What causes mucus plugs?

Causes of Mucus Plugs

Mucus plugs are primarily caused by excessive mucus production, impaired mucociliary clearance, airway inflammation, and chronic bronchial infection, often occurring in respiratory conditions like asthma, chronic bronchitis, and bronchiectasis. 1

Pathophysiological Mechanisms

Excessive Mucus Production

• Goblet cell hyperplasia and metaplasia: Enlargement and increase in number of submucosal glands and goblet cells in the airway epithelium 1
• Inflammatory mediators: Tachykinins (substance P, neurokinin A, neurokinin B) found in sputum of patients with chronic bronchitis that augment airway secretions 1
• Mucin hypersecretion: Predominantly MUC5AC and MUC5B, which contribute to the viscosity and stickiness of mucus 2

Impaired Mucociliary Clearance

• Ciliary dysfunction: Decrease in number and length of cilia in chronic respiratory diseases 1
• Squamous metaplasia: Structural changes in the epithelium that impair normal ciliary function 1
• Airway dehydration: Leads to increased viscosity of mucus, making it difficult to clear 1

Airway Inflammation

• Neutrophilic inflammation: Primary inflammatory cell type in bronchiectasis and chronic bronchitis 1
• Eosinophilic inflammation: Particularly in allergic conditions like asthma and allergic bronchopulmonary aspergillosis (ABPA) 3, 2
• Cytolytic degranulation: Eosinophils exposed to mucus from IL-13-activated airway epithelial cells undergo CD11b- and glycan-dependent degranulation 2

Chronic Bronchial Infection

• Bacterial colonization: Common pathogens include Haemophilus influenzae, Pseudomonas aeruginosa, Moraxella catarrhalis, and Staphylococcus aureus 1
• Bacterial exoproducts: Stimulate mucus production, slow ciliary beating, impair immune effector cell function, and destroy local immunoglobulins 1
• Biofilm formation: Creates a protective environment for bacteria, making them resistant to host defenses and antibiotics 1

Disease-Specific Causes

Asthma

• Airway remodeling: Characterized by smooth muscle hyperplasia and goblet cell hyperplasia 2
• Type 2 inflammation: Innate lymphoid type 2 cells contribute to mucus hypersecretion 2
• Persistent plugs: Mucus plugs in asthma can persist in proximal airways (generations 6-9) for years, fluctuating in length and volume 4

Chronic Bronchitis

• Smoking: Primary cause of goblet cell hyperplasia and mucous gland enlargement 1
• Vicious cycle: Pooling of secretions provides a medium for bacterial growth, which further damages cilia and epithelial cells 1
• Ineffective cough: Decreased expiratory flow leads to retention of secretions 1

Bronchiectasis

• Structural damage: Bronchial dilatation and wall thickening impair normal clearance mechanisms 1
• Chronic infection: Persistent bacterial colonization maintains inflammation and mucus hypersecretion 1
• Diffuse panbronchiolitis: In East Asian populations, characterized by inflammatory nodules and bronchiolectasis 1

Allergic Bronchopulmonary Aspergillosis (ABPA)

• Hypersensitivity reaction: Immune-mediated inflammatory response to Aspergillus fumigatus antigens 3
• Central bronchiectasis: Key diagnostic feature on imaging 3
• High IgE levels: Total IgE ≥500 IU/mL and A. fumigatus-specific IgE ≥0.35 kUA·L−1 3

Clinical Implications

• Mucus plugs cause airway obstruction, leading to ventilation impairment and potentially irreversible bronchiectasis if untreated 3
• In COPD, each 1-point increase in airway mucus plug score is associated with an 8.3% higher risk of moderate-to-severe exacerbations 5
• Mucus plugs in proximal airways have greater effects on spirometry measures than plugs in smaller distal airways 4

Treatment Considerations

• Mucolytics: Acetylcysteine works by breaking disulfide linkages in mucus, lowering viscosity (most effective between pH 7-9) 6
• Airway clearance techniques: Essential for mobilizing secretions in bronchiectasis and chronic bronchitis 1
• Anti-inflammatory therapy: Corticosteroids are the mainstay of treatment for ABPA-related bronchiectasis 3
• Targeted biologics: Tezepelumab has been shown to reduce mucus plugs in patients with moderate-to-severe asthma 7

Recognizing the underlying causes of mucus plugs is crucial for implementing appropriate treatment strategies to break the vicious cycle of mucus hypersecretion, inflammation, and infection in respiratory diseases.