Skip to main content
For Healthcare Professionals

IPF

(Idiopathic Pulmonary Fibrosis)

Overview

Idiopathic pulmonary fibrosis (IPF) was defined as a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause in 20001. IPF occurs primarily in older adults and is limited to the lungs with the histopathological (evidence of patchy involvement of lung parenchyma by fibrosis/architectural distortion, honeycombing in a predominantly subpleural/paraseptal distribution, presence of fibroblast foci) and/or radiological (subpleural, basal-predominant honeycombing and reticular abnormality, with or without traction bronchiectasis) pattern of usual interstitial pneumonia (UIP). The disease is characterized by progressive worsening of dyspnea and lung function, and is associated with a poor prognosis - a median survival time of 2 to 3 years from the time of diagnosis1,2.

 

Epidemiology

There are no large-scale studies of the incidence or prevalence of IPF on which to base formal estimates. The incidence of IPF was estimated at 10.7 cases per 100,000 per year for men and 7.4 cases per 100,000 per year for women in a population-based study from the county of Bernalillo, New Mexico. A study from the United Kingdom reported an overall incidence rate of only 4.6 per 100,000 person-years, but estimated that the incidence of IPF increased by 11% annually between 1991 and 2003. A third study from the United States estimated the incidence of IPF to be between 6.8 and 16.3 per 100,000 persons using a large database of healthcare claims in a health plan. Prevalence estimates for IPF have varied from 2 to 29 cases per 100,000 in the general population. The wide range in these numbers is likely explained by the previous lack of uniform definition used in identifying cases of IPF, as well as by differences in study designs and populations3.

Most epidemiologic studies of IPF focused on Western countries, including the United States, United Kingdom, Denmark, and Italy. However, few studies have investigated this disease in Asia. A recent study in Taiwan found that the annual incidence of IPF ranged from 0.2 to 1.3 new cases per 100,000 person-years in 2001 to 2011, and the cumulative prevalence of IPF increased from 0.2 per 100,000 persons in 2001 to 6.4 per 100,000 persons in 20114.

Pathogenesis

The molecular causes of IPF are not yet fully understood. The current model of IPF pathogenesis suggests three pathophysiologic stages: predisposition, initiation and progression5.

Predisposition: The initial predisposition stage includes processes such as genetic mutations, environmental exposure (routine or otherwise), and aging that predispose an individual to develop lung fibrosis5.

Initiation: The second initiation stage includes defined profibrotic processes, such as transforming growth factor beta (TGF-β) activation, fibrocyte recruitment, epithelial-to-mesenchymal transition (EMT), and activation of the unfolded protein response (UPR), that, when engaged, accelerate profibrotic processes5.

Progression: The final progression stage includes molecular processes that lead directly to fibrosis, such as pathologic fibroblast differentiation, matrix deposition and remodeling, increased matrix stiffness, and profibrotic epigenetic changes within fibroblasts and epithelial cells. Events in the latter stage may bypass the first two stages, leading to persistent mesenchymal cell activation and matrix remodeling5.

To develop therapies for IPF, a clearer understanding is needed of the relationships between the specific molecular pathways that are activated during each stage of IPF. This understanding will inform which stage of the disease therapies target as well as whether targeting one stage of the disease is sufficient to slow progression or whether simultaneous targeting of molecular pathways in each stage of disease is required for effective therapy5.

Risk factors

 

Although IPF is, by definition, a disease of unknown etiology, a number of potential risk factors have been described.

 

Cigarette smoking is strongly associated with IPF, particularly for individuals with a smoking history of more than 20 pack-years. This applies to familial as well as sporadic IPF.

Increased risk for IPF has been found to be associated with a variety of environmental exposures such as metal dusts (brass, lead, and steel) and wood dust (pine). Farming, raising birds, hair dressing, stone cutting/polishing, and exposure to livestock and to vegetable dust/animal dust have also been associated with IPF. However, these observations must be interpreted with great caution, since epidemiologic studies of environmental risk factors are subject to a variety of biases and limitations3.

Several studies have suggested that abnormal acid gastroesophageal reflux, through its presumed association with micro-aspiration, is a risk factor for IPF. Other risk factors such as diabetes mellitus have also been described3.

Recent reports by several investigators have documented that genetic variants within the human telomerase reverse transcriptase (hTERT) or human telomerase RNA (hTR) components of the telomerase gene are associated with familial pulmonary fibrosis and are present in some patients with sporadic IPF. These rare mutations can be found in up to 15% of familial pulmonary fibrosis kindreds and 3% of sporadic idiopathic interstitial pneumonia cases, and result in telomere shortening that ultimately causes apoptosis of cells, including the alveolar epithelial cell3.

Polymorphisms of genes encoding for cytokines (interleukin [IL]-1 ⍺, tumor necrosis factor-⍺, lymphotoxin ⍺, IL-4, IL-6, IL-8, IL-10, and IL-12), enzymes (⍺1- antitrypsin and angiotensin-converting enzyme), profibrotic molecules (transforming growth factor-β1), coagulation pathway genes (plasminogen activator inhibitors-1 and -2), genes for surfactant protein-A and -B, immunomodulatory genes (complement receptor 1, NOD2/CARD15), and matrix metalloproteinase (MMP)-1 have been reported to have increased frequencies in patients with sporadic IPF. Many of these have also been related to disease progression. However, none of these findings has been validated in subsequent studies3.

The median age of patients with IPF was reported to be between 65 and 70 years in all series with a range of 55–80 years. In fact, older age (e.g. 70 years) is the most powerful clinical predictor of the probability of IPF in patients with idiopathic interstitial lung diseases (ILD), while the probability of genuine IPF is extremely low before the age of 50 years6.

References:

  1. Raghu G, et al. Am J Respir Crit Care Med. 2018 Sep 1;198(5):e44-e68.

  2. Spagnolo P, et al. Multidiscip Respir Med. 2012 Nov 12;7(1):42.

  3. Raghu G, et al. Am J Respir Crit Care Med. 2011 Mar 15;183(6):788-824.

  4. Yang SN, et al. Healthcare (Basel). 2020 Dec 21;8(4):580.

  5. Wolters PJ, et al. Annu Rev Pathol. 2014;9:157-79.

  6. Cordier JF, Cottin V. Eur Respir J. 2013 Oct;42(4):916-23.

Reporting adverse events

Please be aware that this website contains promotional information about Boehringer Ingelheim medicines and services. Some of this may not be directly relevant to your scope of practice and it is your own decision whether you choose to view this information.