The Secondary Pulmonary Hypertension Diagnosis is Not Useful in Lung Allocation.

BACKGROUND: In lung transplant, the United Network for Organ Sharing (UNOS) contains a diagnosis of secondary pulmonary hypertension (SPH). SPH and pulmonary arterial hypertension are treated the same in the allocation scoring system. It is not clear whether utilizing the SPH diagnosis instead of the primary diagnosis is helpful to patients or providers. METHODS: Analysis of UNOS data from May 2005 through July 2021, comparing patients listed under the SPH diagnosis with patients listed under COPD and interstitial lung disease (ILD) who met criteria for PH (COPD-PH and ILD-PH, respectively), as well as patients listed under pulmonary arterial hypertension (primary pulmonary hypertension, PPH). Competing-risk analysis examined waitlist and post-transplant outcomes. An exploratory analysis of UNOS spirometry data was performed. RESULTS: Compared to patients listed under the SPH diagnosis, patients with ILD-PH were more likely to undergo transplantation (adjusted HR: 1.34, 95% confidence interval: 1.16-1.54, P < .001), with no significant difference comparing the SPH diagnosis to PPH or to COPD-PH. Waitlist mortality did not vary between groups. Post-transplant survival was lower in patients with PPH (adjusted HR: 1.35, 95% confidence interval: 1.04-1.75, P = .025), with no significant difference comparing the SPH diagnosis to COPD-PH or ILD-PH. Spirometry failed to demonstrate a clear phenotype within the SPH diagnosis. CONCLUSION: In an adjusted analysis, patients with advanced lung disease and secondary PH were more likely to undergo transplantation when listed for ILD than when listed under the SPH diagnosis. The SPH diagnosis is too clinically heterogeneous to be useful in predictive models and should be considered for removal from UNOS.

Extracorporeal Membrane Oxygenation Support in COVID-19 Patients: A Propensity Score Analysis.

Revised guidelines clarify indications for extracorporeal membrane oxygenation (ECMO) support in Coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS). Limited data exist to compare clinical outcomes of COVID-19 ARDS patients to non-COVID-19-related ARDS patients when supported with ECMO. An observational propensity-matched study was performed to compare clinical and ECMO-related complications between COVID-19-related ARDS patients (COVID) and non-COVID-19-related ARDS (Control). COVID- patients cannulated from March 1st, 2020, through June 1st, 2021, were included and matched to patients from the historical cohort at our center from 2012 to 2020 based on age, body mass index (BMI), acute physiology and chronic health evaluation (APACHE) II score, and duration ECMO run. The primary outcome was complications during ECMO therapy. A total of 56 patients were propensity matched 1:1 with a mean age of 40.9 years, BMI 32.1 kg/m2, APACHE II score of 26.6, and duration of ECMO support of 22.6 days. In total 18 COVID-19 patients were observed to have more major bleeding complications (18 vs. 9, p = 0.03). Although not statistically significant, they also had more strokes (6 vs. 3) and required more chest tubes (13 vs. 8). Inpatient mortality was not different. ECMO support in COVID-19 patients is associated with more major bleeding complications, strokes, and chest tube placements. The use of ECMO in patients with COVID-19-related ARDS appears to be associated with an increased risk of complications.

One Year Into the Pandemic: Evolving COVID-19 Outcomes in Lung Transplant Recipients, a Single-center Experience.

