COPD subtypes identified by network-based clustering of blood gene expression.

One of the most common smoking-related diseases, chronic obstructive pulmonary disease (COPD), results from a dysregulated, multi-tissue inflammatory response to cigarette smoke. We hypothesized that systemic inflammatory signals in genome-wide blood gene expression can identify clinically important COPD-related disease subtypes, and we leveraged pre-existing gene interaction networks to guide unsupervised clustering of blood microarray expression data. Using network-informed non-negative matrix factorization, we analyzed genome-wide blood gene expression from 229 former smokers in the ECLIPSE Study, and we identified novel, clinically relevant molecular subtypes of COPD.

Multi-element logic gates for trapped-ion qubits.

Precision control over hybrid physical systems at the quantum level is important for the realization of many quantum-based technologies. In the field of quantum information processing (QIP) and quantum networking, various proposals discuss the possibility of hybrid architectures where specific tasks are delegated to the most suitable subsystem. For example, in quantum networks, it may be advantageous to transfer information from a subsystem that has good memory properties to another subsystem that is more efficient at transporting information between nodes in the network.

Cigarette Smoke Induces Human Epidermal Receptor 2-Dependent Changes in Epithelial Permeability.

The airway epithelium constitutes a protective barrier against inhaled insults, such as viruses, bacteria, and toxic fumes, including cigarette smoke (CS). Maintenance of bronchial epithelial integrity is central for airway health, and defective epithelial barrier function contributes to the pathogenesis of CS-mediated diseases, such as chronic obstructive pulmonary disease. Although CS has been shown to increase epithelial permeability, current understanding of the mechanisms involved in CS-induced epithelial barrier disruption remains incomplete.

Neuropsychologic evaluation and exposure to neurotoxicants.

The history of neuropsychologic assessment describes the development of a psychometric approach to neuropsychologic measurement, based on the initial clinical/theoretical approach exemplified by pioneers, who also discussed different brain functions and hypotheses for clinical exploration and treatment. Early neuropsychologic assessment practices in the USA arose out of the need to screen, diagnose, and treat World War II veterans who returned with brain injuries. Clinical testing was used to determine treatment and rehabilitation potential.

The discordant method: a novel approach for differential correlation.

Motivation: Current differential correlation methods are designed to determine molecular feature pairs that have the largest magnitude of difference between correlation coefficients. These methods do not easily capture molecular feature pairs that experience no correlation in one group but correlation in another, which may reflect certain types of biological interactions. We have developed a tool, the Discordant method, which categorizes the correlation types for each group to make this possible.

Environmental exposure to manganese in air: Associations with tremor and motor function.

Background: Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentially neurotoxic effects of Mn exposure in ambient air on motor function and hand tremor in adult community residents. Mn exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro-manganese smelter, and East Liverpool, a town adjacent to a facility processing, crushing, screening, and packaging Mn products.

Right ventricular diastolic function and exercise capacity in COPD.

Background: Decreased exercise capacity in chronic obstructive pulmonary disease (COPD) is incompletely explained by pulmonary pathologic and physiologic abnormalities. We evaluated the extent to which right ventricular diastolic function (RVDF) is associated with exercise capacity in COPD.

Methods: Fifty-one patients with COPD were evaluated by echocardiography, spirometry, and the 6 min walk test (6MWT).

CD4+ T-Cell Profiles and Peripheral Blood Ex-Vivo Responses to T-Cell Directed Stimulation Delineate COPD Phenotypes.

The heterogeneous clinical phenotypes of chronic obstructive pulmonary disease (COPD) challenge successful drug development. To identify COPD subgroups beyond clinical phenotypes, we interrogated blood immune cell profiles and ex-vivo responses of current and former smokers, with or without COPD, in the longitudinal COPD Genetic Epidemiology study (COPDGene) cohort. CD4+ and CD8+ T cells and monocytes were profiled by flow cytometry.

Identifying Patients with Undiagnosed COPD in Primary Care Settings: Insight from Screening Tools and Epidemiologic Studies.

Objective: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, yet research suggests this disease is greatly underdiagnosed. This literature review sought to summarize the most common and significant variables associated with case-finding or missed cases of COPD to inform more effective and efficient detection of high-risk COPD patients in primary care.

Methods: PubMed and EMBASE were searched for articles describing case-finding and epidemiologic research to detect or characterize new cases of COPD.

Characterization of air manganese exposure estimates for residents in two Ohio towns.

This study was conducted to derive receptor-specific outdoor exposure concentrations of total suspended particulate (TSP) and respirable (dae ≤ 10 µm) air manganese (air-Mn) for East Liverpool and Marietta (Ohio) in the absence of facility emissions data, but where long-term air measurements were available. Our "site-surface area emissions method" used U.S.

Rationale and Design of the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis Study. Alpha-1 Protocol.

Severe deficiency of alpha-1 antitrypsin has a highly variable clinical presentation. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis α1 Study is a prospective, multicenter, cross-sectional study of adults older than age 35 years with PiZZ or PiMZ alpha-1 antitrypsin genotypes. It is designed to better understand if microbial factors influence this heterogeneity.

Circulating soluble receptor for advanced glycation end products (sRAGE) as a biomarker of emphysema and the RAGE axis in the lung.

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease that has been traditionally characterized by incompletely reversible airflow limitation. Yet, the latter is poorly correlated with many other clinically relevant characteristics of the disease. Thus, the identification of biomarkers to more accurately assess this heterogeneity and disease severity may facilitate the discovery and development of new treatments and better management of patients with COPD.

Clinical and Radiologic Disease in Smokers With Normal Spirometry.

