Highly sensitive noninvasive early lung cancer detection using DNA methylation topology in sputum-derived epithelial cells.

Objective: Sputum is a source of exfoliated respiratory epithelial cells transformed early in lung carcinogenesis. Malignant cells are hypomethylated and contain less genomic 5-methylcytosine (5mC). Validating a test that recognizes and quantifies aberrantly hypomethylated cells in sputum, we assessed its potential as a screening tool for detecting early-stage non-small cell lung cancer.

'Physician advocates': a novel strategy for improving the value of hospital care by employing hospitalists part time to support non-hospitalist physicians.

Background And Objective: At many hospitals, private-practice physicians still admit their own patients and are accustomed to autonomy in clinical practice. This creates challenges for hospital's efforts to improve the efficiency, quality, and value of care. Experienced inpatient-focused physicians - 'Physician Advocates' - could act as liaisons between private practitioners and the fast-paced inpatient microsystem.

A Case of Henoch-Schonlein Purpura Associated with Rotavirus Infection in an Elderly Asian Male and Review of the Literature.

BACKGROUND Henoch-Schönlein purpura (HSP), a small vessel vasculitis mediated by deposition of immune-complexes containing IgA in the skin, gut, and glomeruli, often presents with abdominal pain, purpuric rash in the lower extremities and buttocks, joint pain, and hematuria. The disease most commonly targets children but can affect adults who tend to have a worse prognosis. CASE REPORT We discuss a case of HSP in an elderly Chinese male who presented with severe proximal bowel inflammation, vasculitic rash, and proteinuria; he was found to have positive stool rotavirus and giardia.

The inspiratory capacity/total lung capacity ratio as a predictor of survival in an emphysematous phenotype of chronic obstructive pulmonary disease.

Background: Forced expiratory volume in 1 second (FEV1) grades severity of COPD and predicts survival. We hypothesize that the inspiratory capacity/total lung capacity (IC/TLC) ratio, a sensitive measure of static lung hyperinflation, may have a significant association with survival in an emphysematous phenotype of COPD.

Objectives: To access the association between IC/TLC and survival in an emphysematous phenotype of COPD.

Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts.

Background: Little evidence on the validity of simple and widely applicable tools to predict mortality in patients with chronic obstructive pulmonary disease (COPD) exists.

Objective: To conduct a large international study to validate the ADO index that uses age, dyspnoea and FEV(1) to predict 3-year mortality and to update it in order to make prediction of mortality in COPD patients as generalisable as possible.

Design: Individual subject data analysis of 10 European and American cohorts (n=13 914).

Dilated and unreactive pupils and burst-suppression on electroencephalography due to buproprion overdose.

Burst-suppression pattern on electroencephalography (EEG) occurs upon dissociation of the cortex from underlying brain structures. Unless the pattern is a physiologic consequence of administered sedatives, this electroencephalographic pattern is indicative of a poor neurologic outcome and high mortality. We report a case of a 29-year-old female thought to be brain dead based on initial physical examination and EEG findings of burst-suppression, who was later found to have supratherapeutic serum levels of bupropion.

Lung deflation and oxygen pulse in COPD: results from the NETT randomized trial.

Background: In COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume.

Methods: In 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O(2) pulse=VO(2)/HR) at baseline and 6 months.

High prevalence of lung cancer in a surgical cohort of lung cancer patients a decade after smoking cessation.

Background: This study was designed to assess the prevalence of smoking at time of lung cancer diagnosis in a surgical patient cohort referred for cardiothoracic surgery.

Methods: Retrospective study of lung cancer patients (n = 626) referred to three cardiothoracic surgeons at a tertiary care medical center in Southern California from January 2006 to December 2008. Relationships among years of smoking cessation, smoking status, and tumor histology were analyzed with Chi-square tests.

Do faculty intensivists have better outcomes when caring for patients directly in a closed ICU versus consulting in an open ICU?

Background: Intensivists have been associated with decreased mortality in several studies, but in one major study, centers with intensivist-staffed units reported increased mortality compared with controls. We hypothesized that a closed unit, in which a unit-based intensivist directly provides and coordinates care on all cases, has improved mortality and utilization compared with an open unit, in which individual attendings and consultants provide care, while intensivists serve as supervising consultants.

Methods: We undertook the retrospective study of outcomes in 2 intensive care units (ICUs)-a traditional open unit managed by faculty intensivists and a second closed unit overseen by the same faculty intensivists who coordinated the care on all patients in a large community hospital.

Multivariate models of determinants of health-related quality of life in severe chronic obstructive pulmonary disease.

Persons with severe chronic obstructive pulmonary disease (COPD) and similar levels of forced expiratory volume in 1 second (FEV(1)), exercise capacity, and dyspnea have a wide range of health-related quality of life (HRQL). We identified the independent determinants of HRQL in persons with COPD. Comprehensive assessments of physiological, psychosocial, and clinical variables from the National Emphysema Treatment Trial were used.

Differentiating COPD from asthma in clinical practice.

Asthma and chronic obstructive pulmonary disease (COPD) are interrelated diseases of airflow limitation. They share several common origins, symptoms, and treatments, but there are important differences that affect both diagnosis and recommended treatments. In fact, the most important reason for distinguishing COPD from asthma is the difference in treatment strategies.

