Dataset Information

Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing?

ABSTRACT:

Background

Oral corticosteroids (OCSs) are recommended for severe wheezing episodes in children. However, limited evidence supports this intervention in preschool children with outpatient wheezing illnesses.

Objective

We sought to investigate whether OCSs reduce symptom scores during acute lower respiratory tract illnesses (LRTIs) in preschool children with recurrent wheeze.

Methods

We performed post hoc and replication analyses in 2 outpatient cohorts of children aged 1 to 5 years with episodic wheezing participating in clinical trials. We compared symptom scores during LRTIs that were or were not treated with OCSs, adjusting for differences in disease and episode severity covariates. We stratified episodes by severity by using a propensity model. The primary outcome was the area under the curve (AUC) of total symptom scores among the more severe episodes.

Results

Two hundred fifteen participants from the Acute Intervention Management Strategies trial experienced 798 acute LRTIs, 112 of which were defined as severe based on propensity scores. The AUCs of total symptom scores did not differ between the episodes that were (n = 70) and were not (n = 42) treated with OCSs (P = .46) nor was there an OCS treatment effect on individual symptom scores. Similar analyses of the Maintenance Versus Intermittent Inhaled Corticosteroids in Wheezing Toddlers trial, involving 278 participants with 133 severe LRTIs, confirmed the above findings (P = .46 for AUC of total symptoms score comparison).

Conclusion

In 2 separate cohorts of preschool children with episodic wheezing, OCS treatment during clinically significant LRTIs did not reduce symptom severity during acute LRTIs, despite asthma controller medication use during most episodes. These findings need to be confirmed in a prospective randomized controlled trial.

SUBMITTER: Beigelman A

PROVIDER: S-EPMC3810170 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Publications

Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing?

Beigelman Avraham A King Tonya S TS Mauger David D Zeiger Robert S RS Strunk Robert C RC Kelly H William HW Martinez Fernando D FD Lemanske Robert F RF Rivera-Spoljaric Katherine K Jackson Daniel J DJ Guilbert Theresa T Covar Ronina R Bacharier Leonard B LB

The Journal of allergy and clinical immunology 20130314 6

<h4>Background</h4>Oral corticosteroids (OCSs) are recommended for severe wheezing episodes in children. However, limited evidence supports this intervention in preschool children with outpatient wheezing illnesses.<h4>Objective</h4>We sought to investigate whether OCSs reduce symptom scores during acute lower respiratory tract illnesses (LRTIs) in preschool children with recurrent wheeze.<h4>Methods</h4>We performed post hoc and replication analyses in 2 outpatient cohorts of children aged 1 to ...[more]

PMID: 23498594

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Project description:IMPORTANCE:Many preschool children develop recurrent, severe episodes of lower respiratory tract illness (LRTI). Although viral infections are often present, bacteria may also contribute to illness pathogenesis. Strategies that effectively attenuate such episodes are needed. OBJECTIVE:To evaluate if early administration of azithromycin, started prior to the onset of severe LRTI symptoms, in preschool children with recurrent severe LRTIs can prevent the progression of these episodes. DESIGN, SETTING, AND PARTICIPANTS:A randomized, double-blind, placebo-controlled, parallel-group trial conducted across 9 academic US medical centers in the National Heart, Lung, and Blood Institute's AsthmaNet network, with enrollment starting in April 2011 and follow-up complete by December 2014. Participants were 607 children aged 12 through 71 months with histories of recurrent, severe LRTIs and minimal day-to-day impairment. INTERVENTION:Participants were randomly assigned to receive azithromycin (12 mg/kg/d for 5 days; n?=?307) or matching placebo (n?=?300), started early during each predefined RTI (child's signs or symptoms prior to development of LRTI), based on individualized action plans, over a 12- through 18-month period. MAIN OUTCOMES AND MEASURES:The primary outcome measure was the number of RTIs not progressing to a severe LRTI, measured at the level of the RTI, that would in clinical practice trigger the prescription of oral corticosteroids. Presence of azithromycin-resistant organisms in oropharyngeal samples, along with adverse events, were among the secondary outcome measures. RESULTS:A total of 937 treated RTIs (azithromycin group, 473; placebo group, 464) were experienced by 443 children (azithromycin group, 223; placebo group, 220), including 92 severe LRTIs (azithromycin group, 35; placebo group, 57). Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo (hazard ratio, 0.64 [95% CI, 0.41-0.98], P?=?.04; absolute risk for first RTI: 0.05 for azithromycin, 0.08 for placebo; risk difference, 0.03 [95% CI, 0.00-0.06]). Induction of azithromycin-resistant organisms and adverse events were infrequently observed. CONCLUSIONS AND RELEVANCE:Among young children with histories of recurrent severe LRTIs, the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI. More information is needed on the development of antibiotic-resistant pathogens with this strategy. TRIAL REGISTRATION:clinicaltrials.gov Identifier: NCT01272635.

