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Multicenter Study
. 2024 Jul 1;178(7):699-706.
doi: 10.1001/jamapediatrics.2024.1341.

Spirometry Interpretation After Implementation of Race-Neutral Reference Equations in Children

Affiliations
Multicenter Study

Spirometry Interpretation After Implementation of Race-Neutral Reference Equations in Children

Erick Forno et al. JAMA Pediatr. .

Abstract

Importance: The implications of adopting race-neutral reference equations on spirometry interpretation in children remain unknown.

Objective: To examine how spirometry results and patterns change when transitioning from Global Lung Function Initiative (GLI) race-specific reference equations (GLIR, 2012) to GLI race-neutral reference equations (GLIN, 2023).

Design, setting, and participants: Cross-sectional study of spirometry tests conducted in children aged 6 to 21 years between 2012 and 2022 at 2 large academic pediatric institutions in the US. Data were analyzed from September 2023 to March 2024.

Exposures: Data on participant characteristics and raw test measurements were collected. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC z scores and percent predicted were calculated using both GLIR and GLIN. In addition, test results were categorized into normal, obstructive, suspected restrictive, mixed, suspected dysanapsis, and uncategorized patterns based on z scores calculated using GLIR or GLIN.

Main outcomes: For each spirometry result, the difference between z scores and percent predicted when transitioning from GLIR to GLIN was calculated. The proportion of tests with a normal pattern and individual spirometry patterns changed by GLI reference equation applied were also examined.

Results: Data from 24 630 children were analyzed (mean [SD] age, 12.1 [3.8] years). There were 3848 Black children (15.6%), 19 503 White children (79.2%), and 1279 children of other races (5.2%). Following implementation of GLIN, FEV1 and FVC z scores decreased in Black children (mean difference, -0.814; 95% CI, -0.823 to -0.806; P < .001; and -0.911; 95% CI, -0.921 to -0.902; P < .001, respectively), while FEV1 and FVC z scores slightly increased (0.073; 95% CI, 0.069 to 0.076; P < .001). Similar changes were found when using percent predicted. In Black children, the number of tests with a normal pattern decreased from 2642 (68.7%) to 2383 (61.9%) (χ21 = 204.81; P < .001), mostly due to tests with a normal pattern transitioning to a suspected restrictive or uncategorized pattern. Opposite, albeit smaller, changes in spirometry results and patterns were seen in White children. In adjusted models, Black children had approximately 3-fold higher odds than White children of changing spirometry pattern following the implementation of GLIN (adjusted odds ratio, 3.15; 95% CI, 2.86 to 3.48; P < .001).

Conclusions: Pronounced differences in spirometry results and patterns were found when switching between GLI reference equations, which markedly differed by race. These findings suggest that the implementation of GLIN is likely to change the treatment of children with chronic lung diseases that are more prevalent in underrepresented minorities, such as asthma.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Forno reported receiving grant funding from the National Institutes of Health (NIH) and National Science Foundation. Dr Rosas-Salazar reported receiving grant funding from the NIH and has served as a consultant for AstraZeneca and The KOL Connection. No other conflicts were reported.

Figures

Figure 1.
Figure 1.. Changes in Spirometry Results Between Global Lung Function Initiative (GLI) Reference Equations in All Children by Race
The histograms show the distribution of the calculated differences in FEV1, FVC, and FEV/FVC z scores (A-C, respectively) and percent predicted values (D-F, respectively) between GLI reference equations in children of Black, White, and other race (indicated by the colors), with positive values indicating an increase in each spirometry result when transitioning from GLI race-specific reference equations to GLI race-neutral reference equations and vice versa. Other race includes Northeast Asian, Southeast Asian, and other or mixed as per GLI race-specific reference equations.
Figure 2.
Figure 2.. Changes in Spirometry Patterns Between Global Lung Function Initiative (GLI) Reference Equations in All Children by Race
The alluvial plots show shifts in spirometry patterns between GLI reference equations in children of Black (A), White (B), and other (C) race. In each alluvial plot, the stacked bars show the proportion of spirometry patterns (indicated by the colors) using GLI race-specific reference equations (GLIR, left) and GLI race-neutral reference equations (GLIN, right). The bands between stacked bars illustrate how spirometry patterns transitioned following the implementation of GLIR, with the bands’ widths depicting the proportion of the change. For each spirometry pattern, bands that represent 10% or greater change are labeled. Other race includes Northeast Asian, Southeast Asian, and other or mixed as per GLIR.
Figure 3.
Figure 3.. Changes in Spirometry Patterns Between Global Lung Function Initiative (GLI) Reference Equations in Children With Asthma by Race
The alluvial plots show shifts in spirometry patterns between GLI reference equations in children with asthma of Black (A), White (B), and other (C) race. In each alluvial plot, the stacked bars show the proportion of spirometry patterns (indicated by the colors) using GLI race-specific reference equations (GLIR, left) and GLI race-neutral reference equations (GLIR, right). The bands between stacked bars illustrate how spirometry patterns transitioned following the implementation of GLIR, with the bands’ widths depicting the proportion of the change. For each spirometry pattern, bands that represent 10% or greater change are labeled. Other race includes Northeast Asian, Southeast Asian, and other or mixed as per GLI race-specific reference equations.

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