Pulmonary aspergillosis and HIV/AIDS

BACKGROUND

The Aspergillus fungus causes aspergillosis pulmonary infections. Although there are more than 100 Aspergillus species, most human illnesses are caused by Aspergillus fumigatus and Aspergillus niger and, less frequently, Aspergillus flavus and Aspergillus clavatus.

The fungus that causes the infection is commonly found on dead leaves, stored grain, compost piles, and decaying vegetation. People are commonly exposed to the fungus, but it usually only causes infections in individuals who have weakened immune systems, such as HIV/AIDS patients.

The fungal spores are transmitted to humans when they are inhaled. Therefore, the infection primarily affects the lungs. However, if the patient is severely immunocompromised (as in HIV/AIDS or cancer patients), the infection may spread to other organs. In such cases, the infection may cause endophthalmitis (inflammation of the eye that is a medical emergency), endocarditis (infection of the lining of the heart), and abscesses in the heart muscle, kidney, liver, spleen, soft tissue, and bone.

There are four main types of aspergillosis: allergic bronchopulmonary aspergillosis (ABPA), chronic necrotizing Aspergillus pneumonia (CNAP), aspergilloma, and invasive aspergillosis.

According to the U.S. Centers for Disease Control and Prevention (CDC), aspergillosis is not considered an AIDS-defining illness (illness that indicates that the patient's condition has progressed to AIDS).

TYPES OF ASPERGILLOSIS

Allergic bronchopulmonary aspergillosis (ABPA): Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitive reaction to A. fumigatus, which causes inflammation of the airways and air sacs of the lungs. This reaction usually occurs along with asthma and cystic fibrosis (genetic disorder of the mucus in the lungs that causes breathing problems). Allergic fungal sinusitis (inflammation of the sinuses caused by fungal exposure) may also occur. ABPA may worsen asthma symptoms. Repeated episodes of ABPA may cause widespread bronchiectasis (dilation of airway passages) and cause chronic fibrotic lung disease.

About 25% of asthmatics and 50% of patients who have cystic fibrosis are allergic to Aspergillus. However, only a few people develop ABPA. According to surveys and an ABPA registry, only 0.25-0.8% of asthmatics and about seven percent of patients with cystic fibrosis are estimated to have ABPA. The incidence of ABPA in people with asthma who are dependent on steroid inhalers or have associated central bronchiectasis is estimated to be between 7-10%.

Chronic necrotizing Aspergillus pneumonia (CNAP): Chronic necrotizing Aspergillus pneumonia (CNAP) is a rare condition that usually occurs in patients who have weakened immune systems. This condition is frequently associated with underlying lung disease, alcoholism, or long-term corticosteroid therapy. Since the condition usually is not discovered until an autopsy is conducted after the patient has died, the frequency of CNAP may be underestimated. Also, because CNAP is rare, it often remains unrecognized for weeks or months, allowing the fungus spores to multiply in the lungs. CNAP has a reported mortality rate of 10-40%. However, rates as high as 100% have been noted because it often remains undiagnosed for such a long time.

Aspergilloma: An aspergilloma is a fungus ball (mycetoma) that develops in a pre-existing lung cavity (abnormal space between the membranes that line the lungs). Underlying causes of the cavitary disease may include tuberculosis or other necrotizing infection, sarcoidosis (inflammation of the lymph nodes, liver, lungs, and spleen), cystic fibrosis, and emphysematous bullae (blisters under the skin). According to one survey of patients who had cavitary lung disease due to tuberculosis, 17% developed aspergilloma. The ball of fungus may move inside the cavity, but it does not enter the cavity wall. Aspergilloma may cause hemoptysis (blood in the sputum), which may be severe and life threatening.

Invasive aspergillosis: Invasive aspergillosis is a rapidly progressive, often fatal infection that occurs in patients who have extremely weakened immune systems. Patients who have undergone bone marrow transplants or solid organ transplants, those who are neutropenic (low levels of white blood cells called neutrophils), and patients with advanced AIDS or chronic granulomatous disease (inherited disorder that impairs phagocytic cells that normally kill bacteria that enters the body) are susceptible to invasive aspergillosis. The fungus spores invade the blood vessels and infiltrate the membranes that surround the lungs. The infection may spread to other organs, especially the central nervous system (CNS).

