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Importance: Socioeconomically disadvantaged subpopulations are more vulnerable to fine particulate matter (PM2.5) exposure. However, as prior studies focused on individual-level socioeconomic characteristics, how contextual deprivation modifies the association of PM2.5 exposure with cardiovascular health remains unclear. Objective: To assess disparities in PM2.5 exposure association with cardiovascular disease among subpopulations defined by different socioeconomic characteristics. Design, Setting, and Participants: This cohort study used longitudinal data on participants with electronic health records (EHRs) from the All of Us Research Program between calendar years 2016 and 2022. Statistical analysis was performed from September 25, 2023, through February 23, 2024. Exposure: Satellite-derived 5-year mean PM2.5 exposure at the 3-digit zip code level according to participants' residential address. Main Outcome and Measures: Incident myocardial infarction (MI) and stroke were obtained from the EHRs. Stratified Cox proportional hazards regression models were used to estimate the hazard ratio (HR) between PM2.5 exposure and incident MI or stroke. We evaluated subpopulations defined by 3 socioeconomic characteristics: contextual deprivation (less deprived, more deprived), annual household income (≥$50 000, <$50 000), and race and ethnicity (non-Hispanic Black, non-Hispanic White). We calculated the ratio of HRs (RHR) to quantify disparities between these subpopulations. Results: A total of 210â¯554 participants were analyzed (40% age >60 years; 59.4% female; 16.7% Hispanic, 19.4% Non-Hispanic Black, 56.1% Non-Hispanic White, 7.9% other [American Indian, Asian, more than 1 race and ethnicity]), among whom 954 MI and 1407 stroke cases were identified. Higher PM2.5 levels were associated with higher MI and stroke risks. However, disadvantaged groups (more deprived, income <$50 000 per year, Black race) were more vulnerable to high PM2.5 levels. The disparities were most pronounced between groups defined by contextual deprivation. For instance, increasing PM2.5 from 6 to 10 µg/m3, the HR for stroke was 1.13 (95% CI, 0.85-1.51) in the less-deprived vs 2.57 (95% CI, 2.06-3.21) in the more-deprived cohort; 1.46 (95% CI, 1.07-2.01) in the $50 000 or more per year vs 2.27 (95% CI, 1.73-2.97) in the under $50 000 per year cohort; and 1.70 (95% CI, 1.35-2.16) in White individuals vs 2.76 (95% CI, 1.89-4.02) in Black individuals. The RHR was highest for contextual deprivation (2.27; 95% CI, 1.59-3.24), compared with income (1.55; 95% CI, 1.05-2.29) and race and ethnicity (1.62; 95% CI, 1.02-2.58). Conclusions and Relevance: In this cohort study, while individual race and ethnicity and income remained crucial in the adverse association of PM2.5 with cardiovascular risks, contextual deprivation was a more robust socioeconomic characteristic modifying the association of PM2.5 exposure.
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Poluição do Ar , Doenças Cardiovasculares , Renda , Material Particulado , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Material Particulado/efeitos adversos , Renda/estatística & dados numéricos , Idoso , Doenças Cardiovasculares/epidemiologia , Estados Unidos/epidemiologia , Adulto , Etnicidade/estatística & dados numéricos , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etnologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/estatística & dados numéricos , Estudos Longitudinais , Fatores Socioeconômicos , Estudos de Coortes , Grupos Raciais/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etnologia , Disparidades nos Níveis de SaúdeRESUMO
Asthma has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omic signatures of asthma focusing on populations of African ancestry. RNASeq and DNA methylation data are generated from nasal epithelium including cases (current asthma, N = 253) and controls (never-asthma, N = 283) from 7 different geographic sites to identify differentially expressed genes (DEGs) and gene networks. We identify 389 DEGs; the top DEG, FN1, was downregulated in cases (q = 3.26 × 10-9) and encodes fibronectin which plays a role in wound healing. The top three gene expression modules implicate networks related to immune response (CEACAM5; p = 9.62 × 10-16 and CPA3; p = 2.39 × 10-14) and wound healing (FN1; p = 7.63 × 10-9). Multi-omic analysis identifies FKBP5, a co-chaperone of glucocorticoid receptor signaling known to be involved in drug response in asthma, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. This work reveals molecular dysregulation on three axes - increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response - that may play a critical role in asthma within the African Diaspora.
