Bronchiectasis is a syndrome, with many underlying etiologies and associations, that has been defined as an irreversible dilation and destruction of one or more bronchi, and inadequate clearance and pooling of mucus in the airways.6 Bronchiectasis results from the occurrence of one of three main pathologic mechanisms: bronchial wall injury, bronchial lumen obstruction, and traction from adjacent fibrosis. Three important pathogenic components, infection, inflammation, and enzymatic/lytic enzyme release, cause a chronic, self-perpetuating destruction to the airways.6 This leads to the unique progressive airway dilation that is associated with the inflammation in bronchiectasis, as opposed to the small airway narrowing seen in asthma and COPD.6,7 Bronchiectasis is also characterized by persistent microbial infection and inflammatory response with release of microbial toxins and immune mediators. It is estimated that the prevalence in the United States ranges from 4 per 100,000 persons aged 18 to 34 to 271 per 100,000 among those over age 75. Prevalence in underdeveloped countries is likely higher.6 Bronchiectasis is often divided into a form associated with cystic fibrosis (CF) and a non-CF form. Non-CF bronchiectasis will be reviewed first.
A classification system has been devised that classifies bronchiectasis according to anatomic and morphologic patterns or airway dilatation as follows: (1) cylindrical bronchiectasis, in which there is uniform dilatation of the bronchi, which are thick walled and extend to the lung periphery without normal tapering (on a high-resolution CT [HRCT] scan, it has parallel “tram track” lines or “signet ring” appearance); (2) varicose bronchiectasis, which has an irregular and beaded outline of bronchi with alternating areas of constriction and dilatation similar in appearance to saphenous varicosities; (3) cystic bronchiectasis, which is the most severe form and is common in patients with CF, characterized by bronchial dilatation and clusters of round air-filled and fluid-filled cysts, with a honeycomb appearance in patients with CF; and (4) follicular bronchiectasis, which has extensive lymphoid nodules and follicles within thickened bronchial walls. Cystic, cylindrical, and varicose forms may coexist in the same patient. The fourth pattern, follicular bronchiectasis, usually occurs following childhood pneumonia, measles, pertussis, or adenovirus infection.
Although insightful, these definitions are not particularly helpful from a clinical or therapeutic standpoint. Four clinical stereotypes have been defined and are more useful. These are (1) rapidly progressive (early-onset and rapidly progressive diffuse disease with frequent exacerbations and copious sputum); (2) slowly progressive (slow, insidious progression, with an increase in sputum production and exacerbations over decades); (3) indolent disease (patients can be asymptomatic and do not show deterioration); and (4) predominant hemoptysis (recurrent hemoptysis in the setting of very little sputum).7
The most common causes of non-CF bronchiectasis8–10 are listed in Table 2. In general the causes can be divided into idiopathic, postinfectious, or due to an underlying anatomic or systemic disease.11 The condition is most commonly idiopathic in adults.6,8 The prevalence of undiagnosed CF is not known, but studies have suggested it is very low. Patients with focal bronchiectasis, which is localized to a segment or lobe, should undergo bronchoscopy to evaluate for and eliminate an obstructing bronchial lesion. Other indications for bronchoscopy are to obtain a biopsy specimen to determine ciliary disorders and obtain specimens for the diagnosis of mycobacterial disease.12
Table 2 Common Causes of Bronchiectasis
The factor most commonly associated with bronchiectasis in childhood is infection,6 although it is being seen more commonly in adults now, especially with the increased use of HRCT scanning. Radiographic findings obtained with an HRCT scan of the chest have been described in patients with Mycobacterium avium-intracellulare complex (MAC). The most notable finding in bronchiectasis is the presence of small nodular opacities or the “tree-in-bud” appearance. Abnormalities most often occur in the lower lung fields. Treatment with multiple antimicrobial agents may lead to the resolution of these abnormalities, but prolonged therapy for up to 18 months may be necessary.6
