Nebulized Hypertonic Saline for Inpatient Use in Chronic Obstructive Pulmonary Disease
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Sponsor: OhioHealth

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Nebulized Hypertonic Saline for Inpatient Use in Chronic Obstructive 
Pulmonary Disease 
 
Kruti Patel, D.O., Jeffrey Kaufman, D.O.  
 
 
Introduction 
Chronic obstructive pulmonary disease (COPD) continues to be a significant contributor to 
morbidity and mortality with significant resources allocated for inpatient COPD 
exacerbations1,2,3,4, defined on clinical symptoms of increased cough from baseline, a change in 
sputum characteristics from baseline (color, consistency, volume), or increase in the patient’s 
dyspnea from baseline5,6,7.  Current guidelines for treating exacerbations of COPD utilize 
steroids for reducing inflammation, supplemental oxygen for hypoxemia, antibiotics if suspicion 
is for a bacterial cause of the exacerbation, and bronchodilators for symptom control and 
improving airflow per the guidelines published by the Global Initiative for Chronic Obstructive 
Lung Disease8.  Additionally, counseling on cessation of cigarette smoking should be given to 
those still smoking.  Supportive therapy with mechanical ventilation (invasive or non-invasive) 
may be necessary as well as fluid balance management, nutrition, and vaccinations as 
appropriate for Pneumococcal pneumonia and seasonal influenza.  Symptomatic treatment may 
include pulmonary hygiene with chest physiotherapy such as by a respiratory 
therapist/percussion vest/Acapella or flutter valve device, and mucolytics such as guaifenesin or 
N-acetylcysteine (NAC) (as mucolytic or antioxidant)8.   
Although mucolytic therapy is mainly symptomatic and long-term studies are not definitive, 
some patients may have benefit9,10,11,12,13.  Additionally, NAC may have benefit in COPD 
exacerbations14,15,16,17.  However, with the recent drug shortages, NAC is not readily available in 
many hospitals.  With difficulty in obtaining a potentially beneficial medication and with 
significant costs, it is beneficial to explore other possibilities that may deliver equal or better 
options.   
Nebulized hypertonic (3%) saline has been used for sputum induction and as a mucolytic, mainly 
in pediatric populations with bronchiolitis, and in cystic fibrosis patients with 
bronchiectasis18,19,20.  Potential benefits of nebulized hypertonic saline include its availability and 
its costs.  Its packaging includes both individual respules for nebulization and bulk solutions.   
 
 
 

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Methods 
Study Population: 
This study will involve 146 patients admitted to Doctors Hospital in Columbus, Ohio from 
September 2014 through September 2015 with a clinical diagnosis of an acute exacerbation of 
COPD, defined as an increase in the patient’s dyspnea, cough, or change in sputum 
consistency/volume/color from the patient’s baseline during stable conditions. To achieve 80% 
power to detect a clinically significant difference between study groups, a minimum sample size 
of 130 patients (65 in each study group) is necessary.  To account for issues such as patient study 
withdrawal and protocol deviations, a sample size of 146 patients (73 per study group) is ideal. 
 Inclusion Criteria: 
 Patients at least 18 years of age 
 Admitted to Doctors Hospital with a clinical diagnosis of COPD within 24 hours. 
Exclusion Criteria:  
 Patients younger than 18 years of age 
 History of smoking less than twenty pack-years 
 Possibility of other primary cause of the patient’s change in dyspnea or cough (e.g. 
pneumonia, congestive heart failure with pulmonary edema, myocardial infarction) 
 Patient is found  to have a different primary cause after initial enrollment 
 Patients admitted over 24 hours prior to contact by study staff/investigator 
 Non-English speaking subjects  
Hypothesis: 
A clinically significant difference exists between albuterol treatments with nebulized 3% saline 
versus standard saline, for improvements in the patient’s modified Borg dyspnea score during an 
acute exacerbation of COPD. 
Study Design: 
This randomized, single-blind, prospective study will involve 146 patients admitted to Doctors 
Hospital with a clinical diagnosis of an acute exacerbation of COPD. Patients will be randomly 
assigned to 2.5 mg albuterol treatments with either normal saline, as is the standard, or 
hypertonic saline. The Doctors Hospital biostatistician will create a randomization plan that will 
be kept with the consent forms. The investigator or study staff will maintain the list and 
determine the study treatment by subject number.  

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 Once the patient has been identified by the inclusion/exclusion criteria, they will be approached 
by a study staff member and informed of the opportunity to participate in the study. The study 
staff will then provide a detailed explanation of the study and obtain patient consent. 
Once the patient is enrolled, they will receive the 2.5mg  albuterol treatment, and saline solution 
as determined by the randomization plan (Group 1 will receive 0.9% saline and Group 2 will 
receive 3% saline), every six hours for at least the first 24 hours, with allowance for PRN (pro re 
nata= as needed) use every four hours by patient request. The nebulized saline will be kept in the 
pharmacy and will be ordered in the same way as the standard saline. The patient’s dyspnea will 
be evaluated prior to starting the treatment and after the intervention period is completed using 
the Modified Borg Dyspnea Scale21.  The scale will be administered by either the investigator or 
study staff.   
Participation in the study will be complete once the patient is discharged from the hospital. All 
patients will be recommended to have spirometry or full pulmonary function testing as an 
outpatient once stable, if not already obtained.   
Data Storage and Confidentiality  
 
Only de-identified or non-identifiable data will be reported in the study.  Only the research 
investigators and study staff will have access to patient information.  All resulting data will be 
stored in electronic format; files will be stored on a password-protected computer and stored in a 
secured facility with limited access.  Participants will not be excluded on socioeconomic, racial 
or religious identity.  No form of deception will be used.  The data collection and storage 
processes will follow HIPAA guidelines, in accordance with 21 CFR 46.115 (b); to protect both 
confidentiality and privacy of each participant.  All PHI data will be erased or destroyed per 
institution protocol. 
Study Variables: 
 The data to be collected from this study will include:  
 Demographic (age, sex) 
 Treatment group (normal saline/hypertonic saline) 
 Modified Borg Scale Score (pre and post treatment) 
 prn albuterol use  
 30 day readmission 
 30 day all cause mortality 
 Spirometry data within 30 days 
Statistical Analysis: 
 

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We will test the hypothesis that a clinically significant difference in dyspnea scores exists 
between patients who receive hypertonic saline and those who do not.  Descriptive statistics will 
be produced, using means, medians, ranges and standard deviations for continuous variables, and 
percentages for categorical variables.  Independent variables will include modified Borg scores, 
30-day mortality and length of hospital stay.  Inferential statistics will determine statistically 
significant differences between comparison variables, using paired sample t-tests or the 
Wilcoxon signed rank test.  Statistical significance will be evaluated at the 5% (α=0.05) level.  
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