Purpose Bilateral lung transplantation (BLTx) is beneficial for selective candidates including pulmonary hypertension (PH). Primary Arterial and other causes for pulmonary hypotension impact survival. Medical treatment with novel pharmaceuticals provided some amelioration but transplantation remains the long term means for survival. We hypothesized that early survival depends on primary versus secondary PH. Methods A retrospective review of ISHLT registry (05/06/2005 - 12/31/2016); follow up until 2018. The analysis was limited to BLTx patients > 18 yo, excluding multi-organ tx, redo tx, or lobar tx. Primary diagnosis divided as follows: Primary PH (PPH), Secondary PH excluding WHO class 1 (SPH), and non PH diseases. Age (ANOVA &let.03, sex chi sq. < .001) are significant. Results Patient subset had intraoperative mean PA pressures as follows: PPH (n=363) 56.7mmHg (sd 14.8), SPH (n=120) 40.6 (sd 16.0), non PH (n=12185), 28.6 (sd 11.8). ANOVA test between groups was < .001. Mean survival (days) for PPH (n=976) 2677 (CI 2530, 2824), SPH (n=173) 1953 (CI 1695, 2212), and non PH (n=27449) 2663.9 (CI 2633, 2893). Pairwise comparison log rank showed significance between PPH and SPH (chi sq. 11.8 p .001) and SPH non PH (18.0 p < .001). No difference between PPH and non-PH (.932 p=.334). Cumulative proportion surviving for PPH, SPH, and non-PH are 0.9, 0.87, 0.95 (sd err < .03) at 30 days respectively; 0.85, 0.83, 0.92 (sd err < .03) at 90 days; 0.8, 0.75, 0.85 (sd err < .03) at 365 days. Pairwise comparisons by Wilcoxon test was significant < .03 for all groups. Conclusion Despite lower survival at 90 days and 1 year, PPH does not have significantly worse long-term survival than non-PH (see KM curve for details). SPH has decreased early survival. The attrition rate continues to diverge from non-PH and PPH. The differences in outcome between PPH and SPH hold strong implications in the patient selection process Bilateral lung transplantation (BLTx) is beneficial for selective candidates including pulmonary hypertension (PH). Primary Arterial and other causes for pulmonary hypotension impact survival. Medical treatment with novel pharmaceuticals provided some amelioration but transplantation remains the long term means for survival. We hypothesized that early survival depends on primary versus secondary PH. A retrospective review of ISHLT registry (05/06/2005 - 12/31/2016); follow up until 2018. The analysis was limited to BLTx patients > 18 yo, excluding multi-organ tx, redo tx, or lobar tx. Primary diagnosis divided as follows: Primary PH (PPH), Secondary PH excluding WHO class 1 (SPH), and non PH diseases. Age (ANOVA &let.03, sex chi sq. < .001) are significant. Patient subset had intraoperative mean PA pressures as follows: PPH (n=363) 56.7mmHg (sd 14.8), SPH (n=120) 40.6 (sd 16.0), non PH (n=12185), 28.6 (sd 11.8). ANOVA test between groups was < .001. Mean survival (days) for PPH (n=976) 2677 (CI 2530, 2824), SPH (n=173) 1953 (CI 1695, 2212), and non PH (n=27449) 2663.9 (CI 2633, 2893). Pairwise comparison log rank showed significance between PPH and SPH (chi sq. 11.8 p .001) and SPH non PH (18.0 p < .001). No difference between PPH and non-PH (.932 p=.334). Cumulative proportion surviving for PPH, SPH, and non-PH are 0.9, 0.87, 0.95 (sd err < .03) at 30 days respectively; 0.85, 0.83, 0.92 (sd err < .03) at 90 days; 0.8, 0.75, 0.85 (sd err < .03) at 365 days. Pairwise comparisons by Wilcoxon test was significant < .03 for all groups. Despite lower survival at 90 days and 1 year, PPH does not have significantly worse long-term survival than non-PH (see KM curve for details). SPH has decreased early survival. The attrition rate continues to diverge from non-PH and PPH. The differences in outcome between PPH and SPH hold strong implications in the patient selection process

