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Background: Dysregulation of eicosanoids is associated with asthma and a composite of oxylipins, including exhaled leukotriene B4 (LTB4), characterizes childhood asthma. While fractional exhaled nitric oxide (FeNO) has been used as the standard for monitoring steroid responsiveness, the potential utility of eicosanoids in monitoring the therapeutic outcomes remains unclear. We aimed to examine the levels of major eicosanoids representing different metabolic pathways in exhaled breath condensates (EBCs) of children with asthma during exacerbation and after treatment. Methods: Levels of 6 exhaled eicosanoid species in asthmatic children and healthy subjects were evaluated using ELISA. Results: In addition to those previously reported, including LTB4, the levels of exhaled 15‐hydroxyeicosatetraenoic acid (15‐HETE), but not thromboxane B2 (TXB2), showed significant difference between asthmatics (N = 318) and healthy controls (N = 97), particularly the severe group showed the lowest levels of exhaled 15‐HETE. Receiver operating characteristic (ROC) curve analyses revealed similar distinguishing power for the levels of 15‐HETE, FEV1 (forced expiratory volume in the first second), and FeNO, while the 15‐HETE/LTB4 ratio was significantly lower in subjects with asthma as compared to that of healthy controls (p < 0.0001). Analysis of asthmatics (N = 75) during exacerbation and convalescence showed significant improvement in lung function (FEV1, p <.001), but not FeNO, concomitant with significantly increased levels of 15‐HETE (p <.001) and reduced levels of TXB2 (p <.05) at convalescence, particularly for those who at the top 30% level during exacerbation. Further, decreased LTB4 and lipoxin A4 (LXA4) at convalescence were noted only in those at the top 30 percentile during exacerbation. Conclusion: The exhaled 15‐HETE was found to discriminate childhood asthma while decreased levels of exhaled TXB2 and increased levels of 15‐HETE were prominent at convalescence. [ABSTRACT FROM AUTHOR]

Background: Chemokines are important mediators in immune cell recruitment, contributing to allergy development. However, extensive studies of chemokines in the circulation in relation to the presence and development of allergic diseases remain scarce. Our aim was to investigate associations of circulating allergy‐related chemokines with the development of asthma and sensitization cross‐sectionally and longitudinally in a population‐based cohort. Methods: The chemokines CCL17, CCL22, CXCL10, CXCL11 and CCL18 were measured in plasma samples from children in the Manchester Asthma and Allergy Study. Samples were available from cord blood at birth (n = 376), age 1 (n = 195) and age 8 (n = 334). Cross‐sectional and longitudinal association analyses were performed in relation to asthma and allergic sensitization, as well as allergic phenotype clusters previously derived using machine learning in the same study population. Results: In children with asthma and/or allergic sensitization, CCL18 levels were consistently elevated at 1 and/or 8 years of ages. In a longitudinal model including information on asthma from 4 time points (5, 8, 11 and 16 years of ages), we observed a significant association between increasing CCL18 levels at age 1 and a higher risk of asthma from early school age to adolescence (OR = 2.9, 95% CI 1.1–7.6, p =.028). We observed similar associations in longitudinal models for allergic sensitization. Asthma later in life was preceded by increased CXCL10 levels after birth and decreased CXCL11 levels at birth. Conclusion: Elevated CCL18 levels throughout childhood precede the development of asthma and allergic sensitization. The Th1‐associated chemokines CXCL10 and CXCL11 also associated with the development of both outcomes, with differential temporal effects. [ABSTRACT FROM AUTHOR]

Additionally, children with asthma had worse COVID-19 severity scores indicating that asthma may be a risk factor for more severe forms of COVID-19 among children seeking ER care. Asthma/recurrent wheezing and prematurity were associated with LRT involvement and worse COVID-19 severity scores among children seeking ER care. In multivariate analysis, LRT involvement was significantly associated with prematurity and asthma, whereas a more severe COVID-19 score was associated with asthma, prematurity, neurological disease, and age <2 years of age. Asthma is associated with lower respiratory tract involvement and worse clinical score in children with COVID-19. [Extracted from the article]

Background: Exhaled breath condensate (EBC) pH is a promising biomarker of airway inflammation. Lack of method standardization and interstudy variability precludes its use in clinical practice. While endogenous determinants have been described, underlying mechanisms for variability are mostly unknown. Thus, we aimed to assess the association between asthma and EBC pH in children, while studying potential environmental factors for interstudy variability. Methods: A cross‐sectional analysis of exhaled breath condensates from 613 children, aged 7–12 years, was conducted. Assessments included lung function and airway reversibility, exhaled nitric oxide, allergic sensitization, and body mass index (BMI). Indoor air quality (IAQ) was assessed in children's classrooms during 5 school days. Post‐deaeration EBC pH showed a bimodal distribution, and the sample was split into acidic and alkaline groups. Regression models were constructed to assess the effects of asthma and asthma adjusted to IAQ parameters on EBC pH. Results: Following adjustment to gender and BMI, asthma was significantly associated with a lower EBC pH in the acidic group. The effect of asthma on EBC pH was independent of IAQ, in both groups. In the acidic group, EBC pH was significantly affected by temperature [β = −0.09 (−0.15, −0.02)] and PM 2.5 concentration [β = −0.16 (−0.32, −0.01)], and in the alkaline group by relative humidity [β = 0.07 (0.02, 0.13)] and concentration of endotoxins [β = −0.06 (−0.1, −0.01)]. Conclusion: Our study shows that in addition to individual determinants such as asthma, environmental factors may influence and should be taken into consideration when interpreting EBC pH level in children. [ABSTRACT FROM AUTHOR]

Problematic severe asthma remains a significant challenge to manage, accounting for the majority of healthcare utilization among children with asthma. The heterogeneity is recognized and the clinical phenotypes of "difficult‐to‐treat" asthma (DA) and "severe therapy‐resistant asthma" (STRA) help to guide management. Recent evidence supports molecular distinctions between these phenotypes and shows poor correlations between peripheral and airway markers of inflammation, especially in STRA. Airway neutrophils in the context of childhood severe asthma have been explored, but their role in disease causation, protection, or as bystanders remain unknown, and thus, treatment implications are unclear. Several novel management strategies, including once‐daily maintenance therapy, single‐device maintenance and reliever therapy, and novel biological treatments are being increasingly used for DA and STRA. However, pediatric data for efficacy of novel treatments is scarce, and when available, is restricted to adolescents. The aim of this review is to highlight recent advances in objective biomarkers that aid stratification and management of childhood severe asthma and to highlight gaps in pediatric evidence. Specifically, the urgent need for efficacy studies to improve the management of problematic severe asthma in children younger than 12 years. [ABSTRACT FROM AUTHOR]

Background: The Mediterranean diet (MD) has known health benefits, but its specific impact on allergy development is unclear. As part of the PARIS birth cohort follow‐up, we aimed to investigate the adherence of 8‐year‐old children to the MD and its association with allergic/respiratory morbidity at school age. Methods: Diet was assessed using a food frequency questionnaire completed by the parents. Adherence to the MD was assessed based on two scores: the KIDMED index and the Mediterranean Diet Score (MDS). Current allergic diseases (asthma, rhinitis, eczema), lung function indices (FEV1 and FVC), FeNO and specific IgE levels were determined during a health check‐up at 8 years. Associations between levels of adherence to the MD and respiratory/allergic morbidity were studied using multivariable logistic and linear regression models adjusted for potential confounders. Results: A total of 975 children were included in the present study, 35.6% with low adherence to the MD, 55.7% with moderate adherence and 8.7% with high adherence according to the KIDMED index. High family socioeconomic status, any breastfeeding at 6 months and consumption of organic food were associated with higher adherence to the MD. Compared with low adherence, high adherence was associated with lower risk of asthma and sensitization at 8 years, as well as higher FEV1 and FVC. Conclusion: This study suggests a protective effect of high adherence to the MD on allergic and respiratory morbidity at school age. These results need to be confirmed by further longitudinal analyses. A healthy diet may prevent allergic and respiratory morbidity in school‐aged children. [ABSTRACT FROM AUTHOR]

