Interstitial Fibrosis Patterns and Mechanisms

Definition and Key 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, as described by the European Respiratory Review 1, 2
The European Respiratory Review recommends classifying interstitial fibrosis into three distinct patterns based on distribution within the pulmonary lobule: bronchiolocentric fibrosis, nonspecific interstitial pneumonia (NSIP) fibrosis, and usual interstitial pneumonia (UIP) 3, 2

Bronchiolocentric fibrosis is characterized by thickening of peribronchiolar alveolar septa due to collagen deposition, often accompanied by peribronchiolar metaplasia, and most commonly results from centrilobular injury due to inhalation of fumes or dust, aspiration, or systemic diseases with airway inflammation, as reported by the European Respiratory Review 3, 4, 5
Associated conditions include respiratory bronchiolitis from smoking, hypersensitivity pneumonia, asbestosis, Sjögren syndrome, and inflammatory bowel disease-related small airway disease, according to the European Respiratory Review 4, 5, 6

NSIP fibrosis features diffuse alveolar septal thickening by collagen deposition, affecting peribronchiolar, subpleural, and intermediate alveolar septa uniformly, and maintains underlying pulmonary alveolar architecture, creating a "dusty cobweb" appearance, as described by the European Respiratory Review 1, 2, 3
The European Respiratory Review states that NSIP fibrosis results from diffuse alveolar inflammation followed by fibrosis, and is associated with autoimmune connective tissue diseases, drug reactions, and some cases of hypersensitivity pneumonia 4, 5

UIP is characterized by fibrosis accentuated at the periphery of pulmonary lobule, subpleural regions, and adjacent to interlobular septa, with subpleural microscopic honeycombing and relatively normal peribronchiolar alveoli, as reported by the European Respiratory Review 1, 2
The European Respiratory Review recommends recognizing UIP as a distinct pattern, associated with idiopathic pulmonary fibrosis (IPF), and believed to arise from aberrant senescence rather than inflammation, with associated shortened telomeres and mutations in telomerase pathway 4, 5

The European Respiratory Review describes three primary mechanisms driving the different patterns of interstitial fibrosis: inhalation injury or airway inflammation leading to bronchiolocentric fibrosis, diffuse alveolar inflammation resulting in NSIP pattern, and abnormal senescence associated with UIP pattern 5

The European Respiratory Review states that some cases may be unclassifiable due to inadequate biopsy size, advanced disease showing only end-stage fibrosis, alterations from pre-biopsy treatment, or overlapping features between different patterns, and recommends a multidisciplinary approach for accurate diagnosis 2, 3, 6