Pulmonary Medicine

Bronchiectasis

What every physician needs to know:

Bronchiectasis is a disorder characterized pathologically by irreversible bronchial dilatation, and clinically by cough, sputum production, and recurrent respiratory tract infections. Although bronchiectasis was first formally described by Laennec in the early nineteenth century, it has likely affected the human race for as long as pneumonia and tuberculosis have. Airway inflammation, mediated predominantly by neutrophils, is the pathophysiologic hallmark of bronchiectasis. The differential diagnosis of the underlying causes of bronchiectasis is broad and includes infections, genetic disorders, and immunodeficiency states, among others.

Classification:

A number of pathologic classifications for bronchiectasis have been proposed. The most widely cited is the Reid classification (1950), which notes three patterns of bronchiectasis: cyclindrical, varicose, and saccular or cystic. However, these anatomic patterns are not reliably associated with or predictive of specific underlying causes of bronchiectasis.

Are you sure your patient has bronchiectasis? What should you expect to find?

The symptoms of bronchiectasis are protean and are both respiratory and systemic in origin. The clinical hallmark is persistent or recurrent cough and sputum production that is often purulent and of large volume. Bronchiectasis should be suspected in individuals, especially non-smokers, who develop frequent respiratory tract infections requiring antibiotic therapy.

Symptoms of bronchiectasis

  • Respiratory: cough, purulent sputum production, hemoptysis, dyspnea, and chest pain.

  • Systemic: fever, chills, lethargy, and anorexia.

Physical examination findings are often subtle and non-specific: crackles, rhonchi, wheezing, or mid-inspiratory squeaks, clubbing, and—in severe, advanced disease—evidence of right heart failure.

Beware: there are other diseases that can mimic bronchiectasis:

Instruction

Studies have reported a lag time of several years between the onset of symptoms and a formal diagnosis of bronchiectasis. Individuals are often initially thought to have:

  • Chronic obstructive lung disease (especially in smokers)

  • Asthma

  • Tuberculosis

  • Chronic sinus disease

How and/or why did the patient develop bronchiectasis?

The epidemiology of bronchiectasis in the United States and elsewhere has not been well described. In general, about two-thirds of patients are women. An estimated 110,000 patients in the United States have bronchiectasis, with an overall prevalence of about 52 cases/100,000 population. The prevalence of bronchiectasis increases with age and is associated with a significant economic cost of care.

Which individuals are at greatest risk of developing bronchiectasis?

The clinical factors that underlie development of bronchiectasis are broad. One approach to the evaluation is based on consideration of the radiographic distribution of disease:

  • Focal disease arises predominantly from sequelae of prior infections or endobronchial obstruction,

  • Diffuse disease is associated with a more expansive list of possible causes. A specific underlying cause of bronchiectasis can be established in about 75 percent of patients and may alter clinical management, underscoring the importance of a well-conceived diagnostic plan.

Predisposing factors for development of bronchiectasis include:

  • Infections: bacterial (pneumonia), mycobacterial, including tuberculosis and non-tuberculous mycobacterial infections, fungal, and viral.

  • Immunodeficiency states: common variable immunodeficiency, primary or secondary hypogammaglobulinemias, and HIV infection.

  • Genetic conditions: cystic fibrosis (CF), 3704 primary ciliary dyskinesia (PCD).

  • Immune-mediated conditions:allergic bronchopulmonary aspergillosis (ABPA). 2755

  • Endobronchial obstruction: foreign bodies and benign or malignant lesions.

  • Collagen vascular disease: rheumatoid arthritis and Sjogren's syndrome.

  • Aspiration pneumonitis

  • Alpha-1-antitrypsin deficiency

  • Inflammatory bowel disease

  • Congenital anatomical anomalies: Mounier-Kuhn syndrome, Swyer-James syndrome, and Williams-Campbell syndrome.

  • Idiopathic

What laboratory studies should you order to help make the diagnosis, and how should you interpret the results?

In evaluations of a patient with suspected bronchiectasis, two goals are preeminent: establishing the diagnosis and using clinical and radiographic data to proceed with an organized and thoughtful approach to identifying an underlying cause.

