Bronchiectasis: Comprehensive Academic Notes
Definition and Pathophysiology
Bronchiectasis is a chronic respiratory disease characterized by permanent, irreversible bronchial dilatation, chronic cough with daily sputum production, and recurrent bronchial infections, driven by a self-perpetuating vicious cycle of chronic bacterial infection, neutrophilic inflammation, impaired mucociliary clearance, and progressive structural lung damage. 1, 2
The Vicious Cycle Components
- Chronic bacterial infection: Persistent colonization with Haemophilus influenzae, Pseudomonas aeruginosa, Moraxella catarrhalis, Staphylococcus aureus, and Enterobacteriaceae drives disease progression 3, 1, 2
- Neutrophilic inflammation: Excessive neutrophilic inflammation is directly linked to elastin degradation in airways, causing rapid lung function decline and increased exacerbation frequency 3, 1, 2
- Impaired mucociliary clearance: Results from structural bronchiectasis, airway dehydration, excess mucus volume and viscosity, with >70% of patients expectorating sputum daily 3, 1
- Progressive structural damage: Includes bronchial dilatation, bronchial wall thickening, mucus plugging, small airways disease, and emphysema 3
Emerging Paradigm Shift
- Bronchiectasis should be reconceptualized as primarily a chronic inflammatory disease rather than purely an infective disorder, given the limited success of long-term antibiotics in clinical trials 4
- This paradigm shift mirrors the evolution in asthma management, moving from symptom control to permanent suppression of airway inflammation 4
Epidemiology and Clinical Impact
Prevalence and Demographics
- Prevalence ranges from 53 to 566 cases per 100,000 inhabitants, with substantial variation by region 3
- In the United States, approximately 500,000 people have non-CF bronchiectasis 5
- Prevalence increases dramatically with age: 7 per 100,000 in individuals aged 18-34 years versus 812 per 100,000 in those ≥75 years 5
- More common in women than men (180 vs 95 per 100,000) 5
Disease Burden
- Quality of life impairment in bronchiectasis equals that of severe COPD and idiopathic pulmonary fibrosis 1, 2
- 50% of European patients experience ≥2 exacerbations annually, with one-third requiring hospitalization 1, 2
- Exacerbations drive mortality, lung function decline, and healthcare costs 1
- Age-adjusted mortality rate is 1437.7 per 100,000 3
- Up to 30% mortality at 1-year follow-up after suffering an exacerbation, particularly with comorbid COPD 3
- Economic burden is similar to COPD, increasing with disease severity, hospitalizations, intensive care needs, and inhaled antibiotic use 3
Impact of Pseudomonas aeruginosa Infection
P. aeruginosa infection confers a 3-fold increased mortality risk, 7-fold increased hospitalization risk, and one additional exacerbation per patient per year—making aggressive identification and treatment of this pathogen absolutely critical. 3, 1, 2
Etiology and Associated Conditions
Common Causes
- Post-infectious: Prior pneumonia, tuberculosis, nontuberculous mycobacteria, severe measles, whooping cough 5, 6
- Genetic conditions: α1-antitrypsin deficiency, primary ciliary dyskinesia, cystic fibrosis 5
- Autoimmune diseases: Rheumatoid arthritis, inflammatory bowel disease 5
- Allergic bronchopulmonary aspergillosis (ABPA) 5
- Immunodeficiency syndromes: Common variable immunodeficiency 5
- Idiopathic: Up to 38% of cases have no identifiable cause 5
Associated Comorbidities (US Data)
Geographic Variations
- Post-inflammatory bronchiectasis remains very common in developing countries as a sequel to pulmonary tuberculosis, whooping cough, and severe measles 6
- Cystic fibrosis is the most common cause of generalized bronchiectasis in developed countries 6
Diagnostic Approach
Imaging Confirmation
High-resolution CT (HRCT) without contrast is the gold standard for confirming permanent bronchial dilatation and establishing the diagnosis of bronchiectasis. 1, 2, 5
- HRCT typically shows dilated airways, airway thickening, and mucus plugging 5
- Bronchography was historically the investigation of choice but has been replaced by HRCT 6
Initial Diagnostic Workup
