PurposeHS is a rare but potentially fatal complication of Lung Transplantation (LT), association with DU has been hypothesized. Optimal screening methods to prevent/diagnose HS early are uncertain. Both pulmonary DU PCR and daily Serum Ammonium Screening (SAS) have been suggested. We investigated HS and the association with DU PCR and SAS.MethodsWe included all LT recipients from 07/2019-02/2020 and 10/2021-03/2022 with available donor bronchial wash samples from the LT Biobank. Briefly, DNA was extracted using Qiagen DNA kit and Mollicute PCR performed using an AMPIPROBE® Ureaplasma spp. / M. genitalium / M. hominis Assay Kit. Generation of a cycle number (Ct) value of 30 was considered positive as recommended by manufacturer. Recipients were prospectively followed for HS symptoms for 30 d post-LT. Daily ammonia serum levels were measured for the first 14 days (d) as per center-specific practice, and thereafter if clinically indicated. HS was defined by new neurological symptoms and the presence of elevated serum ammonium (>70 umol/l). We compared patients who developed HS with to those who did not.ResultsOf 139 LT recipients, 4 (2.8%) developed HS during the study period. Recipient and donor characteristics of LT recipients with and without HS are shown in Table A. All HS cases were diagnosed within the first 14 days, while daily SAS was in place, median time to HS was 7.5 days (IQR 4,11). DU PCR was found to be positive in 4.3% (6/139) at transplant. Only 1/4 cases of HS was associated with a positive DU PCR. HS was treated with Moxifloxacin/Doxycycline combination (4/4) for a median duration of 14d (IQR 12,14), 2/4 received renal replacement therapy. No patient died within 180 days post HS diagnosis.ConclusionHS was a rare complication in our LT cohort. The low prevalence of DU detection in our cohort questions the utility of donor screening. Daily SAS of the recipient might add to early HS diagnosis. HS is a rare but potentially fatal complication of Lung Transplantation (LT), association with DU has been hypothesized. Optimal screening methods to prevent/diagnose HS early are uncertain. Both pulmonary DU PCR and daily Serum Ammonium Screening (SAS) have been suggested. We investigated HS and the association with DU PCR and SAS. We included all LT recipients from 07/2019-02/2020 and 10/2021-03/2022 with available donor bronchial wash samples from the LT Biobank. Briefly, DNA was extracted using Qiagen DNA kit and Mollicute PCR performed using an AMPIPROBE® Ureaplasma spp. / M. genitalium / M. hominis Assay Kit. Generation of a cycle number (Ct) value of 30 was considered positive as recommended by manufacturer. Recipients were prospectively followed for HS symptoms for 30 d post-LT. Daily ammonia serum levels were measured for the first 14 days (d) as per center-specific practice, and thereafter if clinically indicated. HS was defined by new neurological symptoms and the presence of elevated serum ammonium (>70 umol/l). We compared patients who developed HS with to those who did not. Of 139 LT recipients, 4 (2.8%) developed HS during the study period. Recipient and donor characteristics of LT recipients with and without HS are shown in Table A. All HS cases were diagnosed within the first 14 days, while daily SAS was in place, median time to HS was 7.5 days (IQR 4,11). DU PCR was found to be positive in 4.3% (6/139) at transplant. Only 1/4 cases of HS was associated with a positive DU PCR. HS was treated with Moxifloxacin/Doxycycline combination (4/4) for a median duration of 14d (IQR 12,14), 2/4 received renal replacement therapy. No patient died within 180 days post HS diagnosis. HS was a rare complication in our LT cohort. The low prevalence of DU detection in our cohort questions the utility of donor screening. Daily SAS of the recipient might add to early HS diagnosis.

