Author : Dr Jerry Nick National Jewish Medical and Research Center, Denver
2008-12-29
2008-12-29
Bronchiectasis : Causes, clinical manifestations, and treatment
Introduction
Bronchiectasis
is not a single disease, but the result of many different conditions
where the medium sized bronchi (air passages of the lung) are abnormally
dilated, distorted, and thick-walled. Nearly always, these abnormal
bronchi are chronically inflamed and infected by bacteria. The essential
symptom is chronic production of sputum (a mixture of coughed up airway
surface liquids, white blood cells and mucus).
The
process occurs in airways that have sustained injury and a subsequent
loss of structural integrity of muscle, elastic tissue, and sometimes
bronchial cartilage. This makes the abnormal dilated airways
susceptible to bacterial infection, which leads to continuous irritation
and inflammation. This inflammation further damages lung tissue,
disrupts normal bronchi function, and predisposes the bronchial wall to
further infection with bacteria. Patients with bronchiectasis typically
have recurrent flares (exacerbations) of their symptoms with increasing
frequency and severity over the course of years or decades [1].
Normal bronchial health
The
normal bronchi are typically a smooth walled, branching, and gradually
tapering tubular structure, akin to the branches of a tree. The healthy
bronchi permit more than 10,000 liters of air to flow daily through the
lungs of the typical adult. However, the air routinely contains noxious
chemicals, particles, bacteria and viruses.
Despite
these exposures, the healthy human airways are maintained in a nearly
sterile state by the body’s immune system, which includes patrolling
white blood cells, a mucus blanket, chemical defenses, and cough. The
mucus blanket is a thin layer of water, mucus cells, and chemical
defenses that are constantly moving like a slow river from the smaller
more distant tubes to the larger more central airways (sometimes called
the ‘mucociliary escalator’). The components of the mucus blanket and
the constant renewing of the surfaces keep the lungs clear of debris and
infection. Renewal happens through “clearance,” which in the normal
lung has two major mechanisms, the mucociliary escalator (with cough)
and the ingestion of infection by host defense cells (phagocytosis). In
the larger conducting airways, cough can easily clear large quantities
of mucus or foreign matter. Effective cough is an explosive release of
air, with high airflows that generate shearing forces within the
airways. Cough is stimulated to remove an irritating substance (e.g.
excess mucus, pool water, or an inhaled peanut). Bronchiectasis develops
when clearance is persistently ineffective or overwhelmed, or when the
immune defense of an individual is impaired.
What is Bronchiectasis?
In
bronchiectasis the “-ectasis” refers to abnormal widening of conducting
airways. Other changes of the bronchi can include thickening,
irregularities, dilations and herniations (out-pouching) of the walls.
These changes occur slowly, over months to years. With these
abnormalities occur chronic respiratory symptoms such as cough and
sputum production. In addition to the distortion of the shape of the
airway, the surfaces of the bronchi develop areas of scarring, and the
mucus producing glands become enlarged. All of these changes impede the
effective physical clearing of debris from the lungs.
The segment of a lung from a child who died of cystic fibrosis demonstrates typical features of bronchiectasis, including plugging of the dilated airways with mucous, pus, and localized bleeding (courtesy of Joseph R. Siebert, PhD and Joel E. Haas, M.D., used with permission).
What are the symptoms of Bronchiectasis?
Bronchiectasis
can cause a wide range of symptoms, but the most common is cough. The
cough is typically associated with the production and expectoration of
sputum. Severe cases typically have a greater quantity of sputum
production. Occasionally, people with bronchiectasis may cough up blood.
Wheezing, shortness of breath and pleurisy (chest pain with breathing)
may also be due to bronchiectasis. More general symptoms of tiredness,
fevers, breathlessness, and arthritis are other symptoms experienced by
people with bronchiectasis [1].
How is Bronchiectasis diagnosed?
The
anatomic changes of bronchiectasis are most clearly identified using
computed tomography of the chest (CT scans). Similar changes can be seen
on x-rays of the chest, but are more difficult to detect in mild cases.
