Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score-adjusted Cox models. We calculated postestimation marginalized standardized risks for 1-year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1- and 4-year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6-36.0 and aHR 3.8; 95%CI: 1.8-8.0, respectively). Each 1-point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08-1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%-21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1-13.2) but not over longer follow-up. Preoperative frailty is associated with an increased risk of death after lung transplantation.

Background. Lung transplantation remains the only treatment for end-stage lung disease. Availability of suitable lungs does not parallel this growing trend. Centers using donation after cardiac death (DCD) donor lungs report comparable outcomes with those from brain-dead donors. Donor assessment protocols and consistent surgical teams have been advocated when considering using the use of DCD donors. We present our experience using lungs from Maastricht category III DCD donors. Methods. Starting 2007 to July 2016, 73 DCD donors were assessed, 44 provided suitable lungs that resulted in 46 transplants. A 2012 to October 2016 comparative cohort of 379 brain-dead donors were assessed. Recipient and donor characteristics and primary graft dysfunction (PGD) and survival were monitored. Results. Seventy-three DCD (40% dry run rate) donors assessed yielded 46 transplants (23 double, 6 right, and 17 left). Comparative cohort of 379 brain-dead donors yielded 237 transplants (112 double, 43 right, and 82 left). One-and 3-year recipient survival was 91% and 78% for recipients of DCD lungs and 91% and 75% for recipients of lungs from brain-dead donors, respectively. PGD 2 and 3 in DCD recipients at 72 hours was 4 of 46 (9%) and 6 of 46 (13%), respectively. Comparatively, brain-dead donor recipient cohort at 72 hours with PGD 2 and 3 was 23 of 237 (10%) and 41 of 237 (17%), respectively. Conclusions. Our experience reaffirms the use of lungs from DCD donors as a viable source with favorable outcomes. Recipients from DCD donors showed equivalent PGD rate at 72 hours and survival compared with recipients from brain-dead donors. (C) 2018 by The Society of Thoracic Surgeons

Rationale: Anecdotally, short lung transplant candidates suffer from long waiting times and higher rates of death on the waiting list compared with taller candidates.Objectives: To examine the relationship between lung transplant candidate height and waiting list outcomes.Methods: We conducted a retrospective cohort study of 13,346 adults placed on the lung transplant waiting list in the United States between 2005 and 2011. Multivariable-adjusted competing risk survival models were used to examine associations between candidate height and outcomes of interest. The primary outcome was the time until lung transplantation censored at 1 year.Measurements and Main Results: The unadjusted rate of lung transplantation was 94.5 per 100 person-years among candidates of short stature (<162 cm) and 202.0 per 100 person-years among candidates of average stature (170-176.5 cm). After controlling for potential confounders, short stature was associated with a 34% (95% confidence interval [CI], 29-39%) lower rate of transplantation compared with average stature. Short stature was also associated with a 62% (95% CI, 24-96%) higher rate of death or removal because of clinical deterioration and a 42% (95% CI, 10-85%) higher rate of respiratory failure while awaiting lung transplantation.Conclusions: Short stature is associated with a lower rate of lung transplantation and higher rates of death and respiratory failure while awaiting transplantation. Efforts to ameliorate this disparity could include earlier referral and listing of shorter candidates, surgical downsizing of substantially oversized allografts for shorter candidates, and/or changes to allocation policy that account for candidate height.

OBJECTIVES:End-stage lung disease continues to rise despite the lack of suitable lung donors, limiting the numbers of lung transplants performed each year. Expanded donor criteria, use of donation after cardiac death donors and the advent of ex vivo lung perfusion have resulted only in a slight increase in donor lung utilization. Organ donors with prior cardiac surgery (DPCS) present risks and technical challenges; however, they may be a potential source of suitable lung allografts with an experienced procurement surgeon. We present our experience having evaluated potential lung donors with a prior history of cardiac surgery, resulting in successful transplant outcomes.METHODS:This is a single-institution retrospective review of brain-dead organ donors that were evaluated for lung donation in the period 2012-15. Donor and recipient characteristics were collected. Post-lung transplant survival was recorded.RESULTS:From 2012 to 2015, 259 donors were evaluated, 12 with a prior history of cardiac surgery of which 4 had coronary artery bypass, 3 had aortic root replacement, 2 had aortic valve replacement, 1 pulmonary embolectomy, 1 two-time reoperative valve replacement and 1 paediatric congenital ventricular septal defect repair. DPCS, 6/12 (50% dry run) provided suitable allografts generating six single-lung transplants (three right and three left, 1 donor provided twin single-lung transplants) and one double-lung transplant. Interval between cardiac surgery and procurement for those rejected was median 5840 (IQR 2350-8640) days and interval for the donors that provided allografts was median 438 (IQR 336-1095) days (Mann-Whitney, P = 0.07). Recipient 1-year survival from DPCS is 100%. Recipient 1-year survival was 92% in allografts explanted from donors with no prior cardiac surgery (2012-13).CONCLUSION:To date, this is the largest single-centre experience using lung allografts from brain-dead DPCS. Our experience shows despite predicted technical difficulties, with good communication between thoracic and abdominal teams, successful transplant outcomes are possible, when surgeons with experience in reoperative cases are sent for lung procurements.