In the early months of the coronavirus disease 2019 (COVID-19) pandemic, our center reported a mortality rate of 34% in a cohort of 32 lung transplant recipients with COVID-19 between March and May 2020. Since then, there has been evolving knowledge in prevention and treatments of COVID-19. To evaluate the impact of these changes, we describe the clinical presentation, management, and outcomes of a more recent cohort of lung transplant recipients during the second surge and provide a comparison with our first cohort. Methods: We conducted a retrospective cohort study that included all consecutive lung transplant recipients who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. We compared baseline demographics and major outcomes between the first- and second-surge cohorts. Results: We identified 47 lung transplant recipients (median age, 60; 51% female) who tested positive for severe acute respiratory syndrome coronavirus 2 between November 2020 and February 28, 2021. The current cohort had a higher proportion of patients with mild disease (34% versus 16%) and fewer patients with a history of obesity (4% versus 25%). Sixty-six percent (n = 31) required hospitalization and were treated with remdesivir (90%) and dexamethasone (84%). Among those hospitalized, 77% (n = 24) required supplemental oxygen, and 22% (n = 7) required invasive mechanical ventilation. The overall 90-d mortality decreased from 34% to 17% from the first cohort to the second (adjusted odds ratio, 0.26; 95% confidence interval, 0.08-0.85; P = 0.026). Conclusions: Although COVID-19-associated mortality rate in lung transplant recipients at our center has decreased over time, COVID-19 continues to be associated with significant morbidity and mortality.

Lung Transplantation for Pulmonary Fibrosis Associated With Hermansky-Pudlak Syndrome. A Single-center Experience.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, platelet storage defect with resultant bleeding diathesis, and pulmonary fibrosis. The bleeding diathesis associated with HPS had long been considered a contraindication to lung transplantation; consequently, few reports of successful lung transplantation for HPS exist. Methods: In the largest case series on lung transplant for HPS, we describe the characteristics of 11 lung transplant candidates with HPS-related pulmonary fibrosis, and the management and outcomes of 7 patients who underwent lung transplantation. Results: Of the 7 patients transplanted, 30-d survival was 85.7% (6/7). Six patients had at least 2 y of follow-up available with a 1-y survival of 83.3% and a 2-y survival of 83.3% (5/6). The median age at referral was 48 y (range 29-62 y). Eight patients (72.7%) were of Puerto Rican ancestry with confirmed type 1 HPS mutation. Six out of 7 patients received prophylaxis for bleeding diathesis, with a majority receiving desmopressin; 1 patient was administered aminocaproic acid infusion, and another received 2 units of platelets before surgery. Estimated blood loss and the amount of intraoperative blood product administered was highly variable with or without prophylaxis. Median blood loss was 400 mL (range 125-750) and estimated blood products administered was 700 mL (range 490-4043). Conclusions: HPS should not be considered a contraindication for lung transplantation. Although patients with HPS seem to have an increased risk of massive hemorrhage, the risk is unpredictable. Transplant teams should prepare a preoperative plan in consultation with hematology and consider the use of prophylactic platelet transfusion and desmopressin.

Identification of Lung Transplant Recipients With a Survival Benefit After Fundoplication.

BACKGROUND: Gastroesophageal reflux disease (GERD) and aspiration of enteric contents are associated with worse outcomes after lung transplantation. The purpose of this study was to elucidate populations of patients who benefit the most from fundoplication after lung transplantation. METHODS: Lung transplantations from 2001 to 2019 (n = 971) were retrospectively reviewed and stratified by fundoplication before (n = 128) or after (n = 24) chronic lung allograft dysfunction (CLAD) development vs patients who did not undergo fundoplication. Patients with a fundoplication before CLAD were propensity matched to patients without a fundoplication. The primary outcome of interest was posttransplant survival. Time-to-event rates were calculated using a multivariable Cox proportional hazards model and Kaplan-Meier functions. RESULTS: Fundoplication before CLAD improved posttransplant survival before and after propensity matching, and it remained a significant predictor after adjusting for baseline characteristics (hazard ratio [HR],0.57; 95 % confidence interval [CI], 0.4 to 0.8; P = .001). Transplant recipients with a restrictive disorder (HR, 0.46; 95 % CI, 0.3 to 0.73; P = .001), age younger than 65 years (HR, 0.48; 95 % CI, 0.32 to 0.71; P < ;0.001), and with both single (HR, 0.47; 95 % CI, 0.28 to 0.79; P = .005) and double (HR, 0.55; 95 % CI, 0.32 to 0.93; P = .027) lung transplants had a significant decrease in mortality after fundoplication. The effect was present after excluding early deaths and CLAD diagnoses. Gastroesophageal reflux disease diagnosed by pH, impedance, or esophagogastroduodenoscopy was not associated with worse outcomes. Among patients with CLAD, a fundoplication was an independent predictor of post-CLAD survival (HR, 0.27; 95 % CI; 0.12 to 0.61; P = .002). CONCLUSIONS: Fundoplication before or after CLAD development is an independent predictor of survival. Younger patients with restrictive disease, independent of the type of transplant, have a survival benefit. Gastroesophageal reflux disease diagnosed by conventional methods was not associated with worse survival.

