Asthma is a chronic disease affecting millions of children worldwide, and in severe cases requires hospitalization. The etiology of asthma is multifactorial, caused by both genetic and environmental factors. In recent years, the role of the early-life gut microbiome in relation to asthma has become apparent, supported by an increasing number of population studies, in vivo research, and intervention trials. Numerous early-life factors, which for decades have been associated with the risk of developing childhood asthma, are now being linked to the disease through alterations of the gut microbiome. These factors include cesarean birth, antibiotic use, breastfeeding, and having siblings or pets, among others. Association studies have highlighted several specific microbes that are altered in children developing asthma, but these can vary between studies and disease phenotype. This demonstrates the importance of the gut microbial ecosystem in asthma, and the necessity of well-designed studies to validate the underlying mechanisms and guide future clinical applications. In this review, we examine the current literature on the role of the gut microbiome in childhood asthma and identify research gaps to allow for future microbial-focused therapeutic applications in asthma.

There is a significant delay between symptom onset and diagnosis of childhood asthma, but the impact of this delay on asthma outcomes has not been well understood.

We sought to study the association of delayed diagnosis of asthma with asthma exacerbations (AEs) in children.

Using the Mayo Clinic birth cohort, we identified children with a diagnosis of asthma from electronic health records. We defined onset date as the date when subjects first met predetermined asthma criteria ascertained by an electronic health records-based natural language processing algorithm. Delay in diagnosis (DD) was defined as first diagnosis >30 days from onset date (vs timely diagnosis [TD] within 30 days). The primary outcome was AE after the index date (for DD: first diagnosis date vs for TD: clinic visit at similar delay from diagnosis as matched DD counterpart). A Cox proportional hazard model was used to test the association between delayed diagnosis status and risk of AE, adjusting for sociodemographics, care quality, and asthma severity.

Among 537 matched pairs of DD and TD (median age at index date: 4.1 years), a total of 344 and 253 children in DD and TD, respectively, had ≥1 AE during median follow-up period of 9.3 years. Children in the DD group had a significantly increased risk of AE compared to TD (adjusted hazard ratio: 1.53; 95% CI: 1.28, 1.80; P < .001).

DD of asthma in children is associated with an increased risk of AE compared to TD. TD of asthma should be an important priority in childhood asthma management.

In the past 3 decades, the overall prevalence of asthma appears to be plateauing, although large geographic and socioeconomic variation is evident. Overall, asthma prevalence slightly decreased in most age groups, except for school-aged children. Of note, asthma mortality steadily decreased, potentially highlighting improved asthma management strategies. Several epidemiologic studies indicate that a complex interplay between genetic, environmental, and immunologic factors predisposes individuals to asthma inception and persistence across different life stages. Established risk factors for preschool wheezing to asthma persistence comprise a combination of pre- and post-natal parameters including the maternal history of asthma, prematurity, caesarian section, early-life respiratory infections, exposure to air pollution or tobacco smoke, and allergic polysensitization. On the other hand, persistence into adulthood is mainly driven by disease severity, allergic multimorbidity, relevant comorbidities, severe respiratory infections, and tobacco smoke exposure. It is evident that asthma prevention strategies do not fit a "one size fits all" concept and key environmental interventions should be tailored to different regions of the world. Undoubtedly, the heterogeneity of asthma as a disease is at least partly reflected in the reported epidemiologic measures, and continuing, methodologically rigorous studies will allow us to unravel some of the observed discrepancies.

Respiratory infections in early life are an identified risk factor for asthma. We hypothesized that infection-prevention measures during the coronavirus disease 2019 (COVID-19) pandemic influenced the risk of respiratory morbidity and aeroallergen sensitization in early childhood.

We compared respiratory morbidity and aeroallergen sensitization in children born before and during the pandemic.

We compared a COVID-19 category (exposed children; n = 1661) to a pre-COVID-19 category (nonexposed children; n = 1676) by using data from the prospective population-based NorthPop Birth Cohort study in Sweden. Data on respiratory morbidity and concomitant medication were retrieved from national registers. Prospectively collected data on respiratory morbidity using web-based questionnaires at 9 and 18 months of age were applied. At age 18 months, serum IgE levels to aeroallergens were determined (n = 1702).

The risk of developing any respiratory tract infection (adjusted odds ratio [aOR] = 0.33 [95% CI, 0.26-0.42]), bronchitis (aOR = 0.50 [95% CI, 0.27-0.95]) and croup (aOR = 0.59 [95% CI, 0.37-0.94]) were decreased in the COVID-19 category. The risk of wheeze in the first 9 months was lower in the COVID-19 category (aOR = 0.70 [95% CI, 0.55-0.89]). There were also fewer prescriptions of antibiotics in the COVID-19 category. The prevalence of aeroallergen sensitization was similar between categories.

Children born during the COVID-19 pandemic demonstrated significantly decreased risks of respiratory infections and prescribed antibiotics until 18 months of age compared to children born before the COVID-19 pandemic. Whether this will affect the risk of developing asthma in childhood is being followed.

Children with preschool asthma suffer disproportionally more often from severe asthma exacerbations with emergency visits and hospital admissions than school children. However, there are only a few reports on characteristics, hospitalization, phenotypes and symptoms in this age cohort.

This analysis of an ongoing prospective trial of Tiotropium bromide in preventing severe asthma exacerbations (the TIPP study) assessed baseline characteristics, hospitalizations and symptoms in 100 children with severe preschool asthma. Children aged 1-5 years were analyzed at study enrollment and daily symptoms were recorded by an electronic diary [Pediatric Asthma Caregiver Diary (PACD)] for the following four weeks until randomization.

At enrollment, the total number of severe asthma exacerbations, defined as three days systemic steroid use or hospitalization in the last 24 months, was mean (±SD) 5.8 ± 5.7 and the test for respiratory and asthma control in kids (TRACK) was mean 46.9 ± 19.0. Daily recording of symptoms by the PACD revealed that only 7 patients were controlled at randomization, whereas 35 were partially and 58 were uncontrolled according to GINA.

