Lung function tracks an individual percentile established early in life largely determining the level of maximal function reached as a young adult, which in turn affects cumulative risk of lung ...disease as people age. This understanding emphasizes the need to identify modifiable environmental risk factors and maximize early lung function. Lung development begins in utero and is characterized by a carefully choreographed series of events. Optimal coordinated functioning of many complex processes and their networks of interaction are necessary for normal lung development and the maintenance of respiratory health. They increasingly understand that lung function trajectories are largely established by in utero factors. Epidemiological studies implicate exposure to ambient air pollution, especially particulate matter (PM), with increased early childhood respiratory disease. Air pollution remains a major pediatric public health focus because of its ubiquity and projections that exposure patterns may increase over the coming years because of climate change. Here, Wright highlights the study by Decrue and colleagues that stresses that infants born preterm may be particularly vulnerable to in utero exposure to ambient air pollutant effects on respiratory outcomes.
In this issue of the Journal of Allergy and Clinical Immunology, Shah et al sought to address the methodologic limitations of prior studies by leveraging a longitudinal, de-identified primary care ...database in the United Kingdom, including a large representative sample (N = 353,173) of perimenopausal and postmenopausal women in the United Kingdom primary care population, to examine associations between HRT use (estrogen alone and/or an estrogen-progesterone combination vs no use ever) and incident asthma over a 17-year follow-up period.1 HRT status was updated annually, and participants were counted as users only in the years during which they used HRT. ...chronic psychologic stress contributes to sex-specific health effects via cross-talk between glucocorticoids and sex steroids.5 Overlapping research links many of these exposures to respiratory health and related comorbidities (obesity) in a sex-specific manner. ...the evolving field of life course research has increasingly enhanced our understanding of the relative importance of exposures during different life stages in relation to health trajectories.6 Across the lifespan, exposure within critical windows can have more significant and lasting effects on health than those of exposures outside these windows. A National Institute of Environmental Health Sciences workshop identified a need for traditional targeted environmental biomonitoring coupled with untargeted discovery of unknown exposures and biologic response pathways as critical tools in exposomic research.10 Leveraging an exposome framework in future research focused on relevant life stages such as pregnancy (as depicted in Fig 1) will constitute windows of opportunity to further elucidate the role of reproductive hormones in women’s respiratory health across the lifespan.
The influence of particulate air pollution on respiratory health starts in utero. Fetal lung growth and structural development occurs in stages; thus, effects on postnatal respiratory disorders may ...differ based on timing of exposure.
We implemented an innovative method to identify sensitive windows for effects of prenatal exposure to particulate matter with a diameter less than or equal to 2.5 μm (PM2.5) on children's asthma development in an urban pregnancy cohort.
Analyses included 736 full-term (≥37 wk) children. Each mother's daily PM2.5 exposure was estimated over gestation using a validated satellite-based spatiotemporal resolved model. Using distributed lag models, we examined associations between weekly averaged PM2.5 levels over pregnancy and physician-diagnosed asthma in children by age 6 years. Effect modification by sex was also examined.
Most mothers were ethnic minorities (54% Hispanic, 30% black), had 12 or fewer years of education (66%), and did not smoke in pregnancy (80%). In the sample as a whole, distributed lag models adjusting for child age, sex, and maternal factors (education, race and ethnicity, smoking, stress, atopy, prepregnancy obesity) showed that increased PM2.5 exposure levels at 16-25 weeks gestation were significantly associated with early childhood asthma development. An interaction between PM2.5 and sex was significant (P = 0.01) with sex-stratified analyses showing that the association exists only for boys.
Higher prenatal PM2.5 exposure at midgestation was associated with asthma development by age 6 years in boys. Methods to better characterize vulnerable windows may provide insight into underlying mechanisms.
Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex.
We implemented ...innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter≤2.5μm (PM2.5) and children's neurodevelopment.
We assessed 267 full-term urban children's prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors OEs, commission errors CEs, hit reaction time HRT, and HRT standard error HRT-SE on the Conners' CPT-II), and memory (general memory GM index and its components — verbal VEM and visual VIM memory, and attention-concentration AC indices on the WRAML-2) assessed at age 6.5±0.98years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined.
Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31–38weeks with lower IQ, at 20–26weeks gestation with increased OEs, at 32–36weeks with slower HRT, and at 22–40weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18–26weeks with reduced VIM, at 12–20weeks with reduced GM).
