Survival Outcomes of Lung Transplant Recipients From Donors With Abnormal Kidney Function.

BACKGROUND: Recovering lungs with pulmonary edema due to abnormal kidney function is considered one of the expanded selection criteria for lung transplant. The aim of this study is to assess lung transplant recipients' survival from donors with abnormal kidney function and to determine differences in lung recovery rates from donors with and donors without abnormal kidney function. METHODS: We reviewed the United Network for Organ Sharing registry for first-time adult lung transplant donors and recipients from June 2005 to March 2017. Donor kidney function was categorized into three groups based on estimated glomerular filtration rate: group I, greater than 60 mL/min; group II, 15 to 59 mL/min; and group III, less than 15 mL/min. Recipient survival was stratified based on estimated glomerular filtration rate using Kaplan-Meier. A multivariate Cox Regression model with known risk factors that affect survival was used to compare survival among groups. Comparison of lung recovery among the three groups was also performed. RESULTS: Lung recovery rates were 29.7% (15,670 of 52,747), 19.4% (3879 of 20,040), and 18.1% (704 of 3898) for groups I, II, and III, respectively. The 1-, 3-, and 5-year recipient survival rates were 86.2%, 69.2%, and 55.7% for group I; 84.9%, 66.9%, and 53.8% for group II; and 85.5%, 65.3%, and 50.3% for group III, respectively (adjusted P = .25; multivariate Cox regression method). When group I was used as reference, the adjusted hazard ratio for group II was 1.04 (95% CI, 0.98-1.10) and for group III, it was 1.08 (95% CI, 0.96-1.23), after adjusting with the multivariate Cox regression model. CONCLUSIONS: There was no significant difference in lung recipient survival. The lung recovery rate from donors with abnormal kidney function was lower compared with that of donors with normal kidney function.

Clinical course of SARS-CoV-2 infection and recovery in lung transplant recipients.

BACKGROUND: Reports on outcomes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in lung transplant recipients remain limited. METHODS: We performed a single-center, observational study of outcomes in lung transplant recipients diagnosed with SARS-CoV-2 between 5/1/2020 and 3/15/2022 that were followed for a median of 123 days. We analyzed changes in spirometry, acute lung allograft dysfunction (ALAD) incidence, hospitalization, mechanical ventilation needs, secondary infection, and survival. RESULTS: In our cohort of 336 patients, 103 developed coronavirus disease (COVID) (27 pre-Delta, 20 Delta, and 56 Omicron-era). Twenty-five patients (24%) required hospitalization and 10 patients ultimately died (10%). Among 85 survivors who completed ambulatory spirometry, COVID-19 did not alter change in forced expiratory volume in 1 s (FEV1 ) or forced vital capacity (FVC) over time compared to the preceding 6 months. The pre-COVID FEV1 change was -0.05 ml/day (IQR -0.50 to 0.60) compared to -0.20 ml/day (IQR -1.40 to 0.70) post-COVID (p = .16). The pre-COVID change in FVC was 0.20 ml/day (IQR -0.60 to 0.70) compared to 0.05 ml/day (IQR -1.00 to 1.10) post-COVID (p = .76). Although the cohort overall had stable lung function, 33 patients (39%) developed ALAD or accelerated chronic lung allograft dysfunction (FEV1 decline >10% from pre-COVID baseline). Nine patients (35%) with ALAD recovered lung function. Within 3 months of acute COVID infection, 18 patients (17%) developed secondary infections, the majority being bacterial pneumonia. Finally, vaccination with at least two doses of mRNA vaccine was not associated with improved outcomes. CONCLUSIONS: This study describes the natural history of SARS-CoV-2 infection in a large cohort of lung transplant recipients. Although one third of patients develop ALAD requiring augmented immunosuppression, infection with SARS-CoV-2 is not associated with worsening lung function.

Feasibility and Safety of Low-Dose Mesenchymal Stem Cell Infusion in Lung Transplant Recipients.

