The association between vitamin D status and the rate of exacerbations requiring oral corticosteroids in preschool children with recurrent wheezing.
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ABSTRACT:
SUBMITTER: Beigelman A
PROVIDER: S-EPMC4086617 | biostudies-literature | 2014 May
REPOSITORIES: biostudies-literature
Publications
The association between vitamin D status and the rate of exacerbations requiring oral corticosteroids in preschool children with recurrent wheezing.
Beigelman Avraham A Zeiger Robert S RS Mauger David D Strunk Robert C RC Jackson Daniel J DJ Martinez Fernando D FD Morgan Wayne J WJ Covar Ronina R Szefler Stanley J SJ Taussig Lynn M LM Bacharier Leonard B LB
The Journal of allergy and clinical immunology 20140401 5
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Project description:BackgroundOral corticosteroids (OCSs) are recommended for severe wheezing episodes in children. However, limited evidence supports this intervention in preschool children with outpatient wheezing illnesses.ObjectiveWe sought to investigate whether OCSs reduce symptom scores during acute lower respiratory tract illnesses (LRTIs) in preschool children with recurrent wheeze.MethodsWe 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.ResultsTwo 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).ConclusionIn 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.
| S-EPMC3810170 | biostudies-literature
Project description:BackgroundDaily inhaled glucocorticoids are recommended for young children at risk for asthma exacerbations, as indicated by a positive value on the modified asthma predictive index (API) and an exacerbation in the preceding year, but concern remains about daily adherence and effects on growth. We compared daily therapy with intermittent therapy.MethodsWe studied 278 children between the ages of 12 and 53 months who had positive values on the modified API, recurrent wheezing episodes, and at least one exacerbation in the previous year but a low degree of impairment. Children were randomly assigned to receive a budesonide inhalation suspension for 1 year as either an intermittent high-dose regimen (1 mg twice daily for 7 days, starting early during a predefined respiratory tract illness) or a daily low-dose regimen (0.5 mg nightly) with corresponding placebos. The primary outcome was the frequency of exacerbations requiring oral glucocorticoid therapy.ResultsThe daily regimen of budesonide did not differ significantly from the intermittent regimen with respect to the frequency of exacerbations, with a rate per patient-year for the daily regimen of 0.97 (95% confidence interval [CI], 0.76 to 1.22) versus a rate of 0.95 (95% CI, 0.75 to 1.20) for the intermittent regimen (relative rate in the intermittent-regimen group, 0.99; 95% CI, 0.71 to 1.35; P=0.60). There were also no significant between-group differences in several other measures of asthma severity, including the time to the first exacerbation, or adverse events. The mean exposure to budesonide was 104 mg less with the intermittent regimen than with the daily regimen.ConclusionsA daily low-dose regimen of budesonide was not superior to an intermittent high-dose regimen in reducing asthma exacerbations. Daily administration led to greater exposure to the drug at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; MIST ClinicalTrials.gov number, NCT00675584.).
| S-EPMC3247621 | biostudies-literature
Project description:BackgroundIn young healthy children, assessing airflow limitation may be difficult because of narrowing of the airways, which is a pathology of asthma, and responsiveness to bronchodilators.ObjectiveWe investigated whether lung sound analysis could predict the development of recurrent wheezing (RW), which is one of the signs of asthma.MethodsIn healthy children aged 3 to 24 months, we recorded and analyzed lung sounds before and after inhalation of bronchodilators and conducted a questionnaire survey. The children were followed up and assessed for the development of RW at age 3 years.ResultsOf the 62 patients analyzed, 19 (30.6%) developed RW. The parameters ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (RPF50) and ratio of power and frequency at 75% of the highest frequency of the dB power spectrum (RPF75), calculated by lung sound analysis, were lower in the RW group, with odds ratios of 0.77 (95% CI = 0.61-0.98) and 0.81 (95% CI = 0.66-0.99), respectively. The rate of change of lung sound analysis parameters after bronchodilator inhalation did not differ among the participants as a group; however, in the subgroup of children with a history of atopic dermatitis, the fourth area under the curve (B4) divided by the total area under the curve of 100 Hz to the highest frequency of the dB power spectrum (AT) and difference between the values of the ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (ΔRPF50) were elevated in the RW group (P = .015 and P = .041, respectively). In the subgroup of children with total a IgE level greater than 20 kUA/L, the sensitivities and specificities for predicting the development of RW were 85.7% (95% CI = 48.7-99.3) and 68.8% (95% CI = 44.4-85.8), respectively, when the cutoff value of ΔRPF50 was set at 10.5%.ConclusionThe method of lung sound analysis allows noninvasive assessment of the airway, including airway hypersensitivity, in young children and may predict the risk of development of RW.
| S-EPMC10796953 | biostudies-literature
Project description: Not available
| S-EPMC6504562 | biostudies-literature
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.
2024-01-29 | GSE254019 | GEO
Project description:The innate mechanisms associated with viral exacerbations in preschool children with recurrent wheezing are not understood. We assessed differential gene expression in blood neutrophils from preschool children with recurrent wheezing, stratified by aeroallergen sensitization, at baseline and after exposure to polyinosinic-polycytidylic acid (poly(I:C)). We also examined whether poly(I:C)-stimulated blood neutrophils influenced airway epithelial gene expression. Blood neutrophils were purified and cultured overnight with poly(I:C) and underwent next-generation sequencing with Reactome pathway analysis. Primary human small airway epithelial cells were treated with poly(I:C)-treated neutrophil culture supernatants and were analyzed for Type 1 interferon gene expression with a targeted array. Symptoms and exacerbations were assessed in participants over 12 months. 436 genes were differently expressed in neutrophils from children with versus without aeroallergen sensitization at baseline, with significant downregulation of Type 1 interferons. These Type 1 interferons were significantly upregulated in sensitized children after poly(I:C) stimulation. Confirmatory experiments demonstrated similar upregulation of Type 1 interferons in IL-4 treated neutrophils stimulated with poly(I:C). Poly(I:C)-treated neutrophil supernatants from children with aeroallergen sensitization also induced a Type 1 interferon response in epithelial cells. Children with aeroallergen sensitization also had higher symptom scores during exacerbations and these symptom differences persisted for three days after prednisolone treatment. We conclude that Type 1 interferon responses are dysregulated in preschool children with aeroallergen sensitization, which is in turn associated with exacerbation severity. Given the importance of Type 1 interferon signaling in viral resolution, additional studies of neutrophil Type 1 interferon responses are needed in this population.
