Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic obstructive pulmonary disease.

Regular short-acting inhaled beta-agonist therapy is of uncertain benefit in patients with chronic obstructive pulmonary disease (COPD). We conducted a randomized, concealed, double-blind, placebo-controlled crossover trial in two periods, each of 3-mo duration, involving 53 patients with a smoking history of > 20 pack-years, an FEV1 of < 70% predicted, and an FEV1/VC ratio of < 0.7 after inhalation of 200 microg albuterol. All patients received regular ipratropium bromide at 20 microg per puff in 2 puffs four times daily, beclomethasone at 250 microg per puff or equivalent corticosteroid in 2 puffs twice daily, and open-label inhaled albuterol as needed. Interventional therapy consisted of regular inhaled albuterol (100 microg per puff, in 2 puffs four times daily) versus placebo. Patients used twice as much active albuterol in the regular use period (mean: 8.07 puffs of coded and 4.68 puffs of open-label medication; total: 12.75 puffs daily) than during the as-needed period (mean: 6.34 puffs of open-label albuterol daily). Despite greater beta-agonist use, patients showed similar results during treatment and control periods for all outcomes. Differences between active and placebo periods were: FEV1: -0.04 L (95% confidence interval [CI]: -0.09 to 0.01 L); slow vital capacity: 0.04 L (95% CI: -0.12 to 0.20 L); 6-min walk test distance: -3.1 m (95% CI: -16.8 to 10.5 m); and Chronic Respiratory Questionnaire scores for dyspnea: 0.02 (95% CI: -0.13 to 0.16); fatigue: -0.02 (95% CI: -0.25 to 0.20); mastery: 0.01 (95% CI: -0.20 to 0.24); and emotional function: 0.02 (95% CI: -0.20 to 0.24). We found that in patients with COPD, use of regular short-acting inhaled beta-agonists resulted in twice as much beta-agonist use without physiologic or clinical benefit as did use on an as-needed basis.

Budesonide aqueous nasal spray and pressurized metered dose inhaler in the treatment of adult patients with seasonal allergic rhinitis.

Budesonide, a topical corticosteroid used in the treatment of seasonal allergic rhinitis, can be administered to the nose as an aerosol via a pressurized metered dose inhaler (pMDI) or as a metered nasal pump spray. Studies have shown that about 64% (256 micrograms) of a nominal dose of 400 micrograms budesonide pMDI preparation is delivered to the patient compared with 100% of the nominal dose of the pump spray. The present study was undertaken to assess the efficacy and safety of budesonide delivered via a nasal pMDI twice daily (Rhinocort pMDI, at 400 micrograms/day) with an aqueous suspension of budesonide delivered via a metered nasal pump spray once daily (Rhinocort Aqua, at 256 micrograms/day or 400 micrograms/day). The multicenter, double-blind, randomized, placebo-controlled, parallel-group study was conducted in 318 patients (154 men, 164 women; aged 12-67 years) with ragweed-induced seasonal allergic rhinitis. A 1-week baseline period was followed by a 3-week treatment. Nasal symptoms were recorded by the patients, adverse events were noted, an overall evaluation of treatment efficacy was made, and urine cortisol and creatinine levels were measured. Substantial or total control of symptoms was achieved in 83.8% of patients treated with 256 micrograms of aqueous budesonide, 76.3% with 400 micrograms of aqueous budesonide, and 80.8% with 400 micrograms of budesonide pMDI; these were all significantly different (p < 0.001) compared with placebo (23.4% of patients). There were no significant differences in the 24-hour urine cortisol levels between the groups and there were few, infrequent adverse events, similar between the groups and resolved completely on discontinuation of treatment. It was concluded that budesonide, given once daily as 256 micrograms or 400 micrograms in an aqueous suspension or twice daily as 400 micrograms in a pMDI provides good alleviation of the symptoms of seasonal allergic rhinitis with no significant risk of suppression of urine cortisol.

Effect of increasing doses of beta agonists on spirometric parameters, exercise capacity, and quality of life in patients with chronic airflow limitation.

BACKGROUND: A study was undertaken to determine the impact of different doses of inhaled terbutaline on peak flow rates, spirometric parameters, functional exercise capacity, and quality of life in patients with chronic airflow limitation. METHODS: A double blind, randomised, placebo controlled, multiple crossover trial was conducted with treatment periods of one week. Patients with a clinical diagnosis of chronic airflow limitation and FEV1 below 70% predicted after administration of bronchodilator were recruited from secondary care respiratory practices, and the effect of 500, 1000, and 1500 micrograms inhaled terbutaline four times daily on spirometric parameters (FEV1, FVC), maximum inspiratory pressures, six minute walking distance, and health-related quality of life (Chronic Respiratory Disease Questionnaire, Quality of Well Being, Standard Gamble) was measured. RESULTS: Twenty five patients completed the trial. Peak flow rates and FEV1 showed statistically significant but clinically trivial improvement on the higher drug doses. Results of maximum inspiratory pressure measurements, walk test distance, and quality of life measures showed minimal differences on the different dosages, and none of the differences approached conventional statistical significance. CONCLUSIONS: Regular use of beta agonists in doses higher than two puffs four times a day is very unlikely to provide additional functional or symptomatic benefit to patients with chronic airflow limitation.

The effect of increasing doses of beta-agonists on airflow in patients with chronic airflow limitation.

OBJECTIVE: To determine the increase in FEV1 associated with increasing doses of inhaled terbutaline and salbutamol, the reproducibility of the increase in FEV1, and the reproducibility of the associated optimal bronchodilator dose, in patients with chronic airflow limitation (CAL). DESIGN: Double-blind, randomized, controlled trial examining spirometric response to cumulative doses of bronchodilators. PATIENTS AND SETTING: Patients with clinical diagnosis of CAL, FEV1 below 70% predicted, and FEV1 to FVC ratio less than 0.7 after administration of bronchodilator recruited from secondary care respirology practices. MEASURES OF OUTCOME: The estimates of maximum and optimal bronchodilation, as well as the associated drug dosages, were established in each patient on three occasions (twice on terbutaline and once on salbutamol). The 'optimal' drug dose was defined as the lowest dose associated with an FEV1 not exceeded by 50 ml on any other dose. MAIN RESULTS: Thirty-five patients completed the trial. FEV1 improved from 0.93 to a maximum of 1.191 with terbutaline (average of the two administrations) and from 0.951 to 1.141 with inhaled salbutamol (difference in increase in FEV1 between terbutaline and salbutamol P = 0.006). In less than 50% of cases administration of more than four puffs of bronchodilator resulted in FEV1 increase by more than 50 ml. The average dose of salbutamol and terbutaline associated with optimal bronchodilation were 430 micrograms and 1160 micrograms respectively. Patients varied widely in the optimal dose. Estimates of optimal dose were not reproducible (intraclass correlation coefficient < 0.5). CONCLUSION: Substantial incremental increase in FEV1 in response to increasing doses of beta-agonists beyond those commonly used in clinical practice is restricted to a minority of patients. Lack of reproducibility limits the clinical usefulness of establishing the optimal dose of beta-agonist for a given patient.