Persistent Asthma In Children Research Articles

Pollen as a mediator between environmental greenness during pregnancy and infancy periods and childhood persistent asthma: A nationwide retrospective birth cohort study in Japan

The association between environmental greenness and childhood asthma remains unclear. Pollen has been proposed as a potential mechanism of detrimental associations. This study aimed to elucidate the mechanisms underlying the association between environmental greenness during the pre-, peri-, and postnatal periods and childhood persistent asthma. A nationwide retrospective birth cohort study was conducted using data from the Japan Medical Data Center (JMDC). Child-mother dyads between January 2010 and January 2017 were identified, and four subcohorts were developed based on the timing of exposure to the highest greenness season. The exposure of interest was environmental greenness levels between June and September, quantified using the normalized difference vegetation index (NDVI). The primary outcome was persistent asthma in children aged 4–5 years. Causal mediation analysis was conducted to evaluate pollen as a mediator between NDVI and asthma. In these analyses, linear and modified Poisson regression models were used to evaluate the association of NDVI with pollen levels and childhood persistent asthma. The analyses were stratified by metropolitan and non-metropolitan areas. Clinically meaningful confounders and predictors of asthma were adjusted in the statistical models. A total of 100,273 child-mother dyads were included in the entire cohort, with 24.1% of the children having persistent asthma at the ages of 4–5 years. Higher environmental greenness was associated with higher pollen levels. The modified Poisson regression models showed higher environmental greenness was associated with a slightly higher risk of persistent childhood asthma. In metropolitan areas, significant detrimental natural direct effects of NDVI were observed; however, the natural indirect effects were uncertain. A large part of the association between environmental greenness and childhood persistent asthma in metropolitan areas was attributed to mechanisms other than those involving pollen. The associations in non-metropolitan areas remain uncertain. Further studies are required to elucidate the underlying mechanisms.

Joint associations of air pollutants during pregnancy, infancy, and childhood with childhood persistent asthma: Nationwide database study in Japan

The joint effect of air pollutants at relatively low levels requires further investigation. Here, a database study was performed to evaluate the effects of exposure to mixtures of air pollutants during pregnancy, infancy, and childhood on childhood persistent asthma. We used the Japan Medical Data Center database, which provides access to family linkages and healthcare provider addresses, and included child-mother dyads in which the child was born between January 2010 and January 2017. The exposure of interest was ground-level air pollutants, and the primary outcome was childhood persistent asthma at 45 years of age, as defined based on outpatient and inpatient asthma disease codes and/or asthma medication dispensing claims. The weighted quantile sum (WQS) regression was used to evaluate the effects of air pollutant mixtures on 52,526 child-mother dyads from 1149 of 1907 municipalities (60.3 %) in Japan. The WQS regression models showed that with every 10th percentile increase in the WQS index, ground-level air pollutants during pregnancy, infancy, and childhood increased the risk of childhood persistent asthma by an odds ratio of 1.04 (95 % CI: 1.02–1.05; p<0.001), 1.02 (95 % CI: 1.01–1.03; p<0.001), and 1.03 (95 % CI: 1.01–1.04; p<0.001), respectively. Moreover, particulate matter with an aerodynamic diameter ≤ 2.5 µm was assigned the highest weight across all three exposure periods. Relatively high weights were assigned to suspended particulate matter and photochemical oxidants during pregnancy, carbon monoxide during infancy, and photochemical oxidants during childhood. Our study showed that a mixture of low-level air pollutants has a detrimental association with childhood persistent asthma.

Bronchiolitis recovery and the use of High Efficiency Particulate Air (HEPA) Filters (The BREATHE Study): study protocol for a multi-center, parallel, double-blind, randomized controlled clinical trial