Invasive aspergillosis is estimated to occur in 5-13% of bone marrow transplant recipients, 5-25% of patients who have received heart or lung transplants, and 10-20% of patients receiving intensive chemotherapy for leukemia. Although there have been reports of invasive aspergillosis in patients who have healthy immune systems, it is extremely rare. Invasive aspergillosis is associated with a high rate of mortality (30-95%).

CAUSES

In general, aspergillosis rarely occurs in patients who have healthy immune systems.

The Aspergillus fungus causes aspergillosis pulmonary infections. Although there are more than 100 Aspergillus species, most human illnesses are caused by Aspergillus fumigatus and Aspergillus niger and, less frequently, Aspergillus flavus and Aspergillus clavatus.

The cells and tissues of Aspergillus hyphae (filaments that make up the body of a fungus) are distinct from other fungi. The hyphae have frequent septae that branch at 45-degree angles. The fungus is commonly found on dead leaves, stored grain, compost piles, and decaying vegetation.

Allergic bronchopulmonary aspergillosis (ABPA): An allergic reaction to the fungus is possible and most common among asthmatics or cystic fibrosis patients. The first time or several times after the body is exposed to an allergen, the immune system becomes sensitized. During this process, the body's white blood cells develop immunoglobulin E (IgE) antibodies to the fungus. Once sensitized, the antibodies quickly detect the fungus allergen when it enters the body. These antibodies trigger the release of chemical mediators, which cause allergy symptoms such as hives, rash, tearing eyes, and runny nose. When the hypersensitivity reaction is triggered, alveoli (tiny air sacs in the lung) become inflamed and their walls fill up with white blood cells.

Chronic necrotizing Aspergillus pneumonia (CNAP): Individuals who have underlying pulmonary diseases (including chronic obstructive pulmonary disease, interstitial lung disease, and previous chest surgery) and altered immune status due to chronic corticosteroid therapy, alcoholism, collagen vascular disease, or chronic granulomatous disease (inherited disorder that impairs phagocytic cells that normally kill bacteria that enters the body) have an increased risk of developing chronic necrotizing Aspergillus pneumonia (CNAP).

Aspergilloma: Aspergilloma typically develops in patients who have preexisting cavities in the lungs (abnormal spaces between the membranes that cover the lungs). Underlying causes of the cavitary disease may include tuberculosis or other necrotizing infections (flesh-killing infections), sarcoidosis (inflammation of the lymph nodes, liver, lungs, and spleen), cystic fibrosis, and emphysematous bullae (blisters under the skin). Aspergillomas may also develop in patients with invasive aspergillosis or chronic necrotizing Aspergillus pneumonia (CNAP).

Invasive aspergillosis: When a human host inhales the fungus spores, the organism enters the lungs. Macrophages (white blood cells that kill microorganisms that enter the body) and neutrophils (white blood cells that destroy foreign substances that enter the body) will engulf the invading fungus to prevent infection. However, many species of Aspergillus produce toxic metabolites that may prevent macrophages and neutrophils from engulfing them. Individuals who are taking corticosteroids or have immunodeficiencies (such as HIV/AIDS and chronic granulomatous disease) have impaired macrophage and neutrophil function, making it even more difficult to fight off the fungus. Consequently, patients who are immunocompromised are unable to fight off the invading fungus, and therefore, suffer from pulmonary infections.

SYMPTOMS

Allergic bronchopulmonary aspergillosis (ABPA): Common symptoms include fever, inflamed airways, mucous plugs, blood in sputum, wheezing and cough. The pulmonary infiltrates may not be responsive to antibacterial therapy. Patients who have asthma may experience a worsening of asthmatic symptoms.

Chronic necrotizing Aspergillus pneumonia (CNAP): Patients who have chronic necrotizing Aspergillus pneumonia (CNAP) typically have an underlying disease like steroid-dependent chronic obstructive pulmonary disease (COPD). Symptoms are usually nonspecific and may include fever, night sweats, cough, and weight loss.