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Asma , População Negra , Metilação de DNA , Mucosa Nasal , Proteínas de Ligação a Tacrolimo , Humanos , Asma/genética , Asma/metabolismo , Mucosa Nasal/metabolismo , Proteínas de Ligação a Tacrolimo/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Feminino , Masculino , População Negra/genética , Adulto , Redes Reguladoras de Genes , Fibronectinas/metabolismo , Fibronectinas/genética , Estudos de Casos e Controles , Regulação da Expressão Gênica , Pessoa de Meia-Idade , MultiômicaRESUMO
Background: An estimated 3 billion people, largely in low- and middle-income countries, rely on unclean fuels for cooking, heating, and lighting to meet household energy needs. The resulting exposure to household air pollution (HAP) is a leading cause of pneumonia, chronic lung disease, and other adverse health effects. In the last decade, randomized controlled trials of clean cooking interventions to reduce HAP have been conducted. We aim to provide guidance on how to interpret the findings of these trials and how they should inform policy makers and practitioners.Methods: We assembled a multidisciplinary working group of international researchers, public health practitioners, and policymakers with expertise in household air pollution from within academia, the American Thoracic Society, funders, nongovernmental organizations, and global organizations, including the World Bank and the World Health Organization. We performed a literature search, convened four sessions via web conference, and developed consensus conclusions and recommendations via the Delphi method.Results: The committee reached consensus on 14 conclusions and recommendations. Although some trials using cleaner-burning biomass stoves or cleaner-cooking fuels have reduced HAP exposure, the committee was divided (with 55% saying no and 45% saying yes) on whether the studied interventions improved measured health outcomes.Conclusions: HAP is associated with adverse health effects in observational studies. However, it remains unclear which household energy interventions reduce exposure, improve health, can be scaled, and are sustainable. Researchers should engage with policy makers and practitioners working to scale cleaner energy solutions to understand and address their information needs.
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Poluição do Ar , Países em Desenvolvimento , Humanos , Biomassa , Consenso , Sociedades , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Exposure to air pollutants and other environmental factors increases the risk of adverse pregnancy outcomes. There is growing evidence that adverse outcomes related to air pollution disproportionately affect racial and ethnic minorities. The objective of this paper is to explore the importance of race as a risk factor for air pollution-related poor pregnancy outcomes. METHODS: Studies investigating the effects of exposure to air pollution on pregnancy outcomes by race were reviewed. A manual search was conducted to identify missing studies. Studies that did not compare pregnancy outcomes among two or more racial groups were excluded. Pregnancy outcomes included preterm births, small for gestational age, low birth weight, and stillbirths. RESULTS: A total of 124 articles explored race and air pollution as risk factors for poor pregnancy outcome. Thirteen percent of these (n=16) specifically compared pregnancy outcomes among two or more racial groups. Findings across all reviewed articles showed more adverse pregnancy outcomes (preterm birth, small for gestational age, low birth weight, and stillbirths) related to exposure to air pollution among Blacks and Hispanics than among non-Hispanic Whites. CONCLUSION: Evidence support our general understanding of the impact of air pollution on birth outcomes and, specifically, of disparities in exposure to air pollution and birth outcomes for infants born to Black and Hispanic mothers. The factors driving these disparities are multifactorial, mostly social, and economic factors. Reducing or eliminating these disparities require interventions at individual, community, state, and national level.
