Bronchiectasis

Diffuse bronchiectasis develops most often in patients with genetic, immunologic, or anatomic defects that affect the airways. In developed countries, the cause of many cases appears initially to be idiopathic, probably partly because onset is so slow that the triggering problem is not readily evident at the time bronchiectasis is recognized. With newer, improved genetic and immunologic testing, an increasing number of reports describe finding an etiology in these idiopathic cases after careful, systematic evaluation.

Cystic fibrosis Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more (CF) is commonly associated with this condition, and previously undiagnosed CF may account for up to 20% of idiopathic cases. Even heterozygous patients, who typically have no clinical manifestations of CF, may have an increased risk of bronchiectasis.

Immunodeficiencies such as common variable immunodeficiency Common Variable Immunodeficiency (CVID) Common variable immunodeficiency (acquired or adult-onset hypogammaglobulinemia) is characterized by low immunoglobulin (Ig) levels with phenotypically normal B cells that can proliferate but... read more (CVID) may also lead to diffuse disease, as may rare abnormalities in airway structure. Undernutrition and human immunodeficiency virus (HIV) infection also appear to increase risk.

Congenital defects in mucociliary clearance such as primary ciliary dyskinesia (PCD) syndromes may also be a cause, explaining almost 3% of previously idiopathic cases.

Diffuse bronchiectasis sometimes complicates common autoimmune disorders, such as rheumatoid arthritis Rheumatoid Arthritis (RA) Rheumatoid arthritis is a chronic systemic autoimmune disease that primarily involves the joints. Rheumatoid arthritis causes damage mediated by cytokines, chemokines, and metalloproteases.... read more or Sjögren syndrome Sjögren Syndrome Sjögren syndrome is a relatively common chronic, autoimmune, systemic, inflammatory disorder of unknown cause. It is characterized by dryness of the mouth, eyes, and other mucous membranes ... read more , and can occur in the setting of hematologic malignancy, organ transplant, or due to the immune compromise associated with treatment in these conditions. Bronchiectasis can also be related to more common conditions, including chronic obstructive pulmonary disease (COPD) Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more , asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more , or chronic, recurrent aspiration.

Allergic bronchopulmonary aspergillosis Allergic Bronchopulmonary Aspergillosis (ABPA) Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to Aspergillus species (generally A. fumigatus) that occurs almost exclusively in patients with asthma... read more , a hypersensitivity reaction to Aspergillus species that occurs most commonly in people with asthma, but sometimes in patients with CF, can cause or contribute to bronchiectasis.

In developing countries, most cases are probably caused by tuberculosis Tuberculosis (TB) Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial infection. Tuberculosis most commonly affects the lungs. Symptoms include... read more , particularly in patients with impaired immune function due to undernutrition Overview of Undernutrition Undernutrition is a form of malnutrition. (Malnutrition also includes overnutrition.) Undernutrition can result from inadequate ingestion of nutrients, malabsorption, impaired metabolism, loss... read more or human immunodeficiency virus (HIV) infection Human Immunodeficiency Virus (HIV) Infection Human immunodeficiency virus (HIV) infection results from 1 of 2 similar retroviruses (HIV-1 and HIV-2) that destroy CD4+ lymphocytes and impair cell-mediated immunity, increasing risk of certain... read more .

Focal bronchiectasis typically develops as a result of untreated pneumonia or obstruction (eg, due to foreign bodies, tumors, postsurgical changes, lymphadenopathy). Mycobacteria (tuberculous or nontuberculous) can both cause focal bronchiectasis and colonize the lungs of patients with bronchiectasis due to other disorders (see table Factors Predisposing to Bronchiectasis Factors Predisposing to Bronchiectasis ).

As the disease progresses, chronic inflammation and hypoxemia cause neovascularization of the bronchial (not the pulmonary) arteries. Bronchial artery walls rupture easily, leading to hemoptysis, which can be massive and life threatening. Other vascular complications include pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels may become constricted... read more due to vasoconstriction, arteritis, and sometimes shunt from bronchial to pulmonary vessels.

Colonization with multidrug-resistant organisms can lead to chronic, low grade airway inflammation. This inflammation can progress, causing recurrent exacerbations and worsen airflow limitation on pulmonary function tests.

