Patients with Bronchiolitis Obliterans Syndrome (BOS) Have Later Onset of Acute Rejection Than BOS-Free Patients

Abstract

Purpose Chronic lung allograft dysfunction (CLAD) is the most important complication after lung transplantation (LTx), which is classified bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Acute rejection (AR) is a high potential risk factor for BOS. Therefore, we have analyzed our clinical database to search the missing link between AR and BOS. Methods From January 2015 to March 2020, 746 patients underwent LTx in our institute. In this cohort, 88 patients suffered from AR (11.8%). These patients were divided in patients with BOS and without BOS. Results Our AR incident was also a risk factor of BOS (p=0.003). Mean age AR patients amounted to 47.1 years old. Forty-five patients were male (51.1%). Transplant indication was lung fibrosis (n=32, 36.4%), COPD (n=27, 30.7%), cystic fibrosis (n=13, 14.8%), bronchiectasis (n=4, 4.5%), pulmonary hypertension (n=3, 3.4%), sarcoidosis (n=2, 2.3%), re-transplantation (n=4, 4.5%) and others (n=3). Nine (10.2%) patients showed primary graft dysfunction (PGD) Grade 2-3. At follow-up, 29 (33%) patients developed BOS. Transplant indications did not differ between BOS patients and BOS-free patients. Similarly, age, gender, and PGD Grade 2-3 did not differ between groups. Incidence of infection was significantly higher in BOS than BOS-free patients (p=0.0002). The infections occurred before the AR (n=12) after AR (n=12) and after BOS episode (n=7) in BOS patients (There were repeated infection episodes in 6 patients). Moreover, the first episode of AR occurred earlier in BOS-free patients than that of BOS patients (5.5 months vs. 14.6 months, respectively: p=0.003) Conclusion In our cohort, infection is a risk factor for BOS in patients with AR. However, the infection episode occurred not only after AR but also before AR and after BOS. That means, it could not be related between AR and BOS. The most significant difference was in the first AR phase.