Although the activity of nitric oxide (NO) synthases are increased in lung tissue of patients with cystic fibrosis, the concentrations of nasal and exhaled NO have recently been found to be decreased in cystic fibrosis. This could either be due to reduced NO formation or metabolism of NO within airway fluids. In this study, the stable NO metabolites, nitrate and nitrite, were determined in the saliva and sputum of 18 stable cystic fibrosis patients, 21 cystic fibrosis patients during a pulmonary exacerbation, and in saliva and endotracheal secretions of normal controls. Median saliva concentrations of NO metabolites (nitrate plus nitrite) were 704 µmol/l (95% confidence interval (CI) 419 to 1477) in stable cystic fibrosis patients, 629 µmol/l (95% CI 382 to 1392) in cystic fibrosis patients presenting with pulmonary exacerbation, and 313 µmol/l (95% CI 312 to 454) in controls. Median sputum NO metabolite concentration in stable cystic fibrosis was 346 µmol/l (95% CI 311 to 504). This was not significantly diVerent from cystic fibrosis patients presenting with pulmonary exacerbation (median 184 µmol/l, 95% CI 249 to 572), but significantly higher than in endotracheal secretions of controls (median 144 µmol/l, 95% CI 96 to 260). Sputum NO metabolite concentration in cystic fibrosis pulmonary exacerbation significantly increased during antibiotic treatment. A positive correlation was observed between sputum NO metabolites and lung function in stable cystic fibrosis, suggesting less airway NO formation in cystic fibrosis patients with more severe lung disease. These data indicate that decreased exhaled NO concentrations in cystic fibrosis patients may be due to retention and metabolism of NO within the airway secretions. However, sputum NO metabolites are not a useful marker of airway inflammation in cystic fibrosis lung disease. (Arch Dis Child 1998;78:49-53)
Treatment with recombinant human deoxyribonuclease I (rhDNase) is currently used as therapy for cystic fibrosis (CF) lung disease. Hypertonic saline (HS) acts as an expectorant promoting mucus secretion and augmenting the volume of sputum. We evaluated the individual and combined effects of HS and rhDNase in vitro on the viscoelasticity of CF sputum. Sputum samples were collected from nine CF patients to use for in vitro testing. Aliquots of CF sputum (0.20 to 0.40 g) were subjected to the following protocols: (1) negative control sample without any treatment; (2) positive control sample, adding 10% volume of normal saline (0.9% NaCl); (3) application of hypertonic saline (HS-3% NaCl); (4) combining approximately 100 nM concentration of rhDNase with protocols 2 and 3. The samples in protocols 2 through 4 were incubated for 30 min at 37 degrees C. For each protocol, CF sputum was analyzed at baseline and at 30 min for spinnability by filancemeter and viscoelasticity by magnetic microrheometry. Spinnability decreased for the sputum samples that were treated with rhDNase, in combination with either HS or normal saline. Treatment with HS alone and combined treatment with rhDNase and HS decreased log G* (the principal viscoelasticity index) to the same degree. Saline alone and rhDNase in normal saline both increased the predicted cough clearability of the sputum; however, the combined treatment with rhDNase and hypertonic saline had the best overall effect on cough clearability. The change in predicted mucociliary clearability, although greatest after HS, was not significant. These in vitro results suggest that combined treatment with rhDNase and HS should be evaluated further as a potential mucotropic approach to augment the clearance of purulent sputum in CF lung disease.
Therapy with exogenous surfactants is currently used for the treatment of respiratory distress syndrome of the newborn (RDS) and is under investigation for treatments related to adult RDS. However, the possible use of exogenous surfactant as a means of enhancing mucus clearance in other respiratory diseases has not been addressed. We therefore studied the effects of an artificial surfactant (Curosurf) on in vivo tracheal mucus velocity in intubated pentobarbital-anaesthetized dogs.Five dogs were randomly administered, on separate occasions, either vehicle (saline) or 10 mg Curosurf by means of local instillation via a catheter into the right lung. Tracheal mucus was collected by inserting a soft-bristled cytology brush to the level of the carina, and analysed for viscoelasticity by microrheometry. Mucociliary clearability in vivo, tracheal mucus velocity (TMV) in mm·min -1 , was determined by bronchoscopic observation of charcoal marker particle transit times. The initial placement of charcoal was at the same level of the lower trachea that mucus was collected from. The effect of ciliary beat frequency was assessed on the frog palate assay by a videoscopic technique.In the dog, TMV was significantly increased after administration of surfactant. The values of TMV in the vehicle-and surfactant-treated dogs were 6.3±4.0 vs 25.6±6.5 mm·min -1 (SD), respectively. There were no discernible differences between prevehicle and postvehicle TMV values, and no significant differences in any mucus viscoelastic parameter, as determined by magnetic rheometry. There were also no significant changes in the viscoelastic or surface properties of mucus incubated with surfactant in vitro; however, ciliary beat frequency increased following administration of surfactant in the frog palate assay (from 3.6±0.4 to 8.5±3.2 Hz). The stimulation of TMV may be due either to a direct effect on ciliary function, to a reduction in the viscosity of the periciliary fluid, or to a more efficient interaction between the mucus and the cilia.In view of these results, we suggest that exogenous surfactant administration may provide a new therapeutic approach in treating conditions of impaired mucus clearance.
Poor sputum clearance has been related to sputum adhesion tension. In this study, we describe a modified du Noüy ring method for measuring the surface tension (gamma) of small samples of sputum and for comparinge the calculated work of adhesion (Wad) for sputum specimens with the measured mucociliary transportability (MCTR) and cough transportability (CTR). The gamma, as measured by this method, correlates with gamma measured by sputum contact angle on a low-surface-energy solid (R2 = 0.368, P = 0.03). There is a small but significant difference in measurements made by these two methods (P = 0.03). Wad calculated from the surface tension ring method is inversely correlated with CTR (R2 = 0.181, P = 0.004) but has no correlation with MCTR in this study. The miniaturized ring method gives accurate and reproducible measurements of the surface tension of small amounts of respiratory secretions. Because sputum behaves enough like a liquid that the assumptions made in using the Young equation to calculate Wad appear valid, we also showed that the Neumann equation can be used to determine the surface tension of sputum by its contact angle on tetrafluoroethylene (Teflon).
Amiloride inhalation as treatment for cystic fibrosis (CF) lung disease has been shown in independent studies to increase mucus clearance by ciliary and/or cough action and to retard the decline in lung function. It is hypothesized that amiloride therapy decreases the excess sodium and water absorption that is a characteristic of CF airway epithelium and that it leads to an improvement in the rheologic properties of mucus favoring airway mucus clearance. The aim of this study was to investigate whether amiloride treatment (5 x 10(-3) M amiloride in one-third normal saline four times a day) would change sputum electrolyte composition in patients with CF after 25 wk of therapy as compared with placebo (one-third normal saline), and whether appropriate changes in sputum water content and rheologic properties would accompany any changes in electrolyte composition. Sputum samples were obtained from six patients with CF undergoing amiloride therapy, using the dental cotton protection technique to avoid salivary contamination. The samples were stored at -80 degrees C until analyzed. For electrolyte analyses an aliquot of the sputum (minimum, 30 mg) was analyzed with ion-selective electrodes for sodium and potassium, and a chloride meter was used to measure chloride content. Chronic (25-wk) amiloride therapy increased significantly the sputum sodium (94.8 +/- 16.4 to 121.4 +/- 15.4 mmol/L, p = 0.001) and chloride (64.4 +/- 11.8 to 77.2 +/- 8.0 mmol/L, p = 0.10) content when compared with 25 wk of saline treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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