Moving Away from Segregated Lung Function Equations: Effects of Transitioning to Race-Neutral References in Children

In the United States, minority populations, particularly the Black population, have consistently borne a disproportionate burden of asthma risk and morbidity and have historically exhibited lower average lung function than their White peers. The erroneous attribution of low baseline lung function to race (a social rather than physiologic construct) led to acceptance of lower lung function trajectories as “normal” for Black individuals (1, 2). Because spirometry constitutes the main objective clinical marker of airway function, this led to systematic normalization of lung disease in this population, further perpetuating and exacerbating health inequities (3, 4). Recently, there has been increasing recognition of the failures caused by artificial race “corrections” or segregations in various areas of medicine, and lung function references have been no exception.

The Global Lung Function Initiative global reference equations (GLI-Global) differ from previous race-specific equations in that data from populations of different ancestral origins were pooled to better represent a “global” population (5). GLI-Global included data from 74,000 White, Black, Northeast Asian, and Southeast Asian individuals and employed careful methodology to ensure that each group contributed equal proportions to the equations. The American Thoracic Society and European Respiratory Society now recommend the use of “race-neutral” z-scores to track lung function and quantify impairment in lung disease (5, 6).

The increasing adoption of race-neutral equations has appropriately prompted examination of the clinical impacts for different patient populations. In adults with chronic obstructive pulmonary disease, GLI-Global z-scores demonstrated better correspondence with exacerbation risk than Global Initiative for Chronic Obstructive Lung Disease–National Health and Nutrition Examination Survey fixed parameters, suggesting that GLI-Global more accurately estimated disease severity (7). A retrospective analysis of patients listed for lung transplant showed that transition from race-specific to GLI-Global reference equations would have increased the proportion of Black patients meeting transplant criteria and would have shortened their wait times (8). Although the most recent Lung Allocation Scores no longer include FVC, this further illustrates the shortcomings of race-specific spirometry references. Within the pediatric population, a recent study including 24,000 children demonstrated that transition from race-specific to GLI-Global equations caused an almost −1.0 change in FEV₁ z-score (zFEV₁) and zFVC for Black children (9). However, the potential effects on asthma diagnosis and management have not been well described.

In this issue of the Journal, Non and colleagues (pp. 464–476) explore the implications of adopting GLI-Global equations in pediatrics, including lung function impairment classification and relationship between z-scores and asthma diagnosis and healthcare use (10). The authors leveraged data from the Environmental Influences on Child Health Outcomes (ECHO) Program, a “cohort of cohorts” that consists of over 65,000 children from 69 sites throughout the United States (11). Within ECHO, the authors focused on 8,719 children 5–12 years old who had spirometry measurements. This nested cohort included 2,014 (24%) children with asthma. Importantly, the cohort was diverse in terms of parent-reported race and ethnicity (54% White, 19% Black, 19% Hispanic, and 8% other, including 5% multiracial).

The clearest findings from the analysis were the implications for Black children. Switching from race-specific equations to GLI-Global, the proportion of Black children classified as having low lung function increased from 5% to 19%, and those with a moderate to severe zFEV₁ deficit increased from 1% to 4.5%. The effect on White, Asian, and Hispanic children was modest, with changes of <2% in both classifications. Of note, FEV₁/FVC z-scores remained lower for Black children than for the other groups, regardless of reference equations used. The authors also examined the impact of race-neutral equations on pediatric asthma. Consistent with known epidemiologic data, Black children were more likely to have asthma and asthma-related emergency department visits or hospitalizations. For Black children, changing from race-specific to GLI-Global equations shifted the relationship between asthma probability and zFEV₁, meaning that for any given zFEV₁, the probability of asthma for Black children was closer to that of other groups, although still elevated compared with White children. Conversely, for a given probability of asthma, zFEV₁ was lower for Black children using GLI-Global than with race-specific equations. As a result, disparities in asthma diagnosis proportions between White and Black children with a given zFEV₁ were partially reduced. Moreover, using GLI-Global revealed that Black children with asthma tend to have lower lung function than their peers of reported White race. A similar pattern was seen for the relationship between zFEV₁ and the probability of emergency department visit or hospitalization for asthma. These findings reinforce the appropriateness of using race-neutral predictive equations in children.

The study by Non and colleagues has several significant strengths, including the large sample size from across the United States, the large proportion of non-White participants reflecting our diverse population, and the evaluation of not only changes in lung function z-scores but also the relationship between lung function, asthma diagnosis, and healthcare use. However, restriction of the analysis to prepubertal children limits generalizability to older age groups. Emergency department visits and hospitalizations were dichotomized into “none versus any,” likely because of the low frequency of the outcomes. Including other clinical outcomes such as symptom control would have improved estimation of the clinical impact from changing equations.

Significant clinical implications are anticipated for this reclassification of lung function, but long-term effects are still unknown. The adoption of race-neutral reference equations will have implications for children of all racial backgrounds, most markedly for Black children. A higher proportion of Black children will be classified as having low lung function, which may be more commensurate with their asthma morbidity. Recognizing low lung function may allow more appropriate and timely asthma management, population-based interventions for vulnerable communities, and ultimately better asthma control. With the adoption of race-neutral equations, we may see shifts in prescribing practices for controller medications and biologics. Future study is needed to measure the effects of the change to race-neutral equations in terms of asthma treatment, morbidity, and acute care use.

Our role as stewards of lung health is to advocate for the respiratory well-being of all. The use of race-specific reference equations has historically meant normalizing lower lung function in vulnerable populations, thus perpetuating the harm incurred by these individuals for generations. Although changing to race-neutral lung function equations will by no means erase the inequities of the past, it is an important step forward in acknowledging the disparities in lung health that are still present today.