Despite protective therapy with inhaled corticosteroids (ICS), most children of this severe asthma cohort were only partially or uncontrolled according to GINA guidelines.

Background and Objectives: Childhood asthma represents a significant global public health issue and is the most common chronic disease among children. Hospitalization costs, especially for intensive care, are quite high. This study aimed to evaluate the characteristics, prognosis, and preventable risk factors of patients admitted to the Pediatric Intensive Care Unit (PICU) due to severe asthma exacerbations. Materials and Methods: We assessed patients admitted to the Ankara Bilkent City Hospital PICU from January 2013 to December 2022 diagnosed with asthma based on The Global Initiative for Asthma (GINA) criteria. The collected data encompassed demographic and clinical characteristics, intensive care treatments, hospitalization duration, atopic conditions, and respiratory viral panel results. The current clinical status was assessed using hospital records and caregiver interviews, with a focus on recent emergency admissions, ongoing treatments, exacerbation frequency, and asthma control based on GINA guidelines. Results: The study comprised 83 patients with a mean age of 72.9 (±45.5) months, predominantly male (63.9%). The average follow-up duration post-discharge was 40.7 ± 26.9 months. Patients received respiratory support in the PICU for a mean of 3.8 (±2.8) days and systemic steroid therapy for 4 (±1.5) days. Respiratory viral panel results identified pathogens in 42 patients, with rhinovirus being the most frequent. Post-discharge, 72.3% of patients continued follow-up at pediatric allergy clinics. Of the 60 patients contacted, 67.5% were on current asthma treatment and 48.2% had experienced an exacerbation in the past year. Asthma management steps remained unchanged for 33 patients, decreased for 13, and increased for 47 (44.6%). Asthma maintenance treatments pre-admission and post-discharge showed that 44.6% (n = 47) of the patients required an increase in their GINA treatment step after PICU admission, which was statistically significant (p < 0.001). History of atopic dermatitis was a significant risk factor for escalating treatment steps in both univariate and multivariate analyses (p = 0.018, p = 0.03). Conclusions: We found that admission to the PICU due to severe asthma exacerbation not only increases the risk of recurrent asthma exacerbations but also serves as a risk factor for stepping up maintenance treatment according to GINA guidelines during long-term follow-up.

Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting.

To investigate in situ virus-specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma.

We included 493 episodes of acute respiratory illnesses in 277 children aged 0-3 years from the COPSAC2010 mother-child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high-sensitivity MesoScale Discovery kits and compared between children with and without viral PCR-identification in nasopharyngeal samples. Finally, we investigated whether the virus-specific immune response was associated with asthma by age 6 years.

Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN-ɣ, TNF-α, CCL4, CXCL10 and IL-10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL-10 (FDR <0.05) during viral episodes compared to children not developing asthma.

We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL-10) immune mediator level. This provides insight into the interplay between early-life viral infections, airway immunity and asthma development.

Recent evidence indicates that Maternal Supplementation with Long-Chain n-3 Fatty Acids During Pregnancy Substantially Mitigates Offspring's Asthma. Adding information regarding its cost-utility will undoubtedly allow its adoption, or not, in clinical practice guidelines. This research aimed to determine the cost-utility of LCPUFA supplementation in the third trimester of pregnancy to reduce the risk of wheezing and asthma in infants in Colombia.

A Markov model was formulated to estimate the cost and quality-adjusted life-years (QALYs) attributed to individuals with severe asthma in Colombia, with a time horizon of five years and a cycle length of two weeks. Probabilistic sensitivity analysis and a value of information (VOI) analysis were conducted to evaluate the uncertainties in the case base. Cost-utility was assessed at a willingness-to-pay (WTP) value of US$5180. All costs were adjusted to 2021 with a 5% annual discounting rate for cost and QALYs.

The mean incremental cost of LCPUFA supplementation versus no supplementation was US-43.65. The mean incremental benefit of LCPUFA supplementation versus no supplementation was 0.074 QALY. The incremental cost-utility ratio was estimated at US$590.68 per QALY. The outcomes derived from our primary analysis remained robust when subjected to variations in all underlying assumptions and parameter values.

Supplementation strategy supplementation with long-chain n-3 fatty acids during pregnancy is cost-effective in reducing the risk of developing asthma during childhood in Colombia.

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 respiratory tract infections have been linked to the development of asthma, but studies on the burden and subtypes of common infections in asthma development are sparse.

To examine the association between burden of early life infections, including subtypes, with the risk of asthma from age 3 to 10 years and lung function at age 10 years.

We included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, for whom infections such as colds, acute tonsillitis, acute otitis media, pneumonia, gastroenteritis, and fever were registered prospectively in daily diaries at age 0 to 3 years and asthma was diagnosed longitudinally from age 3 to 10 years. The association between the burden of infection and subtypes and risk of asthma was analyzed by generalized estimating equations.

The children experienced a median of 16 infections (interquartile range, 12-23 infections) at age 0 to 3 years. Children with a high burden of infections (above the median) had an increased risk of asthma at age 3 to 10 years (adjusted odds ratio = 3.61; 95% CI, 2.39-5.45; P < .001), which was driven by colds, pneumonia, gastroenteritis, and fever episodes (P < .05) but not by acute otitis media and tonsillitis. Lower lung function measures at age 10 years were associated with the burden of pneumonia but not the overall infection burden. The association between colds and the risk of asthma was significantly higher in children with allergic rhinitis at age 6 years (P interaction = .032).

A high burden of early life infections in terms of colds, pneumonia, gastroenteritis, and fever is associated with an increased risk of developing asthma, particularly in children with respiratory allergy. Strategies to diminish these early life infections may offer a path for the primary prevention of childhood asthma.

Asthmatic symptoms often start during early childhood. Impulse oscillometry (IOS) is feasible in preschool children who may be unable to reliably perform spirometry measurements.

