17q21 Variants Disturb Mucosal Host Defense in Childhood Asthma.

Rationale: The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes.Objectives: To identify biological targets underlying the escalated viral susceptibility associated with the clinical phenotype mediated by the 17q21 locus.Methods: Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 with wheezing at preschool age, 104 asthmatic) within the ALLIANCE (All-Age-Asthma) cohort, with a median age of 10.0 (range, 1.0-20.0) years, was conducted to explore the impact of their 17q21 genotype (SNP rs72163891). Concurrently, nasal secretions from the same patients and visits were collected, and high-sensitivity mesoscale technology was employed to measure IFN protein levels.Measurements and Main Results: This study revealed that the 17q21 risk allele induces a genotype- and asthma/wheeze phenotype-dependent enhancement of mucosal GSDMB expression as the only relevant 17q21-encoded gene in children with preschool wheeze. Increased GSDMB expression correlated with the activation of a type-1 proinflammatory, cell-lytic immune, and natural killer signature, encompassing key genes linked to an IFN type-2-signature (IFNG, CXCL9, CXCL10, KLRC1, CD8A, GZMA). Conversely, there was a reduction in IFN type 1 and type 3 expression signatures at the mRNA and protein levels.Conclusions: This study demonstrates a novel disease-driving mechanism induced by the 17q21 risk allele. Increased mucosal GSDMB expression is associated with a cell-lytic immune response coupled with compromised airway immunocompetence. These findings suggest that GSDMB-related airway cell death and perturbations in the mucosal IFN signature account for the increased vulnerability of 17q21 risk allele carriers to respiratory viral infections during early life, opening new options for future biological interventions.The All-Age-Asthma (ALLIANCE) cohort is registered at www.clinicaltrials.gov (pediatric arm, NCT02496468).

A novel syndrome of silent rhinovirus-associated bronchoalveolitis in children with recurrent wheeze.

BACKGROUND: Rhinovirus (RV) infections trigger wheeze episodes in children. Thus, understanding of the lung inflammatory response to RV in children with wheeze is important. OBJECTIVES: This study sought to examine the associations of RV on bronchoalveolar lavage (BAL) granulocyte patterns and biomarkers of inflammation with age in children with treatment-refractory, recurrent wheeze (n = 616). METHODS: Children underwent BAL to examine viral nucleic acid sequences, bacterial cultures, granulocyte counts, and phlebotomy for both general and type-2 inflammatory markers. RESULTS: Despite the absence of cold symptoms, RV was the most common pathogen detected (30%), and when present, was accompanied by BAL granulocytosis in 75% of children. Compared to children with no BAL pathogens (n = 341), those with RV alone (n = 127) had greater (P < .05) isolated neutrophilia (43% vs 16%), mixed eosinophils and neutrophils (26% vs 11%), and less pauci-granulocytic (27% vs 61%) BAL. Children with RV alone furthermore had biomarkers of active infection with higher total blood neutrophils and serum C-reactive protein, but no differences in blood eosinophils or total IgE. With advancing age, the log odds of BAL RV alone were lower, 0.82 (5th-95th percentile CI: 0.76-0.88; P < .001), but higher, 1.58 (5th-95th percentile CI: 1.01-2.51; P = .04), with high-dose daily corticosteroid treatment. CONCLUSIONS: Children with severe recurrent wheeze often (22%) have a silent syndrome of lung RV infection with granulocytic bronchoalveolitis and elevated systemic markers of inflammation. The syndrome is less prevalent by school age and is not informed by markers of type-2 inflammation. The investigators speculate that dysregulated mucosal innate antiviral immunity is a responsible mechanism.

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

BACKGROUND: 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. OBJECTIVES: This study addresses the knowledge gap by investigating the transition from preschool wheeze to asthma using multiomic profiling. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impaired interferon response in plasmacytoid dendritic cells from children with persistent wheeze.