There are an increasing number of immune deficiencies that have been associated with bronchiectasis. Ciliary disorders are considered to be primary disorders of immune defense, as airway clearance mechanisms contribute an important component of barrier immunity. Acquired adult-onset hypogammaglobulinemia may involve one or more of the immunoglobulin classes. IgG subclass deficiencies may be present even with normal total IgG levels. Patients with HIV infection have been found to have a high incidence of bronchiectasis, which may in part be due to recurrent bronchopulmonary infections (especially Pneumocystis-proved pneumonia and Mycobacterium intracellulare infection). The bronchiectasis observed in HIV-infected patients is particularly aggressive. Allergic bronchopulmonary aspergillosis (ABPA) predisposes patients to bronchiectasis as a consequence of a persistent complex immune response to airway colonization by Aspergillus. This type of bronchiectasis most commonly involves the central airways, distinguishing it from other types of bronchiectasis.6
Clinical findings from a retrospective chart review of patients with confirmed bronchiectasis included cough (90%), chronic daily sputum production (76%), dyspnea (72%), hemoptysis (56%), and pleuritic chest pain (46%). Two symptoms that are also very common are rhinosinusitis and fatigue. The most common physical findings were crackles (70%) and wheezing or rhonchi (<50%). Daily cough and sputum production have been reported in HIV-positive patients with bronchiectasis confirmed by CT scan in <39% of cases. The disease is more common in women and most commonly presents in the sixth decade of life.6
Pulmonary function study results may be normal if the involvement of bronchiectasis is localized and mild. With diffuse disease, pulmonary function tests may reveal an obstructive ventilatory defect with hyperinflation and impaired diffusing capacity of the lung for carbon monoxide. Airway hyperresponsiveness has been seen in up to 40% of patients with bronchiectasis in some series. On the other hand, some patients with diffuse disease may present with a combined obstructive and restrictive ventilatory defect. Pulmonary function tests are not useful in distinguishing bronchiectasis from other obstructive airway diseases.6 Laboratory studies in patients with bronchiectasis include a mild degree of leukocytosis, usually without a left shift; an increase in the erythrocyte sedimentation rate; mild anemia; and hypergammaglobulinemia.
Routine chest radiographs can be used but are insensitive to exclude the diagnosis, detecting abnormalities in only 50% of patients. Findings are abnormal in approximately 50% of patients with proven bronchiectasis. The classic finding of tram tracks, representing thickened dilated bronchial walls, is best seen on radiographs obtained from a lateral view. Other findings include hyperinflation and air trapping, increased linear markings, rounded opacities that represent areas of focal pneumonia, and ring shadows that represent dilated airways seen en face. Although bronchography was the historical gold standard for confirming the diagnosis, HRCT scanning has become the current diagnostic standard for the detection of bronchiectasis. It is both highly sensitive and specific for the diagnosis of bronchiectasis.
Today, HRCT scanning is the method used in nearly all cases of bronchiectasis. Given the high sensitivity of HRCT scanning, it has become much easier to diagnose the disorder, which may account for the increased awareness and prevalence of the disease. Standard criteria for the diagnosis of bronchiectasis on HRCT scans have been established. The most specific criteria are an internal bronchus diameter that is wider than its adjacent artery (signet ring formation), the failure of the bronchi to taper as they move toward the periphery of the lung parenchyma, and bronchi visualized in the outer 1 to 2 cm of the lung fields.13 Secondary criteria include excessive bronchial wall thickening, impacted mucus, and crowding of the bronchi. Figure 1 shows the characteristic large bronchi in a patient with Kartagener syndrome. MRI has similar sensitivity and specificity and can be used in cases where radiation must be avoided.
