Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Apr 17;22(1):109.
doi: 10.1186/s12931-021-01711-1.

Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management

Fabrizio Luppi  1 , Meena Kalluri  2 , Paola Faverio  1 , Michael Kreuter  3 , Giovanni Ferrara  4   5
Affiliations
Review

Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management

Fabrizio Luppi et al. Respir Res. .

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with an estimated median survival time of 3-5 years after diagnosis. This condition occurs primarily in elderly subjects, and epidemiological studies suggest that the main risk factors, ageing and exposure to cigarette smoke, are associated with both pulmonary and extrapulmonary comorbidities (defined as the occurrence of two or more disorders in a single individual). Ageing and senescence, through interactions with environmental factors, may contribute to the pathogenesis of IPF by various mechanisms, causing lung epithelium damage and increasing the resistance of myofibroblasts to apoptosis, eventually resulting in extracellular matrix accumulation and pulmonary fibrosis. As a paradigm, syndromes featuring short telomeres represent archetypal premature ageing syndromes and are often associated with pulmonary fibrosis. The pathophysiological features induced by ageing and senescence in patients with IPF may translate to pulmonary and extrapulmonary features, including emphysema, pulmonary hypertension, lung cancer, coronary artery disease, gastro-oesophageal reflux, diabetes mellitus and many other chronic diseases, which may lead to substantial negative consequences in terms of various outcome parameters in IPF. Therefore, the careful diagnosis and treatment of comorbidities may represent an outstanding chance to improve quality of life and survival, and it is necessary to contemplate all possible management options for IPF, including early identification and treatment of comorbidities.

Keywords: Ageing; Comorbidities; Coronary artery disease; Emphysema; Gastro-oesophageal reflux; Idiopathic pulmonary fibrosis; Senescence; Survival.

PubMed Disclaimer

Conflict of interest statement

Fabrizio Luppi reports personal fees from Roche and Boehringer-Ingelheim outside the submitted work. Meena Kalluri reports personal fees from Roche and Boehringer-Ingelheim outside the submitted work. Paola Faverio reports personal fees from Boehringer-Ingelheim outside the submitted work. Michael Kreuter reports research grants from Galapagos, Roche and Boehringer-Ingelheim. He reports personal fees from Galapagos, Roche and Boehringer-Ingelheim outside the submitted work. Giovanni Ferrara reports personal fees from Astra Zeneca, Roche and Boehringer-Ingelheim outside the submitted work.

Figures

Fig. 1
Fig. 1
Molecular-level hallmarks of ageing that lead to pulmonary fibrosis ( modified from reference [14])
Fig. 2
Fig. 2
Impact of idiopathic pulmonary fibrosis and comorbidities on mortality (from reference [41])
See this image and copyright information in PMC

References

    1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An Official ATS/ERS/JRS/ALAT Statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788–824. doi: 10.1164/rccm.2009-040GL. - DOI - PMC - PubMed
    1. Collard HR, King TE, Bartelson BB, Vourlekis JS, Schwarz MI, Brown KK. Changes in clinical and physiologic variables predict survival in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2003;168:538–542. doi: 10.1164/rccm.200211-1311OC. - DOI - PubMed
    1. Buendía-Roldán I, Mejía M, Navarro C, Selman M Idiopathic pulmonary fibrosis: clinical behavior and aging associated comorbidities. Respir Med. 2017;129:46–52. doi: 10.1016/j.rmed.2017.06.001. - DOI - PubMed
    1. Collard HR, Moore BB, Flaherty KR, Brown KK, Kaner RJ, King TE, Jr, et al. Acute exacerbations of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2007;176:636–643. doi: 10.1164/rccm.200703-463PP. - DOI - PMC - PubMed
    1. Collard HR, Ryerson CJ, Corte TJ, Jenkins G, Kondoh Y, Lederer DJ, et al. Acute exacerbation of idiopathic pulmonary fibrosis an international working group report. Am J Respir Crit Care Med. 2016;194:265–275. doi: 10.1164/rccm.201604-0801CI. - DOI - PubMed