# High density lipoproteins, disease severity and clinical outcomes in patients with idiopathic pulmonary fibrosis

**Authors:** Anna J. Podolanczuk, Hillary Mulder, John S. Kim, Megan L. Neely, Robert J. Kaner, Jamie L. Todd

PMC · DOI: 10.1186/s12931-026-03511-x · Respiratory Research · 2026-02-17

## TL;DR

This study found that higher levels of a protein called ApoA1 in the blood are linked to fewer hospitalizations in patients with a lung disease called idiopathic pulmonary fibrosis.

## Contribution

The study identifies ApoA1 as a potential biomarker for predicting respiratory hospitalization risk in idiopathic pulmonary fibrosis patients.

## Key findings

- Higher ApoA1 levels were associated with lower risk of respiratory hospitalization in IPF patients.
- The association between ApoA1 and hospitalization remained significant after adjusting for demographic and clinical variables.
- PON-1 and HDL-C levels were not significantly linked to mortality or hospitalization outcomes.

## Abstract

Dysregulation of lipid metabolism is implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We assessed associations between circulating levels of high-density lipoprotein-cholesterol (HDL-C) and its components apolipoprotein A-1 (ApoA1) and paraoxonase-1 (PON-1) and disease severity and outcomes in patients with IPF.

The cohort comprised 284 patients enrolled in the IPF-PRO Registry. We analyzed associations between HDL-C, ApoA1 and PON-1 levels at enrollment and measures of disease severity at enrollment (using linear regression) and outcomes during follow-up (using Cox models). Models were adjusted for demographic and clinical variables, including cardiovascular disease and statin use, assessed at enrollment.

In unadjusted models, higher ApoA1 and lower PON-1 were associated with higher FVC % predicted at enrollment. Median follow-up was 40 months. In unadjusted models, higher ApoA1 at enrollment was associated with lower risks of all-cause mortality (hazard ratio [HR] 0.32 [95% CI: 0.16, 0.64] per unit higher log2 ApoA1) and respiratory hospitalization (HR 0.25 [0.11, 0.57] per unit higher log2 ApoA1). In analyses adjusted for demographic and clinical variables, the association with respiratory hospitalization remained significant (HR 0.30 [95% CI: 0.10, 0.88; p = 0.029]), but the association with all-cause mortality was no longer significant (HR 0.44 [95% CI: 0.18, 1.08; p = 0.074]). Levels of PON-1 or HDL-C were not associated with all-cause mortality or respiratory hospitalization.

In a real-world cohort of patients with IPF, a higher circulating level of ApoA1 was associated with a lower risk of respiratory hospitalization. ApoA1 is a potential prognostic biomarker in patients with IPF.

## Linked entities

- **Proteins:** APOA1 (apolipoprotein A1), PON1 (paraoxonase 1)
- **Diseases:** idiopathic pulmonary fibrosis (MONDO:0800029)

## Full-text entities

- **Genes:** APOA1 (apolipoprotein A1) [NCBI Gene 335] {aka AMYLD3, HPALP2, apo(a)}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, PON1 (paraoxonase 1) [NCBI Gene 5444] {aka ESA, MVCD5, PON}
- **Diseases:** inflammation (MESH:D007249), fibrosis (MESH:D005355), diabetes (MESH:D003920), lung injury (MESH:D055370), lung inflammation (MESH:D011014), death (MESH:D003643), IPF (MESH:D054990), cardiovascular disease (MESH:D002318), vascular (MESH:D057772), heart failure (MESH:D006333), ILD (MESH:D017563), pulmonary fibrosis (MESH:D011658), coronary artery disease (MESH:D003324)
- **Chemicals:** oxygen (MESH:D010100), carbon monoxide (MESH:D002248), triglycerides (MESH:D014280), carbon (MESH:D002244), lipid peroxide (MESH:D008054), bleomycin (MESH:D001761), cholesterol (MESH:D002784), DLco (-), silica (MESH:D012822), pirfenidone (MESH:C093844), lipid (MESH:D008055), alcohol (MESH:D000438), nintedanib (MESH:C530716)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12911027/full.md

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12911027/full.md

---
Source: https://tomesphere.com/paper/PMC12911027