Diffusing capacity of the lung for carbon monoxide: association with long-term outcomes after lung transplantation in a 20-year longitudinal study.

RATIONALE: The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (D LCOcor) measures gas movement across the alveolar-capillary interface. We hypothesised that D LCOcor is a sensitive measure of injurious allograft processes disrupting this interface. OBJECTIVES: To determine the prognostic significance of the D LCOcor trajectory on chronic lung allograft dysfunction (CLAD) and survival. METHODS: A retrospective analysis was conducted of all bilateral lung transplant recipients at a single centre, between January 1998 and January 2018, with one or more D LCOcor measurements. Low baseline D LCOcor was defined as the failure to achieve a D LCOcor >75% predicted. Drops in D LCOcor were defined as >15% below recent baseline. RESULTS: 1259 out of 1492 lung transplant recipients were included. The median (range) time to peak D LCOcor was 354 (181-737) days and the mean±sd D LCOcor was 80.2±21.2% pred. Multivariable analysis demonstrated that low baseline D LCOcor was significantly associated with death (hazrd ratio (HR) 1.68, 95% CI 1.27-2.20; p<0.001). Low baseline D LCOcor was not independently associated with CLAD after adjustment for low baseline forced expiratory volume in 1 s or forced vital capacity. Any D LCOcor declines ≥15% were significantly associated with death, independent of concurrent spirometric decline. Lower percentage predicted D LCOcor values at CLAD onset were associated with shorter post-CLAD survival (HR 0.75 per 10%-unit change, p<0.01). CONCLUSION: Low baseline D LCOcor and post-transplant declines in D LCOcor were significantly associated with survival, independent of spirometric measurements. We propose that D LCOcor testing may allow identification of a subphenotype of baseline and chronic allograft dysfunction not captured by spirometry. There may be benefit in routine monitoring of D LCOcor after lung transplantation to identify patients at risk of poor outcomes.

Design Principles for High-Temperature Superconductors with a Hydrogen-Based Alloy Backbone at Moderate Pressure.

Hydrogen-based superconductors provide a route to the long-sought goal of room-temperature superconductivity, but the high pressures required to metallize these materials limit their immediate application. For example, carbonaceous sulfur hydride, the first room-temperature superconductor made in a laboratory, can reach a critical temperature (T_{c}) of 288 K only at the extreme pressure of 267 GPa. The next recognized challenge is the realization of room-temperature superconductivity at significantly lower pressures. Here, we propose a strategy for the rational design of high-temperature superconductors at low pressures by alloying small-radius elements and hydrogen to form ternary H-based superconductors with alloy backbones. We identify a "fluorite-type" backbone in compositions of the form AXH_{8}, which exhibit high-temperature superconductivity at moderate pressures compared with other reported hydrogen-based superconductors. The Fm3[over ¯]m phase of LaBeH_{8}, with a fluorite-type H-Be alloy backbone, is predicted to be thermodynamically stable above 98 GPa, and dynamically stable down to 20 GPa with a high T_{c}∼185 K. This is substantially lower than the synthesis pressure required by the geometrically similar clathrate hydride LaH_{10} (170 GPa). Our approach paves the way for finding high-T_{c} ternary H-based superconductors at conditions close to ambient pressures.

Normothermic ex vivo lung perfusion in clinical lung transplantation.

