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Pulmonary Alveolar Proteinosis

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Synonyms of Pulmonary Alveolar Proteinosis

Disorder Subdivisions

General Discussion

Pulmonary alveolar proteinosis (PAP) is a rare lung disorder characterized by the accumulation of grainy material consisting mostly of protein and fat (lipoproteinaceous material) in the air sacs of the lungs (alveoli). Breathing often becomes progressively difficult. The disorder occurs in different forms, ranging from mild to severe, and can affect individuals of any age. PAP may occur secondary to many environmental exposures or underlying diseases. However, most cases of PAP occur for no known reason (idiopathic or primary PAP). An extremely rare form of PAP occurs in newborns (congenital PAP).

Symptoms

The symptoms of idiopathic and secondary PAP vary greatly from case to case. Some individuals may exhibit no apparent symptoms (asymptomatic). Others may experience difficult breathing (dyspnea) and shortness of breath upon exertion. Breathing difficulties often become progressively worse. A dry, chronic cough may develop that is sometimes associated with mucous development (sputum).

Some affected individuals may develop general symptoms such as fatigue, weight loss, chest pain and a general feeling of ill health (malaise). In rare cases, affected individuals may experience the coughing up of blood (hemoptysis), rounding and swelling (clubbing) of the tips of the fingers, and cyanosis, a condition in which abnormal bluish discoloration of the skin occurs because of low levels of circulating oxygen in the blood.

Some individuals with PAP become susceptible to repeated respiratory infections. In some cases, PAP may progress to cause life-threatening respiratory failure. In other cases, the symptoms may resolve without treatment (spontaneous resolution).

An extremely rare form of PAP occurs in some newborns (congenital PAP). Affected infants may experience difficulty breathing (dyspnea). Additional symptoms that occur less frequently include chest pains, failure to thrive, and fever, which is usually associated with respiratory infection. Life-threatening complications such as respiratory distress often occur early during infancy.

Causes

Most cases of PAP occur for no known reason (idiopathic).

Some researchers believe that idiopathic PAP may actually be an autoimmune disorder. Autoimmune disorders are caused when the body’s natural defenses against "foreign" or invading organisms begin to attack healthy tissue for unknown reasons. In some cases of PAP, antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) have been found. GM-CSF is a protein that assists in the production certain cells (i.e., granulocytes and macrophages). Researchers speculate that antibodies against GM-CSF results in impaired function of macrophages within the alveolar sacs, which, in turn, results in the accumulation of lipoproteinaceous material.

Researchers have determined that some cases of PAP occur secondary to a variety of causes including exposure to certain chemicals or minerals such as silica, aluminum or insecticides; underlying malignancy such as lymphoma or leukemia; immunosupressive medications; and certain infections such as nocardiosis or cytomegalovirus.

An extremely rare form of PAP occurs at birth (congenital PAP). Researchers believe this form of PAP is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Affected Populations

PAP affects men more often than women by a ratio of 2-4 to 1. The disorder may occur in individuals of any age from newborns to the elderly. Most cases affect adults between the ages of 20-50. More than 400 cases have been reported in the medical literature.

Related Disorders

Symptoms of the following disorders can be similar to those of PAP. Comparisons may be useful for a differential diagnosis:

Pneumonia is an acute infection of the alveolar spaces and/or the interstitial tissue of the lung. A whole lobe or only a part of a lobe can be involved. The pneumonia may be caused by different bacteria, viruses, fungi, or protozoa. Pneumonia is often preceded by upper respiratory infection. Symptoms usually start suddenly, with a shaking chill, sharp pain in the affected side of the chest, a cough, a high fever, and a headache. Breathing is difficult and painful.

Idiopathic pulmonary fibrosis is an inflammatory lung disorder characterized by abnormal formation of fibrous tissue (fibrosis) between tiny air sacs (alveoli) or ducts in the lungs. Coughing and rapid, shallow breathing occur with moderate exercise. The skin may appear slightly bluish (cyanotic) due to lack of circulating oxygen. Complications such as infection, emphysema or heart problems may develop. The exact cause of idiopathic pulmonary fibrosis is unknown (idiopathic). (For more information on this disorder, choose "idiopathic pulmonary fibrosis" as your search term in the Rare Disease Database.)

Acute respiratory distress syndrome (ARDS) is a type of severe, acute lung dysfunction affecting all or most of both lungs that occurs as a result of illness or injury. Although it is sometimes called adult respiratory distress syndrome, it may also affect children. Major symptoms may include breathing difficulties (dyspnea), rapid breathing (tachypnea), excessively deep and rapid breathing (hyperventilation) and insufficient levels of oxygen in the circulating blood (hypoxemia). ARDS may develop in conjunction with widespread infection in the body (sepsis) or as a result of pneumonia, trauma, shock, severe burns, aspiration of food into the lung, multiple blood transfusions, and inhalation of toxic fumes, among other things. It usually develops within 24 to 48 hours after the original illness or injury and is considered a medical emergency. It may progress to involvement of other organs. (For more information on this disorder, choose "acute respiratory distress" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
A diagnosis of pulmonary alveolar proteinosis is suspected based upon a thorough clinical evaluation, a detailed patient history, identification of characteristic symptoms and a variety of specialized tests including bronchoalveolar lavage (BAL). During a BAL a narrow tube (bronchoscope) is slid down the windpipe and a sterile solution is passed through the tube washing out (lavaging) cells. After removing the tube, the cells can then be studied.

