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Overview of Interstitial Lung Diseases


Joyce Lee

, MD, MAS, University of Colorado Denver

Last full review/revision Jun 2021| Content last modified Jun 2021
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Interstitial lung disease (also called diffuse parenchymal disease) is a term used to describe a number of different disorders that affect the interstitial space. The interstitial space consists of the walls of the air sacs of the lungs (alveoli) and the spaces around blood vessels and small airways. Interstitial lung diseases result in abnormal accumulation of inflammatory cells in lung tissue, cause shortness of breath and cough, and have similarities in their appearance on imaging studies but are otherwise unrelated. Some of these diseases are very unusual.

Early in the course of these diseases, white blood cells, macrophages, and protein-rich fluid accumulate in the interstitial space, causing inflammation. If the inflammation persists, scarring (fibrosis) may replace normal lung tissue. As alveoli are progressively destroyed, thick-walled cysts (called honeycombing because they resemble the cells of a beehive) are left in their place. The condition resulting from these changes is called pulmonary fibrosis.

Although the various interstitial lung diseases are separate and have different causes, they have some similar features. All lead to a decreased ability to transfer oxygen to the blood, and all cause stiffening and shrinkage of the lungs, which makes breathing difficult and causes cough. However, being able to eliminate carbon dioxide from the blood is usually not a problem.


Unusual Interstitial Lung Diseases





Slow-developing (over weeks to months) or sudden, severe symptoms

Shortness of breath


Stopping the drug that is causing symptoms

Corticosteroids (sometimes effective)

Many classes of drugs may cause this disease.

The disease is often more severe in older people.

The effects of some drugs on the lungs are similar to those of systemic lupus erythematosus (lupus).

The extent and severity of the disease are sometimes related to how large the drug dose was and how long the drug was taken.

Alveolar hemorrhage syndromes (bleeding in the lungs)

Most commonly, coughing up blood (hemoptysis)

Anemia due to chronic blood loss

Kidney failure (sometimes)

Corticosteroids and cytotoxic drugs (such as cyclophosphamide )

Blood transfusions if needed because of blood loss

Oxygen therapy for a low level of oxygen in the blood

In these rare disorders, blood leaks from small, thin-walled blood vessels (capillaries), often because of an autoimmune reaction.

Massive bleeding can cause death.

Difficulty breathing


Chest pain

Sometimes coughing up blood

Lung transplantation


This rare disorder occurs in young women.

It may worsen during pregnancy.


Causes of Interstitial Lung Diseases



Autoimmune disorders

Organic dust

Bird droppings and molds


Amiodarone, bleomycin, busulfan, carbamazepine, checkpoint inhibitors, chlorambucil, cocaine, cyclophosphamide, gold, methotrexate, nitrofurantoin, sulfasalazine, and sulfonamides


Aluminum powder, asbestos, beryllium, metals, sulfur dioxide, talc

Genetic disorders

Fabry disease, familial pulmonary fibrosis, Gaucher disease, Hermansky-Pudlak syndrome, neurofibromatosis, Niemann-Pick disease (rare), pulmonary alveolar microlithiasis, pulmonary alveolar proteinosis, and tuberous sclerosis

Idiopathic* interstitial pneumonias

Therapeutic or industrial radiation-related

Radiation therapy for cancer

Other disorders

* Idiopathic means with no known cause.

Diagnosis of Interstitial Lung Diseases

  • Chest computed tomography

  • Pulmonary function testing

  • Arterial blood gas analysis

Because interstitial lung diseases cause symptoms that are similar to those of much more common disorders (for example, pneumonia, chronic obstructive pulmonary disease [COPD]), they may not be suspected at first. When an interstitial lung disease is suspected, diagnostic testing is done. Testing can vary by the disease suspected but tends to be similar.

Most people have a chest x-ray, computed tomography (CT) of the chest, pulmonary function tests, and often arterial blood gas analysis. CT is more sensitive than chest x-ray and helps doctors make a more specific diagnosis. CT is done using techniques that maximize resolution (high-resolution CT). Pulmonary function tests often show that the volume of air that the lungs can hold is abnormally small. Arterial blood gas tests measure the levels of oxygen and carbon dioxide in the arterial blood and determine the acidity (pH) of the blood.

To confirm the diagnosis, doctors sometimes remove a small sample of lung tissue for microscopic examination (lung biopsy) using a procedure called fiberoptic bronchoscopy. A lung biopsy done this way is called transbronchial lung biopsy. Many times, a larger tissue sample is needed and must be removed surgically, sometimes with use of a thoracoscope (a procedure called video-assisted thoracoscopic lung biopsy).

Blood tests may be done. They usually cannot confirm the diagnosis but are done as part of the search for other, similar disorders.

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Air Pollution-Related Illness
Illnesses linked to air pollution are categorized as environmental lung diseases. Exposure to air pollution for an extended period may increase respiratory infections and symptoms of respiratory disorders, such as coughing. In which of the following groups is long-term exposure to air pollution especially likely to increase respiratory infections and symptoms of respiratory disorders?
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