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Poluição do Ar , Nascimento Prematuro , Feminino , Gravidez , Recém-Nascido , Estados Unidos/epidemiologia , Humanos , Resultado da Gravidez , Natimorto , Nascimento Prematuro/epidemiologia , Recém-Nascido de Baixo Peso , Poluição do Ar/efeitos adversosRESUMO
BACKGROUND: Ambient fine particulate matter (PM2.5) exposure has been related to cardiometabolic diseases, but the underlying biological pathways remain unclear at the population level. OBJECTIVE: To investigate the effect of PM2.5 exposure on changes in multiple cardiometabolic biomarkers across different exposure durations. METHOD: Data from a prospective cohort study were analyzed. Ten cardiometabolic biomarkers were measured, including ghrelin, resistin, leptin, C-peptide, creatine kinase myocardial band (CK-MB), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), N-terminal pro B-type natriuretic peptide (NT-proBNP), troponin, and interleukin-6 (IL-6). PM2.5 levels across exposure durations from 1 to 36 months were assessed. Mixed effect model was used to estimate changes in biomarker levels against 1 µg/m3 increase in PM2.5 level across different exposure durations. RESULTS: Totally, 641 participants were included. The average PM2.5 exposure level was 9 µg/m3. PM2.5 exposure was inversely associated with ghrelin, and positively associated with all other biomarkers. The magnitudes of these associations were duration-sensitive and exhibited a U-shaped or inverted-U-shaped trend. For example, the association of resistin were ß = 0.05 (95% CI: 0.00, 0.09) for 1-month duration, strengthened to ß = 0.27 (95% CI: 0.14, 0.41) for 13-month duration, and weakened to ß = 0.12 (95% CI: -0.03, 0.26) for 24-month duration. Similar patterns were observed for other biomarkers except for CK-MB, of which the association direction switched from negative to positive as the duration increased. Resistin, leptin, MCP-1, TNF-alpha, and troponin had a sensitive exposure duration of nearly 12 months. Ghrelin and C-peptide were more sensitive to longer-term exposure (>18 months), while NT-proBNP and IL-6 were more sensitive to shorter-term exposure (<6 months). CONCLUSION: PM2.5 exposure was associated with elevated levels in cardiometabolic biomarkers related to insulin resistance, inflammation, and heart injury. The magnitudes of these associations depended on the exposure duration. The most sensitive exposure durations of different biomarkers varied.
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Poluentes Atmosféricos , Poluição do Ar , Doenças Cardiovasculares , Humanos , Poluentes Atmosféricos/análise , Leptina , Grelina , Resistina , Estudos Prospectivos , Negro ou Afro-Americano , Peptídeo C , Interleucina-6 , Fator de Necrose Tumoral alfa , Material Particulado/toxicidade , Material Particulado/análise , Biomarcadores , Doenças Cardiovasculares/epidemiologia , Troponina , Exposição AmbientalRESUMO
BACKGROUND: Breast cancer survivors face long-term sequelae compared to the general population, suggesting altered metabolic profiles after breast cancer. We used metabolomics approaches to investigate the metabolic differences between breast cancer patients and women in the general population, aiming to elaborate metabolic changes among breast cancer patients and identify potential targets for clinical interventions to mitigate long-term sequelae. METHODS: Serum samples were retrieved from 125 breast cancer cases recruited from the Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), and 125 healthy controls selected from Chicago Multiethnic Prevention and Surveillance Study (COMPASS). We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) combined with fold change to select metabolic features associated with breast cancer. Pathway analyses were conducted using Mummichog to identify differentially enriched metabolic pathways among cancer patients. As potential confounders we included age, marital status, tobacco smoking, alcohol drinking, type 2 diabetes, and area deprivation index in our model. Random effects of residence for intercept was also included in the model. We further conducted subgroup analysis by treatment timing (chemotherapy/radiotherapy/surgery), lymph node status, and cancer stages. RESULTS: The entire study participants were African American. The average ages were 57.1 for cases and 58.0 for controls. We extracted 15,829 features in total, among which 507 features were eventually selected by our criteria. Pathway enrichment analysis of these 507 features identified three differentially enriched metabolic pathways related to prostaglandin, leukotriene, and glycerophospholipid. The three pathways demonstrated inconsistent patterns. Metabolic features in the prostaglandin and leukotriene pathways exhibited increased abundances among cancer patients. In contrast, metabolic intensity in the glycerolphospholipid pathway was deregulated among cancer patients. Subgroup analysis yielded consistent results. However, changes in these pathways were strengthened when only using cases with positive lymph nodes, and attenuated when only using cases with stage I disease. CONCLUSION: Breast cancer in African American women is associated with increase in serum metabolites involved in prostaglandin and leukotriene pathways, but with decrease in serum metabolites in glycerolphospholipid pathway. Positive lymph nodes and advanced cancer stage may strengthen changes in these pathways.
