Jose A. Castro-Rodriguez

SIBLINGS, DAY-CARE ATTENDANCE, AND THE RISK OF ASTHMA AND WHEEZING DURING CHILDHOOD

BACKGROUND Young children with older siblings and those who attend day care are at increased risk for infections, which in turn may protect against the development of allergic diseases, including asthma. However, the results of studies examining the relation between exposure to other children and the subsequent development of asthma have been conflicting. METHODS In a study involving 1035 children followed since birth as part of the Tucson Childrens Respiratory Study, we determined the incidence of asthma (defined as at least one episode of asthma diagnosed by a physician when the child was 6 to 13 years old) and the prevalence of frequent wheezing (more than three wheezing episodes during the preceding year) in relation to the number of siblings at home and in relation to attendance at day care during infancy. RESULTS The presence of one or more older siblings at home protected against the development of asthma (adjusted relative risk for each additional older sibling, 0.8; 95 percent confidence interval, 0.7 to 1.0; P=0.04), as did attendance at day care during the first six months of life (adjusted relative risk, 0.4; 95 percent confidence interval, 0.2 to 1.0; P=0.04). Children with more exposure to other children at home or at day care were more likely to have frequent wheezing at the age of 2 years than children with little or no exposure (adjusted relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.8; P=0.01) but were less likely to have frequent wheezing from the age of 6 (adjusted relative risk, 0.8; 95 percent confidence interval, 0.6 to 1.0; P=0.03) through the age of 13 (adjusted relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). CONCLUSIONS Exposure of young children to older children at home or to other children at day care protects against the development of asthma and frequent wheezing later in childhood.

Efficacy of Inhaled Corticosteroids in Infants and Preschoolers With Recurrent Wheezing and Asthma: A Systematic Review With Meta-analysis

OBJECTIVE. To compare the efficacy of inhaled corticosteroids in infants and preschoolers with recurrent wheezing or asthma. METHODS. Randomized, prospective, controlled trials published January 1996 to March 2008 with a minimum of 4 weeks of inhaled corticosteroids versus placebo were retrieved through Medline, Embase, and Central databases. The primary outcome was wheezing/asthma exacerbations; secondary outcomes 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. RESULTS. Of eighty-nine studies identified, 29 (N = 3592 subjects) met the criteria for inclusion. Patients who received inhaled corticosteroids had significantly less wheezing/asthma exacerbations than those on placebo (18.0% vs 32.1%); posthoc subgroup analysis suggests that this effect was higher in those with a diagnosis of asthma than wheeze but was independent of age (infants versus preschoolers), atopic condition, type of inhaled corticosteroid (budesonide metered-dose inhaler versus fluticasone metered-dose inhaler), mode of delivery (metered-dose inhaler versus nebulizer), and study quality (Jadad score: <4 vs ≥4) and duration (<12 vs ≥12 weeks). In addition, children treated with inhaled corticosteroids had significantly fewer withdrawals caused by wheezing/asthma exacerbations, less albuterol use, and more clinical and functional improvement than those on placebo. CONCLUSIONS. Infants and preschoolers with recurrent wheezing or asthma had less wheezing/asthma exacerbations and improve their symptoms and lung function during treatment with inhaled corticosteroids.

Randomized trial of salbutamol via metered-dose inhaler with spacer versus nebulizer for acute wheezing in children less than 2 years of age

The aim of this study was to compare the efficacy of salbutamol delivered via a metered‐dose inhaler with a spacer and facial mask (MDI‐S) vs. a nebulizer (NEB) for the treatment of acute exacerbations of wheezing in children. In a single‐blind, prospective, randomized clinical trial, 123 outpatients (1–24 months of age), presenting with “moderate to severe” wheezing, were seen in the emergency department. Children were randomly assigned to one of two salbutamol treatment groups. In the first hour, the MDI‐S group received 2 puffs (100 μg/puff) every 10 min for 5 doses, and the NEB group received 0.25 mg/kg every 13 min for 3 doses. If the clinical score was >5 at the end of the first hour, the patients received another hour of the same treatment and also betamethasone (0.5 mg/kg intramuscular). On enrollment and after the first and the second hour of treatment each child had a validated clinical score assigned by a blinded investigator.