In many cases, bronchiectasis is incidentally identified by CT scans before significant symptoms or breathing problems occur [2]. Early patterns of disease include uneven inflation of the lung, bronchial wall thickening, and small blockages of the airways [2].
CT findings of more severe disease include airways that fail to taper
normally in diameter, increased ratio of airway to artery size, and
nodules (representing obstruction of the airways by mucus).
What causes Bronchiectasis?
In
people with bronchiectasis, one (or more) of the protective functions
of the immune system are dysregulated, or inadequate to keep the lungs
clear of infection. Worldwide, the most common cause of bronchiectasis
is damage caused by severe, untreated, or prolonged pulmonary infections
in childhood. Less commonly, abnormalities from birth defects, direct
airway injuries, or toxic exposures may lead to bronchiectasis.
An important clue to the cause of bronchiectasis is whether the damage occurs only in a single lobe of the lung (focal bronchiectasis), or is spread in multiple lobes of the lung (diffuse bronchiectasis). The distribution of bronchiectasis can be determined easily by CT scan. Focal bronchiectasis is usually the result of obstruction of a single large bronchi with a foreign object, a tumor, or due to unusual development of the airway. In some cases, a severe infection or pneumonia of a single lobe can result in focal bronchiectasis years later in life. Diffuse bronchiectasis is usually the result of an underlying immune deficiency, or an infection, or toxic exposure that involved multiple lobes of the lungs.
An important clue to the cause of bronchiectasis is whether the damage occurs only in a single lobe of the lung (focal bronchiectasis), or is spread in multiple lobes of the lung (diffuse bronchiectasis). The distribution of bronchiectasis can be determined easily by CT scan. Focal bronchiectasis is usually the result of obstruction of a single large bronchi with a foreign object, a tumor, or due to unusual development of the airway. In some cases, a severe infection or pneumonia of a single lobe can result in focal bronchiectasis years later in life. Diffuse bronchiectasis is usually the result of an underlying immune deficiency, or an infection, or toxic exposure that involved multiple lobes of the lungs.
Table 1: Diseases associated with the development of bronchiectasis
Diffuse Bronchiectasis
Infection (primary)
Bacteria: Klebsiella pneumonia, S. aereus, Haemophilus influenzae, B. pertussis
Mycobacteria: M. tuberculosis, NTM
Mycoplasma
Viruses: Influenza, Adenoviruses, Measles, HIV
Fungus
Allergic bronchopulmonary aspergillosis (ABPA)
Mucoid impaction
Bronchocentric granulomatosis
Cystic Fibrosis (CF)
Primary ciliary dyskinesia
Kartagener’s syndrome
Young’s syndrome
Immunodeficiency states
IgG deficiency
IgG subclass deficiency
IgA deficiency
Leukocyte dysfunction
Lymphocyte dysfunction
Complement deficiencies
α1-antitrypsin deficiency
Autoimmune or hyperimmune disorders
Rheumatoid arthritis
Ulcerative colitis
Cutaneous vaculitis
Hashimoto’s thyroiditis
Pernicious anemia
Primary biliary cirrhosis
Relapsing polychondritis
Celiac disease
Yellow nail syndrome
Diseases of tracheal or bronchial cartilage
Williams-Campbell syndrome
Tracheobronchomegaly
(Mounier-Kuhn)
Inhalation of noxious fumes and dust anhydrous ammonia, silica, sulfur dioxide, talc, cork, bakelite,
Heroin
Chronic fibrosing diseases
Chronic gastric aspiration
Marfan’s syndrome
Heart-lung transplant
Idiopathic (without known cause)
Focal Bronchiectasis
Infection (primary)
Klebsiella pneumonia, S. aereus, Haemophilus influenzae, M.tuberculosis, NTM
Luminal bronchus obstruction
Foreign body
Broncholith
Endobronchial tumor
Mucoid impaction
Bronchial stenosis
Extrinsic bronchus obstruction lymph node, aneurysm, tumor, granuloma
Pulmonary sequestration
Unilateral hyperlucent lung (Swyer-James syndrome)
Historically the most common causes of bronchiectasis have been severe lung infections during the vulnerable periods of childhood [3]. Serious infections such as whooping cough (Bordetella pertussis) or severe viral infections may lead to bronchiectasis by interrupting the ordered growth and maturation of the lung. An apparent decrease in bronchiectasis over the past decades is attributed to the development of antibiotics, immunizations, and improved overall childhood health. Decreases in childhood respiratory illnesses (e.g. measles, chicken pox, tuberculosis, influenza) and improved management of the occasional complicating bacterial infections have decreased the incidence of bronchiectasis.
