Lung Function In Early Childhood Research Articles

Relationships between lung function, allergy, and wheezing in urban children

BackgroundAllergic sensitization and low lung function in early childhood are risk factors for subsequent wheezing and asthma. However, it is unclear how allergic sensitization impacts lung function over time. ObjectiveTo test whether allergy influences lung function and whether these factors synergistically increase the risk of continued wheezing in childhood. MethodsWe analyzed longitudinal measurements of lung function (spirometry, impulse oscillometry) and allergic sensitization (aeroallergen skin tests, serum allergen-specific IgE) throughout early childhood in the Urban Environmental and Childhood Asthma study which included high-risk urban children living in disadvantaged neighborhoods. Intraclass correlation coefficients (ICC) were calculated to assess lung function stability. Cluster analysis identified low, medium, and high allergy trajectories, which were compared to lung function and wheezing episodes in linear regression models. A variable selection model assessed predictors at age 5 for continued wheezing through age 12. ResultsLung function adjusted for growth was stable (ICC 0.5–0.7) from ages 5–12 years and unrelated to allergy trajectory. Lung function and allergic sensitization were associated with wheezing episodes in an additive fashion. In children with asthma, measuring lung function at age 5 added little to the medical history for predicting future wheezing episodes through age 12. ConclusionIn high-risk urban children, age-related trajectories of allergic sensitization were not associated with lung function development, however, both indicators were related to continued wheezing. These results underscore the importance of understanding early life factors that negatively impact lung development and suggest that treating allergic sensitization may not alter lung function development in early to mid-childhood.

Dose-dependent impact of human milk feeding on tidal breathing flow-volume loop parameters across the first 2 years of life in extremely low-birth-weight infants: a cohort study.

Preterm infants with higher consumption of HM had significantly less airway obstruction across the first 2 years, suggesting that human milk may contribute in a dose-dependent manner to improve lung function in early childhood in former preterm infants born ELBW. • Human milk feeding reduces the risk of prematurity-related morbidities, including necrotizing enterocolitis, sepsis, lower respiratory tract infections, and BPD. Both exclusive and partial human milk feeding appear to be associated with a lower risk of BPD in preterm infants. • This cohort study of 180 preterm infants with birth weight < 1000 g found that exposure to human milk during hospitalization improves airway obstruction markers tPTEF/tE z-score over the first 2 years of corrected age in a dose-dependent manner.

Prenatal Ambient Air Pollutant Mixture Exposure and Early School-age Lung Function.

Analyses included 198 mother-child dyads recruited from two hospitals and affiliated community health centers in Boston, Massachusetts, USA. Daily prenatal pollutant exposures were estimated using satellite-based hybrid chemical-transport models, including nitrogen dioxide(NO2), ozone(O3), and fine particle constituents (elemental carbon [EC], organic carbon [OC], nitrate [NO3 -], sulfate [SO4 2-], and ammonium [NH4 +]). Spirometry was performed at age 6.99 ± 0.89 years; forced expiratory volume in 1s (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75) z-scores accounted for age, sex, height, and race/ethnicity. We examined associations between weekly-averaged prenatal pollution mixture levels and outcomes using Bayesian Kernel Machine Regression-Distributed Lag Models (BKMR-DLMs) to identify susceptibility windows for each component and estimate a potentially complex mixture exposure-response relationship including nonlinear effects and interactions among exposures. We also performed linear regression models using time-weighted-mixture component levels derived by BKMR-DLMs adjusting for maternal age, education, perinatal smoking, and temperature. Most mothers were Hispanic (63%) or Black (21%) with ≤12 years of education (67%). BKMR-DLMs identified a significant effect for O3 exposure at 18-22 weeks gestation predicting lower FEV1/FVC. Linear regression identified significant associations for O3, NH4 +, and OC with decreased FEV1/FVC, FEV1, and FEF25-75, respectively. There was no evidence of interactions among pollutants. In this multi-pollutant model, prenatal O3, OC, and NH4 + were most strongly associated with reduced early childhood lung function.

