Pediatric Bronchiectasis Treatment & Management

In addition to the treatment of an identified underlying disorder in patients with bronchiectasis, therapy is aimed at preventing further airway damage and optimizing lung growth by reducing airway secretions and facilitating their removal through airway clearance techniques. The principles of managing bronchiectasis are to identify and treat any underlying cause and associated conditions, prompt diagnosis, treatment and prevention (when possible) of acute exacerbations, managing nutritional and psychosocial issues, improving airway clearance and capacity for physical activity, regular surveillance for complications of bronchiectasis, ongoing education and promotion of general health measures, including avoiding tobacco smoke, encouraging exercise, cough hygiene and recommended vaccinations, and as much as possible normalizing psychological development. 

Pharmacotherapy may be used to enhance bronchodilation and to improve mucociliary clearance.

Antibiotics can be used to prevent and treat recurrent infections, often polymicrobial, and diminish bacterial load and the associated cycle of infection and inflammation. Choice of antibiotics is usually based on the findings of bronchoalveolar lavage or sputum culture. Secretions can be mobilized with chest physiotherapy and mucolytic agents. The goal of therapy is to mobilize secretions and to reduce the infectious and inflammatory load, thereby preventing progression of airway destruction. The main pathogens associated with bronchiectasis are non-typeable H influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas in later disease. Occasionally, surgery may be considered.

As previously stated, treatment for bronchiectasis primarily revolves around antibiotics for infections, airway clearance measures, and bronchodilators for any airway hyperreactivity, with the caveat that this approach is not fully evidence based. Randomized trials of these treatment options lack proper control groups. In children, many of the therapies have been used in cystic fibrosis (CF). However, non-CF bronchiectasis may not always respond the same as CF. The markers used to assess therapy effectiveness have included the volume of sputum production and the clearance of a radiolabeled aerosol from the lung. More meaningful studies that focus on measures such as rate of respiratory exacerbations and quality of life and improvement in lung function and radiographic findings are needed.

Randomized placebo-controlled trials of inhaled corticosteroids in patients with non-CF bronchiectasis showed no significant improvement in lung function. Inhaled corticosteroids may have a role in regulating the host response and halting inflammatory damage to the lung. However, Cochrane reviews and guidelines found no evidence for the effective use of inhaled corticosteroids with or without a long acting beta agonist in children with non-CF bronchiectasis without a history of asthma. ^{[34, 35]} In children with underlying asthma, it is important to continue inhaled corticosteroids on a chronic basis.

A study of 27 children with stable non-CF bronchiectasis looked at the effects of withdrawal of inhaled corticosteroids. ^[36] After 12 weeks, they found the patients had increased airway reactivity and decreased neutrophilic apoptosis in induced sputum, but no change in symptom scores, forced expiratory volume in 1 second (FEV₁), oxygen saturation, sputum neutrophil ratios, sputum tumor necrosis factor-alpha, or interleukin 8. Systemic corticosteroids may be used to treat any acute reactive airway component, when appropriate.

Bronchodilators are indicated when bronchial hyperreactivity is evident. These agents are used to improve ciliary beat frequency and, thus, facilitate mucus clearance. However, no randomized studies have validated their usefulness in the management of bronchiectasis. 

Although beta agonists may improve ciliary function and airway clearance, ensure that they are not adversely affecting lung function. Some patients with bronchiectasis experience paradoxic bronchoconstriction with beta-agonist therapy. This is likely secondary to loss of airway tone due to beta-agonist relaxation of bronchial smooth muscle superimposed on already weakened bronchial cartilage in the bronchiectatic airway. Therefore, assessing bronchodilator response before beginning such therapy is critical. If no significant bronchodilator response is observed, the ciliary effects by themselves are not great enough to warrant such therapy.

