An increased alveolar CD4 + CD25 + Foxp3 + T-regulatory cell ratio in acute respiratory distress syndrome is associated with increased 30-day mortality

Adamzik, Michael; Broll, Jasmin; Steinmann, Jörg; Westendorf, Astrid Maria; Rehfeld, Irene; Kreissig, Carla; Peters, Jürgen

PURPOSE: Cell therapy may become an option for lung injury treatment. However, no data are available on the alveolar presence and time course of CD4+ CD25 + Foxp3 + T-regulatory lymphocyte cells (Tregs) in acute respiratory distress syndrome (ARDS). Accordingly, we (1) measured the ratio of CD4 + CD25 + Foxp3 + Tregs to all (CD4+) lymphocytes in the bronchoalveolar lavage (BAL) of ARDS patients and of control subjects without lung disease and (2) assessed their impact on 30-day mortality. METHODS: In a prospective study, the ratios of CD4 + CD25 + Foxp3 + T-regulatory cells to all CD4+ cells were measured (FACS) within 24 h of the patients’ ICU referral in the BAL and in the blood of 47 patients with ARDS (32 males, 15 females; mean age 44 years ±13) as well as in 8 controls undergoing elective abdominal surgery (5 men, 3 women; mean age 49 years ±4). BAL concentrations of several cytokines were also measured in ARDS patients. RESULTS: Tregs were detected in the BAL of control subjects and ARDS patients. However, the mean ratio of Tregs to all CD4+ lymphocytes was threefold greater in ARDS non-survivors (16.5 %; p = 0.025) and almost twofold greater in ARDS survivors (9.0 %; p = 0.015) compared to controls (5.9 %). Multivariate Cox regression analysis revealed the ratio of CD4 + CD25 + Foxp3 + T-regulatory lymphocytes to all CD4+ lymphocytes in the BAL to be an important and independent prognostic factor for 30-day survival (HR 6.5; 95 % CI, 1.7–25; p = 0.006). CONCLUSION: An increased T-regulatory cell ratio in the admission BAL of patients with ARDS is an important and independent risk factor for 30-day mortality.