Todd A. Jusko

Objective: Existing research suggests that vaccine antibody response can be attenuated by environmental factors, but limited studies have assessed the association with air pollutants. We hypothesize that air pollution exposure early in life can alter immune response in later childhood.Methods: We obtained serum antibody levels of tetanus, diphtheria, and pertussis measured in vaccinated children ages 4-6 years from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) cohort in Mexico. We constructed 1-km2 fine particulate matter (PM2.5) and nitrogen dioxide (NO2) models over the Mexico City Metropolitan Area, which we geocoded to participants’ home addresses. We employed linear mixed-effects models to examine the association between early life exposure to PM2.5 and NO2, measured as averaged pollutants exposures in the first year of life, and log-transformed tetanus, diphtheria, and pertussis (Tdap) antibody levels in later childhood (ages 4-6). Models included random intercepts for participant and were adjusted for temperature, sex, child age at blood draw, maternal age at birth, BMI, and socioeconomic status.Results: 299 children contributed to antibody levels at 4 years (n=287) and 6 years (n=12). We observed negative but imprecise associations with both pollutants. Per 1 µg/m3 increase in one-year postnatal PM2.5, Tdap antibody levels decreased by 3.47% (95%CI: -7.35, 0.57%), 3.37% (95%CI: -7.18, 0.60%), and 2.56% (95%CI: -6.93, 2.02%) respectively. Per 1 µg/m3 increase in one-year postnatal NO2, Tdap antibody levels decreased by 3.89% (95%CI: -7.22, -0.45%), 3.51% (95%CI: -6.81, -0.09%), and 1.93% (95%CI: -5.74, 2.04%) respectively.Conclusion: We found preliminary evidence suggesting decreased antibody levels in response to postnatal PM2.5 and NO2 exposure, though not all results were significant. Additional work is necessary to explore associations for different types of routine vaccinations and at different critical time windows.

Mounting evidence suggests that early-life lead exposure alters immune system functions, including T-cell–dependent antibody responses to childhood immunizations. However, no studies have identified critical windows of susceptibility to lead exposure. The aim of this study was to identify perinatal critical windows of lead exposure that are associated with antibody responses to anti-MMR (measles, mumps, and rubella virus) and anti-DTP (anti-diphtheria, tetanus, and pertussis toxoids) vaccinations in Hispanic school-aged (mean ± standard deviation: 4.8 ± 0.6 years) children. Weekly lead exposure—from 16 weeks before to 14 weeks after birth—was measured in deciduous teeth from 271 children enrolled in the PROGRESS study. Serum levels of anti-MMR and anti-DTP antibodies were measured by a Luminex multiplexed microbead array immunoassay. Time-varying associations between log2-transformed dentine lead concentrations and log2-transformed antibody levels were estimated by fitting distributed lag nonlinear models. A 2-fold higher dentine lead concentration in the first 3 weeks postpartum was associated with an average –4.29% lower antitetanus level (95% CI, –8.22 to –0.20). A perinatal (1 week before to 1 week after birth) critical window of lead exposure demonstrated an average –3.44% (95% CI, –7.05 to 0.30) lower anti-diphtheria antibody level. Our study suggests that early-life lead exposure may contribute to immune dysfunction by reducing children’s antibody responses to scheduled vaccinations.

Cancer-related fatigue is a prevalent, debilitating condition, and preliminary evidence suggests a relationship between higher diet quality and lower fatigue. Serum-based carotenoids, Vitamin A, and Vitamin E are biomarkers of fruit and vegetable intake and therefore diet quality. To further elucidate the link between diet quality and cancer-related fatigue, associations were assessed between these serum-based nutrients and fatigue among American adults with special attention to cancer history. Data were analyzed from the United States 2005–2006 National Health and Nutrition Examination Survey dataset. Ten carotenoids, vitamin A, vitamin E, and γ-tocopherol were measured from fasting blood samples and fatigue was patient-reported. Associations between carotenoid concentration and fatigue were estimated using ordinal logistic regression models. Adjusted models included a diagnosis of cancer (with the exception on nonmelanoma skin cancer, yes/no), age, body mass index, race/ethnicity, education, and exercise habits as covariates, and additional models included a cancer × nutrient interaction. Of 4,091 participants, 272 (8.0%) reported a history of cancer. Greater fatigue was associated with lower serum trans-lycopene, retinyl palmitate, and retinyl stearate (all P < 0.05) in separate models adjusting for potential confounders. For these nutrients, a one-SD increase in nutrient was associated with a 6.8%–9.9% lower risk of greater fatigue. Among cancer survivors only (n = 272), statistically significant associations were not observed between any of the nutrients and fatigue. In conclusion, greater serum concentrations of carotenoid biomarkers were associated with less fatigue. These results support further exploration into relationships between carotenoid intake, diet quality, and persistent fatigue.Significance:Cancer-related fatigue often persists for years into survivorship, reduces quality of life, and prevents people from returning to their lives before cancer. Interventions to address cancer-related fatigue are much needed. Herein, serum carotenoids were associated with lower fatigue, thereby supporting further development of nutritional interventions to address fatigue in survivorship.

