Faculty Bibliography

BACKGROUND:The spectrum of mortality outcomes by cause in populations with/without dyspnoea has not been determined. The study aimed to evaluate whether dyspnoea, a symptom, predicts cause-specific mortality differences between groups. The hypothesis was that diseases that result in chronic dyspnoea, those originating from the heart and lungs, would preferentially result in heart and lung disease mortality in those with baseline dyspnoea (relative to no dyspnoea) when followed over time. METHODS:A population-based sample of 11 533 Bangladeshis was recruited and followed for 11-12 years and cause-specific mortality evaluated in those with and without baseline dyspnoea. Dyspnoea was ascertained by trained physicians. The cause of death was determined by verbal autopsy. Kaplan-Meier survival curves, the Fine-Gray competing risk hazards model and logistic regression models were used to determine group differences in cause-specific mortality. RESULTS:Compared to those not reporting dyspnoea at baseline, the adjusted HRs were 6.4 (3.8 to 10.7), 9.3 (3.9 to 22.3), 1.8 (1.2 to 2.8), 2.2 (1.0 to 5.1) and 2.8 (1.3 to 6.2) for greater risk of dying from chronic obstructive pulmonary disease (COPD), asthma, heart disease, tuberculosis and lung cancer, respectively. In contrast, there was a similar risk of dying from stroke, cancer (excluding lung), liver disease, accidents and other (miscellaneous causes) between the dyspnoeic and non-dyspnoeic groups. In addition, the HR was 2.1 (1.7 to 2.5) for greater all-cause mortality in those with baseline dyspnoea versus no dyspnoea. CONCLUSIONS:Dyspnoea, ascertained by a single question with binary response, predicts heart and lung disease mortality. Individuals reporting dyspnoea were twofold to ninefold more likely to die of diseases that involve the heart and/or lungs relative to the non-dyspnoeic individuals. Therefore, in those with chronic dyspnoea, workup to look for the five common dyspnoeic diseases resulting in increased mortality (COPD, asthma, heart disease, tuberculosis and lung cancer), all treatable, should reduce mortality and improve the public health.

Early childhood is a critical stage for the foundation and development of both the microbiome and host. Early-life antibiotic exposures, cesarean section, and formula feeding could disrupt microbiome establishment and adversely affect health later in life. We profiled microbial development during the first 2 years of life in a cohort of 43 U.S. infants and identified multiple disturbances associated with antibiotic exposures, cesarean section, and formula feeding. These exposures contributed to altered establishment of maternal bacteria, delayed microbiome development, and altered alpha-diversity. These findings illustrate the complexity of early-life microbiome development and its sensitivity to perturbation.

BACKGROUND:Exposure to inorganic arsenic (iAs), a class I carcinogen, affects several hundred million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%) varies across individuals, reflecting differences in arsenic metabolism capacity. METHODS:The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal component (PC) analysis of arsenic species. RESULTS:Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (second methylation step), and PC2 appears to represent capacity to convert iAs to MMA (first methylation step). PC1 was positively associated (P <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negatively associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations. CONCLUSIONS:Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions. IMPACT/CONCLUSIONS:This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles.

OBJECTIVE: Carotid intima-media thickness (IMT) is a validated surrogate marker of preclinical atherosclerosis and is predictive of cardiovascular morbidity and mortality. Research on the association between IMT and diet, however, is lacking, especially in low-income countries or low-BMI populations. DESIGN: Cross-sectional analysis. Dietary intakes were measured using a validated, thirty-nine-item FFQ at baseline cohort recruitment. IMT measurements were obtained from 2010-2011. SETTING: Rural Bangladesh. SUBJECTS: Participants (n 1149) randomly selected from the Health Effects of Arsenic Longitudinal Study, an ongoing, population-based, prospective cohort study established in 2000. Average age at IMT measurement was 45.5 years. RESULTS: Principal component analysis of reported food items yielded a 'balanced' diet, an 'animal protein' diet and a 'gourd and root vegetable' diet. We observed a positive association between the gourd/root vegetable diet and IMT, as each 1 sd increase in pattern adherence was related to a difference of 7.74 (95 % CI 2.86, 12.62) mum in IMT (P<0.01), controlling for age, sex, total energy intake, smoking status, BMI, systolic blood pressure and diabetes mellitus diagnoses. The balanced pattern was associated with lower IMT (-4.95 (95 % CI -9.78, -0.11) mum for each 1sd increase of adherence; P=0.045). CONCLUSIONS: A gourd/root vegetable diet in this Bangladeshi population positively correlated with carotid IMT, while a balanced diet was associated with decreased IMT.

