The histopathological and transcriptomic profiles of lung tissue in patients with idiopathic pulmonary fibrosis (IPF) differ across the central and peripheral regions, according to a study published in BMJ Open Respiratory Research.

IPF is an interstitial lung disease for which lung transplantation is sometimes indicated. The consensus around IPF pathogenesis is that fibroblast/myofibroblast dysregulation occurs as a result of recurrent epithelial injuries from unknown stimuli, causing excessive remodeling of the extracellular matrix. 

Histological analysis reveals that the central regions of the lungs are typically spared from fibrosis, while the immediate subpleural parenchyma typically demonstrates microscopic honeycombing and scarring. It is in the peripheral one-third of the lung that pulmonary lesions are most clearly observed. 

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The authors of the current study sought to investigate if genetic expression was different in the central portion of the lungs in patients with IPF, given that this area is relatively spared from morphological changes. They obtained paired central and peripheral lung explanted biopsies from 13 individuals with IPF and 8 controls (non-IPF donors). The IPF lung donors had all undergone lung transplantation, indicating that they had severe disease. 

Read more about IPF etiology 

The lung samples were classified and scored according to the level of fibrosis observed. In addition, researchers carefully quantified the levels of honeycombing, inflammation, and pulmonary hypertension in each specimen. RNA was then extracted from these tissues and sequenced. 

The results revealed that the central portions of the IPF lung specimens had significantly lower levels of fibrosis, honeycombing, and inflammation than the paired peripheral specimens. In contrast, IPF peripheral lung samples displayed advanced fibrosis and architectural disruption. As for the control group, no lung specimens displayed fibrosis, and only 2 out of 8 demonstrated inflammation. 

The research team also determined that different histopathological and transcriptomic profiles existed between the central and peripheral lung specimens of individuals with IPF. For example, they discovered that the central regions of the lungs underwent a different course of fibrosis progression than the peripheral regions. In addition, they found that the central lung had only mild extracellular matrix deposition, making it a potential target for myofibroblast activity intervention. 


Huang Y, Guzy R, Ma SF, et al. Central lung gene expression associates with myofibroblast features in idiopathic pulmonary fibrosisBMJ Open Respir Res. 2023;10(1):e001391. doi:10.1136/bmjresp-2022-001391