Purpose Antimicrobial overuse contributes to antimicrobial resistance in lung transplant recipients (LTRs). Guidance on assessment of the quantity and appropriateness of antimicrobial prescribing is required in LTRs for standardized management. This study aims to define the expected appropriate antibiotic prescribing of clinical scenarios in LTRs using a modified Delphi method. Methods We developed an online questionnaire to solicit from ISHLT membership and Delphi Panel members regarding the appropriate treatment of 21 common clinical scenarios treated with systemic antimicrobials. Consensus was predefined as 80% agreement on the importance of each metric. The metrics that did not achieve the consensus on questionnaire were presented to an online multidisciplinary Delphi panel consisting of 25 experts from various disciplines (infectious diseases (6), pediatric infectious diseases (1), respirology (8), cardiology (2), cardiothoracic surgery (5), immunology (1) and pharmacy (1)) within ISHLT. An independent non-content expert conducted the panel. Results Following the initial online survey, 69 responses were received. Consensus on the antimicrobial management was reached on 20% (20/ 98) of questions related to 21 clinical scenarios. The survey was modified and shortened (based on relevancy, controversy of topic and consensus) to 38 questions in 10 clinical scenarios. Eleven further questions were removed due to redundancy. In total, 27 questions related to 10 clinical scenarios were discussed on-line among the Delphi Panel. Consensus was reached among 77% (21/ 27) of questions. Consensus was not reached regarding the antimicrobial management of the following 6 clinical syndromes: 1) CMV (duration of secondary prophylaxis); 2) Burkholderia cepacia pneumonia (duration of therapy); 3) RSV (duration of therapy); 4) Mycobacterium abscessus (intra operative antimicrobials); 5) Aspergillus (treatment of culture negative BAL but galactomannan BAL +) and 6) LVAD deep infection (initial empirical antimicrobial coverage). Conclusion This study resulted in expert consensus for defined levels of appropriate antibiotic prescribing in majority of clinical scenarios assessed in LTRs. These results can be aid in antimicrobial stewardship adjudications in LTRs. Antimicrobial overuse contributes to antimicrobial resistance in lung transplant recipients (LTRs). Guidance on assessment of the quantity and appropriateness of antimicrobial prescribing is required in LTRs for standardized management. This study aims to define the expected appropriate antibiotic prescribing of clinical scenarios in LTRs using a modified Delphi method. We developed an online questionnaire to solicit from ISHLT membership and Delphi Panel members regarding the appropriate treatment of 21 common clinical scenarios treated with systemic antimicrobials. Consensus was predefined as 80% agreement on the importance of each metric. The metrics that did not achieve the consensus on questionnaire were presented to an online multidisciplinary Delphi panel consisting of 25 experts from various disciplines (infectious diseases (6), pediatric infectious diseases (1), respirology (8), cardiology (2), cardiothoracic surgery (5), immunology (1) and pharmacy (1)) within ISHLT. An independent non-content expert conducted the panel. Following the initial online survey, 69 responses were received. Consensus on the antimicrobial management was reached on 20% (20/ 98) of questions related to 21 clinical scenarios. The survey was modified and shortened (based on relevancy, controversy of topic and consensus) to 38 questions in 10 clinical scenarios. Eleven further questions were removed due to redundancy. In total, 27 questions related to 10 clinical scenarios were discussed on-line among the Delphi Panel. Consensus was reached among 77% (21/ 27) of questions. Consensus was not reached regarding the antimicrobial management of the following 6 clinical syndromes: 1) CMV (duration of secondary prophylaxis); 2) Burkholderia cepacia pneumonia (duration of therapy); 3) RSV (duration of therapy); 4) Mycobacterium abscessus (intra operative antimicrobials); 5) Aspergillus (treatment of culture negative BAL but galactomannan BAL +) and 6) LVAD deep infection (initial empirical antimicrobial coverage). This study resulted in expert consensus for defined levels of appropriate antibiotic prescribing in majority of clinical scenarios assessed in LTRs. These results can be aid in antimicrobial stewardship adjudications in LTRs.

