Place-based heterogeneity in lung transplant recipient outcomes.

Place is defined as a social or environmental area of residence with meaning to a patient. We hypothesize there is an association between place and the clinical outcomes of lung transplant recipients in the United States. In a retrospective cohort study of transplants between January 1, 2010, and December 31, 2019, in the Scientific Registry of Transplant Recipients, multivariable Cox regression models were used to test the association between place (through social and environmental factors) with readmission, lung rejection, and survival. Among 18,465 recipients, only 20% resided in the same county as the transplant center. Recipients from the most socially vulnerable counties when compared to the least vulnerable were more likely to have COPD as a native disease, Black or African American race, and travel long distances to reach a transplant center. Higher local life expectancy was associated with lower likelihood for readmission (odds ratio [OR] = 0.90, 95% confidence interval [CI]: 0.84, 0.98, p = .01). Higher social vulnerability was associated with a higher likelihood of lung rejection (OR = 1.37, [CI]: 1.07, 1.76, p = .01). There was no association of residence with posttransplant survival. Recipient place-based factors were associated with complications and processes of care after transplant and warrant further investigation.

Lung transplant waitlist outcomes in the United States and patient travel distance.

There is a broad range of patient travel distances to reach a lung transplant hospital in the United States. Whether patient travel distance is associated with waitlist outcomes is unknown. We present a cohort study of patients listed between January 1, 2006 and May 31, 2017 using the Scientific Registry of Transplant Recipients. Travel distance was measured from the patient's permanent zip code to the transplant hospital using shared access signature URL access to Google Maps, and assessed using multivariable competing risk regression models. There were 22 958 patients who met inclusion criteria. Median travel distance was 69.7 miles. Among patients who traveled > 60 miles, 41.2% bypassed a closer hospital and sought listing at a more distant hospital. In the adjusted models, when compared to patients who traveled ≤60 miles, patients who traveled >360 miles had a 27% lower subhazard ratio (SHR) for waitlist removal (SHR 0.73, 95% confidence interval [CI]: 0.60, 0.89, P = .002), 16% lower subhazard for waitlist death (SHR 0.84; 95% CI 0.73-0.95, P = .07), and 13% increased likelihood for transplant (SHR 1.13, 95% CI: 1.07, 1.20, P < .001). Many patients bypassed the nearest transplant hospital, and longer patient travel distance was associated with favorable waitlist outcomes.

Perspectives on donor lung allocation from both sides of the Atlantic: The United States.

Donor lung allocation in the United States focuses on decreasing waitlist mortality and improving recipient outcomes. The implementation of allocation policy to match deceased donor lungs to waitlisted patients occurs through a unique partnership between government and private organizations, namely the Organ Procurement and Transplantation Network under the Department of Health and Human Services and the United Network for Organ Sharing. In 2005, the donor lung allocation algorithm shifted toward the prioritization of medical urgency of waitlisted patients instead of time accrued on the waitlist. This led to the Lung Allocation Score, which weighs over a dozen clinical variables to predict a 1-year estimate of survival benefit, and is used to prioritize waitlisted patients. In 2017, the use of local allocation boundaries was eliminated in favor of a 250 nautical mile radius from the donor hospital as the first unit of distance used in allocation. The next upcoming iteration of donor allocation policy is expected to use a continuous distribution algorithm where all geographic boundaries are eliminated. There are additional opportunities to improve donor lung allocation, such as for patients with high antibody titers with access to a limited number of donors.

The Association Between Lung Recipient Travel Distance and Posttransplant Survival.

INTRODUCTION: Recipient travel distance may be an unrecognized burden in lung transplantation. DESIGN: Retrospective single-center cohort study of all adult (≥18 years) first-time lung-only transplants from January 1, 2010, until February 28, 2017. Recipient distance to transplant center was calculated using the linear distance from the recipient's home zip code to the Cleveland Clinic in Cleveland, Ohio. RESULTS: 569 recipients met inclusion criteria. Posttransplant graft survival was 85%, 88%, 91%, and 91% at 1 year and 49%, 52%, 57%, and 56% at 5 years posttransplant for recipient travel distances of ≤50, >50 to ≤250, >250 to ≤500, and >500 miles, respectively ( P = .10). DISCUSSION: We found no significant relationship between recipient travel distance and posttransplant graft survival. In carefully selected recipients, travel distance is not a significant barrier to successful posttransplant outcomes which may be important for patient decision-making and donor allocation policy. These data should be validated in a national cohort.

