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

Division of Pulmonary, Allergy, Critical Care and Sleep, University of Minnesota, USA. Minneapolis Veterans Affairs Medical Center, Pulmonary, 111N, One Veterans Drive, Minneapolis, MN 55417, kunis001{at}umn.edu

Kathryn L. Rice

Pulmonary Section, Minneapolis Veterans Affairs Medical Center, USA

Edward N. Janoff

Division of Infectious Diseases, Colorado Center for AIDS Research, University of Colorado Health Sciences Center, USA

Thomas S. Rector

Center for Chronic Disease Outcomes Research and Center for Epidemiological and Clinical Research, Minneapolis Veterans Affairs Medical Center, USA, Department of Medicine, University of Minnesota, USA

Dennis E. Niewoehner

Pulmonary Section, Minneapolis Veterans Affairs Medical Center, USA, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Minnesota, USA

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 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.

Conclusion: 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

Key Words: 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

Therapeutic Advances in Respiratory Disease, Vol. 2, No. 2, 55-64 (2008)
DOI: 10.1177/1753465808088902


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