Severe asthma (SA) affects less than 5% of the pediatric asthma population but is considered to account for approximately half of total pediatric asthma healthcare costs. For children with allergic SA not requiring omalizumab, the economic burden of allergic comorbidities was €174.50 representing 17.8% of direct SA costs and 15.8% of global SA costs (Figure S1). Allergic comorbidities, including food allergies (FA) and allergic rhinitis (AR), are frequent in children with SA.1 The presence of FA and AR increases asthma severity 1-6 and medication use.4-6 Treating AR improves asthma symptoms.3 However, the economic burden of allergic comorbidities in children with SA has been poorly studied. The mean overall cost of SA was €3,982.00 over the six-month study period.7 For children with allergic SA, the mean cost attributed to allergic comorbidities was €2,803.00 representing 48.1% of the direct SA costs and 45.8% of the global SA costs (Figure S1). [Extracted from the article]

Background: Exposure to indoor moisture damage and visible mold has been found to be associated with asthma and respiratory symptoms in several questionnaire‐based studies by self‐report. We aimed to define the prospective association between the early life exposure to residential moisture damage or mold and fractional exhaled nitric oxide (FeNO) and lung function parameters as objective markers for airway inflammation and asthma in 6‐year‐old children. Methods: Home inspections were performed in children's homes when infants were on average 5 months old. At age 6 years, data on FeNO (n = 322) as well as lung function (n = 216) measurements were collected. Logistic regression and generalized additive models were used for statistical analyses. Results: Early age major moisture damage and moisture damage or mold in the child's main living areas were significantly associated with increased FeNO levels (>75th percentile) at the age of 6 years (adjusted odds ratios, 95% confidence intervals, aOR (95% CI): 3.10 (1.35‐7.07) and 3.16 (1.43‐6.98), respectively. Effects were more pronounced in those who did not change residential address throughout the study period. For lung function, major structural damage within the whole home was associated with reduced FEV1 and FVC, but not with FEV1/FVC. No association with lung function was observed with early moisture damage or mold in the child's main living areas. Conclusion: These results underline the importance of prevention and remediation efforts of moisture and mold‐damaged buildings in order to avoid harmful effects within the vulnerable phase of the infants and children's immunologic development. [ABSTRACT FROM AUTHOR]

Asthma has now become one of the most common atopic disorders not only in developed countries but also in many developing countries. The etiology is likely due to a complex interaction between genetic and environmental factors. In many Asian countries, the prevalence of asthma has also been documented by validated instruments to be increasing rapidly over the past two decades. However, studies in rural areas in Asia with a traditional farming environment revealed markedly lower asthma prevalence when compared with residents in nearby cities despite having similar genetic background. Among the environmental factors implicated in the pathogenesis of asthma, air pollution, dietary patterns, viral infections, and early microbial exposure have been studied extensively around the world. Asia provides many opportunities to study these potential factors as there are many ethnic groups living in distinctly different environments. The understanding of the roles of these factors in affecting the early immune system and subsequent development of asthma will enable us to develop potential primary preventive strategies against a disease which affects millions worldwide. [ABSTRACT FROM AUTHOR]

Background: It is unclear in which periods of life lung function deficits develop, and whether these are affected by risk factors such as asthma, bronchial hyper‐responsiveness (BHR) and allergic comorbidity. The goal of this systematic review was to identify temporal associations of asthma, BHR and allergic comorbidity with large and small lung function development from birth until peak function in early adulthood. Methods: We searched MEDLINE, EMBASE, Web of Science and CINAHL for papers published before 01.01.2020 on risk factors and lung function measurements of large and small airways. Studies were required to report lung function at any time point or interval from birth until peak lung function (age 21‐26) and include at least one candidate risk factor. Results: Of the 45 papers identified, 44 investigated cohorts and one was a clinical trial with follow‐up. Asthma, wheezing, BHR and allergic sensitization early in life and to multiple allergens were associated with a lower lung function growth of large and small airways during early childhood compared with the control populations. Lung function development after childhood in subjects with asthma or persistent wheeze, although continuing to grow at a lower level, largely tracked parallel to non‐affected individuals until peak function was attained. Clinical implications and future research: Deficits in lung function growth develop in early childhood, and children with asthma, BHR and early‐life IgE (poly)sensitization are at risk. This period is possibly a critical window of opportunity to identify at‐risk subjects and provide treatment aimed at preventing long‐term sequelae of lung function. [ABSTRACT FROM AUTHOR]

Overall, children below 3 years of age incurred 3.6 times higher asthma costs and in particular 9.3 times higher asthma-related hospitalization costs than those aged 4 and older. The substantially higher costs in the first 3 years of life reflect the challenge of managing asthma in young children because, despite the early diagnosis, they were frequently hospitalized for asthma and other respiratory conditions. Right panel, direct medical costs related to other respiratory conditions, total and by components gl Figures S3 and S4 respectively present the sex- and SES-stratified age trends of costs related to asthma and other respiratory conditions. Between 4 and 18 years of age, per child-year asthma-related costs steadily declined, but at a slower rate of -14.1%, while hospitalization costs declined by -30.0% every year. [Extracted from the article]

Background: There are limited data describing lung function changes in children after an asthma exacerbation. Our hypothesis was that lung function does not fully recover in children in the months following an asthma exacerbation. Methods: We used a data set of children with asthma where lung function (including FEV1, FEV1/FVC ratio and FEF25‐75) was measured at 3‐month intervals over a year. Mixed‐level models compared spirometry measured on two occasions 3 months apart before a single exacerbation (assessments 1 and 2) with measurements made on two occasions after the exacerbation (assessments 3 and 4), with adjustment for covariates. Changes in spirometry over a year were also analysed across those with exacerbations in no, one or more than one 3‐month periods. Results: For the 113 children who had a single exacerbation, spirometry measured at assessments 1 or 2 did not differ from measurements at assessments 3 or 4 when the whole population was considered. When stratified into tertiles by change in %FEV1 between assessments 2 and 3, those with the greater reduction were more likely to be treated with long‐acting beta‐agonist, but in this category, %FEV1 at assessment 4 had returned to the value at assessment 1. %FEV1 did not change over a 12‐month period within and between the three exacerbation categories (n = 809). Conclusion: One or more asthma exacerbation was not associated with a fall in lung function for the whole population. In a subset of individuals, lung function does fall after an exacerbation but returns to pre‐exacerbation values after a period of months. [ABSTRACT FROM AUTHOR]

Background: Cardio‐metabolic risk factors might have an adverse effect on respiratory outcomes, but associations in children are unknown. We aimed to study the longitudinal associations of cardio‐metabolic risk factors with lung function and asthma at school age. We also examined whether any association was explained by child's body mass index (BMI). Methods: In a population‐based cohort study among 4988 children, cardio‐metabolic risk factors were measured at 6 and 10 years and included blood pressure, cholesterol, triglycerides, insulin, and C‐reactive protein (CRP) concentrations. At age 10 years, lung function was measured by spirometry and current physician‐diagnosed asthma was assessed by questionnaire. Results: After adjustment for confounders, child's BMI, and multiple testing, we observed that a higher diastolic blood pressure at the age of 6 years was associated with a higher forced vital capacity (FVC) at the age of 10 years (Z‐score difference (95% CI): 0.05 (0.01, 0.08), per SDS increase in diastolic blood pressure). Also, child's CRP concentrations above the 75th percentile at both ages 6 and 10 years were related to a lower FVC as compared to CRP concentrations below the 75th percentile at both ages (Z‐score difference (95% CI) −0.21 (−0.36, −0.06)). No consistent associations of other cardio‐metabolic risk factors with respiratory outcomes were observed. Conclusion: Blood pressure and CRP, but not lipids and insulin, were associated with lower lung function but not with asthma. The underlying mechanisms and long‐term effects of these associations require further investigation. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the role of body mass index with regard to exercise performance, exercise‐induced bronchoconstriction (EIB), and respiratory symptoms in 7‐ to 16‐year‐old children. Methods: A total of 1120 outdoor running exercise challenge test results of 7‐ to 16‐year‐old children were retrospectively reviewed. Lung function was evaluated with spirometry, and exercise performance was assessed by calculating distance per 6 minutes from the running time and distance. Respiratory symptoms in the exercise challenge test were recorded, and body mass index modified for children (ISO‐BMI) was calculated for each child from height, weight, age, and gender according to the national growth references. Results: Greater ISO‐BMI and overweight were associated with poorer exercise performance (P <.001). In addition, greater ISO‐BMI was independently associated with cough (P =.002) and shortness of breath (P =.012) in the exercise challenge. However, there was no association between ISO‐BMI and EIB or with wheeze during the exercise challenge. Conclusion: Greater ISO‐BMI may have a role in poorer exercise performance and appearance of respiratory symptoms during exercise, but not in EIB in 7‐ to 16‐year‐old children. [ABSTRACT FROM AUTHOR]

