A Review of Interstitial Lung Diseases. Paul J. Wolters, MD Associate Professor Department of Medicine University of California San Francisco

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1 A Review of Interstitial Lung Diseases Paul J. Wolters, MD Associate Professor Department of Medicine University of California San Francisco

2 Outline 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

3 Why it is Important to be Aware of ILD s

4 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

5 Clinical Classification 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

6 Clinical History Idiopathic usual interstitial pneumonitis (UIP) = IPF nonspecific interstitial pneumonitis (NSIP) desquamative interstitial pneumonitis (DIP) respiratory bronchiolitis ILD (RBILD) acute interstitial pneumonitis (AIP) Unclassified Drugs Collagen Vascular Joint c/o Sicca sx Skin rash Raynaud s Occupational/Environmental -Asbestos -Birds/Molds/Organic Material (HP)

7 Exam: Clues to diagnosis 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

8 CXR is Not Useful for Differentiating ILD s HP IPF CVD-ILD NSIP

9 High resolution CT (HRCT) mm collimation Images taken every 10 mm Supine, prone and expiratory images

10 HRCT is the Key to Diagnosing ILD s Pattern of abnormality on HRCT scan may suggest a specific ILD. HRCT findings guide subsequent diagnostic tests. HRCT findings may be sufficient for diagnosis.

11 Usual Interstitial Pneumonia (UIP) Irregular lines in a patchy, basilar, subpleural distribution Traction bronchiectasis minimal Ground glass opacities. Honeycomb lung

12 Nonspecific Interstitial Pneumonitis (NSIP) Ground glass opacities (100%) Consolidation (98%) Nodules (96%) Traction bronchiectasis (95%) Intralobular reticulation (87%) Lower lobe predominance

13 Desquamative Interstitial Pneumonia (DIP) Ground glass opacity with a basilar, subpleural, and lower lobe distribution Lower lobe reticular opacities

14 Hypersensitivity Pneumonitis 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

15 Sarcoidosis Perilymphatic nodules Peribronchial nodules GGO Upper lobe predominant, +/- fibrosis

16 Diagnostic Algorithm Suspected PF Detailed history, PE + HRCT + PFTs/Labs Diagnostic Non-diagnostic 1. IPF 2. Sarcoidosis 3. CV-ILD 4. Hypersensitivity pneumonitis 5. Rare disease (LAM, PAP) Lung biopsy

17 Multidisciplinary approach Agreement increased with multidisciplinary approach Step Assessment Method Information Provided Agreement (κ) Individual HRCT 2 Individual 3 4 Discussion (clinician and radiologist) Individual (clinician, radiologist and pathologist) HRCT, clinical data HRCT, clinical data HRCT, clinical data, SLB Discussion HRCT, clinical data, SLB Step Modified from: Flaherty KR, et al. Am J Respir Crit Care Med. 2004;170:

18 Case 1

19 Case 1 57 year old man 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

20 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

21 Case 1 PFTs FVC 5.10 (83%) FEV (90%) FEV1/FVC 0.87 TLC 7.40 (88%) DLCO (57%)

22 CXR

23 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

24 HRCT

25 HRCT

26 HRCT

27 HRCT

28 HRCT

29 HRCT

30 HRCT

31 Serological evaluation ANA negative RF = 4

32 What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Surgical lung biopsy 4. No additional testing; diagnosis is clear

33 VATS

34 VATS

35 Usual Interstitial Pneumonia (UIP) Temporal heterogeneity Subpleural accentuation of fibrosis Regions of normal lung Microscopic honeycombing Fibroblast Foci

36 Diagnosis of IPF Management Enrolled in clinical trial Pulmonary rehabilitation Weight loss (if overweight) Lung transplant referral

37 IPF: Published Definition 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. ATS/ERS. Am J Respir Crit Care Med. 2000;161:

38 Survival Median survival for IPF is 2 3 years No proven therapy IPF Modified from Bjoraker JA. Am J Respir Crit Care Med. 1998;157:

39 Case 2

40 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

41 Case 2 Social: former smoker (18 pk/yrs); office worker. Family: No history of ILD 135/80 hr 90 rr 14 94% RA (90% walking) Dry inspiratory crackles at both bases Normal cardiac examination No clubbing, joint deformities, rashes

42 CXR

43 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

44 HRCT

45 HRCT

46 HRCT

47 HRCT

48 HRCT

49 HRCT

50 Serological evaluation ANA 1:80, speckled RF = 18, cyclic citrullinated antibody (CCP) negative

51 What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Surgical lung biopsy 4. No additional testing; diagnosis is clear

52 VATS

53 VATS

54 VATS

55 Nonspecific Interstitial Pneumonitis (NSIP) Uniform involvement of the lung with Septal thickening Interstitial inflammation (lymphocytes) +/ Fibrosis

56 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

57 Additional serologies RNP negative Scl70 negative SSA, SSB negative Jo 1 negative, CPK 104

58 Diagnosis of NSIP Management Treated with prednisone and mycophenolate (CellCept) Pulmonary rehabilitation

59 NSIP Distinguishing NSIP from UIP is a challenge! Patients usually younger, more likely to be women Honeycombing on HRCT is uncommon in NSIP Surgical biopsy shows diffuse thickening of alveolar septae and few if any fibroblast foci

60 IPF NSIP

61 IPF NSIP

62 IPF NSIP

63 NSIP The diagnosis of NSIP should prompt you to go back to look for an etiology Occult connective tissue disease Drug reaction Hypersensitivity pneumonitis

64 Case 3

65 Case 3 43 year old man Subacute progressive dyspnea PMH: mild obstructive sleep apnea on CPAP 6 cm H20, seasonal allergies Meds: cetirizine, multivitamin

66 Case 3 Social: non smoker, banker, no known exposures, no pets. Family: no history of ILD BP 116/56, hr 60, rr16, 98% RA (88% walking) Moderately obese Lungs clear to auscultation

67 Case 3 PFTs: FVC 3.17 (73%) FEV (77%) FEV1/FVC 0.77 TLC 4.65 (82%) DLCO 15.1 (58%)

68 CXR

69 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

70 HRCT

71 HRCT

72 HRCT

73 HRCT

74 HRCT

75 HRCT

76 HRCT expiratory views

77 HRCT expiratory views

78 HRCT expiratory views

79 Serological Evaluation ANA negative RF 12 SS A, SS B negative

80 What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. BAL and transbronchial biopsy 3. Surgical lung biopsy 4. No additional testing; diagnosis is clear

81 VATS Biopsy: Low Power

82 VATS Biopsy: High Power

83 VATS Biopsy: High Power

84 Hypersensitivity Pneumonitis Airwaycentric inflammation Poorly formed granuloma (giant cell) Areas of organizing pneumonia

85 What additional testing would you perform next in this patient? 1. Bronchoalveolar lavage (BAL) 2. Sputum culture 3. Serum precipitins 4. Additional history 5. No additional testing; diagnosis is clear

86 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. Additional history

87 Hypersensitivity Pneumonitis Management Remove antigen (Relocated from new home) Treat with prednisone Pulmonary rehabilitation

88 Thank you!

89 UCSF Interstitial Lung Disease Clinic Clinical Coordinator: (415) Clinic fax: (415)

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