitoring at most subsequent 

followup outpatient visits, 

spirometry is preferable, but 

measurement of peak expiratory 

flow (PEF) with a peak flow meter

is generally sufficient. Patients 

should be instructed to be 

attentive to fetal activity. Serial 

ultrasound examinations starting 

at 32 weeks gestation may be 

considered for patients who have 

suboptimally controlled asthma 

and for women with moderateto-severe asthma. Ultrasound 

examinations are also helpful after

recovery from a severe exacerbation.
4 NAEPP Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment

- Control of factors contributing to 

asthma severity. Identifying and 

controlling or avoiding such 

factors as allergens and irritants, 

particularly tobacco smoke, that 

contribute to asthma severity 

can lead to improved maternal 

well-being with less need for 

medications. (See figure 7.)

- Patient education. Asthma control 

is enhanced by ensuring access to 

education about asthma and about 

the skills necessary to manage it—

such as self-monitoring, correct 

use of inhalers, and following a 

plan for managing asthma long 

term and for promptly handling 

signs of worsening asthma.

- A stepwise approach to pharmacologic therapy. In this approach to 

achieving and maintaining asthma 

control, the dose and number of 

medications and the frequency of 

administration are increased as 

necessary, based on the severity 

of the patient’s asthma, and are 

decreased when possible.

Recommendations for Pharmacologic

Treatment of Asthma During Pregnancy

Stepwise approach for managing 

asthma. To develop recommendations

for the stepwise approach to the pharmacologic treatment of asthma in pregnant women, the Working Group first

considered the stepwise approach in the

EPR—Update 2002, which was based

on systematic review of the evidence

from medication effectiveness studies in

nonpregnant adults and children. The

Working Group also considered EPR-2

1997 and the Asthma and Pregnancy

Report 1993.

The effectiveness of medications is

assumed to be the same in pregnant

women as in nonpregnant women,

although there are no studies that 

directly test this assumption. Based 

on their current systematic review of 

evidence from safety studies of asthma

medications during pregnancy, the

Working Group then tailored existing

recommendations for stepwise therapy.

Refer to figures 1, 2, and 3 for a complete list of recommended therapies and

medication dosages in the stepwise

approach to managing asthma. The 

following information highlights the

rationale for the preferred 

medications.

• Step 1: Mild Intermittent Asthma.

Short-acting bronchodilators, 

particularly short-acting inhaled beta2-

agonists, are recommended as quickrelief medication for treating symptoms

as needed in patients with intermittent

asthma. Albuterol is the preferred

short-acting inhaled beta2-agonist

because it has an excellent safety profile

and the greatest amount of data related

to safety during pregnancy of any currently available inhaled beta2-agonist.

Women’s experience with these drugs is

extensive, and no evidence has been

found either of fetal injury from the use

of short-acting inhaled beta2-agonists or

of contraindication during lactation.

• Step 2: Mild Persistent Asthma.

The preferred treatment for longterm-control medication in Step 2 

is daily low-dose inhaled corticosteroid. This preference is based 

on the strong effectiveness data in 

nonpregnant women6, 7 as well as

effectiveness and safety data in pregnant women that show no increased

risk of adverse perinatal outcomes.

Budesonide is the preferred inhaled

corticosteroid because more data are

available on using budesonide in pregnant women than are available on

other inhaled corticosteroids, and the

data are reassuring. It is important to

note that there are no data indicating

that the other inhaled corticosteroid

preparations are unsafe during pregnancy. Therefore, inhaled corticosteroids other than budesonide may 

be continued in patients who were

well controlled by these agents prior

to pregnancy, especially if it is thought

that changing formulations may 

jeopardize asthma control.

Cromolyn, leukotriene receptor antagonists, and theophylline are listed as

alternative but not preferred therapies.

Cromolyn has an excellent safety 

profile, but it has limited effectiveness

compared with inhaled corticosteroids.

Leukotriene receptor antagonists have

been demonstrated to provide statistically significant but modest improvements in children and nonpregnant

adults with asthma, although in studies comparing overall efficacy of the

two drugs, most outcomes clearly

favor inhaled corticosteroids.