Basic laboratory studies may be helpful in the evaluation:

  • Sputum gram stain and culture are critical to identifying specific pathogens and directing appropriate antibiotic therapy.

  • CBC with differential count should be obtained.

In selected cases, one should also consider:

  • Serum quantitative immunoglobulin levels, including IgG subclasses

  • Alpha-1-antitrypsin level

  • Serum IgE level and aspergillus precipitins

  • Autoimmune disease serologies, including CRP, RF, ANA, SSA/B, ANCA

  • HIV test

  • CFTR genetic mutation analysis

What imaging studies will be helpful in making or excluding the diagnosis of bronchiectasis?

The high resolution chest CT scan is the most important study used in identifying the presence and distribution of bronchiectasis. Bronchial dilatation, bronchial wall thickening, and the absence of normal airway tapering characterize the disorder (Figure 1) (Figure 2).

Figure 1.

This chest CT scan image demonstrates airway dilatation and bronchial wall thickening, characteristic of bronchiectasis.

Figure 2.

This chest CT scan image demonstrates findings of diffuse bronchiectasis in a coronal plane.

Recognizing the radiographic distribution and pattern of bronchiectasis may also be helpful in suggesting a specific diagnosis. For example, the presence of central bronchiectasis with mucus impaction is highly suggestive of allergic bronchopulmonary aspergillosis (ABPA). 2755 Bronchiectasis involving the right middle lobe and lingula, particularly if associated with nodular densities, is characteristic of nontuberculous mycobacterial infection. 4379

The role of the chest X-ray is relatively limited, as it is often normal or revealing of nonspecific findings.

What non-invasive pulmonary diagnostic studies will be helpful in making or excluding the diagnosis of bronchiectasis?

Pulmonary diagnostic studies are an important part of the work-up of bronchiectasis:

  • Pulmonary function testing 3553, including spirometry before and after bronchodilator administration, measurement of lung volumes, and diffusing capacity, is important in establishing the degree of physiologic impairment. Airflow obstruction, often accompanied by hyperinflation, is a classic finding. The diffusing capacity may be reduced in advanced disease.

  • Cardiopulmonary exercise testing and the six-minute walk test are useful in evaluating ventilatory function and in identifying the presence of exertional hypoxemia.

What diagnostic procedures will be helpful in making or excluding the diagnosis of bronchiectasis?

In selected patients, clinicians should consider:

  • Evaluation for gastroesophageal reflux disease (GERD)

  • Speech Pathology consultation to evaluate possible risk of aspiration

  • Sweat chloride testing for CF

  • Assessment of ciliary function for primary ciliary dyskinesia (PCD)

  • Flexible fiberoptic bronchoscopy (FOB)

  • 1743 FOB is not routinely indicated for the diagnosis of bronchiectasis, but the procedure may be useful in obtaining material for culture and in evaluation of hemoptysis, which commonly complicates bronchiectasis.

What pathology/cytology/genetic studies will be helpful in making or excluding the diagnosis of bronchiectasis?

Genetic studies for entities like CF and primary ciliary dyskinesia may be warranted in some--especially younger patients with diffuse bronchiectasis. The role of pathology and cytology studies in the initial diagnosis of bronchiectasis is generally limited.

If you decide the patient has bronchiectasis, how should the patient be managed?

Management of patients with bronchiectasis is multifaceted and includes both supportive and specific measures. Core therapeutic interventions include antimicrobial therapy, airway clearance techniques, anti-inflammatory agents, surgery, and treatments for specific underlying conditions. Unfortunately, evidence-based data available to guide the clinician in the use of many of these options are lacking.

Antibiotic Therapy

Antibiotic therapy is the mainstay of management of bronchiectasis. Goals include treatment of acute infectious exacerbations and prevention of future episodes.