Currently, tuberculosis is the single leading infectious cause of bronchiectasis on a world wide basis. These cases are predominantly found in developing nations or areas with very limited access to standard medical treatment. In contrast, the largest single cause of bronchiectasis in western industrialized countries is the progressive genetic disorder cystic fibrosis (CF). The genetic defect in CF results in the secretion of unusually thick, dehydrated, and sticky mucus in the bronchi, as well as many other tissues of the body [4]. A hallmark of bronchiectasis due to cystic fibrosis is that the disease is most severe in the upper lobes of the lung.
Another important genetic disorder which leads to bronchiectasis is primary ciliary dyskinesia (PCD). This disorder of the cilia (hairlike projections which line the airways) leads to dysfunctional mucus clearance and chronic sinus and lung problems. In people with PCD, the mucus blanket is not regularly renewed because the cilia are unable to propel it out of the lung. As a result, particles and infections are more frequent and persist longer, thus leading to airway damage over time. In PCD, cough and other mechanisms of airways clearance appear to provide partial adaptation to overcome disordered ciliary function. Individuals with PCD develop bronchiectasis with a lower lobe predominance.
Often, the exact cause of bronchiectasis in an individual is never determined [5]. Many of the causes of bronchiectasis are extremely rare conditions (see Table 1). Even lung specialists (pulmonologists) may be unfamiliar with some of these diseases, and often the tests used to diagnose each condition are expensive or not widely available. In the absence of a clear diagnosis, bronchiectasis is often referred to as “idiopathic.” Adding to the confusion is that while infections of the airway can cause bronchiectasis, infections of the airway are also a common complication of bronchiectasis. Often patients come to medical attention due to airway infections, and when bronchiectasis is discovered, it is assumed that the infection caused the bronchiectasis [6]. However, it is likely that in many cases, a primary abnormality of the host defense, such as PCD or CF initiated the bronchiectasis, and the infection was a secondary complication.
Not all causes of bronchiectasis originate from an infection or a genetic defect of host defense. For example, the lung defenses can be overwhelmed by aspiration, such as the inadvertent inhalation of a large particle. An inhaled peanut can impede the protective mechanisms of the bronchi. The peanut may become stuck within the bronchi and be unable to be expelled by cough. The stuck peanut blocks the normal passage of mucus and leads to persistent inflammation and can ultimately cause focal bronchiectasis. Not infrequently, a secondary infection may occur.
Foreign body aspiration offers an example of combined disordered clearance and intense inflammation leading to bronchiectasis. The greatest risk of bronchiectasis occurs when objects are present for a long time, and are made of substances that irritate the airway. Objects such as peanuts or other organic foreign matter provoke an inflammatory response, which secondarily can injury the airway. Many experts believe that all types of bronchiectasis start with obstruction of the small and medium-sized airways, either with inhaled objects or plugs of mucus.
