Clinical and histological comparison of smoking and non-smoking patients with severe asthma in the U-BIOPRED cohort

Rationale: Smoking results in deteriorated clinical and inflammatory outcomes in severe asthma [Thomson et al; JACI 2013]. We aimed to compare clinical, inflammatory and histological characteristics between smoking and non-smoking severe asthma patients. Methods: This was a cross-sectional analysis of the U-BIOPRED adult severe asthma cohort. Clinical, sputum and endobronchial biopsy (immunohistochemistry) data were collected. Group comparisons were undertaken between smokers, ex-smokers and non-smokers and between (ex-)smokers and non-smokers with one-way ANOVA, independent T-test, Mann-Whitney U and Chi-square analyses. Results: Current smokers had significantly lower post-salbutamol FEV1/FVC %predicted (mean±SD; 75.8±13.2%) than ex-smokers and non-smokers (84.6±15.1 and 84.7±16.2; p=0.014 ). There was a significantly higher number of mast cells within the airway smooth muscle layer in (ex-)smokers compared with non-smokers (median(interquartile range); 18.4(9.6-35.8)cells/mm2 versus 10.3(3.0-14.2); p=0.044 ), in contrast to the mast cells in the epithelium and submucosa ( p=0.113 and p=0.787 ). The lamina reticularis was thicker in (ex-)smokers compared with non-smokers (9.7±2.0µm versus 8.5±1.4; p=0.006) and thicker in current smokers compared with ex-smokers and non-smokers (10.4±2.8µm versus 9.4±1.5 versus 8.6±1.4; p=0.010 ). Conclusion: Severe asthma patients who smoke have lower post-bronchodilator lung function than ex-smokers and non-smokers. Notably, smokers and ex-smokers also exhibit a greater number of mast cells within the airway smooth muscle layer and a thicker lamina reticularis suggesting more prominent airway remodeling by smoking in severe asthma.