Characterizing proximity and transfers of deceased organ donors to donor care units in the United States.

Some United States organ procurement organizations transfer deceased organ donors to donor care units (DCUs) for recovery procedures. We used Organ Procurement and Transplantation Network data, from April 2017 to June 2021, to describe the proximity of adult deceased donors after brain death to DCUs and understand the impact of donor service area (DSA) boundaries on transfer efficiency. Among 19 109 donors (56.1% of the cohort) in 25 DSAs with DCUs, a majority (14 593 [76.4%]) were in hospitals within a 2-hour drive. In areas with DCUs detectable in the study data set, a minority of donors (3582 of 11 532 [31.1%]) were transferred to a DCU; transfer rates varied between DSAs (median, 27.7%, range, 4.0%-96.5%). Median hospital-to-DCU driving times were not meaningfully shorter among transferred donors (50 vs 51 minutes for not transferred, P < .001). When DSA boundaries were ignored, 3241 cohort donors (9.5%) without current DCU access were managed in hospitals within 2 hours of a DCU and thus potentially eligible for transfer. In summary, approximately half of United States deceased donors after brain death are managed in hospitals in DSAs with a DCU. Transfer of donors between DSAs may increase DCU utilization and improve system efficiency.

Benefits of Aeroallergen Testing on Oral Corticosteroid Bursts in Adults with Asthma.

BACKGROUND: Aeroallergen testing can improve precision care for persistent asthma and is recommended by the U.S. clinical guidelines. How testing benefits diverse populations of adults with asthma, and the importance of the testing modality used, are not fully understood. OBJECTIVE: We sought to evaluate whether receipt of aeroallergen testing was associated with a reduction in oral corticosteroid (OCS) bursts. METHODS: We used electronic health record data to conduct a retrospective, observational cohort study of adults with asthma who were prescribed an inhaled corticosteroid and had an Allergy/Immunology visit in a large health system between 1/1/2017-6/30/2022. Negative binomial regression models were used to evaluate whether OCS bursts in the 12-month period after an initial visit were reduced for patients who received aeroallergen testing. We also measured differences in benefit after excluding patients with chronic obstructive pulmonary disease (COPD) and smoking histories, and whether testing receipt was via skin prick or serum. RESULTS: 668/1,383 (48.3%) patients received testing. Receipt of testing was not associated with fewer bursts in all patients (incidence rate ratio (IRR)=0.83 versus no testing, p=0.059), but it was among never smokers without COPD (417/844 tested, IRR=0.68, p=0.004). The receipt of skin testing was associated with fewer bursts in all patients (418/1,383 tested, IRR=0.77, p=0.02) and among never smokers without COPD (283/844 tested, IRR=0.59 versus no testing, p=0.001). CONCLUSION: Guideline-concordant aeroallergen testing in the context of Allergy/Immunology care was associated with clinical benefit in a real-life, diverse cohort of adults with asthma. This benefit varied according to patient comorbidities and the testing modality.

Provider beliefs and practices regarding the management of obesity in lung transplant recipients.

Obesity at the time of lung transplant is associated with decreased survival. How providers manage obesity after lung transplantation is unknown. We performed an international survey of lung transplant providers to assess beliefs and practices regarding post-transplant obesity management. Eighty-one providers initiated the survey and 73 (90%) completed the full survey. Respondents were primarily North American-based pulmonary physicians. Nearly all providers believe treating obesity improves quality of life (99%) and survival (95%) after lung transplantation, but that only 41% of patients attempting weight loss are successful. While respondents nearly always recommend diet (96%), exercise (92%), and dietician consultation (89%), they less frequently recommend prescription weight loss medications (29%) or bariatric surgery (11%). Lung transplant providers are motivated to treat obesity in transplant recipients. However, there is a gap between general obesity treatment guidelines and lung transplant practice. Additional training, education, and trials in this population could address this gap.

Lung Donation and Transplant Recipient Outcomes at Independent vs Hospital-Based Donor Care Units.

