title: Intermittent inhaled corticosteroid therapy versus placebo for persistent asthma in children and adults.
abstract: BACKGROUND
  International guidelines advocate using daily inhaled corticosteroids (ICS) in the management of children and adults with persistent asthma. However, in real world clinical settings, these medicines are often used at irregular intervals by patients. Recent evidence suggests that the use of intermittent ICS, with treatment initiated at the time of early symptoms, may still have benefits for reducing the severity of an asthma exacerbation.
  
  
  OBJECTIVE
  To compare the efficacy and safety of intermittent ICS versus placebo in the management of children and adults diagnosed with, or suspected to have, symptoms of mild persistent asthma.
  
  
  METHODS
  We searched the Cochrane Airways Group Specialised Register of trials (CAGR), the ClinicalTrials.gov website and the World Health Organization (WHO) trials portal in March 2015.
  
  
  METHODS
  We included randomised controlled trials (RCTs) that compared intermittent ICS versus placebo in children and adults with symptoms of persistent asthma. No co-interventions were permitted other than rescue relievers and oral corticosteroids used during exacerbations.
  
  
  METHODS
  Two review authors independently assessed trials for inclusion, methodological quality and extracted data. The primary efficacy outcome was the risk of asthma exacerbations requiring oral corticosteroids and the primary safety outcome was serious adverse health events. Secondary outcomes included exacerbations, lung function tests, asthma control, adverse effects, and withdrawal rates. Quality of the evidence was assessed using the GRADE criteria.
  
  
  RESULTS
  Six trials (representing 490 preschool children, 145 school-aged children and 240 adults) met the inclusion criteria. Study durations were 12 to 52 weeks. Results for preschool children were presented in a separate analysis as this represents a distinct clinical condition, not necessarily related to the development of long term asthma.There was a reduction in the risk of patients experiencing one or more exacerbations requiring oral corticosteroids in older children (145 participants, odds ratio (OR) 0.57; 95% confidence interval (CI) 0.29 to 1.12, low quality evidence) and adults with asthma (240 participants, OR 0.10; 95% CI 0.01 to 1.95, low quality evidence). These analyses were each based on the findings of a single study. No group difference was observed in the risk of serious adverse health events (385 participants; OR 1.00; 95% CI 0.14 to 7.25, moderate quality evidence). Compared to the placebo group, there was an insufficient number of participants to make firm conclusions whether the intermittent ICS group displayed any reduction in the rate of hospitalisations, day time and night time symptoms scores, or adverse events. Lung function tests reported by a single study favoured the use of ICS. There was no significant group difference in growth rate of children, or overall withdrawals.In preschool children with frequent wheezing episodes, the use of intermittent ICS at the onset of early symptoms reduced the likelihood of requiring rescue oral corticosteroids by half (490 participants; OR: 0.48; 95% CI 0.31 to 0.73, moderate quality evidence with minimal heterogeneity). Intermittent therapy was associated with fewer serious adverse events (439 participants; OR 0.42; 95% CI 0.17 to 1.02, low quality evidence). There was no significant difference in hospitalisations or in a single study measuring parent perceived quality of life. However, intermittent therapy was associated with improvements in both day time and night time symptoms. There was no increase in the rates of withdrawals, and overall and treatment-specific adverse events.
  
  
  CONCLUSIONS
  In children and adults with mild persistent asthma, two studies have shown that the use of intermittent ICS at the time of exacerbation reduced the chances of needing oral corticosteroids by half. This result is statistically significant if we assume that the effect size is the same for each study population (fixed effects model), but is not statistically significant when using a random effects model. However, the paucity of published evidence limits our conclusions towards the 'as-needed' use of this medication. The small number of studies and participants were the major reasons for downgrading the overall quality of the findings. A corresponding result was found in preschool children with wheeze. In this age group, an improvement in day time and night time asthma symptoms score and parental perceived quality of life of children similarly favoured the ICS group. However, there was no statistical difference in hospitalisation rates in any group. This treatment was not associated with any significant increase in adverse events. There was no growth suppression noted with the use of intermittent ICS in either preschool or school-aged children. Considering the limited number of available studies, we emphasise the need for more randomised controlled studies in order to confirm these findings.
authors.affiliation: University of Auckland, Auckland, New Zealand.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Chong
authors.forename: Cheyaanthan
authors.initials: C
authors.lastname: Haran
authors.forename: Bhupendrasinh F
authors.initials: BF
authors.lastname: Chauhan
authors.forename: Innes
authors.initials: I
authors.lastname: Asher
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D006801:Humans; D007223:Infant; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents