Rethinking Race in Lung Function: The Shift to Race-Neutral Spirometry Interpretation

Normative values for lung function have traditionally been determined by age, sex, height, and self-reported race.¹ The inclusion of race has become increasingly controversial, as it implies that the observed differences in lung function among individuals of different races are solely due to genetic factors.²

While hereditary factors may play some role, lung function is influenced by numerous environmental factors such as access to prenatal care, smoke exposure (both direct and second-hand), childhood infections, nutrition, and ambient air quality (Figure). These factors, many linked to social determinants of health (SDH), likely play a larger role in the observed differences in lung function between races than ancestral origin.² Conflating race - a predominantly social construct - with inherent biological differences has been increasingly recognized as a fundamentally flawed approach to pulmonary function test interpretation.

Figure.

Determinants of lung health encompass a broad range of factors, including genetic predisposition, exposures during in utero development, nutrition, level of education, childhood infections, exercise, smoking, air quality, and access to healthcare. These factors are often intertwined with race, underscoring the importance of addressing systemic racism and socioeconomic inequities as part of a systematic public health strategy to improve lung health across different racial groups. While the risk factors listed here are subdivided into distinct time periods, many risk factors exert a negative effect on lung health across the age spectrum.

Spurred by these discussions, and with a clear agenda to reduce racial bias in pulmonary function test interpretation, the American Thoracic Society (ATS) recommended the worldwide adoption of a ‘race-neutral’ set of spirometry reference equations in pulmonary function (PF) laboratories in 2023.³ In this article, we outline the complexities associated with this recommendation, and the resulting impact on spirometry interpretation and patient care.

What does race-neutral spirometry mean?

Mayo Clinic and many other PF laboratories internationally currently employ the Global Lung Function Initiative (GLI) 2012 ‘multiethnic’ spirometry reference equations.¹ These provide normative values for four ancestral origin categories: Caucasian, Black (including African American), Northeast Asian (including individuals from Korea and China; north of the Huaihe River and Qinling Mountains), and Southeast Asian (including individuals from Thailand, Taiwan, and China; south of the Huaihe River and Qinling Mountains).¹ For patients who do not self-identify in these categories, GLI investigators have recommended the use of ‘Other/Mixed’ reference equations, which represent an average of the equations for the other four categories (GLI-Other).

The race-composite GLI-Other equations have been proposed as a ‘race-neutral’ option⁴ but faced criticism due to the Caucasian predominance in the database used to develop these reference values. In response, GLI-Global equations were recently created by assigning different weights to each of the four ancestral origin categories, to ensure that the final equations represent an equal contribution from all four.⁵

We simulated the impact of transitioning from GLI-2012 multiethnic to ‘race-neutral’ GLI Global equations on spirometry interpretation in over 100,000 Mayo Clinic patients.⁶ Using GLI-Global changed spirometry interpretation (i.e., normal, obstruction, or preserved ratio impaired spirometry [PRISm]) in 10% of patients, with the greatest change seen among Black and Southeast Asian individuals. The most common change was the increased frequency of PRISm, defined as a reduced forced expiratory volume in the first second (FEV₁) and/or forced vital capacity (FVC) with a normal FEV₁/FVC ratio.⁶ Further testing with lung volume measurements is recommended in this setting to determine if these findings are due to a restrictive process or occult obstruction. ⁷

While transitioning to a race-neutral approach does not change the frequency of obstruction (i.e., low FEV₁/FVC ratio) in Black individuals, GLI Global does result in a reduction in percent predicted FEV₁ in these patients. In practice, this translates into increased severity grading of airflow obstruction in Blacks. Two recent studies have suggested around 20% of Black patients would be impacted, with the most common change being a reclassification from mild to moderate obstruction.^{7, 8} Table 1 provides a summary of other changes in lung function interpretation resulting from the use of a race-neutral approach.

Table 1:

Changes in lung function interpretation resulting from the use of GLI Global, a recently introduced race-neutral approach. Individuals who self-identify as Black are most affected by this transition ⁶ Increase (↑), decrease (↓), relative change by <5% (─), 5–15% (1 arrow), 16–30% (2 arrows), 31–50% (3 arrows), >50% (4 arrows).

	Affected spirometry tests	PRISma	Obstruction	Severity of Impairment
Black	15%	↑↑↑↑	─	Increased
White	7%	↓↓	↑	Decreased
Northeast Asian	11%	↓↓↓	↓↓	Decreased
Southeast Asian	12%	↑↑↑	↓↓↓	Increased

^aPRISm: preserved ratio impaired spirometry.