All patients with suspected bronchiectasis must undergo a comprehensive etiological workup to identify treatable underlying causes. 2
Essential Laboratory Testing
- Complete blood count with differential 5
- Serum immunoglobulin quantification: IgG, IgA, IgE, IgM 2, 5
- Testing for allergic bronchopulmonary aspergillosis 2, 5
- Sputum cultures for bacteria, mycobacteria, and fungi 2, 5
Pulmonary Function Testing
- Prebronchodilator and postbronchodilator spirometry 5
- More than 50% of patients have airflow obstruction, but restrictive, mixed ventilatory patterns, and preserved lung function are also frequently observed 3
- Breathlessness is one of the strongest predictors of mortality 3
Critical Pitfall
Failure to perform an adequate etiological workup risks missing treatable causes like immunodeficiency or ABPA, which require specific targeted therapies beyond standard bronchiectasis management. 1
Treatment Goals and Principles
Primary Objectives
The primary objectives of bronchiectasis management are preventing exacerbations, reducing symptom burden, improving quality of life, and preventing disease progression (lung function decline and mortality). 1, 2
Treatment Framework
- Treatment must target all four key components of the disease: chronic bronchial infection, inflammation, impaired mucociliary clearance, and structural lung damage 7
- No therapies are currently specifically licensed by regulatory authorities in Europe or the USA for the treatment of bronchiectasis 3
- Treatment responses differ from cystic fibrosis bronchiectasis, and extrapolation from CF management should be avoided 3, 7
Non-Pharmacological Management
Airway Clearance Techniques
All patients with chronic productive cough or difficulty expectorating sputum must be taught airway clearance techniques by a trained respiratory physiotherapist—this is a cornerstone of bronchiectasis management. 7, 2
Specific Techniques and Protocols
- Techniques include active cycle of breathing, postural drainage, and manual or mechanical devices 1, 2
- Sessions should last 10-30 minutes, performed once or twice daily 7, 2
- Consider intermittent positive pressure breathing or non-invasive ventilation during acute exacerbations to reduce work of breathing 7
Monitoring and Optimization
- Annual assessment by respiratory physiotherapist to optimize airway clearance regimen 2
Critical Pitfall
Underutilization of airway clearance techniques despite strong evidence represents a major gap in bronchiectasis care. 1
Pulmonary Rehabilitation
Patients with impaired exercise capacity should participate in pulmonary rehabilitation programs—this is a strong recommendation with high-quality evidence. 2
Benefits
- Improved exercise capacity 1, 2
- Reduced cough symptoms 1, 2
- Enhanced quality of life 1, 2
- Decreased exacerbation frequency 2
Implementation
- Regular exercise participation is essential 7
Critical Pitfall
Underutilization of pulmonary rehabilitation despite strong evidence represents another major gap in bronchiectasis care. 1
Mucoactive Treatments
- Consider long-term mucoactive treatment for patients with difficulty expectorating sputum, poor quality of life, or failure of standard airway clearance techniques 7
- Consider humidification with sterile water or normal saline to facilitate airway clearance 7
- Nebulization of saline to loosen tenacious secretions is recommended 5
Important Contraindication
Do not routinely use recombinant human DNase (dornase alfa) in adults with non-CF bronchiectasis, as it may worsen outcomes. 7
Pharmacological Management
Antibiotic Therapy for Acute Exacerbations
Exacerbations, which typically present with increased cough and sputum and worsened fatigue, must be treated with 14 days of antibiotics to reduce the risk of treatment failure and improve outcomes. 7, 2, 5
Antibiotic Selection Protocol
- Selection should be based on previous sputum culture results 7, 2
- Obtain sputum cultures before starting antibiotics whenever possible 7, 2
Pathogen-Specific Antibiotic Recommendations
- Streptococcus pneumoniae: Amoxicillin 500mg three times daily for 14 days 7
- Haemophilus influenzae (beta-lactamase negative): Amoxicillin 500mg three times daily for 14 days 7
