The key goal in lung donation remains the improvement of graft preservation with the ultimate objective of increasing the number and quality of lung transplants (LTx). Therefore, in recent years the field of graft preservation focused on improving outcomes related to solid organ regeneration and restoration. In this contest Ex-Vivo Lung Perfusion (EVLP) plays a crucial role with the purpose to increase the donor pool availability transforming marginal and/or declined donor lungs suitable for transplantation. Aim of this proof of concept is to test the safety, suitability and feasibility of a new tilting dome for EVLP designed considering the dorsal lung areas as the \"Achilles\' heel\" of the EVLP due to a more fluid accumulation than in the supine standard position.

UNASSIGNED: Recent reports have suggested that coronavirus disease 2019 (COVID-19) infection can cause pneumonitis even in the absence of clinical symptoms and COVID-19 associated pulmonary inflammation can persist resulting in long-term fibrosis. This single-center study utilized standardized immunological testing to determine whether lungs from COVID-19 seropositive donors, indicative of past COVID-19 infection, can be safely used for clinical transplantation.
UNASSIGNED: The study included 90 consecutive lung transplant procedures incorporating donor serological testing for past COVID-19 infection. Donors were negative for active COVID-19 infection and met institutional criteria to be used for lung transplantation. The outcomes of lung transplant recipients were compared between donors with and without serological evidence of past COVID-19 infection.
UNASSIGNED: No significant difference was found in post-transplant survival rates between recipients of lungs obtained from donors with serological evidence compared to those without. Additionally, there were no significant differences in primary graft dysfunction grade 3 rates or other post-transplant clinical parameters, such as operative time, ischemic time, extracorporeal membrane oxygenation use, intensive care unit stay, and hospital stay.
UNASSIGNED: Our findings suggest that lungs from COVID-19 seropositive donors, but not active COVID-19 infection are safe and feasible for transplantation, yielding comparable post-transplant outcomes to donors who are negative COVID-19 antibodies. This study supports the utilization of lungs from donors with historic COVID-19 infection as long as they meet current transplant criteria, potentially addressing the concerns related to the use of such organs.

BACKGROUND: Exposure to air pollution post lung transplant has been shown to decrease graft and patient survival. This study examines the impact of air pollution exposure in the first 3 months post-transplant on baseline (i.e. highest) forced expiratory volume in 1s (FEV1) achieved and development of chronic lung allograft dysfunction (CLAD).
METHODS: Double-lung transplant recipients (n=82) were prospectively enrolled for comprehensive indoor and personal environmental monitoring at 6- and 12-weeks post-transplant and followed for >4 years. Associations between clinical and exposure variables were investigated using an exposomics approach followed by analysis with a Cox Proportional Hazards model. Multivariable analyses were used to examine the impact of air pollution on baseline % predicted FEV1 (defined as the average of the 2 highest values achieved post-transplant) and risk of CLAD.
RESULTS: Multivariable analysis revealed a significant inverse relationship between personal black carbon (BC) levels and baseline % FEV1. The multivariable model indicated that patients with higher-than-median exposure to BC (>350 ng/m3) attained a baseline % FEV1 that was 8.8% lower than those with lower-than-median BC exposure (p = 0.019). Cox proportional hazards model analysis revealed that patients with high personal BC exposure had a 2.4 times higher hazard risk for CLAD than patients with low BC exposure (p = 0.045).
CONCLUSIONS: Higher personal BC levels during the first 3 months post-transplant decreases baseline FEV1 and doubles the risk of CLAD. Strategies to reduce BC exposure early following lung transplant may help improve lung function and long-term outcomes.

