Wheezing Preschool Children Research Articles

Lung sound analysis for predicting recurrent wheezing in preschool children

BackgroundIn young healthy children, assessing airflow limitation may be difficult because of the 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), 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 3 years of age. ResultsOf the 62 patients analyzed, 19 (30.6%) developed RW. The parameters RPF50 and RPF75, calculated by lung sound analysis, were lower in the RW group, with odds ratios (95% CI) of 0.77 (0.61–0.98) and 0.81 (0.66–0.99), respectively. The change rate of lung sound analysis parameters after bronchodilator inhalation was not different among all participants; however, in the subgroup of children with a history of atopic dermatitis, B4/AT and ΔRPF50 were elevated in the RW group (P = .015 and P = .041, respectively). In the subgroup of children with total IgE >20 kUA/L, the sensitivity and specificity (95% CI) for predicting the development of RW were 85.7% (48.7-99.3) and 68.8% (44.4-85.8), respectively, when the cutoff value of ΔRPF50 was set at 10.5%. ConclusionThe lung sound analysis method allows noninvasive assessment of the airway, including airway hypersensitivity, in young children and may predict the risk of developing RW.

Social determinants of health influence preschool and caregiver experiences during symptoms and exacerbations of wheezing

BackgroundSocial determinants of health have been inadequately studied in preschool children with wheezing and their caregivers but may influence the care received. ObjectiveTo evaluate the symptom and exacerbation experiences of wheezing preschool children and their caregivers, stratified by risk of social vulnerability, over 1 year of longitudinal follow-up. MethodsA total of 79 caregivers and their preschool children with recurrent wheezing and at least 1 exacerbation in the previous year were stratified by a composite measure of social vulnerability into “low” (N = 19), “intermediate” (N = 27), and “high” (N = 33) risk groups. Outcome measures at the follow-up visits included child respiratory symptom scores, asthma control, caregiver-reported outcome measures of mental and social health, exacerbations, and health care utilization. The severity of exacerbations reflected by symptom scores and albuterol use and exacerbation-related caregiver quality of life were also assessed. ResultsPreschool children at high risk of social vulnerability had greater day-to-day symptom severity and more severe symptoms during acute exacerbations. High-risk caregivers were also distinguished by lower general life satisfaction at all visits and lower global and emotional quality of life during acute exacerbations which did not improve with exacerbation resolution. Rates of exacerbation or emergency department visits did not differ, but intermediate- and high-risk families were significantly less likely to seek unscheduled outpatient care. ConclusionSocial determinants of health influence wheezing outcomes in preschool children and their caregivers. These findings argue for routine assessment of social determinants of health during medical encounters and tailored interventions in high-risk families to promote health equity and improve respiratory outcomes.

The ADEM2 project: early pathogenic mechanisms of preschool wheeze and a randomised controlled trial assessing the gain in health and cost-effectiveness by application of the breath test for the diagnosis of asthma in wheezing preschool children

BackgroundThe prevalence of asthma-like symptoms in preschool children is high. Despite numerous efforts, there still is no clinically available diagnostic tool to discriminate asthmatic children from children with transient wheeze at preschool age. This leads to potential overtreatment of children outgrowing their symptoms, and to potential undertreatment of children who turn out to have asthma. Our research group developed a breath test (using GC-tof–MS for VOC-analysis in exhaled breath) that is able to predict a diagnosis of asthma at preschool age. The ADEM2 study assesses the improvement in health gain and costs of care with the application of this breath test in wheezing preschool children.MethodsThis study is a combination of a multi-centre, parallel group, two arm, randomised controlled trial and a multi-centre longitudinal observational cohort study. The preschool children randomised into the treatment arm of the RCT receive a probability diagnosis (and corresponding treatment recommendations) of either asthma or transient wheeze based on the exhaled breath test. Children in the usual care arm do not receive a probability diagnosis. Participants are longitudinally followed up until the age of 6 years. The primary outcome is disease control after 1 and 2 years of follow-up. Participants of the RCT, together with a group of healthy preschool children, also contribute to the parallel observational cohort study developed to assess the validity of alternative VOC-sensing techniques and to explore numerous other potential discriminating biological parameters (such as allergic sensitisation, immunological markers, epigenetics, transcriptomics, microbiomics) and the subsequent identification of underlying disease pathways and relation to the discriminative VOCs in exhaled breath.DiscussionThe potential societal and clinical impact of the diagnostic tool for wheezing preschool children is substantial. By means of the breath test, it will become possible to deliver customized and high qualitative care to the large group of vulnerable preschool children with asthma-like symptoms. By applying a multi-omics approach to an extensive set of biological parameters we aim to explore (new) pathogenic mechanisms in the early development of asthma, creating potentially interesting targets for the development of new therapies.Trial registrationNetherlands Trial Register, NL7336, Date registered 11–10-2018.