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Neoplasias da Mama , Metaboloma , Feminino , Humanos , Negro ou Afro-Americano , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Metabolômica/métodosRESUMO
This study aimed to investigate the joint effect of neighborhood disadvantages on asthma prevalence and evaluate whether individual-level variables protect residents against neighborhood disadvantages. Data from the Chicago Multiethnic Prevention and Surveillance Study (from 2013-2020) were analyzed. Eight neighborhood characteristics were measured using the Chicago Health Atlas, including neighborhood unsafety, limited access to healthy food, neighborhood alienation, severe rent burden, vacant housing, single-parent household, neighborhood poverty, and unemployment. A structured questionnaire measured asthma diagnosis (childhood or adulthood) and individual-level variables including sex, age, income, education, and race. Weighted quantile sum (WQS) regression was used to evaluate the impact of neighborhood disadvantages. Stratified analysis was performed by income and education. A total of 6,592 participants (mean age = 53.5 (standard deviation, 11.1) years) were included. Most of the study population were non-Hispanic Black (82.5%) and reported an annual household income less than $15,000 (53%). Asthma prevalence was 23.6%. The WQS index, which represents the overall neighborhood disadvantages, was associated with asthma prevalence (odds ratio = 1.14, 95% confidence interval: 1.07, 1.22) when adjusted for individual-level confounders. Neighborhood poverty contributed 40.8% to the overall impact, followed by vacant housing (23.1%) and neighborhood alienation (22.9%). When stratified by individual-level income or education, no difference was observed for the association between WQS index and asthma prevalence.
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Asma , Negro ou Afro-Americano , Humanos , Pessoa de Meia-Idade , Asma/epidemiologia , Chicago , Características da Vizinhança , PrevalênciaRESUMO
Background: Sickle cell trait/disease (SCT/SCD) are enriched among Black people and associated with various comorbidities. The overrepresentation of these characteristics prevents traditional regression approach obtaining convincing evidence for the independent effect of SCT/SCD on other health outcomes. This study aims to investigate the association between SCT/SCD and COVID-19-related outcomes using causal inference approaches that balance the covariate. Methods: We leveraged electronic health record (EHR) data from the University of Chicago Medicine between March 2020 and December 2021. Demographic characteristics were retrieved. Medical conditions were identified using ICD-10 codes. Five approaches, including two traditional regression approaches (unadjusted and adjusted) and three causal inference approaches [covariate balancing propensity score (CBPS) matching, CBPS weighting, and CBPS adjustment], were employed. Results: A total of 112,334 patients were included in the study, among which 504 had SCT and 388 SCD. Patients with SCT/SCD were more likely to be non-Hispanic Black people, younger, female, non-smokers, and had a diagnosis of diabetes, heart failure, asthma, and cerebral infarction. Causal inference approaches achieved a balanced distribution of these covariates while traditional approaches failed. Across these approaches, SCD was consistently associated with COVID-19-related pneumonia (odds ratios (OR) estimates, 3.23 (95% CI: 2.13-4.89) to 2.57 (95% CI: 1.10-6.00)) and pain (OR estimates, 6.51 (95% CI: 4.68-9.06) to 2.47 (95% CI: 1.35-4.49)). While CBPS matching suggested an association between SCD and COVID-19-related acute respiratory distress syndrome (OR = 2.01, 95% CI: 0.97-4.17), this association was significant in other approaches (OR estimates, 2.96 (95% CI: 1.69-5.18) to 2.50 (95% CI: 1.43-4.37)). No association was observed between SCT and COVID-19-related outcomes in causal inference approaches. Conclusion: Using causal inference approaches, we provide comprehensive evidence for the link between SCT/SCD and COVID-19-related outcomes.
