Title : Is Small Airway Dysfunction (SAD) common and an exacerbation risk biomarker in the well-controlled asthmatic?
Abstract:
Rationale and Aims of study: Recent surveys suggest that over 50% of adult asthmatics remain uncontrolled despite guideline-based standard therapy. As a potential cause SAD is often under-recognized as a major site of airway obstruction and inflammation related to the lack of assessment with current tools, like impulse oscillometry (IOS), thus under-treatment may explain inadequate control. The aims of our study were to investigate whether SAD is present in patients with well-controlled asthma, and, if so, whether SAD is a risk factor for future exacerbations in this phenotype.
Methods: This observational ATLANTIS study included 773 extensively characterized asthmatics, with SAD assessed by IOS at baseline and 90 controls, with exacerbations monitored longitudinally over a 12-month observation period. Well-controlled asthma was defined as an ACQ-6 score of < 0.75 at baseline, SAD was defined by R5-20 and/or AX by Z score values of +> 1.645 RSD, and/or X5 Z scores values of -<1.645 RSD.
Results: SAD was present in 30-40% of well-controlled patients with asthma. In the multivariate analysis, we found that R5-20 defined SAD was associated with increased risk of future exacerbations, independent of age, male sex, smoking habits, GINA Step 4-5, previous exacerbations, peripheral blood eosinophilia, and FEV1% predicted, with a hazard ratio of 2.31 (95% CI is 1.10-4.88), P = 0.028.
Conclusion: We have addressed an undervalued and frequently under-recognized treatable trait by showing that SAD is a common, sensitive, early independent biomarker for exacerbation risk in well-controlled asthma. Early risk recognition of this phenotype, and appropriate therapy with extrafine inhaled corticosteroids has the potential to prevent such asthma morbidities, and long term lung function loss.
