Racism in Medicine: Spirometry

Case

The hospitalist admits a 49-year-old man with a 20-pack-year history of tobacco use and chronic cough for a viral illness featuring dyspnea and hypoxia. After a short observation period, his symptoms resolve, but the hospitalist suspects that the patient has COPD and refers him for PFTs. His PFT results, using adjusted on account that the patient is Black, do not meet the criteria for a diagnosis of COPD. As a result, the patient receives only tobacco cessation counseling and no further intervention. He continues to have a chronic cough with sputum production but does not receive COPD-specific therapies and is lost to follow-up after finding out he does not have COPD.

Background

Spirometry is used to measure lung function by measuring air volumes and flow.

Lung volumes vary widely among individuals, so efforts have been made to create normal ranges for FEV1, FVC, etc.
Most modern spirometers use variables like age, sex, height, and race to calculate norms.

How did we get here?

A History of Race & Spirometry

Thomas Jefferson’s “Notes on the State of Virginia”, published in 1787, discusses a “difference in the structure of the pulmonary apparatus” of slaves; however, he offered no scientific evidence to support this claim.

John Hutchinson invented the first spirometer in the 1840s. The spirometer’s initial uses were to study the fitness of police forces, to help life insurance companies, and to diagnose TB. He noted that height correlated well with vital capacity despite substantial variability among patients. In studying coal miners, he posited that occupation/environmental factors played a role.

Samuel Cartwright, a slaveholder and plantation physician, used spirometry to support slavery in “Cotton is King and Pro-Slavery Arguments”, published in 1860:

“The result is, that the expansibility of the lungs is considerably less in the black than the white race of similar size, age, and habit. A white boy expelled from his lungs a larger volume of air than a negro half a head taller and three inches larger around the chest. The deficiency in the negro may be safely estimated at 20 per cent, according to a number of observations I have made at different times.”
Samuel Cartwright, Cotton is King and Pro-Slavery Arguments

After the Civil War, the US Sanitary Commission led a anthropometric survey of US soldiers entitled “Investigations in the Military and Anthropological Statistics of American Soldiers”, published in 1869. This survey included detailed information about soldiers according to race (e.g., “chest volume” measured using a spirometer). Without much context, it noted “The great difference of the mean volume found for the black race from that which seems to belong to the whites, cannot fail to attract attention at the first glance.”

A 1922 study published in JAMA entitled “Diagnostic Value of Determining Vital Capacity of Lungs in Children” made a first attempt at defining empiric norms.

Researchers used the spirometer to measure lung volumes of children aged 6-16 years of age, with the goal of establishing age-based normal values and determining factors that vary with lung volume.
They found a “normal standard” for white boys of 2.01 L/m², and a small set of black children had an average lung volume of 1.57 L/m².

Thus, lung differences based on race, which appear to have started with the musings of Thomas Jefferson, made their way into most medical textbooks by the early/mid-20th century, an era marked by an interest in eugenics.

Later, a 1974 study entitled “Ethnic differences in lung function: evidence for proportional differences” published in the International Journal of Epidemiology, suggested using race as a scaling factor.

“There is anthropometric evidence that, for given height, whites, of European descent, have a 13.2% larger chest volume at full inspiration than blacks, of African descent, and this accounts almost completely for the differences in total lung capacity… It is proposed that, until further evidence is forthcoming, for normal values a scaling factor of 1.132 should be used for the major lung volumes to account for the ethnic differences between Africans and Europeans.”
Rossiter CE, Weill H. Ethnic differences in lung function: evidence for proportional differences. Int J Epidemiol. 1974 Mar;3(1):55-61

Finally, a 1999 study entitled “Spirometric reference values from a sample of the general U.S. population” published in the American Journal of Respiratory and Critical Care Medicine, using data from the National Health and Nutrition Examination Survey (NHANES III), found that “Caucasian subjects had higher mean FVC and FEV1 values than did Mexican-American and African-American subjects across the entire age range”. This study is the basis on which essentially all modern spirometers incorporate race correction.

“Our data suggest that the practice of deriving African-American reference values by using an adjustment factor of approximately 12 to 15% applied to the Caucasian values does approximate the difference between the two groups.”
Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87

Covariates with FEV1 and FVC in NHANES III:

Age and height
- “Sitting height can to some degree account for between-race differences, but a common equation that includes sitting height is not as accurate as separate race/ethnic equations that do not include sitting height.”
No mention of socioeconomic status (except that all lived in “households”), occupation, zip code, etc

Following the completion of the Human Genome Project, a 2010 study entitled “Genetic Ancestry in Lung-Function Predictions” published in the New England Journal of Medicine, acknowledged concerns with “race correction”, namely the imprecision of self-reported race. The study aimed to investigate the correlation between lung function and “genetic ancestry” (based on genetic analysis and identification of “ancestry informative markers”). The researchers’ goal was to move toward being able to use genomics to determine the specific gene variants underlying observed variations (i.e., lung volumes).

