Nelson Burton

Serial Development of Pulmonary Hypertension in Patients with Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a disease with very high mortality. Objective: We sought to characterize serial changes in pulmonary artery pressures (PAP) in patients with advanced IPF who survive to transplant. Methods: Retrospective analysis of IPF patients comparing mean PAP at the time of initial evaluation for transplan- tation (mPAPbaseline) with mPAP at the time of transplant (mPAPfollow-up). The measurements were correlated with New York Heart Association (NYHA) functional class and oxygen requirements. Results: The final cohort consisted of 44 patients with serial right heart catheterization data. The mean mPAPbaseline and mPAPfollow-up were 22.5 and 32.7 mm Hg, respectively. 38.6% (17/44) of the patients had pulmonary hypertension (PH) at baseline. The majority of the non-PH patients developed PH during the serial time interval with a subsequent incidence of 77.8%. At the time of transplant, 86.4% of the patients had PH. There was a significant association between transplant NYHA class, severity of PH and oxygen requirements. Transplant NYHA class IV patients had a higher rate of mPAP change. The severity of PH at the time of transplant did not affect transplant outcomes. Conclusion: PH is common and progressive in patients with advanced IPF who are transplant candidates. Serial change and severity of PAP elevations have a significant association with oxygen requirements and functional status, but not transplant outcomes. Whether or not progressive PH has a significant impact on outcomes without transplantation requires further study.

Prevalence and impact of coronary artery disease in idiopathic pulmonary fibrosis

INTRODUCTIONnIdiopathic Pulmonary Fibrosis (IPF) is a progressive disease with a poor prognosis for which there is no effective medical therapy. An awareness of comorbidities that are treatable and might impact outcomes in these patients is therefore very important. We sought to determine the prevalence of coronary artery disease (CAD) in IPF patients in comparison to a control group of patients with chronic obstructive pulmonary disease (COPD). We also sought to assess the impact of CAD on IPF patient outcomes.nnnPATIENTS AND METHODSnIPF and COPD transplant candidates whose work-up included left heart catheterization were categorized as having significant CAD, non-significant CAD or no disease. The risk factor profile and prevalence of CAD in both groups was compared.nnnRESULTSnThere were 73 IPF and 56 COPD patients. The prevalence of CAD was 65.8% in the IPF group compared to 46.1% in the COPD patients (p<0.028). Significant disease was present in 28.8% of IPF patients vs.16.1% of the COPD patients (p<0.081). Unsuspected significant CAD was found in 18% of IPF patients versus 10.9% of COPD patients (p<0.004). Outcomes of IPF patients with significant CAD was worse than those with no or non-significant disease (p<0.003) with a median survival of 572 days from the time of left heart catheterization.nnnCONCLUSIONnThere is a higher prevalence of CAD in IPF patients compared to a similarly matched COPD group. This increased association appeared to be independent of common coronary artery risk factors. IPF patients with significant CAD appear to have worse outcomes.

Comparison of bronchiolitis obliterans syndrome to other forms of chronic lung allograft dysfunction after lung transplantation

BACKGROUNDnThe radiographic presence of allograft infiltrates is atypical of bronchiolitis obliterans (BO) and inconsistent with the definition of bronchiolitis obliterans requires that restrictive processes are ruled out. The natural history of these other forms of chronic allograft dysfunction has not been well characterized. We examined the prognostic significance of radiographic and spirometric restrictive processes in comparison to BOS among lung transplant recipients.nnnMETHODSnWe performed a retrospective review of lung transplant recipients with chronic lung allograft dysfunction (CLAD) as defined by spirometry. Subgroups based on the presence or absence of persistent radiographic abnormalities were labeled as non-specific (CLAD-NS) and CLAD due to BOS (CLAD-BOS), respectively. The CLAD-BOS group was further divided into obstructive (OBOS) and restrictive (RBOS) phenotypes based on spirometry. Groups were compared with respect to survival and decline in forced expiratory volume in 1 second (FEV(1)).nnnRESULTSnAmong 241 lung transplant recipients, 96 (40%) were identified as having CLAD, of whom 62 (65%) had CLAD-BOS and 34 (35%) CLAD-NS. No difference between groups was identified with respect to post-CLAD survival or decline in FEV(1). CLAD-BOS subgroups included 35 (56%) patients with OBOS and 27 (44%) with RBOS. There was no difference in these subgroups with respect to survival or subsequent FEV(1) decline.nnnCONCLUSIONSnPatients with CLAD and persistent radiographic infiltrates have a similar prognosis to BOS patients but may still represent a clinically distinct phenotype. BOS patients frequently exhibited a restrictive pattern on spirometry, which also did not offer further prognostic information, but could still represent a unique disease phenotype.

