CD8+ T-cell counts: an early predictor of risk and mortality in critically ill immunocompromised patients with invasive pulmonary aspergillosis

Introduction: Critically ill immunocompromised (CIIC) patients with pulmonary infection are a population at high risk for invasive pulmonary aspergillosis (IPA). The host defenses are important factors to consider in determining the risk and outcome of infection. Quantification of changes in the status of host immunity could be valuable for clinical diagnosis and outcome prediction. Methods: We evaluated the quantitative changes in key humoral and cellular parameters in CIIC patients with pulmonary infection and their potential influence on the risk and prognosis of IPA. We monitored the evolution of these parameters in 150 CIIC patients with pulmonary infection on days 1, 3 and 10 (D1, D3 and D10) following ICU admission. The primary outcome was 28-day mortality. Follow-up included 60- and 90-day mortality. Results: Among the 150 CIIC patients included in this study, 62 (41.3%) had microbiological evidence of IPA. Compared with patients without IPA, CD3(+), CD8(+), CD28(+)CD4(+) and CD28(+)CD8(+) CD28(+)CD8(+) T-cell counts (D1, D3 and D10) and B-cell counts (D1 and D3) were significantly reduced in patients with IPA (P < 0.05). Multivariate regression analysis revealed that CD8(+) (D3 and D10) (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.23 to 0.46; OR 0.68, 95% CI 0.56 to 0.80), CD28(+)CD8(+) (D3) (OR 0.73, 95% CI 0.61 to 0.86) and CD3(+) (D10) (OR 0.81, 95% CI 0.63 to 0.98) T-cell counts were independent predictors of IPA in CIIC patients. Receiver operating characteristic analysis of immune parameters predicting 28-day mortality revealed area under the curve values of 0.82 (95% CI 0.71 to 0.92), 0.94 (95% CI 0.87 to 0.99), and 0.94 (95% CI 0.85 to 0.99) for CD8(+) T-cell counts (D1, D3 and D10, respectively) and 0.84 (95% CI 0.75 to 0.94), 0.92 (95% CI 0.85 to 0.99) and 0.90 (95% CI 0.79 to 0.99) for CD28(+)CD8(+) T-cell counts (D1, D3 and D10, respectively). Kaplan-Meier survival analysis provided evidence that CD8(+) and CD28(+)CD8(+) T-cell counts (<149.5 cells/mm(3) and <75 cells/mm(3), respectively) were associated with early mortality in CIIC patients with IPA (logrank test; P < 0.001). Conclusions: CD8(+) and CD28(+)CD8(+) T-cell counts were significantly lower in CIIC patients with IPA than in non-IPA patients. Lower CD8(+) and CD28(+)CD8(+) T-cell counts in CIIC patients with pulmonary infection were associated with higher risk and early mortality in IPA and may be valuable for clinical diagnosis and outcome prediction.