BACKGROUND: Impaired interferon response and allergic sensitization may contribute to virus-induced wheeze and asthma development in young children. Plasmacytoid dendritic cells (pDCs) play a key role in antiviral immunity as critical producers of type I interferons. pDCs also express the high-affinity IgE receptor through which type I interferon production may be negatively regulated. Whether antiviral function of pDCs is associated with recurrent episodes of wheeze in young children is not well understood. OBJECTIVE: We sought to evaluate the phenotype and function of circulating pDCs in children with a longitudinally defined wheezing phenotype. METHODS: We performed multiparameter flow cytometry on PBMCs from 38 children presenting to the emergency department with an acute episode of respiratory wheeze and 19 controls. RNA sequencing on isolated pDCs from the same individuals was also performed. For each subject, their longitudinal exacerbation phenotype was determined using the Western Australia public hospital database. RESULTS: We observed a significant depletion of circulating pDCs in young children with a persistent phenotype of wheeze. The same individuals also displayed upregulation of the FcεRI on their pDCs. Based on transcriptomic analysis, pDCs from these individuals did not mount a robust systemic antiviral response as observed in children who displayed a nonrecurrent wheezing phenotype. CONCLUSIONS: Our data suggest that circulating pDC phenotype and function are altered in young children with a persistent longitudinal exacerbation phenotype. Expression of high-affinity IgE receptor is increased and their function as major interferon producers is impaired during acute exacerbations of wheeze.

Role of epithelial barrier function in inducing type 2 immunity following early-life viral infection.

BACKGROUND: Preschool wheeze attacks triggered by recurrent viral infections, including respiratory syncytial virus (RSV), are associated with an increased risk of childhood asthma. However, mechanisms that lead to asthma following early-life viral wheezing remain uncertain. METHODS: To investigate a causal relationship between early-life RSV infections and onset of type 2 immunity, we developed a neonatal murine model of recurrent RSV infection, in vivo and in silico, and evaluated the dynamical changes of altered airway barrier function and downstream immune responses, including eosinophilia, mucus secretion and type 2 immunity. RESULTS: RSV infection of neonatal BALB/c mice at 5 and 15 days of age induced robust airway eosinophilia, increased pulmonary CD4+ IL-13+ and CD4+ IL-5+ cells, elevated levels of IL-13 and IL-5 and increased airway mucus at 20 days of age. Increased bronchoalveolar lavage albumin levels, suggesting epithelial barrier damage, were present and persisted following the second RSV infection. Computational in silico simulations demonstrated that recurrent RSV infection resulted in severe damage of the airway barrier (epithelium), triggering the onset of type 2 immunity. The in silico results also demonstrated that recurrent infection is not always necessary for the development of type 2 immunity, which could also be triggered with single infection of high viral load or when the epithelial barrier repair is compromised. CONCLUSIONS: The neonatal murine model demonstrated that recurrent RSV infection in early life alters airway barrier function and promotes type 2 immunity. A causal relationship between airway barrier function and type 2 immunity was suggested using in silico model simulations.

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.

Periconceptional maternal diet quality and offspring wheeze trajectories: Japan Environment and Children's Study.

BACKGROUND: The role of prenatal diet on childhood wheezing and subsequent risk of asthma is inconclusive, which may be partly due to the heterogeneity in wheezing phenotypes. We aimed to identify wheeze trajectories in early childhood and to examine their associations with periconceptional maternal diet quality. METHODS: Data from 70,530 mother-child pairs of liveborn singletons from the Japan Environment and Children's Study were analysed. Wheezing was reported by caregivers using a modified International Study of Asthma and Allergies in Childhood questionnaire yearly from 1 to 4 years of age, from which trajectories were derived using group-based trajectory modelling. Maternal diet in the year preceding the first trimester of pregnancy was assessed using a validated food frequency questionnaire; overall diet quality was determined using the balanced diet score based on the Japanese Food Guide Spinning Top. Bayesian inference of multinomial logistic regression models was performed to examine the association between maternal diet quality and wheeze trajectory in early childhood. RESULTS: We identified four wheeze trajectories: 'never/infrequent' (69.1%; reference group), 'early-childhood onset' (6.2%), 'transient early' (16.5%) and 'persistent' (8.2%). After adjustment for confounders, a higher quartile of maternal balanced diet score was associated with a lower risk of belonging to the 'transient early' and 'persistent' wheeze trajectories compared with the 'never/infrequent' wheeze trajectory by 10% of both. Maternal balanced diet score was not associated with belonging to the 'early-childhood onset' wheeze trajectory. CONCLUSION: Improving maternal diet quality prior to conception may reduce certain wheeze phenotypes in early childhood.

