A Review of Interstitial Lung Diseases
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1 Outline A Review of Interstitial Lung Diseases Paul J. Wolters, MD Associate Professor Department of Medicine University of California San Francisco Overview of diagnosis in ILD Why it is important Definition/Classification High-resolution CT scan Multidisciplinary approach Cases Interactive format (ARS) Review of radiology and pathology Questions/Discussion Why it is Important to be Aware of ILD s Don t stop with pulmonary fibrosis Reasons for a specific diagnosis: Many forms are treatable Treatments depend on diagnosis Prognosis varies Eligibility for clinical trials 1
2 Clinical Classification Clinical History Pulmonary Fibrosis Exposure-related: - Occupational - Environmental - Avocational - Medication Desquamative interstitial pneumonia (DIP) Acute interstitial pneumonia (AIP) Nonspecific interstitial pneumonia (NSIP) Idiopathic interstitial pneumonia (IIP) Idiopathic pulmonary fibrosis (IPF) Connective tissue disease: - Scleroderma - Rheum. arthritis - Sjogrens - UCTD Respiratory bronchiolitis interstitial lung dis. (RBILD) Cryptogenic organizing pneumonia (COP) Lymphocytic interstitial pneumonia (LIP) Other: - Sarcoidosis - Vasculitis/Diffuse alveolar hemorrhage (DAH) - Langherhans cell histiocytosis (LCH) - Lymphagioleiomyomatosis (LAM) - Pulmonary alveolar proteinosis (PAP) - Eosinophilic pneumonias - Neurofibromatosis - Inherited disorders - Chronic aspiration - Inflammatory bowel disease Idiopathic usual interstitial pneumonitis (UIP) = IPF nonspecific interstitial pneumonitis (NSIP) desquamative interstitial pneumonitis (DIP) respiratory bronchiolitis ILD (RBILD) acute interstitial pneumonitis (AIP) Unclassified Drugs Occupational/Environmental -Asbestos -Birds/Molds/Organic Material (HP) Collagen Vascular Joint c/o Sicca sx Skin rash Raynaud s Exam: Clues to diagnosis CXR is Not Useful for Differentiating ILD s Lung: Crackles on exam. Findings c/w sarcoid: Uveitis, skin rash, erythema nodosum, hepatomegaly. Findings c/w CVD: Synovitis, rash, sclerodactaly. Findings c/w IPF: Clubbing HP CVD-ILD IPF NSIP 2
3 High-resolution CT () is the Key to Diagnosing ILD s mm collimation Images taken every 10 mm Supine, prone and expiratory images Pattern of abnormality on scan may suggest a specific ILD. findings guide subsequent diagnostic tests. findings may be sufficient for diagnosis. Usual Interstitial Pneumonia (UIP) Nonspecific Interstitial Pneumonitis (NSIP) Irregular lines in a patchy, basilar, subpleural distribution Traction bronchiectasis minimal Ground glass opacities. Honeycomb lung Ground glass opacities (10) Consolidation (98%) Nodules (96%) Traction bronchiectasis (95%) Intralobular reticulation (87%) Lower lobe predominance 3
4 Desquamative Interstitial Pneumonia (DIP) Hypersensitivity Pneumonitis Ground glass opacity with a basilar, subpleural, and lower lobe distribution Lower lobe reticular opacities Subacute phase : multifocal or diffuse GGO poorly defined centrilobular nodules Subacute and chronic phases : mosaic perfusion air trapping on expiratory images CT may be normal in some cases Sarcoidosis Diagnostic Algorithm Perilymphatic nodules Peribronchial nodules GGO Upper lobe predominant, +/- fibrosis Detailed history, PE + Suspected PF + PFTs/Labs Diagnostic Non-diagnostic 1. IPF 2. Sarcoidosis 3. CV-ILD 4. Hypersensitivity pneumonitis 5. Rare disease (LAM, PAP) Lung biopsy 4
5 Multidisciplinary approach Agreement increased with multidisciplinary approach Agreement (κ) Step Assessment Method Information Provided 1 Individual 2 Individual 3 4 Discussion (clinician and radiologist) Individual (clinician, radiologist and pathologist) 5 Discussion, clinical data, clinical data, clinical data, SLB, clinical data, SLB Case 1 Step Modified from: Flaherty KR, et al. Am J Respir Crit Care Med. 2004;170: year old man Case 1 Abnormal CXR 3 months prior to presentation (notes normal CXR from 5 years ago) Mild dyspnea on exertion, no cough PMH: GERD for 30 years Meds: omeprazole 40mg daily Case 1 Social: lifetime non-smoker, some mold in home, pharmacist Family: no history of ILD 114/73 hr 70 rr 16 96% RA (93% walking) Dry inspiratory crackles at both bases Normal cardiac examination No clubbing, joint deformities, rashes 5
6 PFTs FVC 5.10 (83%) FEV (9) FEV1/FVC 0.87 TLC 7.40 (88%) DLCO (57%) Case 1 CXR What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Serological evaluation 4. High resolution CT scan 5. Surgical lung biopsy 6. No additional testing; diagnosis is clear 98% 2%
7 7