Purpose Various etiologies of pulmonary hypertension (PH) and their comorbidities may impact post-lung transplantation (LTx) outcomes. We hypothesized that primary PH, scleroderma PH, and other secondary PH differ in post-tx survival. Methods ISHLT registry was investigated (05/06/2005 -12/31/2016) for bilateral LTx patients > 18 yo excluding multi-organ tx, redo tx, or lobar tx. Primary diagnosis for tx divided as follows: Primary PH (PPH), other Secondary PH (SPH), scleroderma PH (sclPH), and non PH. Age and gender PPH against all 3 groups p < .001, other demographics NS p < .06. Results Kaplan Meier survival (days, mean) PPH (n=937) 2677 (CI 2530, 2824); SPH (n=173) 1953 (CI 1695, 2212); non PH (n=27449) 2664.0 (CI 2633, 2694); SclPH (n=221) 2448.4 (CI 2175, 2721). Log rank tests show significant difference between PPH and SPH (11.8, p=.001), SPH and non PH (18.0, p < .001), and SPH and SclPH (4.3, p=.036). PPH, SPH, non PH, and SclPH showed survival rates of .9, .87, .95, and .97 (std. err < .03) at 30 days; .85, .83, .92, .93 (std. err <.03) at 90 days; .8, .75, .85, and .83 (std. err < .03) at 365 days. Wilcoxon tests show statistical significant difference between PPH and SPH (5.1, p=.024) PPH and non PH (9.7, p=.002), SPH and non PH (16.9, p < .001) and SPH and SclPH (4.3, p=.039). There was no significance between PPH and Scl PH (.100 p=.752) or non PH and Scl PH (1.6 p=.202). Conclusion PPH survival has worse early survival but better long-term survival. The etiology of scleroderma did not impact survival compared to non-PH. Survival after secondary PH and the outcomes observed may impact risk stratification in certain centers, especially in the setting of challenging regulatory realities.

Background. The presence of frailty or prefrailty in older adults is a risk factor for postsurgical complications. The frailty phenotype can be improved through long-term resistance and aerobic training. It is unknown whether short-term preoperative interventions targeting frailty will help to mitigate surgical risk. The purpose of this study was to determine the proportion of frail and prefrail patients presenting to a thoracic surgical clinic who could benefit from a frailty reduction intervention.Methods. A prospective cohort study was performed at a single-site thoracic surgical clinic. Starting October 1, 2014, surgical candidates 60 years of age or older who consented to be screened were included. Patients were screened using an adapted version of Fried's phenotypic frailty criteria: weakness (grip strength), slow gait (15-foot walk), unintentional weight loss, self-reported exhaustion, and low self-reported physical activity (Physical Activity Scale for the Elderly). Prefrailty was identified when participants demonstrated one to two frailty characteristics; frailty was identified when participants demonstrated three to five frailty characteristics.Results. Of 180 eligible patients, 126 consented, and 125 completed screening. Thirty-nine participants (31%) were not frail, 71 (57%) were prefrail, and 15 (12%) were frail. Exhaustion was the most common frailty symptom (34%). Frailty prevalence did not significantly differ among men and women (men: 10%, women: 14%; p = 0.75).Conclusions. We found a high proportion of prefrail and frail patients among patients deemed candidates for thoracic surgical procedures. This finding indicates that frailty may be underrecognized. Substantial numbers of patients may be considered for a presurgical frailty reduction intervention. (C) 2017 by The Society of Thoracic Surgeons

