Allergic bronchopulmonary aspergillosis
Encyclopedia
In medicine
, allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system
(a hypersensitivity response
) to the fungus
Aspergillus
(most commonly Aspergillus fumigatus
). It occurs most often in patients with asthma
or cystic fibrosis
. Aspergillus spore
s are ubiquitous in soil and are commonly found in the sputum
of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses
.
ABPA causes airway
inflammation
which can ultimately be complicated by sacs of the airways (bronchiectasis
). The disease may cause airway constriction (bronchospasm
). Besides asthma and cystic fibrosis, ABPA can also resemble other conditions such as eosinophilic pneumonia
.
The exact criteria for the diagnosis of ABPA are not agreed upon. Chest X-ray
s and CT scans, raised blood levels of IgE
and eosinophil
s, immunological tests for Aspergillus together with sputum staining
and sputum culture
s can be useful. Biopsies
are rarely needed. Treatment consists of corticosteroids and antifungal
medications.
s of poorly controlled asthma
, with wheezing, cough
, shortness of breath and exercise intolerance
. They also have symptoms reminding of bronchiectasis
, such as chronic sputum
production, coughing up brownish mucoid plugs or even blood (the latter is called hemoptysis
), and recurrent infections (with fever
and malaise
). However, since the infiltrates in ABPA indicate eosinophilic pneumonia
, they do not respond to treatment with antibiotics. There may be unexplained worsening of asthma or cystic fibrosis
.
more than 10% and there is a raised serum IgE more than 1000 ng/ml.
Chest radiography shows various transient abnormalities:
Aspergillus specific tests:
Fungal hyphae may be seen in the sputum.
The immune reaction is suppressed using oral corticosteroids:
Mucus plugs may be removed by bronchoscopic aspiration. It is almost impossible to eradicate the fungus but frequently itraconazole
(an anti-fungal) is used in combination with steroid therapy, which often results in a reduction of the steroid dose required. Regular monitoring of the condition includes chest x-rays, pulmonary function tests
, and serum IgE. The antibody levels usually fall as the disease is controlled, but they may rise again as an early sign of flare-ups.
There are also case reports of the use of omalizumab in the treatment of ABPA.
or cystic fibrosis
. It is estimated that ABPA may be present in between 0.5 and 2% of all asthma patients, and in between 1 and 15% of cystic fibrosis patients.
response (atopic
, with formation of immunoglobulin E
or IgE) and a type III hypersensitivity
response (with formation of immunoglobulin G
or IgG). The reaction of immunoglobulin E with Aspergillus antigen
s results in mast cell
degranulation
with bronchoconstriction
and increased capillary
permeability
. Immune complexes (a type III reaction) and inflammatory cells are then deposited within the mucous membrane
s of the airways, leading to necrosis
(tissue death) and an eosinophilic
infiltrate. Type 2 T helper cell
s secreting interleukin 4
and interleukin 5
, and attraction of neutrophils
by interleukin 8
seem to play an important role.
In spite of this pronounced immune reaction, the fungus is not cleared from the airways. Proteolytic enzymes are released by the immune cells, and toxins are released by the fungi. Together these result in bronchiectasis
, most pronounced in the central parts of the airways. Repeated acute episodes left untreated can result in progressive pulmonary fibrosis
that is often seen in the upper zones and can give rise to a similar radiological appearance to that produced by tuberculosis
.
This model explains the main features of episodic bronchospasm, increased mucus production and plugging of distal airways, leading to their collapse and subsequent bronchiectasis.
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
, allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
(a hypersensitivity response
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
) to the fungus
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
Aspergillus
Aspergillus
Aspergillus is a genus consisting of several hundred mold species found in various climates worldwide. Aspergillus was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli...
(most commonly Aspergillus fumigatus
Aspergillus fumigatus
Aspergillus fumigatus is a fungus of the genus Aspergillus, and is one of the most common Aspergillus species to cause disease in individuals with an immunodeficiency....
). It occurs most often in patients with asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
or cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
. Aspergillus spore
Spore
In biology, a spore is a reproductive structure that is adapted for dispersal and surviving for extended periods of time in unfavorable conditions. Spores form part of the life cycles of many bacteria, plants, algae, fungi and some protozoa. According to scientist Dr...
s are ubiquitous in soil and are commonly found in the sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
of healthy individuals. A. fumigatus is responsible for a spectrum of lung diseases known as aspergilloses
Aspergillosis
Aspergillosis is the name given to a wide variety of diseases caused by fungi of the genus Aspergillus. The most common forms are allergic bronchopulmonary aspergillosis, pulmonary aspergilloma and invasive aspergillosis. Most humans inhale Aspergillus spores every day...
.
ABPA causes airway
Airway
The pulmonary airway comprises those parts of the respiratory system through which air flows, conceptually beginning at the nose and mouth, and terminating in the alveoli...
inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
which can ultimately be complicated by sacs of the airways (bronchiectasis
Bronchiectasis
Bronchiectasis is a disease state defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. It is classified as an obstructive lung disease, along with emphysema, bronchitis, asthma, and cystic fibrosis...