Background: A diet rich in fruits and vegetables has been suggested to counteract the oxidative stress and inflammation that characterize asthma. We aimed to assess the association between vegetable and fruit diversity consumption and asthma and its related outcomes in school‐aged children. Methods: Participants included 647 children (49% females, aged 7‐12 years) recruited from 20 public schools across the city of Porto, in Portugal. Vegetable intake and fruit intake were ascertained using a single self‐reported 24‐hour recall questionnaire. A diversity score was built taking into account the different number of individual vegetables and fruits consumed and categorized into two groups based on the total reported median consumption, which was rounded to the nearest whole number (≤3 and >3, for vegetables; and ≤1 and >1, for fruits). A questionnaire was used to enquire about self‐reported medical diagnosis of asthma and respiratory symptoms. Airway inflammation was assessed measuring exhaled fractional nitric oxide concentration (eNO) and was categorized into two groups (<35 and ≥35 ppb). The association between fruit and vegetable diversity and respiratory outcomes was examined using logistic regression models, adjusting for confounders. Results: A higher vegetable diversity consumption per day was negatively associated with having self‐reported asthma (OR = 0.67; 95% CI 0.47, 0.95), while having a vegetable diversity consumption superior to 3 items per day was negatively associated with levels of eNO ≥ 35 ppb (OR = 0.38; 95% CI 0.16, 0.88) and breathing difficulties (OR = 0.39; 95% CI 0.16, 0.97). Conclusion: Eating a greater variety of vegetables was associated with a lower chance of airway inflammation and prevalence of self‐reported asthma in school children. [ABSTRACT FROM AUTHOR]

Background: While infant bronchiolitis contributes to substantial acute (eg, severity) and chronic (eg, asthma development) morbidities, its pathobiology remains uncertain. We examined the integrated relationships of local (nasopharyngeal) and systemic (serum) responses with bronchiolitis morbidities. Methods: In a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we applied a network analysis approach to identify distinct networks (modules)—clusters of densely interconnected metabolites—of the nasopharyngeal and serum metabolome. We examined their individual and integrated relationships with acute severity (defined by positive pressure ventilation [PPV] use) and asthma development by age 5 years. Results: In 140 infants, we identified 285 nasopharyngeal and 639 serum metabolites. Network analysis revealed 7 nasopharyngeal and 8 serum modules. At the individual module level, nasopharyngeal‐amino acid, tricarboxylic acid (TCA) cycle, and carnitine modules were associated with higher risk of PPV use (r >.20; P <.001), while serum‐carnitine, amino acid, and glycerophosphorylcholine (GPC)/glycerophosphorylethanolamine (GPE) modules were associated with lower risk (all r < −.20; P <.05). The integrated analysis for PPV use revealed consistent findings—for example, nasopharyngeal‐TCA (adjOR: 2.87, 95% CI: 1.68‐12.2) and serum‐GPC/GPE (adjOR: 0.54, 95% CI: 0.38‐0.80) modules—and an additional module—serum‐glucose‐alanine cycle module (adjOR: 0.69, 95% CI: 0.56‐0.86). With asthma risk, there were no individual associations, but there were integrated associations (eg, nasopharyngeal‐carnitine module; adjOR: 1.48, 95% CI: 1.11‐1.99). Conclusion: In infants with bronchiolitis, we found integrated relationships of local and systemic metabolome networks with acute and chronic morbidity. Our findings advance research into the complex interplay among respiratory viruses, local and systemic response, and disease pathobiology in infants with bronchiolitis. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the association of serum periostin levels with clinical features in children with asthma. Methods: Children with physician‐diagnosed asthma who attended regularly to an outpatient pediatric allergy and asthma center were enrolled in the study along with control subjects. Asthma severity and control status of the patients were evaluated according to the recent GINA guidelines. Results: A total of 158 children (125 with asthma and 33 age‐ and sex‐matched control subjects) with a median age of 10.2 years (range 5.9‐17.0) were enrolled. Asthma severity was mild in 41 (32.8%), moderate in 63 (50.4%), and severe in 21 (16.8%) children. Children with asthma had significantly higher periostin levels than controls (53.1 ± 13.1 vs 43.0 ± 11.2 ng/mL, P <.001). The mean serum periostin levels in children with severe asthma (63.8 ± 10.8) were significantly higher than in children with moderate asthma (53.3 ± 12.7) and mild asthma (47.4 ± 11.1) (P <.001). Results of multivariable logistic regression analysis demonstrated an association between serum periostin levels and asthma severity in children (OR, 1.10; 95% CI, 1.04‐1.15, P <.001). When analyzed for the best cut‐off value with the highest combined sensitivity and specificity, a cut‐off value of 52 ng/mL for serum periostin level was obtained with sensitivity, specificity, PPV, and NPV of 100%, 50%, 29%, and 100%, respectively. Conclusion: Although serum periostin levels are higher in children with asthma, its diagnostic role in identifying children with severe asthma is limited. [ABSTRACT FROM AUTHOR]

Background: Much of our knowledge of childhood asthma comes from questionnaire‐based studies. Our main aim was to assess the agreement between parental‐reported data at 12 years of age and data from two national Swedish registers. Methods: Data were obtained from the prospective, longitudinal, population‐based Children of Western Sweden cohort, which focused on children born in 2003. The parents answered questionnaires at six months and one, four, eight and 12 years of age. Personal identity numbers linked 3634 children to the Swedish Prescribed Drug Register (SPDR) and the National Patient Register (NPR). Results: At 12 years of age, there was substantial overall agreement between the asthma medication reported by the parents in the questionnaire and the SPDR for any asthma medication (94.8%, kappa 0.71) and maintenance treatment (95.3%, kappa 0.68). In contrast, the agreement between the outpatient asthma diagnoses in the NPR and the questionnaire‐based asthma was 30.5% and it was 32.8% between the NPR and the dispensed asthma medication in the SPDR. Hospitalization was rare for obstructive diseases after early childhood, and 38.2% of the 12‐year‐old children only received a short‐acting beta agonist, with no maintenance treatment. Conclusion: There was good agreement between the questionnaire‐based data on asthma medication and the national drug register, but the National Patient Register provided incomplete information on asthma diagnoses, probably because it did not include primary care diagnoses. The results show that well‐constructed parental questionnaires can provide reliable data on childhood asthma. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials (RCTs) suggest a protective effect of high‐dose vitamin D supplementation in pregnancy on offspring risk of persistent wheeze, but only in some individuals, which might be explained by variations in vitamin D pathway genes. This study aimed to investigate the effect of vitamin D supplementation by maternal and offspring vitamin D receptor (VDR) genotype and GC genotype, encoding vitamin D binding protein (VDBP), in two RCTs. Methods: In the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) RCT, we analyzed the effect of high‐dose vitamin D during pregnancy on the risk of persistent wheeze age 0‐3 years by variants in single nucleotide polymorphisms (SNPs) in VDR (rs1544410, rs2228570, rs7975128, rs7975232) and GC (rs4588, rs7041). Replication was sought in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Results: In COPSAC2010, VDR SNP rs1544410 influenced the effect of high‐dose vitamin D: maternal Pinteraction =.049 and child Pinteraction =.001, with the largest effect in offspring from mothers with TT genotype: hazard ratio (95% CI), 0.26 (0.10‐0.68), P =.006, and no effect among CT or CC genotypes: 0.85 (0.48‐1.51), P =.58 and 0.94 (0.47‐1.89), P =.87, respectively. However, these findings were not replicated in VDAART. There was no significant effect modification from maternal or offspring GC genotype in either COPSAC2010 or VDAART: all Pinteraction ≥.17. Conclusions: We found that the effect of high‐dose vitamin D supplementation during pregnancy on offspring risk of persistent wheeze was significantly influenced by VDR genotype in the COPSAC2010 RCT, but not VDAART, which may be due to population differences. [ABSTRACT FROM AUTHOR]

