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

Edward Dompeling, MD; Constant P. van Schayck, PhD; Petrus M. van Grunsven, MD; Cees L. A. van Herwaarden, MD, PhD; Reinier Akkermans, MSc; Johan Molema, MD, PhD; Hans Folgering, MD, PhD; and Chris van Weel, MD, PhD
[+] Article, Author, and Disclosure Information

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).

Copyright 2004 by the American College of Physicians

Ann Intern Med. 1993;118(10):770-778. doi:10.7326/0003-4819-118-10-199305150-00003
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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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Figure 1.
Forced expiratory volume in 1 second before and after bronchodilator therapy during the 4-year study period.Top left.nTop right.Bottom left.111

All patients ( = 48). Patients with asthma. Patients with chronic obstructive pulmonary disease. BDP = beclomethasone dipropionate; FEV = forced expiratory volume in one second; E = the extrapolated end point if bronchodilator therapy alone had been continued during the third and fourth years of treatment; E = the extrapolated end point with a correction for regression to the mean; pre = prebronchodilator FEV ; post = postbronchodilator FEV .

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Figure 2.
The histamine PC20 values during the 4-year study period.Left panel.Right panel.C20

Patients with asthma. Patients with chronic obstructive pulmonary disease. BDP = beclomethasone dipropionate; P = provoking concentration of histamine that induces a 20% decrease in forced expiratory volume in 1 second.

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Figure 3.
A theoretical comparison between the effects of beclomethasone therapy and ongoing bronchodilator therapy on the time to development of a certain severe degree of chronic airflow limitation.11111111

Comparison is based on data from the study. The prebronchodilator forced expiratory volume in 1 second (FEV ) at the start of the 4-year intervention study was 2.07 L; the annual decline was 0.160 L/y without inhaled corticosteroid therapy and 0.100 L/y with corticosteroid therapy (both asthmatics and patients with chronic obstructive pulmonary disease). Assuming that the annual decline in FEV remains stable over the course of time. The time before an FEV of 1.0 L is reached without corticosteroid intervention equals (2.07 1.0)/0.160, or 6.7 years; and time to an FEV of 1.0 L with corticosteroid intervention equals 0.5 + ([2.07 + 0.23 1.0]/0.100), or 13.5 years (0.5 is the delay caused by the increase in FEV during months 1 to 6 of beclomethasone and 0.23 is the absolute increase in FEV during this period). Time to an FEV level of 0.5 L without corticosteroid intervention equals (2.07 0.5)/0.160, or 9.8 years; and time to an FEV of 0.5 L with corticosteroid equals 0.5 + ([2.07 + 0.23 0.5]/0.10), or 18.5 years. It appears that corticosteroid intervention almost doubles the time before low levels of lung function (0.5 to 1.0 L) are reached.

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