Although studies show that maternal smoking during pregnancy increases the risks of respiratory outcomes in childhood, evidence concerning the effects of household environmental tobacco smoke (ETS) ...exposure remains inconsistent.
We conducted a population-based study comprised of 5,019 seventh and eighth-grade children in 14 Taiwanese communities. Questionnaire responses by parents were used to ascertain children's exposure and disease status. Logistic regression models were fitted to estimate the effects of ETS exposures on the prevalence of asthma, wheeze, and bronchitic symptoms.
The lifetime prevalence of wheeze was 11.6% and physician-diagnosed asthma was 7.5% in our population. After adjustment for potential confounders, in utero exposure showed the strongest effect on all respiratory outcomes. Current household ETS exposure was significantly associated with increased prevalence of active asthma, ever wheeze, wheeze with nighttime awakening, and bronchitis. Maternal smoking was associated with the increased prevalence of a wide range of wheeze subcategories, serious asthma, and chronic cough, but paternal smoking had no significant effects. Although maternal smoking alone and paternal smoking alone were not independently associated with respiratory outcomes, joint exposure appeared to increase the effects. Furthermore, joint exposure to parental smoking showed a significant effect on early-onset asthma (OR, 2.01; 95% CI, 1.00-4.02), but did not show a significant effect on late-onset asthma (OR, 1.17; 95% CI, 0.36-3.87).
We concluded that prenatal and household ETS exposure had significant adverse effects on respiratory health in Taiwanese children.
Obesity and early puberty have been reported to be mutually causative. We investigated the causal relationship between adiposity and early puberty by performing bidirectional Mendelian randomization ...(MR) and longitudinal data analyses.
We used information from the Taiwan Children Health Study (3109 adolescents aged 11–12 years) with 17 body mass index (BMI)- and 10 puberty-related single-nucleotide polymorphisms (SNPs) to produce genetic instrumental variables (IVs). The two-stage least squares (2SLS) method, MR sensitivity analysis, and survival analysis were used to explore and confirm causality.
Regression estimates from IVs revealed that significantly increased association of BMI with early puberty was noted (coefficients: 0.13, 0.10, and 0.09; 95% CI: 0.07–0.19, 0.02–0.19, and 0.02–0.16 for all participants, male adolescents, and female adolescents, respectively). Genetic IVs for puberty were not associated with BMI. MR sensitivity and two-sample MR analyses produced similar results. Longitudinal analysis results revealed that prepubertal overweight and obesity could predict early onset of puberty. However, after excluding children with a history of overweight and obesity at the age of 7–12 years, early puberty was not found to trigger new-onset of overweight and obesity at the age of 18 years in either sex.
Higher adiposity may lead to early puberty. However, the causal effects of early puberty on adiposity accumulation were not supported by our data. Targeted interventions to reduce childhood obesity are strongly recommended to prevent obesity-related comorbidities, as well as early puberty onset.
•Table of Contents Summary: Higher adiposity may lead to early puberty. However, we did not support the causality from early puberty to future adiposity.•What's known on this subject: Studies surveying the causal direction from early puberty to later onset of obesity have been highly heterogeneous.•What this study adds: Using MR analysis and a longitudinal study, we confirmed the causal direction from adiposity to early puberty in both sexes.
Background
Studies on early puberty and incident asthma have reported inconsistent results and are mainly performed in females. In this longitudinal study, we investigated the causal relationship ...between pubertal maturation and asthma through Mendelian randomization (MR) and explored the joint effect of overweightness and early pubertal maturation on asthma.
Methods
We used data from the Taiwan Children Health Study with longitudinal follow‐ups of 2991 children aged 11‐17 years. Six puberty‐related single‐nucleotide polymorphisms (combined into a weighted allelic score) were used to yield genetic instrumental variables for early puberty. Early pubertal maturation was defined as reaching a certain pubertal stage earlier than the median age for that stage. Incident asthma cases were calculated by excluding children with a history of asthma prior to that age.
