Extended Exhaled NO Measurement Differentiates between Alveolar and Bronchial Inflammation

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Abstract
Lower respiratory tract inflammation can be detected by measuring exhaled nitric oxide (NO) concentration at a single exhalation flow rate, but this does not differentiate between alveolar and bronchial NO production. We assessed alveolar NO concentration and bronchial NO flux with an extended method of measuring exhaled NO at several exhalation flow rates in 40 patients with asthma, 17 patients with alveolitis, and 57 healthy control subjects. Bronchial NO flux was higher in asthma (2.5 ± 0.3 nl/s, p < 0.001) than in alveolitis (0.7 ± 0.1 nl/s) and healthy control subjects (0.7 ± 0.1 nl/s). Alveolar NO concentration was higher in alveolitis (4.1 ± 0.3 ppb, p < 0.001) than in asthma (1.1 ± 0.2 ppb) and healthy control subjects (1.1 ± 0.1 ppb). In asthma, bronchial NO flux correlated with serum level of eosinophil protein X (EPX) (r = 0.60, p < 0.001) and bronchial hyperresponsiveness (r = 0.55, p < 0.001). In alveolitis, alveolar NO concentration correlated inversely with pulmonary diffusing capacity (r = − 0.55, p = 0.022) and pulmonary restriction. Glucocorticoid treatment or allergen avoidance normalized bronchial NO flux in asthma and decreased alveolar NO concentration toward normal in alveolitis. In conclusion, extended exhaled NO measurement can be used to separately assess alveolar and bronchial inflammation and to assess disease activity/severity in asthma and alveolitis.