An acute change in lung allocation score and survival after lung transplantation: a cohort study.

BACKGROUND: Lung transplantation is an effective treatment for patients with advanced lung disease. In the United States, lungs are allocated on the basis of the lung allocation score (LAS), a composite measure of transplantation urgency and utility. Clinical deteriorations result in increases to the LAS; however, whether the trajectory of the LAS has prognostic significance is uncertain. OBJECTIVE: To determine whether an acute increase in the LAS before lung transplantation is associated with reduced posttransplant survival. DESIGN: Retrospective cohort study of adult lung transplant recipients listed for at least 30 days between 4 May 2005 (LAS implementation) and 31 December 2010 in the United Network for Organ Sharing registry. An acute increase in the LAS was defined as an LAS change (LASΔ) greater than 5 units between the 30 days before and the time of transplantation. Multivariable Cox proportional hazard models were used to examine the relationship between an LASΔ >5 and posttransplant graft survival. SETTING: All U.S. lung transplantation centers. PATIENTS: 5749 lung transplant recipients. MEASUREMENTS: Survival time after lung transplantation. RESULTS: 702 (12.2%) patients experienced an LASΔ >5. These patients had significantly worse posttransplant survival (hazard ratio, 1.31 [95% CI, 1.11 to 1.54]; P = 0.001]) after adjustment for the LAS at transplantation (LAS-T) and other clinical covariates. The effect of an LASΔ >5 was independent of the LAS-T, underlying diagnosis, center volume, or donor characteristics. LIMITATION: Analysis was based on center-reported data. CONCLUSION: An acute increase in LAS before transplantation is associated with posttransplant survival after adjustment for LAS-T. Further emphasis on serial assessment of the LAS could improve the ability to offer accurate prediction of survival after transplantation. PRIMARY FUNDING SOURCE: National Institutes of Health.

Residential history, the electronic health record, and clinical medicine: A descriptive study in a lung transplant cohort.

Neighborhood level social determinants of health are commonly measured using a patient's most recent residential location. Not accounting for residential history, and therefore missing accumulated stressors from prior social vulnerabilities, could increase misclassification bias. We tested the hypothesis that the electronic health record could capture the residential history of lung transplant patients -a vulnerable population. After applying the Social Vulnerability Index (SVI) to individual residential histories, the most recent SVI equaled the first SVI in only 15.4% (58/374) of patients. There is a need for databases with residential histories to inform place-based determinants of health and applications to patient care.

Assessing the causal effect of organ transplantation on the distribution of residual lifetime.

Because the number of patients waiting for organ transplants exceeds the number of organs available, a better understanding of how transplantation affects the distribution of residual lifetime is needed to improve organ allocation. However, there has been little work to assess the survival benefit of transplantation from a causal perspective. Previous methods developed to estimate the causal effects of treatment in the presence of time-varying confounders have assumed that treatment assignment was independent across patients, which is not true for organ transplantation. We develop a version of G-estimation that accounts for the fact that treatment assignment is not independent across individuals to estimate the parameters of a structural nested failure time model. We derive the asymptotic properties of our estimator and confirm through simulation studies that our method leads to valid inference of the effect of transplantation on the distribution of residual lifetime. We demonstrate our method on the survival benefit of lung transplantation using data from the United Network for Organ Sharing.

The Past, Present, and Near Future of Lung Allocation in the United States.

The first official donor lung allocation system in the United States was initiated by the United Network of Organ Sharing in 1990. The initial policy for lung allocation was simple with donor lungs allocated based on ABO match and the amount of time the candidates accrued on the waiting list. Donor offers were first given to candidates' donor service area. In March 2005, the implementation of the lung allocation score (LAS) was the major change in organ allocation. International adoption of the LAS-based allocation system can be seen worldwide.

