Vast differences exist between the actions physicians report that they take and the patient's perception of those actions. Several patient satisfaction survey results are presented in this article. Many show that although patients are not often satisfied with their treatments or with the side effects they experience from medications, they are, in general, very satisfied with their physicians. These research studies point out that a very real "communications gap" exists between physicians and patients when examined from the patient's perspective.

BACKGROUND. Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators. METHODS. Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma. RESULTS. The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol. CONCLUSIONS. An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.

BACKGROUND: Inhaled long-acting beta2 agonists improve lung function and health status in symptomatic chronic obstructive pulmonary disease (COPD), whereas inhaled corticosteroids reduce the frequency of acute episodes of symptom exacerbation and delay deterioration in health status. We postulated that a combination of these treatments would be better than each component used alone. METHODS: 1465 patients with COPD were recruited from outpatient departments in 25 countries. They were treated in a randomised, double-blind, parallel-group, placebo-controlled study with either 50 microg salmeterol twice daily (n=372), 500 microg fluticasone twice daily (n=374), 50 microg salmeterol and 500 microg fluticasone twice daily (n=358), or placebo (n=361) for 12 months. The primary outcome was the pretreatment forced expiratory volume in 1s (FEV1) after 12 months treatment' and after patients had abstained from all bronchodilators for at least 6h and from study medication for at least 12h. Secondary outcomes were other lung function measurements, symptoms and rescue treatment use, the number of exacerbations, patient withdrawals, and disease-specific health status. We assessed adverse events, serum cortisol concentrations, skin bruising, and electrocardiograms. Analysis was as predefined in the study protocol. FINDINGS: All active treatments improved lung function, symptoms, and health status and reduced use of rescue medication and frequency of exacerbations. Combination therapy improved pretreatment FEV1 significantly more than did placebo (treatment difference 133 mL, 95% CI 105-161, p<0.0001), salmeterol (73 mL, 46-101, p<0.0001), or fluticasone alone (95 mL, 67-122, p<0.0001). Combination treatment produced a clinically significant improvement in health status and the greatest reduction in daily symptoms. All treatments were well tolerated with no difference in the frequency of adverse events, bruising, or clinically significant falls in serum cortisol concentration. INTERPRETATION: Because inhaled long-acting beta2 agonists and corticosteroid combination treatment produces better control of symptoms and lung function, with no greater risk of side-effects than that with use of either component alone, this combination treatment should be considered for patients with COPD.

STUDY OBJECTIVES: To examine and compare the efficacy and safety of salmeterol xinafoate, a long-acting inhaled beta2-adrenergic agonist, with inhaled ipratropium bromide and inhaled placebo in patients with COPD. DESIGN: A stratified, randomized, double-blind, double-dummy, placebo-controlled, parallel group clinical trial. SETTING: Multiple sites at clinics and university medical centers throughout the United States. PATIENTS: Four hundred eleven symptomatic patients with COPD with FEV1 < or = 65% predicted and no clinically significant concurrent disease. Interventions: Comparison of inhaled salmeterol (42 microg twice daily), inhaled ipratropium bromide (36 microg four times a day), and inhaled placebo (2 puffs four times a day) over 12 weeks. RESULTS: Salmeterol xinafoate was significantly (p < 0.0001) better than placebo and ipratropium in improving lung function at the recommended doses over the 12-week trial. Both salmeterol and ipratropium reduced dyspnea related to activities of daily living compared with placebo; this improvement was associated with reduced use of supplemental albuterol. Analyses of time to first COPD exacerbation revealed salmeterol to be superior to placebo and ipratropium (p < 0.05). Adverse effects were similar among the three treatments. CONCLUSIONS: These collective data support the use of salmeterol as first-line bronchodilator therapy for the long-term treatment of airflow obstruction in patients with COPD.

This randomized controlled trial examined the benefits of combining an inhaled corticosteroid, fluticasone propionate (F), with an inhaled long-acting beta(2)-agonist, salmeterol (S), to treat the inflammatory and bronchoconstrictive components of chronic obstructive pulmonary disease (COPD). A total of 691 patients with COPD received the combination of F and S (FSC), S (50 mcg), F (500 mcg), or placebo twice daily via the Diskus device for 24 weeks. A significantly greater increase in predose FEV(1) at the endpoint was observed after FSC (156 ml) compared with S (107 ml, p = 0.012) and placebo (-4 ml, p < 0.0001). A significantly greater increase in 2-hour postdose FEV(1) at the endpoint was observed after treatment with FSC (261 ml) compared with F (138 ml, p < 0.001) and placebo (28 ml, p < 0.001). There were greater improvements in the Transition Dyspnea Index with FSC (2.1) compared with F (1.3, p = 0.033), S (0.9, p < 0.001), and placebo (0.4, p < 0.0001). The incidence of adverse effects (except for an increase in oral candidiasis with FSC and F) was similar among the treatment groups. We conclude that FSC improved lung function and reduced the severity of dyspnea compared with individual components and placebo.