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Children with sickle cell disease (SCD) are particularly prone to pneumococcal infection and administration of Prevenar 13 pneumococcal vaccine in Nigerian children with SCD is yet to be wide spread. This call for the need to study humoral immune responses stimulated by Prevenar 13 pneumococcal vaccine in SCD children to confirm the benefit or otherwise for the use of Prevenar 13 pneumococcal vaccine. Method: The levels of humoral (innate and adaptive) immune factors and associated nutritionally essential trace elements were determined following Prevenar 13 pneumococcal vaccination of 23 Nigerian children with SCD. Serum innate humoral immune factors [Complement factors (C1q and C4), transferrin, ferritin, and C-reactive protein (CRP)] and adaptive humoral immune factors [IgG, IgA, IgM, and IgE] were determined using ELISA. Nutritionally essential trace elements such as iron (Fe), copper (Cu), and zinc (Zn) were measured also using an atomic absorption spectrophotometer. Results: The serum levels of certain innate humoral immune factors (ferritin, CRP, and C4), only one adaptive humoral immune factors (IgE), and essential trace elements (Fe, Zn, and Cu) were significantly elevated in children with SCD post Prevenar 13 pneumococcal vaccination when compared to prevaccination levels. Conclusion: Vaccination of children with SCD with Prevenar 13 pneumococcal vaccine was associated with increased levels of more innate humoral immune factors than adaptive factors. This study thus supports the administration of Prevenar 13 pneumococcal vaccination to children with SCD.
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This study aims to investigate the race/ethnicity-specific association between blood type and COVID-19 susceptibility during March, 2020 and December, 2021 using data from the electronic health record at the University of Chicago Medicine. The study population was stratified into four groups: non-Hispanic White, non-Hispanic Black, Hispanic, and other. Log-binomial generalized mixed model was used to estimate the relative risk (RR) and 95% confidence interval (CI). When compared to blood type O, type B was associated with positive COVID-19 test in Blacks (RR = 1.12, 95% CI: 1.02-1.23), Whites (RR = 1.28, 95% CI: 0.99-1.66), and Hispanic (RR = 1.36, 95% CI: 0.97-1.92).
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RATIONALE: Studies identify prenatal household air pollution (HAP) exposure and maternal psychological distress (PMPD) as independent factors contributing to gestational ill-health and adverse birth outcomes. OBJECTIVE: We investigated the impact of PMPD on fetal biometric parameters (FBP) in HAP-exposed pregnant Nigerian women. METHODS: The randomized controlled trial (RCT; ClinicalTrials.gov NCT02394574) investigated effects of HAP exposure in pregnant Nigerian women (n = 324), who customarily cooked with polluting fuels (firewood or kerosene). Half of the women (intervention group) were given CleanCook ethanol stoves to use for 156 days during the study. Once a month, all women were administered an abridged version of the SF-12v2TM health-related quality of life questionnaire to assess psychological distress. Using mixed effects linear regression models, adjusted for relevant covariates, we analyzed associations between the women's exposure to PM2·5 (particulate matter with an aerodynamic diameter<2·5 microns) from HAP, their PMPD scores, and FBP (ultrasound estimated fetal weight [UEFW], head circumference [HC], abdominal circumference [AC], femur length [FL], biparietal diameter [BPD], estimated gestational age [GA] and intrauterine growth restriction [IUGR]), and birth anthropometric measures (birth weight [BW] and birth length [BL]). RESULTS: PMPD negatively impacted UEFW, HC, FL, BPD and BL (p<0·05). Controls (kerosene/firewood users) experienced significantly higher PMPD compared with ethanol-stove users (p<0·05). The mediation analysis revealed that the proportion of the outcome (fetal biometrics, birth anthropometrics, IUGR and GA), which can be explained via PMPD by groups (intervention vs. control) after adjusting for confounding variables was 6·2% (0·062). No significant correlation was observed between levels of PM2.5 exposure and PMPD scores. CONCLUSIONS: PMPD was an independent mediator of adverse fetal biometric parameters in pregnant women, who were exposed to HAP from burning of firewood/kerosene. Formulating preventative measures to alleviate maternal distress during pregnancy and reducing exposure to HAP is important from public health perspectives.