Application of Place-Based Methods to Lung Transplant Medicine.

Lung transplantation is an increasingly common lifesaving therapy for patients with fatal lung diseases, but this intervention has a critical limitation as median survival after LT is merely 5.5 years. Despite the profound impact of place-based factors on lung health, this has not been rigorously investigated in LT recipients-a vulnerable population due to the lifelong need for daily life-sustaining immunosuppression medications. There have also been longstanding methodological gaps in transplant medicine where both time and place have not been measured; gaps which could be filled by the geospatial sciences. As part of an exploratory analysis, we studied recipients transplanted at our center over a two-year period. The main outcome was at least one episode of rejection within the first year after transplant. We found recipients averaged 1.7 unique residential addresses, a modest relocation rate. Lung rejection was associated with census tracts of predominantly underrepresented minorities or where English was not the primary language as measured by the social vulnerability index. Census tracts likely play an important role in measuring and addressing geographic disparities in transplantation. In a future paradigm, patient spatial data could become an integrated part of real time clinical care to aid in personalized risk stratification and personalized delivery of healthcare.

COVID-19 and lung transplant patients.

COVID-19 is a novel respiratory disease leading to high rates of acute respiratory failure requiring hospital admission. It is unclear if specific patient populations such as lung transplant patients are at higher risk for COVID-19. Some reports suggest that transplant patients may not be at higher risk if proper social distancing and preventive measures are employed. Efforts to ensure the safety of wait-listed patients, transplant recipients, and healthcare workers are underway. Recommendations for the care of lung transplant patients during the COVID-19 pandemic are discussed and will likely change as the pandemic evolves.

Patient Travel Distance and Post Lung Transplant Survival in the United States: A Cohort Study.

BACKGROUND: In response to a longstanding Federal mandate to minimize the role of geography in access to transplant in the United States, we assessed whether patient travel distance was associated with lung transplant outcomes. We focused on the posttransplant time period, when the majority of patient visits to a transplant center occur. METHODS: We present a cohort study of lung transplants in the United States between January 1, 2006, and May 31, 2017. Travel distance was measured from the patient's permanent home zip code to the transplant center using SAS URL access to GoogleMaps. We leveraged data from the US Census, US Department of Agriculture, and the Economic Innovations Group to assess socioeconomic status. Multivariable Cox models were used to assess graft survival. RESULTS: We included 18 128 patients who met the inclusion criteria. Median distance was 69.6 miles. Among patients who traveled >60 miles to reach a transplant center, 41.8% bypassed a closer center and sought care at a more distant center. Patients traveling longer distances sought care at centers with a higher annual transplant volume. In the adjusted Cox Model, patients who traveled >360 miles had a slightly higher risk for posttransplant graft failure than patients traveling ≤60 miles (hazard ratio 1.09; 95% CI, 1.01-1.18), and a higher risk for treated acute rejection (hazard ratio, 1.63; 95% CI, 1.43-1.86). CONCLUSIONS: Travel distance was significantly associated with post lung transplant survival. However, this effect was relatively modest. Patient travel distance is an important component of access to lung transplant care.

Extremes of Age Decrease Survival in Adults After Lung Transplant.

BACKGROUND: Age has been implicated as a factor in the plateau of long-term survival after lung transplant. METHODS: We used data from the Scientific Registry of Transplant Recipients to identify all recipients of lung transplant aged ≥18 years of age between January 1, 2006, and February 19, 2015. A total of 14,253 patients were included in the analysis. Survival was estimated using a nonproportional hazard model and random-survival forest methodology was used to examine risk factors for death. Final selection of model variables was performed using bootstrap aggregation. Age was analyzed as both a continuous and categorical variable (age <30, 30-55, and >55 years). Risk factors for death were obtained for the entire cohort and additional age-specific risk factors were identified for each age category. RESULTS: The median age at transplant was 59 years. There were 1,098 (7.7%) recipients <30 years, 4,201 (29.5%) 30 to 55 years, and 8,954 (62.8%) >55 years of age. Age was the most significant risk factor for death at all time-points following transplant and its impact becomes more prominent as time from transplant increases. Risk factors for death for all patients included extremes of age, higher creatinine, single lung transplant, hospitalization before transplant, and increased bilirubin. Risk factors for death differed by age with social determinants of health disproportionately affecting survival for those in the youngest age category. CONCLUSIONS: The youngest and oldest adult recipients experienced the lowest posttransplant survival through divergent pathways that may present opportunities for intervention to improve survival after lung transplant.