Comparison of wait times and mortality for idiopathic pulmonary fibrosis patients listed for single or bilateral lung transplantation

BACKGROUNDnLung transplantation is the one form of solid-organ transplantation in which there is the option for patients to receive one or two organs. Idiopathic pulmonary fibrosis (IPF) candidates can be accommodated by either procedure but the decision about these two options remains controversial. Therefore, we sought to determine whether IPF patients listed for bilateral lung transplantation only had longer wait times and higher mortality on the waiting list than those listed for single lungs only. Patients with chronic obstructive pulmonary disease (COPD) were also analyzed as a comparison group.nnnMETHODSnThis study was a retrospective analysis of the Organ Procurement and Transplantation Network database of patients with IPF and COPD listed for lung transplantation between May 2005 and December 2007. An analysis of wait times and mortality in this era as well as the pre-lung allocation score (pre-LAS) era of 2002 to 2004 was performed.nnnRESULTSnOf the 1,339 patients with IPF listed for lung transplantation, 31.7% were listed for bilateral lung transplantation only, 41% for single-lung transplantation only and 27.3% for either procedure. Patients listed for the bilateral procedure only were at greater risk of dying on the transplant list (p < 0.003), and were less likely to receive a lung transplant (p < 0.012). No difference in outcomes was seen in the COPD patients. Comparatively, in the pre-LAS era, wait times and mortality on the list for IPF patients were significantly greater for all forms of transplantation.nnnCONCLUSIONSnThere has been a significant improvement in wait times and mortality for IPF patients since the inception of the LAS system. Nonetheless, despite the goal of transplant equity, IPF patients listed for bilateral lung transplantation might have a clinically meaningful increased risk of pre-transplant mortality. The choice of procedures therefore needs to be made with careful consideration of patients survival both pre- and post-transplantation. Evaluation of transplant outcomes should not only be based on post-transplant survival, but should also account for the impact of the choice of procedure.

Genomic phenotype of non-cultured pulmonary fibroblasts in idiopathic pulmonary fibrosis

Activated fibroblasts are the central effector cells of the progressive fibrotic process in idiopathic pulmonary fibrosis (IPF). Characterizing the genomic phenotype of isolated fibroblasts is essential to understanding IPF pathogenesis. Comparing the genomic phenotype of non-cultured pulmonary fibroblasts from advanced IPF patients and normal lungs revealed novel genes, biological processes and concomitant pathways previously unreported in IPF fibroblasts. We demonstrate altered expression in proteasomal constituents, ubiquitination-mediators, Wnt, apoptosis and vitamin metabolic pathways and cell cycle regulators, suggestive of loss of cellular homeostasis. Specifically, FBXO32, CXCL14, BDKRB1 and NMNAT1 were up-regulated, while RARA and CDKN2D were down-regulated. Paradoxically, pro-apoptotic inducers TNFSF10, BAX and CASP6 were also found to be increased. This comprehensive description of altered gene expression in isolated IPF fibroblasts underscores the complex biological processes characteristic of IPF and may provide a foundation for future research into this devastating disease.

Heart transplantation in a patient with isolated noncompaction of the left ventricular myocardium

We describe a patient with isolated noncompaction of the left ventricle who presented with worsening congestive heart failure and was successfully treated with heart transplantation. The prognosis for these patients is poor because of accelerated event rates of fatal arrhythmias, thromboemboli, and profound left ventricular decompensation. Only 7 patients with isolated noncompaction of the left ventricle have been reported to have undergone heart transplantation. Herein we describe a patient with isolated noncompaction of the left ventricle who underwent successful heart transplantation.

Successful Use of Cyclosporine in a Lung Transplant Recipient with Tacrolimus-Associated Hemolytic Uremic Syndrome

Hemolytic-uremic syndrome (HUS) is a rare, but well-described complication in organ transplant recipients maintained on cyclosporine immunosuppression. Tacrolimus is a newer agent with similar immunosuppressant efficacy. In cases of cyclosporine-related HUS in renal transplant recipients, tacrolimus has been used successfully without recurrence of HUS. Tacrolimus has been reported to cause HUS in renal and more recently in cardiac transplant patients. We report a case of HUS in a lung transplant recipient receiving tacrolimus who was subsequently converted to cyclosporine without recurrence of HUS.

Native lung complications in single-lung transplant recipients and the role of pneumonectomy.

