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
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.
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[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.
- "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. "
- [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.
- [Show abstract] [Hide abstract] ABSTRACT: Background: The regular administration of beta(2)-agonists may be associated with the development of tolerance to their effects. Purpose: To assess the effect of regular beta(2)-agonist use on respiratory function and beta(2)-receptor function in asthmatic patients. Data Sources: Comprehensive searches of the EMBASE, MEDLINE, and CINAHL databases from 1966 to June 2003 and references of identified articles and reviews. Study Selection: Randomized, placebo-controlled trials that studied at least 1 week of regular beta(2)-agonist administration in patients with asthma and did not allow "as-needed" beta(2)-agonist use in the placebo group. Data Extraction: Outcomes measured in the active treatment and placebo groups were the change in FEV, in response to treatment and subsequent beta(2)-agonist administration, the provocative concentration of bronchoconstrictive agents causing a 20% reduction in FEV1 (PC20), and in vitro variables of leukocyte beta(2)-receptor function. Data Synthesis: Pooled results of 22 trials showed that regular beta(2)-agonist use, compared with placebo, did not change the mean FEV, after treatment or the net FEV, treatment effect but substantially reduced the following: the peak FEV, response to subsequent beta(2)-agonist administration (change, -17.8% [95% CI, -27.2% to -8.5%]); the FEV, dose response to subsequent beta(2)agonists (-34.8% [CI, -45.7% to -24%]); the PC20 to combined bronchoconstrictive stimuli (-26% [CI, -37% to -11%]); and leukocyte beta(2)-receptor density (-18.3% [CI, -31.6% to -5.1%]), binding affinity (-23.1% [CI, -39.4% to -6.8%]), and in vitro response to isoproterenol (-32.7% [CI, -56.5% to -9.0%]). Conclusion: Regular beta(2)-agonist use for at least 1 week in patients with asthma results in tolerance to the drug's bronchodilator and nonbronchodilator effects and may be associated with poorer disease control compared with placebo.