Results
The results of MR analysis revealed that early pubertal maturation was associated with active asthma (OR = 1.18; 95% CI: 1.08‐1.28); this effect was significant in male children. Early pubertal maturation significantly increased the risk of incident asthma outcomes at 12 and 17 years of age in both sexes (hazard ratio = 2.15; 95% CI: 1.21‐3.84). Taking non‐overweight and non–early puberty children as the reference group, we observed a synergistic effect of overweightness and early pubertal maturation on asthma risk (OR = 1.08; 95% CI: 1.04‐1.11) in children of both sexes.
Conclusions
Early screening and intervention for obesity are recommended to prevent future early pubertal onset and asthma occurrence.
Through Mendelian randomization analysis, we discovered that early pubertal maturation led to asthma in 2991 children from Taiwan Children Health Study. Early pubertal maturation significantly increased the risk of incident asthma outcomes at 12 and 17 years of age in both sexes. Childhood overweight and early pubertal maturation exerted synergistic effect on asthma risk. Colour figure can be viewed at wileyonlinelibrary.com
Background
We tested the hypothesis that multiple obesity‐related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep‐disorder breathing (SDB), and sleep quality) are ...associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively.
Methods
In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross‐sectional logistic regression, one‐sample MR, summary‐level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway.
Results
In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per inter‐quartile range (IQR) increase observed for sleep quality (odds ratio OR = 1.42; 95% confidence interval CI: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00–1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio HR = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17).
Conclusion
Among the examined factors, the most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children's sleep quality and preventing obesity comorbidities such as SDB.
Obesity and asthma are common chronic diseases and have been reported to be mutually causative. We investigated the causal direction of the relationship between adiposity and asthma using genetic ...markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis.
We used data from the Taiwan Children Health Study with 24 body mass index (BMI)-single-nucleotide polymorphisms (SNPs, combined into a weighted allelic score) and 16 asthma-SNPs (combined into two weighted allelic scores, separately for asthma inflammatory and antioxidative genes) to yield genetic IVs for adiposity and asthma, respectively.
The weighted allele score for BMI was strongly associated with adiposity (p = 2 × 10
) and active asthma (p = 0.03). The two-stage least square regression risk ratio (RR) for the effect of BMI on asthma was 1.04 (95% confidence interval: 1.00-1.07, p = 0.03). Although the weighted asthma genetic scores were significantly associated with asthma (p = 8.4 × 10
), no association was seen for genetically instrumented asthma with BMI using MR. Central obesity was the most accurate predictor of asthma. Adiposity showed higher causal effects on asthma in boys and children with non-atopic asthma. Sensitivity analysis for MR revealed no directional genetic pleiotropy effects. The causal effect RRs of BMI on asthma were 1.04, 1.08, and 1.03 for inverse-variance weighted, MR-Egger regression (slope), and weighted median methods, respectively, all in accordance with the MR estimates.
High adiposity may lead to asthma, whereas the effects of asthma on adiposity accumulation are likely to be small.
Mediators linking obesity to childhood asthma Chen, Yang‐Ching; Huang, Yen‐Tsung; Pan, Wen‐Harn ...
Pediatric allergy and immunology,
October 2022, 2022-10-00, 20221001, Letnik:
33, Številka:
10
Journal Article
Recenzirano
Background
Obesity and asthma are highly associated, but the mechanisms underlying the association remain unknown. We examined five mediators linking obesity with childhood asthma: (1) pulmonary ...function impairment, (2) airway inflammation, (3) physical fitness, (4) sleep‐disordered breathing (SDB), and (5) early puberty.
Methods
A Mendelian randomization (MR) study with mediation analysis of data obtained from 5965 children as part of the Taiwan Children Health Study. Observational analysis, MR two‐stage least‐squares method, and MR sensitivity analysis were carried out to investigate each causal pathway. Prospective cohort analyses were used to strengthen the findings.
