Critical windows of susceptibility for the effects of prenatal exposure to heat and heat variability on gestational growth.

BACKGROUND: Studies have shown that prenatal heat exposure may impact fetal growth, but few studies have examined the critical windows of susceptibility. As extreme heat events and within season temperature variability is expected to increase in frequency, it is important to understand how this may impact gestational growth. OBJECTIVES: We investigated associations between various measures of weekly prenatal heat exposure (mean and standard deviation (SD) of temperature and heat index (HI), derived using temperature in °C and dew point) and term birthweight or odds of being born small for gestational age (SGA) to identify critical windows of susceptibility. METHODS: We analyzed data from mother-child dyads (n = 4442) in the Boston-based Children's HealthWatch cohort. Birthweights were collected from survey data and electronic health records. Daily temperature and HI values were obtained from 800 m gridded spatial climate datasets aggregated by the PRISM Climate Group. Distributed lag-nonlinear models were used to assess the effect of the four weekly heat metrics on measures of gestational growth (birthweight, SGA, and birthweight z-scores). Analyses were stratified by child sex and maternal homelessness status during pregnancy. RESULTS: HI variability was significantly associated with decreased term birthweight during gestational weeks 10-29 and with SGA for weeks 9-26. Cumulative effects for these time periods were -287.4 g (95% CI: -474.1 g, -100.8 g for birthweight and 4.7 (95% CI: 1.6, 14.1) for SGA. Temperature variability was also significantly associated with decreased birthweight between weeks 15 and 26. The effects for mean heat measures on term birthweight and SGA were not significant for any gestational week. Stratification by sex revealed a significant effect on term birthweight in females between weeks 23-28 and in males between weeks 9-26. Strongest effects of HI variability on term birthweight were found in children of mothers who experienced homelessness during pregnancy. Weekly HI variability was the heat metric most strongly associated with measures of gestational growth. The effects observed were largest in males and those who experienced homelessness during pregnancy. DISCUSSION: Given the impact of heat variability on birthweight and risk of SGA, it is important for future heat warnings to incorporate measure of heat index and temperature variability.

Postnatal exposure to PM2.5 and weight trajectories in early childhood.

BACKGROUND: Inconsistent evidence has assessed the impact of air pollution exposure on children's growth trajectories. We investigated the role of 90-day average postnatal fine particulate matter (PM2.5) exposures by estimating the magnitude of effects at different ages, and the change in child weight trajectory by categories of exposure. METHODS: We obtained weight values from electronic health records at each hospital visit (males = 1859, females = 1601) from birth to 6 years old children recruited into the Boston-based Children's HealthWatch cohort (2009-2014). We applied mixed models, adjusting for individual and maternal confounders using (1) varying-coefficient models allowing for smooth non-linear interaction between age and PM2.5, (2) factor-smooth interaction between age and PM2.5 quartiles. Additionally, we stratified by sex and low birthweight (LBW) status (≤2500 g). RESULTS: Using varying-coefficient models, we found that PM2.5 significantly modified the association between age and weight in males, with a positive association in children younger than 3 years and a negative association afterwards. In boys, for each 10 µg/m3 increase in PM2.5 we found a 2.6% increase (95% confidence interval = 0.8, 4.6) in weight at 1 year of age and a -0.6% (95% confidence interval = -3.9, 2.9) at 5 years. We found similar but smaller changes in females, and no differences comparing growth trajectories across quartiles of PM2.5. Most of the effects were in LBW children and null for normal birthweight children. CONCLUSIONS: This study suggests that medium-term postnatal PM2.5 may modify weight trajectories nonlinearly in young children, and that LBW babies are more susceptible than normal-weight infants.

Origin of exhaled breath particles from healthy and human rhinovirus-infected subjects.

BACKGROUND: Exhaled breath studies suggest that humans exhale fine particles during tidal breathing, but little is known of their physical origin in the respiratory system during health or disease. METHODS: Particles generated by 3 healthy and 16 human rhinovirus (HRV)-infected subjects were counted using an optical particle counter with nominal diameter-size bins ranging between 0.3 and 10 µm. Data were collected from HRV-infected subjects during tidal breathing. In addition, data from healthy subjects were collected during coughs, swallows, tidal breathing, and breathing to total lung capacity (TLC) and residual volume (RV). Using general additive models, we graphed exhaled particle concentration versus airflow during exhalation. Exhaled particles were collected from expired air on gelatin filters and analyzed for HRV via quantitative PCR. RESULTS: HRV-infected subjects exhaled from 0.1 to 7200 particles per liter of exhaled air during tidal breathing (geometric mean = 32 part/L). A small fraction (24%) of subjects exhaled most (81%) of the particles measured and 82% of particles detected were 0.300-0.499 µm. Minute ventilation, maximum airflow during exhalation, and forced expiratory volume 1 second (FEV(1) % predicted) were positively correlated with particle production. No human rhinovirus was detected in exhaled breath samples. Three healthy subjects exhaled less than 100 particles per liter of exhaled air during tidal breathing and increased particle concentrations more with exhalation to RV than with coughing, swallowing, or rapid exhalation. CONCLUSIONS: Submicron particles were detected in the exhaled breath of healthy and HRV-infected subjects. Particle concentrations were correlated with airflow during the first half of exhalation, and peaked at the end of exhalation, indicating both lower and upper airways as particle sources. The effect of breathing maneuver suggested a major contribution from lower airways, probably the result of opening collapsed small airways and alveoli.

An optimized method to detect influenza virus and human rhinovirus from exhaled breath and the airborne environment.

Respiratory viruses are difficult to characterize in the airborne environment due to their low concentration and the presence of a wide range of inhibitors. As a first step in studying airborne viruses, we optimized molecular biology methods to quantify influenza viruses and human rhinovirus. Quantitative PCR was used as an endpoint to evaluate RNA extraction techniques and reverse transcription protocols. We found that a Trizol-chloroform extraction and MultiScribe RT increased virus detection 10-fold compared to methods used in published field studies of airborne respiratory viruses. Virus was recovered without inhibition from samples contaminated with up to 50 microg/sample of particulate matter. The methods developed can be used in studies of airborne respiratory viruses.

Influenza virus in human exhaled breath: an observational study.

BACKGROUND: Recent studies suggest that humans exhale fine particles during tidal breathing but little is known of their composition, particularly during infection. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a study of influenza infected patients to characterize influenza virus and particle concentrations in their exhaled breath. Patients presenting with influenza-like-illness, confirmed influenza A or B virus by rapid test, and onset within 3 days were recruited at three clinics in Hong Kong, China. We collected exhaled breath from each subject onto Teflon filters and measured exhaled particle concentrations using an optical particle counter. Filters were analyzed for influenza A and B viruses by quantitative polymerase chain reaction (qPCR). Twelve out of thirteen rapid test positive patients provided exhaled breath filter samples (7 subjects infected with influenza B virus and 5 subjects infected with influenza A virus). We detected influenza virus RNA in the exhaled breath of 4 (33%) subjects--three (60%) of the five patients infected with influenza A virus and one (14%) of the seven infected with influenza B virus. Exhaled influenza virus RNA generation rates ranged from <3.2 to 20 influenza virus RNA particles per minute. Over 87% of particles exhaled were under 1 microm in diameter. CONCLUSIONS: These findings regarding influenza virus RNA suggest that influenza virus may be contained in fine particles generated during tidal breathing, and add to the body of literature suggesting that fine particle aerosols may play a role in influenza transmission.