Determinants of increased exhaled nitric oxide in patients with suspected asthma

Abstract

Exhaled nitric oxide (FE NO) has been proposed as a marker of asthmatic inflammation, but it is unclear whether FE NO 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 FE NO in patients with suspected asthma, by means of multinomial logistic regression analysis. The FE NO 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 FE NO 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 FE NO (≥3 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 FE NO, but further analyses stratified by atopy showed significant associations between asthma and high FE NO both in atopic and nonatopic patients. We conclude that in patients with symptoms suggesting asthma, slightly elevated and high levels of FE NO are associated with sputum eosinophilia, whereas asthma is significantly associated only with high levels of FE NO, irrespective of atopy. The results suggest that FE NO is primarily a marker of airway eosinophilia, and that only high values of FE NO may be useful to identify patients with atopic or nonatopic asthma.