Single-lung transplant recipients may develop complications in their native lungs that may have an impact on outcomes. One potential therapeutic option is native lung pneumonectomy. The purpose of this study was to assess the impact of native lung complications on post-transplant survival in single-lung transplant recipients. We also aimed to determine the morbidity and mortality associated with native lung pneumonectomy (NLP). A retrospective review of all single-lung transplant recipients at our institution from January 1, 1998 to July 15, 2008 was performed. Patients were stratified to one of three groups: no native lung complications; native lung complications requiring native lung pneumonectomy; and native lung complications not managed with native lung pneumonectomy. Survival post-transplant and post-native lung complication were the primary end-points of the study. Significant native lung complications developed in 25 of 180 single-lung transplants (13.8%). Median post-transplant survival was lower in single-lung transplant recipients with significant native lung complications (3.2 years vs 5.3 years, p = 0.002). NLP was performed in 11 patients. Post-operative complications developed in 4 of 11 cases (36.4%), but all patients survived to hospital discharge. There was no significant difference in median survival between single-lung transplant recipients undergoing native lung pneumonectomy and single-lung transplant recipients without native lung complications (4.3 years vs 5.1 years, p = 0.478). Native lung complications impact post-transplant survival in single-lung transplant recipients and may partly explain why outcomes with single-lung transplantation are inferior to those of bilateral lung transplantation. NLP can be performed with acceptable morbidity and mortality.

Bronchiolitis obliterans syndrome: utility of the new guidelines in single lung transplant recipients

BACKGROUNDnBronchiolitis obliterans syndrome is defined by a >20% decrease from baseline in the forced expiratory volume in 1 second (FEV(1)). Recently, a consensus panel under the auspices of the International Society for Heart and Lung Transplantation proposed a new stage, designated potential BOS or BOS 0-p. This study sought to validate retrospectively this new stage in a cohort of single-lung transplant recipients.nnnMETHODSnA retrospective analysis of serial pulmonary function tests in 43 single-lung transplant recipients was performed. Baseline FEV(1) and midflow rate (FEF(25-75%)) were determined and compared with the most recent set of pulmonary function tests in clinically stable patients.nnnRESULTSnThe sensitivity of the FEF(25-75%) at <or=75% of baseline for subsequently detecting BOS Stage 1 was 80%, with a specificity of 82.6%. For the patients with idiopathic pulmonary fibrosis, the sensitivity was 62.5% and the specificity was 100.0%, whereas in the patients with chronic obstructive lung disease, the sensitivity was 91.7% and the specificity was 69.2%. Different cutoff points for the FEF(25-75%) also were tested and are shown in receiver operator curves. Likelihood ratios for the different cutoff points also were calculated. Five of 9 (55.6%) patients qualified for BOS 0-p using the FEV(1) parameter (FEV(1) of 81-90% of baseline) alone.nnnCONCLUSIONnThe FEF(25-75%) seems to be a useful criterion for predicting BOS development in single-lung transplant recipients. The FEF(25-75%) might best be used with likelihood ratios for different values rather than for 1 defined cutoff point of or=75% of baseline. The value of the second criterion that constitutes BOS 0-p (FEV(1), 81-90%of baseline) remains uncertain.

Clinical Outcomes of Advanced Heart Failure Patients with Cardiogenic Shock Treated with Temporary Circulatory Support Before Durable LVAD Implant.

Temporary circulatory support (TCS) is used to improve hemodynamics in patients with cardiogenic shock as a bridge to durable ventricular assist device (dVAD). Data from dVAD recipients with or without TCS (extracorporeal membranous oxygenation [ECMO], n = 14; TandemHeart [TH], n = 26) were evaluated. Clinical characteristics and hemodynamics were analyzed for patients before and after TCS and compared with profile 1 (n = 29) or profile 2–3 (n = 269) patients without TCS before dVAD. Extracorporeal membranous oxygenation patients had the highest use of preoperative mechanical ventilation, vasopressors, and the highest HeartMate II risk score before dVAD (p < 0.01). Patients receiving TCS before dVAD implant had hemodynamics comparable with patients in Profiles 2–3 and superior to that of Profile 1 patients without TCS. Operative survival after dVAD was lower in patients receiving ECMO (57%) compared with Profile 1 patients receiving TH (88%), Profile 1 without TCS (82%), or Profile 2–3 patients (97%; all p < 0.01). Despite improved clinical stability with TCS, patients bridged to a dVAD have event-free survival that parallels patients in profile 1 without TCS. Our data suggest that patients requiring TCS before dVAD implant should be still classified Interagency Registry for Mechanically Assisted Circulatory Support profile 1.