Can measures of small airway dysfunction aid with the diagnosis or management of asthma exacerbations? A systematic review.

Background: Asthma exacerbations are acute episodes with worsened symptoms and decreased lung function. Current diagnosis relies on clinical assessment and spirometry, lacking a gold standard test. Interest in small airways tests suggests they may identify treatable traits. This review examines evidence for using small airways tests in diagnosing and managing exacerbations.

Methods: The protocol was prospectively registered on PROSPERO, and the systematic review followed standard methodology. Multiple electronic databases were searched, including MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCOhost) and Cochrane Central Register of Controlled Trials (Cochrane Library). The search strategy combined subject headings and keywords related to asthma exacerbations and small airway function tests. Observational studies and randomised controlled trials (RCTs) assessing these tests for detecting or monitoring exacerbations in adults (≥18 years) were included, without language or date restrictions. Risk of bias was evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias 2 tool for RCTs.

Results: Seven studies (six observational, one RCT) met the inclusion criteria. Five included forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), also referred to as maximal mid-expiratory flow; one used isolated forced expiratory flow measures (FEF25, FEF50 and FEF75); and one included multiple breath washout (MBW). No study specifically tested whether small airway function tests improved the diagnosis or monitoring of exacerbations. However, all showed worsening small airway measures during exacerbations, which improved on recovery. FEF25-75 showed greater percentage change than forced expiratory volume in one second postrecovery. The MBW study reported increased acinar ventilation heterogeneity (Sacin) and conductive ventilation heterogeneity (Scond), suggesting small airway involvement.

Conclusion: Conducting physiological tests for small airway function appears feasible during an exacerbation. These tests may have utility in the diagnosis or monitoring of acute asthma exacerbations. However, existing studies are heterogeneous and further research is needed.

Prospero Registration Number: CRD42024494994.