Childhood Wheeze Research Articles

Objective detection of wheeze at home by parents through a digital device: usage patterns and relationship with SABA administration.

Wheezing is an important indicator of exacerbated respiratory symptoms in early childhood and must be monitored to regulate pharmacological therapy. However, parents' subjective perception of wheezing in their children is not always precise. We investigated the objective identification of children's wheezing by parents using a digital wheeze detector (WheezeScanTM, OMRON Healthcare Co. Ltd), its longitudinal usage patterns, and its relationship with SABA administration. We conducted a secondary nested analysis of data from the intervention arm of a multi-center randomized controlled trial completed in 2021-2022 in Berlin (Germany), London (United Kingdom), and Istanbul (Turkey). Children aged 4 to 84 months with doctor's diagnosed wheezing (GINA step 1 or 2) were included. Using an electronic diary (Wheeze-MonitorTM, TPS), parents monitored and recorded for 120 days at home the presence or absence of their child's wheezing, detected both, with WheezeScanTM ("objective" wheezing), and subjective ("perceived" wheezing). Parents also recorded the child's symptoms, medication intake, and family quality of life. Questionnaires regarding symptom control, quality of life, and parental self-efficacy were answered at baseline and after 90 and 120 days. Eighty-one/87 families completed the intervention arm of the study. WheezeScanTM was on average used 0.7 (SD 0.6) times a day, with each patient reporting a positive, negative, or "error" outcome on average in 57%, 39%, and 5% of measurements, respectively. The use of WheezeScanTM declined slightly during the first 90 days of monitoring and steeply thereafter. Repeated usage of WheezeScanTM in the same day was more frequent after a "wheeze" (HR 1.5, 95% CI 1.37-1.65, p < 0.001) and an "error" (HR 2.01, 95% CI 1.70-2.38, p < 0.001) result, compared to a "no wheeze" outcome. The average per-patient daily agreement between "objective" and "perceived" wheezing/non-wheezing was 75% at the start of the monitoring period and only weakly persisted as time passed (Spearman's rho=0.09). The frequency of short-acting beta-2-agonists (SABA) administration was lower in days with closely interspaced consecutive device uses during which the patient's status was perceived as "never wheeze" (32/455, 7%) than in those perceived as "persistent wheeze" (53/119, 44%; OR 36.6, 95% CI [14.3, 94.1]). Daily use of a digital WheezeScanTM at home allows parents to detect their child's unperceived wheezing and discloses to caregivers the longitudinal patterns of a child's wheezing disorder. Digital monitoring of wheezing also highlights poor adherence to guidelines in SABA administration for wheezing children, with under-treatment being much more frequent than over-treatment. This pioneering study opens new perspectives for further investigation of digital wheeze detectors in the early diagnosis and proper self-management of wheezing disorders in childhood.

Air quality and wheeze symptoms in a rural children's cohort near a drying saline lake

BackgroundIn California, climate change and competing water demands are intensifying the desiccation of the Salton Sea, a large land-locked “sea” situated near the southeastern rural US-Mexico border region known as the Imperial Valley. MethodsTo examine the possible effects of living near a saline lake on children's respiratory health, we analyzed the relationship between respiratory health symptoms and ambient PM concentrations among a predominantly Latino/Hispanic cohort of 722 school age children. Guardians completed a survey of their child's wheeze and respiratory health symptoms over the past 12 months, adapted from the International Study of Asthma and Allergies in Childhood (ISAAC). Exposure to dust storm hours (hourly concentrations >150 μg/m3 for PM10) was estimated using a network of regulatory monitors. ResultsBetween 2017 and 2019, children were exposed to 98 to 395 dust event hours annually. We observed disparate effects for dust events and wheeze among children living near the Salton Sea. Every additional 100 dust storm hours per year among children living near the Sea (<11 km) was associated with a 9.5 percentage point increase in wheeze (95% CI: 3.5, 15.4), a 4.6 percentage point increase in bronchitic symptoms (95% CI: 0.18, 10.2) and a 6.7 percentage point increase in sleep disturbance due to wheeze (95% CI: 0.96, 12.4). Similarly, increases in PM10 were also associated with greater reported wheeze and bronchitic symptoms among those living near the Sea, compared to children living ≥11 km from the Sea. There was no association of dust storms or PM10 with wheeze or bronchitic symptoms among the children residing farther from the Sea. ConclusionWe observed stronger adverse impacts of PM10 and dust events on respiratory health among those living closer to the drying Salton Sea, compared to children living farther away. In this community of predominantly low-income residents of color, these impacts raise environmental justice concerns about the effects of the drying Salton Sea on public health.