BackgroundAcute viral bronchiolitis is the most common reason for hospitalization of infants in the USA. Infants hospitalized for bronchiolitis are at high risk for recurrent respiratory symptoms and wheeze in the subsequent year, and longer-term adverse respiratory outcomes such as persistent childhood asthma. There are no effective secondary prevention strategies. Multiple factors, including air pollutant exposure, contribute to risk of adverse respiratory outcomes in these infants. Improvement in indoor air quality following hospitalization for bronchiolitis may be a prevention opportunity to reduce symptom burden. Use of stand-alone high efficiency particulate air (HEPA) filtration units is a simple method to reduce particulate matter ≤ 2.5 µm in diameter (PM2.5), a common component of household air pollution that is strongly linked to health effects.MethodsBREATHE is a multi-center, parallel, double-blind, randomized controlled clinical trial. Two hundred twenty-eight children < 12 months of age hospitalized for the first time with bronchiolitis will participate. Children will be randomized 1:1 to receive a 24-week home intervention with filtration units containing HEPA and carbon filters (in the child’s sleep space and a common room) or to a control group with units that do not contain HEPA and carbon filters. The primary objective is to determine if use of HEPA filtration units reduces respiratory symptom burden for 24 weeks compared to use of control units. Secondary objectives are to assess the efficacy of the HEPA intervention relative to control on (1) number of unscheduled healthcare visits for respiratory complaints, (2) child quality of life, and (3) average PM2.5 levels in the home.DiscussionWe propose to test the use of HEPA filtration to improve indoor air quality as a strategy to reduce post-bronchiolitis respiratory symptom burden in at-risk infants with severe bronchiolitis. If the intervention proves successful, this trial will support use of HEPA filtration for children with bronchiolitis to reduce respiratory symptom burden following hospitalization.Trial registrationNCT05615870. Registered on November 14, 2022.

Use of methacoline challenge test to detect bronchial hyperresponsiveness in children with persistent rhinitis

Purpose: The incidence of persistent rhinitis in childhood is increasing day by day. Since bronchial hyperreactivity (BHR) and asthma can also be seen in a significant proportion of patients with persistent rhinitis, the use of markers that may indicate the risk of developing asthma in these patients is very important in clinical follow-up. In this study, it was aimed to demonstrate the relationship between persistent rhinitis and asthma in childhood using the bronchial methacoline challenge test (BMCT) and to investigate other factors associated with the risk of developing asthma in patients with persistent rhinitis.&#x0D; Materials and Methods: Patients aged 6-18 years who presented with findings of persistent rhinitis were evaluated with a detailed history, physical examination, and spirometry. Patients with normal examination findings and spirometry findings, and patients whose examination findings and nasal inflammation findings were compatible with moderate-to-severe rhinitis were included in the study, and their atopy status was evaluated by skin prick test, and their BHR was evaluated by BMCT.&#x0D; Results: Seventy-three patients were included in the study. The mean age was 9±2.7years, 45.2% of the patients were male. 63% of the patients were allergic and family history of allergy was present in 45.2% of the patients. 82.2% of the patients had BHR detected with BMCT. The median blood eosinophil count (BEC) was 320/mm3 and the IgE level was 160kU/L. Patients with atopy had statistically significantly higher IgE and BEC values compared with non-allergic patients. Patients with BHR were found to be younger, and had higher median BEC values. In multivariant analysis, it was observed that the patient's age300/mm3, and IgE levels&gt;250IU/L increased the probability of detecting BHR with BMCT. &#x0D; Conclusion: Care should be taken for every patient with persistent rhinitis because of the risk of BHR and asthma. Atopy examinations should be performed, but the possibility of developing BHR and asthma should not be overlooked even in the patients who are non- allergic.

The longitudinal association between asthma severity and physical fitness among new York City public school youth

