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Causes[edit]

There are many causes that can induce or contribute to the development of bronchiectasis. The frequency of the different causes varies with geographic location.[1] Cystic fibrosis is identifed as a cause in up to half of cases.[2] Bronchiectasis without CF is known as non-CF bronchiectasis. Historically, about half of all case of non-CF bronchiectasis were found to be idiopathic, or without a known cause.[3] However, more recent studies using a more comprehensive evauation have found a etiology in 60 to 90% of patients.[4][5][6]

Cystic fibrosis[edit]

Cystic fibrosis is the most common life-threatening autosomal recessive disease in the United States and Europe.[7] It is a genetic disorder that affects the lungs, but also the pancreas, liver, kidneys, and intestine.[8] It is caused by mutations in the CFTR protein, a chloride channel expressed in epithelial cells.[9] Lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation.[10] In later stages, changes to the structure of the lung, such as bronchiectasis, occur. Around 5 to 10% of all patients with cystic fibrosis develop bronchiectasis.[11]

Airway obstruction[edit]

An airway obstruction can be caused by an either a intraluminal mass such as a tumor or a foreign body.[12] The presence of an airway obstruction leads to a cycle of inflammation.[13] It is important to identify the presence of an obstruction because surgical resection is often curative if obstruction is the cause.[14] In adults, foregn body aspiration is often associated with an altered state of consciousness. The foreign body is often unchewed food, or part of a tooth or crown.[15] Bronchiectasis that results from foregn body aspiration generally occurs in the right lung in the lower lobes or posterior segments of the upper lobes.[16]

Pulmonary infections[edit]

A range of bacterial, mycobacterial, and viral lung infections are asociated with the development of bronchiectasis. Bacterial infections commonly associated with bronchiectasis include P. aeruginosa, H. influenzae, and S. pneumoniae.[17] Gram-negative bacteria are more commonly implicated than gram-positive organism.[18] A history of mycobacterial infections such as tuberculosis can lead to damage of the airways that predisposes to bacterial colonization.[19] Severe viral infections in childhood can also lead to bronchiectasis through a similar mechanism.[20] Nontuberculous mycobacteria infections such as mycobacterium avium complex are found to be a cause in some patients.[21] Recent studies have also shown Nocardia infections to been implicated in bronchiectasis.[22]

Impaired host defenses[edit]

Impairments in host defenses that lead to bronchiectasis may be congenital, such as with primary ciliary dyskinesia, or acquired, as with the prolonged use of immunosuppressive drugs.[23] Additionally, these impairments may be localized to the lungs, or systemic throughout the body. In these states of immunodeficiency, there is a weakened immune system response to severe infections that repeatedly affect the lung and eventually result in bronchial wall injury.[24] HIV/AIDS is an example of an acquired immunodeficiency that can lead to the development of bronchiectasis.[25]

Allergic bronchopulmonary aspergillosis[edit]

Allergic bronchopulmonary aspergillosis is an inflammatory disease caused by hypersensitivity to the fungus Aspergillus fumigatus.[26] It is suspected in patients with a long history of asthma and symptoms of bronchiectasis such as a productive, mucopurulent cough.[27] Imaging often shows peripheral and central airway bronchiectasis, which is unusual in patients with bronchiectasis caused by other disorders.[28]

Autoimmune diseases[edit]

Several autoimmune diseases have been associated with bronchiectasis. Specifically, individuals with rheumatoid arthritis and Sjögren syndrome have increased rates of bronchiectasis.[29][30] In these diseases, the symptoms of bronchiectasis usually presents later.[31] Other autoimmune disesases such as ulcerative colitis and Crohn's disease also have an association with bronchiectasis.[32] Additionally, graft-versus-host disease in patients who have underwent stem cell transplantation can lead to bronchiectasis as well.[33]

Injury[edit]

Inhalation of ammonia and other toxic gases can cause bronchiectasis.[34] Chronic pulmonary aspiration of stomach acid from esophageal reflux or a hiatal hernia can also lead to bronchiectasis.[35]

Congenital Causes[edit]

Bronchiectasis may result from congenital disorders that affect cilia motility or ion transport.[36] A common genetic cause is cystic fibrosis, which affects chloride ion transport.[37] Primary ciliary dyskinesia is a rare genetic disorder that leads to immotility of cilia and can lead to situs inversus.[38] When situs inversus is accompanied by chronic sinusitis and bronchiectasis, this is known as Kartagener's syndrome.[39] Other rarer causes include Young's syndrome[40] and Williams-Campbell syndrome.[41] Individuals with alpha 1-antitrypsin deficiency have been found to be particularly susceptible to bronchiectasis, due to the loss of inhibition to enzyme elastase which cleaves elastin.[42] This decreases the ability of the alveoli to return to normal shape during expiration.[43]

Cigarette smoking and COPD[edit]

A causal role for cigarette smoking in bronchiectasis has not been demonstrated.[44] Nonetheless, cigarette smoking can worsen pulmonary function and accelerate the progression of disease that is already present.[45][46]

Bronchiectasis secondary to a large carcinoid tumor (not shown) that was completely obstructing the bronchus proximally. The yellowish discoloration of lung parenchyma reflects obstructive pneumonia.


