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.

Cystic fibrosis sputum stimulates CD18-independent neutrophil migration across endothelial cells.

Excessive neutrophil recruitment to the lung underlies inflammatory-mediated lung damage in cystic fibrosis (CF). Neutrophils can migrate to the lung using either a CD18-dependent or CD18-independent mechanism. To determine if one of these migratory pathways is preferentially utilized by neutrophils migrating to the CF airways, this study examined the CD18 dependency of neutrophil transendothelial migration stimulated by the soluble fraction of CF sputum (SOL). Results demonstrate the preferential use of the CD18-independent migratory mechanism by both control and CF neutrophils and suggest that selective blocking of the CD18-independent migration pathway may offer a means of decreasing neutrophil influx to the CF airways.

Role of arterial hypoxemia and pulmonary mechanics in exercise limitation in adults with cystic fibrosis.

We tested the hypothesis that maximal exercise performance in adults with cystic fibrosis is limited by arterial hypoxemia. In study 1, patients completed two maximal exercise tests, a control and a test with 400 ml of added dead space. Maximal O2 consumption was significantly lower in the added dead space study vs. control (1.04 +/- 0.15 vs. 1.20 +/- 0.11 l/min; P < 0.05), with no difference in peak ventilation. There was significant O2 desaturation during exercise that was equal in both control and added dead space studies. The decrease in maximal O2 consumption with added dead space suggests that maximal exercise in cystic fibrosis is limited by respiratory factors. We subsequently examined whether pulmonary mechanics or arterial hypoxemia limits maximal exercise performance. In study 2, patients completed two maximal exercise tests, a control and a test with 400 ml of added dead space while also breathing 38% O2. Added dead space was used to overcome the suppressive effects of hyperoxia on minute ventilation. Maximal O2 consumption was significantly higher with added dead space and 38% O2 vs. control (1.62 +/- 0.16 vs. 1.43 +/- 0.14 l/min; P < 0.05). Peak ventilation and O2 saturation were significantly greater in the added dead space and 38% O2 test vs. control. The increase in maximal O2 consumption and peak ventilation with added dead space and 38% O2 suggests that maximal exercise in cystic fibrosis is limited by arterial hypoxemia.

Use of the gas exchange threshold to noninvasively determine the lactate threshold in patients with cystic fibrosis.

OBJECTIVE: The anaerobic threshold (AT) is a submaximal index related to endurance exercise performance, which is usually determined by the measurement of blood lactate concentration during an incremental exercise test (lactate threshold [LT]). The LT, and thus the AT, can also be detected noninvasively in normal subjects by means of the gas exchange threshold (GET). This study was undertaken to validate the use of GET in patients with cystic fibrosis (CF) with a wide range of disease severity, and to assess the reproducibility of this index. METHODS: In patients with CF (FEV(1) range, 23 to 118% of predicted) and control subjects, gas exchange was measured breath by breath during the incremental exercise tests to allow determination of the GET. Arterialized-venous blood was sampled for determination of the LT. The GET and LT were determined in a blinded manner. RESULTS: The mean differences (GET - LT) for control subjects (n = 18) and patients with CF (n = 23) were - 40 mL/min and + 10 mL/min, respectively, neither being significantly different from zero. The limits of agreement were +/- 550 mL/min and +/- 410 mL/min, respectively. The mean test-retest differences in GET for control subjects (n = 14) and patients with CF (n = 12) were - 50 mL/min and 0 mL/min, respectively, neither being significantly different from zero; the respective limits of reproducibility were +/- 450 mL/min and +/- 350 mL/min. CONCLUSIONS: This study demonstrates that in patients with CF, the GET can be used to obtain an unbiased estimate of the LT, and that the GET is reproducible.