We sought to evaluate the use of IOS in a multicenter, multiethnic high-risk asthma cohort titled the Vitamin D Antenatal Asthma Reduction Trial.

The trial recruited pregnant women whose children were followed from birth to age 8 years. Lung function was assessed with IOS at ages 4, 5, and 6 years and spirometry at ages 5, 6, 7, and 8 years. Asthma status, respiratory symptoms, and medication use were assessed with repeated questionnaires from birth to age 8 years.

In total, 220 children were included in this secondary analysis. Recent respiratory symptoms and short-acting β2-agonist use were associated with increased respiratory resistance at 5 Hz at age 4 years (β = 2.6; 95% CI, 1.0 to 4.4; P = .002 and β = 3.4; 95% CI, 0.7 to 6.2; P = .015, respectively). Increased respiratory resistance at 5 Hz at age 4 years was also associated with decreased lung function from ages 5 to 8 years (β = -0.3; 95% CI, -0.5 to -0.1; P < .001 for FEV1 at 8 years) and active asthma at age 8 years (β = 2.0; 95% CI, 0.2 to 3.8; P = .029).

Increased respiratory resistance in preschool IOS is associated with frequent respiratory symptoms as well as school-age asthma and lung function impairment. Our findings suggest that IOS may serve as a potential objective measure for early identification of children who are at high risk of respiratory morbidity.

Respiratory infections are a leading cause of child morbidity worldwide, and asthma is the most common chronic disorder in childhood. Both conditions associate with high socioeconomic costs and are major reasons for medication prescriptions and hospitalizations in children. Vitamin D deficiency has concomitantly increased with asthma prevalence and is hypothesized to play a key role in the development. Current evidence suggests that high prenatal and early childhood vitamin D could be protective against respiratory infections and asthma in some studies where several mechanisms are proposed. However, other studies have reported no effects on these outcomes. Therefore, future large intervention studies on this topic are warranted. Mechanistic studies have shown that vitamin D holds antimicrobial properties by inducing production of several peptides through altered gene expression. Others have shown a complex interplay between asthma risk genotypes, the sphingolipid pathway, and prenatal vitamin D in early childhood asthma. Vitamin D has also been suggested to change both airway immune and microbiota profiles, which are directly related to asthma risk. Finally, systemic low-grade inflammation seems to be regulated by vitamin D exposure. This review presents the current literature of the primary preventive effect of vitamin D on early childhood asthma and respiratory infections. Mechanisms of actions are discussed, and gaps in knowledge are highlighted to facilitate planning of future intervention trials.

Prediction of asthma in preschool children is challenging and lacks objective indicators. The aim is to observe and analyze the variances between impulse oscillometry (IOS) and fractional expiratory nitric oxide (FeNO) in preschool children with wheezing, establish a joint prediction model, and explore the diagnostic value of combining IOS with FeNO in diagnosing asthma among preschool children.

This study enrolled children aged 3-6 years with wheezing between June 2021 and June 2022. They were categorized as asthmatic (n=104) or non-asthmatic (n=109) after a 1-year follow-up. Clinical data, along with IOS and FeNO measurements from both groups, underwent univariate regression and multiple regression analyses to identify predictive factors and develop the most accurate model. The prediction model was built using the stepwise (stepAIC) method. The receiver operating characteristic curve (ROC), calibration curve, Hosmer-Lemeshow test, and decision curve analysis (DCA) were employed to validate and assess the model.

During univariate analysis, a history of allergic rhinitis, a history of eczema or atopic dermatitis, and measures including FeNO, R5, X5, R20, Fres, and R5-R20 were found to be associated with asthma diagnosis. Subsequent multivariate analysis revealed elevated FeNO, R5, and X5 as independent risk factors. The stepAIC method selected five factors (history of allergic rhinitis, history of eczema or atopic dermatitis, FeNO, R5, X5) and established a prediction model. The combined model achieved an AUROC of 0.94, with a sensitivity of 0.89 and specificity of 0.88, surpassing that of individual factors. Calibration plots and the HL test confirmed satisfactory accuracy.

This study has developed a prediction model based on five factors, potentially aiding clinicians in early identification of asthma risk among preschool children.

Wheezing is a high pitched, whistling sound generated when air flows through narrowed airways and is often equated with asthma. However, wheezing may be a presenting symptom of various other conditions including structural lesions of the airways, foreign body aspiration, pulmonary infections as well as cardiac causes. Underlying etiology of wheezing may also vary with age. Detailed history, physical examination, and laboratory investigations are often required to identify the underlying etiology of wheezing. Additional studies may sometimes be needed to accurately identify the underlying etiology such as pulmonary function test or spirometry, chest radiography (chest X-ray), and bronchoscopy. This review article discusses the common causes of wheezing encountered in clinical practice. [Pediatr Ann. 2024;53(5):e189-e194.].

The aim of this systematic review and meta-analysis was to analyse the efficacy of azithromycin in acute bronchiolitis and wheezing.

PubMed, Scopus, and Web of Science databases were searched for randomized controlled trials comparing azithromycin to placebo in children <2 years of age. Main outcomes were progress of acute wheezing episode and recurrence of wheezing. We used random-effects model to calculate mean difference (MD) with 95% confidence interval (CI) or risk ratios (RR) with CI.

We screened 1604 abstracts and included 7 studies. Risk of bias was low in three and had some concerns in four studies. Need for intensive care unit treatment was assessed in four studies (446 children) and the risk difference was 0.0% (CI -2.0 to 2.0; low quality evidence). Hospitalization duration was -0.27 days shorter in the azithromycin group (MD-0.27, CI -0.47 to -0.07; three studies; moderate quality evidence). Azithromycin did not prevent recurrence of wheezing (RR 0.84, CI 0.45-1.56; three studies), hospital readmissions (RR 1.14, CI 0.82-1.60; four studies).

We found moderate quality evidence that azithromycin may reduce hospitalization duration. Low certainty evidence suggests that azithromycin does not reduce the need for intensive care unit treatment. Furthermore, azithromycin did not prevent wheezing recurrence.

