BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) have been detected in inflammatory lung diseases including asthma and have been attributed to increased expression and activity of inducible nitric oxide synthase (iNOS) within the airways. However, previous studies of exhaled NO in patients with bronchiectasis have yielded conflicting results, with reports of both increased and normal NO values. Recent evidence from animal models suggests that chronic airway infection reduces NO production within the lung, despite causing increased iNOS expression. We tested the hypothesis that, in human subjects with bronchiectasis, chronic airway infection reduces NO output from the conducting airways. METHODS: Using a recently described two-compartment model, we measured separately the contributions of the conducting airways and the alveoli to exhaled NO in nine patients with stable bronchiectasis and eight control subjects before and after inhaled glucocorticoid therapy. RESULTS: We found that airway NO output was significantly lower in bronchiectasis than in normal airways whereas NO output from the alveoli was similar to that of control subjects. High-dose inhaled glucocorticoid therapy did not alter airway or alveolar NO production. CONCLUSIONS: These findings demonstrate that, in patients with bronchiectasis, airway NO output is reduced and that iNOS does not contribute significantly to airway NO production.
BACKGROUND: Increased concentrations of exhaled nitric oxide (NO) have been detected in inflammatory lung diseases including asthma and have been attributed to increased expression and activity of inducible nitric oxide synthase (iNOS) within the airways. However, previous studies of exhaled NO in patients with bronchiectasis have yielded conflicting results, with reports of both increased and normal NO values. Recent evidence from animal models suggests that chronic airway infection reduces NO production within the lung, despite causing increased iNOS expression. We tested the hypothesis that, in human subjects with bronchiectasis, chronic airway infection reduces NO output from the conducting airways. METHODS: Using a recently described two-compartment model, we measured separately the contributions of the conducting airways and the alveoli to exhaled NO in nine patients with stable bronchiectasis and eight control subjects before and after inhaled glucocorticoid therapy. RESULTS: We found that airway NO output was significantly lower in bronchiectasis than in normal airways whereas NO output from the alveoli was similar to that of control subjects. High-dose inhaled glucocorticoid therapy did not alter airway or alveolar NO production. CONCLUSIONS: These findings demonstrate that, in patients with bronchiectasis, airway NO output is reduced and that iNOS does not contribute significantly to airway NO production.