Reduced protection against exercise induced bronchoconstriction after chronic dosing with salmeterol.

The purpose of the present study was to assess the degree of protection of inhaled salmeterol against exercise-induced bronchoconstriction (EIB) after chronic compared with single dosing in patients with asthma. Twelve patients with exercise-induced asthma took part in a randomized double-blind crossover study to compare the duration of action of inhaled salmeterol 50 micrograms twice daily for 4 weeks with that of placebo. A standardized exercise test was performed at 6 h and 12 h after dosing on the first and last day of each treatment period. Salmeterol produced significant protection against EIB at 6 and 12 h after the first dose in comparison with placebo, whereas there was no significant attenuation of EIB after 4 weeks of chronic treatment with salmeterol. The percentage fall in FEV1 after exercise challenge at 6 h was (first dose): placebo 34.8 +/- 4.9% vs. salmeterol 11.9 +/- 2.8% (P < 0.05); (4 weeks): placebo 32.9 +/- 5.3% vs. salmeterol 24.0 +/- 4.4% (NS). These results suggest that tachyphylaxis may develop to the functional antagonism of salmeterol against EIB.

Salmeterol provides prolonged protection against exercise-induced bronchoconstriction in a majority of subjects with mild, stable asthma.

In patients with asthma, exercise-induced symptoms are well recognized and frequently limiting. Currently available beta 2-receptor agonists have a short duration of action and breakthrough symptoms may occur. We studied the efficacy of the recently developed long acting inhaled beta 2-agonist salmeterol with respect to protection against exercise-induced bronchoconstriction. Twelve patients with mild to moderate, stable asthma were recruited (age range 21-33 years). They each underwent treadmill exercise tests, with target heart rate of approximately 90% of predicted maximum, 1, 6 and 12 h after a single dose of salmeterol 50 micrograms, salbutamol 200 micrograms and placebo. Patients breathed through a two-way valve, inspiring dry air from a compressed air cylinder via a Douglas bag to maintain constant humidity. The primary efficacy variable analysed was the maximum percentage fall in FEV1 and FVC from pre-exercise readings within the first 30 min post-exercise. At 1 h post-dose there was significant protection in terms of fall in mean +/- SEM FEV1 in response to exercise challenge after either salmeterol (0.83 +/- 6.2%) or salbutamol (3.8 +/- 5.5%) as compared with placebo (27.1 +/- 7.3%). At 6 h post-dose, fall in FEV1 on salmeterol was 11.3 +/- 3.8% as compared with salbutamol, 28.0 +/- 5.7% and placebo, 32.0 +/- 7.0%. At 12 h post-dosing there was still significant protection in terms of fall in FEV1 in the salmeterol treated group, 12.8 +/- 4.9%, as compared with salbutamol, 28.7 +/- 4.9% and placebo, 25.4 +/- 7.3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Controlled trial of supervised exercise training in chronic bronchitis.

In a controlled trial of exercise retraining in patients with severe chronic bronchitis, 33 subjects were followed for a mean period of 10.3 months. The exercise programme was supervised once a week, and daily training comprised a 12-minute walk and simple stair climbing exercises. The subjects in the exercise group showed a highly significant improvement in their walking distance, attaining a maximum increase of 24% after eight to 12 months. There was also considerable subjective improvement. The control group did not improve. No significant changes in cardiorespiratory function or muscle strength were seen. Simple exercise rehabilitation is of benefit to patients with disabling obstructive lung disease.

The effect of astemizole on exercise-induced asthma.

Astemizole, a new oral long acting antihistamine devoid of significant central, sedative or anticholinergic effects, was studied in nine patients with exercise-induced asthma. Most patients received some protection with the active drug after 1 week of treatment (10 mg daily) and all showed less of a fall in FEV1 on exercise 1 week after stopping the drug compared with an initial placebo period (P less than 0.01). A significant reduction in histamine-induced skin reaction (weal size) was also demonstrated (P less than 0.01).

Bronchial provocation studies in farmers allergic to storage mites.

In an investigation of the relationship between storage mites and symptoms of allergic respiratory disease in farmers exposed to hay and grain dust, the clinical responses suggested an immediate type-I hypersensitivity. This study confirmed that farmers are exposed to large numbers of mites, particularly while feeding cattle. Storage mites may be an important cause of asthma in the farming community and should also be considered in the differential diagnosis of farmers lung.

Beta-adrenoceptor subtypes mediating the airways response to BRL 35135 in man.

1 The purpose of the study was to assess the bronchorelaxant effects of the beta3-adrenoceptor agonist BRL 35135 in normal human airways. 2 Eight healthy male subjects were studied, having previously demonstrated airways responsiveness to inhaled salbutamol 200 microg, with a group mean (+/- s.e. mean) fall in airways resistance (Raw), from baseline, of 37 +/- 5%. 3 Subjects attended the laboratory on 3 separate days, having fasted and taken placebo (PL) or nadolol 20 mg (N20), 2 h previously. 4 After 30 min rest, baseline measurements of Raw, serum potassium, glucose and free fatty acid were performed before subjects were given single oral doses of BRL 35135 8 mg (BRL) or placebo BRL. Measurements were repeated 60 min after the BRL or placebo BRL were given. 5 There was a significant (P < 0.05) fall in Raw (% change from baseline, as means and 95% CI) with PL/BRL: -32(-18, -46), compared with either PL/PL: -8(5, -21), or N20/BRL: -11(2, -24). There was no significant difference between PL/PL and N20/BRL. 6 A similar pattern to Raw was observed for both of the beta2-mediated metabolic responses which were also antagonised by nadolol. For the potassium response (mmol l(-1)), there was a significant (P < 0.05) difference between PL/BRL: -0.50(-0.31, -0.69), in comparison with either PL/PL: 0.08(-0.11, 0.27) or N20/BRL: 0.09(-0.10, 0.28), but values for PL/PL and N20/BRL were not significantly different. In contrast, with the free fatty acid response (nmol 1(-1)), the increase seen with N20/BRL: 85(1.0, 171.0) was significantly (P < 0.05) different from PL/PL: 3.7(-82.3, 89.8), but was not different from PL/BRL: 132.5(46.5, 218.5). 7 In conclusion, BRL 35135 produced airways, potassium and glucose responses which were antagonised by nadolol, whereas the lipolysis response was not. This suggests that there are not functional beta3-adrenoceptors in human airways.

