Exhaled nitric oxide identifies the persistent eosinophilic phenotype in severe refractory asthma

Abstract

The fractional concentration of exhaled nitric oxide (FENO) is increased in asthma, correlates with eosinophilic inflammation, and decreases after steroid therapy. We sought to examine whether persistent eosinophilia would be accompanied by an increased FENO level despite steroid therapy in patients with severe refractory asthma (SRA) as manifestations of steroid resistance. Subjects with SRA, subjects with mild-moderate asthma, and healthy control subjects had FENO measured, followed by endobronchial biopsy and bronchoalveolar lavage. Tissue and bronchoalveolar lavage inflammatory cells were assessed for all subjects, and eosinophil status (EOS+/EOS-) was determined for subjects with SRA. Twenty-four subjects with SRA, 15 subjects with moderate-mild asthma, and 17 healthy control subjects were studied. Subjects with EOS+ SRA had significantly higher median FENO levels compared with levels in subjects with EOS- SRA (P = .0084) and all other groups. In subjects with SRA, FENO levels correlated with tissue eosinophils (r(s) = 0.54, P = .007), lymphocytes (r(s) = 0.40, P = .003), and mast cells (r(s) = 0.44, P = .05). FENO levels of greater than 72.9 ppb were associated with a sensitivity of 0.56 and a specificity of 1.0 for EOS+ status in subjects with SRA. FENO measurement identified the subgroup of subjects with SRA with persistent eosinophilia despite steroid therapy. Further studies are needed on the use of FENO to monitor response to therapy over time in subjects with SRA.