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.

Pathophysiology

Bronchiectasis is an abnormal dilation of the proximal and medium-sized bronchi (>2 mm in diameter) caused by weakening or destruction of the muscular and elastic components of the bronchial walls. Affected areas may show a variety of changes, including transmural inflammation, edema, scarring, and ulceration, among other findings. Distal lung parenchyma may also be damaged secondary to persistent microbial infection and frequent post obstructive pneumonia.

Bronchiectasis can be congenital but is most often acquired.

Congenital Bronchiectasis usually affects infants and children. These cases result from developmental arrest of the bronchial tree.

Acquired forms occur in adults and older children and require an infectious insult, impairment of drainage, airway obstruction, and/or a defect in host defense. The tissue is also damaged in part by the host response of neutrophilic proteases, inflammatory cytokines, nitric oxide, and oxygen radicals. This results in damage to the muscular and elastic components of the bronchial wall. Additionally, peribronchial alveolar tissue may be damaged, resulting in diffuse peribronchial fibrosis.

The result is abnormal bronchial dilatation with bronchial wall destruction and transmural inflammation. The most important functional finding of altered airway anatomy is severely impaired clearance of secretions from the bronchial tree.
Impaired clearance of secretions causes colonization and infection with pathogenic organisms, contributing to the purulent expectoration commonly observed in patients with bronchiectasis. The result is further bronchial damage and a vicious cycle of bronchial damage, bronchial dilation, impaired clearance of secretions, recurrent infection, and more bronchial damage.

History

The classic clinical manifestations of bronchiectasis are cough and daily mucopurulent sputum production, often lasting months to years. Blood-streaked sputum or hemoptysis may result from airway damage associated with acute infection. Less specific symptoms include dyspnea, pleuritic chest pain, wheezing, fever, weakness, and weight loss.
A rare variant known as dry bronchiectasis manifests as episodic hemoptysis with little-to-no sputum production. Dry bronchiectasis is usually a sequela of tuberculosis and is found in the upper lobes.
Bronchiectasis is a morphologic diagnosis. Thus, it may exist with relatively few symptoms.
Although patients may report repetitive pulmonary infections that require antibiotics over several years, a single episode of a severe infection, often in childhood, may result in bronchiectasis.^[7] These include tuberculosis, pertussis, or severe bacterial pneumonia. Today, CF is the most common cause of bronchiectasis in children and young adults.^[10]
Exacerbations of bronchiectasis that are caused by acute bacterial infections are often heralded by the onset of increased sputum production over baseline, increased viscidity of sputum, and, occasionally, a foul odor of the sputum. Rarely, low-grade fever may occur. Patients may experience an increase in generalized constitutional symptoms, such as fatigue and malaise, as well as increased dyspnea, shortness of breath, wheezing, or pleuritic pain.
With secondary infection or poorly treated pneumonia, the discrete pathogens are often unknown. However, most patients relate a history of childhood infections that may include tuberculosis, pertussis, or Mycoplasma infection.^[7]
Most individuals have never smoked (55%) or have smoked too little to account for their degree of cough, findings of obstruction on spirometry testing, and daily sputum production.
Chronic productive cough is prominent,^[71] occurring in up to 98% of patients. Sputum is typically produced on a daily basis in greater than 70% of patients, with one study reporting production in 96% of patients.^[72] Some patients produce sputum only with acute upper respiratory tract infections, but otherwise they have quiescent disease.
Sputum is typically mucoid and relatively odorless. During infectious exacerbations, however, sputum becomes purulent and may develop an offensive odor.
In the past, total daily sputum amount has been used to characterize the severity of bronchiectasis, with less than 10 mL defined as mild bronchiectasis, 10-150 mL defined as moderate bronchiectasis, and greater than 150 mL defined as severe bronchiectasis. Today, bronchiectasis is most often classified by radiographic findings. In patients with CF, the volume of sputum produced is generally much greater than that associated with other etiologies of bronchiectasis.
Hemoptysis occurs in 56-92% of patients with bronchiectasis. Hemoptysis is more commonly observed in dry bronchiectasis. Hemoptysis is generally mild and manifested by blood flecks in the patient's usual purulent sputum. This is often the factor that leads patients to consult a physician. Bleeding usually originates from dilated bronchial arteries, which contain blood at systemic (rather than pulmonary) pressures. Therefore, massive hemoptysis may occur but is rarely a cause of death.^{[10, 72, 73]}
Dyspnea may occur in as many as 72% of patients; a 2006 review reported a rate of 62%.^[72] Dyspnea typically occurs in patients with extensive bronchiectasis observed on chest radiographs. Marked dyspnea is more likely to be secondary to a concomitant illness, such as chronic bronchitis or emphysema.
Wheezing is commonly reported and may be due to airflow obstruction following destruction of the bronchial tree. Similar to dyspnea, it may also be secondary to concomitant conditions such as asthma.
Pleuritic chest pain is an intermittent finding, occurring in 19-46% of patients.^[72] It is most commonly secondary to chronic coughing but also occurs in the setting of acute exacerbation.
Fatigue is commonly reported (73% of patients).^[72] Weight loss often occurs in patients with severe bronchiectasis. This is believed to be secondary to increased caloric requirements associated with the increased work of coughing and clearing secretions. Weight loss suggests advanced disease but is not diagnostic of bronchiectasis.
Fever may occur in the setting of acute infectious exacerbations.
Urinary incontinence occurs more frequently in women with bronchiectasis versus age-matched controls (47% vs 12%).^[74] The etiology of this is unclear.