  • Acute infectious exacerbations of bronchiectasis are characterized by worsening cough, increased sputum volume and purulence, fever, and malaise. Antibiotic choice is best guided by sputum gram stain and culture and antibiotic susceptibility testing. Common pathogens include Haemophilus influenza, Pseudomonas aeruginosa, Streptococcus pneumoniae, and Staphylococcus aureus. An oral respiratory quinolone is a reasonable choice for initial empirical treatment, but antibiotic coverage should be narrowed when possible. The optimal duration of the antibiotic course is not well established, but a minimum of fourteen days is reasonable. Intravenous antibiotics should be used to treat resistant pathogens when dictated by sputum analysis, for severe exacerbations, and in patients who fail to respond to oral antibiotics.

  • Currently, there is considerable interest in the role of aerosolized antibiotics in treating acute and chronic infections with gram negative pathogens, such as Pseudomonas aeruginosa. One advantage of the inhaled delivery route is that high drug concentrations can be achieved in the lung with relatively low systemic absorption. Clinical trials of inhaled tobramycin have demonstrated a positive microbiologic effect, with dramatic reduction in the number of Pseudomonas aeruginosa organisms; however, clinical efficacy has not been conclusively established. A number of clinical trials are currently under way to evaluate the efficacy of other inhaled antibiotics, including aztreonam and ciprofloxacin.

  • A strategy of rotating antibiotics has been used for decades to prevent acute exacerbations of bronchiectasis; however, no evidence-based data are available to support its benefit, and this approach should not be used routinely.

Airway Clearance Techniques

One of the hallmarks of bronchiectasis is the presence of thick, tenacious mucus that is difficult to mobilize and expectorate. Airway clearance techniques are designed to enhance mucociliary clearance and improve ventilatory function. Pharmacologic approaches to enhancing airway clearance include:

  • Bronchodilators: Drugs like albuterol are best used in patients with reversible airflow obstruction. No high-quality studies have been reported that address the efficacy of routine use of bronchodilators in bronchiectasis.

  • Hyperosmolar agents: A 7 percent formulation of nebulized hypertonic saline used twice daily has been found efficacious in cystic fibrosis (CF), but its use has not been evaluated in non-CF bronchiectasis. Nebulized 3 percent saline, used twice daily, is prescribed by some experts on an off-label basis.

  • Use of inhaled mannitol in bronchiectasis is currently the focus of an ongoing international clinical trial.

  • Mucolytics: rhDNA-ase, which is efficacious in CF, should not be used in non-CF bronchiectasis, where it has been shown to be potentially deleterious.

Non-pharmacological methods used in the treatment of bronchiectasis include chest percussion therapy with postural drainage and the use of oscillatory positive expiratory pressure devices and vibration vests. These techniques are widely used and are probably of benefit, but they have not been adequately studied or compared.

Anti-inflammatory Agents

Airway inflammation is an important feature in the pathogenesis of bronchiectasis, so considerable interest has arisen in the potential role of anti-inflammatory therapies.

  • Systemic corticosteroids may be useful for short-term use in the treatment of acute infectious exacerbations of bronchiectasis. However, long-term use of systemic corticosteroids cannot be supported, except for treatment of known steroid-responsive causes, such as ABPA.

  • In small clinical trials, inhaled corticosteroids have been found to decrease sputum volume and sputum inflammatory markers. However, inhaled corticosteroids have not been shown to improve lung function or to reduce the incidence of acute infectious exacerbations.

  • Macrolide antibiotics have potent anti-inflammatory effects and are used in the treatment of other airways diseases, such as CF, diffuse panbronchiolitis, and obliterative bronchiolitis. In bronchiectasis, agents like azithromycin may decrease sputum volume and reduce the frequency of acute exacerbations. Of note, macrolide therapy should be avoided in patients with known or suspected nontuberculous mycobacterial infections. The impact of macrolides on sputum microbiology and resistance patterns has not been adequately studied.

Large, well-designed clinical trials of these anti-inflammatory agents are clearly warranted.

Surgery

Surgery in the management of bronchiectasis is generally reserved for refractory hemoptysis or for those patients who fail medical management,, especially those with focal disease. No studies are available that compare surgical with medical therapy, but retrospective studies have demonstrated that surgery for bronchiectasis may be performed with acceptable morbidity and mortality. Lung transplantation, typically bilateral, is an option for those with advanced disease.

