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Rationale: Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objectives: By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods: We performed a genome-wide association study of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate genome-wide association study and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n = 1,278) and adults from the UKBiobank (n = 369,157). Measurements and Main Results: CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP (hedgehog interacting protein), DSP, and NPNT as potential molecular targets based on colocalization of their expression. A higher dysanapsis genetic risk score was associated with obstructive spirometry among 5-year-old children and among adults in the fifth, sixth, and seventh decades of life. Conclusions: CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development, and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endophenotype link between the genetic variations associated with lung function and COPD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The potential for choline metabolism to influence the development of diabetes has received increased attention. Previous studies on circulating choline metabolites and incident diabetes have been conducted in samples of older adults, often with a high prevalence of risk factors. RESEARCH DESIGN AND METHODS: Participants were from year 15 of follow-up (2000-2001) in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (n = 3,133, aged 33–45 years) with plasma choline metabolite (choline, betaine, and trimethylamine N-oxide [TMAO]) data. We quantified associations between choline metabolites and 15-year risk of incident diabetes (n = 387) among participants free of diabetes at baseline using Cox proportional hazards regression models adjusted for sociodemographics, health behaviors, and clinical variables. RESULTS: Betaine was inversely associated with 15-year risk of incident diabetes (hazard ratio 0.76 [95% CI 0.67, 0.88] per 1-SD unit betaine), and TMAO was positively associated with 15-year risk of incident diabetes (1.11 [1.01, 1.22] per 1-SD unit). Choline was not significantly associated with 15-year risk of incident diabetes (1.05 [0.94, 1.16] per 1-SD). CONCLUSIONS: Our findings are consistent with other published literature supporting a role for choline metabolism in diabetes. Our study extends the current literature by analyzing a racially diverse population-based cohort of early middle-aged individuals in whom preventive activities may be most relevant. [ABSTRACT FROM AUTHOR]

The article presents a study which hypothesized that lower childhood socioeconomic status (SES), assessed by lower parental educational attainment, would be associated with smaller adult airway tree caliber relative to lung volume. Topics discussed include characteristics of multi-ethnic study of atherosclerosis lung study participants stratified by highest educational degree obtained by both parents, ways lower childhood SES are assessed, and findings of the study.

Key Points: Question: Do children who resolve dyslipidemic non–high-density lipoprotein cholesterol (non–HDL-C) levels by adulthood have attenuated risk of developing cardiovascular disease (CVD) events? Findings: Among 5121 children pooled from 6 prospective cohort studies in the US and Finland (mean follow-up, 8.9 years after age 40 years), individuals who had dyslipidemic non–HDL-C in childhood that resolved during adulthood did not have a significantly increased risk of fatal or nonfatal CVD events (hazard ratio, 1.13) than those whose non–HDL-C levels were persistently within the guideline-recommended range in childhood and adulthood. Meaning: Children in whom dyslipidemic non–HDL-C resolves by adulthood have similar risk of CVD to those who never had dyslipidemia. Importance: Elevated non–high-density lipoprotein cholesterol (non–HDL-C; a recommended measure of lipid-related cardiovascular risk) is common in children and increases risk of adult cardiovascular disease (CVD). Whether resolution of elevated childhood non–HDL-C levels by adulthood is associated with reduced risk of clinical CVD events is unknown. Objective: To examine the associations of non–HDL-C status between childhood and adulthood with incident CVD events. Design, Setting, and Participants: Individual participant data from 6 prospective cohorts of children (mean age at baseline, 10.7 years) in the US and Finland. Recruitment took place between 1970 and 1996, with a final follow-up in 2019. Exposures: Child (age 3-19 years) and adult (age 20-40 years) non–HDL-C age- and sex-specific z scores and categories according to clinical guideline–recommended cutoffs for dyslipidemia. Main Outcomes and Measures: Incident fatal and nonfatal CVD events adjudicated by medical records. Results: Over a mean length of follow-up of 8.9 years after age 40 years, 147 CVD events occurred among 5121 participants (60% women; 15% Black). Both childhood and adult non–HDL-C levels were associated with increased risk of CVD events (hazard ratio [HR], 1.42 [95% CI, 1.18-1.70] and HR, 1.50 [95% CI, 1.26-1.78] for a 1-unit increase in z score, respectively), but the association for childhood non–HDL-C was reduced when adjusted for adult levels (HR, 1.12 [95% CI, 0.89-1.41]). A complementary analysis showed that both childhood non–HDL-C levels and the change between childhood and adulthood were independently associated with the outcome, suggesting that from a preventive perspective, both childhood non–HDL-C levels and the change into adulthood are informative. Compared with those whose non-HDL-C levels remained within the guideline-recommended range in childhood and adulthood, participants who had incident non–HDL-C dyslipidemia from childhood to adulthood and those with persistent dyslipidemia had increased risks of CVD events (HR, 2.17 [95% CI, 1.00-4.69] and HR, 5.17 [95% CI, 2.80-9.56], respectively). Individuals who had dyslipidemic non–HDL-C in childhood but whose non-HDL-C levels were within the guideline-recommended range in adulthood did not have a significantly increased risk (HR, 1.13 [95% CI, 0.50-2.56]). Conclusions and Relevance: Individuals with persistent non–HDL-C dyslipidemia from childhood to adulthood had an increased risk of CVD events, but those in whom dyslipidemic non–HDL-C levels resolve by adulthood have similar risk to individuals who were never dyslipidemic. These findings suggest that interventions to prevent and reduce elevated childhood non–HDL-C levels may help prevent premature CVD. This study of individual participant data from 6 pooled cohorts assesses whether resolution of elevated childhood non–high-density lipoprotein cholesterol (non–HDL-C) by adulthood is associated with reduced risk of clinical cardiovascular disease (CVD) events. [ABSTRACT FROM AUTHOR]