Contemporary Issues in Lung Transplant Allocation Practices.

PURPOSE OF REVIEW: To discuss the current state of donor lung allocation in the United States, and future opportunities to increase the efficiency of donor lung allocation. RECENT FINDINGS: The current donor lung allocation system prioritizes clinical acuity by use of the Lung Allocation Score (LAS) which has reduced waitlist mortality since its implementation in 2005. Access to donor lungs can be further improved through policy changes using broader geographic sharing, and developing new technology such as ex vivo lung perfusion to recover marginal donor lungs. SUMMARY: The number of lung transplants in the U.S. continues to increase annually. However, the demand for donor lungs continues to be outpaced by an ever growing waitlist. Efficient allocation can be achieved through improved allocation policies and new technology.

Survival Benefit of Lung Transplantation in the Modern Era of Lung Allocation.

RATIONALE: Lung transplantation is an accepted and increasingly employed treatment for advanced lung diseases, but the anticipated survival benefit of lung transplantation is poorly understood. OBJECTIVES: To determine whether and for which patients lung transplantation confers a survival benefit in the modern era of U.S. lung allocation. METHODS: Data on 13,040 adults listed for lung transplantation between May 2005 and September 2011 were obtained from the United Network for Organ Sharing. A structural nested accelerated failure time model was used to model the survival benefit of lung transplantation over time. The effects of patient, donor, and transplant center characteristics on the relative survival benefit of transplantation were examined. MEASUREMENTS AND MAIN RESULTS: Overall, 73.8% of transplant recipients were predicted to achieve a 2-year survival benefit with lung transplantation. The survival benefit of transplantation varied by native disease group (P = 0.062), with 2-year expected benefit in 39.2 and 98.9% of transplants occurring in those with obstructive lung disease and cystic fibrosis, respectively, and by lung allocation score at the time of transplantation (P < 0.001), with net 2-year benefit in only 6.8% of transplants occurring for lung allocation score less than 32.5 and in 99.9% of transplants for lung allocation score exceeding 40. CONCLUSIONS: A majority of adults undergoing transplantation experience a survival benefit, with the greatest potential benefit in those with higher lung allocation scores or restrictive native lung disease or cystic fibrosis. These results provide novel information to assess the expected benefit of lung transplantation at an individual level and to enhance lung allocation policy.

Chronic obstructive pulmonary disease in patients with atrial fibrillation: Insights from the ARISTOTLE trial.

BACKGROUND: Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood. METHODS: We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors. RESULTS: COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p=0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p<0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p=0.617). CONCLUSIONS: COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.

Influenza-like symptoms in the college dormitory environment: a survey taken during the 1999-2000 influenza season.

The effect of dormitory environments on the transmission of the influenza virus in college students is not well understood. During the 1999-2000 flu season, dormitory residents at a college campus in Chicago were surveyed about their living conditions and influenza-like symptoms (ILS). The survey had a 42 percent response ratio (721 of 1,704). Students who had > or = 50 percent carpeting in their room were at significantly lower risk for ILS (p = .02). Although the risk of ILS increased for roommates who shared sleeping quarters compared with those who slept in different rooms (RR = 4.3), the difference was not statistically significant. No evidence was found that ILS risk was affected by washroom, laundry, or dining settings, or by demographics, including gender or year in college. The survey instrument detected strong relations between ILS and the dormitory room environment, in contrast with other settings in the dormitory. Further research on transmission may focus on the room environment.