Published data are minimal on using

leukotriene receptor antagonists during pregnancy; however, animal safety

data submitted to the FDA are reassuring. Thus, leukotriene receptor

antagonists are an alternative but 

not preferred treatment for pregnant

women whose asthma was successfully

controlled with this medication prior

to their pregnancy. Theophylline has

demonstrated clinical effectiveness in

some studies and has been used for

years in pregnant women with asthma.

It also, however, has the potential for

serious toxicity resulting from excessive dosing and/or select drug-drug

interactions (e.g., with erythromycin).

Using theophylline during pregnancy

requires careful titration of the dose

and regular monitoring to maintain

the recommended serum theophylline

concentration range of 5–12 mcg/mL.

• Step 3: Moderate Persistent Asthma.

Two preferred treatment options are

noted: either a combination of lowdose inhaled corticosteroid and a 

long-acting inhaled beta2-agonist, or

increasing the dose of inhaled corticosteroid to the medium dose range. No

data from studies during pregnancy

clearly delineate that one option is 

recommended over the other.

Limited data describe the effectiveness

and/or safety of using combination

therapy during pregnancy, but strong

evidence from randomized controlled

trials in nonpregnant adults shows

that adding long-acting inhaled beta2-

agonist to a low dose of inhaled 

corticosteroid provides greater asthma

control than only increasing the dose

of corticosteroid.7 The pharmacologic

and toxicologic profiles of long-acting

and short-acting inhaled beta2-agonists

are similar; there is justification for

expecting long-acting inhaled beta2-

agonists to have a safety profile similar to that of albuterol, for which

there are data related to safety during

pregnancy. Two long-acting inhaled

beta2-agonists are available—salmeterol and formoterol. Limited observational data exist on their use during 

pregnancy; salmeterol might be chosen

because it has been available longer in

the United States.

Increasing the dose of inhaled corticosteroid to medium dose will benefit

many patients, and, as noted previously, the data on using inhaled corticosteroids during pregnancy—including

studies of large birth registries—are

reassuring.

• Step 4: Severe Persistent Asthma.

If additional medication is required

after carefully assessing patient technique and adherence with using Step 3
Quick Reference 5

medication, then the inhaled corticosteroid dose should be increased within

the high-dose range, and the use of

budesonide is preferred. If this is insufficient to manage asthma symptoms,

then the addition of systemic corticosteroid is warranted; although the data

are uncertain about some risks of oral

corticosteroids during pregnancy,

severe uncontrolled asthma poses a

definite risk to the mother and fetus.

Management of acute exacerbations.

Asthma exacerbations have the potential

to lead to severe problems for the fetus.

Therefore, asthma exacerbations during

pregnancy should be managed aggressively. Refer to figure 4 for home treatment of asthma exacerbation, figure 5

for emergency department and hospital

management, and figure 6 for medications and dosages.

Pharmacologic management of allergic

rhinitis. Rhinitis, sinusitis, and gastroesophageal reflux are conditions that 

are often associated with asthma, are

frequently more troublesome during

pregnancy, and may exacerbate coexisting asthma. If these conditions are 

present, appropriate treatment is an 

integral part of asthma management.

These topics were outside the scope of

the current evidence-based review, but 

relevant studies on the safety of rhinitis

medications during pregnancy were

reviewed in order to present the following recommendations.

• Intranasal corticosteroids are the most

effective medications for the management of allergic rhinitis and have a

low risk of systemic effect when used

at recommended doses. Montelukast,

a leukotriene receptor antagonist, can

be used for the treatment of allergic

rhinitis—but minimal data are available on the use of this medication 

during pregnancy.

• The current second-generation antihistamines of choice are loratadine or

cetirizine.

• There may be a relationship between

use of oral decongestants in early

pregnancy and a rare birth defect, 

gastroschisis; however, the absolute

risk of gastroschisis in exposed fetuses

is still extremely small. If nasal decongestion is indicated in early pregnancy,

an external nasal dilator, short-term

topical oxymetazoline, or intranasal

corticosteroid can be considered

before use of oral decongestants.

