Mark K. Robbins

Ischemia-reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome.

BACKGROUND Bronchiolitis obliterans syndrome (BOS) is the most common cause of long-term morbidity and mortality after lung transplantation. Our hypothesis was that early ischemia-reperfusion injury after lung transplantation increases the risk of BOS. METHODS Data on 134 patients who had lung transplantation between January 1, 1990 and January 1, 2000, was used for univariate and multivariate logistic regression analysis. RESULTS After lung transplantation, 115 patients (115 of 134, 86%) survived more than 3 months. In that group, 41 patients developed BOS, of which 23 had progressive disease. Univariate analysis revealed that ischemia-reperfusion injury (p = 0.017) and two or more acute rejection episodes (p = 0.032) were predictors of BOS onset, whereas ischemia-reperfusion injury (p = 0.011) and cytomegalovirus infection (p = 0.009) predicted progressive BOS. Multivariate logistic regression analysis showed that ischemia-reperfusion injury was an independent predictor for both BOS development and BOS progression. Two or more acute rejection episodes were also an independent predictor of BOS development, whereas cytomegalovirus infection was an independent predictor of progressive BOS. CONCLUSIONS Ischemia-reperfusion injury increases the risk of BOS after lung transplantation.

Circulating Fibrocytes Correlate With Bronchiolitis Obliterans Syndrome Development After Lung Transplantation: A Novel Clinical Biomarker

BACKGROUND Development of bronchiolitis obliterans syndrome (BOS) after lung transplantation confers increased patient morbidity and mortality. Fibrocytes are circulating bone marrow-derived mesenchymal cell progenitors that influence tissue repair and fibrosis. Fibrocytes have been implicated in chronic pulmonary inflammatory processes. We investigated the correlation of circulating fibrocyte number with BOS development in lung transplant patients. METHODS We prospectively quantified circulating fibrocyte levels among lung transplant patients. Patients were stratified according to the development of BOS as indicated by predicted forced expiratory volume in 1 second. Fibrocyte activity was analyzed by flow cytometry (cluster of differentiation 45+, collagen 1+) in a blinded manner related to clinical presentation. RESULTS Thirty-nine patients (61.5% men) underwent double (33.3%), left (25.6%), or right (41.0%) lung transplantation. Average patient age was similar between BOS and non-BOS patients (58.3±3.9 vs 60.3±2.0 years, p=0.67). Chronic obstructive lung disease was the most common indication for lung transplantation (41.0%). Median forced expiratory volume in 1 second was lower among BOS patients compared with non-BOS patients (1.08 vs. 2.18 L/s, p=0.001). Importantly, circulating fibrocyte numbers were increased in BOS patients compared with non-BOS patients (8.91 vs 2.96×10(5) cells/mL, p=0.03) by flow cytometry and were incrementally increased with advancing BOS stage (p=0.02). CONCLUSIONS Increased circulating fibrocyte levels correlate with the development of BOS after lung transplantation and positively correlate with advancing BOS stage. Quantification of circulating fibrocytes could serve as a novel biomarker and possible therapeutic target for BOS development in lung transplant patients.

A Neuropsychological Normative Database for Lung Transplant Candidates

Psychologists are increasingly asked to make decisions regarding patient candidacy for transplantation. Despite the growing incidence of lung transplantation, normative research regarding cognitive functioning and end-stage obstructive lung disease is lacking. Hence, data are presented on 100 consecutively referred candidates for lung transplantation. The group data suggest essentially normal functioning on most cognitive tests for the majority of transplant candidates. Exceptions were seen on measures of attentional set shifting and short-term visual memory, which were impaired in nearly one fourth of this population. Additionally, one half of the patients displayed deficient performance on the Buschke Selective Reminding Test, with subjects at greater risk for severe rather than mild deficits. Unlike prior research, our group data suggest that there is potential risk of short-term noncontextual verbal memory difficulties because of end-stage pulmonary disease. Personality testing data, e.g., elevations on MMPI-2 scales measuring depression and anxiety, are also discussed.

Coronary risk stratification in patients with end-stage lung disease.

BACKGROUND Significant coronary artery disease (CAD) has been a contraindication for listing patients for lung transplantation. We hypothesize that coronary risk stratification can help identify a sub-set of patients who need additional diagnostic tools and intervention. METHODS We performed a retrospective review of 72 consecutive patients who underwent lung transplantation at our institution from 1995 to 2000. Further, a review of patients who are currently listed for transplantation yielded 48 patients. We then identified the various risk factors for CAD, the diagnostic tools used, and pre-operative intervention. Risk factors identified included smoking history, diabetes, hypertension, hypercholesterolemia, CAD, congestive heart failure, age >50, and arrhythmias. Based on these risk factors, the patients were then classified into 2 groups: low risk (< or =1 risk factors) and high risk (> or =2 risk factors). We identified the patients in each group who underwent coronary angiography (CA), those with angiographic evidence of CAD, and those who received pre-operative intervention. RESULTS Of the 72 patients who underwent lung transplantation, 48 were identified as at high risk for CAD. Of these, 5 patients had CAD diagnosed before surgery using CA, and 1 patient received pre-operative intervention. Of the 48 patients currently on the lung transplant list, we identified 28 patients as high risk for CAD, 12 of whom were noted to have CA, and 2 of whom received pre-operative intervention. CONCLUSIONS Although CAD was once a contraindication for lung transplantation, pre-operative risk stratification allows identification of CAD with CA in a high-risk group. We believe that by using appropriate pre-operative cardiac intervention, patients with severe CAD could successfully undergo lung transplantation.

Pulmonary Capillary Hemangiomatosis Associated with CREST Syndrome: A Case Report and Review of the Literature

This is a report of fatality immediately after administration of epoprostenol. The patient was previously diagnosed with CREST syndrome and associated interstitial lung disease. She developed worsening pulmonary hypertension and was clinically diagnosed with pulmonary veno-occlusive disease. The patient developed flash pulmonary edema and arrested after administration of low-dose epoprostenol in the intensive care unit. An autopsy revealed the patient suffered from pulmonary capillary hemangiomatosis. We review our case and what is known about this rare disease.

Posttransplantation lymphoproliferative disease involving the pituitary gland

Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD.