Relationship of exhaled nitric oxide to asthma severity and phenotypes

Abstract

Rationale Exhaled nitric oxide (FE NO) is a non-invasive marker of airway inflammation in asthma and tracks with eosinophilic markers. FE NO has not been found to correlate with asthma severity as defined by the NHLBI (Sippel J.M. JACI, 106(4),645–50. 2000) though this did not include tissue assessment of airway inflammation. Methods Normal subjects (n=14) and subjects with asthma (n=31) of all severities (severe n=17), based on symptoms, lung function, and use of systemic steroids (Wenzel S, JACI 11(6),1345–52,2003) participated in asthma protocols that included questionnaires, lung function, blood draws, sputum induction and lung tissue and lavage analysis. Results were compiled in a large database and a retrospective analysis was performed. FE NO was measured according to the ATS at 50mL/s using an Ionics-Sievers NOA 280 (Boulder, CO). The correlations between FE NO and severity, inflammatory phenotype (eosinophil + or -) and other clinical features were examined. Results No correlation was found between asthma severity and FE NO (p=0.30). However, eosinophic positive severe asthmatics (Wenzel S, AJRCCM, 160(3), 1001–8, 1999) had higher levels of FE NO than eosinophil negative subjects (p=0.02). There was no association between FE NO and FEV I or FVC (p=0.49; p=0.40, respectively), atopy, intubations, hospitalizations, or symptom scores, potentially attributable to small sample size. Conclusion FE NO did not correlate with severity or other clinical features yet did identify the subgroup with severe eosinophil positive asthma. Further studies are needed to determine whether FE NO measurement can be used to monitor more severe asthmatics to guide therapy and to identify subjects with steroid resistance.