The Role of Neighborhood Disadvantage, Systemic Inflammation, and Acute Chest Syndrome in Children with Sickle Cell Disease
Authors: Anum Shaniqua Johnson , Rammah Amal , Symanski Elaine , Flanagan Jonathan M. , Gollamudi Jahnavi 
Published: December 2023

Introduction: Acute chest syndrome (ACS) is a frequent pulmonary complication of sickle cell disease (SCD) and is a leading cause of morbidity and mortality in both children and adults with SCD. In addition to biological factors, there is increasing recognition that social and environmental factors, such as low socioeconomic status and air pollution, respectively, play a role in disease processes. Current evidence suggests that neighborhood disadvantage influences cardiopulmonary outcomes in non-SCD populations. The disproportionate presence of polluting industries and major roadways near disadvantaged neighborhoods could impact lung health in children with SCD, and exposure to toxic metals has also been linked to worsening systemic inflammation. Yet, the impact of neighborhood disadvantage on inflammation in ACS has not been assessed. The goal of this study is to investigate the effects of neighborhood disadvantage on inflammatory markers in children presenting with ACS.

Methods: We enrolled children in our institution with SCD (all genotypes) aged 2-21 years of age with and without a history of ACS. We abstracted clinical information including sex, age, number of ACS episodes up to enrollment, and residential address. In addition, blood samples were collected during routine hematology appointments and hospitalizations for ACS. Plasma cytokine levels were measured using multiplex assays on a subset of participants. Using census tract-level data on poverty, education, housing and employment from the US Census, we computed the area deprivation index (ADI) for census tracts across the greater Houston area and assigned an ADI score to each study subject based on their geocoded address at the time of visit. We dichotomized ADI at the median value (99.0; minimum 42.4, maximum of 156.5) across the study area into “high” and “low” deprivation categories.

Results: Forty-four participants met inclusion criteria with complete ADI, clinical and cytokine data. Mean age was 11.6 years (SD 5.1), 52% were male, and 66% lived in a high ADI tract. In children over 10 years of age (n=24), there were higher levels of IL-4, IL-6, IL-8, and IL-13 in those from high ADI areas compared to those from low ADI areas [median concentrations (pg/mL): 139.2 vs 75.7, p=0.53; 17.18 vs 11.92, p=0.67; 15.85 vs 5.38, p=0.20; 19.28 vs 8.30, p=0.38, respectively]. Similarly, IL-4, IL-6, and IL-13 levels were higher in children 10 years and younger from high ADI areas, though not statistically significant. There were no differences between median ADI for patients without a history of ACS and those with recurrent ACS (107.7 vs 108.1, p=0.9).

Conclusion: In Houston children with SCD, especially 10 years and older, there were overall higher levels of systemic inflammation in those from high ADI areas compared to those from low ADI areas. However, these findings did not reach statistical significance. There was also no significant difference in ADI scores based on frequency of admissions for ACS. Future studies are needed to analyze cytokines from a larger cohort of patients with SCD and compare ACS outcomes to other regions for a more powered, comprehensive investigation.