Azithromycin may reduce hospitalization time in acute bronchiolitis and wheezing episodes among children aged less than two. Azithromycin administrated during the acute wheezing period, does not have preventive effect on wheezing recurrence. Azithromycin seemed to have similar adverse event profile than placebo. Future studies with clinically relevant outcomes, and sufficient sample sizes are needed, before implementing azithromycin into clinical use.

Respiratory infections and wheeze have a considerable impact on the health of young children and consume significant healthcare resources. We aimed to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood.

Environmental risk factors including: daycare attendance; breastfeeding; siblings; damp within the home; environmental tobacco smoke (ETS); child's bedroom flooring; animal exposure; road traffic density around child's home; and solid fuel pollution within home were assessed in children recruited to the GO-CHILD multicentre prospective birth cohort study. Follow-up information on respiratory infections (bronchiolitis, pneumonia, otitis media and cold or flu), wheeze and cough symptoms, healthcare utilisation and medication prescription was collected by postal questionnaires at 12 and 24 months. Log binomial and ordered logistic regression models were fitted to the data.

Follow-up was obtained on 1344 children. Daycare was associated with increased odds of pneumonia (odds ratio [OR] = 2.39, 95% confidence interval [CI]: 1.04-5.49), bronchiolitis (OR = 1.40, 1.02-1.90), otitis media (OR = 1.68, 1.32-2.14) and emergency department attendance for wheeze (RR = 1.81, 1.17-2.80). Breastfeeding beyond 6 months was associated with a reduced odds of bronchiolitis (OR = 0.55, 0.39-0.77) and otitis media (OR = 0.75, 0.59-0.99). Siblings at home was associated with an increased odds of bronchiolitis (OR = 1.65, 1.18-2.32) and risk of reliever inhaler prescription (RR = 1.37, 1.02-1.85). Visible damp was associated with an increased odds of wheeze (OR = 1.85, 1.11-3.19), and risk of reliever inhaler (RR = 1.73, 1.04-2.89) and inhaled corticosteroid prescription (RR = 2.61, 1.03-6.59). ETS exposure was associated with an increased odds of primary care attendance for cough or wheeze (OR = 1.52, 1.11-2.08). Dense traffic around the child's home was associated with an increased odds of bronchiolitis (OR = 1.32, 1.08-2.29).

Environmental factors likely influence the wide variation in infection frequency and symptoms observed in early childhood. Larger population studies are necessary to further inform and guide public health policy to decrease the burden of respiratory infections and wheeze in young children.

Bacteriophage (also known as phage) communities that inhabit the gut have a major effect on the structure and functioning of bacterial populations, but their roles and association with health and disease in early life remain unknown. Here, we analyze the gut virome of 647 children aged 1 year from the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) mother-child cohort, all deeply phenotyped from birth and with longitudinally assessed asthma diagnoses. Specific temperate gut phage taxa were found to be associated with later development of asthma. In particular, the joint abundances of 19 caudoviral families were found to significantly contribute to this association. Combining the asthma-associated virome and bacteriome signatures had additive effects on asthma risk, implying an independent virome-asthma association. Moreover, the virome-associated asthma risk was modulated by the host TLR9 rs187084 gene variant, suggesting a direct interaction between phages and the host immune system. Further studies will elucidate whether phages, alongside bacteria and host genetics, can be used as preclinical biomarkers for asthma.

Whether cesarean section (CS) is a risk factor for asthma in offspring is controversial. The purpose of this study was to investigate the association between CS and asthma in children/adolescents.

Pubmed, Embase, Web of Science, and Cochrane Library electronic databases were searched for cohort studies on the relationship between mode of delivery and asthma in children/adolescents up to February 2023. Birth via CS was considered an exposure factor. Asthma incidence was taken as a result.

Thirty-five cohort studies (thirteen prospective and twenty-two retrospective cohort studies) were included. The results showed that the incidence of asthma was higher in CS offspring (odds ratio (OR) = 1.18, P < 0.001) than in the vaginal delivery (VD) group. Partial subgroup analyses showed a higher incidence of asthma in female offspring born via CS (OR = 1.26, P < 0.001) compared with the VD group, while there was no difference in males (OR = 1.07, P = 0.325). Asthma incidence was higher in CS offspring than in the VD group in Europe (OR = 1.20, P < 0.001), North America (OR = 1.15, P < 0.001), and Oceania (OR = 1.06, P = 0.008). This trend was not found in the Asian population (OR = 1.17, P = 0.102). The incidence of atopic asthma was higher in offspring born via CS (OR = 1.14, P < 0.001) compared to the VD group. The CS group had a higher incidence of persistent asthma, but the difference did not reach statistical significance (OR = 1.15, P = 0.063).

In this meta-analysis, CS may be a risk factor for asthma in offspring children/adolescents compared with VD. The relationship between CS and asthma was influenced by sex and region.

Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood.

We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5-18 years in the COPSAC2000 birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children.

In the COPSAC2000 cohort, 133 had asthma between age 5 and 18 years, and in the COPSAC2010 cohort, 112 had asthma between age 5 and 10 years. In the COPSAC2000 cohort, asthma and aeroallergen sensitization were both associated with higher FeNO from age 5 to 18 years: adjusted geometric mean ratio (aGMR), 1.22 (1.08-1.35), p < .01, and 1.41 (1.21-1.65), p < 0.001, respectively. However, asthma was associated with increased FeNO among children with aeroallergen sensitization: 1.44 (1.23-1.69), p < .0001, whereas asthma was associated with decreased FeNO among nonsensitized children: 0.80 (0.65-0.99), p = .05 (p-interaction<.0001 for asthma x sensitization). Replication in the COPSAC2010 cohort showed similar results (p-interaction <.01). Further, blood eosinophil count, total-IgE, bronchodilator response, and bronchial hyperreactivity were all associated with increased FeNO among children sensitized to aeroallergens, but not among nonsensitized children.