Purpose There is a paucity of studies assessing the incidental finding of histoplasmosis in the explanted tissue from lung transplant recipients (LTRs). Thus, there are currently no recommendations for the management of Histoplasmosis in the explanted organ of LTRs. This study aims to describe our experience in the management of histopathologic evidence of Histoplasmosis, encountered unexpectedly in the explanted tissue of LTRs at the time of transplantation. Methods We retrospectively identified LTRs at the Toronto program from 2010-2017, with histopathologic evidence of Histoplasma in the lung explanted tissue. Results Of 810 LTRs, 6 recipients had Histoplasmosis in the explanted organ (incidence 0.75%, clinical characteristics shown in Table 1. None of the 6 patients had a previously known diagnosis of Histoplasmosis. All of them lived in Ontario, Canada, and only one had traveled abroad in the past five years (to Florida, USA). All 6 patients had lung parenchyma and lymph node involvement in the histopathology findings, with necrotizing granulomas and fungal spores compatible with Histoplasmosis. All patients received antifungal pre-emptive therapy after transplant: 4 (67%) Itraconazole and 2 (33%) voriconazole for a mean duration of 4.8 months (IQR, 2.82-8.1 months). No patients in this group developed posttransplant Histoplasmosis (median follow up of 3.0 years [IQR 2.0-4.1 years]). Conclusion The unexpected finding of histoplasmosis in the explanted tissue of LTRs was infrequent (0.75%) in this non-endemic area. None of the patients, all of whom received antifungal therapy, developed active Histoplasmosis post-transplant.

Purpose Cystic fibrosis (CF) can lead to end stage lung disease for which lung transplantation can be a life-saving therapy. CF has systemic manifestations that can lead to other end organ damage. In addition, immune suppression following single organ transplantation has adverse effects including end stage renal disease. Multi-organ transplant in CF has had a significant impact on long-term survival of CF patients. In this study, we aim to assess the impact of multi-organ transplant on the survival of CF patients. Methods This is a retrospective review of all CF patients who have been multi-organ recipients after their initial lung transplant (March 1988 to July 2020). Lung re- transplant only were excluded. Results From 435 lung transplant recipients we identified 19 patients with CF who had received multi-organ transplant either simultaneously with the lung transplant or consecutively over time. 7 recipients received simultaneously 15 organs that included: 1 heart and lung, 5 lung and liver and 1 lung, liver, pancreas. The median survival for this group was: 8.9 years. 12 recipients received consecutively 30 organs that included: 6 lung followed by kidney transplant; 1 lung followed by liver transplant; 1 lung followed by combined kidney+liver; 1 lung followed by combined kidney + pancreas; 1 lung followed by liver and then kidney transplant; 1 lung transplant followed by a second lung transplant and later on kidney transplant and finally 1 lung followed by another lung transplant and later on combined kidney+ pancreas.The median survival of these multiorgan recipients is 14 years. The current median survival for CF patients in our program excluding re-transplants is 8.2 years. Conclusion Lung transplant for CF offers survival benefit and improved quality of life, such that a subgroup of these patients qualify for a second and even a third organ transplant to further prolong life.

Purpose BAL GM has higher sensitivity than traditional culture methods. However, smaller studies have documented higher false positivity in the early post-transplant period. This study aimed to evaluate the rate of IA in patients who had a negative fungal culture and positive BAL GM in the first 30 days post lung transplant. Methods We retrospectively identified LTRs from January 2010 to January 2017, who had a negative Aspergillus culture and positive BAL GM with an index cutoff value of ≥1.0 in the first 30 days post-transplant. Development of IA within 30 days after the initial positivity was evaluated. ISHLT definitions were used to define IA and colonization. Results We reviewed 791 LTRs; 119 patients had negative fungal culture and a positive BAL GM in the first 30 days post-transplant. 59% (70/119) were male, mean age 53 years old, 15% (18/119) had cystic fibrosis. 3% (4/119) of the patients had IA at the time of initial positive BAL GM. Of the other 115 patients, 112 were noted to be positive only once, 3 were positive two or more times. 63% (73/115) received preemptive antifungal therapy. None of them developed IA. 37% (42/115) did not receive preemptive antifungal therapy, and only 7% (3/42) developed IA. Conclusion In the absence of antifungal therapy, 7% (3/42) of LTRs subsequently developed IA following positive BAL GM >1.0 in the first 30 days post-transplant. Further characterization of patients with positive BAL GM during the first month may be helpful in devising the pre-emptive antifungal therapy in the early period after lung transplantation.

