Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma

Koopmans, Julia

doi:10.1136/thx.2005.051292

Cited by 26 publications

(22 citation statements)

References 34 publications

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“…Moreover, improvements in lung function, symptom scores and bronchial hyper-responsiveness following inhaled fluticasone (500 μg daily) in combination with salmeterol (100 μg daily) treatment were associated with changes in sputum α2 macroglobulin and albumin rather than in sputum cell counts [131] and also reduced serum IL-5 and peripheral blood eosinophil numbers [132].…”

Section: Moderate Persistent Asthmamentioning

confidence: 98%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

123

106

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International audienceInhaled corticosteroid (ICS) therapy in combination with long-acting β-adrenergic agonists represents the most important treatment for chronic airways diseases such as asthma and chronic obstructive pulmonary disease (COPD). ICS therapy forms the basis for treatment of asthma of all severities, improving asthma control, lung function and preventing exacerbations of disease. Use of ICS has also been established in the treatment of COPD, particularly symptomatic patients, who experience useful gains in quality of life, likely from an improvement in symptoms such as breathlessness and in reduction in exacerbations, and an attenuation of the yearly rate of deterioration in lung function. The addition of long-acting β-agonist (LABA) therapy with ICS increases the efficacy of ICS effects in moderate-to-severe asthma. Thus, a 800 μg daily dose of the ICS budesonide reduced severe exacerbation rates by 49% compared to a low dose of 200 μg daily, and addition of the LABA formoterol to budesonide (800 μg) led to a 63% reduction. In COPD, the effects of ICS are less prominent but there are beneficial effects on the decline in FEV and the rate of exacerbations. A reduction in the rate of decline in FEV of 16 ml/year with a 25% reduction in exacerbation rate has been reported with the salmeterol and fluticasone combination. A non-significant 17.5% reduction in all-cause mortality rate with ICS and LABA is reported. Chronic inflammation is a feature of both asthma and COPD, although there are site and characteristic differences. ICS targets this inflammation although this effect of ICS is less effective in patients with severe asthma and with COPD; however, addition of LABA may potentiate the anti-inflammatory effects of ICS. An important consideration is the presence of corticosteroid insensitivity in these patients. Currently available ICS have variably potent binding activities to specific glucocorticoid receptors, leading to inhibition of gene expression by either binding to DNA and inducing anti-inflammatory genes or by repressing the induction of pro-inflammatory mediators. Local side effects of ICS include oral candidiasis, hoarseness and dysphonia, while systemic side effects, such as easy bruising and reduction in growth velocity or bone mineral densitometry, are usually restricted to doses above maximally recommended doses. Use of LABA alone in patients with asthma increases the risk of asthma-related events including deaths, but this is less observed with the combination of ICS and LABA. Therefore, use of LABA alone is not recommended for asthma therapy. Future progress in ICS development will be characterised by the introduction of ICS with greater efficacy with a limited side-effect profile, and by longer-acting ICS that can be used in combination with once-daily LABAs. Other agents that could improve the efficacy of corticosteroids or reverse corticosteroid insensitivity may be added to ICS. ICS in combination with LABAs will continue to remain the main focus of treatment of airways diseases

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Section: Moderate Persistent Asthmamentioning

confidence: 98%

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

123

106

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“…[233][234][235][236][237][238] The trials were published between 1999 and 2006 ( Table 55). Four were multi-centre studies and two single-centre studies.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Four were multi-centre studies and two single-centre studies. Sample sizes were 54 and 282 in the two single-centre studies 236,237 and ranged between 349 and 3421 participants in the multi-centre studies. All but one trial 233 reported that a power calculation was undertaken and sample sizes suggest that adequate power was met.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…All but one trial 233 reported that a power calculation was undertaken and sample sizes suggest that adequate power was met. However, in the Koopmans and colleagues study 236 analysis was based on sputum eosinophils as the primary outcome, with lung function and symptoms as secondary outcomes. The sample size of 54 may not be powered for these secondary outcomes.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…235 Three trials compared 500 µg/day FP with FP/SAL 500/100 µg/day. [236][237][238] One trial compared FP 1000 µg/day with FP/SAL 1000/100 µg/day.…”

Section: Study Characteristicsmentioning

confidence: 99%

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Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Shepherd¹,

Rogers²,

Anderson³

et al. 2008

Health Technol Assess

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Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children

Ducharme

Chróinín

Greenstone

et al. 2010

Cochrane Database of Systematic Reviews

132

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Background Long-acting inhaled ß2-adrenergic agonists (LABAs) are recommended as ’add-on’ medication to inhaled corticosteroids (ICS) in the maintenance therapy of asthmatic adults and children aged two years and above. Objectives To quantify in asthmatic patients the safety and efficacy of the addition of LABAs to ICS in patients insufficiently controlled on ICS alone. Search methods We identified randomised controlled trials (RCTs) through electronic database searches (the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE and CINAHL), bibliographies of RCTs and correspondence with manufacturers until May 2008. Selection criteria We included RCTs if they compared the addition of inhaled LABAs versus placebo to the same dose of ICS in children aged two years and above and in adults. Data collection and analysis Two review authors independently assessed studies for methodological quality and extracted data. We obtained confirmation from the trialists when possible. The primary endpoint was the relative risk (RR) of asthma exacerbations requiring rescue oral corticosteroids. Secondary endpoints included pulmonary function tests (PFTs), rescue beta2-agonist use, symptoms, withdrawals and adverse events. Main results Seventy-seven studies met the entry criteria and randomised 21,248 participants (4625 children and 16,623 adults). Participants were generally symptomatic at baseline with moderate airway obstruction despite their current ICS regimen. Formoterol or salmeterol were most frequently added to low-dose ICS (200 to 400 μg/day of beclomethasone (BDP) or equivalent) in 49% of the studies. The addition of a daily LABA to ICS reduced the risk of exacerbations requiring oral steroids by 23% from 15% to 11% (RR 0.77, 95% CI 0.68 to 0.87, 28 studies, 6808 participants). The number needed to treat with the addition of LABA to prevent one use of rescue oral corticosteroids is 41 (29, 72), although the event rates in the ICS groups varied between 0% and 38%. Studies recruiting adults dominated the analysis (6203 adult participants versus 605 children). The subgroup estimate for paediatric studies was not statistically significant (RR 0.89, 95% CI 0.58 to 1.39) and includes the possibility of the superiority of ICS alone in children. Higher than usual dose of LABA was associated with significantly less benefit. The difference in the relative risk of serious adverse events with LABA was not statistically significant from that of ICS alone (RR 1.06, 95% CI 0.87 to 1.30). The addition of LABA led to a significantly greater improvement in FEV1 (0.11 litres, 95% 0.09 to 0.13) and in the proportion of symptom-free days (11.88%, 95% CI 8.25 to 15.50) compared to ICS monotherapy. It was also associated with a reduction in the use of rescue short-acting ß2-agonists (−0.58 puffs/day, 95% CI −0.80 to −0.35), fewer withdrawals due to poor asthma control (RR 0.50, 95% CI 0.41 to 0.61), and fewer withdrawals due to any reason (RR 0.80, 95% CI 0.75 to 0.87). There was no statistically significant group difference ...

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Adding salmeterol to an inhaled corticosteroid: long term effects on bronchial inflammation in asthma

Cited by 26 publications

References 34 publications

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Inhaled corticosteroids as combination therapy with β-adrenergic agonists in airways disease: present and future

Systematic review and economic analysis of the comparative effectiveness of different inhaled corticosteroids and their usage with long-acting beta2 agonists for the treatment of chronic asthma in adults and children aged 12 years and over

Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children

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