Slowing the Deterioration of Asthma and Chronic Obstructive Pulmonary Disease Observed during Bronchodilator Therapy by Adding Inhaled Corticosteroids: A 4-Year Prospective Study

  1. Edward Dompeling, MD;
  2. Constant P. van Schayck, PhD;
  3. Petrus M. van Grunsven, MD;
  4. Cees L. A. van Herwaarden, MD, PhD;
  5. Reinier Akkermans, MSc;
  6. Johan Molema, MD, PhD;
  7. Hans Folgering, MD, PhD; and
  8. Chris van Weel, MD, PhD
  1. From the University of Nijmegen, Nijmegen, the Netherlands. Requests for Reprints: Edward Dompeling, MD, Department of Family Medicine, University of Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. Acknowledgments: The authors thank L. Bierman and A. Raaymakers for doing the pulmonary function and bronchial hyper-responsiveness measurements; and P. Mulder and H.J.M. van den Hoogen for giving statistical advice. Grant Support: In part by grants from the Dutch Asthma Foundation (numbers 86.28 and 88.35), Glaxo BV (Zeist, The Netherlands), and Boehringer Ingelheim BV (Alkmaar, the Netherlands).

    Abstract

    Objective: To determine if deterioration in patients with asthma or chronic obstructive pulmonary disease (COPD) during bronchodilator therapy could be slowed by additional treatment with an inhaled corticosteroid.

    Design: A 4-year prospective study.

    Setting: Twenty-nine general practices in the catchment area of the University of Nijmegen, Nijmegen, the Netherlands.

    Patients: The study included 56 patients (28 with asthma and 28 with COPD) who showed an annual decrease in the forced expiratory volume in 1 second (FEV1) of at least 80 mL in combination with at least two exacerbations per year during bronchodilator therapy alone. Forty-eight patients completed the study.

    Intervention: During the first 2 years of treatment, patients received only bronchodilator therapy (salbutamol, 400 g, or ipratropium bromide, 40 g). During years 3 and 4, they received additional treatment with beclomethasone dipropionate, 400 g two times daily.

    Results: Prebronchodilator FEV1 increased 458 mL/y (95% CI, 233 to 683 mL/y) during the first 6 months of beclomethasone treatment; FEV1 then decreased 102 mL/y (CI, 57 to 147 mL/y) during months 7 to 24. The annual decline in FEV1 during beclomethasone treatment was less than the decline of 160 mL/y seen before beclomethasone therapy (difference, 58 mL/y; 95% CI, 2 to 87 mL/y). Only in patients with asthma did beclomethasone treatment improve bronchial hyper-responsiveness (assessed by determining the concentration of histamine that provoked a 20% decrease in FEV1 [PC20]) by 3.0 doubling doses per year (95% CI, 0.8 to 5.2 doses per year). Beclomethasone treatment was associated with improvement in peak expiratory flow rate, alleviation of symptoms, and a decrease in the number of exacerbations in both patient groups.

    Conclusion: Adding beclomethasone, 800 g daily, slowed the unfavorable course of asthma or COPD seen with bronchodilator therapy alone. This effect was most evident in asthmatic patients.

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    1. Ann Intern Med May 15, 1993 vol. 118 no. 10 770-778
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