WHAT ARE THE SIGNS AND SYMPTOMS OF INTERSTITIAL PNEUMONIA?

The signs and symptoms of interstitial pneumonia include progressively worse discomfort while breathing, fever, occasional wheezing, blue discoloration of the skin, and an abnormal enlargement of the end of the fingers (known as clubbing). There also tends to be a non-productive cough for one to three years. The term “non-productive” means that no phlegm is brought up when the person coughs. When the doctor listens to the lung sounds while breathing, he/she can hear a crackling noise on the bottom of both sides of the lungs.

For people with lymphoid interstitial pneumonia (LIP), enlargement of lymph nodes or lymph vessels may occur. Lymph nodes are small egg shaped structures in the body that help fight against infection. Lymph vessels are tube-shaped structures that carry lymph throughout the body. Lymph is a milky fluid that contains proteins, fats, and white blood cells (which help the body fight off diseases).

People with LIP may also experience enlargement of the liver, spleen, and parotid glands. The spleen is an organ next to the stomach that helps fight infection and removes and destroys worn-out red blood cells. The parotid gland is the largest of three pairs of glands that produce saliva. Enlargement of these glands is present in about 33% of adult patients.

WHAT CAUSES INTERSTITIAL PNEUMONIA?

Causes of interstitial pneumonia include infection with a bacteria known as Pneumocystis carinii, inhaling poisons, and radiation exposure. Radiation is a type of energy in the form of waves or streams of particles. Radiation is often used to treat cancer which is any of a large group of malignant diseases characterized by an abnormal, uncontrolled growth of new cells in one of the body organs or tissues.

Interstitial pneumonia can be a rare complication of measles. Measles is a viral illness that leads to a fever and a characteristic rash. Some other forms of pneumonia, such as viral pneumonia, can lead to interstitial pneumonia. Viral pneumonia is pneumonia that is caused by a virus. In lymphoid interstitial pneumonia, what seems to happen is that there is an increased production of lymphocytes in responses to the presence of viruses in the body.

Individual viruses or combinations of viruses may be responsible for interstitial pneumonia. Some types of viruses that may be responsible for lymphoid interstitial pneumonia include HIV, the Epstein-Barr virus, and human T-cell leukemia virus (HTLV) type 1. Traces of these viruses have been found in individuals with interstitial pneumonia. Epstein-Barr virus is one of the most common viruses in the world.

HTLV is a virus that causes T-cell leukemia. Leukemia is a type of cancer in the blood in which bone marrow (a tissue that fills the openings of bones) is replaced by early forms of white blood cells. In T-cell leukemia, the T-cells (types of white blood cells) are malignant, meaning that these cells grow in an abnormal and uncontrolled way.

Hypersensitive reactions to certain medications can lead to interstitial pneumonia. Some of these medications include the anti-cancer drugs Methotrexate, Busulfan, and Chlorambucil, as well as the blood pressure medication, Hexamethonium.

Interstitial pneumonia can also be an autoimmune reaction, meaning that the body’s defense system attacks the body by mistake. The reason why interstitial pneumonia is thought to be possibly an autoimmune reaction is because it often accompanies other autoimmune disorders (see the next section). In fact, about 30% of people with interstitial pneumonia have autoimmune disorders.

With regards to a genetic component, patients with allele types named “HLA-DR5” and “HLA-DR6” are predisposed to developing a diffuse visceral lymphocytosis syndrome with lymphoid interstitial pneumonia. An allele is a form of a gene. Genes are units of material contained in a person's cells that contain coded instructions as for how certain bodily characteristics (such as eye color) will develop. Diffuse visceral lymphocytosis syndrome is a condition in which lymphocytes infiltrate salivary gland, tear glands, lung tissue, kidney tissue, stomach tissue, intestinal tissue, and breast tissue. The salivary glands are the glands in the mouth that produce saliva. A gland is an organ in the body made of special cells that form and release materials such as fluid.

WHAT OTHER DISORDERS ARE ASSOCIATED WITH INTERSTITIAL PNEUMONIA?

