Lung function changes in children exposed to mine fire smoke in infancy.

BACKGROUND AND OBJECTIVE: Chronic, low-intensity air pollution exposure has been consistently associated with reduced lung function throughout childhood. However, there is limited research regarding the implications of acute, high-intensity air pollution exposure. We aimed to determine whether there were any associations between early life exposure to such an episode and lung growth trajectories. METHODS: We conducted a prospective cohort study of children who lived in the vicinity of the Hazelwood coalmine fire. Lung function was measured using respiratory oscillometry. Z-scores were calculated for resistance (R5 ) and reactance at 5 Hz (X5 ) and area under the reactance curve (AX). Two sets of analyses were conducted: (i) linear regression to assess the cross-sectional relationship between post-natal exposure to mine fire-related particulate matter with an aerodynamic diameter of less than 2.5 micrometres (PM2.5 ) and lung function at the 7-year follow-up and (ii) linear mixed-effects models to determine whether there was any association between exposure and changes in lung function between the 3- and 7-year follow-ups. RESULTS: There were no associations between mine fire-related PM2.5 and any of the lung function measures, 7-years later. There were moderate improvements in X5 (ß: -0.37 [-0.64, -0.10] p = 0.009) and AX (ß: -0.40 [-0.72, -0.08] p = 0.014), between the 3- and 7-year follow-ups that were associated with mean PM2.5 , in the unadjusted and covariance-adjusted models. Similar trends were observed with maximum PM2.5 . CONCLUSION: There was a moderate improvement in lung stiffness of children exposed to PM2.5 from a local coalmine fire in infancy, consistent with an early deficit in lung function at 3-years after the fire that had resolved by 7-years.

Longitudinal effects of prenatal exposure to plastic-derived chemicals and their metabolites on asthma and lung function from childhood into adulthood.

BACKGROUND AND OBJECTIVE: Environmental exposure to phthalates and bisphenol A (BPA), chemicals used in the production of plastics, may increase risk for asthma and allergies. However, little is known about the long-term effects of early life exposure to these compounds. We investigated if prenatal exposure to these compounds was associated with asthma, allergy and lung function outcomes from early childhood into adulthood in a cohort study. METHODS: Maternal serum samples collected from 846 pregnant women in the Raine Study were assayed for BPA and phthalate metabolites. The children of these women were followed up at 5, 13 and 22 years where spirometry and respiratory questionnaires were conducted to determine asthma and allergy status. Lung function trajectories were derived from longitudinal spirometry measurements. Multinomial logistic regression and weighted quantile sum regression was used to test associations of individual and chemical mixtures with asthma phenotypes and lung function trajectories. RESULTS: Effects of prenatal BPA and phthalates on asthma phenotypes were seen in male offspring, where BPA was associated with increased risk for persistent asthma, while mono-iso-butyl phthalate and mono-iso-decyl phthalate was associated with increased risk for adult asthma. Prenatal BPA had no effect on lung function trajectories, but prenatal phthalate exposure was associated with improved lung function. CONCLUSION: Prenatal BPA exposure was associated with increased likelihood of persistent asthma in males, while prenatal phthalate exposure was associated with increased likelihood of adult asthma in males. Results suggest that prenatal exposure to prenatal BPA and phthalates affect asthma risk, particularly in males, however lung function was not adversely affected.

No association between in utero exposure to emissions from a coalmine fire and post-natal lung function.

BACKGROUND AND OBJECTIVE: Studies linking early life exposure to air pollution and subsequent impaired lung health have focused on chronic, low-level exposures in urban settings. We aimed to determine whether in utero exposure to an acute, high-intensity air pollution episode impaired lung function 7-years later. METHOD: We conducted a prospective cohort study of children who lived in the vicinity of a coalmine fire. Respiratory function was measured using the forced oscillation technique (FOT). Z-scores for resistance at 5 Hz (R5), reactance at 5 Hz (X5) and area under the reactance curve (AX) were calculated. Two sets of analyses were conducted to address two separate questions: (1) whether mine fire exposure (a binary indicator; conceived after the mine fire vs in utero exposed) was associated with the respiratory Z-scores; (2) whether there was any dose-response relationship between fire-related PM2.5 exposure and respiratory outcomes among those exposed. RESULTS: Acceptable lung function measurements were obtained from 79 children; 25 unexposed and 54 exposed in utero. Median (interquartile range) for daily average and peak PM2.5 for the exposed children were 4.2 (2.6 - 14.2) and 88 (52-225) µg/m3 respectively. There were no detectable differences in Z-scores between unexposed and exposed children. There were no associations between respiratory Z-scores and in utero exposure to PM2.5 (daily average or peak). CONCLUSION: There was no detectable effect of in utero exposure to PM2.5 from a local coalmine fire on post-natal lung function 7-years later. However, statistical power was limited.