Prenatal metal mixtures and early childhood lung function

BACKGROUND AND AIM: Individual metal exposures have been linked to child lung health, however associations with prenatal metal mixtures has not been described. We employed a novel statistical approach to examine associations between prenatal exposure to 18 metals and child lung function. METHODS: Analyses included 135 mothers and children enrolled in the longitudinal PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. Urinary metals were analyzed in prenatal maternal spot urine with inductively coupled plasma-mass spectrometer-triple quadrupole. Children performed impulse oscillometry (IOS) at age 4 years; IOS z-scores adjusted for age, sex, race/ethnicity and height and weight. We employed Bayesian Weighted Quantile Sum (BWQS) regression to examine associations between prenatal metal mixture exposure and IOS z-scores, adjusting for gestational age at spot urine collection, urinary creatinine, maternal education and gestational age at delivery. Sex-specific effects were explored. RESULTS:Sixty three percent (N=84) and 36% (N=48) of children self-reported Black and Hispanic ethnicity, respectively. Children were aged a median 4.2 years (IQR 3.7, 4.9) at the time of IOS and 52% (N=70) were male. In adjusted models, prenatal metal mixtures were associated with increased R5 (R5 z-score β= 0.26, 95% credible interval, CI, 0.01, 0.49) and R20 (R20 z-score, β= 0.29, 95% CI 0.00, 0.57), measures of total and large airway resistance, respectively. BWQS metal mixture weights identified that for both R5 and R20, Nickel, Lead, Barium, and Antimony had the largest proportional weights; Cadmium and Copper had larger weights for R5 while tin and manganese had lerger weights for R20. Girls were more vulnerable to the effects of metal mixtures on R5 while boys were more vulnerable to effects on R20. CONCLUSIONS:Prenatal metal mixture exposures were associated with impaired airway mechanics at age four years, with a suggestion of a sex-differential response. KEYWORDS: Prenatal, metal mixtures, lung function

Infant Nasopharyngeal Microbiota Subphenotypes and Early Childhood Lung Function: Evidence from a Rural Ghanaian Pregnancy Cohort.

Early life respiratory microbiota may increase risk for future pulmonary disease. Associations between respiratory microbiota and lung health in children from low- and middle-income countries are not well-described. Leveraging the Ghana Randomized Air Pollution and Health Study (GRAPHS) prospective pregnancy cohort in Kintampo, Ghana, we collected nasopharyngeal swabs in 112 asymptomatic children aged median 4.3 months (interquartile range (IQR) 2.9, 7.1) and analyzed 22 common bacterial and viral pathogens with MassTag polymerase chain reaction (PCR). We prospectively followed the cohort and measured lung function at age four years by impulse oscillometry. First, we employed latent class analysis (LCA) to identify nasopharyngeal microbiota (NPM) subphenotypes. Then, we used linear regression to analyze associations between subphenotype assignment and lung function. LCA suggest that a two-class model best described the infant NPM. We identified a higher diversity subphenotype (N = 38, 34%) with more pathogens (median 4; IQR 3.25, 4.75) and a lower diversity subphenotype (N = 74, 66%) with fewer pathogens (median 1; IQR 1, 2). In multivariable linear regression models, the less diverse NPM subphenotype had higher small airway resistance (R5-R20 = 17.9%, 95% CI 35.6, 0.23; p = 0.047) compared with the more diverse subphenotype. Further studies are required to understand the role of the microbiota in future lung health.

Low gestational vitamin D level and childhood asthma are related to impaired lung function in high-risk children

Lung function impairment in early life often persists into adulthood. Therefore, identifying risk factors for low childhood lung function is crucial. We examined the effect of 25-hydroxyvitamin D (25[OH]D) level and childhood asthma phenotype on childhood lung function in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). The 25(OH)D level was measured at set time points in mothers during pregnancy and in children during early life. On the basis of parental reports, children were categorized into 3 clinical phenotypes: asymptomatic/infrequent wheeze, early transient wheeze, and asthma at age 6 years. Lung function was assessed with impulse oscillometry at ages 4, 5, and 6 years and with spirometry at ages 5 and 6 years. A total of 570 mother-child pairs were included in this post hoc analysis. Mean gestational 25(OH)D-level quartiles were negatively associated with child respiratory resistance at 5 Hz (R5) from age 4 to 6 years (β, -0.021 kPa/L/s; 95% CI, -0.035 to -0.007; P= .003) and positively associated with FEV1 (β, 0.018 L; 95% CI, 0.005-0.031; P= .008) and forced vital capacity (β, 0.022 L; 95% CI, 0.009-0.036; P= .002) from age 5 to 6 years. Children with asthma at age 6 years had lower lung function from age 4 to 6 years than the asymptomatic/infrequent wheeze group (β, 0.065 kPa/L/s; 95% CI, 0.028 to 0.102; P< .001 for R5 and β, -0.063 L; 95% CI, -0.099 to -0.028; P< .001 for FEV1). Low gestational 25(OH)D level and childhood asthma are important risk factors for decreased lung function in early childhood.

