Faculty Bibliography

BACKGROUND:The Lung Allocation Score (LAS) significantly improved outcomes and waitlist mortality in lung transplantation. However, mortality remains high for the sickest waitlist candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system has met significant resistance, and would require years to implement. This study evaluates if a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered waitlist mortality. METHODS:The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within 250 nautical-mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS≥50 (high-LAS) to be prioritized within a 500 nautical-mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary endpoints were waitlist mortality and post-transplant 1-year survival. RESULTS:6,538 waitlist candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in waitlist mortality. Post-transplant 1-year survival was minimally affected. CONCLUSIONS:Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased waitlist mortality and increased organ utilization. Importantly, these changes do not appear to lead to clinically significant changes in post-transplant 1-year survival.

We conducted a retrospective review of thoracic transplant recipients (22 heart and 16 lung transplant recipients) prospectively enrolled in a single-center observational study of HCV NAT+ organ transplantation in HCV NAT- recipients. All recipients were treated with 8 weeks of glecaprevir-pibrentasvir (GP) for HCV viremia in addition to standard triple immunosuppression post-transplant. Thoracic transplant recipients of HCV NAT- organs were used as a control (24 heart and 22 lung transplant recipients). Our primary outcome was to assess the effect of GP on tacrolimus dose requirements. Secondary objectives included assessing drug interactions with common post-transplant medications, adverse effects, and the need to hold or discontinue GP therapy. The median tacrolimus concentration-to-dose (CDR) in the cohort was 184 (99-260) during GP therapy and 154 (78-304) over the first month after GP (p=0.79). Trends in median tacrolimus CDR were similar on a per-week basis and per-patient basis. In three instances, concomitant posaconazole and GP led to hyperbilirubinemia and interruption of posaconazole. GP therapy was held in one heart transplant recipient, and discontinued in another, due to unresolving hyperbilirubinemia. Utilization of GP to treat HCV viremia post-thoracic transplant is feasible and safe, but requires modifications to post-transplant pharmacotherapy and careful monitoring for adverse effects.