Severe persistent childhood asthma is associated with low physical activity and may be associated with poor physical fitness. Research on the asthma severity-fitness association longitudinally and across sociodemographic subgroups is needed to inform fitness interventions targeting youth with asthma. We evaluated the relationship between asthma severity (categorized as severe, mild, or no asthma) and subsequent fitness in New York City (NYC) public school youth enrolled in grades 4–12 using the NYC Fitnessgram dataset (2010–2018). Longitudinal mixed models with random intercepts were fit to test the association between asthma severity and one-year lagged fitness z-scores by clustering repeated annual observations at the student level. Models were adjusted for sex, race/ethnicity, grade level, poverty status, time, and stratified by sociodemographic factors. The analytic sample included 663,137 students (51% male; 31% non-Hispanic Black, 40% Hispanic; 55% in grades 4–8, 70% high poverty; 87%, 11% and 1% with no, mild, and severe asthma, respectively). Students with severe asthma and mild asthma demonstrated −0.19 (95% CI, −0.20 to −0.17) and − 0.10 (95% CI, −0.11 to −0.10), respectively, lower fitness z-scores in the subsequent year relative to students without asthma. After stratifying by demographics, the magnitude of the asthma severity-fitness relationship was highest for non-Hispanic white vs. all other racial/ethnic subgroups, and was similar across sex, grade level, and household poverty status. Overall, we observed an inverse longitudinal relationship between asthma severity and subsequent fitness among urban youth, particularly non-Hispanic Whites. Future research should examine how neighborhood-level factors impact the asthma severity-fitness relationship across racial/ethnic subgroups.

Lifetime lung function trajectories and COPD: when the train derails

Increasing recognition that chronic respiratory disease originates in early life has shifted the paradigm away from traditional concepts of chronic obstructive pulmonary disease (COPD) as solely a smoker's disease. 1 Martinez FD Early-life origins of chronic obstructive pulmonary disease. N Engl J Med. 2016; 375: 871-878 Crossref PubMed Scopus (277) Google Scholar Building on Fletcher and Peto's landmark publication highlighting smoking-related decline of FEV1, 2 Fletcher C Peto R The natural history of chronic airflow obstruction. BMJ. 1977; 1: 1645-1648 Crossref PubMed Scopus (1800) Google Scholar multiple cohort studies have since implicated altered lung function trajectories originating in childhood in the accelerated development of lung disease. 3 Berry CE Billheimer D Jenkins IC et al. A distinct low lung function trajectory from childhood to the fourth decade of life. Am J Respir Crit Care Med. 2016; 194: 607-612 Crossref PubMed Scopus (114) Google Scholar , 4 Lange P Celli B Agustí A et al. Lung-function trajectories leading to chronic obstructive pulmonary disease. N Engl J Med. 2015; 373: 111-122 Crossref PubMed Scopus (346) Google Scholar , 5 McGeachie MJ Yates KP Zhou X et al. Patterns of growth and decline in lung function in persistent childhood asthma. N Engl J Med. 2016; 374: 1842-1852 Crossref PubMed Scopus (350) Google Scholar , 6 Stern DA Morgan WJ Wright AL Guerra S Martinez FD Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study. Lancet. 2007; 370: 758-764 Summary Full Text Full Text PDF PubMed Scopus (429) Google Scholar This work has revealed that many individuals tend to track along a lung function percentile established in childhood, such that those who begin life at a lower lung function percentile because of adverse perinatal or chronic childhood respiratory conditions are hindered from reaching maximal peak lung function as young adults. Even with the normal age-related rate of lung function decline, these individuals stay on a path with an increased lifetime risk for COPD. Importantly, multiple identified early-life risk factors—including those experienced in utero—alter developmental programming, affecting the timing and course of progression to chronic lung disease. 7 Postma DS Bush A van den Berge M Risk factors and early origins of chronic obstructive pulmonary disease. Lancet. 2015; 385: 899-909 Summary Full Text Full Text PDF PubMed Scopus (318) Google Scholar Lifetime spirometry patterns of obstruction and restriction, and their risk factors and outcomes: a prospective cohort studyTo our knowledge, this is the first study to characterise lifetime phenotypes of obstruction and restriction simultaneously using objective data-driven techniques and unique life course spirometry measures of FEV1/FVC ratio and FVC from childhood to middle age. Mixed and obstructive-only patterns indicate those who might benefit from early COPD interventions. Those with the restrictive-only pattern had evidence of true lung restriction and were at increased risk of multimorbidity by middle age. Full-Text PDF

Роль факторов риска в детском возрасте на формирование хронической обструктивной болезни легких

