OVERVIEW: What every practitioner needs to know

Are you sure your patient has bronchiectasis? What are the typical findings for this disease?

Bronchiectasis is defined as dilatation of the bronchi usually associated with thickened bronchial walls and decreased airway wall stiffness. The most common symptoms are chronic cough, usually productive or wet, and recurrent chest infections. Patients may also have dyspnea or wheezing or persistently abnormal chest radiographs. Figure 1 and Figure 2 demonstrate the typical findings of bronchiectasis on the frontal and lateral chest radiograph. Figure 3 and Figure 4 demonstrate the typical findings of bronchiectasis on chest computed tomographic scan. Figure 5 shows the typical airflow obstruction at low lung volume that is seen with bronchiectasis.

What other disease/condition shares some of these symptoms?

Identification of bronchiectasis simply identifies structural airway damage without detection of an underlying disease process to explain the cause of the damage. Once identified, a specific underlying disease should be sought to explain why the bronchiectasis is present. It should be noted that despite extensive investigation, bronchiectasis will remain “idiopathic” in up to 50% of patients.

What caused this disease to develop at this time?

The most common cause of bronchiectasis in North American children is cystic fibrosis (CF). Currently all states screen for CF in the newborn period. Steatorrhea and failure to thrive are also common features of CF.

Immunodeficiency states that predispose the child to repeated lower respiratory tract infections are another common underlying cause of bronchiectasis. If repeated infections are concentrated in the sinopulmonary regions, IgG or IgA deficiency is likely; if there are severe recurrent multisystem infections, a more serious immunodeficiency (e.g., T-cell deficiency or HIV infection) may be present. Neutrophil dysfunction is another potential underlying immunodeficiency.

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Severe lower respiratory tract infections can cause bronchiectasis. The cause varies with geographic location and immunization status. These infections might include measles, varicella, adenovirus, Mycobacterium tuberculosis, atypical mycobacterium, Mycoplasma, Streptococcus, Staphylococcus, and pertussis.

Repeated aspiration, either due to swallowing dysfunction or after gastroesophageal reflux, often leads to bronchiectasis. Inhalation of toxic gases, such as chlorine or ammonia, can cause bronchiectasis.

Primary ciliary dyskinesia (PCD), also known as immotile cilia syndrome, is a genetic disorder of ciliary function that can lead to bronchiectasis. Chronic otitis and rhinitis with recurrent sinusitis are nearly universal. Fifty percent of PCD patients will have dextrocardia and situs inversus (Kartagener syndrome).

Bronchiectasis can occur distal to an airway obstruction such as a retained airway foreign body or compressed airway from adenopathy. In children, endobronchial tumors are rare.

Allergic bronchopulmonary aspergillosis, or allergic bronchopulmonary mycosis, can cause bronchiectasis. This is usually a complication of long-standing asthma or CF.

Bronchiectasis rarely occurs as a complication of rheumatic or autoimmune disease or inflammatory bowel disease in children.

Congenital bronchiectasis may be seen with Williams-Campbell syndrome, Mournier Kuhn syndrome, or yellow nail syndrome. Bronchiectasis may occur in connective tissue deficiency syndromes such as Marfan syndrome or Ehlers-Danlos syndrome. Bronchiectasis may be seen with some bronchopulmonary foregut malformations such as sequestration.

Pathophysiologic Characteristics of Bronchiectasis

Bronchiectasis usually occurs after either significant airway injury or infection or as a result of long-standing airway inflammation. It can be present acutely after an infection or insult, with resolution on healing, or it can progress to irreversible airway damage. Depending on the underlying cause, bronchiectasis can be localized or diffuse. Once significant airway damage has occurred, a vicious cycle of impaired mucociliary clearance, recurrent or persisting infection, and a robust inflammatory reaction leads to self-perpetuating and progressive airway damage.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

The diagnosis of bronchiectasis is made by high-resolution chest computed tomography (CT). Bronchography is seldom indicated. Once bronchiectasis has been identified, an underlying cause should be sought.