Fraction of exhaled nitric oxide is elevated through childhood in children with asthma and is correlated with asthma-associated traits depending on the presence of aeroallergen sensitization. These findings indicate that FeNO is only a valid asthma biomarker in children with concurrent aeroallergen sensitization, which is important for guideline recommendations on the clinical use of FeNO.

Asthma is the most common chronic disease in childhood and a rise in prevalence has been observed concomitantly with changing dietary habits in the Western world. This change has favored a more Westernized diet characterized by high intake of processed food and fat in contrast to a Mediterranean diet high in fruit, vegetable and fish intake. This has resulted in a decreased intake of several antioxidants and micronutrients including n-3 long-chained polyunsaturated fatty acids and vitamin D that are speculated to have anti-inflammatory effects and hold immunoregulatory properties. Several observational studies have investigated associations between dietary intake and wheeze and asthma but only few large well-conducted randomized controlled trials (RCTs) have been performed investigating the primary preventive effect of micronutrient supplementations. Currently, the recommendations from the Global Initiative for Asthma (GINA) for primary prevention of asthma in children do not include maternal dietary changes or supplementations during pregnancy, although the most recent report mentions both specific dietary patterns and micronutrients as potential protective supplementation regimes. This review will present the current literature and future research needs focusing on primary and secondary prevention of both early and late childhood asthma from dietary intake during pregnancy and early childhood to highlight potential preventive effects of specific dietary patterns and micronutrient supplements, which may facilitate the planning of future clinical trials in search of a preemptive strategy.

Episodes of asthma-like symptoms in young children are common, but little is known about risk factors and their patterns for the daily symptom burden.

We investigated a variety of possible risk factors and their age-related impact on the number of asthma-like episodes during age 0 to 3 years.

The study population included 700 children from the Copenhagen Prospective Studies on Asthma in Childhood2010 mother-child cohort followed prospectively from birth. Asthma-like symptoms were recorded until age 3 by daily diaries. Risk factors were analyzed by quasi-Poisson regressions, and interaction with age was explored.

Diary data were available in 662 children. Male sex, maternal asthma, low birth weight, maternal antibiotic use, high asthma exacerbation polygenic risk score, and high airway immune score were associated with a higher number of episodes in a multivariable analysis. Maternal asthma, preterm birth, caesarean section, and low birth weight showed an increasing impact with age, whereas sibling(s) at birth showed a decreased association with age. The remaining risk factors had a stable pattern during age 0 to 3 years. For every additional clinical risk factor (male sex, low birth weight, and maternal asthma) a child had, we found 34% more episodes (incidence rate ratio: 1.34, 95% confidence interval: 1.21-1.48; P < .001).

Using unique day-to-day diary recordings, we identified risk factors for the burden of asthma-like symptoms in the first 3 years of life and described their unique age-related patterns. This provides novel insight into the origin of asthma-like symptoms in early childhood that potentially pave a path for personalized prognostics and treatment.

Early life asthma phenotyping remains an unmet need in pediatric asthma. In France, severe pediatric asthma phenotyping has been done extensively; however, phenotypes in the general population remain underexplored. Based on the course and severity of respiratory/allergic symptoms, we aimed to identify and characterize early life wheeze profiles and asthma phenotypes in the general population.

ELFE is a general population based birth cohort; which recruited 18,329 newborns in 2011, from 320 maternity units nationwide. Data was collected using parental responses to modified versions of ISAAC questionnaire on eczema, rhinitis, food allergy, cough, wheezing, dyspnoea and sleep disturbance due to wheezing at 3 time points: post-natal (2 months), infancy (age 1) and pre-school (age 5). We built a supervised trajectory for wheeze profiles and an unsupervised approach was used for asthma phenotypes. Chi squared (χ2) test or fisher's exact test was used as appropriate (p < 0.05).

Wheeze profiles and asthma phenotypes were ascertained at age 5. Supervised wheeze trajectory of 9161 children resulted in 4 wheeze profiles: Persistent (0.8%), Transient (12.1%), Incident wheezers at age 5 (13.3%) and Non wheezers (73.9%). While 9517 children in unsupervised clusters displayed 4 distinct asthma phenotypes: Mildly symptomatic (70%), Post-natal bronchiolitis with persistent rhinitis (10.2%), Severe early asthma (16.9%) and Early persistent atopy with late onset severe wheeze (2.9%).

We successfully determined early life wheeze profiles and asthma phenotypes in the general population of France.

Recurrent wheezing is a common clinical problem in early childhood, which is associated with significant morbidity. There is no international consensus on the management and prevention of recurrent wheezing; therefore, identifying the risk factors associated with recurrent wheezing is crucial to prevent episodes of wheezing in young children.

In this retrospective study, we collected the data of 24,737 patients who were admitted to our hospital between 27th April 2012 and 11th September 2019. After screening for patients with wheezing, we identified 8572 patients with a primary diagnosis of pneumonia with wheezing. Patients' clinical data were collected from the hospital medical records. Patients were stratified for age in the groups of < 6 months, 6-12 months, and > 12 months.

Among the 8569 pediatric pneumonia patients with wheezing, there were 343 patients with recurrent wheezing. Most enrolled patients were under 6 months of age (45.17%) and had a normal birth weight (86.95%). Winter was the most common onset season for the first episode of wheezing, while spring was the most common season for the second episode of wheezing for those with recurrent wheezing. The univariate and multivariate logistic regression analysis for the risk factor associated with recurrent wheezing showed that male gender, past history of respiratory and cardiovascular diseases, low birth weight, development of severe pneumonia, and PICU admission were significantly associated with recurrent wheezing.

Male gender, past history of respiratory and cardiovascular diseases, low birth weight, severe pneumonia, and PICU admission are independent risk factors of recurrent wheezing in the pediatric population.

Lung function testing is used in diagnosing asthma and assessing asthma control. Spirometry is most commonly used, but younger children can find performing this test challenging. Non-volitional tests such as airwave oscillometry (AOS) may be helpful in that population. We compared the success of spirometry and AOS in assessing bronchodilator responsiveness in children.