An analysis of literature on COPD in children has shown that COPD arises from an accelerated decline in lung function, an inability to achieve normal lung function after childhood, or a combination of the two. Risk factors for the development of COPD are considered negative environmental influences; maternal smoking, intrauterine development disorders, prematurity, low birth weight, bronchopulmonary dysplasia, as well as frequent or severe respiratory infections in childhood (especially respiratory syncytial virus and rhinovirus) that prevent the full growth and development of the lungs; asthma in childhood; early allergic sensitization and/or a rare genetic disorder (alpha‑1 antitrypsin deficiency), childhood chronic cough, parental history of respiratory disease, and low educational attainment. Particularly vulnerable are children from socio-economically low strata of the population, in particular, from among the indigenous population of multi-ethnic countries. In low- and middle-income countries, diagnosing COPD is difficult, and the disease may go undiagnosed. Bronchial asthma in childhood can be considered as an independent risk factor for COPD in adulthood. At the same time, the asthma-COPD overlap syndrome is widespread, the risk of which is especially high among individuals with persistent and severe childhood asthma, which is highly dependent on genetics. Targeted programs are needed to reduce the risk of adverse pulmonary outcomes in disadvantaged children, as well as the integration of specialized outreach services into primary health care. The WHO COPD core package includes protocols for assessing, diagnosing and managing COPD, as well as modules on healthy lifestyles, including smoking cessation and self-help, and development of rehabilitation services.

Biologic therapies for asthma in underserved populations

Black and Hispanic children living in disadvantaged urban environments in the USA face a disproportionate burden of asthma, experiencing the highest rates of morbidity and mortality in the country. 1 Altman MC Calatroni A Ramratnam S et al. Endotype of allergic asthma with airway obstruction in urban children. J Allergy Clin Immunol. 2021; 148: 1198-1209 Summary Full Text Full Text PDF PubMed Scopus (11) Google Scholar The repeated exacerbations that accompany severe eosinophilic asthma in these populations can lead to loss of lung function, increased asthma severity, and progression to a pattern of fixed obstructive lung disease by early adulthood. 2 O'Brian AL Lemanske Jr, RF Evans MD Gangnon RE Gern JE Jackson DJ Recurrent severe exacerbations in early life and reduced lung function at school age. J Allergy Clin Immunol. 2012; 129: 1162-1164 Summary Full Text Full Text PDF PubMed Scopus (27) Google Scholar , 3 McGeachie MJ Yates KP Zhou X et al. Patterns of growth and decline in lung function in persistent childhood asthma. N Engl J Med. 2016; 374: 1842-1852 Crossref PubMed Scopus (350) Google Scholar Worryingly, in a substantial proportion of these children, conventional guideline-directed therapies, such as corticosteroids and long-acting β agonists, do not improve asthma control. Consequently, the identification of novel therapeutic strategies represents an important unmet need for underserved Black and Hispanic children living in urban areas. 4 Gonzalez Burchard E Borrell LN Need for racial and ethnic diversity in asthma precision medicine. N Engl J Med. 2021; 385: 2297-2298 Crossref PubMed Scopus (5) Google Scholar Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trialPhenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. Full-Text PDF

From the Pages of AllergyWatch

For this edition of “From the Pages of AllergyWatch,” I have chosen articles from the January to February 2022 AllergyWatch. The first article, with comments from Dr Hernandez-Trujillo, presents evidence that younger children have lower rates of severe reactions to oral food challenges. The next article, with comments from Dr Knox, followed a prospective birth cohort, reporting that although most children outgrew their cow's milk sensitivity, many did have allergic diseases at adolescence. The previous article, with comments from Dr Chipps, presents follow-up data from the Childhood Asthma Management Program that identify risk factors for the development of severe persistent asthma in children.

Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium

In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. Prevalence of early and persistent childhood wheeze and asthma incidence. Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Maternal obesity, gestational weight gain, and offspring asthma and atopy

