Time Course of Change in Bronchial Reactivity with an Inhaled Corticosteroid in Asthma

Vathenen, A.S.; Knox, Alan J.; Wisniewski, A; Tattersfield, Anne E.

doi:10.1164/ajrccm/143.6.1317

Cited by 168 publications

(81 citation statements)

References 5 publications

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“…In the present study, airway reactivity and lung function remained stable in both groups of patients for 12 weeks after ICS withdrawal/reduction, although the placebo-treated patients were more symptomatic during this period, observations that are in keeping with the data of JUNIPER et al [18] and HAAHTELA et al [19]. In contrast, other investigators [20][21][22] have found that the beneficial effects of ICS, in terms of control of symptoms, lung function and airway reactivity, are not maintained after cessation of therapy. There is no single explanation for the conflicting results of the aforementioned studies.…”

Section: Discussionsupporting

confidence: 91%

Does ketotifen have a steroid-sparing effect in childhood asthma?

Canny

Reisman²,

Levison³

1997

Eur Respir J

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In view of the possible systemic side-effects of inhaled corticosteroids (ICS), a study was performed to determine whether ketotifen (versus placebo) can replace or allow a reduction in the dose of ICS required for the maintenance treatment of childhood asthma.Sixty six children (aged 6-13 yrs) with asthma (confirmed by methacholine challenge), who were maintained on ICS, at a dose of ≤1 mg·day -1 , were selected, and 52 subjects completed the trial. Children on long-term oral steroids or cromoglycate were excluded. After a 4 week baseline period, the children were randomized to receive ketotifen, 2 mg·day -1 , or placebo for 32 Weeks. Between weeks 13-20 of the study, the daily dose of steroid was tapered by 25% every second week to the minimum dose tolerated by the patients. For the remainder of the study (Weeks 21-32) the patients continued on this dose (if tolerated). Beta 2 -agonists were allowed, as necessary, for symptom relief During the baseline period, the mean daily ICS dosage was 432 µg in the ketotifen group versus 408 µg in the placebo group (NS). Among the patients who completed the study, the average ICS dosage during the final phase of the study (Weeks 21-32) was only 18% of baseline in the ketotifen group versus 35% in the placebo group (NS). Lung function, diurnal variability in peak flow rates and methacholine sensitivity (provocative concentration producing a 20% fall in forced expiratory volume in one second (PC20)) remained unchanged in both groups throughout the study. During the last 12 weeks of the study, the ketotifen-treated patients were symptomatically better controlled.In the present study, ketotifen did not have a greater steroid-sparing effect than placebo.

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Section: Discussionsupporting

confidence: 91%

Does ketotifen have a steroid-sparing effect in childhood asthma?

Canny

Reisman²,

Levison³

1997

Eur Respir J

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“…day -1 [6,7,31,32], have reported improvements from baseline in morning PEF of 20±40 L . min -1 and in AHR of 1±2 doubling doses.…”

Section: Discussionmentioning

confidence: 97%

Optimal asthma control, starting with high doses of inhaled budesonide

et al. 2000

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The aim of this study was to determine whether outcomes in poorly controlled asthma can be further improved with a starting dose of inhaled budesonide higher than that recommended in international guidelines.The study had a parallel-group design and included 61 subjects with poorly controlled asthma, randomized to receive 3,200 mg or 1,600 mg budesonide daily by Turbuhaler1 for 8 weeks (double-blind), then 1,600 mg . day -1 for 8 weeks (single-blind), followed by 14 months of open-label budesonide dose down-titration using a novel algorithm, with a written asthma crisis plan based on electronic peak expiratory flow monitoring. The primary outcome variable for weeks 1±16 was change in airway hyperresponsiveness (AHR), and, for the open-label phase, mean daily budesonide dose.By week 16, there were large changes from baseline in all outcomes, with no significant differences between the 3,200-and 1,600-mg . day -1 starting dose groups (AHR increased by 3.2 versus 3.0 doubling doses, p=0.7; morning peak flow increased by 134 versus 127 L . min -1 , p=0.8). Subjects starting with 3,200 mg . day -1 were 3.8 times more likely to achieve AHR within the normal range, as defined by a provocative dose of histamine causing a 20% fall in forced expiratory volume in one second (PD20) of $3.92 mmol by week 16 (p=0.03). During dose titration, there was no significant difference in mean budesonide dose (1,327 versus 1,325 mg . day -1 , p>0.3). Optimal asthma control was achieved in the majority of subjects (at completion/withdrawal: median symptoms 0.0 days . week -1 , b 2 -agonist use 0.2 occasions . day -1 , and PD20 2.4 mmol).In subjects with poorly controlled asthma, a starting dose of 1,600 mg . day -1 budesonide was sufficient to lead to optimal control in most subjects. The high degree of control achieved, compared with previous studies, warrants further investigation. Eur Respir J 2000; 15: 226±235.

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“…The magnitude of the reduction differs, but often airway responsiveness remains abnormally increased [50]. When therapy is discontinued, airway responsiveness usually returns to pretreatment levels [53][54][55].…”

Section: Anti-mediator Effectsmentioning

confidence: 99%

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

Chung

Caramori

Adcock

2009

Eur J Clin Pharmacol

121

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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Time Course of Change in Bronchial Reactivity with an Inhaled Corticosteroid in Asthma

Cited by 168 publications

References 5 publications

Does ketotifen have a steroid-sparing effect in childhood asthma?

Does ketotifen have a steroid-sparing effect in childhood asthma?

Optimal asthma control, starting with high doses of inhaled budesonide

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

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