Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study

Spears, M., McSharry, C., Chaudhuri, R. , Weir, C.J., de Wet, C. and Thomson, N.C. (2013) Smoking in asthma is associated with elevated levels of corticosteroid resistant sputum cytokines—an exploratory study. PLoS ONE, 8(8), e71460. (doi: 10.1371/journal.pone.0071460) (PMID:23951170) (PMCID:PMC3739804)

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<p>Background: Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.</p> <p>Objectives: To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.</p> <p>Methods: Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.</p> <p>Results: Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers wi</p> <p>Conclusion: Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.</p>

Item Type:Articles
Glasgow Author(s) Enlighten ID:Thomson, Professor Neil and Weir, Christopher and Spears, Dr Mark and Chaudhuri, Dr Rekha and McSharry, Dr Charles
Authors: Spears, M., McSharry, C., Chaudhuri, R., Weir, C.J., de Wet, C., and Thomson, N.C.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:PLoS ONE
Publisher:Public Library of Science
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in PLoS ONE 8(8):e71460
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
441801Mechanisms and treatment of relative corticosteroid resistance in smokers with asthmaMark SpearsScottish Executive Health Department (SEHHD-CSO)CAF/06/07III -IMMUNOLOGY