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. 2025 Sep;168(3):688-696.
doi: 10.1016/j.chest.2025.03.027. Epub 2025 Apr 11.

Characterizing Patients With Sarcoidosis With Obstructive Respiratory Physiology

Daniel VanDerhoef  1 , Nicholas Marka  2 , Benjamin Langworthy  2 , Nikhil Kapur  3 , Bharat Thayagarajan  4 , David M Perlman  5 , Maneesh Bhargava  6
Affiliations

Characterizing Patients With Sarcoidosis With Obstructive Respiratory Physiology

Daniel VanDerhoef et al. Chest. 2025 Sep.

Abstract

Background: Lung involvement occurs in > 95% of sarcoidosis cases. The World Association of Sarcoidosis and Other Granulomatous Disorders Organ Assessment Instrument does not assign the likelihood of lung involvement based on pulmonary function test (PFT) results. Clinical characteristics linked to normal and abnormal physiologic pattern on PFTs in sarcoidosis are incompletely understood.

Research question: What is the frequency of obstructive physiology (OP), restrictive physiology (RP), or normal physiology in patients with sarcoidosis, and are there laboratory parameters linked to these different patterns?

Study design and methods: We evaluated 253 patients with sarcoidosis according to their PFT findings and grouped them into OP, RP, and normal spirometry. These PFTs were correlated to demographic, clinical, and laboratory parameters. In some cases, the PFT abnormalities were correlated with proteins in the Olink metabolic and immune response protein panels.

Results: Of the 253 cases studied, 64% had normal spirometry, 20% had OP, and 15% had RP. Abnormal PFT findings were more frequent in male individuals, with 61.2% of the OP group and 82.1% of the RP group (P = .002). The average lymphocyte percentage was lower in OP vs RP (normal, 21.5%; OP, 17.3%; RP, 23.7%; P = .04), soluble IL-2 receptor was lower in OP vs normal (normal, 632.1 U/mL; OP, 335.5 U/mL; RP, 563.4 U/mL; P = .026), and C-reactive protein was lower in OP vs RP and in normal vs RP (normal, 11.7 mg/L; OP, 8.2 mg/L; RP, 35.6 mg/L; P = .018). Those with RP had less splenic involvement (normal, 21.5%; OP, 21.6%; RP, 2.6%; P = .008). Five immune response proteins had differential abundance in the three comparison groups.

Interpretation: Most of the sarcoidosis study cohort had normal spirometry findings. When abnormal, OP was more common than RP. There may be a difference in immune mechanisms in those with OP compared with those with RP or normal spirometry values. Continued comprehensive assessments of serum proteins may identify biomarkers to identify physiologic abnormalities and guide management.

Keywords: airway obstruction; airway restriction; proteomics; sarcoidosis.

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Conflict of interest statement

Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. B. reports a relationship with aTyr Pharma Inc and Kinavent Sciences that each include acting as site Principal Investigator for clinical trials. D. V. is a sub-investigator in the NIMBLE study, with funding through the GSK research grant support. Funds from this are given to the HealthPartners Institute. None declared (N. M., B. L., N. K., B. T., D. M. P.).

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