Outpatient management of Post-COVID syndrome - single center experience.

BACKGROUND: COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management. OBJECTIVES: To describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic. METHODS: We retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020-12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment. RESULTS: In treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea. CONCLUSIONS: Our descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment.

Crossroads between Autoimmunity and COVID-19 in Lung Transplant Recipients.

The presence of a certain group of auto-antibodies (AAbs) is known to correlate with the severity of COVID-19. It is, however, unknown if such AAbs are prevalent and impact COVID-19-related outcomes in lung transplant recipients (LTRs) who are immunosuppressed. We performed a retrospective study of LTRs with COVID-19 and analyzed samples before and after COVID-19 for IgG AAbs. AAbs analysis was carried out using autoimmune and coronavirus microarray and the resulting cross-sectional differences in Ab-scores and clinical variables were analyzed using Fischer's Exact test for categorical variables and a paired t-test for continuous variables. Linear regression was used to analyze the differences in Ab-scores and COVID-19 severity. LTRs with non-severe [NS gp (n = 10)], and severe [S gp (n = 8)] COVID-19 disease were included. Ferritin and acute respiratory failure were higher in the S group (p = 0.03; p < 0.0001). Among the AAbs analyzed, interferon-related AAbs (IFN-alpha2, IFN-beta, IFN lamba, IFN-epsilon), eight interleukin-related AAbs, and several tissue-related AAbs were also found to be changed significantly from pre- to post-COVID-19 (p < 0.05). IFN-lambda (p = 0.03) and IL-22 (p = 0.002) were significantly associated with COVID-19 severity and remained significant in linear regression analysis while controlling for other variables. AAbs are common in LTRs, and certain groups of antibodies are particularly enhanced in LTRs with severe COVID-19. Preliminary observations of this study need to be confirmed by a larger sample size.

Management of donor-specific antibodies in lung transplantation.

The formation of antibodies against donor human leukocyte antigens poses a challenging problem both for donor selection as well as postoperative graft function in lung transplantation. These donor-specific antibodies limit the pool of potential donor organs and are associated with episodes of antibody-mediated rejection, chronic lung allograft dysfunction, and increased mortality. Optimal management strategies for clearance of DSAs are poorly defined and vary greatly by institution; most of the data supporting any particular strategy is limited to small-scale retrospective cohort studies. A typical approach to antibody depletion may involve the use of high-dose steroids, plasma exchange, intravenous immunoglobulin, and possibly other immunomodulators or small-molecule therapies. This review seeks to define the current understanding of the significance of DSAs in lung transplantation and outline the literature supporting strategies for their management.

Epidermal Growth Factor Receptor Inhibition Is Protective in Hyperoxia-Induced Lung Injury.

Aims: Studies have linked severe hyperoxia, or prolonged exposure to very high oxygen levels, with worse clinical outcomes. This study investigated the role of epidermal growth factor receptor (EGFR) in hyperoxia-induced lung injury at very high oxygen levels (>95%). Results: Effects of severe hyperoxia (100% oxygen) were studied in mice with genetically inhibited EGFR and wild-type littermates. Despite the established role of EGFR in lung repair, EGFR inhibition led to improved survival and reduced acute lung injury, which prompted an investigation into this protective mechanism. Endothelial EGFR genetic knockout did not confer protection. EGFR inhibition led to decreased levels of cleaved caspase-3 and poly (ADP-ribosyl) polymerase (PARP) and decreased terminal dUTP nick end labeling- (TUNEL-) positive staining in alveolar epithelial cells and reduced ERK activation, which suggested reduced apoptosis in vivo. EGFR inhibition decreased hyperoxia (95%)-induced apoptosis and ERK in murine alveolar epithelial cells in vitro, and CRISPR-mediated EGFR deletion reduced hyperoxia-induced apoptosis and ERK in human alveolar epithelial cells in vitro. Innovation. This work defines a protective role of EGFR inhibition to decrease apoptosis in lung injury induced by 100% oxygen. This further characterizes the complex role of EGFR in acute lung injury and outlines a novel hyperoxia-induced cell death pathway that warrants further study. Conclusion: In conditions of severe hyperoxia (>95% for >24 h), EGFR inhibition led to improved survival, decreased lung injury, and reduced cell death. These findings further elucidate the complex role of EGFR in acute lung injury.