Nine-Year Trend in the Prevalence of Allergic Diseases and Their Associated Factors in Young Adults.

INTRODUCTION: Notably, few studies have evaluated the recent changes in the prevalence of allergic diseases in young adults. Studies examining the risk of allergy in two populations with similar social backgrounds, other than the region in which they live, are rare. METHODS: First-year students from Hokkaido University were enrolled in this study between 2011 and 2019. A questionnaire survey was conducted to determine the annual prevalence of current wheeze, seasonal allergic rhinitis (SAR), and perennial allergic rhinitis (PAR) in nonsmoking young adults. Trends in the presence of these disease conditions were evaluated based on their hometowns (Hokkaido and outside Hokkaido separately) due to the low prevalence of cedar pollen allergies in Hokkaido. The association between these disease conditions and body mass index (BMI) was also assessed. RESULTS: The prevalence of current wheeze and PAR food allergies did not change in both regions. SAR showed a significantly increasing trend; however, the prevalence of SAR was higher among those whose place of origin was not Hokkaido. Current wheeze was positively associated with obesity (p < 0.05), whereas the high prevalence of SAR was not associated with body weight. In contrast, a lean body type was significantly associated with a higher prevalence of PAR (p < 0.05). DISCUSSION/CONCLUSION: The prevalence of current wheeze was stable and that of PAR has decreased over the past 9 years. However, the prevalence of SAR in Hokkaido has been increasing in Japanese young adults. A differential association between current wheeze and BMI was observed when comparing PAR and SAR.

Viral and non-viral episodes of wheezing in early life and the development of asthma and respiratory phenotypes among urban children.

BACKGROUND: Viral wheezing is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early-life wheezing illnesses relates to childhood respiratory and asthma phenotypes. METHODS: Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years. We identified wheezing illnesses and the corresponding viral etiology (PCR testing of nasal mucus) during the first 3 years of life. Six phenotypes of respiratory health were identified at 10 years of age based on trajectories of wheezing, allergic sensitization, and lung function. We compared the etiology of early wheezing illnesses to these wheezing respiratory phenotypes and the development of asthma. RESULTS: In the first 3 years of life, at least one virus was detected in 324 (67%) of the 483 wheezing episodes documented in the study cohort. Using hierarchical partitioning we found that non-viral wheezing episodes accounted for the greatest variance in asthma diagnosed at both 7 and 10 years of age (8.0% and 5.8% respectively). Rhinovirus wheezing illnesses explained the most variance in respiratory phenotype outcome followed by non-viral wheezing episodes (4.9% and 3.9% respectively) at 10 years of age. CONCLUSION AND RELEVANCE: Within this high-risk urban-residing cohort in early life, non-viral wheezing episodes were frequently identified and associated with asthma development. Though rhinovirus wheezing illnesses had the greatest association with phenotype outcome, the specific etiology of wheezing episodes in early life provided limited information about subsequent wheezing phenotypes.

Preventing progression of preschool wheezing to asthma: Opportunities for intervention.