BACKGROUND: More than 80% of donor lungs are potentially injured and therefore not considered suitable for transplantation. With the use of normothermic ex vivo lung perfusion (EVLP), the retrieved donor lung can be perfused in an ex vivo circuit, providing an opportunity to reassess its function before transplantation. In this study, we examined the feasibility of transplanting high-risk donor lungs that have undergone EVLP. METHODS: In this prospective, nonrandomized clinical trial, we subjected lungs considered to be high risk for transplantation to 4 hours of EVLP. High-risk donor lungs were defined by specific criteria, including pulmonary edema and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PO(2):FIO(2)) less than 300 mm Hg. Lungs with acceptable function were subsequently transplanted. Lungs that were transplanted without EVLP during the same period were used as controls. The primary end point was primary graft dysfunction 72 hours after transplantation. Secondary end points were 30-day mortality, bronchial complications, duration of mechanical ventilation, and length of stay in the intensive care unit and hospital. RESULTS: During the study period, 136 lungs were transplanted. Lungs from 23 donors met the inclusion criteria for EVLP; in 20 of these lungs, physiological function remained stable during EVLP and the median PO(2):FIO(2) ratio increased from 335 mm Hg in the donor lung to 414 and 443 mm Hg at 1 hour and 4 hours of perfusion, respectively (P<0.001). These 20 lungs were transplanted; the other 116 lungs constituted the control group. The incidence of primary graft dysfunction 72 hours after transplantation was 15% in the EVLP group and 30% in the control group (P=0.11). No significant differences were observed for any secondary end points, and no severe adverse events were directly attributable to EVLP. CONCLUSIONS: Transplantation of high-risk donor lungs that were physiologically stable during 4 hours of ex vivo perfusion led to results similar to those obtained with conventionally selected lungs. (Funded by Vitrolife; ClinicalTrials.gov number, NCT01190059.).

Restrictive allograft syndrome post lung transplantation is characterized by pleuroparenchymal fibroelastosis.

We previously described restrictive allograft syndrome as a form of chronic lung allograft dysfunction, demonstrating restrictive pulmonary function decline. However, the histopathological correlates of restrictive allograft syndrome have yet to be satisfactorily described. We hypothesized that pulmonary pleuroparenchymal fibroelastosis, as has recently been described in bone marrow transplant recipients, may also be present in the lungs of patients with restrictive allograft syndrome. Retrospective review of 493 patients who underwent lung transplantation between 1 January 1996 and 30 June 2009, was conducted. Out of 47 patients with clinical features of restrictive allograft syndrome, 16 had wedge biopsy, re-transplant lung explant, or autopsy lung specimens available for review. All lungs showed varying degrees of pleural fibrosis. Fifteen of 16 showed parenchymal fibroelastosis, characterized by hypocellular collagen deposition with preservation and thickening of the underlying alveolar septal elastic network. The fibroelastosis was predominantly subpleural in distribution, with some cases also showing centrilobular and paraseptal distribution. A sharp demarcation was often seen between areas of fibroelastosis and unaffected lung parenchyma, with fibroblastic foci often present at this interface. Concurrent features of obliterative bronchiolitis were present in 14 cases. Another common finding was the presence of diffuse alveolar damage (13 cases), usually in specimens obtained <1 year after clinical onset of restrictive allograft syndrome. The single specimen in which fibroelastosis was not identified was obtained before the clinical onset of chronic lung allograft dysfunction, and showed features of diffuse alveolar damage. In conclusion, pleuroparenchymal fibroelastosis is a major histopathologic correlate of restrictive allograft syndrome, and was often found concurrently with diffuse alveolar damage. Our findings support a temporal sequence of diffuse alveolar damage followed by the development of pleuroparenchymal fibroelastosis in the histopathologic evolution of restrictive allograft syndrome.

Topological Analysis of Functions on Arbitrary Grids: Applications to Quantum Chemistry.

Algorithms are presented for performing a topological analysis of an arbitrary function, evaluated on an arbitrary grid of points. These algorithms work strictly by post-processing the data and require no additional function evaluations. This is achieved by connecting the grid points with a neighborhood graph, allowing the topological analysis to be recast as a problem in the graph theory. The flexibility of the approach is demonstrated for various applications involving analysis of the charge and magnetically induced current densities in molecules, where features of the neighborhood graph are found to correspond to chemically relevant topographical properties, such as Bader charges. These properties converge using orders of magnitude fewer grid points than uniform-grid approaches while exhibiting an appealing O[N log(N)] scaling of the computational cost. The issue of grid bias is discussed in the context of graph-based algorithms and strategies for avoiding this bias are presented. Python implementations of the algorithms are provided.

Stochastic nodal surfaces in quantum Monte Carlo calculations.

Treating the fermionic ground state-problem as a constrained stochastic optimization problem, a formalism for fermionic quantum Monte Carlo is developed that makes no reference to a trial wave function. Exchange symmetry is enforced by nonlocal terms appearing in the Green's function corresponding to an additional walker propagation channel. Complemented by a treatment of diffusion that encourages the formation of a stochastic nodal surface, we find that an approximate long-range extension of walker cancellations can be employed without introducing significant bias, reducing the number of walkers required for a stable calculation. A proof-of-concept implementation is shown to give a stable fermionic ground state for simple harmonic and atomic systems.

