What is obstructive small airway disease?

Obstructive Small Airway Disease

Obstructive small airway disease refers to pathological changes in airways ≤2 mm in diameter (small bronchi and bronchioles) that cause increased airflow resistance through inflammation, fibrosis, mucus obstruction, wall thickening, and eventual airway obliteration and loss. 1

Anatomical Definition

Small airways are specifically defined as those with an internal diameter ≤2 mm without cartilage in their walls, including the membranous and respiratory bronchioles distal to the terminal bronchioles. 1 These peripheral airways are the major sites of increased airflow resistance in COPD and represent a critical component distinct from emphysema (which involves parenchymal destruction). 2

Key Pathological Features

The disease manifests through several interconnected mechanisms that progressively worsen airflow obstruction:

Structural Changes

• Goblet cell hyperplasia: Appearance and increase in number of mucus-producing cells 2
• Increased intraluminal mucus: Causes direct lumen obstruction 2
• Wall thickening: Increased wall muscle mass and fibrosis leading to decreased airway diameter 2
• Inflammatory infiltration: Predominantly lymphocytic, neutrophilic, or eosinophilic cells in the submucosa 1, 3
• Loss of alveolar attachments: Reduces the tethering forces that normally keep airways open 2
• Airway obliteration and complete loss: Progressive narrowing leading to eventual disappearance of airways 2, 1

Functional Consequences

The pathological abnormalities contribute to increased resistance to airflow through six primary mechanisms: (1) lumen obstruction by mucus, (2) changes in lining fluid properties, (3) increased wall thickening with decreased diameter, (4) smooth muscle contraction, (5) loss of alveolar attachments, and (6) complete obliteration of small airways. 2

Clinical Significance and Disease Progression

Small airway disease plays a greater role in mild to moderate COPD, while emphysema becomes the dominant factor in severe disease. 2 This is a critical distinction for understanding disease evolution:

Early Disease (GOLD 1-2)

• Terminal bronchioles decrease by 40-43% compared to control smokers 4
• Transitional bronchioles decrease by 56-59% 4
• These changes occur even in lung samples with normal alveolar surface area, indicating small airway destruction precedes emphysema development 4
• The early stages are characterized by unevenly distributed narrowing of peripheral airways 2

Disease Progression

• Small airways disease is present in early COPD and becomes more widespread as disease progresses 3
• In mild to moderate airflow limitation, the decrease in maximum flow could be secondary to either loss of recoil or small airway abnormalities such as inflammation, deformity, narrowing, and obliteration 2
• As severity increases, emphysema becomes the predominant factor limiting airflow 2

Clinical Manifestations

Patients with obstructive small airway disease may present with:

• Cough with or without mucous hypersecretion 1
• Bronchial hyperresponsiveness 1
• Incomplete or irreversible airflow limitation 1
• Poor spirometry results with reduced FEV1/FVC ratio 5
• Increased lung hyperinflation 6
• Impaired quality of life 6

Diagnostic Challenges

Normal chest radiographs and HRCT limitations make direct visualization difficult, as HRCT resolution is limited to airways >2 mm in diameter. 1 However, indirect signs can be detected:

Direct HRCT Signs

• Airway dilation and wall thickening 1
• Nodular branching (2-4 mm) 1
• Tree-in-bud abnormalities 1

Indirect HRCT Signs

• Air-trapping (mosaic attenuation on expiratory scans) 1
• Subsegmental atelectasis 1

Functional Testing

• When changes are mild and not accompanied by obvious reduction in maximum expiratory flow, increased resistance in small airways may be detected by tests that assess inhomogeneous functional behavior of the lung 2
• Decreased midexpiratory flow rates indicate small airway dysfunction 5

Important Clinical Distinctions

Obstructive small airway disease must be distinguished from emphysema within the COPD spectrum. 7, 1 In COPD, small airway disease represents the airway component (inflammation, increased wall muscle mass, fibrosis, narrowing) as distinct from emphysema (parenchymal destruction with loss of alveolar attachments). 7, 1

The disease also occurs in multiple non-COPD contexts including nonbronchiectatic suppurative airway disease, inflammatory bowel disease-related lung involvement, diffuse panbronchiolitis, asbestos exposure, connective tissue diseases, and post-infectious states. 1, 5

Treatment Implications

Early identification of individuals with subclinical small airway disease may allow prevention of further progression to airway loss and potential emphysema development. 8 The development of inhalers containing extra-fine particles allows small airways to be pharmacologically targeted, with recent clinical trials showing efficacy of extra-fine triple therapy. 3

The presence of airway eosinophilia predicts better bronchodilator response to β-agonists and provides rationale for anti-inflammatory treatment in specific cases. 7

Common Pitfalls

• Failing to recognize that small airway disease is the primary site for onset and progression of airflow obstruction in COPD, not just a secondary feature 8
• Assuming normal imaging excludes significant small airway disease, as chest radiographs are often normal despite clinically significant bronchiolar disease 1
• Not appreciating that small airway destruction occurs before emphysema develops, particularly the loss of terminal and transitional bronchioles in mild COPD 4
• Missing the opportunity for early intervention in mild or moderate COPD when small airway disease is the dominant pathology and potentially more reversible 4