PURPOSE: We hypothesize that home monitoring and telehealth utilizing data from a mobile healthcare application in conjunction with laboratory values and chest imaging, can replace an outpatient appointment.
METHOD(S): Our study is comprised of patients who have received a single or bilateral lung transplant or a heart/lung transplant.Before our patients are discharged from their inpatient stay after Transplantation, the application for home monitoring is installed on their smart phone. This application was specifically designed for Lung Transplant Patients. A blood pressure cuff and spirometer are provided and linked to their mobile device using Bluetooth. A weighing scale is also provided which uses a cellular connection to a secure cloud relaying data to the patient's phone and to EPIC. Additional data including (e.g. temperature, pulse oximetry) are manually entered into the application. Physical fitness (steps) is also monitored. The team who created the application enabled the data to flow from the application to our electronic medical record. Alerts are set for each piece of data and any abnormal value is sent to our team's EPIC in-basket for further action.Patients who are compliant with their home monitoring are offered telehealth. Patients are sent for laboratory testing and imaging the week of the appointment close to their home.
RESULT(S): As of October 1, 2019, we have enrolled fifty patients in our home monitoring program. Fourteen patients are now one - year post transplant. Twelve of these patients are compliant with home monitoring. Eight of them have had telehealth visits throughout the year with five receiving the majority of their care utilizing home monitoring and telehealth. These visits occur bimonthly for the first three months after transplant and then monthly for the first year.
CONCLUSION(S): Home monitoring and telehealth visits can replace outpatient visits in the first year following lung transplantation. Patients find the devices easy to use and are satisfied with the care they receive during their telehealth visits. Additionally, telehealth improves patient quality of life by reducing visits to the medical center and avoiding additional costs such as parking and time off work. It also limits pathogen exposure. Long term use may enable early detection of rejection or infection.
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PURPOSE: Azole antifungals are commonly prescribed for fungal prophylaxis (ppx) following lung transplant, but have many side effects and drug interactions. Isavuconazole, a new broad-spectrum azole antifungal, may obviate these issues.
METHOD(S): We retrospectively reviewed all lung transplant recipients (LTR) from February 2018 through September 2019 who received either ISA or POS for fungal ppx for 3 months post-transplant. Prior to February 2019 all patients received POS for ppx. Starting February 2019, POS was replaced by ISA at standard dosing. All patients received basiliximab induction and standard triple immunosuppression post-transplant. Surveillance bronchoscopies were performed at 1, 3, 6, and 12 months post-transplant.
RESULT(S): In total, we reviewed 24 LTR who received ISA and 29 who received POS. Baseline characteristics were similar between groups. Median duration of follow-up was significantly shorter for the ISA group (137 vs. 340 days, p<0.01). Breakthrough fungal infections occurred in 3 (13%) and 2 (7%) patients in the ISA and POS groups, respectively (p=0.65). All ISA patients developed oropharyngeal candidiasis; in the POS group there was one each of candida empyema and mold colonization. Post-ppx fungal infections occurred in 1 (4%) and 5 (17%) patients in the ISA and POS groups, respectively (p=0.20). All of these were mold colonization except for one case of oropharyngeal candidiasis. There was no difference between fungal-infection free survival based on Kaplan-Meier analysis (p=0.69). POS was held in two cases and discontinued in 1 patient due to a drug interaction causing hepatotoxicity compared to zero patients receiving ISA (p=0.24).
CONCLUSION(S): Breakthrough fungal infections were similar between LTR receiving ISA or POS for fungal ppx. Longer follow-up of ISA patients is needed for definitive comparison of long-term infection risk. POS was discontinued in more patients due to drug interactions. ISA is a reasonable choice for primary fungal ppx in LTR.
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PURPOSE: Adequate pain control is essential following lung transplantation to reduce patient stress and minimize perioperative complications. Enhanced recovery after surgery (ERAS) protocols have demonstrated improvements in patient experience and reduced length of stay. However, the implementation of these protocols has not yet extended to the lung transplant population.
METHOD(S): We retrospectively reviewed all lung transplant recipients (LTR) at our institution from February 2018 to August 2019. An opioid-sparing, multimodal pain regimen was implemented that included preemptive analgesia with gabapentin and acetaminophen (APAP) pre-transplant; liposomal bupivacaine intercostal nerve block (INB) in the operating room; and a combination of APAP, gabapentin, and methocarbamol post-op with opioids given as indicated. Serratus anterior plane block was used for refractory pain.
RESULT(S): In total, we reviewed 48 LTR. The mean LAS was 43.74 and 21% were on mechanical ventilation or ECMO pre-transplant. Frequency of protocol adherence for each agent was as follows: liposomal bupivacaine INB (71%), APAP (100%), gabapentin (98%), methocarbamol (27%), and ketorolac (33%). Seven patients (15%) required a serratus plane block for refractory pain. Pain scores peaked at a median of 5 on postoperative day (POD) 1 and declined to a median of 3 by POD 3. By POD 4 only 54% of patients were still receiving opioids at a median of 15 mg oral morphine equivalents per day (IQR, 0-59). Only 3 patients were discharged on opioids and they were all on opioids pre-transplant. The median duration of mechanical ventilation was 1 day (IQR, 0.64-1.69) and 81% were extubated before 48 hours. The median hospital length of stay was 8 days (IQR, 6-15) and 30-day mortality was 0%.
CONCLUSION(S): Enhanced recovery and opioid-sparing pain protocols are feasible in LTR leading to minimal opioid use and acceptable pain scores. Outcomes with ERAS protocols should be compared to standard-of-care postoperative management.
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BACKGROUND:Several studies have described improved survival with double lung transplantation (DLT) compared to single lung transplantation (SLT) in pulmonary fibrosis. To avoid the innate selection bias of including patients exclusively listed for SLT or DLT, this study analyzed those deemed appropriate for either procedure at time of listing. METHODS:All consecutive adult lung transplants for idiopathic pulmonary fibrosis (IPF) provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (N=11), or patients listed only for SLT (N=1834) or DLT (N=2372) were excluded. Group stratification was based on the ultimate procedure (SLT vs DLT). Group propensity matching was performed based on 24 recipient/donor characteristics. Recipient demographics, donor demographics, and outcomes were compared between groups. RESULTS:During the study period, 45% (974/2179) and 55% (1205/2179) of patients ultimately received SLT and DLT, respectively. After propensity matching, 466 matched patients remained in each group. SLT patients were less likely to require prolonged (>48 hours) ventilator support than DLT patients. There was also a trend towards reduced rates of post-transplant renal failure and hospital length of stay in SLT recipients. Whether analyzed by time of listing or time of transplant, survival was similar between groups. CONCLUSIONS:In recipients concurrently listed for SLT and DLT, overall survival was similar regardless of the eventual procedure. These data suggests that the previously purported survival advantage for DLT may purely represent selection bias, and should not preclude the use of SLT in appropriately-selected IPF patients.

