Bronchiectasis

Bronchiectasis

Definition

Bronchiectasis is an abnormal and permanent dilatation of bronchi. It may be either focal, involving airways supplying a limited region of pulmonary parenchyma, or diffuse, involving airways in a more widespread distribution. Recent studies have estimated there to be about 110,000 patients with bronchiectasis in the United States. It is a disorder that typically affects older individuals; approximately two-thirds of patients are women.

Pathology

The bronchial dilatation of bronchiectasis is associated with destructive and inflammatory changes in the walls of medium-sized airways, often at the level of segmental or subsegmental bronchi. Airway inflammation is primarily mediated by neutrophils and results in up-regulation of enzymes such as elastase and matrix metalloproteinases. The normal structural components of the wall, including cartilage, muscle, and elastic tissue, are destroyed and may be replaced by fibrous tissue. The dilated airways frequently contain pools of thick, purulent material, while more peripheral airways are often occluded by secretions or obliterated and replaced by fibrous tissue. Additional microscopic features include bronchial and peribronchial inflammation and fibrosis, ulceration of the bronchial wall, squamous metaplasia, and mucous gland hyperplasia. The parenchyma normally supplied by the affected airways is abnormal, containing varying combinations of fibrosis, emphysema, bronchopneumonia, and atelectasis. As a result of the inflammation, vascularity of the bronchial wall increases, with associated enlargement of the bronchial arteries and anastomoses between the bronchial and pulmonary arterial circulations.

Three different patterns of bronchiectasis have been described. In cylindrical bronchiectasis, the involved bronchi appear uniformly dilated and end abruptly at the point that smaller airways are obstructed by secretions. In varicose bronchiectasis, the affected bronchi have an irregular or beaded pattern of dilatation resembling varicose veins. In saccular (cystic) bronchiectasis, the bronchi have a ballooned appearance at the periphery, ending in blind sacs without recognizable bronchial structures distal to the sacs.

Etiology and Pathogenesis

Bronchiectasis is a consequence of inflammation and destruction of the structural components of the bronchial wall. Infection is the usual cause of the inflammation; microorganisms such as Pseudomonas aeruginosa and Haemophilus influenzae produce pigments, proteases, and other toxins that injure the respiratory epithelium and impair mucociliary clearance. The host inflammatory response induces epithelial injury, largely as a result of mediators released from neutrophils. As protection against infection is compromised, the dilated airways become more susceptible to colonization and growth of bacteria. Thus, a reinforcing cycle can result, with inflammation producing airway damage, impaired clearance of microorganisms, and further infection, which then completes the cycle by inciting more inflammation.

Infectious Causes

Adenovirus and influenza virus are the main viruses that cause bronchiectasis in association with lower respiratory tract involvement. Virulent bacterial infections, especially with potentially necrotizing organisms such as Staphylococcus aureus, Klebsiella, and anaerobes, remain important causes of bronchiectasis when antibiotic treatment of a pneumonia is not given or is significantly delayed. Infection with Bordetella pertussis, particularly in childhood, has also been classically associated with chronic suppurative airways disease. Bronchiectasis has been reported in patients with HIV infection, perhaps at least partly due to recurrent bacterial infection. Tuberculosis, a major cause of bronchiectasis worldwide, can produce airway dilatation by a necrotizing effect on pulmonary parenchyma and airways and indirectly as a consequence of airway obstruction from bronchostenosis or extrinsic compression by lymph nodes. Nontuberculous mycobacteria are frequently cultured from patients with bronchiectasis, often as secondary infections or colonizing organisms. However, it has also been recognized that these organisms, especially those of the Mycobacterium avium complex, can serve as primary pathogens associated with the development and/or progression of bronchiectasis.

Impaired host defense mechanisms are often involved in the predisposition to recurrent infections. The major cause of localized impairment of host defenses is endobronchial obstruction. Bacteria and secretions cannot be cleared adequately from the obstructed airway, which develops recurrent or chronic infection. Slowly growing endobronchial neoplasms such as carcinoid tumors may be associated with bronchiectasis. Foreign-body aspiration is another important cause of endobronchial obstruction, particularly in children. Airway obstruction can also result from bronchostenosis, from impacted secretions, or from extrinsic compression by enlarged lymph nodes.

Generalized impairment of pulmonary defense mechanisms occurs with immunoglobulin deficiency, primary ciliary disorders, or cystic fibrosis (CF). Infections and bronchiectasis are therefore often more diffuse. With panhypogammaglobulinemia, the best described of the immunoglobulin disorders associated with recurrent infection and bronchiectasis, patients often also have a history of sinus or skin infections. Selective deficiency of an IgG subclass, especially IgG2, has also been described in a small number of patients with bronchiectasis.

