Small Airways Response to Bronchodilators in Adults with Asthma or COPD: A Systematic Review

Abstract

Background

Bronchodilator responsiveness (BDR) is commonly used in the diagnosis of lung disease. Although small airways dysfunction is a feature of asthma and COPD, physiological tests of small airways are not included in guidelines for BDR testing. This systematic review assessed the current evidence of BDR using small airways function in asthma and COPD.

Methods

The systematic review used standard methodology with the protocol prospectively registered on PROSPERO (CRD42020164140). Electronic medical databases (EMBASE and Medline) were searched using related keywords. Abstracts and full texts were screened independently by two reviewers. Studies that reported the change of physiological small airways function and FEV₁ were included in the review. The revised Cochrane risk of bias tool for RCT and NIH quality assessment tool for cohort and cross-sectional studies were used to evaluate the studies.

Results

A total of 934 articles were identified, with 12 meeting the inclusion criteria. Ten studies included asthma patients, 1 study included COPD patients and 1 study included both asthma and COPD. A total of 1104 participants were included, of whom 941 were asthmatic, 64 had COPD and 109 were healthy controls. Studies were heterogeneous in design including the device, dose and time intervals for BDR assessment. A small airway BDR was seen for most tests in asthma and COPD, including oscillometry (R5-20, reactance (X5), area of reactance (AX) and resonant frequency (Fres)) and Maximal Mid Expiratory Flow.

Conclusion

There is a measurable BDR in the small airways. However, with no consensus on how to assess BDR, studies were heterogeneous. Further research is needed to inform how BDR should be assessed, its clinical impact and place in routine clinical practice.

Keywords:

• asthma
• COPD
• bronchodilator
• reversibility
• small airways function

Abbreviations

COPD, chronic obstructive pulmonary disease; ATS, American Thoracic Society; ERS, European Thoracic Society; FVC, forced vital capacity; FEV₁, forced expiratory volume in the first second; MMEF, maximal mid-expiratory flow; SABA, short-acting beta2 agonists; BDR, bronchodilator response; pMDI, pressurized metered dose inhalers; SAMA, short-acting muscarinic antagonists; SAF, small airways function; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; FOT, forced oscillometry; IOS, impulse oscillometry; FEF_25-75, forced expiratory flow between 25% and 75% of FVC; FEF₅₀, forced expiratory flow at 50% of FVC; SBW, single breath washout; RCT, randomized controlled trials; GINA, Global Initiative of Asthma; GOLD, Global Initiative for Chronic Obstructive Lung Disease; SVN, small volume jet nebulizers; DPI, dry powder inhalers; SD, standard deviation; R5, resistance at 5Hz; R5-R20, the difference between R5 and R20; R20, resistance at 20Hz; X5, reactance at 5Hz; Fres, resonant frequency; AX, area of reactance; ARTP, Association for Respiratory Technology & Physiology.

Disclosure

Prof. Dr. Elizabeth Sapey reports grants from MRC, Wellcome Trust, HDRUK, British Lung Foundation, Alpha 1 Foundation, and NIHR, outside the submitted work. The authors report no other conflicts of interest in this work.