Chest x-ray is usually abnormal and may be diagnostic. X-ray findings suggestive of bronchiectasis involve thickening of the airway walls and/or airway dilation; typical findings include ill-defined linear perihilar densities with indistinctness of the central pulmonary arteries, indistinct rings due to thickened airways seen in cross section (parallel to the x-ray beam), and “tram lines” (or tram-track sign) caused by thickened, dilated airways perpendicular to the x-ray beam. Dilated airways filled with mucous plugs can also cause scattered elongated, tubular opacities.

Radiographic patterns may differ depending on the underlying disease; bronchiectasis due to cystic fibrosis develops predominantly in the upper lobes, whereas bronchiectasis due to an endobronchial obstruction causes more focal x-ray abnormalities.

High-resolution computed tomography (CT) is the test of choice for defining the extent of bronchiectasis, and is very sensitive and specific. Typical CT findings include airway dilation (in which the inner lumen of 2 or more airways exceed the diameter of the adjacent artery) and the signet ring sign, in which a thickened, dilated airway appears adjacent to a smaller artery in transaxial view. Lack of normal bronchial tapering can result in visible medium-sized bronchi extending almost to the pleura. "Tram lines" are easily visible on CT.

As airway damage increases over time, bronchiectasis changes progress from cylindrical to varicose and then cystic findings on imaging. Atelectasis Atelectasis Atelectasis is collapse of lung tissue with loss of volume. Patients may have dyspnea or respiratory failure if atelectasis is extensive. They may also develop pneumonia. Atelectasis is usually... read more , consolidation, mucous plugs, and decreased vascularity are nonspecific findings. In traction bronchiectasis, pulmonary fibrosis pulls or distorts airways in ways that simulate bronchiectasis on imaging.

Pulmonary function tests Overview of Tests of Pulmonary Function Pulmonary function tests provide measures of airflow, lung volumes, gas exchange, response to bronchodilators, and respiratory muscle function. Basic pulmonary function tests available in the... read more can be helpful for documenting baseline function and for monitoring disease progression. Bronchiectasis causes airflow limitation (reduced forced expiratory volume in 1 second [FEV1] with reduction in the FEV1/FVC ratio); the FEV1 may improve in response to beta-agonist bronchodilators. In more advanced cases, progressive fibrosis may result in decreases in forced vital capacity (FVC), evidence of a restrictive defect on lung volume measurements, and a decreased diffusing capacity for carbon monoxide (DLCO).

During an exacerbation-free period, all patients should have expectorated or induced sputum cultured to determine the predominant colonizing bacteria and their sensitivities. This information helps with antibiotic selection during exacerbations.

A complete blood count (CBC) and differential can help determine the severity of disease activity and identify eosinophilia, which may suggest complicating diagnoses.

Staining and cultures of sputum for bacterial, mycobacterial (Mycobacterium avium complex and M. tuberculosis), and fungal (Aspergillus species) organisms may also help identify the cause of chronic airway inflammation.

Clinically significant nontuberculous mycobacterial infection is diagnosed by finding high colony counts of these mycobacteria in cultures from serial sputum samples or from bronchoalveolar lavage fluid in patients who have granulomas on biopsy or concurrent radiologic evidence of disease.

When the cause of bronchiectasis is unclear, additional testing based on the history and imaging findings may be done. Tests may include the following:

Patients who have laboratory evidence of immuodeficiency should be referred for to an immunology specialist for evaluation because test results are often challenging to interpret. Additional specialized testing may also be required to confirm the type of immunodeficiency present and determine treatment options.

Primary ciliary dyskinesia should be considered if adults with bronchiectasis also have chronic sinus disease or otitis media, particularly if problems have persisted since childhood. Bronchiectasis in such patients may have right middle lobe and lingular predominance, and infertility in males or dextrocardia may be present. Nasal or oral exhaled nitric oxide level is frequently low. Definitive diagnosis requires examination of a nasal or bronchial epithelial sample for abnormal ciliary structure using transmission electron microscopy.

The diagnosis of PCD should typically be done in specialized centers because evaluation can be challenging. Nonspecific structural defects can be present in up to 10% of cilia in healthy people and in patients with pulmonary disease, and infection can cause transient dyskinesia. Ciliary ultrastructure may also be normal in some patients with PCD syndromes, requiring further testing to identify abnormal ciliary function.

