The initial response of the host to the disease

1. ILD-an introduction-II The initial response of the host to the disease process is inflammationin the air spaces and alveolar walls, causing an acute phase of intraluminal and mural alveolitis In chronic phase, inflammation will spread to adjacent portions of the interstitium and vasculature and eventually produce interstitial fibrosis, Inflammation also can involve the conducting airways and BO and BOOP are probably part of ILD

2. ILD-an introduction-III Interstitial Lung Disease • Scarring and distortion of lung tissue  derangement of gas exchange and ventilatory function. • Inflammation also can involve the conducting airways  bronchiolitis obliterans associated with an organizing pneumonia • Although diverse etiology, similarity of symptoms, comparable appearance of chest imaging studies , consistent alterations in pulmonary physiology and typical histologic features.

3. ILD-an introduction-IV Interstitial Lung Diseases • Approximately 150 known individual disease are characterized by some interstitial lung involvement, either as primary or as a part of a multiorgan process, as may occur in the collagen vascular diseases. • Chest radiograph is of limited aid in classification, however HRCT scanning of chest enhanced diagnostic accuracy.

4. Classification of Interstitial Lung Disease • Classification: known and unknown causes; further divided into subgroups according presence or absence of granulomas in interstitial or vascular areas. There may be an acute phase, but usually a chronic one • Known causes, the largest group comprises occupational and environmental inhalant exposures. Organic dusts and various irritative or noxious gases. The number of ILDs of unknown cause is IPF,. Sarcoidosis, and ILD associated with collagen vascular disorder.

5. Alveolar and interstitial inflammatory lung diseases • Similarity of symptoms, comparable apperance of CxR, consistent alterations in pulmonary physiology, and typical histologic features • Approximate 180 known individual diseases have interstitial lung involvement • Classified as known or unknown causes with or without granuloma formation

6. Major Categories of Alveolar and Interstitial Inflammatory Lung Diseases (1) Lung response: alveolitis, interstitial inflammation Known cause: • Asbestos, • Fumes, gases • Drugs ( antibotics) and chemotherapy drugs • Radiation • Aspiration pneumonia • Redidual of ARDS

7. Major Categories of Alveolar and Interstitial Inflammatory Lung Diseases (2) Unknown cause • IPF • Collagen vascular Disease • Pulmonary hemorrhage syndromes • Pulmonary alveolar proteinosis • Lymphocytic infiltrative disorder • Eosinophilic pneumonia • Lymphagioleiomyomatosis

8. Major Categories of Alveolar and Interstitial Inflammatory Lung Diseases (3) Unknown cause • Amyloidosis • Inherited diseases ( tuberous sclerosis, neurofibromatosis,Niemann-Pick disease, Gaucher’s disease etc) • Gastrointestinal or liver diseases ( crohn’s disease, primary biliar cirrhosis, chronic active hepatitis, ulcerative colitis) • Graft vs host disease ( bone marrow transplatation)

9. Major Categories of Alveolar and Interstitial Inflammatory Lung Diseases (4) Lung response: as above but with granuloma Known cause • Hypersensitivity pneumonia ( organic dusts) • Inorganic dusts: beryllium, silica Unknown cause • Sarcodosis • Langerhans cell granulomatosis ( eosinophic granuloma ) • Granulmatous vasculitis: Wegener’s grulomatosis, allergic granulomatosis of Churg-Strauss, lymphomatoid garanulomatosis • Bronchocentic granulomatosis

10. Clinical Classification of ILD • Connective tissue disease • Treatment-related or Drug -induced • Primary( Unclassified) disease • Occupational and Environmental diseases: Inorganic, Organic • Idiopathic Fibrosis Disorders

11. Collagen vascular disease associated Scleroderma Polymyositis-Dermatomyositis SLE RA AS MCTD Primary Sjogren's syndrome Behcet's syndrome

12. Occupational & Environmental Silicosis Asbestosis Beryllium Talc Farmer's lung Bird breeder's lung Tobacco grower's lung Coffee worker's lung etc....

13. Drug and treatment induced Antibiotics Antiarrhythmics Antiinflammatory Anticonvulsant Chemotherapeutic agents

14. CLASSIFICATION OF IIP(IMMUNOCOMPETENT HOST) Idiopathic interstitial pneumonia (IIP) Respiratory bronchiolitis-associated interstitial lung disease (RBILD) Idiopathic pulmonary fibrosis/Usual interstitial pneumonia (UIP) Desquamative interstitial pneumonia (DIP) Nonspecific interstitial pneumonia (NSIP) Acute interstitial pneumonia (AIP) ATS/ERS.Am J Respir Crit Care Med. 2000;161:646.

15. PATHOLOGIC CLASSIFICATION OF IDIOPATHIC PULMONARY FIBROSIS -------------------------------------------------------- • Usual interstitial pneumonia (UIP) • Desquamative interstitial pneumonia (DIP)/respiratory bronchiolitis interstitial lung disease (RBILD) • Acute interstitial pneumonia (AIP, Hamman-Rich disease) • Nonspecific interstitial pneumonia (NSIP)

16. CONTRASTING PATHOLOGIC FEATURES OF THE IDIOPATHIC INTERSTITIAL PNEUMONIAS --------------------------------------------------------------------------------------------------------------------------------- Features UIP DIP/RBILD AIP NSIP --------------------------------------------------------------------------------------------------------------------------------- Temporal appearance Variegated Uniform Uniform Uniform Interstitial inflammation Scant Scant Scant Usually prominent Collagen fibrosis patchy Variable, diffuse (DIP) No Variable, diffuse or focal, mild (RBILD) Fibroblast proliferation Fibroblast foci No Diffuse Occasional, diffuse, or rare fibroblast foci BOOP No No No Occasional, focal Honeycomb change Yes No No Rare Intraalveolar Occasional, diffuse (DIP) or No Occasional, patchy macrophage focal peribronchiolar (RBILD) accumulation Hyaline membranes No No Occasional, focal No ------------------------------------------------------------------------------------------------------------------------------------

17. CONTRASTING CLINICAL FEATURES OF THE IDIOPATHIC INTERSTITIAL PNEUMONIAS -------------------------------------------------------------------------------------------------------------------------- Features UIP DIP RBILD AIP NSIP ----------------------------------------------------------------------------------------------------------------------- Mean age, yr 57 42 36 49 49 Occurrence in children No Rare No Rare Occasionally Onset Insidious Insidious Insidious Acute Subacute, insidious Mortality rate (mean survival) 68% (5-6 yr) 27% (12 yr) 0% 62% (1-2 mo) 11% (17 mo) Response to steroids Poor Good Good Poor Good Complete recovery possible No Yes Yes Yes Yes ------------------------------------------------------------------------------------------------------------------------

19. INFLAMMATORY RESPONSE OF THE LUNG Fixed macrophage Recognition Capillary endothelial cell Antigen Circulating leukocyte Capillary Recruitment Monocyte Removal Infiltrating leukocyte Phagocytic leukocyte (macrophage) Fibrous matrix (scar issue) Activated leukocyte Resolution Chemotactic cytokine wave Fibroblast Slide courtesy of RM Strieter, MD.