Physical Examination

Findings are nonspecific and may be attributed to other conditions. Most commonly, crackles, rhonchi, wheezing, and inspiratory squeaks may be heard upon auscultation. General findings may include digital clubbing, cyanosis, plethora, wasting, and weight loss. Nasal polyps and signs of chronic sinusitis may also be present. In advanced disease, the physical stigmata of cor pulmonale may be observed. Note the following:

• Crackles and rhonchi are often observed in association with active infections and acute exacerbations
• Crackles are nonspecific and may occur in as many as 73% of patients^[72]
• Scattered wheezing may be heard in approximately one third of patients; wheezing may be due to airflow obstruction from secretions, destruction of the bronchial tree leading to airway collapsibility, or a concomitant condition^{[10, 72]}
• Digital clubbing is an inconsistent finding in approximately 2-3% of patients^[72] ; it is more frequent in patients with moderate-to-severe bronchiectasis
• Cyanosis and plethora are rare findings secondary to polycythemia from chronic hypoxia.

Wasting and weight loss are suggestive of advanced disease but are not diagnostic of bronchiectasis. In severe cases, findings are consistent with cor pulmonale. Right-sided heart failure may be observed, including peripheral edema, hepatomegaly, and hypoxia. This can ultimately lead to progressive respiratory failure.^[69]
Cystic fibrosis (CF), Young syndrome, primary ciliary dyskinesia, and alpha1-antitrypsin (AAT) deficiency require aggressive treatment, as well as genetic counseling for patients and their families. Likewise, congenital abnormalities should be identified as such for the patient and their family.
Foreign body obstruction needs to be excluded as an etiology in all patients.

Differentials

• Alpha1-Antitrypsin Deficiency
• Asthma
• Bronchitis
• Chronic Bronchitis
• Chronic Obstructive Pulmonary Disease
• Cystic Fibrosis
• Emphysema
• Empyema, Pleuropulmonary
• Gastroesophageal Reflux Disease
• Pneumonia, Aspiration
• Pneumonia, Bacterial
• Tuberculosis

In a typical patient, bronchiectasis is suspected on the basis of the clinical presentation, especially if purulent sputum is present and other conditions (eg, pneumonia, lung abscess) have been ruled out. A sputum analysis may be used to further strengthen clinical suspicion.
Radiographic studies, specifically CT scanning, then may be used to confirm the diagnosis. Once the diagnosis is confirmed, additional laboratory testing may be useful to determine the underlying cause. Although many causes are untreatable, identifying treatable conditions is paramount. In a significant percentage of patients, no readily identifiable cause is found.
The choice of laboratory tests may vary and should be tailored to the individual patient and clinical situation. However, high-resolution CT (HRCT) scanning is the criterion standard for the diagnosis of bronchiectasis.^{[75, 76, 77]}
The anatomical distribution of bronchiectasis may be important in helping diagnose any associated condition or cause of bronchiectasis, as follows:

