Early-life Infections, Bacteria and Childhood Asthma Development: The Generation R Study

Most likely, an important part of the origins of asthma lie in early life. In this thesis, we identified early-life exposures, specifically infections and bacteria, leading to an increased risk of adverse respiratory health in childhoo

Air pollution and childhood respiratory consultations in primary care:A systematic review

Background: Outdoor air pollution is a known risk factor for respiratory morbidity worldwide. Compared with the adult population, there are fewer studies that analyse the association between short-term exposure to air pollution and respiratory morbidity in children in primary care. Objective: To evaluate whether children in a primary care setting exposed to outdoor air pollutants during short-term intervals are at increased risk of respiratory diagnoses. Methods: A search in Medline, the Cochrane Library, Web of Science and Embase databases throughout March 2023. Percentage change or risk ratios with corresponding 95% CI for the association between air pollutants and respiratory diseases were retrieved from individual studies. Risk of bias assessment was conducted with the Newcastle-Ottawa Scale (NOS) for cohort or case-control studies and an adjusted NOS for time series studies. Results: From 1366 studies, 14 were identified as meeting the inclusion criteria. Most studies had intermediate or high quality. A meta-analysis was not conducted due to heterogeneity in exposure and health outcome. Overall, studies on short-term exposure to air pollutants (carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and particulate matter ≤10 μm (PM10)) were associated with increased childhood respiratory consultations in primary care. In general, exposure to ozone was associated with a reduction in respiratory consultations. Conclusions: The evidence suggests CO, SO2, NO2, PM10 and PM2.5 are risk factors for respiratory diseases in children in primary care in the short term. However, given the heterogeneity of the studies, interpretation of these findings must be done with caution. PROSPERO registration number: CRD42022259279.</p

Air pollution and childhood respiratory consultations in primary care:A systematic review

Background: Outdoor air pollution is a known risk factor for respiratory morbidity worldwide. Compared with the adult population, there are fewer studies that analyse the association between short-term exposure to air pollution and respiratory morbidity in children in primary care. Objective: To evaluate whether children in a primary care setting exposed to outdoor air pollutants during short-term intervals are at increased risk of respiratory diagnoses. Methods: A search in Medline, the Cochrane Library, Web of Science and Embase databases throughout March 2023. Percentage change or risk ratios with corresponding 95% CI for the association between air pollutants and respiratory diseases were retrieved from individual studies. Risk of bias assessment was conducted with the Newcastle-Ottawa Scale (NOS) for cohort or case-control studies and an adjusted NOS for time series studies. Results: From 1366 studies, 14 were identified as meeting the inclusion criteria. Most studies had intermediate or high quality. A meta-analysis was not conducted due to heterogeneity in exposure and health outcome. Overall, studies on short-term exposure to air pollutants (carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2) and particulate matter ≤10 μm (PM10)) were associated with increased childhood respiratory consultations in primary care. In general, exposure to ozone was associated with a reduction in respiratory consultations. Conclusions: The evidence suggests CO, SO2, NO2, PM10 and PM2.5 are risk factors for respiratory diseases in children in primary care in the short term. However, given the heterogeneity of the studies, interpretation of these findings must be done with caution. PROSPERO registration number: CRD42022259279.</p

Influence of maternal vomiting during early pregnancy on school-age respiratory health

