On-demand use of bronchodilators showed less decline in ventilatory function in asthma or bronchitis than continuous use
ACP J Club. 1992 May-June;116:69. doi:10.7326/ACPJC-1992-116-3-069
van Schayck CP, Dompeling E, van Herwaarden CL, et al. Bronchodilator treatment in moderate asthma or chronic bronchitis: continuous or on demand?: A randomised controlled study. BMJ. 1991 Dec 7;303:1426-31.
To evaluate continuous and on-demand long-term bronchodilator treatment of moderate asthma or chronic bronchitis.
Randomized, crossover trial lasting 2 years. Outcome assessment was blinded.
29 general practices in the Netherlands.
223 patients aged ≥ 30 years with asthma or chronic bronchitis and moderate airflow obstruction (forced expiratory volume in 1 s [FEV1] ≥ 50% of predicted) or bronchial hyper-responsiveness (provocative concentration of histamine causing 20% decline in FEV1 [PC20 histamine] ≤ 8 g/L), and who were expected to respond to bronchodilator monotreatment, were included. Those with other pulmonary or life-threatening diseases or with dependency on corticosteroids were excluded.
During an 8-week washout period, all medications but the 2 study drugs were stopped. Patients were randomized either to receive medication on demand (n = 110) or continuously (n = 113), as well as to dry powder inhalations of either salbutamol or ipratropium bromide. The continuous dosage was 4 inhalations of 400-mg salbutamol or 40-mg ipratropium bromide daily. The on-demand group inhaled medications only during exacerbations or periods of dyspnea. After 1 year patients switched drugs but continued with their administration schedules.
Main outcome measures
Decline in FEV1, PC20 histamine, respiratory symptoms, quality of life, and drug preferences were measured every 6 months.
160 patients (72%) completed the study. 27 patients dropped out because of inadequate response to continuous treatment compared with 13 failures of treatment on demand (P = 0.03). After adjusting for age, sex, smoking, and initial FEV1 the decline in FEV1 was -0.072 L/y for continuously treated patients and -0.020 L/y for the on-demand group (difference, 0.052 L/y, 95% CI 0 to 0.106 L/y, P = 0.05). Bronchial responsiveness increased slightly with continuous treatment in chronic bronchitis after 12 months. Exacerbations, perceived health, symptoms, and quality of life were similar in both groups and unchanged during the study. Study outcomes were similar for both drugs and both diseases. Patients in the on-demand group preferred salbutamol.
When compared with on-demand therapy, continuous bronchodilator treatment with salbutamol or ipratropium worsened decline in forced expiratory volume in patients with moderate asthma or bronchitis.
Sources of funding: Dutch Asthma Foundation and Boehringer Ingelheim Netherlands.
Address for article reprint: Dr. C.P. van Schayck, Nijmegen University, P.O. Box 9101, Nijmegen 6500 HB, The Netherlands.
Morbidity and mortality from asthma have been rising over the past decade despite significant advances in our understanding of the pathogenesis of this disease. Most asthma experts now recommend anti-inflammatory agents for management of asthma. In addition, a growing body of evidence suggests that overuse or continuous use of β-adrenergic bronchodilators can actually worsen asthma, perhaps contributing to morbidity and mortality.
The primary finding that continuous bronchodilator treatment led to a greater decline in FEV1 of 0.052 L/y is of concern and clinically relevant, although the causes for this decline are unknown. One proposed hypothesis is that continuous β-adrenergic treatment leads to increased bronchial hyper-responsiveness. This was not found for all patients in this study but has been observed before (1, 2). The second intriguing finding is that continuous treatment with ipratropium (an anticholinergic agent) also resulted in a significant decline in ventilatory function. This finding deserves further clinical investigation.
Although the potential deleterious effects of continuous bronchodilator treatment in asthma and chronic bronchitis have not been fully elucidated, clinicians should be cautious in prescribing these agents on a continuous basis. Patients with asthma may be better served by using continuous aerosol steroids (or cromolyn) and bronchodilators when needed. The new long-acting adrenergic bronchodilators should be studied carefully before they are prescribed routinely.
James T. Li, MD, PhD
Mayo ClinicRochester, Minnesota, USA
James T. Li, MD, PhD
Rochester, Minnesota, USA
2. van Schayck CP, Graafsma SJ, Visch MB, et al. Increased bronchial hyperresponsiveness after inhaling salbutamol during one year is not caused by subsensitization to salbutamol. J Allergy Clin Immunol. 1990;86:793-800.