Background: Over the last few decades, the level of pollen from birch and homologous trees has increased in parts of Europe. Sensitization to birch pollen allergens (principally Bet v 1) has been associated with food cross‐reactivity called pollen food allergy syndrome (PFAS). Objective: To evaluate changes in allergic diseases due to IgE sensitization over 25 years in asthmatic children. Methods: This was a cross‐sectional retrospective study conducted in Paris. We analyzed two cohorts of asthmatic children with similar characteristics explored between 1993‐1999 (old cohort = OC) and 2012‐2018 (recent cohort = RC). Results: 121 children were in the OC and 120 in the RC. An increase in sensitization to tree pollens was found especially for birch pollen, which was 11.6% in the OC and 31% in the RC (P =.0002). Allergic rhinitis prevalence was significantly higher in the RC than in the OC (96% vs 52%, respectively, P <.0001). IgE‐mediated food allergy increased from 6% to 16% in the OC and RC, respectively, (P =.01) mainly due to PFAS. In the RC, a higher mean Bet v 1‐specific IgE level was observed in children with PFAS compared to children without (105.7 KU/L ± 17.8 and 48.9 kU/L ± 15.7, respectively, P <.05). Conclusion: Allergic rhinitis and food allergy with tree pollen sensitization have increased in Paris over 25 years mainly due to PFAS. Environmental factors could be responsible for these modifications as described in the literature. [ABSTRACT FROM AUTHOR]

Background: A high dose of folic acid during pregnancy may increase the risk of asthma, wheezing, and respiratory disease in childhood. Folate acid can modify inflammation and immune susceptibility of offspring with some epigenetic differentiation, including DNA methylation. This study evaluated associations between maternal folate levels during pregnancy and childhood wheezing; furthermore, the study assessed whether maternal folate‐modified DNA methylation is related to asthma. Methods Participants in the current study were 6651 mother‐child pairs who had complete data on characteristics and who had completed at least one of the International Study of Asthma and Allergies in Childhood questionnaires when the child was 1, 2, 4, and 7 years of age. Moreover, a case‐control study to assess DNA methylation at 7 years of age was conducted among 136 children who experienced wheezing and a control group of 139 children with no history of allergies. Results The median of maternal serum was 16.76 nmol/L, assayed by chemiluminescent immunoassay. We found significantly increased adjusted odds ratios of childhood wheezing at 2 years age according to maternal folate levels, compared with the lowest folate quartile (odds ratio [95% confidence interval] = highest; 1.27 [1.03, 1.56], and second, 1.27 [1.05, 1.55]); however, no changes were observed at 1, 4, and 7 years of age. In a case‐control study, no association of maternal folate levels with DNA methylation was observed. Conclusion Our results suggest that maternal folate did not affect persistent wheezing in school‐aged children, or DNA methylation of gasdermin B, orosomucoid‐like 3, and Ikaros family zinc finger 3 at 7 years of age. [ABSTRACT FROM AUTHOR]

Background: Evidence about the association of high blood eosinophil count with asthma exacerbation is inconsistent and unclear. The objective of this meta‐analysis was to determine whether elevated blood eosinophil count predicts asthma exacerbation. Methods: We searched MEDLINE, EMBASE, and additional databases, without any language restriction. We also checked the reference lists of the included studies and of relevant systematic reviews. The main outcome was the occurrence of asthma exacerbation. We calculated global pooled odds ratios (ORs) and their 95% confidence intervals (CIs) and performed predefined subgroup analyses. We appraised the quality of the studies using Newcastle‐Ottawa Scale, examined the heterogeneity between studies, assessed publication bias, and carried out sensitivity analyses. Results: Among 1567 retrieved publications, 23 observational studies comprising 155,772 participants met the inclusion criteria. High blood eosinophil count was associated with higher odds of asthma exacerbation [OR: 1.31 (95% CI: 1.16, 1.49)], specifically with asthma‐related outpatient visits [OR: 1.46 (95% CI: 1.25, 1.70)] and emergency department visits [OR: 1.63 (95% CI: 1.29, 2.07)]. A significant association was observed starting from an eosinophils' cutoff value of 200 cells/μl. The association was observed for cohort studies [OR: 1.30 (95%CI: 1.13, 1.49)], North American studies [OR: 1.43 (95%CI: 1.31, 1.57)], Asian populations [OR: 1.67 (95%CI: 1.34, 2.08)], children [OR: 1.38 (95%CI: 1.22, 1.56)], and studies that adjusted for inhaled corticosteroids therapy [OR: 1.42 (95%CI: 1.28, 1.56)]. Conclusions: Blood eosinophil counts ≥ 200 cells/µL are associated with asthma exacerbation. Blood eosinophil count is a modifiable factor that could be addressed in asthma management strategies. [ABSTRACT FROM AUTHOR]

Background: To date, there is no comprehensive study examining how asthma diagnosed in childhood or adolescence is associated with diagnoses of subsequent non‐communicable diseases (NCDs) during adulthood. Our study aimed to examine the associations between pediatric asthma and several adult NCDs, with temporality and long interval times between asthma and NCD diagnoses. Methods: We used RAND Indonesian Family Life Survey Fifth Wave (IFLS5) fielded in 2014‐2015, to study whether being diagnosed with pediatric asthma at 0‐19 years of age was associated with increased risks of hypertension, diabetes, rheumatoid arthritis, stomach diseases, kidney diseases, and heart diseases or stroke diagnosed in adulthood. We used the weighted Poisson regression adjusting for age, sex, urbanicity, and insurance status to estimate risk ratios. Subgroup analyses were performed by sex and age of asthma and other NCD diagnoses. Results: Pediatric asthma significantly increased risks of hypertension, diabetes, and stomach diseases diagnosed at 20 years of age or above. Males with pediatric asthma diagnosed at 0‐10 years of age had significantly higher risk of hypertension, while females with pediatric asthma diagnosed at 0‐10 years of age had significantly higher risks of diabetes and stomach diseases. Females with pediatric asthma diagnosed at 11‐19 years of age had significantly higher risks of diabetes, arthritis, stomach diseases, and kidney diseases. We also found varying associations by age of NCD diagnosis. Conclusion: Our results suggest pediatric asthma is associated with increased risks of several adult NCDs, and these associations may vary by sex and age of asthma and other NCD diagnoses. [ABSTRACT FROM AUTHOR]

Background: Asthmatic children on corticosteroids can develop hypothalamic‐pituitary‐adrenal axis suppression (HPAS). Single nucleotide polymorphisms (SNPs) rs242941 and rs1876828 of the corticotrophin‐releasing hormone receptor 1 (CRHR1) gene were associated with lower stimulated cortisol (F) levels, whereas rs41423247 of the glucocorticoid receptor (NR3C1) gene was associated with higher basal F levels. The objective of the current study was to confirm whether these three SNPs are associated with HPAS in asthmatic children. Methods: DNA was extracted from saliva obtained from 95 asthmatic children, who had previously undergone basal F and metyrapone testing. Thirty‐six children were classified as suppressed. Non‐suppressed children were subclassified according to their post‐metyrapone adrenocorticotropin (PMTP ACTH) level into a middle (106‐319 pg/mL) and a high (>319 pg/mL) ACTH response group. TaqMan® polymerase chain reaction assays were utilized. Results: Only rs41423247 was inversely associated with HPAS (OR = 0.27 [95% CI 0.06‐0.90]). Its GC genotype was inversely associated with HPAS (log odds = −1.28, P =.021). √PMTP ACTH was associated with CC (effect size = 10.85, P =.005) and GC genotypes (effect size = 4.06, P =.023). The C allele is inherited as a dominant trait (effect size = −1.31 (95% CI −2.39‐−0.33; P =.012). In the high ACTH response group, both genotypes affected the PMTP ACTH (effect sizes 1.41 and 15.46; P‐values.023 and <2 × 10−26 for GC and CC, respectively). Conclusions: The C allele of rs41423247 was found to be protective against HPAS. CC genotype is associated with the highest PMTP ACTH response. [ABSTRACT FROM AUTHOR]