Lung transplant recipients (LTR) are susceptible to severe COVID-19 and had lower immune responses to primary SARS-CoV-2 vaccination as compared to the general population and to other solid organ transplant recipients. As immunity induced by booster vaccination and natural infection has increased since the beginning of the pandemic in the general population, immunity acquired by LTR is not well documented. Humoral and cellular immunity to SARS-CoV-2 was monitored in February and May 2023 in 30 LTR and compared to that of health care workers (HCW) and nursing home residents (NHR). LTR had significantly lower levels of SARS-CoV-2 binding and neutralizing antibodies and lower IFN-γ responses to Wuhan, Delta and XBB1.5 variants as compared to HCW and NHR. Humoral immunity decreased between the two visits whereas cellular immunity remained more stable. The persistent defect in SARS-CoV-2 immunity in LTR should encourage continued monitoring and preventive measures for this vulnerable population.

Background. Varicella-zoster virus (VZV) is a human neurotropic virus which commonly causes infection during childhood, presenting as chickenpox. Later in life it may reactivate as herpes zoster. We report a rare manifestation of reactivation of VZV infection presenting as cutaneous vasculitis and varicella pneumonia in a lung transplant recipient. Case presentation. A 65-year-old man was lung transplanted bilaterally for emphysema and had repeated posttransplant chest infections and colonization with Pseudomonas aeruginosa. Nine months post-transplant he presented with dyspnoea and a cutaneous vasculitis-like eruption with a predilection over face, thorax and distal extremities. Initially, VZV reactivation was not suspected due to absence of the typical vesicular eruptions. The diagnosis was confirmed by VZV PCR from the swabs of the ulcer after skin punch biopsy of a lesion and from bronchoalveolar lavage (BAL). The histology of skin biopsy demonstrated epithelial damage and vascular damage but no typical epithelial virus associated changes. The patient responded to antiviral therapy with total remission of rash and VZV DNA was finally not detectable from repeated BAL after 29 days of therapy. However, the pulmonary radiological features and dyspnoea persisted due to reasons possibly unrelated to the VZV infection. Conclusion. Had it not been for the patient to mention the resemblance of the vasculitic rash with his primary VZV infection, the diagnosis would easily have been overlooked. In this case, the biopsy did not show typical histopathologic findings of VZV-vasculitis. What led the diagnosis was a PCR from the wound swab taken after the punch biopsy. This case serves as a reminder for atypical presentation of common conditions in immunosuppressed patients and that extensive diagnostic sampling may be warranted in this group.

Background: Primary graft dysfunction (PGD) has detrimental effects on recipients following lung transplantation. Here, we determined the contemporary trends of PGD in a national database, factors associated with the development of PGD grade 3 (PGD3) and ex vivo lung perfusion\'s (EVLP) effect on this harmful postoperative complication. Methods: The United Network for Organ Sharing database was queried from 2015 to 2023, and recipients were stratified into No-PGD, PGD1/2, or PGD3. The groups were analyzed with comparative statistics, and survival was determined with Kaplan-Meier methods. Multivariable Cox regression was used to determine factors associated with increased mortality. PGD3 recipients were then stratified based on EVLP use prior to transplantation, and a 3:1 propensity match was performed to determine outcomes following transplantation. Finally, logistic regression models based on select criteria were used to determine risk factors associated with the development of PGD3 and mortality within 1 year. Results: A total of 21.4% of patients were identified as having PGD3 following lung transplant. Those with PGD3 suffered significantly worse perioperative morbidity, mortality, and had worse long-term survival. PGD3 was also independently associated with increased mortality. Matched EVLP PGD3 recipients had significantly higher use of ECMO postoperatively; however, they did not suffer other significant morbidity or mortality as compared to PGD3 recipients without EVLP use. Importantly, EVLP use prior to transplantation was significantly associated with decreased likelihood of PGD3 development, while having no significant association with early mortality. Conclusions: EVLP is associated with decreased PGD3 development, and further optimization of this technology is necessary to expand the donor pool.