Neonatal and early infancy antibiotic exposure is associated with childhood atopic dermatitis, wheeze and asthma

Antibiotics are frequently administered in the neonatal period and early infancy. Little is known about the long-term health consequences of early life antibiotic exposure. The objective is to investigate the association between neonatal and early life (0–6 months) antibiotic treatment and the development of atopic dermatitis, asthma and the use of inhaled corticosteroid medication later in childhood. We analyzed data obtained from hospital records and national registers in a cohort of 11,255 children. The association between early antibiotic exposure and the outcomes were analyzed using logistic regression. Confounding factors were included in the model. Neonatal antibiotic therapy for confirmed infection was associated with childhood atopic dermatitis (adjusted odds ratio 1.49; 95% confidence interval 1.15–1.94). Antibiotic therapy by six months of age was more common in children developing atopic dermatitis (adjusted odds ratio 1.38; 95% confidence interval 1.15–1.64), asthma (adjusted odds ratio 1.56; 95% confidence interval 1.32- 1.85) and inhaled corticosteroid medication use (adjusted odds ratio 1.88; 95% confidence interval 1.66–2.13). Conclusions: Neonatal antibiotic therapy for confirmed or clinically diagnosed infection is associated with increased risk of atopic dermatitis later in childhood. Antibiotic treatment before six months of age is associated with atopic dermatitis, asthma and inhaled corticosteroid use.What is known:• The use of antibiotics early in life has been associated with an increased risk of developing atopic dermatitis or asthma.• Confounding by indication or reverse causation may underlie the observed associations.What is new:• Our results demonstrate that neonatal antibiotic therapy for confirmed or clinically diagnosed infection was associated with increased risk of atopic dermatitis and antibiotic treatment before six months of age was associated with atopic dermatitis, asthma and inhaled corticosteroid use in analyses adjusted for confounding factors.

Rates of Acute Wheezing in Children During the COVID-19 Pandemic in Rayong Province, Thailand

Rates of Acute Wheezing in Children During the COVID-19 Pandemic in Rayong Province, Thailand

Environmental exposures associated with early childhood recurrent wheezing in the mother and child in the environment birth cohort: a time-to-event study

BackgroundAntenatal factors and environmental exposures contribute to recurrent wheezing in early childhood.AimTo identify antenatal and environmental factors associated with recurrent wheezing in children from birth to 48 months in the...

Prenatal exposure to phthalates and childhood wheeze and asthma in the PROGRESS cohort

IntroductionPrenatal phthalate exposure may influence lung development and lead to wheezing and asthma in childhood, and these associations may vary by sex. Despite ubiquity of exposure, there is limited epidemiologic data on these associations in Latin America. MethodsWe assessed 593 mother-child dyads enrolled in the Programming Research in Obesity, Growth, Environment, and Social Stressors birth cohort in Mexico City. We quantified 15 phthalate metabolites in 2nd and 3rd trimester maternal urine. Report of ever wheeze, wheeze in the past 12 months (current wheeze) and ever asthma were obtained using a validated survey when children were 4 and 6 years of age. We examined individual associations with modified Poisson models. Mixture effects were assessed using Bayesian Weighted Quantile Sum (BWQS) regression. All models were adjusted for child's sex, maternal age and education at enrollment, and parity. ResultsIn Poisson models, a doubling of mono (carboxy-isononyl) phthalate (MCNP) during the 2nd trimester was associated with higher risk of wheeze (RR: 1.14, 95 % CI: 1.01, 1.29), and asthma (RR: 1.44, 95 % CI: 1.05, 1.97) at 4 years of age. Higher concentrations of the sum of di-isononyl phthalate metabolites (∑DiNP) during the 2nd trimester were also associated with asthma at 4 years of age (RR: 1.30, 95 % CI: 1.04, 1.61). Mixture associations of phthalate metabolite concentrations during the 2nd trimester and asthma at 4 years of age were stronger in males (BWQS, OR: 1.94, 95 % CI: 0.90, 4.60; 90 % CrI: 1.04, 3.73) compared to females (BWQS, OR: 1.23, 95 % CI: 0.56, 2.88; 90 % CrI: 0.61, 2.55). Additionally, we observed stronger inverse associations between prenatal phthalate mixtures during the 3rd trimester and current wheeze at 4 and 6 years of age in females (BWQS, OR: 0.54, 90 % CrI: 0.35, 0.82; OR: 0.45, 90 % CrI: 0.22, 0.84) compared to males (BWQS, OR: 0.95, 90 % Cri: 0.68, 1.35; OR: 0.97, 90 % CrI: 0.59, 1.54). ConclusionsPrenatal phthalate metabolite concentrations were associated with respiratory outcomes in childhood, with some evidence of sex specific effects. Future work investigating phthalate exposure and wheeze trajectories/lung function will be important for understanding how these may predict later disease.

