Interstitial lung disease (ILD) is not a single condition but a group of more than 200 disorders that cause inflammation and scarring in the tissue surrounding the air sacs of the lungs. The causes range from workplace dust exposure and autoimmune diseases to medication side effects, infections, and inherited genetic variants. In a significant number of cases, no cause is ever identified, and the disease is classified as “idiopathic.”
How ILD Damages the Lungs
The interstitium is the thin layer of tissue between the air sacs in your lungs and the blood vessels that carry oxygen into your bloodstream. When this tissue becomes inflamed or scarred, it stiffens and thickens, making it harder for oxygen to pass through. Over time, this scarring (called fibrosis) can become permanent, progressively reducing lung function. What triggers that initial inflammation varies widely, which is why pinpointing the cause matters so much for treatment.
Autoimmune and Connective Tissue Diseases
When the immune system attacks the body’s own tissues, the lungs are frequently caught in the crossfire. Several autoimmune conditions carry a well-documented risk of ILD, though the likelihood varies dramatically by disease. Roughly 47% of people with systemic sclerosis (scleroderma) develop ILD, making it the autoimmune condition most closely linked to lung scarring. About 11% of people with rheumatoid arthritis and 6% of those with lupus also develop the disease.
In these cases, the same chronic inflammation that damages joints, skin, or other organs gradually inflames the lung tissue. Because autoimmune ILD can develop silently before causing noticeable breathing problems, doctors often monitor lung function in patients with these conditions even when they have no respiratory symptoms.
Inhaled Dusts and Workplace Exposures
Breathing in certain mineral or industrial dusts over months or years is one of the oldest known causes of ILD. The CDC identifies three primary forms: asbestosis from asbestos fibers, silicosis from silica dust, and coal workers’ pneumoconiosis (black lung) from coal mine dust. Other dusts that can cause the same type of damage include aluminum, iron, talc, mica, and graphite particles.
These diseases tend to develop slowly. Workers may be exposed for years or even decades before scarring becomes severe enough to cause shortness of breath. Construction workers, miners, sandblasters, and anyone who cuts or grinds stone or concrete face the highest risk. The tiny particles lodge deep in the lungs where the body cannot clear them effectively, triggering a persistent inflammatory response that eventually produces scar tissue.
Organic Dusts and Allergens
Not all inhaled triggers are industrial. Hypersensitivity pneumonitis is a form of ILD caused by repeated exposure to organic particles that provoke an allergic-type reaction in the lungs. Over 300 substances are known to cause it. Some of the most common include proteins in bird feathers and droppings (bird fancier’s lung), mold growing on hay, straw, and grain (farmer’s lung), bacteria in hot tub water vapor (hot tub lung), and fungi or bacteria growing inside humidifiers and HVAC systems.
Less obvious sources include mold dust from sugar cane processing, fungi on cheese, and dust from mushroom cultivation. Unlike mineral dust diseases, hypersensitivity pneumonitis can sometimes be reversed if the trigger is identified and eliminated early. If exposure continues, though, the inflammation progresses to permanent fibrosis.
Medications That Can Trigger ILD
Dozens of medications list lung inflammation or scarring as a potential side effect. The risk varies by drug class, but a few categories stand out.
- Cancer treatments: Many chemotherapy drugs can damage lung tissue, including bleomycin, gemcitabine, and cyclophosphamide. Newer immunotherapy drugs (immune checkpoint inhibitors) also carry risk, particularly when two types are combined. A class of targeted cancer drugs called mTOR inhibitors are significant causes of lung toxicity.
- Heart medications: Amiodarone, a widely used drug for irregular heart rhythms, causes lung toxicity in up to 5% of patients. Heart rhythm drugs as a class carry one of the highest risks of drug-induced ILD.
- Rheumatology drugs: Methotrexate, commonly prescribed for rheumatoid arthritis, is a well-known cause. Biologic medications that block a protein called TNF-alpha are also linked to ILD, which creates a difficult clinical situation since the autoimmune diseases they treat can independently cause lung scarring.