The impact of a race-neutral approach on patients and patient care

Race-adjustment in spirometry testing normalizes the lower mean observed lung function in certain racial/ethnic groups, including Blacks and Southeast Asians. This can lead to underdiagnosis of lung disease and may contribute to health inequities. ⁹

Benefits of adopting a race-neutral approach

An important benefit of adopting a race-neutral approach is the potential for earlier diagnosis of pulmonary disease in underrepresented populations. For example, adoption of race-neutral reference equations in Black children led to a doubling in the number of diagnoses of uncontrolled asthma.¹⁰ Earlier diagnosis and assessment of greater disease severity should in turn lead to earlier initiation and appropriate escalation of treatment for such patients. Similarly, the increased identification of PRISm may lead to earlier diagnosis of restrictive lung disease such as pulmonary fibrosis.⁶

A race-neutral approach also stands to benefit underrepresented populations by qualifying them earlier for specific treatments that rely on predicted lung function thresholds, such as non-invasive ventilation for neuromuscular disease¹¹ or pulmonary rehabilitation for chronic obstructive pulmonary disease.¹² When compared to standard multiethnic equations, the use of race-neutral equations led to higher lung allocation scores for Black patients, potentially increasing their priority for lung transplantation.^{13, 14}

The transition to a race-neutral approach may also allow members of underrepresented groups to qualify more readily for disability compensation that relies on impairment assessments that use percent predicted lung function cutoffs.³

Challenges of adopting a race-neutral approach

On the other hand, adopting a single set of reference equations may disqualify patients from necessary treatments in certain instances. For example, surgical resection remains the preferred treatment for early-stage lung cancer over radiation or chemotherapy. When thoracic surgeons were presented with spirometry data for Black patients using race-neutral rather than race-specific reference equations, the absolute likelihood of recommending surgery dropped by 26%.¹⁵ This would only deepen disparities that Black patients already encounter when accessing surgical procedures in the US.^{16, 17}

Originally, race adjustment was implemented to enable more Black Americans to work in cotton processing mills in the 1970s. The reference values used at that time, derived from White males, prevented Black job applicants from being hired when pre-employment spirometry tests were required.¹⁸ A transition back to a single reference approach may exclude non-Whites from certain jobs that require occupational spirometry screening, such as firefighting. Without widespread awareness of how implementation of race-neutral equations affects lung function estimates, this could add systematic bias in job opportunities, compounding implicit and explicit biases already entrenched in societal hiring practices.

Transitioning to a race-neutral approach might also result in higher premiums for life and health insurance, further compounding existing disparities in healthcare access. While a race-neutral approach could uncover previously unidentified health risks and more severe lung disease in certain racial/ethnic groups ³, subsequent recommendations for additional diagnostic testing and management could potentially aggravate the socioeconomic inequities in healthcare access that these groups have historically and continue to face due to longstanding racial discrimination. Moreover, this transition could potentially heighten stress and concern among these groups, who may perceive their lung function as worsening solely due to a change in a prediction equation. This highlights the need for both provider and patient education about these changes.

Areas of uncertainty

The effects of adopting a race-neutral approach for spirometry interpretation on White individuals are less clear. Although changes in predicted lung function using various race-neutral equations tend to be less prominent for this group, ⁶ the overall number of individuals potentially affected in most U.S. communities is likely higher compared to other groups. Potential unintended consequences for White individuals vary depending on the specific equation used and may include delayed diagnoses and reduced eligibility for specific treatments. ^{3, 13}

Another area of uncertainty concerns the impact of this approach on underrepresented populations other than Black individuals. Although GLI equations for Caucasian individuals include Hispanics,¹⁹ significant variability exists within Hispanic subgroups. U.S. adults of Hispanic/Latino ethnicity (i.e., Dominican and Puerto Rican individuals) have been previously shown to have a lower mean predicted FEV₁ and FVC compared to other Hispanics, and the impact of a race-neutral approach on these subgroups remains unclear.²⁰ In addition, a general observation from our study indicated that the use of the GLI Global equation resulted in worse predicted lung function in Southeast Asians, and slightly better in Northeast Asians. ⁶ The smallest change when transitioning to GLI Global was among those who did not self-identify in these four disease categories.⁶ Further studies are necessary to better understand the full implications of these findings.