BACKGROUND:Anastomotic complications occur in 7% to 18% of lung transplant recipients, among which airway dehiscence (AD) is particularly catastrophic. Using multi-institutional registry data, this study compared preoperative recipient/donor risk factors and outcomes in patients with and without AD and analyzed the effect of extracorporeal membrane oxygenation (ECMO) on the incidence of AD. METHODS:Data on adult lung transplants from 2007 to 2017 were provided by the Scientific Registry of Transplant Recipients. Patients receiving isolated lobar transplantation and patients with unknown AD status were excluded. Multivariable logistic regression identified independent risk factors for AD. Kaplan-Meier curves and log-rank tests describe mortality and graft survival. RESULTS:Of 18 122 lung transplants, 275 (1.5%) experienced AD. While the incidence of ECMO steadily increased from 0.7% to 5.9% over the study period, the incidence of AD remained relatively constant. Multivariable analysis revealed recipient male gender and prolonged ( > 48 hours) posttransplant mechanical ventilation as independent predictive factors for AD, while advanced donor age and single left lung transplant were protective factors. Recipient chronic steroid use, recipient diabetes, donor diabetes, and donor smoking history were not predictive of AD. Mortality and graft failure were significantly worse in the AD group. CONCLUSIONS:Despite increased ECMO utilization, the incidence of AD has remained stable. Multiple independent risk factors for AD were identified and poor postoperative outcomes confirmed. However, many known impediments to wound healing such as recipient chronic steroid use, recipient and donor diabetes, and donor smoking were not identified as risk factors for AD, reinforcing the critical role of technical performance.

Objective: Anastomotic complications occur in 77%-18% of lung transplants, but no large multi-institutional analyses to determine risk factors for airway dehiscence (AD) exist. Using national registry data, we compared pre-operative recipient/donor risk factors and post-operative outcomes in patients with and without AD.
Method(s): Data on adult lung transplants between 2007 and 2017 were provided by the Scientifc Registry of Transplant Recipients. Recipient/donor demographics were compared with regards to AD, and multivariable logistic regression identifed independent risk factors for AD. Kaplan-Meier curves and log-rank tests described mortality and graft survival.
Result(s): Two hundred and seventy-fve/18,122 recipients (1.5%) experienced AD. These recipients were more often male (71.6% vs. 59.6%, P < 0.001), obese (20.1% vs. 15.6%, P = 0.041), transplanted from intensive care unit (17.5% vs. 1 1 . 0 % , P = 0.001), and mechanically ventilated (11.6% vs. 6.9%, P = 0.002). AD was not associated with recipient steroid use (51.9% vs. 47.7%, P = 0.194) or lung disease diagnosis group. Donor diabetes (8.0% vs. 7.0%, P = 0.482) and donor smoking (7.4% vs. 9.0%, P = 0.449) were also not associated with AD. Patients with AD were more likely to have received bilateral lungs (78.5% vs. 68.3%, P < 0.001) and less likely to have received a single left lung (6.5% vs. 17.3%, P < 0.001). Cold ischemia time between 2 and 4 hours was less common in the AD group (17.2% vs. 23.7%, P = 0.013). Multivariable analysis revealed recipient obesity and donor gunshot death as independent predictive factors for AD, while donor age >40 and single left lung transplant were negative predictive factors (Table SA10-1). Mortality and graft failure were both signifcantly higher in the AD group (Fig. SA10-1).
Conclusion(s): We identifed independent risk factors for AD and confrmed poor post-operative outcomes. However, many known impediments to wound healing such as chronic steroid use, diabetes, and smoking did not appear to be associated with AD

