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Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2022)

Lung transplantation is a life-saving therapy for a carefully selected subset of patients with end-stage lung diseases. Life expectancy post-transplant is modest with a median survival of 5.5-6.5 years. The identification of potentially modifiable risk factors for poor outcomes after lung transplant is of great importance. In this dissertation, we explore the impacts of neighborhood-level social and environmental factors on lung transplant outcomes using mixed effects semiparametric and parametric survival models to estimate the hazard of death or graft failure. We find that neighborhood disinvestment, operationalized as the ZIP code level Social Vulnerability Index (SVI) is associated with a 6% increase in the hazard of death or graft failure after transplant, though this finding does not reach statistical significance. We utilize previously reported estimates of annual PM2.5 levels in North America to create ZIP code estimates of average yearly exposure. We find that annual PM2.5 exposure above the EPA standard of 12 ug/m3 is associated with an 8% increase in the hazard of death or graft failure. Furthermore, this relationship appears to hold true at lower thresholds of exposure. Understanding the effects of social and environmental factors on lung transplant outcomes will allow transplant practitioners to better identify patients at high risk of poor outcomes. It may also direct future policy decisions to mitigating these risks.

    Cover page: Social and Environmental Impacts on Lung Transplant Outcomes
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2022)
    Despite the common detection of non-donor specific anti-HLA antibodies (non-DSAs) after lung transplantation, their clinical significance remains unclear. In this retrospective single-center cohort study of 325 lung transplant recipients, we evaluated the association between donor-specific HLA antibodies (DSAs) and non-DSAs with subsequent CLAD development. DSAs were detected in 30% of recipients and were associated with increased CLAD risk, with higher HRs for both de novo and high MFI (>5000) DSAs. Non-DSAs were detected in 56% of recipients, and 85% of DSA positive tests had concurrent non-DSAs. In general, non-DSAs did not increase CLAD risk in multivariable models accounting for DSAs. However, non-DSAs in conjunction with high BAL CXCL9 levels were associated with increased CLAD risk. Multivariable proportional hazards models demonstrate the importance of the HLA antibody-CXCL9 interaction: CLAD risk increases when HLA antibodies (both DSAs and non-DSAs) are detected in conjunction with high CXCL9. Conversely, CLAD risk is not increased when HLA antibodies are detected with low CXCL9. This study supports the potential utility of BAL CXCL9 measurement as a biomarker to risk stratify HLA antibodies for future CLAD. The ability to discriminate between high versus low-risk HLA antibodies may improve management by allowing for guided treatment decisions.
      Cover page: The allograft injury marker CXCL9 determines prognosis of anti-HLA antibodies after lung transplantation.
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2022)

      Background

      Chronic lung allograft dysfunction (CLAD) phenotype determines prognosis and may have therapeutic implications. Despite the clarity achieved by recent consensus statement definitions, their reliance on radiologic interpretation introduces subjectivity. The Center for Computer Vision and Imaging Biomarkers at the University of California, Los Angeles (UCLA) has established protocols for chest high-resolution computed tomography (HRCT)-based computer-aided quantification of both interstitial disease and air-trapping. We applied quantitative image analysis (QIA) at CLAD onset to demonstrate radiographic phenotypes with clinical implications.

      Methods

      We studied 47 first bilateral lung transplant recipients at UCLA with chest HRCT performed within 90 d of CLAD onset and 47 no-CLAD control HRCTs. QIA determined the proportion of lung volume affected by interstitial disease and air-trapping in total lung capacity and residual volume images, respectively. We compared QIA scores between no-CLAD and CLAD, and between phenotypes. We also assigned radiographic phenotypes based solely on QIA, and compared their survival outcomes.

      Results

      CLAD onset HRCTs had more lung affected by the interstitial disease (P = 0.003) than no-CLAD controls. Bronchiolitis obliterans syndrome (BOS) cases had lower scores for interstitial disease as compared with probable restrictive allograft syndrome (RAS) (P < 0.0001) and mixed CLAD (P = 0.02) phenotypes. BOS cases had more air-trapping than probable RAS (P < 0.0001). Among phenotypes assigned by QIA, the relative risk of death was greatest for mixed (relative risk [RR] 11.81), followed by RAS (RR 6.27) and BOS (RR 3.15).

      Conclusions

      Chest HRCT QIA at CLAD onset appears promising as a method for precise determination of CLAD phenotypes with survival implications.
        Cover page: Quantitative Image Analysis at Chronic Lung Allograft Dysfunction Onset Predicts Mortality
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