Abstract

Biomarkers for the acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) are urgently needed to provide better patient management. We aimed to investigate whether serum 1,25(OH)2D3 (1,25-dihydroxy vitamin D3) levels predict AE-IPF and whether they could be a potential prognostic biomarker for IPF. This prospective study included 72 patients with IPF (31 with stable IPF and 41 with AE-IPF). All participants were recruited during hospitalisation at Tianjin Chest Hospital and were followed up for at least 12 months. Demographics, comorbidities, arterial blood gas, and serum biochemical profile, radiological features, and anti-fibrotic therapy were evaluated. Serum concentrations of 1,25(OH)2D3 and transforming growth factor beta1 (TGFβ1) were detected using enzyme-linked immunosorbent assay (ELISA). Risk factors for AE-IPF were identified using multivariate analysis. Prognostic factors were assessed using Kaplan-Meier and Cox regression analyses. Baseline values of alveolar-arterial oxygen difference (A-aDO2) (40.85 mmHg vs 29.2 mmHg, p =0.035), white blood cell counts (10.09 ± 4.2×109/L vs 7.46 ± 7.84×109/L, p <0.001), percentage of monocytes (7.36 ± 1.36% vs 6.6 ± 1.2%, p =0.017), C-reactive protein (CRP) (2.1 mg/dL vs 1.12 mg/dL, p =0.015) and procalcitonin (PCT) (36.59% vs 3.23%, p <0.001) were significantly higher in AE-IPF patients than in stable IPF patients. Instead, the mean concentration of serum calcium and 1,25(OH)2D3 at baseline were higher in IPF patients with stable disease than in those with acute exacerbation (2.17 ± 0.13 nmol/L vs 2.09 ± 0.13 nmol/L, p =0.023 and 16.62 pg/mL vs 11.58 pg/mL, p <0.001, respectively). In multivariate analysis, a higher proportion of patients with lower serum 1,25(OH)2D3 levels experienced AE-IPF (OR 0.884, 95% CI 0.791-0.987, p =0.029), and rising serum PCT level (PCT > 0.05 ng/mL) was associated with an increased risk of mortality (HR 3.664, 95% CI 1.010-12.900, p =0.043). Decreased serum 1,25(OH)2D3 is associated with an increased risk of acute exacerbation for patients with IPF. A high serum PCT level is predictive of worse prognosis in IPF patients. 1,25(OH)2D3 may be a potential biomarker for AE-IPF, while PCT could be a prognostic biomarker for IPF.

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