Evaluating Novel Prognostic Markers and Preventative Therapies for Chronic Lung Allograft Dysfunction after Lung Transplantation

• Author / Creator

  Li, David J

• Introduction: Survival following lung transplantation remains limited by chronic lung allograft dysfunction (CLAD). Few therapeutic options have been shown to be effective in established CLAD thus early detection and prevention are key.
  Objective: We aimed to identify potential early prognostic radiographic markers on lung ventilation-perfusion (VQ) scans and evaluate our center’s strategy of using azithromycin prophylactically to prevent CLAD.
  Methods: Retrospective cohort studies were conducted using prospectively collected data from the University of Alberta lung transplant program databases on patients transplanted between January 1, 2004, and December 31, 2016, in conjunction with supporting data from clinical databases to address the questions of interest. Inclusion was boundaried at 2016 to allow a minimum of 5 years of follow-up to facilitate risk of primary outcome of interest, CLAD. Inclusion criteria were all adult double lung transplants with sufficient data for each study; single lung, heart-lung, and living lobar lung transplants were excluded given some outcomes of interest are not defined in these population. PGD and CLAD grades were defined per consensus guideline definitions and an additional syndrome of baseline lung allograft dysfunction (BLAD) was defined as per our published definition of failure to achieve spirometry measures of at least 80% predicted on 2 consecutive tests at least 3 weeks apart. In part i) we examined how mismatched perfusion defects detected on VQ scans affected survival and in part ii) we assessed the prognostic implications of abnormal left-right lung perfusion differential on VQ scans. In part iii), we examined the association between use of azithromycin prophylaxis and survival and lung function.
  Results: i) 169/340 patients (49%) had a relative perfusion differential > 10% on 3-months VQ scan. Patients with increased perfusion differential had increased risk of death or retransplantation (p=0.011) and of CLAD onset (p=0.012) after adjustment for other radiographic/endoscopic abnormalities; ii) 35/373 patients (9%) had VQ scans with perfusion defects. Patients with PD had similar 1-year survival (100% vs. 98%, p=1.00), overall survival (log rank p=0.90) and peak FEV1% predicted (94% [SD 20%] vs. 92% [SD 21%]; p=0.58). Anticoagulation did not affect these relationships; iii) 344/445 patients (77%) received azithromycin prophylaxis [median time from transplant 51 days]. Azithromycin prophylaxis was associated with improved survival (hazard ratio [HR] 0.60 [95% confidence interval [CI] 0.44-0.84]; p=0.002) in our adjusted model and with reduced unadjusted risks of CLAD onset (HR 0.64 [95% CI 0.44-0.94]; p=0.025) and BLAD (odds ratio 0.55 [95% CI 0.35-0.86]; p=0.009).
  Conclusion: i) Wide left-right lung perfusion differential was associated with increased adjusted risk of death and CLAD onset; ii) mismatched perfusion defects on lung VQ scans were not associated with survival; iii) azithromycin prophylaxis was associated with improved survival after lung transplant, potentially through reducing BLAD risk.

• Subjects / Keywords

  • Lung transplantation
  • Chronic lung allograft dysfunction

• Graduation date

  Fall 2023

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-h22h-zc35

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.