Financial Disclosures

Dr. Busse has served on the Speakers’ Bureaus

of Aventis, GlaxoSmithKline, and Merck; 

he has served on the Advisory Boards of

AstraZeneca, Aventis, Pfizer, and Schering; 

he has received funding/grant support for

research projects from Aventis, Fujisawa,

GlaxoSmithKline, Hoffmann LaRoche, Pfizer,

and Wyeth; he has served as a consultant for

Bristol-Myers Squibb, Dynavax, Fujisawa,

Hoffmann LaRoche, and Wyeth.

Dr. Cloutier has received funding/grant 

support for research projects from

GlaxoSmithKline.

Dr. Dombrowski has none.

Dr. Nelson has served on the Speakers’

Bureaus of AstraZeneca and GlaxoSmithKline;

he has received funding/grant support for

research projects from Altana, AstraZeneca,

Dey Laboratories, Eli Lilly, Epigenesis, and

IVAX; he has served as a consultant for

Altana, AstraZeneca, Aventis, Dey

Laboratories, Dynavax Technologies,

Genentech, GlaxoSmithKline, Integrated

Therapeutics Group, Protein Design

Laboratories, Rigel Pharmaceuticals, UCB, 

and Wyeth.

Dr. Reed has served on the Speakers’ Bureaus

of Abbott Laboratories, Bristol-Myers Squibb,

Enzon, GlaxoSmithKline, Pfizer, Roche, 

and Somerset; he has received funding/grant

support for research projects from Health

Resources and Services Administration,

National Institutes of Health, Abbott

Laboratories, AstraZeneca, Aventis, 

Bristol-Myers Squibb, Eli Lilly, Forrest

Laboratories, GlaxoSmithKline, Janssen,

Johnson & Johnson, Merck, Novartis,

Organon, Pfizer, Roche, Schering, Somerset,

and Wyeth-Averst; he has served as a consultant for Abbott Laboratories, Bristol-Myers

Squibb, Enzon, GlaxoSmithKline, Pfizer, and

Somerset.

Dr. Schatz has served on the Speakers’ Bureaus

of AstraZeneca and Merck; he has received

funding/grant support for research projects

from Aventis and GlaxoSmithKline.

Dr. Scialli has none.

Dr. Stoloff has served on the Speakers’

Bureaus of Alcon, AstraZeneca, Aventis,

Genentech, GlaxoSmithKline, Pfizer, and

Schering; he has served as a consultant for

Alcon, AstraZeneca, Aventis, Genentech,

GlaxoSmithKline, Pfizer, and Schering.

Dr. Szefler has received funding/grant support

for research projects from the National

Institutes of Health, AstraZeneca, and Russ

Pharmaceuticals; he has served as a consultant

for AstraZeneca, Aventis, GlaxoSmithKline,

and Merck.

National Asthma Education and Prevention

Program Asthma and Pregnancy Working

Group

William W. Busse, M.D., Chair, University

of Wisconsin Medical School, Madison, WI

Michelle Cloutier, M.D., Connecticut

Children’s Medical Center, Hartford, CT

Mitchell Dombrowski, M.D., St. John

Hospital, Detroit, MI

Harold S. Nelson, M.D., National Jewish

Medical and Research Center, Denver, CO

Michael Reed, Pharm.D., Rainbow Babies

and Children’s Hospital, Cleveland, OH

Michael Schatz, M.D., M.S., KaiserPermanente Medical Center, San Diego, CA

Anthony R. Scialli, M.D., Georgetown

University Hospital, Washington, DC

Stuart Stoloff, M.D., University of Nevada

School of Medicine, Reno, NV

Stanley Szefler, M.D., National Jewish

Medical and Research Center, Denver, CO
6 NAEPP Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment

Step down

Review treatment every 1–6 months; a gradual 

stepwise reduction in treatment may be possible.

Step up

If control is not maintained, consider step up. First,

review patient medication technique, adherence, and

environmental control.