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Poluição do Ar , Angústia Psicológica , Poluição do Ar/análise , Biometria , Etanol/análise , Feminino , Desenvolvimento Fetal , Retardo do Crescimento Fetal , Humanos , Querosene/análise , Exposição Materna/efeitos adversos , Nigéria , Material Particulado/efeitos adversos , Material Particulado/análise , Gravidez , Qualidade de Vida , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: Low birthweight, intrauterine growth restriction (IUGR) and perinatal mortality have been associated with air pollution. However, intervention studies that use ultrasound measurements to assess the effects of household air pollution (HAP) on fetal biometric parameters (FBP) are rare. We investigated the effect of a cookstove intervention on FBP and IUGR in a randomized controlled trial (RCT) cohort of HAP-exposed pregnant Nigerian women. METHODS: We recruited 324 women early in the second trimester of pregnancy. Between 16 and 18 weeks, we randomized them to either continue cooking with firewood/kerosene (control group) or receive a CleanCook stove and ethanol fuel (intervention group). We measured fetal biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and ultrasound-estimated fetal weight (U-EFW) in the second and third trimesters. The women were clinically followed up at six regular time points during their pregnancies. Once during the women's second trimester and once during the third, we made 72-h continuous measurements of their personal exposures to particulate matter having aerodynamic diameter < 2.5 µm (PM2.5). We adopted a modified intent-to-treat approach for the analysis. Differences between the intervention and control groups on impact of HAP on fetal growth trajectories were analyzed using mixed effects regression models. RESULTS: There were no significant differences in fetal growth trajectories between the intervention and control groups. CONCLUSIONS: Larger studies in a setting of low ambient air pollution are required to further investigate the effect of transitioning to a cleaner fuel such as ethanol on intrauterine growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT02394574 ; September 2012.
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Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Culinária , Desenvolvimento Fetal , Material Particulado/análise , Adolescente , Adulto , Etanol , Feminino , Retardo do Crescimento Fetal , Feto/diagnóstico por imagem , Habitação , Humanos , Querosene , Exposição Materna , Troca Materno-Fetal , Nigéria , Gravidez , Ultrassonografia Pré-Natal , Madeira , Adulto JovemRESUMO
RATIONALE: Lung 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. OBJECTIVE: We 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. METHODS: We 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. RESULTS: Mean 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. CONCLUSIONS: This 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.
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Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Poluição do Ar , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar em Ambientes Fechados/análise , Criança , Pré-Escolar , Culinária , Exposição Ambiental/análise , Feminino , Humanos , Pulmão , Masculino , Nigéria , Oscilometria , Material Particulado/análise , GravidezRESUMO
BACKGROUND: There is both higher mortality and morbidity from cancer in low and medium income countries (LMICs) compared with high income countries (HICs). Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs. Unfortunately, clinical trials remain low in LMICs due to poor infrastructure and paucity of experienced personnel to execute clinical trials. There is an urgent need to build local capacity for evidence-based treatment for cancer patients in LMICs. METHODS: We conducted a survey at facilities in four Teaching Hospitals in South West Nigeria using a checklist of information on various aspects of clinical trial activities. The gaps identified were addressed using resources sourced in partnership with investigators at HIC institutions. RESULTS: Deficits in infrastructure were in areas of patient care such as availability of oncology pharmacists, standard laboratories and diagnostic facilities, clinical equipment maintenance and regular calibrations, trained personnel for clinical trial activities, investigational products handling and disposals and lack of standard operating procedures for clinical activities. There were two GCP trained personnel, two study coordinators and one research pharmacist across the four sites. Interventions were instituted to address the observed deficits in all four sites which are now well positioned to undertake clinical trials in oncology. Training on all aspects of clinical trial was also provided. CONCLUSIONS: Partnerships with institutions in HICs can successfully identify, address, and improve deficits in infrastructure for clinical trial in LMICs. The HICs should lead in providing funds, mentorship, and training for LMIC institutions to improve and expand clinical trials in LMIC countries.
