Recognizing pulmonary fibrosis is critical

Pulmonary fibrosis is a common threat for many patients with interstitial lung disease (ILD)1–7


ILDs are a heterogeneous group of over 200, mostly rare, lung disorders that vary in etiology, many of which are fibrotic.*8–15

lung disorders that vary in etiology


Reproduced with permission of the ©ERS 2020. European Respiratory Review 27 (150)180076; DOI: 10.1183/16000617.0076-2018. Published December 21, 2018.
*E.g. asbestosis, silicosis.

Fibrotic ILDs are characterized by irreversible scarring of lung tissue, known as pulmonary fibrosis.12–16


Epidemiological studies have shown that incidence of ILD has been increasing over the last three decades.18–21

Although individual fibrotic ILDs are rare, collectively they affect a considerable number of patients, representing a substantial burden of disease.17

In Europe, the prevalence of ILD is estimated to be 6.3–76.0 per 100,000 people. In the US, ILD prevalence is estimated at 74.3 per 100,000.22

Prevalence of ILD in USA, Belgium, Greece, Malta and France*22

prevalence of ild


Reprinted from Advances in Therapy, Olson A, Hartmann N, Patnaik P, et al., Estimation of the prevalence of progressive fibrosing interstitial lung diseases: systematic literature review and data from a physician survey, 38, 854–867, 2020, Springer Nature.

*Based on 16 physician survey publications assessing prevalence of ILD, individual ILDs associated with fibrosis and progressive fibrosing ILDs. Five publications reported overall ILD prevalence, estimated at 6.3–76.0 per 100,000 people in Europe (four studies) and 74.3 per 100,000 in the USA (one study).22

Progressive pulmonary fibrosis

Pulmonary fibrosis can be progressive, which is associated with worse outcomes.7,12–15,23 Idiopathic pulmonary fibrosis (IPF) is considered as the most typical progressive fibrosing ILD: all patients with IPF by definition have progressive disease.23

Progressive pulmonary fibrosis can become a key driver of irreversible lung damage and early mortality that warrants urgent referral and identification.12–15

Pulmonary fibrosis scars and stiffens tissue, making it harder to breathe3,16,24–27

pulmonary fibrosis scars and stiffens tissue

Fibrotic ILDs cause irreversible lung damage – early recognition and referral can help reduce the substantial burden of disease10,12–17,28,29


Amidst the heterogeneous group of lung disorders that make up ILDs, ILD is also a common manifestation of connective tissue diseases (CTDs), such as rheumatoid arthritis (RA), systemic sclerosis (SSc) and polymyositis (PM)/dermatomyositis (DM).30–34 
CTD-ILDs can have varied clinical presentations and disease courses.35

ILD often develops early in the course of a CTD, and may even be the first manifestation of a previously undiagnosed or unrecognized CTD.30,31,34,36

prevalence of ctds and ctd ilds


Prevalence figures sourced as midpoint values from ranges for CTD and CTD-ILD prevalence as follows: RA prevalence 500–1000 per 100,000;38–40 RA-ILD prevalence 10%–30% of RA.37, 43–46 SSc prevalence 7.2–44.3 per 100,000;41 SSc-ILD prevalence 42% of SSc.42

Maintain a high level of suspicion for ILD in known CTD patients — subclinical disease is common32


Symptoms associated with pulmonary fibrosis in ILD, including cough, fatigue, and dyspnea, negatively impact patients’ quality of life, mental wellbeing, social interactions, and work capacity.47–49

Symptoms common to most ILDs10,50

dry cough

A dry cough that doesn’t get better
shortness of breath

Shortness of breath, especially with mild physical activity

ipf finger clubbing

For IPF, finger clubbing (widening and rounding of the tips of fingers)

As disease progresses, the symptoms that patients with fibrotic ILDs experience worsen.3,5,49

Your early recognition and referral is critical because once lung function is lost, it’s lost forever10,16,28,29

Shared mechanisms of progressive pulmonary fibrosis

Learn about the common pathophysiological mechanisms behind fibrogenesis and how it explains self-sustaining disease behavior in fibrotic ILDs.


Interstitial lung disease, or ILD, encompasses a wide variety of chronic lung diseases such as idiopathic pulmonary fibrosis, chronic hypersensitivity pneumonitis, idiopathic nonspecific pulmonary fibrosis, sarcoidosis, ILD associated with connective tissue diseases, such as systemic sclerosis-ILD, inflammatory conditions, such as rheumatoid arthritis, and ILD associated with exposure to occupational or environmental irritants.

A proportion of patients with ILD develop a progressive fibrosing phenotype independent from their ILD classification, with a disease course similar to IPF. Many of these patients show a restrictive pattern on pulmonary function testing. Their pulmonary fibrosis is driven by an abnormal wound healing response following repeated injury, regardless of the cause of that injury. Mediators released in response to alveolar epithelial and/or vascular endothelial injury include chemokines, endothelin 1, thrombin and numerous growth factors.

The abnormal healing response is believed to be due to an imbalance of such mediators, which creates a pro-fibrotic environment. The pro-fibrotic environment drives recruitment, proliferation, activation, and trans-differentiation of resident interstitial fibroblasts into contractile myofibroblasts.    Myofibroblasts may also be derived from the trans-differentiation of other cell types, including pericytes, circulating fibrocytes, endothelial and epithelial cells. These myofibroblasts produce excessive extracellular matrix components. The accumulation of these components, combined with collagen cross-linking and contraction, distort the tissue architecture and alter gas exchange.

This fibrotic scarring can also lead to occlusion of the local microvasculature, contributing to hypoxia. Once initiated, pulmonary fibrosis can become self-sustaining independent of the original trigger.   This happens through multiple feed-forward amplification loops as a result of increased matrix stiffness, tissue pressure, and hypoxia.

Pulmonary fibrosis is irreversible, and its progression leads to impaired gas exchange, increasing shortness of breath, a continually reduced quality of life, and ultimately to respiratory failure. Early recognition of pulmonary fibrosis is vital, given the significant morbidity and mortality associated with progressive fibrosing ILD.


CTD, connective tissue disease; CTD-ILD, connective tissue disease-associated interstitial lung disease; DM, dermatomyositis; ILD, interstitial lung disease; IPF, idiopathic pulmonary fibrosis; PM, polymyositis; RA, rheumatoid arthritis; RA-ILD, rheumatoid arthritis-associated interstitial lung disease; SSc, systemic sclerosis; SSc-ILD, systemic sclerosis-associated interstitial lung disease.

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