Specific Therapy

When indicated, targeted therapy should be provided for specific conditions underlying bronchiectasis. Examples include systemic corticosteroids for ABPA, immunoglobulin replacement therapy for hypogammaglobulinemias and common variable immunodeficiency (CVID), and antimycobacterial antibiotics for mycobacterial infections.

What is the prognosis for patients managed in the recommended ways?

The natural history and prognosis of bronchiectasis unrelated to cystic fibrosis are not well established. Some studies have suggested a more rapid loss of lung function and an overall worse prognosis than for CF-related bronchiectasis. Respiratory causes appear to account for a majority of deaths. Factors associated with a poor prognosis include advanced age and infection with Pseudomonas aeruginosa.

What other considerations exist for patients with bronchiectasis?

Genetic counseling should be considered for patients with CF and their families; in addition, patients should be referred to a center with expertise in the care of CF. For patients with primary ciliary dyskinesis, consultation with a fertility expert should be considered.

Preventive measures like influenza and pneumococcal vaccinations are also important in patients with bronchiectasis. Nutrition evaluation should be considered for patients with weight loss or evidence of malnutrition.

What’s the evidence?

Weycker, D, Edelsberg, J, Oster, G, Tino, G. "Prevalence and economic burden of bronchiectasis". Clin Pulm Med. vol. 12. 2005. pp. 205-209.

A retrospective review of an insurance claims database to address the prevalence of bronchiectasis in the United States.

Pasteur, MC, Bilton, D, Hill, AT. "Britsh Thoracic Society guideline for non-CF bronchiectasis". Thorax. vol. 65. 2010. pp. i1-i58.

A recently published comprehensive guideline for the diagnosis and management of non-CF bronchiectasis.

O' Donnell, AE. "Bronchiectasis". Chest. vol. 134. 2008. pp. 815-823.

A recent review of non-CF bronchiectasis.

Barker, AF. "Bronchiectasis". N Engl J Med. vol. 346. 2002. pp. 1383-1393.

An older but often cited review of bronchiectasis.

Crosbie, PAJ, Woodhead, MA. "Long-term macrolide therapy in chronic inflammatory airway diseases". Eur Respir J. vol. 33. 2009. pp. 171-181.

This article summarizes the status of macrolide therapy for a number of airway diseases, including bronchiectasis.

Shoemark, A, Ozerovitch, L, Wilson, R. "Aetiology in adult patients with bronchiectasis". Respir Med. vol. 101. 2007. pp. 1163-1170.

A study that reports the causes of bronchiectasis in a cohort of patients from the United Kingdom. A specific cause of bronchiectasis was identified in about 75 percent of patients, and management was altered in about a third of them.

Tsang, KW, Tan, KC, Ho, PL, Ooi, GC, Ho, JC, Mak, J, Tipoe, GL, Ko, C, Yan, C, Lam, WK, Chan-Yeung, M. "Inhaled fluticasone in bronchiectasis: A 12-month study". Thorax. vol. 60. 2005. pp. 239-243.

A clinical trial of 86 patients with bronchiectasis treated with fluticasone for twelve months. Sputum volume was reduced, but the frequency of exacerbations was not. No change in pulmonary function tests was noted.

Bilton, D, Henig, N, Morrisey, B, Gotfried, M. "Addition of inhaled tobramycin to ciprofloxacin for acute exacerbations of Pseudomonas aeruginosa infection in adult bronchiectasis". Chest. vol. 130. 2006. pp. 1503-1510.

A prospective trial that compares ciprofloxacin plus inhaled tobramycin versus ciprofloxacin plus placebo in the treatment of acute exacerbations with Pseudomonas aeruginosa. A significant decrement in organism burden in sputum was noted, but clinical efficacy could not be established.

Loebinger, MR, Wells, AU, Hansell, DM, Chinyanganya, N, Devaraj, A, Meister, M, Wilson, R. "Mortality in bronchiectasis: A long-term study assessing the factors that influence survival". Eur Respir J. vol. 34. 2009. pp. 843-849.

A report on ninety-one patients with bronchiectasis (56% with idiopathic etiology) from the United Kingdom, followed for a period of thirteen years. The death rate was higher than expected. Factors associated with mortality were reported.
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