Bronchiectasis 

Author: Ethan E Emmons, MD

Updated: Feb 4, 2013

http://emedicine.medscape.com/article/296961-overview

Practice Essentials

Bronchiectasis is an uncommon disease, most often secondary to an infectious process, that results in the abnormal and permanent distortion of one or more of the conducting bronchi or airways.

Signs and symptoms

Clinical manifestations of bronchiectasis are as follows:

Cough and daily mucopurulent sputum production, often lasting months to years (classic)

Blood-streaked sputum or hemoptysis from airway damage associated with acute infection

Dyspnea, pleuritic chest pain, wheezing, fever, weakness, fatigue, and weight loss Rarely, episodic hemoptysis with little to no sputum production (ie, dry

bronchiectasis)

Exacerbations of bronchiectasis from acute bacterial infections may produce the following signs:

Increased sputum production over baseline Increased viscidity of sputum A foul odor of the sputum (occasional) Low-grade fever (rare) Increased constitutional symptoms (eg, fatigue, malaise) Increased dyspnea, shortness of breath, wheezing, or pleuritic pain

Findings on physical examination are nonspecific and may include the following:

Crackles, rhonchi, scattered wheezing, and inspiratory squeaks on auscultation Digital clubbing (2-3% of patients; more frequent in moderate-to-severe cases) Cyanosis and plethora with polycythemia from chronic hypoxia (rare) Wasting and weight loss Nasal polyps and signs of chronic sinusitis Physical stigmata of cor pulmonale, in advanced disease

See Clinical Presentation for more detail.

Diagnosis

The diagnosis of bronchiectasis involves the following:

A compatible history of chronic respiratory symptoms (eg, daily cough and purulent sputum production)

Sputum analysis may strengthen clinical suspicion Chest radiography is occasionally sufficient for confirming the diagnosis High-resolution computed tomography (HRCT) scanning is the standard test for

diagnosis[1, 2, 3]

Tests to identify underlying illnesses include the following:

Quantitative immunoglobulin levels, to exclude hypogammaglobulinemia Quantitative serum alpha1-antitrypsin (AAT) levels, to rule out AAT deficiency Aspergillus precipitins and serum total IgE levels, to diagnose ABPA Autoimmune screening tests

Vitamin D deficiency is common in bronchiectasis and correlates with markers of disease severity. Chalmers et al measured serum 25-hydroxyvitamin-D by immunoassay in 402 stable patients with bronchiectasis and found that 50% were vitamin D deficient (levels below 25 nmol/L), compared with only 12% of matched controls, and 43% were vitamin D insufficient (25-74 nmol/L). Vitamin D–deficient bronchiectasis patients were more likely to be colonized with Pseudomonas aeruginosa, had lower forced expiratory volume in 1 second (FEV1) percent predicted, and had more frequent pulmonary exacerbations.  [4]

Pulmonary function test results may be normal or abnormal; abnormalities are as follows:

Abnormalities may reflect underlying comorbidities and predisposing conditions The most common abnormality is an obstructive airway defect, which is not usually

reversible with bronchodilator therapy A subgroup of patients have hyperreactive airways that will respond to

bronchodilators Yearly decline in FEV1 is greater in patients with bronchiectasis

Expected general findings on posterior-anterior and lateral chest radiographs include the following:

Increased pulmonary markings Honeycombing Atelectasis Pleural changes

Specific findings on chest radiographs may include the following:

Linear lucencies and parallel markings radiating from the hila (tram tracking) in cylindrical bronchiectasis

Dilated bronchi in varicose bronchiectasis Clustered cysts in cystic bronchiectasis

Noteworthy CT findings in bronchiectasis include the following:

Cylindrical bronchiectasis has parallel tram track lines, or it may have a signet-ring appearance composed of a dilated bronchus cut in a horizontal section with an adjacent pulmonary artery representing the stone

The diameter of the bronchus lumen is normally 1-1.5 times that of the adjacent vessel; a diameter greater than 1.5 times that of the adjacent vessel suggests bronchiectasis

Varicose bronchiectasis has irregular or beaded bronchi, with alternating areas of dilatation and constriction

Cystic bronchiectasis has large cystic spaces and a honeycomb appearance; this contrasts with the blebs of emphysema, which have thinner walls and are not accompanied by proximal airway abnormalities

See Workup for more detail.

Management

Treatment modalities include the following:

Antibiotics and chest physiotherapy are the mainstays Bronchodilators Corticosteroid therapy Dietary supplementation Oxygen (reserved for hypoxemic patients with severe disease) Hospitalization for severe exacerbations Surgical therapies

Acceptable antibiotic regimens for mild to moderately ill outpatients include 7-10 days of any of the following:

Amoxicillin Tetracycline Trimethoprim-sulfamethoxazole A newer macrolide (eg, azithromycin[5] or clarithromycin[6, 7] ) A second-generation cephalosporin A fluoroquinolone

For patients with moderate-to-severe symptoms, parenteral administration of the following antibiotics may be indicated:

An aminoglycoside (eg, gentamicin, tobramycin) and An antipseudomonal synthetic penicillin, a third-generation cephalosporin, or a

fluoroquinolone Tobramycin, for patients infected with mucoid Pseudomonas species

American Thoracic Society recommendations for treatment of Mycobacterium avium complex (MAC) infection in the setting of bronchiectasis are as follows:

Combination therapy with clarithromycin, rifampin, ethambutol

Consider streptomycin as a possible fourth drug Continue therapy until the patient's culture results have been negative for 1 year The typical duration of therapy is 18-24 months

Surgical resection of involved bronchiectatic sites is an important adjunct to therapy for patients with focal disease that is poorly controlled by antibiotics. Other indications for surgical intervention may include the following:

Reduction of acute infective episodes Reduction of excessive sputum production Massive hemoptysis (alternatively, bronchial artery embolization may be attempted) Foreign body or tumor removal Consideration in the treatment of MAC or Aspergillus species infections

See Treatment and Medication for more detail.

Image library

This CT scan depicts areas of both cystic bronchiectasis and varicose bronchiectasis.

Background

Bronchiectasis is an uncommon disease, most often secondary to an infectious process, that results in the abnormal and permanent distortion of one or more of the conducting bronchi or airways. First described by Laennec in 1819, later detailed by Sir William Osler in the late 1800s, and further defined by Reid in the 1950s, bronchiectasis has undergone significant changes in regard to its prevalence, etiology, presentation, and treatment.[8]

Bronchiectasis can be categorized as a chronic obstructive pulmonary disease manifested by airways that are inflamed and easily collapsible, resulting in air flow obstruction with shortness of breath, impaired clearance of secretions (often with disabling cough), and occasionally hemoptysis. Severe cases can result in progressive impairment with respiratory failure.[9, 10]

Bronchiectasis most commonly presents as a focal process involving a lobe, segment, or subsegment of the lung. Far less commonly, it may be a diffuse process involving both lungs; these cases most often occur in association with systemic illnesses, such as cystic fibrosis (CF), sinopulmonary disease, or both. The majority of this article will address non-CF related bronchiectasis.

Diagnosis is usually based on a compatible clinical history of chronic respiratory symptoms, such as a daily cough and viscid sputum production (see Clinical), and characteristic radiographic findings on CT scans, such as bronchial wall thickening and luminal dilatation (see Workup).

Antibiotics and chest physiotherapy are the mainstay modalities. Additionally, management of underlying conditions, such as hypogammaglobulinemia or alpha1-antitrypsin deficiency, is essential to the overall treatment. Surgery is an important adjunct to therapy in some patients with advanced or complicated disease. (See Treatment.)

For a discussion of this disorder in children, see the article Pediatric Bronchiectasis.

Pathophysiology

Bronchiectasis is an abnormal dilation of the proximal and medium-sized bronchi (>2 mm in diameter) caused by weakening or destruction of the muscular and elastic components of the bronchial walls. Affected areas may show a variety of changes, including transmural inflammation, edema, scarring, and ulceration, among other findings. Distal lung parenchyma may also be damaged secondary to persistent microbial infection and frequent postobstructive pneumonia. Bronchiectasis can be congenital but is most often acquired.[8]

Congenital bronchiectasis usually affects infants and children. These cases result from developmental arrest of the bronchial tree.

