Bronchiectasis in children without cystic fibrosis: Management

INTRODUCTION — Bronchiectasis in children is defined as the presence of abnormal bronchial dilatation on chest computed tomography scans, in combination with a clinical syndrome of recurrent or persistent wet/productive cough, airway infection, and/or inflammation infections [1-3]. Although cystic fibrosis (CF) is the most common cause of pediatric bronchiectasis in resource-abundant settings, other causes predominate worldwide. Pediatric bronchiectasis unrelated to CF remains underrecognized, undertreated, and underserviced [4,5].

Management of bronchiectasis in children without CF is discussed below. This includes children with bronchiectasis related to underlying diseases such as primary ciliary dyskinesia and immunodeficiency. However, when underlying causes are identified, additional therapies are usually indicated. Other aspects of bronchiectasis in this population are discussed separately. (See "Bronchiectasis in children: Pathophysiology and causes" and "Bronchiectasis in children: Clinical manifestations and evaluation" and "Primary ciliary dyskinesia (immotile-cilia syndrome)".)

The management of CF-related bronchiectasis is discussed in detail in separate topic reviews. (See "Cystic fibrosis: Overview of the treatment of lung disease" and "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection" and "Cystic fibrosis: Management of pulmonary exacerbations" and "Cystic fibrosis: Management of advanced lung disease".)

OVERVIEW — Optimal clinical care for children with bronchiectasis improves clinical outcomes. For those with mild disease, optimal care can halt the progression and sometimes even reverse the disease [3,6]. Unfortunately, children with bronchiectasis unrelated to cystic fibrosis (CF) often have poorer access to multidisciplinary clinics and resultant poorer lung function outcomes compared with children with CF [5]. Also, they have a worse outcome in growth and their parents experience more stress and anxiety compared with children with CF [7].

●Aged-based care – Bronchiectasis care for children differs from that for adults in several ways:

•Care must be tailored to the child's age and understanding, and education and support includes the parents or other caregivers.

•Diagnostic and treatment methods, such as airway clearance techniques, may differ according to age.

•Therapeutic choices may differ because of the biologic differences between pediatric and adult bronchiectasis, which include altered pathogen profiles (bacteria [8] and microbiota [9]), age-related immunologic responses [10], and treatment outcomes [3].

•Comorbidities and underlying etiologies are substantially different between adults and children [11]. (See "Bronchiectasis in children: Clinical manifestations and evaluation".)

●Components of management – Bronchiectasis is best managed in a multidisciplinary clinic. Treatment and long-term management are aimed at curtailing the cycle of infection and inflammation. In contrast with adults with bronchiectasis, clinicians should be cognizant that upon diagnosing bronchiectasis in children, their lung function can be preserved in the long term and even improve [12] if their bronchiectasis is optimally managed [3,13].

Optimal management includes:

•Early diagnosis – To ensure optimal care and minimize disease progression. (See "Bronchiectasis in children: Clinical manifestations and evaluation".)

•Identification and treatment of underlying causes – Such as immunodeficiencies, aspiration, or structural lesions such as tracheoesophageal fistula (table 1). (See 'Identification and treatment of underlying causes' below.)

•Management of acute exacerbations – Includes antibiotics and airway clearance therapies (table 2). (See 'Management of acute pulmonary exacerbations' below.)

•Maintenance therapy:

-For all patients, this includes airway clearance techniques (chest physiotherapy) and regular monitoring to track disease progression and identify any complications as well as the first appearance of new pathogens. (See 'For all patients' below.)

-For selected patients, this may include antibiotics to eradicate Pseudomonas aeruginosa, chronic antibiotics, inhaled mucolytics, bronchodilators, and/or glucocorticoids. (See 'For selected patients' below.)

•Supportive care – Measures to improve general lung health, including avoidance of tobacco smoke and other lung irritants, immunizations, optimizing nutrition, and self-management education and support for the child and family. (See 'Supportive care' below.)

•Management of advanced lung disease – May include management of hemoptysis, supplemental oxygen, surgery, or lung transplantation. (See 'Management of advanced lung disease' below.)

These steps are detailed in the remainder of this topic review.

IDENTIFICATION AND TREATMENT OF UNDERLYING CAUSES — All patients should be thoroughly evaluated to determine if there is a specific cause or contributor to the bronchiectasis, such as a focal bronchial obstruction or an immunodeficiency. Treatment for the underlying disorder may help prevent further progression or, in some cases, even reverse the bronchiectasis (table 1) [6]. (See "Bronchiectasis in children: Clinical manifestations and evaluation" and "Bronchiectasis in children: Pathophysiology and causes".)

Additional treatable traits include treating any new acquired pathogens (see 'Pathogenesis' below) and complications of bronchiectasis. (See 'Routine monitoring' below.)

MANAGEMENT OF ACUTE PULMONARY EXACERBATIONS — Prompt identification and treatment of acute pulmonary exacerbations is a critical component of management. Exacerbations may be managed as an outpatient or in hospital, and the choice largely depends on the severity.

