Chest
Volume 101, Issue 1, January 1992, Pages 160-165
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Theophylline and Salbutamol Improve Pulmonary Function in Patients with Irreversible Chronic Obstructive Pulmonary Disease

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To investigate the efficacy of bronchodilators in patients with irreversible chronic obstructive pulmonary disease (COPD), we conducted a double-blind, randomized, four-phase, crossover comparison between placebo, oral theophylline, inhaled salbutamol, and a combination of both drugs in 12 patients with stable COPD (mean age, 63 years) whose increase in forced expiratory volume in 1 s (FEV1) was ≤15 percent following 200 µg of inhaled salbutamol. Patients received two weeks of therapy with each of the test regimens. Both theophylline and salbutamol resulted in statistically significant improvement in FEV1, forced vital capacity (FVC), slow vital capacity (SVC), residual volume (RV), airway resistance (Raw), and maximum expiratory flow rate at 50 percent of vital capacity ( V˙50). In most instances, there were no significant differences between theophylline and salbutamol. Combination therapy produced significantly greater improvement in FEV1, FVC, V50, Raw, and RV than either agent alone. The two drugs interacted in an additive fashion. Neither of the drugs, used singly, significantly reduced the severity or incidence of symptoms. The reduction in dyspnea and wheeze during combination therapy approached statistical significance (p=0.06) and patient preference was significantly in favor of the combination regimen. None of the active treatments produced significantly more side effects than placebo. We conclude that theophylline and inhaled salbutamol produce significant, and approximately equal, improvement in pulmonary function in patients traditionally classified as suffering from “irreversible” COPD. The combination of theophylline and inhaled salbutamol generally results in additional improvement over that obtained with either drug used alone and this improvement is reflected by reduced symptomatology and treatment preference.

(Chest 1992; 101:160-65)

Section snippets

Patients

The study population consisted of patients with stable, nonasthmatic, irreversible, COPD. Patients younger than 70 years of age with a clinical diagnosis of COPD, FEV1 <60 percent of predicted normal, and an FEV1/FVC ratio <0.7 were identified via chart review from the outpatient respiratory clinic of St Michael's Hospital. Patients identified by initial chart review were subsequently excluded, on the basis of detailed review, if they had the following: (1) their FEV1 or FVC values differed by

RESULTS

On the basis of initial chart review, 100 patients with a diagnosis of COPD and age ≤70 years were identified. Of the 100 patients screened, only 14 met all the entry criteria and were willing to participate in the study. Two patients discontinued, one during the theophylline titration period for reasons unrelated to the study and the other during the second treatment phase due to severe dyspnea (at which time he was receiving theophylline). Anthropomorphic and clinical data for the 12 patients

DISCUSSION

The results of our study demonstrate that both theophylline and inhaled salbutamol produced significant, and generally equivalent, spirometric improvement in patients with COPD whose airflow limitation was classified as irreversible on the basis of their acute FEV1 response to inhaled salbutamol. Additional, statistically significant improvement occurred when the two drugs were administered in combination. For most patients, the magnitude of spirometric improvement was clinically important,

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  • Cited by (0)

    Supported by a grant from Purdue Frederick.

    Manuscript received October 2; revision accepted April 12.

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