Acquired forms occur in adults and older children and require an infectious insult, impairment of drainage, airway obstruction, and/or a defect in host defense. The tissue is also damaged in part by the host response of neutrophilic proteases, inflammatory cytokines, nitric oxide, and oxygen radicals. This results in damage to the muscular and elastic components of the bronchial wall. Additionally, peribronchial alveolar tissue may be damaged, resulting in diffuse peribronchial fibrosis.[11]

The result is abnormal bronchial dilatation with bronchial wall destruction and transmural inflammation. The most important functional finding of altered airway anatomy is severely impaired clearance of secretions from the bronchial tree.

Impaired clearance of secretions causes colonization and infection with pathogenic organisms, contributing to the purulent expectoration commonly observed in patients with bronchiectasis. The result is further bronchial damage and a vicious cycle of bronchial damage, bronchial dilation, impaired clearance of secretions, recurrent infection, and more bronchial damage.[12]

In 1950, Reid characterized bronchiectasis as cylindrical, cystic, or varicose in nature.[13]

Cylindrical bronchiectasis involves diffuse mucosal edema, with resultant bronchi that are dilated but have straight, regular outlines that end squarely and abruptly (see the image below).

Cylindrical bronchiectasis with signet-ring appearance. Note that the luminal airway diameter is greater than the diameter of the adjacent vessel.

Cystic or saccular bronchiectasis has ulceration with bronchial neovascularization. The result is a ballooned appearance and sometimes air-fluid levels (see the image below).

Cystic and cylindrical bronchiectasis of the right lower lobe on a posterior-anterior chest radiograph.

Varicose bronchiectasis has a bulbous appearance with a dilated bronchus and interspersed sites of relative constriction and, potentially, obstructive scarring. The latter may subsequently result in postobstructive pneumonitis and additional parenchymal damage (see the image below).

Varicose bronchiectasis with alternating areas of bronchial dilatation and constriction.

Etiology

Causes of bronchiectasis include the following:

Primary infections

Bronchial obstruction Aspiration Cystic fibrosis Primary ciliary dyskinesia Allergic bronchopulmonary aspergillosis Immunodeficiency states Congenital anatomic defects Connective-tissue disorders Alpha1-antitrypsin (AAT) deficiency Autoimmune diseases Idiopathic inflammatory disorders Autosomal dominant polycystic kidney disease Traction from other processes Toxic gas exposure

Primary infections

Bronchiectasis may be the sequela of a variety of necrotizing infections that are either inadequately treated or not treated at all. Primary infection (ie, in the absence of intrinsic defects or noninfectious extrinsic insults) was a particularly common cause of bronchiectasis in developed countries prior to the widespread use of antibiotics[14] and it remains important in developing countries, where antibiotics are used inconsistently.[15, 16]

Typical offending organisms that have been known to cause bronchiectasis include the following[17, 14] :

Klebsiella species Staphylococcus aureus Mycobacterium tuberculosis Mycoplasma pneumoniae Nontuberculous mycobacteria Measles virus Pertussis virus Influenza virus Herpes simplex virus Certain types of adenovirus

Infection with respiratory syncytial virus in childhood may also result in bronchiectasis.

Mycobacterium avium complex (MAC) infection deserves special mention. It has a propensity to occur in the setting of human immunodeficiency virus (HIV) infection as well as in hosts who are immunocompetent.[18]

MAC infection has been observed especially in women who are nonsmokers; are older than 60 years; do not have a known predisposing pulmonary disorder; and tend to voluntarily suppress cough.[19] Sputum smear in these cases is positive for acid-fast bacilli, and CT scan shows small regular nodules and findings of bronchiectasis.[20, 21, 19]

Once a patient develops bronchiectasis, many of these same organisms colonize the damaged bronchi and may cause ongoing damage and episodic infectious exacerbations. The

organisms found most typically include Haemophilus species (47-55% of patients) and Pseudomonas species (18-26% of patients).[22, 23]

Although not a primary cause of bronchiectasis, P aeruginosa often causes chronic bronchial infection in patients with non-CF bronchiectasis via a mechanism involving biofilm formation and the release of virulence factors. This suggests that Pseudomonas species may promote disease progression, and that infection with these species may be related to worsening lung function and increased morbidity and mortality.[24]

Bronchial obstruction

Focal postobstructive bronchiectasis may occur in a number of clinical settings (eg, endobronchial tumors, broncholithiasis, bronchial stenosis from infections, encroachment of hilar lymph nodes, foreign body aspiration). Right-middle lobe syndrome is a specific type of bronchial obstruction that may result in bronchiectasis. It results from an abnormal angulation of the lobar bronchus at its origin, predisposing it to obstruction, subsequent infection, and development of bronchiectasis.

Aspiration

In adults, foreign body aspiration often takes place in the setting of altered mental status and involves unchewed food. Patients may also aspirate chewed materials from the stomach, including food, peptic acid, and microorganisms.

After aspiration, a postobstructive pneumonia may occur, with subsequent development of focal bronchiectasis. Bronchiectasis may also develop in the setting of chronic aspiration. Further recognized is that a history of gastroesophageal reflux is a risk factor for aspiration and that the organism Helicobacter pylori may play a role in the development of bronchiectasis in this group of patients.[25, 26, 27]

Cystic fibrosis

CF is a multisystem disorder that affects the chloride transport system in exocrine tissues, primarily secondary to a defect in the CF transmembrane regulator (CFTR) protein. CF and its variants are the most common cause of bronchiectasis in the United States and other industrialized nations.

CF is an autosomal recessive disease affecting approximately 1 in 2,500 whites and 1 in 17,000 blacks in the United States.[28] In was estimated that in 2005, 10,000 adults in the United States would have CF, comprising 40% of the total CF population.[29]

Multiple genetic variants of CF exist, and the risk to patients that have genetic heterozygous mutations remains to be elucidated. However, a reasonable assumption is that patients with CF can be divided into 2 groups: (1) those with classic disease that is readily diagnosed based on clinical and laboratory data and (2) those with less severe disease that manifests later in life and who have ambiguous genetic testing results.[30, 31, 32]

The major pulmonary finding in CF is bronchiectasis, which is an almost universal feature of this disease. It may be the sole feature of CF in adults or those with genetic variations of the disease. Bronchiectasis associated with CF is believed to occur secondary to mucous

plugging of proximal airways and chronic pulmonary infection, especially with mucoid P aeruginosa.[33]

Young syndrome

Young syndrome is clinically similar to CF and may represent a genetic variant of CF. It is most often observed in middle-aged men in North America and is a leading cause of male infertility.[34]

Patients with Young syndrome have bronchiectasis (often predominant in the lower lobes), sinusitis, and obstructive azoospermia. However, they do not display the other findings of CF. The pathogenesis of bronchiectasis in these patients is believed to be similar to that of bronchiectasis in CF. The criterion standard for diagnosis of Young syndrome is electron microscopic analysis of the structure of the cilia.

Primary ciliary dyskinesia

Primary ciliary dyskinesia is a group of inherited disorders that may affect 1 in 15,000-30,000 population. It is manifested by immotile or dyskinetic cilia and/or sperm. This may lead to poor mucociliary clearance, recurrent pulmonary infections, and, ultimately, bronchiectasis.[35, 36]

A variant of this condition, initially described by Kartagener, encompassed the clinical triad of situs inversus, nasal polyps or sinusitis, and bronchiectasis in the setting of immotile cilia of the respiratory tract.[37]

Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to inhaled Aspergillus antigen that is characterized by bronchospasm, bronchiectasis, and immunologic evidence of a reaction to Aspergillus species.[38] ABPA should be suspected in patients with a productive cough who also have a long history of asthma-type symptoms that do not respond to conventional therapy.

Bronchiectasis is believed to be secondary to airway plugging by viscid secretions containing hyphae of Aspergillus species. The resulting bronchiectasis is thin-walled and affects the central and medium-sized airways.

CT scanning of the chest demonstrates central airway bronchiectasis, differentiating this condition from other causes of bronchiectasis. Other features of ABPA include eosinophilia, elevated immunoglobulin E (IgE) levels, and dramatic responses to therapeutic corticosteroids.

Immunodeficiency states

Immunodeficiency states may be congenital or acquired. The most common congenital conditions (albeit rare) involve B-lymphocyte functions. Hypogammaglobulinemia in these cases may take one of the following forms[39, 40, 41, 42] :

Immunoglobulin G (IgG) subclass deficiency X-linked agammaglobulinemia Immunoglobulin A (IgA) deficiency Immunoglobulin M (IgM) deficiency Immunoglobulin E (IgE) deficiency

Patients with hypogammaglobulinemia usually present in childhood with repeated sinus or pulmonary infections, although the disorder has been diagnosed in adults who did not have a history of repeated infections. Establishing the diagnosis is important because gammaglobulin replacement may reduce the number of infections and resultant lung injury.