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Ensaios Clínicos como Assunto/organização & administração , Neoplasias/terapia , Fortalecimento Institucional/organização & administração , Humanos , Modelos Organizacionais , NigériaRESUMO
Human epidermal growth factor receptor 2 (HER2) subtype of breast cancer is aggressive, leading to a poor outcome. Targeted therapy with trastuzumab has been shown to be effective in the treatment of HER2-positive breast cancer. Cardiotoxicity is a specific adverse effect associated with trastuzumab. The initial formulation of trastuzumab was intravenous, but presently, a subcutaneous formulation (Herceptin SC) is available. Insufficient data on the response rate and cardiotoxic effects of trastuzumab among indigenous Black populations exist. In all studies evaluating the efficacy and toxicity of trastuzumab alone or in combination with chemotherapy, indigenous Black populations in Africa were not included, yet they are the ones most likely to benefit from highly effective cancer medicines. This is partly due to poor oncology clinical trial infrastructure in sub-Saharan Africa. The ARETTA study protocol (ClinicalTrials.gov identifier: NCT03879577) is a phase II multicenter feasibility study to evaluate the efficacy and toxicity of docetaxel given every 3 weeks for 4 cycles plus trastuzumab in 60 previously untreated women with nonmetastatic breast cancer. The primary endpoint is to assess the proportion of patients with complete pathologic response. Secondary endpoints include the number of patients who require dose delays in docetaxel and trastuzumab attributed to hematologic, GI, and cardiac toxicity. Pharmacokinetic profiles of subcutaneous trastuzumab will also be determined. The ARETTA study will provide important information on the clinical response and cardiac safety of subcutaneous trastuzumab in combination with docetaxel among indigenous African women with nonmetastatic breast cancer. It can also be used as a blueprint for conducting biomarker-driven oncology clinical trials in low-resource settings such as sub-Saharan Africa.
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Neoplasias da Mama , Terapia Neoadjuvante , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Docetaxel/efeitos adversos , Feminino , Humanos , Estudos Multicêntricos como Assunto , Nigéria , Trastuzumab/efeitos adversosRESUMO
There are limited data examining the consequences of environmental exposure to arsenic on the immune system in adults, particularly among smokers. Smoking has been shown to exacerbate or contribute to impaired immune function in men chronically exposed to arsenic. In contrast, vitamin D (VitD) is known to have a positive influence on innate and adaptive immune responses. The effect of circulating VitD on arsenic-associated immune dysfunction is not known. Here we examine the relationship of arsenic exposure and T cell proliferation (TCP), a measure of immune responsiveness, and circulating VitD among adult men and women in Bangladesh. Arsenic exposure was assessed using total urinary arsenic as well as urinary arsenic metabolites all adjusted for urinary creatinine. TCP was measured ex vivo in cryopreserved peripheral blood mononuclear cells from 614 adult participants enrolled in the Bangladesh Health Effects of Arsenic Longitudinal Study; serum VitD was also evaluated. The influence of cigarette smoking on arsenic-induced TCP modulation was assessed only in males as there was an inadequate number of female smokers. These studies show that arsenic suppressed TCP in males. The association was significantly strong in male smokers and to a lesser extent in male non-smokers. Interestingly, we found a strong protective effect of high/sufficient serum VitD levels on TCP among non-smoking males. Furthermore, among male smokers with low serum VitD (â20 ng/ml), we found a strong suppression of TCP by arsenic. On the other hand, high VitD (>20 ng/ml) was found to attenuate effects of arsenic on TCP among male-smokers. Overall, we found a strong protective effect of VitD, when serum levels were >20 ng/ml, on arsenic-induced inhibition of TCP in men, irrespective of smoking status. To our knowledge this is the first large study of immune function in healthy adult males and females with a history of chronic arsenic exposure.
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Arsênio/toxicidade , Exposição Ambiental/efeitos adversos , Fumar/imunologia , Linfócitos T/efeitos dos fármacos , Vitamina D/sangue , Adulto , Idoso , Arsênio/urina , Bangladesh/epidemiologia , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Fumar/epidemiologia , Linfócitos T/imunologia , Vitamina D/imunologiaRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMO
OBJECTIVE: The aim of the descriptive, cross sectional, questionnaire-based study reported here was to explore the causes of low productivity in non-communicable diseases research among postgraduate scholars and early career researchers in Nigeria and identify measures that could facilitate increased research output. RESULTS: The 89 respondents were masters-level, doctoral scholars and resident doctors who attended a workshop. Majorities of the respondents (over 70%) either agreed or strongly agreed that factors contributing to poor non-communicable diseases research productivity include a dearth of in-country researchers with specialized skills, inability of Nigerian researchers to work in multidisciplinary teams, poor funding for health research, sub-optimal infrastructural facilities, and limited use of research findings by policy makers. Almost all the respondents (over 90%) agreed that potential strategies to facilitate non-communicable diseases research output would include increased funding for research, institutionalization of a sustainable, structured capacity building program for early career researchers, establishment of Regional Centers for Research Excellence, and increased use of research evidence to guide government policy actions and programs.