Rationale: Frailty represents an increased vulnerability to adverse health outcomes. The frailty phenotype conceptual model (three or more patient attributes of wasting, exhaustion, low activity, slowness, and weakness) is associated with increased morbidity and mortality in geriatric populations. Objectives: Our objective was to describe the risks associated with frailty in patients with chronic obstructive pulmonary disease. Methods: Data from the National Emphysema Treatment Trial (NETT) were retrospectively analyzed. The frailty phenotype conceptual model was operationalized as three or more frailty parameters (a body mass index decrease >= 5% of over 12 months, self-reported exhaustion, low 6-minute walk distance, or physical activity or respiratory muscle strength in the lowest quartile). Frail participants were compared with participants with two or fewer frailty parameters. Participants were followed starting 12 months after NETT randomization (to minimize surgical effect) for 24 months. Univariate, multivariate, Kaplan-Meier, and Cox proportional hazard analyses were performed, adjusting for treatment arm, age, modified Medical Research Council dyspnea scale, sex, and baseline forced expiratory volume in 1 second (FEV1). Multiple imputation was used for missing values. Results: The participants (N = 902) were predominantly white (94.5%) males (59.5%), with a median age of 67 years (interquartile range, 63-70 yr) and a median FEV1 % predicted of 26 (interquartile range, 20-33). Six percent of the participants (95% confidence interval [CI], 4.5 to 7.6) were frail. The incidence rate of frailty was 6.4 per 100 person-years. Frail participants reported significantly worse disease-specific and overall quality of life by St. George's Respiratory Questionnaire total score (mean difference of 11.6; 95% CI, 7.6 to 15.6; P < 0.001), mental composite on Medical Outcomes Survey Short Form-36 (mean difference 6.8; 95% CI, 10.0 to -3.6; P < 0.001), and physical composite scores on Medical Outcomes Survey Short Form-36 (mean difference -16.7; 95% CI, - 21.3 to 12.1; P = 0.001). Frail participants had an increased rate of hospitalization (adjusted hazard ratio, 1.6; 95% CI, 1.1 to 2.5; P= 0.02) and an adjusted increase in hospital use of 8.0 days (95% CI, 4.4 to 11.6; P < 0.001) compared with nonfrail participants. Frail participants had a higher mortality rate (adjusted hazard ratio, 1.4; 95% CI, 0.97 to 2.0; P = 0.07). Conclusions: Among adults with chronic obstructive pulmonary disease, our measure of frailty (modified from the Fried frailty phenotype) was associated with incident and longer-duration hospitalization, and with poor quality of life.

Severe sepsis is a systemic response to infection that results in organ dysfunction. Microvascular dysregulation characterized by hyporesponsive and heterogeneous blood flow is implicated in the pathogenesis of organ failure. Although the renin-angiotensin system (RAS) has known effects on the microvasculature and is activated in sepsis, the relationships between RAS and organ injury in human sepsis remain unclear. We hypothesized that systemic RAS mediators are associated with microvascular hyporesponsiveness and organ dysfunction in human sepsis. We studied 30 severe sepsis subjects, and healthy volunteers served as controls. Septic subjects were studied 24 hours after the initial recognition of organ dysfunction; 12 subjects were enrolled such that an initial study was also performed 8 hours after organ dysfunction. Plasma was analyzed for plasma renin activity (PRA) and angiotensin II (Ang II) concentration. Organ failure was assessed quantitatively with the Sequential Organ Failure Assessment (SOFA) score. Using near-infrared spectroscopy, we measured the rate of increase in the oxygen saturation of microvascular hemoglobin in thenar muscles after 5 minutes of forearm ischemia. In so doing, we assessed bulk arteriolar and capillary hemoglobin influx to the tissue during reactive hyperemia. At 8 hours, Ang II was markedly elevated and significantly correlated with the extent of organ failure in septic subjects. After 24 hours of resuscitation to achieve clinically defined end points of preload and arterial pressure, Ang II remained elevated in septic subjects. There was a strong linear relationship between PRA and Ang II in the systemic circulation. Notably, both PRA and Ang II significantly and negatively correlated with the rate of microvascular reoxygenation during reactive hyperemia in septic subjects. We conclude that RAS is activated in severe sepsis, and systemic RAS mediators correlate with measures of microvascular dysregulation and organ failure.

A bronchoscope can be used to examine the mucosal surface of the airways for abnormalities associated with a variety of lung diseases. The diagnosis of these abnormalities through the process of bronchoscopy is based, in part, on changes in airway wall color. Therefore it is important to characterize the normal color inside the airways. We propose a standardized method to calibrate the bronchoscopic imaging system and to tabulate the normal colors of the airway. Our imaging system consists of a Pentium PC and video frame grabber, coupled with a true color bronchoscope. The calibration procedure uses 24 standard color patches. Images of these color patches at three different distances (1, 1.5, and 2 cm) were acquired using the bronchoscope in a darkened room, to assess repeatability and sensitivity to illumination. The images from the bronchoscope are in a device-dependent Red-Green-Blue (RGB) color space, which was converted to a tri-stimulus image and then into a device-independent color space sRGB image by a fixed polynomial transformation. Images were acquired from five normal human volunteer subjects, two cystic fibrosis (CF) patients and one normal heavy smoker subject. The hue and saturation values of regions within the normal airway were tabulated and these values were compared with the values obtained from regions within the airways of the CF patients and the normal heavy smoker. Repeated measurements of the same region in the airways showed no measurable change in hue or saturation.

Current methods for detecting successful gene transfer to airway epithelia involve obtaining a sample of the target tissue. This may affect the longevity of expression of the transgene under evaluation. We describe a laser fluorescence bronchoscopic system that can detect the expression of the fluorescent protein, green fluorescence protein (GFP), in the airway of monkeys that have been transfected with adenovirus, without the need for obtaining tissue. This technique will have applications in pre-clinical and clinical studies of gene transfer to airway epithelia and other surface epithelia accessible by endoscopy.