As was mentioned in the last section, autoimmune disorders such as Sjogren’s syndrome (see above), celiac sprue, rheumatoid arthritis, and progressive systemic sclerosis are associated with interstitial pneumonia. Celiac sprue is an uncommon, long-term disorder, in which the lining of the small intestine wastes away, becomes inflamed, and is damaged by a protein known as gluten. This protein is found in wheat, rye, barley, and other cereals. The intestine is a tube shaped structure that is part of the digestive tract. It stretches from an opening in the stomach to the anus (rear end) and occupies most of the lower parts of the belly. The small intestine is a part of the intestine that takes in all of the nutrients that the body needs.

Rheumatoid arthritis is a disorder in which the body's defense system attacks its own tissues, causing inflammation of bone joints. A joint is a place where two bones contact each other. Progressive systemic sclerosis is a rare condition in which the body mistakenly attacks many organs and tissues of the body. Too much collagen builds up in people with progressive systemic sclerosis. Collagen is a protein found in the skin. As a result of the collagen build up, the skin becomes thick and tight.

Lymphoid interstitial pneumonia (LIP) is associated with HIV, a type of sexually transmitted disease. LIP is also associated with human T-cell leukemia virus (HTLV) type 1, (see last section). The association of LIP, HIV, and HTLV seems to be common in people with African ancestry. Of note is that LIP appears to cluster is southwestern Japan, where HTLV is common.

Lymphoid interstitial pneumonia is associated with other conditions such as lymphoma, Hashimoto thyroiditis, myasthenia gravis, pernicious anemia, autoerythrocyte sensitization syndrome, chronic active hepatitis, common variable immunodeficiency, and allogenic bone marrow transplantation. These conditions are described below.

Lymphoma is cancer of the lymphatic tissue. Lymphatic tissue is a network of fibers and cells that contain various degrees of lymphocytes (types of white blood cells). Hashimoto thyroiditis is a disease in which the immune system attacks and destroys the thyroid gland. The thyroid gland is a butterfly-shaped organ located in the front of the neck that plays an important role in metabolism. Metabolism is the chemical actions in cells that release energy from nutrients or use energy to create other substances.

Myasthenia gravis is a type of disorder in which the muscles get weak and tire easily as a result of poor conduction (transmission) of nerve impulses. Anemia is a condition in which there is an abnormally low amount of hemoglobin in the blood. Hemoglobin is substance present in red blood cells that help carry oxygen to cells in the body. Vitamin B12 is necessary for the formation of red blood cells. Pernicious anemia is a type of anemia caused by a lack of intrinsic factor, which is a substance needed to absorb vitamin B12 from the digestive tract.

Autoerythrocyte sensitization syndrome is a rare bruising disorder that mostly affects people with severe emotional disturbance. Chronic active hepatitis is continuing inflammation of the liver. The liver is the largest organ in the body and is responsible for filtering (removing) harmful chemical substances, producing important chemicals for the body, and other important functions.

Common variable immunodeficiency is a disorder characterized by low levels of antibodies in the blood and an increased susceptibility to infections. Antibodies are types of proteins that are formed by the body to destroy foreign proteins known as antigens. Allogenic bone marrow transplantation is an operation that replaces affected bone-marrow with a healthy one taken from donor. Bone marrow is a type of tissue that fills the inside of bones.

DOES INTERSTITIAL PNEUMONIA BEGIN SLOWLY OR QUICKLY?

Interstitial pneumonia begins slowly and for this reason, the condition often goes untreated for many months. In fact, many patients are mistakenly treated for other diseases instead. Because of this problem, breathing ability can be significantly deteriorated by the time the condition is diagnosed.

IS THERE A DIFFERENCE IN THE NUMBERS OF MEN AND WOMEN THAT DEVELOP INTERSTITIAL PNEUMONIA?

Men have a slightly higher rate of developing interstitial pneumonia. Approximately 29 per 100,000 men develop interstitial pneumonia whereas 26 out of 100,000 women develop it.