Tests that determine how well the lungs are functioning may also be performed. Chest x-rays and computed tomography (CT scan) may also be used to assist diagnosis by revealing extensive white patches within the lungs. During a CT scan, a computer and x-rays are used to create a film showing cross-sectional images of internal structures such as the lungs.

A diagnosis of PAP may be confirmed by transbronchial lung biopsy, a procedure during which a thin, flexible tube (bronchoscope) is inserted through the nose or mouth and guided through the windpipe to the lungs to remove tissue for microscopic examination.

Treatment
The treatment of PAP varies from case to case depending upon the age of an affected individual and severity of the disease. Approximately one-third of individuals with idiopathic PAP will improve without treatment (spontaneous remission). The other two-thirds may be treated by a whole lung lavage, a procedure in which one lung is cleansed with a salt solution while the other is pumped with pure oxygen. In some cases, the procedure may need to be performed once; in others it may need to be repeated many times over several years.

In secondary PAP removal and avoidance of the causative agent (e.g., silica exposure) or treatment of the underlying disorder may improve symptoms.

Treatment for congenital PAP is symptomatic and supportive. According to the medical literature, successful lung transplantation has been used to treat some infants with congenital PAP. Genetic counseling may be beneficial for families of individuals with the congenital form of PAP.

Investigational Therapies

Researchers are studying granulocyte-macrophage colony-stimulating factor (GM-CSF) as a potential treatment for individuals with PAP. Initial studies have demonstrated some improvement of symptoms with treatment with GM-CSF. However, more research is necessary to determine the long-term safety and effectiveness of this treatment for individuals with PAP.

Lung transplantation has been used to treat adults with PAP as a last resort. According to the medical literature, in some cases, PAP has recurred in adults who have received lung transplantation.

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 web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

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

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to Pulmonary Alveolar Proteinosis

Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.

References

TEXTBOOKS
McDonald JW. Pulmonary Alveolar Proteinosis. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:677.

REVIEW ARTICLES
Trapnell BC, et al., Pulmonary alveolar proteinosis. New Engl J Med. 2003;349:2527-39.

Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2002;166:215-35.

Mazzone P, Thomassen MJ, Kavuru M. Our new understanding of pulmonary alveolar proteinosis: what an internist needs to know. Cleve Clin J Med. 2001;68:977-8, 981-2, 984-5.

DeMello DE, Lin Z. Pulmonary alveolar proteinosis: a review. Pediatr Pathol Mol Med. 2001;20:413-32.

JOURNAL ARTICLES
Uchida K, et al., High-affinity autoantibodies specifically eliminate granulocyte-macrophage colony-stimulating factor activity in the lungs of people with idiopathic pulmonary alveolar proteinosis. Blood. 2004;103:1089-98.

Thomassen MJ, et al., Elevated IL-10 inhibits GM-CSF synthesis in pulmonary alveolar proteinosis. Autoimmunity. 2003;36:285-90.

Arbiser ZK, et al., Pulmonary alveolar proteinosis mimicking idiopathic pulmonary fibrosis. Ann Diagn Pathol. 2003;7:82-6.

Hashizume T, Pulmonary alveolar proteinosis successfully treated with ambroxol. Intern Med. 2002;41:1175-8.

Collard B, et al., Pulmonary alveolar proteinosis. JBR-BTR. 2002;85:260-3.

Ayadi H, Ayoub AK. Familial alveolar proteinosis. Rev Pneumol Clin. 2002;58:245-8.

Cheng SL, et al., Pulmonary alveolar proteinosis: treatment by bronchofiberscopic lobar lavage. Chest. 2002;122:1480-5. Comment in: Chest. 2002;122:1123-4.

Huddleston CB, et al., Lung transplantation in children. Ann Surg. 2002;236:270-6.

Briens E, et al., Pulmonary alveolar proteinosis. Rev Mal Respir. 2002;19:166-82.

Ben-Abraham R, et al., Pulmonary alveolar proteinosis: step-by-step perioperative care of whole lung lavage procedure. Heart Lung. 2002;31:43-9.

Barraclough RM, Gilles AJ. Pulmonary alveolar proteinosis: a complete response to GM-CSF therapy. Thorax. 2001;56:664-5.

Thompson CT, Tirone PA. Pulmonary alveolar proteinosis: a pediatric case study. Pediatr Nurse. 2000;26:587-91, 597.

FROM THE INTERNET
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:265120; Last Update:1/9/2004.

Vaughan DJ. Alveolar Proteinosis. eMedicine. Last Updated; October 31, 2002:10pp. Available at: www.emedicine.com/ped/topic75.htm

Gotway M. Alveolar Proteinosis. eMedicine. Last Updated; May 24, 2002:9pp. Available at: www.emedicine.com/radio/topic21.htm

Olade R. Pulmonary Alveolar Proteinosis. eMedicine. Last Updated; February 19, 2003:11pp. Available at: www.emedicine.com/med/topic1927.htm

Report last updated: 2008/05/06 00:00:00 GMT+0