Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive lung disease characterized by the scarring and thickening of lung tissue, which makes breathing progressively more difficult. The term “idiopathic” indicates that the precise cause of the disease remains unknown. Despite this unknown origin, extensive research has identified several factors that are associated with an increased risk of developing this serious condition.
Genetic Influences
While IPF is not strictly inherited, a family history of the condition, referred to as familial pulmonary fibrosis, significantly increases an individual’s susceptibility. This suggests a genetic predisposition rather than a direct inheritance pattern.
Specific genetic variations have been linked to an elevated risk of IPF. The most commonly identified and strongest genetic risk factor is a mutation in the MUC5B gene, which is associated with an approximate 7-fold increase in IPF risk. Other genes involved in maintaining telomere length, such as TERT and TERC, also play a role. Genes related to surfactant production, including SFTPC and SFTPA2, have also been implicated. These genetic factors increase an individual’s predisposition to IPF but do not guarantee its development, indicating a complex interplay with other factors.
Environmental Triggers
Inhaled substances and prolonged environmental exposures are strongly associated with a heightened risk of developing IPF. Cigarette smoking, both current and past, shows a consistent and strong association with IPF. The risk of IPF generally increases with the intensity and duration of smoking.
Occupational exposures to various dusts and fumes can also contribute to lung injury over time. Metal dust, such as from welding or grinding, wood dust, silica, and asbestos fibers are examples of substances that can damage lung tissue with chronic inhalation.
Other environmental factors, though less definitively established, are under ongoing investigation. These include chronic exposure to certain molds, specific agricultural dusts, and potentially severe air pollution. Agricultural work itself, involving exposure to various dusts, vapors, and fumes, has been associated with an increased risk of IPF.
Other Contributing Factors
Beyond genetic predispositions and environmental exposures, several other factors contribute to the risk of IPF. These elements are diverse and encompass biological and health-related aspects.
Age is a significant non-modifiable risk factor, with IPF primarily affecting older adults, typically those over 50-60 years of age. The incidence of IPF increases sharply with advancing age; for instance, the estimated incidence for individuals aged 75 years or older ranges from 27.1 to 76.4 cases per 100,000 person-years. This age-related increase highlights that IPF is largely a disease of aging.
Men are more frequently affected by IPF than women. Worldwide, the incidence is estimated at 10.7 cases per 100,000 person-years for males compared to 7.4 cases per 100,000 person-years for females. This sex-based difference is consistently observed across various populations.
Gastroesophageal Reflux Disease (GERD), characterized by the backflow of stomach acid into the esophagus, is strongly associated with IPF. It is estimated that up to 90 percent of people with IPF also have GERD, often without typical symptoms like heartburn. The mechanism linking GERD to IPF is thought to involve repeated microaspiration of tiny stomach contents into the lungs, leading to chronic inflammation and subsequent scarring.
Certain viral infections have been explored as potential contributors to IPF, although the exact mechanisms are still being researched. Chronic or recurrent infections with viruses such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and Hepatitis C virus (HCV) have been suggested to play a role. A meta-analysis indicated that persistent viral infections, including EBV, CMV, human herpesvirus 7 (HHV7), and human herpesvirus 8 (HHV8), significantly increase the risk of developing IPF.