Goals of Therapy: Asthma Control

• Minimal or no chronic

symptoms day or night

• Minimal or no exacerbations

• No limitations on activities;

no school/work missed

• Maintain (near) normal 

pulmonary function

• Minimal use of shortacting inhaled beta2-

agonist‡

• Minimal or no adverse

effects from medications

Stepwise Approach for Managing Asthma During Pregnancy and Lactation: Treatment Figure

1

Classify Severity: Clinical Features Before

Treatment or Adequate Control

Medications Required To Maintain

Long-Term Control

Step 4

Severe 

Persistent

Symptoms/

Day

Symptoms/

Night

PEF 

or FEV1

PEF Variability Daily Medications

• Preferred treatment:

- High-dose inhaled corticosteroid

AND

- Long-acting inhaled beta2-agonist

AND, if needed,

- Corticosteroid tablets or syrup long term (2 mg/kg per day, generally not to exceed 60 mg per 

day). (Make repeat attempts to reduce systemic corticosteroid and maintain control with 

high-dose inhaled corticosteroid.*) 

• Alternative treatment:

- High-dose inhaled corticosteroid*

AND

- Sustained release theophylline to serum concentration of 5–12 mcg/mL.

Continual

Frequent

Daily

>1 night/week

>2 days/week but

<daily

>2 nights/month

≤2 days/week

≤2 nights/month

≤60%

>30%

>60%–<80%

>30%

≥80%

20%–30%

≥80%

<20%

• Preferred treatment:

EITHER

- Low-dose inhaled corticosteroid* and long-acting inhaled beta2-agonist

OR

- Medium-dose inhaled corticosteroid.*

If needed (particularly in patients with recurring severe exacerbations):

- Medium-dose inhaled corticosteroid* and long-acting inhaled beta2-agonist.

• Alternative treatment:

- Low-dose inhaled corticosteroid* and either theophylline or leukotriene receptor antagonist.†

If needed:

- Medium-dose inhaled corticosteroid* and either theophylline or leukotriene receptor antagonist.†

• Preferred treatment:

- Low-dose inhaled corticosteroid.*

• Alternative treatment (listed alphabetically): cromolyn, leukotriene receptor antagonist† 

OR sustained-release theophylline to serum concentration of 5–12 mcg/mL.

Step 3

Moderate

Persistent

Step 2

Mild

Persistent

• No daily medication needed.

• Severe exacerbations may occur, separated by long periods of normal lung function and no 

symptoms. A course of systemic corticosteroid is recommended.

• Short-acting bronchodilator: 2–4 puffs short-acting inhaled beta2-agonist‡ as needed for symptoms.

• Intensity of treatment will depend on severity of exacerbation; up to 3 treatments at 20-minute intervals or a single nebulizer 

treatment as needed. Course of systemic corticosteroid may be needed.

• Use of short-acting inhaled beta2-agonist‡ >2 times a week in intermittent asthma (daily, or increasing use in persistent asthma) 

may indicate the need to initiate (increase) long-term-control therapy.

* There are more data on using budesonide during pregnancy than on using other inhaled corticosteroids.

† There are minimal data on using leukotriene receptor antagonists in humans during pregnancy, although there are reassuring animal data submitted to FDA.

‡ There are more data on using albuterol during pregnancy than on using other short-acting inhaled beta2-agonists.

Step 1

Mild

Intermittent

Quick

Relief

All Patients

• The stepwise approach is meant to assist, not replace, the clinical decisionmaking

required to meet individual patient needs.

• Classify severity: assign patient to most severe step in which any feature occurs (PEF

is percent of personal best; FEV1 is percent predicted).

• Gain control as quickly as possible (consider a short course of systemic corticosteroid),

then step down to the least medication necessary to maintain control.

• Minimize use of short-acting inhaled beta2-agonist‡ (e.g., use of approximately one

canister a month even if not using it every day indicates inadequate control of asthma

and the need to initiate or intensify long-term-control therapy).

• Provide education on self-management and controlling environmental factors that

make asthma worse (e.g., allergens, irritants).

• Refer to an asthma specialist if there are difficulties controlling asthma or if Step 4

care is required. Referral may be considered if Step 3 care is required.

Notes
Quick Reference 7

Inhaled Corticosteroids (See Estimated Comparative Daily Dosages for Inhaled Corticosteroids [Figure 3].)

