Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma.

Introduction: Severe eosinophilic asthma is characterised by frequent exacerbations and a relative insensitivity to steroids. Experimentally, smoking may induce eosinophilic airway inflammation, but the impact in patients with severe asthma is not clear.
Objective: To investigate the association between smoking exposure in patients with severe asthma, and eosinophilic inflammation and activation, as well as airway autoimmunity and steroid responsiveness.
Methods: Patients with severe asthma according to European Respiratory Society/American Thoracic Society criteria were assessed with sputum samples, analysed by cell differential count, and for the presence of free eosinophil granules (FEGs), autoantibodies against eosinophil peroxidase (EPX) and macrophage receptor with collagenous structure (MARCO). A subgroup of patients with eosinophilic airway inflammation was re-assessed after a 2-week course of prednisolone.
Results: 132 severe asthmatics were included in the study. 39 (29.5%) patients had ≥10 pack-years of smoking history: 36 (27.3%) were former smokers and three (2.3%) current smokers; and 93 (70.5%) had <10 pack-years exposure. Eosinophilic airway inflammation was more prevalent among patients with ≥10 pack-years (66.7%), compared to patients with <10 pack-years (38.7%, p=0.03), as was the level of FEGs (p=0.001) and both anti-EPX and anti-MARCO (p<0.05 and p<0.0001, respectively). Omitting current smokers did not affect these associations. Furthermore, prednisolone reduced, but did not normalise, sputum eosinophils in patients with a ≥10 pack-year smoking history.
Conclusion: In patients with severe asthma, a former smoking history is associated with eosinophilic airway inflammation and activation and relative insensitivity to steroids, as well as airway autoimmunity.
Competing Interests: Conflict of interest: D.K. Klein declares no competing interests. A. Silberbrandt declares no competing interests. L. Frøssing declares payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from GlaxoSmithKline, in the 36 months prior to manuscript submission. M. Hvidtfeldt declares no competing interests. A. von Bülow declares grants from Novartis Healthcare, Denmark; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline and Novartis; and participation on a data safety monitoring board or advisory board for Novartis, all in the 36 months prior to manuscript submission. P. Nair reports grants and personal fees from AstraZeneca, grants from Novartis, grants and personal fees from Teva, grants from Sanofi, grants and personal fees from Roche, personal fees from Novartis, personal fees from Merck, personal fees from Equillium, grants from Foresee, outside the submitted work. M. Mukherjee reports grants from Canadian Institutes of Health Research, grants from Methapharm Specialty Pharmaceuticals, personal fees from AstraZeneca, personal fees from GlaxoSmithKline, outside the submitted work. C. Porsbjerg declares grants, consulting fees and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK, all in the 36 months prior to manuscript submission.
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