Recurrent wheezing in preschool children is heterogeneous and results from numerous genetic and environmental risk factors, which result in the same final clinical manifestation of acute episodes of wheezing but have distinct underlying mechanisms. Effective disease-modifying approaches, therefore, need to target the pathways driving the symptoms. We have good evidence to show that targeting airway eosinophilia alone in early-life preschool wheezing and using inhaled corticosteroids is not disease-modifying. Although airway remodelling develops early in preschool wheezing, the challenge is identifying suitable treatments for structural airway changes. There is increasing evidence for the role of lower airway bacterial infection contributing to wheeze episodes, but clinical trials investigating the impact of targeted antibiotic treatment on disease modification are needed. There is also increasing data supporting an association between lower airway neutrophilia and wheezing in a subgroup of preschool children, but direct causation and the role of neutrophil function remain unknown. Finally, there is encouraging preliminary data for the role of inactivated mixed bacterial lysates in children with non-allergic, infection-associated wheeze episodes, but the impact on longer-term outcomes and their mechanism of action is unknown. This review outlines a range of potential novel targets and approaches that may enable secondary prevention of asthma from preschool wheezing. In parallel, the potential for harm when interventions are introduced indiscriminately is highlighted. Some of the challenges that need to be addressed, including trial designs allowing tailored interventions, the need for non-invasive biomarkers for targeted interventions, and ensuring extended and long-term follow-up after intervention, are highlighted.

Is asthma in children still increasing? 20-year prevalence trends in northern Sweden.

BACKGROUND: In the present study, we describe prevalence trends of asthma and investigate the association with asthma symptoms, use of asthma medication, and asthma severity among 8-year-old children in Norrbotten, Sweden in 1996, 2006, and 2017. METHODS: Within the Obstructive Lung Disease in Northern Sweden (OLIN) studies, three pediatric cohorts were recruited in 1996, 2006, and 2017 respectively. Identical methods were used; all children in first and second grade (median age 8 years) in three municipalities were invited to a parental questionnaire survey, completed by n = 3430 in 1996 (97% participation), n = 2585 in 2006 (96%), and n = 2785 in 2017 (91%). The questionnaire included questions about respiratory symptoms and diagnosis, treatment, and severity of asthma. RESULTS: The prevalence of wheezing was stable during the study, 10.1% in 1996; 10.8% in 2006; and 10.3% in 2017, p = .621, while physician-diagnosed asthma increased: 5.7%, 7.4%, and 12.2%, p < .001. The use of asthma medication in the last 12 months increased: 7.1%, 8.7%, and 11.5%, p < .001. Among children diagnosed with asthma, the prevalence of asthma symptoms, the impact on daily life, and severe asthma decreased, while the use of inhaled corticosteroids increased from 1996 until 2017. CONCLUSION: The prevalence of wheezing was stable among 8-year-old in this area from 1996 to 2017, while the prevalence of physician-diagnosed asthma doubled but without an increase in asthma morbidity. The increase of physician-diagnosed asthma without a coincident increase in asthma morbidity can partly be explained by more and earlier diagnosis among those with mild asthma.

Urinary eosinophil-derived neurotoxin is associated with reduced lung function in pediatric asthma.

INTRODUCTION: Eosinophil-derived neurotoxin (EDN) is a biomarker for eosinophilic activation. Urinary (u) EDN may allow non-invasive monitoring of asthma, but clinical recommendations are lacking. We assessed the potential of uEDN as a marker of disease activity in pediatric asthma. METHODS: We assessed urine samples of 371 children from the German ALLIANCE study cohort, from which we had: 169 preschool wheezers (<6 years), 80 asthmatics (≥6 years), and 122 healthy controls using the ImmunoCAP™ EDN Assay. Creatinine (Cr)-adjusted uEDN values were analyzed using correlations, association tests, (non) parametric statistics, multiple linear, and multivariable regression. RESULTS: uEDN/uCr values were higher in atopic versus non-atopic preschool-aged subjects (p = .035) and associated with the sum of allergen-specific IgE in younger (r = 0.24, p = .003), and older subjects (r = 0.23, p = .043). uEDN/uCr was marginally a good determinant for atopy (p = .078, for subjects aged <6 years, and p = .058 for subjects ≥6 years). Children with the T2-high phenotype had higher uEDN/uCr (p < .001) versus T2-low-irrespective of using uEDN/uCr or blood eosinophils in combination to allergen sIgE for disease phenotyping. uEDN/uCr significantly correlated with reduced lung function among asthmatics (FEV1 z-scores: r = -0.30, p = .007, and FEV1/FVC z-scores: r = -0.24, p = .038). Using multivariable modeling, uEDN/uCr was an independent determinant of FEV1 (p = .038), and to a lesser extent, FEV1/FVC (p = .080). CONCLUSIONS: uEDN/uCr may serve as a non-invasive biomarker for clinical features such as lung function in pediatric asthma. We highlight the utility of uEDN/uCr as a biomarker that can be easily assessed using widely available robust diagnostic immunoassays.

