Information on the following diseases can be found in the Related Disorders section of this report:

• Interstitial Pneumonia
• Extrinsic Allergic Alveolitis

The first symptom associated with idiopathic pulmonary fibrosis is often progressive shortness of breath (dyspnea). Also, affected individuals may exhibit a persistent dry cough. Over time, the shortness of breath will be apparent with progressively less exertion until, eventually, it may occur even when the individual is at rest.

Additional symptoms may include loss of appetite, weight loss, fatigue, weakness, fever, and vague chest pains. Ends of the fingers or toes may become broadened and shiny (clubbed). When oxygen circulation in the blood is poor, the skin may appear bluish (cyanotic).

Because the immune system is weakened, infections may more readily occur in individuals with this disease. Serious complications may develop, including emphysema, pulmonary infections, respiratory failure because of lack of oxygen in the blood (hypoxemia), blood clots (emboli), high blood pressure of the arteries within the lungs (pulmonary hypertension), and/or heart disease. Severity of symptoms may vary widely from case to case.

The exact cause of idiopathic pulmonary fibrosis is not known (idiopathic). Some researchers believe that scleroderma (changes in collagen tissue in the lungs), a blood factor associated with rheumatoid arthritis, or an autoimmune factor may be causes. Autoimmune disorders are caused when the body's natural defenses against "foreign" or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons.

Additional theories as to the cause of idiopathic pulmonary fibrosis include viral illnesses, allergic reactions, and/or exposure to certain environmental factors, such as tobacco smoke or occupational pollutants. However, this disease is not limited to people who have used tobacco. Some researchers believe the scarring process is a reaction to microscopic injury to the lung. More research is necessary to determine the exact cause of this disorder.

In a few extremely rare, sporadic cases, a familial pattern has been detected that leads to the idea that some individuals may be genetically predisposed to idiopathic pulmonary fibrosis. There is evidence that, in such cases, a mutation of the gene encoding pulmonary surfactant protein (SP-C protein) may influence susceptibility to idiopathic pulmonary fibrosis. The gene in question has been traced to a site on the long arm of chromosome 10 (10q22.2-23.1).

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22, and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome, and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further subdivided into many bands that are numbered. For example, "chromosome 10q22.2-23.1" refers to a region on the long arm of chromosome 10 between bands 22.2 and 21.1. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Idiopathic pulmonary fibrosis affects males and females in equal numbers. The disorder usually becomes apparent during middle age, somewhere between 40 and 70 years of age. The disorder usually develops slowly over the course of several years. Because this disease is thought to be under-diagnosed, it is difficult to have an accurate sense of how many people are affected.

Symptoms of the following lung disorders can be similar to those of idiopathic pulmonary fibrosis. Comparisons may be useful for a differential diagnosis:

Interstitial pneumonia is characterized by breathing difficulty and is thought to be a variation of idiopathic pulmonary fibrosis. It can begin gradually. The abnormal lung tissue growths tend to be more uniform than those of idiopathic pulmonary fibrosis. This disorder usually has a favorable response to treatment with systemic corticosteroid drugs.

Extrinsic allergic alveolitis is a lung disorder similar to idiopathic pulmonary fibrosis. The disorder is caused by repeated or constant exposure to organic substances that usually produce short-term, mild episodes of breathlessness associated with lung irritation or allergic reactions. However, repeated attacks tend to be progressively more severe, and may be characterized by fever, breathing difficulty, crackling sounds during breathing (rales), bluish appearance of the skin (cyanosis), and blood in the sputum. (For more information on this disorder, choose "extrinsic allergic alveolitis" as your search term in the Rare Disease Database.)
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Diagnosis
A diagnosis of idiopathic pulmonary fibrosis may be suspected based upon a thorough clinical evaluation and a detailed patient history. A diagnosis may be confirmed based upon a variety of specialized tests, including chest x-rays, computer assisted tomographic scans, pulmonary function tests to measure how well the lungs take in and exhale oxygen and how efficiently they transfer oxygen to the blood, blood tests that reveal low levels of oxygen in the blood, and removal and microscopic examination of lung tissue (lung biopsy).