Background: Previous research suggests that children who experience asthma may be less physically active; however, results have been inconclusive. This study aimed to investigate whether the presence of asthma or wheeze is associated with lower physical activity levels in children, and whether sex, body mass index or earlier asthma or wheeze status modifies the association. Methods: This study was conducted in 391 HealthNuts participants in Melbourne, Australia. Asthma and wheeze data were collected via questionnaire at age 4 and 6, and physical activity was measured through accelerometry. Using adjusted linear regression models, the cross‐sectional and longitudinal associations were investigated. Results: There was no evidence of a difference in time spent in moderate‐to‐vigorous physical activity (MVPA) at age 6 years between children with and without asthma at age 4; children with asthma spent 8.3 minutes more time physically active per day (95% CI: −5.6, 22.1, P =.24) than children without asthma. Similar results were seen for children with current wheeze (5.8 minutes per day more, 95% CI: −5.9, 17.5, P =.33) or ever wheeze or asthma (7.7 minutes per day more, 95% CI: −4.8, 20.2, P =.23) at age 4 years. Comparable null results were observed in the cross‐sectional analyses. Interaction with BMI could not be assessed; however, previous asthma or wheeze status and sex were not found to modify these associations. Conclusion: This analysis found no evidence of asthma hindering physical activity in these young children. These results are encouraging, as they indicate that the Australian asthma and physical activity public health campaigns are being effectively communicated and adopted by the public. [ABSTRACT FROM AUTHOR]

Background: There remains an unmet need in objective tests for diagnosing asthma in children. The objective of this study was to investigate the potential of metabolomic profiles of exhaled breath condensate (EBC) to discriminate stable asthma in Asian children in the community. Methods: One hundred and sixty‐five Asian children (92 stable asthma and 73 non‐asthmatic controls) participating in a population‐based cohort were enrolled and divided into training and validation sets. Nuclear magnetic resonance‐based metabolomic profiles of EBC samples were analyzed by using orthogonal partial least squares discriminant analysis. Results: EBC metabolomic signature (lactate, formate, butyrate, and isobutyrate) had an area under the receiver operator characteristic curve (AUC) of 0.826 in discriminating children with and without asthma in the training set, which significantly outperformed FeNO (AUC = 0.574; P <.001) and FEV1/FVC % predicted (AUC = 0.569; P <.001). The AUC for EBC metabolomic signature was 0.745 in the validation set, which was slightly but not significantly lower than in the testing set (P =.282). We further extrapolated two potentially involved metabolic pathways, including pyruvate (P = 1.67 × 10−3; impact: 0.14) and methane (P = 1.89 × 10−3; impact: 0.15), as the most likely divergent metabolisms between children with and without asthma. Conclusion: This study provided evidence supporting the role of EBC metabolomic signature to discriminate stable asthma in Asian children in the community, with a discriminative property outperforming conventional clinical tests such as FeNO or spirometry. [ABSTRACT FROM AUTHOR]

Background: Low adherence to asthma controllers is known to increase the risk of uncontrolled disease and poor health outcomes. We aimed to study risk factors of long‐term adherence to preventive medications in children and adolescents with asthma. Methods: Adherence was assessed during a two‐year period in 155 children with asthma followed in a tertiary pediatric asthma outpatient clinic using percentage of days covered (PDC) based on physician prescriptions and pharmacy claims data. The risk factor analysis included age, sex, ethnicity, BMI, atopic comorbidity, spirometry incentives, and fractional exhaled nitric oxide (FeNO). Results: Ninety‐five children, 50 (53%) males, mean age of 16.3 years (SD, 2.36), received at least one prescription for asthma controllers in the study period. Fifty‐two (54%) children were classified as non‐adherent with a PDC cutoff at 80%. Adherence was negatively associated with age: adherence ratio (AR) 0.84 (95% CI, 0.73‐0.95), P =.008; forced expiratory volume in 1 second (FEV1): AR per L 0.6 (0.91‐1.0), P =.03; unfilled inhaled beta‐2‐agonist prescription: AR 0.45 (0.23‐0.89), P =.02; and FeNO level: AR per ppb 0.98 (0.97‐0.99), P =.03, where age and FeNO retained significance in multivariate analysis. Type and number of asthma controllers were not associated with adherence. Conclusions: This study shows low adherence to preventive medication among half of the children with asthma, which is associated with increasing age and FeNO level. Therefore, an extra effort should be directed toward teenagers transitioning from pediatric to adult medicine and toward inhaled corticosteroid‐treated patients with elevated FeNO to increase their adherence to asthma controllers. [ABSTRACT FROM AUTHOR]

Background: Airway hyper‐responsiveness (AHR) is a common feature in asthma. The use of AHR in predicting active asthma or the persistence of AHR in childhood is poorly understood. By analyzing longitudinal connections including different measures of AHR, lung function, and inflammation markers, we sought to identify the best available method for predicting persistence of AHR and identification of later active asthma. Methods: We tested 105 asthmatic children aged 3‐7 years with fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and AHR evaluated by indirect methods (hypertonic saline and exercise challenge). Ten years later, 64 children participated in the follow‐up visit and were tested with FeNO, IOS, spirometry, and methacholine challenge. At both study visits, blood samples were collected, and a questionnaire was completed. Results: Asthma was in remission in 66% of patients at adolescence. AHR measured by hypertonic saline challenge at preschool age was associated with asthma symptoms (OR 10.2; 95% CI 2.8, 37.3) but not with AHR estimated with methacholine challenge 10 years later. AHR measured by exercise challenge was not associated with AHR or recent asthma symptoms in adolescence. Preschool eosinophilia continued until adolescence in 87% of patients but was not associated with AHR or subjective signs of asthma 10 years later. Wheezy preschoolers with atopy had a higher risk for AHR in adolescence (OR 4.1; 95% CI 1.0, 16.2). Conclusion: Results from hypertonic saline challenge are associated with persistent asthma symptoms even after a decade. AHR measured by indirect methods at preschool age did not predict AHR in adolescence. [ABSTRACT FROM AUTHOR]

Background: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. Methods: We recruited children between 3 and 6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. Results: Seventy‐four children, mean (standard deviation (SD)) age of 4.32 years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age‐dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P =.003); however, 46% had an LCI in the abnormal range. FEV0.75z‐score improved from −1.66 to −1.17 (P =.05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well‐controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. Conclusions: Lung clearance index demonstrates a persistent deficit post‐exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children. [ABSTRACT FROM AUTHOR]

Background: The inability to objectively diagnose childhood asthma before age five often results in both under‐treatment and over‐treatment of asthma in preschool children. Prediction tools for estimating a child's risk of developing asthma by school‐age could assist physicians in early asthma care for preschool children. This review aimed to systematically identify and critically appraise studies which either developed novel or updated existing prediction models for predicting school‐age asthma. Methods: Three databases (MEDLINE, Embase and Web of Science Core Collection) were searched up to July 2019 to identify studies utilizing information from children ≤5 years of age to predict asthma in school‐age children (6‐13 years). Validation studies were evaluated as a secondary objective. Results: Twenty‐four studies describing the development of 26 predictive models published between 2000 and 2019 were identified. Models were either regression‐based (n = 21) or utilized machine learning approaches (n = 5). Nine studies conducted validations of six regression‐based models. Fifteen (out of 21) models required additional clinical tests. Overall model performance, assessed by area under the receiver operating curve (AUC), ranged between 0.66 and 0.87. Models demonstrated moderate ability to either rule in or rule out asthma development, but not both. Where external validation was performed, models demonstrated modest generalizability (AUC range: 0.62‐0.83). Conclusion: Existing prediction models demonstrated moderate predictive performance, often with modest generalizability when independently validated. Limitations of traditional methods have shown to impair predictive accuracy and resolution. Exploration of novel methods such as machine learning approaches may address these limitations for future school‐age asthma prediction. [ABSTRACT FROM AUTHOR]