Figure Jump LinkFigure 1 Large internal diameter of the bronchi (greater than the accompanying vessel), which is diagnostic of bronchiectasis (large arrows). From the author's personal files.Grahic Jump Location
The pattern of distribution of the bronchiectatic changes on HRCT can help narrow the differential diagnosis.14 Focal changes suggest mechanical obstruction, congenital bronchial atresia, or a necrotizing pneumonia. Diffuse changes that have a central predominance suggest ABPA or cartilage deficiency syndromes. More peripheral changes seen predominantly in the upper lung regions suggest CF, sarcoidosis, or postradiation fibrosis. Peripheral middle lobe changes are seen with atypical mycobacterial infections and immotile cilia syndrome. Peripheral changes in the lower lung fields should prompt consideration of aspiration, fibrotic lung disease (traction bronchiectasis), HIV, hypogammaglobulinemia, transplant rejection, and prior infection. Most cases of diffuse lower lobe bronchiectasis will be idiopathic.
Differential Diagnosis/Additional Testing
Additional testing includes a workup to detect the underlying cause and microbiologic examination of the sputum. Additional tests include sweat chloride testing, ciliary structure and function examination, immunoglobulin levels, HIV, α1-antitrypsin, rheumatoid factor and ANA levels, barium swallow, and Aspergillus antigen.12 The choice of additional testing should be prompted by the history, associated symptoms, and radiographic patterns.9,10 Studies have shown that a specific cause can be identified in many cases, and this has led to a modification in the treatment in up to 50% of patients.13 In some cases, such as ABPA or immunodeficiencies, specific therapy may prevent disease progression.15 Bronchiectasis should be distinguished from COPD (particularly chronic bronchitis).6 Both diseases present with cough, sputum production, wheezing, and dyspnea. Exacerbations are common in both disorders, although the volume of sputum production is greater in patients with bronchiectasis. Recurrent fever and hemoptysis are less likely to be found in patients with chronic bronchitis. The presence of Pseudomonas in the sputum may be helpful to the diagnosis. The incidence of Pseudomonas aeruginosa is approximately 31% in patients with bronchiectasis, but only 2% to 4% in patients with COPD.
Bronchiectasis can also be confused with interstitial fibrosis, especially in patients with end-state fibrosis who have a honeycomb appearance seen on a chest radiograph. This parenchymal honeycomb appearance may mimic the air-filled cysts of bronchiectasis.
The objectives of management for bronchiectasis are the relief of symptoms, the prevention of complications, the control of exacerbations, and a reduction in mortality. Unfortunately, only a small number of well-designed trials in small numbers of patients have been performed in patients with non-CF bronchiectasis. Many of the current recommendations are extrapolated from those done in patients with CF.13
General Supportive Measures
Vaccination against influenza and pneumococcal pneumonia are also recommended, although they have not been proven to change important outcomes in these patients.13
Airway Clearance Techniques
Postural drainage and chest physiotherapy are useful to enhance the gravity-aided clearance of secretions. Alternative treatment includes the use of a flutter device, a positive expiratory pressure mask, chest oscillation, and humidification of inspired air.6,8
The role of pulmonary rehabilitation and inspiratory muscle training has been investigated in only one well-designed trial, but it has been suggested that rehabilitation increases exercise tolerance in patients with bronchiectasis.8
Most patients with bronchiectasis have significant airway hyperresponsiveness, presumably as a result of transmural airway inflammation. The routine use of bronchodilators has the added potential advantage of the stimulation of mucociliary clearance, which is associated with the use of p-adrenergic agents. Both aerosolized p-agonist therapy and aerosolized anticholinergic therapy should be tried when there is evidence of reversible airway obstruction.6,8