BACKGROUND: Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting, might lead to a suboptimal maternal nutritional status during pregnancy and subsequently to adverse respiratory health in the offspring. The role of common vomiting symptoms on offspring's respiratory health is unclear. We examined the associations of maternal daily vomiting during early pregnancy with childhood respiratory outcomes, and potential explaining factors. METHODS: This study was embedded in a population‐based prospective cohort study from early pregnancy onwards among 4232 mothers and their children. Maternal vomiting during early pregnancy was assessed by a questionnaire. At age 10 years, information on current wheezing and ever asthma was obtained by a questionnaire, and lung function was measured by spirometry at our research center. We used multiple regression analyses to assess the associations of maternal daily vomiting during early pregnancy with childhood respiratory outcomes. RESULTS: Compared to children from mothers without daily vomiting during early pregnancy, children from mothers with daily vomiting during early pregnancy had a higher forced expiratory flow when 75% of the forced vital capacity (FVC) is exhaled (Z‐score difference [95% confidence interval, CI]: 0.13 [0.03, 0.23]), and an increased risk of current wheezing and ever asthma ([odds ratio, OR] [95% CI]: 1.75 [1.10, 2.79] and 1.61 [1.13, 2.31], respectively). These associations were fully explained by sociodemographic factors, but not sex or lifestyle‐, infectious‐, or growth‐related factors. Maternal daily vomiting during early pregnancy was not associated with forced expiratory volume in 1 s (FEV(1)), FVC, and FEV(1)/FVC. CONCLUSION: Only sociodemographic factors explain the associations of maternal daily vomiting during early pregnancy with childhood respiratory outcomes

Maternal hemoglobin and iron status in early pregnancy and risk of respiratory tract infections in childhood:A population-based prospective cohort study

Background: Maternal hemoglobin and iron status measures during pregnancy might affect the developing fetal respiratory system leading to adverse respiratory conditions. Our aim was to assess the associations of maternal hemoglobin and iron status measures during pregnancy with the risk of respiratory tract infections in children until 10 years of age. Methods:In a population-based cohort study among 5134 mother–child pairs, maternal hemoglobin and iron status including ferritin, transferrin, and transferrin saturation were measured during early pregnancy. In children, physician-attended respiratory tract infections from age 6 months until 10 years were assessed by questionnaires. Confounder-adjusted generalized estimating equation modeling was applied. Results: After taking multiple testing into account, high maternal ferritin concentrations and low maternal transferrin saturation during pregnancy were associated with an overall increased risk of upper, not lower, respiratory tract infections until age 10 years of the child [OR (95% CI: 1.23 (1.10, 1.38) and 1.28 (1.12, 1.47), respectively)]. High maternal transferrin saturation during pregnancy was associated with a decreased and increased risk of upper respiratory tract infections at 1 and 6 years, respectively, [OR (95% CI: 0.60 (0.44, 0.83) and 1.54 (1.17, 2.02))]. Observed associations were suggested to be U-shaped (p-values for non-linearity ≤.001). Maternal hemoglobin and iron status measures during pregnancy were not consistently associated with child's gastroenteritis and urinary tract infections, as proxies for general infection effects. Conclusion: High maternal ferritin and low transferrin saturation concentrations during early pregnancy were most consistently associated with an overall increased risk of child's upper, not lower, respiratory tract infections.</p

The influence of Epstein-Barr virus and cytomegalovirus on childhood respiratory health: A population-based prospective cohort study

Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection are common in early childhood. CMV infection favours a T-helper-1 and EBV infection a T-helper-2 cell response, possibly leading to disbalanced T-helper cell response, and subsequent risk of asthma or atopy. Objective: To study the associations of EBV and CMV with lung function, asthma and inhalant allergic sensitization at school age. Methods: This study among 3546 children was embedded in a population-based prospective cohort. At age 6 years, serum IgG levels against EBV and CMV were measured by ELISA. At age 10 years, lung function was measured by spirometry, asthma by questionnaire and inhalant allergic sensitization by skin prick test. Results: Unadjusted models showed that seropositivity for EBV was associated with a higher FEV1 and FEF75 (Z-score difference (95% CI): 0.09 (0.02, 0.16) and 0.09 (0.02, 0.15)), while seropositivity for CMV was not. Specific combinations of viruses showed that seropositivity for EBV was only associated with FEV1 and FEF75 in the presence of seropositivity for CMV (0.12 (0.04, 0.20)) and 0.08 (0.01, 0.15)). Seropositivity for CMV in the absence of seropositivity for EBV was associated with an increased risk of inhalant allergic sensitization (OR (95% CI): 1.31 (1.02, 1.68)). All effect estimates attenuated into non-significant mainly after adjustment for child's ethnicity. Seropositivity for EBV or CMV was not associated with asthma. Conclusions and Clinical Relevance: Associations of EBV and CMV infections in early childhood with school-age lung function and inhalant allergic sensitization are explained by ethnicity, or sociodemographic and lifestyle-related factors

