Interstitial lung disease Approach to ILD In collagen vascular disease Division of pulmonology Jeung Eun Park

Contents Definition of ILD Classification of ILD Approach of patients with ILD ILD in collagen vascular disease

Interstitial lung disease (ILD) Diffuse Interstitial Lung Disease (DILD, ILD) Diffuse Parenchymal Lung Disease (DPLD) A heterogeneous group of lung parenchymal disease by varying patterns of inflammation and fibrosis Aloveoli, alveolar epithelium, capillary endothelium The spaces between these structures Perivascular and lymphatic tissues

Clinical features Exertional dyspnea CXR : Bilateral diffuse interstitial infiltrates PFT : Restrictive pattern Increased alveolar-arterial oxygen difference Absence of pulmonary infection or neoplasm Pathology : inflammation and/or fibrosis or granuloma

2002 ATS/ERS Classification Interstitial lung disease ILD of known causes (drug, environ, CVD) Idiopathic Interstitial Pneumonia (IIP) Granulomatous ILD (sarcoidosis) Other forms of ILD (LAM, HX) Idiopathic Pulmonary Fibrosis (IPF) = UIP IIP other than IPF Respiratory bronchiolitis– associated interstitial lung disease Desquamative interstitial pneumonia Acute interstitial pneumonia Cryptogenic organizing pneumonia Nonspecific interstitial pneumonia Lymphocytic interstitial pneumonia 2002 ATS/ERS Classification

2002 ATS/ERS

IPF vs non-IPF Idiopathic pulmonary fibrosis (IPF) UIP Most Common type Most Poor prognosis

2002 ATS/ERS

Radiographic features of the idiopathic interstitial pneumonias Clinical Diagnosis Usual Radiographic Features Typical Findings on HRCT IPF Basal-predominant reticulation abnormality with volume loss Peripheral, basal, subpleural reticulation with honeycombing, traction bronchiectasis, and focal ground-glass attenuation NSIP Ground-glass and reticular opacification Peripheral, basal, subpleural, symmetrical ground-glass attenuation with irregular lines and consolidation COP Patchy bilateral consolidation Subpleural or peribronchial patchy consolidation and/or nodules AIP Diffuse ground-glass density/consolidation Diffuse consolidation and ground-glass opacification, often with lobular sparing and late traction bronchiectasis DIP Ground-glass opacity Peripheral, lower lung zone ground-glass attenuation with reticulation and/or small cysts RB-ILD Bronchial wall thickening, ground-glass opacification Diffuse bronchial wall thickening with poorly defined centrilobular nodules and patchy ground-glass opacification LIP Reticular opacities and nodules Diffuse centrilobular nodules, ground-glass attenuation, septal and bronchovascular wall thickening, and thin-walled cysts

UIP NSIP NSIP BOOP DAD DAD UIP in a 63-year-old man with pSS. This image demonstrates coarse reticular opacities in both lungs with associated traction bronchiectasis and subpleural honeycombing. NSIP shows extensive ground glass abnormality, with associated reticular abnormality and traction bronchiectasis. BOOP: obtained at the level of the inferior pulmonary vein shows patchy areas of ground-glass attenuation and consolidation with a subpleural or peribronchovascular distribution in both lungs. DAD :show patchy and geographic distribution of ground-glass attenuation with consolidation bilaterally in the upper and middle lung zones DAD

UIP NSIP UIP: mixed pattern (정상조직과 병변 조직이 혼재) irregular interstitial fibrosis (solid arrow) with mononuclear cell infiltration and foci of fibroblastic proliferation (arrowheads). Intervening normal lung tissue is also seen (open arrows NSIP :shows uniform interstitial fibrous thickening with infiltration of a few mononuclear cells DAD shows diffuse interstitial thickening with fibroblastic proliferation and mononuclear cell infiltration. BOOP : shows intraalveolar fibroblastic plugging (arrows) in alveolar spaces and alveolar duct AIP DAD BOOP

