Bronchiectasis

Kevin D. Shaw

Bronchiectasis is defined as an anatomic distortion of the normally tapering bronchi, characterized by persistent airway dilation, wall thickening, fibrosis, epithelial destruction, and failure to branch normally. The origin of the word comes from the Greek roots “bronkhos,” referring to windpipe, and “ektasis,” meaning a stretching out. Rene Laënnec, a French physician and father of the stethoscope, first characterized the condition in 1819. In 1950, Lynne Reid performed careful anatomic dissection in comparison to radiographic appearance of bronchiectasis on contrast bronchography, and described three separate but often overlapping morphologies. Since her work, bronchiectasis has generally been described as cylindrical, varicose, or saccular.

Bronchiectasis may best be considered an effect, rather than a cause, of pulmonary disease. It is almost always secondary to a state of chronic inflammation and repeated infections, which over time cause neutrophilic infiltration and subsequent destruction of the airway walls. A “vicious cycle” of bronchiectasis has been well recognized by many authors, and explains the persistence of symptoms and frequency of exacerbations: chronic airway infection leads to inflammation and airway wall damage with impaired mucociliary clearance, ultimately predisposing to further infection. Treatments for bronchiectasis are varied, and target each of these steps in the cycle.

Bronchiectasis is typically seen later in life, often in the fifth and sixth decades. Because bronchiectasis is a consequence of an underlying condition, investigation of the etiology should be performed.

PRESENTATION

Bronchiectasis can be identified in asymptomatic patients, and does not necessarily have a “classic” presentation. A patient may present with complaints of a chronic, wet cough, repeated episodes of chest congestion or infection, shortness of breath, wheezing, audible crackles, or hemoptysis. Physical examination may be notable for coarse crackles, occasional wheezing, a barrel chest, cachexia, and in severe cases, clubbing. Pulmonary function testing is frequently abnormal, with a mixture of obstructive and restrictive processes identified in mild cases. Severe bronchiectasis almost always presents with severe obstructive physiology.

Chest imaging is often diagnostic, but bronchiectasis may be missed on plain films. Contrast bronchography is no longer performed routinely, but had been used prior to computed tomography (CT) to define abnormal airway anatomy. Currently, high resolution CT scanning is the imaging modality of choice to identify and characterize bronchiectasis. Persistent airway dilation is the norm, often with surprisingly dilated airways seen near the periphery. On axial imaging, the “signet ring” sign is often appreciated: defined by an airway inner diameter exceeding that of the adjacent pulmonary artery, resembling a stone mounted on a ring. In addition, airway wall thickening, sometimes with adjacent fibrosis, may be found.

Radiographically, bronchiectasis can be divided into one of Reid’s three categories. Cylindrical bronchiectasis is defined as persistent airway dilation in the medium-sized bronchi, and the absence of normal tapering that is expected as airways head toward the pleural surface. There are often near normal numbers of branching subdivisions of smaller airways when compared to controls. Varicose bronchiectasis is defined by its areas of airway outpouching and narrowing, similar to a varicose vein seen in cross section. Saccular bronchiectasis is characterized by large mucus-filled cysts, typically subpleural, which result from destruction and cavitation of normal bronchial anatomy. Although saccular bronchiectasis was originally thought to originate from the most distal bronchi, it is now recognized that the number of branching airway subdivisions in saccular disease is often markedly decreased, suggesting a proximal destructive process spreading into the distal parenchyma. Saccular bronchiectasis is typically associated with worsened symptoms, decreased lung function, worsened prognosis, and a higher incidence of Pseudomonas aeruginosa infection than the other two types of bronchiectasis.

The term traction bronchiectasis refers to the abnormally widened airways seen in the setting of parenchymal volume loss, as is often found in pulmonary fibrosis. Whether this is true bronchiectasis or pseudobronchiectasis is debatable, as these patients do not typically present with typical symptoms of chronic wet cough and do not exhibit similar airway pathology of chronic inflammation, repeated infection, and airway wall thickening. In acute pneumonia, similar volume loss secondary to consolidation can mimic bronchiectasis on chest imaging. This is also not true bronchiectasis, as it disappears with resolution of the pneumonia.

