Faculty Bibliography

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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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.

Background: Therapies targeting the inflammatory process revealed inconsistent results in Idiopathic Pulmonary Fibrosis (IPF). Aerosolized Interferon Gamma (IFN-y) has been proposed as a novel therapy. Additionally, changes in the host airway microbiome have been associated with inflammatory tone and, in IPF, may be associated with disease progression.We evaluate whether treatment with aerosolized IFN-y impacts the lower airway microbiome or host immune phenotype. Methods: Patients with IPF were enrolled in an aerosolized IFNy trial. Patients underwent a bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of BAL samples were used to evaluate the lower airway microbiome. Cytokines were measured by Luminex on plasma, BAL fluid and BAL cell supernatant. Findings: IFN-y treatment did not change alpha or beta diversity of the lung microbiome and few taxonomic changes in low abundant taxa occurred (Figure 1). The measured cytokines were unchanged in plasma, however, there was an increase in IFN-y and a decrease in Fit 3 Ligand, IFN-A2 and IL- 5 in BAL cell supernatant, and TNF-B in BAL. Multiple correlations between taxa and inflammatory cytokines were found. Network analysis showed correlations were more abundant between lung microbial taxa and local inflammatory cytokines (either in BAL or by ex vivo BAL cell production) than between lung microbial taxa and systemic inflammatory cytokines. Importantly, analysis showed persistent of these association post IFN treatment. Interpretation: This data suggests that the lower airway microbiome has an independent effect on host immune tone and thus may provide a novel therapeutic target for treatment of IPF

BACKGROUND AND OBJECTIVES/OBJECTIVE:Over 70% of smokers visit a physician annually, and physicians are well-positioned to assist patients in smoking cessation. Residency offers the ideal setting to train physicians in best practices for treatment of nicotine dependence. We hypothesized that experiential learning during a smoking cessation medical clinic (SCMC) rotation would be associated with an improvement in smoking cessation practice of internal medicine (IM) interns in outpatient primary care and inpatient settings. METHODS:This was a prospective study performed at a large university-affiliated hospital. Forty IM interns rotated through SCMC. After a lecture on nicotine addiction and treatment, interns treated SCMC patients under direct supervision of an attending pulmonologist. Interns' smoking cessation practices before and after SCMC rotation were evaluated through chart review over 1 year. Upon study completion, a survey to assess confidence was administered. Paired t tests measured changes in rates of identifying smokers, offering pharmacological treatment and counseling. RESULTS:A total of 5,622 outpatient and 683 inpatient charts of interns' encounters with patients were reviewed. Following SCMC rotation, there was an increase in identifying active smokers (7.1% versus 18.7%), prescribing therapy for smoking cessation (6.5% versus 18.0%), and providing counseling (30.9% versus 42.3%) to outpatients. For inpatients, there was an increase in nicotine replacement during admission (12.9% versus 37.4%) and prescription of therapy upon discharge (5.7% versus 16.1%). Interns reported confidence in providing appropriate counseling and treatment. CONCLUSIONS:SCMC experience positively impacted smoking cessation treatment by IM interns, causing a measurable change in their practice.