Predicting corticosteroid response in chronic obstructive pulmonary disease using exhaled nitric oxide.
BACKGROUND
Predicting corticosteroid response in COPD is important but difficult. Response is more likely to occur in association with eosinophilic airway inflammation, for which the fraction of exhaled nitric oxide (Fe(NO)) is a good surrogate marker.


OBJECTIVE
We aimed to establish whether Fe(NO) levels would predict the clinical response to oral corticosteroid in COPD.


METHODS
We performed a double-blind, crossover trial of steroid in patients with COPD. After a 4-week washout of inhaled steroids, patients received prednisone 30 mg/d or matching placebo, in random order, with an intervening 4-week washout. The predictive values of Fe(NO) for clinically significant changes in 6-minute-walk distance (6MWD), spirometry (FEV(1)), and St. George's Respiratory Questionnaire (SGRQ) were calculated.


RESULTS
A total of 65 patients (mean FEV(1) = 57% predicted) were randomized. With prednisone, there was a net increase of 13 m in 6MWD (P = 0.02) and 0.06 L in postbronchodilator FEV(1) (P = 0.02) compared with placebo. The change in SGRQ was not significant. Using receiver operator characteristic analysis, the area under the curve for an increase of 0.2 L in FEV(1) was 0.69 (P = 0.04) with an optimum Fe(NO) cut-point of 50 ppb. The positive and negative predictive values were 67 and 82%, respectively. FE(NO) was not a significant predictor for changes in 6MWD or SGRQ.


CONCLUSIONS
Fe(NO) is a weak predictor of short-term response to oral corticosteroid in COPD, its usefulness being limited to predicting increase in FEV(1). Clinical trial registered with www.anzctr.org.au (ACTRN12605000683639).
Dummer
Jack F
JF
Dunedin and Christchurch Schools of Medicine, University of Otago, Dunedin, New Zealand.
Epton
Michael J
MJ
Cowan
Jan O
JO
Cook
Julie M
JM
Condliffe
Robin
R
Landhuis
C Erik
CE
Smith
Andrew D
AD
Taylor
D Robin
DR
D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000378:metabolism / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D017079:Exercise Tolerance / Q000187:drug effects; D045853:Exhalation; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D011237:Predictive Value of Tests; D011241:Prednisone / Q000378:metabolism / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D011788:Quality of Life; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D016138:Walking
D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D009569:Nitric Oxide; D011241:Prednisone