The primary disorders associated with ciliary dysfunction, termed primary ciliary dyskinesia , are responsible for 5–10% of cases of bronchiectasis. Primary ciliary dyskinesia is inherited in an autosomal recessive fashion. Numerous defects are encompassed under this category, including structural abnormalities of the dynein arms, radial spokes, and microtubules; mutations in heavy and intermediate chain dynein have been described in a small number of patients. The cilia become dyskinetic; their coordinated, propulsive action is diminished, and bacterial clearance is impaired. The clinical effects include recurrent upper and lower respiratory tract infections, such as sinusitis, otitis media, and bronchiectasis. Because normal sperm motility also depends on proper ciliary function, males are generally infertile (Chap. 340). Additionally, since visceral rotation during development depends upon proper ciliary motion, the positioning of normally lateralized organs becomes random. As a result, approximately half of patients with primary ciliary dyskinesia fall into the subgroup of Kartagener's syndrome, in which situs inversus accompanies bronchiectasis and sinusitis.

In CF (Chap. 253), the tenacious secretions in the bronchi are associated with impaired bacterial clearance, resulting in colonization and recurrent infection with a variety of organisms, particularly mucoid strains of P. aeruginosa but also S. aureus, H. influenzae, Escherichia coli, and Burkholderia cepacia.

Noninfectious Causes

Some cases of bronchiectasis are associated with exposure to a toxic substance that incites a severe inflammatory response. Examples include inhalation of a toxic gas such as ammonia or aspiration of acidic gastric contents, though the latter problem is often also complicated by aspiration of bacteria. An immune response in the airway may also trigger inflammation, destructive changes, and bronchial dilatation. This mechanism is presumably important for bronchiectasis with allergic bronchopulmonary aspergillosis (ABPA), which is due at least in part to an immune response to Aspergillus organisms that have colonized the airway (Chap. 249).

In 1-antitrypsin deficiency, the usual respiratory complication is the early development of panacinar emphysema, but affected individuals may occasionally have bronchiectasis. In the yellow nail syndrome, which is due to hypoplastic lymphatics, the triad of lymphedema, pleural effusion, and yellow discoloration of the nails is accompanied by bronchiectasis in approximately 40% of patients.

Clinical Manifestations

Patients typically present with persistent or recurrent cough and purulent sputum production. Repeated, purulent respiratory tract infections should raise clinical suspicion for bronchiectasis. Hemoptysis occurs in 50–70% of cases and can be due to bleeding from friable, inflamed airway mucosa (Chap. 34). More significant, even massive bleeding is often a consequence of bleeding from hypertrophied bronchial arteries. Systemic symptoms such as fatigue, weight loss, and myalgias can also occur.

When a specific infectious episode initiates bronchiectasis, patients may describe a severe pneumonia followed by chronic cough and sputum production. Alternatively, patients without a dramatic initiating event often describe the insidious onset of symptoms. In some cases, patients are either asymptomatic or have a nonproductive cough, often associated with "dry" bronchiectasis in an upper lobe. Dyspnea or wheezing generally reflects either widespread bronchiectasis or underlying chronic obstructive pulmonary disease. With exacerbations of infection, the amount of sputum increases, and it becomes more purulent and often more bloody; systemic symptoms, including fever, may also be prominent.

Physical examination of the chest overlying an area of bronchiectasis is quite variable. Any combination of crackles, rhonchi, and wheezes may be heard, all of which reflect the damaged airways containing significant secretions. As with other types of chronic intrathoracic infection, clubbing may be present. Patients with severe diffuse disease, particularly those with chronic hypoxemia, may have associated cor pulmonale and right ventricular failure.

Radiographic and Laboratory Findings

Though the chest radiograph is important in the evaluation of suspected bronchiectasis, the findings are often nonspecific. At one extreme, the radiograph may be normal with mild disease. Alternatively, patients with saccular bronchiectasis may have prominent cystic spaces, either with or without air-liquid levels, corresponding to the dilated airways. These may be difficult to distinguish from enlarged airspaces due to bullous emphysema or from regions of honeycombing in patients with severe interstitial lung disease. Other findings are due to dilated airways with thickened walls, which result from peribronchial inflammation. These dilated airways are often crowded together in parallel. When seen longitudinally, the airways appear as "tram tracks"; when seen in cross-section, they produce "ring shadows." Because the dilated airways may be filled with secretions, the lumen may appear dense rather than radiolucent, producing an opaque tubular or branched tubular structure.