Pulmonary exacerbations are common (averaging three episodes/year) and are important drivers of disease progression [14]. They have been shown to impair quality of life (QoL) and are stressful for parents. Severe exacerbations predict subsequent decline in forced expiratory volume in one second (FEV₁) [15]. Also, exacerbations lead to high resource use [16] and substantial costs when hospitalized (approximately USD $24,500 per hospitalization) [17,18].

Definition — We use the following characteristics to define an acute pulmonary exacerbation, as outlined by the European Respiratory Society [1]:

●Increased respiratory symptoms (predominantly increased cough with or without increased sputum quantity and/or purulence) for ≥3 days. Other respiratory symptoms may include breathlessness, wheeze, chest pain, or hemoptysis. The presence of dyspnea (increased work of breathing) or hypoxemia suggest a more severe exacerbation (irrespective of duration).

●Other findings that support the diagnosis but may not be present are:

•Changes in chest auscultation findings and chest radiographs

•Systemic symptoms such as fever, fatigue, malaise, or change in child's behavior or appetite

•Laboratory indices of inflammation such as elevated C-reactive protein, neutrophilia, and interleukin-6 (these are not routinely used for clinical decision-making)

•New infiltrates on chest radiograph

Other definitions of an acute pulmonary exacerbation have been used but are similar in that they focus primarily on changes in clinical symptoms [19].

Pathogenesis — Acute exacerbations are associated with increased infection/inflammation and excessive airway secretions. Treatment approaches target these mechanisms. Either viral or bacterial pathogens may be involved:

●Viruses – A virus can be identified at the beginning of 48 to 53 percent of exacerbations [20,21]. The common viruses identified are rhinovirus, coronaviruses, influenza, parainfluenza, adenoviruses, and respiratory syncytial virus, respectively [20,21]. When compared with nonviral exacerbations, viral-related exacerbations tend to be more severe and are more likely to require hospitalization [22]. Although rhinoviruses are common, it is uncertain whether they cause acute exacerbations because it can also be detected in up to 40 percent of asymptomatic children without bronchiectasis [23,24].

●Bacteria – An important role for bacteria in acute exacerbations is suggested by studies in adults, in whom acute exacerbations are associated with increased bacteria density and inflammation, and treatment reverses these changes, with concurrent improvement in exercise capacity and health-related QoL [25,26]. There are no such studies in children, likely because of the difficulty of obtaining lower airway specimens in young children.

The most commonly isolated bacteria in children with bronchiectasis during stable state are non-encapsulated Haemophilus influenzae, Streptococcus pneumonia, Moraxella catarrhalis, and Staphylococcus aureus [8]. P. aeruginosa is rare in high-income pediatric cohorts and in young children but is more often detected in low-income countries, older children, and those with underlying diseases with advanced lung damage [8,27]. Biofilms without P. aeruginosa have been described in the lower airways of children with bronchiectasis [28].

Antibiotics — All published pediatric guidelines recommend using antibiotics to treat bronchiectasis exacerbations (table 2) [1,29]. The method of administration (oral and/or inhaled or intravenous antibiotics) depends on the severity of the exacerbation. The antibiotic should be selected based on the individual's lower airway microbiology and sensitivities from the most recent sputum cultures (see 'Routine monitoring' below). If no recent cultures are available at the time of a pulmonary exacerbation, we initiate empiric antibiotics while waiting for the results of a new sputum culture (in children who are able to expectorate sputum). Bronchoalveolar lavage is occasionally undertaken to obtain lower respiratory tract samples for culture, but its use is limited to patients who fail to respond to usual therapy or if atypical or antibiotic-resistant pathogens are suspected [3].

●Oral antibiotics – For most children without P. aeruginosa infection, amoxicillin-clavulanate is an appropriate first-line treatment because it covers the common organisms found in children with bronchiectasis [1,21,29]. The typical course of treatment is 14 days. Other oral antibiotics may be selected if the patient is allergic to penicillin or based upon the patient's lower airway microbiology or historical response to antibiotics.

The efficacy of amoxicillin-clavulanate was shown in a randomized trial in which it was superior to placebo (BEST-1) [20]. In another trial (BEST-2), azithromycin was effective for nonsevere exacerbations as well but also induced macrolide-resistant organisms and the treatment response was slower than for amoxicillin-clavulanate [21]. Hence, amoxicillin-clavulanate is the first-choice empirical antibiotic but azithromycin might be useful for some patients, such as those with penicillin allergy or those who require less frequent dosing to improve adherence.

For children with chronic P. aeruginosa infection, ciprofloxacin is usually an appropriate first-line choice [1]. Other choices include inhaled aminoglycosides or colistin as the initial treatment, based on culture sensitivities and the child's specific characteristics (eg, some young children are unable to tolerate inhaled antibiotics).

●Intravenous antibiotics – Intravenous antibiotics are reserved for severe exacerbations or when symptoms/signs persist after a long course (usually approximately four weeks) of oral antibiotics. For antibiotic selection, it is reasonable to use principles of treatment similar to those used for acute exacerbations in children with cystic fibrosis (CF), which are outlined in a separate topic review. (See "Cystic fibrosis: Antibiotic therapy for pulmonary exacerbations".)