Usual Dosages for Long-Term-Control Medications During Pregnancy

and Lactation*

Figure

2

Medication Dosage Form Adult Dose

Methylprednisolone

Prednisolone

Prednisone

Salmeterol

Formoterol

Fluticasone/Salmeterol

Cromolyn

Montelukast

Zafirlukast

Theophylline

2, 4, 8, 16, 32 mg tablets

5 mg tablets,

5 mg/5 cc,

15 mg/5 cc

1, 2.5, 5, 10, 20, 50 mg tablets

5 mg/cc, 5 mg/5 cc

MDI 21 mcg/puff

DPI 50 mcg/blister

DPI 12 mcg/single-use capsule

DPI 100, 250, or

500 mcg/50 mcg

MDI 1 mg/puff

Nebulizer 20 mg/ampule

10 mg tablet

10 or 20 mg tablet

Liquids, sustained-release

tablets, and capsules

• 7.5–60 mg daily in a single dose in a.m. or qod as needed

for control

• Short-course “burst” to achieve control: 40–60 mg per

day as single dose or 2 divided doses for 3–10 days

2 puffs q 12 hours

1 blister q 12 hours

1 capsule q 12 hours

1 inhalation bid; dose depends on severity of asthma

2–4 puffs tid-qid

1 ampule tid-qid

10 mg qhs

40 mg daily (20 mg tablet bid)

Starting dose 10 mg/kg/day up to 300 mg max; usual max

800 mg/day

DPI, dry powder inhaler; MDI, metered-dose inhaler.

*Adapted from EPR—Update 2002.

Notes: • The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to therapy.

• Some doses may be outside package labeling, especially in the high-dose range.

Long-Acting Inhaled Beta2-Agonists (Should not be used for symptom relief or for exacerbations. Use with inhaled

corticosteroids.)

Combined Medication

Cromolyn 

Leukotriene Receptor Antagonists

Methylxanthines (Serum monitoring is important [serum concentration of 5–12 mcg/mL at steady state].)

Figure Estimated Comparative Daily Dosages for Inhaled Corticosteroids* 3

Drug

Beclomethasone CFC

42 or 84 mcg/puff

Beclomethasone HFA

40 or 80 mcg/puff

Budesonide DPI

200 mcg/inhalation

Flunisolide

250 mcg/puff

Fluticasone

MDI: 44, 110, or 220 mcg/puff

DPI: 50, 100, or 250

mcg/inhalation

Triamcinolone acetonide

100 mcg/puff

Adult Low Daily Dose 

168–504 mcg

80–240 mcg

200–600 mcg

500–1,000 mcg

88–264 mcg

100–300 mcg

400–1,000 mcg

Adult Medium Daily Dose 

504–840 mcg

240–480 mcg

600–1,200 mcg

1,000–2,000 mcg

264–660 mcg

300–750 mcg

1,000–2,000 mcg

Adult High Daily Dose 

>840 mcg

>480 mcg

>1,200 mcg

>2,000 mcg

>660 mcg

>750 mcg

>2,000 mcg

DPI, dry powder inhaler; MDI, metered-dose inhaler.

*Adapted from EPR—Update 2002.

Systemic Corticosteroids (Applies to all three corticosteroids.)
8 NAEPP Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment

Management of Asthma Exacerbations During Pregnancy and Lactation:

Home Treatment

Figure

4

Assess Severity

Measure PEF: Value <50% personal best

or predicted suggests severe exacerbation

Note signs and symptoms: Degrees of

cough, breathlessness, wheeze, and chest

tightness correlate imperfectly with 

severity of exacerbation

Accessory muscle use and suprasternal

retractions suggest severe exacerbation

Note presence of fetal activity*

Initial Treatment

Short-acting inhaled beta2-agonist: up 

to 3 treatments of 2–4 puffs by MDI at 

20-minute intervals or single nebulizer

treatment

Good Response

Mild Exacerbation

PEF >80% predicted or personal best.

No wheezing or shortness of breath.

Response to short-acting inhaled 

beta2-agonist sustained for 4 hours.

Appropriate fetal activity.*

Treatment:

• May continue short-acting inhaled

beta2-agonist every 3–4 hours for

24–48 hours.

• For patients on inhaled corticosteroid, double dose for 7–10 days.

Incomplete Response

Moderate Exacerbation

PEF 50%–80% predicted or personal

best.

Persistent wheezing and shortness of 

breath.

Decreased fetal activity.*

Treatment:

• Add oral corticosteroid.

• Continue short-acting inhaled

beta2-agonist.

