What is small airway disease?

What is Small Airway Disease?

Small airway disease refers to pathological processes affecting airways with an internal diameter of 2 mm or less that lack cartilage in their walls, characterized by variable degrees of cellular inflammation (lymphocytic, neutrophilic, eosinophilic, or granulomatous), fibrosis, and architectural distortion. 1

Anatomical Definition

• Small airways are defined as those with an internal diameter ≤2 mm without cartilage in their walls 1
• These airways include the membranous and respiratory bronchioles, which are distal to the terminal bronchioles 1
• The small airways constitute the primary site where airflow obstruction begins and progresses in chronic lung diseases 2, 3

Pathological Features

The disease manifests through three key pathological processes:

• Cellular inflammation: Can be lymphocytic, neutrophilic, eosinophilic, or granulomatous in nature 1
• Fibrosis: Occurs in the airway walls and surrounding tissue, leading to smooth muscle hyperplasia and wall thickening 1, 4
• Architectural distortion: Results in airway narrowing, obliteration, and eventual complete airway loss 1, 2

In asbestos-related small airway disease specifically, inflammation and fibrosis occur in the walls of membranous bronchioles with smooth muscle hyperplasia, while respiratory bronchioles show fibrosis extending into alveolated portions 1

Clinical Significance

Small airway disease has substantial clinical consequences:

• Associated with poor lung function, increased hyperinflation, and impaired quality of life 2, 5
• Present in early stages of COPD and becomes more widespread as disease progresses 3
• Can cause cough with or without mucous hypersecretion and bronchial hyperresponsiveness 1
• May result in incomplete or irreversible airflow limitation 1

Diagnostic Challenges

A critical pitfall is that small airways cannot be directly visualized on standard imaging:

• HRCT resolution is limited to airways >2 mm in diameter, so normal bronchioles cannot be visualized 1
• Chest radiographs are often normal despite clinically significant bronchiolar disease 1
• Direct HRCT signs include airway dilation, wall thickening, nodular branching (2-4 mm), and tree-in-bud abnormalities 1
• Indirect HRCT signs include air-trapping (mosaic attenuation on expiratory scans) and subsegmental atelectasis 1

Expiratory CT imaging is essential because air trapping appears as focal zones of hypoattenuation that lack normal increase in attenuation on expiratory images 6

Distinction from Related Conditions

Small airway disease must be distinguished from conditions affecting larger airways:

• Excludes bronchiolar abnormalities associated with asthma, COPD/emphysema, and bronchiectasis when those are the primary diagnoses 1
• In COPD specifically, small airway disease represents the airway component (inflammation, increased wall muscle mass, fibrosis, narrowing) as distinct from emphysema (parenchymal destruction) 4
• The relative contribution of small airway disease versus emphysema to airflow limitation varies by disease severity—small airways play a greater role in mild to moderate COPD, while emphysema dominates in severe disease 4

Associated Conditions

Small airway disease occurs in multiple clinical contexts:

• Nonbronchiectatic suppurative airway disease (bronchiolitis) 1
• Inflammatory bowel disease-related lung involvement 1
• Diffuse panbronchiolitis (primarily in Japan, Korea, and China) 1
• Asbestos exposure 1
• Connective tissue diseases including Sjögren's syndrome 1
• Post-infectious states 1

The pathogenesis of cough in bronchiolitides is unknown, but inflammation, fibrosis, and architectural distortion of small airways—with or without mucous hypersecretion and bronchial hyperresponsiveness—almost certainly contribute 1