What is interstitial fibrosis?

Interstitial Fibrosis

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

Definition and Classification

• Interstitial fibrosis represents a pattern of lung injury where excessive extracellular matrix, primarily collagen, accumulates in the interstitial spaces between alveoli 1
• The European Respiratory Review classifies interstitial fibrosis into three distinct patterns based on distribution within the pulmonary lobule 1:
  • Bronchiolocentric fibrosis
  • Nonspecific interstitial pneumonia (NSIP) fibrosis
  • Usual interstitial pneumonia (UIP)

Specific Patterns of Interstitial Fibrosis

Bronchiolocentric Fibrosis

• Characterized by thickening of peribronchiolar alveolar septa due to collagen deposition 1
• Often accompanied by peribronchiolar metaplasia 1
• Most commonly results from centrilobular injury due to inhalation of fumes or dust, aspiration, or systemic diseases with airway inflammation 1
• Associated conditions include respiratory bronchiolitis from smoking, hypersensitivity pneumonia, asbestosis, Sjögren syndrome, and inflammatory bowel disease-related small airway disease 1

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, and some cases of hypersensitivity pneumonia 1

Usual Interstitial Pneumonia (UIP)

• Characterized by fibrosis accentuated at the periphery of pulmonary lobule, subpleural regions, and adjacent to interlobular septa 1
• Features subpleural microscopic honeycombing and relatively normal peribronchiolar alveoli 1
• Associated with idiopathic pulmonary fibrosis (IPF) 1
• Believed to arise from aberrant senescence rather than inflammation, with associated shortened telomeres and mutations in telomerase pathway 1

Pathophysiological Mechanisms

• Three primary mechanisms drive the different patterns of interstitial fibrosis 1:
  • Inhalation injury or airway inflammation leading to bronchiolocentric fibrosis
  • Diffuse alveolar inflammation resulting in NSIP pattern
  • Abnormal senescence associated with UIP pattern

Clinical Significance and Progression

• Interstitial fibrosis may have an unpredictably progressive course, manifesting as progression of pulmonary fibrosis with increasing impairment of lung function 2
• Progressive fibrosis leads to poor prognosis and is characterized by ongoing tissue remodeling 2, 3
• Repetitive alveolar epithelial injury triggers the early development of fibrosis, which combined with dysregulated wound repair and fibroblast dysfunction leads to ongoing tissue remodeling 3

Diagnostic Challenges

• 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 1
• A multidisciplinary approach is recommended for accurate diagnosis 1
• Chronic inflammation has been demonstrated to be the pathological basis of fibrosis in many cases 4

Treatment Considerations

• Antifibrotic medications like pirfenidone and nintedanib have been shown to slow disease progression in idiopathic pulmonary fibrosis, a specific form of interstitial fibrosis 5, 3
• Despite advancements in understanding the pathophysiology, therapeutic options for interstitial fibrosis, particularly in IPF, remain limited and non-curative 6
• Ongoing research into molecular mechanisms is critical for the development of targeted therapies that could potentially halt disease progression 6

Potential Complications

• Pulmonary function may be permanently impaired, even after cessation of therapy in drug-induced interstitial fibrosis 7
• Chronic pulmonary reactions can occur insidiously with manifestations including malaise, dyspnea on exertion, cough, and altered pulmonary function 7
• The severity of chronic pulmonary reactions and their degree of resolution appear to be related to the duration of exposure after the first clinical signs appear 7