CHAPTER 84
Allergic and Autoimmune Diseases of the Lungs
The lungs are particularly prone to allergic reactions because they are exposed to large quantities of airborne substances that commonly cause allergic reactions (called antigens), including dusts, pollens, fungi, and chemicals. Exposure to irritating dusts or airborne substances, often when a person is at work, may increase the likelihood of an allergic respiratory reaction. Allergic reactions involving the lungs may also occur from eating a certain food or taking a certain drug.
The body reacts to an antigen by forming proteins that react with antigens (antibodies). In a normal immune response, antibodies typically bind to an antigen, thereby rendering it harmless (see page 1096). Sometimes, however, when the antibody and antigen interact, inflammation and tissue damage occur; this is called an allergic reaction. Allergic reactions are classified by the various mechanisms that are involved in causing the tissue damage. Many allergic reactions involve a combination of more than one type of tissue damage. Some allergic reactions depend on antigen-specific lymphocytes (a type of white blood cell) rather than on antibodies. It is believed that some types of allergic reactions decrease as people age.
Hypersensitivity Pneumonitis
Hypersensitivity pneumonitis (extrinsic allergic alveolitis) is a type of inflammation in and around the tiny air sacs (alveoli) and smallest airways (bronchioles) of the lung caused by an allergic reaction to inhaled organic dusts or, less commonly, chemicals.
Dusts that contain microorganisms or proteins may cause an allergic reaction in the lungs.
People may develop fever, cough, chills, and shortness of breath within 4 to 8 hours of re-exposure to substances to which they are sensitized.
Doctors use chest x-rays and tests of lung function to determine whether there is a problem with the lungs.
The substance that is causing the reaction can often be identified by using a blood test.
People who work with substances that are likely to cause allergic reactions should use protective equipment, such as face masks, during work.
People who can avoid re-exposure usually recover, but they sometimes need to take corticosteroids to reduce lung inflammation.
Causes
Many types of dust can cause allergic reactions in the lungs. Organic dusts that contain microorganisms or proteins and chemicals, such as isocyanates, may cause hypersensitivity pneumonitis. Farmer’s lung, which results from repeated inhalation of heat-loving (thermophilic) bacteria in moldy hay, is a well-known example of hypersensitivity pneumonitis. Air conditioner lung is another example. It occurs when contaminated humidifiers or air conditioners (especially large systems in office buildings) circulate antigens that are capable of causing a hypersensitivity reaction.
Only a small number of people who inhale these common dusts develop allergic reactions. Only a small percentage of those people who develop allergic reactions suffer irreversible damage to the lungs. Generally, a person must be exposed repeatedly over time before sensitivity and resultant disease develop.
Lung damage appears to result from damage done by lymphocytes, a type of white blood cell. Initial exposures to the dusts sensitize lymphocytes. Some lymphocytes then help to produce antibodies that play a role in tissue damage. Other lymphocytes participate directly in inflammation after subsequent antigen exposure. Recurrent exposure to the antigen results in a chronic inflammatory response, which is manifested by a buildup of white blood cells in the walls of the alveoli and small airways. This buildup leads progressively to symptoms and disease.
Symptoms and Diagnosis
If a person has developed hypersensitivity to an organic dust, then fever, cough, chills, and shortness of breath typically appear 4 to 8 hours after re-exposure to it. Wheezing is unusual. If the person has no further contact with the antigen, symptoms usually diminish over a day or two, but complete recovery may take weeks.
In a slower form of hypersensitivity pneumonitis (subacute form), cough and shortness of breath may develop over days or weeks and sometimes may be so severe that the person needs to be hospitalized.
With chronic hypersensitivity pneumonitis, a person repeatedly comes in contact with an antigen over months to years, and lung scarring (fibrosis) may result. Shortness of breath during exercise, cough, fatigue, and weight loss may gradually progress over months or years. Eventually, the disease may lead to respiratory failure (see page 524). Older people may be more prone to chronic, progressively worsening disease because they have been exposed to an antigen for a long period of time.
