Interstitial Lung Disease Overview

Interstitial Lung Disease

• A heterogeneous group of diseases, some common, some rare, comprising about 15% of respiratory clinical practice.
• Characterized by diffuse parenchymal lung injury/inflammation progressing to fibrosis.
• Airways are typically spared.
• Frequently used synonymously with pulmonary fibrosis, though the term should be used only when there is histological evidence of fibrosis.
• Most diffuse lung diseases cause fibrosis to varying degrees.

Common Features

• Clinical: Dry cough, breathlessness.
• Lung function: Restrictive pattern (reduced air flow due to reduced expansion of lung parenchyma, impacting total lung capacity, vital capacity, residual volume & lung compliance). Specific lung function tests (FVC, FEV1, carbon monoxide transfer) may show abnormalities.
• Radiology: Reticulo-nodular shadowing as seen on CXR and high-resolution CT scans of the thorax.

Open Lung Biopsy

• Can identify peripheral fibrosis in idiopathic pulmonary fibrosis.

CXR (Chest X-ray)

• Shows imaging characteristics of interstitial lung disease (e.g., bilateral basilar reticular abnormalities and/or ground-glass appearance on high-resolution CT scans).

Aetiology

• Many causes with varying treatment; diagnosis requires careful consideration as treatment for one disease may be disastrous for another. More than 150 causative entities.
• 75% of cases have an unknown cause (idiopathic).
• 25% are attributable to known causes (e.g., idiopathic pulmonary fibrosis, occupational exposures).

Pathogenesis

• Traditionally, inflammation in septa (alveoli) was thought to be the primary pathology leading to diffuse septal (interstitial) fibrosis.
• Now, epithelial injury is considered the primary event, triggering fibroblast activation, leading to fibrosis.

Mechanisms of Fibrosis

• Injury to alveolar epithelial cells (e.g., from smoke or pollutants).
• Activation of inflammatory cells (e.g., lymphocytes) and endothelial cells.
• Release of fibrogenic cytokines & growth factors (TNF-α, IL-4, TGF-β, endothelin-1).
• Proliferation of fibroblasts, transforming into myofibroblasts, producing extracellular matrix, thus leading to fibrosis.

Classification of Interstitial Lung Disease

• Exudative: Collagen laid down in walls, incorporation of exudates into the walls affects the bases of the lungs. Includes idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis), systemic diseases (e.g., connective tissue diseases, systemic sclerosis), pneumoconioses (e.g., asbestosis).
• Granulomatous: Granulomas are often found in areas of the lung that aren't the bases of the lung, such as the upper lobes. Includes sarcoidosis, extrinsic allergic alveolitis, pneumoconiosis (silicosis).

Simple Diagnosis Classification

• Clinical diagnoses: Acute interstitial pneumonia (e.g., preceded by respiratory infections, poor prognosis), idiopathic pulmonary fibrosis (UK Cryptogenic fibrosing alveolitis) [including idiopathic, males, late 60s, 20/100,000], desquamative interstitial pneumonia (DIP) [e.g., males, middle aged, less severe than UIP, smokers, asbestos], non-specific interstitial pneumonia.
• Pathological patterns: Reflect the stage of disease from acute phases to eventual fibrosis. Note categories of usual interstitial pneumonia (UIP), myxoid fibrosis, septal inflammation, desquamative interstitial pneumonia (DIP), various degrees of fibrosis.

Presentation

• Symptoms: Typically dyspnea on exertion, fatigue, cough.
• Signs: Clubbing, bilateral end-expiratory crackles (e.g., Velcro crepitations), signs of right-heart failure.

Other Features

• Fatigue (may occur even without dyspnea).
• Cough (may be the only symptom).
• Non-specific systemic symptoms (fever, weight loss).
• Incidental abnormalities in lung function tests.
• Abnormal X-ray in the absence of symptoms.

Criteria for Diagnosis

• Abnormal lung function tests with evidence of restriction (e.g., reduced vital capacity) and impaired gas exchange.
• Basal reticular abnormalities with ground-glass appearance on high-resolution CT scans.
• Lung biopsy or bronchoalveolar lavage (BAL) showing no features to support another diagnosis.

Interstitial Lung Disease - Additional Procedures

• Open lung biopsy.
• Video-assisted thoracoscopic surgery (VATS).

Common Conditions

• Idiopathic pulmonary fibrosis.
• Extrinsic allergic alveolitis (e.g., farmer's lung, bird fancier's lung).
• Asbestos-related diseases.

Idiopathic Pulmonary Fibrosis (Specific details)

• Insidious onset, with dyspnea and tachycardia.
• Most common in the fourth and fifth decade.
• No known etiology; pathogenesis uncertain.
• Some genetic abnormalities are implicated.
• Mutations in serum surfactant protein C may damage type II alveolar epithelial cells.

Honeycomb Lung

• End-stage chronic interstitial fibrosis (any cause, e.g., idiopathic pulmonary fibrosis, extrinsic allergic alveolitis, sarcoidosis).
• Morphology: cystic air spaces coalesce, dilated bronchi and alveoli, septal fibrosis, inflammation, focal squamous metaplasia, smooth muscle proliferation of terminal bronchioles.

Complications and Outcome

• Complications: Fibrosis reducing pulmonary capillary network →pulmonary hypertension; right heart failure/cor pulmonale.
• Prognosis: Mild, focal fibrosis can sometimes resolve in a few cases. Marked fibrosis typically follows a severe outcome, including death due to respiratory or cardiac failure (e.g., 70% mortality in the acute phase).

Extrinsic Allergic Alveolitis

• Hypersensitivity pneumonitis.
• Caused by an immune response to inhaled antigens.
• Defect in antigen-specific T lymphocyte function.
• Various exposures can trigger this, including bird droppings, animal proteins, animal urine (farmer's lung). Mouldy hay is a strong inducer.
• Acute exposure—type III hypersensitivity reaction producing immune complexes at the site of allergen entry. The complexes activate the complement system, leading to inflammation. Symptoms include dyspnea, fever and cough within 4-8 hours of exposure, resolving within 12-24 hours.
• Chronic exposure—type IV hypersensitivity reaction, produces small granulomas in 70% of cases. Associated with many lymphocytes, scanty neutrophils, eosinophils, mast cells. Interstitial fibrosis leading to insidious onset of cough and dyspnea.
• In 5% of cases, this leads to chronic pulmonary fibrosis and honeycomb lung.
• Lavage (fluid sample) characteristics: T4/T8 lymphocytes dominant, slight increase in neutrophils and eosinophils.

Asbestos-Related Disease

• Occupational exposure to asbestos (mining, refining, insulation, dockyards).
• Risk of disease increases with duration and intensity of exposure.
• Specific asbestos types (e.g., blue and brown) over 8mm long can trigger disease and persist in tissues.
• Possible outcomes include: pleural plaques (benign collagen plaques), pleural effusions & pleural thickening, asbestosis (interstitial lung fibrosis, maximal at lung bases), malignant mesothelioma, lung carcinoma.
• Long latent period (up to 50 years) between exposure and disease onset.
• Asbestos bodies: long thin asbestos fibers coated with hemosiderin and protein, forming characteristic brown filamentous bodies in sputum (bead/drumstick pattern).

Imaging (e.g., CXR)

• Characteristic imaging findings for each condition, including asbestosis and the presence of asbestos bodies.

Explore the complexities of interstitial lung disease, a mix of common and rare conditions affecting respiration. Understand key features such as clinical symptoms, lung function patterns, and radiological findings. Delve into the importance of open lung biopsy for diagnosing peripheral fibrosis.