A Case Report of Breakthrough Infections With 2 SARS-CoV-2 Variants in a Lung Transplant Patient.

A lung transplant (LT) patient developed 2 distinct episodes of COVID-19, confirmed by whole-genome sequencing, which was caused by the Delta, and then followed 6 weeks later, by the Omicron variant. The clinical course with Omicron was more severe, leading us to speculate that Omicron may not be any milder among LT patients. We discuss the potential mechanisms behind the Omicron not being any milder among LT patients and emphasize the need for outcomes data among these patients. Until such data become available, it may be prudent to maintain clinical equipoise as regards the relative virulence of the newer variants among LT patients.

COVID-19 Vaccination is Associated With Favorable Outcomes Among Lung Transplant Patients With Breakthrough Infections.

BACKGROUND: There are limited data regarding the clinical efficacy of COVID-19 vaccines among lung transplant (LT) patients. METHODS: We included all LT patients diagnosed with COVID-19 between March 1, 2020, and December 10, 2021 (n = 84; median age 55, range, 20-73 years; males 65.5%). The study group was divided into 3 groups based on the vaccination status (patients who did not complete the primary series for any of the vaccines: n = 58; those with 2 doses of messenger RNA (mRNA) or 1 dose of the adenoviral vector vaccine, vaccinated group: n = 16; those with at least 1 additional dose beyond the primary series, boosted group: n = 10). RESULTS: Pulmonary parenchymal involvement on chest computed tomography scan was less common among the boosted group (P = .009). The proportion of patients with new or worsening respiratory failure was significantly lower among the vaccinated and boosted groups and these patients were significantly more likely to achieve the composite endpoint of oxygen-dependence free survival (P = .02). On multivariate logistic regression analysis, higher body mass index, restrictive lung disease as the transplant indication, and preinfection chronic lung allograft dysfunction were independently associated with acute or acute on chronic respiratory failure while being on therapeutic dose anticoagulation and having received the booster dose had a protective effect. CONCLUSION: COVID-19 vaccines appear to have several favorable effects among LT patients with breakthrough infections including lower likelihood of allograft involvement on imaging (among boosted patients), need of hospitalization, and complications such as new or worsening respiratory failure.

Diaphragmatic plication among lung transplant patients: A single-center experience.

BACKGROUND: There is lack of data reporting outcomes among patients needing diaphragmatic plication (DP) during or after lung transplantation (LT). We sought to assess the association of DP with post-transplant spirometry among other outcomes. METHODS: We included all patients who underwent LT between 2012 and 2016 (n = 324, mean age 56.3±13.4 years; M:F 198:126). We compared early and late outcomes based on the need for DP. RESULTS: The frequency of diaphragmatic dysfunction (DD) on pre-transplant fluoroscopy was 52.2%. A total of 38 DP procedures were performed among 37 patients (11.4% of LT patients). DP was done for anatomic (sizing or spacing issues) or functional indications (symptomatic DD). While patients with DP had significantly lower spirometry throughout the 3-year follow-up period, their slope of decline, functional assessments at the first annual visit, the risk of CLAD, and mortality were similar to patients without DP. A sub-group analysis limited to patients with restrictive lung diseases as the transplant indication had similar findings. CONCLUSIONS: Pre-transplant DD is common among LT candidates although it did not predict the need for DP. DP may be performed for functional or anatomic indications especially for addressing the donor-recipient size mismatch. Despite the lack of favorable effect on post-transplant spirometry, patients undergoing DP have acceptable and comparable early and late outcomes.

