Faculty Bibliography

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.