BACKGROUND: Chronic lung allograft dysfunction (CLAD) limits survival following lung transplant, but substantial lung damage occurs before diagnosis by traditional methods. We hypothesized that small airway gene expression patterns could identify CLAD risk before spirometric diagnosis and predict subsequent graft failure.
METHODS: Candidate genes from 4 rejection-associated transcript sets were assessed for associations with CLAD or graft failure in a derivation cohort of 156 small airway brushes from 45 CLAD cases and 37 time-matched controls with >1-year stable lung function. Candidate genes not associated with CLAD and time to graft failure were excluded, yielding the Airway Inflammation 2 (AI2) gene set. Area under the receiver operating curve (AUC) for CLAD and competing risks of death or graft failure were assessed in an independent validation cohort of 37 CLAD cases and 37 controls.
RESULTS: Thirty-two candidate genes were associated with CLAD and graft failure, comprising the AI2 score, which clustered into 3 subcomponents. The AI2 score identified CLAD before its onset, in early and late post-CLAD brushes, as well as in the validation cohort (AUC 0.69-0.88). The AI2 score association with CLAD was independent of positive microbiology, CLAD stage, or CLAD subtype. However, transcripts most associated with CLAD evolved over time from CLAD onset. The AI2 score predicted time to graft failure and retransplant-free survival in both cohorts (p ≤ 0.03).
CONCLUSIONS: This airway inflammation gene score is associated with CLAD development, graft failure, and death. Future studies defining the molecular heterogeneity of airway inflammation could lead to endotype-targeted therapies.

Mounier-Kuhn syndrome, characterized by tracheal dilatation due to the loss of elastic fibers and smooth muscle cells, is a rare condition, often leading to recurrent respiratory infections from impaired mucociliary clearance.

BACKGROUND: Transplants with hearts and lungs from donors with hepatitis C virus (HCV D+) have been proven safe and effective since development of direct-acting antivirals, yet the presence of HCV + persists as a reason to decline organs.
METHODS: We identified adult candidates listed January 1, 2015-March 8, 2023 for heart or lung transplant using the Scientific Registry of Transplant Recipients. We identified individual-level and center-level characteristics associated with listing to consider HCV D+ offers using multilevel logistic regression in a multivariable framework.
RESULTS: Over the study period, the annual percentage of candidates willing to consider HCV D+ offers increased for both heart (9.5%-74.3%) and lung (7.8%-59.5%), as did the percentage of centers listing candidates for HCV D+ heart (52.9%-91.1%) and lung (32.8%-82.8%) offers. Candidates at centers with more experience with HCV D+ transplants were more likely to consider HCV D+ organ offers. After adjustment, listing center explained 70% and 78% of the residual variance in willingness to consider HCV D+ hearts and lungs, respectively.
CONCLUSIONS: Although listing for consideration of HCV D+ offers has increased, it varies by transplant center. Center-level barriers to consideration of HCV D+ organs reduce recipients\' transplant access.

BACKGROUND: To assess changes in bone density and vertebral body height of patients undergoing lung transplant surgery using computed tomography (CT).
METHODS: This institutional review board (IRB) approved retrospective observational study enrolled patients with a history of lung transplant who had at least two chest CT scans. Vertebral body bone density (superior, middle, and inferior sections) and height (anterior, middle, and posterior sections) were measured at T1-T12 at baseline and follow up CT scans. Changes in the mean bone density, mean vertebral height, vertebral compression ratio (VBCR), percentage of anterior height compression (PAHC), and percentage of middle height compression (PMHC) were calculated and analyzed.
RESULTS: A total of 93 participants with mean age of 58 ± 12.3 years were enrolled. The most common underlying disease that led to lung transplants was interstitial lung diseases (57 %). The inter-scan interval was 34.06 ± 24.8 months. There were significant changes (p-value < 0.05) in bone density at all levels from T3 to T12, with the greatest decline at the T10 level from 163.06 HU to 141.84 HU (p-value < 0.05). The average VBCR decreased from 96.91 to 96.15 (p-value < 0.05).
CONCLUSIONS: Routine chest CT scans demonstrate a gradual decrease in vertebral body bone density over time in lung transplant recipients, along with evident anatomic changes such as vertebral body bone compression. This study shows that utilizing routine chest CT for lung transplant recipients can be regarded as a cost-free tool for assessing the vertebral body bone changes in these patients and potentially aiding in the prevention of complications related to osteoporosis.