ECMO Long Haulers: A Distinct Phenotype of COVID-19-Associated ARDS With Implications for Lung Transplant Candidacy.

BACKGROUND: Studies indicate that the recovery from coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome may be slower than other viral pneumonia. There are limited data to guide decisions among patients who need extracorporeal membrane oxygenation (ECMO) support, especially the expected time of recovery and considering lung transplantation (LT). METHODS: This was a retrospective chart review of patients with COVID-19-associated acute respiratory distress syndrome placed on ECMO between March 1, 2020, and September 15, 2021 (n = 20; median age, 44 y; range, 22-62 y; male:female, 15:5). We contrasted the baseline variables and clinical course of patients with and without the need for ECMO support >30 d (ECMO long haulers, n = 10). RESULTS: Ten patients met the criteria for ECMO long haulers (median duration of ECMO, 86 d; range, 42-201 d). The long haulers were healthier at baseline with fewer comorbidities but had worse pulmonary compliance and higher partial pressure of CO2. They had a significantly higher number of membrane oxygenator failures, changes to their cannulation sites, and suffer more complications on ECMO. One of the long hauler was bridged to LT while another 6 patients recovered and were discharged. Overall survival was better among the ECMO long haulers (70% versus 20%; 9.3, 1.2-73; P = 0.03). CONCLUSIONS: Despite worse pulmonary physiology, frequent complications, and a tortuous hospital course that may appear to portend a poor prognosis, ECMO long haulers have the potential to recover and be weaned off ECMO without the need for LT. A customized approach comprising a more conservative timeline for the consideration of LT may be prudent among these patients.

Characteristics and outcomes among vaccinated lung transplant patients with breakthrough COVID-19.

BACKGROUND: Despite multiple studies evaluating the immunological responsiveness to vaccines, the clinical effectiveness of the two-dose mRNA vaccine schedule among lung transplant (LT) patients has not been evaluated. METHODS: We included LT patients who tested positive for SARS-CoV-2 on a nasopharyngeal swab between March 1, 2020, and August 25, 2021 (n = 70). The study group was divided based on their vaccination status. RESULTS: During the study period, 14 fully vaccinated LT patients with one of the mRNA vaccines tested positive for COVID-19 (median age 54, range 30-62 years, M:F 9:5). The vaccinated cohort was younger with bilateral LT, have suppurative conditions as the transplant indication, and present with milder symptoms. However, pulmonary parenchymal involvement was seen among all 12 patients where computed tomography (CT) of chest was available. The laboratory profile indicated a more subdued inflammatory response among the vaccinated group. A lower proportion of vaccinated patients developed respiratory failure, needed ICU admission or ventilator support, although none of the differences achieved statistical significance. None of the vaccinated patients succumbed to COVID-19 during the study period, while the 4-week mortality among unvaccinated patients was nearly 15% (8/56). CONCLUSIONS: In this cohort of vaccinated LT patients who developed breakthrough COVID-19, the clinical course, risk of complications, and outcomes trended better than unvaccinated patients. However, universal involvement of the allograft demonstrates the continued vulnerability of these patients to significant sequelae from COVID-19. Future studies may evaluate the incremental protection of vaccination after the completion of the third dose of mRNA vaccines among LT patients.

Post-infection pulmonary sequelae after COVID-19 among patients with lung transplantation.

