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Trends in high-sensitivity cardiac troponin I (hs-cTnI) after lung transplant (LT) and its clinical value are not well stablished. This study aimed to determine kinetics of hs-cTnI after LT, factors impacting hs-cTnI and clinical outcomes. LT recipients from 2015 to 2017 at Toronto General Hospital were included. Hs-cTnI levels were collected at 0–24 h, 24–48 h and 48–72 h after LT. The primary outcome was invasive mechanical ventilation (IMV) >3 days. 206 patients received a LT (median age 58, 35.4% women; 79.6% double LT). All patients but one fulfilled the criteria for postoperative myocardial infarction (median peak hs-cTnI = 4,820 ng/mL). Peak hs-cTnI correlated with right ventricular dysfunction, >1 red blood cell transfusions, bilateral LT, use of EVLP, kidney function at admission and time on CPB or VA-ECMO. IMV>3 days occurred in 91 (44.2%) patients, and peak hs-cTnI was higher in these patients (3,823 vs. 6,429 ng/mL, p < 0.001 after adjustment). Peak hs-cTnI was higher among patients with had atrial arrhythmias or died during admission. No patients underwent revascularization. In summary, peak hs-TnI is determined by recipient comorbidities and perioperative factors, and not by coronary artery disease. Hs-cTnI captures patients at higher risk for prolonged IMV, atrial arrhythmias and in-hospital death.

BackgroundChronic lung allograft dysfunction (CLAD) is the major cause of death post-lung transplantation, with acute cellular rejection (ACR) being the biggest contributing risk factor. Although patients are routinely monitored with spirometry, FEV1 is stable or improving in most ACR episodes. In contrast, oscillometry is highly sensitive to respiratory mechanics and shown to track graft injury associated with ACR and its improvement following treatment. We hypothesize that intra-subject variability in oscillometry measurements correlates with ACR and risk of CLAD.MethodsOf 289 bilateral lung recipients enrolled for oscillometry prior to laboratory-based spirometry between December 2017 and March 2020, 230 had ≥ 3 months and 175 had ≥ 6 months of follow-up. While 37 patients developed CLAD, only 29 had oscillometry at time of CLAD onset and were included for analysis. These 29 CLAD patients were time-matched with 129 CLAD-free recipients. We performed multivariable regression to investigate the associations between variance in spirometry/oscillometry and the A-score, a cumulative index of ACR, as our predictor of primary interest. Conditional logistic regression models were built to investigate associations with CLAD.ResultsMultivariable regression showed that the A-score was positively associated with the variance in oscillometry measurements. Conditional logistic regression models revealed that higher variance in the oscillometry metrics of ventilatory inhomogeneity, X5, AX, and R5-19, was independently associated with increased risk of CLAD (p < 0.05); no association was found for variance in %predicted FEV1.ConclusionOscillometry tracks graft injury and recovery post-transplant. Monitoring with oscillometry could facilitate earlier identification of graft injury, prompting investigation to identify treatable causes and decrease the risk of CLAD.

Background. Primary graft dysfunction (PGD) is a form of acute respiratory failure that complicates 30% of bilateral lung transplants. Higher grades of PGD correlate with higher severity of respiratory failure and unfavorable outcomes. Immediate PGD determination posttransplant‚ however, is not always predictive of PGD over subsequent days or intensive care unit outcomes. We aimed to evaluate whether extravascular lung water index (ELWI) measured immediately post bilateral lung transplant was associated with higher severity of PGD at 72 h and duration of mechanical ventilation. Methods. We conducted a prospective, observational study of bilateral lung transplant patients admitted to the intensive care unit. ELWI measurements were performed at admission, 6, 12, 24, 36, 48, 60, and 72 h following transplant or until extubation. We evaluated the association between admission ELWI and 72-h PGD grade and duration of mechanical ventilation. Results. Across 56 patients enrolled, 268 transpulmonary thermodilution measurements were conducted. At admission, median ELWI increased with PGD grade (grade 1: 9 mL/kg [interquartile range (IQR), 8–11 mL/kg]‚ grade 2 [10 mL/kg (IQR, 8–12 mL/kg)]‚ and grade 3 [17 mL/kg (IQR, 14–19 mL/kg); P < 0.001]). Using multivariable Poisson regression analysis adjusting for confounders, admission ELWI elevation was associated with higher severity of PGD at 72 h (incidence rate ratio [IRR], 1.06; 95% confidence interval, 1.01-1.12) and duration of mechanical ventilation (IRR, 1.62; 95% confidence interval, 1.23-2.14). The combination of an ELWI of ≥13 mL/kg and partial pressure of oxygen/fraction of inspired oxygen ≤ 100 within 6 h of admission had high sensitivity (75%) and specificity (100%) for grade 3 PGD at 72 h (area under the curve, 0.95) and performed better than ELWI or partial pressure of oxygen/fraction of inspired oxygen alone. Conclusions. Our exploratory study demonstrates an association between admission ELWI and high grades of PGD at 72 h and longer duration of ventilation. These results provide the impetus to study whether goal-directed ELWI algorithms can improve transplant outcomes.

