Daily inhaled corticosteroids (ICS) are the recommended mainstay of treatment in children and adults with persistent asthma. Yet often, ICS are used intermittently by patients or recommended by physicians to be used only at the onset of exacerbations.
The aim of this review was to compare the efficacy and safety of intermittent versus daily ICS in the management of children and adults with persistent asthma and preschool-aged children suspected of persistent asthma.
We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to December 2011.
We included randomised controlled trials (RCTs) that compared intermittent ICS versus daily ICS in children and adults with persistent asthma. No co-interventions were permitted other than rescue relievers and oral corticosteroids used during exacerbations.
Two review authors independently assessed trials for inclusion, methodological quality and extracted data. The primary efficacy outcome was the number of patients with one or more exacerbations requiring oral corticosteroids and the primary safety outcome was the number of patients with serious adverse health events. Secondary outcomes included exacerbations, lung function tests, asthma control, adverse effects, withdrawal rates and inflammatory markers. Equivalence was assumed if the risk ratio (RR) estimate and its 95% confidence interval (CI) were between 0.9 and 1.1.
Six trials (including one trial testing two relevant protocols) met the inclusion criteria for a total of seven group comparisons. The four paediatric trials (two involving preschool children and two school-aged children) and two adult parallel-group trials, lasting 12 to 52 weeks, were of high methodological quality. A total of 1211 patients with confirmed, or suspected, persistent asthma contributed to the meta-analyses. There was no statistically significant group difference in the risk of patients experiencing one or more exacerbations requiring oral corticosteroids (1204 patients; RR 1.07; 95% CI 0.87 to 1.32). The patients' age, severity of airway obstruction, step-up protocol used during exacerbations and trial duration did not significantly influence the primary efficacy outcome. No group difference was observed in the risk of patients with serious adverse health events (1055 patients; RR 0.82; 95% CI 0.33 to 2.03). Compared to the daily ICS group, the intermittent ICS group displayed a smaller improvement in change from baseline peak expiratory flow rate (PEFR) by 2.56% (95% CI -4.49% to -0.63%), fewer symptom-free days (standardised mean difference (SMD) -0.15 (95% CI -0.28 to -0.03), fewer asthma control days -9% (95% CI -14% to -4%), more use of rescue β(2)-agonists by 0.12 puffs/day (95% CI 0 to 0.23) and a greater increase from baseline in exhaled nitric oxide of 16.80 parts per billion (95% CI 11.95 to 21.64). There was no significant group difference in forced expiratory volume in one second (FEV(1)), quality of life, airway hyper-reactivity, adverse effects, hospitalisations, emergency department visits or withdrawals. In paediatric trials, intermittent ICS (budesonide and beclomethasone) were associated with greater growth by 0.41 cm change from baseline (532 children; 95% CI 0.13 to 0.69) compared to daily treatment.
In children and adults with persistent asthma and in preschool children suspected of persistent asthma, intermittent and daily ICS strategies did not significantly differ in the use of rescue oral corticosteroids and the rate of severe adverse health events, neither did they reach equivalence. Daily ICS was superior to intermittent ICS in several indicators of lung function, airway inflammation, asthma control and reliever use. Both treatments appeared safe, but a modest growth suppression was associated with daily, compared to intermittent, inhaled budesonide and beclomethasone. The clinician should carefully weigh the potential benefits and harm of each treatment option, taking into account the unknown long-term (> one year) impact of intermittent therapy on lung growth and lung function decline.
[Show abstract][Hide abstract] ABSTRACT: In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and⁄or gaps in the previous guidelines.
Four clinical questions were identified as a focus for the updated guideline: the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy; the initiation of adjunct therapy to inhaled corticosteroids (ICS) for uncontrolled asthma; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever, and as a reliever and a controller; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan. The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics. In addition, literature searches were performed to identify relevant systematic reviews and randomized controlled trials. The panel formally assessed and graded the evidence, and made 34 recommendations.
The updated guideline recommendations outline a role for inclusion of assessment of sputum eosinophils, in addition to standard measures of asthma control, to guide adjustment of controller therapy in adults with moderate to severe asthma. Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations. New recommendations for the adjustment of controller medication within written action plans are provided. Finally, priority areas for future research were identified.
The present clinical practice guideline is the first update of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committee's new guideline development process. Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide updates reflecting new evidence.
Canadian respiratory journal: journal of the Canadian Thoracic Society 03/2012; 19(2):127-64. · 1.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inhaled corticosteroids are used extensively in the treatment of asthma and chronic obstructive lung disease due to their demonstrated efficacy in reducing exacerbations and improving overall control. Their beneficial effect is based on their broad anti-inflammatory and immunosuppressive effects. The available inhaled corticosteroids vary in their therapeutic index based on individual drug potency, pharmacokinetics and specific delivery system. Although ICS are used in all age groups including children, younger and smaller children may be at a greater risk for adverse systemic effects as they can receive higher mg/kg doses of ICSs compared to older children. Most of the benefit from ICSs occurs in the low-medium dose range with minimal additional improvement with higher doses, although some patients may benefit from these higher doses. While ICS are the preferred agents for managing persistent asthma in all ages, their benefit in COPD is less convincing. When used appropriately, ICSs have few adverse events at low-medium doses but risk increases with high dose ICS. Although several new drugs are being developed and evaluated, it is unlikely that any of these new medications will replace ICS as the preferred initial long-term controller therapy for asthma but more effective initial controller therapy could be developed for COPD.
American Journal of Respiratory and Critical Care Medicine 01/2013; 187(8). DOI:10.1164/rccm.201210-1853PP · 13.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Intermittent ICS treatment with SABA in response to symptoms, is an emerging strategy for control of mild-to-moderate asthma, and recurrent wheezing. This systematic revue compares the efficacy of daily vs. intermittent ICS among preschoolers, children and adults with persistent wheezing and mild to moderate stable persistent asthma.
Systematic review of randomized, placebo-controlled trials with a minimum of 8 weeks of daily (daily ICS with rescue SABA during exacerbations) vs. intermittent ICS (ICS plus SABA at the onset of symptoms), were retrieved through different databases. Primary outcome was asthma exacerbations; secondary outcomes were pulmonary function tests, symptoms, days without symptoms, SABA use, corticosteroids use, days without rescue medication use, expired nitric oxide and serious adverse events.
Seven trials (1367 participants) met inclusion criteria there was no statistically significant difference in the rate of asthma exacerbations between those with daily vs. intermittent ICS (0.96; 95% CI: 0.86, 1.06, I(2) = 0%). In the sub-group analysis, no differences were seen in duration of studies, step-up strategy or age. However, compared to intermittent ICS, the daily ICS group had a significant increase in asthma-free days and non-significant decreases in rescue SABA use and exhaled nitric oxide measurement.
No significant differences between daily and intermittent ICS in reducing the incidence of asthma exacerbations was found. However, the daily ICS strategy was superior in many secondary outcomes. Therefore, this study suggests to not change daily for intermittent ICS use among preschoolers, children with persistent wheezing and adults with mild-to-moderate stable persistent asthma. International prospective register of systematic reviews http://www.crd.york.ac.uk/PROSPERO/ (CRD42012003228).
Respiratory medicine 06/2013; 107(8). DOI:10.1016/j.rmed.2013.05.005 · 3.09 Impact Factor
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