Preliminary Analysis of PM2.5 Exposure and Cytokine Expression in Sickle Cell Disease Patients Presenting With Non-Asthmatic Wheezing

Background: Airborne particulate matter <2.5 m (PM2.5) may trigger inflammation in patients with sensitive immune profiles, particularly Sickle Cell Disease (SCD) patients with nonasthmatic wheezing.The impact and pathophysiology of PM2.5 on these SCD patients is not well understood.This preliminary analysis examines associations between PM2.5 and cytokine expression-the production of immune signaling proteins associated with environmental stressors-in this population.Methods: This is a secondary analysis of data from a cohort of adults with SCD, which included 80 participants with documented non-asthmatic wheezing.Cytokine levels were measured from blood samples using 184-protein multiplex immunoassays.Participants' residential addresses were geocoded and linked to public environmental datasets to estimate exposure to PM2.5.Exploratory associations between PM2.5 exposure and cytokine expression were assessed using longitudinal adjusted linear regression models, corrected for multiple comparisons.Results: Molecular and pathological connections between relevant cytokines were identified using STRING Database, UniProt, KEGG Pathways, and Enrichr.A targeted literature review identified key pathways with inflammatory associations to PM2.5.Preliminary findings suggest that exposure to PM2.5 is associated with differential (both positive and negative) expression of several inflammatory cytokines and chemokines in adults with SCD and non-asthmatic wheezing.This may indicate immune signaling disruption. Conclusion:Pathway analysis and existing literature indicate that mechanisms may include altered macrophage functionality or polarization due to abnormal chemokine signaling and recruitment, adhesion properties, airway epithelial damage, or oxidative stress.