Rationale: Quantitative interstitial abnormalities (QIAs) are early measures of lung injury automatically detected on chest computed tomography scans. QIAs are associated with impaired respiratory health and share features with advanced lung diseases, but their biological underpinnings are not well understood. Objectives: To identify novel protein biomarkers of QIAs using high-throughput plasma proteomic panels within two multicenter cohorts. Methods: We measured the plasma proteomics of 4,383 participants in an older, ever-smoker cohort (COPDGene [Genetic Epidemiology of Chronic Obstructive Pulmonary Disease]) and 2,925 participants in a younger population cohort (CARDIA [Coronary Artery Disease Risk in Young Adults]) using the SomaLogic SomaScan assays. We measured QIAs using a local density histogram method. We assessed the associations between proteomic biomarker concentrations and QIAs using multivariable linear regression models adjusted for age, sex, body mass index, smoking status, and study center (Benjamini-Hochberg false discovery rate–corrected P ⩽ 0.05). Measurements and Main Results: In total, 852 proteins were significantly associated with QIAs in COPDGene and 185 in CARDIA. Of the 144 proteins that overlapped between COPDGene and CARDIA, all but one shared directionalities and magnitudes. These proteins were enriched for 49 Gene Ontology pathways, including biological processes in inflammatory response, cell adhesion, immune response, ERK1/2 regulation, and signaling; cellular components in extracellular regions; and molecular functions including calcium ion and heparin binding. Conclusions: We identified the proteomic biomarkers of QIAs in an older, smoking population with a higher prevalence of pulmonary disease and in a younger, healthier community cohort. These proteomics features may be markers of early precursors of advanced lung diseases. [ABSTRACT FROM AUTHOR]

Background: Longitudinal association of television (TV) viewing and moderate- to vigorous-intensity physical activity (MVPA) with pericardial adipose tissue (PAT) is unclear. Methods: We studied Coronary Artery Risk Development in Young Adults Study participants transitioning from early to middle age at Coronary Artery Risk Development in Young Adults (CARDIA) exam years 15 (2000–2001; N = 1975, mean age = 40.4, 55.4% women, 45.3% Black) and 25 (2010–2011). TV viewing (in hours per day) and MVPA (in exercise units) were measured using a self-report questionnaire. PAT volume (in milliliters) was measured using computed tomography. Multivariable linear regression was used to examine the associations of tertiles of 10-year change (years 25–15) in TV viewing and MVPA with a concurrent change in PAT with adjustments for covariates. Results: Participants in the highest tertile of 10-year increase in TV viewing had a greater increase in PAT (β = 2.96 mL, P <.01). Participants in both middle (β = −3.93 mL, P <.01) and highest (β = −6.22 mL, P <.01) tertiles of 10-year changes in MVPA had smaller mean increases in PAT over 10 years when compared with the lowest tertile in fully adjusted models. Conclusions: Reducing or maintaining early-midlife levels of TV viewing and increasing MVPA may be associated with less PAT accumulation with age. [ABSTRACT FROM AUTHOR]