Artificial intelligence and wheezing in children: where are we now?

Wheezing is a common condition in childhood, and its prevalence has increased in the last decade. Up to one-third of preschoolers develop recurrent wheezing, significantly impacting their quality of life and healthcare resources. Artificial Intelligence (AI) technologies have recently been applied in paediatric allergology and pulmonology, contributing to disease recognition, risk stratification, and decision support. Additionally, the COVID-19 pandemic has shaped healthcare systems, resulting in an increased workload and the necessity to reduce access to hospital facilities. In this view, AI and Machine Learning (ML) approaches can help address current issues in managing preschool wheezing, from its recognition with AI-augmented stethoscopes and monitoring with smartphone applications, aiming to improve parent-led/self-management and reducing economic and social costs. Moreover, in the last decade, ML algorithms have been applied in wheezing phenotyping, also contributing to identifying specific genes, and have been proven to even predict asthma in preschoolers. This minireview aims to update our knowledge on recent advancements of AI applications in childhood wheezing, summarizing and discussing the current evidence in recognition, diagnosis, phenotyping, and asthma prediction, with an overview of home monitoring and tele-management.

Early life ambient ozone exposure and the development of asthma and wheeze in children

Early life ambient ozone exposure and the development of asthma and wheeze in children

The role of flexible bronchoscope in the evaluation of chronic cough with and without wheeze in children

BackgroundChronic cough in children is a challenging symptom for clinicians. So, we aimed in this study to evaluate the diagnostic role of flexible bronchoscope in differentiating between the underlying causes of chronic wet cough and chronic cough associated with wheeze.MethodsThis was a prospective cross-sectional study conducted on children referred to Tanta University Hospitals and Ain-Shams University Hospitals between January 2021 and January 2023, presenting with a primary complaint of chronic cough lasting more than 4 weeks. The children were further classified into two groups: the first group included children with chronic wet cough not associated with wheezing (Cohort A) and the second group included children with chronic cough associated with wheezing (Cohort B).ResultsThe study enrolled 64 children. During clinical evaluation, 25 (39.1%) children had a chronic cough without wheezing and 39 (60.9%) had a chronic wheezy cough. Bronchoscopic examination findings indicated a notable disparity between the two groups of patients with chronic cough (p=0.006). Among Cohort A patients, the most prevalent bronchoscopic observation was purulent inflammatory secretions in 16 cases (64.0%), followed by congenital airway anomalies in 3 cases (12.0%). Conversely, Cohort B patients exhibited congenital airway anomalies as the primary finding in 14 cases (35.9%), followed by purulent secretions in 7 cases (17.9%).ConclusionFlexible bronchoscopy is a valuable and safe tool for diagnosing chronic cough in children. It helped differentiate between the underlying causes of chronic cough in children with and without wheezing.

Associations of environmental chemical exposures measured in personal silicone wristbands with sociodemographic factors, COVID-19 restrictions, and child respiratory health

