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The lung allocation score (LAS) was initiated in May 2005 to allocate lungs based on medical urgency and posttransplant survival. The purpose of this study was to determine if there is an association between an elevated LAS at the time of transplantation and increased postoperative morbidity and mortality.The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant recipients agedor= 12 years who received transplants between April 5, 2006, and December 31, 2007 (n = 3,836). Recipients were stratified into three groups: LAS50 (n = 3,161, 83.87%), LAS 50 to 75 (n = 411, 10.9%), and LASor= 75 (n = 197, 5.23%), referred to as low LAS (LLAS), intermediate LAS (ILAS), and high LAS (HLAS), respectively. The primary outcome was posttransplant graft survival at 1 year. Secondary outcomes included length of stay and in-hospital complications.HLAS recipients had significantly worse actuarial survival at 90 days and 1 year compared with LLAS recipients. When transplant recipients were stratified by disease etiology, a trend of decreased survival with elevated LAS was observed across all major causes of lung transplant. HLAS recipients were more likely to require dialysis or to have infections compared with LLAS recipients (P.001). In addition, length of stay was higher in the HLAS group when compared with the LLAS group (P.001).HLAS is associated with decreased survival and increased complications during the transplant hospitalization. Whereas the LAS has improved organ allocation through decreased waiting list deaths and waiting list times, lower survival and higher morbidity among HLAS recipients suggests that continued review of LAS scoring is needed to ensure optimal long-term transplant survival.

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. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

In May 2005, the lung allocation score (LAS) was introduced as a means of allocating donor lungs in order to decrease wait-list mortality and prioritize candidates based on medical urgency and posttransplant survival. The purpose of this study was to assess changes in recipient wait-list times and mean LAS since the introduction of the LAS model.The United Network for Organ Sharing provided de-identified patient-level data. The study population consisted of all patients in the United States with a reported LAS (n = 3529) undergoing lung transplantation between May 7, 2005 and November 7, 2007. The study period was divided into 6-month intervals. The Kruskal-Wallis test was used to assess differences in variables with nonparametric distributions. The nonparametric trends test was used to determine significance of trends over time.There was a significant decrease in wait-list time during the study period, while LAS among transplant recipients increased (p0.001). There was no significant change in FVC (49.3 +/- 17.5%, p = 0.48) or pulmonary capillary wedge pressure (11.1 +/- 5.8 mm Hg, p = 0.23); however, there was a significant increase in age (51.5 +/- 13.9 years, p0.001) during the study period. When stratified by etiology, the LAS increased for both interstitial pulmonary fibrosis and COPD patients (p0.001). Moreover, the overall number of patients listed for transplantation as well as the LAS among transplant candidates increased (p0.001).Two years after initiation of the LAS model, wait-list times continue to decrease while mean LAS continued to increase. This increase in LAS among transplant recipients was observed most notably in patients with interstitial pulmonary fibrosis and COPD, and reflected in an increased mean LAS at the time of listing.

The risk factors for venous thromboembolism (VTE) following lung transplantation are not well established. We aimed to estimate the incidence of VTE and to identify the risk factors for VTE after lung transplantation.We performed a nested case-control study within the cohort of 121 patients who underwent lung transplantation at our center between August 2001 and July 2005. Control subjects were matched to case patients on the number of days from the time of transplant. Cox proportional hazards models were used to identify risk factors for VTE.Twenty-four patients had deep vein thromboses, and 6 patients had pulmonary emboli (3 patients had both) [22% of the cohort]. In multivariate models, older age (p0.05), diabetes mellitus (p = 0.03), and pneumonia (p = 0.02) were associated with a higher rate of VTE.VTE is a frequent complication of lung transplantation. Older age, diabetes, and pneumonia increase the rate of VTE. Future studies of intensive VTE prophylaxis may be warranted.

