Sickle-Cell Trait and Atopic and Inflammatory Disease in Children

Roughly 9% of African-Americans carry 1 copy of the sickle β-globin allele [sickle-cell trait (SCT)]. The sickle allele may affect the host responses in a way that protects against sequelae of malaria. Besides the association with sporadic episodes of erythrocyte sickling, acute chest syndrome, and sudden death, the SCT is generally regarded as asymptomatic. Separately, and for unclear reasons, the African-Americans have an elevated risk compared to whites for several immune-mediated diseases, including asthma, eczema, and other respiratory conditions. We propose to determine whether the SCT contributes to the elevated risk of these inflammatory conditions. We performed a retrospective cohort study of children with and without the sickle trait to assess the risk for common immune-mediated conditions. The cohorts were individually matched, and multiple logistic regression was used with variables selected using a backward stepwise approach. A second approach (case-control design) assessed the odds of the SCT among African-Americans with and without asthma. We found 2,481 children with and 4,962 matched patients without the SCT in the cohort design. The sickle trait was associated with greater odds for several immune-mediated conditions in a multivariable analysis, but not associated with asthma (odds ratio, OR=1.10, P=0.212). In an adjusted case-control analysis (n=20,000), the sickle trait was weakly associated with asthma [adjusted odds ratio (aOR)=1.46, 1.01-2.13]. In both the designs and in all statistical models used, we found that the SCT was associated with bronchitis (aOR=1.71, 1.09-2.67) and eczema (aOR=1.74, 1.23-2.46). The SCT may contribute to an increased risk for eczema and asthma-like symptoms in the African-American children.