Hubert J. Ford

Post-transplantation Lymphoproliferative Disease Epstein-Barr Virus DNA Levels, HLA-A3, and Survival

RATIONALE Elevation in Epstein-Barr virus (EBV) circulating DNA has been proposed as a marker for development of post-transplant lymphoproliferative disease (PTLD), but few published data exist in the study of lung-transplant recipients. OBJECTIVES To determine if elevated EBV DNA levels, in combination with other risk factors, were predictive of PTLD. METHODS We conducted a retrospective, single-center study examining all lung transplant recipients (n = 296) and EBV DNA levels (n = 612) using real-time TaqMan polymerase chain reaction. There were 13 cases of PTLD overall, of which 5 occurred in the era of EBV DNA monitoring. MEASUREMENTS AND MAIN RESULTS EBV DNA levels were distributed differently among seropositive and seronegative patients, with the latter having higher values (P < 0.0001). Among the cohort of pretransplantation seropositive patients, there was one diagnosed with PTLD. The EBV DNA level in this patient was elevated at the time of PTLD diagnosis (sensitivity = 100%, specificity = 100% for PTLD). Among the cohort of pretransplantation seronegative patients, there were four with a diagnosis of PTLD. In all four patients, the EBV DNA level was detectable (sensitivity = 100%, specificity = 24%), but in only two was it elevated (sensitivity = 50%, specificity = 22%). HLA-A3 expression in the recipient and/or donor conferred additional risk for PTLD among the seronegative patients (P = 0.026 to 0.003). No other PTLD risk factor was found. CONCLUSIONS EBV DNA levels are a useful but imperfect predictor of PTLD in patients with lung transplants. Pretransplant EBV status affected the results of the assay and should be considered when interpreting test results. HLA-A3 was strongly linked to PTLD and may be a novel marker of PTLD risk.

Thermodilution and Fick cardiac outputs differ: impact on pulmonary hypertension evaluation.

BACKGROUND The relationship between thermodilution and indirect Fick cardiac output determination methods has not been well described. OBJECTIVE To describe the relationship between these two cardiac output determination methods in patients evaluated for pulmonary hypertension and to highlight potential clinical implications. METHODS A retrospective review of charts of all adult patients who underwent a right heart catheterization (RHC) between January 1, 2007 and November 10, 2010, and participated in the pulmonary hypertension program of the pulmonary division at an academic institution was conducted. For validation, the charts of all patients who underwent RHC during the same period within the cardiology division were reviewed. RESULTS A total of 198 patients underwent 213 RHCs, 79 (40%) of whom had pulmonary arterial hypertension, were included. Forty-three per cent of patients had >20% difference between thermodilution and Fick. The average difference (thermodilution - Fick ±SD) was -0.39±2.03 L⁄min (n=213; P=0.006). There was no significant difference in bias or variability between thermodilution and Fick among patients with tricuspid regurgitant jet velocity (TRJ) of <3 m⁄s versus those with TRJ >3 m⁄s (-0.41±2.10 L⁄min versus -0.36±1.93 L⁄min, respectively; P=0.87). In a multivariable analysis, the thermodilution-Fick difference increased with age (P=0.001). DISCUSSION The presence of such discrepancy in 36% of patients evaluated for heart failure and⁄or heart transplant validated the results. In total, 37% of the 1315 procedures (213 performed by pulmonologists and 1102 performed by cardiologists) had a difference of >20% between thermodilution and Fick. CONCLUSION Significant discrepancy exists between thermodilution and indirect Fick methods. This discrepancy potentially impacts pulmonary arterial hypertension prognostication and diagnosis, and is independent of TRJ.

Long-term outcomes of the bronchial artery embolization are diagnosis dependent

Background: Bronchial artery embolization (BAE) is an established, safe, and effective procedure for the treatment of hemoptysis but long-term outcomes of the BAE have never been investigated before. Objectives: To retrospectively analyze long-term outcomes of the BAE. Materials and Methods: A retrospective chart analysis was done from the hospital central database for all patients undergoing the BAE over a consecutive 14-year period (January 2000-February 2014). A total of 58 patients were identified from the database. Eight patients were excluded due to the lack of follow-up. Data such as patient demographics, reason for hemoptysis, medical imaging results, bronchoscopy findings, recurrence rates, and morbidity/mortality rates after the BAE were collected. Results: Eighty three embolizations were performed in 50 patients. The median follow-up was of 2.2 years. Cystic fibrosis (CF) bronchiectasis was the most common etiology (21/50), followed by non-CF bronchiectasis (9/50). Cavitary lung disease occurred in 12/50 patients, an additional 4/50 had cancer (primary lung and metastatic), and one patient had antineutrophil cytoplasmic antibody (ANCA) vasculitis. In three patients the etiology was unknown. Postprocedural complications occurred in 5/83 (6%) patients, two patients with two major complications - stroke (one) and paraplegia (one) - and three patients with minor complications - chest pain (two) and bronchial artery dissection (one). A total of 15/50 patients died during the follow-up. Three patients died of hemoptysis, and the remaining deaths were unrelated to the procedure or hemoptysis. Twenty four patients had recurrent hemoptysis. A Kaplan-Meier analysis revealed an excellent long-term survival that was 85% at 10 years. Conclusions: The BAE is a safe and effective procedure with excellent overall long-term survival.

Tadalafil Therapy for Sarcoidosis-Associated Pulmonary Hypertension

Sarcoidosis-associated pulmonary hypertension (SAPH) is estimated to occur in at least 5% or more of sarcoidosis patients, and it contributes to significant morbidity and mortality. Optimal therapy for SAPH is not well established. We performed a 24-week open-label trial of tadalafil for SAPH at 2 academic medical centers. Subjects were required to have confirmed sarcoidosis plus a right heart catheterization within 12 months of enrollment showing a mean pulmonary artery pressure ≥ 25 mmHg, a pulmonary artery wedge pressure ≤ 15 mmHg, and a calculated pulmonary vascular resistance ≥ 3 Wood units. Subjects received 20 mg/day of tadalafil for the first 4 weeks and then 40 mg/day for the subsequent 20 weeks. Sixteen patients were screened, 12 of whom met criteria for enrollment. At 24 weeks, there was no overall improvement in 6-minute walk distance (6MWD). Five of the 12 subjects dropped out of the study early (2 for social reasons, 3 for medical reasons). There was no significant change in short form 36, St. Georges respiratory questionnaire, or maximum Borg dyspnea scores over the 24 weeks. There were no significant adverse events or laboratory abnormalities clearly related to tadalafil in the cohort. The study did not meet the primary end point of change in 6MWD because of the small sample size. Tadalafil was generally safely administered in this cohort of SAPH patients. There was a relatively high dropout rate but no major adverse events and no clinical worsening. Larger studies are needed to explore this question further. (Trial registration: ClinicalTrials.gov identifier: NCT01324999)

S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension: S100A12 in pulmonary hypertension

Molecular biomarkers are needed to refine prognostication and phenotyping of pulmonary hypertension (PH) patients. S100A12 is an emerging biomarker of various inflammatory diseases. This study aims to determine the prognostic value of S100A12 in PH.