Infection (primary)
Bacteria: Klebsiella pneumonia, S. aereus, Haemophilus influenzae, B. pertussis
Mycobacteria: M. tuberculosis, NTM
Mycoplasma
Viruses: Influenza, Adenoviruses, Measles, HIV
Fungus
Allergic bronchopulmonary aspergillosis (ABPA)
Mucoid impaction
Bronchocentric granulomatosis
Cystic Fibrosis (CF)
Primary ciliary dyskinesia
Kartagener’s syndrome
Young’s syndrome
Immunodeficiency states
IgG deficiency
IgG subclass deficiency
IgA deficiency
Leukocyte dysfunction
Lymphocyte dysfunction
Complement deficiencies
α1-antitrypsin deficiency
Autoimmune or hyperimmune disorders
Rheumatoid arthritis
Ulcerative colitis
Cutaneous vaculitis
Hashimoto’s thyroiditis
Pernicious anemia
Primary biliary cirrhosis
Relapsing polychondritis
Celiac disease
Yellow nail syndrome
Diseases of tracheal or bronchial cartilage
Williams-Campbell syndrome
Tracheobronchomegaly
(Mounier-Kuhn)
Inhalation of noxious fumes and dust anhydrous ammonia, silica, sulfur dioxide, talc, cork, bakelite,
Heroin
Chronic fibrosing diseases
Chronic gastric aspiration
Marfan’s syndrome
Heart-lung transplant
Idiopathic (without known cause)
Focal Bronchiectasis
Infection (primary)
Klebsiella pneumonia, S. aereus, Haemophilus influenzae, M.tuberculosis, NTM
Luminal bronchus obstruction
Foreign body
Broncholith
Endobronchial tumor
Mucoid impaction
Bronchial stenosis
Extrinsic bronchus obstruction lymph node, aneurysm, tumor, granuloma
Pulmonary sequestration
Unilateral hyperlucent lung (Swyer-James syndrome)
Historically the most common causes of bronchiectasis have been severe lung infections during the vulnerable periods of childhood [3]. Serious infections such as whooping cough (Bordetella pertussis) or severe viral infections may lead to bronchiectasis by interrupting the ordered growth and maturation of the lung. An apparent decrease in bronchiectasis over the past decades is attributed to the development of antibiotics, immunizations, and improved overall childhood health. Decreases in childhood respiratory illnesses (e.g. measles, chicken pox, tuberculosis, influenza) and improved management of the occasional complicating bacterial infections have decreased the incidence of bronchiectasis.
Currently, tuberculosis is the single leading infectious cause of bronchiectasis on a world wide basis. These cases are predominantly found in developing nations or areas with very limited access to standard medical treatment. In contrast, the largest single cause of bronchiectasis in western industrialized countries is the progressive genetic disorder cystic fibrosis (CF). The genetic defect in CF results in the secretion of unusually thick, dehydrated, and sticky mucus in the bronchi, as well as many other tissues of the body [4]. A hallmark of bronchiectasis due to cystic fibrosis is that the disease is most severe in the upper lobes of the lung.
Another important genetic disorder which leads to bronchiectasis is primary ciliary dyskinesia (PCD). This disorder of the cilia (hairlike projections which line the airways) leads to dysfunctional mucus clearance and chronic sinus and lung problems. In people with PCD, the mucus blanket is not regularly renewed because the cilia are unable to propel it out of the lung. As a result, particles and infections are more frequent and persist longer, thus leading to airway damage over time. In PCD, cough and other mechanisms of airways clearance appear to provide partial adaptation to overcome disordered ciliary function. Individuals with PCD develop bronchiectasis with a lower lobe predominance.
Often, the exact cause of bronchiectasis in an individual is never determined [5]. Many of the causes of bronchiectasis are extremely rare conditions (see Table 1). Even lung specialists (pulmonologists) may be unfamiliar with some of these diseases, and often the tests used to diagnose each condition are expensive or not widely available. In the absence of a clear diagnosis, bronchiectasis is often referred to as “idiopathic.” Adding to the confusion is that while infections of the airway can cause bronchiectasis, infections of the airway are also a common complication of bronchiectasis. Often patients come to medical attention due to airway infections, and when bronchiectasis is discovered, it is assumed that the infection caused the bronchiectasis [6]. However, it is likely that in many cases, a primary abnormality of the host defense, such as PCD or CF initiated the bronchiectasis, and the infection was a secondary complication.
Not all causes of bronchiectasis originate from an infection or a genetic defect of host defense. For example, the lung defenses can be overwhelmed by aspiration, such as the inadvertent inhalation of a large particle. An inhaled peanut can impede the protective mechanisms of the bronchi. The peanut may become stuck within the bronchi and be unable to be expelled by cough. The stuck peanut blocks the normal passage of mucus and leads to persistent inflammation and can ultimately cause focal bronchiectasis. Not infrequently, a secondary infection may occur.