BackgroundMaternal obesity may affect offspring asthma and atopic disease risk by altering fetal immune system development. However, few studies evaluate gestational weight gain (GWG). ObjectiveTo evaluate relationships between maternal body mass index (BMI), GWG, and persistent wheeze, eczema, allergy, and asthma risk in offspring through middle childhood. MethodsA total of 5939 children from Upstate KIDS, a population-based longitudinal cohort of children born in upstate New York (2008-2019) were included in the analysis. Persistent wheeze or asthma, eczema, and allergy were maternally reported at multiple study time points throughout early and middle childhood. Poisson regression models with robust SEs were used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) for offspring atopic outcomes by maternal prepregnancy BMI and GWG. ResultsPrepregnancy BMI was associated with increased risk of persistent wheeze by 3 years of age even after adjustments for maternal atopy (class I obesity: aRR, 1.58; 95% CI, 1.13-2.20; class II or III obesity: aRR, 1.69; 95% CI, 1.22-2.35). Associations with reported asthma in middle childhood did not reach statistical significance. Furthermore, no associations were found between prepregnancy BMI and atopic outcomes in either early or middle childhood. GWG was not associated with higher risk of early childhood persistent wheeze or middle childhood asthma. ConclusionMaternal prepregnancy BMI was associated with increased risk of offspring wheeze, whereas excessive GWG was generally not associated with childhood asthma or atopy.

Caregiver Experiences Managing Persistent Childhood Asthma During the COVID-19 Pandemic.

COVID-19 has adversely affected child wellness, but it is unclear whether the pandemic led to changes in home management of chronic diseases like asthma. We surveyed 93 caregivers of children with persistent asthma from 2 ongoing asthma trials to measure changes in home asthma management, stressors, access to health care, and caregivers' worry about COVID-19 affecting their child's health. We conducted descriptive analyses, and assessed whether caregiver worry about COVID-19 was associated with asthma management, stressors, health care access, or recent symptoms. Most (80%) caregivers worried that COVID-19 would affect their child's health, and >50% restricted their child's physical activity to avoid asthma symptoms. We observed a dose-dependent relationship between increasing worry about COVID-19 and activity restrictions, financial hardship, difficulty obtaining asthma medications, and nocturnal asthma symptoms. These findings raise concern that children with persistent asthma may be at particular risk for weight gain and obesity-associated asthma morbidity due to the pandemic.

Heterogeneity of Mild to Moderate Persistent Asthma in Children: Confirmation by Latent Class Analysis and Association With 1-Year Outcomes

To identify latent classes of childhood asthma and determine if latent class assignments predict subsequent lung function abnormalities and exacerbation rate at 12 months of follow-up.2593 children aged 5 to 18 years enrolled in NHLBI clinical trials on mild-to-moderate asthma and who had documented adherence to article or electronic diaries.Latent class analyses were performed on the subjects on the basis of data that had been obtained as part of the clinical trials, which included questionnaires, asthma documentation and characterization by spirometry, asthma control questionnaires, total immunoglobulin E, blood eosinophils, and allergy tests. Primary outcomes included pulmonary function and the exacerbation rate over 1 year of follow-up.Five latent classes were identified. Class 1 was as follows: multiple allergic sensitizations with partially reversible airflow limitation. Class 2 was as follows: multiple sensitization with reversible airflow limitation; Class 3 was as follows: lesser sensitization with reversible airflow limitation. Class 4 was as follows: multiple sensitization with normal lung function. Class 5 was as follows: lesser sensitization with normal lung function. Lesser sensitization means mostly nonsensitivity or monosensitivity. Latent class 2 was the largest group (35.7%), followed by class 4 (27.6%), class 5 (15.0%), class 3 (12.1%), and class 1 (9.4%). Children in class 1 had lower pulmonary function at the end of the first year, with lesser treatment response. Children in class 2 revealed improvement in lung function with treatment, and seemed to respond to any controller therapy, whereas those in class 4 and 5 had a greater response to inhaled corticosteroids. Exacerbations occurred in 52.5% of class 1, 43.0% of class 4, 41.6% of class 2, 36.8% of class 3, and 34.1% of class 5; class 1 had significantly increased exacerbations, compared with that of the other classes. Inhaled corticosteroids treatment significantly reduced exacerbations in classes 1, 2, and 4 but not in classes 3 and 5. Lung function deficits persisted despite treatment of class 1.Exacerbation rates were highest in children with multiple sensitization and partially reversible airflow limitation. Sensitization and lung function measures in children may be useful for predicting future risk in clinical settings.Because these children were all enrolled in asthma clinical trials, the results may not be generalizable to the overall pediatric asthma population, but the results do reveal that children with asthma may benefit from comanagement with an allergist to better predict those at the most risk and need for more than conventional medications.