BackgroundAlthough human biomonitoring of environmental chemicals has been considered a gold standard, these methods can be costly, burdensome, and prone to unwanted sources of variability that may cause confounding. Silicone wristbands have recently emerged as innovative passive samplers for measuring personal exposures. MethodsIn a pilot study from 2019 to 2021 involving 55 children aged 5–9 years in Seattle and Yakima, Washington, we utilized silicone wristbands to explore associations of sociodemographic variables and COVID-19-related restrictions, including school closures, with exposures to numerous chemicals including brominated and organophosphate ester (OPE) flame retardants, polychlorinated biphenyls, polycyclic aromatic hydrocarbons (PAHs), phthalates, and pesticides. We additionally conducted the first analysis testing silicone wristband chemicals as predictors of child wheeze, individually and in mixtures via logistic weighted quantile sum regression (WQS). ResultsAmong 109 semi-volatile organic compounds measured, we detected 40 in >60% of wristbands worn by children continuously for an average of 5 days. Chemicals were generally positively correlated, especially within the same class. Male sex and increasing age were linked with higher exposures across several chemical classes; Hispanic/Latino ethnicity was linked with higher exposures to some phthalates and OPEs. COVID-19 restrictions were associated with lower wristband concentrations of brominated and triaryl OPE flame retardants. Each one-decile higher WQS exposure index was suggestively associated with 2.11-fold [95% CI: 0.93–4.80] higher odds of child wheeze. Risk of child wheeze was higher per 10-fold increase in the PAH chrysene (RR = 1.93[1.07–3.49]), the pesticide cis-permethrin (3.31[1.23–8.91]), and di-isononyl phthalate (DINP) (5.40[1.22–24.0]) ConclusionsOur identification of demographic factors including sex, age, and ethnicity associated with chemical exposures may aid efforts to mitigate exposure disparities. Lower exposures to flame retardants during pandemic restrictions corroborates prior evidence of higher levels of these chemicals in school versus home environments. Future research in larger cohorts is needed to validate these findings.

Deep multiomic profiling reveals molecular signatures that underpin preschool wheeze and asthma

Wheezing in childhood is prevalent, with over one-half of all children experiencing at least 1 episode by age 6. The pathophysiology of wheeze, especially why some children develop asthma while others do not, remains unclear. This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multiomic profiling. Unsupervised, group-agnostic integrative multiomic factor analysis was performed using host/bacterial (meta)transcriptomic and bacterial shotgun metagenomic datasets from bronchial brush samples paired with metabolomic/lipidomic data from bronchoalveolar lavage samples acquired from children 1-17 years old. Two multiomic factors were identified: one characterizing preschool-aged recurrent wheeze and another capturing an inferred trajectory from health to wheeze and school-aged asthma. Recurrent wheeze was driven by type 1-immune signatures, coupled with upregulation of immune-related and neutrophil-associated lipids and metabolites. Comparatively, progression toward asthma from ages 1 to 18 was dominated by changes related to airway epithelial cell gene expression, type 2-immune responses, and constituents of the airway microbiome, such as increased Haemophilus influenzae. These factors highlighted distinctions between an inflammation-related phenotype in preschool wheeze, and the predominance of airway epithelial-related changes linked with the inferred trajectory toward asthma. These findings provide insights into the differential mechanisms driving the progression from wheeze to asthma and may inform targeted therapeutic strategies.

Association of prenatal vitamin E levels with child asthma and wheeze.

We investigated the individual and interaction effects of maternal plasma 𝛂- and ϒ-tocopherol levels (vitamin E isomers) on child asthma and wheeze at age 8-9. Mother-child dyads were enrolled between 2006 and 2011 into the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) prenatal cohort. Maternal second-trimester samples were analyzed for tocopherol and lipid concentrations. We assessed child asthma/wheeze using the International Study of Asthma and Allergies in Childhood (ISAAC) and other self-reported Ent wheeze. In multivariable logistic regression analyses, we assessed associations between vitamin E isomers and child asthma/wheeze outcomes (n = 847 mother-child dyads) and tested for prespecified interaction terms. Median cholesterol-corrected tocopherol levels (interquartile range (IQR)) were 5.0 (4.3-5.7) and 0.8 (0.7-0.9) (umol/mmol) for 𝛂- and ϒ-tocopherol, respectively. Associations between 𝛂-tocopherol and asthma outcome variables were inverse but not statistically significant. In contrast, for ϒ-tocopherol, associations were in the positive direction, but also nonsignificant. Interactions analysis between tocopherols did not reach statistical significance for any outcome. Among children of women with a history of asthma, the likelihood of ever asthma in the child appears to be decreasing with increasing maternal 𝛂-tocopherol levels, whereas this trend was not observed among those without a history of asthma (p-interaction = .05). We observed no associations for prenatal 𝛂- or ϒ-tocopherol concentrations with child asthma/wheeze. We detected some evidence of effect modification by maternal asthma history in associations between 𝛂-tocopherol and child asthma.

