What is interstitial fibrosis?

Interstitial Fibrosis: Definition and Patterns

Interstitial fibrosis is a pathological process characterized by excessive collagen deposition in the lung interstitium, resulting in thickening of alveolar septa and progressive scarring of lung tissue that leads to decreased lung function and impaired gas exchange. 1

Key Patterns of Interstitial Fibrosis

Interstitial fibrosis can be classified into three distinct patterns based on distribution within the pulmonary lobule:

1. Bronchiolocentric Fibrosis

• Characterized by thickening of peribronchiolar alveolar septa due to collagen deposition 1
• Often accompanied by peribronchiolar metaplasia (extension of bronchiolar epithelium onto thickened septa) 1
• Most commonly results from centrilobular injury due to:
  • Inhalation of fumes or dust
  • Aspiration
  • Systemic diseases with airway inflammation 1
• Associated conditions include:
  • Respiratory bronchiolitis from smoking
  • Hypersensitivity pneumonia
  • Asbestosis
  • Sjögren syndrome
  • Inflammatory bowel disease-related small airway disease 1

2. Nonspecific Interstitial Pneumonia (NSIP) Fibrosis

• Features diffuse alveolar septal thickening by collagen deposition 1
• Affects peribronchiolar, subpleural, and intermediate alveolar septa uniformly 1
• Maintains underlying pulmonary alveolar architecture, creating a "dusty cobweb" appearance 1
• Results from diffuse alveolar inflammation followed by fibrosis 1
• Associated with:
  • Autoimmune connective tissue diseases
  • Drug reactions
  • Some cases of hypersensitivity pneumonia
  • Organizing phase of diffuse alveolar damage 1
• Often driven by circulating factors affecting alveolar tissue diffusely 1

3. Usual Interstitial Pneumonia (UIP)

• Fibrosis accentuated at the periphery of pulmonary lobule, subpleural regions, and adjacent to interlobular septa 1
• Characterized by:
  • Subpleural microscopic honeycombing (irregular airspaces lined by bronchial epithelium surrounded by dense fibrosis)
  • Relatively normal peribronchiolar alveoli
  • Fibroblast foci at the interface between fibrotic and less-involved regions 1
• Fibroblast foci appear as bulge-like regions with bland fibroblasts arranged parallel to airspace, within myxoid matrix, with reactive cap of cuboidal epithelial cells 1
• Associated with idiopathic pulmonary fibrosis (IPF) 1
• Believed to arise from aberrant senescence rather than inflammation 1
• Associated with shortened telomeres and mutations in telomerase pathway 1

Physiological Mechanisms Underlying Fibrosis

Three primary mechanisms drive the different patterns of interstitial fibrosis:

1. Inhalation injury or airway inflammation - leading to bronchiolocentric fibrosis 1
2. Diffuse alveolar inflammation - resulting in nonspecific interstitial pneumonia pattern 1
3. Abnormal senescence - associated with usual interstitial pneumonia pattern 1

Clinical Significance and Outcomes

• Interstitial fibrosis can have an unpredictably progressive course 2
• Progression leads to increasing impairment of lung function and poor prognosis 2
• End-stage disease is characterized by irreversible scarring of lung tissue 3
• Progressive fibrosis results in declining lung function that can ultimately be fatal 4
• Antifibrotic treatments (pirfenidone, nintedanib) may slow disease progression but do not halt or reverse established fibrosis 5, 6

Pathophysiological Mechanisms

• Repetitive alveolar epithelial injury triggers early development of fibrosis 6
• Dysregulated wound repair and fibroblast dysfunction lead to ongoing tissue remodeling 6
• Both innate and adaptive immune responses accompany all stages of fibrosis 6
• Chronic inflammation is considered a pathological basis of fibrosis 4
• Excessive extracellular matrix deposition is a hallmark feature 6

Diagnostic Challenges

• Some cases may be unclassifiable due to:
  • Inadequate biopsy size
  • Advanced disease showing only end-stage fibrosis
  • Alterations from pre-biopsy treatment
  • Overlapping features between different patterns 1
• Multidisciplinary approach is essential for accurate diagnosis 1

Understanding the specific pattern of interstitial fibrosis is crucial for determining etiology, guiding treatment decisions, and predicting prognosis in affected patients.