Pulmonary fibrosis develops when repeated injury to lung tissue triggers an abnormal healing response, replacing flexible air sacs with stiff scar tissue. In roughly half of all cases, a specific cause can be identified: workplace exposures, autoimmune diseases, medications, infections, or smoking. When no cause is found, the condition is called idiopathic pulmonary fibrosis (IPF), which accounts for the other large share of diagnoses and is most common in men over 65.
How Lung Scarring Actually Happens
Healthy lungs repair small injuries all the time. In pulmonary fibrosis, that repair process goes wrong. When the thin lining of the air sacs (alveoli) is damaged, the body activates a clotting-like cascade that recruits specialized repair cells called fibroblasts. Normally, these cells lay down a small amount of structural protein, seal the wound, and stop. In pulmonary fibrosis, signaling molecules keep the fibroblasts switched on. They multiply and transform into a more aggressive cell type that produces collagen at an accelerated rate.
The amount of scar tissue that builds up depends on how many of these activated cells are present and how long they keep producing collagen. Over months and years, the normally thin, elastic walls of the air sacs thicken and stiffen. Oxygen can no longer pass through easily, which is why breathlessness during activity is typically the earliest symptom. The scarring is permanent. Once lung tissue is replaced by collagen, it does not return to normal.
Workplace and Environmental Exposures
Breathing in certain dusts and fumes over years is one of the most well-documented triggers. A large meta-analysis found that exposure to vapors, gases, dusts, or fumes on the job accounted for roughly 26% of the attributable risk for IPF. Specific culprits include metal dust and fumes (8% of attributable risk), wood dust (4%), and silica (3%). Asbestos exposure raises the odds of developing IPF by about 58% compared to people without that exposure.
Silica remains a threat in industries like mining, sandblasting, and stone cutting. Asbestos, while banned or restricted in many countries, still lingers in older buildings and continues to cause disease decades after exposure. Agricultural workers face risks from inhaling organic dusts, including mold spores and proteins from bird droppings, which can cause a related condition called hypersensitivity pneumonitis that may progress to fibrosis if exposure continues.
Smoking and Early-Life Tobacco Exposure
Cigarette smoking is one of the strongest modifiable risk factors. A large population-based cohort study found that people who started smoking in childhood had 3.65 times the risk of developing IPF compared to never-smokers. Starting in adolescence carried 2.64 times the risk, and starting in adulthood still doubled it. The earlier someone begins smoking, the greater the cumulative damage to the delicate lining of the air sacs.
Even passive exposure matters. Children born to mothers who smoked around the time of birth had a 26% higher risk of eventually developing IPF, even after adjusting for the child’s own later smoking habits. This suggests that tobacco smoke can prime the lungs for abnormal scarring responses long before symptoms appear.
Autoimmune and Connective Tissue Diseases
The immune system can turn against lung tissue in several autoimmune conditions, triggering inflammation that eventually leads to fibrosis. Systemic sclerosis (scleroderma) is the autoimmune disease most commonly accompanied by interstitial lung disease, but when researchers tracked which patients actually progressed to worsening, permanent fibrosis, rheumatoid arthritis was the most frequent driver, responsible for about 33% of progressive cases. Sjögren’s disease followed at 30%, then scleroderma at 18%, and inflammatory muscle diseases (myositis) at 15%.
Together, rheumatoid arthritis and Sjögren’s disease accounted for more than 63% of progressive pulmonary fibrosis tied to autoimmune conditions. Lupus, mixed connective tissue disease, and dermatomyositis can also cause lung scarring, though less commonly. In these cases, treating the underlying autoimmune disease is part of managing the lung involvement, but fibrosis that has already formed does not reverse.
Medications That Can Damage Lung Tissue
Certain drugs taken over long periods can injure the air sac lining and set off the fibrotic cascade. The heart rhythm medication amiodarone is one of the best-known offenders. It interferes with the normal breakdown of fatty molecules inside immune cells, causing them to accumulate and triggering chronic inflammation. Chemotherapy drugs, particularly bleomycin and cyclophosphamide, are also well-established causes. Bleomycin-related lung damage is dose-dependent, meaning the risk climbs with each additional treatment cycle.
Other medications linked to pulmonary fibrosis include nitrofurantoin (a common antibiotic used for urinary tract infections), the anti-inflammatory drug penicillamine, gold compounds once used for rheumatoid arthritis, and procainamide (another heart rhythm drug). Drug-induced fibrosis is sometimes partially reversible if caught early and the medication is stopped, which makes it one of the few forms where the trajectory can be altered.
Chronic Viral Infections
Persistent viral infections appear to significantly raise the risk of pulmonary fibrosis. A meta-analysis of available evidence found that Epstein-Barr virus (the virus that causes mono) was associated with nearly 10 times the risk of IPF. Human herpesvirus 8 carried about 9 times the risk. Cytomegalovirus and human herpesvirus 7 each roughly doubled to tripled the risk. Notably, it was chronic or latent infections, not acute ones, that drove this association. The theory is that ongoing, low-grade viral activity in lung tissue causes sustained injury to the air sac lining, keeping the abnormal repair cycle active.
COVID-19 has added a new dimension to this picture. Severe lung inflammation during acute infection can leave behind fibrotic changes, though it remains an active area of investigation how often post-COVID lung scarring truly progresses versus stabilizes over time.
Genetics and Family History
Up to 20% of people with IPF have a family member with the same condition, and these familial cases tend to follow a pattern of inheriting a single gene variant from one parent. The strongest known genetic risk factor is a variant in the MUC5B gene, which affects mucus production in the airways. Carrying one copy of this variant increases IPF risk about sixfold. Carrying two copies increases it twentyfold.
Another major group of genetic culprits involves genes that maintain telomeres, the protective caps on the ends of chromosomes. Variants in genes called TERT, TERC, RTEL1, and PARN lead to shorter telomeres and accelerated cellular aging in the lungs. These telomere-related variants account for roughly 15 to 20% of familial pulmonary fibrosis and show up in 2 to 5% of cases that appear to be sporadic (no obvious family history). People with these mutations tend to develop fibrosis at a younger age and have worse outcomes.
Having a genetic predisposition does not guarantee you will develop the disease. These variants increase susceptibility, but environmental exposures, smoking, and other triggers typically act as the match that lights the fuse.
When No Cause Is Found
Idiopathic pulmonary fibrosis is diagnosed when all identifiable causes have been ruled out. It predominantly affects men, who make up about 70 to 78% of cases in large international studies, with the average age at diagnosis around 67 to 70. Diagnosis relies on a characteristic scarring pattern visible on a CT scan, sometimes confirmed with a lung biopsy, and a thorough review of occupational history, medications, and autoimmune markers to exclude other explanations.
Major respiratory societies updated their guidelines in 2022 to define progressive pulmonary fibrosis more precisely. A diagnosis of progressive disease requires at least two of three criteria within a single year: worsening symptoms, worsening lung function on breathing tests, or worsening scarring on imaging. This framework applies to fibrosis from any cause, not just IPF, and helps clinicians identify patients whose disease is advancing despite treatment. A working diagnosis of IPF is also reviewed regularly, since new information can sometimes reclassify the condition as having a specific, treatable cause.