Do Inhaled Steroids Affect Childhood Obesity

Inhaled corticosteroids (ICS) are the mainstay of therapy for persistent asthma in children, but they have side effects, such as slowing of growth

Comparison of the Effects of Beclomethasone Dipropionate and Budesonide in the Treatment of Children with Mild, Persistent Asthma.

ObjectiveTo compare the mean change in peak expiratory flow values in children receiving inhaled beclomethasone dipropionate versus inhaled budesonide in the treatment of mild persistent asthma.MethodThe medical records of 60 patients from the outpatient department (OPD)/emergency room (ER), National Institute of Child Health, Karachi, who received beclomethasone dipropionate (BDP) 200 µg one puff and budesonide (BUD) 200 µg one puff twice a day for treatment of mild persistent asthma from March 10, 2020, to August 10, 2020, were explored.ResultsThe mean age of children was 10.56 ± 3.01 years in the BUD group and 10.05 ± 3.54 years in the BDP group. The mean change in peak expiratory flow % in the BUD group was 15.69 ± 3.59%, and in the BDP group, it was 13.59 ± 4.26% (P-value=0.04)ConclusionBDP and budesonide (BUD) were both found to be effective for the treatment of mild persistent asthma in children. However, we found that BUD had better efficacy compared to BDP.

Inhaled Budesonide vis-à-vis Inhaled Mometasone in Chinese Children with Mild Persistent Asthma: A Single-Center, Retrospective Study

Introduction: A very limited option of inhaled corticosteroids (ICSs) is approved for pediatric use in China because in children the use of ICSs for long periods is associated with dose-dependent growth reduction. Due to the lack of consensus on which is the best ICS-based treatment option to manage mild persistent asthma in children, the present study was performed to evaluate the efficacy and safety of budesonide (BUD)-based therapy vis-à-vis mometasone-based therapy in children with mild persistent asthma. Methods: A single-center, retrospective study was conducted in asthmatic children aged between 6 and 11 years. BUD and mometasone furoate (MF) were administered as per the approved dosing regimen using pressurized metered-dose inhalers via oral inhalation route for a period of 12 weeks. The study outcome was assessed in terms of the forced expiratory volume in 1 s (FEV₁), symptom scores, and nonoccurrence of side effects. Results: Among the 77 asthmatic children, 71 completed the study treatment and were used in carrying out the analysis. The improvement of spirometric parameters like FEV₁, Tiffeneau-Pinelli index (FEV1/forced vital capacity [FVC]), and peak expiratory flow (PEF) values observed in the MF cohort was significantly greater than those of the BUD cohort (p < 0.05 for all). An increase of approximately 12%/child was observed for FEV₁/FVC ratios for the BUD cohort and MF cohorts. After the 12-week study, the PEF_m and PEF_e values increased to about 50 L/min/child for the BUD cohort and about 98 L/min/child for the MF cohort. During the study, no asthma exacerbation event was observed in the MF cohort, whereas 1 child in the BUD cohort had asthma exacerbation in week 4. The use of rescue medication during the study was required for 16.2 and 6% of children, respectively, for BUD and MF cohorts. Owing to low dosing frequency, MF could provide a better treatment approach than BUD due to improved patient compliance. Conclusions: Although both drugs showed improvement in the quality of life of asthmatic children with manageable treatment-emergent adverse effects, the improvement was augmented in MF-treated children. Level of Evidence: The level of evidence was III. Technical Efficacy Stage: The technical efficacy stage was 4.

Genome-wide association study identifies TNFSF15 associated with childhood asthma.