HIV disease, with resultant acquired immunodeficiency syndrome (AIDS), has been implicated in the development of bronchiectasis and demonstrates the accelerated bronchial damage that may occur from repeated infections in patients who are immunosuppressed. Bronchiectasis in HIV infection has occurred with and without obvious preceding pulmonary infection and may occur secondary to immunologic dysfunction from the HIV disease itself.[18, 43, 44]

Congenital anatomic defects

Bronchiectasis can result from a variety of congenital anatomic defects. Bronchopulmonary sequestration is a congenital abnormality classified as either intralobar or extralobar and results in chronic lower respiratory tract infections that lead to bronchiectasis.

Williams-Campbell syndrome (congenital cartilage deficiency) is the absence of cartilage from lobar to first- to second-generation segmental airways that results in extensive peripheral bronchiectasis.[45]

Mounier-Kuhn syndrome (tracheobronchomegaly) is a rare disorder characterized by dilation of the trachea and segmental bronchi (central bronchiectasis).[46]

Swyer-James syndrome (unilateral hyperlucent lung) likely is a developmental disturbance that leads to unilateral bronchiolitis, hyperinflation, and, in some cases, bronchiectasis.

Yellow-nail syndrome is rare. It results in exudative pleural effusions.[47]

Alpha1-antitrypsin (AAT) deficiency

Bronchiectasis has been noted to occur in this rare condition, both in patients with true AAT deficiency and in patients with heterozygous phenotypes.[48, 49, 50, 51]

The pathogenesis of bronchiectasis in this setting is unclear, but it is believed that the AAT abnormalities make patients more susceptible to respiratory tract infections and subsequent bronchial damage.

Autoimmune diseases, connective-tissue disorders, and idiopathic inflammatory disorders

Rheumatoid arthritis is associated with bronchiectasis in a reported 3.2-35% of patients[52, 53,

54] and, in one series, was associated with an unfavorable prognosis.[55] The pathology of bronchiectasis may be increased susceptibility to infections in these patients. Pulmonary disease may occur prior to the onset of the rheumatic process.

Bronchiectasis has been noted in patients with Sjögren syndrome and may be secondary to increased viscosity of mucus with poor airway clearance.[56]

Ankylosing spondylitis is associated with bronchiectasis, but in small numbers.[57]

Systematic lupus erythematosus may present with a variety of pulmonary pathology, including bronchiectasis, which was reported in 21% of patients in one series.[58]

In relapsing polychondritis, bronchiectasis appears to be secondary to primary bronchial damage with resultant recurrent infection.[59]

With inflammatory bowel disease, bronchiectasis has been seen in both ulcerative colitis and Crohn disease. The etiology remains unclear. Pulmonary symptoms may occur prior to the onset of bowel disease.[60]

Sarcoidosis may cause bronchiectasis by a variety of mechanisms, including parenchymal scarring, endobronchial granulomatous inflammation, or extrinsic compression of bronchi.[61]

Marfan syndrome is a connective tissue disorder. The general consensus is that weakness of the connective tissue of the bronchial wall predisposes to bronchiectasis.[62]

Autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) patients have also been shown to have an increased incidence of bronchiectasis on radiographic screening. ADPKD is another of the so-called "ciliopathies," or diseases in which a defect in ciliary function is the primary pathologic finding.[63]

Traction bronchiectasis

Traction bronchiectasis is distortion of the airways secondary to mechanical traction on the bronchi from fibrosis of the surrounding lung parenchyma. Although the airways may become dilated in this situation, the other manifestations of bronchiectasis are lacking. Traction bronchiectasis tends to have an upper lobe distribution in cases of radiation fibrosis and sarcoidosis, while the lower lobe is predominantly involved in cases of interstitial lung disease/ idiopathic pulmonary fibrosis (ILD/IPF).[64]

Toxic gas exposure

Exposure to toxic gas may often cause irreversible damage to the bronchial airways and cystic bronchiectasis. Commonly implicated agents include chlorine gas and ammonia.

Epidemiology

Currently no systematic data are available on the incidence or prevalence of bronchiectasis. A general theory is that the emergence of vaccines and antibiotics in the 20th century resulted in a decline in the rate of bronchiectasis in developed countries.[17]

The best data available suggest that the prevalence of bronchiectasis mirrors the socioeconomic conditions of the population under study, with significantly lower prevalence in areas where immunizations and antibiotics are readily available. Bronchiectasis remains a major cause of morbidity in less-developed countries, especially in countries with limited access to medical care and antibiotic therapy.[15, 16]

United States statistics

Bronchiectasis is relatively uncommon in the United States, with a prevalence of approximately 100,000 cases, based on data from the 1980s. That said, the number of bronchiectasis cases in the United States associated with atypical mycobacteria or other environmental factors reportedly has increased,[20, 21, 65] perhaps due to improved detection techniques for atypical mycobacteria.

Bronchiectasis may be underdiagnosed in general because it is no longer included in survey data and often goes unreported. The exception is bronchiectasis associated with CF; the latter occurs with a prevalence of 1 in 2500 white births. CF is the largest single cause of chronic lung infections and bronchiectasis in industrialized nations.[66]

Native Americans in Alaska comprise a subgroup with higher-than-expected prevalence, with a 4-fold higher rate of bronchiectasis than the general population.[15] Overall, identifying the true frequency remains a challenge, given the lack of specific symptoms and lack of readily available noninvasive screening tests for population studies.

Race-, sex-, and age-related demographics

No racial predilection exists other than those that may be associated with socioeconomic status.

Evidence suggests that non–CF-related bronchiectasis is more common and more virulent in women, particularly slender white women older than 60 years. In these patients, bronchiectasis is often caused by primary Mycobacterium avium complex (MAC) infection and has been called the Lady Windermere syndrome, named after a character in a novel by Oscar Wilde.[67, 68, 19]

In the preantibiotic era, symptoms usually began in the first decade of life, and this continues to hold true in less-developed countries. Currently, in developed countries, the age of onset has moved into adulthood, except in children with CF.[69]

An epidemiologic study of bronchiectasis-associated hospitalizations in the United States demonstrated that the hospitalization rate for this disorder increased from 1993-2006, especially in persons older than 60 years.[70] No specific single underlying diagnosis has been associated with this apparent increase in the burden of disease in the elderly.

Although limited, epidemiologic studies suggest that persons aged 60-80 years have the highest frequency of bronchiectasis—again likely from the rise in atypical mycobacterial

infections. The differences in prevalence between age groups are a direct reflection of the differences in prevalence of the underlying causes of bronchiectasis, lung disease, and/or chronic infections.[71]

Prognosis

In the preantibiotic era, mortality was high, and patients most often died within 5 years after the onset of symptoms. Indeed, a study of 400 patients in 1940 revealed a mortality rate greater than 30%, with most patients dying within 2 years and being younger than 40 years.[72]

By comparison, a retrospective study in 1981, after the widespread use of antibiotics, reported a mortality of 13% after diagnosis.[73]

In the late 1990s, researchers in Finland reported no increased mortality in patients with bronchiectasis versus patients with asthma or chronic obstructive pulmonary disease (COPD). Mortality rates for bronchiectasis, asthma, and COPD were 28%, 20%, and 38%, respectively.[74, 75]

Current mortality is difficult to estimate, given the difficulty in identifying prevalence and the lack of definitive studies. Overall, the prognosis for patients with bronchiectasis is good, but it varies with the underlying or predisposing condition. Bronchiectasis associated with CF carries a worse prognosis.

In general, patients do well if they are compliant with all treatment regimens and practice routine preventive medicine strategies. Common complications include recurrent pneumonia requiring hospitalization, empyema, lung abscess, progressive respiratory failure, and cor pulmonale. Additional complications include chronic bronchial infection, and pneumothorax. Life-threatening hemoptysis may occur but is uncommon. Amyloidosis and metastatic abscesses occurred in the preantibiotic era but are rarely observed today.

At present, mortality is more often related to progressive respiratory failure and cor pulmonale than to uncontrolled infection. One study found age older than 65 years and prior use of long-term oxygen therapy to be risk factors for a poor outcome in patients with bronchiectasis who were admitted to an intensive care unit for respiratory failure.[76]

A 2007 study of adults with non-CF bronchiectasis found that higher mortality was associated with advanced age, poor functional status, more severe disease based on radiographic findings, and evidence of hypoxemia or hypercapnia.[77] Preventive care (ie, vaccinations), regular physician visits, and higher body mass index at baseline were associated with reduced mortality.