Background: Lung function testing in small children is cumbersome. However, reduced variability of tidal breathing recorded using impedance pneumography (IP) during sleep was recently found to be a potential objective marker of wheeze in children aged 1‐5 years. We aimed to investigate how an acute bronchial obstruction (BO) and its severity, and recovery thereof reflect in expiratory variability index (EVI). Methods: EVI was measured using a wearable IP system (Ventica®) during sleep in 40 healthy controls (aged 1.5‐5.9 years) and 30 patients hospitalized due to acute BO (aged 1.3‐5.3 years). In healthy controls, EVI was measured for 1‐3 nights at their homes. Patients were measured for several nights during hospitalization, as practically feasible, and at home 2 and 4 weeks post‐discharge. Results: We received 79 EVI results from 39 controls and 139 from 30 patients. 90% had previous BO episodes, 30% used asthma controller medication before and 100% after hospitalization. Compared to controls, EVI was significantly lower during hospitalization (P <.0001) having significant correlation with number of days to discharge (r = −.38, P =.004). At 2 or 4 weeks post‐discharge, EVI was not significantly different from the controls (P =.14, P =.49, respectively). EVI was significantly associated with chest auscultation findings (P =.0001) being 17.5 (4.9) (median, IQR) with normal auscultation, 15.6 (7.4) in those with prolonged expiration and 11.4 (6.8) in those with wheeze and/or rales and crackles. Conclusions: EVI was found to be a sensitive, objective marker of acute BO, showing strong association with changes in clinical status in wheezy children aged 1‐5 years. [ABSTRACT FROM AUTHOR]

Background: Despite therapeutic advances, asthma prevalence remains high. Psychosocial factors, including maternal mental disorders, may be involved. This study aims to evaluate the association of maternal common mental disorders (CMDs) and their change over time with asthma morbidity in the child and to observe the effect of social support on this association. Methods: This prospective study involved 189 dyads of mothers and their asthmatic children aged between 2 and 14 years, assisted in specialized outpatient clinics. We measured the association of maternal CMD evolution (absent, maintained, or improved over time) with asthma control and visits to the emergency department (ED) due to asthma attacks through Poisson regression analysis. We further stratified the sample according to social support levels to identify a possible effect of this variable on the association of maternal psychological symptoms with asthma morbidity. Results: Compared with mothers who maintained CMD over time, maternal CMD absence had a protective effect on the occurrence of visits to the ED (RR: 0.45; 95% CI: 0.26‐0.79) and maternal CMD improvement was associated with lower risk of uncontrolled asthma in the child (RR: 0.60; 95% CI: 0.37‐0.97). There was a stronger association of maternal CMD improvement with asthma control in the child only for the stratum of mothers with high social support in its three dimensions (affective‐social interaction, emotional‐informational, and material dimensions). Conclusions: Maternal CMD absence and improvement over the study period were protective factors for uncontrolled asthma in the child, mainly in the presence of high social support. [ABSTRACT FROM AUTHOR]

Background: There are sparse real‐world data on severe asthma exacerbations (SAE) in children. This multinational cohort study assessed the incidence of and risk factors for SAE and the incidence of asthma‐related rehospitalization in children with asthma. Methods: Asthma patients 5‐17 years old with ≥1 year of follow‐up were identified in six European electronic databases from the Netherlands, Italy, the UK, Denmark and Spain in 2008‐2013. Asthma was defined as ≥1 asthma‐specific disease code within 3 months of prescriptions/dispensing of asthma medication. Severe asthma was defined as high‐dosed inhaled corticosteroids plus a second controller. SAE was defined by systemic corticosteroids, emergency department visit and/or hospitalization all for reason of asthma. Risk factors for SAE were estimated by Poisson regression analyses. Results: The cohort consisted of 212 060 paediatric asthma patients contributing to 678 625 patient‐years (PY). SAE rates ranged between 17 and 198/1000 PY and were higher in severe asthma and highest in severe asthma patients with a history of exacerbations. Prior SAE (incidence rate ratio 3‐45) and younger age increased the SAE risk in all countries, whereas obesity, atopy and GERD were a risk factor in some but not all countries. Rehospitalization rates were up to 79% within 1 year. Conclusions: In a real‐world setting, SAE rates were highest in children with severe asthma with a history of exacerbations. Many severe asthma patients were rehospitalized within 1 year. Asthma management focusing on prevention of SAE is important to reduce the burden of asthma. [ABSTRACT FROM AUTHOR]

Keywords: allergic rhinitis; asthma; humidifier disinfectant; lung function; nasal patency; olfactory sensitivity EN allergic rhinitis asthma humidifier disinfectant lung function nasal patency olfactory sensitivity 578 582 5 07/17/20 20200701 NES 200701 Abbreviations aHR adjusted hazard ratio aOR adjusted odds ratio AR allergic rhinitis CI confidence interval FeNO fraction of exhaled nitric oxide HD humidifier disinfectant PSKC Panel Study of Korean Children Rrs5 resistance at 5 Hz SAP2017 Seongnam Atopy Project 2017 Koreans continue to experience inhalation hazards caused by humidifier disinfectant (HD)-related respiratory complications because the Korean government does not have an integrated administrative system for identification of xenobiotics, especially for products used in household.1,2 Research indicates that approximately 30% of Korean children were exposed to a HD from 1994 to 2011 and HD products were only sold in Korea market before withdrawal of these products from Korea market in 2011.3 Many researchers have examined the relationship of exposure to HDs with lung injury,4,5 although there is insufficient evidence supporting a relationship between exposure to HD and childhood asthma,1 asthma-related parameters (oscillometric lung function6 and fraction of exhaled nitric oxide [FeNO]), allergic rhinitis (AR), and AR-related parameters (nasal airway volume and olfactory threshold). Compared with no exposure to HD, any exposure to HD was associated with an increased overall risk of asthma (aHR, 1.35; 95% CI, 1.01 to 1.80) and AR (aHR, 1.22; 95% CI, 1.03 to 1.44). To our knowledge, this is the first study to use two independent general population-based studies of children to identify relationships of the duration of HD exposure with asthma, AR, and airway-related parameters. Allergic rhinitis, asthma, humidifier disinfectant, lung function, nasal patency, olfactory sensitivity. [Extracted from the article]

Background: Lung function testing is an essential part of diagnostic workup and monitoring of asthma, but young children are lacking easy, routine testing methods. However, recent discoveries show reduced tidal breathing variability measured using impedance pneumography (IP) at home during sleep as a sign of airway obstruction. In this study, we assessed (a) the discriminative capacity of expiratory variability index (EVI) between healthy controls and young children with recurrent wheeze on‐and‐off controller medication, (b) association between EVI and parentally perceived obstructive symptoms (need for bronchodilator) and (c) measurement success rate. Methods: We included 68 patients (aged 1.0‐5.6) and 40 healthy controls (aged 1.0‐5.9 years). The patients were prescribed a three‐month inhaled corticosteroid (ICS) treatment due to recurrent obstructive bronchitis. We measured EVI using IP at home at the end of the treatment (0W) and 2 (2W) and 4 (4W) weeks after ICS withdrawal. Results: EVI was higher in controls than in patients, and significant within‐patient reduction occurred at 4W as compared to 2W or 0W. Area under curve of the ROC curve (controls vs all patients) at 4W was 0.78 (95% CI 0.70‐0.85). Children who were administered bronchodilator by parental decision had lower EVI than those without bronchodilator need at 4W, but not at 0W or 2W. Patients with parent‐reported airway infection, but no bronchodilator need, had normal EVI. Measurement success rate was 94%. Conclusion: EVI was lower in patients than in controls and it reduced further after controller medication withdrawal, especially in the presence of parentally perceived wheeze symptoms. This technique shows a significant potential for routine lung function testing of wheezy young children. [ABSTRACT FROM AUTHOR]

