Background
Accurate interpretation of pulmonary function test results, which requires valid spirometry reference values, is of material importance to respiratory medicine. In addition to gender, age, and height, race/ethnicity acts as another major determinant of lung function [
1‐
3]. Therefore, it is recommended that spirometry reference values established with healthy people of similar race/ethnicity be applied to a certain population whenever possible. The European Respiratory Society (ERS)/American Thoracic Society (ATS) recommended spirometry reference values that were based on a sample from the third National Health and Nutrition Examination Survey (NHANES III) for population aged 8–80 years in US [
4,
5]. Nonetheless, limited by race/ethnicity classification in NHANES III, spirometry reference values for Asian Americans were unable to be produced through Hankinson et al.’s study [
5].
Previous studies showed that Asian Americans had clinically significantly lower forced expiratory volume in 1 s (FEV
1) and forced vital capacity (FVC) compared with Caucasian people in US [
6‐
11]. Accordingly, a correction factor for FEV
1 and FVC has been developed and calibrated to be applied to NHANES III Caucasian equations when assessing spirometry in Asian Americans. Specifically, 0.94 and 0.88 have been sequentially proposed as the correction factor for FEV
1 and FVC [
4,
12,
13]. A recent systemic review suggested that a correction factor of 0.88 was more suitable than 0.94 to be applied to NHANES III Caucasian reference values for FEV
1 and FVC evaluation in Asian Americans [
14].
In 2012, the Global Lung Function Initiative (GLI-2012) published all-age-covering spirometry predictive equations for multiple ethnicities, including North East (NE) Asian and South East (SE) Asian [
15]. In addition, a set of GLI-2012 equations were designed for individuals of mixed ethnic origin (Mixed) [
15]. Although with mixed results, GLI-2012 equations showed clinically acceptable generalisability to spirometry in several validation samples [
16‐
21]. Therefore, relevant GLI-2012 equations are potentially useful for evaluating lung function of Asian Americans. Nonetheless, performance of GLI-2012 reference equations on assessing spirometry in Asian Americans has not been evaluated.
Asian people, including Asian alone and in combination with other races, account for more than 17.3 million (5.6%) of total American population in 2010 [
22]. Of note, the total US Asian population increased by 5.4 million (45.6%) from 2000 to 2010, and is projected to grow to 48.6 million by 2060 [
23,
24]. Owing to the remarkable quantity and rapid growth of Asian population in US, it is clinically important to assess spirometry reference values that have been recommended for or can be potentially used in that population. Herein, we conducted this study to assess the fitness of relevant GLI-2012 equations and NHANES III reference values for spirometry in Asian Americans.
Discussion
In this population-based cross-sectional analysis of lung function, we were the first to assess the generalisability of relevant GLI-2012 reference equations to spirometry in Asian Americans. In addition, we evaluated the agreement of lung function predictions between the NHANES III Caucasian values with a correction factor of 0.88 for FEV1 and FVC and the GLI-2012 equations for individuals of mixed ethnic origin.
Our findings showed that GLI-2012 Mixed equations adequately fitted FEV
1, FVC, and FEV
1/FVC data of our sample for both gender. GLI-2012 Mixed equations were designed for people of mixed ethnic origin, which we believe current Asian Americans could be categorized into due to the following several reasons. First, in the year 2010, around 16% of Asian Americans were Asian in combination with one or more other races, among whom Asian in combination with White were the majority [
22]. Second, US Asian population consists of more than twenty subgroups, with Chinese, Indian, Filipino, Vietnamese, Korean, and Japanese accounting for the most in quantity [
22]. Third, due to diversities of birth country and years living in US, which is readily translated into difference in environmental exposures and socioeconomic status, Asian Americans may have quite different lung function development [
32‐
37]. Therefore, Asian Americans are genetically, environmentally, and socioeconomically heterogeneous in nature, which may explain the satisfactory performance of GLI-2012 Mixed equations in fitting spirometry data in this sample.
