Chest
Volume 121, Issue 1, January 2002, Pages 151-157
Journal home page for Chest

Clinical Investigations
Asthma
Initial Improvements in Lung Function and Bronchial Hyperresponsiveness Are Maintained During 5 Years of Treatment With Inhaled Beclomethasone Dipropionate and Terbutaline

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Objectives

Treatment with inhaled corticosteroids reduces bronchial hyperresponsiveness and relieves airways obstruction in patients with asthma. Up to now, it is unknown whether initial improvements are maintained over a long period of time. Therefore, we assessed whether initial improvements in FEV1, provocative concentration of histamine causing a 20% fall in FEV1 (PC20), and peak expiratory flow (PEF) persist with a constant dose of inhaled corticosteroids. Furthermore, we investigated whether FEV1, PC20, PEF indexes, and symptom scores improve after increasing the dose of inhaled corticosteroids in patients who did not respond sufficiently to treatment with beclomethasone dipropionate (BDP), 800 μg/d.

Methods

Sixty-eight patients with bronchial hyperresponsiveness and airways obstruction completed a previous study on 3 years of treatment with terbutaline, 500 μg qid, and BDP, 200 μg qid. Fifty-eight of these patients participated in the current extension of another 2.5 years of follow-up. Every 6 months, FEV1 and PC20 were measured. Five patients dropped out of the study, one for pulmonary reasons. Forty-four patients continued treatment with BDP, 800 μg/d (BDP-800 group), and 9 patients received a higher dose of BDP (500 μg tid; BDP-1,500 group) after the first 3 years because of a rapid decline in FEV1 (> 50 mL/yr) despite BDP treatment during the previous study period.

Results

After the initial improvement, the mean slope of individual regression lines for FEV1, PC20, and morning PEF were − 28 mL/yr,− 0.01 doubling concentrations per year, and 0.6 L/min/yr, respectively, in the BDP-800 group. In the BDP-1,500 group, there were no statistically significant improvements in FEV1, PC20, PEF indexes, and symptom scores after increasing the dose of BDP.

Conclusions

We conclude that initial improvements in FEV1, PC20, and PEF are well preserved over 5 years in patients with obstructive airways diseases who are treated with terbutaline and BDP. In the patients who responded sufficiently to 800 μg/d of BDP, there was no accelerated decline in FEV1 compared with the general population. Increasing the dose of BDP in a small group of patients with an accelerated fall in FEV1 (initially treated with a moderate dose of BDP) resulted in no significant improvement in FEV1, PC20, PEF indexes, and symptom scores.

Section snippets

Materials and Methods

The present study (hereafter called the second phase) was a 2.5-year continuation of a previous 3-year evaluation (hereafter called the first phase) of different treatment regimens (β2-agonist alone or in combination with an inhaled corticosteroid or an anticholinergic agent) in patients with bronchial hyperresponsiveness and moderate-to-severe airways obstruction (asthma and COPD).27 Two hundred seventy-four patients aged 18 to 60 years were originally included at six university pulmonary

Results

Fifty-eight of 68 patients were willing to participate in the second phase. These participants were 9.7 years older than the 10 nonparticipants (p < 0.05). There were no further statistically significant differences between these groups, especially not with respect to lung function or bronchial hyperresponsiveness. During the second phase, four subjects dropped out for other than pulmonary reasons. One additional patient receiving BDP, 800 μg/d, had frequent exacerbations and was switched to

Discussion

The second phase of this study was an observational one. With the current knowledge on efficacy of these anti-inflammatory drugs, it is not ethical to withhold patients from treatment with inhaled corticosteroids for years on end. The study shows that in patients with bronchial hyperresponsiveness and airways obstruction who respond to treatment with inhaled BDP and terbutaline, initial improvements in FEV1 percent predicted and PC20 were well maintained over an additional period of 5 years. An

Appendix

The Dutch Chronic Nonspecific Lung Disease Study Group consists of a steering committee (K.F. Kerrebijn, Ph.H. Quanjer, H.J. Sluiter), and members from the Departments of Pulmonology of the University Hospital of Amsterdam (E.M. Pouw, D.F.M.E. Schoonbrood, C.M. Roos, H.M. Jansen), Groningen (P.L.P. Brand, A. de Gooijer, H.A.M. Kerstjens, D.S. Postma, Th.W. van der Mark, H.J. Sluiter, G.H. Koeïter), Leiden (P.M. de Jong, P.J. Sterk, A.M.J. Wever, J.H. Dijkman), Nijmegen (P.N.R. Dekhuijzen,

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    This study was made possible by grants from the Netherlands' Health Research Promotion Program and Glaxo. Medication was supplied by Astra Pharmaceuticals, Boehringer Ingelheim, and Glaxo.

    A complete list of participants is given in the Appendix.

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