Lung transplant is the ultimate option for end stage lung disease pts. Overall survival is halted by rejection and chronic lung allograft dysfunction (CLAD). Gastro-esophageal reflux and aspiration has been considered a risk factor for CLAD. Bile acid aspiration was investigated by targeted metabolomics in the bronchial washings from lung transplant patients. Given the detergent properties of bile acids, their effect of the bronchial district lipids was studied using a lipidomics approach. Bronchial washings (BW) (56 samples) were prospectively collected from 51 patients at routine surveillance post-transplant bronchoscopies. Liquid chromatography-mass spectrometry retrospectively assayed BW for 13 bile acids and 25 lipid families inclusive of 250 lipids. Patients were monitored for CLAD and transbronchial biopsies for rejection and inflammation. Bile acids were detected in all BW. BW from pts with CLAD (22/51) had overall greater levels of bile acids (Mann Whitney p=0.03). Different levels (Kruscal Wallis p<0.05) were noted in BW from pts with early (onset <24 mo) CLAD (19.4 nM/L, IQR 15.2 - 35.8), late CLAD (26, 19.3-55.9), and no-CLAD (17.1, 13.5-26.4). Late CLAD vrs no-CLAD group (p=0.02); late CLAD vrs early CLAD (p=0.05); no difference for early CLAD vrs. no CLAD. Total Bile acids correlated (p<0.0005) with: cholesteryl-esters (CE) (Spearman r=0.6); Sphingomyelin (SM) (r=0.5); dihydrosphingomyelin (dhSM) (r=0.55); lactosyl-ceramide (Lac-Cer) (r=0.6); Lysophosphatidylcholine ether (LPCe) (r=0.5). Bile acids levels, high (upper quartile >27.5 nM/L) vrs. low, showed greater levels (p<0.05) of: CE, SM, dhSM, hexosyl-Cer, Lac-Cer, ganglioside GM3, phosphatidic acid, dipalmitoylphosphatidylcholine phosphatidylcholin ether, lysophosphatidylcholine, LPCe, lysophosphatidylinositol, phosphatidylethanolamine-p, lysophosphatidylethanolamine, lysophosphatidylethanolamine-p, phosphatidylinositol, and acylphosphatidylglycerol. Bile acids assayed by mass spec are detected in all lung transplant bronchial washings. High level of bile acids associate with late CLAD onset and have a significant dose related effect on the bronchial district lipidomic profile.

