Is the increase in bronchial responsiveness or FEV1 shortly after cessation of β2-agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting β2-agonists

C. P. Van Schayck, S. G.M. Cloosterman, I. D. Bijl-Hofland, H. Van Den Hoogen, H. Th M. Folgering, C. Van Weel

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16 Citations (Scopus)

Abstract

Regular use of β2-agonists might result in increased bronchial hyper-responsiveness (BHR) and decreased forced expiratory volume in 1 sec (FEV1). It has been suggested that these possible detrimental effects are not a real deterioration of the disease, but that it might be only a transient (rebound) effect shortly after discontinuing this regular use. Moreover, these effects are thought to occur especially during short-acting and not during long-acting β2-agonists use. The aim of this study was to investigate whether a rebound effect (a pharmacological deterioration effect diminishing after several hours) in FEV1 and PC20 (concentration of histamine causing a 20% fall in FEV1 with regard to baseline) occurred after cessation of regular use of β2-agonists, and whether this occurred both after short-acting and long-acting β2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting β2-agonist (formoterol) or placebo for 12 weeks (double-blind, double-dummy). No other asthma medication was allowed, including inhaled corticosteroids. At the start and every 4 weeks later FEV1 and PC20 were measured, each time at least 12 h after the last doses of study medication, which is in the possible rebound period. To investigate whether a (transient) rebound effect occurred, parameters were additionally measured at least 72 h later after discontinuation of the study medication. After 12 weeks of short-acting β2-agonist use, a drop was seen in FEV1 from 85.6(±2.4)% predicted to 78.8 (±2.9)% predicted, measured 15 h (median) after the last doses of medication. This was significantly different compared to placebo. When measured 168 h (median) later FEV1 recovered to 85.5 (± 2.4)% predicted, comparable to baseline. PC20 decreased with -1.17 (±0.44) doubling dose after 12 weeks of short-acting β2-agonist use, measured 15 h after the last doses of medication, which was significantly different compared to placebo. However, 168 h later PC20 recovered slightly with +0.55 (±0.34) doubling dose, but this value was still lower compared to placebo. In contrast, during long-acting β2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting β2-agonists resulted in a transient (rebound) effect in FEV1 while the effects on PC20 may point to a real deterioration of the disease. Long-acting β-agonist and placebo use showed no changes. We conclude that a mono-therapy of short-acting and not of long-acting β2-agonists might have deleterious effects in asthma.

Original languageEnglish
Pages (from-to)155-162
Number of pages8
JournalRespiratory Medicine
Volume96
Issue number3
DOIs
Publication statusPublished - Mar 2002
Externally publishedYes

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