Maternal asthma during pregnancy and risks of allergy and asthma in progeny: A systematic review and meta-analysis.

BACKGROUND: Clinical and preclinical evidence indicate that in utero maternal asthma exposure increases progeny asthma risk. Whether maternal asthma also increases the risks of progeny allergy is unclear. OBJECTIVES: To synthesise the available evidence on the relationship between in utero exposure to maternal asthma and postnatal asthma, wheezing and allergic diseases (Prospero: CRD42020201538). SEARCH STRATEGY: We systematically searched MEDLINE [PubMed], Embase [Ovid], Web of Science, Informit Health, the Cochrane Library, CINAHL [EBSCOhost], MedNar [Deep Web Technologies], ProQuest Theses and Dissertations, Scopus [Elsevier] and Trove, to the end of 2023. SELECTION CRITERIA: Studies reporting asthma, wheeze and/or allergic disease in progeny of women with and without asthma or with asthma classified by control, exacerbation or severity. DATA COLLECTION AND ANALYSIS: Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring. MAIN RESULTS: Of 134 non-overlapping studies, 127 were included in ≥1 meta-analysis. Maternal asthma ever was associated with greater risks of asthma (65 studies, risk ratio [95% confidence interval] 1.76 [1.57-1.96]), wheeze (35 studies, 1.59 [1.52-1.66]), food allergy (5 studies, 1.32 [1.23-1.40]), allergic rhinitis (7 studies, 1.18 [1.06-1.31]) and allergic dermatitis (14 studies, 1.17 [1.11-1.23]) ever in progeny. Asthma during the pregnancy, more severe, and uncontrolled maternal asthma were each associated with greater risks of progeny asthma. CONCLUSIONS: Children of mothers with asthma are at increased risk for the development of allergic diseases. Whether improved maternal asthma control reduces risks of child allergy as well as asthma requires further investigation.

Association of respiratory virus types with clinical features in bronchiolitis: Implications for virus testing strategies. A systematic review and meta-analysis.

BACKGROUND: Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for bronchiolitis management. To establish effective management strategies, it is crucial to assess whether specific respiratory virus types are correlated with distinct examination features. METHODS: Through a systematic search of three databases, 21 studies were qualitatively analyzed, with 18 used for meta-analysis. Various outcomes like wheezing on auscultation, fever, atopic traits, and infection severity were evaluated. RESULTS: RSV-positive bronchiolitis was associated with a higher need for oxygen supplementation (OR 1.78, 95% CI 1.04-3.02) in 5 studies, while RV-positive bronchiolitis was more frequently linked to personal history of eczema (OR 0.60, 95% CI 0.41-0.88) in 6 studies. No significant differences were observed in the other outcomes examined. CONCLUSIONS: Bronchiolitis caused by RSV or RV presents with similar clinical features. Despite the associations between RSV-positive bronchiolitis and need for oxygen supplementation, and RV-positive bronchiolitis and a history of eczema, our study shows that viral etiology of bronchiolitis cannot be determined solely based on clinical presentation. Tailored management strategies, informed by accurate viral testing, seem crucial in clinical practice for enhancing patient outcomes in severe bronchiolitis.

Emergency management and asthma risk in young Medicaid-enrolled children with recurrent wheeze.