AOS was conducted alongside routine lung function testing. Resistance at 5 Hz (R5), the difference between the resistance at 5 and 20 Hz (R5-20) and the area under the reactance curve (AX) were assessed. Patients between 5 and 16 years old attending clinic with wheeze or asthma were assessed. Patients performed AOS, followed by spirometry and were then given 400 µg salbutamol; the tests were repeated 15 minutes later.

Lung function testing was performed in 47 children of whom 46 (98%) and 32 (68%) performed acceptable baseline oscillometry and spirometry, respectively (p < 0.001). Children unable to perform acceptable spirometry were younger (7.35, range: 5.4-10.3 years) than those who could (10.4, range: 5.5-16.9 years), p < 0.001. The baseline z-scores of AOS R5 correlated with FEV₁ (r = 0.499, p = 0.004), FEF₇₅ (r = 0.617, p < 0.001), and FEV₁/FVC (r = 0.618, p < 0.001). There was a positive bronchodilator response assessed by spirometry (change in FEV₁ ≥ 12%) in eight children which corresponded to a change in R5 of 36% (range: 30%-50%) and a change in X5 of 39% (range: 15%-54%).

Oscillometry is a useful adjunct to spirometry in assessing young asthmatic children's lung function. The degree of airway obstruction, however, might affect the comparability of the results of the two techniques.

Artificial intelligence (AI) models may propagate harmful biases in performance and hence negatively affect the underserved. We aimed to assess the degree to which data quality of electronic health records (EHRs) affected by inequities related to low socioeconomic status (SES), results in differential performance of AI models across SES.

This study utilized existing machine learning models for predicting asthma exacerbation in children with asthma. We compared balanced error rate (BER) against different SES levels measured by HOUsing-based SocioEconomic Status measure (HOUSES) index. As a possible mechanism for differential performance, we also compared incompleteness of EHR information relevant to asthma care by SES.

Asthmatic children with lower SES had larger BER than those with higher SES (eg, ratio = 1.35 for HOUSES Q1 vs Q2-Q4) and had a higher proportion of missing information relevant to asthma care (eg, 41% vs 24% for missing asthma severity and 12% vs 9.8% for undiagnosed asthma despite meeting asthma criteria).

Our study suggests that lower SES is associated with worse predictive model performance. It also highlights the potential role of incomplete EHR data in this differential performance and suggests a way to mitigate this bias.

The HOUSES index allows AI researchers to assess bias in predictive model performance by SES. Although our case study was based on a small sample size and a single-site study, the study results highlight a potential strategy for identifying bias by using an innovative SES measure.

Background and aim Recurrent wheezing is often triggered by viral respiratory infections. The aims of our study were: i) to evaluate whether the addition of a nutraceutical (Leucodif®), could improve the efficacy of montelukast or inhaled steroids (ICS) compared to the single treatment; ii) to verify whether a treatment is more effective than another. Our study was biased by the COVID-19 pandemic, which resulted in a lockdown of almost two months in Italy. Methods The multicenter, open-label study enrolled 84 children aged 2-6 years diagnosed with recurrent wheezing and randomized them into four treatment arms for three months: ICS treatment; ii) montelukast; iii) montelukast + Leucodif; iv) ICS + Leucodif. Children were assessed at baseline and after one, two, and three months of treatment using the TRACK score for both the caregiver and the physician. Results Out of the 84 patients, 18 patients received ICS therapy, 22 patients ICS + Leucodif, 24 patients montelukast, and 20 patients montelukast + Leucodif. All four treatments resulted in a significant reduction in symptoms with no differences among the various groups. Conclusions Our study demonstrates that montelukast therapy appears to be equally effective as ICS therapy and that the addition of the nutraceutical Leucodif does not appear to improve the treatment outcome. However, in our opinion our study was strongly influenced and biased by the lockdown due to the COVID-19 pandemic, which inherently resulted in reduced exposure to the viruses that commonly cause respiratory infections in children.

Wheezing is one of the most common respiratory symptoms in childhood especially in infants. In recent years, the incidence of recurrent wheezing is on the rise worldwide. To investigate the lower airway microbiota in patients with recurrent wheezing and provide insights into clinical diagnosis and treatment.

This study initially enrolled 45 hospitalised children with recurrent wheezing symptoms awaiting complete fiberoptic bronchoscopy. Of these, 13 children with tracheobronchomalacia were excluded. The final population included 32 participants (group A). The control group comprised 23 children who inhaled a foreign body and were admitted to the hospital for fiberoptic bronchoscopy within 24 hours (group B). Deoxyribonucleic acid (DNA) was extracted from the bronchoalveolar lavage fluid (BALF) and amplified for the 16S ribosomal Ribonucleic Acid (rRNA) gene, and sequencing of the microbiome was performed using the Illumina Nova Seq 6000 system.

There were significant differences in the gestational duration (P=0.0458), mode of delivery (P=0.0261), and allergy status (P=0.0000) between groups A and B, but they had similar richness (P=0.8574). There was also a marked difference in the diversity of flora composition between the two groups (P=0.0095). The three most common phyla of microbiota in the two groups were Proteobacteria, Firmicutes, and Bacteroidetes. Species with notably different phyla included Proteobacteria, Bacteroidota, Fusobacteriota, and Acidobacteriota. There was a significant enrichment in the of Proteobacteria and lower levels of Bacteroidota, Fusobacteriota, and Acidobacteriota in group A compared to that in group B.

Significant changes occur in the lower airway microbiota during recurrent wheezing in children. The discovery of beneficial airway bacteria may facilitate the prevention and treatment of recurrent wheezing or asthma in children.

The potential influence of asthma control in early life on long-term outcomes in childhood remains largely unknown.

To examine whether asthma control trajectories in the 2 years after diagnosis in preschoolers are associated with long-term unsatisfactory asthma control.