Lung transplantation disparities based on diagnosis for patients bridging to transplant on extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly utilized as a bridge to lung transplantation, but ECMO status is not explicitly accounted for in the Lung Allocation Score (LAS). We hypothesized that among waitlist patients on ECMO, patients with pulmonary arterial hypertension (PAH) would have lower transplantation rates. METHODS: Using United Network for Organ Sharing data, we conducted a retrospective cohort study of patients who were ≥12 years old, active on the lung transplant waitlist, and required ECMO support from June 1, 2015 through June 12, 2020. Multivariable competing risk analysis was used to examine waitlist outcomes. RESULTS: 1064 waitlist subjects required ECMO support; 40 (3.8%) had obstructive lung disease (OLD), 97 (9.1%) had PAH,138 (13.0%) had cystic fibrosis (CF), and 789 (74.1%) had interstitial lung disease (ILD). Ultimately, 671 (63.1%) underwent transplant, while 334 (31.4%) died or were delisted. The transplant rate per person-years on the waitlist on ECMO was 15.41 for OLD, 6.05 for PAH, 15.66 for CF, and 15.62 for ILD. Compared to PAH patients, OLD, CF, and ILD patients were 78%, 69%, and 62% more likely to undergo transplant throughout the study period, respectively (adjusted SHRs 1.78 p = 0.007, 1.69 p = 0.002, and 1.62 p = 0.001). The median LAS at waitlist removal for transplantation, death, or delisting were 75.1 for OLD, 79.6 for PAH, 91.0 for CF, and 88.3 for ILD (p < 0.001). CONCLUSIONS: Among patients bridging to transplant on ECMO, patients with PAH had a lower transplantation rate than patients with OLD, CF, and ILD.

Geographic Differences in Lung Transplant Volume and Donor Availability During the COVID-19 Pandemic.

BACKGROUND: Regional variation in lung transplantation practices due to local coronavirus disease 2019 (COVID-19) prevalence may cause geographic disparities in access to lung transplantation. METHODS: Using the United Network for Organ Sharing registry, we conducted a descriptive analysis of lung transplant volume, donor lung volume, new waitlist activations, and waiting list deaths at high-volume lung transplant centers during the first 3 months of the pandemic (March 1. 2020, to May 30, 2020) and we compared it to the same period in the preceding 5 years. RESULTS: Lung transplant volume decreased by 10% nationally and by a median of 50% in high COVID-19 prevalence centers (range -87% to 80%) compared with a median increase of 10% (range -87% to 80%) in low prevalence centers (P-for-trend 0.006). Donation services areas with high COVID-19 prevalence experienced a greater decrease in organ availability (-28% range, -72% to -11%) compared with low prevalence areas (+7%, range -20% to + 55%, P-for-trend 0.001). Waiting list activations decreased at 18 of 22 centers. Waiting list deaths were similar to the preceding 5 years and independent of local COVID-19 prevalence (P-for-trend 0.36). CONCLUSIONS: Regional variation in transplantation and donor availability in the early months of the pandemic varied by local COVID-19 activity.

Fundoplication after lung transplantation in patients with systemic sclerosis-related end-stage lung disease.