Patient Education

For patient education information, see the Lung and Airway Center, as well as Chronic Obstructive Pulmonary Disease (COPD).

History

The classic clinical manifestations of bronchiectasis are cough and daily mucopurulent sputum production, often lasting months to years. Blood-streaked sputum or hemoptysis may result from airway damage associated with acute infection. Less specific symptoms include dyspnea, pleuritic chest pain, wheezing, fever, weakness, and weight loss.

A rare variant known as dry bronchiectasis manifests as episodic hemoptysis with little-to-no sputum production. Dry bronchiectasis is usually a sequela of tuberculosis and is found in the upper lobes.

Bronchiectasis is a morphologic diagnosis. Thus, it may exist with relatively few symptoms.

Although patients may report repetitive pulmonary infections that require antibiotics over several years, a single episode of a severe infection, often in childhood, may result in bronchiectasis.[14] These include tuberculosis, pertussis, or severe bacterial pneumonia. Today, CF is the most common cause of bronchiectasis in children and young adults.[17]

Exacerbations of bronchiectasis that are caused by acute bacterial infections are often heralded by the onset of increased sputum production over baseline, increased viscidity of sputum, and, occasionally, a foul odor of the sputum. Rarely, low-grade fever may occur. Patients may experience an increase in generalized constitutional symptoms, such as fatigue and malaise, as well as increased dyspnea, shortness of breath, wheezing, or pleuritic pain.

With secondary infection or poorly treated pneumonia, the discrete pathogens are often unknown. However, most patients relate a history of childhood infections that may include tuberculosis, pertussis, or Mycoplasma infection.[14]

Most individuals have never smoked (55%) or have smoked too little to account for their degree of cough, findings of obstruction on spirometry testing, and daily sputum production.

Chronic productive cough is prominent,[78] occurring in up to 98% of patients. Sputum is typically produced on a daily basis in greater than 70% of patients, with one study reporting production in 96% of patients.[79] Some patients produce sputum only with acute upper respiratory tract infections, but otherwise they have quiescent disease.

Sputum is typically mucoid and relatively odorless. During infectious exacerbations, however, sputum becomes purulent and may develop an offensive odor.

In the past, total daily sputum amount has been used to characterize the severity of bronchiectasis, with less than 10 mL defined as mild bronchiectasis, 10-150 mL defined as moderate bronchiectasis, and greater than 150 mL defined as severe bronchiectasis. Today, bronchiectasis is most often classified by radiographic findings. In patients with CF, the volume of sputum produced is generally much greater than that associated with other etiologies of bronchiectasis.

Hemoptysis occurs in 56-92% of patients with bronchiectasis. Hemoptysis is more commonly observed in dry bronchiectasis. Hemoptysis is generally mild and manifested by blood flecks in the patient's usual purulent sputum. This is often the factor that leads patients to consult a physician. Bleeding usually originates from dilated bronchial arteries, which contain blood at systemic (rather than pulmonary) pressures. Therefore, massive hemoptysis may occur but is rarely a cause of death.[17, 79, 80]

Dyspnea may occur in as many as 72% of patients; a 2006 review reported a rate of 62%.[79]

Dyspnea typically occurs in patients with extensive bronchiectasis observed on chest radiographs. Marked dyspnea is more likely to be secondary to a concomitant illness, such as chronic bronchitis or emphysema.

Wheezing is commonly reported and may be due to airflow obstruction following destruction of the bronchial tree. Similar to dyspnea, it may also be secondary to concomitant conditions such as asthma.

Pleuritic chest pain is an intermittent finding, occurring in 19-46% of patients.[79] It is most commonly secondary to chronic coughing but also occurs in the setting of acute exacerbation.

Fatigue is commonly reported (73% of patients).[79] Weight loss often occurs in patients with severe bronchiectasis. This is believed to be secondary to increased caloric requirements associated with the increased work of coughing and clearing secretions. Weight loss suggests advanced disease but is not diagnostic of bronchiectasis.

Fever may occur in the setting of acute infectious exacerbations.

Urinary incontinence occurs more frequently in women with bronchiectasis versus age-matched controls (47% vs 12%).[81] The etiology of this is unclear.

Physical Examination

Findings are nonspecific and may be attributed to other conditions. Most commonly, crackles, rhonchi, wheezing, and inspiratory squeaks may be heard upon auscultation. General findings may include digital clubbing, cyanosis, plethora, wasting, and weight loss. Nasal polyps and signs of chronic sinusitis may also be present. In advanced disease, the physical stigmata of cor pulmonale may be observed. Note the following:

Crackles and rhonchi are often observed in association with active infections and acute exacerbations

Crackles are nonspecific and may occur in as many as 73% of patients[79]

Scattered wheezing may be heard in approximately one third of patients; wheezing may be due to airflow obstruction from secretions, destruction of the bronchial tree leading to airway collapsibility, or a concomitant condition[17, 79]

Digital clubbing is an inconsistent finding in approximately 2-3% of patients[79] ; it is more frequent in patients with moderate-to-severe bronchiectasis

Cyanosis and plethora are rare findings secondary to polycythemia from chronic hypoxia.

Wasting and weight loss are suggestive of advanced disease but are not diagnostic of bronchiectasis. In severe cases, findings are consistent with cor pulmonale. Right-sided heart failure may be observed, including peripheral edema, hepatomegaly, and hypoxia. This can ultimately lead to progressive respiratory failure.[76]

Diagnostic Considerations

Investigate the possible etiology of a patient's bronchiectasis. Specifically, allergic bronchopulmonary aspergillosis, atypical mycobacterial infections, immunodeficiency states, and autoimmune diseases are causes of bronchiectasis that may be treated effectively once diagnosed.

Cystic fibrosis (CF), Young syndrome, primary ciliary dyskinesia, and alpha1-antitrypsin (AAT) deficiency require aggressive treatment, as well as genetic counseling for patients and their families. Likewise, congenital abnormalities should be identified as such for the patient and their family.

Foreign body obstruction needs to be excluded as an etiology in all patients.

Differential Diagnoses

Alpha1-Antitrypsin Deficiency Asthma Bronchitis Chronic Bronchitis Chronic Obstructive Pulmonary Disease Cystic Fibrosis Emphysema Empyema, Pleuropulmonary Gastroesophageal Reflux Disease Pneumonia, Aspiration Pneumonia, Bacterial Tuberculosis

Approach Considerations

In a typical patient, bronchiectasis is suspected on the basis of the clinical presentation, especially if purulent sputum is present and other conditions (eg, pneumonia, lung abscess) have been ruled out. A sputum analysis may be used to further strengthen clinical suspicion.

Radiographic studies, specifically CT scanning, then may be used to confirm the diagnosis. Once the diagnosis is confirmed, additional laboratory testing may be useful to determine the underlying cause. Although many causes are untreatable, identifying treatable conditions is paramount. In a significant percentage of patients, no readily identifiable cause is found.

The choice of laboratory tests may vary and should be tailored to the individual patient and clinical situation. However, high-resolution CT (HRCT) scanning is the criterion standard for the diagnosis of bronchiectasis.[1, 2, 3]

The anatomical distribution of bronchiectasis may be important in helping diagnose any associated condition or cause of bronchiectasis, as follows:

Bronchiectasis as a result of infection generally involves the lower lobes, the right-middle lobe, and the lingula

Right-middle lobe involvement alone suggests right-middle lobe syndrome, an anatomic dysfunction, or a neoplastic cause with secondary mechanical obstruction

Bronchiectasis caused by cystic fibrosis (CF), Mycobacterium tuberculosis infection , or chronic fungal infections tends to affect the upper lobes, although this is not universal in CF

Allergic bronchopulmonary aspergillosis (ABPA) also affects the upper lobes but usually involves the central bronchi, whereas most other forms of bronchiectasis involve distal bronchial segments

Sputum Analysis

A sputum analysis may reinforce the diagnosis of bronchiectasis and add significant information regarding potential etiologies. Once sputum is allowed to settle, the examination may reveal Dittrich plugs, small white or yellow concretions. A Gram stain and culture result may reveal evidence of microorganisms, including mucoid Pseudomonas species and Escherichia coli, which suggest CF but are not diagnostic.

Chronic bronchial infection with nonmucoid Pseudomonas aeruginosa is becoming much more common in patients with non-CF bronchiectasis. The presence of eosinophils and golden plugs containing hyphae suggests Aspergillus species, although this finding alone is not diagnostic of ABPA.