In children with bronchiectasis, antipseudomonal antibiotics are only used when there is evidence of presence of P. aeruginosa infection on a lower airway specimen or after the failure of an empiric intravenous antibiotic regimen, which covers the common organisms found in children with bronchiectasis. (See 'Pathogenesis' above.)

Airway clearance therapy — In addition to antibiotics, management of acute exacerbations includes:

●Airway clearance techniques – Airway clearance techniques, also known as chest physiotherapy, should be intensified during acute exacerbations [1]. The goal is to help clear the excessive mucus that is seen in an acute exacerbation. Airway clearance techniques are also an important component of maintenance therapy for bronchiectasis [30,31]. (See 'Airway clearance therapy' below.)

●Inhaled airway clearance agents – For children with high sputum load, we suggest treatment with inhaled hypertonic saline (6 to 7%) during an acute exacerbation as an adjunct to antibiotic treatment and airway clearance techniques. Other candidates for this treatment may be identified by an expert pediatric respiratory therapist. The therapy is administered via nebulizer, twice daily, just before performing airway clearance therapy. For some patients, we also use inhaled hypertonic saline as part of maintenance therapy, as discussed below. (See 'Inhaled airway hydrating agents and mucolytics' below.)

MAINTENANCE THERAPY — The aim of maintenance therapy in children and adolescents with bronchiectasis is to decrease the lower airway inflammation/infection and help prevent pulmonary exacerbations, thereby improving quality of life (QoL), symptom control, and long-term outcomes (eg, preservation and/or improvement of lung function).

For all patients

Airway clearance therapy — Airway clearance techniques (often called chest physiotherapy) are standard treatment in all bronchiectasis guidelines. Available studies suggest that airway clearance techniques are beneficial with improved QoL and exercise capacity and reduced cough and sputum volumes [1]. Available techniques include chest percussion, positive airway pressure, forced expirations, and exercise. Given the lack of clear superiority of any one technique, specific choices should be individualized and guided by a specialist in pediatric respiratory therapy. The technique(s) should be selected and taught by pediatric therapists to match the child's age and cognitive stage and to maximize potential benefit and minimize the burden of care [1]. Postural drainage, a standard therapy for children with bronchiectasis in the past, is now rarely used as it may increase gastroesophageal reflux disease and possible aspiration. In practice, airway clearance techniques are used more often by patients who have more severe disease compared with those with milder symptoms/disease, as well as in response to symptoms rather than as a preventative management strategy [32].

Irrespective of the basal frequency, children and adolescents should perform airway clearance therapy more frequently during acute exacerbations of bronchiectasis [13]. (See 'Management of acute pulmonary exacerbations' above.)

In addition, children with bronchiectasis should be encouraged to engage in physical activity. Most children with bronchiectasis have suboptimal levels of physical activity [33]. Barriers to exercise include difficulty keeping up with peers and recreational screen time [34]. While there are no data on the benefits of exercise training, exercise improves airway clearance and exercise training significantly improves cardiovascular fitness and QoL in children with asthma or cystic fibrosis (CF) [33].

Routine monitoring — Children with bronchiectasis should be monitored by a pediatric pulmonology specialist. They should generally be seen every three to six months in an outpatient clinic, including the following serial measures [1]:

●Sputum cultures – Serial sputum cultures help to guide antibiotic selection should an acute exacerbation occur. In addition, they are used to monitor for the initial acquisition of P. aeruginosa and other pathogens that can cause progressive deterioration (eg, Burkholderia cepacia complex). When present, these require prompt treatment. (See 'Early eradication of Pseudomonas aeruginosa' below.)

For patients who can expectorate, we obtain a sputum culture approximately every six months. However, this may not be possible, because most children with mild bronchiectasis do not produce sputum in their baseline state and young children may not be able to produce sputum even during an exacerbation. In some cases, sputum induction may be feasible.

●Spirometry – Outside of disease exacerbations, measures of pulmonary function (forced expiratory volume in one second [FEV₁] and forced vital capacity [FVC]) are often normal for children with mild bronchiectasis and may be abnormal for those with moderate or severe bronchiectasis. An acute decline in FEV₁ (>10 percent) can provide supportive evidence for acute exacerbations, but FEV₁ values may not decline during exacerbations [20,21]. (See "Bronchiectasis in children: Clinical manifestations and evaluation", section on 'Spirometry'.)

●Pulse oximetry – Most children with bronchiectasis have normal oxygen saturation at rest. Low values are sometimes seen during a severe acute exacerbation or in advanced lung disease and may be helpful in decisions regarding hospitalization and oxygen supplementation. (See 'Management of advanced lung disease' below.)

For selected patients

Early eradication of Pseudomonas aeruginosa — New acquisition of P. aeruginosa is associated with exacerbations and/or deteriorating clinical status and lung function [35]. If the sputum culture detects P. aeruginosa, we suggest prompt treatment with antipseudomonal antibiotics in an attempt to eradicate this organism [1], as follows:

●Symptomatic patients – For patients with symptoms that are increased compared with their baseline, treat with intravenous antipseudomonal antibiotics (eg, piperacillin-tazobactam or ceftazidime with tobramycin) for two weeks, followed by inhaled antibiotics (tobramycin or colistin) for 4 to 12 weeks.