Eczema phenotypes and risk of allergic and respiratory conditions in school age children

Background: Eczema phenotypes based on eczema onset and persistence might better identify groups prone to allergic and respiratory conditions than a binary definition of eczema. We examined the associations of childhood eczema phenotypes with allergic sensitization, allergy, asthma and lung function at school age. Methods: This study among 4277 children was embedded in a multi-ethnic population-based prospective cohort study. Five eczema phenotypes (never, early transient, mid-transient, late transient, persistent) based on parental-reported physician-diagnosed eczema from age 6 months until 10 years were identified. At age 10 years, allergic sensitization was measured by skin prick tests, physician-diagnosed allergy and asthma by parent-reported questionnaires, and lung function by spirometry. Adjusted linear, logistic and multinomial regression models were applied. Results: Compared with never eczema, all eczema phenotypes were associated with increased risks of asthma (odds ratios (OR) range (95% confidence interval): 2.68 (1.58, 4.57) to 11.53 (6.65, 20.01)), food and inhalant allergic sensitization (1.72 (1.25, 2.36) to 12.64 (7.20, 22.18)), and physician-diagnosed inhalant allergy (1.92 (1.34, 2.74) to 11.91 (7.52, 18.86)). Strongest effect estimates were observed of early and persistent eczema with the risk of physician-diagnosed food allergy (OR 6.95 (3.76, 12.84) and 35.05 (18.33, 70.00), respectively) and combined asthma and physician-diagnosed allergy (7.11 (4.33, 11.67) and 29.03 (15.27, 55.22), respectively). Eczema phenotypes were not associated with lung function measures. Conclusion: Eczema phenotypes were differentially associated with risks of respiratory and allergic conditions in school-aged children. Children with early transient and persistent eczema might benefit from more intense follow-up for early identification and treatment of asthma and allergies

Maternal and neonatal 25-hydroxyvitamin D concentrations and school-age lung function, asthma and allergy. The Generation R Study

Background: Vitamin D deficiency in early life might affect the developing lung and immune system, and subsequently influence the risk of asthma and allergy in later life. Objective: We examined the associations of 25‐hydroxyvitamin D concentrations in mid‐gestation and at birth with lung function, asthma, inhalant allergic sensitization and inhalant allergy at school‐age. Methods: This study among 4951 children and their mothers was embedded in a population‐based prospective cohort in Rotterdam, the Netherlands. Maternal ve‐ nous blood samples in mid‐gestation and umbilical cord blood samples at birth were used to determine 25‐hydroxyvitamin D concentrations. At age 10 years, lung func‐ tion was measured by spirometry, current asthma and physician‐diagnosed inhalant allergy by questionnaire, and inhalant allergic sensitization by skin prick tests. We used multivariable regression models to examine associations. Results: Higher 25‐hydroxyvitamin D concentrations in mid‐gestation were associ‐ ated with a higher forced vital capacity (FVC), but a lower forced expiratory volume in 1 second/FVC (FEV1/FVC) and a lower forced expiratory flow after exhaling 75% of FVC (FEF75) (Z‐score differences [95% CI] 0.02 [0.00, 0.03], −0.02 [−0.03, −0.01] and −0.01 [‐0.03, −0.00], respectively, per 10 nmol/L 25‐hydroxyvitamin D), but not with asthma. Furthermore, higher 25‐hydroxyvitamin D concentrations in mid‐gesta‐ tion were associated with an increased risk of inhalant allergy (Odds Ratio [95% CI] 1.07 [1.02, 1.12]), but not with inhalant allergic sensitization. After additional adjust‐ ment for child's 25‐hydroxyvitamin D concentrations at the age of 6 years, only the associations of 25‐hydroxyvitamin D concentrations in mid‐gestation with FEV1