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Lung Function and Respiratory Symptoms after Tuberculosis in an American Indian Population. The Strong Heart Study.

ABSTRACT: Rationale: Permanent lung function impairment after active tuberculosis infection is relatively common. It remains unclear which spirometric pattern is most prevalent after tuberculosis.Objectives: Our objective was to elucidate the impact of active tuberculosis survival on lung health in the Strong Heart Study (SHS), a population of American Indians historically highly impacted by tuberculosis. As arsenic exposure has also been related to lung function in the SHS, we also assessed the joint effect between arsenic exposure and past active tuberculosis.Methods: The SHS is an ongoing population-based, prospective study of cardiovascular disease and its risk factors in American Indian adults. This study uses tuberculosis data and spirometry data from the Visit 2 examination (1993-1995). Prior active tuberculosis was ascertained by a review of medical records. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and FEV₁/FVC were measured by spirometry. An additional analysis was conducted to evaluate the potential association between active tuberculosis and arsenic exposure.Results: A history of active tuberculosis was associated with reduced percent predicted FVC and FEV₁, an increased odds of airflow obstruction (odds ratio?=?1.45, 95% confidence interval?= 1.08-1.95), and spirometric restrictive pattern (odds ratio?=?1.73, 95% confidence interval?=?1.24-2.40). These associations persisted after adjustment for diabetes and other risk factors, including smoking. We also observed the presence of cough, phlegm, and exertional dyspnea after a history of active tuberculosis. In the additional analysis, increasing urinary arsenic concentrations were associated with decreasing lung function in those with a history of active tuberculosis, but a reduced odds of active tuberculosis was found with elevated arsenic.Conclusions: Our findings support existing knowledge that a history of active tuberculosis is a risk factor for long-term respiratory impairment. Arsenic exposure, although inversely associated with prior active tuberculosis, was associated with a further decrease in lung function among those with a prior active tuberculosis history. The possible interaction between arsenic and tuberculosis, as well as the reduced odds of tuberculosis associated with arsenic exposure, warrants further investigation, as many populations at risk of developing active tuberculosis are also exposed to arsenic-contaminated water.

SUBMITTER: Powers M

PROVIDER: S-EPMC6944345 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Lung Function and Respiratory Symptoms after Tuberculosis in an American Indian Population. The Strong Heart Study.

Powers Martha M Sanchez Tiffany R TR Welty Thomas K TK Cole Shelley A SA Oelsner Elizabeth C EC Yeh Fawn F Turner Joanne J O'Leary Marcia M Brown Robert H RH O'Donnell Max M Lederer David D Navas-Acien Ana A

Annals of the American Thoracic Society 20200101 1

<b>Rationale:</b> Permanent lung function impairment after active tuberculosis infection is relatively common. It remains unclear which spirometric pattern is most prevalent after tuberculosis.<b>Objectives:</b> Our objective was to elucidate the impact of active tuberculosis survival on lung health in the Strong Heart Study (SHS), a population of American Indians historically highly impacted by tuberculosis. As arsenic exposure has also been related to lung function in the SHS, we also assessed ...[more]

PMID: 31553638

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Project description:BackgroundAmerican Indians have excess risk of depression, which can contribute to cerebrovascular and cognitive disability, with effects on memory, processing speed, executive function, and visuospatial ability. However, studies examining depression and cognition in American Indians are limited; this study aims to report associations of depression with general cognition, verbal fluency and memory, and processing speed.DesignCohort study.SettingThe Cerebrovascular Disease and its Consequences in American Indians study was an ancillary examination of Strong Heart Study participants from 3 U.S. regions.ParticipantsAll eligible were included in this analysis (N=818).MeasurementsParticipants completed evaluations for depressive symptomology, cognition, and physical function-including Center for Epidemiologic Studies Depression (CESD), Modified Mini-Mental State Examination (3MSE), Wechsler Adult Intelligence Scale-Fourth Edition coding (WAIS), Controlled Oral Word Association (COWA), California Verbal and Learning Test, Halstead finger tapping, grip strength, and Short Physical Performance Battery (SPPB) tests. Linear mixed models were adjusted for site, age, sex, education, income, marital status, alcohol, smoking, diabetes, hypertension, obesity, cholesterol, stroke, infarct, and hemorrhage.ResultsSymptoms of depression were common, with 20% (N=138) endorsing CES-D scores of 16+. More depressive symptoms were associated with older age, female sex, lower education, lower income, non-married status, not using alcohol, not smoking, hypertension, diabetes, and stroke. In adjusted analyses, processing speed (WAIS: β -0.13, 95%CI -0.25, -0.03), general cognition (3MSE: β -0.10, 95%CI -0.17, -0.03), verbal fluency (COWA: β -0.10, 95%CI -0.19, -0.01), and motor function (SPPB: β -0.05, 95%CI -0.07, -0.03) were significantly associated with more symptoms of depression.ConclusionThese findings maybe informative for health disparities populations, especially those with depressive risk. Clinicians may require particular training in cultural humility. Future studies should validate use of the CES-D scale in this population; longitudinal studies may focus on causal mechanisms and potential secondary prevention, such as social support. J Am Geriatr Soc 68:1739-1747, 2020.

