Evaluation
Prior history of exacerbation is the most reliable predictor for future exacerbations. Chronic P aeruginosa infection and respiratory comorbidities (eg COPD, asthma, rhinosinusitis) may increase risk for exacerbation; respiratory viral infections (eg, rhinovirus, influenza, Epstein-Barr virus) may also trigger exacerbations. Identification of acute exacerbation may be difficult because onset may be gradual with sputum volume increasing slowly over months. Fever and chills are generally absent, and chest X-ray rarely shows new infiltrates. Ideally, a sputum sample should be obtained at the onset of an exacerbation prior to initiating antibiotic treatment. Furthermore, sputum culture should be repeated if there is no response to the initial antibiotic treatment.
Acute Exacerbation
Acute exacerbation is defined as acute clinical deterioration in patient status that requires changing current bronchiectasis treatment, plus at least three of the following symptoms for ≥48 hours: Cough, sputum volume and/or consistency, sputum purulence, hemoptysis, breathlessness and/or exercise tolerance, and fatigue and/or malaise.
Principles of Therapy
The principles of therapy in bronchiectasis include minimizing the general and respiratory symptoms, optimizing patient and family wellbeing and maintaining a good quality of life, limiting disease progression and preventing complications, maintaining or improving pulmonary function, and avoiding or minimizing adverse effects of the treatment.
Treatment of Acute Exacerbations
Acute exacerbations often result from infections of the upper respiratory tract that can be managed in the outpatient setting. Most outpatients who receive effective antibiotic therapy will have improvement of symptoms within 72 hours. However, no improvement or worsening of symptoms (eg, fevers, chills, malaise) should prompt re-evaluation (repeat chest X-ray and sputum culture). Inpatient management is considered if there is evidence of severe infection (eg tachypnea, acute or acute on chronic respiratory failure, significant decrease in O2 saturation or respiratory function, hypercapnia, hemoptysis, new onset cyanosis, signs of cor pulmonale, hemodynamic instability, and/or impaired cognitive function), concern for patient frailty, need for intravenous therapy, difficulties with compliance, active hemoptysis, and outpatient treatment failure. Exacerbation-associated hemoptysis may occur; minimal bleeding or small amounts of blood admixed with sputum is considered self-limiting while more profuse bleeding requires further evaluation and management.
Specific Therapy for Individual Causes
ABPA
In ABPA, the control of asthma and the prevention of damage from acute exacerbations is crucial. Maintenance oral corticosteroids are considered as well. Additionally, antifungal therapy (eg Itraconazole) remains second-line choice unless there is associated invasive aspergillosis.
Hypogammaglobulinemia
In hypogammaglobulinemia, IV immunoglobulins is administered with guidance and supervision from an immunologist.
Primary Ciliary Dyskinesia
More intensive therapy may be needed in primary ciliary dyskinesia, based on the assumption that disease progression is more likely. There is also an emphasis on physical therapy
Other Conditions
Bronchiectasis may precede, accompany or follow the development of associated diseases such as TB, (HIV), rheumatoid arthritis, sarcoidosis, GERD, chronic rhinosinusitis, nontuberculous mycobacterial infection, COPD, and asthma. Active associated diseases should be treated based on existing guidelines.
Pharmacological therapy
Bronchiectasis_Management 1Treatment of Acute Exacerbation
Antibiotics
Antibiotic therapy is one of the mainstays of treatment for bronchiectasis, used to break the cycle of bacterial infection that leads to inflammation and further lung injury. It is the appropriate therapy for the treatment of exacerbations and chronic active disease. The choice of antibiotics should be based on prior culture results (within the past 12-24 months) when available, success or failure of previous regimens, local antibiotic susceptibility patterns, clinical severity, patient tolerance, and allergies. Most patients have chronic colonization of organisms which is the basis for empiric choice of antibiotic. Amoxicillin or Doxycycline may be used for patients with sputum cultures negative for beta-lactamase-positive H influenzae or P aeruginosa. They are the first-line treatment for patients without previous bacteriological exams. Higher doses may be used for patients with H influenzae colonization.
Quinolones (eg Ciprofloxacin, Levofloxacin) may be used in patients with suspected P aeruginosa colonization and reasonable therapeutic option for oral administration in ambulatory patients and those without previous culture.