PurposePrimary graft dysfunction (PGD) is a form of ischemia reperfusion lung injury that is a major cause of early morbidity and mortality after lung transplantation. Alcohol abuse is known to alter pulmonary immunity, promote alveolar epithelial dysfunction and increase the risk of acute lung injury. The effects of alcohol abuse in donors of lung allografts on transplant outcomes is unknown, and our aim was to examine the incidence of donor alcohol abuse and early effects on graft function following transplantation.Methods and MaterialsWe performed a single center cohort study of lung transplant recipients from 2007-2011, reviewing patient charts for donor information and lung transplant outcome data. Statistical analysis included student's t-test and Mann-Whitney U test.Results195 lung transplant recipients were included in the cohort and 20.5% (N=40) of the recipients had donors with significant alcohol use. Recipients of allografts from alcoholic donors spent more time on mechanical ventilation following transplant when compared to recipients whose donors had no reported alcohol abuse, mean 6.9±12.1 days versus 3.9±8.1 days on the ventilator, (p=0.07). Gas exchange, represented as PaO2/FiO2, was significantly worse in recipients of donors with alcohol abuse following transplant compared to recipients with no donor alcohol abuse (Fig 1).ConclusionsLung transplant recipients who received allografts from alcoholic donors had evidence of graft dysfunction following transplant. We speculate that alcoholic donor allografts may be susceptible to damage from formation of reactive oxygen species, which is exaggerated by the ischemia-reperfusion of transplantation, resulting in an increased rate of PGD. Primary graft dysfunction (PGD) is a form of ischemia reperfusion lung injury that is a major cause of early morbidity and mortality after lung transplantation. Alcohol abuse is known to alter pulmonary immunity, promote alveolar epithelial dysfunction and increase the risk of acute lung injury. The effects of alcohol abuse in donors of lung allografts on transplant outcomes is unknown, and our aim was to examine the incidence of donor alcohol abuse and early effects on graft function following transplantation. We performed a single center cohort study of lung transplant recipients from 2007-2011, reviewing patient charts for donor information and lung transplant outcome data. Statistical analysis included student's t-test and Mann-Whitney U test. 195 lung transplant recipients were included in the cohort and 20.5% (N=40) of the recipients had donors with significant alcohol use. Recipients of allografts from alcoholic donors spent more time on mechanical ventilation following transplant when compared to recipients whose donors had no reported alcohol abuse, mean 6.9±12.1 days versus 3.9±8.1 days on the ventilator, (p=0.07). Gas exchange, represented as PaO2/FiO2, was significantly worse in recipients of donors with alcohol abuse following transplant compared to recipients with no donor alcohol abuse (Fig 1). Lung transplant recipients who received allografts from alcoholic donors had evidence of graft dysfunction following transplant. We speculate that alcoholic donor allografts may be susceptible to damage from formation of reactive oxygen species, which is exaggerated by the ischemia-reperfusion of transplantation, resulting in an increased rate of PGD.

PurposeOur aim was to assess the rate and severity of diverticular disease and related complications in a post-lung transplantation population as well as identify risk factors that might be associated with worse outcomes.Methods and MaterialsWe performed a single center cohort study of lung transplant recipients from 2007-2011. Statistical analyses performed included chi-square and Kaplan-Meier survival estimates were assessed with a log rank test.ResultsThere were 202 patients included in our cohort. 39.1% (n=79) had documented diverticulosis and of those patients, 15% (n=12) required a related surgery post-transplant. 6.5% (n=8) of the 123 patients without documented pre-transplant diverticular disease on screening colonoscopy required a surgery for complicated diverticular disease post-transplant. Patients who underwent diverticular-related surgery post-transplant had a significantly worse survival. [figure 1] Identification of pre-transplant diverticular disease on screening colonoscopy did not impact survival post-transplant.ConclusionsPatients who undergo intra-abdominal surgery for complications related to diverticular disease have significantly poorer survival than those patients who do not require surgery. Optimal assessment of pre-transplant diverticular disease is necessary to prevent excessive morbidity and mortality following transplantation. Our aim was to assess the rate and severity of diverticular disease and related complications in a post-lung transplantation population as well as identify risk factors that might be associated with worse outcomes. We performed a single center cohort study of lung transplant recipients from 2007-2011. Statistical analyses performed included chi-square and Kaplan-Meier survival estimates were assessed with a log rank test. There were 202 patients included in our cohort. 39.1% (n=79) had documented diverticulosis and of those patients, 15% (n=12) required a related surgery post-transplant. 6.5% (n=8) of the 123 patients without documented pre-transplant diverticular disease on screening colonoscopy required a surgery for complicated diverticular disease post-transplant. Patients who underwent diverticular-related surgery post-transplant had a significantly worse survival. [figure 1] Identification of pre-transplant diverticular disease on screening colonoscopy did not impact survival post-transplant. Patients who undergo intra-abdominal surgery for complications related to diverticular disease have significantly poorer survival than those patients who do not require surgery. Optimal assessment of pre-transplant diverticular disease is necessary to prevent excessive morbidity and mortality following transplantation.