Deciding about lung transplantation: informational needs of patients and support persons.

CONTEXT: Information is essential for informed decision making. To date, the informational needs of patients and support persons making the lung transplant decision are unexplored; in addition, the role of support persons in the transplant decision is unknown. OBJECTIVE: To identify the informational needs of patients and support persons attending a transplant clinic for consultation on lung transplantation, and to identify the involvement of support persons in the decision. DESIGN: A qualitative descriptive study and qualitative content analysis. SETTING: Participants were recruited from the Toronto General Hospital Lung Transplant Program. PARTICIPANTS: Twenty-two patients (8 candidates, 14 recipients) and 16 support persons. RESULTS: Most patients made the lung transplant decision in collaboration with their support person and reported receiving adequate information to make an informed decision. Diverse learning needs were identified among and between patients and support persons. Many participants identified the need for more information on practical issues, life after transplantation, and the experiences of transplant recipients. CONCLUSION: Most patients attending a transplant clinic for consultation on lung transplantation felt they made an informed decision; however, modifications to the content, timing, and ways of providing information could enhance the decision-making process for patients and support persons. Specifically, the transplant team can provide information on core lung transplant topics with access to supplementary information to meet specific needs and use materials that vary in source, formats, and time points during the decision-making period.

Role of lung transplantation in the treatment of bronchogenic carcinomas for patients with end-stage pulmonary disease.

PURPOSE: To determine the role of lung transplantation in the treatment of patients presenting with bronchogenic carcinoma and end-stage lung disease. METHODS: An international survey was conducted to determine the outcome of patients with bronchogenic carcinoma in the explanted lung at the time of transplantation. A group of 69 patients was collected from 33 centers. RESULTS: Twenty-six patients underwent 29 lung transplantations for advanced multifocal bronchioloalveolar carcinoma (BAC) as the primary indication for transplantation, and 13 developed a recurrence, with an overall 5-year actuarial survival of 39%. Incidental bronchogenic carcinomas classified as stage I (n = 22), II (n = 12), and III (n = 2), or as incidental multifocal BAC (n = 7), were found in the explanted lung of the remaining 43 patients. The 5-year actuarial survival was 51% in patients with stage I carcinomas, and was significantly better than for patients with stage II and III carcinomas (survival of 14%) or with incidental multifocal BAC (survival of 23%). Time from transplantation to recurrence and from recurrence to death was significantly longer in patients with multifocal BAC than in patients with other types of bronchogenic carcinoma. In addition, the site of recurrence was limited to the transplanted lung in 88% of the patients with multifocal BAC, whereas it was always widespread in patients with other types of bronchogenic carcinoma. CONCLUSION: This study demonstrates that long-term survival can be achieved after lung transplantation in patients with stage I bronchogenic carcinoma or with advanced multifocal BAC.

Bile acid aspiration and the development of bronchiolitis obliterans after lung transplantation.

BACKGROUND: Aspiration of gastroesophageal refluxate may contribute to lung transplant bronchiolitis obliterans syndrome (BOS). We investigated bile acids in bronchoalveolar lavage fluid (BALF) and studied its role in BOS. MATERIALS AND METHODS: Surveillance pulmonary function tests and BALF were evaluated in 120 lung recipients. BOS-(0p-3) was diagnosed after 6 months' survival. BOS was defined as "early" if diagnosed within 12 months after a transplant. BALF was assayed for differential cell count, bile acids, and interleukins 8 and 15. Bile acids were considered elevated if greater than normal serum levels ( or =8 micromol/L). RESULTS: Elevated BALF bile acids were measured in 20 (17%) of 120 patients. BOS was diagnosed in 36 (34%) of 107 patients and judged "early" in 21 (57%) of 36. Median BALF bile acid values were 1.6 micromol/L (range, 0-32 micromol/L) in BOS patients and 0.3 micromol/L (range, 0-16 micromol/L) in non-BOS patients ( P = .002); 2.6 micromol/L (range, 0-32 micromol/L) in early BOS patients and 0.8 micromol/L (range, 0-4.6 micromol/L) in late BOS patients, ( P = .02). Bile acids correlated with BALF IL-8 and alveolar neutrophilia (r = 0.3, P = .0004, and r = 0.3, P = .004, respectively), but not with IL-15. Freedom from BOS was significantly shortened in patients with elevated BALF bile acids (Cox-Mantel test, P = .0001). CONCLUSIONS: Aspiration of duodenogastroesophageal refluxate is prevalent after lung transplantation and is associated with the development of BOS. Elevated BALF bile acids may promote early BOS development via an inflammatory process, possibly mediated by IL-8 and alveolar neutrophilia.

