Acute Respiratory Distress Syndrome Phenotypes After Stem Cell Transplantation: A Latent Class Analysis

Abstract

OBJECTIVE: To identify distinct phenotypes of acute respiratory distress syndrome (ARDS) developing after hematopoietic cell transplantation (HCT), using routinely available clinical data at ICU admission. DESIGN: Multicenter retrospective cohort study using latent class analysis. SETTING: ICUs across three Mayo Clinic campuses (Minnesota, Florida, and Arizona). PATIENTS: A total of 166 adult patients who developed ARDS within 120 days following HCT (96 allogeneic, 70 autologous). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Model selection was based on multiple metrics including Bayesian information criteria, entropy, and Vuong-Lo-Mendell-Rubin Likelihood Ratio testing. A two-class model optimally described the cohort. Class 1 (n = 81) was characterized by worse hypoxemia (P/F ratio 157 vs. 210, p = 0.002), higher Pco2 (41 vs. 36 mm Hg, p < 0.001), and higher bilirubin (1.4 vs. 0.9 mg/dL, p < 0.001) compared with class 2 (n = 85). Both classes included a mix of transplant types, transcending a simple autologous/allogeneic dichotomy, although class 1 had more allogeneic recipients (70.4% vs. 45.9%, p = 0.001). Although time-from-transplant was not a class-defining variable, class 1 occurred later after transplant (30.0 vs. 11.9 d, p < 0.001) with higher frequency of idiopathic pneumonia syndrome (14.8% vs. 2.4%, p = 0.004). Class 2 had more frequent neutropenia (leukocytes 0.4 vs. 5.9 × 109, p < 0.001) and higher frequency of peri-engraftment respiratory distress syndrome (29.4% vs. 9.9%, p = 0.005). Outcomes were significantly worse for class 1 (90-d mortality: 72.8% vs. 48.2%, p = 0.001). An exploratory parsimonious model had good classification accuracy (0.90) using just six variables: leukocyte count, platelet count, bilirubin, Pco2, body mass index, and temperature. CONCLUSIONS: ARDS after HCT comprises two distinct phenotypes with distinct clinical characteristics and outcomes. These phenotypes align with recognized post-HCT lung injury syndromes and may reflect different underlying biological processes. This framework provides a foundation for investigating targeted therapeutic approaches.