DO PEOPLE WITH INTERSTITIAL PNEUMONIA HAVE HIGHER RATES OF CANCER?

Yes, people with interstitial pneumonia have higher rates of cancer that begins in the bronchi of the lungs.

HOW IS INTERSTITIAL PNEUMONIA DIAGNOSED?

Tests of lung functioning are used as part of the diagnostic approach to interstitial pneumonia. These tests show a decrease in the amount of air contained in the lungs at the end of a person’s best effort to take a breath. There is also a decreased amount of oxygen in the blood. Lung functioning tests can also detect impaired diffusion capacity, which is the ability of the lungs to transfer gases across the alveoli. Obstructive airway disease is found in some patients. Obstructive airway disease is a disease characterized by decreased airway size and increased secretions into the airways. A secretion is a substance that is formed and released

X-rays of the lungs are also used diagnose interstitial pneumonia combined with knowledge of the patient’s medical history. X-rays of the lungs of patients with interstitial pneumonia will show patchy shadows and blotchy areas. In early stages, a hazy appearance of ground glass is present in the lungs. The ground glass appearance is common in DIP and RB-ILD.

The lung tissue will have an abnormal, honeycombed appearance, much like a bee hive. This happens in about one third of the cases. The honeycombs are actually holes in the lung that are about 1 centimeter wide. The presence of honeycombs usually represents the end stage of many forms of lung disease. Honeycombing is especially common in UIP.

As was mentioned earlier, some patients with late-stage interstitial pneumonia have a pneumothorax that is noticeable on x-ray. A pneumothorax is the presence of air or gas in the pleural space, causing a lung to collapse. The pleural space is a thin, fluid-filled opening between the pleura of the lungs and the pleura of the chest wall. The pleura is the smooth, moist double layer of flexible tissue that lines the lungs and the chest wall. The pleura often appears thickened in interstitial pneumonia. Pleural effusions (see earlier section) can also be seen on x-ray. It is worth noting that X-rays appear normal in about 16% patients with interstitial pneumonia.

Computerized tomography (CT) scans are also used to help diagnose interstitial pneumonia, detect the extent of disease, and to follow disease progression. CT scanning is an advanced imaging technique that uses x-rays and computer technology to produce more clear and detailed pictures than a traditional x-ray. CT scans can show the widening and destruction of the walls of the bronchi. In active disease, the hazy appearance of ground glass can also be seen. The tissue between the alveoli can appear thickened and distorted.

On CT scans, a network of more transparent areas (known as reticular opacities) can be seen, which is due to lung destruction, honeycombing, and fibrosis (an overgrowth of connective tissue), and bronchiectasis. Bronchiectasis is irreversible widening and destruction of the walls of the bronchi. A similar, widespread, net-like pattern can sometimes be seen on X-rays. Many of the abnormal findings on X-rays and CT scans are found beneath the pleura and towards the bottom of both sides of the lungs.

A technique known as a brochoalveolar lavage (BAL) is sometimes performed, in which a viewing device is placed into one of the bronchi (airways connected to the lungs), salt water is injected into the end of the airway and about 50 to 70% of it is then sucked out by hand. The saltwater is then sent to the laboratory for analysis. The laboratory analysis helps diagnose which bacteria are causing the infection.

The laboratory analysis often finds monocytosis or lymphocytosis. Monocytosis is an increased number of monocytes, which are large oval shaped white blood cells. White blood cells are cells that help the body fight off infections. Lymphocytosis is an increased number of lymphocytes. Lymphocytes are another type of white blood cell.

Lab values can also be helpful in diagnosing lymphoid interstitial pneumonia. For example, in children with LIP and HIV, levels of the lactate dehydrogenase (LDH) are 300-500 International Units per liter (normal level is about 105-333 IU/L). LDH is an enzyme found in many body tissues and organs. An enzyme is a type of protein that helps produce chemical reactions in the body. Injury to organs and tissues often cause a release of LDH into the blood, which raises the level of this enzyme on blood tests. Lactate dehydrogenase levels are not helpful measures in adults when trying to diagnose interstitial pneumonia.