Outcomes of young children hospitalized with acute wheezing.

Wheezing in preschool children is a common symptom. The study aimed to determine an incidence of recurrent wheezing among young children who had been hospitalized with acute wheezing after 12 months. Factors associated with recurrent wheezing were explored. A longitudinal study was conducted among 236 children, aged between 6 months and 5 years, who were hospitalized with acute wheezing in 4 hospitals located in Bangkok and adjacent provinces, Thailand. Demographics, house environments and clinical characteristic data were collected at entry. Serum specific IgE levels against common food and inhalant allergens and serum 25-hydroxyvitamin D (25OHD) concentrations were measured. At entry, the mean age was 24.4 months (SD = 15.7 months). Of 236 hospitalized children with acute wheezing, ninety-four cases (39.8%) were the first wheezing episode of life. By laboratory results, 197 (83.5%) and 56 (23.7%) children were atopic and had vitamin D insufficiency respectively. There were 195 cases completely followed for 12 months. One-year risk of emergency visits and hospitalization due to recurrent wheezing were 49.7% and 23.1% respectively. By multivariable analysis, being the second born child or more, vitamin D insufficiency, "ever wheeze", and allergic rhinitis were significantly associated with recurrent wheezing within 12 months with adjusted odds ratios of 2.5 (95% confidence interval: 1.3-5.3), 2.3 (95% confidence interval: 1.1-4.4), 1.9 (95% confidence interval: 1.2-3.5), and 1.6 (95% confidence interval: 1.3-2.9) respectively. Being the second born child or more, vitamin D insufficiency, ever wheeze, and allergic rhinitis were significant risks of recurrent wheezing.

Exhaled Breath Analysis for Investigating the Use of Inhaled Corticosteroids and Corticosteroid Responsiveness in Wheezing Preschool Children.

Exhaled breath analysis has great potential in diagnosing various respiratory and non-respiratory diseases. In this study, we investigated the influence of inhaled corticosteroids (ICS) on exhaled volatile organic compounds (VOCs) of wheezing preschool children. Furthermore, we assessed whether exhaled VOCs could predict a clinical steroid response in wheezing preschool children. We performed a crossover 8-week ICS trial, in which 147 children were included. Complete data were available for 89 children, of which 46 children were defined as steroid-responsive. Exhaled VOCs were measured by GC-tof-MS. Statistical analysis by means of Random Forest was used to investigate the effect of ICS on exhaled VOCs. A set of 20 VOCs could best discriminate between measurements before and after ICS treatment, with a sensitivity of 73% and specificity of 67% (area under ROC curve = 0.72). Most discriminative VOCs were branched C11H24, butanal, octanal, acetic acid and methylated pentane. Other VOCs predominantly included alkanes. Regularised multivariate analysis of variance (rMANOVA) was used to determine treatment response, which showed a significant effect between responders and non-responders (p < 0.01). These results show that ICS significantly altered the exhaled breath profiles of wheezing preschool children, irrespective of clinical treatment response. Furthermore, exhaled VOCs were capable of determining corticosteroid responsiveness in wheezing preschool children.