Purpose Limitations to survival following LTx include allogeneic responses and primary graft dysfunction. Experimental LTx models aim to differentiate allogeneic, innate and antibody-mediated pathways. Omentum, in clinical practice has been shown to have immunomodulatory properties. Pluripotent properties of activated OC (aOC) have a beneficial T-cell mediated effect shown in-vitro. A novel in vivo imaging strategy was used to track activated T-cells in a murine allogeneic left single-LTx model to assess early implantation responses. Activated T-cell localization was studied after aOC administration in this study. Methods and Materials We generated Cre gene knock-in mice at the IL-2 gene. Their T-cells express Cre upon antigen activation. Reporter genes (luciferase) can detect the expression of Cre. Recipient mice producing luciferase upon IL-2 expression allows tracking of activated T-cells in vivo via a measurable bioluminescence. Left lungs from B.10A donors were transplanted into Rosa26lucif/IL-2Cre recipients. Recipients received intratracheal injections of aOC at D3 & 7 post-LTx (OC-treatment group, N=3). Mice were imaged using the Xenogen IVIS100 on D3, 14 & 21 along anterior and lateral chest (AC, LC) and anterior and lateral abdomen (AA, LA) areas to determine degree of T-cell activation. D21 histological and flow cytometry analyses are reported. Results Day 3 imaging shows photon signals in lung and axillary nodal areas. On D14 & 21, a decrease in signal intensity was seen in the OC-treated group on all 4 views as compared to saline controls. D14: AC p=.6142, LC p=.6439, AA p=.5028, LA p=.2706. D21: AC p=.1638, LC p=.0655, AA p=.151, LA p=.1246. OC increased CD45+ and decreased CD11b+ cell populations in bone marrow. Conclusions An in-vivo allogeneic LTx model to assess the immunosuppressive potential of aOC has been devised. A reduction in the amount of activated T-cells in specific locations is evident. Potential therapeutic roles of aOC to modulate innate responses may now be investigated further.

Type V collagen [col(V)] is found most abundantly in skin, lung, and tendons. Autoimmunity to Col(V) is a risk factor for the development of allograft rejection after lung transplantation. Recent studies of restriction fragment length polymorphisms (RFLP) in the noncoding region of the COL5A1 gene predisposes to development of tendinopathies. The aim of this study is to determine whether RFLPs in the COL5A1 gene are associated with increased risk of acute cellular rejection (ACR) or chronic rejection (BOS, bronchiolitis obliterans syndrome) in lung transplant recipients.

Murine lung T cell receptor (TCR) γδ T cells are intraepithelial cells critical in regulating inflammation. We previously demonstrated in TCR δ−/− mice that bleomycin (blm) induced acute diffuse lung injury (ALI) is associated with delayed epithelial regeneration (1). As TCR γδ T cells are a major source of IL-17 production, we tested if IL-17 knockout (ko) mice would demonstrate similar patterns of Blm-induced ALI.

Mesenchymal stem cells have anti-inflammatory properties and retain their pluripotent potency. Omental stromal cells (OSC) are a recently discovered ample source of such progenitors. We hypothesized that activated OSC could ameliorate acute lung injury (ALI) in our established bleomycin (Blm) mouse model.