●Asymptomatic patients – For patients who are asymptomatic when the P. aeruginosa is first detected (ie, symptoms unchanged from their baseline), use oral ciprofloxacin and/or inhaled antibiotics (tobramycin or colistin) for two weeks, followed by continued inhaled antibiotics for 4 to 12 weeks.

These strategies are based on expert consensus, as outlined in guidance from the European Respiratory Society [1]. The evidence is extrapolated from studies in adults with bronchiectasis that describe improved QoL and reduced exacerbation rates and hospitalizations (compared with pre-eradication) [36-38]. Other evidence is from early eradication regimens in children with CF. No direct evidence is available from children with bronchiectasis unrelated to CF to support the efficacy of early eradication or to guide selection of specific eradication regimens. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Eradication of new isolates of Pseudomonas' and "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Prevention and eradication'.)

Chronic antibiotics — We suggest chronic antibiotic therapy only for selected children with bronchiectasis (table 2) [39]:

●Oral antibiotics – We suggest chronic oral antibiotics for children with frequent exacerbations (>3 per year), especially if the exacerbations are severe (ie, requiring hospitalization) [1]. When chronic antibiotic therapy is indicated, we generally suggest a macrolide (eg, azithromycin) because this is the agent that has been studied in randomized trials in this population.

Azithromycin can be dosed daily, three times a week, or weekly, with a total dose of approximately 30 mg/kg/week (up to 1500 mg/week). The optimal dose and frequency has not been established for this population; in our practice, we select the frequency of dosing based on patient characteristics. We generally use three-times-a-week dosing but may use weekly dosing in settings where directly observed therapy is required or daily dosing if the child has difficulty tolerating larger doses. Other reasonable antibiotic choices include doxycycline (only for children aged >8 years) or trimethoprim-sulfamethoxazole in children who do not tolerate macrolides, even though there are no data on the efficacy of these antibiotics for children with bronchiectasis.

This practice is supported by limited clinical trial data [1,40,41]. The largest trial involved 89 children with non-CF-related bronchiectasis who were randomized to chronic treatment with azithromycin or placebo [40]. At 24 months, azithromycin halved the frequency of exacerbations compared with placebo (rate ratio 0.50, 95% CI 0.35-0.71) [40]. However, children in the azithromycin group developed higher nasal carriage of azithromycin-resistant bacteria (46 versus 11 percent). Despite this, they were significantly less likely (50 percent reduction) to require antibiotics for nonrespiratory acute infections compared with those receiving placebo. A secondary analysis of data from this study showed that the optimal duration of prophylactic azithromycin therapy is between 17 and 62 weeks [42]. Indirect evidence from other populations includes a short-term study in pediatric and adult patients with primary ciliary dyskinesia (a cause for bronchiectasis) [43] and populations with CF. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Azithromycin' and "Primary ciliary dyskinesia (immotile-cilia syndrome)".)

If macrolides are commenced, additional recommended steps are [1]:

•Counseling – Utilize counseling strategies to encourage adherence to the regimen. Adherence to ≥70 percent of the regimen increases efficacy and reduces antibiotic resistance [44].

•Sputum culture – Prior to initiating therapy, obtain a sputum specimen (when possible) to exclude the presence of nontuberculous mycobacteria (NTM). These organisms are rarely detected in children/adolescents with bronchiectasis. If NTM are present, monotherapy with a macrolide antibiotic is not recommended, because it can induce drug resistance in the NTM strain. The decision to treat NTM is not straightforward and should be made in consultation with a specialist/expert in the field.

•Periodic reassessment – Treat for at least six months, with periodic clinical reassessment to determine whether there is clinical benefit. Clinical reassessment is particularly important if the treatment is continued for 24 months or longer.

The recommendation for clinical reassessment reflects a concern that chronic treatment with macrolides may increase antibiotic resistance. Indeed, several studies show that treatment with macrolides promotes the carriage of resistant bacteria [1,40,45]. However, in one of these trials, children in the azithromycin group required 50 percent fewer antibiotics for respiratory exacerbations and also had 50 percent fewer antibiotics for other infections despite the induced resistance [40]. Thus, there were no clear adverse consequences of the treatment-induced changes in antibiotic resistance, at least during the 24-month duration of this trial.

●Inhaled antibiotics – For children who are chronically infected with P. aeruginosa and have frequent exacerbations, oral macrolides are the first-line approach to maintenance treatment, but inhaled tobramycin or colistin may be used as an alternative (eg, for those who cannot tolerate macrolides) or used in conjunction with the oral macrolides. Other options include inhaled ciprofloxacin or gentamicin. By contrast, children with clinically stable bronchiectasis should not be treated with chronic inhaled antibiotics [39].

This strategy is based on indirect evidence from patients with either CF-related bronchiectasis or adult patients with bronchiectasis and chronic P. aeruginosa infection [46]. As an example, a randomized trial in adults found that chronic treatment with inhaled colistin decreased the annual rate of exacerbations, prolonged time to first exacerbation, and decreased severe exacerbations [47]. (See "Cystic fibrosis: Antibiotic therapy for chronic pulmonary infection", section on 'Inhaled antibiotics'.)