Perform a smear and culture of sputum for mycobacteria and fungi. Atypical mycobacterial infection is a common cause of bronchiectasis in the older population, especially in those with underlying structural lung disease.

Complete Blood Count

The CBC is often abnormal in patients with bronchiectasis. Typical findings are nonspecific and include anemia and an elevated white blood cell count with an increased percentage of neutrophils. An increased percentage of eosinophils is one criterion for ABPA. Alternatively, polycythemia secondary to chronic hypoxia may be observed in advanced cases.

Quantitative Immunoglobulin levels

Quantitative immunoglobulin levels, including IgG subclasses, IgM, and IgA, are useful to exclude hypogammaglobulinemia. Note, however, that on rare occasions, bronchiectasis may be seen in patients with antibody production deficiency but normal to low-normal IgG levels. In situations such as these, evaluating antibody response to Haemophilus influenzae and pneumococcal vaccines may be useful.

Quantitative Alpha1-Antitrypsin Levels

Quantitative serum alpha1-antitrypsin (AAT) levels are used to rule out AAT deficiency. In addition to a suggestive family history, clinical features of emphysema that suggest the possibility of AAT deficiency and the need for serum testing include onset at an early age (45 y or less) and the absence of a recognized risk factor (eg, smoking, occupational dust exposure).

Pilocarpine Iontophoresis (Sweat Test)

Pilocarpine iontophoresis (sweat test) was the criterion standard test to evaluate for CF. However, genetic analysis has now become standard and may be performed to look for evidence of mutations consistent with CF and to look for potential variants, such as Young syndrome.[28]

Aspergillus Precipitins and Serum Total IgE levels

Aspergillus precipitins and serum total IgE levels are important in making the diagnosis of ABPA. Diagnostic criteria for ABPA include a total serum IgE level greater than 1000 IU/mL or a greater than 2-fold rise from baseline.

Autoimmune Screening Tests

Rheumatoid factor and/or other screening tests for autoimmune disease may be performed in the appropriate clinical setting. For example, an antinuclear antibody (ANA) assay may also be considered.

Computed Tomography

CT scanning (see the image below), particularly high-resolution CT (HRCT) scanning of the chest, has replaced bronchography as the defining modality of bronchiectasis. CT sensitivity and specificity reportedly are 84-97% and 82-99%, respectively, but may be higher at referral centers.[82]

Additional advantages of HRCT scanning include noninvasiveness, avoidance of possible allergic reactions to contrast media, and information regarding other pulmonary processes. The 3 forms of bronchiectasis in the Reid classification can be visualized by HRCT.[13]

This CT scan depicts areas of both cystic bronchiectasis and varicose bronchiectasis.

The following are noteworthy aspects of CT findings in bronchiectasis:

Cylindrical bronchiectasis has parallel tram track lines, or it may have a signet-ring appearance composed of a dilated bronchus cut in a horizontal section with an adjacent pulmonary artery representing the stone

The diameter of the bronchus lumen is normally 1-1.5 times that of the adjacent vessel; a diameter greater than 1.5 times that of the adjacent vessel is suggestive of bronchiectasis

Varicose bronchiectasis has irregular or beaded bronchi, with alternating areas of dilatation and constriction

Cystic bronchiectasis has large cystic spaces and a honeycomb appearance; this contrasts with the blebs of emphysema, which have thinner walls and are not accompanied by proximal airway abnormalities

For more information on the radiologic approach to bronchiectasis, see Bronchiectasis Imaging.

verview

Bronchiectasis is defined as localized, irreversible dilatation of part of the bronchial tree. Involved bronchi are dilated, inflamed, and easily collapsible, resulting in airflow obstruction and impaired clearance of secretions. Bronchiectasis is associated with a wide range of disorders, but it usually results from necrotizing bacterial infections, such as infections caused by the Staphylococcus or Klebsiella species or Bordetella pertussis.

Hemoptysis is common and may occur in as many as 50% of patients. Episodic hemoptysis with little to no sputum production (dry bronchiectasis) is usually a sequela of tuberculosis. However, massive hemoptysis may occur; bleeding usually originates in dilated bronchial arteries, which contain blood at systemic (rather than pulmonary) pressures.

Diagnosis of bronchiectasis is based on a clinical history of daily viscid sputum production and characteristic computed tomography (CT) scan findings. (See the images below.)

A 27-year-old man diagnosed with reactive airway disease as a child was examined because of frequent respiratory infections. The posteroanterior chest radiograph shows ill-defined pulmonary nodular opacities, mild scoliosis, and moderate

overaeration. High-resolution computed tomography scan in a 75-year-old man with cystic bronchiectasis.

Preferred examination

Chest radiography is usually the first imaging examination, but the findings are often nonspecific and the images may appear normal.[1] High-resolution computed tomography (HRCT) scanning has become the imaging modality of choice for demonstrating or ruling out bronchiectasis and its extent (see the images below). HRCT scanning also helps clinicians to evaluate the status of the surrounding lung tissue and exclude other lesions such as neoplasms.[2]

The high-resolution computed tomography scan shows thick-walled, slightly ectatic bronchi. The patient has cystic fibrosis, which was diagnosed in and

treated since childhood. This high-resolution computed tomography scan through the upper lung zone of the right side demonstrates bronchiectatic changes. Despite conventional antibiotic treatment, the patient continued to be symptomatic. Eventually, she underwent bronchoscopy, and sampled cultures grew Mycobacterium avium-

intracellulare complex. High-resolution computed tomography

scan in a 75-year-old man with cystic bronchiectasis. This high-resolution computed tomography scan in a 13-year-old female adolescent shows left

lower-lobe bronchiectasis, which is secondary to tuberculosis. The high-resolution computed tomography scan demonstrates findings of fluid-filled dilated bronchi in a 65-year-old man with bronchiectasis in the left lower lobe.

Bronchography was the classic modality used and, until the advent of HRCT scanning, was the only imaging method to demonstrate bronchiectasis. Bronchography is performed by instilling an iodine-based contrast material via a catheter or bronchoscope, but it is rarely, if ever, performed today, as HRCT scanning has replaced it as the diagnostic modality of choice. HRCT scanning is noninvasive and has a sensitivity of 96% and a specificity of 93%.[3]

Limitations of techniques

Bronchoscopy is not helpful in diagnosing bronchiectasis, but it may be used to identify underlying abnormalities, such as tumors and foreign bodies.

Chest radiographs may be negative in patients with minor to moderate disease. Many abnormal radiographic findings may be nonspecific, and confirmation using HRCT scanning may be required.

Bronchography is rarely indicated because it is invasive and is associated with allergic reactions to the contrast material. Bronchography also carries the risk of acute bronchoconstriction.

HRCT scanning is the diagnostic modality of choice and has few limitations.

Radiography

Chest radiography helps to identify serious disease, and it was once the standard imaging modality.[4] However, the radiographs may depict no abnormalities, or the findings may be nonspecific in patients with less-severe disease.[5]

Various abnormal radiographic findings have been described as follows (see the images below):

Parallel line opacities (tram tracks) caused by thickened dilated bronchi Ring opacities or cystic spaces as large as 2 cm in diameter resulting from cystic

bronchiectasis, sometimes with air-fluid levels Tubular opacities caused by dilated fluid-filled bronchi Increased size and loss of definition of the pulmonary vessels in the affected areas as

a result of peribronchial fibrosis Crowding of pulmonary vascular markings from the associated loss of volume,

usually caused by mucous obstruction of the peripheral bronchi Oligemia as a result of reduction in pulmonary artery perfusion (severe disease) Signs of compensatory hyperinflation of the unaffected lung

A 27-year-old man diagnosed with reactive airway disease as a child was examined because of frequent respiratory infections. The posteroanterior chest radiograph shows ill-defined pulmonary nodular opacities, mild

scoliosis, and moderate overaeration. This is a close-up radiograph of the left upper lung zone in a 31-year-old woman with chronic cough since childhood. Nodules are present in the left upper lung; the right upper lung was

similarly involved. A 65-year-old woman was examined for chronic cough. The lateral chest radiograph shows overaeration and increased

markings over the heart. This posteroanterior chest radiograph shows overaeration and somewhat-obscured heart borders.

Bronchography

Introduced in 1922, bronchography was the investigation of choice until the introduction of HRCT scanning in the mid 1980s. Currently, bronchography is rarely used. Bronchography is performed by instilling contrast material via a catheter or bronchoscope under fluoroscopic control and plain radiographic imaging. The procedure is unpleasant for the patient and is also associated with temporary impairment of ventilation, as well as allergic and foreign body reactions to the contrast medium. In addition, interpretation of bronchographic images is difficult, owing to underfilling and retained secretions.

