Abstract Rationale Sickle cell lung disease is progressive in nature and remains a significant cause of morbidity and early mortality in people with Sickle Cell Disease (SCD). Despite clinical manifestations beginning in childhood, predictive indicators for developing respiratory complications such as acute chest syndrome and chronic hypoxemia remain understudied. Our research aimed to fill this knowledge gap. We hypothesized that conserved inflammatory pathways were upregulated in both airway and blood samples of children with SCD (cwSCD) compared to healthy controls (HCs). Methods As part of the Sickle Cell Disease Microbiologic and Immunologic Links to Health (SMILE) study, cwSCD and HCs were enrolled at Nationwide Children’s Hospital and Children’s Healthcare of Atlanta. Sixty cwSCD and eleven HCs were enrolled during 2021-2024. Biologic samples (blood, nasopharyngeal swabs, nasal brushings) were collected at baseline health. ‘Omics assessments including metabolomics and proteomics were conducted using MetaboAnalyst, SRplot, and MOFA+ programs. All seventy-one samples underwent proteomic analyses, and fifty-five samples (48 cwSCD, 7 HC) underwent metabolomic analyses. Results At baseline, significant differences were noted between blood and airway multiomic (protein and metabolite) profiles in cwSCD compared to HCs, as well as within specimen types in cwSCD. Furthermore, two distinct metabolic profiles clustered within samples from cwSCD. Proteomics revealed that blood samples from cwSCD were enriched in chemotaxis and cell adhesion/proliferation/differentiation pathways when compared to that of HCs, with concurrent enhanced porphyrin and amino acid metabolism pathways (Figure 1). Interestingly, airway proteomics in cwSCD revealed enrichment for fibrinolysis, growth factor, and cytokine pathways when compared to blood samples from cwSCD (Figure 1). Shared upregulation of inflammatory lipid mediators was seen in both blood and airway samples of cwSCD. Analyses of longitudinal and hospitalization samples are ongoing, along with comparison to cystic fibrosis disease controls. Conclusions Multiomic analyses of blood and airway samples from cwSCD revealed both conserved and distinct inflammatory and hemolytic signatures across body sites at baseline health. This highlights our limited understanding of the physiological implications of SCD and the need for continued research into the significance of these pathways for therapeutic interventions, as well as ongoing analyses into longitudinal changes in these pathways during acute vaso-occlusive events and recovery. This abstract is funded by: NIH
Holligan et al. (Fri,) studied this question.