Increased PM2.5 exposure in specific prenatal windows may be associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups.
•We used data-driven methods to objectively examine sensitive windows of prenatal PM2.5 on childhood neurodevelopment.•Our findings suggested sex-specific, time-dependent associations that may vary dependent on different cognitive domains.•A more definitive understanding of such sex-specific temporal associations may provide insights into underlying mechanisms.
Disease programming reflects interactions between genes and the environment. Unlike the genome, environmental exposures and our response to exposures change over time. Starting in utero, the ...respiratory system and related processes develop sequentially in a carefully timed cascade, thus effects depend on both exposure dose and timing. A multitude of environmental and microbial exposures influence respiratory disease programming. Effects result from toxin-induced shifts in a host of molecular, cellular, and physiologic states and their interacting systems. Moreover, pregnant women and the developing child are not exposed to a single toxin, but to complex mixtures.
Evidence supports an association between maternal exposure to air pollution during pregnancy and children's health outcomes. Recent interest has focused on identifying critical windows of ...vulnerability. An analysis based on a distributed lag model (DLM) can yield estimates of a critical window that are different from those from an analysis that regresses the outcome on each of the 3 trimester-average exposures (TAEs). Using a simulation study, we assessed bias in estimates of critical windows obtained using 3 regression approaches: 1) 3 separate models to estimate the association with each of the 3 TAEs; 2) a single model to jointly estimate the association between the outcome and all 3 TAEs; and 3) a DLM. We used weekly fine-particulate-matter exposure data for 238 births in a birth cohort in and around Boston, Massachusetts, and a simulated outcome and time-varying exposure effect. Estimates using separate models for each TAE were biased and identified incorrect windows. This bias arose from seasonal trends in particulate matter that induced correlation between TAEs. Including all TAEs in a single model reduced bias. DLM produced unbiased estimates and added flexibility to identify windows. Analysis of body mass index z score and fat mass in the same cohort highlighted inconsistent estimates from the 3 methods.
Psychosocial stress contributes to placental oxidative stress. Mitochondria are vulnerable to oxidative stress, which can lead to changes in mitochondrial DNA copy number (mtDNAcn). We examined ...associations of maternal lifetime stress, current negative life events, and depressive and posttraumatic-stress-disorder symptom scores with placental mtDNAcn in a racially/ethnically diverse sample (n = 147) from the Programming of Intergenerational Stress Mechanisms (PRISM) study (Massachusetts, March 2011 to August 2012). In linear regression analyses adjusted for maternal age, race/ethnicity, education, prenatal fine particulate matter exposure, prenatal smoking exposure, and the sex of the child, all measures of stress were associated with decreased placental mtDNAcn (all P values < 0.05). Weighted-quantile-sum (WQS) regression showed that higher lifetime stress and depressive symptoms accounted for most of the effect on mtDNAcn (WQS weights: 0.25 and 0.39, respectively). However, among white individuals, increased lifetime stress and posttraumatic stress disorder symptoms explained the majority of the effect (WQS weights: 0.20 and 0.62, respectively) while among nonwhite individuals, lifetime stress and depressive symptoms accounted for most of the effect (WQS weights: 0.27 and 0.55, respectively). These analyses are first to link increased maternal psychosocial stress with reduced placental mtDNAcn and add to literature documenting racial/ethnic differences in the psychological sequelae of chronic stress that may contribute to maternal-fetal health.
Exposure to environmental toxins during critical periods of prenatal and/or postnatal development may alter the normal course of lung morphogenesis and maturation, potentially resulting in changes ...that affect both structure and function of the respiratory system. Moreover, these early effects may persist into adult life magnifying the potential public health impact. Aberrant or excessive pro-inflammatory immune responses, occurring both locally and systemically, that result in inflammatory damage to the airway are a central determinant of lung structure–function changes throughout life. Disruption of neuroendocrine function in early development, specifically the hypothalamic–pituitary–adrenal (HPA) axis, may alter functional status of the immune system. Autonomic nervous system (ANS) function (sympathovagal imbalance) is another integral component of airway function and immunity in childhood. This overview discusses the evidence linking psychological factors to alterations in these interrelated physiological processes that may, in turn, influence childhood lung function and identifies gaps in our understanding.
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