Background/Rationale: Lung transplant (LTx) candidates with cystic fibrosis (CF) have ventilatory and musculoskeletal limitations contributing to reduced functional capacity.CF LTx candidates participate in prerehabilitation to improve their physical fitness, but perspective training response of CF related clinical factors has not been described.The aims of the study were to: 1) Characterize the muscle training volume response and six-minute walk distance (6MWD) in CF LTx candidates[D1] with rehabilitation 2) Evaluate the determinants of pre-LTx 6MWD at baseline and with rehabilitation.We hypothesized that CF LTx candidates will have significant improvements in aerobic and muscle training volumes despite severe ventilatory limitations.Methods: Singlecenter retrospective cohort study of CF LTx candidates with available pre-transplant exercise data between January 2010-May 2018.LTx candidates participated in supervised center-based rehabilitation 3 times/week until transplantation.Demographics, CF-related characteristics, and aerobic and muscle training volumes were abstracted from chart review.Paired t-tests were used to evaluate the change in 6MWD (start of program, 6 weeks, and every three-months) and weekly treadmill and muscle training volumes (lbs*repetitions*sets).Multivariable regression was used to evaluate the contribution of clinical co-variates on 6MWD pre-transplant.Results: 86 CF LTx candidates (age 32±10 years, 49% males, BMI:19.6±2.8 kg/m 2 ;FEV1: 23±5%, and listing 6MWD of 421±89 meters) were evaluated.At listing, 88% required supplemental oxygen for exercise, 72% had ≥ 3 respiratory exacerbations in the prior year, and 37% were using non-invasive ventilatory (NIV) support at home.Median time on the transplant list was 87 days IQR .With rehabilitation, there was a significant increase in treadmill speed of 0.6 mph (n=74, 95% CI(0.1-1.1),p=0.02) and in both the biceps lbs*repetitions] and the quadriceps training volumes [n=71, 18.8, 95% CI(10.6-27.0)lbs*repetitions, p< 0.0001].The 6MWD did not change pre-transplant [n=42, 1.2 m, 95%CI (-17.5 to 19.9), p=0.90].Oxygen use [High (≥ 4L/min):Low O 2 : -84 95%CI (-143 to -25) meters and Low:No O 2 -43 (-84 to -3) meters, p=0.01] and home NIV support (-57 95%CI (-96 to -19) meters, p=0.004) were associated with lower baseline 6MWD, whereas age, sex, BMI, FEV1, and respiratory exacerbation frequency were not significant.No clinical characteristics were associated with change in 6MWD pre-transplant.Conclusion: CF LTx candidates demonstrated an increase in their exercise training volumes and had preservation of their exercise capacity with rehabilitation.Oxygen use and NIV support were important determinants of lower baseline exercise capacity, whereas 6MWD stability was independent of any identified clinical factors