The guidance on chronic antibiotic use outlined above is based primarily on expert opinion and clinical experience; limited data are available to guide selection of patients for treatment, antibiotic selection, and route of administration (oral versus inhaled) [13,39].

Inhaled airway hydrating agents and mucolytics — We suggest using either inhaled hypertonic saline (6 or 7%) or mannitol as part of the chronic regimen for children with moderate or severe, high, daily symptoms; frequent exacerbations; difficulty in expectoration; and/or poor QoL, consistent with European and Australia/New Zealand guidelines [1,39]. Most of these children should also be treated with chronic oral macrolide antibiotics (see 'Chronic antibiotics' above). Because these inhaled therapies can cause bronchospasm, the first dose should be administered under medical supervision and subsequent doses should be preceded by a bronchodilator to prevent bronchospasm.

The therapy is administered twice daily in the following sequence:

●Albuterol by metered-dose inhaler (to help prevent bronchospasm during therapy)

●Inhaled hypertonic saline (6 or 7%) by nebulizer or mannitol by dry powder inhaler

●Routine airway clearance therapy (chest physiotherapy)

The use of hypertonic saline is primarily based on indirect evidence from patients with CF or from adults with bronchiectasis [48,49]. The only direct evidence in children with bronchiectasis unrelated to CF is from a small randomized crossover trial, which found that incorporating hypertonic saline into the airway clearance regimen improved spirometric parameters (FEV₁ and FVC) [50]. However, a reduction in frequency of exacerbations was only found in the first phase of the study and not in the second phase (after crossover). Of note, this trial used a lower concentration of hypertonic saline (3%) than is typically used in clinical settings (6 or 7%).

Inhaled dry powder mannitol is generally well tolerated and may have some modest benefits for airway clearance in adult bronchiectasis [51,52], but pediatric data are unavailable. Compared with hypertonic saline, mannitol is somewhat easier to administer but can only be used in older children (who are able to cooperate) and is more expensive.

Acetylcysteine (oral or inhaled) has been studied in adults with bronchiectasis, but there is insufficient evidence to support its use. Dornase alpha (DNase) is an established therapy for patients with CF but is not effective and may be harmful in other patients with bronchiectasis, based on studies in adults, and thus is contraindicated. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Mucolytic agents and airway hydration'.)

Bronchodilators and glucocorticoids

●Bronchodilators – Inhaled bronchodilators (beta agonists) are indicated in the following situations [1]:

•As pretreatment before use of inhaled hypertonic saline or mannitol (when those treatments are otherwise indicated)

•For children with coexisting asthma or definite bronchial hyperreactivity (chronic or intermittent use)

For all other patients, there is no evidence to support the routine use of bronchodilators, as there is no evidence of general beneficial effects including on mucociliary clearance [1,53,54]. Rarely, paradoxical response to bronchodilators has been reported in some adults with chronic obstructive pulmonary disease (COPD) and bronchiectasis [55,56].

●Inhaled glucocorticoids – Inhaled glucocorticoids, alone or in combination with bronchodilators, are indicated only for patients with concomitant asthma, as documented with an objective evaluation of airway hyperreactivity and/or eosinophilic airway inflammation [1]. Otherwise, there is no evidence to support their routine use for pediatric or adult patients with bronchiectasis [1,57,58]. (See "Bronchiectasis in adults: Maintaining lung health", section on 'Anti-inflammatory medications'.)

Lack of general benefit from inhaled glucocorticoids was suggested by a small study in children with bronchiectasis who were chronically treated with inhaled glucocorticoids at baseline [59]. Withdrawal of the glucocorticoids caused no change in the frequency of exacerbations, antibiotic use, or inflammatory markers. Some patients had an increase in bronchial hyperreactivity detected with provocative testing.

●Oral glucocorticoids – Oral glucocorticoids are indicated only for selected patients with an exacerbation of concomitant asthma (brief course) or other indications for treatment of coexistent disease, such as allergic bronchopulmonary aspergillosis. (See "Acute asthma exacerbations in children younger than 12 years: Emergency department management", section on 'Management of inflammation' and "Treatment of allergic bronchopulmonary aspergillosis".)

Except for the above indications, systemic glucocorticoids should be avoided for children with bronchiectasis because they depress host immunity, may perpetuate infection, and have adverse effects on growth [1]. (See "Major adverse effects of systemic glucocorticoids".)

SUPPORTIVE CARE

General measures to improve health — The following measures prevent or reduce the severity of respiratory infections and thereby reduce the risk for developing or the progression of bronchiectasis:

●Avoidance of smoke and other irritants – All individuals with bronchiectasis should avoid respiratory irritants, including smoking or exposure to secondhand smoke or vapor from electronic cigarettes (e-cigarettes). Children should be given anticipatory guidance to prevent smoking and vaping initiation, and household members should be counseled and supported in smoking and vaping cessation. Other irritants, such as wood smoke from fires and environmental pollutants, should also be avoided. (See "Control of secondhand smoke exposure" and "Prevention of smoking and vaping initiation in children and adolescents".)