A comparison of the effects of prednisolone and mianserin on ventilatory, exercise and psychometric parameters in patients with chronic obstructive pulmonary disease.

There is controversy as to whether effects on mood play a role in mediating the response to corticosteroids in chronic obstructive pulmonary disease (COPD). If alterations in mood are important, it is conceivable that psychotropic drugs such as mianserin might produce similar responses to prednisolone in patients with COPD. Twelve patients age 62.5 y, with FEV1 29% of predicted and < 15% reversibility to salbutamol completed a randomised, double-blind crossover study. After an initial three week placebo run-in period patients received three weeks of prednisolone 40 mg daily or mianserin 60-90 mg daily with an intervening three week placebo washout period. Full respiratory function tests, bicycle ergometry and 6 minute walks were performed before and after the run-in and at the end of each period. Psychological and functional assessments were also made at each visit. Prednisolone significantly increased FVC, maximum ventilation (VEmax) and maximum heart rate (HRmax) compared with placebo, with mean for the difference of 0.25 l, 2.56 l.min-1 and 12 beats.min-1 respectively. FVC, maximum oxygen uptake (VO2max) and HRmax were also significantly increased with prednisolone compared with mianserin. Anxiety scores were significantly lower with prednisolone compared with placebo. In contrast, mianserin had no significant effects on lung function, exercise or psychological parameters compared with placebo. The improvements in ventilation, exercise and anxiety scores following treatment with prednisolone were not reproduced by mianserin, suggesting that the effects of prednisolone in COPD are unlikely to be due to alterations in mood.

Ipratropium bromide, salbutamol and prednisolone in bronchial asthma and chronic bronchitis.

Eleven patients with bronchial asthma and 10 with chronic bronchitis were treated over four consecutive 3-day periods, firstly with aerosols either of ipratropium bromide (40 microgram four times a day) or of salbutamol (200 microgram four times daily) by random allocation, then the alternate drug, next by both drugs together, and finally with prednisolone (10 mg three times daily) in addition to both drugs. The effects of these four treatment periods were assessed both clinically and by measuring ventilatory capacity, nitrogen slope and progressive exercise testing. Ipratropium bromide and salbutamol produced approximately equal improvements in both diseases, with salbutamol showing a marginal advantage in patients with asthma. The combination of both drugs together more than doubled the FEV1 change in both groups of patients. The addition of prednisolone to both drugs produced a marginal advantage only in those with asthma.

Effects of regular salmeterol on lung function and exercise capacity in patients with chronic obstructive airways disease.

BACKGROUND: The aim of this study was to evaluate the effects of single and chronic dosing with salmeterol on exercise capacity and lung function in patients with chronic obstructive pulmonary disease. METHODS: Twenty nine patients of mean (SE) age 64 (1.5) years, forced expiratory volume in one second (FEV1) 42(3)% of predicted, and 5-15% reversibility to salbutamol 200 micrograms were randomised to receive four weeks treatment with salmeterol 50 micrograms twice daily or placebo in a double blind crossover fashion with a one week washout period in between. Measurements of spirometric parameters, static lung volumes, and exercise capacity were made one and six hours after a single dose, and six hours after the final dose of salmeterol or placebo. RESULTS: Salmeterol produced a small increase in FEV1 at one and six hours after a single dose, and this was maintained after chronic dosing (mean difference and 95% CI versus placebo): single dosing at one hour 0.07 (95% CI 0.02 to 0.11) 1, single dosing at six hours 0.16 (95% CI 0.09 to 0.22) 1, chronic dosing at six hours 0.11 (95% CI 0.03 to 0.19) 1. The increase in forced vital capacity (FVC) was greater with salmeterol than with placebo six hours after single but not chronic dosing: single dosing at six hours 0.17 (95% CI 0.04 to 0.29) 1, chronic dosing at six hours 0.02 (95% CI -0.18 to 0.22) 1. Slow vital capacity was increased after treatment with salmeterol compared with placebo one and six hours after single but not after chronic dosing. There were no significant differences in static lung volumes or exercise capacity after single or chronic dosing with salmeterol compared with placebo. Patients reported a significantly lower Borg score for perceived exertion following the six minute walk after chronic treatment with salmeterol compared with placebo. CONCLUSIONS: Salmeterol produced a small improvement in spirometric values compared with placebo consistent with the degree of reversibility originally shown by the subjects to salbutamol 200 micrograms. This was not associated with improvements in static lung volumes or exercise capacity, but there was some symptomatic benefit in that patients were able to walk the same distance in six minutes with less perceived exertion.