To the Editor,
A major public health concern, food allergy (FA) affects nearly 8% of children in the United States and the prevalence of FA is increasing.1,2 African American (AA) children with FA are at higher risk of developing other atopic comorbidities such as allergic rhinitis and asthma, compared to White children.1,3 Among common food allergens, shellfish allergies are more prevalent among AA children than White children. Additionally, AA children are more likely to be sensitized to cockroach and house dust mite (HDM) compared to White children.3 Shellfish, HDM, and cockroach all share homology across the conserved peptide chain, tropomyosin.4,5 This study aimed to quantify the extent to which sensitization to cockroach and HDM may influence allergy to shellfish and mediate racial differences in allergy outcomes.
Data for the current analyses were derived from the Food Allergy Outcomes Related to White and African American Racial Differences (FORWARD) study, which is a NIH-funded, multicenter prospective cohort of AA, Hispanic/Latinx, and White children with FA at four urban tertiary centers in the United States.3 These centers include Lurie Children’s Hospital and Rush University Medical Center (RUMC) in Chicago, IL, Cincinnati Children’s Medical Center (CCHMC) in Cincinnati, OH, and Children’s National in Washington, DC.
Adjusted logistic regression models were constructed to estimate the odds of a shellfish allergy for AA children compared to White children, while adjusting for sex, age at enrollment, geographic location, and indicators for cockroach and HDM sensitization. Allergy to shellfish was confirmed by chart review and defined by history of IgE-mediated symptoms after consumption of shellfish, a positive skin prick test (SPT), or elevated specific IgE. Sensitization to cockroach and HDM were defined by a positive SPT or elevated specific IgE to cockroach or HDM.
The mediation analysis reports the decomposed effect of the relationship between racial groups and shellfish allergy into the direct pathway and indirect pathway. The indirect pathway between race and shellfish allergy is defined as the effect of the relationship between the two that is mediated through cockroach and HDM sensitization, while the direct effect is understood as the effect of the relationship between the two that is represented by the combination of direct effects and pathways not accounted for in this model. Inferences were made with 50 replications of the bootstrapped standard errors. All statistical analyses were completed using Stata 15 (StataCorp. 2017. Stata Statistical Software: Release 15; College Station, TX: StataCorp LLC.)
In this cohort, 194 children had an environmental allergen result for both HDM and cockroach: 85 White children and 109 African American children were included. Rates of HDM sensitization were significantly higher among AA than White children (55.0% vs. 27.1%, p < .001). Rates of cockroach sensitization were also significantly higher among AA than White children (45.9% vs. 25.9%, p = .004). (Table 1).
TABLE 1.
Demographic and clinical characteristics of population by race
| Total | White non-Hispanic or Latino | African American non-Hispanic or Latino | ||
|---|---|---|---|---|
| N = 194 | N = 85 | N = 109 | p-Value | |
| Gender | .024 | |||
| Male | 120 (61.9%) | 45 (52.9%) | 75 (68.8%) | |
| Female | 74 (38.1%) | 40 (47.1%) | 34 (31.2%) | |
| Enrollment site | .010 | |||
| Cincinnati Children’s | 23 (11.9%) | 16 (18.8%) | 7 (6.4%) | |
| Children’s National | 38 (19.6%) | 12 (14.1%) | 26 (23.9%) | |
| Lurie Children’s | 73 (37.6%) | 36 (42.4%) | 37 (33.9%) | |
| Rush Children’s | 60 (30.9%) | 21 (24.7%) | 39 (35.8%) | |
| Dust mite test | <.001 | |||
| Positive | 83 (42.8%) | 23 (27.1%) | 60 (55.0%) | |
| Cockroach test | .004 | |||
| Positive | 72 (37.1%) | 22 (25.9%) | 50 (45.9%) | |
| Shellfish allergy | <.001 | |||
| Yes | 44 (22.7%) | 9 (10.6%) | 35 (32.1%) | |
| Age at enrollment | 7.2 (3.3) | 6.7 (3.2) | 7.7 (3.2) | .035 |
AA children had increased odds of shellfish allergy (OR: 2.5, 95% CI: 1.0, 6.3) compared to White children when holding all other variables constant (Table 2). Sensitization to HDM (OR: 3.8, 95% CI: 1.4, and sensitization to cockroach (OR: 3.4, 95% CI: 1.3, 8.6) were both associated with increased odds of shellfish allergy.
TABLE 2.