Pre-transplant panel reactive antibody in lung transplant recipients is associated with significantly worse post-transplant survival in a multicenter study.

BACKGROUND: The presence of antibodies to human leukocyte antigens (HLA) prior to transplantation has been linked to worse post-transplant outcomes in many solid organ transplants. The effect of these antibodies is less clear in lung transplant recipients, although previous studies have suggested an increased incidence of allograft dysfunction. METHODS: A retrospective study of all first lung transplant recipients from the University of Toronto (November 1983-July 2001, n = 380) and Duke University (April 1992-June 2000, n = 276) was performed. Demographic data, survival information, and level of last pre-transplant panel reactive antibody (PRA) were collected. PRA level was measured by the complement-dependent cell cytotoxicity assay at both centers. Survival analysis was performed using the Kaplan-Meier method, and groups were compared with the Wilcoxon rank sum test. RESULTS: Of 656 lung transplant recipients, 101 (15.4%) had a PRA greater than 0, 37 (5.6%) had a PRA greater than 10%, and 20 (3.0%) had a PRA greater than 25%. Patients with a PRA greater than 25% had decreased median survival than did the rest of the patients (1.5 vs 5.2 years) and at 1 month (70% vs 90%), 1 year (65% vs 76%), and 5 years (31% vs 50%), respectively (p = 0.006, Wilcoxon's rank sum test) test). CONCLUSION: Significant elevation of PRA prior to lung transplantation is associated with worse survival, especially in the early post-transplant period. This may be due to a direct effect of anti-HLA antibodies on the allograft. The effectiveness of treatments such as plasmapheresis and intravenous immunoglobulin prior to transplantation needs to be evaluated.

Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation.

BACKGROUND: Ex vivo lung perfusion (EVLP) is an effective method to assess and improve the function of otherwise unacceptable lungs, alleviating the shortage of donor lungs. The early results with EVLP have been encouraging, but longer-term results, including functional and patient-reported outcomes, are not well characterized. METHODS: This retrospective single-center study included all lung transplants performed between September 2008 and December 2012. We investigated whether survival or rate of chronic lung allograft dysfunction (CLAD) differed in recipients of EVLP-treated lungs compared with contemporaneous recipients of conventional donor lungs. We also studied functional (highest forced expiratory volume in 1 second predicted, change in 6-minute walk distance, number of acute rejection episodes) and quality of life outcomes. RESULTS: Of 403 lung transplants that were performed, 63 patients (15.6%) received EVLP-treated allografts. Allograft survival for EVLP and conventional donor lung recipients was 79% vs 85%, 71% vs 73%, and 58% vs 57% at 1, 3, and 5 years after transplant, respectively (log-rank p = not significant). Freedom from CLAD was also similar (log-rank p = 0.53). There were no significant differences in functional outcomes such as highest forced expiratory volume in 1 second predicted (76.5% ± 23.8% vs 75.8% ± 22.8%, p = 0.85), change in 6-minute walk distance (194 ± 108 meters vs 183 ± 126 meters, p = 0.57), or the number of acute rejection episodes (1.5 ± 1.4 vs 1.3 ± 1.3, p = 0.36). The EVLP and conventional donor groups both reported a significantly improved quality of life after transplantation, but there was no intergroup difference. CONCLUSION: EVLP is a safe and effective method of assessing and using high-risk donor lungs before transplantation and leads to acceptable long-term survival, graft function, and improvements of quality of life that are comparable with conventionally selected donor lungs.