Current situation and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023

Objective: To explore the incidence and influencing factors of wheezing among children and adolescents aged 3-18 years in 11 cities in China from 2022 to 2023. Methods: From October 2022 to August 2023, 11 cities including Xishuangbanna in Yunnan Province, Suqian in Jiangsu Province, Chifeng and Hohhot in Inner Mongolia, Tangshan in Hebei Province, Changzhi in Shanxi Province, Yinchuan in Ningxia Province, Lanzhou and Dingxi in Gansu Province, Linyi in Shandong Province, and Tonghua in Jilin Province were selected as research sites to recruit kindergarten children and primary and secondary school adolescents in local urban areas. A total of 21 959 children and adolescents were included in this study. Demographic information, wheezing data (whether wheezing has occurred in the past and whether wheezing attacks have occurred in the past one year), personal history, family history and other information were collected through questionnaires. The multivariate logistic regression model was used to analyze the influencing factors of wheezing attacks in the past one year. Results: The mean age of 21 959 children and adolescents was (12.09±3.65) years old, and 52.3% (11 480) were boys. The incidence of wheezing history was 3.7% (816 cases), and the incidence of wheezing attacks in the past year was 2.5% (556 cases). The multivariate logistic regression model analysis results showed that compared with older age, girls, full-term natural delivery, no allergic rhinitis, no family history of allergic diseases, no passive smoking, partial diet, natural conception and childbirth, the children aged 3-18 years with young age, male, partial diet, passive smoking, family history of allergic diseases, allergic rhinitis, cesarean section, premature birth, and assisted reproduction had a higher risk of wheezing [OR (95%CI): 0.86(0.84-0.88), 1.27(1.07-1.51), 2.31(1.95-2.75), 2.09(1.76-2.47), 3.5(2.80-4.37), 4.05(3.39-4.83), 1.20(1.02-1.43), 2.26(1.66-3.09), and 1.67(1.01-2.78)]. Conclusion: From 2022 to 2023, the incidence of wheezing among children aged 3-18 years in China is not significantly higher than before, and childhood wheezing may be related to factors such as children's age, gender, dietary habits, family and personal history of allergic diseases, passive smoking, and perinatal period.

Child Opportunity Index Mobility, Recurrent Wheezing, and Asthma in Early Childhood: A Population-Based Prospective Cohort Study

We prospectively examined associations between mobility in neighborhood opportunity and early childhood recurrent wheezing/asthma. Downward mobility was associated with developing asthma, but not recurrent wheezing, though associations were attenuated after adjusting for family-level socioeconomic status. Elucidating how neighborhoods impact asthma may inform asthma equity initiatives in early childhood.

Associations of Insecticide Exposure with Childhood Asthma and Wheezing: A Population-Based Cross-Sectional Study in Sanya, China.

Insecticide exposure may affect childhood asthma/wheezing, but evidence is scarce in low- and middle-income countries. We conducted a population-based cross-sectional study in Sanya, China. Generalized linear models were adopted to assess the associations of insecticide exposure with childhood asthma/wheezing, reported as odds ratios (ORs) and 95% confidence intervals (CIs). A subgroup analysis was performed to explore the possible effects of sociodemographic and environmental factors on these associations. The median age of the 9754 children was 6.7 years, and 5345 (54.8%) were boys. The prevalences of ever asthma (EA), ever wheezing (EW), and current wheezing (CW) were 7.4%, 5.3%, and 2.9%, respectively. We found a greater prevalence of childhood EA with insecticide exposure (OR = 1.18, 95% CI: 1.00, 1.38). Outdoor insecticide exposure was associated with elevated ORs for EA (1.24, 95% CI: 1.03, 1.50), EW (1.27, 95% CI: 1.03, 1.57), and CW (1.38, 95% CI: 1.04, 1.81). The p for the trend in insecticide exposure frequency was significant for EA (p = 0.001) and CW (p = 0.034). These adverse impacts were pronounced in girls who were exposed to low temperatures. Our findings suggest adverse effects of insecticide use, especially outdoors, on childhood asthma/wheezing. Further studies are warranted to verify this association and develop tailored prevention measures.