Importance: Airflow obstruction on spirometry is universally used to define chronic obstructive pulmonary disease (COPD), and current or former smokers without airflow obstruction may assume that they are disease free.

Objective: To identify clinical and radiologic evidence of smoking-related disease in a cohort of current and former smokers who did not meet spirometric criteria for COPD, for whom we adopted the discarded label of Global Initiative for Obstructive Lung Disease (GOLD) 0.

Design, Setting, And Participants: Individuals from the Genetic Epidemiology of COPD (COPDGene) cross-sectional observational study completed spirometry, chest computed tomography (CT) scans, a 6-minute walk, and questionnaires.

Environmental exposure to manganese in air: Associations with cognitive functions.

Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the cognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) identified as having high levels of environmental airborne Mn from industrial sources. Air-Mn site surface emissions method modeling for total suspended particulate (TSP) ranged from 0.

Identifying cases of undiagnosed, clinically significant COPD in primary care: qualitative insight from patients in the target population.

Background: Many cases of chronic obstructive pulmonary disease (COPD) are diagnosed only after significant loss of lung function or during exacerbations.

Aims: This study is part of a multi-method approach to develop a new screening instrument for identifying undiagnosed, clinically significant COPD in primary care.

Methods: Subjects with varied histories of COPD diagnosis, risk factors and history of exacerbations were recruited through five US clinics (four pulmonary, one primary care).

Abdominal Visceral Adipose Tissue is Associated with Myocardial Infarction in Patients with COPD.

Background: Cardiovascular diseases are frequent and a major cause of death in patients with chronic obstructive pulmonary disease (COPD). In the general population, various fat depots including abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat have been linked to increased risk of cardiovascular diseases. We hypothesize that these adipose tissue compartments are associated with myocardial infarction (MI) in patients with COPD.

Chronic probable PTSD in police responders in the world trade center health registry ten to eleven years after 9/11.

Background: Police enrolled in the World Trade Center Health Registry (WTCHR) demonstrated increased probable posttraumatic stress disorder (PTSD) after the terrorist attack of 9/11/2001.

Methods: Police enrollees without pre-9/11 PTSD were studied. Probable PTSD was assessed by Posttraumatic Stress Check List (PCL).

Salicylate-induced hearing loss and gap detection deficits in rats.

To test the "tinnitus gap-filling" hypothesis in an animal psychoacoustic paradigm, rats were tested using a go/no-go operant gap detection task in which silent intervals of various durations were embedded within a continuous noise. Gap detection thresholds were measured before and after treatment with a dose of sodium salicylate (200 mg/kg) that reliably induces tinnitus in rats. Noise-burst detection thresholds were also measured to document the amount of hearing loss and aid in interpreting the gap detection results.

Reduced Bone Density and Vertebral Fractures in Smokers. Men and COPD Patients at Increased Risk.

Rationale: Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered.

Objectives: To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women.

Relationships between diffusing capacity for carbon monoxide (DLCO), and quantitative computed tomography measurements and visual assessment for chronic obstructive pulmonary disease.

Purpose: To evaluate the relationships between DLCO, and Quantitative CT (QCT) measurements and visual assessment of pulmonary emphysema and to test the relative roles of visual and quantitative assessment of emphysema.

Materials And Methods: The subjects included 199 current and former cigarette smokers from the COPDGene cohort who underwent inspiratory and expiratory CT and also had diffusing capacity for carbon monoxide corrected for alveolar volume (DLCO/VA). Quantitative CT measurements included % low attenuation areas (%LAA-950ins=voxels ≤-950 Hounsfield unit (HU), %LAA-910ins, and %LAA-856ins), mean CT attenuation and 15th percentile HU value on inspiratory CT, and %LAA-856exp (voxels ≤-856 HU on expiratory CT).

Comorbidities of COPD have a major impact on clinical outcomes, particularly in African Americans.

Background: COPD patients have a great burden of comorbidity. However, it is not well established whether this is due to shared risk factors such as smoking, if they impact patients exercise capacity and quality of life, or whether there are racial disparities in their impact on COPD.

Methods: We analyzed data from 10,192 current and ex-smokers with (cases) and without COPD (controls) from the COPDGene cohort to establish risk for COPD comorbidities adjusted for pertinent covariates.

The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues.

Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding.

Blood metal concentrations of manganese, lead, and cadmium in relation to serum ferritin levels in Ohio residents.

The objectives of this study were to assess ferritin-specific profiles of blood metal concentrations such as manganese, lead, and cadmium and to evaluate whether ferritin may affect the behavior of the blood metals in relation to menstruation, menopause, or sex in Ohio residents. Recruited participants included residents from Marietta, East Liverpool, and Mt. Vernon, OH, USA, who were aged 30-75 years and lived at least 10 years in their respective town.

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study.

DNA methylation is a complex, tissue-specific phenomenon that can reflect both endogenous factors and exogenous exposures. Buccal brushings represent an easily accessible source of DNA, which may be an appropriate surrogate tissue in the study of environmental exposures and chronic respiratory diseases. Buccal brushings were obtained from a subset of current and former smokers from the COPDGene study.

Plasma sphingolipids associated with chronic obstructive pulmonary disease phenotypes.

Rationale: Chronic obstructive pulmonary disease (COPD) occurs in a minority of smokers and is characterized by intermittent exacerbations and clinical subphenotypes such as emphysema and chronic bronchitis. Although sphingolipids as a class are implicated in the pathogenesis of COPD, the particular sphingolipid species associated with COPD subphenotypes remain unknown.

Objectives: To use mass spectrometry to determine which plasma sphingolipids are associated with subphenotypes of COPD.