Aspergilloma: About 40-60% of patients with aspergilloma experience hemoptysis (blood in sputum caused by pulmonary bleeding), which may be severe and life threatening. Less common symptoms such as cough and fever may occur.

Invasive aspergillosis: Common symptoms of invasive aspergillosis include fever, cough, dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain, hypoxemia (low levels of oxygen in the blood), and sometimes hemoptysis (blood in sputum).

DIAGNOSIS

Allergic bronchopulmonary aspergillosis (ABPA) :

General: The Cystic Fibrosis Foundation has developed criteria for diagnosing ABPA. A definitive diagnosis can be made if the patient has 1) worsening of symptoms, including cough, wheezing, increased sputum, and decreased pulmonary function; 2) there are elevated levels of (immunoglobulin) IgE (greater than 1,000 IU/mL or a greater than two-fold rise from baseline); 3) there is a positive serological test for Aspergillus; or 4) new infiltrates are detected on a chest X-ray or computerized tomography (CT) scan.

Skin test: A positive skin test may be conducted to determine if elevated levels of IgE are produced in response to the fungus. During the test, an area of the patient's skin is exposed to the allergen and observed for an allergic reaction. Positive results indicate that the patient is allergic to the fungus.

Blood test: A blood test may be performed to determine whether the fungus is present.

Imaging studies: A chest X-ray or computerized tomography (CT) scan may be performed to determine whether there are fungal infiltrates in the lungs.

Chronic necrotizing Aspergillus pneumonia (CNAP) :

General: A definitive diagnosis of invasive aspergillosis or chronic necrotizing Aspergillus pneumonia depends on the demonstration of the organism in the lung tissue .

Sputum-induction for histopathologic testing: A sputum sample analysis can be conducted to determine whether a patient has CNPA. The patient will cough deeply, expelling material from the lungs into a sterile cup. The sample is then taken to a laboratory and placed in a medium under conditions that allow the fungus to grow. A positive culture will identify the disease-causing fungus. Sensitivity of a sputum analysis varies widely (50-90%), and depends on proficiency in using the technique and the experience of the laboratory.

Bronchoalveolar lavage (BAL): Bronchoalveolar lavage may be performed to determine whether patients have CNAP. During the procedure, a bronchoscope (thin, flexible tube) is passed through the mouth or nose into the lungs. Saline is then squirted into a small part of the lung and then collected for analysis. If Aspergillus fungus spores are present, a positive diagnosis is made. This procedure is performed when CNPA is strongly suggested, but the sputum sample is negative. The test has about 90% sensitivity and specificity, if performed correctly.

Aspergilloma :

Chest X-ray: A chest X-ray may detect a preexisting cavity in the lungs, usually in an upper lobe. This cavity may contain a solid mass called a fungus ball. This mass may move inside the cavity if the patient changes positions.

Computerized tomography (CT scan): A computerized tomography (CT) scan can provide a detailed image of the fungus ball. A CT scan can detect multiple aspergillomas in large cavities.

Invasive aspergillosis :

General: Definitive diagnosis of invasive aspergillosis or chronic necrotizing Aspergillus pneumonia depends on the demonstration of the organism in the lung tissue.

Sputum-induction for histopathologic testing: A sputum sample analysis can be conducted to determine whether a patient has aspergillosis. The patient will cough deeply, expelling material from the lungs into a sterile cup. The sample is then taken to a laboratory and placed in a medium under conditions that allow the fungus to grow. A positive culture will identify the disease-causing fungus. Sensitivity of a sputum analysis varies widely (50-90%), and depends on proficiency in using the technique and the experience of the laboratory.

Bronchoalveolar lavage (BAL): Bronchoalveolar lavage may be performed to determine whether patients have invasive aspergillosis. During the procedure, a bronchoscope (thin, flexible tube) is passed through the mouth or nose into the lungs. Saline is then squirted into a small part of the lung and then collected for analysis. If Aspergillus fungus spores are present, a positive diagnosis is made. This procedure is performed when aspergillosis is strongly suggested, but the sputum sample is negative. The test has about 90% sensitivity and specificity, if performed correctly.

