What is the pathophysiology of bronchiectasis?

Pathophysiology of Bronchiectasis

Bronchiectasis pathophysiology centers on a self-perpetuating "vicious cycle" where chronic airway infection triggers inflammation, which impairs mucociliary clearance and causes structural airway destruction, creating conditions that promote further infection. 1

The Core Vicious Cycle

The pathophysiology operates through three interconnected pathogenic elements that continuously amplify each other 1, 2:

• Chronic bronchial infection drives persistent airway inflammation 1
• Neutrophilic inflammation releases proteases that destroy bronchial wall components 1, 3
• Impaired mucociliary clearance leads to mucus stasis and bacterial colonization 1
• Structural lung damage (bronchial dilatation, wall thickening) predisposes damaged airways to further infection 1, 4

Infectious Component

Chronic airways infection, most frequently with Haemophilus influenzae and Pseudomonas aeruginosa, stimulates and sustains lung inflammation. 1

• Pseudomonas aeruginosa infection specifically associates with three-fold increased mortality risk, seven-fold increased hospitalization risk, and one additional exacerbation per patient annually 1
• Other common pathogens include Moraxella catarrhalis, Staphylococcus aureus, and Enterobacteriaceae 1
• Persistent bacterial isolation correlates with increased exacerbation frequency, worse quality of life, and increased mortality 1
• Recurrent bacterial colonization leads to progressive airway injury mediated by neutrophils, T lymphocytes, and monocyte-derived cytokines 5

Inflammatory Mechanisms

Inflammation in bronchiectasis is primarily neutrophilic and closely linked to persistent bacterial infection. 1

• Excessive neutrophilic inflammation drives increased exacerbation frequency and rapid lung function decline through elastin degradation 1, 4
• Neutrophil elastase and collagenase destroy elastic and muscular components of bronchial walls 4, 5
• Cell-mediated immunity, specifically T-cells, plays a supporting role in disease pathophysiology 1
• Inflammatory mediators create a deregulated cytokine network that can persist independent of bacterial colonization 2

Mucociliary Clearance Dysfunction

Impaired mucociliary clearance results from structural bronchiectasis, airway dehydration, and excess mucus volume and viscosity. 1

• More than 70% of bronchiectasis patients expectorate sputum daily with highly variable volumes 1
• Mucus stasis leads to mucus plugging, airflow obstruction, and progressive lung damage 1, 4
• The contractile force of surrounding lung tissue exerts traction on damaged airways, expanding their diameter 5

Structural Changes and Consequences

Bronchiectasis involves permanent destruction of elastic and muscular components of bronchial walls, leading to irreversible abnormal dilation of airways. 4, 5

• Structural changes include bronchial dilatation, bronchial wall thickening, mucus plugging, small airways disease, and emphysema 1
• More than 50% of patients develop airflow obstruction, though restrictive and mixed patterns also occur 1
• Increased bronchial arterial proliferation and arteriovenous malformations predispose to recurrent hemoptysis 5
• Breathlessness results from airflow obstruction, impaired gas transfer, exercise deconditioning, and comorbidities 1, 4

Clinical Implications of Pathophysiology

Exacerbations represent acute amplifications of the vicious cycle and are major determinants of disease progression, associated with increased airways and systemic inflammation and progressive lung damage. 1

• Exacerbations correlate with worse quality of life, daily symptoms, lung function decline, and mortality 1
• In children, each hospitalized exacerbation causes -1.9% predicted FEV₁ decline 1
• Up to 30% mortality occurs at 1-year follow-up after exacerbation, particularly with concurrent COPD 1, 4

Reversibility Considerations

In children and early disease, mild radiographic bronchiectasis (bronchial dilatation) is potentially reversible if treated optimally early, thereby avoiding later lung function deterioration. 1, 4

• Early interruption of the infection/inflammation cycle is necessary to reverse and/or halt disease progression 1
• Adults with untreated bronchiectasis symptoms from childhood have worse disease and poorer prognosis compared to adult-onset bronchiectasis 1
• More than 60% of adults with bronchiectasis have symptoms originating from childhood 1