title: Increased sputum endotoxin levels are associated with an impaired lung function response to oral steroids in asthmatic patients.
abstract: BACKGROUND
  Airway endotoxin might contribute to corticosteroid insensitivity in asthmatic patients.
  
  
  OBJECTIVE
  Because cigarette smoke contains endotoxin, we tested the hypothesis that sputum endotoxin concentrations are increased in cigarette smokers and that endotoxin concentrations are associated with corticosteroid insensitivity in asthmatic patients.
  
  
  METHODS
  Sixty-nine asthmatic patients (never smokers, smokers, and exsmokers) and 20 healthy subjects (never smokers and smokers) were recruited. Fifty-three asthmatic patients received a 2-week course of oral dexamethasone. Serum and induced sputum endotoxin and cytokine concentrations were quantified by using an enzyme immunoassay.
  
  
  RESULTS
  Median (interquartile range [IQR]) sputum endotoxin concentration were not significantly different between asthmatic never smokers (184 endotoxin units [EU]/mL; IQR, 91-310 EU/mL), exsmokers (123 EU/mL; IQR, 39-207 EU/mL), and smokers (177 EU/mL; IQR, 41-772 EU/mL; P = .703) and healthy subjects (164 EU/mL; IQR, 106-373 EU/mL). The lung function response to oral corticosteroids decreased with increasing sputum endotoxin concentrations in the never smokers (linear regression α = .05, Spearman r = -0.503, P = .009) but not in smokers (α = .587, r = -0.282, P = .257), as confirmed by using multiple regression analysis. Asthmatic smokers had higher concentrations of serum endotoxin than asthmatic nonsmokers (0.25 EU/mL [IQR, 0.09-0.39 EU/mL] vs 0.08 EU/mL [IQR, 0.05-0.19 EU/mL], P = .042) unrelated to steroid insensitivity or serum cytokine concentrations. In the asthmatic group sputum endotoxin concentrations correlated with sputum IL-1 receptor antagonist concentrations (r = 0.510, P < .001), and serum endotoxin concentrations significantly correlated with sputum IL-6, IL-8, and chemokine motif ligand 2 concentrations.
  
  
  CONCLUSIONS
  Asthmatic smokers have similar sputum endotoxin concentrations compared with those of asthmatic never smokers. The association between higher sputum endotoxin levels and an impaired lung function response to oral corticosteroids, particularly in asthmatic never smokers, suggests that airway endotoxin might contribute to corticosteroid insensitivity in asthmatic patients.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom. Electronic address: charles.mcsharry@glasgow.ac.uk.
authors.forename: Charles
authors.initials: C
authors.lastname: McSharry
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Spears
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Rekha
authors.initials: R
authors.lastname: Chaudhuri
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Euan J
authors.initials: EJ
authors.lastname: Cameron
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Holger
authors.initials: H
authors.lastname: Husi
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Neil C
authors.initials: NC
authors.lastname: Thomson
mesh_terms: D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism*; D004731:Endotoxins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects*; D013183:Sputum / Q000378:metabolism*
chemical_list: D000305:Adrenal Cortex Hormones; D016207:Cytokines; D004731:Endotoxins
keywords: Asthma; asthma control; endotoxin; oral steroids; smokers; sputum cytokines