A Comparison of Bronchodilator Therapy with or without Inhaled Corticosteroid Therapy for Obstructive Airways Disease

The morbidity from obstructive airways disease (asthma and chronic obstructive pulmonary disease) is considerable, and the mortality rate is rising in several countries. It has been hypothesized that long-term improvement in prognosis might result from vigorous bronchodilator or antiinflammatory therapy. In a multicenter trial we compared three inhalation regimens in which a β₂-agonist (terbutaline, 2000 μg daily) was combined with a corticosteroid (beclomethasone, 800 μg daily), an anticholinergic bronchodilator (ipratropium bromide, 160 μg daily), or placebo. Patients with airways hyperresponsiveness and obstruction who were 18 to 60 years old were followed for 2 1/2 years. Of the 274 patients enrolled, 56 percent had allergies. The mean forced expiratory volume in one second (FEV₁) was 64 percent of the predicted value. The mean PC₂₀ (the concentration of inhaled histamine causing a 20 percent decrease in FEV₁, a measure of hyperresponsiveness) was 0.26 mg per milliliter. Withdrawal from the study, due mainly to pulmonary symptoms, was less frequent in the corticosteroid group (12 of 91 patients) than in the anticholinergic-drug group (45 of 92 patients) or the placebo group (44 of 91 patients; P<0.001). The mean FEV₁ (±SE) increased by 10.3±1.3 percent of the predicted value in the corticosteroid group within three months and remained stable thereafter, whereas it did not change in the other two groups (P<0.001). The PC₂₀ increased by 2.0 doubling concentrations in the corticosteroid group but did not change in the other groups (P<0.001). In the corticosteroid group, patients who did not smoke, who had allergies, or who were less than 40 years old benefited more from their treatment than did those who smoked, did not have allergies, or were over 40, but all subgroups of the corticosteroid group had improvement as compared with the anticholinergic-drug or placebo group. The addition of an inhaled corticosteroid — but not an inhaled anticholinergic agent — to maintenance treatment with a β₂-agonist (terbutaline) substantially reduced morbidity, hyperresponsiveness, and airways obstruction in patients with a spectrum of obstructive airways disease. (N Engl J Med 1992;327:1413–9.), ASTHMA, a disorder characterized by attacks of dyspnea or wheezing and variable airways obstruction, may cause severe morbidity.¹ The mortality from asthma is rising in several countries.^{2 3 4} Chronic obstructive pulmonary disease (COPD) causes progressive loss of lung function, which also leads to increased morbidity and mortality.⁵ Improvement in the prognosis of these diseases should be a major goal of therapy. In asthma, the prognosis is related primarily to the levels of airways obstruction and hyperresponsiveness.^{6 , 7} In COPD, the prognosis is related primarily to age and the initial level of airways obstruction,⁸ and secondarily to smoking, airways hyperresponsiveness, and perhaps reversibility…