GLI-2012 NE Asian equations were built based on two datasets, one collected from North China and the other from South Korea; whereas the GLI-2012 SE Asian equations were derived from a collated dataset consisting of five subsamples from South Asia and a subsample from US [
15]. Quanjer et al. found that the two subsamples of NE Asians had significantly larger lung function than the six subsamples of SE Asians, and therefore they constructed spirometry predictive equations separately for NE Asians and SE Asians [
15]. Not surprisingly, GLI-2012 NE Asian equations led to substantially larger FEV
1 and FVC predictions compared with observed data in our sample for both gender, strongly suggesting against the application of those equations to assessing spirometry in Asian Americans. GLI-2012 SE Asian equations, while performed satisfactorily in fitting FEV
1 and FVC, contributed to significantly larger FEV
1/FVC predictions compared with the observed data, which will potentially result in an overdiagnosis of chronic obstructive pulmonary disease in Asian Americans.
Generally, both the GLI-2012 Mixed equations and the NHANES III Caucasian reference values with a correction factor of 0.88 adequately fitted the lung function data in this sample. However, GLI-2012 equations possess several potential advantages over the NHANES III reference values. First, as all-age-covering spirometry reference values, GLI-2012 equations are valid for people aged 3 to 95 years old [
38]; the NHANES III equations, in contrast, have a comparably narrower valid age range of 8 to 80 years. Of note, in this study we were not able to evaluate the fitness of GLI-2012 equations for spirometry in Asian Americans aged outside 6 to 79 years. Secondly, GLI-2012 equations were designed with a semiparametric predictive modelling method, which was able to fit variance and skewness of spirometry data in addition to the mean value [
39]. Moreover, splines used in GLI-2012 equations modeled age-related variations for spirometry data. NHANES III equations were built based on quadratic function for FEV
1 and FVC and linear function for FEV
1/FVC. Thus, compared with GLI-2012 equations, NHANES III equations were less likely to reflect actual patterns of spirometry data due to their fixed function formats. Thirdly, NHANES III equations for FEV
1/FVC LLN and equations for FEV
1/FVC are same as each other except different intercepts. Therefore, according to NHANES III equations, LLN for FEV
1/FVC differs from FEV
1/FVC by a constant magnitude regardless of a subject’s age. However, since LLN theoretically corresponds to the 5th percentile of spirometry data and lung function varies with age, it is conceptually insufficient to define LLN as a constant difference to the mean for the entire age range. GLI-2012 reference values address this issue by defining LLN with spirometry z-scores, a way comprehensively taking mean, variance, and skewness of spirometry data into consideration.
The GLI-2012 equations have been proposed to be adopted worldwide in order to standardise the interpretation of lung function [
40]. Admittedly, the application of a correction factor to the NHANES III Caucasian reference values offers a practical solution to assessing spirometry in Asian Americans. However, the rationale behind the development of a correction factor, which is only for temporary use, is not conceptually and methodologically ideal. Based on the current findings and what has been discussed above, it is reasonable to regard GLI-2012 Mixed equations as superior to the NHANES III Caucasian reference values with a correction factor for evaluating spirometry in Asian Americans. In particular, the ready availability of spirometry z-scores and LLN from the GLI-2012 equations could possibly provide a convenient approach to the diagnosis and severity stratification of obstructive lung diseases. Therefore, with the rapid increase of Asian population in US, the application of GLI-2012 Mixed equations to Asian Americans is clinically important.
This study has several limitations. First, the sample size of this study is relatively small. However, we would argue that our sample sizes of men and women are both large enough for validating spirometry reference values, which requires at least 150 subjects for each gender [
41]. Second, as shown in Fig.
2, the distributions of age are right skewed in both men and women. Especially for men, the proportion of adults and elderly people is relatively small, which may limit the power of this study in that population. This issue is clinically relevant in that obstructive lung diseases, where lung function references are widely used, are most prevalent in elderly people. As the accrual of NHANES data of Asian Americans, the fitness of GLI-2012 equations could be better evaluated in the near future.