Peripheral inflammation in patients with asthmatic symptoms but normal lung function

Some patients with asthmatic symptoms and eosinophilic airway inflammation have normal lung function and thus do not meet the current diagnostic criteria of asthma. Exhaled nitric oxide (NO) measurement at multiple exhalation flow rates can be used to assess alveolar and bronchial NO output and inflammation. We tested whether alveolar or bronchial NO output is increased in subjects having asthmatic symptoms but normal lung function. Exhaled NO concentration was measured at three exhalation flow rates (100, 175, and 370 mL/s) to assess alveolar NO concentration and bronchial NO flux in 23 patients with asthmatic symptoms but normal lung function ("asthmatic symptoms group"), 40 patients with asthma, and 40 healthy control subjects. The asthmatic symptoms group had increased bronchial NO flux (1.7 +/- 0.3 nL/s, p = 0.016) and alveolar NO concentration (1.8 +/- 0.2 parts per billiant (ppb), p = 0.010) compared with healthy controls (0.7 +/- 0.1 nL/s and 1.0 +/- 0.1 ppb, respectively). Patients with asthma had even higher bronchial NO flux (2.5 0.3 nL/s, p = 0.024) but normal alveolar NO concentration (1.1 +/- 0.2 ppb, p = 0.664). In asthmatic symptoms group, alveolar NO concentration correlated positively with blood eosinophil count and negatively with small airway function (FEF 50% and FEF 75% ). In conclusion, patients with asthmatic symptoms but normal lung function have increased alveolar NO concentration and mildly elevated bronchial NO flux suggesting a more peripheral inflammation than in patients with asthma.