Lung lavage inflammatory patterns and pathogen profiles in preschool children with problematic wheeze

Practicing clinicians regularly encounter the preschool child with intermittent episodes of wheeze. Preschool wheezing episodes account for a large burden of unscheduled ambulatory care visits and hospitalizations across the globe. Recurrent episodes of acute wheeze are often referred to as “problematic.” However, guidelines to treat these children are not based on solid evidence. There are few clinical trials applicable to real-world practice to direct treatment of problematic wheeze. 1 Bacharier LB Guilbert TW Mauger DT Boehmer S Beigelman A Fitzpatrick AM et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: a randomized clinical trial. JAMA. 2015; 314: 2034-2044 Crossref PubMed Scopus (193) Google Scholar , 2 Fitzpatrick AM Jackson DJ Mauger DT Boehmer SJ Phipatanakul W Sheehan WJ et al. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 2016; 138 (1608-1618.e12) Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar , 3 Wallace A Sinclair O Shepherd M Neutze J Trenholme A Tan E et al. Impact of oral corticosteroids on respiratory outcomes in acute preschool wheeze: a randomised clinical trial. Arch Dis Child. 2021; 106: 339-344 Crossref PubMed Scopus (4) Google Scholar A helpful study by Bacharier et al 1 Bacharier LB Guilbert TW Mauger DT Boehmer S Beigelman A Fitzpatrick AM et al. Early administration of azithromycin and prevention of severe lower respiratory tract illnesses in preschool children with a history of such illnesses: a randomized clinical trial. JAMA. 2015; 314: 2034-2044 Crossref PubMed Scopus (193) Google Scholar found that a burst of azithromycin given early during an episode of virus-triggered wheeze in preschool children with a history of recurrent wheeze was effective in preventing the progression of symptoms. Azithromycin treatment was effective in not only the first but subsequent wheeze episodes over 1 year. Although guidelines on the management of preschool wheeze have been published, inconsistencies prevail as to the endorsement of azithromycin to treat acute exacerbations.

Heterogeneity of emergency treatment practices in wheezing preschool children.

Our aim was to survey treatment practices used for preschool children with wheezing in emergency rooms (ER) focussing on inhalation device choice and handling, face mask use, salbutamol dosing and written instructions. We sought to assess whether current protocols are in line with published evidence and guidelines. This is a cross-sectional survey done in paediatric ER units located in Finnish municipalities with more than 10000 inhabitants. Of the 100 units contacted, 50% responded. More than 50% of the units used nebulisers. Only 13% of the units administered salbutamol in single puffs. More than 30% of the units lacked criteria on face mask use. Poor co-operation had no effect on the dose of salbutamol in 62% of the units. Ensuring tight mask-to-face seal was included in the training in 20% of the units. A written action plan was provided to the caregivers in 28% of the units. ER treatment guidelines for preschool children with wheezing are poorly endorsed. Research is needed to identify approaches to guideline implementation that are specific for primary care. Clinical research should focus on strengthening recommendations that are currently not embraced. ER treatment protocols need to be updated and adherence to guidelines should be re-evaluated.

Preschool Wheezing and Gastro-Esophageal Reflux: --Causal or Casual Coincidence? Update from Literature.

Gastroesophageal reflux (GER) and wheeze are two common conditions in children. GER has been advocated as a causative factor for explaining recurrent to persistent respiratory symptoms at any age. This association very often means that many children with cough, wheezing, or recurrent respiratory infections receive empirical anti-reflux medications. The causal relationship is still largely discussed. Compared to the large number of studies in infants and adolescents, literature on the relationship between GER and wheeze in preschool children is scarce and inconclusive. The aim of the present narrative review was to summarize what is known so far, and what the literature has proposed in the last 20 years, on the relationship between preschool wheezing and GER. In preschool children with respiratory symptoms there is a high rate of positivity of reflux testing, for this reason pH-MII testing and endoscopy are recommended. Flexible bronchoscopy may be useful to exclude anatomical abnormalities as the cause of wheezing in infancy and preschool years. Several biomarkers, as well as empirical anti-reflux therapy, have been proposed for the diagnosis of GER-related airway diseases, but the conclusions of these studies are controversial or even conflicting. There is a great need for future clinical trials to confirm or rule out the association.