Project description:BackgroundThe bacterial load of the human lower respiratory tract is at least several times lower than that of the other parts of the body. This study aimed to identify the bacterial composition and colony structure of the lower respiratory tract in infants and children with recurrent wheezing compared with those of children with a bronchial foreign body and clarify whether the length of wheezing in infants can contribute to differences in the lower respiratory tract's bacterial colony structure.MethodsWe collected specimens of alveolar lavage fluid from 48 infants and children who underwent fiberoptic bronchoscopy and were divided into groups: A1 (multiple wheezing: wheezing more than three times in < 1 month), A2 (persistent wheezing: > 1 month), and B (bronchial foreign body; control group). We analyzed the bacterial community structure of alveolar lavage fluid using high-throughput sequencing. The richness and diversity of the microbial communities were assessed by α and β diversity analyses.ResultsA total of 6,644 operational taxonomic units (OTUs) were obtained based on the Illumina Nova sequencing platform and clustered according to those that met the 97% identity threshold, followed by species annotation of the OTU sequences. In the annotation results, 2,608 (39.25%) OTUs were annotated at the genus level. At the genus level, Sphingomonas and Phyllobacterium were significantly higher in group A1 than in group B. There were significantly more Phyllobacterium in group A2 than in group B. Prevotella, Neisseria, and Haemophilus were higher in group B than in groups A1 and A2. The differences in the between-group α and β diversity analyses were statistically significant. The microbial diversity in groups A1 and A2 was significantly less than that in group B, but there was no statistical difference in bacterial community diversity between groups A1 and A2.ConclusionRecurrent wheezing in infants and children is more likely due to alterations in the overall bacterial microecology and disruption of host respiration and immune homeostasis than the effects of a single bacterium.

Project description:Preschool children with recurrent wheezing are heterogeneous, with differing responses to respiratory viral infections. Although neutrophils are crucial for host defense, their function has not been studied in this population. We performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n=16; no sensitization, n=36). Blood neutrophils were purified and cultured overnight with polyinosinic:polycytidylic acid (poly(I:C)) as a viral analog stimulus. Neutrophils underwent next-generation sequencing with Reactome pathway analysis and were analyzed for cytokine secretion, apoptosis, myeloperoxidase and extracellular DNA release. CD14+ monocytes were also exposed to neutrophil culture supernatant and analyzed for markers of M1 and M2 activation. 495 genes, related largely to the innate immune system and neutrophil degranulation, were differently expressed in children with versus without aeroallergen sensitization. Functional experiments identified more neutrophil degranulation and extracellular trap formation (i.e., more myeloperoxidase and extracellular DNA) and less neutrophil pro-inflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (i.e., M2) phenotype in sensitized children and a more pro-inflammatory (i.e., M1) phenotype in non-sensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled healthcare were also higher in children without aeroallergen sensitization after enrollment. Systemic neutrophil responses to viral infection differ by allergic phenotype and may be less effective in preschool children without allergic inflammation. Further studies of neutrophil function are needed in this population, which often has less favorable therapeutic responses to inhaled corticosteroids and other therapies directed at T2-high inflammation.

Dataset Information

Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing?

Background

Objective

Methods

Results

Conclusion

Publications

Do oral corticosteroids reduce the severity of acute lower respiratory tract illnesses in preschool children with recurrent wheezing?

Similar Datasets

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