Purpose Lung transplant (LT) programs typically serve patients from a broad geographic area. A regionalized approach to LT care offers advantages, but patients must relocate or travel to access care. We initiated a small pilot project of a virtual care platform, MyCareConnection (MCC) in LT. We hypothesized that patients and providers would be able to use MCC for communication and monitoring with high satisfaction rates. Methods The pilot began in 01/20, however, in response to the COVID-19 pandemic, we rapidly enrolled many listed and early post-op patients. Exclusion criteria included; limited access to technology (a recent model phone, wifi) or if they were unwilling/ unable to participate. MCC provides access to an online library of educational materials, secure asynchronous texting, a secure video platform, the ability to collect outcome data via surveys and biometrics (BP, HR, temp, SpO2, spirometry, step counts). MCC was used to deliver virtual clinic visits. Tailored home-based physiotherapy was also delivered over MCC (reported separately). Satisfaction was measured by surveys sent to patients, caregivers and staff. Results 165 LT patients are enrolled in MCC (64 pre-LTx, 101 post-LTx), 36% female, mean age 57.7y (range 20-76y). Few patients were ineligible, but the reasons included; personal preference, old OS, no wifi, delisting and death. The primary indications for listing and LT were ILD (45%), COPD (30%) and CF (7%). 70 users (35 clinicians) performed over 998 video calls, and > 3000 sets of biometric data were recorded by patients. Patient and caregiver satisfaction was excellent, with 94% of recipients (n=35) and 100% of caregivers (n=7) reporting that they would recommend MCC to others, and 75% agreeing that it helped them manage their health condition (n=106). Provider satisfaction was high, with over 70% recommending MCC (n=17). Challenges included the rapid shift to virtual care for clinicians used to in-person care. Conclusion We have provided comprehensive, interdisciplinary virtual care to more than 165 LT patients. Good patient and staff satisfaction and high uptake of the MCC platform demonstrates that virtual care is highly desirable and feasible in this population. In person assessments are still required for assessment of some complex issues. Gaps to be addressed include inequitable access to technology because of financial, geographical and other issues.

Purpose Gastroparesis and GERD are very common conditions in patients with end-stage lung disease and can be exacerbated after lung transplantation (LTx). At our center, we routinely test lung transplant recipients (LTRs) for gastric emptying abnormalities and for GERD at 3 months post-transplant. We hypothesized that LTRs with significant gastroparesis and/or GERD are more likely to develop lung injury leading to subsequent CLAD and death. Methods Among 2812 LTRs transplanted at our center between May 1998 and April 2018, we retrospectively analyzed 1071 patients who had a solid gastric emptying study available within seven months post-transplantation. Delayed gastric emptying (DGE) was defined as > 10% gastric retention at four hours and classified based on severity: mild (10-15%), moderate (16 - 35%), and severe (>35%). We obtained routine 24h pH/impedance testing in LTRs from 2004-2015, where GERD was defined as > 48 episodes of acid or non-acid reflux. 295 patients had both gastric emptying and reflux testing available. Cox proportional hazards models were used to determine the association between DGE, GERD, and combined DGE(moderate/severe)+GERD with time to CLAD or death. Results Mild, moderate, and severe DGE was found in 128 (12%), 163 (15.2%), and 302 (28.2%) patients, respectively. DGE alone was not associated with CLAD or death (HR 0.87 [95% CI 0.64-1.19]; HR 1.06 [95% CI 0.81-1.39]; HR 1.07 [95% CI 0.86-1.35]) for mild, moderate, severe, respectively (Figure 1A). Similarly, evidence of GERD alone was not associated with CLAD or death (abstract ISHLT 2017). However, the combination of moderate-severe DGE and GERD was significantly associated with death (HR: 1.81 [95% CI 1.07-3.05]). Conclusion In a single-center lung transplant cohort study, we observed that while DGE or GERD alone are not individually associated with CLAD or death, patients with both moderate-severe DGE and significant GERD had significantly worse survival.

Waiting list mortality for lung transplantation is 15-25%, while only 20% of lungs from multiorgan donors are deemed suitable for transplantation. Ex vivo lung perfusion (EVLP) is a technique to increase the donor pool by reassessing and reconditioning extended criteria donor lungs (ED) that would otherwise be rejected. Previous studies have shown non-inferior short- and mid-term outcomes in EVLP lung transplantation using these lungs. Here, we report the long-term follow-up of our EVLP recipients.

Bronchial complications requiring intervention have been reported in 9 to 13% of lung transplant (LTx) recipients. We sought to assess the incidence and risk factors of bronchial complications in a large single center cohort.