Diagnosis and management of wheeze in pre-school children

Lower respiratory tract illnesses with wheeze occur in around one-third of all pre-school children aged 1–5 years. They are among the most common causes of childhood attendances to emergency departments, accounting for almost 75% of all childhood admissions for wheezing in the UK​[1]​. Although admissions and acute presentations have fallen for school-age children with asthma, […]

Lung function testing and inflammation markers for wheezing preschool children: A systematic review for the EAACI Clinical Practice Recommendations on Diagnostics of Preschool Wheeze.

Preschool wheeze is highly prevalent; 30%-50% of children have wheezed at least once before age six. Wheezing is not a disorder; it is a symptom of obstruction in the airways, and it is essential to identify the correct diagnosis behind this symptom. An increasing number of studies provide evidence for novel diagnostic tools for monitoring and predicting asthma in the pediatric population. Several techniques are available to measure airway obstruction and airway inflammation, including spirometry, impulse oscillometry, whole-body plethysmography, bronchial hyperresponsiveness test, multiple breath washout test, measurements of exhaled NO, and analyses of various other biomarkers. We systematically reviewed all the existing techniques available for measuring lung function and airway inflammation in preschool children to assess their potential and clinical value in the routine diagnostics and monitoring of airway obstruction. If applicable, measuring FEV1 using spirometry is considered useful. For those unable to perform spirometry, whole-body plethysmography and IOS may be useful. Bronchial reversibility to beta2-agonist and hyperresponsiveness test with running exercise challenge may improve the sensitivity of these tests. The difficulty of measuring lung function and the lack of large randomized controlled trials makes it difficult to establish guidelines for monitoring asthma in preschool children.

Reducing the burden of asthma: time to set research and clinical priorities

There is a substantial global burden of asthma in terms of prevalence, morbidity, mortality, and cost. It has been estimated that there are over 300 million people with asthma worldwide, most of whom do not have well controlled symptoms. Long-term trends in country-specific asthma mortality have been dominated by the effects of treatments, with β-adrenoceptor agonist-related increases in mortality in the 1960s and 1980s, and a progressive reduction in mortality from the 1990s into the 21st century attributed to the widespread use of inhaled corticosteroids (ICS). 1 Pavord ID Beasley R Agusti A et al. After asthma: redefining airways diseases. Lancet. 2018; 391: 350-400 Summary Full Text Full Text PDF PubMed Scopus (589) Google Scholar Although the asthma mortality rate has continued to fall in some countries and regions, the estimated global mortality rate has not changed appreciably since 2006. 2 Ebmeier S Thayabaran D Braithwaite I Bénamara C Weatherall M Beasley R Trends in international asthma mortality: analysis of data from the WHO Mortality Database from 46 countries (1993–2012). Lancet. 2017; 390: 935-945 Summary Full Text Full Text PDF PubMed Scopus (169) Google Scholar This absence of change suggests that the progress made in the previous 2 decades might have stalled, and that better implementation of proven current management strategies, together with novel approaches, are required to achieve further reductions in mortality and, more generally, the burden of asthma. The genetics of asthma and the promise of genomics-guided drug target discoveryAsthma is an inflammatory airway disease that is estimated to affect 339 million people globally. The symptoms of about 5–10% of patients with asthma are not adequately controlled with current therapy, and little success has been achieved in developing drugs that target the underlying mechanisms of asthma rather than suppressing symptoms. Over the past 3 years, well powered genetic studies of asthma have increased the number of independent asthma-associated genetic loci to 128. In this Series paper, we describe the immense progress in asthma genetics over the past 13 years and link asthma genetic variants to possible drug targets. Full-Text PDF Advances in understanding and reducing the burden of severe asthma in childrenSevere asthma in children is rare, accounting for only a small proportion of childhood asthma. After addressing modifiable factors such as adherence to treatment, comorbidities, and adverse exposures, children whose disease is not well controlled on high doses of medication form a heterogeneous group of severe asthma phenotypes. Over the past decade, considerable advances have been made in understanding the pathophysiology of severe therapy-resistant asthma in children. However, asthma attacks and hospital admissions are frequent and mortality is still unacceptably high. Full-Text PDF Primary prevention of asthma: from risk and protective factors to targeted strategies for preventionAsthma is a complex disease that often starts in childhood. Genomic and environmental factors as well as aberrant immune maturation early in life can contribute to the onset of disease, with great disparity over time and geographical regions. Epidemiological studies have scrutinised environmental exposures and attempted to translate these exposures into prevention strategies. Some approaches for patients with asthma have been successful (eg, smoking ban, the Finnish Asthma Programme), and primary prevention of wheeze in pre-school children (age 0–5 years) by the supplementation of vitamin D or fish oil, or both, to pregnant women seems promising. Full-Text PDF