BACKGROUND: There is limited data on outcomes among lung transplant (LT) patients who survive Coronavirus disease 2019 (COVID-19). METHODS: Any single or bilateral LT patients who tested positive for SARS-CoV-2 between March 1, 2020, to February 15, 2021 (n = 54) and survived the acute illness were included (final n = 44). Each patient completed at least 3 months of follow-up (median: 4.5; range 3-12 months) after their index hospitalization for COVID-19. The primary endpoint was a significant loss of lung functions (defined as > 10% decline in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1 ) on two spirometries, at least 3 weeks apart compared to the pre-infection baseline). RESULTS: A majority of the COVID-19 survivors had persistent parenchymal opacities (n = 29, 65.9%) on post-infection CT chest. Patients had significantly impaired functional status, with the majority reporting residual disabilities (Karnofsky performance scale score of 70% or worse; n = 32, 72.7%). A significant loss of lung function was observed among 18 patients (40.9%). Three patients met the criteria for new chronic lung allograft dysfunction (CLAD) following COVID-19 (5.6%), with all three demonstrating restrictive allograft syndrome phenotype. An absolute lymphocyte count < 0.6 × 103 /dl and ferritin > 150 ng/ml at the time of hospital discharge was independently associated with significant lung function loss. CONCLUSIONS: A significant proportion of COVID-19 survivors suffer persistent allograft injury. Low absolute lymphocyte counts (ALC) and elevated ferritin levels at the conclusion of the hospital course may provide useful prognostic information and form the basis of a customized strategy for ongoing monitoring and management of allograft dysfunction. TWEET: Twitter handle: @AmitBangaMD Lung transplant patients who survive COVID-19 suffer significant morbidity with persistent pulmonary opacities, loss of lung functions, and functional deficits. Residual elevation of the inflammatory markers is predictive.

Clinical characteristics, management practices, and outcomes among lung transplant patients with COVID-19.

BACKGROUND: There are limited data on management strategies and outcomes among lung transplant (LT) patients with Coronavirus disease 2019 (COVID-19). We implemented management protocols based on the best available evidence and consensus among multidisciplinary teams. The current study reports our experience and outcomes using this protocol-based management strategy. METHODS: We included single or bilateral LT patients who tested positive for SARS-CoV-2 on nasopharyngeal swab between March 1, 2020, to December 15, 2020 (n = 25; median age: 60, range 20-73 years; M: F 17:8). A group of patients with Respiratory Syncytial Virus (RSV) infection during 2016-18 were included to serve as a comparator group (n = 36). RESULTS: As compared to RSV, patients with COVID-19 were more likely to present with constitutional symptoms, spirometric decline, pulmonary opacities, new or worsening respiratory failure, and need for ventilator support. Patients with SARS-CoV-2 infection were less likely to receive a multimodality treatment strategy, and they experienced worse post-infection lung function loss, functional decline, and three-month survival. A significant proportion of patients with COVID-19 needed readmission for worsening allograft function (36.4%), and chronic kidney disease at initial presentation was associated with this complication. Lower pre-morbid FEV1 appeared to increase the risk of new or worsening respiratory failure, which was associated with worse outcomes. Overall hospital survival was 88% (n = 22). Follow-up data was available for all discharged patients (median: 43.5 days, range 15-287 days). A majority had persistent radiological opacities (19/22, 86.4%), with nearly half of the patients with available post-COVID-19 spirometry showing > 10% loss in lung function (6/13, median loss: 14.5%, range 10%-31%). CONCLUSIONS: Despite similar demographic characteristics and predispositions, LT patients with COVID-19 are sicker and experience worse outcomes as compared to RSV. Despite the availability of newer therapeutic agents, COVID-19 continues to be associated with significant morbidity and mortality.

Characteristics and outcomes among lung transplant patients with respiratory syncytial virus infection.