Adjusted logistic regression of shellfish allergy
| Shellfish allergy | |
|---|---|
| Race (Ref.: Non-Hispanic White) | |
| Non-Hispanic African American | 2.5* (1.0,6.3) |
| Dust mite test | 3.8** (1.4,10.1) |
| Cockroach test | 3.4* (1.3,8.6) |
| Sex (Ref.: Male) | |
| Female | 0.9 (0.4,2.1) |
| Enrollment site (Ref: Northwestern/Lurie) | |
| Cincinnati Children’s | 0.7 (0.1,3.2) |
| Children’s National | 0.7 (0.2,2.3) |
| Rush Children’s | 0.4 (0.2,1.1) |
| Age at enrollment (Years) | 1.1 (1.0,1.2) |
Note: Exponentiated coefficients; 95% confidence intervals in brackets.
p < .05,
p < .01.
The results of the mediation analysis (Figure 1) revealed that race (AA vs. White) was associated with a total (indirect and direct) increased odds of shellfish allergy (OR: 4.0, 95% CI: 1.5, 10.7). The decomposed indirect effect mediated through cockroach and HDM sensitization was associated with increased odds of shellfish allergy (OR: 1.8, 95% CI: 1.2, 2.7), and this indirect effect constituted 41.9% of the total association between race/ethnicity and shellfish allergy. The direct effect of race was not significantly associated with shellfish allergy (OR: 2.2, 95% CI: 1.0, 5.1) after accounting for the indirect pathway.
FIGURE 1.
Mediation analysis of race, cockroach sensitization, and shellfish allergy.
In this multicenter longitudinal cohort study, we observed a significant association between race and shellfish allergy. AA children are at more than twice the risk of being allergic to shellfish, and children sensitized to HDM or cockroach have a threefold increased risk of shellfish allergy. (Table 1). A previous study suggests that sensitization to shellfish might occur through inhalation of the similarly structured protein found in cockroach and HDM, tropomyosin.4 There is a high amino acid sequence similarity among HDM (Der f 10), cockroach tropomyosin (Per a 7), and shrimp tropomyosin (Pen a 1).5 The mediation analysis revealed that approximately 42% of the relationship between race and shellfish allergy may be explained by the relationship between race and sensitization to HDM and cockroach, and the relationship between these environmental allergens and shellfish allergy. Additionally, after adjusting for this indirect, environment-mediated pathway, evidence for a direct relationship between race and shellfish allergy largely diminished, suggesting that these environmental allergens may have been driving the previously observed and well-defined relationship between race and shellfish allergy.
An inner-city asthma study has shown that shrimp, cockroach, and HDM IgE levels were highly correlated.6 This study demonstrated that high exposure to cockroach in the home was significantly associated with higher shrimp and cockroach IgE levels.6 The study also showed an association between an immunologic response and sensitization to shellfish, cockroach, and HDM. Our data further advance this understanding by demonstrating a significant link between clinical FA to shellfish and sensitization to cockroach and HDM. It is notable that the majority of AA participants in our cohort reside in socioeconomically disadvantaged areas of Chicago, where cockroach sensitization remains an environmental challenge, especially among urban minority youth.7 An increased respiratory exposure due to higher levels of cockroach allergen in low socioeconomic inner-city areas may provoke cross-sensitization to shellfish allergy in these vulnerable children.
AA children with FA have higher rates of AR and allergic asthma3 and have also been observed to be at higher risk of sensitization to HDM and cockroach.8 This is pertinent to FA because uncontrolled asthma is a risk factor for fatal anaphylaxis in the FA setting,9 which places these AA children with cockroach and HDM sensitization at potentially greater risk of severe reaction to shellfish. This is especially important in the context of previously reported two- to threefold greater risk of fatal food-induced anaphylaxis in AA children relative to White children.10 This study contains several important limitations. First, the children recruited into the FORWARD study are recruited from urban allergy and immunology clinics and therefore may not represent all food-allergic children. Second, although the results provide evidence for the indirect pathway, lack of temporal information limits the ability to draw causal conclusions. Finally, while the model constructed for the mediation analysis represents the most current understanding of FA development, model misspecification, unmeasured confounding, and structural uncertainty may all have introduced bias into the conclusions drawn.
AA children experience higher rates of shellfish allergy, and those living in inner-city neighborhoods are impacted by several interrelated socioeconomic and environmental risk factors such as high exposure to cockroach and HDM. Current data support the hypothesis that tropomyosin is an important link between shellfish allergy, and cockroach and HDM sensitization.4,5 This study builds on this hypothesis and offers evidence to support the conclusion that the racial differences observed in shellfish allergy may be mediated by sensitization to cockroach and HDM. This calls for efforts to improve housing conditions that drive sensitization to cockroach and HDM and may ultimately drive rates of shellfish allergy, particularly among AA children.
FUNDING INFORMATION
National Institutes of Health, Grant/Award Number: R01 AI130384
Footnotes
CONFLICT OF INTEREST
We wish to confirm that there are no known conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome. Furthermore, the listed authors testify on behalf of all members of the FORWARD group that they have no conflicts of interest associated with this publication.
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