Mucolytic drugs are given with the intent of improving tracheobronchial clearance via alteration of sputum consistency. Aerosolized recombinant DNase breaks down DNA released by neutrophils, which accumulates in the airways in response to chronic bacterial infection; however, treatment with this agent has not shown significant benefit in non-CF bronchiectasis. This is presumably due to a lesser component of neutrophils in the airway than in CF. Furthermore, studies have documented evidence of increased exacerbations and hospitalizations when used in patients with non-CF bronchiectasis.  ^[37]

Nebulized acetylcysteine and hypertonic saline are other agents aimed at altering mucous consistency to facility mucus clearance. Nebulized acetylcysteine has not been well studied in patients with non-CF bronchiectasis.  Its use in patients with CF as a mucolytic is based on it’s mechanism of action to depolymerize mucin oligomers. Hypertonic saline is thought to induce liquid flux from the epithelial wall into the mucus allowing increased hydration of airway surface liquid. Hypertonic saline has been shown to aid in the expectoration of secretions, reduce sputum viscosity, improve lung function, decrease sputum pathogenic bacteriology, and improve quality of life in patients with non-CF bronchiectasis. ^[38]

The initial course of treatment may be oral antibiotics and aggressive airway clearance. When possible, antibiotic therapy agents should be tailored to the results of sputum culture.  Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the most common organisms documented in pediatric patients with non-CF bronchiectasis. Staphylococcus aureus and Pseudomonas aeruginosa are most often detected in older children with co-morbidities. ^[39]   Intravenous antibiotic therapy and hospitalization may be necessary for children experiencing exacerbations of endobronchial disease. Exacerbation may be characterized by increased cough or sputum production or changes in pulmonary function. Home intravenous antibiotic therapy may be an option in some situations. Although up to approximately 50% of cases of bronchiectasis exacerbation may be initiated or exacerbated by viruses, antibiotics are considered standard of care due to the perceived high bacterial load density. For an acute exacerbation, antibiotics are recommended for a course of 14 days. 

Antibiotics may be prescribed for long-term use in patients with bronchiectasis to reduce frequency of exacerbations, improve quality of life, and diminish lung function decline. A Cochrane review found that long-term therapy with antibiotics is effective in reducing sputum volume and purulence but has limited impact on the frequency of exacerbations and the natural history of the disease process. ^[40] In addition, long-term antibiotic use may result in the emergence of resistant organisms. A review determined that available evidence shows benefit associated with use of prolonged antibiotics in the treatment of patients with bronchiectasis, at least halving the odds of exacerbation and hospitalization. However, the authors also add that the risk of emerging drug resistance is increased more than threefold. ^[41]  

The most commonly used and recommended long-term antibiotic is azithromycin. Davies and colleagues and Anwar and colleagues suggested that long-term triweekly therapy with azithromycin can be helpful in patients with bronchiectasis. ^{[42, 43]}  This has also been helpful in CF. Macrolide antibiotics, such as erythromycin and azithromycin, have been found to have anti-inflammatory effects, which have been helpful in CF and in some patients with non-CF bronchiectasis. Guidelines suggest long-term macrolide antibiotics in pediatric patients who have been hospitalized more than once or had more than two outpatient exacerbations within a 12-month period. ^{[28, 29]}

However, a study reported that long-term erythromycin treatment changes the composition of respiratory microbiota in patients with non-CF bronchiectasis. In patients without P aeruginosa airway infection, erythromycin did not significantly reduce exacerbations and promoted displacement of H influenzae by more macrolide-tolerant pathogens, including P aeruginosa. The authors added that these findings argue for a cautious approach to chronic macrolide use in patients without P aeruginosa airway infection. ^[44]

Some clinicians treat bronchiectasis with prolonged oral antibiotics on a rotating basis. This is falling into disfavor, as it is in CF. Broad-spectrum antibiotics can be given for a month, followed by a second broad-spectrum drug, followed by a third, and so forth. Another option is to use alternating antibiotics for 7-10 days, with antibiotic-free periods of 7-10 days between each course.

Antibiotics are important parts of therapy during exacerbations of bronchiectasis, with the selection of agents based on culture results. ^[2] It is recommended to attempt eradication of Pseudomonas when first detected using protocols similar to CF protocols. ^[28] Inhaled tobramycin was associated with decreased Pseudomonas aeruginosa load in sputum, improved lung function, and fewer hospitalizations. However, the researchers concluded that inhaled tobramycin is not indicated in non-CF bronchiectasis unless Pseudomonas is detected in the sputum or bronchoalveolar lavage samples. ^[2]  

Aztreonam and Colistin (colistimethate) have come into frequent use as an inhaled antibiotic in patients with cystic fibrosis, and it may find its way into therapy for non-CF bronchiectasis. Other inhaled antibiotics are also in development for cystic fibrosis.

