Racial/ethnic-based spirometry reference equations: Are they accurate for admixed populations?

ABSTRACT BACKGROUND Variation in genetic ancestry among admixed racial/ethnic groups may influence the fit of guideline-recommended spirometry reference equations, which rely on self-identified race/ethnicity. RESEARCH QUESTION What is the influence of genetic ancestry on the fit of the guideline-recommended racial/ethnic-based spirometry reference equations in populations of genetically admixed children? STUDY DESIGN AND METHODS Cross-sectional fit of guideline-recommended racial/ethnic-based spirometry reference equations was evaluated in control subjects from case-control studies of asthma. Anthropometry, blood samples, and spirometric measurements were obtained in 599 healthy admixed children, aged 8 to 21-years. Genetic ancestry was estimated using genome-wide genotype data. Equation fit was determined as a mean z-score between -0.5 and 0.5 and assessed in self-identified African American (N = 275) and Puerto Rican (N = 324) children using the distribution to determine cut points of genetic ancestry. RESULTS For African American children, African American-derived equations fit for predicting FEV 1 and FVC in those with an African ancestry above the median (81-100%), whereas composite equations for “other/mixed” populations fit for predicting FEV 1 and FVC in those with an African ancestry below the median (31-81%). Among Puerto Rican children, White-derived equations fit for predicting FEV 1 , and the composite equations fit for predicting FVC for those with African ancestry above the median (21-88%). In contrast, in Puerto Rican children with African ancestry below the median (6-21%), only equations derived in Whites provide an adequate fit. INTERPRETATION Guideline-recommended spirometry reference equations yielded biased estimates of lung function in admixed populations with high variation of African ancestry. Spirometry is due for reference equations that incorporate genetic ancestry, either for more precise application of the current equations or the derivation and utilization of new equations.