We conducted a multicenter population-based retrospective cohort study, including four Canadian provincial birth cohorts derived from administrative databases. We included preschoolers (aged <5 years) with a diagnosis of asthma, defined as having one hospitalization or two physician visits for asthma within 2 years. Asthma control trajectories, ascertained over four 6-month periods after diagnosis using a validated index, were classified as controlled throughout, improving control, fluctuating control, worsening control, and out of control throughout. Long-term unsatisfactory control was defined as four or more short-acting β₂-agonist average doses per week or an exacerbation, measured within 6 months before index ages 6, 8, 10, 12, 14, and 16 years. Average risk ratios for long-term unsatisfactory control across all index ages were estimated using a robust Poisson model by province and meta-analyzed with a random effects model.

In 50,188 preschoolers with asthma, the pooled average risk of having unsatisfactory control at any index age was 42% (95% confidence interval, 34.6-49.4). Compared with children who were controlled throughout, incrementally higher average risk ratios (95% confidence interval) of long-term unsatisfactory control were observed in each trajectory: improving control, 1.38 (1.28-1.49); fluctuating control, 1.54 (1.40-1.68); worsening control, 1.70 (1.55-1.86) and out of control throughout, 2.00 (1.80-2.21).

Suboptimal asthma control trajectories shortly after a preschool diagnosis were associated with long-term unsatisfactory asthma control. Early control trajectories appear to be promising for predicting the risk for long-term adverse outcomes.

Previous randomised controlled trials (RCTs) suggest antibiotics for treating episodes of asthma-like symptoms in preschool children. Further, high-dose vitamin D supplementation has been shown to reduce the rate of asthma exacerbations among adults with asthma, while RCTs in preschool children are lacking. The aims of this combined RCT are to evaluate treatment effect of azithromycin on episode duration and the preventive effect of high-dose vitamin D supplementation on subsequent episodes of asthma-like symptoms among hospitalised preschoolers.

Eligible participants, 1-5 years old children with a history of recurrent asthma-like symptoms hospitalised due to an acute episode, will be randomly allocated 1:1 to azithromycin (10 mg/kg/day) or placebo for 3 days (n=250). Further, independent of the azithromycin intervention participants will be randomly allocated 1:1 to high-dose vitamin D (2000 IU/day+ standard dose 400 IU/day) or standard dose (400 IU/day) for 1 year (n=320). Participants are monitored with electronic diaries for asthma-like symptoms, asthma medication, adverse events and sick-leave. The primary outcome for the azithromycin intervention is duration of asthma-like symptoms after treatment. Secondary outcomes include duration of hospitalisation and antiasthmatic treatment. The primary outcome for the vitamin D intervention is the number of exacerbations during the treatment period. Secondary outcomes include time to first exacerbation, symptom burden, asthma medication and safety.

The RCTs are approved by the Danish local ethical committee and conducted in accordance with the guiding principles of the Declaration of Helsinki. The Danish Medicines Agency has approved the azithromycin RCT, which is monitored by the local Unit for Good Clinical Practice. The vitamin D RCT has been reviewed and is not considered a medical intervention. Results will be published in peer-reviewed journals and presented at international conferences.

NCT05028153, NCT05043116.

Wheezing diseases are one of the major chronic respiratory diseases in children. To explore the effects of meteorological and environmental factors on the prevalence of children wheezing diseases, clinical data of children hospitalized with wheezing diseases in Suzhou, China from 2013 to 2017 were collected. Meteorological and environmental factors from 2013 to 2017 were obtained from the local Meteorological Bureau and Environmental Protection Bureau. Relationships between wheezing diseases and meteorological and environmental factors were evaluated using Pearson's correlation and multivariate regression analysis. An autoregressive integrated moving average (ARIMA) model was used to estimate the effects of meteorological and environmental variables on children wheezing diseases. Children wheezing diseases were frequently presented in infants less than 12 months old (1897/2655, 58.28%), and the hospitalization rate was highest in winter (1024/3255, 31.46%). In pathogen-positive specimens, the top three pathogens were respiratory syncytial virus (21.35%), human rhinovirus (16.28%) and mycoplasma pneumoniae (10.47%). The seasonality of wheezing children number showed a distinctive winter peak. Children wheezing diseases were negatively correlated with average temperature (P < 0.001, r =  - 0.598). The ARIMA (1,0,0)(0,0,0)₁₂ model could be used to predict temperature changes associated wheezing diseases. Meteorological and environmental factors were associated with the number of hospitalized children with wheezing diseases and can be used as early warning indicators for the occurrence of wheezing diseases and prevalence of virus.

The risk factors determining short- and long-term morbidity following acute respiratory infection (ARI) due to respiratory syncytial virus (RSV) in infancy remain poorly understood.

Our aim was to examine the associations of the upper respiratory tract (URT) microbiome during RSV ARI in infancy with the acute local immune response and short- and long-term clinical outcomes.

We characterized the URT microbiome by 16S ribosomal RNA sequencing and assessed the acute local immune response by measuring 53 immune mediators with high-throughput immunoassays in 357 RSV-infected infants. Our short- and long-term clinical outcomes included several markers of disease severity and the number of wheezing episodes in the fourth year of life, respectively.

We found several specific URT bacterial-immune mediator associations. In addition, the Shannon ⍺-diversity index of the URT microbiome was associated with a higher respiratory severity score (β =.50 [95% CI = 0.13-0.86]), greater odds of a lower ARI (odds ratio = 1.63 [95% CI = 1.10-2.43]), and higher number of wheezing episodes in the fourth year of life (β = 0.89 [95% CI = 0.37-1.40]). The Jaccard β-diversity index of the URT microbiome differed by level of care required (P = .04). Furthermore, we found an interaction between the Shannon ⍺-diversity index of the URT microbiome and the first principal component of the acute local immune response on the respiratory severity score (P = .048).

The URT microbiome during RSV ARI in infancy is associated with the acute local immune response, disease severity, and number of wheezing episodes in the fourth year of life. Our results also suggest complex URT bacterial-immune interactions that can affect the severity of the RSV ARI.

