Inpatient Management of the Acutely Decompensating Lung Transplant Candidate

Lung allocation in the US changed nearly 15 years ago from time accrued on the waiting list to disease severity and likelihood of posttransplant survival, represented by the lung allocation score (LAS). Notably, the risk of death within a year plays a stronger role on the score calculation than posttransplant survival. While this change was associated with the intended decrease in waitlist mortality (most recently reported at 14.6%), it was predictable that transplant teams would have to care for increasingly older and complex candidates and recipients. This urgency-based allocation also led centers to routinely consider transplanting patients with higher acuity, often hospitalized and, not infrequently, in the intensive care unit (ICU). According to the Scientific Registry for Transplant Recipients, from 2009 to 2019, the proportion of lung recipients hospitalized and those admitted to the ICU at the time of transplant increased from 18.9% to 26.8% and from 9.2% to 16.5%, respectively.

A 42-Year-Old Woman With Anemia, Shock, and Ischemic Stroke After Lung Transplantation

A 42-year-old woman with mixed connective tissue disease- associated interstitial lung disease underwent bilateral lung transplantation. She had an uneventful surgery and was extubated 3 h later. Induction immunosuppression therapy included methylprednisolone 500 mg intraoperatively, basiliximab (anti-IL-2 monoclonal antibody) on days 0 and 4 after transplantation, and methylprednisolone 125 mg intravenously bid for 2 days following surgery. Maintenance immunosuppression therapy consisted of prednisone 20 mg daily, mycophenolate mofetil 750 mg bid, and enteral tacrolimus 0.5 mg bid. Both the donor and the recipient were seropositive for cytomegalovirus. Infectious disease prophylaxis consisted of valganciclovir, trimethoprim- sulfamethoxazole, and voriconazole

Lung IFNAR1(hi) TNFR2(+) cDC2 promotes lung regulatory T cells induction and maintains lung mucosal tolerance at steady state

The lung is a naturally tolerogenic organ. Lung regulatory T cells (T-regs) control lung mucosal tolerance. Here, we identified a lung IFNAR1(hi)TNFR2(+) conventional DC2 (iR2D2) population that induces T-regs in the lung at steady state. Using conditional knockout mice, adoptive cell transfer, receptor blocking antibodies, and TNFR2 agonist, we showed that iR2D2 is a lung microenvironment-adapted dendritic cell population whose residence depends on the constitutive TNFR2 signaling. IFN beta-IFNAR1 signaling in iR2D2 is necessary and sufficient for T-regs induction in the lung. The Epcam(+)CD45(-) epithelial cells are the sole lung IFN beta producer at the steady state. Surprisingly, iR2D2 is plastic. In a house dust mite model of asthma, iR2D2 generates lung T(H)2 responses. Last, healthy human lungs have a phenotypically similar tolerogenic iR2D2 population, which became pathogenic in lung disease patients. Our findings elucidate lung epithelial cells IFN beta-iR2D2-T-regs axis in controlling lung mucosal tolerance and provide new strategies for therapeutic interventions

In vivo reprogramming of pathogenic lung TNFR2 + cDC2s by IFNβ inhibits HDM-induced asthma

Asthma is a common inflammatory lung disease with no known cure. Previously, we uncovered a lung TNFR2 conventional DC2 subset (cDC2s) that induces regulatory T cells (T ) maintaining lung tolerance at steady state but promotes T 2 response during house dust mite (HDM)-induced asthma. Lung IFNβ is essential for TNFR2 cDC2s-mediated lung tolerance. Here, we showed that exogenous IFNβ reprogrammed T 2-promoting pathogenic TNFR2 cDC2s back to tolerogenic DCs, alleviating eosinophilic asthma and preventing asthma exacerbation. Mechanistically, inhaled IFNβ, not IFNα, activated ERK2 signaling in pathogenic lung TNFR2 cDC2s, leading to enhanced fatty acid oxidation (FAO) and lung T induction. Last, human IFNβ reprogrammed pathogenic human lung TNFR2 cDC2s from patients with emphysema ex vivo. Thus, we identified an IFNβ-specific ERK2-FAO pathway that might be harnessed for DC therapy

Successful Preoperative Optimization for Lung Transplantation With Transcatheter Mitral Valve Repair