Impact of prenatal and postnatal household air pollution exposure on lung function of 2-year old Nigerian children by oscillometry

RationaleLung function is adversely affected by exposure to household air pollution (HAP). Studies investigating the impact of prenatal and postnatal HAP exposure on early childhood lung development are limited, especially from Sub-Saharan Africa. ObjectiveWe used oscillometry to investigate the impact on lung function of prenatal and postnatal HAP exposure of children born to Nigerian women who participated in a randomized controlled cookstove intervention trial. MethodsWe performed oscillometric measurements (R: airway resistance; X: airway reactance; Fres: resonant frequency; AX: reactance area) in 223 children starting at age of 2 years (ethanol stove, n = 113; firewood/kerosene, n = 110). Personal exposure monitoring assessed mothers' prenatal exposure to particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5). Postnatal HAP exposure was measured by determining household PM2.5 levels. We employed linear regression analysis to examine the association of prenatal and postnatal HAP exposures with children's lung function. Models were adjusted for age, gender, weight, height, group (intervention or control), birthweight and gestational age. ResultsMean age of the children was 2.9 years (standard deviation = 0.3); 120 were boys (53.8%) and 103 were girls (46.2%). Higher postnatal PM2.5 exposures were significantly associated with higher airway reactance at 5 Hz (X5 Hz; p = 0.04) in adjusted models. There were no significant associations between prenatal or postnatal PM2.5 exposure levels and other oscillometry parameters in adjusted regression analysis. ConclusionsThis is the first study to use oscillometry to explore the relationship between HAP exposure and lung function in children as young as 2 years. The findings provide some evidence that increased postnatal HAP exposure may result in poorer lung function in children, although larger studies are needed to confirm observed results. This study indicates that oscillometry is a low-cost and effective method to determine lung function in early childhood.

Breathing: Ambient Air Pollution and Health - Part III

The third part of the DGP statement introduces the current body of knowledge on less studied health outcomes associated with exposure to ambient air pollution: the negative impact on metabolism leading to impaired glucose tolerance and diabetes as well as contribution to the development of neurodegenerative disorders and delayed cognitive function in children. Furthermore, prenatal exposure and adverse effects on mother and child are addressed. Finally, the currently discussed biological mechanisms underlying various health effects associated with exposure to air pollution are described.Differing, but often complementary biological mechanisms create the basis for the diverse health outcomes caused by air pollution. Oxidative stress and a subclinical inflammatory response in the lungs and on a systemic level ("low-grade systemic inflammation") are considered to be key mechanisms. They promote secondary alterations in the body, such as vascular or metabolic processes, and may also result in the currently studied epigenetic phenomena or neuroinflammation. In this context, the health significance of soluble particulate matter and the role of ultrafine particles translocated across biological membranes into blood vessel and transported via the circulation to secondary target organs, such as liver, brain or the fetus, are intensively discussed.Diabetes is one of the leading chronic diseases worldwide, with a prevalence of almost 14 % in Germany. Although lifestyle factors are the main causes, current evidence suggests that long-term exposure to air pollution may additionally increase the risk for type 2 diabetes. Supporting evidence for a causal role of air pollution is provided by studies addressing the regulation of the blood glucose levels in metabolically healthy participants, insulin sensitivity, or pregnancy-related diabetes. Experimental studies provide further support for plausible biological mechanisms. However, prospective studies are needed to gain more evidence, taking multiple lifestyle and environmental factors, such as green space and noise, and an improved individual exposure assessment into account.The aging population has an increased risk of neurodegenerative diseases. First studies point towards a contribution of chronic exposure to air pollution, specifically by particulate matter. Several studies report its association with decreased neurocognitive capacity or an increased prevalence of dementia or Alzheimer's disease in adults. However, the studies are inhomogeneous regarding design, exposure and outcome, leading to inconsistent results. With respect to the influence on neurocognitive development of children, first studies suggest an association between the level of air pollution, e. g. at school, and delayed cognitive development.Even though the evidence for the different biological endpoints during pregnancy is still heterogeneous, the studies generally point towards an adverse impact of air pollution on the maternal and fetal organisms. The strongest evidence exists for low birth weight, with small effect sizes of only some grams, and for a higher incidence of reduced birth weight (< 2500 g). An increased risk for gestational hypertension and preeclampsia underscores the possible impact of exposure to air pollution on the maternal organism. However, the current body of evidence does not yet allow a final conclusion on the influence of intrauterine exposure to air pollution regarding early childhood lung function and development of allergies, particularly in light of the fact that it is hard to distinguish in epidemiological studies between the effects of pre- and postnatal exposure.

Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects

BackgroundIn utero exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) has been linked to child lung function. Overlapping evidence suggests that child sex and exposure timing may modify effects and associations may be mediated through glutathione S-transferase P1 (GSTP1) methylation.MethodsWe prospectively examined associations among prenatal PM2.5 exposure and child lung function and GSTP1 methylation in an urban pregnancy cohort study. We employed a validated satellite-based spatiotemporally resolved prediction model to estimate daily prenatal PM2.5 exposure over gestation. We used Baysian distributed lag interaction models (BDLIMs) to identify sensitive windows for prenatal PM2.5 exposure on child lung function and nasal epithelia GSTP1 methylation at age 7 years, and to examine effect modification by child sex.ResultsBDLIMs identified a sensitive window for prenatal PM2.5 exposure at 35–40 weeks gestation [cumulative effect estimate (CEE) = − 0.10, 95%CI = − 0.19 to − 0.01, per μg/m3 increase in PM2.5] and at 36–40 weeks (CEE = − 0.12, 95%CI = − 0.20 to − 0.01) on FEV1 and FVC, respectively, in boys. BDLIMs also identified a sensitive window of exposure at 37–40 weeks gestation between higher prenatal PM2.5 exposure and increased GSTP1 percent methylation. The association between higher GSTP1 percent methylation and decreased FEV1 was borderline significant in the sample as a whole (β = − 0.37, SE = 0.20, p = 0.06) and in boys in stratified analyses (β = − 0.56, SE = 0.29, p = 0.05).ConclusionsPrenatal PM2.5 exposure in late pregnancy was associated with impaired early childhood lung function and hypermethylation of GSTPI in DNA isolated from nasal epithelial cells. There was a trend towards higher GSTP1 percent methylation being associated with reduced FEV1. All findings were most evident among boys.

Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection.

ObjectivePseudomonas aeruginosa has been suggested as a major determinant of poor pulmonary outcomes in cystic fibrosis (CF), although other factors play a role. Our objective was to investigate the association of early childhood Pseudomonas infection on differences in lung function in adolescence with CF.MethodsTwo populations of subjects with CF were studied: from the Gene Modifier Study (GMS), 346 F508del homozygotes with severe vs. mild adolescent lung disease, and from the Colorado Newborn Screen Study (NBS) 172 subjects diagnosed with CF by newborn screening. Associations of Pseudomonas infection and lung function in early childhood with lung function in adolescence were investigated using multivariate linear regression analyses.ResultsAmong GMS subjects, those with severe adolescent lung disease had worse lung function in childhood (FEV1 25 percentage points lower) compared to subjects with mild adolescent lung disease, regardless of early childhood Pseudomonas status. Among NBS subjects, those with lowest adolescent lung function had significantly lower early childhood lung function and faster rate of decline in FEV1 than subjects with highest adolescent lung function; early Pseudomonas infection was not associated with rate of FEV1 decline. The strongest predictor of adolescent lung function was early childhood lung function. Subjects with a higher percentage of cultures positive for Pseudomonas before age 6 or a lower BMI at 2–4 years old also had lower adolescent lung function, though these associations were not as strong as with early childhood lung function.ConclusionsIn separate analyses of two distinct populations of subjects with CF, we found a strong correlation between lower lung function in early childhood and adolescence, regardless of early childhood Pseudomonas status. Factors in addition to early Pseudomonas infection have a strong impact on lung function in early childhood in CF. Further exploration may identify novel underlying genetic or environmental factors that predispose children with CF to early loss of lung function.

Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

Early childhood lung function is a stronger predictor of adolescent lung function in cystic fibrosis than early Pseudomonas aeruginosa infection

Environment-induced epigenetic reprogramming in genomic regulatory elements in smoking mothers and their children.