Importance: Centralizing deceased organ donor management and organ recovery into donor care units (DCUs) may mitigate the critical organ shortage by positively impacting donation and recipient outcomes. Objective: To compare donation and lung transplant outcomes between 2 common DCU models: independent (outside of acute-care hospitals) and hospital-based. Design, Setting, and Participants: This is a retrospective cohort study of Organ Procurement and Transplantation Network deceased donor registry and lung transplant recipient files from 21 US donor service areas with an operating DCU. Characteristics and lung donation rates among deceased donors cared for in independent vs hospital-based DCUs were compared. Eligible participants included deceased organ donors (aged 16 years and older) after brain death, who underwent organ recovery procedures between April 26, 2017, and June 30, 2022, and patients who received lung transplants from those donors. Data analysis was conducted from May 2023 to March 2024. Exposure: Organ recovery in an independent DCU (vs hospital-based DCU). Main Outcome and Measures: The primary outcome was duration of transplanted lung survival (through December 31, 2023) among recipients of lung(s) transplanted from cohort donors. A Cox proportional hazards model stratified by transplant year and program, adjusting for donor and recipient characteristics was used to compare graft survival. Results: Of 10 856 donors in the starting sample (mean [SD] age, 42.8 [15.2] years; 6625 male [61.0%] and 4231 female [39.0%]), 5149 (primary comparison group) underwent recovery procedures in DCUs including 1466 (28.4%) in 11 hospital-based DCUs and 3683 (71.5%) in 10 independent DCUs. Unadjusted lung donation rates were higher in DCUs than local hospitals, but lower in hospital-based vs independent DCUs (418 donors [28.5%] vs 1233 donors [33.5%]; P < .001). Among 1657 transplant recipients, 1250 (74.5%) received lung(s) from independent DCUs. Median (range) duration of follow-up after transplant was 734 (0-2292) days. Grafts recovered from independent DCUs had shorter restricted mean (SE) survival times than grafts from hospital-based DCUs (1548 [27] days vs 1665 [50] days; P = .04). After adjustment, graft failure remained higher among lungs recovered from independent DCUs than hospital-based DCUs (hazard ratio, 1.85; 95% CI, 1.28-2.65). Conclusions and Relevance: In this retrospective analysis of national donor and transplant recipient data, although lung donation rates were higher from deceased organ donors after brain death cared for in independent DCUs, lungs recovered from donors in hospital-based DCUs survived longer. These findings suggest that further work is necessary to understand which factors (eg, donor transfer, management, or lung evaluation and acceptance practices) differ between DCU models and may contribute to these differences.

Unveiling Hidden Disparities: Evaluating US Multiple Listing Practices in Lung Transplantation.

BACKGROUND: Multiple listing (ML) is a practice utilized to increase the potential for transplant but is controversial due to concerns that it disproportionately benefits patients with greater access to healthcare resources. RESEARCH QUESTION: Is there disparity in ML practices based on social deprivation in the United States and does ML lead to quicker time to transplant? STUDY DESIGN AND METHODS: A retrospective cohort study of adult (>18 years old) lung transplant candidates listed for transplant (2005-2018) was conducted. Exclusion criteria included heart only or heart and lung transplant and patients relisted during the observation period. Data were obtained from the UNOS Standard Transplant Analysis and Research File. The first exposure of interest was social deprivation index (SDI) with a primary outcome of ML status, to assess disparities between ML and SL participants. The second exposure of interest was ML status with a primary outcome of time to transplant, to assess whether implementation of ML leads to quicker time to transplant. RESULTS: 35,890 subjects were included in the final analysis, of whom 791 (2.2%) were ML and 35,099 (97.8%) were SL. ML participants had lower median level of social deprivation (5 units, more often female (60.0% vs 42.3%), and had lower median LAS (35.3 vs 37.3). ML patients were more likely to be transplanted compared to SL patients (OR=1.42, 95%CI [1.17-1.73]), but there was a significantly quicker time to transplant only for whom ML was early (within 6 months of initial listing) (sHR=1.17, 95%CI [1.04-1.32]). INTERPRETATION: ML is an uncommon practice with disparities existing between ML and SL patients on the basis of several factors including social deprivation. ML patients are more likely to be transplanted, but only if they ML early in their transplant candidacy. With changing allocation guidelines, it is yet to be seen how ML will change with the implementation of continuous distribution.