The presence of elevated galactomannan (a major component of the Aspergillus cell wall) levels in bronchoalveolar lavage (BAL) fluid may also indicate invasive aspergillosis

Lung biopsy: An open lung biopsy is the most invasive procedure and has 100% sensitivity and specificity because it provides the greatest amount of tissue for diagnosis. However, this test is only conducted in rare cases when a bronchoscopy is nondiagnostic. The procedure is performed in a hospital while the patient is under general anesthesia. A tube is inserted through the mouth and into the airway that leads to the lungs. After cleaning the skin, the surgeon makes a cut in the chest area and removes a small piece of lung tissue. The wound is closed with stitches. A chest tube may be left in place for one to two days to prevent the lung from collapsing. The tissue sample is taken to a laboratory for a histological examination.

Chest X-ray: A chest X-ray may detect solitary or multiple nodules, cavitary lesions, or alveolar infiltrates in the lungs.

Computerized tomography (CT) scan: A computerized tomography (CT) scan may be helpful in the early diagnosis of aspergillosis. A characteristic halo image (an area of ground-glass infiltrates surrounding nodular densities) may be visible. During the later stages of the disease, the test may show a crescent of air surrounding nodules, which indicates cavitation.

TREATMENT

General: Treatment varies depending on the specific type of aspergillosis. HIV/AIDS patients should receive antiretroviral therapy to restore the body's immune system.

Allergic bronchopulmonary aspergillosis (ABPA): Oral corticosteroids, like prednisone (Deltasone©, Meticorten©, or Orasone©), are the standard treatment for ABPA. Treatment generally lasts about two weeks, followed by a three to six month tapering off period. Patients who experience recurrent or chronic ABPA have also been prescribed oral itraconazole in addition to corticosteroids.

Chronic necrotizing Aspergillus pneumonia (CNAP): Patients typically receive treatment with the antifungal voriconazole (Vfend©). Other antifungals, such as itraconazole (Sporanox©), caspofungin (Cancidas©), or amphotericin B formulations (Fungilin©, Fungizone©, Abelcet©, AmBisome©, Fungisome©, Amphocil©, Amphotec©), have also been used, but they are not as effective as voriconazole.

If the infection does not respond to antifungal therapy, surgical resection (removal of part of the lung) may be considered. Also, aspergillomas may occasionally form in areas of necrotizing pneumonia (pneumonia caused by inhaling foreign substances like vomit or food). These areas may bleed and often require surgical removal of tissues.

Aspergilloma: While surgical removal of the fungal ball is curative, it may not be possible in patients who have limited pulmonary (lung) function. Oral itraconazole (Sporanox©) may provide partial or complete resolution of aspergillomas in about 60% of patients. A medical procedure called intracavitary treatment has also been used in a small number of patients. During the procedure, CT-guided catheters, which are inserted with a needle, inject amphotericin alone or in combination with other drugs like acetylcysteine (Mucomyst© or Mucosil©) and aminocaproic acid (Amicar© or Cyklokapron©).

Bronchial artery embolization (insertion of a substance through a catheter into a blood vessel to stop bleeding) may be used for life-threatening hemoptysis (blood in the sputum) in patients who are unable to undergo surgery. Inserting a catheter into the bronchial artery requires a skilled and experienced radiologist because localizing the abnormal vessel(s) may be challenging.

Invasive aspergillosis: An antifungal called voriconazole (Vfend©) is the standard treatment for invasive aspergillosis. Amphotericin B (Fungilin©, Fungizone©, Abelcet©, AmBisome©, Fungisome©, Amphocil©, Amphotec©) formulations may be considered as a possible treatment before a diagnosis is confirmed in critically ill patients. Caspofungin (Cancidas©) has also been approved for treatment of invasive aspergillosis in patients who are not responding to other therapies.

Combination antifungal therapy has been used to treat patients whose condition worsens with use of just one drug. However, taking azole antifungals (Diflucan©, Nizoral© or Sporanox©) with amphotericin B (Fungilin©, Fungizone©, Abelcet©, AmBisome©, Fungisome©, Amphocil©, Amphotec©) is controversial because the azole antifungals decrease amphotericin-binding sites and may reduce its effectiveness.

