Brandi Pernell

Objectives: Pulmonary complications heavily contribute to poor health outcomes among children with sickle cell disease (SCD). Air pollution is strongly associated with poor pulmonary health, including abnormal pulmonary function, but is understudied in SCD. This study aimed to test the hypothesis that higher ambient air pollution exposures would be associated with increased odds of abnormal lung function among children with SCD. Methods: Monthly average ambient air pollution concentrations and pulmonary function tests (PFTs) were analyzed for 65 children with SCD that resided in Jefferson County, Alabama between 2010 and 2019. Logistic regressions were employed to assess the association between ambient air pollution levels and abnormal PFTs, both unadjusted and adjusted for sex, age, SCD genotype, asthma, and SCD-modifying therapies. Results: Among all criteria air pollutants, elevated concentrations of nitrogen dioxide (NO2) were significantly associated with PFT abnormality. Specifically, a 1 ppb increase in monthly average NO2 concentrations was associated with a higher odds of lower function in the large/medium airways (odds ratio 1.53; 95% CI: 1.01-2.33; P = .047). Conclusion: This is the first study to date demonstrating a connection between NO2 exposure and abnormal pulmonary function among children with SCD. These findings are an important contribution to the growing body of SCD-pollution literature. Given that impaired lung function is a key driver of SCD-related morbidity and mortality, this study lays the groundwork for future investigations into modifiable environmental risk factors for poor SCD-lung health.

Objectives: Asthma is strongly associated with poor health amongst individuals with SCD. Adverse Childhood Experiences (ACEs) are traumatic experiences occurring before 18 years of age. ACEs occur at the individual and familial (original ACEs) levels and expand to the community level (additional ACEs). Chronic exposure to ACEs leads to toxic stress, inflammation, and risk for chronic illnesses, including asthma. This study examined the relationship between ACEs and asthma among children and adolescents with SCD. Methods: Employing a cross-sectional study design, 75 children/adolescents with SCD were screened for ACEs. Prevalence ratios and logistic regressions were used to test the association and independent relationship between ACEs and asthma. Results: Fifty-nine (78%) participants reported exposure to at least 1 ACE. Adolescents exposed to ≥2 original- or ≥4 expanded ACEs (original + additional) were 1.15 times as likely to have asthma compared to those with no/low ACEs (95% CI: 1.03, 1.28, P = .01; 1.07, 1.24, P ≤ .001). Through logistic regression analyses, covarying age, sex, SCD genotype, income, and disease-modifying therapy, original (OR 1.52, 95% CI: 1.031, 2.242), additional (2.43, 95% CI: 1.335, 4.421), and expanded ACEs (1.529, 95% CI: 1.149, 2.036) were all shown to be independently associated with asthma. Conclusion: The findings from this research support our hypothesis that children/adolescents with SCD exposed to a higher number of ACEs have a higher prevalence of asthma compared to low-exposed subjects. This study lays the foundation for future longitudinal and interventional studies aimed to improve SCD-asthma outcomes through ACE-protective mechanisms.

Background: Adverse childhood experiences (ACEs) are linked to poor health outcomes; however, the relationship between ACEs and health outcomes among children and adolescents with sickle cell disease (SCD) has limited documentation in the published literature.Procedure: This retrospective cohort study involved 45 children and 30 adolescents. Participants were screened using the Center for Youth Wellness ACE Questionnaire. Parents completed the questionnaire for children. Adolescents provided self‐report. ACEs were treated as continuous and categorical scales: 0–1 verus ≥2 original ACEs (individual and/or familial level); 0–1 versus ≥2 additional ACEs (community level); and 0–3 versus ≥4 expanded ACEs (original + additional). Pain and acute chest syndrome events were compared using Wilcoxon rank‐sum tests, and correlated with cumulative ACE scores using Spearman's correlation. Multivariable models were fitted to examine the association between ACEs and pain/acute chest syndrome.Results: The cumulative number of original ACEs positively correlated with acute chest syndrome events (rho = .53, p = .003) and pain (rho = .40, p = .028) among adolescents. Adolescents with ≥2 versus 0–1 original ACEs had a higher number of acute chest syndrome events (4.9 ± 2.6 vs. 1.6 ± 2.2, p = .002); however, this association was confounded by asthma. Acute chest syndrome events and hospitalizations for pain did not differ among child ACE groups. Emergency department (ED) pain visits were higher among children with ≥4 versus 0–3 expanded ACEs (1.6 ± 2.8 vs. 3.3 ± 3.2, p = .042), even after controlling for SCD genotype, asthma, disease‐modifying treatment, and follow‐up years (p = .027).Conclusion: ACEs are linked to increased morbidity among children and adolescents with SCD. Prospective studies are needed to further understand this relationship and test ACE‐protective remedies.

IMPACT: This research highlights Adverse Childhood Experiences as a potential risk factor and intervention target contributing to the disproportionate number of individuals with sickle cell disease affected by asthma, a well-established catalyst to the increased morbidity and mortality impacting this high-risk population. OBJECTIVES/GOALS: Adverse Childhood Experiences (ACEs) are strongly associated with asthma. A disproportionate number of individuals with sickle cell disease (SCD) also have asthma. Asthma is strongly associated with increased SCD morbidity and mortality. This study compared the prevalence of asthma among children and adolescents with SCD with and without ACEs. METHODS/STUDY POPULATION: This retrospective cohort study involved 45 children and 30 adolescents with SCD. ACEs were captured using the Center for Youth Wellness Adverse Childhood Experiences Child and Teen Questionnaires, which encompass the original 10 ACEs as well as 7 (child) and 9 (teen) expert-recommended ('expanded') ACEs. ACE exposures were categorized as: Original 0-1 vs. ≥2; Original + Expanded 0-1 vs. ≥2. Asthma prevalence was compared among ≥2 and 0-1 ACE groups using the chi-square (or Fisher’s exact) test. A binary logistic regression was performed to predict the likelihood of asthma while adjusting for characteristics (age, household income and gender) that were statistically different among ACE comparison groups at baseline. RESULTS/ANTICIPATED RESULTS: Among the 45 child participants, 64% had a history of asthma; whereas 50% of teens had a history of asthma. Asthma prevalence was higher among teens with ≥2 vs. 0-1 Original ACEs (89% v. 33%, p=0.014). A history of ≥2 ACEs remained significant (p=0.024) among teens after adjusting for age, household income and gender. There was no significance in asthma prevalence among child ACE comparison groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: Adolescents with ≥2 ACEs had a higher prevalence of asthma compared to subjects with 0-1 ACE. This study, coupled with the cumulative nature of ACEs and the graded-dose response relationship between ACEs and poor health outcomes, highlight the need for larger, longitudinal studies examining the relationship between ACEs, asthma and SCD outcomes.