Is the increase in bronchial responsiveness or FEV1 shortly after cessation ofβ2 -agonists reflecting a real deterioration of the disease in allergic asthmatic patients? A comparison between short-acting and long-acting β2-agonists

Department of General Practice, University of Nijmegen, The Netherlands.
Respiratory Medicine (Impact Factor: 3.09). 04/2002; 96(3):155-62. DOI: 10.1053/rmed.2001.1243
Source: PubMed


Regular use of beta2-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 beta2-agonists use. The aim of this study was to invest gate 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 beta2-agonists, and whether this occurred both after short-acting and long-acting beta2-agonists. Allergic asthmatic patients (n = 134) were randomly allocated to the use of a short-acting (salbutamol), a long-acting beta2-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 FEV 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 beta2-agonist use, a drop was seen in FEV1 from 85.6 (+/- 2.21)% 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 beta2-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 beta2-agonist and placebo use no significant changes were seen. In conclusion, the use of short-acting beta2-agonists resulted in a transient (rebound) effect in FEV while the effects on PC20 may point to a real deterioration of the disease. Long-acting beta2-agonist and placebo use showed no changes. We conclude that a mono-therapy of short-acting and not of long-acting beta2-agonists might have deleterious effects in asthma.

Download full-text


Available from: Chris van Weel, Mar 18, 2015
166 Reads
  • Source
    • "The chronic use of SABA was associated with an increased risk of an acute exacerbation that required an emergency department visit or hospitalization.[18–20] Also, a decrease in lung function after stopping chronic use have been reported with a regular use of SABA.[2122] "
    [Show abstract] [Hide abstract]
    ABSTRACT: A wide range of medications are now available for the treatment of asthma and selection of the optimal treatment combination of agents is essential. This study was designed to evaluate a self-reported drug prescribing pattern for asthma among Nigerian doctors in general practice. It was a cross-sectional survey conducted among general practitioners in six states of Nigeria. For acute severe asthma, 75.9% of the doctors prescribed intravenous methylxanthines, which was combined with oral or inhaled short-acting β(2) agonists (SABA) by 56.3% of them. Systemic steroids were prescribed mainly via the intravenous route by 58.8% of them. Aberrant drugs such as antibiotics, antihistamines, and mucolytics were prescribed by 25.6% of them. For long-term, follow-up treatment of asthma, oral steroids, and oral SABA were commonly prescribed, while inhaled corticosteroids (ICS) and ICS/LABA (long acting beta agonists) were infrequently prescribed. Aberrant drugs such as analgesics, antimalaria, and antihistamines were prescribed by 22.8% of them. About 48% of the doctors had never attended any form of update training on asthma management, whereas, only 16.3% attended update training on asthma within the last year preceding this study. Awareness of international guidelines on asthma treatment was poor among them with only 16.4% being able to mention any correct guideline on asthma management. The poor anti-asthma prescribing behavior among these doctors is associated with a low level of participation at update training on asthma management and poor awareness of asthma guidelines. The Nigerian Medical Association and the Nigerian Thoracic Society should urgently address these problems.
    04/2012; 7(2):78-83. DOI:10.4103/1817-1737.94524
  • [Show abstract] [Hide abstract]
    ABSTRACT: Regular use of long acting beta-2 agonist bronchodilator agents in chronic asthma combined with regular preventer medication gives effective asthma control in adults and adolescents. Patients with chronic asthma are generally treated with a 'preventer medication' to reduce the underlying airways inflammation but often require 'relief' bronchodilators for symptoms. Treatment with regular long acting beta-agonist bronchodilator agents, such as salmeterol (Serevent) or formoterol (Foradile, Oxis) resulted in fewer asthma symptoms by day or night, less relief bronchodilator medication requirement, better lung function, a lower risk of acute worsening of asthma and better quality of life. There were no major adverse effects.There is less information on asthma control in patients who do not use a regular 'preventer medication' or in children under twelve years.
    Cochrane database of systematic reviews (Online) 02/2003; DOI:10.1002/14651858.CD001385 · 6.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In asthmatic patients inadequately controlled on inhaled corticosteroids and/or those with moderate persistent asthma, two main options are recommended: the combination of a long-acting inhaled beta2 agonist (LABA) with inhaled corticosteroids (ICS) or use of a higher dose of inhaled corticosteroids. To determine, in asthmatic patients, the effect of the combination of long-acting beta2 agonists and inhaled corticosteroids compared to a higher dose of inhaled corticosteroids on the incidence of asthma exacerbations, on pulmonary function and on other measures of asthma control and to look for characteristics associated with greater benefit for either treatment option. We identified randomized controlled trials (RCTs) through electronic database searches (MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers until April 2004. RCTs were included that compared the combination of inhaled LABA and ICS to a higher dose of inhaled corticosteroids, in children aged 2 years and older, and in adults with asthma. Studies were assessed independently by two authors for methodological quality and data extraction. Confirmation was obtained from the trialists when possible. The primary endpoint was rate of patients experiencing one or more asthma exacerbations requiring oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), symptoms, use of rescue beta2 agonists, adverse events and withdrawal rates. The meta-analysis was done with RevMan Analyses and the meta-regression, with Stata. Of 593 citations identified, 30 (three pediatric; 27 adult) trials were analysed recruiting 9509 participants, including one study providing two control-intervention comparisons. Only one trial included corticosteroid-naive patients. Participants were symptomatic, generally (N=20 trials) presenting with moderate (FEV1 60-79% of predicted) rather than mild airway obstruction. Trials tested the combination of salmeterol (N=22) or formoterol (N=8) with a median of 400 mcg of beclomethasone or equivalent (BDP-eq) compared to a median of 800 to 1000 mcg/day of BDP-eq. Trial duration was 24 weeks or less in all but four trials. There was no significant group difference in the rate of patients with exacerbations requiring systemic corticosteroids [N=15, RR=0.88 (95% CI: 0.77, 1.02)]. The combination of LABA and ICS resulted in greater improvement from baseline in FEV1 [N=7, WMD=0.10 L (95% CI: 0.07, 0.12)], in symptom-free days [N=8 , WMD=11.90% (95% CI:7.37, 16.44), random effects model], and in the daytime use of rescue beta2 agonists than a higher dose of ICS [N=4, WMD= -0.99 puffs/day (95% CI: -1.41, -0.58), random effects model]. There was no significant group difference in the rate of overall adverse events [N=15, RR=0.93 (95% CI: 0.84, 1.03), random effects model], or specific side effects, with the exception of a three-fold increase rate of tremor in the LABA group [N= 10, RR=2.96 (95%CI: 1.60, 5.45)]. The rate of withdrawals due to poor asthma control favoured the combination of LABA and ICS [N=20, RR=0.69 (95%CI: 0.52, 0.93)]. In adult asthmatics, there was no significant difference between the combination of LABA and ICS and a higher dose of ICS for the prevention of exacerbations requiring systemic corticosteroids. Overall, the combination therapy led to greater improvement in lung function, symptoms and use of rescue beta2 agonists, (although most of the results are from trials of up to 24 weeks duration). There were less withdrawals due to poor asthma control in this group than when using a higher dose of inhaled corticosteroids. Apart from an increased rate of tremor, the two options appear safe although adverse effects associated with long-term ICS treatment were seldom monitored.
    Cochrane database of systematic reviews (Online) 02/2005; 19(4):CD005533. DOI:10.1002/14651858.CD005533 · 6.03 Impact Factor
Show more