PF CAN RESULT FROM A NUMBER OF CAUSES. As shown in the following figure, there are four general categories that can lead to the development of fibrotic lung disease: those of unknown or undetermined cause (teal), those that arise from a systemic autoimmune disease (gray), those that are associated with exposure to an agent known to cause PF (green), and those that have an inherited or genetic component (dark gray).



Systemic autoimmune diseases comprise a group of immunologic disorders that can result in the development of an IIP. These disorders include connective tissue diseases (CTD) such as rheumatoid arthritis (RA), lupus erythematosus (lupus), scleroderma (SSc), polymyositis/dermatomyositis, systemic vasculitis such as ANCA (+) polyangiitis (also called Wegener’s granulomatosis), and Churg-Strauss syndrome. The specific type of lung disease that these disorders cause is based on the underlying autoimmune disorder.8 The most common systemic autoimmune diseases that can result in the development of PF are SSc, RA, and lupus. Patients with CTD are also more likely to develop pulmonary hypertension (high blood pressure in the lungs). It is highly recommended that patients with CTD and symptoms of lung disease be evaluated and followed by a rheumatologist for their CTD and a pulmonologist for their lung disease.

PF can develop through significant exposure to environmental or occupational agents. Exposure to inorganic dust (asbestos, silica, beryllium, hard metal dusts), organic dust (animal proteins, bacteria, molds, fungi), or gases and fumes can contribute to the development of PF. Some of the most common forms of occupational related PF are asbestosis and silicosis. People that work in places or spend extended periods of time where there are high levels of organic dusts can develop hypersensitivity pneumonitis (HP). The two most common types of disease caused by organic dust are “bird fancier’s lung” and “farmer’s lung.” Additionally, exposure to some medications, high-dose radiation, and radiation therapy can also result in the development of PF. Medications such as antibiotics (nitrofurantoin, sulfasalazine), antiarrhythmics (amiodarone, propranolol), anticonvulsants (phenytoin), and chemotherapeutic agents (methotrexate, bleomycin, oxaliplatin) have also been associated with the development of PF.

We know a lot about how some ILDs affect patients, but frequently a cause has not been identified. As its name suggests, the origin and development of IIPs and other idiopathic disorders, such as sarcoidosis, are still not completely understood. The most common form of IIP is IPF. The current thinking is that there is an abnormal response to injury that ultimately results in scarring of the lung.It is also hypothesized that certain environmental and genetic factors may contribute to the development of IPF; as these are more clearly defined, the disease process should be better understood. Ultimately, this should lead to new and effective treatments.

It is estimated that approximately 10–15% of patients with IPF have a form of PF that occurs in families. This is called familial pulmonary fibrosis (FPF) or familial interstitial pneumonitis (FIP). In some families with FPF/FIP, not every affected family member has the same type of IIP. In about half of families with FPF, one or more family members have IPF and another has a different form of IIP. Other forms may include NSIP, DIP, RB-ILD, and COP.

Another rare form of familial or genetic PF is Hermansky-Pudlak syndrome (HPS). There are eight different types of HPS that can be distinguished by the signs, symptoms, and underlying genetic cause; types 1, 2, and 4 are the types associated with the development of PF.

As is suggested by FPF/FIP, there is a growing body of evidence suggesting that genes or genetic variants may predispose certain individuals to developing PF or IPF.

  • Studies have found that some families with a history of more than two cases of IPF carry a mutation in the surfactant protein C (SP-C) gene, which normally helps lungs function correctly.9
  • Another study suggested that the presence of specific genes may predict which IPF patients will have a more severe, rapidly progressing form of the disease.10
  • Shortened telomeres (telomeres protect the fragile ends of chromosomes from deterioration) may be the cause of PF in certain patients as they grow older. Mutations in the genes TERT and TERC result in shortened telomeres and appear to predispose certain individuals to PF.11,12
  • Individuals with variations in the MUC5B gene, which encodes a mucus protein, may have an increased risk between 6–22 times of developing PF depending on family history.13

The clinical implications of the identification of genetic variations that are associated with PF remain unclear, as there are no therapies targeting specific genetic factors for PF. Further, there is limited availability of genetic testing to identify genes that may contribute to PF or IPF. It is therefore important for patients to discuss the potential utility and possible risks of genetic testing with a qualified genetic counselor and their health care provider.


  • Cigarette smoking
  • Prolonged exposure to occupational or environmental contaminants or dusts
  • Viral or bacterial lung infections
  • Certain medicines, such as some antibiotics, antiarrhythmics, anticonvulsants, chemotherapeutic agents, or therapeutic radiation
  • Acid reflux disease (GERD)
  • Genetic predisposition

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Updated April 2013
This information has been approved by Gregory P. Cosgrove, MD (September 2012)