Longitudinal Lower Airway Microbial Signatures of Acute Cellular Rejection in Lung Transplantation.

Rationale: Acute cellular rejection (ACR) after lung transplant is a leading risk factor for chronic lung allograft dysfunction. Prior studies have demonstrated dynamic microbial changes occurring within the allograft and gut that influence local adaptive and innate immune responses. However, the lung microbiome's overall impact on ACR risk remains poorly understood. Objectives: To evaluate whether temporal changes in microbial signatures were associated with the development of ACR. Methods: We performed cross-sectional and longitudinal analyses (joint modeling of longitudinal and time-to-event data and trajectory comparisons) of 16S rRNA gene sequencing results derived from lung transplant recipient lower airway samples collected at multiple time points. Measurements and Main Results: Among 103 lung transplant recipients, 25 (24.3%) developed ACR. In comparing samples acquired 1 month after transplant, subjects who never developed ACR demonstrated lower airway enrichment with several oral commensals (e.g., Prevotella and Veillonella spp.) than those with current or future (beyond 1 mo) ACR. However, a subgroup analysis of those who developed ACR beyond 1 month revealed delayed enrichment with oral commensals occurring at the time of ACR diagnosis compared with baseline, when enrichment with more traditionally pathogenic taxa was present. In longitudinal models, dynamic changes in α-diversity (characterized by an initial decrease and a subsequent increase) and in the taxonomic trajectories of numerous oral commensals were more commonly observed in subjects with ACR. Conclusions: Dynamic changes in the lower airway microbiota are associated with the development of ACR, supporting its potential role as a useful biomarker or in ACR pathogenesis.

Organ Donation, the Non-Perfect Lung Donor, and Variability in Conversion to Transplant.

Rates of lung donation have increased over the past several years. This has been accomplished through the utilization of donors with extended criteria, the creation of donor hospitals or centers, and the optimization of lungs through the implementation of donor management protocols. These measures have resulted in augmenting the pool of available donors thereby decreasing the wait time for lung transplantation candidates. Although transplant programs vary significantly in their acceptance rates of these organs, studies have not shown any difference in the incidence of primary graft dysfunction or overall mortality for the recipient when higher match-run sequence organs are accepted. Yet, the level of comfort in accepting these donors varies among transplant programs. This deviation in practice results in these organs going to lower-priority candidates thereby increasing the waitlist time of other recipients and ultimately has a deleterious effect on an institution's waitlist mortality.

High Lung Transplant Center Volume Is Associated With Increased Survival in Hospitalized Patients.

BACKGROUND: The lung allocation score (LAS) was designed to optimize the use of pulmonary allografts based on anticipated pretransplant survival and posttransplant outcome. Hospital admission status, not included in the LAS, has not been comprehensively investigated with regard to organ allocation. The objective of this study was to determine whether pretransplant hospital admission status was independently associated with posttransplant mortality and whether high center volume was associated with improved survival in that cohort. METHODS: All consecutive adult lung transplants provided by the Scientific Registry of Transplant Recipients were retrospectively reviewed (from 2007 to 2017). Group stratification was performed based on admission status at the time of transplantation. A Cox proportional hazard regression was used to determine independent associations with posttransplant mortality. RESULTS: During the study period, 3747 of 18,416 recipients (20%) were admitted to the hospital at the time of transplantation. Compared with nonadmitted recipients, LAS were significantly higher and waitlist times significantly shorter. Admitted recipients had higher rates of prolonged mechanical ventilation, higher rates of posttransplant dialysis, and longer posttransplant lengths of stay. Pretransplant admission to a low-volume center conferred significantly worse survival compared with nonadmitted patients, and high-volume centers were independently associated with improved survival compared with low-volume centers. CONCLUSIONS: Hospital admission status is associated with increased posttransplant mortality independent of the LAS and the factors from which it is calculated. However, adjusted survival analysis demonstrates that admission to a high-volume center appears to be independently associated with improved survival compared with low-volume centers.

Single and Double Lung Transplantation Have Equivalent Survival for Idiopathic Pulmonary Fibrosis.

BACKGROUND: Several studies have described improved survival with double lung transplant (DLT) compared with single lung transplant (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 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 and 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 toward reduced rates of posttransplant 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 suggest that the previously purported survival advantage for DLT may purely represent selection bias and should not preclude the use of SLT in appropriately selected idiopathic pulmonary fibrosis patients.

Early airway dehiscence: Risk factors and outcomes with the rising incidence of extracorporeal membrane oxygenation as a bridge to lung transplantation.

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.

Rotation in a Smoking Cessation Clinic Improves Nicotine Dependence Treatment Provided by First-Year Internal Medicine Trainees.

BACKGROUND AND OBJECTIVES: 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.