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


OBJECTIVE
To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.


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.


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 with asthma compared to never smokers with asthma.


CONCLUSIONS
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.
Respiratory Medicine, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom. mark.spears@glasgow.ac.uk
Mark
M
Spears
Charles
C
McSharry
Rekha
R
Chaudhuri
Christopher J
CJ
Weir
Carl
C
de Wet
Neil C
NC
Thomson
D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000097:blood*; D003907:Dexamethasone / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology; D016540:Smoking Cessation; D013183:Sputum / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003907:Dexamethasone