Introduction: Lung transplantation is the treatment option for patients with end-stage lung diseases. Recently, cell-free DNA (cfDNA) has emerged as a biomarker for early detection of allograft injury. Elevated cfDNA has most often been associated with the presence of acute rejection or infections. However, we propose the etiology of elevated cfDNA in our case to be related to non-immune or infectious causes.
Method: A retrospective review was performed on the described patient to obtain clinical, radiographic, and treatment data.
Results: A 42-year-old patient was diagnosed with interstitial lung disease with autoimmune features in 2016. Despite initial treatment with nintedanib and mycophenolate, the patient's condition progressively deteriorated.
In June 2023, the patient underwent a left lung transplant. The postoperative course was complicated by severe primary graft dysfunction (PGD), necessitating extracorporeal membrane oxygenation and renal replacement therapy. Several weeks later, the patient was discharged in a stable condition with immunosuppressive and prophylactic therapy. In September 2023, the patient was noted to have elevated cell-free DNA levels of 9.3%. A subsequent bronchoscopy with transbronchial biopsy and bronchoalveolar lavage yielded no evidence of acute cellular rejection or infection, respectively. Given the unexplained elevation of cell-free DNA, it was repeated on 10/08/2023, resulting in 7.40%, and on 11/08/2023, with a decline to 1.84%. In early November 2023, the patient was readmitted with dyspnea and newly onset stridor. CT chest showed moderate narrowing at the distal left bronchial anastomotic site. Bronchoscopic examination revealed granulation tissue obstructing the left main stem bronchus. Ablation using argon plasma coagulation and ballon dilation were performed. Subsequent testing showed a rise in cfDNA up to 3.12% on 11/21/2023, without evidence of rejection or infection.
In late November 2023, the patient presented with respiratory distress in the setting of recurrent bronchial stenosis. Repeated bronchoscopy with multiple balloon dilations was performed due to demonstrated stenosis. Subsequent cell-free DNA measurements showed a decline in cfDNA to 1.00% on 12/27/2023, and 0.22% on 02/01/2024.
Conclusion: In this case study, we propose that elevated levels of cfDNA in the context of lung transplantation may not necessarily signify acute rejection or infection, traditionally considered the primary culprits. It underscores the crucial need to consider alternative etiologies, such as severe primary graft dysfunction and procedural trauma from interventional procedures such as APC.
In conclusion, this report aims to expand our comprehension of factors affecting cfDNA levels in lung transplant recipients, highlighting the importance of differential diagnosis. A precise interpretation of cfDNA elevations is critical to avoid superfluous interventions and treatments that may escalate healthcare costs and morbidity.