Introduction: Gastroesophageal reflux and aspiration are risk factors for chronic lung allograft dysfunction in lung transplant recipients. Patients with systemic sclerosis are at an increased risk of aspiration due to esophageal dysmotility and an ineffective lower esophageal sphincter. The aim of this study is to understand the effect of fundoplication on outcomes in systemic sclerosis recipients. Methods: Between 2001 and 2019, 168 systemic sclerosis patients were referred for lung transplantation-51 (30.3%) were listed and 36 (21.4%) were transplanted. Recipients were stratified whether they underwent a fundoplication (n = 10, 27.8%) or not (n = 26, 72.2%). Freedom from chronic lung allograft dysfunction and survival were analyzed using log-rank test. Multivariable analysis for known risk factors was performed using a Cox-proportional hazards model. Results: Median time to fundoplication after transplantation was 16.4 months (interquartile range: 9.6-25.1) and all were laparoscopic (Dor 50%, Nissen 40%, Toupet 10%). There were no differences in acute rejection ⩾ A1 (26.9% vs 30%), or primary graft dysfunction grades 2-3 at 72 h (42.3% vs 40%) between groups. Recipients with fundoplication had an increased freedom from chronic lung allograft dysfunction (p = 0.035) and overall survival (p = 0.01). Fundoplication was associated with a reduced risk of mortality adjusting for other comorbidities (hazard ratio = 0.13; 95% confidence interval = 0.02-0.65; p = 0.014). Double and single lung transplant did not have different post-transplant survival. Conclusion: Fundoplication in systemic sclerosis lung transplant recipients is associated with greater freedom from chronic lung allograft dysfunction and overall survival. Screening for reflux and aspiration followed by early fundoplication may delay graft deterioration in this population.

COVID-19 in lung transplant recipients: A single center case series from New York City.

There are limited data describing COVID-19 in lung transplant recipients. We performed a single center, retrospective case series study of lung transplant patients followed by the Columbia Lung Transplant program who tested positive for SARS-CoV-2 between March 19 and May 19, 2020. Thirty-two lung transplant patients developed mild (16%), moderate (44%), or severe (41%) COVID-19. The median age of patients was 65 years, and the median time from lung transplant was 5.6 years. Symptoms included cough (66%), dyspnea (50%), fever (47%), and gastrointestinal upset (44%). Patients received hydroxychloroquine (84%), azithromycin (75%), augmented steroids (44%), tocilizumab (19%), and remdesivir (9%). Eleven patients (34%) died at a median time of 14 days from admission. Complications during admission included: acute kidney injury (63%), transaminitis (31%), shock (31%), acute respiratory distress syndrome (25%), neurological events (25%), arrhythmias (22%), and venous thromboembolism (9%). Compared to patients with moderate COVID-19, patients with severe COVID-19 had higher peak white blood cell counts (15.8 vs 7 × 103 /uL, P = .019), C-reactive protein (198 vs. 107 mg/L, P = .010) and D-dimer (8.6 vs. 2.1 ug/mL, P = .004) levels, and lower nadir lymphocyte counts (0.09 vs. 0.4 × 103 /uL, P = .006). COVID-19 is associated with severe illness and a high mortality rate in lung transplant recipients.

What Awaits on the Other Side: Post-Lung Transplant Morbidity and Mortality After Pre-Transplant Hospitalization.

BACKGROUND Morbidity and mortality rates after lung transplantation remain high compared to other solid organ transplants. In the lung allocation score era, patients given the highest priority on the waitlist are those with the greatest severity of illness, who often require preoperative hospitalization. MATERIAL AND METHODS To determine the association of pre-transplant hospitalization with post-transplant outcomes, we retrospectively evaluated 448 lung transplant recipients at our center between January 2010 and July 2017 (114 hospitalized; 334 outpatient). RESULTS Survival was similar between the groups (hazard ratio 0.93 [95% CI 0.61 to 1.42], p=0.738). However, hospitalized patients had longer hospital and intensive care unit length of stay compared to outpatients - 25 vs. 18 days, (p<0.001) and 9.5 vs. 6 days, (p<0.001), respectively. Hospitalized patients had higher rates of Grade 3 primary graft dysfunction - 29.8% vs. 9.6%, p<0.001 - and remained mechanically ventilated longer - 6 vs. 3 days, p<0.001. A greater percentage of hospitalized patients needed a tracheostomy and a re-operation within 30 days - 39.5% vs. 15.3% (p<0.001) and 22.8% vs. 12.0% (p=0.005) - respectively. After discharge, 28% of hospitalized patients required acute rehabilitation compared with 12% of outpatients (p=0.001). CONCLUSIONS While pre-transplant hospitalization is not associated with mortality, it is associated with significant morbidity after transplant.