OBJECTIVES: To describe clinical characteristics of young children presenting to the emergency department (ED) for early recurrent wheeze, and determine factors associated with subsequent persistent wheeze and risk for early childhood asthma. METHODS: Retrospective cohort study of Medicaid-enrolled children 0-3 years old with an index ED visit for wheeze (e.g. bronchiolitis, reactive airway disease) from 2009 to 2013, and at least one prior documented episode of wheeze at an ED or primary care visit. The primary outcome was persistent wheeze between 4 and 6 years of age. Demographics and clinical characteristics were collected from the index ED visit. Logistic regression was used to estimate the association between potential risk factors and subsequent persistent wheeze. RESULTS: During the study period, 41,710 children presented to the ED for recurrent wheeze. Mean age was 1.3 years; 59% were male, 42% Black, and 6% Hispanic. At index ED visits, the most common diagnosis was acute bronchiolitis (40%); 77% of children received an oral corticosteroid prescription. Between 4 and 6 years of age, 11,708 (28%) children had persistent wheeze. A greater number of wheezing episodes was associated with an increased odds of ED treatment with asthma medications. Subsequent persistent wheeze was associated with male sex, Black race, atopy, prescription for bronchodilators or corticosteroids, and greater number of visits for wheeze. CONCLUSIONS: Young children with persistent wheeze are at risk for childhood asthma. Thus, identification of risk factors associated with persistent wheeze in young children with recurrent wheeze might aid in early detection of asthma and initiation of preventative therapies.

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

BACKGROUND: Most 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. METHODS: We 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. RESULTS: The 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. CONCLUSION: Preconception 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.

Respiratory conditions and health symptoms associated with air pollution amongst children aged six years and below in Melusi Informal Settlement, Tshwane Metropolitan Municipality, South Africa: a cross-sectional study.

BACKGROUND: Respiratory conditions and health symptoms associated with air pollution in children are a major public health concern, as their immune systems and lungs are not yet fully developed. This study aimed to assess self-reported respiratory conditions and health symptoms associated with air pollution sources amongst children aged six years and below in Melusi informal settlement, Tshwane Metropolitan Municipality, South Africa. METHODS: With a quantitative cross-sectional study design, parents/caregivers of children aged six years and below (n = 300) from eight Early Childhood Development Centres were invited to participate in the study. This study employed complete sampling, and data was collected using the modified International Study of Asthma and Allergies in Children. The chi-square and multiple logistic regression models were used to analyze data, with p < 0.05 in the adjusted odds ratios considered as being statistically significant. RESULTS: Three models were run to examine the predictors of wheezing in the past 12 months, dry cough, and itchy-watery eyes. The model for asthma was excluded, as only seven participants reported having asthma. Wheeze in the past 12 months was associated with participants living in the area for more than three years (OR 2.96 95%CI: 1.011-8.674). Furthermore, having a dog in the house in the past 12 months was associated with wheeze in the past 12 months (OR 5.98 95%CI: 2.107-16.967). There was an association between duration of stay in a residence and dry cough prevalence (OR 5.63 95%CI: 2.175-14.584). Trucks always or frequently passing near homes was associated with itchy-watery eyes (OR 3.27 95%CI: 1.358-7.889). 59% (59%) of participants perceived the indoor air quality in their homes to be good, while 6% perceived it as poor. In contrast, 36% of participants perceived the outdoor air quality to be good, and 19.7% perceived it as poor. CONCLUSION: The association between perceived air pollution exposure, self-reported respiratory conditions, and health symptoms amongst children is complex. Further research is required to better understand the multifaceted nature of air pollution and its impact on the health of children.

Maternal exposure to smoking and wheezing phenotypes in children: a cohort study of the Japan Environment and Children's Study.

