Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: a prospective study.
BACKGROUND
A subset of patients with chronic obstructive pulmonary disease (COPD) may respond more favorably to inhaled corticosteroids (ICS), but no simple method is currently utilized to predict the presence or absence of ICS responses in patients with COPD.We evaluated the ability of exhaled nitric oxide (FENO) and serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and interleukin-8 [IL-8]) to independently predict spirometric responses to ICS in patients with COPD.


METHODS
Among 60 ex-smokers with severe COPD (mean FEV1 1.07 L, 36% of predicted), we conducted a single-arm, open-label study. Participants spent four weeks free of any ICS, followed by four weeks of ICS use (fluticasone propionate 500 mcg twice daily). FENO, CRP, IL-6, IL-8, and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use.


RESULTS
Baseline FENO, CRP, IL-6, and IL-8 showed no correlations to FEV1 responses to ICS. ICS responders (increase in FEV1 > or = 200 mL after four weeks of ICS) did have significantly higher baseline FENO levels compared with non-responders (46.5 parts per billion [ppb] vs. 25 ppb, p = 0.028). The receiver operating characteristic curve for FENO to discriminate responders from non-responders had an area under curve of 0.72. Baseline serum inflammatory markers did not differ between responders and non-responders.


CONCLUSIONS
In ex-smokers with severe COPD, a measure of local pulmonary inflammation, FENO, may be more closely associated with FEV1 responses to four weeks of ICS than are standard markers of systemic inflammation, serum CRP, IL-6, and IL-8.
Kunisaki
Ken M
KM
Division of Pulmonary, Allergy, Critical Care and Sleep, University of Minnesota, USA. kunis001@umn.edu
Rice
Kathryn L
KL
Janoff
Edward N
EN
Rector
Thomas S
TS
Niewoehner
Dennis E
DE
D000280:Administration, Inhalation; D000368:Aged; D000420:Albuterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D000730:Androstadienes / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D000068298:Fluticasone; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012372:ROC Curve; D000068299:Salmeterol Xinafoate; D012720:Severity of Illness Index; D013147:Spirometry
D000730:Androstadienes; D015415:Biomarkers; D001993:Bronchodilator Agents; D015850:Interleukin-6; D016209:Interleukin-8; D009569:Nitric Oxide; D000068299:Salmeterol Xinafoate; D002097:C-Reactive Protein; D000068298:Fluticasone; D000420:Albuterol