OBJECTIVES Standard donor lung assessment relies on imaging, challenge gases and subjective interpretation of bronchoscopic findings, palpation and visual assessment. Central gases may not accurately represent true quality of the lungs. We report our experience using selective pulmonary vein gases to corroborate the subjective judgement. METHODS Starting, January 2012, donor lungs have been assessed by intraoperative bronchoscopy, palpation and visual judgement of lung collapse upon temporary disconnection from ventilator, central gases from the aorta and selective pulmonary vein gases. Partial pressure of oxygen (pO2) <300 mmHg on FiO2 of 1.0 was considered low. The results of the chest X-ray and last pO2 in the intensive care unit were also collected. Post-transplant primary graft dysfunction and survival were monitored. RESULTS To date, 259 consecutive brain-dead donors have been assessed and 157 transplants performed. Last pO2 in the intensive care unit was poorly correlated with intraoperative central pO2 (Spearman's rank correlation rs = 0.29). Right inferior pulmonary vein pO2 was associated (Mann-Whitney, P < 0.001) with findings at bronchoscopy [clean: median pO2 443 mmHg (25th-75th percentile range 349-512) and purulent: 264 mmHg (178-408)]; palpation [good: 463 mmHg (401-517) and poor: 264 mmHg (158-434)] and visual assessment of lung collapse [good lung collapse: 429 mmHg (320-501) and poor lung collapse: 205 mmHg (118-348)]. Left inferior pulmonary pO2 was associated (P < 0.001) with findings at bronchoscopy [clean: 419 mmHg (371-504) and purulent: 254 mmHg (206-367)]; palpation [good: 444 mmHg (400-517) and poor 282 mmHg (211-419)] and visual assessment of lung collapse [good: 420 mmHg (349-496) and poor: 246 mmHg (129-330)]. At 72 h, pulmonary graft dysfunction 2 was in 21/157 (13%) and pulmonary graft dysfunction 3 in 17/157 (11%). Ninety-day and 1-year mortalities were 6/157 (4%) and 13/157 (8%), respectively. CONCLUSIONS Selective pulmonary vein gases provide corroborative objective support to the findings at bronchoscopy, palpation and visual assessment. Central gases do not always reflect true function of the lungs, having high false-positive rate towards the individual lower lobe gas exchange. Objective measures of donor lung function may optimize donor surgeon assessment, allowing for low pulmonary graft dysfunction rates and low 90-day and 1-year mortality.

Lung transplantation outcomes are challenged by bacterial, viral and fungal infections, noxious triggers that could amplify or promote inflammation and chronic lung allograft dysfunction. We hypothesized the airway lipidome serves as marker of lung infection and related innate immunity. The effects of bacterial, viral and fungal infections on the BW and BAL lipidome from allografts were studied. BW (596) and BAL (199), prospectively collected from 288 pts during surveillance bronchoscopy, were assayed retrospectively by mass-spec for 25 lipid families. Microbiology info was collected. Mann Whitney test used. Bacteria were isolated in 168 BW and 49 BAL, virus in 54 BW and 22 BAL, fungi in 102 BW and 33 BAL. Virus and fungi showed greater BW and BAL total lipid concentration (p BW with bacteria had greater (p BW with virus had greater (p BW with fungi had greater (p The bronchial and broncho-alveolar lipidome of lung allografts is affected by the microbiologic status. Bacteria, virus and fungi have signature lipidomic profile that we speculate associates within the specific bronchial and broncho-alveolar innate immunity.

Lung transplantation is the last option for end stage lung disease. Long term outcomes are halted by rejection and chronic lung allograft dysfunction (CLAD). To date no biological markers have been identified to investigate the immunological and functional status of the allograft. The lipidomic profiles in bronchial washing (BW) and bronchoalveolar lavage (BAL) were studied in association with the histological and functional status of the lung allograft. Post transplantation, 597 bronchial washings (20 ml NS in proximal airways) and 190 bronchoalveolar lavages (100 ml NS in distal airways) were prospectively collected from 287 pts at surveillance bronchoscopies, and in 273 pts 546 transbronchial biopsies. BW and BAL were assayed by Liquid chromatography-mass spectrometry for 250 lipids of 25 lipid families. CLAD was diagnosed in 134/287 pts. BAL collected after CLAD onset (52/190) had reduced dipalmitoylphosphatidylcholine and acylphosphatidylglycerol (p<0.05), while BW (113/597) had greater cholesteryl ester (CE), sphingomyelin (SM), dihydrosphingomyelin (dhSM), lactosylceramide (LacCer), phosphatidylcholine ether (PCe), phosphatidylethanolamine-p (PEp), phosphatidylserine, lysophosphatidylethanolamine (LPE) and lysophosphatidylethanolamine-p (LPEp) and lower ceramide (Cer) (p<0.05). Acute rejection was found in 51 biopsies (38 A1, 13 A2), A0 in 445 and Ax in 50. Airway inflammation was found in 59 biopsies (57 B1, 2 B2), B0 in 333 and Bx in 154. BW collected at time of acute rejection differed (p<0.05) for diacylglycerol (DAG), triacylglycerol, LacCer, LPE and LPEp. BAL collected at time of airway inflammation differed (p<0.05) for DAG, LacCer, N-Acylphosphatidylserine, SM, dhSM, monosialodihexosylganglioside, PCe, Phosphatidylinositol, Pep, whereas BW differed (p<0.05) for CE, Cer, LacCer, PCe, PEp. The bronchial and alveolar lipidomic profile offers different signatures of the functional and immunological status of the lung allograft and varies between BW and BAL. In lungs with acute rejection, differences are found in BW lipidome. Airway inflammation shows changes in BW and BAL. CLAD had an altered profile of the lipids, in particular surfactant phospholipids in BW and BAL. A clinical use of bronchial and alveolar lipidome as a marker of the allograft’s pathophysiology is speculated.