Microbes typically cultured from bronchiectatic patients include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenza, Moraxella catarrhalis, mycobacteria (avium/intracellulare most commonly), and a variety of other Gram-negative organisms including Escherichia coli, Klebsiella pneumoniae, Achromobacter xylosidans, and Stenotrophomonas maltophilia. Fungi are also seen, most commonly Aspergillus species, Scedosporium apiospermum, or Candida species. It is important to differentiate bronchiectasis with colonizing fungus growth from allergic bronchopulmonary aspergillosis (ABPA), one of many potential etiologies of bronchiectasis. More recently, the virome of the bronchiectatic lung is being explored, with increasing importance placed on “top-down” suppression of bacterial growth by bacteriophage present in the airways.

Hemoptysis can be a particularly frightening complication of bronchiectasis for patients and practitioners alike. Patients may encounter flecks of blood only, or “massive hemoptysis” which is considered life threatening in nature. Because hemoptysis is difficult to accurately quantify, the definitions of “massive” often found in literature, ranging from 100 to 1,000 mL per 24 hours, are of limited utility. The source of bleeding is typically a bronchial artery, which has a higher mean arterial pressure compared with the pulmonary artery. In chronic or severe bronchiectasis, bronchial artery hypertrophy is often seen, which is a setup for more frequent and severe bleeding. Hemoptysis can occur while a patient is feeling otherwise well, but often presents in the setting of chest congestion, increased mucus production, and worsening dyspnea.

PATHOGENESIS

Bronchiectasis can be characterized as either diffuse or focal. Diffuse bronchiectasis is often the result of a systemic immunodeficiency, severe inhalation injury, or a congenital condition. Focal bronchiectasis may represent a sequela of prior infection or a singular insult. With focal disease, airway lesions such as tumor or foreign body may be considered, since bronchiectasis can occur in the setting of chronic infection distal to an obstruction.

The underlying mechanisms responsible for the development of bronchiectasis are similar amongst the recognized etiologies. Principal among them is the development of airway damage and inflammation, often resulting from an episode of airway infection. When an infection develops in the setting of obstruction, inflammatory airway debris cannot be efficiently cleared, predisposing to continued inflammation, epithelial damage, and repeated infections. Over time, this cycle of inflammation, obstruction, and infection leads to airway wall damage. Denuded airway epithelium, is often replaced by nonciliated, cuboidal, or squamous epithelium. Loss of basement membrane, smooth muscle, and cartilage integrity leads to tortuous, dilated airways, with thickened, fibrotic airway walls. Microabscesses may form within and alongside bronchial walls, causing further inflammatory and fibrotic damage, as well as airway obstruction. This abnormal airway anatomy with loss of ciliated epithelium predisposes to impaired sputum clearance and further cycles of infection.

The airway infections typically induce chronic neutrophilic infiltrates. The oxidative chemicals released during chronic neutrophil activation play a principle role in the subsequent airway wall trauma. Neutrophil chemotactic factors including interleukin-8, leukotriene B4, and tumor necrosis factor-alpha lead to increased neutrophil infiltration. Release of neutrophil-derived toxic products such as elastase and matrix metalloproteinases results in destruction of basement membrane collagen, elastin, and proteoglycan support molecules with subsequent loss of airway wall integrity. Bronchoalveolar lavage studies have demonstrated increased levels of these chemotactic and toxic factors. Sputum elastase concentration has been correlated with decreased lung function and increased cytokine expression.

A multitude of underlying etiologies have been identified. The most common cause of bronchiectasis is prior lung infection, historically attributed to tuberculosis, measles, or pertussis. These are typically childhood infections, with the ultimate development of bronchiectasis often recognized many years later. However, any necrotizing pneumonia, bacterial or viral, can result in bronchiectasis. Common responsible bacterial pathogens include Streptococcus pneumoniae, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Diffuse postinfectious bronchiectasis is typically related to repeated episodes of pneumonia, although may be due to a single, severe, multifocal episode.

