Fractional exhaled nitric oxide levels in asthma-COPD overlap syndrome: analysis of the National Health and Nutrition Examination Survey, 2007-2012

Purpose: Recent studies propose T(H)2-mediated inflammation in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS). However, little is known about whether fractional exhaled nitric oxide (FeNO) differs between patients with ACOS and those with COPD alone. To address this knowledge gap, a nationally representative sample was analyzed to determine the difference in FeNO levels between patients with ACOS and those with COPD alone in the US population. Patients and methods: This is a cross-sectional analysis of the National Health and Nutrition Examination Survey from 2007 through 2012. All subjects aged >= 40 years with COPD were identified. ACOS was defined as self-reported wheezing in past 12 months plus bronchodilator response (forced expiratory volume increase of >200 mL and >12%) or self-reported physician diagnosis of asthma. Results: A total of 197 subjects with COPD were identified in the National Health and Nutrition Examination Survey. Of these, 23% met the criteria of ACOS. The FeNO level was higher in subjects with ACOS compared with those with COPD alone in both unadjusted (mean 21.2 ppb vs 13.0 ppb; difference, 8.2 [95% CI, 0.2 to 16.2]; P=0.045) and adjusted (difference, 8.2 [95% CI, 0.9 to 15.5]; P=0.03) analyses. Although there was no significant difference among current smokers, the FeNO level was significantly higher in non-current smokers with ACOS than nonsmokers with COPD alone (mean 31.9 ppb vs 20.3 ppb; adjusted difference, 20.5 [95% CI, 4.4 to 36.6]; P=0.02). In a sensitivity analysis using an alternative definition of ACOS, the results did not change materially. The diagnostic value of FeNO to discriminate ACOS from COPD alone was not sufficient, with the area under the curve of 0.63 (95% CI, 0.54 to 0.72). Conclusion: By using nationally representative US data, it was found that 23% of COPD subjects met the ACOS criteria and also that the FeNO level was higher in subjects with ACOS compared with those with COPD alone, particularly in non-current smokers.