RATIONALEFrailty is associated with morbidity and mortality in abdominal organ transplantation but has not been examined in lung transplantation.OBJECTIVESTo examine the construct and predictive validity of frailty phenotypes in lung transplant candidates.METHODSIn a multicenter prospective cohort, we measured frailty with the Fried Frailty Phenotype (FFP) and Short Physical Performance Battery (SPPB). We evaluated construct validity through comparisons with conceptually related factors. In a nested case-control study of frail and nonfrail subjects, we measured serum IL-6, tumor necrosis factor receptor 1, insulin-like growth factor I, and leptin. We estimated the association between frailty and disability using the Lung Transplant Valued Life Activities disability scale. We estimated the association between frailty and risk of delisting or death before transplant using multivariate logistic and Cox models, respectively.MEASUREMENTS AND MAIN RESULTSOf 395 subjects, 354 completed FFP assessments and 262 completed SPPB assessments; 28% were frail by FFP (95% confidence interval [CI], 24-33%) and 10% based on the SPPB (95% CI, 7-14%). By either measure, frailty correlated more strongly with exercise capacity and grip strength than with lung function. Frail subjects tended to have higher plasma IL-6 and tumor necrosis factor receptor 1 and lower insulin-like growth factor I and leptin. Frailty by either measure was associated with greater disability. After adjusting for age, sex, diagnosis, and transplant center, both FFP and SPPB were associated with increased risk of delisting or death before lung transplant. For every 1-point worsening in score, hazard ratios were 1.30 (95% CI, 1.01-1.67) for FFP and 1.53 (95% CI, 1.19-1.59) for SPPB.CONCLUSIONSFrailty is prevalent among lung transplant candidates and is independently associated with greater disability and an increased risk of delisting or death.

