Interstitial Lung Diseases
Interstitial Lung Diseases
AKA Diffuse Parenchymal Lung Diseases
Overview
Characterized by inflammation and/or fibrosis in the lung tissue.
Pulmonary restriction with reduced total lung capacity, forced vital capacity, and forced expiratory volume at one second.
Signs and symptoms:
Progressive dyspnea; most patients initially experience dyspnea only upon exertion but, over time, develop difficulty breathing even during rest.
Dry, non-productive cough is common, and, some patients will present with digit clubbing.
Chest x-rays often show opacities or other abnormalities.
Complication of interstitial lung disease is pulmonary arterial hypertension.
Diagnosis:
Due to the non-specific and overlapping signs and symptoms diagnosis is often difficult, and often involves specialists from multiple fields who can integrate findings from chest imaging, pulmonary function tests, clinical exams, and histological sampling.
Treatment:
Varies, and is often targeted at the underlying disease; in some cases, anti-fibrotic drugs, such as pirfenidone, are helpful.
Histopathology
We draw a very generalized illustration
We draw a healthy alveolar duct opening to alveolar spaces, which are separated by alveolar septi.
In healthy lungs, the alveolar walls are compliant and expand upon inhalation to facilitate gas exchange with the pulmonary capillaries.
Interstitial lung disease develops when, in response to various stimuli, fibroblasts and myofibroblasts proliferate in the ducts and sacs.
These proliferating cells promote extracellular matrix deposition and collagen accumulation.
This leads to alveolar septal thickening; if left unchecked, fibrosis can develop.
The thickened alveolar membranes are stiffer and cannot expand upon inhalation, which inhibits gas exchange.
Types of Interstitial Lung Disease
EXPOSURE
Let's begin with interstitial lung diseases that develop in response to exposure to external agents.
Occupational
Asbestosis and silicosis develop when pulmonary macrophages ingest asbestos fibers or silica dust, which triggers the histological changes we just drew.
– Scarring is diffuse, and ground glass reticular opacities and pleural plaques are seen on chest x-ray.
Coal worker's pneumoconiosis, aka, "black lung" occurs when pulmonary macrophages ingest coal dust.
– Numerous small nodular opacities are visible in chest x-rays.
Hypersensitivity pneumonitis is a type III or mixed type III/type IV hypersensitivity that results from exposure to specific environmental triggers.
– Farmer's lung is caused by exposure to molds that grow in hay or other feed grains; additional examples include "bird fancier's lung" and "humidifier lung."
Drugs
Over 400 drugs can cause interstitial lung disease.
Antibiotics (such as amphotericin B)
Anti-inflammatories (Aspirin and NSAIDS)
Cardiovascular medications (including ACE-inhibitors and beta-blockers)
Chemotherapy drugs
Infections
Examples include aspergillosis, histoplasmosis, and mycobacterial infections.
SYSTEMIC DISORDERS
Connective Tissue Disorders
Many connective tissue disorders are immune or autoimmune pathologies with excessive collagen deposition or mucus reduction; thus, when the lungs are involved, restriction occurs.
Some key examples include: Systemic sclerosis, rheumatoid arthritis, systemic lupus, and sjogren's syndrome.
ANCA vasculitides (ANCA = Anti-Neutrophilic Cytoplasmic Autoantibodies)
These disorders include: Granulomatosis with polyangiitis (aka, Wegener's disease), eosinophilic granulomatosis with polyangiitis (aka, Churg-Strauss syndrome), and, microscopic polyangiitis.
Granulomatous lung diseases
Granulomatous-lymphocytic interstitial lung disease & sarcoidosis.
IDIOPATHIC INTERSTITIAL DISORDERS
The causes of these diseases are unclear, but each is associated with characteristic histological and clinical features; diagnosis is often based on exclusion.
Additional images
Idiopathic pulmonary fibrosis is the most common idiopathic interstitial pneumonia.
It is characterized by a histological pattern called "usual interstitial pneumonia;" this comprises patches of honeycomb patterns and areas of fibroblasts and dense collagen.
Nonspecific interstitial pneumonia is associated with younger women with no history of smoking; this type is sometimes associated with immune or connective tissue disorders.
The histological pattern comprises homogenous areas of fibrosis or cellular inflammation (not honeycomb).
Desquamative interstitial pneumonia develops in cigarette smokers older than 30.
Characterized by diffuse inflammation with pigmented macrophages in the alveoli. The brownish pigments in the macrophages are iron-rich granules commonly found in cigarette smokers' lungs.
Respiratory bronchiolitis-associated interstitial lung disease also affects smokers older than 30 and is characterized by pigmented macrophages; however, in these patients, inflammation is patchy.
Cryptogenic organizing pneumonia is a flu-like illness characterized by collections of collagen, fibroblasts, and myofibroblasts that plug the small airways and alveolar ducts, and alveoli are inflamed.
Be aware that cryptogenic organizing pneumonia was formerly known as bronchiolitis obliterans with organizing pneumonia.
Lymphocytic interstitial pneumonia* is characterized by lymphocytes and plasma cell infiltration into the alveoli and septi.
Acute interstitial pneumonia is characterized by diffuse alveolar damage and thickening, edema, and inflammatory cell infiltration, with possible hyaline membranes forming in the septa.
Acute interstitial pneumonia can quickly lead to respiratory distress.
Be aware that acute interstitial pneumonia is sometimes called Hamman-Rich syndrome.
Others:
Lymphangioleiomyomatosis: Genetic defect; Characterized by smooth muscle cell growth throughout the lungs, kidney, and lymphatic system.
– Almost always in women 30+ years old.
– Often associated with tuberous sclerosis complex (an inherited syndrome).
– Often associated with recurrent pneumothorax.
Pulmonary alveolar proteinosis
– Lipoprotein surfactant accumulates in the alveoli (stains periodic acid-Schiff positive).
– Can be hereditary or autoimmune.
Langerhan's cell histocytosis
– Langerhans cells accumulate in the lungs.
– Associated with cigarette smoking.
Pleural parenchymal fibroelastosis
– Fibrosis that is originally predominant in upper lobes, may progress throughout lung.