BACKGROUND: To describe characteristics and outcomes among lung transplantation (LT) patients with respiratory syncytial virus (RSV) infection and elucidate the predictors of 1-year survival after RSV infection. METHODS: This was a retrospective chart review study among LT patients with RSV infection between 2013 and 2018 (90 episodes among 87 patients; mean age 56.3 ± 13.1 years, M:F 52:35). A contemporaneous control group consisting of LT patients without RSV infection (n = 183) was included. One-year survival after the RSV infection was the primary endpoint. RESULTS: Median time from LT to RSV infection was 30 (1-155) months. Before RSV infection, the median decline in forced vital capacity (FVC) was 9.7 cc (-17.8 to 83 cc) or 0.29% (-1.4% to 4.6%) per month, while the forced expiratory volume (FEV1 ) decline was 7.5 cc (-8.8 to 58 cc) or 0.3% (-0.57% to 4.3%) per month with no statistically significant change after RSV infection. One-year survival among patients with RSV infection was 86.2% (75/87). Pre-infection diagnosis of chronic lung allograft dysfunction (CLAD; adjusted HR: 4.29, 1.08-17.0; P = .038) and FVC or FEV1 decline >10% during 6 months post infection (adjusted HR: 35.1, 3.26-377.1; P = .003) were independently associated with worse survival. On propensity score matched analysis, RSV infection was not associated with worse post-transplant survival (HR with 95% CI: 0.79, 0.47-1.34; P = .38). CONCLUSIONS: A majority of LT patients in the current cohort did not experience an alteration in the trajectory of FVC or FEV1 decline after developing RSV infection, and their post-transplant survival was not adversely impacted. Established CLAD at the time of RSV infection and post infection >10% decline in FVC or FEV1 are independently associated with worse survival after RSV infection.

Spectrum of findings on ventilation‒perfusion lung scintigraphy after lung transplantation and association with outcomes.

BACKGROUND: Air trapping (AT) is one of the hallmarks of allograft dysfunction after lung transplantation (LT). Inert gas‒based ventilation‒perfusion (VQ) lung scintigraphy has excellent sensitivity in the detection of AT. METHODS: We reviewed the charts of patients who underwent single or double LT between January 2012 and December 2014 (N = 193). Patients without a VQ scintigraphy at the first annual visit (n = 16) and those who did not survive till 1 year (n = 26) were excluded (final n = 151, mean age = 55.8 [SD =14] years, male = 85, female = 66). VQ scintigraphy was independently reviewed and reconciled for the presence and severity of AT by 2 investigators blinded to the clinical data (D.F.P. and D.M.). A 3-year post-transplant survival was the primary end-point. RESULTS: AT was common (n = 73, 48.3%). Patients with obstructive lung diseases as the underlying diagnosis (adjusted odds ratio [OR], 4.36, 95% CI: 1.64‒11.6; p = 0.003) and those with lower body mass index (BMI) (BMI < 25 kg/m2 and 25‒30 kg/m2; p < 0.001) had an increased risk of developing AT in the allograft. The presence of AT (adjusted OR, 2.33, 95% CI: 1.01‒5.36; p = 0.04) and peak forced expiratory volume in 1 sec (FEV1) <60% predicted during the first year after LT were independently associated with 3-year mortality. The association of AT with post-transplant mortality was the strongest among patients with BMI <30 kg/m2 and peak FEV1 <60% predicted. CONCLUSIONS: The finding of AT on VQ scintigraphy at the first annual visit after LT is independently associated with worse post-transplant mortality. The sub-group of patients who fail to achieve a peak FEV1 of 60% predicted during the first year after LT appears to be the key driver of this association.

Characteristics and outcomes among patients with community-acquired respiratory virus infections during the first year after lung transplantation.

BACKGROUND: The current study describes the spectrum of community-acquired respiratory infections (CARV) during the first year after lung transplantation (LT). Additionally, we elucidate variables associated with CARV, management strategies utilized, and impact on early and late outcomes. METHODS: This was a retrospective study among patients transplanted between 2012 and 2015 (n = 255, mean age 55.6 ± 13.5 years, M: F 152:103). The diagnosis of CARV was based on the multiplex PCR on nasopharyngeal swab samples. Baseline characteristics, post-transplant variables, and outcomes were compared among patients with and without CARV. RESULTS: Eighty CARV infections developed among a quarter of the study group (n = 62, 24.3%). Rhinovirus/enterovirus was the most commonly isolated CARV (n = 24) followed by coronavirus (n = 17) and RSV (n = 9). A significant proportion of episodes (43.8%) required hospitalization. The use of nasal corticosteroids and left single LT was independently associated with an increased risk of CARV. CARV infections did not impact the lung functions during the first year or the CLAD-free survival at 3 years. CONCLUSIONS: There is a significant burden of CARV infections during the first year after LT. The use of nasal corticosteroids may increase the risk of CARV infection. CARV infections did not impact outcomes.