Surgically treatable valvular heart disease is common in patients with end-stage lung disease. Nevertheless, advanced lung disease is often seen as a contraindication to cardiac surgery, and severe valvular disease is seen as a contraindication to lung transplantation. This report describes the case of a patient presenting with very severe chronic obstructive pulmonary disease and severe mitral regurgitation who was managed with transcatheter mitral valve repair and who subsequently underwent successful lung transplantation. Critical valvular heart disease in patients with chronic respiratory failure may be amenable to transcatheter therapy, which may favorably affect lung transplantation candidacy

Two Decades of Lung Retransplantation: A Single-Center Experience

Lung retransplantation (ReTx) comprises an increasing share of lung transplants and recently has shown improved outcomes. The aim of this study was to identify risk factors affecting overall survival after pulmonary ReTx. The United Network for Organ Sharing database was used to identify patients undergoing lung transplantation at our institution from 1995 to 2014. Of the total 542 lung transplants performed, 87 (16.1%) were ReTxs. The primary outcome was overall survival. Multivariate Cox regression models were used to assess the effect of recipient and donor characteristics on survival. Of the patients who underwent ReTx, median survival was 2 years. Predictors of worse survival include recipient age between 50 and 60 years (relative risk, 4.3; p = 0.02) or older than 60 years (relative risk, 10.2; p < 0.001), and time to ReTx of less than 2 years (relative risk, 3.8; p = 0.01). ReTx for bronchiolitis obliterans syndrome had longer median survival than for restrictive chronic lung allograft dysfunction (2.7 years vs 0.9 years; p = 0.055). Overall survival of ReTx patients after initiation of the lung allocation score was not significantly different (p = 0.21). Lung ReTx outcomes are significantly worse than for primary transplantation but may be appropriate in well-selected patients with certain diagnoses. Lung ReTx in patients older than 50 years or within 2 years of primary lung transplantation was associated with decreased survival. Further work is warranted to identify patients who benefit most from ReTx

Successful bridge to lung transplantation with transcatheter aortic valve replacement

End-stage lung disease and advanced cardiac conditions are frequently seen together and represent a clinical dilemma. Even though both issues may be amenable to surgical management, combining lung transplant with surgical valve repair is rarely done and theoretically associated with increased morbidity and mortality risks, especially in elderly patients. Here, we describe 2 patients presenting with end-stage lung disease and significant aortic stenosis who were successfully bridged to lung transplant via transcatheter aortic valve replacement. Patient 1 was a 66-year-old man who underwent a double lung transplant 56 days after transcatheter aortic valve replacement. Patient 2 was a 70-year-old man who underwent a single right lung transplant 103 days after transcatheter aortic valve replacement. Both patients had uneventful postoperative courses and are alive at the 1-year time point with excellent performance status. This report suggests that transcatheter aortic valve replacement may favorably impact lung transplant candidacy for patients with end-stage lung disease in the setting of severe aortic stenosis, likely representing a better alternative to concomitant aortic valve replacement and lung transplant in elderly patients

The Impact of Donor and Recipient Age: Older Lung Transplant Recipients Do Not Require Younger Lungs

Lung transplantation for patients with end-stage lung disease continues to grow worldwide. Increasing demand for this therapy generates significant waitlist mortality, indicating that alternative sources of donor lungs, such as older donors, are needed. The effect of the donor–recipient age relationship on outcomes remains unclear. A retrospective review of the United Network for Organ Sharing Standard Transplant Analysis and Research database was performed for adult lung recipients from 2005 to 2015. Variables examined included donor age, recipient age, listing diagnosis, episodes of acute cellular rejection in the first year, and survival. Both donors and recipients were stratified according to age ranges. Survival was compared with the log-rank test. Propensity score matching was done stratifying donors younger than 60 years versus older than 60 years for the recipient population of 60 to 69 years. From May 2005 to February 2015, 15,844 patients underwent lung transplantation. Unadjusted comparisons of donor-to-recipient age showed that older donor age appeared to be more relevant for recipients 60 to 69 years old (p = 0.002). Nevertheless, when propensity matching was done based on relevant covariates for recipients in this age range by donors younger or older than 60 years, there were no differences in survival. Our results suggest that even though donor and recipient age may be important in lung transplantation, the interplay between donor and recipient age alone is not an independent determinant of survival. Careful selection of lungs from donors older than 60 years old should be exercised, taking into consideration the totality of donor demographics and risk factors rather than dismissing lungs based on advanced age alone