Characteristics and outcomes of lung cancer in solid organ transplant recipients.

OBJECTIVES: Lung cancer is the third most common malignancy that develops in patients following solid organ transplantation and is the leading cause of cancer deaths in the general population. The aims of this study are to examine the characteristics of patients who developed lung cancer following solid organ transplantation at our institution and to compare their outcomes to those of lung cancer patients without a history of transplant. MATERIALS AND METHODS: We performed a single-institution retrospective study of 44 solid organ transplant recipients who developed lung cancer and compared their characteristics to a cohort of 74 lung cancer patients without a history of transplant. We performed propensity score weighted analyses to compare outcomes between the two groups, including a cox proportional hazards model of overall survival. RESULTS: 52 % of post-transplant patients who developed lung cancer were diagnosed with stage III or IV disease. In the propensity score weighted analysis that accounted for age at diagnosis, sex, lung cancer stage at diagnosis, Charlson comorbidity index score, and ECOG performance score, post-transplant patients were more likely to have squamous cell histology (p < 0.01) and had worse overall survival compared to the non-transplant cohort (HR = 1.88, 95 % CI 1.13-3.12, p = 0.02). The difference in survival remained significant after accounting for differences in lung cancer histology and treatment (HR = 2.40, 95 % CI 1.27-3.78, p < 0.01). CONCLUSIONS: When compared to non-transplant patients with lung cancer, post-transplant patients have worse overall survival after accounting for differences in age, sex, lung cancer stage, comorbidities, and performance status. This survival difference is not solely attributable to differences in tumor histology and treatments received. This may suggest that post-transplant malignancies are more aggressive and difficult to treat.

Primary Spontaneous Pneumothorax in Menstruating Women Has High Recurrence.

BACKGROUND: Primary spontaneous pneumothorax (PSP) is treated on the basis of studies that have predominantly consisted of tall male subjects. Here, we determined recurrence of PSP in average-statured menstruating women and studied prevalence of catamenial pneumothorax (CP) in this population. METHODS: Men and menstruating women, aged 18 to 55 years, without underlying lung disease or substance abuse were retrospectively studied between 2009 and 2015. A chest pathologist reviewed all specimens for thoracic endometriosis. Kaplan-Meier curves were constructed to determine recurrence. RESULTS: The median age of women (n = 33) and men (n = 183) was 33.4 and 31.6 years, respectively. In women, 9 (27%) had left-sided and 24 (73%) had right-sided PSP, treated with tube thoracostomy. Recurrence occurred in 21 women (64%) with median follow-up of 14 months, and they were treated with thoracoscopic pleurodesis. Right PSP had higher recurrence (70%) than left PSP (56%, p = 0.02). Four women (12%) presented with recurrent tension pneumothorax within 6 months. Eight patients (24%) had PSP within 72 hours of menses, meeting clinical criteria of CP. All these were placed on hormonal suppression after initial episode but went on to experience recurrence that was treated with pleurodesis. Classical endometrial glands were not found in any biopsy specimens obtained during the thoracoscopy. In contrast to female subjects, only 8 average-statured men (4.4%) had recurrence (p < 0.001) with a median follow-up of 16 months. CONCLUSIONS: PSP in healthy average-statured menstruating women has high recurrence compared with male counterparts. CP is a clinical diagnosis and often recurs despite hormonal suppression therapy.