TY - JOUR

T1 - Impact of former smoking exposure on airway eosinophilic activation and autoimmunity in patients with severe asthma

AU - Klein, Ditte K

AU - Silberbrandt, Alexander

AU - Frøssing, Laurits

AU - Hvidtfeldt, Morten

AU - von Bülow, Anna

AU - Nair, Parameswaran

AU - Mukherjee, Manali

AU - Porsbjerg, Celeste

N1 - Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Asthma

KW - Autoantibodies

KW - Autoimmunity

KW - Eosinophil Peroxidase

KW - Eosinophils

KW - Humans

KW - Inflammation

KW - Leukocyte Count

KW - Prednisolone

KW - Pulmonary Eosinophilia

KW - Smoking/adverse effects

KW - Sputum

U2 - 10.1183/13993003.02446-2021

DO - 10.1183/13993003.02446-2021

M3 - Journal article

C2 - 35236724

VL - 60

JO - The European respiratory journal

JF - The European respiratory journal

SN - 0903-1936

IS - 4

M1 - 2102446

ER -