Clinical Profile of Episodic Wheezing and Multiple Trigger Wheezing in Preschool Children: A Cross-Sectional Study

AbstractThe objectives of our study were to identify the relative frequency of episodic viral wheeze (EVW) and multiple trigger wheeze (MTW) in preschool children of 1 to 5 years of age with recurrent wheezing and to compare the relevant clinical and sociodemographic parameters in the above phenotypes. This cross-sectional study included 165 children aged 1 to 5 years with recurrent wheeze. Participants were categorized into EVW and MTW based on history according to European Respiratory Society Task Force recommendations 2008. Symptom control was assessed by Global Initiative for Asthma guidelines 2015. Of the total participants, EVW was seen in 55% and MTW in 45%. Children with MTW were significantly older than those with EVW, more atopic, and had higher eosinophil counts. The dominant phenotype seen in our study was EVW. The absence of ocular/nasal allergy and exclusive breastfeeding predicted well-controlled symptoms in EVW and in all preschool wheezers, respectively.

Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation

To identify predictors of future exacerbations and response to inhaled corticosteroid (ICS) treatment in preschool children with recurrent wheezing.This was a study of 1708 well-characterized and medication-adherent children aged 12 to 71 months with recurrent wheezing enrolled in multicenter trials sponsored by the National Heart, Lung, and Blood Institute’s AsthmaNet and Childhood Asthma Research and Education Network.Latent class analysis, a statistical method used to identify group membership, was applied using 10 demographic, sensitization, and exposure variables within the merged data set to identify classes of recurrent wheeze and determine optimal classification. Within each class, annual exacerbation rate and response to daily ICS therapy were defined.Four groups with different patterns of environmental sensitization, exposures, and exacerbations were identified, with highest rates of both exacerbations and ICS response in groups 2 and 4. Annual exacerbation rates (mean ± SEM per year) were 0.65 ± 0.06 for class 1 (“minimal sensitization”), 0.93 ± 0.10 for class 2 (“sensitization with indoor pet exposure”), 0.60 ± 0.07 for class 3 (“sensitization with tobacco smoke exposure”), and 0.81 ± 0.10 for class 4 (“multiple sensitization and eczema”) (P < .001). Notably, current symptoms and historical exacerbations did not differ between groups.Type 2 inflammatory features were a marker for more-frequent exacerbations in children with recurrent preschool wheezing. Researchers in this study identified 4 distinct groups of recurrent wheeze among preschool children, which differed with regard to allergen sensitization and/or exposure as well as annual exacerbation rate and response to ICS therapy. Daily ICS treatment reduced exacerbations rates in groups 2 and 4, but not other groups, in a high-adherence research setting. However, exacerbations still occurred in children with minimal sensitization, likely caused by triggers independent of type 2 inflammation.Preschoolers with recurrent wheeze represent a mixed group. Investigators in this study suggest that those sensitized to allergens in their environment with either indoor pet exposure or eczema are more likely to experience more-frequent exacerbations but also respond better to asthma controller therapy. As we consider early persistent and transient wheezing phenotypes of preschool children, this study adds to a growing literature to help identify our youngest patients with asthma and optimize management to maximize value.