WHAT CAUSES HYPERSENSITIVITY PNEUMONITIS?
| DISEASE | SOURCE OF DUST PARTICLES OR ANTIGENS |
| Air conditioner lung | Humidifiers and air conditioners |
| Bagassosis | Sugarcane |
| Bird fancier’s lung, pigeon breeder’s lung, hen worker’s lung | Droppings from parakeets, pigeons, and chickens |
| Cheese washer’s lung | Cheese mold |
| Chemical worker’s lung | Chemicals used in manufacturing polyurethane foam, molding, insulation, synthetic rubber, and packaging materials |
| Coffee worker’s lung | Unroasted coffee beans |
| Cork worker’s lung (suberosis) | Moldy cork |
| Farmer’s lung | Moldy hay |
| Hot tub lung | Bacteria-contaminated hot tubs and therapy pools |
| Malt worker’s lung | Moldy barley or malt |
| Maple bark stripper’s lung | Infected maple bark |
| Miller’s lung | Weevil-infested wheat flour |
| Mushroom worker’s lung | Mushroom compost |
| Sequoiosis | Moldy sawdust from redwoods |
| Woodworker’s lung | Wood dust |
The diagnosis of hypersensitivity pneumonitis depends on the clinical features, identification (if possible) of the dust or other substance causing the problem, and evidence of the person’s exposure to the suspected agent, as determined by the presence of antibodies on a blood test.
Doctors may suspect the diagnosis based on finding something abnormal on a chest x-ray. Results of pulmonary function tests (see page 454)—which measure the lungs’ capacity to hold air and their ability to move air in and out and to exchange oxygen and carbon dioxide—are used to assess how well the lungs work and may help support a diagnosis of hypersensitivity pneumonitis. When the antigen cannot be identified and the diagnosis is in doubt, re-exposing the recovered person to the antigen that is thought to be responsible and observing the person for symptoms or changes in lung function may occasionally be useful to confirm the diagnosis.
In cases that are not clear, especially when an infection is suspected, doctors may remove small pieces of lung tissue for examination under a microscope (lung biopsies). They may remove the tissue while examining the airways using a viewing tube (bronchoscopy—see page 456). Sometimes, rather than (or in addition to) removing tissue by using a sharp instrument, the person performing bronchoscopy may wash out the lung with fluid (bronchoalveolar lavage) to extract cells for examination. Rarely, a different type of viewing tube (thoracoscope) may be used to examine the lung surface and pleural space, or an operation in which the chest wall is opened (thoracotomy) may be needed to obtain larger pieces of lung tissue (see page 458).
Prevention and Treatment
The best prevention is to avoid exposure to the antigen, but this may be impractical if the person cannot change jobs. Eliminating or reducing dust, wearing protective masks, and using good ventilation systems may help prevent both sensitization and recurrence. However, even the best prevention methods may not be effective.
People who have an acute episode of hypersensitivity pneumonitis usually recover if further contact with the substance is avoided. If the episode is severe, corticosteroids, such as prednisone, reduce symptoms and may help reduce severe inflammation. Prolonged or recurring episodes may lead to irreversible disease and progressive disability.
Eosinophilic Pneumonia
Eosinophilic pneumonia (also called pulmonary infiltrates with eosinophilia syndrome) comprises a group of lung diseases in which eosinophils (a type of white blood cell) appear in increased numbers in the lungs and usually in the bloodstream.
Certain drugs, chemicals, fungi, and parasites may cause eosinophils to accumulate in the lungs.
People may cough, wheeze, or feel short of breath, and some people develop respiratory failure.
Doctors use x-rays and laboratory tests to detect the disorder and determine the cause, especially if parasites are suspected as the cause.
Corticosteroids are usually given.
Eosinophils participate in the immune response of the lung. The number of eosinophils increases during many inflammatory and allergic reactions, including asthma, which frequently accompanies certain types of eosinophilic pneumonia. Eosinophilic pneumonia differs from typical pneumonias in that there is no suggestion that the tiny air sacs of the lungs (alveoli) are infected by bacteria, viruses, or fungi. However, the alveoli and often the airways do fill with eosinophils. Even the blood vessel walls may be invaded by eosinophils, and the narrowed airways may become plugged with an accumulation of secretions (mucus) if asthma develops.
The exact reason that eosinophils accumulate in the lungs is not well understood, and often it is not possible to identify the substance that is causing the allergic reaction. However, there are some known causes of eosinophilic pneumonia, including certain drugs (penicillin, aminosalicylic acid, carbamazepine, naproxen, isoniazid, nitrofurantoin, chlorpropamide, and sulfonamides [such as trimethoprim-sulfamethoxazole]); chemical fumes (nickel inhaled as a vapor); fungi (Aspergillus fumigatus); and parasites (roundworms, including nematodes).
