On the mucus-depleted bovine trachea, the ciliary transport rate of sputum from patients with cystic fibrosis and bronchiectasis of other causes was slow, but the rate was doubled by increasing the sodium chloride content by 90 mM. Increasing the sputum osmolality by inspissation or by the addition of nonelectrolytes had a similar effect. The viscoelasticity of sputum, but not the bovine ciliary beat frequency, was markedly saline dependent over the pathophysiological range. This suggests that low mucus salinity, not (as is generally assumed) its underhydration, contributes to its retention in bronchiectasis due to cystic fibrosis and other causes, probably by affecting its rheology. It also indicates how the genetic defect in cystic fibrosis might lead to impaired mucus clearance. Therapies that increase the osmolality of lung mucus might benefit patients with mucus retention. ( J. Clin. Invest. 1997. 99:9-13.)

We report a double blind placebo-controlled phase II study of the efficacy and safety of nebulized recombinant human DNase (rhDNase) administered for 14 d to adults with bronchiectasis not caused by cystic fibrosis. All were in a stable clinical state at the commencement of the study, and they received (1) rhDNase 2.5 mg twice daily, (2) rhDNase once daily, or (3) placebo (excipient only) inhalation. The outcome measures were spirometry, subjective quality of life/dyspnea, and safety. We also measured the ciliary transportability of the sputum expectorated before and after the treatment period, using the mucus-depleted bovine trachea. The drug was well tolerated, but it produced no significant change in any of the outcome variables or in sputum transportability. When the drug was incubated with bronchiectatic sputum in vitro, a fall in transportability was observed. We discuss possible explanations for the lack of a measurable benefit from rhDNase in this study population, which appears to contrast with the improvements shown in cystic fibrosis using studies of similar design.

Non-pharmacological breathlessness interventions in lung cancer have proven beneficial. Breathlessness is also a major symptom in chronic obstructive pulmonary disease (COPD). This study measured the effectiveness of a non-exercise-based four-week cognitive-behavioural breathlessness intervention, delivered in a group setting for elderly patients with severe COPD. The results of the one-year feasibility study are presented. Patients with COPD were asked to complete the St. George's Respiratory Questionnaire and Hospital Anxiety and Depression Scale six weeks before the intervention, at the start and end of the intervention and at six weeks follow-up. The multidisciplinary intervention used a cognitive-behavioural format to address understanding of COPD and medication, anxiety, panic and depression, activity pacing, relaxation, breathing retraining and goal-setting. Retrospective data on accident & emergency (A&E) attendances and length of hospital stay was collected six months before and six months after the intervention and the data compared to a matched waiting list control group. The results showed significant improvements in depression and health status. There was a non-significant improvement in anxiety. There was a significant reduction in A&E attendance and a non-significant reduction in length of hospital stay in the intervention group, compared to comparative increases in the control group, highlighting the cost-effectiveness of the intervention.

No abstract

Patients with airway infection by Pseudomonas aeruginosa have impaired mucociliary clearance. Pyocyanin is a phenazine pigment produced by P. aeruginosa which is present in the sputum of colonized patients, slows human ciliary beat frequency (CBF) in vitro and slows mucociliary transport in vivo in the guinea‐pig. We have investigated the effect of salmeterol, a long‐acting β2‐adrenoceptor agonist, on pyocyanin‐induced slowing of human CBF in vitro. Salmeterol (2 × 10−7 m) was found to reduce pyocycanin (20 μg ml−1)‐induced slowing of CBF by 53% and the fall in intracellular adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) by 26% and ATP by 29%. Another β2‐adrenoceptor agonist, isoprenaline (2 × 10−7 m), also inhibited pyocyanin‐induced slowing of CBF by 39%. The effects of salmeterol (30 min preincubation) persisted after washing the cells. Propranolol (10−7 m) and the β2‐specific antagonist, ICI 118551 (10−6 m) blocked the protective effects of salmeterol completely, but atenolol (10−6 m) was less effective. These results suggested that the effects of salmeterol on pyocyanin‐induced effects were mediated primarily via the stimulation of β2‐adrenoceptors. Pyocyanin‐induced ciliary slowing is associated with a substantial fall in intracellular cyclic AMP and ATP. Salmeterol reversed the effects of pyocyanin on cyclic AMP and ATP. Mucociliary clearance is an important defence mechanism of the airways against bacterial infection. Salmeterol may benefit patients colonized by P. aeruginosa, not only by its bronchodilator action, but also by protecting epithelial cells from pyocyanin‐induced slowing of CBF.