BACKGROUND: Racemic albuterol is an equal mixture of (R)-albuterol (levalbuterol), which is responsible for the bronchodilator effect, and (S)-albuterol, which provides no benefit and may be detrimental. OBJECTIVE: We sought to compare 2 doses of a single enantiomer, levalbuterol (0.63 mg and 1.25 mg), and equivalent amounts of levalbuterol administered as racemic albuterol with placebo in patients with moderate-to-severe asthma. METHODS: This was a randomized, double-blind, parallel-group trial. Three hundred sixty-two patients 12 years of age or older were treated with study drug administered by means of nebulization 3 times daily for 28 days. The primary endpoint was peak change in FEV1 after 4 weeks. RESULTS: The change in peak FEV1 response to the first dose in the combined levalbuterol group was significantly greater compared with the combined racemic albuterol group (0.92 and 0.82 L, respectively; P =.03), with similar but nonsignificant results after 4 weeks (0.84 and 0.74 L, respectively). Improvement in FEV1 was similar for levalbuterol 0.63 mg and racemic albuterol 2.5 mg and greatest for levalbuterol 1.25 mg. Racemic albuterol 1.25 mg demonstrated the weakest bronchodilator effect, particularly after chronic dosing. The greatest increase in FEV1 was seen after levalbuterol 1.25 mg, especially in subjects with severe asthma. All active treatments were well tolerated, and beta-adrenergic side effects after administration of levalbuterol 0.63 mg were reduced relative to levalbuterol 1.25 mg or racemic albuterol 2.5 mg. At week 4, the predose FEV1 value was greatest in patients who received levalbuterol or placebo when compared with those who received racemic albuterol. The difference was more evident and was statistically significant in patients who were not receiving inhaled corticosteroids. CONCLUSION: Levalbuterol appears to provide a better therapeutic index than the standard dose of racemic albuterol. These results support the concept that (S)-albuterol may have detrimental effects on pulmonary function.

Dry mouth is a common disorder in elderly individuals. It is not, however, necessarily related to decreased salivary flow rate, since subjective feelings of oral dryness have also been found in those with normal flow rates. The aim of this study was to examine in elderly individuals the prevalence of subjective complaints related to dry mouth, and their association with salivary flow rates and the use of systemic medication. In 1990 and 1991, 368 elderly inhabitants of Helsinki, Finland, had their oral health status examined. In addition to the clinical examination, 341 subjects were interviewed regarding different oral and non-oral complaints related to dry mouth. Findings showed that 46%(n = 158) of the subjects had noticed subjective symptoms of dry mouth. Continuous oral dryness was reported by 12%(n = 40) of the subjects, 6% of the men and 14% of the women (p < 0.05). In these 40, the oral and non-oral symptoms were more frequent in subjects reporting continuous dry mouth compared with controls. Continuous dry mouth was clearly associated with the female gender, with mouth breathing and with the use of systemic medications.

STUDY OBJECTIVES: To compare the efficacy and safety of the inhaled corticosteroid fluticasone propionate (FP) and the inhaled long-acting beta(2)-agonist salmeterol (SM), when administered together in a single device (Diskus; GlaxoSmithKline, Inc; Research Triangle Park, NC), with that of placebo and the individual agents alone in patients with COPD. DESIGN: Randomized, double-blind, multicenter, placebo-controlled study. SETTING: Seventy-six investigative sites in the United States. PATIENTS: Seven hundred twenty-three patients > or =40 years of age with COPD and a mean baseline FEV(1) of 42% predicted. INTERVENTIONS: FP (250 microg), SM (50 microg), FP plus SM combined in a single inhaler (FSC), or placebo administered twice daily through the Diskus device for 24 weeks. MEASUREMENTS: Primary efficacy measures were morning predose (ie, trough FEV(1)) for FSC compared with SM and 2-h postdose FEV(1) for FSC compared with FP. Other efficacy measures were as follows: morning peak expiratory flow rate (PEF); transition dyspnea index; chronic respiratory disease questionnaire; chronic bronchitis symptom questionnaire; exacerbations; and other symptomatic measures. RESULTS: At Endpoint (ie, the last on-treatment, post-baseline assessment), treatment with FSC significantly (p < or = 0.012) increased the morning predose FEV(1)(165 mL) compared with SM (91 mL) and placebo (1 mL), and significantly (p < or = 0.001) increased the 2-h postdose FEV(1)(281 mL) compared with FP (147 mL) and placebo (58 mL). Improvements in lung function with FSC compared with FP and SM, and with FP and SM compared with placebo, as measured by the average daily morning PEF, was observed within approximately 24 h after the initiation of treatment, indicating an early onset of effect (p < or = 0.034). Compared with placebo, FSC significantly improved dyspnea, quality of life, and symptoms of chronic bronchitis. The incidence of adverse effects (except for an increase in oral candidiasis with FSC and FP) were similar among the treatment groups. CONCLUSIONS: Treatment with FSC (FP, 250 microg, and SM, 50 microg) twice daily substantially improved morning lung function and sustained these improvements for over a period of 24 weeks compared with FP or SM treatment alone in patients with COPD, with no additional safety concerns for the combination treatment vs that with the individual components.