Symptoms and Diagnosis
Symptoms may be mild or life threatening. Simple eosinophilic pneumonia (Löffler’s syndrome) and similar pneumonias (such as tropical eosinophilia, which is due to infestation by any of several species of nematode worms called filaria) may produce a slight fever and mild respiratory symptoms, if any. A person may cough, wheeze, and feel short of breath but usually recovers quickly. Another disease, known as acute eosinophilic pneumonia, may cause the level of oxygen in the blood to decrease severely and can progress to acute respiratory failure in a few hours or days if not treated.
Chronic eosinophilic pneumonia, which slowly progresses over weeks to months, is a distinct disorder that may also become severe. Life-threatening shortness of breath can develop if the condition is not treated.
With acute eosinophilic pneumonia, tests show large numbers of eosinophils in the blood, sometimes as many as 10 to 15 times the normal number. However, with chronic eosinophilic pneumonia, the numbers of eosinophils in the blood may be normal.
The most conclusive evidence for the diagnosis is that the person’s symptoms occur within a relatively short time after taking a drug or after travel to an area in which exposure to worms was possible. A chest x-ray is abnormal in eosinophilic pneumonia, but similar abnormalities can occur in other conditions. In acute eosinophilic pneumonia, a chest x-ray usually shows small white lines and hazy patches in the lungs, sometimes with large white patches that are characteristic of fluid in the lungs (called edema). Fluid in the chest cavity (pleural effusion) may also develop and be visible on chest x-ray. In chronic eosinophilic pneumonia, the chest x-ray shows white patches located mainly in the outer zones of the lungs that may appear to migrate to new areas of the lung when x-rays are taken later.
Microscopic examination of cells from coughed-up sputum or washings of the alveoli obtained during bronchoscopy typically shows clumps of eosinophils. Other laboratory tests may be performed to search for an infection with fungi or parasites; these tests may include microscopic examination of stool specimens to look for worms and other parasites.
Prognosis and Treatment
Eosinophilic pneumonia may be mild, and people with the disease may get better without treatment. For acute cases, a corticosteroid such as prednisone is usually needed. In chronic eosinophilic pneumonia, prednisone may be needed for many months or even years. If a person develops wheezing, the same treatments used for asthma are given as well (see page 475). If worms or other parasites are the cause, the person is treated with appropriate drugs. Ordinarily, drugs that may be causing the illness are discontinued.
Allergic Bronchopulmonary Aspergillosis
Allergic bronchopulmonary aspergillosis is an allergic lung reaction to a type of fungus (most commonly Aspergillus fumigatus) that occurs in some people with asthma or cystic fibrosis.
People may cough and wheeze, and they sometimes have fever or cough up flecks of blood.
Doctors use chest x-rays, blood tests, and skin tests to make a diagnosis.
Antiasthma drugs are usually given.
If untreated, chronic lung damage may develop.
The fungus Aspergillus fumigatus flourishes in soil, decaying vegetation, foods, dusts, and water. Certain people who inhale the fungus may become sensitized and develop a chronic allergic reaction. Other fungi, including Penicillium, Candida, Curvularia, and Helminthosporium, can cause an identical illness. In some people, the effects of the allergic reaction combine with the effects of the fungus to damage the airways and lungs.
The disorder differs from typical pneumonias caused by bacteria, viruses, and most fungi, in that the fungus does not actually invade the lung tissue and directly destroy it. The fungus colonizes the mucus in the airways of people with asthma or cystic fibrosis (both of whom tend to have increased amounts of mucus) and causes recurrent allergic inflammation in the lung. The tiny air sacs of the lungs (alveoli) become packed primarily with eosinophils. Increased numbers of mucus-producing cells may also appear. If the disease has caused extensive damage, inflammation may cause the central airways to widen permanently, a condition called bronchiectasis (see page 491). Eventually, the lungs are likely to become scarred.
Other forms of aspergillosis can occur. Aspergillus can invade the lungs and cause serious pneumonia in people with an impaired immune system. This condition is an infection, not an allergic reaction (see page 1229). Aspergillus can also form fungus balls (aspergillomas) in cavities and cysts of lungs damaged by another disease, such as tuberculosis; severe bleeding may result.