GI complications after lung transplantation in patients with cystic fibrosis.

STUDY OBJECTIVE: Lung transplantation is now available for patients with cystic fibrosis (CF) and end-stage lung disease. While pulmonary graft function is often considered the major priority following transplantation, the nonpulmonary complications of this systemic disease also continue. We examined the GI complications in a cohort of patients who underwent transplantation. DESIGN: This was a retrospective study of all patients with CF who underwent transplantation between March 1988 and December 1998 in Toronto. Medical records were reviewed, and a short questionnaire was mailed to patients who were alive as of December 1998. RESULTS: There were 80 bilateral lung transplants performed in 75 patients. The questionnaire was distributed to 43 patients, of whom 27 patients (63%) responded. Pancreatic insufficiency requiring enzyme intake was evident in 72 of 75 patients (96%) at the time of surgery. Of three pancreatic-sufficient patients (4%), pancreatic insufficiency was diagnosed in two patients later. Biliary cirrhosis was diagnosed in three patients prior to transplantation. Distal intestinal obstruction syndrome (DIOS) was recorded for 15 patients (20%). Ten patients had a single episode, of which eight episodes occurred early in the postoperative period. Five patients had recurrent episodes. All were medically treated, except for two patients who underwent surgery. Other complications included cholecystitis (n = 3), mucocele of the appendix (n = 1), peptic ulcer disease (n = 3), and colonic carcinoma (n = 1). CONCLUSION: GI complications after lung transplantation are common in patients with CF, and attention should be paid to the risk for DIOS in the early postoperative period. Prevention and early medical treatment are important in order to avoid acute surgery. Close collaboration with the CF clinic, in order to diagnose and treat CF-related complications, is recommended.

Marginal donor lungs: a reassessment.

OBJECTIVE: Lung transplantation is limited by the shortage of suitable donors. To overcome this problem, many programs have begun to use marginal or extended donors after reports suggesting equivalent outcomes with no additional risk. As our use of extended donor lungs increased and our recipient selection criteria expanded, we believed it was appropriate to reevaluate outcomes with extended donor lungs compared with outcomes with standard donor lungs and recipients outside of the currently accepted guidelines. METHODS: We performed a retrospective review of 128 consecutive lung or heart-lung transplants from January 1, 1997, to June 30, 2000. The primary endpoint was 30-day mortality. Donors were considered extended if any one of the following criteria were met: age greater than 55 years, smoking longer than 20 pack-years, presence of chest radiographic film infiltrate, PO (2) of less than 300 mm Hg, or purulent secretions on bronchoscopy. Guideline and nonguideline recipients were defined on the basis of previously published criteria. RESULTS: Of a total of 123 donors, 63 (51%) were extended. Forty-eight donors failed 1 criterion, 10 failed 2 criteria, and 5 failed 3 criteria. One hundred twenty-eight transplants were performed. The 30-day mortality for the standard donor group was 4 (6.2%) of 65 versus 11 (17.5%) of 63 for the extended donor group (P =.047). CONCLUSIONS: Although many extended donor lungs will result in acceptable postoperative function, caution needs to be exercised in the uses of certain extended donor lungs because there seems to be an increased early mortality rate in that group of recipients. Nonguideline recipients appear to have acceptable early mortality, except when they received extended donor lungs.

Twenty-year experience of lung transplantation at a single center: Influence of recipient diagnosis on long-term survival.