Long-term air pollution exposure and the risk of primary graft dysfunction after lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) contributes substantially to both short- and long-term mortality after lung transplantation, but the mechanisms that lead to PGD are not well understood. Exposure to ambient air pollutants is associated with adverse events during waitlisting for lung transplantation and chronic lung allograft dysfunction, but its association with PGD has not been studied. We hypothesized that long-term exposure of the lung donor and recipient to high levels of ambient air pollutants would increase the risk of PGD in lung transplant recipients. METHODS: Using data from 1428 lung transplant recipients and their donors enrolled in the Lung Transplant Outcomes Group observational cohort study, we evaluated the association between the development of PGD and zip-code-based estimates of long-term exposure to 6 major air pollutants (ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, particulate matter 2.5, and particulate matter 10) in both the lung donor and the lung recipient. Exposure estimates used daily EPA air pollutant monitoring data and were based on the geographic centroid of each subject's residential zip code. Associations were tested in both univariable and multivariable models controlling for known PGD risk factors. RESULTS: We did not find strong associations between air pollutant exposures in either the donor or the recipient and PGD. CONCLUSIONS: Exposure to ambient air pollutants, at the levels observed in this study, may not be sufficiently harmful to prime the donor lung or the recipient to develop PGD, particularly when considering the robust associations with other established PGD risk factors.

Inflammatory and tissue injury marker dynamics in pediatric acute respiratory distress syndrome.

BACKGROUNDThe molecular signature of pediatric acute respiratory distress syndrome (ARDS) is poorly described, and the degree to which hyperinflammation or specific tissue injury contributes to outcomes is unknown. Therefore, we profiled inflammation and tissue injury dynamics over the first 7 days of ARDS, and associated specific biomarkers with mortality, persistent ARDS, and persistent multiple organ dysfunction syndrome (MODS).METHODSIn a single-center prospective cohort of intubated pediatric patients with ARDS, we collected plasma on days 0, 3, and 7. Nineteen biomarkers reflecting inflammation, tissue injury, and damage-associated molecular patterns (DAMPs) were measured. We assessed the relationship between biomarkers and trajectories with mortality, persistent ARDS, or persistent MODS using multivariable mixed effect models.RESULTSIn 279 patients (64 [23%] nonsurvivors), hyperinflammatory cytokines, tissue injury markers, and DAMPs were higher in nonsurvivors. Survivors and nonsurvivors showed different biomarker trajectories. IL-1α, soluble tumor necrosis factor receptor 1, angiopoietin 2 (ANG2), and surfactant protein D increased in nonsurvivors, while DAMPs remained persistently elevated. ANG2 and procollagen type III N-terminal peptide were associated with persistent ARDS, whereas multiple cytokines, tissue injury markers, and DAMPs were associated with persistent MODS. Corticosteroid use did not impact the association of biomarker levels or trajectory with mortality.CONCLUSIONSPediatric ARDS survivors and nonsurvivors had distinct biomarker trajectories, with cytokines, endothelial and alveolar epithelial injury, and DAMPs elevated in nonsurvivors. Mortality markers overlapped with markers associated with persistent MODS, rather than persistent ARDS.FUNDINGNIH (K23HL-136688, R01-HL148054).

Vascular endothelial-derived SPARCL1 exacerbates viral pneumonia through pro-inflammatory macrophage activation.

Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury. Endothelial overexpression of SPARCL1 promotes detrimental lung inflammation, with SPARCL1 inducing 'M1-like' macrophages and related pro-inflammatory cytokines, while SPARCL1 deletion alleviates these effects. Mechanistically, SPARCL1 functions through TLR4 on macrophages in vitro, while TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial Sparcl1 overexpression. Finally, SPARCL1 expression is increased in lung ECs from COVID-19 patients when compared with healthy donors, while fatal COVID-19 correlates with higher circulating SPARCL1 protein levels in the plasma. Our results thus implicate SPARCL1 as a potential prognosis biomarker for deadly COVID-19 pneumonia and as a therapeutic target for taming hyperinflammation in pneumonia.