Histologic Patterns of NSIP Cellular NSIP Predominantly chronic interstitial inflammation with lymphocytes & plasma cells Fibrotic NSIP Predominantly variable extent of uniform interstitial fibrosis ± cellular component

Clinico–radiologic–pathologic diagnosis (CRP diagnosis) 병리학적 소견 또는 방사선학적 소견이 진단명이 아니다 !! 형태학적 소견(병리학적 소견, 방사선학적 소견)과 임상진단명을 혼돈해서는 안 된다. Clinician must R/O Connective tissue disease Drug Occupational exposure Environmental exposure Toxic fume Infection

Clinical Dx, if idiopathic Histologic and clinical classification of idiotathic interstitial pneumonias Pathologic Dx Clinical Dx, if idiopathic UIP (pattern) IPF NSIP (pattern) NSIP BOOP (pattern) COP DAD (pattern) AIP LIP (pattern) LIP DIP (pattern) DIP RB-ILD (pattern) RB-ILD

UIP pattern IPF (idiopathic) Drugs Infections Chronic HP Collagen vascular disease Asbestosis

NSIP pattern Idiopathic NSIP Collagen vascular disease HP Drug (methotrexate, amiodarone, etc.) Infection Immunodeficiency including HIV infection

BOOP Pattern Idiopathic process (COP) Organizing diffuse alveolar damage Organizing infections Organization distal to obstruction Organizing aspiration pneumonia Organizing drug reactions, fume, and toxic exposures Collagen vascular disease Extrinsic allergic alveolitis/hypersensitivity pneumonitis Eosinophilic lung disease Inflammatory bowel disease As a secondary reaction in chronic bronchiolitis As a reparative reaction around other processes (including abscesses, Wegener’s granulomatosis, neoplasms, and others)

Common drug-induced ILD Antimicrobial agents Cephalosporins Isoniazid Nitrofurantoin Penicillins Sulfonamides Anti-inflammatory agents Aspirin Gold Methotrexate NSIDs Penicillamine Cardiovascular drugs Amiodarone ACEi β-Blockers Hydralazine Hydrochlorothiazide

Antineoplastic agents CNS drugs Carbamazepine Chlorpromazine Imipramine Phenytoin OHA Chlorpropamide Tolazamide Tolbutamide Antineoplastic agents Bleomycin Busulfan Chlorambucil Cyclophosphamide Melphalan Mercaptopurine Mitomycin Mitomycin C Illicit drugs Cocaine Heroin Methadone Propoxyphene

Frequency of pulmonary involvement in various collagen vascular diseases RadioGraphics, 2002

Dermatomyositis-related ILD (UIP pattern) 결체 조직 질환 (CVD)과 연관된 ILD의 예(I) : CVD-related ILD Dermatomyositis-related ILD (UIP pattern) M/41, Proximal muscle weakness Lung Bx Lung biopsy : irregular intertstitial fibrosis and mononuclear cell infiltration with subpleural predominance HRCT : Muscle Bx UIP pattern

Systemic Sclerosis-related ILD (NSIP) 결체 조직 질환 (CVD)과 연관된 ILD의 예(II) : CVD-related ILD Systemic Sclerosis-related ILD (NSIP) F/50, progressive dyspnea Anti-Scl-70 (+) NSIP pattern

Sjogren syndrome-related ILD (LIP) 결체 조직 질환 (CVD)과 연관된 ILD의 예(III) : CVD-related ILD Sjogren syndrome-related ILD (LIP) HRCT shows centrilobular nodules and branching linear structures (straight arrow) in the right lung. Many thin-walled cysts (curved arrows) were seen in both lungs. (b) Patholoty : shows diffuse lymphocyte infiltration in the peribronchovascular interstitium and surrounding alveolar septa (arrows). LIP pattern

Comparison of survival curves

Am J Respir Crit Care Med Vol, 2005

CHEST ,2006