OBJECTIVES: The objective of this study was to examine the long-term patient outcomes of lung transplantation in a single center. METHODS: Between 1983 and 2003, 521 lung transplants were performed in 501 patients. Major indications were cystic fibrosis (n = 124), chronic obstructive pulmonary disease (n = 88), alpha-1 antitrypsin deficiency (n = 63), pulmonary fibrosis (n = 97), primary pulmonary hypertension (n = 35), Eisenmenger syndrome (n = 21), and miscellaneous end-stage lung diseases (n = 93). RESULTS: The 5-, 10-, and 15-year survivals for all recipients were 55.1% (95% confidence interval: +/-5%), 35.3% (+/-6%), and 26.5% (+/-11%), respectively. The most common causes of death were sepsis and bronchiolitis obliterans syndrome. Despite an increased postoperative mortality rate, patients with primary pulmonary hypertension achieved the best long-term survival (10-year survival: 59%). Recipients with cystic fibrosis without Burkholderia cepacia infection achieved significantly better long-term survival (10-year survival: 52%) than those with Burkholderia cepacia infection (10-year survival: 15%). The 10-year survival was also significantly better in recipients with chronic obstructive pulmonary disease (43%) than in recipients with alpha-1 antitrypsin deficiency (23%). Although the incidence of bronchiolitis obliterans syndrome was similar between recipients with chronic obstructive pulmonary disease (39%) and alpha-1 antitrypsin deficiency (46%), recipients with alpha-1 antitrypsin deficiency died of sepsis more frequently than recipients with chronic obstructive pulmonary disease (27% vs 6%, respectively; P =.0003). CONCLUSIONS: Although bronchiolitis obliterans syndrome and sepsis still limit the durability of the benefit, lung transplantation returns many patients with end-stage lung disease to active and productive lives. Differences in the complications and long-term survival show the important contribution of the recipient diagnosis to the success of lung transplantation.

Factors affecting attainment of paid employment after lung transplantation.

BACKGROUND: Limited data exist regarding return to or attainment of paid employment after lung transplantation. Accordingly, the purpose of our study was to identify the issues relating to paid employment after this procedure. METHODS: We conducted a mailed survey using Dillman's protocol. We mailed questionnaires to surviving Toronto General Hospital lung transplant recipients (n = 190). We used descriptive statistics, t-tests, and chi-square tests to analyze the data. RESULTS: A total of 117 lung transplant recipients completed the questionnaires (70% response rate). The mean age of respondents was 51 +/- 13 years. Fifty-one percent of the sample were women and 72% were married. Cystic fibrosis and chronic obstructive pulmonary disease were the most frequent pre-transplant diagnoses. Fifty-six percent of participants had paid employment at some point before transplant. After transplant, 37% of respondents obtained employment. Individuals who obtained paid employment were more likely to be younger (p = 0.002), to have university degrees (p = 0.02), to report higher health ratings (p = 0.001), and to feel physically able to work (p = 0.01). They also were more likely to express a desire to enter the paid workforce (p < 0.0001); to describe receiving physician encouragement to work (p < 0.0001); to identify the possibility of obtaining paid employment as a primary motivator for the transplantation (p = 0.01); and to report that their previous jobs were available after transplantation (p = 0.01). All individuals who did not obtain paid employment cited personal or transplant-related factors. CONCLUSIONS: Medical and social factors influence attainment of paid employment after lung transplantation. Important components of the pre-transplant assessment are discussion of expectations about attaining employment and openly exploring the recipient's motivation for employment.

Bilateral lung transplantation for metastatic leiomyosarcoma.

As increased experience is gained in the field of lung transplantation, novel applications for this life saving therapy will evolve. We have described a case of bilateral lung transplantation in a young patient with respiratory failure secondary to metastatic leiomyosarcoma that was limited to the lungs. While lung transplantation for malignancy remains a controversial area, this case illustrates that lung transplantation can provide improved quality and quantity of life for highly selected patients with malignant disease.

De novo pulmonary capillary hemangiomatosis occurring rapidly after bilateral lung transplantation.

A 45-year-old woman experienced diffuse bilateral pulmonary capillary hemangiomatosis within 3 months after bilateral lung transplantation. The donor was a 41-year-old man with excellent lung function and without histologic or macroscopic pulmonary lesions at the time of retrieval. This case supports the theory that persistent infection or inflammation may be an inciting factor in uncontrolled angiogenesis, leading ultimately to diffuse pulmonary capillary hemangiomatosis.

Risk quantification of early outcome after lung transplantation: donor, recipient, operative, and post-transplant parameters.