- Pseudomonas aeruginosa: Ciprofloxacin 500-750mg twice daily for 14 days 7
Intravenous Antibiotics
- Consider intravenous antibiotics for patients who are particularly unwell, have resistant organisms, or have failed to respond to oral therapy 7
Long-Term Antibiotic Prophylaxis
Consider long-term antibiotics only for patients with ≥3 exacerbations per year, and only after optimizing airway clearance and treating modifiable underlying causes. 2
For Patients with Chronic Pseudomonas aeruginosa Infection
First-line treatment is long-term inhaled antibiotics (colistin or gentamicin). 1, 7, 2
- This recommendation is based on the dramatic impact of P. aeruginosa on outcomes 1
For Patients without Pseudomonas aeruginosa Infection
First-line treatment is macrolides (azithromycin, erythromycin). 1, 7, 2
- Macrolides are recommended for patients experiencing ≥3 exacerbations per year 1
Monitoring Requirements
- Regular monitoring of sputum pathogens is essential, especially when using long-term antibiotics 2
- Monitor for drug toxicity, particularly with macrolides and inhaled aminoglycosides 2
Concerns and Limitations
- Concerns about antibiotic resistance persist with long-term prophylaxis 8
- Long-term antibiotics have had limited success in clinical trials, suggesting the need to re-evaluate bronchiectasis as purely an infective disorder 4
Treatment of Nontuberculous Mycobacteria
- Treatment with a macrolide (clarithromycin or azithromycin) with ethambutol and a rifamycin (rifabutin or rifampin) as first-line therapy for severe or progressive MAC (Mycobacterium avium complex) symptoms 7
Bronchodilators
Do not routinely offer long-acting bronchodilators for all patients with bronchiectasis. 2
- Use bronchodilators in patients with significant breathlessness, with appropriate inhalation device selection and inhaler technique training 7
- If treatment with bronchodilators does not result in a reduction in symptoms, it should be discontinued 7
- Inhaled bronchodilators (β-agonists and antimuscarinic agents) are indicated for patients with bronchiectasis who have comorbid asthma or chronic obstructive pulmonary disease 5
Inhaled Corticosteroids
Do not routinely offer inhaled corticosteroids unless comorbid asthma or COPD is present. 7, 2
- Inhaled corticosteroids are indicated for patients with bronchiectasis who have asthma or chronic obstructive pulmonary disease 5
- Do not offer long-term oral corticosteroids without other indications, such as ABPA, chronic asthma, COPD, or inflammatory bowel disease 7
Treatment of Allergic Bronchopulmonary Aspergillosis
- For patients with ABPA, immunosuppression with corticosteroids, with or without antifungal agents, is the mainstay of treatment 7
- A tapering dose of corticosteroid is usually used with monitoring of total serum IgE every 6-8 weeks as a marker of disease activity 7
Novel Anti-Inflammatory Therapies
- A new generation of novel anti-inflammatory treatments are under development 9, 4
- Repurposing of anti-inflammatory agents from other diseases could revolutionize patient care 4
Immunizations
All patients with bronchiectasis must receive annual influenza immunization and pneumococcal vaccination to prevent infections and complications. 7, 2, 8
- Consider influenza vaccination in household contacts of patients with immune deficiency and bronchiectasis 7
Surgical Management
Indications for Surgery
Do not offer surgical treatments except for patients with localized disease and high exacerbation frequency despite optimization of all other aspects of management. 7, 2
- Surgery is not performed for adult patients with bronchiectasis except in cases of localized disease and high exacerbation frequency despite optimization of all other aspects of bronchiectasis management 7
Surgical Approach
- Video-assisted thoracoscopic surgery (VATS) is preferred over open surgery to better preserve lung function and reduce scarring 7, 2
- Emergency surgery in unstable patients with massive hemoptysis is associated with higher morbidity and mortality reaching 37% 7
Evolution of Surgical Role
- The role of surgical therapy has evolved from early curative resection for all patients to a more palliative approach 6