Although bronchiectasis is often characterized as “idiopathic,” a careful history may identify prior infections in many patients. In a study performed in Tyler, Texas, 70% of patients were able to identify a lung injury prior to development of bronchiectasis. Of these patients, greater than 50% identified a prior lung infection as the inciting event. In the older population, or those prone to dysphagia, chronic aspiration should be ruled out, especially if the bronchiectasis appears radiographically in the dependent portions of the lungs.

Granulomatous lung diseases, including mycobacterial disease, sarcoidosis, and fungal lung infections are frequent causes of bronchiectasis. Mycobacterial disease is often associated with predominantly right middle lobe and lingular bronchiectasis. In nonsmoking Caucasian women over age 50, there is a relatively increased incidence of right middle lobe or “Lady Windermere” syndrome, often attributed to the right middle lobe’s “fish mouth” orifice and impaired drainage. Chest imaging often shows bronchiectasis with nodules and “tree-in-bud” opacities in these segments. Sarcoidosis and granulomatous fungal infections can involve airway walls, leading to focal areas of obstruction and impaired drainage, with resultant chronic infection and bronchiectasis.

Cystic fibrosis is the most commonly recognized genetic disease predisposing to bronchiectasis. These patients typically develop varicose and saccular changes in all lobes of the lung, but with an upper lobe predominance. Another associated genetic disease is primary ciliary dyskinesia, which may present as Kartagener syndrome (situs inversus, paranasal sinusitis, and bronchiectasis). Due to immotile cilia, these patients experience repeated sinus and pulmonary infections, leading to the subsequent cycle of inflammation and airway destruction. Alpha-1 antitrypsin deficiency may also lead to loss of airway wall integrity, chronic inflammation, and development of bronchiectasis. Other less commonly recognized genetic disorders associated with bronchiectasis include Mounier-Kuhn syndrome (tracheobronchomegaly), Williams-Campbell syndrome (cartilage malformation in distal bronchi), and Young syndrome (sinus and pulmonary infections with infertility).

Allergic bronchopulmonary aspergillosis is defined as a chronic, destructive type III immune complex reaction associated with airway colonization with Aspergillus species. Radiographically, patients typically have central bronchiectasis and fleeting infiltrates associated with episodes of exacerbation. Diagnosis is based on symptoms, consistent radiographs, Aspergillus-specific precipitating antibodies or a positive Aspergillus skin prick test, and an elevated IgE level. For reasons that are not clearly understood, the incidence of ABPA is elevated in the cystic fibrosis population.

Immunodeficiencies, whether congenital (severe combined immunodeficiency, X-linked agammaglobulinemia) or acquired (HIV, stem cell transplant), may lead to bronchiectasis. Patients with history of splenectomy are also at increased risk. Chronic immunosuppression associated with a variety of autoimmune and transplant recipient states may predispose to lung infection, including nontuberculous mycobacteria, with resultant bronchiectatic changes.

A less commonly recognized cause of bronchiectasis is inhalation injury, such as exposure to industrial fires, ethylene oxide (used in gas-sterilization), or other toxic fumes. Bronchiectasis is recognized in 40% of patients with Yellow Nail Syndrome, a condition marked by lymphedema, pleural effusion, and dystrophic yellow nails. Autoimmune conditions including rheumatoid arthritis, ulcerative colitis, Crohn disease, Sjögren syndrome, and systemic lupus erythematosus are all associated with bronchiectasis, independent of tumor necrosis factor inhibitor use.

DIAGNOSTIC TESTING

The diagnostic approach to bronchiectasis is dependent upon symptoms, prior history, and physical examination findings. The workup is 2-fold. The first step is to confirm the presence of bronchiectasis radiographically. The next step in the bronchiectasis workup is to determine the underlying etiology and inciting factors, which relies heavily on history and radiographic features.

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