An International Unit is very similar to a unit but is based on a different type of scale. The value of an International Unit will also differ for each type of substance. A liter is a measurement of the amount of space that a liquid takes up in a container, which is equal to 1.056688 quarts. To understand this better, picture a gallon of milk. It takes 4 quarts of milk to make up one gallon of milk. Since one liter is a little bit less than one quart, 4 liters of milk is a little bit less than one gallon of milk.

Another common laboratory finding in LIP is hypergammaglobulinemia. Hypergammaglobulinemia is an abnormal increase in gamma globulins found in the blood, often in chronic infections diseases. Gamma globulins are globulins (large, globe-shaped proteins) that move to an area known as the gamma region upon electrophoresis.

Electrophoresis is the movement of charged molecules, such as proteins, in an electric field. Electrophoresis produces a graph-like pattern that doctors can examine. One of the areas on the graph is known as the gamma region. Antibodies are types of gamma globulins that are increased on electrophoresis.

A biopsy of the lungs is often needed to diagnose desquamative interstitial pneumonia (see above), especially when other findings cannot lead to a diagnosis. A biopsy is the process of removing living tissue or cells from organs or other body parts of patients for examination under a microscope or in a culture to help make a diagnosis, follow the course of a disease, or estimate a prognosis. A culture is an artificial way to grow cells or tissues in the laboratory.

The biopsy technique used to collect lung tissue specimens is known as a transbronchial lung biopsy. If multiple biopsies are taken from several affected areas of the lungs, this procedure can generally lead to a definitive diagnosis. This biopsy procedure is usually done by a doctor who specializes in the lungs (known as a pulmonologist) or a thoracic surgeon. A thoracic surgeon is a doctor that specializes in surgery of diseases of the chest. If a transbronchial lung biopsy is performed, x-rays are done afterwards to be sure that the patient does not have a post-operative pneumothorax or that if one is present, it is small and stable A pneumothorax is the presence of air or gas in the pleural space, causing a lung to collapse.

In desquamative interstitial pneumonia, the biopsy usually shows a distinctive pattern of widespread and evenly distributed lung inflammation. The most striking feature of the lung biopsy is the presence of numerous macrophages in the alveoli and bronchioles (smallest airways). A macrophage is a type of white blood cell that eats bacteria. Macrophages normally help get rid of bacteria and small particles in the alveoli.

It is important to note that patients with rheumatoid arthritis and progressive systemic sclerosis can have identical laboratory findings as patients with interstitial pneumonia, making it important for the doctor to consider other clinical factors (such as history and symptoms) when making the diagnosis. See above for a description of rheumatoid arthritis and progressive systemic sclerosis.

HOW IS INTERSTITIAL PNEUMONIA TREATED?

Medications are used to treat patients that show symptoms of disease or whose physical functioning is affected. The doctor should weigh the risks and benefits of medication treatment with the patient. A commonly used medication for interstitial pneumonia is corticosteroids. Corticosteroids (such as Prednisone) are a group of drugs that act similarly to a natural chemical in the body known as corticosteroid hormone. Corticosteroid hormones control the body's use of nutrients and the amount of water and salts in the urine. These drugs are used in interstitial pneumonia because they help decrease inflammation.

Corticosteroids are effective in about 10 to 15% of patients with interstitial pneumonia, but cause serious complications in about 26% of individuals. The doctor will decide the best dose of corticosteroids for the patient’s condition and may decrease the dose after a month of treatment.

Patients with UIP and AIP tend to respond poorly to corticosteroids whereas patients with RB-ILD, NSIP, and DIP tend to respond well to corticosteroids. Those who tend to respond well to corticosteroids tend to be young women, those with active inflammation on lung biopsy, and those with a ground glass appearance on CT scans of the chest. See the last section for more information on biopsies and CT scan results.