- Antibiotics: Nitrofurantoin, frequently prescribed for urinary tract infections, is an established cause of drug-induced ILD.
Drug-induced ILD can sometimes resolve after stopping the medication, but not always. The challenge is recognizing it early, since the symptoms (cough, breathlessness) mimic many other conditions.
Smoking and Tobacco Use
Smoking is a direct cause of several specific ILD subtypes. Desquamative interstitial pneumonia, which involves the accumulation of immune cells in the air sacs, is almost exclusively seen in smokers and may be partially reversible with smoking cessation. Respiratory bronchiolitis-associated ILD is another smoking-specific form. More broadly, smoking is the single biggest environmental risk factor for idiopathic pulmonary fibrosis, the most common and most deadly form of ILD. The relationship is dose-dependent: the more pack-years of smoking, the higher the risk.
Infections and Post-COVID Lung Scarring
Severe lung infections can leave behind scarring that qualifies as ILD. COVID-19 brought this risk into sharp focus. People who developed severe COVID pneumonia, particularly those who needed mechanical ventilation or developed acute respiratory distress syndrome, faced the highest risk of lasting lung damage. In many cases the scarring improves gradually over months, but some patients develop permanent fibrosis with ongoing breathing difficulties.
The connection between milder COVID infections and long-term ILD is less clear. Other viral and bacterial pneumonias can also cause post-infectious scarring, though it is less common than with COVID-19 at its peak.
Genetic Risk Factors
Some people carry inherited gene variants that make their lungs more vulnerable to fibrosis. The strongest known genetic risk factor for idiopathic pulmonary fibrosis is a variant in the MUC5B gene, which affects mucus production in the airways. People who carry one copy of this variant have a significantly elevated risk, and those with two copies face even higher odds. Other important gene variants involve TERT, which helps maintain the protective caps on chromosomes, and SFTPC, which plays a role in keeping the air sacs open and functional.
Familial forms of ILD, where multiple family members are affected, tend to appear at a younger age than sporadic cases. If you have a close relative with pulmonary fibrosis, your risk is meaningfully higher than the general population’s, though carrying these gene variants does not guarantee you will develop the disease.
When No Cause Is Found
After all identifiable triggers are ruled out, a large subset of ILD cases are classified as idiopathic interstitial pneumonias, meaning the cause is unknown. Idiopathic pulmonary fibrosis (IPF) is the most common and most serious of these. In the United States alone, nearly 68,000 deaths were attributed to IPF between 2020 and 2022, either as the primary cause or a contributing factor. The death rate rises steeply with age, reaching 67.6 per 100,000 in adults 75 and older, and is higher in men than women.
Other idiopathic forms include nonspecific interstitial pneumonia, cryptogenic organizing pneumonia, and acute interstitial pneumonia. Each behaves differently: some respond well to treatment and carry a relatively good prognosis, while IPF typically worsens over time despite therapy. This is why identifying the specific type of ILD matters as much as identifying the cause.
How Doctors Identify the Cause
High-resolution CT scans are the cornerstone of ILD diagnosis because different causes leave distinct patterns of scarring. A pattern called usual interstitial pneumonia, with honeycomb-like scarring concentrated at the lung bases, is so closely linked to IPF that a lung biopsy often is not needed to confirm it. Other patterns, like ground-glass opacities with subpleural sparing, point toward nonspecific interstitial pneumonia. Random distribution of small nodules with air trapping suggests hypersensitivity pneumonitis.
Beyond imaging, doctors piece together the diagnosis from occupational history, medication lists, blood tests for autoimmune markers, and sometimes genetic testing. A thorough history is often the most revealing diagnostic tool, since many ILD causes hide in the details of a person’s daily environment, hobbies, or workplace exposures that might not seem medically relevant at first glance.