Background: Pulmonary capillary hemangiomatosis (PCH) is a rare cause of pulmonary arterial hypertension with no effective medical therapy and a high risk of mortality. The pathogenesis of PCH is unknown. Methods: We used gene expression analysis to compare lung tissue samples from two patients with PCH to those from seven control subjects. The nodules of proliferating capillaries in PCH patients were needle microdissected from cryostat sections. RNA extraction and labeling were followed by hybridization to U95Av2 oligonucleotide arrays (Affymetrix; Santa Clara, CA). In situ hybridization and immunohistochemistry were also performed. Results: The gene expression profile of PCH allowed for unsupervised clustering from the profile of the lung tissue samples of control subjects. Platelet-derived growth factor (PDGF)-B gene ( PDGFB ), PDGF receptor (PDGFR)-β gene ( PDGFR -β), mast cell-related genes, and type 2 pneumocyte-related genes were found to be overexpressed in PCH lesions. In situ hybridization as well as immunohistochemistry for PDGFB showed expression by type 2 pneumocytes and endothelial cells. Immunohistochemical staining for PDGFR-β localized to pericytic/vascular smooth muscle cells surrounding the proliferating capillaries. CD117 staining confirmed an abundance of mast cells in the lesions, which also stained heavily for PDGFR-β. Conclusions: The expression of the PDGFB and PDGFR- β genes characterizes the nodular proliferations of PCH. Increased numbers of mast cells, pericytes, and type II pneumocytes accompany the endothelial proliferation. The up-regulation of these important angiogenic and antiapoptotic genes suggests a mechanism and potential therapeutic approaches for PCH.

There are no studies focused on skeletal status in patients with diffuse parenchymal lung disease (DPLD). We hypothesized that patients with DPLD referred for lung transplantation would have a high prevalence of osteoporosis related to corticosteroid use or reduced pulmonary function and exercise capacity.Retrospective cohort study.Tertiary care center.Eighty-six patients with DPLD referred to our center for lung transplantation evaluation between March 1999 and April 2004.Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) at the lumbar spine, femoral neck, total hip, and radius at the time of referral. Criteria developed by the World Health Organization were used to define osteopenia and osteoporosis. Fifty-five patients (64%) had usual interstitial pneumonia-pattern lung disease, 14 patients (16%) had nonspecific interstitial pneumonia-pattern lung disease, and 17 patients (20%) had other forms of DPLD. Sixty-four patients (74%) were receiving corticosteroids, and 43 patients (50%) were receiving preventive therapy for osteoporosis. Eleven patients (13%; 95% confidence interval [CI], 7 to 22%) met criteria for osteoporosis at any site, and 49 patients (57%; 95% CI, 46 to 68%) had osteopenia. Lower body mass index (BMI) [adjusted odds ratio (OR), 1.3; 95% CI, 1.1 to 1.6; p = 0.007] and Hispanic ethnicity (adjusted OR, 9.7; 95% CI, 1.8 to 52; p = 0.008) were independently associated with an increased risk of osteoporosis. Linear regression analysis confirmed that BMD at the femoral neck and hip was directly associated with BMI (p0.002). These findings were not affected by adjustment for the use of corticosteroids or osteoporosis prophylaxis, pulmonary function, or exercise performance.Reduced BMD was common in patients with DPLD who were referred for lung transplantation. Lower BMD was associated with lower BMI, whereas there was no association with other clinical factors in our cohort. Hispanic patients with DPLD had a higher risk of osteoporosis than non-Hispanic patients, independent of other variables. Given their increased risk of bone loss, patients with DPLD should undergo screening for osteoporosis and receive prophylaxis and treatment according to published guidelines.

s: Primary graft failure (PGF) is a devastating acute lung injury syndrome following lung transplantation. We sought to identify donor, recipient, and operative risk factors for its development.We conducted a cohort study of 255 consecutive lung transplant procedures performed between October 1991 and July 2000. We defined PGF as follows: (1) diffuse alveolar opacities exclusively involving allograft(s) and developing within 72 h of transplant, (2) a ratio of PaO(2) to fraction of inspired oxygen200 beyond 48 h postoperatively, and (3) no other secondary cause of graft dysfunction identified. Risk factors were assessed individually and adjusted for confounding using multivariable logistic regression models.Tertiary-care academic medical center.The overall incidence was 11.8% (95% confidence interval [CI], 7.9 to 15.9). Following multivariable analysis, the risk factors independently associated with development of PGF were as follows: a recipient diagnosis of primary pulmonary hypertension (PPH; adjusted odds ratio [OR], 4.52; 95% CI, 1.29 to 15.9; p = 0.018), donor female gender (adjusted OR, 4.11; 95% CI, 1.17 to 14.4; p = 0.027), donor African-American race (adjusted OR, 5.56; 95% CI, 1.57 to 19.8; p = 0.008), and donor age21 years (adjusted OR, 4.06; 95% CI, 1.34 to 12.3; p = 0.013) and45 years (adjusted OR, 6.79; 95% CI, 1.61 to 28.5; p = 0.009).Recipient diagnosis of PPH, donor African-American race, donor female gender, and donor age are independently and strongly associated with development of PGF.