If the infection does not respond to antifungal therapy, surgical removal of part of the lung may be considered. Also, aspergillomas may occasionally form in areas of necrotizing pneumonia (pneumonia caused by inhaling foreign substances like vomit or food). These areas may bleed and often require surgical removal.

INTEGRATIVE THERAPIES

Note : Currently, there is insufficient evidence available on the safety and effectiveness of integrative therapies for the prevention or treatment of aspergillosis. The therapies listed below have been studied for fungal infections, respiratory infections, and pneumonia in general, should be used only under the supervision of a qualified healthcare provider, and should not be used in replacement of other proven therapies or preventive measures.

Good scientific evidence :

Probiotics : Limited evidence with day care children suggests supplementation with Lactobacillus GG may reduce number of sick days, frequency of respiratory tract infections, and frequency of related antibiotic treatments. Fermented milk (with yogurt cultures and L. casei DN-114001) may reduce the duration of respiratory infections in elderly people. More research is needed to make a firm conclusion.

Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

Unclear or conflicting scientific evidence :

Bitter orange : Limited available human study found promising results using the oil of bitter orange for treatment of fungal infections. However, due to methodological weakness of this research, further evidence is needed to confirm these results.

Avoid if allergic or hypersensitive to bitter orange or any members of the Rutaceae family. Avoid with heart disease, narrow-angel glaucoma, intestinal colic, or long QT interval syndrome. Avoid if taking anti-adrenergic agents, beta-blockers, QT-interval prolonging drugs, monoamine oxidase inhibitors (MAOIs), stimulants, or honey. Use cautiously with headache, hyperthyroidism (overactive thyroid), or if fair-skinned. Avoid if pregnant or breastfeeding.

Chiropractic : Chiropractic is a healthcare discipline that focuses on the relationship between musculoskeletal structure (primarily the spine) and body function (as coordinated by the nervous system), and how this relationship affects the preservation and restoration of health. The broad term "spinal manipulative therapy" incorporates all types of manual techniques, including chiropractic. Although used with limited success, there is not enough reliable scientific evidence to draw a conclusion on the effects of chiropractic techniques in the management of pneumonia in the elderly.

Avoid with symptoms of vertebrobasilar vascular insufficiency, aneurysms, unstable spondylolisthesis, or arthritis. Avoid with agents that increase the risk of bleeding. Avoid in areas of para-spinal tissue after surgery. Avoid if pregnant or breastfeeding due to a lack of scientific data. Use extra caution during cervical adjustments. Use cautiously with acute arthritis, conditions that cause decreased bone mineralization, brittle bone disease, bone softening conditions, bleeding disorders, or migraines. Use cautiously with risk of tumors or cancers.

Chlorophyll : Chlorophyll is a chemoprotein commonly known for its contribution to the green pigmentation in plants, and is related to protoheme, the red pigment of blood. It can be obtained from green leafy vegetables (broccoli, Brussel sprouts, cabbage, lettuce, and spinach), algae (Chlorella and Spirulina), wheat grass, and numerous herbs (alfalfa, damiana, nettle, and parsley). Chlorophyll may help to regulate immunity in patients with active destructive pneumonia. Further studies are required to further elaborate on the immune-modifying effects of chlorophyll.

Avoid if allergic or hypersensitive to chlorophyll or any of its metabolites. Use cautiously with photosensitivity, compromised liver function, diabetes, or gastrointestinal conditions or obstructions. Use cautiously if taking immunosuppressants or antidiabetes agents. Avoid if pregnant or breastfeeding.

Cranberry : Limited laboratory research has examined the antifungal activity of cranberry. Further research is warranted in this area.

Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium species. Sweetened cranberry juice may affect blood sugar levels. Use cautiously with a history of kidney stones. Pregnant and breastfeeding women should avoid cranberry in higher amounts than what is typically found in foods.

