Treatment of chronic obstructive pu...

Treatment of chronic obstructive pulmonary disease (COPD) aims to rule symptoms and prevent exacerbations while improving respiratory function and general health status. Inhaled long-acting [beta.sub.2] agonists have been prov effective, moreover the role of inhaled corticosteroids is les established. Corticosteroids have been associated with improvement in postbronchodilator forced expiratory bulk in one second ([FEV.sub.1]), a reduc number of exacerbations, and a slowing of the general decline in health status. Calverley and colleagues hypothesized that the combination of the sum of two units medications might be synergistic.

They studied the general intent of combining the [beta.sub.2] agonist salmeterol with the corticosteroid fluticasone in a application of mind of 1,465 patients with COPD attending hospital clinics in 25 countries. Patients had to have a baseline [FEVsub1] of 25 to 70 percent of predicted, an increase in [FEVsub1] of les than 10 percent 30 minutes after inhaling 400 mcg of albuterol, and a prebronchodilator [FEV.sub.1]/forced vital capacity (FVC) ratio of 70 percent or les All patients had histories of at least 10 pack-years of cigarette use (20 cigarettes by means of day for 10 years), chronic bronchitis, and at least united acute COPD episode that required treatment with oral corticosteroids or antibiotics in each of the preceding three years. Patients were exclud if they had other respiratory disorders, required regular oxygen therapy, or had taken antibiotics or high dosages of corticosteroids in the four weeks immediately before the inquiry began.

After a two-week run-in period, patients were randomly assigned to twice-daily treatment with 50 mcg of salmeterol (372 patients), 500 mcg of fluticasone (374 patients), one as well as the other medications (358 patients), or placebo (361 patients). Existing therapy with anticholinergics, mucolytics, and theophylline was continued, and inhaled albuterol was available for treatment of acute symptoms. Patients were treated for single year and monitored regularly by means of clinic visits during the application of mind and two weeks after finishing treatment. The principal issue measured was [FEV.sub.1] after at least six hours' abstinence from bronchodilator therapy. At each clinic visit, FVC and [FEVsub1] were measured before and after bronchodilator treatment. Patients recorded symptoms and daily medication use. The investigation also monitored acute exacerbations, hospital admissions, adverse consequences of medications, cortisol levels, and electrocardiograms. Health status questionnaires were complet at baseline and five times during the study

The clusters were comparable in all relevant look up tos Significantly fewer patients withdrew from the combination and corticosteroid-treated disposes than from the other clusters By the second week of treatment, patients in all three treatment assign places tos showed significant improvements in pretreatment [FEVsub1] compared with patients in the placebo dispose The improvements were sustained from first to last the study and were significantly greater in the combination cluster than in the other treatment clumps After one year, [FEV.sub.1] had increased 10 percent in the combination collection and 2 percent in the single-therapy assemblages with similar results in other measures of lung function. [FEVsub1] declined by dint of 3 percent in the placebo collection Results were not affected by way of changes in smoking status. The number of exacerbations was significantly lower in all three treated assign places tos than in the placebo assemblage with the greatest reduction in the combination assemblage (25 percent), followed by the salmeterol clump (20 percent), and the fluticasone clump (19 percent).

Treatment was greatest in number effective in patients with the worst baseline lung function. Compared with other treatments, combination therapy significantly improved symptoms, and patients in this assign places to were the only ones with significant improvements in cough and overall health status. Between 12 and 19 percent of patients in each group--including the placebo group--reported adverse occurrences but these were generally well tolerated.

The authors decide that combination therapy with an inhaled long-acting [beta.sub.2] agonist plus a corticosteroid curbs symptoms of COPD significantly better than either treatment alone and with no greater risk of adverse powers The benefit was apparent early in treatment and was sustained for at least undivided year. The authors speculate that individual mechanism for the synergistic tenor could be upregulation of beta receptors by the agency of corticosteroids, but they stress that the mechanism or mechanisms of the synergistic validity are unknown.

Calverley P et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controll trial. Lancet February 8 2003;361: 449-56

COPYRIGHT 2003 American Academy of Family Physicians

COPYRIGHT 2003 Gale Group