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Background The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease. Methods Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines. Results and Discussion Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05). Conclusion These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.

Chronic obstructive pulmonary disease (COPD) is a common condition, and one difficult to manage. Available treatments, other than smoking cessation, are only minimally effective, and the knowledge basis for clinical decision making is limited. To identify areas in which further clinical research may lead to significant improvements in the care of patients with COPD, the National Heart, Lung, and Blood Institute convened a Working Group, entitled \"Clinical Research in COPD: Needs and Opportunities,\" on March 21-22, 2002. This group of experts identified important questions in the field and made the following recommendations: (1) establish a multicenter Clinical Research Network to perform multiple, short-term clinical trials of treatments in patients with moderate-to-severe COPD; (2) create a system for the standardized collection, processing, and distribution of lung tissue specimens and associated clinical and laboratory data; (3) develop standards for the classification and staging of COPD; (4) characterize the development and progression of COPD using measures and biomarkers that relate to current concepts of pathogenesis; and (5) evaluate indications for long-term oxygen therapy for patients with COPD.

Chronic obstructive pulmonary disease (COPD) is a group of progressive, debilitating respiratory conditions, including emphysema and chronic bronchitis, characterized by difficulty breathing, lung airflow limitations, cough, and other symptoms. COPD often is associated with a history of cigarette smoking and is the primary contributor to mortality caused by chronic lower respiratory diseases, which became the third leading cause of death in the United States in 2008. Despite this substantial disease burden, state-level data on the prevalence of COPD and associated health-care resource use in the United States have not been available for all states. To assess the state-level prevalence of COPD among adults, the impact of COPD on their quality of life, and the use of health-care resources by those with COPD, CDC analyzed data from the 2011 Behavioral Risk Factor Surveillance System (BRFSS). Among BRFSS respondents in all 50 states, the District of Columbia (DC), and Puerto Rico, 6.3% reported having been told by a physician or other health professional that they had COPD. In addition to the screening question asked of all respondents, 21 states, DC, and Puerto Rico elected to include an optional COPD module. Among persons who reported having COPD and completed the optional module, 76.0% reported that they had been given a diagnostic breathing test, 64.2% felt that shortness of breath impaired their quality of life, and 55.6% were taking at least one daily medication for their COPD. Approximately 43.2% of them reported visiting a physician for COPD-related symptoms in the previous 12 months, and 17.7% had either visited an emergency department or been admitted to a hospital for their COPD in the previous 12 months. Continued surveillance for COPD, particularly at state and local levels, is critical to 1) identify communities that likely will benefit most from awareness and outreach campaigns and 2) evaluate the effectiveness of public health efforts related to the prevention, treatment, and control of the disease.

Pulmonary emphysema results from the destruction of air spaces, with a loss of elastic recoil of the lungs and alveolar capillary surface for gas exchange. In this study, lung-volume–reduction surgery was compared with medical management of emphysema. Surgery had no overall effect on mortality from emphysema. There were identifiable subgroups of patients for whom surgery had either a beneficial or an adverse effect on outcomes. Surgery had no overall effect on mortality. Lung-volume–reduction surgery has been proposed as a palliative treatment for patients with severe emphysema. 1 – 8 Uncertainty about morbidity and mortality; the occurrence, magnitude, and duration of benefit; and preoperative predictors of benefit led us to conduct a federally sponsored, multicenter, randomized clinical trial, the National Emphysema Treatment Trial (NETT). 9 The primary outcomes for the trial were mortality and maximal exercise capacity two years after randomization. Secondary outcomes included the distance walked in six minutes, pulmonary function, quality of life, and degree of dyspnea. An important goal of the trial was to identify patient-selection criteria for lung-volume–reduction surgery. Criteria for inclusion . . .

Limited data exist describing risk factors for mortality in patients having predominantly emphysema. A total of 609 patients with severe emphysema (ages 40-83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p=0.001), oxygen utilization (p=0.04), lower total lung capacity % predicted (p=0.05), higher residual volume % predicted (p=0.04), lower maximal cardiopulmonary exercise testing workload (p=0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p=0.005), and lower upper-to-lower-lung perfusion ratio (p=0.007), and modified BODE (p=0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p=0.005), but not in multivariate analysis (p=0.21). Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death.

Limited data on sex differences in advanced COPD are available. To compare male and female emphysema patients with severe disease. One thousand fifty-three patients (38.8% female) evaluated for lung volume reduction surgery as part of the National Emphysema Treatment Trial were analyzed. Detailed clinical, physiological, and radiological assessment, including quantitation of emphysema severity and distribution from helical chest computed tomography, was completed. In a subgroup (n = 101), airway size and thickness was determined by histological analyses of resected tissue. Women were younger and exhibited a lower body mass index (BMI), shorter smoking history, less severe airflow obstruction, lower Dl(co) and arterial Po(2), higher arterial Pco(2), shorter six-minute walk distance, and lower maximal wattage during oxygen-supplemented cycle ergometry. For a given FEV(1)% predicted, age, number of pack-years, and proportion of emphysema, women experienced greater dyspnea, higher modified BODE, more depression, lower SF-36 mental component score, and lower quality of well-being. Overall emphysema was less severe in women, with the difference from men most evident in the outer peel of the lung. Females had thicker small airway walls relative to luminal perimeters. In patients with severe COPD, women, relative to men, exhibit anatomically smaller airway lumens with disproportionately thicker airway walls, and emphysema that is less extensive and characterized by smaller hole size and less peripheral involvement.

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched \"Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics\" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

This article reports the partial results of a cooperative study sponsored by Medicare and the National Institutes of Health in which medical and surgical management of emphysema were compared. The investigators found that among patients with a severe reduction in lung function, surgery resulted in more deaths during the first 30 days than did medical management and that the condition of patients who survived the surgery was not substantially improved. This article reports the partial results of a large cooperative study. Among patients with a severe reduction in lung function, surgery resulted in more deaths than did medical management. Lung-volume–reduction surgery is a potentially valuable treatment for patients with advanced emphysema. 1 – 8 During the operation, 20 to 35 percent of the emphysematous lung is resected by means of either a median sternotomy or video-assisted thoracoscopy. Generally, lung function, exercise capacity, and the quality of life improve after surgery, but the results vary. 9 The surgical mortality rate ranges from 4 to 15 percent, 3 and one-year mortality rates are as high as 17 percent, 10 although follow-up has often been incomplete. 11 A review of Medicare claims showed that the six-month mortality rate was 16.9 percent. 12 Uncertainty about the risk of lung-volume–reduction surgery, . . .