Notably, some authorities may choose empiric antibiotic therapy based on clinical parameters. Forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) of <60% and daily sputum >20 mL are independently associated with the presence of P aeruginosa. Patients with little sputum and good lung function may only require non-pseudomonal antibiotics. Treatment with cephalosporin, Amoxicillin/clavulanic acid, Doxycycline, oral macrolides or fluoroquinolones is considered in patients with suspected or recent sputum culture with non-pseudomonal beta-lactamase-positive organism. While treatment with Ciprofloxacin (first-line if with no known resistance or prior treatment), Cefepime, Ceftazidime, antipseudomonal Penicillins (Piperacillin/Tazobactam, Aztreonam, Meropenem), Colistin, or IV aminoglycoside (Gentamicin, Tobramycin) is considered in patients with suspected pseudomonal acute exacerbation. It must be noted that Tobramycin should not be used as a monotherapy. Flucloxacillin or Clarithromycin is considered in Methicillin-sensitive S aureus exacerbation. For Methicillin-resistant S aureus exacerbation, oral Rifampicin plus Trimethoprim, oral Rifampicin plus Doxycycline, Vancomycin, or Linezolid are used.
Patients with evidence of severe infection, sepsis or impending respiratory failure should receive broad-spectrum intravenous antibiotics covering Pseudomonas and methicillin-resistant S aureus (MRSA) while awaiting culture results. The typical regimens used include Vancomycin or Linezolid for MRSA plus an antipseudomonal penicillin, third generation cephalosporin, Carbapenem or Aztreonam.
The duration of therapy is not well-defined, but a minimum of 7-10 days has become a frequent practice. Antibiotic therapy of 14 days duration for acute exacerbations, based on microbiologic test results and severity of exacerbation is recommended by the European Respiratory Society. Patients who fail to respond to oral antibiotics should receive intravenous antibiotics for at least 5 days, then transition to an oral regimen if clinical improvement is evident, to complete a total of 14 days.
Bronchodilators
Beta2-agonists may be theoretically beneficial in bronchiectasis since they increase ciliary beat frequency in vitro. Administration of beta2-agonists prior to chest physiotherapy may help produce more sputum during clearance and may help increase expiratory flow rates.
Bronchiectasis_Management 5Corticosteroids
Inhaled or oral corticosteroids should not be routinely prescribed in either short or long-term treatment of bronchiectasis without other indications (eg asthma and/or eosinophilic airway inflammation, COPD, inflammatory bowel disease). It must be noted that systemic corticosteroids are generally not recommended as it can further depress host immunity, promote increased bacterial and fungal colonization, and perpetuate infection.
Other Agents
Antivirals
According to the Centers for Disease Control and Prevention, patients with bronchiectasis are at increased risk for severe COVID-19. Hence, patients presenting with acute exacerbation caused by influenza or COVID-19 should be started on antivirals (eg oral Oseltamivir or Baloxavir; intravenous Peramivir for patients unable to tolerate oral medications).
Nonsteroidal Anti-inflammatory drugs (NSAIDs)
Some studies showed that treatment with Indometacin helps reduce sputum production and improve dyspnea in bronchiectasis patients. Additionally, oral Ibuprofen may help reduce airway inflammation in patients with CF.
Long-Term Therapy
Bacterial pathogens are thought to have an active destructive role, therefore suppressive antibiotic therapies have been used in bronchiectasis patients. It is thought that some organisms (eg P aeruginosa and H influenzae) stimulate neutrophilic and inflammatory mediator response in the airways.
Inhaled Antibiotics
A therapeutic trial of inhaled antibiotics is recommended for patients with P aeruginosa in their sputum and either ≥3 exacerbations per year or those with significant morbidity from fewer exacerbations. Colistin is recommended for patients with chronic P aeruginosa colonization. While Gentamicin is a treatment option for patients with chronic P aeruginosa colonization if Colistin therapy fails and as second-line option after macrolide therapy in non-pseudomonas colonized patients. Inhaled antibiotics may be considered in patients where bronchiectasis is due to CF. Tobramycin or Colistin may improve sputum volume, purulence and exacerbation frequency, sputum P aeruginosa and myeloperoxidase levels, and general well-being b. A significant reduction in bacterial count for P aeruginosa was seen in patients given Colistin therapy. Furthermore, a dose of Tobramycin 300 mg inhaled 12 hourly via nebulizer is used in children >6 years and adults x 28 days on, followed by 28 days off for CF patients. This dose has been used in bronchiectasis patients. Colistin 0.5-1 MIU in children <2 years old and 1-2 MIU in adults and children >2 years old inhaled 12 hourly is used in CF patients. It has been also noted that inhaled Ceftazidime plus Tobramycin given over 12 months improve hospitalization frequency and duration but not lung function or antibiotic usage. Increased time to next exacerbation was seen in patients given inhaled Gentamicin and Ciprofloxacin.