CT findings may include airway lumen of greater diameter than adjacent blood vessel (signet ring sign), “tram track” linear markings, extension of airway markings to the periphery, lack of airway tapering toward the periphery, mucus plugging with centrilobular opacities (“tree in bud”), focal air trapping on prone or expiratory view, and mucus plugging.

Would imaging studies be helpful? If so, which ones?

Findings on chest radiograph that might suggest bronchiectasis include increased interstitial markings, thickened airway walls, dilatated airway lumens, overinflation, or chronic atelectasis.

Confirming the diagnosis

Once the diagnosis of bronchiectasis is made, additional studies looking for a potential underlying cause should be initiated. The clinical history and examination may help direct the evaluation.

Sweat chloride determination for CF (or DNA analysis for CF mutations)

Immunology assessment: complete blood count with differential, serum immunoglobulins, T- and B-cell numbers, antibody response to immunizations, neutrophil function, compliment levels

Tests for infection: Tuberculin skin test (TST, formerly PPD), serologic tests (before and after convalescence if possible), cultures

Tests for aspiration: modified barium swallow (also known as videofluoroscopic swallow study), upper gastrointestinal, pH and impedence probe, radionucleotide milk scan

Tests for allergic bronchopulmonary aspergillosis: Aspergillus skin test, total IgE, IgE specific for Aspergillus, IgG spedific for Aspergillus

Electron microscopic assessment of ciliary ultrastructure for PCD

Tests for airway obstruction (intrinsic or extrinsic): bronchoscopy, chest CT

Pulmonary function testing for children old enough to perform the tests well (usually after age 3-4 years of age) is unlikely to help with diagnosis, but may be a good longitudinal marker of treatment response or disease progression.

If you are able to confirm that the patient has bronchiectasis, what treatment should be initiated?

Most therapy recommended for bronchiectasis is adapted from other suppurative lung conditions such as CF. If an underlying disease that predisposes to bronchiectasis has been identified, initiate therapy directed at that cause. An example might be intravenous immunoglobulin infusions for IgG deficiency. Care for children with CF should be carried out at a specialized accredited center if at all possible.

If the patient is acutely ill with an exacerbation, start supplemental oxygen; if the patient is hypoxic, start empirical antibiotic therapy (directed by culture results if available), and start airway clearance (e.g., chest physical therapy and postural drainage). Inhalation of a short-acting beta agonist (e.g., albuterol) may be helpful. Use of mucolytics (rhDNase, mannitol, hypertonic saline) is controversial and may cause deterioration. Acute exacerbations or deteriorations are often treated in the hospital setting.

For stable patients who are not acutely ill with bronchiectasis, daily airway clearance is recommended. The frequency depends on the severity of cough and sputum production. There are several available options, with no specific technique superior to another: chest percussion, postural drainage, forced exhalation techniques, autogenic drainage, exercise, flutter valve, acapella valve, high-frequency chest compression, positive expiratory pressure valve, and intrapulmonary percussion.

If bronchial reactivity is present (similar to asthma) short-acting beta agonists may help. Inhaled corticosteroids may have some benefit in adults but have not been carefully studied in childhood bronchiectasis.

Use of mucolytics is not well studied, although they are often used. Similarly the use of thrice-weekly macrolides is not well studied in children with non-CF bronchiectasis, but they are often prescribed.

Antibiotics are usually reserved for acute exacerbations and selected based on current or previous culture results. If Pseudomonas is present, attempts at eradication are often recommended in a similar as used in CF protocols (usually inhaled tobramycin and an oral fluoroquinolone). If no culture results are available, antibiotics directed at Streptococcus pneumoniae, Haemophilus influenzae, methicillin-sensitive Staphylococcus aureus, and Moraxella catarrhalis are used.