●Vaccines – Rigorous attention should be given to vaccinations, ensuring timely completion of all routine childhood vaccination series, and particularly the influenza and pneumococcal vaccines. (See "Standard immunizations for children and adolescents: Overview".)

•Influenza vaccination should be given annually. The inactivated influenza vaccine (intramuscular) must be used for any child who might be immunocompromised. The live attenuated influenza vaccine (intranasal) should not be given if there is any possibility that the child is immunocompromised. (See "Seasonal influenza in children: Prevention with vaccines".)

•All children with bronchiectasis should receive the standard pneumococcal conjugate vaccine series (either 15-valent pneumococcal conjugate vaccine [PCV15] or 20-valent pneumococcal conjugate vaccine [PCV20]), as is recommended for healthy children. Children with bronchiectasis and other chronic respiratory illnesses are considered at high risk of invasive pneumococcal disease and may require additional pneumococcal vaccination if their primary series did not include at least one dose of PCV20. This is discussed separately. (See "Pneumococcal vaccination in children", section on 'Immunization of high-risk children and adolescents'.)

●Nutrition – Monitoring nutritional status and growth and optimizing nutrition are important components of health care for children with bronchiectasis, as for children with other chronic illnesses [1]. Growth parameters should be measured at each office visit and tracked on standard growth charts. Children with suboptimal growth warrant intervention, which may include nutritional counseling and sometimes supplemental feeding. (See "Poor weight gain in children older than two years in resource-abundant settings" and "Poor weight gain in children younger than two years in resource-abundant settings: Management".)

Children with bronchiectasis are at risk for undernutrition. As an example, one study found that children with bronchiectasis were three times more likely to have had malnutrition in early childhood before the diagnosis of bronchiectasis compared with matched controls [60].

In addition, poor nutrition is associated with worse lung function. As examples, a retrospective study in children with bronchiectasis showed that worse nutritional state at the time of initial evaluation was associated with abnormal lung function [61]. Similarly, studies in adults show that underweight patients with bronchiectasis had lower lung function (forced expiratory volume in one second [FEV₁] percent predicted) compared with those with healthy weight (64.5±22 versus 73.5±21) [62]. Finally, a large population-based study of 2769 adults with bronchiectasis showed that underweight was associated with increased all-cause mortality among individuals with bronchiectasis [63].

Some of the medical interventions directed at treating the bronchiectasis may improve nutritional status. In the randomized trial of azithromycin for children with bronchiectasis, weight Z-scores improved in children treated with six months of azithromycin compared with placebo [40].

●Vitamin D deficiency – Vitamin D deficiency is common among children and adults with bronchiectasis [1,64]. 25-hydroxyvitamin D concentrations should be monitored periodically and supplementation given to children who are deficient. (See "Vitamin D insufficiency and deficiency in children and adolescents".)

The possibility has been raised that vitamin D deficiency may contribute to the pathogenesis of bronchiectasis. Vitamin D is known to have antiinfective and antiinflammatory properties, as shown in animal models and in vitro studies [65-67]. In addition, a correlation between vitamin D status and disease severity has been shown in multiple studies in children and adults with bronchiectasis [64,68,69]. However, a causal effect of vitamin D deficiency on bronchiectasis has not been established and there is no evidence that supraphysiologic doses of vitamin D are beneficial for patients with bronchiectasis. Indeed, the correlation may reflect the adverse effects of bronchiectasis on nutritional status (reverse causation).

Education and support — Self-management education and support is an important part of chronic disease management and is desired by patients [70,71]. In adults with bronchiectasis, adherence to treatment can be low (16 percent), but those patients who do adhere to treatment have fewer exacerbations and lower perceived treatment burden [72].

Self-management education may include:

●Information about the likely cause of the child's bronchiectasis and expected clinical course

●How to reduce the risk of exacerbations (eg, avoiding smoke and other irritants, measures to avoid respiratory illnesses)

●Personalized plan for maintenance therapy (including airway clearance therapy and immunizations)

●Age-appropriate, regular physical activity

●How to recognize infective exacerbations and initiate antibiotic treatment (dose and duration)

●Personalized action plan for managing exacerbations

●Coordination of care with the primary care clinician on a regular basis

●Contact information for the bronchiectasis care team, including plans for emergency communication

A template for a bronchiectasis action management plan is available from the Children's Bronchiectasis Education, Advocacy and Research Network [73]. Self-management education programs for bronchiectasis have not been standardized or studied [74]. Studies in adults and children are in progress [75].

Children with bronchiectasis and their families also require psychological support to address disease-related stressors, anxiety, and depression. They also require support regarding care of equipment (eg, airway clearance and nebulizers). In an international survey, the top five burdens of bronchiectasis that affected children's quality of life (QoL) as reported by parents are doing airway clearance therapy, medications, exacerbations, symptom/disease management, and cough [18]. The top features that affected the parents' QoL were dedicated time needed to care for the child, challenges of obtaining medical assistance, and strategies to prevent infection.