Episodic viral wheeze and multiple-trigger wheeze in preschool children are neither distinct nor constant patterns. A prospective multicenter cohort study in secondary care.

To evaluate whether episodic viral wheeze (EVW) and multiple-trigger wheeze (MTW) are clinically distinguishable and stable preschool wheezing phenotypes. Children of age 1 to 4 year with recurrent, pediatrician-confirmed wheeze were recruited from secondary care; 189 were included. Respiratory and viral upper respiratory tract infection (URTI) symptoms were recorded weekly by parents in an electronic diary during 12 months. Every 3 months, diary-based symptoms were classified as EVW or MTW and compared to phenotypes assigned by pediatricians based on clinical history. We collected nasal samples for respiratory virus PCR during URTI, respiratory symptoms and in absence of symptoms. Of 660 3-month periods, the diary-based phenotype was EVW in 11%, MTW in 54% and 35% were free from respiratory episodes. Pediatrician-based classification showed 59% EVW and 26% MTW. The Kappa measure of agreement between diary-based and pediatrician-assigned phenotypes was very low (0.12, 95%CI, 0.07-0.17). Phenotypic instability was observed in 32% of cases. PCR was positive in 71% during URTI symptoms, 66% during respiratory symptoms and 38% in the absence of symptoms. This study shows that EVW and MTW are variable over time within patients. Pediatrician classification of these phenotypes based on clinical history does not correspond to prospectively recorded symptom patterns. The applicability of these phenotypes as a basis for therapeutic decisions and prognosis should be questioned.

Lower airway microbiota associates with inflammatory phenotype in severe preschool wheeze

Lower airway microbiota associates with inflammatory phenotype in severe preschool wheeze

Phenotypes of Recurrent Wheezing in Preschool Children: Identification by Latent Class Analysis and Utility in Prediction of Future Exacerbation

Recurrent preschool wheezing is a heterogeneous disorder with significant morbidity, yet little is known about phenotypic determinants and their impact on clinical outcomes. Latent class analysis (LCA) was used to identify latent classes of recurrent preschool wheeze and their association with future exacerbations and inhaled corticosteroid (ICS) treatment response. Data from 5 clinical trials of 1708 children aged 12 to 71 months with recurrent wheezing were merged. LCA was performed on 10 demographic, exposure, and sensitization variables to determine the optimal number of latent classes. The primary outcome was the annualized rate of wheezing exacerbations requiring systemic corticosteroids during the study intervention period; the secondary outcome was the time to first exacerbation. Exploratory analyses examined the effect of daily ICS treatment on exacerbation outcomes. Four latent classes of recurrent wheezing were identified; these were not distinguished by current symptoms or historical exacerbations but differed with regard to allergen sensitization and/or exposures. Annualized exacerbation rates (mean ± SEM/year) were 0.65 ± 0.06 for class 1 ("minimal sensitization"), 0.93 ± 0.10 for class 2 ("sensitization with indoor pet exposure"), 0.60 ± 0.07 for class 3 ("sensitization with tobacco smoke exposure"), and 0.81 ± 0.10 for class 4 ("multiple sensitization and eczema") (P < .001). In a research setting of high adherence, daily ICS treatment improved exacerbation rates in classes 2 and 4 but not the other groups. Sensitization and exposure assessments are useful in the prediction of future exacerbation and may identify children most likely to respond favorably to daily ICS treatment.

Management of recurrent wheeze in pre-school children with a high risk of developing asthma

Wheeze occurs in around one-third of children under 5 years. Rachael Moore-Crouch explains how to manage wheeze in children at a high risk of developing asthma Wheeze is common in pre-school children, with up to one-third of all children developing symptoms. Of these children, one-third will go on to develop asthma by school age. Asthma is difficult to diagnose in pre-school children due to the inability to undertake reliable assessments of lung function to demonstrate reversible airflow obstruction or airway inflammation. The lack of objective testing can lead to over-diagnosis of asthma and inappropriate treatment with inhaled corticosteroids. Where asthma is highly suspected, treatment should be commenced with a carefully observed trial focusing on managing current symptoms with the lowest dose and minimal treatment. Parents should receive clear education and plans for escalation of care.