Self-reactive antibodies associated with bronchiolitis obliterans syndrome subtype of chronic lung allograft dysfunction.

BACKGROUND: Chronic Lung Allograft Dysfunction (CLAD) remains the major limitation in long term survival after lung transplantation. Our objective is to evaluate for the presence of autoantibodies to self-antigens, which is a pathway along with complex interplay with immune as well as non-immune mechanisms that leads to a fibroproliferative process resulting in CLAD. METHODS: Serum profiles of IgG autoantibodies were evaluated using customized proteomic microarray with 124 antigens. Output from microarray analyzed as antibody scores is correlated with bronchiolitis obliterans (BOS) subtype of CLAD using Mann-Whitney U test or Fisher exact test. Autoantibodies were evaluated for their predictive value for progressive BOS using a Cox proportional hazard model. BOS free survival and overall survival was analyzed using Kaplan-Meier survival analysis. RESULTS: Forty- two patients included in the study are grouped into "stable BOS" and "progressive BOS" for comparisons. Pulmonary fibrosis is the major indication for lung transplantation in our cohort. Progressive BOS group had significantly worse survival (p < 0.005). Sixteen IgG autoantibodies are significantly elevated at baseline in progressive BOS group. Six among them correlated with worse BOS free survival (p < 0.05). In addition, these six IgG autoantibodies remain elevated at three months and one year after lung transplantation. CONCLUSION: Pre-existing IgG autoantibodies correlate with progressive BOS and survival in a single center, small cohort of lung transplant recipients. Further validation with larger sample size, external cohort and confirmation with additional tissue, bronchoalveolar lavage samples are necessary to confirm the preliminary findings in our study.

Significance of Best Spirometry in the First Year After Bilateral Lung Transplantation: Association With 3-Year Outcomes.

BACKGROUND: Spirometry is the cornerstone of monitoring allograft function after lung transplantation (LT). We sought to determine the association of variables on best spirometry during the first year after bilateral LT with 3-year posttransplant survival. METHODS: We reviewed charts of patients who survived at least 3 months after bilateral LT (n = 157; age ± SD: 54 ± 13 y, male:female = 91:66). Best spirometry was calculated as the average of 2 highest measurements at least 3 weeks apart during the first year. Airway obstruction was defined as forced expiratory volume in 1-second (FEV1)/forced vital capacity (FVC) ratio <0.7. Survival was compared based on the ventilatory defect and among groups based on the best FEV1 and FVC measurements (>80%, 60%-80%, and <60% predicted). Primary outcome was 3-year survival. RESULTS: Overall, 3-year survival was 67% (n = 106). Obstructive defect was uncommon (7%) and did not have an association with 3-year survival (72% versus 67%, P = 0.7). Although one-half patients achieved an FVC>80% predicted (49%), 1 in 5 (19%) remained below 60% predicted. Irrespective of the type of ventilatory defect, survival worsened as the best FVC (% predicted) got lower (>80: 80.8%; 60-80: 63.3%; <60: 40%; P < 0.001). On multivariate logistic regression analysis, after adjusting for age, gender, transplant indication, and annual bronchoscopy findings, best FVC (% predicted) during the first year after LT was independently associated with 3-year survival. CONCLUSIONS: A significant proportion of bilateral LT patients do not achieve FVC>80% predicted. Although the type of ventilatory defect on best spirometry does not predict survival, failure to achieve FVC>80% predicted during the first year was independently associated with 3-year mortality.