Effects of lung volume reduction surgery on gas exchange and breathing pattern during maximum exercise.

Background: The National Emphysema Treatment Trial studied lung volume reduction surgery (LVRS) for its effects on gas exchange, breathing pattern, and dyspnea during exercise in severe emphysema.

Methods: Exercise testing was performed at baseline, and 6, 12, and 24 months. Minute ventilation (Ve), tidal volume (Vt), carbon dioxide output (Vco(2)), dyspnea rating, and workload were recorded at rest, 3 min of unloaded pedaling, and maximum exercise.

CT metrics of airway disease and emphysema in severe COPD.

Background: CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear.

Methods: Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of -950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject.

Longitudinal change in the BODE index predicts mortality in severe emphysema.

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients.

Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival.

Changes in arterial oxygenation and self-reported oxygen use after lung volume reduction surgery.

Rationale: Lung volume reduction surgery (LVRS) is inconsistently reported to improve arterial oxygenation in patients with chronic obstructive pulmonary disease.

Objectives: We studied the effects of surgery on oxygenation in a large cohort and identified predictors of postoperative oxygenation improvement.

Methods: We evaluated oxygenation in 1,078 subjects with chronic obstructive pulmonary disease enrolled in the National Emphysema Treatment Trial after LVRS compared with medical control subjects, including arterial blood gases, use of supplemental oxygen during treadmill walking, and self-reported use of oxygen during rest, exertion, and sleep.

Inhaled and systemic corticosteroids in chronic obstructive pulmonary disease.

Systemic and local inflammation is central to the pathophysiology of chronic obstructive pulmonary disease (COPD). Increased levels of inflammation have been linked to a more progressive course in COPD and have been shown to be present during an exacerbation. Decreases in inflammatory cytokines, C-reactive protein, and inflammatory cells have been observed with corticosteroid use, suggesting a possible mechanism for a therapeutic benefit of steroids.

Exercise testing in severe emphysema: association with quality of life and lung function.

Six-minute walk testing (6MWT) and cardiopulmonary exercise testing (CPX) are used to evaluate impairment in emphysema. However, the extent of impairment in these tests as well as the correlation of these tests with each other and lung function in advanced emphysema is not well characterized. During screening for the National Emphysema Treatment Trial, maximum ergometer CPX and 6MWT were performed in 1,218 individuals with severe COPD with an average FEV(1) of 26.

Sex, depression, and risk of hospitalization and mortality in chronic obstructive pulmonary disease.

Background: We sought to determine whether depressive or anxiety symptoms are associated with chronic obstructive pulmonary disease (COPD) hospitalization or mortality. These data were collected as part of the National Emphysema Treatment Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs continued medical treatment conducted at 17 clinics across the United States between January 29, 1998, and July 31, 2002.

Methods: Prospective cohort study among participants in the NETT with emphysema and severe airflow limitation who were randomized to medical therapy.

Differentiating COPD from asthma in clinical practice.

It has been recognized that features of chronic obstructive pulmonary disease (COPD) and asthma overlap, often rendering a firm diagnosis difficult to achieve for the clinical practitioner. There are hypotheses suggesting that both asthma and COPD may indeed share common origins with differences in phenotypic presentation being related to disease evolution or interaction between endogenous and exogenous factors. Others suggest that the two conditions are clinically and pathophysiologically distinct.

Population issues in clinical trials.

Inclusion of underrepresented groups in clinical trials is important for several reasons. Age, sex, race, genetic factors, concomitant use of other medications, and comorbid conditions all may play pivotal roles in response to a drug or intervention. Despite the legislation for broader inclusion of underrepresented groups in clinical trials (via the National Institutes of Health [NIH] Revitalization Act of 1993), underrepresentation of particular populations, particularly minorities, continues to be a problem.

Carboxyhemoglobin and its correlation to disease severity in cirrhotics.

Goal: To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as compared with Model for End Stage Liver Disease (MELD) score, Child Pugh score, and clinical parameters.

Background: There are 2 sources of carbon monoxide (CO) in humans, exogenous sources include those such as tobacco smoke and inhaled motor vehicle exhaust. The endogenous source is via the heme-oxygenase pathway, in which a heme molecule is broken down into biliverdin with release of an iron (Fe) and CO molecule.

Improvement in serial cardiopulmonary exercise testing following enzyme replacement therapy in Fabry disease.

Background: Fabry disease is an X-linked genetic disorder resulting in the accumulation of glycosphingolipids in various organs, leading to exercise intolerance and early mortality. Enzyme replacement therapy (ERT) has recently been approved for use in Fabry patients. GOALS OF STUDY: To assess baseline cardiopulmonary exercise characteristics in both invasive and noninvasive tests and to study the impact of ERT on exercise.

Cardiopulmonary exercise testing in Fabry disease.

Background: Fabry disease is a rare X-linked disorder that results from a deficiency in a lysosomal enzyme known as alpha-galactosidase A, with accumulation of globotriaosylceramide (Gl3). Early manifestations include angiokeratomas, acroparesthesias, and hypohidrosis and may progress to renal failure, cardiac dysfunction, and stroke. Patients exhibit decreased exercise tolerance and often complain of fatigue.