Studied FEV1, and genetic makeup, of 777 African-American self-described individuals
Found an inverse correlation between FEV1 and percentage “genetic African ancestry”
- Used this data to extrapolate that 4% of asthma cases may have been misclassified by using standard race-based models, and advocated for (ideally, in the future) using ancestry/genetic based models
Researchers acknowledged “the association between lung function and ancestry found in our study may be the result of factors other than genetic variation, such as premature birth, prenatal nutrition, socioeconomic status, and other environmental factors”

Race is a Social Construct

There is more genetic variability among races than between them.

Any two humans share 99.9% of the same DNA. Of this 0.1% difference, 95.7% of the variability is found between individuals of the same race.

Why do we use skin color to differentiate race?

If most genetic variability exists within groups, why, then, does skin color seem not to?
Melanin production is a response to extreme selection pressure (protection from harsh sun).

A 2021 study entitled “Race and genetics versus ‘race’ in genetics: a systematic review of the use of African ancestry in genetic studies” published in Evolution, Medicine, & Public Health, examined the frequency with which papers were still using “African ancestry” / admixture mapping to define study populations following the Human Genome Project, and after our understanding that there is no genetic basis for race. The study determined that very few tried to explain the findings based on an evolutionary basis, and the “concept of continuous genetic variation was not clearly articulated in any of these papers, presumably due to the paucity of evolutionary science in the college and medical school curricula”.

Why we should not correct for race in spirometry

#1: Using “race” prevents us from examining what measurable factors might truly contribute to differences in PFTs

Initial studies were isolating something that accounted for difference, but it isn’t “race”/skin color
Structural racism likely underlies the difference, and when we use “race” as a proxy for this, it prevents us from identifying and studying these underlying structural factors

A 2022 study entitled “Reconsidering the Utility of Race-Specific Lung Function Prediction Equations” published in the American Journal of Respiratory and Critical Care Medicine, found that percent predicted values for FEV1 and FVC derived from universally applied equations more accurately reflect clinically relevant outcomes than percent predicted values derived from race-specific equations.

“We show that the correlation between FEV1 and respiratory symptoms is different in African American and non-Hispanic White individuals when race-adjusted equations are used but almost identical when no racial adjustment is applied. This argues that race adjustment is not needed in the first place. In fact, it suggests that race adjustment may distort the true relationship between impairment in lung function and resultant symptoms, to the detriment of one racial group.”
Baugh AD et al. Reconsidering the Utility of Race-Specific Lung Function Prediction Equations. Am J Respir Crit Care Med. 2022 Apr 1;205(7):819-829.

Furthermore, the study found that as you add in more covariates [e.g., Adversity-Opportunity Index (AOI), Area Deprivation Index], “race” variability with FEV1 decreases.

#2: Using Race Adjustments can lead to Harm via Underdiagnosis

A 2018 study entitled “Race and Gender Disparities are Evident in COPD Underdiagnoses Across all Severities of Measured Airflow Obstruction” published in the Journal of the COPD Foundation, found that race and gender are associated with significant disparities in diagnosis of COPD.

Among 14,080 PFTs of Black folks, by removing race correction in spirometry results, an additional 414 would be diagnosed with obstructive disease (1.7% increase) and 665 with restrictive disease (4.7% increase)
16.5% difference in FVC when classified as “Black” rather than “White”
- Said differently, a black individual would need to have 16.5% further decline in lung function in order to get diagnosis that a white individual would get (which leads to disparities in treatment access, access to disability, etc.)

#3: Using Race Corrections Doesn’t Help Predict Adverse Events

A 2021 study entitled “Race/Ethnicity, Spirometry Reference Equations, and Prediction of Incident Clinical Events: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study” published in the American Journal of Respiratory and Critical Care Medicine, found no evidence that race/ethnicity-based spirometry reference equations improved the prediction of clinical events compared with race/ethnicity-neutral equations.

Prospective cohort study of 3344 people followed for 10 years (after spirometry from 2004-2006; half with race-corrected values and half without)
Showed that using race-corrected model does not improve prediction of Chronic Lower Respiratory Disease events, and all-cause mortality, when compared to using race-neural modeling

#4: Using Race Corrections Perpetuates the Medical Focus on Race, a Social Construct

“Race, a sociopolitical construct, does not accurately represent genetic variation. The routine use of race in the HPI can perpetuate racial biases and muddle both diagnoses and treatment. Only mention race in the social history if it is meaningful to the patient’s self-identity or explains health disparities arising from racism. All documentation and presentations should avoid the use of stigmatizing, race-based labels.”
Gau J et al, Things We Do for No Reason™: Routine inclusion of race in the history of present illness, Journal of Hospital Medicine 2022

Take-Home Points!

Do not use race correction with spirometry results (or put “white” for correction factor of 1 for all patients)
Advocate for the removal of race correction from spirometry at all institutions
If you get PFT results for a black individual that are “normal” but very close to abnormal, check to see if race correction was used
Continue to be lovely, open-minded physicians not afraid of addressing systemic racism that affects our patients in many ways
Further reading: “Breathing Race Into the Machine: The Surprising Career of the Spirometer from Plantation to Genetics” by Lundy Braun, Professor of Pathology and Laboratory Medicine and Africana Studies at Brown!

Blog post based on Med-Peds Forum talk by Cameron Ulmer, PGY3