Brensocatinib
Brensocatinib is a dipeptidyl peptidase 1 inhibitor indicated for the treatment of non-CF bronchiectasis in adult and pediatric patients 12 years of age and older. It demonstrated a reduction in the annual rate of pulmonary exacerbations compared with placebo in 2 randomized, double-blind, placebo-controlled, parallel-group, multicenter, multinational clinical trials (ASPEN and WILLOW). It is suggested as second-line therapy for patients with ≥2 exacerbations in a year despite antibiotic therapy (eg macrolide, inhaled antibiotics) or those who cannot tolerate ongoing antibiotic therapies.
Intermittent IV Antibiotics
Some authorities recommend intermittent IV antibiotics for patients who have copious sputum production (>60 mL/day) when at steady state and/or who have frequent exacerbations (≥3 episodes/year). They may also be considered in preparation for major surgery including resection of a bronchiectatic region of a lung and other procedures when pulmonary function may be compromised. With intermittent IV antibiotics, patients are hospitalized for 2-3 weeks of antibiotics every 2-3 months. Notably, IV Ceftazidime, Amoxicillin/clavulanic acid and quinolones have been used. Additionally, chest physiotherapy is administered and rest is encouraged. Some authorities have suggested that the intermittent IV antibiotics may decrease the cumulative hospitalization frequency and the need for antibiotic therapy in the medium term.
Macrolides
Example drugs: Azithromycin, Erythromycin
Macrolides should be considered in non-Pseudomonas colonized bronchiectasis patients who suffer from recurrent exacerbations (≥2 per year) or to those with fewer exacerbations but with high symptom burden. Long-term administration of macrolides as preventive therapy can reduce the frequency of exacerbations, the number of patients experiencing at least one exacerbation, time to first exacerbation, sputum purulence, and breathlessness. Macrolides inhibit respiratory mucous secretion by decreasing pulmonary macrophage mucous secretagogue production. They also reduce P aeruginosa exotoxin production which slows human respiratory ciliary beat in vitro and decreases P aeruginosa adherence to damaged airway in vitro. Treatment with macrolides is considered if there is treatment failure after inhaled antibiotics, or as adjunctive therapy to inhaled antibiotics in Pseudomonas-colonized patients with increased frequency of exacerbation. Low-dose macrolide therapy may be continued for 1-2 years before stopping if there is clear clinical improvement or withdrawn if there is no improvement after 3-4 months of therapy.
Other Agents
Treatment with Amoxicillin or Doxycycline is considered in non-Pseudomonas-colonized patients who have had ≥3 exacerbations in a year and is intolerant or unresponsive to combined macrolide and inhaled antibiotic therapy. Bronchodilators may be considered in bronchiectasis patients with breathlessness or with coexisting COPD or asthma; the use should follow the recommendations of the corresponding disease.
Immunization
It must be noted that patients with bronchiectasis should receive standard vaccinations against respiratory pathogens and that immunization of household members may be considered to reduce risk of secondary transmission.
Bronchiectasis_Management 2Coronavirus Disease 2019 (COVID-19)
COVID-19 vaccines should be given according to national public health policies.
Influenza Vaccine
Timely annual influenza vaccination should be given to all patients with bronchiectasis.
Pneumococcal Vaccine
Pneumococcal vaccines are recommended for patients with chronic respiratory diseases. They are typically administered to patients with bronchiectasis.
Pertussis Vaccine
Pertussis vaccine is recommended as a one-time dose as an adult (≥19 years) and may be administered with tetanus and diphtheria booster every ten years.
Respiratory Syncytial Virus (RSV) Vaccine
RSV vaccine is warranted in most patients with bronchiectasis. The timing of vaccination depends on age, severity of disease, and degree of immunocompromise.
Please see Respiratory Syncytial Virus disease management chart for further information.
Nonpharmacological
Patient Education
It is important to encourage the patient to stop smoking (including vaping /e-cigarettes, cannabis) and avoiding lung irritants (eg secondhand smoke, smoke from indoor fires, cleaning agents, dust, fumes). Exposure to fresh air and avoiding airborne pollutants are promoted. Patients should also have adequate nutritional intake with supplementation if needed. Regular exercise is also advocated. The quality of life and exercise endurance is improved with inspiratory muscle training. Immunizations are recommended for coronavirus disease 2019 (COVID-19), influenza, and pneumonia. Lastly, immunizations for measles, rubeola, and pertussis are confirmed.