IJCM_111A: Awareness of third- and fourth-hand smoking and its implications among medical students - A cross sectional study

Background: The term third hand smoke (THS) may have initially appeared in print in 2006, more widely known in 2009. In that work, the researchers stated that 65.2% of non-smokers and 43.3% of smokers believed THS could harm children and such opinions were associated with the imposition of home smoking bans. Fourth-hand smoke, up to two thirds of cigarette butts terminate in the environment. Objective: To estimate awareness and implication of third- and fourth-hand smoking among Medical students. Methodology: A cross sectional study was conducted among Medical students of a Medical College in South India in the month of April 2023. All Medical students whoever gave consent were included in the study. A pre-designed semi-structured questionnaire was administered in google forms to the study participants and informed consent was obtained from the participants. The Beliefs About Third Hand (BATHS) Scale was used to determine beliefs about THS. The data was initially entered to Microsoft Excel 2010 and analysed using statistical package of social science (SPSS trial version 20.0). Results: Among the 360 participants only 35.6% (128) of participants were aware of third hand smoking and 23.3% (84) of participants were aware about fourth hand smoking. Nearly 222(61.6%) participants had opinion of developing asthma, followed by acute respiratory tract infection and wheeze in children when exposed to third hand smoke. Majority 341(94.7%) and 344 (95.6%) participants out of 360 had opinion that smoking should be banned in home environment and public places respectively. Conclusion: The medical students had less awareness about third hand smoke and its effect on human health, hence measures have to be taken to make medical students aware about it. It can be recommended to incorporate third- and fourth-hand smoking as educational messages in the medical curriculum.

Pulmonary immune profiling reveals common inflammatory endotypes of childhood wheeze and suppurative lung disease

Suppurative lung disease and wheezing are common respiratory diseases of childhood, however due to poor understanding of underlying pathobiology, there are limited treatment options and disease recurrence is common. We aimed to profile the pulmonary and systemic immune response in children with wheeze and CSLD for identification of endotypes that can inform improved clinical management. We used clinical microbiology data, highly multiplexed flow cytometry and immunoassays to compare pulmonary (bronchoalveolar lavage (BAL)) and systemic immunity in children with lung disease and controls. Unsupervised analytical approaches were applied to BAL immune data to explore biological endotypes. We identified two endotypes that were analogous in both frequency and immune signature across both respiratory diseases. The hyper-inflammatory endotype had a 12-fold increase in neutrophil infiltration and upregulation of 14 soluble signatures associated with type 2 inflammation and cell recruitment to tissue. The non-inflammatory endotype was not significantly different to controls. We showed these endotypes are measurable in a clinical setting, and can be defined by measuring only three immune factors in BAL. We identified hyper-inflammatory and non-inflammatory endotypes common across paediatric wheeze and CSLD that, if validated in future studies, has the potential to inform clinical management.

Prenatal polycyclic aromatic hydrocarbon exposure and asthma at age 8–9 years in a multi-site longitudinal study

Background and aimStudies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in socio-demographically diverse participants from the ECHO PATHWAYS multi-cohort consortium.MethodsWe included 1,081 birth parent–child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8–9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression.ResultsThe prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically significant.ConclusionsIn a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8–9 years, though some adverse associations were observed among girls.

Vitamin D supply, respiratory viral infections and persistent wheezing in children: how significant is the relationship?

The review discusses the multifaceted effect of vitamin D on antiviral immunity, induction of antimicrobial peptides, functional activity of immunocompetent cells, autophagy processes, clearance of viruses and viral fragments. The relationship between vitamin D and allergic inflammatory cells, its modulating and tolerogenic potential is considered. The inhibitory effect of vitamin D on eosinophils, mast cells, the production of pro-inflammatory and proallergic mediators, and the synthesis of IgE has been shown. The protective role of vitamin D in the development of remodeling and hyperresponsiveness of the respiratory tract has been established by reducing the number of goblet cells, mucus hypersecretion, and the expression of metalloproteinases. The effects of vitamin D on the replication of respiratory viruses and experimental resistance to them through the induction of antimicrobial peptides and other mechanisms have been demonstrated. Data from clinical studies on the preventive effect of vitamin D on the incidence of respiratory infections and episodes of persistent wheezing in children are presented. Children with respiratory syncytial infection and vitamin D deficiency were more likely to require respiratory support and mechanical ventilation. The preventive role of vitamin D in the development of obstructive bronchitis in children and severe bronchiolitis in infants has been shown. It has been established that normal levels of 25(OH)D in the mother significantly reduce the risk of developing bronchial obstruction in the child. Alternative data that do not support a protective effect of vitamin D on respiratory morbidity and wheezing in children are discussed. Further monitoring studies that take into account geographic location and analysis of the dose of cholecalciferol used to assess its preventive role in the development of wheezing and bronchial asthma in children are advisable.

A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development

BackgroundMost previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase. MethodsWe performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms. ResultsThe final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development. ConclusionPreconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children.