Suppl. Table 1. Results of crude and adjusted models describing the association between carotenoid concentrations and fatigue: all model output. For body mass index, estimates are compared to normal weight (18.5-<25 kg/m2); 1=<18.5 kg/m2, 3=25-<30 kg/m2, and 4=≥30 kg/m2). For race/ethnicity, estimates are compared to non-Hispanic White, 1=Mexican American, 2=Other Hispanic, 4=non-Hispanic Black American, 5=Other non-Hispanic race, including multi-racial. For education, estimates are compared to having at least a college education (11= less than a high school education, 12= at least high school but less than a four-year college education, 13=at least a four-year college education).Suppl. Table 2. Results of adjusted model with the nutrient×cancer interaction term to explore the associations between carotenoids and cancer-related fatigue: all model output.Suppl. Table 3. Adjusted odds ratios and 95% confidence intervals for the effects of the nutrient×cancer interaction on fatigue. Models are adjusted for age, body mass index, race/ethnicity, education, physical activity, history of a cancer diagnosis, and nutrient concentration.Suppl. Table 4. Results of adjusted models (no interaction term) describing the association between carotenoid concentrations and fatigue only among cancer survivors: all model output; estimates for race/ethnicity are compared to non-Hispanic Whites, 1=Mexican American, 2=Other Hispanic, 4=non-Hispanic Black American, 5=Other non-Hispanic race, including multi-racial; estimates for body mass index are compared to those of normal weight; and estimates for education are compared to those with at least a college education. Exercise is estimated from metabolic equivalents (MET hours) per week as a continuous variable. Age, Years since Diagnosis, and carotenoid concentration are treated as continuous variables. (n=272)

Cancer-related fatigue is a prevalent, debilitating condition, and preliminary evidence suggests a relationship between higher diet quality and lower fatigue. Serum-based carotenoids, Vitamin A, and Vitamin E are biomarkers of fruit and vegetable intake and therefore diet quality. To further elucidate the link between diet quality and cancer-related fatigue, associations were assessed between these serum-based nutrients and fatigue among American adults with special attention to cancer history. Data were analyzed from the United States 2005–2006 National Health and Nutrition Examination Survey dataset. Ten carotenoids, vitamin A, vitamin E, and γ-tocopherol were measured from fasting blood samples and fatigue was patient-reported. Associations between carotenoid concentration and fatigue were estimated using ordinal logistic regression models. Adjusted models included a diagnosis of cancer (with the exception on nonmelanoma skin cancer, yes/no), age, body mass index, race/ethnicity, education, and exercise habits as covariates, and additional models included a cancer × nutrient interaction. Of 4,091 participants, 272 (8.0%) reported a history of cancer. Greater fatigue was associated with lower serum trans-lycopene, retinyl palmitate, and retinyl stearate (all P < 0.05) in separate models adjusting for potential confounders. For these nutrients, a one-SD increase in nutrient was associated with a 6.8%–9.9% lower risk of greater fatigue. Among cancer survivors only (n = 272), statistically significant associations were not observed between any of the nutrients and fatigue. In conclusion, greater serum concentrations of carotenoid biomarkers were associated with less fatigue. These results support further exploration into relationships between carotenoid intake, diet quality, and persistent fatigue.Significance:Cancer-related fatigue often persists for years into survivorship, reduces quality of life, and prevents people from returning to their lives before cancer. Interventions to address cancer-related fatigue are much needed. Herein, serum carotenoids were associated with lower fatigue, thereby supporting further development of nutritional interventions to address fatigue in survivorship.

