TY - JOUR
T1 - 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
AU - Van Schayck, C. P.
AU - Cloosterman, S. G.M.
AU - Bijl-Hofland, I. D.
AU - Van Den Hoogen, H.
AU - Folgering, H. Th M.
AU - Van Weel, C.
PY - 2002/3
Y1 - 2002/3
N2 - 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.
AB - 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.
KW - Asthma
KW - FEV
KW - Long-acting β-agonists
KW - PC
KW - Short-acting β-agonists
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=0036489999&partnerID=8YFLogxK
U2 - 10.1053/rmed.2001.1243
DO - 10.1053/rmed.2001.1243
M3 - Article
SN - 0954-6111
VL - 96
SP - 155
EP - 162
JO - Respiratory Medicine
JF - Respiratory Medicine
IS - 3
ER -