Epigenetic mechanisms have emerged as links between prenatal environmental exposure and disease risk later in life. Here, we studied epigenetic changes associated with maternal smoking at base pair resolution by mapping DNA methylation, histone modifications, and transcription in expectant mothers and their newborn children. We found extensive global differential methylation and carefully evaluated these changes to separate environment associated from genotype‐related DNA methylation changes. Differential methylation is enriched in enhancer elements and targets in particular “commuting” enhancers having multiple, regulatory interactions with distal genes. Longitudinal whole‐genome bisulfite sequencing revealed that DNA methylation changes associated with maternal smoking persist over years of life. Particularly in children prenatal environmental exposure leads to chromatin transitions into a hyperactive state. Combined DNA methylation, histone modification, and gene expression analyses indicate that differential methylation in enhancer regions is more often functionally translated than methylation changes in promoters or non‐regulatory elements. Finally, we show that epigenetic deregulation of a commuting enhancer targeting c‐Jun N‐terminal kinase 2 (JNK2) is linked to impaired lung function in early childhood.

Preschool oscillometry and lung function at adolescence in asthmatic children.

Reduced lung function in early childhood is associated with persistent symptoms and low lung function later in life. Impulse oscillometry (IOS) is feasible for assessing lung function also in preschool children, and some of the parameters, such as respiratory resistance at 5 Hz (Rrs5) and the frequency dependence of resistance (dRrs/df), have been suggested to reflect small airway dysfunction. Whether changes in preschool IOS predict later lung function remains unknown. The medical data of 154 asthmatic children with IOS performed at 2-7 years and spirometry at 12-18 years were analyzed. IOS and post-bronchodilator spirometry parameters were compared, and the association was estimated in a multivariate model. Measured at preschool age, particularly Rrs5 and dRrs/df were significantly correlated with post-bronchodilator forced expiratory volume in 1 sec (FEV1) at adolescence (Rrs5: r = -0.223, P = 0.005; dRrs/df: r = 0.234, P = 0.004). Although the number of children with decreased FEV1 was low, associations of increased Rrs5 (odds ratio (OR) 5.9, 95% confidence interval (CI) 1.7; 20.9) and decreased dRrs/df (OR 8.2, 95% CI 1.7; 39.6) with decreased FEV1 remained significant in multivariate analyses. Similar findings were observed also with other spirometric parameters. In asthmatic children, preschool IOS is associated with spirometric lung function at adolescence, but the scatter is wide. Normal preschool IOS seems to indicate favourable lung function outcome, whereas in some individuals IOS could potentially be of clinical use, at a younger age than spirometry, to screen lung function deficits and increased risk for later lung function impairment.

The Effect of Birth Weight on Lung Spirometry in White, School-Aged Children and Adolescents Born at Term: A Longitudinal Population Based Observational Cohort Study

To evaluate how birth weight affects lung function measurements in childhood and adolescence in term-born children. We used data for white, term-born, singletons, from the Avon Longitudinal Study of Parents and Children to determine the association between birth weight and lung function at age 8-9 (n=4086) and 14-17 (n=2582) years. z-scores for lung function measures, adjusted for sex, height, and age, were modeled in terms of birth weight z-score adjusted for sex. In addition, gestation and head circumference then confounders (maternal smoking during pregnancy and social class) were added to the model. At age 8-9 years, birth weight z-scores were significantly associated with lung function z-scores (forced expiratory volume in 1 second, forced vital capacity [FVC], and forced mid-expiratory flow between 25% and 75% of FVC). These relationships essentially were unchanged when birth weight z-scores were further adjusted for gestation, head circumference, and confounders, except for forced mid-expiratory flow between 25% and 75% of FVC, which was no longer significant after we adjusted for head circumference and confounders. At age 14-17 years, the associations between adjusted birth-weight z-scores and spirometry z-scores were in general not significant. Estimated differences for forced expiratory volume in 1 second were 30 mL at ages 8-9 years and 33 mL at 14-17 years for 1 kg change in birth-weight standardized for gestation and sex. Birth weight is associated with lung function in term-born children at 8-9 years, but less so at 14-17 years, suggesting that birth weight influences lung function in early childhood but has lesser effect later in life.