Degree of confidence

The accuracy of plain radiographic findings in the diagnosis of bronchiectasis is unknown, because the findings are variable and nonspecific and depend on the severity and extent of the bronchiectasis. However, good correlation exists between the severity of disease as seen on plain images and HRCT scans. Chest radiographic findings may be normal or nonspecific in patients with less-severe disease.

False positives/negatives

Many plain radiographic findings are nonspecific and may be seen in patients with idiopathic pulmonary fibrosis, sarcoidosis, histiocytosis X, rheumatoid lung, and other chronic interstitial lung disorders.

Computed Tomography

The HRCT imaging technique consists of obtaining 1-2 mm collimation scans at 10 mm intervals through the chest with a window level (WL) of –700 Hounsfield units (HU) and a window width (WW) of –1000 HU. The right middle lobe and lingular bronchi cross obliquely and are not optimally depicted on axial HRCT scans; as a result, a gantry angulation of 20° may be required.[6, 7, 8, 9, 10, 11, 12, 13, 14, 15]

On HRCT scans in patients with bronchiectasis, the internal bronchial diameter may be greater than that of the adjacent artery, and there may be a lack of bronchial tapering (the same diameter as the parent branch for >2 cm). The bronchi may be within 1 cm of costal pleura or abut the mediastinal pleura (more specific but less sensitive than an increased ratio), and bronchial wall thickening may be seen (in 68% of patients). A cystic cluster of thin-walled cystic spaces may be present, often with air-fluid levels. (See the image below.)

High-resolution computed tomography scan in a 75-year-old man with cystic bronchiectasis.

In cylindrical bronchiectasis, bronchi coursing horizontally are seen as parallel lines, and vertically oriented bronchi are seen as circular lucencies that are larger than the adjacent pulmonary artery (signet-ring appearance). (See the image below.)

This high-resolution computed tomography scan in a 13-year-old female adolescent shows left lower-lobe bronchiectasis, which is secondary to tuberculosis.

Varicose bronchiectasis may be seen as nonuniform bronchial dilatation. Other findings include the following:

Areas of increased and decreased perfusion and attenuation Tracheomegaly Enlarged mediastinal nodes

Fluid-filled bronchi are revealed as tubular or branching structures when they course horizontally or are revealed as nodules when they are perpendicular to the plane of the CT scan section (see the image below).

The high-resolution computed tomography scan demonstrates findings of fluid-filled dilated bronchi in a 65-year-old man with bronchiectasis in the left lower lobe.

Degree of confidence

HRCT scanning has a sensitivity of 96% and a specificity of 93%,[3] as compared with bronchography, the previous criterion standard.

Bronchial measurements may vary with the use of different WLs and WWs.[16]

Some patients without bronchiectasis have a 1.49:1 bronchus-to-artery ratio; however, the ratio is reliable only if it is greater than 1.5. If the ratio is less than 1.5, other signs, such as bronchial wall thickening and lack of tapering, should be present for the diagnosis of bronchiectasis.

Bronchial wall thickening is optimally seen with a WW of –1000 HU and a WL of –700 HU; higher WL and other WW readings are associated with artifactual wall thickening.[17] This finding is not specific and is also seen in patients with asthma and in those who smoke.

False positives/negatives

The variability of the bronchus-to-artery ratio at high altitudes and in patients with pulmonary hypertension may result in an overdiagnosis because of vasoconstriction in these conditions.

In patients with consolidation, dilated bronchi may not be seen. Cardiac and respiratory artifacts may obscure the results or mimic subtle bronchiectasis in the left lower lobe. Rarely, histiocytosis X and cavitating pulmonary masses mimic cystic bronchiectasis. Traction bronchiectasis occurs in patients with interstitial fibrosis and results from fibrous tethering of the bronchial wall. Traction bronchiectasis is not a true bronchial disorder.

Angiography

Hemoptysis is symptomatic of a potentially life-threatening condition and warrants urgent and comprehensive evaluation of the lung parenchyma, airways, and thoracic vasculature.

Multidetector-row CT angiography permits noninvasive, rapid, and accurate assessment of the cause and consequences of hemorrhage into the airways and helps guide subsequent management. The combined use of thin-section axial scans and more complex reformatted images allows clear depiction of the origins and trajectories of abnormally dilated systemic arteries that may be the source of hemorrhage and that may require embolization.

Bronchiectasis, chronic bronchitis, lung malignancy, tuberculosis, and chronic fungal infection are some of the most common underlying causes of hemoptysis and are easily detected with CT angiography.

(Bronchiectasis Imaging Author: Isaac Hassan, MB, ChB, FRCR, DMRD http://emedicine.medscape.com/article/354167-overview#showall)

Radiography

Posterior-anterior and lateral chest radiographs should be obtained in all patients. Expected general findings include increased pulmonary markings, honeycombing, atelectasis, and pleural changes. Specific findings may include linear lucencies and parallel markings radiating from the hila (tram tracking) in cylindrical bronchiectasis, dilated bronchi in varicose bronchiectasis, and clustered cysts in cystic bronchiectasis. In the appropriate clinical setting, chest radiograph findings are occasionally sufficient for confirming the diagnosis of bronchiectasis.

Pulmonary Function Tests

Pulmonary function test results may be normal or abnormal and may reflect underlying comorbidities as well as providing information regarding predisposing conditions. These tests are useful in obtaining a functional assessment of the patient, as well as allowing for objective determination of the deterioration of a patient's pulmonary function when baseline studies are available.

The most common abnormality is an obstructive airway defect, which may even be found in patients without a prior smoking history. In addition, patients with bronchiectasis have higher rates of yearly decline in forced expiratory volume in 1 second (FEV1) than patients without bronchiectasis.[69, 83] In patients with non-CF bronchiectasis, risk factors for a more rapid decline in FEV1 include colonization with Pseudomonas aeruginosa and higher concentrations of proinflammatory markers.[84]

Obstruction in bronchiectasis is not usually reversible with bronchodilator therapy. However, a subgroup of patients may develop hyperreactive airways in conjunction with their bronchiectasis that will respond to bronchodilators.

Restriction may be observed in patients with severe advanced disease secondary to scarring and atelectasis, but this is not common. Traction bronchiectasis most often occurs in the setting of a restrictive lung defect from underlying fibrosis.

Electron Microscopic Examination

Perform electron microscopic examination of sperm and respiratory epithelium to observe for evidence of primary ciliary structural abnormalities and dyskinesia. These will be found in disorders such as primary ciliary dyskinesia.

Bronchography

Bronchography, although once common, is now used rarely, having been replaced by HRCT scanning.[2] Bronchography is performed by instilling contrast material via a catheter or a bronchoscope and performing plain radiographic imaging. It should be performed only at facilities and by operators skilled in its use. In current practice, it is only of potential value in confirming the location of focal bronchiectasis and in excluding disease elsewhere in the setting of possible surgical resection. This procedure carries the risk of acute bronchoconstriction.

Bronchoscopy

Bronchoscopy is generally not helpful in diagnosing bronchiectasis, but it may be useful in identifying underlying abnormalities, such as tumors, foreign bodies, or other lesions. Bronchoscopy with bronchoalveolar lavage may be used to obtain specimens for staining and culture when a primary infectious etiology or a secondary infection is suspected.

Approach Considerations

The goals of therapy are to improve symptoms, to reduce complications, to control exacerbations, and to reduce morbidity and mortality. Early recognition is essential in bronchiectasis and associated conditions. Additionally, management of underlying conditions, which may include the use of intravenous immunoglobulin or intravenous alpha1-antitrypsin (AAT) therapy, is essential to the overall treatment.

Antibiotics and chest physiotherapy are the mainstay modalities. Other modalities (beyond those for specific associated conditions) may include bronchodilators, corticosteroid therapy, dietary supplementation, and oxygen or surgical therapies. Admitting patients with severe exacerbations of bronchiectasis to the hospital and treating them with intravenous antibiotics, bronchodilators, aggressive physiotherapy, and supplemental nutrition is not uncommon.

Aggressively pursue and treat any associated or known causal condition of the bronchiectasis. The scope of therapies for these associated medical conditions, such as mycobacterial disease and CF, is beyond the scope of this article. See Cystic Fibrosis and Mycobacterium Avium-Intracellulare.

