Race- and Ethnicity-Based Spirometry Reference Equations: Are They Accurate for Genetically Admixed Children?

Area of Science:

• Pulmonary Medicine
• Genetics
• Pediatrics

Background:

• Spirometry reference equations often rely on self-identified race and ethnicity.
• Genetic ancestry variation in admixed populations may affect equation accuracy.
• Current guidelines may not adequately account for genetic diversity.

Purpose of the Study:

• To investigate the influence of genetic ancestry on spirometry reference equation fit in genetically admixed children.
• To evaluate the accuracy of existing race- and ethnicity-based equations in diverse pediatric populations.
• To determine if genetic ancestry improves lung function prediction in children.

Main Methods:

• Cross-sectional study of 599 healthy children (8-21 years) from case-control asthma studies.
• Spirometry, anthropometry, and blood samples collected.
• Genetic ancestry estimated using genome-wide genotype data.
• Fit of guideline-recommended equations assessed using mean z scores in self-identified African American and Puerto Rican children, stratified by genetic ancestry.

Main Results:

• African American-derived equations showed better fit for predicting FEV1 and FVC in children with higher African ancestry.
• Composite equations performed better for those with lower African ancestry.
• For Puerto Rican children, White-derived equations fit best for lower African ancestry, while White and composite equations were used for higher African ancestry.
• Significant bias observed in spirometry estimates based on current equations.

Conclusions:

• Guideline-recommended spirometry equations produce biased lung function estimates in genetically admixed children.
• Incorporating genetic ancestry into spirometry reference equations is crucial for accuracy.
• Future spirometry equations should consider genetic ancestry for improved precision or new derivations.