Transient early wheeze and lung function in early childhood associated with chronic obstructive pulmonary disease genes

It has been hypothesized that a disturbed early lung development underlies the susceptibility to chronic obstructive pulmonary disease (COPD). Little is known about whether subjects genetically predisposed to COPD show their first symptoms or reduced lung function in childhood. We investigated whether replicated genes for COPD associate with transient early wheeze (TEW) and lung function levels in 6- to 8-year-old children and whether cigarette smoke exposure in utero and after birth (environmental tobacco smoke [ETS]) modifies these effects. The association of COPD-related genotypes of 20 single nucleotide polymorphisms in 15 genes with TEW, FEV1, forced vital capacity (FVC), and FEV1/FVC ratio was studied in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort (n= 1996) and replicated in the Child, parents and health: lifestyle and genetic constitution (KOALA) and Avon Longitudinal Study of Parents and Children (ALSPAC) cohorts. AGER showed replicated association with FEV1/FVC ratio. TNS1 associated with more TEW in PIAMA and lower FEV1 in ALSPAC. TNS1 interacted with ETS in PIAMA, showing lower FEV1 in exposed children. HHIP rs1828591 interacted with cigarette smoke exposure in utero in PIAMA and with ETS in ALSPAC, with lower lung function in nonexposed children. SERPINE2, FAM13A, and MMP12 associated with higher FEV1 and FVC, and SERPINE2, HHIP, and TGFB1 interacted with cigarette smoke exposure in utero in PIAMA only, showing adverse effects of exposure on FEV1 being limited to children with genotypes conferring the lowest risk of COPD. Our findings indicate relevant involvement of at least 3 COPD genes in lung development and lung growth by demonstrating associations pointing toward reduced airway caliber in early childhood. Furthermore, our results suggest that COPD genes are involved in the infant's lung response to smoke exposure in utero and in early life.

Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non-smoking mothers

Impaired fetal development is associated with a number of adult chronic diseases and it is believed that these associations arise as a result of the phenomenon of prenatal programming, which involves persisting changes in structure and function of various body organs caused by ambient factors during critical and vulnerable periods of early development. The main goal of the study was to assess the association between lung function in early childhood and prenatal exposure to fine particulate matter (PM(2.5)), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study, personal measurements of PM(2.5) were performed over 48 h in the second trimester of pregnancy. After delivery, infants were followed for 5 years; the interviewers visited participants in their homes to record children's respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months thereafter. In the fifth year of the follow-up, children were invited for standard lung function testing of levels of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)) and forced expiratory volume in 0.5 s (FEV(0.5)). There were 176 children of non-smoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression showed a significant deficit of FVC at the highest quartile of PM(2.5) exposure (beta coefficient = -91.9, P = 0.008), after adjustment for covariates (age, gender, birthweight, height and wheezing). Also FEV(1) level in children was inversely correlated with prenatal exposure to PM(2.5), and the average FEV(1) deficit amounted to 87.7 mL (P = 0.008) at the higher level of exposure. Although the effect of PM(2.5) exposure on FEV(0.5) was proportionally weaker (-72.7, P = 0.026), it was also statistically significant. The lung function level was inversely and significantly associated with the wheezing recorded over the follow-up. The findings showed that significant lung function deficits in early childhood are associated with prenatal exposure to fine particulate matter, which may affect fetal lung growth.

Advances in mechanisms of asthma, allergy, and immunology in 2008

This review summarizes selected articles appearing in 2008 in the Journal. Articles chosen include those improving our understanding of mechanisms of allergic diseases by focusing on human basophil, mast cell, and eosinophil biology; IgE and its high-affinity receptor on various cells; novel properties of omalizumab; airways remodeling; and genetics. Articles from other journals have been included to supplement the topics presented.