• Bronchiectasis as a result of infection generally involves the lower lobes, the right-middle lobe, and the lingula
• Right-middle lobe involvement alone suggests right-middle lobe syndrome, an anatomic dysfunction, or a neoplastic cause with secondary mechanical obstruction
• Bronchiectasis caused by cystic fibrosis (CF), Mycobacterium tuberculosis infection , or chronic fungal infections tends to affect the upper lobes, although this is not universal in CF
• Allergic bronchopulmonary aspergillosis (ABPA) also affects the upper lobes but usually involves the central bronchi, whereas most other forms of bronchiectasis involve distal bronchial segments

Sputum Analysis

A sputum analysis may reinforce the diagnosis of bronchiectasis and add significant information regarding potential etiologies. Once sputum is allowed to settle, the examination may reveal Dittrich plugs, small white or yellow concretions. A Gram stain and culture result may reveal evidence of microorganisms, including mucoid Pseudomonas species and Escherichia coli, which suggest CF but are not diagnostic.
Chronic bronchial infection with nonmucoid Pseudomonas aeruginosa is becoming much more common in patients with non-CF bronchiectasis. The presence of eosinophils and golden plugs containing hyphae suggests Aspergillus species, although this finding alone is not diagnostic of ABPA.
Perform a smear and culture of sputum for mycobacteria and fungi. Atypical mycobacterial infection is a common cause of bronchiectasis in the older population, especially in those with underlying structural lung disease.

Complete Blood Count

The CBC is often abnormal in patients with bronchiectasis. Typical findings are nonspecific and include anemia and an elevated white blood cell count with an increased percentage of neutrophils. An increased percentage of eosinophils is one criterion for ABPA. Alternatively, polycythemia secondary to chronic hypoxia may be observed in advanced cases.

Quantitative Immunoglobulin levels

Quantitative immunoglobulin levels, including IgG subclasses, IgM, and IgA, are useful to exclude hypogammaglobulinemia. Note, however, that on rare occasions, bronchiectasis may be seen in patients with antibody production deficiency but normal to low-normal IgG levels. In situations such as these, evaluating antibody response to Haemophilus influenzae and pneumococcal vacComputed Tomography

CT scanning (see the image below), particularly high-resolution CT (HRCT) scanning of the chest, has replaced bronchography as the defining modality of bronchiectasis. CT sensitivity and specificity reportedly are 84-97% and 82-99%, respectively, but may be higher at referral centers.^[78]
Additional advantages of HRCT scanning include noninvasiveness, avoidance of possible allergic reactions to contrast media, and information regarding other pulmonary processes. The 3 forms of bronchiectasis in the Reid classification can be visualized by HRCT.^[6]

This CT scan depicts areas of both cystic bronchiectasis and varicose bronchiectasis.

The following are noteworthy aspects of CT findings in bronchiectasis:

• Cylindrical bronchiectasis has parallel tram track lines, or it may have a signet-ring appearance composed of a dilated bronchus cut in a horizontal section with an adjacent pulmonary artery representing the stone
• The diameter of the bronchus lumen is normally 1-1.5 times that of the adjacent vessel; a diameter greater than 1.5 times that of the adjacent vessel is suggestive of bronchiectasis
• Varicose bronchiectasis has irregular or beaded bronchi, with alternating areas of dilatation and constriction
• Cystic bronchiectasis has large cystic spaces and a honeycomb appearance; this contrasts with the blebs of emphysema, which have thinner walls and are not accompanied by proximal airway abnormalities

For more information on the radiologic approach to bronchiectasis, see Bronchiectasis Imaging.

Radiography

Posterior-anterior and lateral chest radiographs should be obtained in all patients. Expected general findings include increased pulmonary markings, honeycombing, atelectasis, and pleural changes. Specific findings may include linear lucencies and parallel markings radiating from the hila (tram tracking) in cylindrical bronchiectasis, dilated bronchi in varicose bronchiectasis, and clustered cysts in cystic bronchiectasis. In the appropriate clinical setting, chest radiograph findings are occasionally sufficient for confirming the diagnosis of bronchiectas
The goals of therapy are to improve symptoms, to reduce complications, to control exacerbations, and to reduce morbidity and mortality. Early recognition is essential in bronchiectasis and associated conditions. Additionally, management of underlying conditions, which may include the use of intravenous immunoglobulin or intravenous alpha1-antitrypsin (AAT) therapy, is essential to the overall treatment.
Antibiotics and chest physiotherapy are the mainstay modalities. Other modalities (beyond those for specific associated conditions) may include bronchodilators, corticosteroid therapy, dietary supplementation, and oxygen or surgical therapies. Admitting patients with severe exacerbations of bronchiectasis to the hospital and treating them with intravenous antibiotics, bronchodilators, aggressive physiotherapy, and supplemental nutrition is not uncommon.
Aggressively pursue and treat any associated or known causal condition of the bronchiectasis. The scope of therapies for these associated medical conditions, such as mycobacterial disease and CF, is beyond the scope of this article. See Cystic Fibrosis and Mycobacterium Avium-Intracellulare.
Available treatment guidelines include Chronic cough due to bronchiectasis: ACCP evidence-based clinical practice guidelines and Pulmonary rehabilitation: joint ACCP/AACVPR evidence-based clinical practice guidelines.

