Spirometry Reference Equations and Children of Mixed Race/Ethnicity

Racial/ethnic-based spirometry reference equations recommended in current guidelines produce biased and potentially inaccurate estimates of lung function in children with racially and ethnically mixed ancestry who also have a high variation of African ancestry, according to study results recently published in Chest.

As study authors noted, the American Thoracic Society and European Respiratory Society guidelines recommend use of racial/ethnic-based spirometry reference equations developed by the Global Lung Function Initiative (GLI) “in White, African American, North Asian, and South East Asian adults and children aged 3 to 95 years.” These equations, as well as equations of the Third National Health and Nutrition Examination Survey (NHANES III), are both based on populations in which individuals self-report their ethnic/racial background.

In the current study, investigators assessed the accuracy of these recommended racial/ethnic-based spirometry reference equations in populations of genetically admixed children (ie, children having ancestral contributions from multiple continents). The researchers assessed the cross-sectional fit of racial- and ethnic-based spirometry reference equations from case-controlled studies of asthma. They obtained anthropometry, blood samples, and spirometric measurements from 599 children, aged 8 to 21 years, who were of mixed genetic lineage. Genetic ancestry was gauged using genome-wide genotype data. Equation fit, calculated as a mean z-score, was evaluated in self-identified African American (n = 275) and Puerto Rican (n = 324) children, as was the strata of each population defined by genetic ancestry.

The investigators found that both the GLI and NHANES III equations were appropriate for children identifying as African American at the population level, providing adequate fit for predicting forced expiratory volume in the first second (FEV₁) and forced vital capacity (FVC).

However, the study found that using these equations in genetically admixed children led to misclassifications. African-American-derived equations fit well in predicting FEV₁ and FVC in children identifying as African American who had an African ancestry greater than the median (81.4% to 100.0%), but composite equations for “other” or “mixed” populations fit better in predicting FEV₁ and FVC in those with an African ancestry equal to or less than the median (30.7% to 81.3%). Children identifying as Puerto Rican who also had African ancestry equal to or less than the median (6.4%-21.3%), fared better in both FEV₁ and FVC when using equations derived from a population of White individuals; however, in those with African ancestry more than the median (21.4%-87.5%), equations derived from a White population were appropriate for FEV₁, and the composite equations fit FVC.

“Our findings suggest that African American children with African ancestry above 80% are best fit by equations derived in African American populations, whereas those with African ancestry below 80% are best fit by the GLI composite equation,” said the researchers. “Puerto Rican children with African ancestry below 20% are best fit by equations derived in White populations, whereas no single equation appropriately fits Puerto Rican children with African ancestry above 20%,” they added, noting that these children are best served using equations derived in White populations for predicting FEV₁ and the composite equation for FVC.

Investigators concluded that the current guideline-recommended equations inconsistently fit admixed children and could potentially lead to mistakes in detecting disease, poor medical management, and misjudgment of disease severity.  “Spirometry could benefit from reference equations that incorporate genetic ancestry, either for more precise application of the current equations or the derivation and utilization of new equations,” said the researchers.

Reference

Witonsky J, Elhawary JR, Eng C, Rodríguez-Santana JR, Borrell LN, Burchard EG. Racial/ethnic-based spirometry reference equations: are they accurate for genetically admixed children? Chest. Published online January 13, 2022. doi:10.1016/j.chest.2021.12.664