Association of early life wheeze and lung function

The incidence of wheeze is unknown and the role of early life wheeze in subsequent health is not clearly understood. To calculate the age-specific incidence of wheeze and determine whether wheezing at particular times in early life was predictive of abnormal airway hyperresponsiveness (AHR), percentage of predicted forced expiratory volume in 1 second (FEV1), and current asthma at the age of 6 years. Using data from a birth cohort study with annual report of wheezing (Childhood Allergy Study) and spirometry and methacholine challenge at the age of 6 years, the age-specific incidence of wheeze was determined using Kaplan-Meier estimates. Logistic and linear regression models were used to assess the associations between the presence of age-specific wheezing and the outcomes of current asthma, AHR, and percentage of predicted FEV1 at the age of 6 years. A total of 724 children had parents who completed at least the first annual interview and were therefore included in the study. The 6-year cumulative incidence of wheezing was higher for boys (66.2%; 95% confidence interval, 59.8%- 72.6%) than for girls (47.6%; 95% confidence interval, 41.4%-53.8%). There was no age when wheezing was more strongly associated with either AHR or percentage of predicted FEV1 at 6 years. Only wheeze in the fifth year among boys and wheezing in both the fourth and fifth years in girls were positively predictive of current asthma at the age of 6 years. This is likely because of the definition of current asthma (ever physician diagnosis and either medication or symptoms in last year). Eczema, parental asthma history, and total cord blood IgE did not affect these associations. Wheezing at any particular time in early life may not be predictive of early childhood lung function.

Genetic variation of IL13 as a risk factor of reduced lung function in children and adolescents: A cross-sectional population-based study in Korea

Previous investigations have suggested that genetic variations are associated with reduced lung function in early childhood. This study was conducted to evaluate the association between IL13+2044G-->A, the functionally relevant single nucleotide polymorphism (SNP) in the gene coding IL13, and lung function in early childhood. A total of 1900 subjects aged 10-18 years living in Korea, were randomly recruited. Lung function test and methacholine bronchial provocation test were performed. Multiple regression analysis adjusting for sex, age, height, atopy, and history of passive smoking was done to evaluate effect of IL13+2044G-->A on lung function. Mean (+/-SD) forced expiratory volume in 1 s (FEV(1)) was 2.66 L (+/-0.60) in subjects with the AA or AG genotype (n=982) and 2.75 L (+/-0.57) in subjects with the GG genotype (n=918). IL13+2044G-->A showed a significant association with FEV(1) [in the minor allele dominant model (GG vs. AG+AA), P<0.001]. Interestingly, the association between FEV(1) and IL13+2044G-->A remained still significant in subgroup analysis according to the presence of AHR (P<0.001 in subjects without AHR and P=0.002 in subjects with AHR). Moreover, FEV(1)/FVC (forced vital capacity) ratio also showed a significant association with IL13+2044G-->A in both groups (P<0.001 in subjects without AHR and P<0.001 in subjects with AHR). This cross-sectional study demonstrates that IL13+2044G-->A is significantly associated with a reduced lung function in Korean children and adolescents.

Specific airway resistance in 3-year-old children: a prospective cohort study

The development of a method to assess lung function in young children may provide new insight into asthma development. Plethysmographic measurement of specific airway resistance (sR(aw)) is feasible in this age group. We aimed to identify risk factors associated with low lung function in early childhood in a prospective birth cohort. Children were prenatally assigned to risk group according to parental atopic status (high risk, both parents atopic; medium risk, one parent atopic; low risk, neither parent atopic) and followed prospectively until age 3 years. We measured sR(aw) in 503 symptom-free children using whole-body plethysmography during tidal breathing. 803 of 868 children attended the clinic, of whom 503 obtained satisfactory sR(aw) readings. 200 who wheezed at least once during first 3 years of life had significantly higher sR(aw) than the 303 who had never wheezed (mean difference 5.8%, 95% CI 2.2-9.3, p=0.002). For children who had never wheezed there were significant differences in sR(aw) between risk groups (p<0.001). Children at high risk (n=87) had a higher sR(aw) (geometric mean 1.17 kPa/s, 1.12-1.22) than children at medium risk (n=162; 1.02 kPa/s, 1.00-1.05) and at low risk (54; 1.04 kPa/s, 0.99-1.11). Atopic children (n=62) had significantly higher sR(aw) (1.15 kPa/s, 1.09-1.21) than those who were not atopic (232; 1.05 kPa/s, 1.02-1.07, p=0.002). For non-atopic children, those at high risk (58) had higher sR(aw) (1.13kPa/s, 1.07-1.18) than those at medium risk (125, 1.01kPa/s, 0.98-1.05) or at low risk (49, 1.04 kPa/s, 0.97-1.10, p=0.003). We showed a significant interaction between history of maternal asthma and child's atopic status (p=0.006). Even in the absence of respiratory symptoms, children of atopic parents and those with personal atopy have impaired lung function in early life.