What is interstitial thickening in the lungs?

What is Interstitial Thickening in the Lungs?

Interstitial thickening in the lungs refers to abnormal thickening of the alveolar walls (septa) due to collagen deposition, inflammation, or both, which impairs gas exchange and leads to progressive breathlessness and reduced lung function. 1

Anatomic Definition

The lung interstitium is the tissue space between the alveolar epithelial cells and the capillary endothelial cells. When this space becomes thickened, it represents:

• Collagen deposition and fibrosis that expands the alveolar septal walls 1
• Inflammatory cell infiltration including lymphocytes, plasma cells, and macrophages 1
• Architectural distortion that progressively destroys normal gas-exchanging units 2, 3

The term "interstitial" is somewhat misleading because the disease process frequently extends beyond just the interstitium to involve alveolar spaces, pulmonary microvasculature, and sometimes airways. 3

Three Distinct Patterns of Interstitial Thickening

The European Respiratory Review provides a framework for understanding interstitial thickening based on its distribution within the lung lobule: 1, 4

1. Bronchiolocentric Pattern

• Thickening concentrated around small airways (respiratory bronchioles) with peribronchiolar alveolar septal expansion 1
• Often accompanied by peribronchiolar metaplasia where bronchiolar epithelium extends onto thickened septa 1
• Caused by inhalation injuries (fumes, dust), aspiration, or systemic diseases affecting airways 1, 4
• Associated conditions include smoking-related disease, hypersensitivity pneumonitis, and autoimmune diseases like Sjögren syndrome 4

2. Nonspecific Interstitial Pneumonia (NSIP) Pattern

• Diffuse, uniform thickening affecting all alveolar septa equally (peribronchiolar, subpleural, and intermediate zones) 1
• Maintains underlying lung architecture creating a "dusty cobweb" appearance on microscopy 1, 4
• Results from diffuse alveolar inflammation followed by uniform fibrosis 4
• Commonly seen with autoimmune connective tissue diseases, drug reactions, and hypersensitivity pneumonitis 1, 4
• Better prognosis than other patterns with estimated 15-20% mortality at 5 years and most patients responding to corticosteroids 1

3. Usual Interstitial Pneumonia (UIP) Pattern

• Peripheral and subpleural predominance with microscopic honeycombing in outer lung zones 1
• Heterogeneous appearance with dense scarring adjacent to relatively normal lung tissue 1
• Fibroblastic foci (active areas of fibrosis) at interfaces between scarred and normal tissue 1
• Associated with idiopathic pulmonary fibrosis and has the worst prognosis among fibrotic patterns 4
• Linked to abnormal cellular senescence rather than inflammation 4

Clinical Significance and Consequences

The primary consequence of interstitial thickening is impaired gas exchange, which manifests as: 2, 3

• Progressive dyspnea on exertion that worsens over months to years 1
• Dry, nonproductive cough 1
• Crackles (rales) on lung examination 1
• Restrictive lung function pattern with reduced lung volumes 1, 3
• Hypoxemia that worsens with exercise 1
• Diminished exercise tolerance and quality of life 2

Diagnostic Approach

High-resolution CT (HRCT) is the primary imaging modality for characterizing interstitial thickening patterns: 1

• Ground-glass opacities indicate active inflammation or early fibrosis 1
• Reticular opacities represent established septal thickening 1
• Honeycombing indicates end-stage fibrosis with architectural destruction 1
• Distribution pattern (subpleural vs. diffuse vs. bronchiolocentric) guides differential diagnosis 1, 4

Lung biopsy remains important when imaging is indeterminate, showing: 1

• Degree and pattern of collagen deposition 1
• Presence of inflammatory cells and their distribution 1
• Architectural preservation versus destruction 1
• Specific features like fibroblastic foci or granulomas 1

Common Pitfalls

Chest radiography is insensitive for detecting early interstitial thickening and may appear normal in up to 20% of cases with established disease. 1, 5 Do not rely on chest X-ray alone to exclude interstitial lung disease.

The diagnosis requires multidisciplinary discussion integrating clinical, radiologic, and pathologic data, as observer agreement improves substantially when all modalities are considered together rather than in isolation. 1

Not all interstitial thickening is irreversible—some patterns (particularly NSIP and organizing pneumonia) respond well to treatment, while others (UIP pattern) are generally progressive despite therapy. 1, 4 The specific pattern determines prognosis and treatment approach.

Smoking cessation is critical when smoking-related interstitial disease is identified, as up to 90% of patients show resolution with cessation alone. 6