Chest Physiotherapy
Effective chest physiotherapy can improve mucus drainage, reduce inflammation and susceptibility to infections, and improve quality of life. Referral to a chest physiotherapist for a more tailored technique is recommended.
Airway Clearance Therapy
Patients should learn different airway clearance techniques and exercises. Airway clearance techniques should include active cycle of breathing techniques, manual techniques (percussion, shaking, vibrations, over pressure), postural drainage, positive expiratory pressure (PEP), oscillating PEP, autogenic drainage, inspiratory muscle training (IMT), high frequency chest wall oscillation, intrapulmonary percussive ventilation, and intermittent positive pressure breathing. Airway clearance techniques should be performed 1-2 times per week for a minimum of 10 minutes up to 30 minutes per session. The frequency and duration may be adjusted according to individual needs. Inhalation exercises (eg IMT, expiration with the glottis open in the lateral posture) when done together with pulmonary rehabilitation, increase the beneficial effects of these programs. Additionally, airway clearance therapy has been shown to reduce peripheral airway obstruction, decrease inflammatory cells in sputum, improve exercise capacity, increase sputum volume, and reduce impact of cough on quality of life. Lastly, airway clearance techniques may enhance sputum clearance during acute exacerbations.
Pulmonary Rehabilitation
Pulmonary rehabilitation is recommended for patients with shortness of breath or limited exercise capacity. Studies on pulmonary rehabilitation have shown significant improvements (increased exercise capacity, improved quality of life, longer interval to next exacerbation) in patients.
Bronchopulmonary Hygiene
Bronchopulmonary hygiene is one of the mainstays in the treatment of bronchiectasis, with unknown long-term effectiveness. It aids in removing secretions from the lower airway in patients with mucus hypersecretion and expectoration problems. Systemic hydration enhanced by nebulization with saline remains a necessity in patients with mucous plugging and viscous secretions. Lastly, mucolytics (eg Acetylcysteine) alter characteristic of sputum and may aid expectoration of secretions.
Oxygen (O2) Therapy
Long-term O2 therapy may be considered for patients whose respiratory status is unstable with impending respiratory failure, especially patients with underlying COPD. Non-invasive ventilation may be considered in patients with bronchiectasis with respiratory failure, hypercapnia, and in need of hospitalization intermittently.
Bronchiectasis_Management 3Surgery
Surgery should be confined to patients with failed medical treatment, localized and troublesome disease. The recurrence of cough and sputum production in the remaining bronchial tree often occurs or recurrent hemoptysis.
The goals of surgery include foreign body or tumor removal, which could besurgical or bronchoscopic, removal of lobes or segments of disease that are the most damaged and may be contributing to acute exacerbations, removal of overwhelming viscous secretions, mucous impaction or plugs, control of hemoptysis, and removal of multi-drug resistant MAC or Aspergillus sp infection.
Bronchiectasis_Management 4Lung Resection
Lung resection may be considered in patients with localized disease and frequent exacerbations who were deemed unresponsive to medical and nonpharmacologic treatment.
Indications for lung resection include:
- Therapeutic failure after 1 year of medical treatments
- Severe or frequent exacerbations with significant impact in patient’s quality of life
- Recurrent refractory or massive hemoptysis (>600 mL/day)
- Bronchiectasis due to obstruction secondary to a tumor
- Presence of localized severely damaged, nonfunctional pulmonary lobe or segment that may cause sepsis and further lung damage
Lung resection is the preferred management option for patients with massive hemoptysis refractory to bronchial artery embolization, while video-assisted thoracoscopic surgery (VATS) is preferred over open surgery due to lower complication rates, better preservation of lung function, reduced scarring, and shorter days of hospitalization. However, VATS is not recommended in the presence of calcified nodes near hilar vessels or major parenchymal or pleural fibrosis.
Lung Transplantation
Lung transplantation may be considered in patients ≤65 years with FEV1 <30% and unstable lung function or rapid progressive respiratory deterioration despite aggressive medical treatment. Patients with massive hemoptysis, severe secondary pulmonary hypertension (HTN), diffuse bilateral disease, or respiratory failure may be considered for lung transplantation.