The airway response and cardiovascular and hypokalaemic effects of fenoterol, salbutamol, and terbutaline given in multiples of standard doses from metered-dose inhalers were studied in ten patients with mild asthma. In a double-blind, crossover, placebo-controlled study the subjects received 2, 6, and 18 puffs of each drug with intervals of 90 min, and forced expiratory volume in 1 s, heart rate, QTc interval, plasma potassium concentration, tremor, and bronchial reactivity to histamine were measured. All three drugs produced similar bronchodilatation. However, the rises in heart rate, QTc interval, and tremor and the fall in plasma potassium were greater after fenoterol than after salbutamol or terbutaline. The maximum mean (SD) increases in heart rate for fenoterol, salbutamol, and terbutaline were 29 (24) bpm, 8 (9) bpm, and 8 (14) bpm, respectively; falls in plasma potassium were 0.76 (0.62) mmol/l, 0.46 (0.32) mmol/l, and 0.52 (0.39) mmol/l, respectively. Fenoterol afforded no additional protection against histamine compared with salbutamol. These findings suggest that at doses based on those used in clinical practice fenoterol causes more adverse effects than salbutamol or terbutaline. The most likely explanation for these effects is that fenoterol has been marketed at a higher dose than the other beta 2-agonists; fenoterol may in addition be less selective for beta 2 receptors.

There is controversy about the role of beta-agonists in asthma mortality, and the impact of asthma management plans remains unclear. We compared blood beta-agonist levels in patients dying from asthma with those in controls, and estimated the risks associated with specific classes of medication and patterns of management. We identified 89 asthma deaths and recruited 322 patients presenting to hospitals with acute asthma. A questionnaire was administered to the next of kin in 51 cases, and to 202 controls. Blood drawn from 35 cases and 229 controls was assayed for salbutamol. Smoking, drinking, and family problems were significantly more likely among the cases of asthma death than among the controls. The two groups were reasonably well matched with regard to markers of chronic asthma severity. Cases of asthma death were significantly less likely than controls to use a peak flow meter. Written action plans were associated with a 70% reduction in the risk of death. Use of nebulized bronchodilators or oral steroids was significantly more likely in cases of asthma death. Mean blood salbutamol concentrations were 2.5 times higher in cases of asthma. The use of oral steroids for an attack of asthma reduced the risk of death by 90%. More widespread adoption of written asthma management plans, with less reliance on beta-agonists and closer medical supervision, should reduce asthma mortality.

BACKGROUND: Montelukast, an oral, once-daily leukotriene receptor antagonist, provides protection against exercise-induced bronchoconstriction. OBJECTIVE: To evaluate the effect of 8 weeks of therapy with salmeterol aerosol or montelukast on exercise-induced bronchoconstriction in adults with asthma. DESIGN: 8-week multicenter, randomized, double-blind study. SETTING: 17 asthma treatment centers in the United States. PATIENTS: 191 adults with asthma who had documented exercise-induced bronchoconstriction. INTERVENTION: Qualified patients were randomly assigned to double-blind treatment with montelukast (10 mg once in the evening) or salmeterol (50 microg [2 puffs] twice daily). MEASUREMENTS: Changes in pre-exercise and postexercise challenge values; percentage inhibition in the maximal percentage decrease in FEV1; the area above the FEV1-time curve; and time to recovery of FEV1 at days 1 to 3, week 4, and week 8 of treatment. RESULTS: By day 3, similar and statistically significant reductions in maximal percentage decrease in FEV1 were seen with both therapies. Sustained improvement occurred in the montelukast group at weeks 4 and 8; at these time points, the bronchoprotective effect of salmeterol decreased significantly. At week 8, the percentage inhibition in the maximal percentage decrease in FEV1 was 57.2% in the montelukast group and 33.0% in the salmeterol group (P = 0.002). By week 8, 67% of patients receiving montelukast and 46% of patients receiving salmeterol had a maximal percentage decrease in FEV1 of less than 20%. CONCLUSIONS: The bronchoprotective effect of montelukast was maintained throughout 8 weeks of study. In contrast, significant loss of bronchoprotection at weeks 4 and 8 was seen with salmeterol. Long-term administration of montelukast provided consistent inhibition of exercise-induced bronchoconstriction at the end of the 8-week dosing interval without tolerance.