In patients with idiopathic pulmonary fibrosis (IPF), airway-soluble colony-stimulating factor-1 receptor  (CSF1R) can play a role in predicting disease progression, according to findings from a single-center, retrospective study published in ERJ Open Research.

To date, 2 antifibrotic treatments—pirfenidone and nintedanib—have demonstrated efficacy in slowing the progression of IPF; however, neither agent has the ability to halt or reverse the fibrogenesis associated with the disorder. An urgent unmet clinical need exists for the development of more effective therapies for IPF and the identification of potential biomarkers.

Recently, the CSF1-CSF1R pathway has surfaced as a therapeutic target in patients with IPF, with higher concentrations of CSF1 in serum and bronchoalveolar lavage (BAL) fluid from patients with the disease compared with controls. In fact, CSF1R may be activated by interleukin-34 (IL-34), which is a structurally unrelated ligand. IL-34 and CSF1 actually have distinct sequence homology and tissue expression, as well as many nonredundant roles.

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Recognizing that the role played by the CSF1-CSF1R axis in IPF remains to be elucidated, the researchers sought to establish whether plasma and BAL levels of CSF1, CSF1R, and IL-34 are linked to IPF, and whether these levels may serve as biomarkers of mortality from IPF.

Read more about experimental therapies for patients with IPF

Participants were diagnosed with IPF via multidisciplinary team discussion in accordance with current international guidelines. All healthy volunteers comprised individuals with no history of lung disease or infection in the prior 6 months. The mean age of the study cohort was 71.5 years. Overall, 62% of those in the study were male.

Study results revealed that IL-34 and CSF1 were undetectable in the plasma from most participants. Plasma CSF1R, however, was detectable in all participants, with the levels similar and thus not statistically significant between individuals with IPF and controls (227.79±181.14 ng/mL vs 175.10±96.34 ng/mL, respectively; P =.68).

Although all 3 proteins—CSF1, CSF1R, and IL-34—could be detected in BAL, statistically significantly higher levels of CSF1 and CSF1R were seen among patients with IPF than among controls:

  • CSF1: 42.65±48.42 pg/mL vs 18.94±17.15 pg/mL, respectively; P =.04
  • CSF1R: 1.98±1.13 ng/mL vs 1.16±0.83 ng/mL; P =.001

Of note, CSF1R concentrations in human BAL fluid were approximately 100-fold lower than plasma concentrations among all participants, whereas CSF1 concentrations were approximately 10-fold higher in human BAL vs plasma. Further, “IL-34 levels were at or below the lower level of the assay performance.”

Based on outcome analysis, BAL sCSF1R level was associated with an elevated risk for mortality (hazard ratio, 1.63; 95% CI, 0.97-2.74; P =.064). In fact, those individuals with a CSF1R level above the median had a significantly worse 3-year survival than those with a CSF1R level below the median (P =.02).

Among 58 individuals for whom progression data could be collected, progressors exhibited a significantly higher mean BAL CSF1R concentration than did nonprogressors (2.12±1.32 vs 1.75±0.94, respectively; P =.28).

“Our study provides, to our knowledge, the first evidence [of] a role [for] airway sCSF1R in IPF,” the authors noted. “Additional research is needed to validate these findings and determine how sCSF1R levels can inform clinical decision-making in IPF,” they concluded.


Oldham JM, Johnson KW, Albers GJ, et al. Airway soluble CSF1R predicts progression in patients with idiopathic pulmonary fibrosis. ERJ Open Res. Published online July 17, 2023. doi:10.1183/23120541.00690-2022