Subjects in a Population Study with High Levels of FENO Have Associated Eosinophil Airway Inflammation

Background. Measurement of fraction of exhaled nitric oxide (FENO) is a promising tool to increase validity in epidemiological studies of asthma. The association between airway inflammation and FENO has, however, only been examined in clinical settings and may be biased by selection of patients with asthma. Methods. In a population study with FENO registrations on 370 individuals, we identified nine subjects out of thirty subjects with high levels of FENO (>85th percentile, 30.3 ppb), irrespective of presence of respiratory symptoms, and 21 control subjects with FENO at median levels (11.1-16.4 ppb) willing to undergo bronchoscopy and bronchoalveolar lavage (BAL), all nonsmokers. FENO was measured in accordance with ATS criteria, and the examination also included spirometry, methacholine challenge test, and sampling of exhaled breath condensate (EBC). Results. Subjects with high FENO levels had significantly higher median the percentage of eosinophils in BAL than controls (2.1 versus 0.6, P < .006), and there was a significant association between FENO and the percentage of eosinophils in BAL (ρ=0.6, P < .002) and ECP in BAL (ρ=0.65, P < .05) examining the whole group, but no association with gender, FEV1, or degree of metacholine sensitivity or any of the biomarkers in EBC. All subjects with high FENO had respiratory symptoms, but only three had diagnosed asthma. There were a significant association between hydrogen peroxide in EBC and the percentage of neutrophils in bronchial wash. Conclusion. High FENO levels signal asthmatic or allergic respiratory disease in a population-based study. FENO levels are associated with degree of eosinophil airway inflammation as measured by the percentage of eosinophils and ECP in BAL.