Phenotypes of lung function impairment in patients with sarcoidosis vary by race, sex

Key takeaways:

• The restriction phenotype, typically associated with sarcoidosis, was only found in 47% of patients with abnormal lung function.
• Black and white patients had differing phenotype prevalence.

Patients with sarcoidosis of different races and sexes had differing frequencies of lung function impairment phenotypes, according to study results published in Annals of the American Thoracic Society.

Michelle Whitfield Sharp

“Significant health disparities exist in sarcoidosis,” Michelle Whitfield Sharp, MD, MHS, co-director of the sarcoidosis program and assistant professor of medicine at Johns Hopkins University, told Healio. “Our results not only found race and sex differences in pulmonary function phenotypes, but also found significant differences in pulmonary function severity, with Black individuals having significantly worse pulmonary function compared to white individuals. More work is needed to address health disparities in sarcoidosis.”

In a retrospective cohort study, Sharp and colleagues analyzed 602 patients (median age, 51 years; 64% women; 57% Black) diagnosed with sarcoidosis from a tertiary referral center between 2005 and 2015 to describe the occurrence of various pulmonary function phenotypes and determine if phenotypes significantly varied by race and sex.

Researchers assessed pulmonary function test (PFT) data, such as FEV₁, FVC and diffusing capacity of the lung for carbon monoxide (DL_CO), as well as demographic data.

To account for different phenotypes in sarcoidosis patients, researchers classified four based on lung function impairment: restriction (FVC < the lower limit of normal [LLN] and FEV₁/FVC LLN), obstruction (FEV₁/FVC < LLN), combined restriction and obstruction (FVC < LLN and FEV₁/FVC < LLN) and isolated gas transfer defect (DL_CO < LLN, no restrictive or obstructive defect). Additionally, using Global Lung Function Initiative equations, they figured out FEV₁, FVC and DL_CO percent predicted.

Further, to evaluate how phenotypes differ by race, sex, disease duration and tobacco use, researchers conducted chi-squared analyses and multiple linear regressions.

Phenotype prevalence

Researchers found 562 (93%) patients with pulmonary involvement, including 56% with abnormal pulmonary function.

All the defined phenotypes of lung function impairment were found in the cohort but in varying percentages. The most prevalent phenotype was restriction (47%), followed by obstruction (22%), combined restriction and obstruction (16%) and isolated reduction in DL_CO (15%).

“It is important to know that sarcoidosis is not only a restrictive lung disease,” Sharp told Healio. “Clinicians should be aware of the various pulmonary function phenotypes in sarcoidosis and consider assessing more than lung spirometry in patients with pulmonary sarcoidosis.”

In terms of the phenotype prevalence by race, researchers found that at 66%, the majority of white patients showed no lung impairment, whereas this was only found in 26% of Black patients. In Black patients, the restriction phenotype had the highest prevalence (41%), but this was not the case in white patients (9%).

Additionally, more white patients had the obstruction phenotype than Black patients (17% vs. 9%).

Sex also demonstrated differences in phenotype frequency. For example, the obstruction phenotype occurred in more men than women (19% vs. 9%; P = .001). Additionally, the restriction phenotype was more common in women than men (30% vs. 21%; P = .031).

Researchers also found phenotype differences in disease duration and tobacco use. Compared with the restriction, obstruction and isolated DL_CO phenotypes, patients with the combined restriction and obstruction phenotype showed the greatest disease duration (median, 10 years; P = .037) and, alongside those with an isolated reduction in DL_CO, had an increased number of current smokers.

Lung function measures

When evaluating percent predicted measures of lung function, researchers observed poorer lung function in Black patients than white patients and in women than men.

For Black patients, this result persisted in every phenotype but the combined one. For women, this result was observed in the restriction and obstruction phenotypes, but poorer lung function in the combined phenotype was observed in men, according to researchers.

After adjusting for sex, tobacco use, disease duration and organ involvement in regression models, researchers further found that Black patients had more decreased lung function than white patients in FVC percent predicted (–16.39; 95% CI, –19.49 to –13.29), FEV₁ percent predicted (–13.41; 95% CI, –16.77 to –10.04) and DL_CO percent predicted (–16.2; 95% CI, –19.8 to –12.6).

In this adjusted model, women had greater DL_CO percent predicted (4.45; 95% CI, 0.89-8; P = .014) than men.

“Clinical trials and prospective studies of pulmonary sarcoidosis should keep the pulmonary function phenotypes in mind,” Sharp told Healio. “These findings raise the question of whether using FVC percent predicted as the sole primary outcome measure of pulmonary function in clinical studies assessing treatment response in sarcoidosis is appropriate.”

This study by Sharp and colleagues adds important findings related to sarcoidosis and its different phenotypes, specifically that the restrictive phenotype, which researchers wrote is historically linked to sarcoidosis, only occurred in 47% of patients with abnormal lung function. This finding calls for reevaluation of the measures that are used in trials on patients with sarcoidosis, according to an accompanying editorial by Ogugua Ndili Obi, MD, MPH, MSc, assistant professor of medicine at East Carolina University.

“Although FVC is certainly an important clinical endpoint that should be incorporated into clinical trials, the findings of Sharp and colleagues reinforce that it is not representative of all (or even most) patients with pulmonary sarcoidosis (irrespective of radiographic pattern) and therefore should not be the sole criterion or focal point by which the success or failure of an intervention is determined,” Obi wrote. “In fact, these data suggest that continuing to focus on FVC as the sole or most significant primary endpoint in clinical trials evaluating therapies in pulmonary sarcoidosis may inadvertently misclassify potentially efficacious drugs/interventions as not effective for the majority of patients for whom a demonstrable change in FVC may not be feasible by virtue of their disease phenotype.”

For more information:

Michelle Sharp, MD, MHS, can be reached at msharp5@jhmi.edu.

Reference:

• Obi ON. Ann Am Thorac Soc. 2023;doi:10.1513/AnnalsATS.202208-731ED.