2025-03-10 | GSE261070 | GEO
Project description:Recurrent wheezing in the preschool children is a common clinical problem, often associated with significant morbidity related to acute episodes. The management of these children has been complicated by a paucity of high-quality clinical trials in this age group. To fill this knowledge gap, National Heart, Lung, and Blood Institute's asthma research networks have performed a series of clinical trials in an effort to provide practitioners with guidance on appropriate management strategies. These studies establish daily inhaled corticosteroid (ICS) therapy in toddlers at high risk for subsequent asthma as an effective approach for the prevention of exacerbations and symptom reduction, but without evidence of disease-modifying properties. Additional studies have confirmed substantial heterogeneity in ICS response, in terms of both efficacy and effect on linear growth. Treatment with intermittent high-dose ICS was demonstrated to be an alternative approach to daily low-dose ICS for preventing severe exacerbations in toddlers with intermittent but significant wheeze and a positive modified asthma predictive index. This review details the findings and clinical implications derived from these studies, discuss the utility of biomarkers and the role of oral corticosteroids during acute exacerbations, and summarizes ongoing clinical trials in this age group.
| S-EPMC4715860 | biostudies-literature
Project description:BackgroundPreschool 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.ObjectiveWe performed functional immunophenotyping on isolated blood neutrophils from 52 preschool children with recurrent wheezing (aeroallergen sensitization, n = 16; no sensitization, n = 36).MethodsBlood 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.ResultsA total of 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 (ie, more myeloperoxidase and extracellular DNA) and less neutrophil proinflammatory cytokine secretion in children with aeroallergen sensitization. Neutrophils also shifted CD14+ monocytes to a more anti-inflammatory (ie, M2) phenotype in sensitized children and a more proinflammatory (ie, M1) phenotype in nonsensitized children. Although both groups experienced viral exacerbations, annualized exacerbation rates prompting unscheduled health care were also higher in children without aeroallergen sensitization after enrollment.ConclusionsSystemic 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 type 2-high inflammation.
| S-EPMC10841272 | biostudies-literature
Project description:IntroductionPreschool wheezers are at high risk of recurrent attacks triggered by respiratory viruses, sometimes exacerbated by exposure to allergens and pollution. Because of the COVID-19 infection, the lockdown was introduced, but the effects on preschool wheezers are unknown. We hypothesized that there would be an improvement in outcomes during the lockdown, and these would be lost when the lockdown was eased.Materials and methodsPatients underwent medical visits before and after the COVID-19 lockdown. We recorded the childhood Asthma Control Test (cACT) and a clinical questionnaire. Data on symptoms, the need for medications and the use of healthcare resources were recorded. We compared these data with retrospective reports from the preceding year and prospectively acquired questionnaires after lockdown.ResultsWe studied 85 preschool wheezers, mean age 4.9 years. During the lockdown, cACT score was significantly higher (median 25 vs. 23); families reported a dramatic drop in wheezing episodes (51 vs. none), significant reductions in the day and nighttime symptoms, including episodes of shortness of breath (p < .0001); the use of salbutamol and oral corticosteroids (OCS) dropped significantly (p < .0001) and 79 (95%) patients needed no OCS bursts during the lockdown. Finally, patients had significantly fewer extra medical examinations, as well as fewer Emergency Room visits (p < .0001). All were improved compared with the same time period from the previous year, but outcomes worsened significantly again after lockdown (cACT median: 22).ConclusionsDuring the national lockdown, children with persistent preschool wheeze showed a significant clinical improvement with reduction of respiratory symptoms, medication use for exacerbations, and use of healthcare resources. This trend reversed when lockdown restrictions were eased.
| S-EPMC8251173 | biostudies-literature
Project description:Preschool children with recurrent wheezing are a heterogeneous population with many underlying biological pathways that contribute to clinical presentations. Although the morbidity of recurrent wheezing in preschool children is significant, biological studies in this population remain quite limited. To address this gap, this study performed untargeted plasma metabolomic analyses in 68 preschool children with recurrent wheezing to identify metabolomic endotypes of wheezing. K-means cluster analysis was performed on metabolomic dataset including a total of 1382 named and unnamed metabolites. We identified three metabolomic clusters which differed in symptom severity, exacerbation occurrence, and variables associated with social disadvantage. Metabolites that distinguished the clusters included those involved in fatty acid metabolism, fatty acids (long chain monounsaturated fatty acids, long chain polyunsaturated fatty acids, and long chain saturated fatty acids), lysophospholipids, phosphatidylcholines, and phosphatidylethanolamines. Pathway analyses identified pathways of interest in each cluster, including steroid metabolism, histidine metabolism, sphingomyelins, and sphingosines, among others. This study highlights the biologic complexity of recurrent wheezing in preschool children and offers novel metabolites and pathways that may be amenable to future study and intervention.
| S-EPMC11233605 | biostudies-literature