Associations of early-life pet ownership with asthma and allergic sensitization: A meta-analysis of more than 77,000 children from the EU Child Cohort Network.

BACKGROUND: Studies examining associations of early-life cat and dog ownership with childhood asthma have reported inconsistent results. Several factors could explain these inconsistencies, including type of pet, timing, and degree of exposure. OBJECTIVE: Our aim was to study associations of early-life cat and dog ownership with asthma in school-aged children, including the role of type (cat vs dog), timing (never, prenatal, or early childhood), and degree of ownership (number of pets owned), and the role of allergic sensitization. METHODS: We used harmonized data from 77,434 mother-child dyads from 9 birth cohorts in the European Union Child Cohort Network when the child was 5 to 11 years old. Associations were examined through the DataSHIELD platform by using adjusted logistic regression models, which were fitted separately for each cohort and combined by using random effects meta-analysis. RESULTS: The prevalence of early-life cat and dog ownership ranged from 12% to 45% and 7% to 47%, respectively, and the prevalence of asthma ranged from 2% to 20%. There was no overall association between either cat or dog ownership and asthma (odds ratio [OR] = 0.97 [95% CI = 0.87-1.09] and 0.92 [95% CI = 0.85-1.01], respectively). Timing and degree of ownership did not strongly influence associations. Cat and dog ownership were also not associated with cat- and dog-specific allergic sensitization (OR = 0.92 [95% CI = 0.75-1.13] and 0.93 [95% CI = 0.57-1.54], respectively). However, cat- and dog-specific allergic sensitization was strongly associated with school-age asthma (OR = 6.69 [95% CI = 4.91-9.10] and 5.98 [95% CI = 3.14-11.36], respectively). There was also some indication of an interaction between ownership and sensitization, suggesting that ownership may exacerbate the risks associated with pet-specific sensitization but offer some protection against asthma in the absence of sensitization. CONCLUSION: Our findings do not support early-life cat and dog ownership in themselves increasing the risk of school-age asthma, but they do suggest that ownership may potentially exacerbate the risks associated with cat- and dog-specific allergic sensitization.

Does machine learning have a role in the prediction of asthma in children?

Asthma is the most common chronic lung disease in childhood. There has been a significant worldwide effort to develop tools/methods to identify children's risk for asthma as early as possible for preventative and early management strategies. Unfortunately, most childhood asthma prediction tools using conventional statistical models have modest accuracy, sensitivity, and positive predictive value. Machine learning is an approach that may improve on conventional models by finding patterns and trends from large and complex datasets. Thus far, few studies have utilized machine learning to predict asthma in children. This review aims to critically assess these studies, describe their limitations, and discuss future directions to move from proof-of-concept to clinical application.

The EU Child Cohort Network's core data: establishing a set of findable, accessible, interoperable and re-usable (FAIR) variables.

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.

Associations between respiratory and vascular function in early childhood.

BACKGROUND AND OBJECTIVE: The link between respiratory and vascular health is well documented in adult populations. Impaired lung function is consistently associated with thicker arteries and higher incidence of cardiovascular disease. However, there are limited data on this relationship in young children and the studies that exist have focussed on populations at high risk of cardiorespiratory morbidity. We determined if an association exists between respiratory and cardiovascular function in young children and, if so, whether it is confounded by known cardiorespiratory risk factors. METHODS: Respiratory and vascular data from a prospective cohort study established to evaluate the health implications 3 years after coal mine fire smoke exposure in children aged 3-5 years were used. Respiratory function was measured using the forced oscillation technique and included resistance at 5 Hz (R5 ), reactance at 5 Hz (X5 ) and area under the reactance curve (AX). Vascular health was measured by carotid intima-media thickness (ultrasound) and pulse wave velocity (arterial tonometry). Regression analyses were used to examine the relationship between the respiratory Z-scores and cardiovascular measures. Subsequent analyses were adjusted for potential confounding by maternal smoking during pregnancy, maternal education and exposure to fine particulate matter <2.5 µm in aerodynamic diameter (PM2.5 ). RESULTS: Peripheral lung function (X5 and AX), but not respiratory system resistance (R5 ), was associated with vascular function. Adjustment for maternal smoking, maternal education and early life exposure to PM2.5 had minimal effect on these associations. CONCLUSION: These observations suggest that peripheral lung stiffness is associated with vascular stiffness and that this relationship is established early in life.

