What causes bronchiectasis?

From the Guidelines

Bronchiectasis is primarily caused by a vicious cycle of chronic bronchial infection, inflammation, impaired mucociliary clearance, and structural lung damage, with the most common infectious agents being Haemophilus influenzae and Pseudomonas aeruginosa. This cycle leads to the destruction of the airway walls, resulting in the characteristic abnormal widening and scarring of the bronchial tubes. The underlying causes of bronchiectasis can be diverse, including severe or recurrent respiratory infections, genetic conditions such as cystic fibrosis, primary ciliary dyskinesia, and alpha-1 antitrypsin deficiency, as well as autoimmune disorders and immunodeficiency disorders 1.

Key Factors Contributing to Bronchiectasis

• Chronic airways infection with Haemophilus influenzae and Pseudomonas aeruginosa stimulates and sustains lung inflammation, leading to an increased frequency of exacerbations, worse quality of life, and increased mortality 1.
• Inflammation in bronchiectasis is primarily neutrophilic and closely linked to persistent bacterial infection, with excessive neutrophilic inflammation contributing to an increased frequency of exacerbations and rapid lung function decline 1.
• Impaired mucociliary clearance, due to structural bronchiectasis, airway dehydration, excess mucus volume, and viscosity, further contributes to the disease process by preventing mucus stasis and the associated mucus plugging, airflow obstruction, and progressive lung damage 1.

Recent Guidelines and Recommendations

The European Respiratory Society guidelines for the management of adult bronchiectasis emphasize the importance of improving quality of life and stopping disease progression, with a focus on preventing or suppressing acute and chronic bronchial infection, improving mucociliary clearance, and reducing the impact of structural lung disease 1. Similarly, the British Thoracic Society guideline for the use of long-term macrolides in adults with respiratory disease highlights the potential benefits of macrolides in breaking the vicious cycle of chronic bacterial infection, inflammation, impaired mucociliary clearance, and structural lung disease in bronchiectasis 1.

Clinical Implications

The management of bronchiectasis should prioritize the prevention of exacerbations, improvement of mucociliary clearance, and reduction of inflammation, with the goal of improving quality of life, reducing morbidity, and mortality. This can be achieved through a combination of antimicrobial therapy, airway clearance techniques, and anti-inflammatory treatments, as well as addressing underlying causes and comorbidities 1.

From the Research

Causes of Bronchiectasis

• Bronchiectasis is a complex, heterogeneous disorder with multiple underlying causes, including:
  • Severe infections 2
  • Mycobacterial disease 2
  • Autoimmune conditions 2, 3
  • Hypersensitivity disorders 2
  • Genetic conditions 2, 4
• The disease can also be caused by acquired conditions, such as post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD) 5
• In some cases, the cause of bronchiectasis is unknown, with around 30-40% of patients having an unknown cause 4

Pathophysiology of Bronchiectasis

• The pathophysiology of bronchiectasis is understood in terms of interdependent concepts of:
  • Chronic infection 2, 6, 5, 4, 3
  • Inflammation 2, 6, 5, 4, 3
  • Impaired mucociliary clearance 2, 6, 4, 3
  • Structural lung damage 2, 6, 5, 4, 3
• Neutrophilic inflammation is characteristic of the disease, with elevated levels of harmful proteases such as neutrophil elastase associated with worse outcomes 2
• The presence of airway infection together with chronic inflammation, airway mucociliary dysfunction, and lung damage are key components of the vicious vortex model that better describes the pathophysiology of bronchiectasis 4