Lung Transplantation
Indications for Transplant Referral
Consider transplant referral in bronchiectasis patients aged 65 years or less if the FEV1 is <30% with significant clinical instability or if there is rapid progressive respiratory deterioration despite optimal medical management. 7
Additional Factors for Earlier Referral
General Considerations
- Patients with advanced generalized bronchiectasis should be considered for lung transplantation 6
- Lung transplant may be considered for patients with severely impaired pulmonary function, frequent exacerbations, or both 5
Pediatric-Specific Considerations
Management Principles
- Recent guidelines from the European Respiratory Society and Thoracic Society of Australia and New Zealand emphasize early diagnosis and optimized management in children and adolescents 8
- Management strategies encompass airway clearance techniques, mucoactive agents, pulmonary rehabilitation, bronchodilators and inhaled corticosteroids tailored to individual needs and age-appropriate techniques 8
Antibiotic Management in Children
- Antibiotics play key roles in preventing exacerbations, eradicating pathogens, and managing acute exacerbations, guided by culture sensitivities and symptoms 8
- Long-term antibiotic prophylaxis, particularly macrolides, aims to reduce exacerbations, although concerns about antibiotic resistance persist 8
Multidisciplinary Approach
- Optimal management of pediatric bronchiectasis requires a multidisciplinary approach, including physiotherapy, pharmacotherapy, and vaccinations 8
Prognostic Factors and Outcomes
Mortality Risk Factors
Mortality is higher in patients with frequent and severe exacerbations, Pseudomonas aeruginosa infection, and comorbidities such as COPD. 1, 5
- Breathlessness is one of the strongest predictors of mortality 3
Disease Progression
- Exacerbations are associated with progressive decline in lung function and decreased quality of life 5
Phenotypes, Endotypes, and Treatable Traits
Heterogeneity Challenge
- The heterogeneity of bronchiectasis remains one of the most challenging aspects of management 9
- Phenotypes and endotypes of bronchiectasis have been identified to help find "treatable traits" and partially overcome disease complexity 9
Novel Concept of Disease Activity
- A novel concept of disease activity has important implications for clinical practice and future research 4
- This concept emphasizes early identification of at-risk individuals 4
Key Clinical Pitfalls and How to Avoid Them
Underutilization of Non-Pharmacological Therapies
The most common pitfall is underutilization of airway clearance techniques and pulmonary rehabilitation despite strong evidence for their benefit. 1
- Solution: Ensure all patients with chronic productive cough are referred to respiratory physiotherapy and those with impaired exercise capacity to pulmonary rehabilitation 2
Inadequate Management of P. aeruginosa
Failure to identify and treat P. aeruginosa infection aggressively given its dramatic impact on outcomes (3-fold mortality increase, 7-fold hospitalization increase). 1
- Solution: Regular sputum cultures, aggressive eradication protocols for new P. aeruginosa isolation, and consideration of long-term inhaled antibiotics for chronic infection 2
Incomplete Etiological Workup
Inadequate etiological workup missing treatable causes like immunodeficiency or ABPA. 1
- Solution: Ensure all patients undergo comprehensive initial workup including immunoglobulin quantification and ABPA testing 2
Inappropriate Extrapolation from Cystic Fibrosis
Extrapolating treatments from cystic fibrosis bronchiectasis, as treatment responses are different. 7
Inappropriate Use of Dornase Alfa
Using recombinant human DNase (dornase alfa) in non-CF bronchiectasis, which may worsen outcomes. 7
- Solution: Avoid dornase alfa in non-CF bronchiectasis 7
Overuse of Inhaled Corticosteroids
Routinely prescribing inhaled corticosteroids without comorbid asthma or COPD. 2
Future Directions and Research Gaps
Emerging Therapies
- Promising treatments in development include novel anti-inflammatory therapies 9
- Repurposing of anti-inflammatory agents from other diseases could revolutionize patient care 4