Prognostic Value of RV Function Before and After Lung Transplantation

AbstractObjectivesWe investigated the effects of lung transplantation on right ventricular (RV) function as well as the prognostic value of pre- and post-transplantation RV function.BackgroundAlthough lung transplantation success has improved over recent decades, outcomes remain a challenge. Identifying predictors of mortality in lung transplant recipients may lead to improved long-term outcomes after lung transplantation.MethodsEighty-nine (age 60 ± 6 years, 58 men) consecutive patients who underwent single or double lung transplantation and had pre- and post-transplantation echocardiograms between July 2001 and August 2012 were evaluated. Echocardiographic measurements were performed before and after lung transplantation. Left ventricular (LV) and RV longitudinal strains were analyzed using velocity vector imaging. Cox proportional prognostic hazard models predicting all-cause death were built.ResultsThere were 46 all-cause (52%) and 17 cardiac (19%) deaths during 43 ± 33 months of follow-up. After lung transplantation, echocardiography showed improved systolic pulmonary artery pressure (SPAP) (50 ± 19 mm Hg to 40 ± 13 mm Hg) and RV strain (−17 ± 5% to −18 ± 4%). No pre-transplantation RV parameter predicted all-cause mortality. After adjustment for age, sex, surgery type, and etiology of lung disease in a Cox proportional hazards model, both post-transplantation RV strain (hazard ratio: 1.13, 95% confidence interval: 1.04 to 1.23, p = 0.005), and post-transplantation SPAP (hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.05, p = 0.011) were independent predictors of all-cause mortality. When post-transplantation RV strain and post-transplantation SPAP were added the clinical predictive model based on age, sex, surgery type, and etiology, the C-statistic improves from 0.60 to 0.80 (p = 0.002).ConclusionsAlterations of RV function and pulmonary artery pressure normalize, and post-transplantation RV function may provide prognostic data in patients after lung transplantation. Our study is based on a highly and retrospectively selected group. We believe that larger prospective studies are warranted to confirm this result

Pretransplant gastroesophageal reflux compromises early outcomes after lung transplantation

ObjectivesGastroesophageal reflux disease (GERD) is implicated as a risk factor for bronchiolitis obliterans syndrome after lung transplantation, but its effects on acute rejection, early allograft function, and survival are unclear. Therefore, we sought to systematically understand the time-related impact of pretransplant GERD on graft function (spirometry), mortality, and acute rejection early after lung transplantation.MethodsFrom January 2005 to July 2008, 215 patients underwent lung transplantation; 114 had preoperative pH testing, and 32 (28%) had objective evidence of GERD. Lung function was assessed by forced 1-second expiratory volume (FEV1; percent of predicted) in 97 patients, mortality by follow-up (median, 2.2 years), and acute rejection by transbronchial biopsy.ResultsPretransplant GERD was associated with decreased FEV1 early after lung transplantation (P = .01) such that by 18 months, FEV1 was 70% of predicted in double lung transplant patients with GERD versus 83% among non-GERD patients (P = .05). A similar decrease was observed in single lung transplantation (50% vs 60%, respectively; P = .09). GERD patients had lower survival early after transplant ( P = .02)—75% versus 90%. Presence of GERD did not affect acute rejection (P = .6).ConclusionsFor lung transplant recipients, pretransplant GERD is associated with worse early allograft function and survival, but not increased acute rejection. The compromise in lung function is substantial, such that FEV1 after double lung transplant in GERD patients approaches that of single lung transplant in non-GERD patients. We advocate thorough testing for GERD before lung transplantation; if identified, aggressive therapy early after transplant, including fundoplication, may prove efficacious

Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients

While chronologic age can be precisely defined, clinical manifestations of advanced age occur in different ways and at different rates across individuals. The observed phenotype of advanced age likely reflects a superposition of several biological aging mechanisms which have gained increasing attention as the world contends with an aging population. Even within the immune system, there are multiple age-associated biological mechanisms at play, including telomere dysfunction, epigenetic dysregulation, immune senescence programs, and mitochondrial dysfunction. These biological mechanisms have associated clinical syndromes, such as telomere dysfunction leading to short telomere syndrome (STS), and optimal patient management may require recognition of biologically based aging syndromes. Within the clinical context of lung transplantation, select immune aging mechanisms are particularly pronounced. Indeed, STS is increasingly recognized as an indication for lung transplantation. At the same time, common aging phenotypes may be evoked by the stress of transplantation because lung allografts face a potent immune response, necessitating higher levels of immune suppression and associated toxicities, relative to other solid organs. Age-associated conditions exacerbated by lung transplant include bone marrow suppression, herpes viral infections, liver cirrhosis, hypogammaglobulinemia, frailty, and cancer risk. This review aims to dissect the molecular mechanisms of immune aging and describe their clinical manifestations in the context of lung transplantation. While these mechanisms are more likely to manifest in the context of lung transplantation, this mechanism-based approach to clinical syndromes of immune aging has broad relevance to geriatric medicine

A single-institution study of concordance of pathological diagnoses for interstitial lung diseases between pre-transplantation surgical lung biopsies and lung explants

Abstract Background By comparing diagnoses made by pre-transplant surgical lung biopsy (SLB) and the final pathologic diagnosis of the explanted pathology (EP), we aimed to study the factors that could impact pathologic diagnoses in patients with interstitial lung disease (ILD). Methods We retrospectively reviewed the lung transplant database at Cleveland Clinic [01/01/2006–12/31/2013] to include all lung transplant recipients with a prior diagnosis of ILD. Two pulmonary pathologists independently reviewed each SLB and lung explant. The diagnoses were labeled as concordant (same diagnosis on SLB and explant) or discordant (diagnosis on SLB and explant were different) by consensus. Results Of 389 patients transplanted for ILD, 217 had an SLB before transplant. Pathological diagnoses were concordant in 190 patients (87.6%) [165 UIP (86.8%), 13 NSIP (6.8%), 8 CHP (4.2%) and 4 other diagnoses (2.1%). In 27 cases (12.4%), the diagnosis on SLB differed from EP. 8/27 were diagnosed with UIP on SLB and of these, 5 were re-classified as NSIP. 14/19 (73.7%) patients with a SLB diagnosis “other than UIP” were re-categorized as UIP based on explant. Discordant cases had a greater time between SLB and EP than concordant cases (1553 days vs 1248 days). Conclusions The pathologic diagnosis of ILD by SLB prior to lung transplant is accurate in most patients, but may be misleading in a small subset of patients. The majority of discordant cases that were reclassified as UIP could be due to a sampling error, or perhaps, an increased time from the date of the SLB to transplant. Future studies examining how multidisciplinary consensus diagnosis affects this discordance are necessary