Project description:BackgroundEpigenetic modifications, including DNA methylation (DNAm), are often related to environmental exposures, and are increasingly recognized as key processes in the pathogenesis of chronic lung disease. American Indian communities have a high burden of lung disease compared to the national average. The objective of this study was to investigate the association of DNAm and lung function in the Strong Heart Study (SHS). We conducted a cross-sectional study of American Indian adults, 45-74 years of age who participated in the SHS. DNAm was measured using the Illumina Infinium Human MethylationEPIC platform at baseline (1989-1991). Lung function was measured via spirometry, including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), at visit 2 (1993-1995). Airflow limitation was defined as FEV1 < 70% predicted and FEV1/FVC < 0.7, restriction was defined as FEV1/FVC > 0.7 and FVC < 80% predicted, and normal spirometry was defined as FEV1/FVC > 0.7, FEV1 > 70% predicted, FVC > 80% predicted. We used elastic-net models to select relevant CpGs for lung function and spirometry-defined lung disease. We also conducted bioinformatic analyses to evaluate the biological plausibility of the findings.ResultsAmong 1677 participants, 21.2% had spirometry-defined airflow limitation and 13.6% had spirometry-defined restrictive pattern lung function. Elastic-net models selected 1118 Differentially Methylated Positions (DMPs) as predictors of airflow limitation and 1385 for restrictive pattern lung function. A total of 12 DMPs overlapped between airflow limitation and restrictive pattern. EGFR, MAPK1 and PRPF8 genes were the most connected nodes in the protein-protein interaction network. Many of the DMPs targeted genes with biological roles related to lung function such as protein kinases.ConclusionWe found multiple differentially methylated CpG sites associated with chronic lung disease. These signals could contribute to better understand molecular mechanisms involved in lung disease, as assessed systemically, as well as to identify patterns that could be useful for diagnostic purposes. Further experimental and longitudinal studies are needed to assess whether DNA methylation has a causal role in lung disease.

Project description:Metabolism of inorganic arsenic (iAs) is subject to inter-individual variability, which is explained partly by genetic determinants.We investigated the association of genetic variants with arsenic species and principal components of arsenic species in the Strong Heart Family Study (SHFS).We examined variants previously associated with cardiometabolic traits (~ 200,000 from Illumina Cardio MetaboChip) or arsenic metabolism and toxicity (670) among 2,428 American Indian participants in the SHFS. Urine arsenic species were measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS), and percent arsenic species [iAs, monomethylarsonate (MMA), and dimethylarsinate (DMA), divided by their sum × 100] were logit transformed. We created two orthogonal principal components that summarized iAs, MMA, and DMA and were also phenotypes for genetic analyses. Linear regression was performed for each phenotype, dependent on allele dosage of the variant. Models accounted for familial relatedness and were adjusted for age, sex, total arsenic levels, and population stratification. Single nucleotide polymorphism (SNP) associations were stratified by study site and were meta-analyzed. Bonferroni correction was used to account for multiple testing.Variants at 10q24 were statistically significant for all percent arsenic species and principal components of arsenic species. The index SNP for iAs%, MMA%, and DMA% (rs12768205) and for the principal components (rs3740394, rs3740393) were located near AS3MT, whose gene product catalyzes methylation of iAs to MMA and DMA. Among the candidate arsenic variant associations, functional SNPs in AS3MT and 10q24 were most significant (p < 9.33 × 10-5).This hypothesis-driven association study supports the role of common variants in arsenic metabolism, particularly AS3MT and 10q24. Citation: Balakrishnan P, Vaidya D, Franceschini N, Voruganti VS, Gribble MO, Haack K, Laston S, Umans JG, Francesconi KA, Goessler W, North KE, Lee E, Yracheta J, Best LG, MacCluer JW, Kent J Jr., Cole SA, Navas-Acien A. 2017. Association of cardiometabolic genes with arsenic metabolism biomarkers in American Indian communities: the Strong Heart Family Study (SHFS). Environ Health Perspect 125:15-22;?http://dx.doi.org/10.1289/EHP251.

Project description:BackgroundThe prevalence of variant alleles among single nucleotide polymorphisms (SNPs) is not well known for many minority populations. These population allele frequencies (PAFs) are necessary to guide genetic epidemiology studies and to understand the population specific contribution of these variants to disease risk. Large differences in PAF among certain functional groups of genes could also indicate possible selection pressure or founder effects of interest. The 50K SNP, custom genotyping microarray (CARe) was developed, focusing on about 2,000 candidate genes and pathways with demonstrated pathophysiologic influence on cardiovascular disease (CVD).MethodsThe CARe microarray was used to genotype 216 unaffected controls in a study of pre-eclampsia among a Northern Plains, American Indian tribe. The allelic prevalences of 34,240 SNPs suitable for analysis, were determined and compared with corresponding HapMap prevalences for the Caucasian population. Further analysis was conducted to compare the frequency of statistically different prevalences among functionally related SNPs, as determined by the DAVID Bioinformatics Resource.ResultsOf the SNPs with PAFs in both datasets, 9.8%,37.2% and 47.1% showed allele frequencies among the American Indian population greater than, less than and either greater or less than (respectively) the HapMap Caucasian population. The 2,547 genes were divided into 53 functional groups using the highest stringency criteria. While none of these groups reached the Bonferroni corrected p value of 0.00094, there were 7 of these 53 groups with significantly more or less differing PAFs, each with a probability of less than 0.05 and an overall probability of 0.0046.ConclusionIn comparison to the HapMap Caucasian population, there are substantial differences in the prevalence among an American Indian community of SNPs related to CVD. Certain functional groups of genes and related SNPs show possible evidence of selection pressure or founder effects.