Transition to adult care systems — Adolescents with bronchiectasis require extra support and guidance during the transition to adult health care systems, similar to adolescents with other chronic diseases. Poor transitional care may lead to deterioration in health [76,77]. Most pediatric hospitals have a policy on transition, but there are no universally accepted, quality metrics specific for transition care. The Australian and New Zealand guideline recommended that "health services should provide transitional care that supports the requirements of adolescents with bronchiectasis. A purposeful, planned and developmentally appropriate transition, which includes engagement of the pediatric and adult multidisciplinary teams, utilization of transition guidelines, and clear documentation of transfer processes are key goals as they transition from child to adult health services" [39].

Internet resources — Online resources related to bronchiectasis for health care providers and families include:

●Children's Bronchiectasis Education, Advocacy and Research Network

●Centre for Research Excellence in Lung Health – Especially for First Nations children in Australia

MANAGEMENT OF ADVANCED LUNG DISEASE

Complications — Complications and comorbidities of bronchiectasis are shown in the table (table 3). Particular attention should be paid to hemoptysis and hypoxemia, which tend to be associated with advanced bronchiectasis.

Hemoptysis — Any degree of hemoptysis warrants attention. In a study of 300 children admitted to intensive care with hemoptysis in the United States, bronchiectasis was the cause in 10 percent and was an independent risk factor for in-hospital mortality [78].

Management of hemoptysis depends upon the cause and severity. Children with hemoptysis should be carefully monitored, and most require hospitalization.

●Small-volume hemoptysis – When the hemoptysis is small volume and mixed with purulent sputum, it is usually related to an acute pulmonary exacerbation and often resolves with appropriate management for the exacerbation. (See 'Management of acute pulmonary exacerbations' above.)

●Large-volume hemoptysis – Large-volume hemoptysis is rare in children with bronchiectasis but may be life-threatening. When present, it indicates abnormal bronchial artery and/or neovascularization with bronchopulmonary anastomoses in the distal branches of bronchi. The abnormal anastomoses and bronchial artery hyperplasia can increase bronchial blood flow to as much as one-third of the cardiac output [79]. As bronchiectasis progresses in severity, the bronchial artery diameter increases, which escalates the risk and life-threatening consequences of hemoptysis [80].

Management of hemoptysis is discussed separately. (See "Hemoptysis in children".)

Hypoxemia — For children with severe bronchiectasis and intermittent or chronic hypoxemia, we suggest supplemental oxygen. This is rare, and the management is extrapolated from the management of patients with advanced cystic fibrosis (CF)-related lung disease or chronic obstructive pulmonary disease (COPD).

In the COPD population, chronic hypoxemia and airway obstruction are known to contribute to vascular remodeling of the pulmonary arteries and arterioles [81], increasing the risk of pulmonary hypertension. Supplemental oxygen delays or ameliorates the complications of chronic hypoxemia, which include adverse effects on physical and cognitive function and quality of life (QoL). (See "Long-term supplemental oxygen therapy".)

Surgery — Surgery to remove lobes affected by bronchiectasis is uncommon in children in high-income countries. It is more common in low-resource settings, where bronchiectasis is more likely to be severe and poorly controlled [82-85].

Lobectomy should only be considered after maximal medical therapies have failed and when the child's QoL remains significantly impaired [1]. This is more common in low- and middle-income countries, where approximately 20 percent of pediatric patients with bronchiectasis unrelated to CF are candidates for lobectomy, due to socioeconomic constraints and barriers to adhering to optimal therapy [86]. Candidates for lobectomy are patients with severe localized disease and/or recurrent hemoptysis that can be addressed by resection of a bronchiectatic lobe. Other important considerations are the underlying etiology of the bronchiectasis (which can predict disease progression) and availability of appropriate surgical expertise and perioperative care.

Evidence is limited regarding outcomes after surgical management of bronchiectasis. While there are many reports on its benefit, most are from one country with no matching comparisons. In one retrospective study in children with bronchiectasis unrelated to CF, outcomes for 29 children who underwent lobectomy were compared with an age-matched group who were managed medically [87]. The groups had similar outcomes including frequency of acute pulmonary exacerbations, pulmonary function tests, and body mass index Z-scores, suggesting that surgical management had no significant effect. However, this study may have had suboptimal matching because the surgical group had indicators of more severe disease at baseline (clubbing and growth delay). Better surgical outcomes were described in a meta-analysis that included a subgroup of five pediatric studies, in which approximately 60 percent of children had resolution of symptoms and 37 percent had improvement, with acceptable morbidity (13.5 percent) and mortality (2.5 percent) [88].

Lung transplant is an option for children with advanced lung disease. Although lung transplantation is often used for advanced lung disease in patients with CF, it is rarely needed in pediatric bronchiectasis [89,90].

INVESTIGATIONAL THERAPIES — Investigational therapies, undertaken only in adults with bronchiectasis, are discussed in a separate topic review (see "Bronchiectasis in adults: Treatment of acute and recurrent exacerbations", section on 'Experimental approaches'). Studies are underway to identify the biomarkers of host response to various treatments and long-term outcomes in patients with bronchiectasis [91].

