Abstract
BackgroundA subset of severe asthma patients has fixed airways obstruction, which is characterized by incomplete reversibility to bronchodilator challenge. We aimed to elucidate the factors associated with fixed airways obstruction in a cohort of patients with severe asthma in Singapore.Methods245 patients from the Singapore General Hospital-Severe Asthma Phenotype Study (SGH-SAPS) were screened. These patients fulfilled World Health Organization criteria for "treatment-resistant severe asthma" and were all on combination of high-dose inhaled corticosteroids and long-acting beta2 agonists. 76 patients had pre- and postbronchodilator lung function tests and were selected for analysis. They were divided into two groups based on postbronchodilator (Post BD) forced expiratory volume in one second, PostBDFEV1 % predicted: ≥70% (Non-Fixed Obs) and < 70% (Fixed Obs). We compared clinical and demographic parameters between the two groups.ResultsPatients in the Fixed Obs group were more frequently past or current smokers and had a higher pack-year smoking history. Overall, pack-year smoking history had a modest negative correlation with PostBDFEV1 % predicted. Atopy, allergen sensitization (type and numbers), comorbidities, symptoms, health care utilization and medication use did not differ between the two groups. The prebronchodilator FEV1 % predicted, FEV1/FVC and FVC % predicted were significantly lower in the Fixed Obs group. In addition, prebronchodilator FVC % predicted accounted for more variability than FEV1/FVC in predicting PostBDFEV1% predicted.ConclusionSmoking is associated with fixed airways obstruction in patients with treatment-resistant severe asthma in Singapore. Furthermore, our results suggest that both small and large airways obstruction contribute independently to fixed airways obstruction in severe asthma.
Highlights
A subset of severe asthma patients has fixed airways obstruction, which is characterized by incomplete reversibility to bronchodilator challenge
Only 18% of our cohort of 245 patients had fixed airways obstruction and our smoking rates (22%) among the Fixed Obs and Non-Fixed Obs groups are lower than the two studies, yet we found a significant association between smoking and fixed airways obstruction
Asthma has traditionally been attributed to large airway pathology [41], but we found that forced vital capacity (FVC) accounted for more variability than Forced expiratory volume in one second (FEV1)/FVC in predicting postbronchodilator FEV1, suggesting that small airways disease is at least as important as large airways disease in contributing to fixed airways obstruction
Summary
A subset of severe asthma patients has fixed airways obstruction, which is characterized by incomplete reversibility to bronchodilator challenge. Studies in American [11], European [12,13,14,15], Canadian [16] and East Asian [17,18] cohorts have identified diverse but sometimes conflicting risk factors for fixed airways obstruction in asthma, including male sex, older age, longer duration of illness, smoking, eosinophilic airway inflammation, atopy and increased airway hyper-responsiveness. These inconsistent results could reflect differences in study methodologies, or the influence of gene-environment factors. This is the first report to characterize fixed airways obstruction among asthmatics in a Southeast Asian cohort
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