Asthma control during long term treatment with regular inhaled salbutamol and salmeterol

Abstract

Background-The adverse eVects of long term treatment of asthma with the short acting agonist fenoterol have been established in both epidemiological and clinical studies. A study was undertaken to investigate the eYcacy and safety of long term treatment with salbutamol and salmeterol in patients with mild to moderate bronchial asthma. Methods-In a two centre double dummy crossover study 165 patients were randomly assigned to receive salbutamol 400 µg qid, salmeterol 50 µg bid, or placebo via a Diskhaler. All patients used salbutamol as required for symptom relief. The study comprised a four week run in and three treatment periods of 24 weeks, each of which was followed by a four week washout. Asthma control was assessed by measuring mean morning and evening peak expiratory flow rate (PEFR), a composite daily asthma score, and minor and major exacerbation rates. Washout assessments included methacholine challenge and bronchodilator dose response tests. Analysis was by intention to treat. Results-Data from 157 patients were analysed. Relative to placebo, the mean morning PEFR increased by 30 l/min (95% CI 26 to 35) for salmeterol but did not change for salbutamol. Evening PEFR increased by 25 l/min (95% CI 21 to 30) and 21 l/min (95% CI 17 to 26), respectively (p<0.001). Salmeterol improved the asthma score compared to placebo (p<0.001), but there was no overall diVerence with salbutamol. Only daytime symptoms were improved with salbutamol. The minor exacerbation rates were 0.29, 0.88, and 0.97 exacerbations/patient/ year for salmeterol, salbutamol and placebo, respectively (p<0.0001 for salmeterol). The corresponding major exacerbation rates were 0.22, 0.51 and 0.40, respectively (p<0.03 for salmeterol). For salbutamol the asthma score deteriorated over time (p<0.01), and the time spent in major exacerbation was significantly longer compared with placebo (12.3 days (95% CI 4.2 to 20.4)) versus 8.4 days (95% CI 5.2 to 11.6), p = 0.02). There was no evidence of rebound deterioration in asthma control, lung function, or bronchial hyperresponsiveness following cessation of either active treatment, and no evidence of tolerance to salbutamol or salmeterol. Conclusions-Regular treatment with salmeterol is eVective in controlling asthma symptoms and reduces minor more than major exacerbation rates. Salbutamol was associated with improved daytime symptoms but subtle deterioration in asthma control occurred over time. Salbutamol should therefore be used only as required. (Thorax 1998;53:744-752)

Airway resistance variability and response to bronchodilator in children with asthma

“…Similarly, the current study found that asthmatics who were not taking LABA, but were taking ICS and could be classified as mild persistent asthma were the most variable, with highest baseline Rrs SD and greatest decrease in Rrs SD with BD. In contrast, subjects that received LABA with corticosteroids and could be classified as moderate persistent asthmatics had the lowest baseline Rrs SD of the asthma subjects and the smallest decrease with BD, perhaps indicating that LABA may contribute to reduced variability similar to reduced exacerbations reported in some other studies [45,46]. While a prospective study is needed to confirm a relationship of short-term variation in Rrs to long-term variation in airway function and symptoms, this may be important, especially since it has been recently shown that fluctuation analysis of variation in airway function can predict the risk of asthma exacerbations [8].…”

“…Also, the distinction of severity is problematic once treatment is initiated and some of the differences observed may be due more to therapy than to severity. Indeed, in a 20-month cross-over study by TAYLOR et al [45], asthma symptoms and variation in PEFR were higher in asthmatic subjects receiving SABA compared with subjects receiving a LABA. Similarly, the current study found that asthmatics who were not taking LABA, but were taking ICS and could be classified as mild persistent asthma were the most variable, with highest baseline Rrs SD and greatest decrease in Rrs SD with BD.…”

Effects of formoterol and budesonide on GM-CSF and IL-8 secretion by triggered human bronchial epithelial cells

“…A reduced exacerbation frequency was one of the major findings of studies combining inhaled steroid with long-acting b 2 -agonists [2,21]. As asthma exacerbations may be initiated at the epithelial level by secretion of chemokines and growth factors, it was the study9s objective to investigate some of these aspects in vitro.…”

ß<SUB>2</SUB>-Agonist enantiomers: is there a glitch with the chiral switch?

“…This approach has been adopted because of the inflammatory nature of asthma and because, somewhat controversially, regular use of shortacting b 2 -agonists at best confers no distinct benefit on overall asthma control [2], and at worst may cause a deterioration [3].A number of possible mechanisms have been proposed to explain the adverse effects of chronic short-acting b 2 -agonist therapy [4], but the debate continues. One possible explanation currently under consideration is related to the fact that b 2 -agonists are chiral and are administered as racemic mixtures of a pharmacologically active eutomer (e.g.…”

“…This approach has been adopted because of the inflammatory nature of asthma and because, somewhat controversially, regular use of shortacting b 2 -agonists at best confers no distinct benefit on overall asthma control [2], and at worst may cause a deterioration [3].…”