Manual and mechanical interventions such as chest percussion, vibration, postural drainage, cough-assist devices, and airway oscillation (ie, Flutter®, acapella®, Aerobika® devices) are used to facilitate sputum volume and mucous expectoration. The goal is to facilitate individualized effective airway clearance. ^[45] These techniques or devices are often used daily in order to be most effective and may be used in combination.  These devices serve as adjuncts to the cough, which is the most effective and efficient manner of clearing the airway.  Patients can be trained to do huff coughing with airway clearance to help expectorate loosened mucus.

Prior to the wide availability of broad-spectrum antimicrobials, both Field and Clark demonstrated a gradual symptomatic improvement of some children who did not undergo surgical therapy for bronchiectasis. ^{[7, 11]} In 1993, Lewiston recommended that surgery be delayed, unless symptomatically necessary, until the patient is aged 6-12 years because of the possibility for clinical improvement. Surgery is also delayed in children with stable disease that can be controlled with medical therapy.

Otgun and associates, in a retrospective study, concluded that the decision for bronchiectasis surgery should be made in cooperation with the chest disease unit. ^[3] Furthermore, anatomic localization of disease should be mapped with radiography and scintigraphic studies. Otgun and associates found the morbidity and mortality rates to be within acceptable ranges. In unilateral bronchiectasis, total excision and pneumonectomy, as opposed to leaving residual disease, was found to be well tolerated and most beneficial to the child.  Consideration of future transplant candidacy should be made before proceeding with thoracic surgery. 

Pulmonary segmental resection

Pulmonary segmental resection may be beneficial when damage is severe, well localized and the etiology non-recurring in a symptomatic patient. Preoperative documentation of severe abnormalities in ventilation and/or perfusion to the affected portion of the lung, such as with a lung scan, is often helpful.

Transplantation

For patients with severe progressive disease, transplantation has worked as well as selected patients with other lung diseases. ^[4] Transplantation has predominantly been used in patients with CF.  At times the underlying condition such as certain immunodeficiency states may preclude consideration for lung transplant. 

No specific activity limitations are necessary. Exercise generally promotes increased mucociliary clearance, which may enhance airway clearance in patients with bronchiectasis. However, exercise-induced dyspnea may require further investigation using exercise testing to evaluate for limitation or hypoxemia.  Those with advanced disease generally will limit themselves as needed.  If a patient has very low lung function, assessment of oxygen saturation during activity should be done to identify possible desaturation requiring O2 supplementation. 

Childhood immunization for pneumococci, Haemophilus influenzae  type B, measles, and pertussis has reduced bronchiectasis. Screening for tuberculosis and other successful public health measures minimizes the risk of this disease in children.

Aggressive appropriate therapy of lower respiratory tract infections may prevent bronchiectasis. However, because some viruses predispose to bronchiectasis, this therapy is not always successful.

Therapy of the child with chronic or recurrent respiratory problems due to recurrent aspiration and/or gastroesophageal reflux disease is important to reduce the likelihood of developing bronchiectasis.

Although routine care of patients with bronchiectasis is successfully provided by a primary care physician, a pediatric pulmonologist must be consulted for all infants and children with bronchiectasis. The subspecialist should be an integral part of the child's care and should manage most of the pulmonary aspects of the bronchiectasis and the underlying disease.

If recurrent aspiration is a contributing factor, a pediatric gastroenterologist should have input into the child's care. Pediatric immunologists should help manage children with HIV infection or immunoglobulin deficiencies. If the child has an underlying rheumatologic disorder, a pediatric rheumatologist should be consulted on a regular basis.

Physical therapists or respiratory therapists are important and helpful in the chest physiotherapy techniques. Whether manually performed or performed with one of the mechanical devices, the procedure needs to be thoroughly learned and periodically reviewed with the therapist.

Consider transferring the care of the child with refractory bronchiectasis to a pediatric pulmonary center for clinical deterioration, frequent or increased symptoms, or hemoptysis.

Children with bronchiectasis should be monitored throughout their lives by a clinician comfortable with the management of chronic lung disease. Children should be seen frequently, generally every 3-6 months, when stable and should be seen more frequently if they are not stable.  The CF Foundation recommends quarterly visits including lung function for all persons with CF.

Spirometry is recommended at every visit in children older than 6 years. Chest radiograph need not be empirically repeated. If the clinical course changes, a radiograph should be part of the assessment.