Project description:Many rural populations, including American Indian communities, that use private wells from groundwater for their source of drinking and cooking water are disproportionately exposed to elevated levels of arsenic. However, programs aimed at reducing arsenic in American Indian communities are limited. The Strong Heart Water Study (SHWS) is a randomized controlled trial aimed at reducing arsenic exposure among private well users in American Indian Northern Great Plains communities. The community-led SHWS program installed point-of-use (POU) arsenic filters in the kitchen sink of households, and health promoters delivered arsenic health communication programs. In this study we evaluated the efficacy of these POU arsenic filters in removing arsenic during the two-year installation period. Participants were randomized into two arms. In the first arm households received a POU arsenic filter, and 3 calls promoting filter use (SHWS mobile health (mHealth) & filter arm). The second arm received the same filter and phone calls, and 3 in-person home visits and 3 Facebook messages (SHWS intensive arm) for program delivery. Temporal variability in water arsenic concentrations from the main kitchen faucet was also evaluated. A total of 283 water samples were collected from 50 households with private wells from groundwater (139 filter and 144 kitchen faucet samples). Ninety-three percent of households followed after baseline had filter faucet water arsenic concentrations below the arsenic maximum contaminant level of 10 μg/L at the final visit during our 2 year study period with no difference between study arms (98 % in the intensive arm vs. 94 % in the mHealth & filter arm). No significant temporal variation in kitchen arsenic concentration was observed over the study period (intraclass correlation coefficient = 0.99). This study demonstrates that POU arsenic filters installed for the community participatory SHWS program were effective in reducing water arsenic concentration in study households in both arms, even with delivery of the POU arsenic filter and mHealth program only. Furthermore, we observed limited temporal variability of water arsenic concentrations from kitchen faucet samples collected over time from private wells in our study setting.

Project description:Rationale: Exposure to inorganic arsenic, through drinking naturally-contaminated water, is an established cause of lung cancer. Evidence on the impact of arsenic exposure on lung function, however, is less conclusive. The evidence available, mostly from populations exposed to water arsenic levels >100 ?g/L, suggests that arsenic exposure is associated with lower lung function. Prospective studies and studies examining low-to-moderate levels of water arsenic exposure (<50 ?g/L) the level relevant for U.S. populations, are very limited. Objectives: We evaluated the association between chronic low-to-moderate arsenic exposure with lung function and disease in an American Indian population. Methods: The Strong Heart Study is a multicenter prospective study of cardiovascular disease and its risk factors among American Indian adults. The present analysis, in 2,166 adults, used urinary arsenic measurements at baseline (1989–1991) and lung symptoms and function assessment by standardized spirometry at the second examination (1993–1995). We evaluated associations between arsenic exposure and airflow obstruction, defined as ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70, and restrictive pattern, defined as FEV1/FVC ratio greater than 0.70 and FVC less than 80% predicted; respiratory symptoms; and self-reported physician diagnosis of nonmalignant respiratory disease. Results: The prevalence of airflow obstruction between 1993 and 1995 was 21.4% (463/2,166); restrictive pattern was 14.5% (314/2,166). Median urinary arsenic concentrations were higher in participants with airflow obstruction (11.0 ?g/g creatinine) compared to those without obstruction (9.8 ?g/g creatinine), and higher in those with restrictive pattern (12.0 ?g/g) compared to those without restrictive pattern (9.4 ?g/g). The odds ratio (95% confidence interval) for obstructive and restrictive patterns comparing the 75th to 25th percentile of arsenic was 1.13 (0.96–1.32) and 1.27 (1.01–1.60), respectively, after adjustment for age, sex, education, study site, smoking status, smoking pack-year, estimated glomerular filtration rate, tuberculosis, and body mass index. Emphysema, cough 4–6 times a day, phlegm, and stopping for breath were also positively associated with arsenic. Conclusions: In this American Indian population, exposure to low-to-moderate levels of inorganic arsenic, as measured in urine, was positively associated with restrictive pattern as measured by spirometry, self-reported emphysema diagnosis, self-reported shortness of breath, and more frequent cough and phlegm among those with cough, independent of smoking status. These findings suggest that low-to-moderate arsenic exposure can contribute to nonmalignant lung disease, and may be associated with restrictive lung disease.

Dataset Information

Lung Function and Respiratory Symptoms after Tuberculosis in an American Indian Population. The Strong Heart Study.

Publications

Lung Function and Respiratory Symptoms after Tuberculosis in an American Indian Population. The Strong Heart Study.

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