Heterogeneity of Lung Function Phenotypes in Sarcoidosis: Role of Race and Sex Differences

Abstract

Rationale: Historically, sarcoidosis was described as a restrictive lung disease, but several alternative phenotypes of pulmonary function have been observed. Pulmonary function phenotypes in sarcoidosis may represent different clinical and/or molecular phenotypes. Objectives: To characterize the prevalence of different pulmonary function phenotypes in a large and diverse sarcoidosis cohort from a tertiary care referral center. Methods: We identified individuals seen between 2005-2015 with a confirmed diagnosis of sarcoidosis. Data were collected from the first pulmonary function test (PFT) performed at our institution which included spirometry and diffusing capacity of the lung for carbon monoxide (Dl_CO). Demographics and clinical data were collected. Chi-squared analyses and multiple linear regressions were done to assess statistical differences and associations. Global Lung Function Initiative equations were used to calculate percent predicted measurements for spirometry and Dl_CO. Results: Of 602 individuals with sarcoidosis, 93% (562) had pulmonary involvement, 64% (385) were female, and 57% (341) were Black. Of those with pulmonary involvement, 56% had abnormal pulmonary function. Lung function impairment phenotypes included: 47% restriction, 22% obstruction, 15% isolated reduction in Dl_CO, and 16% combined obstructive restrictive phenotype. Restriction was the most common PFT phenotype among Black individuals (41%), while no lung impairment was most common among White individuals (66%) (P < 0.001). Males more frequently had obstruction (19%) compared with females (9%) P = 0.001, and females had more restriction (30%) compared with males (21%) P = 0.031. Conclusions: Among individuals with sarcoidosis and pulmonary function impairment, less than half demonstrated a restrictive phenotype. There were significant differences in pulmonary function phenotypes by race and sex.

Keywords: pulmonary disease; respiratory function tests; sarcoidosis.

Figure 1.

Inclusion of participants for analysis.

Figure 2.

Prevalence of pulmonary function phenotypes by A) Race and B) Sex. Restriction was defined as FVC < the lower limit of normal (LLN) with FEV₁/FVC ⩾ (LLN), obstruction as FEV₁/FVC ⩽ LLN with FVC ⩾ LLN, combined (obstruction/restriction) as FVC < LLN and FEV₁/FVC < LLN, and isolated gas transfer defect as Dl_CO < LLN with no restrictive or obstructive defect. Normal was defined as not having any impairment. Dl_CO = diffusing capacity of the lung for carbon monoxide; FEV₁ = forced expiratory volume in one second; FVC = forced vital capacity; LLN = lower limit of normal.