Treatment
There are no drugs currently approved by the FDA for the treatment of IPF. Systemic corticosteroid drugs may be administered in the hope that they will prevent lung changes before such changes become widespread or permanent. High doses may be recommended at first, followed by a lower maintenance dosage. Some cases that prove resistant to steroid therapy may improve with the purine antagonist drug, azathioprine. Imaging techniques may be useful to monitor progressive lung changes. Oxygen administered in high concentrations may be helpful if oxygen in the blood is diminished. Antibiotics may be required if bacterial infections develop. Digitalis or diuretic drugs may be recommended if heart problems arise.

Exercise and oxygen replacement therapy may also be recommended for individuals with idiopathic pulmonary fibrosis. These treatments are symptomatic and supportive only. Treatment options will vary greatly from case to case depending upon the severity of the disorder and the preferences of the managing physician.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

A double-blind study of the drug Actimmune, a form of interferon, was discontinued (2007) because the drug was not effective against diopathic pulmonary fibrosis.

The drug pirfenidone received orphan drug status from the U.S. Food and Drug Administration (FDA) in 2004 for the treatment of idiopathic pulmonary fibrosis. This drug is currently (2007) in a Phase III study for which patients are being recruited. For information, contact the sponsor, InterMune, at (888) 486-6411 or medinfo@intermune.com.

An IPF Registry has been established at New York University School of Medicine. For information, contact Sue Chow at (212) 263-6411 or sue.chow@med.nyu.edu.

Johns Hopkins University and the Celgene Corporation are sponsoring a Phase II trial (2007) of the use of the drug thalidomide to stop the progression of fibrosis in IPF. For information, contact Victoria Santopietro at (410) 550-4764 or vicci@jhu.edu.

Lung transplants are under investigation as a possible treatment for severe cases of idiopathic pulmonary fibrosis. Effectiveness and side effects of this procedure have not been fully documented and more extensive research is being pursued.

The drug, bosentan (Tracleer), is currently in Phase III clinical trials for IPF. Patients are being recruited for locations around the world, including many in the United States. These trials are sponsored by the manufacturer, Actelion, Inc., and are described on www.clinicaltrials.gov.

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Pulmonary Fibrosis, Idiopathic. Entry No:178500; Last Update:5/13/2004.

TEXTBOOKS
Beers MH, Berkow R, eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:.

Berkow R, ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003.

Fishman AP. Ed. Pulmonary Diseases and Disorders. 2nd ed. McGraw-Hill Companies. New York, NY; 1988.

REVIEW ARTICLES
Thannickal VJ, Toews GB, White ES, et al. Mechanisms of pulmonary fibrosis. Annu Rev2004;55:395-417.

Dunsmore SE, Shapiro SD. The bone marrow leaves its scar: new concepts in pulmonary fibrosis. J Clin Invest. 2004;113:180-82.

Davies HR, Richeldi L. Idiopathic pulmonary fibrosis: current and future treatment options. Am J Respir Med. 2002;1:211-24.

Geiser T. Idiopathic pulmonary fibrosis—a disorder of alveolar wound repair? Swiss Med Wkly. 2003;133(29-30):405-11.

Davies HR, Richeldi L, Walters EH. Immunomodulatory agents for idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2003;(3):CD002880.

Richeldi L, Davies HR, Ferrara G, et al. Corticosteroids for Idiopathic pulmonary fibrosis. Cochrane Database Syst Rev. 2003;(3):CD002880.

Antoniou KM, Ferdoutsis E, Bouros D. Interferons and their application in the diseases of the lung. Chest. 2003;123:209-16.

Green FH. Overview of pulmonary fibrosis. Chest. 2002;122(6Suppl):293S-298S.

Pardo A, Selman M. Idiopathic pulmonary fibrosis: new insights into its pathogenesis. Int J Biochem Cell Biol. 2002;34:1534-38.

Pardo A, Selman M. Molecular mechanisms of pulmonary fibrosis. Front Biosci. 2002;7:d1743-61.

FROM THE INTERNET
What is Pulmonary Fibrosis? Pulmonary Fibrosis Foundation. April 21, 2004. 2pp.
www.pulmonaryfibrosis.org/ipf.htm

Clinical Trials. Research on Pulmonary Fibrosis. nd. 2pp.
www.pulmonaryfibrosis.org/research.htm

Search Lung USA. American Lung Association. ©2004. 7pp.
www.lungusa.org/site/apps/s/content.asp

Pulmonary Fibrosis. The Canadian Lung Association. ©2004. 7pp.
www.lung.ca/diseases/pulmonary_fibrosis.html