Hyperammonemia syndrome (HS) is a rare and life-threatening complication in Lung Transplant Recipients (LTRs) resulting in brain edema and death if not promptly treated. An association with Ureaplasma urealyticum, Ureaplasma parvum and Mycoplasma hominis (urea splitting organisms) infection has been suggested.

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.

Lung transplantation is offered at only four centres in Canada. The Toronto Lung Transplant Program has used Telehealth, a secure two-way videoconferencing system, to improve access to consultations for transplant. Mortality differences and transplant candidacy outcomes in patients seen in-person vs. via Telehealth were examined to ensure that Telehealth is not inferior to conventional visits.

CMV seronegative recipients receiving a seropositive allograft (D+/R-) are at a high risk of developing CMV disease. Our program increased the duration of CMV prophylaxis from 6 to 9 months in high risk patients from May 2013 onwards. Here, we present the impact of the change in our protocol on the incidence of CMV infection, disease, and side effects.

Lung transplantation using RNA+ hepatitis C (HCV+) donors to seronegative recipients is not currently performed due to the very high risk of transmission. Previous reports have shown poor survival when this practice was applied. The emergence of new direct-acting antiviral drugs (DAA) suggests a high chance of sustained virologic response in immunocompetent patients. We report here successful transplantation of lungs from HCV+ donor to HCV- recipient. The recipient was an HCV- patient with chronic lung allograft dysfunction. Viral transmission occurred early posttransplant but excellent clinical outcomes were observed including elimination of HCV after 12 weeks of treatment using DAAs.

Antibody-mediated rejection (AMR) in lung transplantation remains a diagnostic and therapeutic challenge. Intensive resources with attendant risks, including plasmapheresis (PLEX), IVIG and immunosuppressive agents are used to treat AMR without clarity as to whether treatments lead to improvement in function or survival. We performed a retrospective, single-center cohort study and identified all patients who underwent PLEX as part of treatment for suspected AMR between 2008-2014. AMR was diagnosed based on the presence of a combination of declining graft function, donor-specific antibodies (DSA), acute lung injury and/or c4d deposition on pathology. Primary outcome was change in Forced Expiratory Volume (FEV1) between pre and post-AMR treatment. An increase in FEV1 of minimum 10% was considered improvement post-therapy. Mean pre and post-treatment FEV1 were compared using paired t-test. Median survival time was estimated using Kaplan Meier analysis. A total of 74 patients were treated for AMR with at least PLEX and IVIG. HLA-DQ DSA were present in 84% of the cohort. Median time from transplant to PLEX was 139 days. Median survival post-transplant was 3.2 years (95% CI 2.6, 3.8), and post-PLEX was 2.5 years (95% CI 0.6, 4.4). 45 patients had FEV1 data available both pre and post-treatment. Mean change in FEV1 from peak value to treatment was -1.02L (-39%). Pulse steroids preceded treatment in 89% of cases. Anti-thymocyte globulin was used in 21/74 (28%) cases, with no improvement in FEV1, OR 0.45 (95% CI 0.11, 1.83). FEV1 improved post-treatment in 90% of those not on a mycophenolate regimen compared to 40% who were (p=0.005). Overall, there was no improvement between mean FEV1 pre and post-AMR treatment (1.38 L vs. 1.36L, p=0.81) or long-term (1.38 L vs. 1.50 L, p=0.11). FEV1 improved in 22% of patients at first testing post-treatment, and 51% later post-treatment, and did not differ whether treatment was within or beyond 1 year of transplant (57% vs. 48%, p=0.55). Chronic lung allograft dysfunction was present in 67% of patients post-treatment. Readmission to hospital within 90 days of treatment occurred in 8% of patients, with 2/3 due to infection. Lung function did not significantly improve post-treatment for AMR, regardless of time to treatment from transplant. Overall outcomes in suspected AMR remain poor with limited survival despite current therapies.