Foreign body aspiration offers an example of combined disordered clearance and intense inflammation leading to bronchiectasis. The greatest risk of bronchiectasis occurs when objects are present for a long time, and are made of substances that irritate the airway. Objects such as peanuts or other organic foreign matter provoke an inflammatory response, which secondarily can injury the airway. Many experts believe that all types of bronchiectasis start with obstruction of the small and medium-sized airways, either with inhaled objects or plugs of mucus.
Vicious Cycles
Once
bronchiectasis is established, the now compromised clearance mechanisms
of the airways results in repeated or prolonged respiratory infections;
the chronic infections take up residence in the irregularities (nooks
and crannies) of the airways, and continue a self-perpetuating cycle.
Infection leads to inflammation and the inflammation further damages the
airway.
Once
established, the anatomic changes of bronchiectasis impair the normal
control, prevention, and resolution of infection in the airways of the
lung. Thus a ‘vicious cycle’ of bronchiectasis is entered: the
recurrence or persistence of airway infection and inflammation leading
to further structural damage which predisposes to prolonged infection [7].
The response to infection (inflammation) causes more damage to the
airway which supports the persistence of infection. In other words, the
abnormal airway physically and biochemically impairs restoration of
normal airway biology.
Once the permanent anatomic changes of bronchiectasis are present in an individual, the pattern of respiratory disease are well recognized. Patients typically have intermittent pulmonary exacerbations with increasing frequency, and progressive decline in pulmonary function. The rate of this disease progression is widely variable, and dependent on clinical, environmental, and genetic factors.
Once the permanent anatomic changes of bronchiectasis are present in an individual, the pattern of respiratory disease are well recognized. Patients typically have intermittent pulmonary exacerbations with increasing frequency, and progressive decline in pulmonary function. The rate of this disease progression is widely variable, and dependent on clinical, environmental, and genetic factors.
Treating Bronchiectasis
Therapies
for patients with bronchiectasis aim to improve bronchial health by
improving airway clearance, controlling infections and decreasing
inflammation. The best studied form of bronchiectasis is caused by CF,
and treatments proven to be effective in CF are often applied to
bronchiectasis of other causes in the absence of specific,
evidence-based approaches.
Airway Clearance: A cornerstone of the treatment of bronchiectasis is to improve clearance of mucus from the airways to reduce obstruction and infection of the bronchi. Exercise, inhaled medication, and mechanical devices are often recommended to improve airway clearance. Inhaled bronchodilators may decrease the accumulation of debris and mucus in patients with bronchiectasis.
Airway Clearance: A cornerstone of the treatment of bronchiectasis is to improve clearance of mucus from the airways to reduce obstruction and infection of the bronchi. Exercise, inhaled medication, and mechanical devices are often recommended to improve airway clearance. Inhaled bronchodilators may decrease the accumulation of debris and mucus in patients with bronchiectasis.
A
large range of mechanical devices are available that vibrate the chest
and airway in order to improve mucus clearance. Some use mechanical
devices applied to the chest, others pulse pressured air into the
airways, and others use restrictive valves against which a patient may
breath. The classic technique commonly used for children with CF is
called “postural drainage and percussion.” The child sits, stands, or
lies in a position that will help free up mucus as their chest and back
are pounded or clapped by family members or respiratory therapists.
Adults with bronchiectasis usually prefer an airway clearance technique
that can be done without assistance. A mechanical “vest” (shown on
right) has been developed that reproduces the effect of handclapping to
the chest. A fitted vest is coupled to a pneumatic compressor capable of
high frequency oscillation and compression of the chest wall. Many
other devices are available that combine the action of blowing against
pressure with vibration to open the airways and help mobilize the thick
mucus. No method or technique has been shown to be clearly superior.
However, individuals can usually identify the mode that works best for
them, with the goal of facilitating sputum expectoration.