). The disease may cause airway constriction (bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...
). Besides asthma and cystic fibrosis, ABPA can also resemble other conditions such as eosinophilic pneumonia
Eosinophilic pneumonia
Eosinophilic pneumonia is a disease in which a certain type of white blood cell called an eosinophil accumulates in the lung. These cells cause disruption of the normal air spaces where oxygen is extracted from the atmosphere. Several different kinds of eosinophilic pneumonia exist and can occur...
.
The exact criteria for the diagnosis of ABPA are not agreed upon. Chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...
s and CT scans, raised blood levels of IgE
Immunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...
and eosinophil
Eosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
s, immunological tests for Aspergillus together with sputum staining
Gram staining
Gram staining is a method of differentiating bacterial species into two large groups ....
and sputum culture
Sputum culture
A sputum culture is a test to detect and identify bacteria or fungi that infect the lungs or breathing passages. Sputum is a thick fluid produced in the lungs and in the adjacent airways. A sample of sputum is placed in a sterile container and sent to the laboratory for testing...
s can be useful. Biopsies
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
are rarely needed. Treatment consists of corticosteroids and antifungal
Antifungal
* Antifungal medication, a medication used to treat fungal infection s such as athlete's foot , ringworm, candidiasis, etc.* Antifungal protein, a protein family* an adjective referring to a fungicide compound...
medications.
Symptoms
Patients with allergic bronchopulmonary aspergillosis often have symptomSymptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s of poorly controlled asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, with wheezing, cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...
, shortness of breath and exercise intolerance
Exercise intolerance
Exercise intolerance is a condition where the patient is unable to do physical exercise at the level or for the duration that would be expected of someone in his or her general physical condition, or experiences unusually severe post-exercise pain, fatigue, or other negative effects...
. They also have symptoms reminding of bronchiectasis
Bronchiectasis
Bronchiectasis is a disease state defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. It is classified as an obstructive lung disease, along with emphysema, bronchitis, asthma, and cystic fibrosis...
, such as chronic sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....
production, coughing up brownish mucoid plugs or even blood (the latter is called hemoptysis
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...
), and recurrent infections (with fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
and malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
). However, since the infiltrates in ABPA indicate eosinophilic pneumonia
Eosinophilic pneumonia
Eosinophilic pneumonia is a disease in which a certain type of white blood cell called an eosinophil accumulates in the lung. These cells cause disruption of the normal air spaces where oxygen is extracted from the atmosphere. Several different kinds of eosinophilic pneumonia exist and can occur...
, they do not respond to treatment with antibiotics. There may be unexplained worsening of asthma or cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
.
Diagnosis
A complete blood count usually reveals eosinophiliaEosinophilia
Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
more than 10% and there is a raised serum IgE more than 1000 ng/ml.
Chest radiography shows various transient abnormalities:
- consolidation, infiltrates or collapse
- thickened bronchial wall markings
- peripheral shadows
- signs of bronchiectasisBronchiectasisBronchiectasis is a disease state defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. It is classified as an obstructive lung disease, along with emphysema, bronchitis, asthma, and cystic fibrosis...
, typically in a central location
Aspergillus specific tests:
- precipitating antibodies to aspergillus species in >90% of cases
- aspergillus-specific IgE RAST testRAST testA RAST test is a blood test used to determine to what substances a person is allergic. This is different from a skin allergy test, which determines allergy by the reaction of a person's skin to different substances....
- skin-prick test is almost always positive to Aspergillus fumigatus
Fungal hyphae may be seen in the sputum.
Treatment
The aim of treatment is to suppress the immune reaction to the fungus and to control bronchospasm.The immune reaction is suppressed using oral corticosteroids:
- a high dose of prednisolonePrednisolonePrednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
or prednisonePrednisonePrednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
(30 to 45 mg per day) in acute attacks - a lower maintenance dose (5–10 mg per day)
Mucus plugs may be removed by bronchoscopic aspiration. It is almost impossible to eradicate the fungus but frequently itraconazole
Itraconazole
Itraconazole , invented in 1984, is a triazole antifungal agent that is prescribed to patients with fungal infections. The drug may be given orally or intravenously.-Medical uses:...
(an anti-fungal) is used in combination with steroid therapy, which often results in a reduction of the steroid dose required. Regular monitoring of the condition includes chest x-rays, pulmonary function tests
Spirometry
Spirometry is the most common of the pulmonary function tests , measuring lung function, specifically the measurement of the amount and/or speed of air that can be inhaled and exhaled...
, and serum IgE. The antibody levels usually fall as the disease is controlled, but they may rise again as an early sign of flare-ups.
There are also case reports of the use of omalizumab in the treatment of ABPA.
Epidemiology
Estimating the prevalence of ABPA has been made difficult by lack of uniform diagnostic criteria and standardised tests. It usually occurs as a complication of other chronic lung disease, in particular asthmaAsthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
or cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
. It is estimated that ABPA may be present in between 0.5 and 2% of all asthma patients, and in between 1 and 15% of cystic fibrosis patients.