CT, especially with high-resolution images 1.0–1.5 mm thick, provides an excellent view of dilated airways (Fig. 252-1). Consequently, it is now the standard technique for detecting or confirming the diagnosis of bronchiectasis.

Figure 252-1




High-resolution CT scan of bronchiectasis showing dilated airways in both lower lobes and in the lingula. When seen in cross-section, the dilated airways have a ringlike appearance. (From SE Weinberger: Principles of Pulmonary Medicine, 4th ed. Philadelphia, Saunders, 2004, with permission.)




Examination of sputum often reveals an abundance of neutrophils and colonization or infection with a variety of possible organisms. Appropriate staining and culturing of sputum often provide a guide to antibiotic therapy.

When bronchiectasis is focal, fiberoptic bronchoscopy may reveal an underlying endobronchial obstruction. In other cases, upper lobe involvement may be suggestive of either tuberculosis or ABPA. With more widespread disease, measurement of sweat chloride levels for CF, structural or functional assessment of nasal or bronchial cilia or sperm for primary ciliary dyskinesia, and quantitative assessment of immunoglobulins may explain recurrent airway infection.

Pulmonary function tests may demonstrate airflow obstruction as a consequence of diffuse bronchiectasis or associated chronic obstructive lung disease. Bronchial hyperreactivity, e.g., to methacholine challenge, and some reversibility of the airflow obstruction with inhaled bronchodilators are relatively common.

Figure 252-2 illustrates a diagnostic approach based on clinical suspicion and radiographic findings. As the differential diagnosis for focal versus diffuse bronchiectasis is different, the radiographic distribution of disease can serve as a starting point of the diagnostic workup. This algorithm should not imply that all studies be obtained in all patients with bronchiectasis. Rather, the workup should be dictated by a careful assessment of the clinical scenario. In a patient with focal bronchiectasis, for example, documentation of a prior pneumonia in the same location may suffice. Evaluation for immunoglobulin deficiency and CF should be considered for young patients with bronchiectasis and sino-pulmonary disease.

Figure 252-2




Diagnostic approach to bronchiectasis. AFB, acid-fast bacilli; CXR, chest X-ray; GERD, gastroesophageal reflux disease; HRCT, high-resolution computed tomography; PFT, pulmonary function testing.



Bronchiectasis: Treatment

Therapy has several major goals: (1) treatment of infection, particularly during acute exacerbations; (2) improved clearance of tracheobronchial secretions; (3) reduction of inflammation; and (4) treatment of an identifiable underlying problem.

Antibiotics are the cornerstone of bronchiectasis management. For patients with infrequent exacerbations characterized by an increase in quantity and purulence of the sputum, antibiotics are used only during acute episodes. Although choice of an antibiotic should be guided by Gram's stain and culture of sputum, empiric coverage (e.g., with amoxicillin, trimethoprim-sulfamethoxazole, or levofloxacin) is often given initially. Infection with P. aeruginosa is of particular concern, as it appears to be associated with greater rate of deterioration of lung function and worse quality of life. When Pseudomonas is present, oral therapy with a quinolone or parenteral therapy with an aminoglycoside, carbapenem, or third-generation cephalosporin is appropriate based on antibiotic sensitivity patterns. There are no firm guidelines for length of therapy, but a 10–14 day course or longer is typically administered.

A variety of mechanical methods and devices accompanied by appropriate positioning can facilitate drainage in patients with copious secretions. Though commonly employed and probably beneficial, these airway-clearance techniques have been poorly studied, and their efficacy is not proven. Pharmacologic agents are also employed to promote bronchopulmonary hygiene. Mucolytic agents to thin secretions and allow better clearance are controversial. Aerosolized recombinant DNase, which decreases viscosity of sputum by breaking down DNA released from neutrophils, has been shown to improve pulmonary function in CF but may be deleterious and should be avoided in bronchiectasis not associated with CF. Bronchodilators to improve obstruction and aid clearance of secretions are particularly useful in patients with airway hyperreactivity and reversible airflow obstruction.

Although surgical therapy was common in the past, more effective antibiotic and supportive therapy has largely replaced surgery. However, when bronchiectasis is localized and the morbidity is substantial despite adequate medical therapy, surgical resection of the involved region of lung should be considered.

When massive hemoptysis, often originating from the hypertrophied bronchial circulation, does not resolve with conservative therapy, including rest and antibiotics, therapeutic options are either surgical resection or bronchial arterial embolization (Chap. 34). Although resection may be successful if disease is localized, embolization is preferable with widespread disease.