BACKGROUND: Previous studies have shown that prenatal maternal smoking and maternal secondhand smoke exposure during pregnancy were associated with an increased risk of wheezing and asthma development. However, few studies have examined the influence of different sources of tobacco exposure in different perinatal timeframes (preconception, prenatal, and postnatal) on wheezing phenotypes in children. Using national survey data from Japan, we investigated the effects of exposure to tobacco smoke during pregnancy on wheezing phenotypes in children before the age of 3 years. METHODS: Pregnant women who lived in the 15 regional centers in the Japan Environment and Children's Study were recruited. We obtained information on prenatal and postnatal exposure to active and secondhand smoke (SHS) and wheeze development up to 3 years of age. Multiple logistic regression analysis was performed to determine the association between tobacco smoke exposure and wheezing phenotypes in children. RESULTS: We analyzed 73,057 singleton births and identified four longitudinal wheezing phenotypes: never wheezing; early transient wheezing (wheezing by age 1 year but not thereafter); late-onset wheezing (wheezing by age 2-3 years but not beforehand); and persistent wheezing. Maternal smoking during pregnancy was significantly associated with early transient and persistent wheezing in children compared with no maternal smoking [early transient wheezing: 1-10 cigarettes per day, adjusted odds ratio (aOR) 1.43, 95% confidence interval (CI) 1.23-1.66; ≥ 11 cigarettes per day, aOR 1.67, 95% CI 1.27-2.20; persistent wheezing: 1-10 cigarettes per day, aOR 1.64, 95% CI 1.37-1.97; ≥ 11 cigarettes per day, aOR 2.32, 95% CI 1.70-3.19]. Smoking cessation even before pregnancy was also significantly associated with increased risk of early transient wheezing, late-onset wheezing, and persistent wheezing in children. Moreover, maternal exposure to SHS during pregnancy was significantly associated with increased risk of early transient and persistent wheezing compared with no such exposure. CONCLUSIONS: Maternal smoking before and throughout pregnancy was associated with wheeze development in children up to 3 years of age. It appears that smoking is detrimental compared to never smoking, regardless of whether individuals quit smoking before or after becoming aware of the pregnancy.

Rhinovirus-induced wheeze was associated with asthma development in predisposed children.

AIM: This study explored whether early-life factors, such as rhinovirus-induced wheeze and allergic sensitisation, were related to asthma at 11 years of age. METHODS: We focused on 107 children aged 6-48 months, who attended the paediatric emergency department at Astrid Lindgren's Children's Hospital in Stockholm, Sweden, with acute wheeze in 2008-2012. They also attended follow-up visits at 11 years of age and were compared with 46 age-matched healthy controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with logistic regression. RESULTS: We found that 62.6% of the acute wheeze cases had asthma at 11 years of age. Rhinoviruses at inclusion were the only common airway viruses associated with an increased asthma risk (OR 2.4, 95% CI 1.02-5.6). Other increased risks were parental heredity for asthma and/or allergies (adjusted OR 3.4, 95% CI 1.1-9.9) and allergic sensitisation at 2 years of age (adjusted OR 3.0, 95% CI 1.02-8.7). The highest prevalence of asthma was when children had both rhinovirus-induced wheeze at inclusion and allergic sensitisation at 7 years of age. CONCLUSION: Our findings highlight the importance of hereditary factors and allergic sensitisation on the development of asthma and suggest that rhinoviruses are associated with asthma development in predisposed children.

Chorioamnionitis and respiratory outcomes in prematurely born children: a systematic review and meta analysis.

INTRODUCTION: To conduct a systematic review and meta-analysis of the association between chorioamnionitis and respiratory outcomes of prematurely born children. CONTENT: Pubmed, Medline and Embase were searched for relevant studies. Studies were included if they assessed prematurely born children, who had been exposed to chorioamnionitis and had either lung function testing or assessment of wheeze or asthma following NICU discharge. Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality. One reviewer extracted the data and these were checked by a second reviewer. SUMMARY: A total of 1,237 studies were identified, but only eight which included 35,000 infants, fulfilled the inclusion criteria. One study looked at both lung function results and wheeze or asthma in childhood. Four of five studies found an association between wheeze/asthma in childhood and exposure to chorioamnionitis: the overall Odds Ratio (OR) for developing wheeze/asthma in childhood was OR 1.71 (95 % CI: 1.55-1.89). Four studies looked at lung function in childhood, three of which showed no statistically significant association between chorioamnionitis exposure and altered lung function. One study found lower lung function in those exposed to chorioamnionitis and lower expiratory flows with increasing levels of chorioamnionitis (forced expiratory flow at 50 % of exhaled forced vital capacity (=FEF50) p=0.012, forced expiratory flow at 25-75 % of the forced vital capacity is exhaled (=FEF25-75) p=0.014). OUTLOOK: There was a significant association between chorioamnionitis and the development of wheeze or asthma in childhood, but overall not in impairment of lung function.