Exhaled nitric oxide, systemic inflammation, and the spirometric response to inhaled fluticasone propionate in severe chronic obstructive pulmonary disease: A prospective study

Abstract

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 (F E NO) and serum inflammatory markers (C-reactive protein [CRP], interleukin-6 [IL-6], and interleukin-8 ) to independently predict spirometric responses to ICS in patients with COPD. Methods: Among 60 ex-smokers with severe COPD (mean FEV 1 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). F E NO, CRP, IL-6, IL-8, and pre-bronchodilator spirometry were measured immediately before and after the four weeks of ICS use. Results: Baseline F E NO, CRP, IL-6, and IL-8 showed no correlations to FEV 1 responses to ICS. ICS responders (increase in FEV 1 ≥ 200 mL after four weeks of ICS) did have significantly higher baseline F E NO levels compared with non-responders (46.5 parts per billion [ppb] vs. 25 ppb, p = 0.028). The receiver operating characteristic curve for F E NO 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. Conclusion:In ex-smokers with severe COPD, a measure of local pulmonary inflammation, F E NO, may be more closely associated with FEV 1 responses to four weeks of ICS than are standard markers of systemic inflammation, serum CRP, IL-6, and IL-8 Keywords: Androstadienes / tu (therapeutic use), anti-inflammatory agents / tu (therapeutic use), breath tests, C-reactive protein, inflammation / bl (blood), interleukin-6 / bl (blood), interleukin-8 / bl (blood), nitric oxide / du (diagnostic use), pulmonary disease, chronic obstructive Abbreviations ATS = American Thoracic Society AUC = area under curve COPD = chronic obstructive pulmonary disease CRP = C-reactive protein F E NO = fraction of exhaled nitric oxide FEV 1 = forced expiratory volume in one second FVC = forced vital capacity ICS = inhaled corticosteroid IL-6 = interleukin-6 IL-8 = interluekin-8 IQR = interquartile range ppb = parts per billion

Characterization of airway inflammation in patients with COPD using fractional exhaled nitric oxide levels: a pilot study

“…Antus et al reported that in 58 COPD patients with acute exacerbation, patients with increased FeNO at the time of exacerbation responded better to treatment with corticosteroids and bronchodilators 15. Similarly, after 4 weeks of treatment with ICS in a study of 60 ex-smokers with severe COPD, ICS responders had significantly higher baseline FeNO levels compared with non-responders 16. Akamatsu et al studied 14 patients with COPD and found that FeNO >35 ppb and evidence of atopy predicted improvement in FEV 1 with ICS/LABA when added to tiotropium 17.…”

“…A reduction in eosinophilic airway inflammation has also been shown to reduce the number of future COPD exacerbations 2. Other investigators have determined that FeNO levels may be predictive of greater treatment response to corticosteroids and bronchodilator therapy 15,16. Antus et al reported that in 58 COPD patients with acute exacerbation, patients with increased FeNO at the time of exacerbation responded better to treatment with corticosteroids and bronchodilators 15.…”

The recent advances of phenotypes in acute exacerbations of COPD

“…Currently, FeNO is regarded as the most promising indicator 39. Some studies have reported that patients with high FeNO levels will have a good response to corticosteroids and greater improvement in FEV 1 39,40. The reason for this result may be due to the fact that the FeNO level correlated well with the eosinophils, which is a good predictor for the response to corticosteroids 41,42.…”

Exhaled nitric oxide in diagnosis and management of respiratory diseases

“…[79] FENO may have a role in the monitoring of anti-inflammatory therapy of COPD and can be used to identify patients who may respond to steroids. Clearly, further studies are needed in this area.…”