Lung Abscess

Lung abscess is defined as pulmonary parenchymal necrosis and cavitation resulting from infection. The development of a lung abscess implies a high microorganism burden as well as inadequate microbial clearance from the airways. Aspiration is the most common cause; factors that portend an increased risk of aspiration include esophageal dysmotility, seizure disorders, and neurologic conditions causing bulbar dysfunction. Other predisposing conditions for lung abscess include periodontal disease and alcoholism.

Microbiology

Anaerobic bacteria are the most common causative organisms for lung abscess. Aerobic or facultative bacteria such as S. aureus, Klebsiella pneumoniae, Nocardia sp., and gram-negative organisms, as well as nonbacterial pathogens like fungi and parasites, may also cause abscess formation. In the immunocompromised host, aerobic bacteria and opportunistic pathogens may predominate. Multiple isolates are more commonly seen in all patients when anaerobic and aerobic cultures are done.

Clinical Manifestations

The symptoms of lung abscess are typical of pulmonary infection in general and may include cough, purulent sputum production, pleuritic chest pain, fever, and hemoptysis. In anaerobic infection, the clinical course may evolve over an extended period of time, and some patients may be asymptomatic. More acute presentations are typical of infection with aerobic bacteria.

Physical examination is often unrevealing. Rales or evidence of consolidation may be present. Fetid breath and poor dentition may be diagnostic clues. Clubbing or hypertrophic pulmonary osteoarthropathy may occur in chronic cases.

The chest radiograph classically reveals one or two thick-walled cavities in dependent areas of the lung, particularly the upper lobes and posterior segments of the lower lobes (Fig. 252-3). An air-fluid level is often present. CT of the chest is helpful in defining the size and location of the abscess, as well as to evaluate for additional cavities and the presence of pleural disease. Cavitary lesions in nondependent regions like the right middle lobe or anterior segments of the upper lobes should raise the possibility of other etiologies, including malignancy.

Figure 252-3




Cross-sectional CT image from a patient with an anaerobic lung abscess showing two contiguous thick-walled cavitary lesions in the right lower lobe with air-fluid levels. (From WT Miller Jr: Diagnostic Thoracic Imaging. New York, McGraw-Hill, 2006, with permission.)



Laboratory studies may reveal leukocytosis, anemia, and an elevated erythrocyte sedimentation rate.

Diagnosis

The diagnosis of lung abscess is based on clinical symptoms, identification of predisposing conditions, and chest radiographic findings. The differential diagnosis includes mycobacterial infection, pulmonary sequestration, malignancy, pulmonary infarction, and an infected bulla.

Identification of a causative organism is an ideal but challenging goal. Anaerobic bacteria are particularly difficult to isolate. Blood, sputum cultures, and, when appropriate, pleural fluid cultures should be obtained from patients with lung abscess. The role of fiberoptic bronchoscopy with bronchoalveolar lavage or protected-specimen brush for diagnosis or drainage of lung abscess is controversial. The relatively low yield, especially with anaerobic lung abscess, should be balanced against the risk of rupture of the abscess cavity with spillage into the airways. Bronchoscopy is perhaps most useful to rule out airway obstruction, mycobacterial infection, or malignancy. Other less commonly utilized methods for microbiologic sampling are transtracheal or transthoracic aspiration.

Lung Abscess: Treatment

For many years, penicillin was the mainstay of empiric antibiotic therapy for lung abscess. Due to the emergence of -lactamase–producing organisms, clindamycin (150 mg–300 mg every 6 h) is now standard therapy. Other agents, such as carbapenems and -lactam/-lactamase inhibitor combinations, may be useful in selected cases. Metronidazole alone is associated with a high treatment failure rate. When possible, the choice of antibiotics should be guided by microbiologic results.

The duration of treatment for lung abscess is controversial. Four to six weeks of antibiotic therapy is typically employed, though a more extended course is favored by some experts. Treatment failure suggests the possibility of a noninfectious etiology.

While surgery has had a limited role in treatment in the antibiotic era, indications include refractory hemoptysis, inadequate response to medical therapy, or the need for a tissue diagnosis when there is concern for a noninfectious etiology.

In general, outcomes for patients with classic anaerobic lung abscess are favorable, with a 90–95% cure rate. Higher mortality rates have been reported in immunocompromised patients, those with significant comorbidities, and infection with P. aeruginosa, S. aureus, and K. pneumoniae.