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Nitric oxide (NO) stimulates the ciliary motility of the airway epithelium, thereby assisting in the regulation of mucociliary transport in the respiratory tract. In the present study, to elucidate a possible involvement of NO in mucociliary disturbance in diffuse panbronchiolitis (DPB), we measured nasal clearance time (NCT) using the saccharin test, NO concentration in the exhaled air with a chemiluminescence analyzer, and electrolyte concentration in the sputum. Compared with healthy nonsmokers and smokers, patients with DPB showed a lower NO concentration in the exhaled air (p < 0.05), prolonged NCT (p < 0.01), and a higher Cl concentration in the sputum (p < 0.05). Among these variables, exhaled NO concentration was negatively correlated with NCT (p < 0.01) and sputum Cl concentration (p < 0.05). These results suggest that the inhibition of NO generation associated with an elevated Cl concentration in the airway surface liquid may contribute to airway mucociliary dysfunction in DPB.

Sputum samples were collected from 15 immotile cilia syndrome (ICS) cases, 12 diffuse panbronchiolitis (DPB) cases, and 11 bronchiectasis without ICS (BE) cases, during stable clinical state, to clarify the physicochemical properties of sputum from patients with ICS and to compare them with the properties of sputum from patients with DPB and BE. We measured sputum rheological properties and concentrations of several biochemical components. In ICS, spinnability was higher than that in DPB. No significant difference was seen between ICS and the other cases regarding other rheological properties. Albumin was lower, but fucose, sialic acid, and IgA were higher in ICS than in DPB. Although no significant difference was seen between ICS and BE, the sialic acid/albumin ratio was higher and the sialic acid/fucose ratio was lower in ICS than in BE. These results revealed that sputum from ICS cases was characterized by an absolutely or relatively increased mucus component with high spinnability and by a decreased extravascular transudate component. In view of these rheological properties, sputum from ICS cases was not always indicated to be associated with efficiency in cough clearance. The results suggested that chronic airway inflammation in ICS is not such a serious problem compared with DPB and BE.

Diffuse panbronchiolitis (DPB) is a disease characterized clinically by chronic airflow limitation, therefore patients with DPB are frequently treated with bronchodilators. However, there have been no reports on bronchodilator effects in patients with DPB. Because bronchodilator effects can be influenced by low baseline level of pulmonary function, we evaluated acute responses to inhaled metaproterenol (10 mg) in 31 patients with DPB and in 40 patients with pulmonary emphysema. Patients of both groups were clinically diagnosed, and, in addition, by usage of high-resolution computed tomography. All the subjects in both groups had a post-bronchodilator FEV1/FVC less than 0.7. There was no difference in baseline FEV1 between either group; FEV1 was 1.24 +/- 0.64 l (47.1 +/- 17.8% pred) in DPB vs. 1.24 +/- 0.64 l (51.0 +/- 19.0% pred) in pulmonary emphysema. Two indices, post FEV1/pre FEV1 and post FEV1-pre FEV1/predicted FEV1, were used for the judgement of bronchodilator response. Post FEV1/pre FEV1 was 110.3 +/- 9.3% in DPB and 119.9 +/- 17.1% in pulmonary emphysema. Post FEV1-pre FEV1/predicted FEV1 was 4.5 +/- 4.2% in DPB and 8.6 +/- 6.2% in pulmonary emphysema. Bronchodilator responses for both indices was larger in pulmonary emphysema than in DPB (both, p less than 0.01). It has been reported that post FEV1/pre FEV1 correlates negatively to baseline FEV1 and that post FEV1-pre FEV1/predicted FEV1 is positively correlated to baseline FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

The phase difference between mouth flow and chest flow in cases of pulmonary diseases measured using a body box was compared with those in normal subjects. Phase differences in chronic pulmonary emphysema (CPE) and diffuse panbronchiolitis (DPB) patients increased compared to normal subjects, but remained normal in interstitial pneumonitis patients (Normal: 3.76 +/- 1.71, CPE: 10.70 +/- 4.93, DPB: 10.81 +/- 3.15, IP: 3.83 +/- 0.15 degrees). In addition, there was a good correlation with FEV1.0, FEV1.0% and RV/TLC (r: -0.634, -0.610 and 0.803). The analysis of phase differences during rest breathing is clinically useful because it is non-effort dependent and can evaluate the degree of airway disorders.

We analysed sputum properties based on certain clinical information such as sputum volume, its gross appearance, the diagnosis, and difficulty in expectoration. We also compared sputum properties, clinical information and the effects of inhalation drugs on sputum in vitro, and on this basis evaluated the indications and limitations of inhalation therapy. It appears that inhalation therapy is limited by sputum properties, because the properties of large amounts of sputum, purulent sputum, and sputum expectorated with great difficulty are apparently different from those of other types of sputum. The effect of inhalation drugs on sputum was studied in vitro. Distilled water and normal saline showed as mucolytic agents. Bromhexine was acids in solution. The acidity caused the sputum to gel and reduced its mucolytic effect. Tyloxapole was alkaline in solution. The alkalinity decreased the mucociliary transport rate (MTR). Acetylcysteine had a marked mucolytic effect and decreased the MTR. There was a particular desire to develop drugs which improved MTR, because MTR is impaired by large amounts of sputum and sputum expectorated with great difficulty as well as in the case of sputum from diffuse panbronchiolitis patients.

We studied the effect indomethacin (IND) on electrical properties of airway epithelial cells and on sputum production in patients with chronic respiratory infection. Addition of IND (3 x 10(-6) M) to the mucosal side of Ussing chamber reduced short-circuit current from 5.9 +/- 1.2 to 1.7 +/- 0.5 microA/cm2 (p less than 0.001, n = 12) in canine cultured tracheal epithelium, an effect that was dependent on CI. Inhalation of IND for two weeks resulted in a decrease in the amount of sputum from 208 +/- 25 to 102 +/- 19 ml/day, (p less than 0.01, n = 13), and the concentrations of cyclooxygenase products in the sputum without alteration of inflammatory parameters. These results indicate that IND inhalation is a promising therapy in improving excessive sputum production and that this effect may be attributable to inhibition of Cl secretion and the subsequent reduction in water movement toward the airway lumen.