Alveolar Extracellular Vesicles May Protect Some Patients With Chronic Aspiration From Pneumonia.

Abstract

Aspiration pneumonia (PNA) is a significant cause of morbidity and mortality. Up to 30% of healthy older adults may aspirate; however, many individuals with chronic aspiration do not develop PNA. We hypothesize that some patients with chronic aspiration may have distinct immune profiles that protect against PNA. We prospectively enrolled 23 adults with profound swallowing impairment and objective evidence of chronic aspiration, and 5 controls without aspiration. All patients underwent bronchoalveolar lavage. Samples were analyzed for pH, cytokines, and markers of immune cell function. Extracellular vesicles (EVs) were isolated from alveolar fluid by ultracentrifugation, and EV protein composition was analyzed by mass spectrometry. Of 23 chronic aspirators (median age 63 [61-69], 87% male), 14 (61%) had no PNA and 9 (39%) had ≥ 1 PNA in 2 years. There was no difference in the penetration-aspiration score, patient-reported outcome scores, markers of inflammation, neutrophil function, or pH in the alveolar fluid between groups. Compared to chronic aspirators without PNAs, those with PNAs had a significantly higher alveolar EV concentration (5.6 × 10¹¹ particles/mL [1.9 × 10¹¹-8.2 × 10¹¹] vs. 1.5 × 10¹¹ particles/mL [8.8 × 10¹⁰-3.3 × 10¹¹], p = 0.02). Protein analysis revealed that EVs in aspirators without PNA were enriched in proteins related to an immune response to bacteria, including inhibition of endopeptidases that are used as virulence factors by some pneumonia-causing organisms. Patients with chronic aspiration who are not prone to developing pneumonia exhibit a distinct alveolar immune phenotype which may be protective against lung injury. These extracellular-mediated pathways may serve as future diagnostic and therapeutic targets. Level 3.