- 2026-05-14
- Respiratory research 27(1)
- Wei Liu
- Yu Sun
- Ling Zhao
- Shu Wang
- Guowu Zhou
- Shiyao Wang
- Sheng Xie
- Jing Geng
- Bingbing Xie
- Aimin Wang
- Huaping Dai
Study Design
- Type
- Observational
- Sample size
- n = 82
- Population
- 82 patients with IPF undergoing TBLC and 22 healthy controls
- Methods
- prospective and observational study; TBLC specimens; multiphoton microscopy to extract collagen features; multivariate logistic regression
Objective
The prognostic value of deep-tissue microstructure profiling derived from transbronchial lung cryobiopsy (TBLC) specimens in idiopathic pulmonary fibrosis (IPF) remains poorly explored. This study aims to bridge this gap by quantitatively extracting collagen features in heterogeneous pathological regions using multiphoton microscopy (MPM), and providing novel insights into the potential of collagen features as sensitive biomarkers for predicting severity and disease progression in IPF.Methods
In this prospective and observational study, a total of 82 patients with IPF undergoing TBLC and 22 healthy controls were enrolled. The differences in collagen features between the normal/mild and moderate/severe groups were compared. Multivariate logistic regression was used to identify collagen features associated with disease progression.Results
Histopathologically, 62.2% of the cohort exhibited a probable usual interstitial pneumonia (UIP) pattern. PERMANOVA indicated pronounced divergent collagen topographies among the five pathological regions (F = 14.14, R2 = 0.233, P = 0.001). Collagen features in histologically appeared normal regions exhibited significant collagen micro-remodeling compared to healthy controls (P = 0.01). Specifically, in advanced regions comprised of destructive regions and honeycombing regions, the anisotropy index (P < 0.001), eccentricity (P = 0.007), and local solidity heterogeneity (P = 0.03) were found to be decreased in comparison to the alveolar preserved fibrotic regions, while the crosslink spacing (P = 0.001) was expanded. In the moderate-to-severe group categorized by FVC% predicted, local orientation heterogeneity was markedly elevated (P = 0.01), and the crosslink spacing expanded (P = 0.008). In the moderate-to-severe group categorized by DLCO% predicted, the collagen fiber complexity network was reduced (P = 0.002). After adjusting for GAP score and antifibrotic therapy, the elevated gabor_l4_th120_mean was independently associated with disease progression (OR = 3.25, P = 0.009). In contrast, increased collagen fiber independent index (OR = 0.27, P = 0.008) and longer collagen fiber length (OR = 0.35, P = 0.03) were identified as protective factors.Conclusions
MPM imaging successfully mapped the spatial heterogeneity of the fibrotic microenvironment in IPF by quantifying collagen signatures. The morphological and structural features of collagen fibers could serve as promising pathological biomarkers for precisely assessing the severity and progression of IPF.