Background: Primary schools represent important environments for biodiversity exposure and thus may play a crucial role on early‐life immunomodulation, protecting against allergic sensitization. The aim of this study was to understand how the exposure to different levels of species richness surrounding urban primary schools may influence the development of allergic diseases and asthma in children. Methods: A species richness index (SRI), evaluating habitat diversity in terms of amphibians, birds, reptiles, and small mammals, was estimated and attributed to 20 primary schools in the city of Porto, Portugal. The SRI was measured considering a 100 m straight‐line buffer around the schools. Children who attended the participating schools were invited to participate in the study, performed spirometry with bronchodilation and skin‐prick tests, and had their parents fill a questionnaire concerning allergy and asthma symptoms, as well as demographic and socioeconomic data. Asthma was defined according to three distinct criteria. Results: The study results showed significant and positive associations between the exposure to species richness in schools and the forced expiratory volume at the first second (FEV1) and forced vital capacity (FVC) parameters both before and after bronchodilation, independently of the asthma and atopic status. Fully adjusted models revealed that a unitary increment in the SRI was associated with an average increase of approximately 2 and 3 mL in FEV1 and FVC, respectively. Conclusion: Species richness in school surroundings may impact lung function development in children. However, this increase in lung function was not associated with any clinically relevant protective effect on allergy and asthma development. [ABSTRACT FROM AUTHOR]

Background: Synergistic role of exposure to cats, dogs, and farm animals during infancy on the risk of childhood asthma and allergy remains unknown. Objectives: To investigate independent and synergistic associations between exposure to indoor pets and farm animals during infancy and the risk of asthma and allergy by age 5. Methods: We studied 3781 children participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. At age 5, a validated version of the International Study of Asthma and Allergies in Childhood questionnaire was administered to collect information on asthma and allergic disease, and exposure to indoor pets and farm animals during the first year of life. Allergen‐specific IgE antibodies were analyzed from serum samples. Statistical analyses employed Cox proportional hazards and logistic regression. Results: Having a dog in the house was inversely associated with the risk of asthma (HR 0.60; 95% CI, 0.38‐0.96), allergic rhinitis (OR 0.72; 95% CI, 0.53‐0.97), and atopic sensitization (OR 0.77; 95% CI, 0.63‐0.96). Having a cat was associated with a decreased risk of atopic eczema (OR 0.68; 95% CI, 0.51‐0.92). Farm animals were neither independently nor in synergy with indoor pets associated with the outcomes. Conclusion: Having a dog or cat in the house during the first year of life may protect against childhood asthma and allergy. We did not find a synergistic association between cat, dog, and farm animal exposure on the risk of childhood asthma and allergy. Future research should identify specific causative exposures conferred by indoor pets and whether they could be recommended for allergy prevention. [ABSTRACT FROM AUTHOR]

Background: Inhalation of fine particulate matter (PM) can cause systematic inflammation and oxidative stress, which may further aggravate the development and progression of asthma. Although nutritional intake of fatty acids and antioxidants may attenuate some effects of fine PM, the role of the inflammatory potential of diet has not been addressed. Therefore, we aimed to investigate possible modulatory effects of dietary inflammatory potential on the association between indoor air pollution and childhood asthma–related outcomes. Methods: In a sample of 501 children (48.1% females, aged 7‐12 years) from 20 public schools located in Porto, Portugal, we evaluated airway reversibility, exhaled nitric oxide levels, atopy, and current respiratory symptoms. Dietary inflammatory index was calculated based on information collected through a reported 24‐hour recall questionnaire, and participants were categorized as having an anti‐inflammatory or pro‐inflammatory diet. Concentrations of indoor PM2.5 and PM10 were measured to assess indoor air quality. Generalized linear mixed models were used to investigate the proportion of effects explained by the exposure to PM2.5 and PM10. Results: After adjustment, the exposure effect of PM2.5 and PM10 levels on children with asthma was higher for those having a pro‐inflammatory diet (OR = 1.44, 95% CI: 1.01‐2.21; and OR = 1.29, 95% CI: 1.03‐1.68, respectively) compared to those having an anti‐inflammatory diet. Conclusion: These findings suggest that the quality of diet might affect the association between indoor pollution and asthma in children, highlighting the relevance of children's diet as a potential protective factor to pollutant exposure in childhood asthma. [ABSTRACT FROM AUTHOR]

There is growing concern regarding the long‐term outcomes of early and poorly controlled childhood asthma, either of which can potentially lead to the development of severe asthma in adults and irrecoverable loss of lung function leading to chronic obstructive pulmonary disease. These outcomes of inadequately controlled asthma should prompt a change in practice to better and/or earlier identify children at risk of adverse respiratory outcomes of asthma, to monitor disease progression, and to design intervention strategies that could either prevent or reverse asthma progression in children. The careful follow‐up of spirometry over time—in the form of lung function trajectories, the application of biomarkers to assist in the diagnosis of early asthma and medication selection for these patients, as well as methods to identify patients at risk of asthma attacks—can be used to develop individualized management strategies for children with asthma. It is now time for asthma specialists to communicate this information to patients, parents, and primary care physicians and to incorporate them into routine clinical assessments of children with asthma. In time, these concepts of risk management and prevention can be refined to provide a more comprehensive approach to asthma care so as to prevent adverse respiratory outcomes from poorly controlled childhood asthma. [ABSTRACT FROM AUTHOR]

Background: Bronchial allergen provocation (BAP) is an established tool for the diagnosis of allergy in patients with asthma, but its use is limited by the potential risk of severe asthmatic reactions. Nasal provocation testing (NPT) may be an alternative safe method and does not require sophisticated equipment. Objective: The aim of this prospective study was to evaluate the concordance of both methods in patients with asthma and house dust mite (HDM) sensitization. Methods: A total of 112 patients with HDM sensitization underwent BAP and had the following parameters analysed: decrease in FEV1, exhaled NO, and total and specific IgE. Within 12 weeks, NPT with HDM was performed in 74 patients with a median age of 9 years (range, 5‐16 years). The results were evaluated using the Lebel score which quantifies major symptoms like rhinorrhea, nasal obstruction, sneezes and minor symptoms, such as pruritus, conjunctivitis and pharyngitis. Results: Fifty‐seven of 74 patients had an early asthmatic reaction, of which 41 were identified using the Lebel score. The Lebel score had a sensitivity of 71.9% and a positive predictive value (PPV) of 89.1%. In addition, an eNO ≥ 10 ppb (AUC 0.78), a specific IgE Dermatophagoïdes pteronyssinus ≥ 25.6 kU/L (AUC 0.76) and a specific IgE Dermatophagoïdes farinae ≥ 6.6 kU/L (AUC 0.78) were good predictors of an early asthmatic reaction. Conclusion: A sequential use of NPT prior to BAP is justified to establish the relevance of HDM allergy. In patients with a negative NPT, BAP is still recommended to rule out a HDM‐induced asthmatic reaction. [ABSTRACT FROM AUTHOR]

Dog-associated non-allergen exposures were derived from residual effect of dog presence in the main model for the association between dog allergen exposure and asthma morbidity. Asthma morbidity outcomes by dog allergen exposure and sensitization to dog allergen Further, the effects of animal-associated non-allergen exposure derived from the presence of other animals and exposures to allergens were tested and found not to be consistently associated with asthma morbidity, except for mouse allergen (Table S3). Even when exposure to other animal allergens was included in the model, dog allergen exposure remained significantly associated with respiratory outcomes, which suggests that dog allergen is an independent risk factor for asthma morbidity. [Extracted from the article]