Antibiotics are the cornerstone for the treatment of exacerbations of bronchiectasis. They are used to treat acute exacerbations, to prevent exacerbations, or to reduce the bacterial burden.10 Early in the disease process, patients are typically colonized with Haemophilus influenzae. As the disease progresses, Psuedomonas spp predominate. Other pathogens include Moraxella catarrhalis, Aspergillus, and MAC.7Staphylococcus aureus is uncommon, and if repeatedly isolated, should prompt the consideration of undiagnosed CF.11 Early, when the bacterial flora include Streptococcus pneumoniae and H influenzae, treatment with TMP-SMX, ampicillin-clavulanate acid, or one of the newer macrolide agents is effective. In patients who have been colonized with Pseudomonas, oral therapy requires the use of a fluoroquinolone.10 In some cases, IV administration of antipseudomonal antibiotics is required.6 Whether prophylactic antibiotic therapy is necessary remains an unresolved question. Strategies that have been tried include a high oral or IV dose for a prolonged period (4 weeks), pulsed courses of antibiotics with on/off periods, and regular aerosolized therapy.6,11,16 Strategies for prophylaxis with low-dose antibiotics range from daily to 1 week of each month. Daily inhaled antibiotic prophylaxis is now recommended in patients with CF who have been colonized with P aeruginosa. In non-CF bronchiectasis, this approach is reserved for patients with severe disease, manifested by copious purulent sputum and frequent exacerbations, who fail to respond to other approaches. Both inhaled tobramycin and gentamicin have been shown to decrease bacterial density, but the benefits seem to be less than those seen in patients with CF. In addition, adverse events such as bronchospasm are more common.17
Although intense airway inflammation characterizes bronchiectasis, few studies have looked at the efficacy of corticosteroids in the treatment of this disorder. Inhaled steroids have been suggested as alternative therapy and may be useful in some patients, especially those with significant airway hyperreactivity. It has been shown that inhaled corticosteroids can reduce the levels of inflammatory mediators and improve dyspnea and cough. However, a systematic review found no significant improvement in pulmonary function.8,13 Short courses of oral corticosteroid therapy are often used during acute exacerbations. Nonsteroidal antiinflammatory agents, such as indomethacin (not available in the United States), have been used in Europe, either orally or by inhalation.8 Leukotriene receptor antagonists may be of benefit in patients with bronchiectasis because they can inhibit neutrophil-mediated inflammation. However, there have been no randomized controlled trials published concerning patients in this population.8 Macrolides suppress inflammation, independent of their antimicrobial action, and have improved the clinical status and lung function of patients in a few small studies of bronchiectasis.16,17 Long-term use needs to be balanced against potential side effects, including gastrointestinal, cardiac, and auditory. The possibility of MAC infection must also be excluded as macrolide monotherapy increases the likelihood of resistance.17 Further study is needed before they can be recommended routinely.
Mucolytic Agents and Hydration
Adequate oral hydration and the use of nebulized solutions may improve airway mucus clearance.6 Acetylcysteine is beneficial in some patients. To date, there have been no randomized, controlled clinical trials showing mucolytics to be of benefit in the treatment of non-CF bronchiectasis. Recombinant human DNase breaks down DNA that is released from degenerating bacteria and neutrophils. DNA has a tendency to form thick, viscous gels. DNase improves the clearance of secretions and pulmonary function and reduces the number of hospitalizations in patients with CF, but has not been found to be useful in non-CF bronchiectasis. One study has suggested that DNase was ineffective and potentially harmful in >300 adult outpatients with idiopathic bronchiectasis who were in stable condition.18 Therapy with inhaled mannitol may improve impaired mucociliary clearance by inducing an influx of fluid into the airways and has shown clinical promise in patients with non-CF bronchiectasis.8,17 This is particularly exciting because it is easier to inhale a dry powder than to use a nebulizer. One small study has also shown benefit with nebulized hypertonic saline.17
In patients with localized bronchiectasis, surgical removal of the most affected segment or lobe may be considered. The major indications for surgery include the partial obstruction of a segment or lobe due to a tumor or the presence of a highly resistant organism in the affected area, such as MAC or Aspergillus. Patients require significant pulmonary function to withstand surgery. Surgery may also be performed for massive hemoptysis in patients with adequate pulmonary reserve, although the increased success of bronchial artery embolization for hemoptysis makes surgery less desirable.6,10,11
Patients with bronchiectasis and CF were initially considered not to be good transplant candidates because of concerns about overwhelming infection after the use of prolonged immunosuppression. However, double-lung transplantation has been successful in patients with CF, and the St. Louis International Transplant Registry lists >1,000 patients with CF and >200 non-CF bronchiectasis patients who have undergone lung transplantation, with a 1-year survival rate of 72% and a 4-year survival rate of 49% in patients with CF.9,11