OBJECTIVE: Recent evidence has suggested that polycyclic aromatic hydrocarbons (PAHs) may contribute to cardiometabolic and kidney dysfunction by increasing oxidative stress, but little is known about impacts in childhood. STUDY DESIGN: We performed cross-sectional analyses of 660 adolescents aged 12-19 years in the 2003-2008 National Health and Nutrition Examination Survey (NHANES), using levels of 10 monohydroxylated urinary PAH metabolites as our exposure. Our primary outcomes of interest were biomarkers of oxidative stress and renal function, including estimated glomerular filtration rate (eGFR), urinary albumin to creatinine ratio (ACR), insulin resistance, and serum uric acid, gamma glutamyl transferase (GGT) and C-reactive protein (CRP). RESULTS: We observed statistically significant associations between PAH metabolites and levels of serum GGT, CRP, uric acid and eGFR. Each 100% increase in 2-hydroxyphenanthrene was related to a 3.36% increase in uric acid (95% CI: 0.338-6.372; p=0.032), a 3.86% increase in GGT (95% CI: 1.361-6.362; p=0.005) and a 16.78% increase in CRP (95% CI: 1.848-31.689; p=0.029). Each 100% increase in 4-hydroxyphenanthrene was associated with a 6.18% increase in GGT (95% CI: 4.064-8.301; p<0.001) and a 13.66% increase in CRP (95% CI: 2.764-24.564; p=0.017). Each 100% increase in 9-hydroxyfluorene was associated with a 2.58% increase in GGT (95% CI: 0.389-4776; p=0.024). Each 100% increase in 3-hydroxyphenanthrene was associated with a 2.66% decrease in eGFR (95% CI: -4.979 to -0.331; p=0.028). CONCLUSIONS: Urinary PAH metabolites were associated with serum uric acid, GGT and CRP, suggesting possible impacts on cardiometabolic and kidney function in adolescents. Prospective work is needed to investigate the potential long-term health consequences of these findings.

BACKGROUND: Taurine (2-aminoethanesulfonic acid), a conditionally essential sulfur-containing amino acid, is mainly obtained from diet in humans. Experimental studies have shown that taurine's main biological actions include bile salt conjugation, blood pressure regulation, anti-oxidation, and anti-inflammation. METHODS: We conducted a prospective case-control study nested in the New York University Women's Health Study, a cohort study involving 14,274 women enrolled since 1985. Taurine was measured in pre-diagnostic serum samples of 241 stroke cases and 479 matched controls. RESULTS: There was no statistically significant association between serum taurine and stroke risk in the overall study population. The adjusted ORs for stroke were 1.0 (reference), 0.87 (95% CI, 0.59-1.28), and 1.03 (95% CI, 0.69-1.54) in increasing tertiles of taurine (64.3-126.6, 126.7-152.9, and 153.0-308.5 nmol/mL, respectively). A significant inverse association between serum taurine and stroke risk was observed among never smokers, with an adjusted OR of 0.66 (95% CI, 0.37-1.18) and 0.50 (95% CI, 0.26-0.94) for the second and third tertile, respectively (p for trend = 0.01), but not among past or current smokers (p for interaction < 0.01). CONCLUSIONS: We observed no overall association between serum taurine and stroke risk, although a protective effect was observed in never smokers, which requires further investigation. Taurine, Stroke, Epidemiology, Prospective, Case-control study, NYUWHS.

BACKGROUND: Ischemic heart disease (IHD) mortality has been on the decline in the United States for decades. However, declines in IHD mortality have been slower in certain groups, including young women and black individuals. HYPOTHESIS: Trends in IHD vary by age, sex, and race in New York City (NYC). Young female minorities are a vulnerable group that may warrant renewed efforts to reduce IHD. METHODS: IHD mortality trends were assessed in NYC 1980-2008. NYC Vital Statistics data were obtained for analysis. Age-specific IHD mortality rates and confidence bounds were estimated. Trends in IHD mortality were compared by age and race/ethnicity using linear regression of log-transformed mortality rates. Rates and trends in IHD mortality rates were compared between subgroups defined by age, sex and race/ethnicity. RESULTS: The decline in IHD mortality rates slowed in 1999 among individuals aged 35-54 years but not >/=55. IHD mortality rates were higher among young men than women age 35-54, but annual declines in IHD mortality were slower for women. Black women age 35-54 had higher IHD mortality rates and slower declines in IHD mortality than women of other race/ethnicity groups. IHD mortality trends were similar in black and white men age 35-54. CONCLUSIONS: The decline in IHD mortality rates has slowed in recent years among younger, but not older, individuals in NYC. There was an association between sex and race/ethnicity on IHD mortality rates and trends. Young black women may benefit from targeted medical and public health interventions to reduce IHD mortality.

The main purpose of this study was to identify policy maker opinions and attitudes towards children's environmental health (CEH), potential barriers to child-specific protective legislation and implementation in northwest China, and evaluate knowledge and attitudes about CEH before and after an educational conference. We conducted seventy-two interviews with regional officials, researchers and non-governmental organization representatives from five provinces, and surveyed participants (forty-seven) before and after an educational conference in northwest China about CEH. Interviews identified general consensus among participants of the adverse effects of air pollution on children, yet few participants knew of policies to protect them. Barriers identified included limited funding and enforcement, weak regional governments and absence of child-specific policy-making. After the conference, substantially greater self-efficacy was identified for lead, mercury, air pollution and polychlorinated biphenyls (+0.57-0.72 on a 1-5 Likert scale, p = 0.002-0.013), and the scientific knowledge for the role of environment in children's health (+0.58, p = 0.015), and health care provider control (+0.52, p = 0.025) were rated more strongly. We conclude that policy makers in Northwest China appreciate that children are uniquely vulnerable, though additional regulations are needed to account for that vulnerability. Further research should examine effectiveness of the intervention on a larger scale and scope, and evaluate the usefulness of such interventions in translating research into improved care/reduced exposure to environmental hazards.