Physical therapy : Early evidence suggests that chest physiotherapy techniques such as postural drainage, external help with breathing, percussion, and vibration are not better that receiving advice of deep breathing instructions in the treatment of serious pneumonia. Additional evidence is needed in this area.

Not all physical therapy programs are suited for everyone, and patients should discuss their medical history with their qualified healthcare professionals before beginning any treatments. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the literature, although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used during pregnancy, and although reports of major adverse effects are lacking in the available literature, caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.

Probiotics : Probiotics are beneficial bacteria (sometimes referred to as "friendly germs") that help to maintain the health of the intestinal tract and aid in digestion. They also help keep potentially harmful organisms in the gut (harmful bacteria and yeasts) under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be consumed as capsules, tablets, beverages, powders, yogurts, and other foods. Although some clinical studies support the use of probiotics for pneumonia, there is insufficient evidence to draw any firm conclusions.

Probiotics are generally considered safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

Propolis : Propolis is a natural resin created by bees to make their hives. Propolis is made from the buds of conifer and poplar trees and combined with beeswax and other bee secretions. Animal and laboratory studies suggest that propolis may be a beneficial treatment for various types of fungal infections. Additional research is needed to confirm these findings.

Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey, or Balsam of Peru. Severe allergic reactions have been reported. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.

Sea buckthorn : Sea buckthorn (Hippophae rhamnoides) is found throughout Europe and Asia, particularly eastern Europe and central Asia. The plant's orange fruit and the oil from its pulp and seeds have been used traditionally for lung conditions, including coughing and phlegm reduction. Human study supports the use of sea buckthorn in pneumonia, although more clinical research is necessary.

Avoid if allergic or hypersensitive to sea buckthorn, its constituents, or members of the Elaeagnaceae family. Use cautiously in patients with cancer, high blood pressure, or bleeding disorders. Avoid doses higher than those found in foods if pregnant or breastfeeding.

Seaweed, kelp, bladderwrack : Bladderwrack (Fucus vesiculosus) is a brown seaweed found along the northern coasts of the Atlantic and Pacific oceans and North and Baltic seas. Another seaweed that grows alongside bladderwrack is Ascophyllum nodosum, and it is often combined with bladderwrack in kelp preparations. Laboratory research suggests that bladderwrack may have antifungal activity. However, reliable human studies to support this use are currently lacking in the available literature.

Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.

Thyme : Thyme has been used medicinally for thousands of years. Beyond its common culinary application, it has been recommended for many indications based on proposed antimicrobial, antitussive, spasmolytic, and antioxidant activity. Thyme essential oil and thymol have been shown to have antifungal effects. Currently, there is insufficient reliable human evidence to recommend for or against the use of thyme or thymol as a treatment for fungal infections.

Avoid if allergic or hypersensitive to thyme, members of the Lamiaceae (mint) family, any component of thyme, or rosemary (Rosmarinus officinalis). Avoid oral ingestion or non-diluted topical application of thyme oil due to potential toxicity. Avoid topical preparations in areas of skin breakdown or injury or in atopic patients due to multiple reports of contact dermatitis. Use cautiously with gastrointestinal irritation or peptic ulcer disease due to anecdotal reports of gastrointestinal irritation. Use cautiously with thyroid disorders due to observed anti-thyrotropic effects in animal research of the related species Thymus serpyllum. Avoid if pregnant or breastfeeding.

Vitamin A : Limited available study did not find an effect of a moderate dose of vitamin A supplementation on the duration of uncomplicated pneumonia in underweight or normal-weight children aged younger than five years. However, a beneficial effect was seen in children with high basal serum retinol concentrations.

Avoid if allergic or hypersensitive to vitamin A. Vitamin A toxicity may occur if taken at high dosages. Use cautiously with liver disease or alcoholism. Smokers who consume alcohol and beta-carotene may be at an increased risk for lung cancer or heart disease. Vitamin A appears safe in pregnant women if taken at recommended doses; however, vitamin A excess, as well as deficiency, has been associated with birth defects. Use cautiously if breastfeeding because the benefits or dangers to nursing infants are not clearly established.