Rationale: Inflammation contributes to lung function decline and the development of chronic obstructive pulmonary disease. Omega-3 fatty acids have antiinflammatory properties and may benefit lung health. Objectives: To investigate associations of omega-3 fatty acids with lung function decline and incident airway obstruction in a diverse sample of adults from general-population cohorts. Methods: Complementary study designs: 1) longitudinal study of plasma phospholipid omega-3 fatty acids and repeated FEV1 and FVC measures in the NHLBI Pooled Cohorts Study and 2) two-sample Mendelian randomization (MR) study of genetically predicted omega-3 fatty acids and lung function parameters. Measurements and Main Results: The longitudinal study found that higher omega-3 fatty acid levels were associated with attenuated lung function decline in 15,063 participants, with the largest effect sizes for the most metabolically downstream omega-3 fatty acid, docosahexaenoic acid (DHA). An increase in DHA of 1% of total fatty acids was associated with attenuations of 1.4 ml/yr for FEV1 (95% confidence interval [CI], 1.1-1.8) and 2.0 ml/yr for FVC (95% CI, 1.6-2.4) and a 7% lower incidence of spirometry-defined airway obstruction (95% CI, 0.89-0.97). DHA associations persisted across sexes and smoking histories and in Black, White, and Hispanic participants, with associations of the largest magnitude in former smokers and Hispanic participants. The MR study showed similar trends toward positive associations of genetically predicted downstream omega-3 fatty acids with FEV1 and FVC. Conclusions: The longitudinal and MR studies provide evidence supporting beneficial effects of higher levels of downstream omega-3 fatty acids, especially DHA, on lung health. [ABSTRACT FROM AUTHOR]

The article explores the connection between lung function patterns in early adulthood and the risk of developing interstitial abnormalities (QIAs) later in life on chest CT scans. It investigates how various trajectories of forced vital capacity (FVC) percentage predicted, a lung function measure, are linked to the likelihood of future interstitial abnormalities. It gain insights into how early-life lung function may influence the development of interstitial lung disease (ILD).

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) in U.S. adults is over 30%, yet the role of lifestyle factors in the etiology of NAFLD remains understudied. We examined the associations of physical activity, by intensity and type, and television viewing with prevalent NAFLD. Methods: Cross-sectional analysis of a population-based sample of 2726 Black (49%) and White (51%) adults (Mean (SD) age, 50 (3.6) years; 57.3% female) from the CARDIA study. Exposures were aerobic activity by intensity (moderate, vigorous; hours/week); activity type (aerobic, muscle-strengthening; hours/week); and television viewing (hours/week), examined concurrently in all models and assessed by validated questionnaires. Our outcome was NAFLD (liver attenuation < 51 Hounsfield Units), measured by non-contrast computed tomography, after exclusions for other causes of liver fat. Covariates were sex, age, race, study center, education, diet quality, smoking status, alcohol consumption, and body mass index or waist circumference. Results: 648 participants had NAFLD. In the fully adjusted modified Poisson regression model, the risk ratios per interquartile range of each exposure were moderate-intensity aerobic activity, 1.10 (95% CI, 0.97–1.26); vigorous-intensity aerobic activity, 0.72 (0.63–0.82); muscle-strengthening activity, 0.89 (0.80–1.01); and television viewing, 1.20 (1.10–1.32). Relative to less active participants with higher levels of television viewing, those who participated in ≥2 h/week of both vigorous-intensity aerobic and muscle-strengthening activity and <7 h/week of television viewing had 65% lower risk of NAFLD (risk ratio = 0.35, 95% CI = 0.23–0.51). Conclusion: Adults who follow public health recommendations for vigorous-aerobic and muscle-strengthening activity, as well as minimize television viewing, are considerably less likely to have NAFLD than those who do not follow the recommendations and who have relatively high levels of television viewing. [ABSTRACT FROM AUTHOR]