TY - JOUR
T1 - Increased sputum endotoxin levels are associated with an impaired lung function response to oral steroids in asthmatic patients
AU - Mcsharry, Charles
AU - Spears, Mark
AU - Chaudhuri, Rekha
AU - Cameron, Euan J.
AU - Husi, Holger
AU - Thomson, Neil C.
N1 - Funding Information:
Disclosure of potential conflict of interest: This study was funded by the Greater Glasgow Health Board (GEN13-10) . H. Husi has been employed by the University of Glasgow and the University of Edinburgh and has received or has grants pending from the European Union and the Wellcome Trust . The rest of the authors declare that they have no relevant conflicts of interest.
Funding Information:
Supported by the Greater Glasgow Health Board endowment (grant no. GEN13-10 ). M.S. was supported by the Chief Scientist Office (grant no. CAF/06/07 ).
Publisher Copyright:
© 2014 American Academy of Allergy, Asthma & Immunology.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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. Conclusion 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.
AB - 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. Conclusion 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.
KW - Asthma
KW - asthma control
KW - endotoxin
KW - oral steroids
KW - smokers
KW - sputum cytokines
UR - http://www.scopus.com/inward/record.url?scp=84913573359&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2014.08.022
DO - 10.1016/j.jaci.2014.08.022
M3 - Article
C2 - 25262463
AN - SCOPUS:84913573359
SN - 0091-6749
VL - 134
SP - 1068
EP - 1075
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 5
ER -