BACKGROUND: We have previously shown bone marrow-derived mesenchymal stem cells (MSCs) may shift immune responses toward anti-inflammatory pathways and stabilize the course of obstructive chronic lung allograft syndrome (o-CLAD) after lung transplantation. In this study, we measured the response of lower dose infusions. METHODS: We infused low-dose MSCs intravenously in 13 patients who had developed moderate-to-severe o-CLAD. Three had previously received an infusion of MSCs from a different donor and were re-dosed at 1 × 106 MSC/kg, while 5 received a first dose at 1 × 106 MSC/kg and five received an even lower dose at 0.5 × 106 MSC/kg. We recorded pulmonary function tests before and after infusion, and patients were followed clinically for 12 months. RESULTS: Infusions were well tolerated, and no significant adverse events were recorded in the first 30 days. There was significant decline (mean ± SD) in forced vital capacity (FVC) (3.49 ± 1.03 vs 3.18 ± 0.94 L, P = .03) and forced expiratory volume in 1 second (FEV1) (2.28 ± 0.86 vs 1.77 ± 0.49 L, P = .04) over the year preceding infusion. FVC (3.18 ± 0.94 vs 3.46 ± 0.99 L, P = .53) and FEV1 was not significantly changed (1.77 ± 0.49 vs 1.88 ± 0.75, P = .72) when comparing values immediately prior to infusion to those obtained 1 year after infusion, indicating a possible stabilizing effect on lung function decline due to o-CLAD. CONCLUSION: Intravenous infusions of bone marrow-derived MSCs are well tolerated in lung transplant recipients with moderate-to-severe CLAD. Low-dose MSCs appear to slow progression of CLAD in some patients.

Refractory chylous effusions in lymphangioleiomyomatosis patient post lung transplant.

Lymphangioleiomyomatosis is a rare systemic disorder of unknown etiology that affects young women almost exclusively. Chylous effusions are known to be associated with lymphangioleiomyomatosis and may be difficult to treat. We present the case of a 37-year-old female who received bilateral lung transplantation for lymphangioleiomyomatosis complicated by refractory chylothorax and chylous ascites, ultimately controlled through repeated, open surgical procedures and percutaneous lymphatic embolization interventions. The combined surgical and interventional radiological approach, while not novel in their own right, suggests that a multi-modal interventional approach may be required in refractory cases.

Unilateral Versus Bilateral Lung Transplantation: Do Different Esophageal Risk Factors Predict Chronic Allograft Failure?

GOALS: To assess the effect of unilateral versus bilateral lung transplantation (LTx) on esophageal motility and gastroesophageal reflux, and the association with the development of obstructive chronic lung allograft dysfunction (o-CLAD). BACKGROUND: We have shown that esophagogastric junction outflow obstruction, incomplete bolus transit, and proximal reflux are all independent risk factors for the development of chronic allograft failure. However, it remains unclear whether these factors are influenced by the type of surgery and how this relates to allograft failure. STUDY: Patients post-LTx (n=48, 24 female; aged 20 to 73 y) completed high-resolution impedance manometry and 24-hour pH/impedance. RESULTS: Patients who had undergone unilateral LTx were more likely to exhibit esophagogastric junction outflow obstruction (47% vs. 18%; P=0.046) and less likely to exhibit hypocontractility (0% vs. 21%; P=0.058) than those who had undergone bilateral LTx. Although the proportion of patients exhibiting gastroesophageal reflux was no different between groups (33% vs. 39%; P=0.505), those undergoing bilateral LTx were more likely to exhibit proximal reflux (8% vs. 37%; P=0.067). Univariate Cox proportion hazards regression analysis did not show a difference between unilateral versus bilateral LTx in the development of o-CLAD (hazard ratio=1.17; 95% confidence interval, 0.48-2.85; P=0.723). CONCLUSION: The type of LTx performed seems to lead to different risk factors for the development of o-CLAD. Physicians should be aware of these differences, as they may need to be taken into account when managing patient's post-LTx.

Pulmonary Neuroendocrine Cell Hyperplasia Associated with Surfactant Protein C Gene Mutation.

Familial interstitial lung disease (ILD) is defined as presence of ILD in 2 or more family members. Surfactant protein C (SFTPC) gene mutations are rare, but well-known cause of familial ILD. We reported a 20-year-old male, who was referred for lung transplantation. He was symptomatic at age 3 and underwent surgical lung biopsy at age 6, which revealed a nonspecific interstitial pneumonia (NSIP) pattern. Genetic workup revealed a novel SFTPC mutation in the first intron with a C to A transversion. At age 21, he underwent bilateral lung transplantation. Explanted lung histology suggested NSIP. In addition there was pulmonary neuroendocrine cell (PNEC) hyperplasia and carcinoid tumorlets. His mother had undergone lung transplantation several years earlier, and her explanted lung showed similar pathology. SFTPC mutations are inherited in an autosomal dominant pattern. Various types of ILD have been associated with SFTPC mutation including NSIP, usual interstitial pneumonia (UIP), and desquamative interstitial pneumonia (DIP). PNEC hyperplasia has been described to occur in association with lung inflammation but has not been previously described with familial ILD associated with SFTPC mutation.

