Infants and preschoolers with recurrent wheezing or asthma had fewer episodes of wheezing or asthma exacerbations, reduced symptoms, and improved lung function during treatment with inhaled corticosteroids, according to the results of a systematic review with meta-analysis reported in the March issue of Pediatrics.

“Trying to find the best treatment for a preschooler with wheeze is a common and troublesome clinical challenge,” write Jose A. Castro-Rodriguez, MD, PhD, from Pontificia Universidad Católica de Chile, Santiago, and Gustavo J. Rodrigo, MD, from Central de las Fuerzas Armadas, Montevideo and Facultad de Medicina Claeh, Prado y Salt Lake, Punta del Este, Maldonado, Uruguay. “The most recent international guidelines recommend the use of low-dose inhaled corticosteroids (ICSs) as the preferred controller therapy, with leukotriene modifiers as an alternative, for the management of persistent asthma in children under the age of 5. The treatment of those children with intermittent, viral-induced wheezing or low/intermediate probability of asthma remains controversial.”

The goal of this meta-analysis was to compare the efficacy of inhaled corticosteroids vs placebo in infants and preschoolers with recurrent wheezing or asthma. The investigators searched MEDLINE, EMBASE, and Central databases for randomized, prospective, controlled trials published from January 1996 to March 2008 in which treatment for at least 4 weeks with inhaled corticosteroids was compared vs placebo. Wheezing/asthma exacerbations were the main endpoint, and secondary endpoints were withdrawal caused by wheezing/asthma exacerbations, changes in symptoms score, pulmonary function (peak expiratory flow and forced expiratory volume in 1 second [FEV1]), or use of albuterol.

Inclusion criteria were met by 89 studies enrolling a total of 3592 subjects. Compared with patients receiving placebo, those receiving inhaled corticosteroids had significantly less wheezing/asthma exacerbations (18.0% vs 32.1%). This effect was stronger for patients diagnosed with asthma vs those with wheeze, according to post hoc subgroup analysis. However, this effect was independent of age (infants vs preschoolers), atopic condition, type of inhaled corticosteroid (budesonide metered-dose inhaler vs fluticasone metered-dose inhaler), mode of delivery (metered-dose inhaler vs nebulizer), and study quality (Jadad score: < 4 vs ≥ 4) and duration (< 12 vs ≥ 12 weeks).

Compared with children receiving placebo, those receiving inhaled corticosteroids had significantly fewer withdrawals caused by wheezing/asthma exacerbations, less use of albuterol, and more clinical and functional improvement.

“Infants and preschoolers with recurrent wheezing or asthma had less wheezing/asthma exacerbations and improve[ment in] their symptoms and lung function during treatment with inhaled corticosteroids,” the study authors write. “The widespread guideline recommendations and recent task force report to use ICSs in infants/preschoolers with recurrent episodes of wheeze (of appropriate severity) are supported by the present meta-analysis.”

Dr. Castro-Rodriguez has received lecturing and consultancy fees from Merck Sharp & Dohme, GlaxoSmithKline, and Grünenthal. Dr. Rodrigo has participated as a lecturer and speaker in scientific meetings and courses under the sponsorship of Boehringer Ingelheim, GlaxoSmithKline, AstraZeneca, Dr Esteve SA, and Merck Sharp & Dome, and he also received honoraria as a consultant for Cydex Inc and Discovery Laboratories.

Pediatrics. 2009;123:e519-e525.
Clinical Context

Wheezing is common in young children, with nearly 30% having at least 1 episode before age 3 years, and with a cumulative prevalence of wheeze being 50% at age 6 years. In nearly 80% of cases, asthma also begins before age 6 years.

Although both diagnosis and treatment of these conditions in infants and preschoolers can be challenging, the most current international guidelines recommend the use of low-dose inhaled corticosteroids as the preferred controller therapy to manage persistent asthma in children younger than 5 years. Because of conflicting results in some studies, a more critical approach of the use of inhaled corticosteroids in preschool-aged children with recurrent wheezing is required.
Study Highlights

* This meta-analysis aimed to compare the efficacy of inhaled corticosteroids vs placebo in infants and preschoolers with recurrent wheezing or asthma.
* Investigators searched MEDLINE, EMBASE, and Central databases for randomized, prospective, controlled trials published from January 1996 to March 2008.
* Inclusion criteria were treatment for at least 4 weeks with inhaled corticosteroids vs placebo.
* The main endpoint was wheezing/asthma exacerbations.
* Secondary endpoints were withdrawal caused by wheezing/asthma exacerbations, changes in symptoms score, pulmonary function (peak expiratory flow and forced expiratory volume in 1 second), or albuterol use.
* 89 studies were identified that met inclusion criteria; these enrolled a total of 3592 subjects.
* Patients receiving inhaled corticosteroids vs placebo had significantly less wheezing/asthma exacerbations (18.0% vs 32.1%).
* Number needed to treat with inhaled corticosteroids to significantly reduce wheezing and exacerbations was 7.
* Post hoc subgroup analysis showed that this effect was stronger for patients diagnosed with asthma vs patients with wheeze.
* This effect was independent of age (infants vs preschoolers), atopic condition, type of inhaled corticosteroid (budesonide metered-dose inhaler vs fluticasone metered-dose inhaler), delivery mode (metered-dose inhaler vs nebulizer), and study quality (Jadad score: < 4 vs ≥ 4) and duration (< 12 vs ≥ 12 weeks).
* Withdrawals caused by wheezing/asthma exacerbations were significantly fewer with inhaled corticosteroids (by nearly 50%) vs placebo.
* Compared with children receiving placebo, those receiving inhaled corticosteroids also had less use of albuterol and more clinical and functional improvement.
* The investigators concluded that infants and preschoolers with recurrent wheezing or asthma had less wheezing/asthma exacerbations, reduction in their symptoms, and improvement in lung function during treatment with inhaled corticosteroids.
* They also suggest that these results support the current recommendations of most international asthma guidelines to use inhaled corticosteroids in infants and preschoolers with recurrent episodes of wheeze of appropriate severity.

Pearls for Practice

* A meta-analysis showed that infants and preschoolers with recurrent wheezing or asthma had less wheezing/asthma exacerbations, reduction in their symptoms, and improvement in lung function during treatment with inhaled corticosteroids. These findings support the current recommendations of most international asthma guidelines to use inhaled corticosteroids in infants/preschoolers with recurrent episodes of wheeze of appropriate severity.
* The effect of inhaled corticosteroids vs placebo on wheezing/asthma exacerbations was stronger for patients diagnosed with asthma vs patients with wheeze, according to post hoc subgroup analysis. However, this effect was independent of age, atopic condition, type of inhaled corticosteroid used, mode of delivery, and study quality and duration.

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