Clinical diagnoses of asthma and reactive airway disease (RAD) in young children are subjective. We examined how often children were diagnosed with asthma versus RAD, and whether preventive care and 2-year clinical outcomes differed based on initial diagnosis.

We conducted a retrospective cohort analysis of children (2-7 years) from a university-based general pediatrics practice who had been diagnosed with RAD or asthma. We performed adjusted comparisons between groups for time until subsequent asthma-related care. We also compared delivery of asthma-related healthcare services, corticosteroid and controller prescriptions, and action plans within 2 years of index diagnosis, using bivariate and regression analyses.

Four hundred three children were included (64% male, 67% Black, 25% Hispanic). RAD was diagnosed in 62% of index visits, and was more likely than asthma to be diagnosed in emergency settings. In the full sample, the time between index visit and subsequent asthma care did not differ between groups, after adjustment for index location. For subjects with complete 24-month follow-up (N = 300), no between-group differences were found in adjusted analyses. Most children with RAD received action plans and controller medications only after a subsequent asthma diagnosis, on average, 9 months after their index visit.

RAD diagnoses were linked to delayed delivery of preventive care measures, but within 2 years of initial diagnosis, clinical outcomes for those diagnosed with RAD and asthma did not differ. To facilitate clear communication and timely treatment, a prompt diagnosis of asthma, rather than RAD, should be considered for children with asthma symptoms.

The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50->80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool-aged children with LCI and determine its utility in predicting persistent wheeze.

LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF₆  multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4 symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5 years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW).

At age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z-score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p < .01), IS (mean (SD): -0.14 (0.59), p < .01), and NCS (mean (SD): -0.08 (1.06), p < .01). LCI z-score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87).

LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.

This study aimed to elicit pediatric emergency physician's treatment choices for preschool-aged children with wheeze, determine the characteristics of the presenting child that influence treatment choices, and determine whether there is clinical equipoise by eliciting physician willingness to enroll these children in a placebo-controlled trial of corticosteroids.

Discrete choice experiments varying the characteristics of the presenting child were designed to elicit Canadian emergency physician's treatment choices, both in the emergency department (ED) and at discharge, for young children presenting with wheeze and their willingness to enroll in a randomized controlled trial (RCT).

Most physicians chose to treat children with albuterol both in the ED and at discharge for all clinical scenarios. The proportion of physicians who chose to treat children with oral corticosteroids both in the ED and at discharge varied widely (from 12% to 81%) across all scenarios. Physician preference whether preschool children with wheeze should be treated with corticosteroids varied depending on the child's age, history of atopy, and previous and continuous wheeze. Between 73% and 86% of physicians were willing to enroll these children in an RCT indicating clinical equipoise.

Physician treatment choices varied widely indicating clinical equipoise as to the effectiveness of corticosteroids in this population of patients. Management choices with respect to albuterol and corticosteroids were not consistent with published national and international guidelines. In line with this finding, physician's considerable willingness to enroll these children in an RCT may suggest that they are seeking guidance on how to manage these patients.

Gastroesophageal reflux disease occurs when gastric contents flow back into the esophagus and produce symptoms. Recurrent wheezing affects the quality of life for the patient and family. The association of gastroesophageal reflux with recurrent wheezing is suggested by different studies. The purpose of this study was to explore this relationship and to evaluate the outcome after appropriate treatment.A retrospective study on 85 children with recurrent wheezing, admitted in a pediatric gastroenterology regional center in Romania was performed. 24-hour continuous esophageal pH monitoring was used to evaluate the presence of gastroesophageal reflux and the results were interpreted using the Boix Ochoa score. All patients with positive score received treatment with proton pump inhibitors and they were evaluated again after 2 months.Gastroesophageal reflux was present in 71 children (83.5%), while 14 (16.5%) had a negative score, with a statistic significance (χ2 = 6.88, P = .0086, 95% confidence interval). After 2 months treatment with proton pump inhibitors, the Boix Ochoa score was still positive in 15 patients (21.13%).Recurrent wheezing is a solid reason for evaluating the presence of gastroesophageal reflux by 24-hour continuous esophageal pH-metry. Adequate treatment of gastroesophageal reflux solves also the recurrent wheezing in the majority of patients.

This study investigated the prevalence of wheezing, asthma, and eczema among Australian children using longitudinal data from birth to 15 years of age. This study also examined the association between maternal health status during pregnancy and their offspring's respiratory and allergic morbidities using sex-segregated data.

This study used data from the Longitudinal Study of Australian Children (LSAC) where approximately 5000 children of a birth cohort across Australia were surveyed in 2004. These children were followed biennially in eight waves up to their age of 15 years until 2018. The status of the children's wheezing, asthma, and eczema were reported by the mothers upon doctors' diagnosis (for asthma) or self-assessment (for wheezing or eczema). Binomial logistic regression models were used to analyse associations between maternal health during pregnancy and their children's health outcomes.

Asthma prevalence among 0-1-year aged children was 11.7%, increased to 15.4% when the children were 10-11 years old, and then decreased to 13.6% when they were 14-15 years old. Wheezing and eczema were most prevalent when the children were 2-3 years old (26.0 and 17.8% respectively) and were least prevalent when the children were 14-15 years old (7.3 and 9.5% respectively). Maternal asthma, smoking during pregnancy, and pre-pregnancy obesity were significantly associated with an increased risk of wheezing and asthma in Australian children. Childhood eczema was associated only with maternal asthma. These associations were stronger among male children up to age 10-11 and during adolescence (12-15 years of age), female children were more prone to wheezing, asthma, and eczema.

This is a comprehensive longitudinal study of Australian children (0-15 years of age) to assess the prevalence (with sex-specific differences) of wheezing, asthma and eczema as well as the association between these respiratory and allergic morbidities and maternal health during pregnancy. The study findings suggest that careful medical and obstetric monitoring, improved specific age-sex wise risk factor prevention for children and health promotion for pregnant women would help protect child health.