Background: A missense variant (rs6967330) of the gene encoding cadherin‐related family member 3 (CDHR3) was associated with recurrent severe exacerbations in pre‐schoolers. However, there were limited data on its relationship with pre‐school lung function and school‐age asthma. This study replicated the association between polymorphic markers at the region of CDHR3 around rs6967330 and wheezing phenotypes in two independent cohorts of Chinese children. Methods: Ten tagging SNPs located 10 kb around rs6967330 were selected by HaploView 5.0 based on 1000 Genomes database for Southern Han Chinese. Their associations with wheezing and lung function were examined in 1341 Chinese pre‐school children, while those for asthma phenotypes were examined in an independent group of 2079 school‐age children. Genotypic and haplotypic associations were analyzed by multivariate regression, and generalized multifactor dimensionality reduction was used to examine epistatic interactions for wheezing traits. Results: The mean (SD) age of pre‐school cohort was 4.7 (1.0) years. Rs6967330 was associated with current wheeze (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.09‐2.43) and its severity (OR 1.64, 95% CI 1.10‐2.44) among pre‐school children. This SNP was also associated with school‐age asthma (OR 1.32, 95% CI 1.04‐1.69). The minor allele of rs408223 was associated with lower FEV0.5 (β = −2.411, P =.004) and FEV0.5/FVC (β = −1.292, P =.015). Lower spirometric indices were also associated with minor allele of rs140154310. GAC haplotype from rs4730125, rs6967330, and rs408223 was associated with pre‐school current wheeze and school‐age asthma. Epistatic interaction was found between unrelated CDHR3 SNPs for FEV0.5 among pre‐schoolers. Conclusion: CDHR3 is a candidate gene for early‐life wheezing, school‐age asthma, and lung function in Chinese children. [ABSTRACT FROM AUTHOR]

Background: Data addressing short‐ and long‐term respiratory morbidity in moderate‐late preterm infants are limited. We aim to determine the incidence of recurrent wheezing and associated risk and protective factors in these infants during the first 3 years of life. Methods: Prospective, multicenter birth cohort study of infants born at 32+0 to 35+0 weeks' gestation and followed for 3 years to assess the incidence of physician‐diagnosed recurrent wheezing. Allergen sensitization and pulmonary function were also studied. We used multivariate mixed‐effects models to identify risk factors associated with recurrent wheezing. Results: A total of 977 preterm infants were enrolled. Rates of recurrent wheezing during year (Y)1 and Y2 were similar (19%) but decreased to 13.3% in Y3. Related hospitalizations significantly declined from 6.3% in Y1 to 0.75% in Y3. Independent risk factors for recurrent wheezing during Y2 and Y3 included the following: day care attendance, acetaminophen use during pregnancy, and need for mechanical ventilation. Atopic dermatitis on Y2 and male sex on Y3 were also independently associated with recurrent wheezing. Palivizumab prophylaxis for RSV during the first year of life decreased the risk or recurrent wheezing on Y3. While there were no differences in rates of allergen sensitization, pulmonary function tests (FEV0.5) were significantly lower in children who developed recurrent wheezing. Conclusions: In moderate‐to‐late premature infants, respiratory symptoms were associated with lung morbidity persisted during the first 3 years of life and were associated with abnormal pulmonary function tests. Only anti‐RSV prophylaxis exerted a protective effect in the development of recurrent wheezing. [ABSTRACT FROM AUTHOR]

Background: Most studies addressing the association between RSV and recurrent wheezing (RW) and asthma have been conducted in patients at risk for lung morbidity. Data in full‐term infants are limited. Methods: The risk of RW/asthma during the first 5 years of life in full‐term infants hospitalized with RSV during the first year (Y) of life was estimated using 2010‐16 data from three claims databases in USA (Truven MarketScan Commercial Claims and Encounters Database [CCAE], Truven Health MarketScan Multi‐State Medicaid [MDCD], and Optum Clinformatics Extended Data Mart‐Socio‐Economic Status [SES]). Full‐term infants with and without RSV infection and ≥ 2 years of continuous health plan enrollment from birth were included. Incidence rates of RW/asthma, cumulative incidence, adjusted incidence rate ratios (aIRR), and odds ratios (aOR) were calculated. Results: During the 16‐year study, 38,494 (CCAE), 62 846 (MDCD), and 23 099 (SES) matched infant pairs were included in each cohort. In the CCAE database, RW/asthma incidence/1000 patient‐years (69.7 vs 28.7, aIRR: 2.4 [2.3‐2.5]); cumulative incidence (17.6%‐25.2% vs 5.0%‐11.4%); and aOR (Y2: 4.1 [3.9‐4.4]; Y3: 3.2 [3.0‐3.3]; Y4: 2.9 [2.7‐3.1]; Y5: 2.6 [2.5‐2.9]) were higher in the RSV vs. non‐RSV cohort. Results in the SES insured population were comparable, while cumulative incidence and aIRR were higher in the Medicaid population (MDCD). Conclusion: Although there are limitations in this study, including possible coding errors and missing covariates, we showed that full‐term infants with severe RSV infection during the first year of life, spanning several respiratory seasons and a geographically diverse population, are at significant risk of RW/asthma during childhood. [ABSTRACT FROM AUTHOR]

Background: Childhood asthma is often preceded by early wheeze. Usually, wheezing episodes are recorded retrospectively, which may induce recall bias. Aims and objectives: The aim of this study was to investigate true‐positive recall of parent‐reported wheeze at 1 year of age, its determinants, and its implications for asthma and lung function at 6 years of age. Methods: The PASTURE (Protection Against Allergy—Study in Rural Environments) study followed 880 children from rural areas in 5 European countries from birth to age 6 years. Wheeze symptoms in the first year were asked weekly. At age 6, parent‐reported asthma diagnosis was ascertained and lung function measurements were conducted. Correct parental recall of wheeze episodes at the end of the first year was assessed for associations with lung function, asthma, and the asthma risk locus on chromosome 17q21. Results: Parents correctly recalled wheeze after the first year in 54% of wheezers. This true‐positive recall was determined by number of episodes, timing of the last wheeze episode, and parental asthma. Independently from these determinants, true‐positive recall predicted asthma at age 6 years (odds ratio 4.54, 95% confidence interval (CI) [1.75‐14.16]) and impaired lung function (β = −0.62, 95% CI [−1.12; −0.13], P‐value =.02). Associations were stronger in children with asthma risk SNPs on chromosome 17q21. Conclusion: Correct parental recall of wheezing episodes may reflect clinical relevance of early wheeze and its impact on subsequent asthma and lung function impairment. Questions tailored to parental perception of wheezing episodes may further enhance asthma prediction. [ABSTRACT FROM AUTHOR]

Background: Lung function impairment among asthmatic children begins in early life, and biomarkers for identifying this impairment are needed. The chitinase‐like protein YKL‐40 has been associated with asthma and lung function in adults, but studies in children have yielded conflicting results. We evaluated the potential of YKL‐40 and other systemic biomarkers for identifying lung function deficits in children with asthmatic symptoms. Methods: We determined the levels of serum YKL‐40, periostin, and high‐sensitivity C‐reactive protein (hs‐CRP) from the blood samples of 49 children with asthmatic symptoms. Lung function was assessed with impulse oscillometry (IOS) and spirometry, combined with an exercise challenge and a bronchodilator test. Fractional exhaled nitric oxide was measured at multiple flow rates. Results: Serum levels of YKL‐40 showed significant correlations with most IOS indices at baseline (P =.008‐.039), but there was no association between YKL‐40 and spirometry parameters. Neither periostin nor hs‐CRP were associated with baseline lung function. Children with a significant response in either the exercise challenge or the bronchodilator test had increased serum levels of YKL‐40 (P =.003) and periostin (P =.035). YKL‐40 correlated significantly with the blood neutrophil count (rs =.397, P =.005) but was not associated with biomarkers of eosinophilic inflammation. Conclusion: Serum YKL‐40 is a potential biomarker for lung function deficits in children with asthmatic symptoms. These deficits appear to be focused on small airways and may remain undetected with spirometry. [ABSTRACT FROM AUTHOR]