PurposeLung transplantation is and established treatment option for end stage lung disease, although long-term clinical outcomes are halted by the onset of bronchiolitis obliterans syndrome and chronic lung allograft dysfunction (CLAD). To date diagnosis of CLAD relies on pulmonary function tests. No biologic marker has yet been clearly established to corroborate or anticipate the diagnosis. We sought to investigate role of broncho-alveolar surfactant phospholipids as a marker of CLAD by using a targeted lipidomic methodology.MethodsPost transplantation, 222 bronchial washing samples were prospectively collected from 90 patients during surveillance bronchoscopies. Utilizing Liquid chromatography-mass spectrometry methods, samples were retrospectively assayed in a semiquantitative fashion for surfactant phospholipids.ResultsCLAD was diagnosed in 30/90 patients, and 47 bronchial washing samples were collected after the clinical diagnosis of CLAD was established. Samples collected after development of CLAD had lower levels dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG) (Mann-Whitney, p<0.05), and greater levels of sphingomyelin (SM) and e-phosphatidylcholine (ePC) (Mann-Whitney, p<0.05). No significance was noted for other species of phosphatidylcholine (PC) dihydrosphingmyelin (dhSM), phosphatidylinositol (PI), lysophosphatidylcholine (LPC), and lysophosphatidylcholine-ester (eLPC). The table shows median, range and p-values.ConclusionSurfactant phospholipids may serve as biologic marker of CLAD as measured in bronchial washings from post lung transplant patients. In particular bronchial washings from lungs with CLAD showed an altered surfactant phospholipid profile with reduced levels of DPPC and PG, and increased levels of SM and ePC. With further exploration, the change in lipid profile could be used as early detection for the development of CLAD. PurposeLung transplantation is and established treatment option for end stage lung disease, although long-term clinical outcomes are halted by the onset of bronchiolitis obliterans syndrome and chronic lung allograft dysfunction (CLAD). To date diagnosis of CLAD relies on pulmonary function tests. No biologic marker has yet been clearly established to corroborate or anticipate the diagnosis. We sought to investigate role of broncho-alveolar surfactant phospholipids as a marker of CLAD by using a targeted lipidomic methodology. Lung transplantation is and established treatment option for end stage lung disease, although long-term clinical outcomes are halted by the onset of bronchiolitis obliterans syndrome and chronic lung allograft dysfunction (CLAD). To date diagnosis of CLAD relies on pulmonary function tests. No biologic marker has yet been clearly established to corroborate or anticipate the diagnosis. We sought to investigate role of broncho-alveolar surfactant phospholipids as a marker of CLAD by using a targeted lipidomic methodology. MethodsPost transplantation, 222 bronchial washing samples were prospectively collected from 90 patients during surveillance bronchoscopies. Utilizing Liquid chromatography-mass spectrometry methods, samples were retrospectively assayed in a semiquantitative fashion for surfactant phospholipids. Post transplantation, 222 bronchial washing samples were prospectively collected from 90 patients during surveillance bronchoscopies. Utilizing Liquid chromatography-mass spectrometry methods, samples were retrospectively assayed in a semiquantitative fashion for surfactant phospholipids. ResultsCLAD was diagnosed in 30/90 patients, and 47 bronchial washing samples were collected after the clinical diagnosis of CLAD was established. Samples collected after development of CLAD had lower levels dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG) (Mann-Whitney, p<0.05), and greater levels of sphingomyelin (SM) and e-phosphatidylcholine (ePC) (Mann-Whitney, p<0.05). No significance was noted for other species of phosphatidylcholine (PC) dihydrosphingmyelin (dhSM), phosphatidylinositol (PI), lysophosphatidylcholine (LPC), and lysophosphatidylcholine-ester (eLPC). The table shows median, range and p-values. CLAD was diagnosed in 30/90 patients, and 47 bronchial washing samples were collected after the clinical diagnosis of CLAD was established. Samples collected after development of CLAD had lower levels dipalmitoylphosphatidylcholine (DPPC) and phosphatidylglycerol (PG) (Mann-Whitney, p<0.05), and greater levels of sphingomyelin (SM) and e-phosphatidylcholine (ePC) (Mann-Whitney, p<0.05). No significance was noted for other species of phosphatidylcholine (PC) dihydrosphingmyelin (dhSM), phosphatidylinositol (PI), lysophosphatidylcholine (LPC), and lysophosphatidylcholine-ester (eLPC). The table shows median, range and p-values. ConclusionSurfactant phospholipids may serve as biologic marker of CLAD as measured in bronchial washings from post lung transplant patients. In particular bronchial washings from lungs with CLAD showed an altered surfactant phospholipid profile with reduced levels of DPPC and PG, and increased levels of SM and ePC. With further exploration, the change in lipid profile could be used as early detection for the development of CLAD. Surfactant phospholipids may serve as biologic marker of CLAD as measured in bronchial washings from post lung transplant patients. In particular bronchial washings from lungs with CLAD showed an altered surfactant phospholipid profile with reduced levels of DPPC and PG, and increased levels of SM and ePC. With further exploration, the change in lipid profile could be used as early detection for the development of CLAD.

