Effect of four weeks' high dose ipratropium bromide

In a randomised, double blind crossover study the effect of high dose ipratropium bromide (200 pg three times daily given by metered dose inhaler for four weeks) on lung mucociliary clearance and on the wet weight and mean apparent viscosity of sputum was compared with that of placebo. Six smokers, six ex-smokers, and three non-smokers (12 men and three women, median age 60 years) were studied. Eight subjects had chronic obstructive lung disease (median FEV1 46% predicted) and seven had asthma (FEV1 70% predicted). Seven subjects produced sputum regularly, two of whom had asthma. Clearance of secretions was measured by an inhaled radioaerosol technique. The number of coughs and the wet weight, radioactive content, and mean apparent viscosity of sputum produced during the six hour observation period were recorded, as was the mean wet weight of sputum produced during the last two 24 hour periods ending each treatment. Comparison with placebo showed that treatment with high dose ipratropium bromide was associated with a significant increase in the penetration index of inhaled particles, but there was no significant change in alveolar deposition of particles or in tracheobronchial clearance, uncorrected or corrected for sputum expectorated. The wet weight of sputum produced, its radioactive content, and mean apparent viscosity were similar after treatment with ipratropium bromide and placebo. These results show that high dose inhaled treatment with the synthetic anticholinergic bronchodilator ipratropium bromide for four weeks is not associated with detectable modification of the clearance of secretions from the lungs, or of sputum volume or viscosity. The synthetic anticholinergic drug ipratropium bromide is an effective bronchodilator when given by metered dose inhaler 40 pg (that is, two puffs) four times daily, and this dosage for a week does not alter the clearance of secretions from the lungs. 1 2 Reports of the effects of higher doses of ipratropium bromide come from studies in which only single doses were given. Doses ofup to 400 pg caused greater and longer lasting bronchodilatation,38 while doses of up to 200 pg did not affect lung mucociliary clearance.5 9 Bearing in mind the effect of atropine on secretions and lung clearance, 10 we have looked more closely for any deleterious effect of treatment with ipratropium bromide inhaled in high doses. We report here the effects on sputum production and apparent viscosity Address for reprint requests: Dr RG Taylor, Department ofThoracic Medicine, Royal Free Hospital, London NW3 2QG. Accepted 17 September 1985 and on lung mucociliary clearance of four weeks' treatment with ipratropium bromide 200 pg three times daily given by metered dose inhaler to patients with airflow obstruction. Table 1 Details of the patients and their usual medication Male:female 12:3 Age: median (range) (y) 60 (27-71) Smoking habit (n) Smoker 6 Ex-smoker 6 Non-smoker 3 Diagnosis Chronic obstructive lung disease (n) 8 Median (range) (% predicted FEVy) 46 (24-70) Asthma (n) 7 Median (range) (% predicted FEVy) 70 (29-91) Medication: number normally taking: Inhaled fi adrenoceptor agonist 13 Oral and inhaled #2 adrenoceptor agonist 4 Inhaled corticosteroid 9 Oral and inhaled corticosteroid 3 Inhaled ipratropium bromide (standard dose) 2 Inhaled sodium cromoglycate I Oral aminophylline 7 295 group.bmj.com on October 20, 2017 Published by http://thorax.bmj.com/ Downloaded from