Available treatment guidelines include Chronic cough due to bronchiectasis: ACCP evidence-based clinical practice guidelines and Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based clinical practice guidelines.

Supportive Treatment

The following general measures are recommended:

Smoking cessation Avoidance of second-hand smoke Adequate nutritional intake with supplementation, if necessary Immunizations for influenza and pneumococcal pneumonia[85, 86]

Confirmation of immunizations for measles, rubeola, and pertussis

Oxygen therapy is reserved for patients who are hypoxemic with severe disease and end-stage complications, such as cor pulmonale.

Patients with cystic fibrosis (CF) should be cared for at specialized CF treatment centers that address all aspects of the disease, including nutritional and psychologic aspects.

ntibiotic Therapy

Antibiotics have been the mainstay of treatment for more than 40 years. Oral, parenteral, and aerosolized antibiotics are used, depending on the clinical situation.

In acute exacerbations, broad-spectrum antibacterial agents are generally preferred. However, if time and the clinical situation allows, sampling of respiratory secretions during an acute exacerbation may allow treatment with antibiotics based on specific species identification.

Acceptable choices for the outpatient who is mild to moderately ill include any of the following:

Amoxicillin Tetracycline Trimethoprim-sulfamethoxazole A newer macrolide (eg, azithromycin[5] or clarithromycin[6, 7] ) A second-generation cephalosporin A fluoroquinolone

In general, the duration of antibiotic therapy for mild to moderate illness is 7-10 days.

For patients with moderate-to-severe symptoms, parenteral antibiotics, such as an aminoglycoside (gentamicin, tobramycin) and an antipseudomonal synthetic penicillin, a third-generation cephalosporin, or a fluoroquinolone, may be indicated. Patients with bronchiectasis from CF are often infected with mucoid Pseudomonas species, and, as such, tobramycin is often the drug of choice for acute exacerbation.

Infection with Mycobacterium avium complex (MAC) provides special treatment challenges. For the treatment of MAC in the setting of bronchiectasis, the American Thoracic Society recommends a 3- to 4-drug treatment regimen with clarithromycin, rifampin, ethambutol, and possibly streptomycin that is continued until the patient's culture results are negative for 1 year. The typical duration of therapy may be 18-24 months.

Regular antibiotic regimens

Some patients with chronic bronchial infections may need regular antibiotic treatment to control the infectious process. Some clinicians prefer to prescribe antibiotics on a regular basis or for a set number of weeks each month.

The oral antibiotics of choice are the same as those mentioned previously. Potential regimens include daily antibiotics for 7-14 days of each month, alternating antibiotics for 7-10 days with antibiotic-free periods of 7-10 days, or a long-term daily dose of antibiotics. For patients with severe CF and bronchiectasis, intermittent courses of intravenous antibiotics are sometimes used.[87, 88]

Aerosolized antibiotics

In the past several years, the nebulized route of antibiotic administration has received more attention because it is capable of delivering relatively high concentrations of drugs locally with relatively few systemic adverse effects.[89] This is particularly beneficial in treating patients with chronic infection from P aeruginosa. Currently, inhaled tobramycin is the most widely used nebulized treatment for patients with bronchiectasis from either CF or non-CF causes of bronchiectasis.[90, 91, 92, 93, 94] Gentamicin[95] and colistin[96] have also been used.

No significant studies have examined the long-term use of inhaled antibiotics in patients with non-CF bronchiectasis. A study by Govan et al found sustained long-term benefit (12 mo) of inhaled gentamicin in this subgroup, along with an acceptable side effect profile.[97] Optimal dosing regimen of inhaled gentamicin still needs to be elucidated.

Bronchial Hygiene

Good bronchial hygiene is paramount in the treatment of bronchiectasis, because of the tenacious sputum and defects in clearance of mucus in these patients. Postural drainage with percussion and vibration is used to loosen and mobilize secretions.

Devices available to assist with mucus clearance include flutter devices,[98, 99] intrapulmonic percussive ventilation devices, and incentive spirometry.[100] Although consistent benefits from these techniques are lacking and vary with patient motivation and knowledge, a review did report improvement in patients’ cough-related quality of life scores.[101]

A relatively new device called the "Vest" system is a pneumatic compression device/vest that is worn by the patient periodically throughout the day. It is essentially technique independent and has variable success, especially in patients with CF. Significant controlled trials have not been performed in patients with non-CF bronchiectasis.

Nebulization with concentrated (7%) sodium chloride solutions appears to be beneficial, particularly in patients with CF-related bronchiectasis.[102, 103, 104] Mucolytics, such as acetylcysteine, are also often tried but do not appear to be universally beneficial. However, maintaining adequate general hydration, which may improve the viscidity of secretions, is important.

Aerosolized recombinant DNase has been shown to benefit patients with CF.[105, 106] This enzyme breaks down DNA released by neutrophils, which accumulates in the airways in

response to chronic bacterial infection. However, improvement has not been definitively shown in patients with bronchiectasis from other causes.[107]

Bronchodilator Therapy

Bronchodilators, including beta-agonists and anticholinergics, may help some patients with bronchiectasis, presumably reversing bronchospasm associated with airway hyperreactivity and improving mucociliary clearance.[108, 109, 110] High-quality, large, randomized clinical trials of bronchodilator treatment in bronchiectasis have not been performed, however.

Anti-inflammatory Therapy

The rationale of anti-inflammatory therapy is to modify the inflammatory response caused by the microorganisms associated with bronchiectasis and subsequently reduce the amount of tissue damage. Inhaled corticosteroids,[111] oral corticosteroids,[112] leukotriene inhibitors,[113]

and nonsteroidal anti-inflammatory agents[113] have all been examined.

Although evidence suggests some benefit from the use of these agents, findings are not universally definitive. One study reported that inhaled corticosteroids are beneficial compared with placebo in patients with bronchiectasis, particularly those with associated P aeruginosa infections.[114]

A double-blind, placebo controlled 6-week crossover study with 20 patients using beclomethasone dipropionate (750 mcg bid) showed reduced mean sputum volume and improved forced expiratory volume in 1 second (FEV1) at 6 weeks. A similar study of 24 patients using fluticasone propionate (500 mcg bid) showed reduced sputum leukocyte density and reduced levels of inflammatory mediators but no change in pulmonary function.

A study by Tsang et al showed benefit of inhaled fluticasone in patients with chronic P aeruginosa infection and bronchiectasis.[114] Another study showed improvement in quality-of-life scores with inhaled steroids in patients with steady-state bronchiectasis.[115]

Azithromycin has known anti-inflammatory properties and long-term use has been studied in patients with both CF and non-CF bronchiectasis. In non-CF patients, azithromycin has been shown to decrease exacerbations and improve spirometry and microbiologic profiles.[116, 117] In CF patients a meta-analysis suggests that it improves lung function, especially in those patients colonized with Pseudomonas.[104]

A practical approach is to use tapering oral corticosteroids and antibiotics for acute exacerbations and to consider inhaled corticosteroids for daily use in patients with significant obstructive physiology on pulmonary function testing and evidence of reversibility suggesting airway hyperreactivity. However, Kapur et al reported that the evidence supporting the use of inhaled steroids in adults with stable bronchiectasis is insufficient.[118]

Adjunctive Surgical Resection

Surgery is an important adjunct to therapy in some patients with advanced or complicated disease.[119] Surgical resection for bronchiectasis can be performed with acceptable morbidity and mortality in patients of any age.[92, 120, 121]

In general, surgery should be reserved for patients who have focal disease that is poorly controlled by antibiotics. The involved bronchiectatic sites should be completely resected for optimal symptom control. Other indications for surgical intervention may include the following:

Reduction of acute infective episodes Reduction of excessive sputum production Massive hemoptysis (Alternatively, bronchial artery embolization may be attempted

for the control of hemoptysis.) Foreign body or tumor removal Consideration in the treatment of MAC or Aspergillus species infections

Complications of surgical intervention include empyema, hemorrhage, prolonged air leak, and persistent atelectasis.

Patient selection plays an important role in perioperative mortality rates, which may be as low as 1% in the surgical treatment of segmental or even multisegmental bronchiectasis.

Lung Transplantation

Single- or double-lung transplantation has been used as treatment of severe bronchiectasis, predominantly when related to CF. In general, consider patients with CF and bronchiectasis for lung transplantation when FEV1 falls below 30% of the predicted value. Female patients and younger patients may need to be considered sooner.