Poor Response

Severe Exacerbation

PEF <50% predicted or personal best.

Marked wheezing and shortness 

of breath.

Decreased fetal activity.*

Treatment:

• Add oral corticosteroid.

• Repeat short-acting inhaled 

beta2-agonist immediately.

• If distress is severe and nonresponsive, call your clinician immediately and proceed to emergency

department; consider calling 

ambulance or 911.

Contact clinician for followup

instructions.

Contact clinician urgently (this day)

for instructions.

Proceed to emergency department.

MDI, metered-dose inhaler; PEF, peak expiratory flow.

*Fetal activity is monitored by observing whether fetal kick counts decrease over time.
Quick Reference 9

Management of Asthma Exacerbations During Pregnancy and Lactation: 

Emergency Department and Hospital-Based Care*

Figure

5

Initial Assessment

History, physical examination (auscultation, use of accessory muscles, heart rate, respiratory rate), PEF or FEV1, oxygen saturation, and other tests as indicated

Initiate fetal assessment (consider continuous electronic fetal monitoring and/or biophysical profile if pregnancy has reached fetal viability)

FEV1 or PEF >50%

• Short-acting inhaled beta2-agonist by

MDI or nebulizer, up to three doses in

first hour

• Oxygen to achieve O2 saturation ≥95%

• Oral systemic corticosteroid if no immediate response or if patient recently took

oral systemic corticosteroid

FEV1 or PEF <50% (Severe Exacerbation)

• High-dose short-acting inhaled beta2-

agonist by nebulization every 20 minutes

or continuously for 1 hour plus inhaled

ipratropium bromide 

• Oxygen to achieve O2 saturation >95%

• Oral systemic corticosteroid

Impending or Actual Respiratory Arrest

• Intubation and mechanical ventilation

with 100% O2

• Nebulized short-acting inhaled beta2-

agonist plus inhaled ipratropium bromide 

• Intravenous corticosteroid

Repeat Assessment

Symptoms, physical examination, PEF, O2 saturation, 

other tests as needed 

Continue fetal assessment

Admit to Hospital

Intensive Care

(see box below)

Moderate Exacerbation

FEV1 or PEF 50%–80% predicted/personal best 

Physical exam: moderate symptoms

• Short-acting inhaled beta2-agonist every 

60 minutes

• Systemic corticosteroid

• Oxygen to maintain O2 saturation >95%

• Continue treatment 1–3 hours, provided 

there is improvement

Severe Exacerbation

FEV1 or PEF <50% predicted/personal best

Physical exam: severe symptoms at rest,

accessory muscle use, chest retraction

History: high-risk patient

No improvement after initial treatment

• Short-acting inhaled beta2-agonist hourly or

continuously plus inhaled ipratropium bromide 

• Oxygen

• Systemic corticosteroid

Good Response

• FEV1 or PEF ≥70%

• Response sustained 60 minutes after last

treatment

• No distress

• Physical exam: normal

• Reassuring fetal status

Incomplete Response

• FEV1 or PEF ≥50% but <70%

• Mild or moderate symptoms

• Continue fetal assessment

Poor Response

• FEV1 or PEF <50%

• PCO2 >42 mmHg

• Physical exam: symptoms severe,

drowsiness, confusion

• Continue fetal assessment

Individualized Decision re:

Hospitalization

Discharge Home

• Continue treatment with short-acting

inhaled beta2-agonist

• Continue course of oral systemic 

corticosteroid 

• Initiate or continue inhaled corticosteroid

until review at medical followup

• Patient education

- Review medicine use

- Review/initiate action plan

- Recommend close medical followup

Admit to Hospital Ward • Short-acting inhaled beta2-agonist plus

inhaled ipratropium bromide 

• Systemic (oral or intravenous) 

corticosteroid

• Oxygen

• Monitor FEV1 or PEF, O2 saturation,

pulse

• Continue fetal assessment until patient

stabilized

Admit to Hospital Intensive Care • Short-acting inhaled beta2-agonist hourly

or continuously plus inhaled ipratropium

bromide 

• Intravenous corticosteroid

• Oxygen

• Possible intubation and mechanical 

ventilation

• Continue fetal assessment until patient

stabilized

Discharge Home

• Continue treatment with short-acting inhaled beta2-agonist

• Continue course of oral systemic corticosteroid 

• Initiate or continue inhaled corticosteroid until review at

medical followup

• Patient education

- Review medicine use

- Review/initiate action plan

- Recommend close medical followup

Improve

FEV1, forced expiratory volume in 1 second; MDI, metered-dose inhaler; PCO2, carbon dioxide partial pressure; PEF, peak expiratory flow.