Disease mechanism
For an unknown reason, patients with allergic bronchopulmonary aspergillosis develop a hypersensitivity response, both a type IType I hypersensitivity
Type I hypersensitivity is an allergic reaction provoked by reexposure to a specific type of antigen referred to as an allergen, or to a nonimmunologic stimulus like cold weather or exercise...
response (atopic
Atopy
Atopy or atopic syndrome is a predisposition toward developing certain allergic hypersensitivity reactions.Atopy may have a hereditary component, although contact with the allergen must occur before the hypersensitivity reaction can develop ....
, with formation of immunoglobulin E
Immunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...
or IgE) and a type III hypersensitivity
Type III hypersensitivity
Type III hypersensitivity occurs when antigens and antibodies are present in roughly equal amounts, causing extensive cross-linking.-Presentation:...
response (with formation of immunoglobulin G
Immunoglobulin G
Immunoglobulin G are antibody molecules. Each IgG is composed of four peptide chains — two heavy chains γ and two light chains. Each IgG has two antigen binding sites. Other immunoglobulins may be described in terms of polymers with the IgG structure considered the monomer.IgG constitutes 75%...
or IgG). The reaction of immunoglobulin E with Aspergillus antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s results in mast cell
Mast cell
A mast cell is a resident cell of several types of tissues and contains many granules rich in histamine and heparin...
degranulation
Degranulation
Degranulation is a cellular process that releases antimicrobial cytotoxic molecules from secretory vesicles called granules found inside some cells...
with bronchoconstriction
Bronchoconstriction
Bronchoconstriction is the constriction of the airways in the lungs due to the tightening of surrounding smooth muscle, with consequent coughing, wheezing, and shortness of breath. Bronchoconstriction can also be due to an accumulation of thick mucus....
and increased capillary
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...
permeability
Vascular permeability
Vascular permeability, often in the form of capillary permeability, characterizes the capacity of a blood vessel wall to allow for the flow of small molecules or even whole cells in and out of the vessel. Blood vessel walls are lined by a single layer of endothelial cells...
. Immune complexes (a type III reaction) and inflammatory cells are then deposited within the mucous membrane
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...
s of the airways, leading to necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
(tissue death) and an eosinophilic
Eosinophil granulocyte
Eosinophil granulocytes, usually called eosinophils or eosinophiles , are white blood cells that are one of the immune system components responsible for combating multicellular parasites and certain infections in vertebrates. Along with mast cells, they also control mechanisms associated with...
infiltrate. Type 2 T helper cell
T helper cell
T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...
s secreting interleukin 4
Interleukin 4
Interleukin-4, abbreviated IL-4, is a cytokine that induces differentiation of naive helper T cells to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4. The cell that initially produces IL-4, thus inducing Th0 differentiation, has not been identified, but recent...
and interleukin 5
Interleukin 5
Interleukin 5 or IL-5 is an interleukin produced by T helper-2 cells and mast cells. Its functions are to stimulate B cell growth and increase immunoglobulin secretion. It is also a key mediator in eosinophil activation. IL-5 is a 115-amino acid -long TH2 cytokine that is part of the...
, and attraction of neutrophils
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
by interleukin 8
Interleukin 8
Interleukin-8 is a chemokine produced by macrophages and other cell types such as epithelial cells. It is also synthesized by endothelial cells, which store IL-8 in their storage vesicles, the Weibel-Palade bodies...
seem to play an important role.
In spite of this pronounced immune reaction, the fungus is not cleared from the airways. Proteolytic enzymes are released by the immune cells, and toxins are released by the fungi. Together these result in bronchiectasis
Bronchiectasis
Bronchiectasis is a disease state defined by localized, irreversible dilation of part of the bronchial tree caused by destruction of the muscle and elastic tissue. It is classified as an obstructive lung disease, along with emphysema, bronchitis, asthma, and cystic fibrosis...
, most pronounced in the central parts of the airways. Repeated acute episodes left untreated can result in progressive pulmonary fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
that is often seen in the upper zones and can give rise to a similar radiological appearance to that produced by tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
.
This model explains the main features of episodic bronchospasm, increased mucus production and plugging of distal airways, leading to their collapse and subsequent bronchiectasis.
Patient Support
The Fungal Research Trust funded Aspergillus Website provides patient support at Aspergillosis Patients Support Website and a highly active support group at Aspergillus Support.External links
- Allergic Bronchopulmonary Aspergillosis - GP Notebook
- Allergic Bronchopulmonary Aspergillosis - The Merck Manuals Online Medical Library
- Medpix. ABPA radiology pictures
- The Aspergillus Website Treatment Section.
- Aspergillus - Aspergillus Website (Diagnosis, Treatment, Cases, Images, Educational video)
- Aspergillus Patients Support - Aspergillus Patients (Questions & Answers, Support Group)