Etymology:
Derived from “interstitial,” referring to the supportive tissue surrounding alveoli and capillaries, and “fibrosis,” meaning the formation of excess fibrous connective tissue.
What is it?
Interstitial fibrosis is a pathological condition characterized by excessive deposition of fibrous connective tissue within the pulmonary interstitium. It results in thickening and scarring of alveolar walls, bronchovascular bundles, and interlobular septa, impairing gas exchange and reducing lung compliance. The condition encompasses a wide spectrum of diseases, including idiopathic conditions (e.g., Idiopathic Pulmonary Fibrosis [IPF]), autoimmune diseases (e.g., systemic sclerosis), environmental exposures (e.g., asbestosis), infections, and drug reactions.
Caused by:
Idiopathic (most common cause): Idiopathic pulmonary fibrosis (IPF), characterized by the UIP pattern.
Infection: Chronic infections such as tuberculosis, fungal infections, or viral infections (e.g., COVID-19, influenza).
Reduced lung compliance and impaired oxygen diffusion.
Progressive dyspnea and exercise intolerance.
Structural Changes:
Bronchovascular Bundles: Fibrosis around bronchovascular bundles results in architectural distortion and traction bronchiectasis caused by retraction forces exerted by fibrotic tissue.
Interlobular Septa: Thickening and fibrosis of interlobular septa lead to reticular patterns visible on imaging, contributing to honeycombing in advanced disease and impaired lung compliance.
Interalveolar Septa: Fibrotic thickening of interalveolar septa results in a thickened alveolar-capillary membrane, loss of normal alveolar architecture, and formation of fibroblastic foci with progression to honeycombing in severe cases.
Pathophysiology:
Initial injury to alveolar epithelial or capillary endothelial cells triggers an inflammatory response.
Chronic inflammation leads to fibroblast activation and excessive deposition of extracellular matrix (e.g., collagen).
Fibrosis thickens the alveolar-capillary membrane, impairing gas exchange and reducing lung compliance.
Pathology:
Gross: Firm, shrunken lungs with fibrotic areas, often in a patchy or diffuse distribution.
Microscopic:
Interstitial thickening with collagen deposition.
Inflammatory infiltrates (lymphocytes, macrophages) in early stages.
Fibroblastic foci and honeycombing in advanced cases.
Radiology:
CXR:
Findings: Reticular or reticulonodular opacities, predominantly in lower lung zones. Subpleural fibrosis may appear as linear opacities in early disease.
Associated Findings: Volume loss, traction bronchiectasis, and cystic changes in advanced disease.
CT (High-Resolution Computed Tomography [HRCT]):
Parts: Predominantly involves subpleural regions, interlobular septa, interalveolar septa, and bronchovascular bundles. Specific patterns include:
UIP (e.g., IPF): Subpleural and basal predominance.
Sarcoidosis: Upper and mid-lobe predominance, often perilymphatic.
Hypersensitivity Pneumonitis (HP): Diffuse or mid-zone predominance with ground-glass opacities and mosaic attenuation.
Asbestosis: Subpleural and basal fibrosis with associated pleural plaques.
Drug-Induced Fibrosis: Basilar (amiodarone, bleomycin) or diffuse (methotrexate, nitrofurantoin).
Size:
Honeycombing involves cystic airspaces measuring 3?10 mm, often clustered.
Reticulations include linear opacities of varying thickness.
Traction bronchiectasis shows dilated bronchi due to fibrotic retraction.
Shape:
Honeycomb cysts are rounded or polygonal clusters in subpleural regions.
Reticulations are linear and irregular, following interlobular septa.
Reticulonodular changes may accompany NSIP due to active inflammation.
Position:
Subpleural predominance: Typical of UIP (e.g., IPF) and asbestosis.
Upper lobe predominance: Seen in sarcoidosis, silicosis, and certain drug reactions.
Lower lobe predominance: Observed in UIP, NSIP, asbestosis, and drug reactions like amiodarone.
Diffuse involvement: Seen in hypersensitivity pneumonitis (chronic stage), lymphangioleiomyomatosis (LAM), pulmonary Langerhans cell histiocytosis (PLCH), and post-viral interstitial fibrosis (e.g., COVID-19, influenza).
Bronchovascular regions: Fibrosis centered around bronchovascular bundles is common in sarcoidosis, connective tissue diseases, and certain drug reactions (e.g., penicillamine).
Post-infectious fibrosis: Often lower lobe predominant, following bacterial or fungal pneumonias.
Character:
UIP pattern: Subpleural reticulations, honeycombing, and traction bronchiectasis with minimal ground-glass opacities.
NSIP pattern: Patchy ground-glass opacities with diffuse fibrosis and less architectural distortion.
Sarcoidosis: Peribronchovascular nodules with potential upper lobe fibrosis in chronic stages.
Time:
Early-stage: Ground-glass opacities with minimal fibrosis.
Late-stage: Established honeycombing, traction bronchiectasis, and significant architectural distortion.
Other Relevant Imaging Modalities:
MRI: Rarely used but can show fibrotic bands and architectural distortion.
PET-CT: Highlights areas of active inflammation or metabolically active lesions.
Ultrasound: Rarely used but may help detect pleural-based abnormalities and guide procedures.
Pulmonary Function Tests (PFTs):
Restrictive pattern with reduced forced vital capacity (FVC) and total lung capacity (TLC).
Markedly reduced diffusing capacity of the lungs for carbon monoxide (DLCO).
Management:
Address the underlying cause: Treat autoimmune diseases with immunosuppressive therapy. Discontinue offending drugs in drug-induced fibrosis. Antifibrotic therapy in idiopathic pulmonary fibrosis (e.g., pirfenidone, nintedanib).
Supportive care: Oxygen therapy for hypoxemia. Pulmonary rehabilitation to improve physical function.
Advanced therapy: Lung transplantation in severe cases.
Recommendations:
Early diagnosis and treatment to slow progression.
Monitor progression with serial PFTs and imaging.
Encourage smoking cessation and avoid exposure to environmental lung irritants.
Vaccinations (influenza, pneumococcal) to reduce the risk of infections.
Key Points and Pearls:
Interstitial fibrosis is an umbrella term for a variety of diseases, with UIP and NSIP being common patterns.
The hallmark of the radiological diagnosis is the presence of reticulations, reticulonodular patterns, honeycombing, traction bronchiectasis, and bronchiolectasis, which are frequently subpleural in location.
HRCT is essential for distinguishing patterns and guiding management.
Upper lobe predominance is seen in conditions such as sarcoidosis and silicosis, while lower lobe predominance is typical of UIP and asbestosis.
Diffuse involvement can suggest hypersensitivity pneumonitis or certain drug reactions.
Thickened interlobular septa and bronchovascular bundle involvement are critical features of advanced fibrosis.
Early identification of the underlying cause is crucial for effective treatment.
Difference Between
Pulmonary Fibrosis and Interstitial Fibrosis:
Pulmonary fibrosis is a general term encompassing all lung scarring, whereas interstitial fibrosis specifically refers to scarring of the interstitial lung tissue.
All interstitial fibrosis is pulmonary fibrosis, but not all pulmonary fibrosis is interstitial.