Vitamin C : Vitamin C (ascorbic acid) is a water-soluble vitamin that is necessary for the body form collagen in bones, cartilage, muscle, and blood vessels. It also aids in the absorption of iron. Vitamin C may play a role in pneumonia prevention. However, further research is needed.

Avoid if allergic or sensitive to vitamin C product ingredients. Vitamin C is generally considered safe in amounts found in foods. Vitamin C supplements are also generally considered safe in most individuals if taken in recommended doses. Avoid high doses of vitamin C with glucose 6-phosphate dehydrogenase deficiency, kidney disorders or stones, liver cirrhosis, gout, or paroxysmal nocturnal hemoglobinuria (bleeding disorder). It is unclear if vitamin C supplements in doses higher than Dietary Reference Intake recommendations are safe for pregnant or breastfeeding women. Vitamin C is naturally found in breast milk.

Yerba santa : Chumash Native Americans and other California tribes have used yerba santa (Eriodictyon californicum) and other related species (Eriodictyon crassifolium, Eriodictyon trichocalyx) for many centuries in the treatment of pulmonary (lung) conditions, saliva production, and to stop bleeding of minor cuts and scrapes. There is an extensive clinical history of the use of Eriodictyon extracts in pulmonary conditions such as pneumonia. However, additional study is needed.

Avoid if allergic or hypersensitive to Eriodictyon species. Use cautiously in children. Avoid if pregnant or breastfeeding.

Zinc : Results from large clinical trials suggest that supplementation with zinc may reduce the incidence of lower respiratory infections. However, a recent study does not support the use of zinc supplementation in the management of acute lower respiratory infections requiring hospitalization in indigenous children living in remote areas. Due to conflicting results, further research is needed before a conclusion can be drawn. Future studies could examine whether these adult populations have a similar response.

Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride because evidence of safety and effectiveness are currently lacking. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

Fair negative scientific evidence :

Zinc : Limited available study found that zinc supplementation does not seem to lessen the duration of tachypnea, hypoxia, chest indrawing, inability to feed, lethargy, severe illness, or hospitalization for pneumonia in children.

Zinc is generally considered safe when taken at the recommended dosages. Avoid zinc chloride because evidence of safety and effectiveness are currently lacking. Avoid with kidney disease. Use cautiously if pregnant or breastfeeding.

Traditional or theoretical uses lacking sufficient evidence :

Bromelain : Bromelain is a digestive enzyme that comes from the stem and the fruit of the pineapple plant. Bromelain has been suggested as a potential treatment for pneumonia. Additional research is needed in this area.

Avoid if allergic to bromelain, pineapple, honeybee, venom, latex, birch pollen, carrots, celery, fennel, cypress pollen, grass pollen, papain, rye flour, wheat flour, or members of the Bromeliaceae family. Use cautiously with a history of bleeding disorders, stomach ulcers, heart disease, or liver or kidney disease. Use cautiously before dental or surgical procedures or while driving or operating machinery. Avoid if pregnant or breastfeeding.

Goldenseal : Goldenseal is one of the five top-selling herbal products in the United States. Berberine, a compound in goldenseal, has been found to have antimicrobial properties in animal and laboratory studies. Although goldenseal has been suggested as a potential treatment for pneumonia, there is currently a lack of clinical research evaluating its effects for this indication.

Avoid if allergic or hypersensitive to goldenseal or any of its constituents (like berberine and hydrastine). Use cautiously with bleeding disorders, diabetes, or low blood sugar levels. Avoid if pregnant or breastfeeding.

PREVENTION

Aspergillosis is less likely to develop in individuals who have healthy immune systems. Therefore, patients who have HIV/AIDS should receive highly active antiretroviral therapy (HAART), which suppresses HIV and subsequently boosts the body's immune system.

Preventative antifungal therapy and the use of laminar air flow (LAF) or high-efficiency particulate air (HEPA) filters in hospital rooms of patients who receive bone marrow transplants and other high-risk patients may prevent invasive aspergillosis. These filters help trap the microscopic fungal spores before they are able to circulate in the air.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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• HIV InSite. http://hivinsite.ucsf.edu. Accessed May 12, 2009.
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• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009. Accessed May 12, 2009.
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