Publications by authors named "Graham Barr"

Article Synopsis
  • Accelerated decline in lung function is linked to chronic respiratory diseases, and while genetics play a role, few genetic connections have been found.
  • This study aimed to investigate genetic variants associated with lung function decline using genome-wide association studies (GWAS) across diverse populations in multiple cohorts.
  • They identified 361 significant genetic variants potentially related to lung function declines, with some replicated in additional cohorts, indicating strong genetic influences on respiratory health.
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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.

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  • Serum IgG deficiency is linked to increased risks of exacerbations in chronic obstructive pulmonary disease (COPD), but the impact of lower normal range levels is uncertain.
  • A study involving 1,497 smokers analyzed the relationship between serum IgG levels and COPD exacerbations, finding that levels below the 35th percentile (1225 mg/dL) heightened exacerbation risk.
  • Specifically, low levels of IgG1 and IgG2 subclasses were significantly correlated with severe exacerbations, indicating that even mild impairments in IgG can affect disease severity in at-risk individuals.
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Rationale: Rheumatoid arthritis (RA) has been implicated in interstitial lung disease (ILD) as majority of studies have been comprised of patients with known RA. However, it remains unclear whether an underlying risk for RA in combination with genetic risk for pulmonary fibrosis is associated with radiological markers of early lung injury and fibrosis in broader population samples.

Objective: Determine whether genetic and serological biomarkers of RA risk in combination with the (rs35705950) risk allele (T) are associated with interstitial lung abnormalities (ILA) on computed tomography (CT) scans.

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High-resolution full lung CT scans now enable the detailed segmentation of airway trees up to the 6th branching generation. The airway binary masks display very complex tree structures that may encode biological information relevant to disease risk and yet remain challenging to exploit via traditional methods such as meshing or skeletonization. Recent clinical studies suggest that some variations in shape patterns and caliber of the human airway tree are highly associated with adverse health outcomes, including all-cause mortality and incident COPD.

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Background: Lung structure and cardiac structure and function are associated cross-sectionally. The classic literature suggests relationships of airways disease to cor pulmonale and emphysema to reduced cardiac output (CO) but longitudinal data are lacking.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study was a multicentre longitudinal COPD case-control study of participants 50-79 years with ≥10 pack-years smoking without clinical cardiovascular disease.

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  • Researchers are investigating how artificial intelligence (AI) can help measure functional small airways disease (fSAD) in chronic obstructive pulmonary disease (COPD) using just one CT scan instead of the two traditionally required.
  • They studied over 2,500 participants and found strong correlations between the new AI method and existing measures of lung function, confirming its effectiveness.
  • The new AI technique for estimating fSAD proved to be more reliable and repeatable compared to standard methods, suggesting it could enhance clinical assessments of COPD.
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  • A study investigated the link between urinary metal levels (both nonessential and essential) and the progression of coronary artery calcium (CAC), a marker for cardiovascular disease, in participants from the Multi-Ethnic Study of Atherosclerosis (MESA).
  • Results showed that higher levels of metals like cadmium, tungsten, uranium, and cobalt were associated with significantly increased CAC levels over 10 years, indicating a potential risk factor for cardiovascular disease.
  • The findings suggest that exposure to certain metals has a comparable impact on coronary calcification as traditional cardiovascular risk factors, emphasizing the need for further research into environmental influences on heart health.
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Robust quantification of pulmonary emphysema on computed tomography (CT) remains challenging for large-scale research studies that involve scans from different scanner types and for translation to clinical scans. Although the domain shifts in different CT scanners are subtle compared to shifts existing in other modalities (e.g.

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  • The SPIROMICS Study of Early COPD Progression (SOURCE) aims to investigate the biological reasons behind early-stage COPD in younger individuals who smoke, addressing a gap in current medical knowledge that hinders treatment development.
  • The study plans to enroll 649 participants aged 30-55 with a history of smoking, alongside 40 never-smoker controls, to collect comprehensive health data and analyze potential mechanisms of disease progression.
  • SOURCE seeks to use advanced imaging and biospecimen collection methods over three years to enhance understanding of COPD and contribute to better prevention and treatment strategies.
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Rationale: Identification and validation of circulating biomarkers for lung function decline in COPD remains an unmet need.

Objective: Identify prognostic and dynamic plasma protein biomarkers of COPD progression.

Methods: We measured plasma proteins using SomaScan from two COPD-enriched cohorts, the Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene), and one population-based cohort, Multi-Ethnic Study of Atherosclerosis (MESA) Lung.

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Individuals with chronic obstructive pulmonary disease (COPD) are often at risk for or have comorbid cardiovascular disease and are likely to die of cardiovascular-related causes. To prioritize a list of research topics related to the diagnosis and management of patients with COPD and comorbid cardiovascular diseases (heart failure, atherosclerotic vascular disease, and atrial fibrillation) by summarizing existing evidence and using consensus-based methods. A literature search was performed.