Antibiotics: Control of infections (decreasing pathogens) with the use of antibiotics may decrease the damages caused by bacteria and the bacterial stimulation of inflammation. Anti-microbial therapy may be used chronically or intermittently using medications that target the probable pathogens identified from an individual’s sputum examination. Two antibiotics have now been shown to be effective for this purpose, for individuals with CF who are chronically infected with the bacteria P. aeruginosa. Tobramycin solution for inhalation (TOBI® ) when prescribed in one-month intervals (followed by one month off treatment), has been shown to improve lung function and reduce the frequency of exacerbations in the setting of chronic P. aeruginosa infections [8]. A second antibiotic, azithromycin (taken orally), has been shown to have similar benefits. No other chronic antibiotic treatment is currently recommended [9]. In some individuals, inhaled antibiotics can be irritating and cause cough and wheezing. Additionally, the use of any antibiotic has the potential to select or predispose one to the development of antibiotic resistant organisms.
Further suggested therapies include vaccine administration (for the prevention of influenza and strains of pneumococcal pneumonia) and nutritional support if necessary.
Lung transplantation: For people with CF who are approaching respiratory failure, lung transplantation has been a possible option. In other forms of brochiectasis, the role of transplant is less clear, but should be considered in the setting of advance lung disease that is progressing towards respiratory failure.
Individuals with bronchiectasis have a wide range of disease severity and prognosis. Generally, life expectancy correlates to extent of lung damage. Patients usually have a daily cough, which produces sputum. However, individuals with bronchiectasis typically have flares or exacerbations of their symptoms, which often include increased cough, sputum production and breathlessness. Without intervention these flares may increase in frequency and severity over the course of years or decades. Ultimately, patients may die during a flare of disease or due to progressive respiratory failure [10].
Therapies, including antibiotics, sputum clearance, and vaccinations, are intended to control symptoms and prevent worsening of disease. When therapies work well, a much improved quality of life may result. Goals of treatment include less cough, absence of fatigue, decreased frequency and fewer flares of disease. Perhaps more importantly, with effective therapy, the progression toward respiratory failure may also be forestalled or prevented. The prognosis of bronchiectasis is dependent on the underlying cause of the condition, but in all cases, a comprehensive treatment plan may improve the outlook.
Antibiotics: Control of infections (decreasing pathogens) with the use of antibiotics may decrease the damages caused by bacteria and the bacterial stimulation of inflammation. Anti-microbial therapy may be used chronically or intermittently using medications that target the probable pathogens identified from an individual’s sputum examination. Two antibiotics have now been shown to be effective for this purpose, for individuals with CF who are chronically infected with the bacteria P. aeruginosa. Tobramycin solution for inhalation (TOBI® ) when prescribed in one-month intervals (followed by one month off treatment), has been shown to improve lung function and reduce the frequency of exacerbations in the setting of chronic P. aeruginosa infections [8]. A second antibiotic, azithromycin (taken orally), has been shown to have similar benefits. No other chronic antibiotic treatment is currently recommended [9]. In some individuals, inhaled antibiotics can be irritating and cause cough and wheezing. Additionally, the use of any antibiotic has the potential to select or predispose one to the development of antibiotic resistant organisms.
Further suggested therapies include vaccine administration (for the prevention of influenza and strains of pneumococcal pneumonia) and nutritional support if necessary.
Lung transplantation: For people with CF who are approaching respiratory failure, lung transplantation has been a possible option. In other forms of brochiectasis, the role of transplant is less clear, but should be considered in the setting of advance lung disease that is progressing towards respiratory failure.
Individuals with bronchiectasis have a wide range of disease severity and prognosis. Generally, life expectancy correlates to extent of lung damage. Patients usually have a daily cough, which produces sputum. However, individuals with bronchiectasis typically have flares or exacerbations of their symptoms, which often include increased cough, sputum production and breathlessness. Without intervention these flares may increase in frequency and severity over the course of years or decades. Ultimately, patients may die during a flare of disease or due to progressive respiratory failure [10].
Therapies, including antibiotics, sputum clearance, and vaccinations, are intended to control symptoms and prevent worsening of disease. When therapies work well, a much improved quality of life may result. Goals of treatment include less cough, absence of fatigue, decreased frequency and fewer flares of disease. Perhaps more importantly, with effective therapy, the progression toward respiratory failure may also be forestalled or prevented. The prognosis of bronchiectasis is dependent on the underlying cause of the condition, but in all cases, a comprehensive treatment plan may improve the outlook.
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