Chronic lung allograft dysfunction subtype analysis by computed tomography volumetry.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation. Of the two subtypes, restrictive allograft syndrome (RAS) is characterized by a larger lung volume decrease and worse prognosis than bronchiolitis obliterans syndrome (BOS). We used computed tomography (CT) volumetry to classify CLAD subtypes and determined their clinical impact. METHODS: Adult primary lung transplants performed 2003-2015 (n = 167) were retrospectively evaluated for CLAD and subclassified with CT volumetry. Lung volume decrease of < 15% from baseline resulted in BOSCT-vol and ≥15% resulted in RASCT-vol diagnosis. Clinical impact of CLAD subtypes was defined, and the prognostic value of different lung function, radiological, and lung volume parameters present at the time of CLAD diagnosis were compared. RESULTS: CLAD affected 43% of patients and was classified with CT volumetry as BOSCT-vol in 89% and RASCT-vol in 11%. Median graft survival estimate in RASCT-vol was significantly decreased compared to BOSCT-vol (1.6 vs. 9.7 years, P = .038). At CLAD onset, RASCT-vol diagnosis (P = .05), increased lung density (P = .007), and more severe FEV1 (P = .004) decline from baseline, increased graft loss risk in multivariate analysis. CONCLUSIONS: CT volumetry serves to identify lung transplant patients with a poor clinical outcome but should be validated in prospective trials.

Systemic Dosing of Thymosin Beta 4 before and after Ischemia Does Not Attenuate Global Myocardial Ischemia-Reperfusion Injury in Pigs.

The use of cardiopulmonary bypass (CPB) and aortic cross-clamping causes myocardial ischemia-reperfusion injury (I-RI) and can lead to reduced postoperative cardiac function. We investigated whether this injury could be attenuated by thymosin beta 4 (TB4), a peptide which has showed cardioprotective effects. Pigs received either TB4 or vehicle and underwent CPB and aortic cross-clamping for 60 min with cold intermittent blood-cardioplegia and were then followed for 30 h. Myocardial function and blood flow was studied by cardiac magnetic resonance and PET imaging. Tissue and plasma samples were analyzed to determine the amount of cardiomyocyte necrosis and apoptosis as well as pharmacokinetics of the peptide. In vitro studies were performed to assess its influence on blood coagulation and vasomotor tone. Serum levels of the peptide were increased after administration compared to control samples. TB4 did not decrease the amount of cell death. Cardiac function and global myocardial blood flow was similar between the study groups. At high doses a vasoconstrictor effect on mesentery arteries and a vasodilator effect on coronary arteries was observed and blood clot firmness was reduced when tested in the presence of an antiplatelet agent. Despite promising results in previous trials the cardioprotective effect of TB4 was not demonstrated in this model for global myocardial I-RI.