Airway nitric oxide output is reduced in bronchiectasis.

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.

Hypercapnic acidosis does not modulate the severity of bacterial pneumonia-induced lung injury.

OBJECTIVE: Deliberate induction of hypercapnic acidosis protects against lung injury after ischemia-reperfusion, endotoxin-induced, and ventilation-induced lung injury. The efficacy of hypercapnic acidosis in bacterial lung infection, a common cause of acute respiratory distress syndrome, is not known. Furthermore, its effect may differ depending on the presence or absence of antibiotic therapy. We investigated whether hypercapnic acidosis-induced by adding CO2 to inspired gas-would protect against acute lung injury induced by pulmonary Escherichia coli instillation in an in vivo model in the presence and absence of effective antibiotic therapy. DESIGN: Prospective randomized animal study. SETTING: University research laboratory. SUBJECTS: Adult male Wistar-Kyoto rats. INTERVENTIONS: The animals were anesthetized and ventilated. In series 1, rats were administered intravenous ceftriaxone (100 mg x kg) and randomized to normocapnia (Normocapnia-ABx; Fico2 0.00, n = 10) or hypercapnia (Hypercapnia-ABx; Fico2 0.05, n = 10) groups. E. coli (8.4 x 10 colony forming units) was instilled intratracheally. Series 2 animals did not receive antibiotics. They were randomized to normocapnia (Normocapnia, n = 10) or hypercapnia (Hypercapnia, n = 10) groups, and intratracheal E. coli was administered. All animals were ventilated for 6 hrs. MEASUREMENTS AND MAIN RESULTS: In series 1, there were no differences between Hypercapnia-ABx and Normocapnia-ABx groups with regard to: (a-a)o2 gradient (mean +/- sem; 215 +/- 13 vs. 252 +/- 22 mm Hg), Pao2, bronchoalveolar lavage neutrophil count, static lung compliance, or histologic injury. Lung bacterial yield was not different between the groups. In series 2, in the absence of antibiotic therapy, there were no differences between Hypercapnia and Normocapnia groups in: (a-a)o2 gradient (mean +/- sem, 345 +/- 25 vs. 332 +/- 23 mm Hg), systemic Pao2, bronchoalveolar lavage neutrophil count, or static lung compliance. Lung bacterial yield was not altered by hypercapnia in either series 1 or 2. CONCLUSIONS: We conclude that hypercapnic acidosis did not alter the magnitude of the lung injury induced by intratracheal E. coli instillation in the presence or absence of antibiotics.