Pre-existing self-reactive IgA antibodies associated with primary graft dysfunction after lung transplantation.

BACKGROUND: Primary graft Dysfunction (PGD) results in significant mortality and morbidity after lung transplantation (LT). The objective of this study was to evaluate if pre-existing antibodies to self-antigens in sera of LT recipients are associated with PGD. METHODS: The serum profiles of IgG and IgA autoantibodies were analyzed using a customized proteomic microarray bearing 124 autoantigens. Autoantibodies were analyzed using Mann-Whitney U test or Fisher exact test. The association of the autoantibodies with clinical phenotypes and survival was analyzed by Kaplan-Meier Survival Analysis. Receiver operating curve characteristics (ROC) were calculated to evaluate the predictive value of the autoantibodies for PGD. RESULTS: 51 patients were included in this study. Autoantigen microarray analysis on the pre-transplantation samples identified 17 IgA and 3 IgG autoantibodies which were significantly higher in recipients who developed PGD compared to those who did not (adjusted p < .05 and fold change>1.5). 6 IgA Abs were significantly associated with survival. Taken as a panel, an elevation of 6 IgA Abs had significant predictive value for PGD. Area under the curve value for the panel was 0.9413 for PGD with ROC analysis. Notably, 6 of the 17 IgA autoantigen targets are belong to proteoglycan family of extracellular matrix proteins. CONCLUSION: Pre-existing IgG and IgA autoantibodies in LT patients correlate with PGD and with survival in a single center, small cohort of lung transplant recipients. Further validation is needed to confirm the findings in the study.

Characteristics and Outcomes of Lung Transplant Candidates With Preexisting Renal Dysfunction.

BACKGROUND: The proportion of lung transplant candidates with comorbid renal dysfunction (RD) may rise as sicker patients are being considered for lung transplant (LT). There is lack of data regarding the characteristics and outcome of patients with RD and the role of simultaneous lung-kidney transplant (SLuKi) among these patients. METHODS: The United Network of Organ Sharing database was queried for adult patients (18 years or older) undergoing LT between 1995 and 2014. Pretransplant RD was defined as estimated glomerular filtration rate (eGFR), using the Chronic Kidney Disease Epidemiology Collaboration equation of <60 mL/min/1.73 m2 at the time of transplant listing. The recipient, donor, and procedure-related variables and survival were compared among patients with RD undergoing LT alone (split on the basis of eGFR impairment: 30-60 mL/min/1.73 m2 and ≤ 30 mL/min/1.73 m2) vs those with SLuKi. RESULTS: The frequency of pretransplant RD was 5.42% (n = 1337). Patients with RD have significantly higher 1-year mortality (23.2% vs 15%; P < .001) and 3-year mortality (38.3% vs 28%; P < .001) than patients with eGFR > 60mL/min/1.73 m2. The proportion of patients with RD undergoing SLuKi was 2.84% (38 of 1337). Both the number and proportion of patients undergoing SLuKi progressively increased during the study period, especially in the lung allocation score era (30 of 38 SLuKi patients in the post lung allocation score era (linear R2 = 0.641, P < .001). The patients who underwent SLuKi were significantly younger, had lower body mass index, serum albumin, and listing eGFR (P < .001 for all comparisons). Patients with SLuKi were more likely to have cystic fibrosis or vascular diseases as the underlying diagnosis (29.7% vs 13.8%, P = .004). Despite higher need of early dialysis support after transplant, there was no difference in the 30-day, 1-year, or 3-year survival between the 2 groups. CONCLUSIONS: A significant proportion of LT candidates have a pre-existing RD, and this comorbidity is associated with significantly worse 1- and 3-year survival. Despite being the sicker group at baseline, patients with RD who undergo SLuKi have 1-year outcomes similar to patients with LT alone.