Small airway disease is longitudinally linked with asthma control, such that measurement of small airway disease by impulse oscillometry can help clinicians to assess patients’ asthma exacerbation risk. These were among study findings recently published in The Lancet Respiratory Medicine.

Although small airway disease is reported among a large proportion of patients with asthma across the spectrum of severity, with a higher prevalence in those with severe asthma, the association between small airway disease and asthma outcomes has yet to be clarified. To address this, investigators conducted a noninterventional, longitudinal analysis of patients with mild, moderate, or severe stable asthma in the Assessment of Small Airways Involvement in Asthma (ATLANTIS) trial ( Identifier: NCT02123667).

This observational prospective cohort study sought to determine which small airway parameters were most strongly associated with control of asthma, exacerbations of asthma, and quality of life (QoL). Asthma control was established via use of Asthma Control Test (ACT) and Asthma Control Questionnaire 6 (ACQ-6) scores. An asthma exacerbation was defined as a substantial deterioration of asthma signaled by at least 1 of the following: (1) need for a systemic corticosteroid course (for ≥3 days); (2) hospitalization for asthma; and (3) emergency department or urgent care presentation for asthma. QoL was determined via use of the European Quality of Life (EuroQoL 5D-5L) score.

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Patients in the study were recruited via medical databases and advertisements in 9 countries across the globe between June 30, 2014, and March 3, 2017. All individuals eligible to participate needed to have a clinical diagnosis of asthma for at least 6 months and were aged 18 to 65 years.

The participants were followed for up to 1 year, with visits taking place at baseline, at 6 months, and at 12 months. Physiologic tests were administered to the participants, including spirometry, lung volumes, multiple breath nitrogen washout (MBNW), impulse oscillometry, and percent decrease in forced vital capacity (FVC) during methacholine challenge. For the purpose of evaluating small airway disease, computed tomography (CT) densitometry was performed.

A total of 773 participants were included in the longitudinal study. The median patient age was 46 years (range: 34 to 54 years). A total of 99 individuals without airway obstruction served as controls. Overall, 58% of the participants were female. Per univariate analysis, lung volumes, impulse oscillometry, MBNW, and forced expiratory flow at 25% to 75% of FVC were significantly associated with asthma control and asthma exacerbations (P <.0001 for all).

Per multivariate analysis, the ordinal score — a composite of impulse oscillometry biomarkers — independently predicted asthma control and asthma exacerbations in a model with other known predictors, including Global Initiative for Asthma (GINA) severity score, history of prior exacerbations, forced expiratory volume in 1 second (FEV1), and blood eosinophils. When the ordinal score was added to the model, however, the contribution of FEV1 was no longer significant.

 A major limitation of the current study is the low prevalence of exacerbations, since this cohort was not enriched for exacerbations. Therefore, the role played by small airway disease in a cohort with a higher prevalence of exacerbations might be the topic of a future study. 

The researchers concluded that for optimal care of patients with asthma, small airway function should be evaluated, along with large airway function and biomarkers as part of asthma phenotyping. This will aid in an improved understanding of the risk for poor asthma outcomes among individual patients.

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Kraft M, Richardson M, Hallmark B, et al; ATLANTIS study group. The role of small airway dysfunction in asthma control and exacerbations: a longitudinal, observational analysis using data from the ATLANTIS study. Lancet Respir Med. Published online March 2, 2022. doi:10.1016/S2213-2600(21)00536-1

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