4/17/2010 C ini n ca c l a Ev E a v l a ua u t a ion o n of o ILD U dat a e t e i n I LDs
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1 Update in ILDs Diagnosis 101: Clinical Evaluation April 17, 2010 Jay H. Ryu, MD Mayo Clinic, Rochester MN Clinical Evaluation of ILD Outline General aspects of ILDs Classification of ILDs Clinical evaluation of ILDs Diagnostic approach Illustrative case Summary References When to consider ILD: Diffuse lung infiltrates on CXR or CT Restrictive pulmonary dysfunction Isolated reduction in DL CO or exercise-induced induced desaturation Unexplained chronic dyspnea and/or cough, crackles Underlying systemic disease or other risk factors, e.g. exposures General Concepts Diffuse infiltrative disease affecting the lung parenchyma Many clinicopathologic entities included; heterogeneous category No universally accepted classification of ILDs 1
2 Classification of ILDs Potential parameters for classification Clinical presentation, e.g. acute vs. chronic Histopathologic findings Radiologic pattern Responsiveness to corticosteroids Cause - known vs. unknown (ATS/ERS. AJRCCM 2002) Known Cause Connective tissue diseases Environmental & occupational exposures Drugs Smoking (RB-ILD/DIP, Pulmonary Langerhans Cell Histiocytosis, AEP) Radiation Unknown Cause IPF Other interstitial pneumonias (COP, NSIP, LIP, AIP) Sarcoidosis Eosinophilic pneumonias Vasculitis LAM, PAP, etc. (Ryu et al. Mayo Clin Proc 2007) Potential Mimics Infections Neoplasms Bronchiectasis and bronchiolitis Pulmonary edema (CHF, ARDS) Pulmonary hemorrhage Neuromuscular diseases Aspiration, etc 2
3 Diagnosis n % of total % Bx proven Sarcoidosis IPF/UIP CTD-ILDs HP Other IIPs Undefined fibrosis Total n = 315 (Thomeer et al. Respir Med 2004) Diagnostic Evaluation History, physical examination Chest x-ray CBC, chemistry panel, urinalysis High-resolution CT chest PFTs Additional selective testing: HP serology, connective tissue disease serology, ANCA, anti-gbm Ab, BNP, echocardiography Lung biopsy (bronchoscopy, VATS/thoracotomy) History Demographics Exposures: smoking, drugs, occupational, environmental Previous and concurrent illnesses Familial disorders Clinical manifestations Tempo of the process Physical Examination Lung auscultation Digital clubbing Extrapulmonary signs Pulmonary Function Testing Usually, restrictive defect with reduced lung volumes (TLC, VC), reduced diffusing capacity, and normal FEV1/FVC ratio Obstructive or mixed defect - pulmonary Langerhans cell histiocytosis, LAM, sarcoidosis, Wegener s granulomatosis, ILD with underlying COPD/emphysema, associated pleural disease or chest wall disorder Normal or isolated diffusion abnormality - early interstitial lung diseases 3
4 Diagnostic Evaluation 3 Pivotal Parameters: Clinical context Tempo of the disease process (acute, subacute, chronic) Radiologic pattern Pattern of opacities Distribution Associated findings INTERSTITIAL LUNG DISEASES HRCT Findings Pattern of parenchymal infiltrates: reticular, nodular, ground-glass/consolidation, glass/consolidation, cystic Distribution: diffuse vs localized, peripheral vs central, upper vs lower, bronchovascular bundle Associated abnormalities: traction bronchiectasis, mosaic pattern, pleural disease, adenopathy, etc. Diagnostic Evaluation of ILD Clinical context Tempo (history, examination, labs, CXRs, PFTs) High-resolution CT Chest (pattern, distribution, associated features) Specific Diagnosis Further Testing Biopsy? Diagnosis A category sufficiently distinct to establish: Prognosis Therapeutic/management action or both 4
5 Diagnostic Testing Purpose Arrive at a diagnostic category that will establish a prognosis, dictate a therapeutic action, or both Reduce clinical uncertainty Lung Biopsy Histopathologic features have varying disease specificity. Histopathologic pattern alone may not suffice for a diagnosis. Correlation with clinical & radiologic context is a must in ILDs. Case Presentation 58M ex-smoker (quit 30 yr ago), real estate developer, referred 5/05 for IPF management. Chronic persistent cough x 4 yr, slowly progressive exertional dyspnea. CT chest abnormal; VATS biopsy 4/05 showed UIP. 2 episodes of pneumonias past 6 mo. No relevant occupational or environmental exposures. PMH: depression, hypercholesterolemia, obesity Medications: omeprazole, fenofibrate Case Presentation 58M 3/05 Physical exam: BMI 27, bibasilar Velcro crackles, VATS scar, mild clubbing. PFT: abnormal, mild restriction TLC 65% pred FVC 50% pred FEV1 52% pred FEV1/FVC 82.3 DLCO 40% pred 5
6 VATS Lung Biopsy VATS Lung Biopsy Case Follow-up Diagnosis: IPF/UIP. Treatment: N-acetylcysteine. Lung transplant evaluation. July 2005 (3 mo later), hospitalized for fever, hemoptysis, lung infiltrates, microscopic hematuria. P-ANCA positive (MPO Ab 60.1, NL <6), c-anca negative. Treated with IV methylprednisolone, then prednisone 60 mg/d & cyclophosphamide 150 mg/d. Hospitalized x 2 ½ wk. Gradual improvement. DIAGNOSIS: : UIP with microscopic polyangiitis (not IPF) 58M 3/05 11/06 6
7 % predicted UIP Microscopic Polyangiitis Months TLC FVC DLCO Usual Interstitial Pneumonia Idiopathic (IPF) Known cause or underlying disease: Connective tissue diseases, vasculitis Chronic hypersensitivity pneumonitis Asbestosis Drugs Genetic disorders - familial pulmonary fibrosis, Hermansky-Pudlak, dyskeratosis congenita, ABCA3 gene mutation, telomerase mutations Others - infections, aspiration, pulmonary artery sarcoma, etc. SUMMARY ILDs are heterogeneous, diffuse infiltrative diseases of known and unknown causes, affecting the lung parenchyma. Clinical context, tempo of the disease process, and HRCT pattern are the pivotal parameters in the diagnostic process. Accurate diagnosis of ILDs requires judicious clinico-radiologic-pathologic correlation. References Leslie KO. My approach to interstitial lung disease using clinical, radiological and histopathological patterns. J Clin Pathol 2009;62: Ryu JH, Daniels CE, Hartman TE, Yi ES. Diagnosis of interstitial lung diseases. Mayo Clin Proc 2007;82: Collard HR, King TE Jr. Demystifying idiopathic interstitial pneumonia. Arch Intern Med 2003;163: American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med 2002;165:
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