In “Race Adjusted for Social and Environmental Disparities Is the Principal Determinant of T2 HIGH Inflammation in Children With Severe Asthma,” Teague and colleagues report findings from an extensively characterized cohort of children with severe asthma. We recognize the value of this cohort and the importance of investigating inequities in childhood asthma outcomes. However, we are deeply concerned that the manuscript converts an observed association with caregiver-reported racial classification into claims of biological determination and suggests recommendations for race-based clinical decision-making. The publication’s most visible and influential claims give us the greatest cause for concern:
- The title identifies race as the “principal determinant” of T2-high inflammation.
- The abstract says that race and ethnicity “should guide” treatment.
- The discussion states that Black race “confers” the highest odds of inflammation.
- The manuscript concludes that unmeasured confounding is unlikely to diminish the “impact” of race.
These claims substantially exceed what the reported study design and reported measurements can establish, as discussed below:
- The authors acknowledge that race is a sociopolitical construct but then treat caregiver-reported racial classification as if it were an independent biological exposure. Statistical adjustment does not transform race into a biological trait. A remaining race coefficient can reflect racialization and its many incompletely measured consequences, residual confounding, selection, measurement error, model specification, and differences in clinical pathways. It cannot establish that race itself causes inflammation.
- The manuscript also refers to structured interview based racial self-report as “a proxy method for genetic studies.” This is scientifically inappropriate. Race, ethnicity, genetic ancestry, genetic similarity, and experiences of racism are distinct constructs. Neither caregiver-reported race nor socially assigned race is a valid substitute for genetic ancestry. Conversely, genetic ancestry would not capture racism or racialized social conditions. The repeatedly used phrase “Black race and ethnicity” further conflates race and ethnicity without enough information about how the underlying variables were elicited and combined.
The 2023 National Academies of Sciences, Engineering, and Medicine consensus report, Using Population Descriptors in Genetics and Genomics Research, specifically recommends that researchers not use race as a proxy for human genetic variation, avoid typological thinking, directly assess relevant environmental exposures, tailor descriptors to the scientific question, and disclose how labels were selected and assigned. Although this is not primarily a genomic study, the authors expressly invoke concepts of genetics and genetic ancestry, and these principles directly address the interpretive error at issue.
- The title implies that relevant social and environmental disparities were comprehensively adjusted away and that race remains a salient factor with causal potential. In fact, most of the adjustment variables are ZIP Code–level contextual proxies:
- Median area income
- Social vulnerability
- Population density
- Urban residence
- Traffic proximity
- Modeled outdoor pollution
These are not individual exposure measurements. ZIP Codes are heterogeneous administrative units that do not resolve household resources, residential history, school environments, indoor allergens, mold, pests, building quality, secondhand smoke, diet, occupation-related household exposures, personal pollutant dose, discrimination, psychosocial stress, health-care quality, or cumulative life-course exposures.
The authors acknowledge that they did not account for environmental variation within ZIP Codes, duration of residence, social mobility, neighborhood violence, vitamin D, secondhand smoke, access to specialty care, adherence, nutrition, indoor exposures, and regional land use. These omissions are not peripheral or mere limitations. They are plausible mechanisms linking racialized conditions to allergy, sensitization, inflammatory physiology, referral, treatment, and hospitalization.
It is therefore incorrect to reason that because the race coefficient remained after adjustment, measured social and environmental factors cannot explain the association. At most, the study demonstrates that the chosen variables, at their available spatial and temporal resolution and under the specified models, could not explain the entire association.
- The authors use E-values to conclude that it is unlikely that unmeasured confounding would diminish the impact of race and ethnicity. That conclusion is over broad. An E-value cannot establish that a social classification has a biological effect. Nor does it validate the causal interpretation of a coefficient when the exposure has no singular manipulable meaning.
- The clinical recommendation is unsupported and risks harm: The authors recommend that clinicians consider race when selecting treatment and suggest earlier biologics for Black children. The study directly measured eosinophils and allergen sensitization—the biological features relevant to T2-directed treatment. If those measurements are clinically indicated, they should be obtained in all eligible children. Race should not substitute for them or alter treatment thresholds. A race-based recommendation could encourage clinicians to assume T2-high disease in Black children and overlook it in children assigned to other groups, producing both overtreatment and undertreatment.
This is especially concerning because the manuscript carries the authority of a clinical-practice journal. Titles, abstracts, and “impact on management” summaries are often the most widely read portions of an article. Caveats deep in the Discussion will not neutralize a title declaring race a “principal determinant” or an abstract directing clinicians to use race in treatment decisions. Such language can be incorporated into education, clinical heuristics, reviews, artificial-intelligence systems, and future algorithms long after the original limitations are forgotten.
Our intention here is not to minimize the observed disparity or the need for further study. Rather, we affirm that the observed association may be important precisely because it signals that children classified as Black encounter different cumulative environments, exposures, and systems of care. However, describing race itself as the determinant redirects inquiry away from those mechanisms and risks naturalizing an inequity as an innate characteristic of Black children.
The scientifically and clinically responsible conclusion is narrower: in this selected cohort, caregiver-reported Black racial classification was associated with greater odds of meeting the study’s T2-high definition after adjustment for the measured covariates. The mechanisms remain unresolved. Treatment should be guided by directly measured phenotype, clinical history, and therapeutic response.
We believe prompt correction is important to prevent an unsupported race-based clinical message from being incorporated into asthma care and future research.
Sincerely,
Ariangela J. Kozik, PhD
Khalil Savary, MD
Stephanie Lovinsky-Desir, MD, MS