Causes of Bronchiectasis
Category Etiologies
Autoimmune disease Rheumatoid arthritis

Sjögren syndrome

Impaired host defenses Cystic fibrosis

Primary ciliary dyskinesia

Primary immunodeficiency

HIV/AIDS

Job's syndrome

Post-infective Bacterial pneumonia

Mycobacterium infection

Congenital Tracheobronchomegaly (Mounier-Kuhn syndrome)

Marfan syndrome

Williams–Campbell syndrome

Alpha-1 antitrypsin deficiency

Hypersensitivity Allergic bronchopulmonary aspergillosis
Inflammatory bowel disease Ulcerative colitis

Crohn's disease

Malignancy Chronic lymphocytic leukemia

Graft-versus-host disease

Obstruction Tumor

Foreign body aspiration

Lymphadenopathy

Other Pneumonia

Chronic aspiration

Smoke inhalation

Radiation-induced lung disease

Yellow nail syndrome


Management[edit]

A comprehensive approach to the management of bronchiectasis is essential.[47] It is important to establish whether an underlying modifiable cause, such as immunoglobulin deficiency or alpha-1 antitrypsin deficiency is present.[48] The next steps include controlling infections and bronchial secretions, relieving airway obstructions, removing affected portions of lung by surgery, and preventing complications.[49]

Airway Clearance[edit]

The goal of airway clearance is to loosen secretions and interrupt the cycle of inflammation and infection.[50] Airway clearance techniques improve breathlessness, cough, and help patients cough up phlegm and mucus plugs.[51] Airway clearance usually employs an inhaled agent (hypertonic saline) with chest physiotherapy, such as high-frequency chest wall oscillation.[52] Many airway clearance techniques and devices exist. The choice of a technique or device is based on the the frequency and tenacity of phlegm, patient comfort, cost, and the patient's ability to use the the technique or device with minimal interference to their lifestyle.[53] Mucolytic agents such as dornase alfa are not recommended for individuals with non-CF bronchiectasis.[2] Mannitol is a hyperosmolar agent that is thought to hydrate airway secretions, however, clinical trials with it have failed to demonstrate efficacy.[54]

Bronchodilators[edit]

Some clinical trials have shown a benefit with inhaled bronchodilators in select patients with bronchiectasis.[2] In patients with demonstrated bronchodilator reversibility on spirometry, the use of inhaled bronchodilators resulted in improved dyspnea, cough, and quality of life without any increase in adverse events.[55] However, overall there is a lack of data to recommend use of bronchodilators in all patients with bronchiectasis.[56]

Anti-inflammatory therapies[edit]

The two most commonly used classes of anti-inflammatory therapies are macrolides and corticosteroids.[2]

Macrolides exert immunomodulatory effects on the host inflammatory reponse without systemic suppression of the immune system.[2] These effects include modifying mucus production, inhibitition of biofilm production, and suppression of nflammatory mediators.[18] Three large multicenter, randomized trials have shown reduced rates of exacerbations and improved cough and dyspnea with use of macrolide therapy.[57] The impact of adverse effects of macrolides such as gastrointestinal symptoms, hepatotoxicity, and increased antimicrobial resistance needs ongoing review and study.[58]

Inhaled corticosteroid therapy to can reduce sputum production and decrease airway constriction over a period of time, helping prevent progression of bronchiectasis.[59] Long term use of high-dose inhaled corticosteroids can lead to adverse conseqeunces such as cataracts and osteoporosis.[2] It is not recommended for routine use in children.[60] One commonly used therapy is beclometasone dipropionate.[61]

Antibiotics[edit]

Antibiotics are used in bronchiectasis to eradicate P. aeruginosa or MRSA, to suppress the burden of chronic bacterial colonization, and to treat exacerbations.[2] The use of daily oral nonmacrolide antibiotic treatment has been studied in small case series, but not in randomized trials.[62] The role of inhaled antibiotics in non-CF bronchiectasis has recently evolved with two society guidelines and a systematic review suggesting a therapeutic trial of inhaled antibiotics in patients with three or more exacerbations per year and P. aeruginosa in their sputum.[63][64] Options for inhaled antibiotics include aerosolized tobramycin, inhaled ciprofloxacin, aerosolized aztreonam, and aerosolized colistin.[18]

Surgery[edit]

The primary role of surgery in the management of bronchiectasis is in localized disease to remove segments of lung or to control massive hemoptysis.[18] Additionally, surgery is used to remove an airway obstruction that is contributing to bronchiectasis. The goals are conservative, aiming to control specific disease manifestations rather than cure or eliminate all areas of bronchiectasis.[65] Surgical case series have shown low operative mortality (less than 2%) and improvement of symptoms in the majority of patients selected to receive surgery.[66] However, no randomized clinical trials have been performed evaluating the efficacy of surgery in bronchiectasis.[65]




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