*Adapted from EPR-2 1997.
10 NAEPP Working Group Report on Managing Asthma During Pregnancy: Recommendations for Pharmacologic Treatment

Figure Medications and Dosages for Asthma Exacerbations During Pregnancy and Lactation*

6

Dosages

2.5–5 mg every 20 minutes for

3 doses, then 2.5–10 mg every 

1–4 hours as needed, or 10–15

mg/hour continuously

4–8 puffs every 20 minutes up to 4

hours, then every 1–4 hours as needed

See albuterol dose.

See albuterol dose.

1.25–2.5 mg every 20 minutes for 

3 doses, then 1.25–5 mg every 1–4

hours as needed, or 5–7.5 mg/hour

continuously

See albuterol dose.

0.3–0.5 mg every 20 minutes for 

3 doses sq

0.25 mg every 20 minutes for 

3 doses sq

0.5 mg every 30 minutes for 3 doses,

then every 2–4 hours as needed 

4–8 puffs as needed

3 mL every 30 minutes for 3 doses,

then every 2–4 hours as needed

4–8 puffs as needed

120–180 mg/day in 3 or 4 divided

doses for 48 hours, then 60–80

mg/day until PEF reaches 70% 

of predicted or personal best

0.15 mg/kg (minimum dose 2.5 mg)

every 20 minutes for 3 doses, then

0.15–0.3 mg/kg up to 10 mg every

1–4 hours as needed, or 0.5 mg/kg/

hour by continuous nebulization

4–8 puffs every 20 minutes for 3

doses, then every 1–4 hours inhalation

maneuver; use spacer/holding chamber

See albuterol dose; thought to be half

as potent as albuterol on a mg basis.

See albuterol dose.

0.075 mg/kg (minimum dose 1.25 mg)

every 20 minutes for 3 doses, then

0.075–0.15 mg/kg up to 5 mg every

1–4 hours as needed, or 0.25 mg/kg/

hour by continuous nebulization

See albuterol dose; thought to be half

as potent as albuterol on a mg basis.

0.01 mg/kg up to 0.3–0.5 mg every

20 minutes for 3 doses sq

0.01 mg/kg every 20 minutes for 3 doses,

then every 2–6 hours as needed sq

0.25 mg every 20 minutes for 3 doses,

then every 2 to 4 hours

4–8 puffs as needed

1.5 mL every 20 minutes for 3 doses,

then every 2–4 hours

4–8 puffs as needed

1 mg/kg every 6 hours for 48 hours,

then 1–2 mg/kg/day (maximum = 60

mg/day) in 2 divided doses until PEF

is 70% of predicted or personal best

Albuterol

Nebulizer solution

(5.0 mg/mL, 

2.5 mg/3mL,

1.25 mg/3mL, 

0.63 mg/3 mL)

MDI

(90 mcg/puff)

Bitolterol

Nebulizer solution

(2 mg/mL)

MDI

(370 mcg/puff)

Levalbuterol (R-albuterol)

Nebulizer solution

(0.63 mg/3 mL,

1.25 mg/3 mL)

Pirbuterol

MDI

(200 mcg/puff)

Epinephrine 

1:1000 (1 mg/mL)

Terbutaline

(1 mg/mL)

Ipratropium bromide

Nebulizer solution

(0.25 mg/mL)

MDI

(18 mcg/puff)

Ipratropium with albuterol

Nebulizer solution

(Each 3 mL vial contains 0.5 mg ipratropium bromide and 

2.5 mg albuterol)

MDI

(Each puff contains 

18 mcg ipratropium 

bromide and 90 mcg 

albuterol)

Prednisone

Methylprednisolone

Prednisolone

Only selective beta2-agonists are recommended. For optimal delivery, dilute

aerosols to minimum of 3 mL at gas flow

of 6–8 L/min.