Symptoms and Diagnosis
The first indications of allergic bronchopulmonary aspergillosis are usually progressive symptoms of asthma, such as wheezing and shortness of breath, and a mild fever. The person usually does not feel well. Brownish flecks or plugs may appear in coughed-up sputum.
Repeated chest x-rays show areas that look like pneumonia, but they appear to migrate to new areas of the lung, most often in the upper parts. With long-standing disease, chest x-rays or computed tomography (CT) may show widened airways, which are often plugged with mucus; this appearance is similar to one that would be found in a person who has a lung tumor. The fungus itself, along with excess eosinophils, may be seen when the sputum is examined under the microscope. Blood tests reveal high levels of eosinophils and antibodies to Aspergillus. Skin testing can determine if the person is allergic to Aspergillus, but the test does not distinguish between allergic bronchopulmonary aspergillosis and a simple allergy to Aspergillus, which may occur in people who have allergic asthma without aspergillosis.
Treatment
Because Aspergillus appears in many places in the environment, the fungus is difficult to avoid. Antiasthma drugs, especially corticosteroids, are used to treat allergic bronchopulmonary aspergillosis (see table on page 479). Antiasthma drugs also open up the airways, making it easier to cough up mucus plugs and clear out the fungus. The corticosteroid prednisone, taken initially in high doses, and then over a long period of time in lower doses, may prevent progressive lung damage. Most specialists recommend oral corticosteroids; the inhaled kind has not been shown to work well for this condition. The antifungal drug itraconazole is sometimes used in addition to corticosteroids to help eliminate the fungus from the lung. Allergy shots (desensitization) may cause complications and are not recommended.
Because the lung damage may worsen gradually without causing any noticeable changes in symptoms, chest x-rays, pulmonary function tests (see page 454), levels of eosinophils in the blood, and amounts of immunoglobulin E (IgE) antibody are regularly monitored. As the disease is controlled, the eosinophil and antibody levels usually fall, but they may rise again as an early sign of flare-ups.
Goodpasture’s Syndrome
Goodpasture’s syndrome is an uncommon autoimmune disorder in which bleeding into the lungs and progressive kidney failure occur.
People usually are short of breath and cough up blood.
Laboratory tests on samples of blood and urine and chest x-rays are needed to make the diagnosis.
Corticosteroids, cyclophosphamide (a chemotherapy drug), and plasmapheresis are used to try to prevent permanent lung and kidney damage.
This disease usually affects young men. Some people appear to be genetically susceptible to Goodpasture’s syndrome. In these people, substances in the environment, such as tobacco smoke and some solvents, or a viral upper respiratory infection can cause them to produce antibodies against certain parts of their own bodies. Thus, Goodpasture’s syndrome is actually an autoimmune rather than an allergic disease. These antibodies usually damage certain structures in the walls of the tiny air sacs (alveoli) and capillaries of the lungs and in the filtering apparatus of the kidneys. The antibodies trigger inflammation that interferes with lung and kidney function. Presumably, they are the direct cause of the disease.
Symptoms and Diagnosis
A person with this disease typically develops shortness of breath and coughs up blood. Symptoms can quickly become severe: Breathing can fail, and large amounts of blood can be lost. At the same time, the kidneys can rapidly fail. There may be small amounts of blood in the urine.
Laboratory tests reveal the characteristic antibodies in the blood. Urine examination reveals blood and protein in the urine. Anemia is often present. A chest x-ray shows abnormal white patches (due to lung bleeding) in both lungs. A needle biopsy specimen of kidney tissue shows microscopic deposits of antibodies in a specific pattern.
Treatment
The disease may very rapidly lead to severe loss of lung function, a complete loss of kidney function, and death. High doses of corticosteroids (such as prednisone) and cyclophosphamide are given intravenously to suppress the activity of the immune system, and the person undergoes plasmapheresis—a procedure in which blood is removed from the circulation, the unwanted antibodies are removed, and the blood cells are returned to the circulation (see box on page 1030). The early use of this combination of treatments may help preserve lung and kidney function. Once damage occurs to the kidneys, it is usually permanent.
Many people may need supportive care until the disease runs its course. People may require supplemental oxygen or may need to be on a ventilator for a period of time. Blood transfusions may also be needed. If the kidneys fail, kidney dialysis or a kidney transplant may be required.