Bronchoscopy is indicated when an anatomic or obstructive lesion is suspected.

A bronchiectasis exacerbation is defined as a patient with bronchiectasis with deterioration for at least 48 hours in ≥ 3 of the following symptoms (1 Diagnosis reference Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more ):

The degree of testing depends on the severity of the clinical presentation. For patients with mild to moderate exacerbations, repeat sputum cultures to confirm the causative organism and sensitivity patterns may be sufficient. These tests help narrow antibiotic coverage and exclude opportunistic pathogens.

For more severely ill patients, a CBC, chest x-ray, and possibly other tests may be warranted to exclude common complications of serious pulmonary infection, such as lung abscess Lung Abscess Lung abscess is a necrotizing lung infection characterized by a pus-filled cavitary lesion. It is most commonly caused by aspiration of oral secretions by patients who have impaired consciousness... read more and empyema.

Acute exacerbations are treated with antibiotics, inhaled bronchodilators (particularly if patients are wheezing), and increased attempts at mucus clearance, using mechanical techniques, treatment of dehydration (if present), humidification, and nebulized saline (and mucolytics for patients with CF). Inhaled or oral corticosteroids are frequently given to treat airway inflammation and worsening airway obstruction. Antibiotic choice depends on previous culture results and whether or not patients have CF (8 Treatment references Bronchiectasis is dilation and destruction of larger bronchi caused by chronic infection and inflammation. Common causes are cystic fibrosis, immune defects, and recurrent infections, though... read more ).

Initial antibiotics for patients without CF and with no prior culture results should be effective against H. influenzae, M. catarrhalis, S. aureus, and S. pneumoniae. Examples include amoxicillin/clavulanate, azithromycin, clarithromycin, and trimethoprim/sulfamethoxazole. Patients with known P. aeruginosa colonization or more severe exacerbations should receive antibiotics effective against this organism (eg, ciprofloxacin 500 mg orally twice a day or levofloxacin 500 mg orally once a day) until repeat culture results are available. Antibiotics should be adjusted based on culture results and are given for a typical duration of 14 days, especially if P. aeruginosa is detected. Shorter courses are reserved for patients with mild disease.

Initial antibiotic selection for patients with CF is guided by previous sputum culture results (done routinely in all patients with CF). During childhood, common infecting organisms are S. aureus and H. influenzae, and quinolone antibiotics such as ciprofloxacin and levofloxacin may be used. In the later stages of CF, infections involve highly resistant strains of certain gram-negative organisms including P. aeruginosa, Burkholderia cepacia, and Stenotrophomonas maltophilia. In patients with infections caused by these organisms, treatment is with multiple antibiotics (eg, tobramycin, aztreonam, ticarcillin/clavulanate, ceftazidime, cefepime). Intravenous administration is frequently required.

Significant hemoptysis is usually treated with bronchial artery embolization, but surgical resection may be considered if embolization is ineffective and pulmonary function is adequate.

Superinfection with mycobacterial organisms Nontuberculous Mycobacterial Infections There are over 170 recognized species of mycobacteria, mostly environmental. Environmental exposure to many of these organisms is common, but most exposures do not cause infection and many infections... read more such as M. avium complex almost always requires multiple drug regimens that include clarithromycin or azithromycin; rifampin or rifabutin; and ethambutol. Drug therapy is typically continued until sputum cultures have been negative for 12 months.

Surgical resection is rarely indicated but may be considered when bronchiectasis is localized, medical therapy has been optimized, and the symptoms are intolerable. In certain patients with diffuse bronchiectasis, especially cystic fibrosis, lung transplantation Lung and Heart-Lung Transplantation Lung or heart-lung transplantation is an option for patients who have respiratory insufficiency or failure and who remain at risk of death despite optimal medical treatment. (See also Overview... read more is also an option.

Five-year survival rates as high as 65 to 75% have been reported when a heart-lung or double lung transplantation is done, and outcomes are similar regardless of whether bronchiectasis was due to CF or another cause. Pulmonary function usually improves within 6 months, and improvement may be sustained for at least 5 years.