8 Serological evaluation What additional testing would you perform next in this patient? ANA negative 1. Bronchoalveolar lavage (BAL) RF = 4 2. BAL and transbronchial biopsy 3. Surgical lung biopsy 4. No additional testing; diagnosis is clear 4 33% 27%
9 VATS VATS Usual Interstitial Pneumonia (UIP) Temporal heterogeneity Subpleural accentuation of fibrosis Regions of normal lung Microscopic honeycombing Fibroblast Foci Diagnosis of IPF Management Enrolled in clinical trial Pulmonary rehabilitation Weight loss (if overweight) Lung transplant referral 9
10 IPF: Published Definition Survival Median survival for IPF is 2 3 years No proven therapy A specific form of chronic fibrosing interstitial pneumonia limited to the lung and associated with the histologic appearance of usual interstitial pneumonia on surgical lung biopsy. IPF ATS/ERS. Am J Respir Crit Care Med. 2000;161: Modified from Bjoraker JA. Am J Respir Crit Care Med. 1998;157: Case 2 Case 2 63-year-old woman 5-month history of shortness of breath and nonproductive cough PMH: hypertension, treated for TB exposure in 1980, arthritis Medications: diltiazem 10
11 Case 2 Social: former smoker (18 pk/yrs); office worker. Family: No history of ILD 135/80 hr 90 rr 14 94% RA (9 walking) Dry inspiratory crackles at both bases Normal cardiac examination No clubbing, joint deformities, rashes CXR What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Serological evaluation 4. High resolution CT scan 5. Surgical lung biopsy 6. No additional testing; diagnosis is clear 92% 2% 4% 2%
12 12
13 Serological evaluation ANA 1:80, speckled RF = 18, cyclic citrullinated antibody (CCP) negative What additional testing would you perform next in this patient? VATS 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Surgical lung biopsy 4. No additional testing; diagnosis is clear 69% 22% 9%
14 VATS VATS Nonspecific Interstitial Pneumonitis (NSIP) Uniform involvement of the lung with Septal thickening Interstitial inflammation (lymphocytes) +/- Fibrosis What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Additional serologies 4. No additional testing; diagnosis is clear 39% 61%
15 RNP negative Scl70 negative Additional serologies SSA, SSB negative Jo-1 negative, CPK 104 Diagnosis of NSIP Management Treated with prednisone and mycophenolate (CellCept) Pulmonary rehabilitation NSIP IPF NSIP Distinguishing NSIP from UIP is a challenge! Patients usually younger, more likely to be women Honeycombing on is uncommon in NSIP Surgical biopsy shows diffuse thickening of alveolar septae and few if any fibroblast foci 15
16 IPF NSIP IPF NSIP NSIP The diagnosis of NSIP should prompt you to go back to look for an etiology Occult connective tissue disease Drug reaction Hypersensitivity pneumonitis Case 3 16
17 43 year old man Case 3 Subacute progressive dyspnea Case 3 Social: non-smoker, banker, no known exposures, no pets. Family: no history of ILD PMH: mild obstructive sleep apnea on CPAP 6 cm H20, seasonal allergies Meds: cetirizine, multivitamin BP 116/56, hr 60, rr16, 98% RA (88% walking) Moderately obese Lungs clear to auscultation Case 3 CXR PFTs: FVC 3.17 (73%) FEV (77%) FEV1/FVC 0.77 TLC 4.65 (82%) DLCO 15.1 (58%) 17
18 What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Echocardiogram 4. High resolution CT scan 5. Surgical lung biopsy 6. No additional testing; diagnosis is clear 98% 3%
19 expiratory views 19
20 expiratory views expiratory views Serological Evaluation What additional testing would you perform next in this patient? ANA negative RF 12 SS-A, SS-B negative 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Surgical lung biopsy 4. No additional testing; diagnosis is clear 68% 18% 15%
21 VATS Biopsy: Low Power VATS Biopsy: High Power VATS Biopsy: High Power Hypersensitivity Pneumonitis Airwaycentric inflammation Poorly formed granuloma (giant cell) Areas of organizing pneumonia 21
22 What additional testing would you perform next in this patient? Additional history 1. Bronchoalveolar lavage (BAL) 2. Sputum culture 3. Serum precipitins 4. Additional history 5. No additional testing; diagnosis is clear 8% 26% 5 16% Patient recently moved to a new home built on the site of a former pigeon farm. There is ongoing construction of new units around his home and lots of dust Hypersensitivity Pneumonitis Thank you! Management Remove antigen (Relocated from new home) Treat with prednisone Pulmonary rehabilitation 22
23 UCSF Interstitial Lung Disease Clinic Clinical Coordinator: (415) Clinic fax: (415)
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