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Article Synopsis
  • - This study examined how exposure to various metals in urine relates to cardiovascular disease (CVD) and overall mortality, involving a diverse group of 6,599 U.S. adults over nearly two decades.
  • - Researchers found significant links between higher urinary levels of metals like cadmium, copper, and uranium and increased risks for developing CVD and higher all-cause mortality rates.
  • - Specifically, those in the highest quartile of metal exposure had up to 1.68 times greater risk of all-cause mortality compared to those with the lowest levels, highlighting a concerning relationship between metal exposure and health outcomes.
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Background: Forty to fifty percent of women and 13%-22% of men experience an osteoporosis-related fragility fracture in their lifetimes. After the age of 50 years, the risk of hip fracture doubles in every 10 years. x-Ray based DXA is currently clinically used to diagnose osteoporosis and predict fracture risk.

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Background: Valid, high-resolution estimates of population-level exposure to air pollutants are necessary for accurate estimation of the association between air pollution and the occurrence or exacerbation of adverse health outcomes such as Chronic Obstructive Pulmonary Disease (COPD).

Objectives: We produced fine-scale individual-level estimates of ambient concentrations of multiple air pollutants (fine particulate matter [PM], NO, NO, and O) at residences of participants in the Subpopulations and Intermediate Outcomes in COPD Air Pollution (SPIROMICS Air) study, located in seven regions in the US. For PM, we additionally integrated modeled estimates of particulate infiltration based on home characteristics and measured total indoor concentrations to provide comprehensive estimates of exposure levels.

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Article Synopsis
  • Dysanapsis is the mismatch between airway size and lung size that can lead to COPD risk; it first appears early in life.
  • Researchers analyzed genetic factors linked to dysanapsis through a genome-wide association study involving over 11,000 adults.
  • They found specific genetic variants and developed a genetic risk score that correlated with obstructive lung function in both children and adults, suggesting dysanapsis may connect genetic factors to lung health issues across a person's life.
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Ground-glass opacities (GGOs) in the absence of interstitial lung disease are understudied. To assess the association of GGOs with white blood cells (WBCs) and progression of quantified chest computed tomography emphysema. We analyzed data of participants in the SPIROMICS study (Subpopulations and Intermediate Outcome Measures in COPD Study).

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It is unknown whether air pollution is associated with radiographic features of interstitial lung disease in individuals with chronic obstructive pulmonary disease (COPD). To determine whether air pollution increases the prevalence of interstitial lung abnormalities (ILA) or percent high-attenuation areas (HAA) on computed tomography (CT) in individuals with a heavy smoking history and COPD. We performed a cross-sectional study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), focused on current or former smokers with COPD.

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Rates of emphysema progression vary in chronic obstructive pulmonary disease (COPD), and the relationships with vascular and airway pathophysiology remain unclear. We sought to determine if indices of peripheral (segmental and beyond) pulmonary arterial dilation measured on computed tomography (CT) are associated with a 1-year index of emphysema (EI; percentage of voxels <-950 Hounsfield units) progression. Five hundred ninety-nine former and never-smokers (Global Initiative for Chronic Obstructive Lung Disease stages 0-3) were evaluated from the SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) cohort: rapid emphysema progressors (RPs;  = 188, 1-year ΔEI > 1%), nonprogressors ( = 301, 1-year ΔEI ± 0.

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Individuals with chronic obstructive pulmonary disease (COPD) have airflow obstruction and maldistribution of ventilation. For those living at high altitude, any gas exchange abnormality is compounded by reduced partial pressures of inspired oxygen. Does residence at higher altitude exposure affect COPD outcomes, including lung function, imaging characteristics, symptoms, health status, functional exercise capacity, exacerbations, and mortality? From the SPIROMICS (Subpopulation and Intermediate Outcome Measures in COPD Study) cohort, we identified individuals with COPD living below 1,000 ft (305 m) elevation ( = 1,367) versus above 4,000 ft (1,219 m) elevation ( = 288).

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Background: Higher 25-hydroxyvitamin D (25(OH)D) concentrations in serum has a positive association with pulmonary function. Investigating genome-wide interactions with 25(OH)D may reveal new biological insights into pulmonary function.

Objectives: We aimed to identify novel genetic variants associated with pulmonary function by accounting for 25(OH)D interactions.

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Smaller mean airway tree caliber is associated with airflow obstruction and chronic obstructive pulmonary disease (COPD). We investigated whether airway tree caliber heterogeneity was associated with airflow obstruction and COPD. Two community-based cohorts (MESA Lung, CanCOLD) and a longitudinal case-control study of COPD (SPIROMICS) performed spirometry and computed tomography measurements of airway lumen diameters at standard anatomical locations (trachea-to-subsegments) and total lung volume.

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Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium.

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