Results
The increased asthma risk associated with obesity was found to be mostly mediated through impaired pulmonary function, low physical fitness, and early puberty. In the MR analysis, body mass index was negatively associated with FEV1/FVC and physical fitness index (β = −2.17 and −0.71; 95% CI, −3.92 to −0.42 and −1.30 to −0.13, respectively) and positively associated with early puberty (OR, 1.09; 95% CI, 1.02–1.17). High FEV1/FVC and physical fitness index reduced asthma risk (OR, 0.98 and 0.93; 95% CI, 0.97–0.99 and 0.88–0.98, respectively), whereas SDB and early puberty increased the risk of asthma (OR, 1.03 and 1.22; 95% CI, 1.01–1.05 and 1.05–1.42, respectively). Temporal causality was strengthened in prospective cohort analyses. The three main mediators were low physical fitness, impaired pulmonary function, and early puberty, with mediation proportions of 73.76%, 61.63%, and 27.66%, respectively.
Conclusions
Interventions promoting physical fitness and pulmonary function might effectively reduce obesity‐induced asthma risk.
The association between neutrophil extracellular traps (NETs) and response to inhaled corticosteroids (ICS) in asthma is unclear. To better understand this relationship, we analyzed the blood ...transcriptomes from children with controlled and uncontrolled asthma in the Taiwanese Consortium of Childhood Asthma Study using weighted gene coexpression network analysis and pathway enrichment methods. We identified 298 uncontrolled asthma-specific differentially expressed genes and one gene module associated with neutrophil-mediated immunity, highlighting a potential role for neutrophils in uncontrolled asthma. We also found that NET abundance was associated with nonresponse to ICS in patients. In a neutrophilic airway inflammation murine model, steroid treatment could not suppress neutrophilic inflammation and airway hyperreactivity. However, NET disruption with deoxyribonuclease I (DNase I) efficiently inhibited airway hyperreactivity and inflammation. Using neutrophil-specific transcriptomic profiles, we found that
was associated with ICS nonresponse in asthma, which was validated in human and murine lung tissue.
expression was also negatively correlated with pulmonary function change after ICS treatment. In summary, steroids fail to suppress neutrophilic airway inflammation, highlighting the potential need to use alternative therapies such as leukotriene receptor antagonists or DNase I that target the neutrophil-associated phenotype. Furthermore, these results highlight CCL4L2 as a potential therapeutic target for individuals with asthma refractory to ICS.
Summary
Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic ...search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and their ratio (FEV1/FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random‐effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1/FVC ratio (mean difference MD = −3.61%; 95% confidence interval CI = −4.58%, −2.64%) and a higher percent‐predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood.
Background
Adiposity is a key risk factor for asthma and impaired pulmonary function.
Objectives
We aimed to identify the critical period of life course adiposity for asthma in childhood and young ...adulthood, and to determine whether associations of adiposity and asthma vary across ages.
Methods
Birth weight and body mass index (BMI) from birth to 17 years of age were assessed in 6130 children from the Taiwan Children Health Study. Logistic regression for asthma outcome and linear regression for pulmonary function outcome were used to investigate associations of adiposity with asthma. Seventeen BMI‐related single‐nucleotide polymorphisms were used to obtain genetic instrumental variables for adiposity to perform Mendelian randomization (MR) analysis.
Results
Using both regression model and MR analyses, we confirmed that the critical period of adiposity in predicting childhood asthma would be before age 6 years. Further, we discovered that the sensitive period of adiposity gain related to young adulthood asthma was the prepubertal stage. Risks of asthma at age 17 per unit increase in z‐score of the BMI increased from 0.94 (95% CI: 0.79–1.11) at birth, and became greater than 1.00 between age 11 and 12, then increased to 1.08 (95% CI: 0.95–1.22) at age 17. The associations of life course BMI with asthma and pulmonary function impairment at age 12 and with asthma at age 17 increased with age. The aforementioned association was most prominent among central obesity indicators.
Conclusions
To prevent asthma in childhood and young adulthood, we should aim at promoting healthy growth at the toddler period and prepubertal stage.
PDF