Purpose: Controversy remains over the mortality benefit of single (SLT) versus double lung transplantation (DLT) in idiopathic pulmonary fibrosis (IPF). Independent of this controversy, hesitancy to perform SLT in this population exists on the basis of unclear one year functional status. We compared functional status at one year between IPF patients listed for both who ultimately received SLT or DLT. Method(s): All consecutive adult lung transplants for IPF provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (2007-2017). Isolated lobar transplants (n=4), patients listed only for SLT (n=1834) or DLT (n=2372), and patients with missing functional status data (n=715) were excluded. Group stratification was based on the ultimate procedure (SLT or DLT). Group propensity matching was performed based on 25 recipient/donor characteristics. We compared 'good functional status' defined as >70%, at one year. Result(s): During the study period, 45% (660/1464) and 55% (804/1464) of patients listed for both procedures ultimately received SLT and DLT, respectively. After propensity matching, 341 matched patients remained in each group. Donor and recipient characteristics were similar (Table). There was no statistically significant difference in 'good functional status' at one year between SLT (77%, 264/341) and DLT (81%, 275/341) (p=0.301). The same trend is present for patients younger than 50 who receive SLT (82%, 23/28) versus DLT (94%, 34/36) (p=0.225), and patients between 50 and 60 who receive SLT (78%, 86/110) versus DLT (84%, 97/115) (p=0.305). The opposite trend is noted in patients older than 70 who receive SLT (72%, 13/18) versus DLT (61%, 11/18) (p=0.725). Conclusion(s): In this cohort of lung transplant recipients listed for both SLT and DLT, functional status was statistically similar between groups, even in younger recipients. This data suggests that SLT should not be precluded in IPF patients on the basis of expected functional status at one year.

Therapies targeting inflammation reveal inconsistent results in idiopathic pulmonary fibrosis (IPF). Aerosolised interferon (IFN)-gamma has been proposed as a novel therapy. Changes in the host airway microbiome are associated with the inflammatory milieu and may be associated with disease progression. Here, we evaluate whether treatment with aerosolised IFN-gamma in IPF impacts either the lower airway microbiome or the host immune phenotype. Patients with IPF who enrolled in an aerosolised IFN-gamma trial underwent bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of bronchoalveolar lavage fluid (BALF) was used to evaluate the lung microbiome. Biomarkers were measured by Luminex assay in plasma, BALF and BAL cell supernatant. The compPLS framework was used to evaluate associations between taxa and biomarkers. IFN-gamma treatment did not change alpha or beta diversity of the lung microbiome and few taxonomic changes occurred. While none of the biomarkers changed in plasma, there was an increase in IFN-gamma and a decrease in Fit-3 ligand, IFN-alpha2 and interleukin-5 in BAL cell supernatant, and a decrease in tumour necrosis factor-beta in BALF. Multiple correlations between microbial taxa common to the oral mucosa and host inflammatory biomarkers were found. These data suggest that the lung microbiome is independently associated with the host immune tone and may have a potential mechanistic role in IPF.