We investigated the role of race/ethnicity in the derivation of reference equations in 2 large multiethnic cohorts. We found that effect modification by race/ethnicity explained less than 1% of the variability in lung function, although the mean lung function for a given age and height was lower for participants of African origin compared with whites. Spirometry reference equations that consider race/ethnic groups pooled together are justified statistically and were found to improve precision compared with race/ethnic-specific equations.
When the currently recommended, race/ethnic-specific reference equations were developed more than 10 years ago, consideration was given to deriving a single reference equation for all race/ethnic groups (6
). However, the authors ultimately decided to follow the 1991 ATS recommendations to select reference equations on the basis of the “ethnic origin” of the subjects being tested and to avoid potential extrapolation of data (16
), given the relatively limited overlap in the range of height of Mexican Americans and whites in NHANES III.
The single, multiethnic equations presented here can address some, but not all, of the problems with race/ethnic-specific reference equations that we previously outlined. First, the multiethnic equations have improved precision because they are derived from the full cohort instead of from smaller samples for each race/ethnicity. and show similar slopes and similar predicted values for the predicted FEV1
by using the additive equation derived here compared with the 1999 NHANES III-derived equations. However, the mean width of the 95% confidence interval for the predicted FEV1
among women using separate equations was approximately 100 mL for each race/ethnic group. Although a minimal, clinically important difference for the FEV1
has not been firmly established, there has been some suggestion that a change in FEV1
of 100 mL can be perceived by patients (17
). Using the single reference equation decreases the width of the confidence interval for predicted FEV1
in women by approximately one third.
Second, as race/ethnic-specific reference equations are problematic for patients of multiple race/ethnic backgrounds, multiethnic equations would be valuable for patients of mixed race/ethnicity. For some mixed-race/ethnicities, such as Mexican Americans, our findings suggest that mean lung volumes are the same among Mexican Americans and whites of the same age and height. However, main effect terms are required for African Americans, Chinese Americans, and non-Mexican Hispanics, reflecting mean differences in lung function compared with those of whites of the same age and height that are observed, but that are not fully accounted for in the literature (2
The inclusion of race/ethnic terms implies that one would still need to identify an individual's race/ethnicity to determine the inclusion of these terms in the prediction equations. However, the size of the coefficient could be adjusted on the basis of ancestry, something that is not feasible for the race-specific equations (18
). As ancestral informative markers become increasingly available in research and ultimately clinical settings, this coefficient could be individualized much more easily than could race/ethnic-specific equations.
Finally, despite the longstanding approach of separate reference equations by race/ethnicity, relatively few studies have examined this issue. Jacobs et al. (3
) found significant interactions for FEV1
and FVC among whites and African Americans by using the interaction terms of race/ethnicity by sex by frame size. However, this 3-way interaction term is difficult to compare with the NHANES III reference equations, because the latter are stratified by gender due to effect modification by gender. A second small study of 80 Asian Americans and whites reported different relations of age and height to FVC (i.e., different slopes for the regression line) but not to FEV1
). This finding was probably a false positive given that we were unable to replicate the findings in the MESA Lung Study, which included a much larger sample of Chinese Americans.
Sitting height has been suggested to account for a proportion of race/ethnic discrepancy. In the 1999 NHANES III reference equation derivations (6
), sitting height explained some variability by race/ethnicity in a common equation that included all race/ethnicities but was less accurate than separate equations that did not include sitting height. The addition of sitting height did not improve separate race/ethnic equations that contained standing height. However, sitting height includes only one dimension of thoracic size, and the similar predicted FEV1
/FVC ratio among whites, African Americans, and Mexican Americans suggests that there are proportional differences related to frame size.
A strength of this investigation was the replication of the NHANES III findings in another cohort, the MESA Lung Study, which included non-Mexican Hispanic Americans and Chinese Americans. Both cohorts were multiethnic and used very similar spirometry methods. Predicted spirometry values in MESA calculated from the equations derived here produce values similar to observed MESA spirometry; similar results were previously obtained by applying the 1999 NHANES-derived equations to MESA (14
We limited this analysis to adults who had likely achieved a plateau in lung function value with age and, hence, avoided the need for spline-based approaches, which are more important for pediatric samples (10
). Direct inferences were therefore available from the linear models. However, our general findings are also likely to apply to spline-based approaches.
We acknowledge that there is some variation in predicted spirometry depending on which prediction equation is used. Comparing the 1999 NHANES-derived equations with equations derived here yields similar results for the equation derived on an additive scale, but a difference of greater than 10% on the log scale. This variation is slightly higher than the inherent variability of greater than 5% that can occur within an individual and a similar variability between spirometers. However, the primary intent of this paper was not to create new reference equations, but to fully investigate the issue of race/ethnicity in spirometry.
In summary, our findings show that there was no evidence of interaction by race/ethnicity on an additive or log scale in 2 large multiethnic cohorts. Less than 1% of the variability in lung function was explained by interaction terms for race/ethnicity across the 3 major US race/ethnic groups. Multiethnic rather than race/ethnic-specific spirometry reference equations are applicable for the US population.