Local sensitivity patterns should help select the specific antibiotic. High-dose amoxicillin is often the first line of therapy. The role of prophylactic or long-term antibiotic use is unknown, but such regimens raise concern about adverse antibiotic pressure and development of resistance.

Surgical resection of bronchiectatic areas should be reserved for life-threatening hemoptysis in which bronchial artery embolization has failed or for isolated segmental bronchiectasis that is persistently symptomatic despite aggressive medical management.

For progressive end-stage lung disease, double lung transplantation may be an option. CF is a common indication for lung transplantation in some centers.

What are the possible outcomes of bronchiectasis?

The prognosis depends on what, if any, underlying condition has caused the bronchiectasis and how severe the airway damage is at the time of diagnosis. For CF, the patient’s life span is likely to be shortened considerably. If aggressive medical treatment is effective, progression of bronchiectasis may be slow and the life span can be normal. Repeated exacerbations requiring intensified treatment are common.

There is little evidence-based medicine to guide therapy. Airway clearance and intermittent antibiotic treatment are generally low risk.

What causes this disease and how frequent is it?

The incidence is unknown; it is perhaps from 3.7 to 52/100,000 population. Prevalence increases with increasing age. Genetically related causes of bronchiectasis include CF (autosomal recessive), PCD (autosomal recessive), and X-linked hypogammaglobulinemia.

How do these pathogens/genes/exposures cause the disease?

Bronchiectasis is believed to result from the vicious cycle of airway insult followed by intense inflammatory response resulting in structural disruption of the airway mucosa and airway wall. This airway disruption impairs normal mucociliary clearance, which causes retained secretions and recurrent infection, perpetuating the inflammatory response. Chronic injury and prolonged inflammation further damages the airway integrity.

What complications might you expect from the disease or treatment of the disease?

Exacerbations of bronchiectasis occur commonly and are manifested by increased cough, sputum production, and malaise. Hospitalization for intravenous antibiotics may be necessary if outpatient oral antibiotics are unsuccessful. Hemoptysis, which can be massive, is a serious complication of bronchiectasis. Progressive bronchiectasis leads to chronic respiratory failure, cor pulmonale, and death.

How can bronchiectasis be prevented?

Children should receive all recommended immunizations.

Smoking and other dangerous air environments should be avoided.

Genetic counseling should be included.

For patients with CF, good nutritional status is related to better pulmonary status.

What is the evidence?

Pasteur, MC, Bilton, D, Hill, AT. “British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis”. Thorax. vol. 65. 2010. pp. i1-58. (Comprehensive and excellent discussion of non-CF bronchiectasis in both adults and children.)

Redding, GJ. “Bronchiectasis in children”. Pediatr Clin North Am. vol. 56. 2009. pp. 157-71.

Stillwell, PC. “Bronchiectasis. In: Light MJ, Homnick DN, Schechter MS, et al, eds. Pediatric Pulmonology”. Elk Grove Village, IL: American Academy of Pediatrics. vol. 2011. pp. 365-75.

Farrell, PM, Rosenstein, BJ, White, TB. “Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report”. J Pediatr. vol. 153. 2008. pp. S4-14.

Flume, PA, O’Sullivan, BP, Robinson, KA. “Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health”. Am J Respir Crit Care Med. vol. 176. 2007. pp. 957-69.

Ongoing controversies regarding etiology, diagnosis, treatment

The diagnosis of bronchiectasis can be challenging, particularly before fairly significant airway damage is visible on chest CT. Similarly, identifying an underlying cause of the bronchiectasis can be challenging. Unlike CF, in which elaborate multicentered research can be conducted to evaluate treatment options, non-CF bronchiectasis faces more obstacles for research success. Exciting research opportunities to better understand the role of inhaled mucolytics (e.g., mannitol, hypertonic saline), inhaled antibiotics, chronic oral antibiotics, and airway clearance techniques are available.