PurposeFrailty is associated with morbidity and mortality in other solid organ transplant populations. It is under-examined in lung transplant, however. We measured frailty prevalence, construct validity, and association with delisting or death before transplant in candidates for lung transplant.MethodsWe performed a preliminary analysis of lung transplant candidates from four U.S. centers enrolled in the Lung Transplant Body Composition prospective cohort study. Frailty was assessed by the Fried Frailty Index (FFI; range 0-5, higher score denotes poorer functioning) as well as the Short Physical Performance Battery (SPPB; range 0-12, lower score denotes poorer functioning). Because sarcopenia (low muscle mass) may underpin the frailty phenotype, we measured muscle mass by whole-body DEXA and calculated the appendicular skeletal muscle index (ASMI) in a subset of subjects. We evaluated construct validity by testing correlations between frailty measures and ASMI, forced vital capacity % predicted (FVC %), body mass index (BMI), age, six minute walk distance (6MWD), and Lung Allocation Score (LAS). To evaluate predictive validity, we determined the association between frailty measures and delisting or death on the waitlist with logistic regression.ResultsBy FFI, 38% were frail (n = 133/351) and 12% by SPPB (n = 25/208). The strength and direction of correlations between the FFI and SPPB and other measures were as hypothesized. Worse frailty scores correlated with lower ASMI (FFI: -0.35; SPPB 0.18), lower 6MWD (FFI: -0.26; SPPB: 0.36), and higher LAS (FFI: 0.32; SPPB: -0.54) (all p<0.05), but not with age, BMI, or FVC %. In unadjusted analyses, each 1-point worsening in the FFI or SPPB was associated with ~1/3-increased odds of delisting or death before transplant (FFI: OR 1.37, 95% CI: 1.07-1.77) (SPPB: OR 1.32, 95% CI: 1.13-1.55). After adjusting for age, gender, FVC %, BMI, creatinine, LAS, and center, the SPPB, but not FFI, remained significant (OR: 1.38, 95% CI: 1.02-1.88).ConclusionThe FFI and SPPB exhibit reasonable construct validity as frailty measures in lung transplant candidates. Frail patients appear to be at increased risk of delisting or death prior to transplant. Further work will examine the relationship between pre-operative frailty and mortality after transplant. Refinement of the frailty construct may improve its prognostic utility in this population. PurposeFrailty is associated with morbidity and mortality in other solid organ transplant populations. It is under-examined in lung transplant, however. We measured frailty prevalence, construct validity, and association with delisting or death before transplant in candidates for lung transplant. Frailty is associated with morbidity and mortality in other solid organ transplant populations. It is under-examined in lung transplant, however. We measured frailty prevalence, construct validity, and association with delisting or death before transplant in candidates for lung transplant. MethodsWe performed a preliminary analysis of lung transplant candidates from four U.S. centers enrolled in the Lung Transplant Body Composition prospective cohort study. Frailty was assessed by the Fried Frailty Index (FFI; range 0-5, higher score denotes poorer functioning) as well as the Short Physical Performance Battery (SPPB; range 0-12, lower score denotes poorer functioning). Because sarcopenia (low muscle mass) may underpin the frailty phenotype, we measured muscle mass by whole-body DEXA and calculated the appendicular skeletal muscle index (ASMI) in a subset of subjects. We evaluated construct validity by testing correlations between frailty measures and ASMI, forced vital capacity % predicted (FVC %), body mass index (BMI), age, six minute walk distance (6MWD), and Lung Allocation Score (LAS). To evaluate predictive validity, we determined the association between frailty measures and delisting or death on the waitlist with logistic regression. We performed a preliminary analysis of lung transplant candidates from four U.S. centers enrolled in the Lung Transplant Body Composition prospective cohort study. Frailty was assessed by the Fried Frailty Index (FFI; range 0-5, higher score denotes poorer functioning) as well as the Short Physical Performance Battery (SPPB; range 0-12, lower score denotes poorer functioning). Because sarcopenia (low muscle mass) may underpin the frailty phenotype, we measured muscle mass by whole-body DEXA and calculated the appendicular skeletal muscle index (ASMI) in a subset of subjects. We evaluated construct validity by testing correlations between frailty measures and ASMI, forced vital capacity % predicted (FVC %), body mass index (BMI), age, six minute walk distance (6MWD), and Lung Allocation Score (LAS). To evaluate predictive validity, we determined the association between frailty measures and delisting or death on the waitlist with logistic regression. ResultsBy FFI, 38% were frail (n = 133/351) and 12% by SPPB (n = 25/208). The strength and direction of correlations between the FFI and SPPB and other measures were as hypothesized. Worse frailty scores correlated with lower ASMI (FFI: -0.35; SPPB 0.18), lower 6MWD (FFI: -0.26; SPPB: 0.36), and higher LAS (FFI: 0.32; SPPB: -0.54) (all p<0.05), but not with age, BMI, or FVC %. In unadjusted analyses, each 1-point worsening in the FFI or SPPB was associated with ~1/3-increased odds of delisting or death before transplant (FFI: OR 1.37, 95% CI: 1.07-1.77) (SPPB: OR 1.32, 95% CI: 1.13-1.55). After adjusting for age, gender, FVC %, BMI, creatinine, LAS, and center, the SPPB, but not FFI, remained significant (OR: 1.38, 95% CI: 1.02-1.88). By FFI, 38% were frail (n = 133/351) and 12% by SPPB (n = 25/208). The strength and direction of correlations between the FFI and SPPB and other measures were as hypothesized. Worse frailty scores correlated with lower ASMI (FFI: -0.35; SPPB 0.18), lower 6MWD (FFI: -0.26; SPPB: 0.36), and higher LAS (FFI: 0.32; SPPB: -0.54) (all p<0.05), but not with age, BMI, or FVC %. In unadjusted analyses, each 1-point worsening in the FFI or SPPB was associated with ~1/3-increased odds of delisting or death before transplant (FFI: OR 1.37, 95% CI: 1.07-1.77) (SPPB: OR 1.32, 95% CI: 1.13-1.55). After adjusting for age, gender, FVC %, BMI, creatinine, LAS, and center, the SPPB, but not FFI, remained significant (OR: 1.38, 95% CI: 1.02-1.88). ConclusionThe FFI and SPPB exhibit reasonable construct validity as frailty measures in lung transplant candidates. Frail patients appear to be at increased risk of delisting or death prior to transplant. Further work will examine the relationship between pre-operative frailty and mortality after transplant. Refinement of the frailty construct may improve its prognostic utility in this population. The FFI and SPPB exhibit reasonable construct validity as frailty measures in lung transplant candidates. Frail patients appear to be at increased risk of delisting or death prior to transplant. Further work will examine the relationship between pre-operative frailty and mortality after transplant. Refinement of the frailty construct may improve its prognostic utility in this population.

Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.

PurposeLung transplantation remains the only treatment for end-stage lung disease with a growing influx of individuals on the waiting list. Availability of suitable lungs for transplant does not parallel this growing trend. The use of lungs from donation after cardiac death (DCD) has been suggested to have equal results to those procured from brain dead donors. Although, concern still exists regarding organ quality and the potential for increased incidence of pulmonary graft dysfunction. We present our experience using lung allografts from Maastricht category III DCD donors.MethodsStarting January 2007 we performed lung transplants using organs procured from DCD donors. A retrospective review of recipient's clinical outcomes was conducted. In particular primary graft dysfunction and survival was monitored and compared to the cohort of patients transplanted in the same period using organs procured from brain dead donors.ResultsTo date 35 DCD donors have been evaluated yielding 19 transplants with a 46% rate of dry runs. Recipient survival is 100% at 3-month, and 94% at one year. One recipient died at 8 months post transplant. Comparatively, our 12-month survival in 401 recipients from brain dead donors is 89%. Table 1 and 2 show the donor and recipient characteristics.ConclusionFigView Large Image Figure ViewerDownload Hi-res image Download (PPT) PurposeLung transplantation remains the only treatment for end-stage lung disease with a growing influx of individuals on the waiting list. Availability of suitable lungs for transplant does not parallel this growing trend. The use of lungs from donation after cardiac death (DCD) has been suggested to have equal results to those procured from brain dead donors. Although, concern still exists regarding organ quality and the potential for increased incidence of pulmonary graft dysfunction. We present our experience using lung allografts from Maastricht category III DCD donors. Lung transplantation remains the only treatment for end-stage lung disease with a growing influx of individuals on the waiting list. Availability of suitable lungs for transplant does not parallel this growing trend. The use of lungs from donation after cardiac death (DCD) has been suggested to have equal results to those procured from brain dead donors. Although, concern still exists regarding organ quality and the potential for increased incidence of pulmonary graft dysfunction. We present our experience using lung allografts from Maastricht category III DCD donors. MethodsStarting January 2007 we performed lung transplants using organs procured from DCD donors. A retrospective review of recipient's clinical outcomes was conducted. In particular primary graft dysfunction and survival was monitored and compared to the cohort of patients transplanted in the same period using organs procured from brain dead donors. Starting January 2007 we performed lung transplants using organs procured from DCD donors. A retrospective review of recipient's clinical outcomes was conducted. In particular primary graft dysfunction and survival was monitored and compared to the cohort of patients transplanted in the same period using organs procured from brain dead donors. ResultsTo date 35 DCD donors have been evaluated yielding 19 transplants with a 46% rate of dry runs. Recipient survival is 100% at 3-month, and 94% at one year. One recipient died at 8 months post transplant. Comparatively, our 12-month survival in 401 recipients from brain dead donors is 89%. Table 1 and 2 show the donor and recipient characteristics. To date 35 DCD donors have been evaluated yielding 19 transplants with a 46% rate of dry runs. Recipient survival is 100% at 3-month, and 94% at one year. One recipient died at 8 months post transplant. Comparatively, our 12-month survival in 401 recipients from brain dead donors is 89%. Table 1 and 2 show the donor and recipient characteristics. Conclusion

