Associations of pulmonary microvascular blood volume with per cent emphysema and CT emphysema subtypes in the community: the MESA Lung study.

Background: Pulmonary microvasculature alterations are implicated in emphysema pathogenesis, but the association between pulmonary microvascular blood volume (PMBV) and emphysema has not been directly assessed at scale, and prior studies have used non-specific measures of emphysema.

Methods: The Multi-Ethnic Study of Atherosclerosis Lung Study invited participants recruited from the community without renal impairment to undergo contrast-enhanced dual-energy CT. Pulmonary blood volume was calculated by material decomposition; PMBV was defined as blood volume in the peripheral 2 cm of the lung.

A Pilot Randomized Clinical Trial of Pediatric Cystic Fibrosis Pulmonary Exacerbations Treatment Strategies.

Despite the high prevalence and clear morbidity of cystic fibrosis (CF) pulmonary exacerbations (PEx), there have been no published clinical trials of outpatient exacerbation management. To assess the feasibility of a pediatric clinical trial in which treatment of mild PEx is assigned randomly to immediate oral antibiotics or tailored therapy (increased airway clearance alone with oral antibiotics added only for prespecified criteria). The outcome on which sample size was based was the proportion of tailored therapy participants who avoided oral antibiotics during the 28 days after randomization.

Incidence of interstitial lung abnormalities: the MESA Lung Study.

Background: The incidence of newly developed interstitial lung abnormalities (ILA) and fibrotic ILA has not been previously reported.

Methods: Trained thoracic radiologists evaluated 13 944 cardiac computed tomography scans for the presence of ILA in 6197 Multi-Ethnic Study of Atherosclerosis (MESA) longitudinal cohort study participants >45 years of age from 2000 to 2012. Five percent of the scans were re-read by the same or a different observer in a blinded fashion.

Pulmonary Blood Volume Among Older Adults in the Community: The MESA Lung Study.

Background: The pulmonary vasculature is essential for gas exchange and impacts both pulmonary and cardiac function. However, it is difficult to assess and its characteristics in the general population are unknown. We measured pulmonary blood volume (PBV) noninvasively using contrast enhanced, dual-energy computed tomography to evaluate its relationship to age and symptoms among older adults in the community.

The effect of inhaled hypertonic saline on lung structure in children aged 3-6 years with cystic fibrosis (SHIP-CT): a multicentre, randomised, double-blind, controlled trial.

Background: In the Saline Hypertonic in Preschoolers (SHIP) study, inhaled 7% hypertonic saline improved the lung clearance index in children aged 3-6 years with cystic fibrosis, but it remained unclear whether improvement is also seen in structural lung disease. We aimed to assess the effect of inhaled hypertonic saline on chest CT imaging in children aged 3-6 years with cystic fibrosis.

Methods: Children with cystic fibrosis were enrolled in this multicentre, randomised, double-blind, controlled study at 23 cystic fibrosis centres in Spain, Denmark, the Netherlands, Italy, France, Belgium, the USA, Canada, and Australia.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness.

Reference values for high attenuation areas on chest CT in a healthy, never-smoker, multi-ethnic sample: The MESA study.

Background And Objective: Normative values for HAA-a quantitative, CT-based measure of subclinical ILD-in healthy adults are needed to improve interpretability in clinical and research settings.

Methods: HAA was measured on full-lung CT in 3110 participants in the MESA study. Clinical prediction models were developed using a healthy never-smoker subset with normal spirometry (n = 696).

Current work hours and coronary artery calcification (CAC): The Multi-Ethnic Study of Atherosclerosis (MESA).

Background: Long work hours may be associated with adverse outcomes, including cardiovascular disease. We investigated cross-sectional associations of current work hours with coronary artery calcification (CAC).

Methods: Participants (n = 3046; 54.

Endothelin-1, cardiac morphology, and heart failure: the MESA angiogenesis study.

Background: Circulating levels of endothelin-1 (ET1) are elevated in heart failure and predict poor prognosis. However, it is not clear whether ET1 elevation is an adaptive response, maladaptive response, or an epiphenomenon of heart failure. In this study, we evaluated the relationships between ET1, cardiac morphology, and incident heart failure or cardiovascular death in participants with no evidence of clinical cardiovascular disease at the time ET1 was measured.

Inhaled hypertonic saline in preschool children with cystic fibrosis (SHIP): a multicentre, randomised, double-blind, placebo-controlled trial.

Background: Inhaled hypertonic saline enhances mucociliary clearance, improves lung function, and reduces pulmonary exacerbations in people with cystic fibrosis older than age 6 years. We aimed to assess the effect of inhaled hypertonic saline on the lung clearance index (LCI)-a measure of ventilation inhomogeneity-in children aged 3-6 years with cystic fibrosis.

Methods: The Saline Hypertonic in Preschoolers (SHIP) Study was a randomised, double-blind, placebo-controlled trial at 25 cystic fibrosis centres in Canada and the USA.

Ambient air pollution and pulmonary vascular volume on computed tomography: the MESA Air Pollution and Lung cohort studies.

Background: Air pollution alters small pulmonary vessels in animal models. We hypothesised that long-term ambient air pollution exposure would be associated with differences in pulmonary vascular volumes in a population-based study.