Normative data for multiple breath washout outcomes in school-aged Caucasian children.

BACKGROUND: The multiple breath nitrogen washout (N2MBW) technique is increasingly used to assess the degree of ventilation inhomogeneity in school-aged children with lung disease. However, reference values for healthy children are currently not available. The aim of this study was to generate reference values for N2MBW outcomes in a cohort of healthy Caucasian school-aged children. METHODS: N2MBW data from healthy Caucasian school-age children between 6 and 18 years old were collected from four experienced centres. Measurements were performed using an ultrasonic flowmeter (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) and were analysed with commercial software (Spiroware version 3.2.1, Eco Medics AG). Normative values and upper limits of normal (ULN) were generated for lung clearance index (LCI) at 2.5% (LCI2.5%) and at 5% (LCI5%) of the initial nitrogen concentration and for moment ratios (M1/M0 and M2/M0). A prediction equation was generated for functional residual capacity (FRC). RESULTS: Analysis used 485 trials from 180 healthy Caucasian children aged from 6 to 18 years old. While LCI increased with age, this increase was negligible (0.04 units·year-1 for LCI2.5%) and therefore fixed ULN were defined for this age group. These limits were 7.91 for LCI2.5%, 5.73 for LCI5%, 1.75 for M1/M0 and 6.15 for M2/M0, respectively. Height and weight were found to be independent predictors of FRC. CONCLUSION: We report reference values for N2MBW outcomes measured on a commercially available ultrasonic flowmeter device (Exhalyzer D, Eco Medics AG) in healthy school-aged children to allow accurate interpretation of ventilation distribution outcomes and FRC in children with lung disease.

Early life exposure to coal mine fire smoke emissions and altered lung function in young children.

BACKGROUND AND OBJECTIVE: Long-term respiratory risks following exposure to relatively short periods of poor air quality early in life are unknown. We aimed to evaluate the association between exposure to a 6-week episode of air pollution from a coal mine fire in children aged <2 years, and their lung function 3 years after the fire. METHODS: We conducted a prospective cohort study. Individual exposure to 24-h average and peak concentrations of particulate matter with an aerodynamic diameter <2.5 µm in diameter (PM2.5 ) during the fire were estimated using dispersion and chemical transport modelling. Lung function was measured using the forced oscillation technique (FOT), generating standardized Z-scores for resistance and reactance at a frequency of 5 Hz (Rrs5 and Xrs5 ), and area under the reactance curve (AX). We used linear regression models to assess the associations between PM2.5 exposure and lung function, adjusted for potential confounders. RESULTS: Of the 203 infants originally recruited, 84 aged 4.3 ± 0.5 years completed FOT testing. Median (interquartile range, IQR) for average and peak PM2.5 were 7.9 (6.8-16.8) and 103.4 (60.6-150.7) µg/m3 , respectively. The mean ± SD Z-scores for Rrs5 , Xrs5 and AX were 0.56 ± 0.80, -0.76 ± 0.88 and 0.72 ± 0.92, respectively. After adjustment for potential confounders including maternal smoking during pregnancy, a 10 µg/m3 increase in average PM2.5 was significantly associated with worsening AX (ß-coefficient: 0.260; 95% CI: 0.019, 0.502), while the association between a 100-µg/m3 increase in peak PM2.5 and AX was borderline (0.166; 95% CI: -0.002, 0.334). CONCLUSION: Infant exposure to coal mine fire emissions could be associated with long-term impairment of lung reactance.

Ventilation inhomogeneity in infants with recurrent wheezing.

BACKGROUND: The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing. OBJECTIVE: To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls. METHODS: This is a case-control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography. RESULTS: LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (-0.11 to 0.63) vs -0.58 (-0.79 to 0.36), p<0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (>1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05). CONCLUSIONS: Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.