Purpose Our group has hypothesized that the frailty phenotype might help identify those at high risk of early complications after lung transplantation. The prevalence of pre-transplant frailty among transplant recipients and the impact of frailty on outcomes after transplantation is not known. Methods and Materials We performed an interim analysis of the first 46 consecutive lung transplant recipients ≥50 years old enrolled in the Lung Transplant Body Composition (LTBC) study at our center. All LTBC participants undergo a structured frailty assessment during transplant evaluation. Frailty was defined as the presence of ≥3 of the following: unintentional weight loss ≥ 4.5kg, low walking speed, self-reported exhaustion, low activity level, and low grip strength. Wilcoxon rank sum tests, Chi-square tests, Fisher’s exact tests, and log-rank tests were used to compare frail and non-frail participants. Results The mean (SD) age was 62 (5) yrs, 34% were ≥ 65 yrs, 44% were female, 13% were African-American, 54% had ILD, 14% had COPD, 2% had CF, 4% were underweight, 13% were obese, the median LAS was 42 (IQR 33 to 51), 48% were bilateral, and 11 (24%) were frail. Frail recipients were more frequently African-American (37% vs. 6%, p = 0.02) but were similar with regard to age, gender, BMI, diagnosis, LAS score, PA pressure, and use of cardiopulmonary bypass. There were non-significant trends toward more intraoperative complications (28% vs 6%, p = 0.08), postoperative complications (64% vs 37%, p = 0.17), unplanned returns to the OR (18% vs 6%, p = 0.24), and deaths on the ventilator (18% vs 2%, p = 0.14) among frail vs non-frail recipients, respectively. The 30-day mortality rate was 18% among frail and 0% among non-frail (p = 0.01). Conclusions The frail phenotype is prevalent among lung transplant recipients over 50 years old at our center and is not associated with diagnosis or LAS score. Our finding of an unadjusted association of frailty with poor outcomes should be interpreted cautiously. These findings merit additional study.

BACKGROUND:Lung transplants, in particular, have the highest rate of infections among solid organ transplant recipients. However, there is no existing objective measure to predict the development of infections. We report the correlation between Cylex ImmuKnow (ng/mL ATP) values and various infectious syndromes in a large prospective cohort of lung transplant recipients.METHODS:We followed up 175 lung transplants that developed 129 infectious episodes. Multiple logistic regression analysis was performed; generalized estimating equations were used to determine the odds ratio for infections.RESULTS:The median ImmuKnow values in cytomegalovirus disease (49.3 ng/mL ATP), viral infection (70 ng/mL ATP), and bacterial pneumonia (92 ng/mL ATP) were significantly different from stable state (174.8 ng/mL ATP). The median ImmuKnow values of fungal disease (85 ng/mL ATP) and tracheobronchitis (123 ng/mL ATP) had a tendency to be lower than stable state (P=0.10), whereas patients with fungal colonization had comparable ImmunKnow values (167 vs. 174.8 ng/mL ATP). Of the patients colonized with fungus who subsequently developed fungal disease within 100 days, the median value of ImmuKnow was significantly lower than in those who did not develop fungal disease (22.5 vs. 183.5 ng/mL ATP; P<0.0001). Generalized estimating equation regression analysis showed ImmuKnow values less than or equal to 100 ng/mL ATP to be an independent predictor of infections (odds ratio 2.81).CONCLUSIONS:Cylex ImmuKnow assay monitoring has the potential to identify the patients at risk of developing infection and those colonized with fungus that are at risk of developing disease.

Human metapneumovirus (hMPV) has recently been shown to be a prominent cause of respiratory infections in immunocompromised hosts, and is associated with high morbidity and mortality. We report a case of hMPV pneumonia in a lung transplant recipient presenting with respiratory failure and sepsis syndrome. hMPV was diagnosed by polymerase chain reaction, and treated with intravenous ribavirin with a successful outcome.