Determinants of increased exhaled nitric oxide in patients with suspected asthma

Exhaled nitric oxide (FENO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FENO in clinical use selects patients primarily according to their atopic or asthmatic status. The aim of this study was to investigate the determinants of increased FENO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FENO of 132 patients referred because of symptoms suggestive of asthma were studied, and the explanatory factors tested included atopy according to prick skin tests, clinical asthma according to lung function tests, sputum eosinophilia and bronchial hyperresponsiveness (BHR). Slightly elevated FENO levels were significantly explained only by sputum eosinophilia (OR: 3.7; 95% CI: 1.1-13.1; P = 0.04), but for high levels of FENO (greater than or equal to3 SD of predicted), clinical asthma (OR: 16.3; 95% CI: 5.4-49.7; P < 0.0001) and sputum eosinophilia (OR: 12.0; 95% CI: 4.1-35.0; P > 0.0001) were the characteristics with the highest prediction, followed by atopy and BHR. A significant interaction between asthma and atopy was observed relating to the effect on high FENO, but further analyses stratified by atopy showed significant associations between asthma and high FENO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FENO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FENO, irrespective of atopy. The results suggest that FENO is primarily a marker of airway eosinophilia, and that only high values of FENO may be useful to identify patients with atopic or nonatopic asthma.