Methods: The Multi-Ethnic Study of Atherosclerosis recruited adults in six US cities.

Air pollution and subclinical interstitial lung disease: the Multi-Ethnic Study of Atherosclerosis (MESA) air-lung study.

We studied whether ambient air pollution is associated with interstitial lung abnormalities (ILAs) and high attenuation areas (HAAs), which are qualitative and quantitative measurements of subclinical interstitial lung disease (ILD) on computed tomography (CT).We performed analyses of community-based dwellers enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. We used cohort-specific spatio-temporal models to estimate ambient pollution (fine particulate matter (PM), nitrogen oxides (NO), nitrogen dioxide (NO) and ozone (O)) at each home.

High-Attenuation Areas on Chest Computed Tomography and Clinical Respiratory Outcomes in Community-Dwelling Adults.

Rationale: Areas of increased lung attenuation visualized by computed tomography are associated with all-cause mortality in the general population. It is uncertain whether this association is attributable to interstitial lung disease (ILD).

Objectives: To determine whether high-attenuation areas are associated with the risk of ILD hospitalization and mortality in the general population.

Plasma Soluble Receptor for Advanced Glycation End Products in Idiopathic Pulmonary Fibrosis.

Rationale: The receptor for advanced glycation end products (RAGE) is underexpressed in idiopathic pulmonary fibrosis (IPF) lung, but the role of RAGE in human lung fibrosis remains uncertain.

Objectives: To examine (1) the association between IPF risk and variation at rs2070600, a functional missense variant in AGER (the gene that codes for RAGE), and (2) the associations between plasma-soluble RAGE (sRAGE) levels with disease severity and time to death or lung transplant in IPF.

Methods: We genotyped the rs2070600 single-nucleotide polymorphism in 108 adults with IPF and 324 race-/ethnicity-matched control subjects.

Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study.

Rationale: Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-β and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-β, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking.

Cholesterol, lipoproteins and subclinical interstitial lung disease: the MESA study.

We investigated associations of plasma lipoproteins with subclinical interstitial lung disease (ILD) by measuring high attenuation areas (HAA: lung voxels between -600 and -250 Hounsfield units) in 6700 adults and serum MMP-7 and SP-A in 1216 adults age 45-84 without clinical cardiovascular disease in Multi-Ethnic Study of Atherosclerosis. In cross-sectional analyses, each SD decrement in high density lipoprotein cholesterol (HDL-C) was associated with a 2.12% HAA increment (95% CI 1.

Secondhand Smoke Exposure and Subclinical Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis.

Background: Few studies have evaluated the association between secondhand smoke (SHS) and subclinical cardiovascular disease among ethnically diverse populations. This study assesses the impact of SHS on inflammation and atherosclerosis (carotid intima-media thickness, coronary artery calcification, and peripheral arterial disease).

Methods And Results: We examined 5032 nonsmoking adults aged 45 to 84 years without prior cardiovascular disease participating in the Multi-Ethnic Study of Atherosclerosis (MESA) from 2000 to 2002.

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.

Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study.

Objective: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp-PLA2 mass and activity and the risk of developing clinical PAD and low ankle-brachial index (ABI).

Approach And Results: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged ≥65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD.

Job Strain, Occupational Category, Systolic Blood Pressure, and Hypertension Prevalence: The Multi-Ethnic Study of Atherosclerosis.

Objective: To assess associations of occupational categories and job characteristics with prevalent hypertension.

Methods: We analyzed 2517 Multi-Ethnic Study of Atherosclerosis participants, working 20+ hours per week, in 2002 to 2004.

Results: Higher job decision latitude was associated with a lower prevalence of hypertension, prevalence ratio = 0.

Associations of work hours, job strain, and occupation with endothelial function: the Multi-Ethnic Study of Atherosclerosis (MESA).

Objective: To investigate associations of work hours, job control, job demands, job strain, and occupational category with brachial artery flow-mediated dilation (FMD) in 1499 Multi-Ethnic Study of Atherosclerosis participants.

Methods: Flow-mediated dilation was obtained using high-resolution ultrasound. Mean values of FMD were examined across categories of occupation, work hours, and the other exposures using regression analyses.

Occupational risk factors for COPD phenotypes in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

Introduction: The contribution of occupational exposure to the risk of chronic obstructive pulmonary disease COPD in population-based studies is of interest. We compared the performance of self-reported exposure to a newly developed JEM in exposure-response evaluation.

Methods: We used cross-sectional data from Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of 45-84 year olds free of clinical cardiovascular disease at baseline.

Genome-wide study of percent emphysema on computed tomography in the general population. The Multi-Ethnic Study of Atherosclerosis Lung/SNP Health Association Resource Study.

Rationale: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering.

Objectives: To complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States.

Methods: We determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than -950 HU on cardiac scans.

Associations of occupation, job control and job demands with intima-media thickness: the Multi-Ethnic Study of Atherosclerosis (MESA).

Objectives: Occupation has been linked to cardiovascular disease (CVD) incidence and mortality, but few studies have investigated occupation in relation to early atherosclerotic disease. This study examined associations between various occupational characteristics and carotid artery intima-media thickness (IMT) in a multi-ethnic sample.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 adults aged 45-84 years and free of clinical CVD (response rate 60%, 51% female).