It is also important to note that the database used to develop GLI Global also lacks representation from many large global populations, especially from Africa, Asia, and South America. Further research is needed in these wider populations to truly move towards globally representative race-neutral equations. Lastly, research is needed to better clarify if incorporation of SDH into predictive lung function values should be considered.

Is race-neutral spirometry interpretation ready for implementation?

The exclusion of race from normative values in lung function assessments can reduce inherent biases and expose modifiable risk factors associated with structural racism. Current studies suggest that single-reference equations in spirometry are as effective, if not superior, to race-adjusted equations when considering clinical and radiographic endpoints. ^{3, 21} For example, race-neutral approaches may more accurately estimate breathlessness,²² better correlate with lung volume measurements,⁶ and match race-specific approaches in explaining chest CT abnormalities.⁷ Race-neutral approaches may also better predict overall survival,^{23, 24} although this might be coincidental given that lung disease does not significantly contribute to the mortality gap between Blacks and Whites.³

Many argue that, as a profession, we also have a collective ethical responsibility to minimize risk for historically disadvantaged groups already at higher risk for lung disease.⁷ In this context, a strategy that favors increased sensitivity over specificity may be of greater overall benefit,⁷ albeit with the potential for greater healthcare utilization. Other potential negative consequences of implementing race-neutral equations can be mitigated. As an example, greater use of alternate methods for lung function assessment such as cardiopulmonary exercise testing may obviate the potential pitfalls of a race-neutral approach to spirometry interpretation in patients who are being considered for lung cancer resection or certain occupations. Longitudinal follow-up and in-depth counseling may also help address patient concerns, although this may be more intricate and demanding than it initially appears.²⁵

As societies become increasingly diverse and multicultural, more people may feel that they do not fit into a specific race/ethnicity category. Indeed, those who self-identified in the Other/Mixed category in our study were also the youngest.⁶ However, as we search for the perfect race-neutral approach, we should be aware of the unintended consequences of its application. A summary of the pros and cons of transitioning to a race-neutral approach in spirometry interpretation is presented in Table 2. Some experts have also raised important questions about whether this “one-size-fits-all” race-composite approach represents a step away from precision medicine, in an era where omics-based strategies are increasingly employed to tailor diagnoses and therapies at the individual level.²⁶

Table 2:

Pros and cons of adopting a race-neutral approach in spirometry interpretation.

Race-Neutral Approach in Spirometry
Pros	Cons
General population:	General population:
- Better correlation with disease burden	- Scarcity of effective race-neutral options
- Better correlation with overall survival	- Uncertain impact on White individuals and non-Black underrepresented groups
- Unmasking modifiable SDHa
Black individuals:	Black individuals:
- Earlier evaluation & diagnosis of lung diseases	- Decreased candidacy for lung surgery
- Enhanced eligibility for treatments (pulmonary rehabilitation, non-invasive ventilation etc.)	- Increased premiums  - Concerns for employment
- Enhanced eligibility for lung transplantation
- Enhanced eligibility for compensation in disability cases

^aSocial determinants of health

Finally, it is worth emphasizing that discussions on the impact of a race-neutral approach in spirometry must extend beyond its impact on testing interpretation, and consistently both acknowledge and address the broader sources of ingrained racial bias that persist in our U.S. healthcare system. There remains an urgent need for systemic reforms to eliminate the deep-seated racial inequalities in healthcare. Expanding the dialogue and looking for methods to remove race from spirometric measurements represents just one small step in the long overdue journey to meaningful change.

Conclusion

Continued use of race-specific normative equations is not a viable long-term strategy as we seek to reduce systemic racism in medicine. Transitioning to a race-neutral method like GLI Global is a promising alternative to race-specific approaches in spirometry interpretation that attempts to reduce bias and inequities in pulmonary function test interpretation. Professional societies endorsing it have highlighted research gaps and the need for more studies on the impact of race on spirometry interpretation. ^{3, 21} Until these gaps are filled, careful consideration should be given to the application of spirometry results, recognizing uncertainties in categorizing lung function that falls near the lower limit of normal, and underlining the continued importance of placing pulmonary function testing results within an appropriate clinical context.

Abbreviations:

ATS

American Thoracic Society

FEV₁

Forced Expiratory Volume in the First Second

FVC

Forced Vital Capacity

GLI

Global Lung Function Initiative

PF

Pulmonary Function

PRISm

Preserved Ratio Impaired Spirometry

SDH

Social Determinants of Health