PROGNOSIS — In early stages, pediatric bronchiectasis can be stabilized and even reversed [6,92]. This contradicts the traditional experience in adults, in which bronchiectasis was traditionally defined as an irreversible dilatation of the airways.

Across a broader range of severity, optimal management can lead to stabilization or improvement in lung function [12,15,61]. As an example, in a study of 131 indigenous children with long-term follow-up (median nine years after diagnosis), rates of acute lower respiratory infections declined with advancing age and median forced expiratory volume in one second (FEV₁) was 90 percent predicted (interquartile range 81 to 105) [93]. These encouraging respiratory outcomes in late childhood or early adolescence reflect optimal management of these patients in a multidisciplinary setting. By contrast, other studies describe higher rates of disease progression (eg, 30 percent) and mortality (7 percent) [94].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Bronchiectasis" and "Society guideline links: Hemoptysis" and "Society guideline links: Primary ciliary dyskinesia".)  

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Bronchiectasis in children (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Causes of bronchiectasis – Although cystic fibrosis (CF) is the most common cause of pediatric bronchiectasis in resource-abundant settings, other causes predominate worldwide (table 1). Pediatric bronchiectasis unrelated to CF remains underrecognized, undertreated, and underserviced. Early diagnosis of bronchiectasis and treatment of underlying causes are critical. (See 'Identification and treatment of underlying causes' above.)

●Acute pulmonary exacerbations – Acute exacerbations should be promptly treated with antibiotics, which are selected empirically or, ideally, based on sputum culture results (table 2). Oral antibiotics (eg, amoxicillin-clavulanate for 14 days) are used for mild exacerbations. Intravenous antibiotics are used for severe exacerbations or for nonresponders to oral antibiotics. Airway clearance therapy should also be intensified during an acute exacerbation. (See 'Management of acute pulmonary exacerbations' above.)

●Maintenance therapy – Medical therapies are outlined in the table (table 2).

•All patients – Optimal maintenance therapy for children with bronchiectasis includes:

-Airway clearance therapy (chest physiotherapy) using an age-appropriate technique. The frequency depends on the child's characteristics. Available techniques include chest percussion, positive airway pressure, forced expirations, and exercise. (See 'Airway clearance therapy' above.)

-Routine monitoring, consisting of multidisciplinary clinical review, spirometry, sputum culture, and pulse oximetry. (See 'Routine monitoring' above.)

•Selected patients – Additional measures for selected patients are:

-When Pseudomonas aeruginosa is first detected in sputum cultures, we suggest early eradication with a course of antipseudomonal antibiotics rather than no treatment (Grade 2C). This is based on expert opinion and indirect evidence from studies of early eradication in CF and in adults with bronchiectasis. A typical regimen is intravenous antibiotics for two weeks, followed by continued inhaled antibiotics for 4 to 12 weeks. (See 'Early eradication of Pseudomonas aeruginosa' above.)

-For patients with frequent exacerbations (>3 times per year), we suggest initiating chronic prophylactic antibiotics (Grade 2B). For most patients, we suggest a macrolide (eg, azithromycin) as the preferred agent for chronic antibiotic therapy rather than other antibiotics (Grade 2C). Limited clinical trial data suggest that chronic prophylactic antibiotic therapy reduces the frequency of exacerbations; however, it also promotes the carriage of resistant bacteria. We prefer azithromycin because it is the agent that has been studied in this population, as well as in patients with CF. Inhaled tobramycin or colistin may be used as an alternative or in addition to chronic oral antibiotics in children who are chronically infected with P. aeruginosa who have frequent exacerbations. (See 'Chronic antibiotics' above.)

-For children with moderate or severe daily symptoms, frequent exacerbations, and/or difficulty in expectoration, we suggest routine use of either inhaled hypertonic saline (6 or 7%) or inhaled dry powder mannitol (Grade 2C). The treatment should be given twice daily before airway clearance techniques. Each dose should be preceded by a bronchodilator to reduce the risk of bronchospasm. (See 'Inhaled airway hydrating agents and mucolytics' above.)

-Children with coexisting asthma or definite bronchial hyperreactivity should be treated with bronchodilators and inhaled glucocorticoids as indicated for the asthma. For children without coexisting asthma, these drugs should not be used (except as pretreatment for inhaled therapy, as noted above), as there is no evidence that they are beneficial. (See 'Bronchodilators and glucocorticoids' above.)

●Supportive care – Other important aspects of care include avoiding smoke and other respiratory irritants and ensuring optimal nutrition and immunizations. In addition, self-management education and support can improve adherence and outcomes, which may include an individualized bronchiectasis action management plan. (See 'Supportive care' above.)

●Prognosis – With optimal management of pediatric bronchiectasis, lung function often stabilizes or improves with age. A minority of children progress to advanced lung disease. Complications of advanced lung disease include hemoptysis, which can be life-threatening, and (rarely) hypoxemia (table 3). (See 'Management of advanced lung disease' above and 'Prognosis' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Khoulood Fakhoury, MD, and Adaobi Kanu, MD, who contributed to earlier versions of this topic review.