As effective as nebulized therapy if patient

is able to coordinate.

Has not been studied in severe asthma exacerbations. Do not mix with other drugs.

Has not been studied in severe asthma

exacerbations.

0.63 mg of levalbuterol is equivalent to

1.25 mg of racemic albuterol for both

efficacy and side effects.

Has not been studied in severe asthma

exacerbations.

No proven advantage of systemic therapy

over aerosol.

No proven advantage of systemic therapy

over aerosol.

May mix in same nebulizer with albuterol.

Should not be used as first-line therapy;

should be added to beta2-agonist therapy.

Dose delivered from MDI is low and has

not been studied in asthma exacerbations.

Contains EDTA to prevent discoloration.

This additive does not induce 

bronchospasm.

For outpatient “burst” use 40–60 mg 

in single or 2 divided doses for adults

(children: 1–2 mg/kg/day, maximum 

60 mg/day) for 3–10 days.

Short-Acting Inhaled Beta2-Agonists

Systemic Corticosteroids (Dosages and comments apply to all three corticosteroids)

Anticholinergics

Medications Adult Dose Child Dose Comments

* Adapted from EPR—Update 2002.

Notes: • The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to therapy.

• No advantage has been found for higher dose corticosteroids in severe asthma exacerbations, nor is there any advantage for intravenous administration over oral therapy 

provided gastrointestinal transit time or absorption is not impaired. The usual regimen is to continue the frequent multiple daily dose until the patient achieves an FEV1

or PEF of 50 percent of predicted or personal best and then lower the dose to twice daily. This usually occurs within 48 hours. Therapy following a hospitalization or 

emergency department visit may last from 3 to 10 days. If patients are then started on inhaled corticosteroids, studies indicate there is no need to taper the systemic 

corticosteroid dose. If the followup systemic corticosteroid therapy is to be given once daily, one study indicates that it may be more clinically effective to give the dose in 

the afternoon at 3 p.m., with no increase in adrenal suppression.54

Systemic (Injected) Beta2-Agonists
Quick Reference 11

Summary of Control Measures for Environmental Factors

That Can Make Asthma Worse*

Figure

7

Allergens:

Reduce or eliminate exposure to the allergen(s) the patient is sensitive to, including:

• Animal dander: Remove animal from house, or, at a minimum, keep animal out of patient’s bedroom and seal or cover

with a filter the air ducts that lead to the bedroom.

• House-dust mites:

- Essential: Encase mattress in an allergen-impermeable cover; encase pillow in an allergen–impermeable cover or wash it 

weekly; wash sheets and blankets on the patient’s bed in hot water weekly (water temperature of >130 ̊F is necessary for 

killing mites).

- Desirable: Reduce indoor humidity to less than 50 percent; remove carpets from the bedroom; avoid sleeping or lying on 

upholstered furniture; remove carpets that are laid on concrete.

• Cockroaches: Use poison bait or traps to control. Do not leave food or garbage exposed.

• Pollens (from trees, grass, or weeds) and outdoor molds: To avoid exposure, adults should stay indoors—especially during

the afternoon—with the windows closed during the season in which they have problems with outdoor allergens.

• Indoor mold: Fix all leaks and eliminate water sources associated with mold growth; clean moldy surfaces. Consider 

reducing indoor humidity to less than 50 percent.

Tobacco Smoke:

Advise patients and others in the home who smoke to stop smoking or to smoke outside the home. Discuss ways to reduce

exposure to other sources of tobacco smoke, such as from daycare providers and the workplace.

Indoor/Outdoor Pollutants and Irritants:

Discuss ways to reduce exposures to the following:

• Wood-burning stoves or fireplaces

• Unvented stoves or heaters

• Other irritants (e.g., perfumes, cleaning agents, sprays)

*Adapted from EPR-2 1997.

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QUICK REFERENCE

U.S. DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

National Heart, Lung, and Blood Institute

NIH Publication No. 05-5246

Originally Printed March 2004

Revised January 2005

For more information, contact:

NHLBI Health Information Center

P.O. Box 30105

Bethesda, MD 20824-0105

Phone: 301-592-8573; fax: 301-592-8563; TTY: 240-629-3255

Web: http://www.nhlbi.nih.gov