Study objectives To examine whether relative hypoperfusion to the apical one third of the lungs as determined by lung scintigraphy predicts a favorable functional outcome following bilateral lung volume reduction surgery (LVRS). Methods We performed a retrospective analysis of 128 patients who underwent bilateral LVRS. An apical perfusion fraction (AP%), defined as the percentage of total lung perfusion to the apical one third of both lungs, was derived for each patient by quantitative scintigraphy technique. Pulmonary function testing and 6-min walk test (6MWT) data were obtained preoperatively and 3 to 6 months postoperatively. Results The mean (± SD) improvement in FEV 1 was 309 ± 240 mL, 209 ± 293 mL, and 116 ± 224 mL for patients with an AP% of ≤ 10%, 11 to 20%, and > 20%, respectively (p = 0.01, analysis of variance[ANOVA]). The likelihood of experiencing an increase in FEV 1 ≥ 200 mL was 68% for those with an AP% ≤ 10% but only 31% for those with an AP% > 20%. Preoperative and postoperative 6MWT data were available for 109 of 128 patients. Improvement was 250 ± 252 feet, 205 ± 299 feet, and 77 ± 200 feet for patients with AP% ≤ 10%, 11 to 20%, and > 20%, respectively (p = 0.04, ANOVA). While 50% of those with an AP%≤ 10% improved their 6MWT by ≥ 180 feet, only 21% of those with an AP% > 20% did so. Conclusion This retrospective analysis suggests that quantification of apical perfusion by nuclear scintigraphy assists in predicting the likelihood of short-term functional improvement after LVRS.

Pulmonary embolism (PE) is a common disorder that is accompanied by significant morbidity and mortality. Although anticoagulation is the standard treatment for PE, thrombolytic therapy, with its ability to produce rapid clot lysis, has long been considered an attractive alternative. Although many studies have been performed over the past three decades, however, the indications for the use of thrombolytic agents in patients with PE remain controversial. In this article, we review the medical literature and provide evidence-based guidelines for the use of thrombolytic therapy. We will also discuss the practical aspects of PE thrombolysis.

To characterize the course of patients with advanced sarcoidosis who have been listed for lung transplantation and to identify prognostic factors for death while they are on the waiting list.Retrospective cohort study.Tertiary-care university hospital.Forty-three patients with sarcoidosis who have been listed for lung transplantation at the University of Pennsylvania Medical Center.A multivariable explanatory analysis using a Cox proportional hazards model was performed to determine risk factors that are independently associated with mortality while patients await transplantation.Twenty-three of the 43 patients (53%) died while awaiting transplantation. The survival rate of listed patients (as determined by the Kaplan-Meier method) was 66% at 1 year, 40% at 2 years, and 31% at 3 years. In a univariate analysis, the following factors were significantly associated with death on the waiting list: PaO(2)or = 60 mm Hg (relative risk [RR], 3.4; 95% confidence interval [CI], 1.2 to 9.3); mean pulmonary artery pressureor = 35 mm Hg (RR, 3.2; 95% CI, 1.1 to 9.5); cardiac indexor = 2 L/min/m(2) (RR, 2.8; 95% CI, 1.2 to 6.6), and right atrial pressure (RAP)or = 15 mm Hg (RR, 7.6; 95% CI, 3.0 to 19.3). Multivariable analysis revealed that RAPor = 15 mm Hg was the only independent prognostic variable (RR, 5.2; 95% CI, 1.6 to 16.7; p = 0.006). Twelve patients underwent lung transplantation. Survival after transplantation determined by the Kaplan-Meier method was 62% at both 1 and 2 years, and 50% at 3 years.Patients with advanced sarcoidosis awaiting lung transplantation have a high mortality rate with a median survival of2 years. Mortality is most closely linked to elevated RAP. While earlier referral may diminish the mortality rate of patients on the waiting list for transplantation, further improvements in posttransplantation outcomes will be necessary to ensure that this procedure truly bestows a survival benefit.