Alveolar host response in acute respiratory distress syndrome

This thesis presents a series of translational studies investigating the alveolar host response in the patients with acute respiratory distress syndrome (ARDS), integrating molecular, cellular, and clinical perspectives. ARDS is a heterogeneous syndrome characterized by acute hypoxemic respiratory failure, high mortality, and limited treatment options. A deeper understanding of localized host responses may support the development of targeted therapies and improved diagnostics.
The thesis begins with a comprehensive review of the alveolar immune landscape, highlighting neutrophils and macrophages as dominant cell populations and underscoring the heterogeneity of immune responses across etiologies and disease stages. Building on this foundation, high-dimensional single-cell proteomics was applied to characterize alveolar immune profiles in ARDS patients with different underlying causes. The results revealed pathogen-specific differences in immune activation and maturation, tightly linked to local cytokine profiles and patient outcomes.
Subsequent work focused on the fibroproliferative response in COVID-19-related ARDS, demonstrating that early fibroproliferation is associated with increased short-term mortality but does not reliably predict long-term fibrotic sequelae. Another study evaluated the diagnostic utility of exhaled breath metabolites in large patient cohorts. Although metabolite-based algorithms achieved moderate accuracy, they fell short of clinical applicability, reflecting the challenges of translating breathomics into practice.
Together, these studies illustrate the compartmentalized and dynamic nature of alveolar host responses in ARDS, encompassing inflammation, immune regulation, and tissue remodeling. They emphasize the importance of functional immune profiling, longitudinal assessment, and integration of molecular and clinical data to advance precision approaches for this complex syndrome.