Reduced CDHR3 expression in children wheezing with rhinovirus.

Rhinovirus-induced wheezing in young children has been associated with increased asthma risk at school age. Recently, the transmembrane protein cadherin-related family member 3 (CDHR3) was identified as the RV-C receptor and the genetic variant rs6967330 (p.Cys529Tyr) was reported to be associated with enhanced RV-C binding and increased replication in vitro. The aim of this study was to examine rs6967330 genotypes and mRNA expression of CDHR3 in relation to presence of rhinovirus and clinical symptoms in children with acute wheezing and compare to a group of age-matched healthy children. rs6967330;G>A was genotyped (n=216), and CDHR3 mRNA expression was measured in peripheral blood leukocytes (n=69) from a subgroup of children wheezing with RV infection acute and at a follow-up visit 2-3months later, and in healthy controls. Standardized TaqMan assays were used. The risk allele rs6967330-A was over-represented in the wheezing group (P<.001). Reduced mRNA levels of CDHR3 were found in children with acute wheezing as compared to the control group (P=.001). Children with the rs6967330 genotypes AA/AG showed the largest differences in CDHR3 expression between acute and follow-up visit (P<.04). Preschool children with RV-induced wheezing were shown to have reduced CDHR3 mRNA levels, which might result in an increased permeability of the epithelial layers of the airways and thereby an increased vulnerability. Thus, measuring CDHR3 mRNA levels might help to identify a more severe phenotype of wheezing preschool children.

Recurrent wheeze and its relationship with lung function and airway inflammation in preschool children: a cross-sectional study in South Korea

BackgroundRelationship between recurrent wheeze and airway function and inflammation in preschool children is not fully known.ObjectiveTo investigate the relationship between recurrent wheeze and airway inflammation, lung function, airway hyper-reactivity (AHR)...

Treatment of preschool children presenting to the emergency department with wheeze with azithromycin: A placebo-controlled randomized trial.

BackgroundAntibiotics are frequently used to treat wheezing children. Macrolides may be effective in treating bronchiolitis and asthma.MethodWe completed a prospective, double-blinded, randomized placebo-control trial of azithromycin among pre-school children (12 to 60 months of age) presenting to the emergency department with wheeze. Patients were randomized to receive either five days of azithromycin or placebo. Primary outcome was time to resolution of respiratory symptoms after treatment initiation. Secondary outcomes included the number of days children used a Short-Acting Beta-Agonists during the 21 day follow-up and time to disease exacerbation during the following six months (unscheduled health care visit or treatment with an oral corticosteroid for acute respiratory symptoms).ResultsOf the 300 wheezing children recruited, 222 and 169 were analyzed for the primary and secondary outcomes, respectively. The treatment groups had similar demographics and clinical parameters at baseline. Median time to resolution of respiratory symptoms was four days for both treatment arms (interquartile range (IQR) 3,6; p = 0.28). Median number of days of Short-Acting Beta-Agonist use among those who received azithromycin was four and a half days (IQR 2, 7) and five days (IQR 2, 9; p = 0.22) among those who received placebo. Participants who received azithromycin had a 0.91 hazard ratio for time to six-month exacerbation compared to placebo (95% CI 0.61, 1.36, p = 0.65). A pre-determined subgroup analysis showed no differences in outcomes for children with their first or repeat episode of wheezing. There was no significant difference in the proportion of participants experiencing an adverse event.ConclusionAzithromycin neither reduced duration of respiratory symptoms nor time to respiratory exacerbation in the following six months after treatment among wheezing preschool children presenting to an emergency department. There was no significant effect among children with either first-time or prior wheezing.