BACKGROUND: Because there is no reliable evaluation system of recipient acuity after lung transplantation, comparing patients among centers is difficult. The purpose of our study was to identify risk factors for 30-day mortality and prolonged intensive care unit stay and to develop a scoring system to evaluate the severity of impairment and to predict surgical outcomes. METHODS: We prospectively collected data from 122 lung transplant recipients and from 119 donors from January 1997 to June 2000. We assessed donor, recipient, and operative factors; ischemic time; and immediate post-operative physiologic parameters to identify risk factors for 30-day mortality and prolonged intensive care unit stay. Furthermore, we sub-classified these factors into grades to develop a scoring system for predicting surgical outcomes. RESULTS: Cardiopulmonary bypass use, body mass index >25 kg/m2, immediate post-operative systolic pulmonary arterial pressure, trend of oxygenation index from 12 to 24 hours after transplantation, and the Acute Physiology and Chronic Health Evaluation II score correlated significantly with outcomes, and the sum of these 5 scores correlated strongly with outcomes (p < 0.0001). CONCLUSIONS: We conclude that the total score of these 5 risk factors could be used to predict 30-day mortality and prolonged intensive care unit stay. This scoring system also will facilitate standardization among transplant centers in evaluating post-transplant severity of illness.

Inspiratory and expiratory helical CT of normal adults: comparison of thin section scans and minimum intensity projection images.

SUMMARY: To evaluate and compare thin section CT scans (TSS) and minimum intensity projection images (MinIPs) in healthy individuals, 10 nonsmokers with normal pulmonary function tests were studied using ten 1-mm collimated, helically acquired TSS images after full inspiration and expiration at two anatomic levels. Ten-millimeter-thick MinIPs were generated from the helical scans. Two thoracic radiologists compared TSS and MinIPs for artifacts and air trapping. Hounsfield unit (HU) measurements of TSS and MinIPs were obtained. The lung parenchyma on MinIPs demonstrates a smooth anterior-to-posterior attenuation gradient, accentuated by expiration. Motion and beam-hardening artifacts on TSS images resulted in regions of high and low attenuation on MinIPs, respectively. Expiratory TSS and MinIPs demonstrated air trapping (n = 31/40; range, 0-25%; mean, 7.2%). In comparison with TSS, MinIPs improved the conspicuity of air trapping (n = 20) and appeared to detect more air trapping (n = 7). No statistical differences were found when comparing the mean HU values of TSS and MinIPs. MinIPs demonstrated a smooth anterior-to-posterior attenuation gradient. Compared with TSS, MinIPs improve the conspicuity of air trapping in healthy individuals. Therefore, expiratory MinIPs may be useful in detecting air trapping as a result of disease.

Revisiting the pathologic finding of diffuse alveolar damage after lung transplantation.

BACKGROUND: Diffuse alveolar damage (DAD) is a non-specific pathologic diagnosis frequently encountered after lung transplantation. We examined the relationship between DAD and different forms of chronic lung allograft dysfunction (CLAD). METHODS: We reviewed the results of 4,085 transbronchial biopsies obtained from 720 lung transplant recipients. DAD detected in biopsies within 3 months and newly detected DAD after 3 months were defined as early DAD and late new-onset DAD, respectively. Among patients with CLAD (FEV(1) <80% baseline), restrictive allograft syndrome (RAS) was defined by a decline in total lung capacity to <90% baseline and bronchiolitis obliterans syndrome (BOS) as CLAD without restrictive allograft syndrome (RAS). Kaplan-Meier analyses and multivariate proportional hazard models were used. RESULTS: DAD was observed in 320 of 720 (44.4%) patients at least once; early and late new-onset DAD were observed in 264 of 707 (37.3%) and 87 of 655 (13.3%) patients, respectively. Early DAD was associated with significantly higher 90-day mortality (20 of 264 [7.6%] vs 11 of 443 [2.5%]; p = 0.001). Moreover, among 502 bilateral lung transplant recipients who had sufficient pulmonary function tests to distinguish BOS and RAS, early DAD was associated with earlier BOS onset (hazard ratio [HR] 1.24; confidence interval [CI] 1.04 to 1.47; p = 0.017; median time of BOS onset: 2,902 vs 4,005 days). Conversely, treated as a time-varying covariate, late new-onset DAD was a significant risk factor for RAS in a Cox model (HR 36.8; CI 18.3 to 74.1; p < 0.0001). CONCLUSIONS: Early DAD is associated with early mortality and BOS, and late new-onset DAD increases the risk of RAS.