Giant cell interstitial pneumonia in patients without hard metal exposure: analysis of 3 cases and review of the literature.

Giant cell interstitial pneumonia is a rare lung disease and is considered pathognomonic for hard metal lung disease, although some cases with no apparent hard metal (tungsten carbide cobalt) exposure have been reported. We aimed to explore the association between giant cell interstitial pneumonia and hard metal exposure. Surgical pathology files from 2001 to 2004 were searched for explanted lungs with the histopathologic diagnosis of giant cell interstitial pneumonia, and we reviewed the associated clinical histories. Mass spectrometry, energy-dispersive x-ray analysis, and human leukocyte antigen typing data were evaluated. Of the 455 lung transplants, 3 met the histologic criteria for giant cell interstitial pneumonia. Patient 1 was a 36-year-old firefighter, patient 2 was a 58-year-old welder, and patient 3 was a 45-year-old environmental inspector. None reported exposure to hard metal or cobalt dust. Patients 1 and 2 received double lung transplants; patient 3 received a left single-lung transplant. Histologically, giant cell interstitial pneumonia presented as chronic interstitial pneumonia with fibrosis, alveolar macrophage accumulation, and multinucleated giant cells of both alveolar macrophage and type 2 cell origin. Energy-dispersive x-ray analysis revealed no cobalt or tungsten particles in samples from the explanted lungs. None of the samples had detectable tungsten levels, and only patient 2 had elevated cobalt levels. The lack of appropriate inhalation history and negative analytical findings in the tissue from 2 of the 3 patients suggests that giant cell interstitial pneumonia is not limited to individuals with hard metal exposure, and other environmental factors may elicit the same histologic reaction.

Mayo clinic experience of lung transplantation in pulmonary lymphangioleiomyomatosis.

OBJECTIVES: Lymphangioleiomyomatosis (LAM) is a rare, cystic lung disease that generally results in progressive decline in lung function. Despite advancement of pharmacological therapy for LAM, lung transplantation remains an important option for women with end-stage LAM. METHODS: Patients with LAM undergoing lung transplantation at the Mayo Clinic campuses in Rochester, Minnesota and Jacksonville, Florida since 1995 were retrospectively reviewed. RESULTS: Overall, 12 women underwent lung transplantation. Nine of 12 (75%) underwent double lung transplant. The mean age was 42 ± 8 years at the time of transplant. One patient (8%) had a chylothorax and 7 (58%) had recurrent pneumothoraces, 4 (33%) of which required pleurodesis. All had diffuse, cystic lung disease on chest CT consistent with LAM which was confirmed in the explant of all patients. The average length of ICU and hospital stays were 5 ± 4 and 19 ± 19 days, respectively. Mild to moderate anastomotic ischemia was evident in all patients but resolved with time. No patient was treated with sirolimus pre-transplant. Seven patients received sirolimus post-transplant; however, clinical benefit was documented in only 2 patients, 1 of which was treated for large retroperitoneal cysts with ureteral obstruction and another with persistent chylothorax and retroperitoneal lymphangioleimyomas. Five patients are deceased. The median survival by Kaplan-Meier analysis was 119 months with a median follow-up of 68 months (range 2-225 months). CONCLUSIONS: Lung transplant remains a viable treatment for patients with end-stage LAM. The role of sirolimus peri-transplantation remains ill-defined.

Traumatic bronchial rupture and platypnea-orthodeoxia.

A patient with blunt trauma and traumatic bronchial rupture and lung collapse had prominent symptoms of platypnea-orthodeoxia syndrome. These symptoms were relieved by bronchial repair. The syndrome is rarely seen and is usually associated with a patent foramen ovale or atrial septal defect. The syndrome has not been described previously in association with traumatic bronchial rupture.

Fatal arterial gas embolism in an adult 1 year after bilateral sequential lung transplantation.

Fatal systemic air embolism (SAE) related to positive pressure ventilation is a rare complication. Case reports in the pediatric literature usually relate to complications in ventilating neonates and are more common. We describe what we believe to be the first such case in an adult ventilated with a high-frequency oscillating ventilator (HFOV) for acute respiratory distress syndrome (ARDS). The patient had undergone bilateral sequential lung transplantation 12 months earlier for idiopathic pulmonary fibrosis. Radiographic findings showed cerebral and aortic gas embolization and livedo reticularis with widespread cerebral infarction and cerebral edema.