Suppl. Table 1. Results of crude and adjusted models describing the association between carotenoid concentrations and fatigue: all model output. For body mass index, estimates are compared to normal weight (18.5-<25 kg/m2); 1=<18.5 kg/m2, 3=25-<30 kg/m2, and 4=≥30 kg/m2). For race/ethnicity, estimates are compared to non-Hispanic White, 1=Mexican American, 2=Other Hispanic, 4=non-Hispanic Black American, 5=Other non-Hispanic race, including multi-racial. For education, estimates are compared to having at least a college education (11= less than a high school education, 12= at least high school but less than a four-year college education, 13=at least a four-year college education).Suppl. Table 2. Results of adjusted model with the nutrient×cancer interaction term to explore the associations between carotenoids and cancer-related fatigue: all model output.Suppl. Table 3. Adjusted odds ratios and 95% confidence intervals for the effects of the nutrient×cancer interaction on fatigue. Models are adjusted for age, body mass index, race/ethnicity, education, physical activity, history of a cancer diagnosis, and nutrient concentration.Suppl. Table 4. Results of adjusted models (no interaction term) describing the association between carotenoid concentrations and fatigue only among cancer survivors: all model output; estimates for race/ethnicity are compared to non-Hispanic Whites, 1=Mexican American, 2=Other Hispanic, 4=non-Hispanic Black American, 5=Other non-Hispanic race, including multi-racial; estimates for body mass index are compared to those of normal weight; and estimates for education are compared to those with at least a college education. Exercise is estimated from metabolic equivalents (MET hours) per week as a continuous variable. Age, Years since Diagnosis, and carotenoid concentration are treated as continuous variables. (n=272)

Cancer-related fatigue is a prevalent, debilitating condition, and preliminary evidence suggests a relationship between higher diet quality and lower fatigue. Serum-based carotenoids, Vitamin A, and Vitamin E are biomarkers of fruit and vegetable intake and therefore diet quality. To further elucidate the link between diet quality and cancer-related fatigue, associations were assessed between these serum-based nutrients and fatigue among American adults with special attention to cancer history. Data were analyzed from the United States 2005–2006 National Health and Nutrition Examination Survey dataset. Ten carotenoids, vitamin A, vitamin E, and γ-tocopherol were measured from fasting blood samples and fatigue was patient-reported. Associations between carotenoid concentration and fatigue were estimated using ordinal logistic regression models. Adjusted models included a diagnosis of cancer (with the exception on nonmelanoma skin cancer, yes/no), age, body mass index, race/ethnicity, education, and exercise habits as covariates, and additional models included a cancer × nutrient interaction. Of 4,091 participants, 272 (8.0%) reported a history of cancer. Greater fatigue was associated with lower serum trans-lycopene, retinyl palmitate, and retinyl stearate (all P < 0.05) in separate models adjusting for potential confounders. For these nutrients, a one-SD increase in nutrient was associated with a 6.8%–9.9% lower risk of greater fatigue. Among cancer survivors only (n = 272), statistically significant associations were not observed between any of the nutrients and fatigue. In conclusion, greater serum concentrations of carotenoid biomarkers were associated with less fatigue. These results support further exploration into relationships between carotenoid intake, diet quality, and persistent fatigue.Significance: Cancer-related fatigue often persists for years into survivorship, reduces quality of life, and prevents people from returning to their lives before cancer. Interventions to address cancer-related fatigue are much needed. Herein, serum carotenoids were associated with lower fatigue, thereby supporting further development of nutritional interventions to address fatigue in survivorship.

Experimental and epidemiological evidence suggests that environmental toxicants may influence susceptibility to influenza and respiratory syncytial virus (RSV). The objective of the present study was to estimate the association between blood lead concentrations and the odds of child influenza or RSV infection. A test-negative, case-control study was conducted among 617 children, <4 years of age, tested for influenza/RSV from 2012–2017 in Rochester, NY. There were 49 influenza cases (568 controls) and 123 RSV cases (494 controls). Blood lead concentrations reported in children’s medical records were linked with influenza/RSV lab test results. Covariables were collected from medical records, birth certificates, and U.S. census data. In this sample, evidence of an association between blood lead levels and RSV or influenza diagnosis was not observed. Children with a lead level ≥1 μg/dL vs. <1 μg/dL had an adjusted odds ratio (aOR) and 95% confidence limit of 0.95 (0.60, 1.49) for RSV and 1.34 (0.65, 2.75) for influenza. In sex-specific analyses, boys with lead concentrations ≥1 μg/dL vs. <1 μg/dL had an aOR = 1.89 (1.25, 2.86) for influenza diagnosis, while the estimates were inconsistent for girls. These results are suggestive of sex-specific associations between blood lead levels and the risk of influenza, although the sample size was small.