Abstract Background Anti-human leukocyte antigen (HLA) antibody testing was approved by the Japanese government in 2018. As such, there was no longitudinal data regarding the HLA-sensitization of lung transplant (LTX) patients in Japan. We therefore set out to measure anti-HLA antibodies from all our LTX patients during their annual follow-up to characterize the sensitization status in the Japanese population. Methods The cross-sectional study was conducted for consecutive LTX recipients who underwent transplantation from January 2000 to January 2020 at Tohoku University Hospital (TUH). The serum from the recipients was screened for anti-HLA antibody with the panel-reactive assay (PRA) and the donor-specific antibodies (DSA). Results Sensitization was reviewed in 93 LTX recipients, showing 23 positive (24.7%) and 70 negative (75.3%) PRA. More sensitized recipients were found in recent transplantations (60.9% (14/23), ≤5 years post LTX) than in older transplantations (17.4% (4/23), 5–10 years or 21.7% (5/23), ≥10 years post LTX) (p = 0.04). Even fewer recipients had DSA (5.4%, 5/93), among whom 4/5 (80%) were recently transplanted. Conclusion The rate of PRA positive LTX recipients in our population was lower compared with those in previous reports from US and Europe. More sensitized LTRs were found in recent transplantations than the older cohort, and DSA was identified primarily in the recent recipients. Due to several limitations, it is still unclear whether the sensitization would be related the development of CLAD or survival, yet this study would be fundamental to the future anti-HLA body study in Japanese population.

Abstract Background Development of primary lung cancer in donor lung post-lung transplantation is very rare, with few described cases. The safety of stereotactic ablative radiotherapy (SABR) for early-stage lung cancer arising from donor lung is unclear. Case presentation Herein, we present a case of a patient with a Stage IB adenocarcinoma arising from donor lung 8 years post-double lung transplantation, which was performed due to advanced emphysema. The patient was ineligible for surgical management due to chronic lung allograft dysfunction, which significantly compromised pulmonary function. Full dose SABR was delivered with curative intent after a discussion with the patient. The patient tolerated the treatment well, with one episode of subacute toxicity that resolved with treatment. There was no evidence of recurrence at 15 months post-treatment and the patient’s pulmonary function did not deviate from the pre-SABR baseline. Conclusions SABR appears feasible for medically-inoperable early-stage primary lung adenocarcinoma in the setting of previous double-lung transplantation.

Idiopathic pulmonary fibrosis is a fatal lung disease characterized by progressive and excessive accumulation of myofibroblasts and in the lung. Connective-tissue growth factor (CTGF) exacerbates pulmonary fibrosis in radiation-induced lung fibrosis, and in this study, we demonstrate upregulation of CTGF in a rat lung fibrosis model induced by an adenovirus vector encoding active TGF-β1 (AdTGF-β1). We show that CTGF is also upregulated in patients with idiopathic pulmonary fibrosis. Expression of CTGF was upregulated in vascular smooth muscle cells cultured from fibrotic lungs on Days 7 and 14 as well as endothelial cells sorted from fibrotic lungs on Days 14 and 28. These findings suggest contributions of different cells in maintaining the fibrotic phenotype during fibrogenesis. Treatment of fibroblasts with recombinant CTGF along with TGF-β increases profibrotic markers in fibroblasts, confirming the synergistic effect of recombinant CTGF with TGF-β in inducing pulmonary fibrosis. Also, the fibrotic extracellular matrix upregulated CTGF expression, compared with the normal extracellular matrix, suggesting that not only profibrotic mediators but also a profibrotic environment contributes to fibrogenesis. We also showed that pamrevlumab, a CTGF inhibitory antibody, partially attenuates fibrosis in the model. These results suggest that pamrevlumab could be an option for treatment of pulmonary fibrosis. [ABSTRACT FROM AUTHOR]