Supportive Treatment

The following general measures are recommended:

• Smoking cessation
• Avoidance of second-hand smoke
• Adequate nutritional intake with supplementation, if necessary
• Immunizations for influenza and pneumococcal pneumonia^{[81, 82]}
• Confirmation of immunizations for measles, rubeola, and pertussis

Oxygen therapy is reserved for patients who are hypoxemic with severe disease and end-stage complications, such as cor pulmonale.
Patients with cystic fibrosis (CF) should be cared for at specialized CF treatment centers that address all aspects of the disease, including nutritional and psychologic aspects.

Antibiotic Therapy

Antibiotics have been the mainstay of treatment for more than 40 years. Oral, parenteral, and aerosolized antibiotics are used, depending on the clinical situation.
In acute exacerbations, broad-spectrum antibacterial agents are generally preferred. However, if time and the clinical situation allows, sampling of respiratory secretions during an acute exacerbation may allow treatment with antibiotics based on specific species identification.
Acceptable choices for the outpatient who is mild to moderately ill include any of the following:

• Amoxicillin
• Tetracycline
• Trimethoprim-sulfamethoxazole
• A newer macrolide (eg, azithromycin^[83] or clarithromycin^{[84, 85]} )
• A second-generation cephalosporin
• A fluoroquinolone

In general, the duration of antibiotic therapy for mild to moderate illness is 7-10 days.
For patients with moderate-to-severe symptoms, parenteral antibiotics, such as an aminoglycoside (gentamicin, tobramycin) and an antipseudomonal synthetic penicillin, a third-generation cephalosporin, or a fluoroquinolone, may be indicated. Patients with bronchiectasis from CF are often infected with mucoid Pseudomonas species, and, as such, tobramycin is often the drug of choice for acute exacerbation.
Infection with Mycobacterium avium complex (MAC) provides special treatment challenges. For the treatment of MAC in the setting of bronchiectasis, the American Thoracic Society recommends a 3- to 4-drug treatment regimen with clarithromycin, rifampin, ethambutol, and possibly streptomycin that is continued until the patient's culture results are negative for 1 year. The typical duration of therapy may be 18-24 months.

Regular antibiotic regimens

Some patients with chronic bronchial infections may need regular antibiotic treatment to control the infectious process. Some clinicians prefer to prescribe antibiotics on a regular basis or for a set number of weeks each month.
The oral antibiotics of choice are the same as those mentioned previously. Potential regimens include daily antibiotics for 7-14 days of each month, alternating antibiotics for 7-10 days with antibiotic-free periods of 7-10 days, or a long-term daily dose of antibiotics. For patients with severe CF and bronchiectasis, intermittent courses of intravenous antibiotics are sometimes used.^{[86, 87]}

Aerosolized antibiotics

In the past several years, the nebulized route of antibiotic administration has received more attention because it is capable of delivering relatively high concentrations of drugs locally with relatively few systemic adverse effects.^[88] This is particularly beneficial in treating patients with chronic infection from P aeruginosa. Currently, inhaled tobramycin is the most widely used nebulized treatment for patients with bronchiectasis from either CF or non-CF causes of bronchiectasis.^{[89, 90, 91, 92, 93]} Gentamicin^[94] and colistin^[95] have also been used.
No significant studies have examined the long-term use of inhaled antibiotics in patients with non-CF bronchiectasis. A study by Govan et al found sustained long-term benefit (12 mo) of inhaled gentamicin in this subgroup, along with an acceptable side effect profile.^[96] Optimal dosing regimen of inhaled gentamicin still needs to be elucidated.