Consultations

A pulmonologist or other practitioner skilled in caring for patients with bronchiectasis should be consulted. All patients with CF should be referred to a regional center with the resources and trained personnel to care for patients with CF, including nutritional and psychological care.

Long-Term Monitoring

The interval of follow-up care is determined by the patient's clinical condition and associated conditions or causes. Patients with CF should optimally be monitored at a center specialized in the care of CF.

Medication Summary

No specific medical therapy exists for the treatment of bronchiectasis. Pharmacologic therapy focuses on the treatment of infectious exacerbations that these patients commonly experience, most often in the form of an acute bronchitis-type syndrome.

The most widely accepted and commonly used medications in the treatment of acute infectious processes associated with bronchiectasis include antibiotics, beta-agonists, inhaled corticosteroids, and expectorants. Other more controversial medications have been previously mentioned in this article for completeness but are not discussed here.

Antibiotics

Class Summary

These are the mainstays of treatment of patients with bronchiectasis and infectious exacerbations. The route of antibiotic administration varies with the overall clinical condition, with most patients doing well on outpatient regimens. Some patients benefit from a set regimen of antibiotic therapy, such as therapy for 1 week of every month.

The choice of antibiotic is provider dependent, but, in general, the antibiotic chosen should have a reasonable spectrum of coverage, including the most common gram-positive and gram-negative organisms. Treatment of the patient who is more ill or the patient with CF often requires intravenous anti-Pseudomonas species coverage with an aminoglycoside, most often in combination with an antipseudomonal synthetic penicillin or cephalosporin. Aerosolized tobramycin has been found effective in patients with cystic fibrosis (CF).

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Clarithromycin (Biaxin)

Clarithromycin is a semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, causing bacterial growth inhibition.

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Azithromycin (Zithromax, Zmax)

Azithromycin is an azalide, a subclass of the macrolide antibiotics. Following oral administration, it is absorbed rapidly and widely distributed throughout body. Its mechanism of action is interference with microbial protein synthesis.

Azithromycin is effective against a wide range of organisms, including the most common gram-positive and gram-negative organisms. It has additional coverage of so-called atypical infections, such as Chlamydia, Mycoplasma, and Legionella species. This agent is indicated for treatment of patients with mild-to-moderate infections, including acute bronchitic infections that may be observed with bronchiectasis.

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Trimethoprim and sulfamethoxazole (Septra DS, Bactrim DS)

Trimethoprim-sulfamethoxazole is a synthetic combination antibiotic. Each tab contains 80 mg of trimethoprim and 400 mg of sulfamethoxazole. It is rapidly absorbed after oral administration. The mechanism of action involves blockage of 2 consecutive steps in biosynthesis of nucleic acids and proteins needed by many microorganisms.

This agent provides coverage for common forms of both gram-positive and gram-negative organisms, including susceptible strains of Streptococcus pneumoniae and Haemophilus influenzae. It is indicated in the treatment of acute and chronic bronchitic symptoms in patients with bronchiectasis.

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Doxycycline (Doryx, Oraxyl, Vibramycin)

Doxycycline is a broad-spectrum, synthetically derived bacteriostatic antibiotic in the tetracycline class. It is an alternative agent for patients who cannot be given macrolides or penicillins.

Doxycycline is almost completely absorbed, concentrates in bile, and is excreted in urine and feces as a biologically active metabolite in high concentrations. It inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. It may block dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

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Levofloxacin (Levaquin)

Fluoroquinolones should be used empirically in patients likely to develop exacerbation due to resistant organisms to other antibiotics. Levofloxacin is rapidly becoming a popular choice in pneumonia. It is the L stereoisomer of the D/L parent compound ofloxacin, the D form being inactive.

This agent is good for monotherapy, with extended coverage against Pseudomonas species and excellent activity against pneumococcus. It acts by inhibition of DNA gyrase activity. Bioavailability of the oral form reportedly is 99%.

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Tobramycin (TOBI)

Tobramycin is an aminoglycoside specifically developed for administration with a nebulizer system. When inhaled, it is concentrated in airways, where it exerts an antibacterial effect by disrupting protein synthesis. Tobramycin is active against a wide range of gram-negative organisms, including P aeruginosa. It is indicated for treatment of patients with CF and P aeruginosa infection.

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Gentamicin

A water-soluble injectable antibiotic of aminoglycoside group, gentamicin acts by inhibiting normal protein synthesis; it is active against variety of pathogenic organisms, including P aeruginosa. For treatment of Pseudomonas species, it is often used in combination with an antipseudomonal synthetic penicillin or cephalosporin.

In patients with bronchiectasis, gentamicin (or other aminoglycosides) may be indicated in setting of severe respiratory tract infection or CF. Dosing regimens are numerous; adjust dose based on creatinine clearance (CrCl) and changes in volume of distribution. Gentamicin may be administered IV or IM.

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Amikacin

Amikacin irreversibly binds to the 30S subunit of bacterial ribosomes; it blocks the recognition step in protein synthesis and causes growth inhibition. It is indicated for gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Amikacin is effective against P aeruginosa. Use patient's ideal body weight (IBW) for dosage calculation. The same principles of drug monitoring for gentamicin apply to amikacin.

Inhaled Beta Agonist

Class Summary

Although no long-term studies have been performed with inhaled beta-agonists, these medications are routinely used in patients with bronchiectasis for multiple reasons. Bronchiectasis may cause an obstructive defect on pulmonary function testing that may respond to inhaled beta-agonists. Many older patients with bronchiectasis often have a concomitant illness, such as chronic obstructive pulmonary disease, that responds to inhaled beta-agonists.

Finally, in the acute infectious bronchitic exacerbation that occurs in patients with bronchiectasis, patients may develop transient obstructive airway physiology that may improve with an inhaled beta-agonist. Along these same lines, many patients are started on inhaled steroids for long-term airway stabilization, but the efficacy of these medications in bronchiectasis is questionable, and any effect simply may be secondary to the treatment of other concomitant obstructive airway diseases.

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Salmeterol (Serevent Diskus)

By relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, salmeterol can relieve bronchospasms. It also may facilitate expectoration.

Salmeterol has been shown to improve symptoms and morning peak flows. It may be useful when bronchodilators are used frequently. More studies are needed to establish the role for these agents.

The bronchodilating effect of salmeterol lasts >12 h. This agent is used on a fixed schedule in addition to regular use of anticholinergic agents. When salmeterol is administered at high or more frequent doses than recommended, the incidence of adverse effects is higher.

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Albuterol sulfate (Proventil, Ventolin)

Albuterol is a relatively selective beta2-adrenergic bronchodilator that, when inhaled, relaxes bronchial smooth muscle and inhibits release of mediators of immediate hypersensitivity from cells, especially mast cells.

Albuterol is administered in a metered-dose aerosol unit for oral inhalation. It is indicated for prevention and relief of bronchospasm from any cause, including those observed in patients with bronchiectasis.

nhaled Corticosteroids

Class Summary

Studies suggest a benefit of inhaled corticosteroids in bronchiectasis, although the optimal dosing remains to be determined. No significant studies of oral steroid therapy in patients with bronchiectasis have been performed.

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Beclomethasone (Qvar)

Beclomethasone inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It is readily absorbed through the nasopharyngeal mucosa and GI tract. It has a weak hypothalamic-pituitary-adrenal (HPA) axis inhibitory potency when applied topically.

Various dose preparations are available and must be titrated in conjunction with other medications the patient is taking; most inhaled oral medications have an effect in 24 hours.

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Fluticasone inhaled (Flovent Diskus)

Fluticasone may decrease the number and activity of inflammatory cells, in turn decreasing airway hyperresponsiveness. It also has vasoconstrictive activity.

Expectorants

Class Summary

One of the hallmarks of bronchiectasis is a chronic, thick, viscid sputum production. In bronchiectasis, it is extremely difficult for the body's natural mucociliary clearance mechanisms to adequately clear the sputum produced. Although definitive evidence is lacking, expectorants are expected to increase respiratory tract fluid secretions and to help loosen phlegm and bronchial secretions.

By reducing the viscosity of secretions, expectorants increase the efficacy of the mucociliary clearance system. Expectorants are often marketed in combination with decongestants, which may provide some patients additional relief.

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Guaifenesin (Mucinex)

The product contains 600 mg of guaifenesin in a sustained-release formulation intended for oral administration. It increases respiratory tract fluid secretions and helps to loosen phlegm and bronchial secretions. Humibid LA and guaifenesin are indicated for patients with bronchiectasis complicated by tenacious mucus and/or mucous plugs.