Some physicians use cytotoxic drugs, in combination with corticosteroids, to treat interstitial pneumonia. Cytotoxic dugs, such as Cytoxan and Azathioprine, are drugs that kill certain cells in the body. Medications that widen the bronchi (known as bronchodilators) are used to treat wheezing.

For patients who do not respond to high doses of corticostreroids, alkylating medications (a type of anti-cancer drug) are sometimes used. Only doctors that are experienced with the usage and side effects of this type of medication should prescribe these drugs. When prescribed, alkylating medications are usually given for weeks at a time. The progression of the disease and complete blood count (CBC) tests need to be monitored when taking this type of medication. The CBC test shows the number of various types of red and white blood cells. The way in which alkylating medications treat interstitial pneumonia is unclear.

Treatment of interstitial pneumonia can last many months and usually involves bed rest and oxygen therapy. Oxygen supplements may be needed if lab findings indicate decreased oxygen levels. Physical activity may need to be reduced if the patient is experiencing decreased oxygen levels. However, on an outpatient basis, depending on the patient’s condition, the doctor may prescribe an exercise course such as walking a long corridor or several flights of steps.

It is important for patients to monitor changes in their saliva or phlegm as this may be the only sign of infection. Associated lung infections will be treated with antibiotics. Progression of the disease can be monitored by follow-up CT scans. It is worth noting that patients with LIP who do not have symptoms and whose physical functioning is not affected may not require treatment.

WHAT IS THE PROGNOSIS FOR PEOPLE WITH INTERSTITIAL PNEUMONIA?

The prognosis for people with interstitial pneumonia varies based on the type of disease they have. However, in general terms the prognosis is poor, with 87% of patients dying from causes related to this condition. Most patients with interstitial pneumonia die within 6 months to a few years because of lung or heart failure. The average length of survival is four to six years. In general, the prognosis of patients with interstitial pneumonia is better when patients are on a combination of therapies. Patients with acute interstitial pneumonia may die quickly even with supportive therapy.

For patients with usual interstitial pneumonia (see above), recovery is not possible. About 45% of people with UIP live past 5 years and only 10% respond to treatment. About 68% of people with UIP eventually die from this condition. Similarly, about 62% of patients with AIP die from that condition. The average person with AIP only lives for only 1 to 2 months.

For patients with LIP, the prognosis is variable, with a disease duration between 1 month and 11 years. LIP is often stable for months without treatment and sometimes improves spontaneously. It is common however for symptoms to recur.

For patients with LIP who do not have HIV infection, half improve with treatment, but relapse is common. Despite treatment, end stage fibrosis may occur. Fibrosis is the production of firm connective tissue (scar tissue). In the past, high death rates were reported in older patients with LIP, but death rates in patients with LIP are inexact due to the lack of follow-up studies. It is noteworthy that patients with LIP and HIV have better survival rates and a slower decline in CD4 T-cells (types of white blood cells) than patients with LIP but not HIV.

The situation is much better for patients with desquamative interstitial pneumonia, in which about 70% of patients live for 10 years or more. In fact, the average person with DIP lives for 12 years. About 27% of people with DIP die from this condition. The prognosis for people with DIP improves when they quit smoking and start taking corticosteroids (see last section).

About 11% of people with NSIP die from this condition, with the average length of survival being 17 months. The situation is best for people with RB-ILD, as it is rare for people to die from this mild condition.

WHAT ELSE IS INTERSTITAL PNEUMONIA KNOWN AS?

Interstitial pneumonia is also known as giant cell pneumonia, giant cell interstitial pneumonia, Hecht pneumonia, diffuse fibrosing pneumonia, alveolitis, and Hamman-Rich syndrome.

WHAT IS THE ORIGIN OF THE TERM, INTERSTITIAL PNEUMONIA?

Interstitial pneumonia comes from the Latin word “inter” meaning “between,” the Latin word “sistere” meaning “to stand,” and the Greek word “pneumon” meaning “lung.” Put the words together and you have “to stand between lung.”