Genome-wide association studies (GWASs) of asthma have identified several risk alleles and loci, but most have been conducted in individuals with European-ancestry. Studies in Asians, especially children, are still lacking. We aimed to identify susceptibility loci by performing the first GWAS of asthma in Korean children with persistent asthma. We used a discovery set of 741 children with persistent asthma as cases and 589healthy children and 551healthy adults as controls to perform a GWAS. We validated our GWAS findings using UK Biobank data. We then used the Genotype-Tissue Expression database to identify expression quantitative trait loci of candidate variants. Finally, we quantified proteins of genes associated with asthma. Variants at the 17q12-21locus and SNPs in CYBRD1 and TNFSF15genes were associated with persistent childhood asthma at genome-wide thresholds of significance. Four SNPs in the TNFSF15gene were also associated with childhood-onset asthma in British white participants in the UK Biobank data. The asthma-associated rs7856856-C allele, the lead SNP, was associated with decreased TNFSF15 expression in whole blood and in arteries. Korean children with asthma had lower serum TNFSF15levels than controls, and those with the asthma risk rs7856856-CC genotype exhibited the lowest serum TNFSF15levels overall, especially asthmatic children. Our GWAS of persistent childhood asthma with allergic sensitization identified a new susceptibility gene, TNFSF15, and replicated associations at the 17q12-21 childhood-onset asthma locus. This novel association may be mediated by reduced expression of serum TNFSF15 and loss of suppression of angiogenesis.

Efficacy of Leukotriene Modifiers for the Treatment of Persistent Asthma in Children

The purpose of this study was to evaluate the use of the leukotriene modifiers (LTMs), zafirlukast and montelukast, in children with asthma managed by an inner city pediatric pulmonary practice. A retrospective chart review was done of children 6 years of age with persistent asthma seen at Connecticut Children's Medical Center and prescribed LTM drugs. Eighty-three children whose asthma control was adequately assessed both before and after addition of a LTM to his/her treatment regimen was included in the study. There were statistically significant improvements in several parameters of asthma control following initiation of LTM use, including provider assessment score (p = 0.0005), number of hospitalizations and unscheduled visits (clinic or emergency department; p &lt; 0.0001), use of oral corticosteroids (p = 0.0015), spirometry severity score (p = 0.0015), and spirometry test results (FEV1, FEV1/FVC, FEF, FEF25-75%; p &lt; 0.005 for all). These results suggest that montelukast and zafirlukast help to improve asthma control in young patients with persistent asthma.

Developmental patterns in the nasopharyngeal microbiome during infancy are associated with asthma risk

BackgroundStudies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma.ObjectivesIn this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma.MethodsChildren participating in the Childhood Origins of Asthma study (N = 285) provided nasopharyngeal mucus samples in the first 2 years of life, during routine healthy study visits (at 2, 4, 6, 9, 12, 18, and 24 months of age), and during episodes of respiratory illnesses, all of which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and we correlated these with presence of asthma at 6, 8, 11, 13, and 18 years of age.ResultsOf the 4 microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood.ConclusionIn infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma.

Network study of nasal transcriptome profiles reveals master regulator genes of asthma

Nasal transcriptomics can provide an accessible window into asthma pathobiology. Our goal was to move beyond gene signatures of asthma to identify master regulator genes that causally regulate genes associated with asthma phenotypes. We recruited 156 children with severe persistent asthma and controls for nasal transcriptome profiling and applied network-based and probabilistic causal methods to identify severe asthma genes and their master regulators. We then took the same approach in an independent cohort of 190 adults with mild/moderate asthma and controls to identify mild/moderate asthma genes and their master regulators. Comparative analysis of the master regulator genes followed by validation testing in independent children with severe asthma (n= 21) and mild/moderate asthma (n= 154) was then performed. Nasal gene signatures for severe persistent asthma and for mild/moderate persistent asthma were identified; both were found to be enriched in coexpression network modules for ciliary function and inflammatory response. By applying probabilistic causal methods to these gene signatures and validation testing in independent cohorts, we identified (1) a master regulator gene common to asthma across severity and ages (FOXJ1); (2) master regulator genes of severe persistent asthma in children (LRRC23, TMEM231, CAPS, PTPRC, and FYB); and (3) master regulator genes of mild/moderate persistent asthma in children and adults (C1orf38 and FMNL1). The identified master regulators were statistically inferred to causally regulate the expression of downstream genes that modulate ciliary function and inflammatory response to influence asthma. The identified master regulator genes of asthma provide a novel path forward to further uncovering asthma mechanisms and therapy.