Safety of long-acting β agonists for the treatment of asthma: clearing the air

Concerns about the safety of long-acting β2-agonist (LABA) therapy, has led to the appearance of multiple publications and recommendations. This review critically examines the available clinical evidence and safety requirements for LABA use. On the basis of nearly 20 systematic reviews and databases, the authors conclude that LABA monotherapy significantly increases the risk of asthma-related adverse effects. We also conclude that the use of LABAs concomitantly with inhaled corticosteroids (ICS) significantly reduces asthma hospitalisations and is not associated with life-threatening events and asthma-related deaths, especially when concurrent use of LABAs and ICS can be reasonably assured (use of a single inhaler device). An appropriate clinical study would require an extremely large sample, making it impractical. Finally, some of the new US Food and Drug Administration (FDA) recommendations have caused confusion and do not appear to be fully evidence based. Although limited by low statistical power, the evidence supports the use of LABAs plus ICS in a single inhaler device (to increase adherence and reduce the potential use of LABA monotherapy) for all patients (not only children) with moderate to severe asthma.

Relation between pulse oximetry and clinical score in children with acute wheezing less than 24 months of age

The aim of this study was to determine the relation between transcutaneous hemoglobin oxygen saturation, measured by pulse oximetry (SpO2), and clinical score values in 138 infants (mean ± SD, 6.6 ± 5.5 months of age) with acute wheezing episodes presenting in a primary care outpatient setting. A single investigator evaluated the severity of the acute wheezing episodes by assigning a clinical score and was unaware of the SpO2 values. Another investigator measured SpO2 values on all subjects. The mean (± SD) SpO2 value was 98.2 ± 1.1% for children with clinical scores of 2–5 (n = 32); 95.4 ± 1.5% for those with scores of 6–7 (n = 82), and 92.9 ± 2% for children with scores of 8–10 (n = 24), (P < 0.001 by Bonferronis multiple comparison, when all two‐way comparisons were done for each pair of results). The clinical score showed a good correlation with SpO2 (r = −0.76; 95% CI, −0.83 to −0.68).

Efficacy of inhaled corticosteroids in wheezy infants/preschoolers.

We read with interest the article by Brand et al. regarding the use of ciclesonide in wheezy preschool children. Discussing their results, the authors mention our systematic review on the efficacy of ICS in infants/preschoolers with wheeze or asthma, published a couple of years ago. Brand and colleagues stated on it: “Although a recent metaanalysis of preschool wheezing studies showed superiority of ICS over placebo, there was a high degree of clinical and statistical heterogeneity between studies..” However, we totally disagree with this assertion; because, our systematic review showed that effects sizes were consistent, with only two outcomes explored (mean change from baseline in symptom score and in albuterol use) showing substantial statistical heterogeneity. On the contrary, primary outcome (wheezing/asthma exacerbations [WAEs]), and the remainder secondary outcomes (withdrawals caused by WAEs and mean change from baseline in PEF and FEV1) were statistically homogeneous (I Z 10% and I Z 0%, respectively). Concerning clinical heterogeneity, we performed a sensitivity analysis of the primary outcome to explore the influence of different factors such as the type of disease, age, atopic status, methodological quality of studies, method of ICS delivery, and ICS choice. Although a clinical and statistical WAE reduction appeared in both wheeze and asthmatic groups, subgroup analysis suggests that this effect could be more relevant in children with a diagnosis of asthma. On the other hand, this beneficial effect was independent of age, atopic condition, type of ICS (budesonide or fluticasone), mode of delivery, and study quality and duration. Curiously, regarding the results of the Brand and colleagues, they appear as consistent with our review. Thus, we found that treatment of 7 subjects with ICS therapy prevents one child from experiencing a WAE (95%