Last updated March 14, 2022

Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients


Hospitalized Adult and Pediatric Patients Without Cystic Fibrosis

  1. Recombinant human dornase alfa should not be used in adults and children with non-CF bronchiectasis.
  2. Routine use of bronchodilators to aid in secretion clearance is not recommended.
  3. Routine use of aerosolized N-acetylcysteine to improve airway clearance is not recommended.

Adult and Pediatric Patients With Neuromuscular Disease, Respiratory Muscle Weakness, or Impaired Cough

The use of aerosolized agents to change sputum physical properties or improve airway clearance cannot be recommended for patients with NMD or weakness due to insufficient evidence.

Postoperative Adult and Pediatric Patients

  1. Mucolytics cannot be recommended for use in the treatment of atelectasis due to insufficient evidence.
  2. Routine administration of bronchodilators to postoperative patients is not recommended.

Recommendation Grading



Effectiveness of Pharmacologic Airway Clearance Therapies in Hospitalized Patients

Authoring Organization

Publication Month/Year

December 1, 2015

Supplemental Implementation Tools

Decision Aid

Document Type


External Publication Status


Country of Publication


Document Objectives

The purpose of this guideline is to provide guidance to clinicians in the identification, selection, and delivery of medication for airway clearance. This guideline does not include the use of medication for patients with cystic fibrosis, as this has been addressed.

Target Patient Population

Patients require airway clearance therapy

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Older adult

Health Care Settings

Emergency care, Hospital


Assessment and screening, Management, Treatment

Diseases/Conditions (MeSH)

D006493 - Heparin, D058109 - Airway Management, D020545 - Respiratory Mucosa


airway restriction, difficult airway, airway management, mucolytics

Source Citation

Respir Care 2015;60(7):1071–1077


Number of Source Documents
Literature Search Start Date
January 1, 1966
Literature Search End Date
June 30, 2015
Description of External Review Process
Vanderbilt Evidence Practice Center SOP was followed.
Specialties Involved
Critical Care, Geriatric Medicine, Internal Medicine General, Pediatrics, Pulmonology
Description of Systematic Review
The AARC commissioned a systematic review, and AARC committee members participated in the review process. As a collaborative effort, the AARC team and the Vanderbilt Evidence-based Practice Center (EPC) developed the key questions and inclusion and exclusion criteria and engaged in identification and review of abstracts. AARC members involved in the work were paired with EPC staff to maintain rigor and protect against bias. This team previously reviewed the benefits and harmful effects of non-pharmacologic airway clearance techniques in hospitalized subjects. Similar to what was described in the nonpharmacologic airway clearance therapy clinical practice guideline, no high-level evidence was available. Because the recommendations are based on low-level evidence, the guideline developers did not use a formal guideline development process. Rather, the recommendations are based on a consensus of the committee, informed by a systematic review of the literature (see the "Supporting Documents" field) and clinical experience. The systematic review helped frame the issues and allowed the identification of potential harmful effects.
List of Questions
What disease/condition require airway clearance therapy?
Description of Study Criteria
Studies needed to include individuals over 1 year of age without cystic fibrosis who were receiving pharmacologic agents to promote airway clearance and who were either hospitalized (but not postoperative) or postoperative, had neuromuscular disease or respiratory muscle weakness, or had impaired cough (see Table 1 in the systematic review). The reviewers excluded studies of subjects with cystic fibrosis, as the Cystic Fibrosis Foundation recently published guidelines specifically related to airway clearance. Studies had to report on an agent of interest explicitly used to promote airway clearance and include a treatment group and an appropriate comparison group. Comparators included other pharmacologic airway clearance approaches, no airway clearance intervention, or placebo. The reviewers also required that the studies addressed one of the outcomes related to the effects of the drug on mucus clearance outlined in Table 1 in the systematic review. They included studies with any length of follow-up and in the hospital setting (i.e., not home or outpatient clinic-based).
Description of Search Strategy
The reviewers used the search strategies provided in the online appendix to retrieve relevant research on pharmacologic agents that promote mucus clearance. The primary literature search employed the MEDLINE (via the PubMed interface) and EM BASE databases. The search strategies used a combination of subject heading terms appropriate for each database and key words relevant to airway clearance and pharmacologic agents (e.g., sputum clearance, albuterol, anticholinergics). The reviewers limited searches to literature published in English since 1970 to ensure that older agents would be represented. The searches were last conducted in July 2014. The reviewers imported all citations into an electronic database and into the DistillerSR program (Evidence Partners, Ottawa, Ontario, Canada) for screening. They also manually searched the reference lists of included studies and of recent narrative and systematic reviews and meta-analyses addressing airway clearance in adults to locate citations of potential relevance.
Description of Study Selection
Once potential articles were identified, the reviewers examined the abstracts to determine whether the studies met the inclusion criteria. Two reviewers separately evaluated each abstract for inclusion or exclusion. If one reviewer concluded that the article could be eligible for the review based on the abstract, it was retained for full text assessment. Two reviewers independently assessed the full text of each included study using a standardized form with questions stemming from the inclusion/exclusion criteria. Disagreements between reviewers were resolved by a senior reviewer. The group of abstract and full text reviewers included expert clinicians and health services researchers, and it was required that studies be excluded by at least one clinician and one methodologist.
Description of Evidence Analysis Methods
The reviewers extracted data on study design, population characteristics (including age, underlying conditions, and need for mechanical ventilation), intervention characteristics (including type and duration of intervention and concomitant therapies), and key outcomes into evidence tables. In addition to outcomes related to intervention effectiveness, they extracted all data available on harmful effects of airway clearance agents. Harmful effects encompass the full range of specific negative effects, including the narrower definition of adverse events. The reviewers determined that the differences among populations, interventions, controls, and outcome measures rendered meta-analysis inappropriate. Thus, analysis remained qualitative. The reviewers assessed quality using separate tools as appropriate by study design. Tools included the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for cohort studies. They rated the quality for key outcomes for which data were provided; if a study noted, for example, that a given outcome was not significantly different between groups but did not provide the relevant data, they did not rate quality for that outcome. Two reviewers independently assessed quality for each study, with final decisions made via discussion to reach consensus or by third-party adjudication by a senior methodologist as needed. The reviewers used the parameters outlined in Table 2 in the systematic review to translate quality ratings into final levels (good, fair, poor). They considered that good studies could not have any criteria rated as high risk of bias. For studies with unclear ratings, they considered the likelihood that a factor would bias a given outcome and the importance of the limitation and downgraded the final level as appropriate. A total of 4,303 abstracts and 31 O full-text papers were reviewed, and 8 papers (comprising 9 unique studies) met inclusion criteria (see Fig. 1 in the systematic review for a flow chart). The 9 studies (reported in 8 publications) that met review criteria included 5 randomized controlled trials (RCTs), 3 crossover RCTs, and one retrospective cohort study.
Description of Evidence Grading
The reviewers used the parameters outlined in Table 2 of the systematic review (see the 'Supporting Documents" field) to translate quality ratings into final levels (good, fair, poor). They considered that good studies could not have any criteria rated as high risk of bias. For studies with unclear ratings, they considered the likelihood that a factor would bias a given outcome and the importance of the limitation and downgraded the final level as appropriate.
Description of Recommendation Grading
Description of Funding Source
AARC funded Clinical Document Development
Company/Author Disclosures
Dr. Rubin has disclosed relationships with GlaxoSmithKline, lnspiRx, Fisher & Paykel Healthcare, and Philips Respironics. Ms. O'Malley has disclosed a relationship with Pari Respiratory Equipment. The other authors have disclosed no conflicts of interest.
Percentage of Authors Reporting COI