Bronchial Hygiene

Good bronchial hygiene is paramount in the treatment of bronchiectasis, because of the tenacious sputum and defects in clearance of mucus in these patients. Postural drainage with percussion and vibration is used to loosen and mobilize secretions.
Devices available to assist with mucus clearance include flutter devices,^{[97, 98]} intrapulmonic percussive ventilation devices, and incentive spirometry.^[99] Although consistent benefits from these techniques are lacking and vary with patient motivation and knowledge, a review did report improvement in patients’ cough-related quality of life scores.^[100]
A relatively new device called the "Vest" system is a pneumatic compression device/vest that is worn by the patient periodically throughout the day. It is essentially technique independent and has variable success, especially in patients with CF. Significant controlled trials have not been performed in patients with non-CF bronchiectasis.
Nebulization with concentrated (7%) sodium chloride solutions appears to be beneficial, particularly in patients with CF-related bronchiectasis.^{[101, 102, 103]} Mucolytics, such as acetylcysteine, are also often tried but do not appear to be universally beneficial. However, maintaining adequate general hydration, which may improve the viscidity of secretions, is important.
Aerosolized recombinant DNase has been shown to benefit patients with CF.^{[104, 105]} This enzyme breaks down DNA released by neutrophils, which accumulates in the airways in response to chronic bacterial infection. However, improvement has not been definitively shown in patients with bronchiectasis from other causes.^[106]

Bronchodilator Therapy

Bronchodilators, including beta-agonists and anticholinergics, may help some patients with bronchiectasis, presumably reversing bronchospasm associated with airway hyperreactivity and improving mucociliary clearance.^{[107, 108, 109]} High-quality, large, randomized clinical trials of bronchAnti-inflammatory Therapy

The rationale of anti-inflammatory therapy is to modify the inflammatory response caused by the microorganisms associated with bronchiectasis and subsequently reduce the amount of tissue damage. Inhaled corticosteroids,^[110] oral corticosteroids,^[111] leukotriene inhibitors,^[112] and nonsteroidal anti-inflammatory agents^[112] have all been examined.
Although evidence suggests some benefit from the use of these agents, findings are not universally definitive. One study reported that inhaled corticosteroids are beneficial compared with placebo in patients with bronchiectasis, particularly those with associated P aeruginosa infections.^[113]
A double-blind, placebo controlled 6-week crossover study with 20 patients using beclomethasone dipropionate (750 mcg bid) showed reduced mean sputum volume and improved forced expiratory volume in 1 second (FEV₁) at 6 weeks. A similar study of 24 patients using fluticasone propionate (500 mcg bid) showed reduced sputum leukocyte density and reduced levels of inflammatory mediators but no change in pulmonary function.
A study by Tsang et al showed benefit of inhaled fluticasone in patients with chronic P aeruginosa infection and bronchiectasis.^[113] Another study showed improvement in quality-of-life scores with inhaled steroids in patients with steady-state bronchiectasis.^[114]
Azithromycin has known anti-inflammatory properties and long-term use has been studied in patients with both CF and non-CF bronchiectasis. In non-CF patients, azithromycin has been shown to decrease exacerbations and improve spirometry and microbiologic profiles.^[115] In CF patients a meta-analysis suggests that it improves lung function, especially in those patients colonized with Pseudomonas.^[103]
A practical approach is to use tapering oral corticosteroids and antibiotics for acute exacerbations and to consider inhaled corticosteroids for daily use in patients with significant obstructive physiology on pulmonary function testing and evidence of reversibility suggesting airway hyperreactivity. However, Kapur et al reported that the evidence supporting the use of inhaled steroids in adults with stable bronchiectasis is insufficient.^[116]
odilator treatment in bronchiectasis have not been performed, however.

Medication Summary

No specific medical therapy exists for the treatment of bronchiectasis. Pharmacologic therapy focuses on the treatment of infectious exacerbations that these patients commonly experience, most often in the form of an acute bronchitis-type syndrome.
The most widely accepted and commonly used medications in the treatment of acute infectious processes associated with bronchiectasis include antibiotics, beta-agonists, inhaled corticosteroids, and expectorants. Other more controversial medications have been previously mentioned in this article for completeness but are not discussed here