Telemedicine with a Cell-Free DNA Based Monitoring Approach Maintains Lung Allograft Function While Reducing Frequency of Invasive Bronchoscopy

PURPOSE: The need to reduce in-person clinic visits during the COVID-19 pandemic necessitated a significant reduction in traditional lung transplant surveillance with bronchoscopy and clinic-based pulmonary function testing (PFT). We hypothesized that a screening strategy that utilized cell free DNA (CareDx: Allosure), a non-invasive marker of molecular allograft injury, to determine the need for for-cause diagnostics would yield equivalent lung function stability as traditional monitoring using surveillance bronchoscopy and clinic performed PFTs in lung transplant recipients. METHODS: We compared the change in FEV1, the prevalence of donor-specific HLA antibodies (DSA), and frequency of hospitalization over parallel 6-month timespans in 2 cohorts of LTRs assessed during the 1(st) 3 years of their transplant. The 1(st) cohort (N=65) was monitored from 3/2019 to 9/2019 by in-clinic PFT, surveillance bronchoscopy, DSA, and the 2(nd) cohort (N=73) was monitored from 3/2020-9/2020 with telemedicine, home spirometry, surveillance dd-cfDNA, and DSA testing every 1-3 months. In cohort 2, patients with >10% decline in home FEV1, and/or dd-cfDNA>1% underwent for-cause bronchoscopy and/or further diagnostic evaluation. Surveillance PFTs were conducted once between 7/20 and 9/20 in cohort 2 to assess the stability of lung function. For both cohorts, a minimum interval of 150 days and a maximum interval of 200 days was used for analysis of spirometric change. RESULTS: There were significantly fewer bronchoscopies/patient (pt) in cohort 2 vs cohort 1 (0.91 vs 1.8, p <0.01). Despite reduced bronchoscopic surveillance, the median % change in FEV1 over 6 months did not differ between cohort 1 vs cohort 2 (1.04% vs 1.01 % p =0.51). Further, there was a comparable prevalence of any level HLA-DSA in cohort 1 vs 2 (32% vs 31% p=0.26). The total incidence of hospitalizations was similar in cohort 1 vs 2 (0.98 events/pt. vs. 1.03 events/pt. P=0.25). CONCLUSION: The use of non-invasive cell-free DNA testing with home spirometry screening appears to yield comparable medium-term allograft outcomes, as compared to conventional clinic-based PFTs and surveillance bronchoscopy. Further multi-center studies are warranted to determine if this approach can reduce invasive procedures while maintaining equivalent outcomes in clinically meaningful parameters.