Chest
Volume 104, Issue 4, October 1993, Pages 1101-1107
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Clinical Investigations: COPD/Asthma
Effects of Theophylline Withdrawal in Severe Chronic Obstructive Pulmonary Disease

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To determine the value of theophylline in the maintenance therapy of patients with severe chronic obstructive pulmonary disease (COPD), we conducted a trial of theophylline therapy withdrawal in 38 clinically stable patients with severe COPD (FEV1 <60 percent) predicted. Symptoms, lung function, blood gases, and 6-min walking distance were assessed on days 1 and 2. Quality of life and overall dyspnea were scored using four different clinical rating scales. Theophylline therapy was continued in 20 patients and replaced by placebo from day 3 on in the remainder; measurements were repeated on days 5 and 6. Withdrawal of theophylline therapy resulted in significant (p<0.05) deterioration in lung function, exercise performance, and two indices of overall dyspnea, and a significant increase in scoring of symptoms and auscultation findings. Individual analysis revealed a clinically relevant deterioration in 72 percent of patients from whom theophylline therapy was withdrawn, while only 15 percent of patients receiving theophylline exhibited deterioration. No major side effects were observed. Our data show that about half of the patients with severe COPD can be considered as theophylline responders. The response of these patients to withdrawal of theophylline therapy suggests that the clinical effectiveness of this drug cannot be explained exclusively by bronchodilation. Due to the inherent difficulties in predicting response to theophylline, its effectiveness in patients with severe COPD should be determined individually, including assessment of exercise performance and ratings of dyspnea.

Section snippets

Patients

We stdied 39 patients aged 40 to 80 years. Diagnosis followed the guidelines of the American Thoracic Society.11 Patients were included on the basis of the following criteria: (1) history of prolonged cigarette smoking and gradual progression of dyspnea on exertion over many years; (2) no history of atopy; (3) stable clinical condition as judged by discharge from hospital being planned within the next week; (4) absence of other major medical problems such as congestive heart failure, liver

Patients

We studied 39 patients who fulfilled the inclusion criteria. Randomization resulted in 18 patients being assigned to the placebo group and 21 being assigned to the theophylline group. One male patient in the theophylline group did not complete the study due to an acute exacerbation unrelated to the study. Mean age ± SD of the 38 patients who completed the study was 66.2±8.2 years, with no significant difference between groups. Two patients in the placebo group and one patient in the

Discussion

The present study demonstrates small but significant deteriorations in lung function, PaCO2, exercise performance, symptoms and auscultation, and two indices of overall dyspnea 2 days after theophylline therapy withdrawal. Analysis of individual data reveals clinically relevant deterioration after withdrawal of theophylline therapy in more than half of the patients.

Theophylline has been a first-line drug in the treatment of chronic obstructive airway disease for decades. In recent years, it has

Acknowledgment

This investigation was part of the doctoral thesis of R. E. Wegner.

References (29)

  • TandonMK et al.

    Bronchodilator treatment for partially reversible chronic obstructive airways disease

    Thorax

    (1991)
  • GuyattGH et al.

    Bronchodilators in chronic air-flow limitation: effects on airway function, exercise capacity, and quality of life

    Am Rev Respir Dis

    (1987)
  • SahayJN et al.

    A comparative trial of ipratropium bromide (Atrovent), controlled release theophylline (Phyllocontin), and a combination of these in patients with reversible airflow obstruction

    Br J Clin Pract

    (1986)
  • BleeckerER et al.

    Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease

    Am J Med

    (1991)
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