Idiopathic Interstitial Pneumonias. Carlos H. Previgliano MD Associate Professor Radiology Louisiana State University Shreveport
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1 Idiopathic Interstitial Pneumonias Carlos H. Previgliano MD Associate Professor Radiology Louisiana State University Shreveport
2 Idiopathic Interstitial Pneumonias Idiopathic interstitial pneumonias are a group of diffuse parenchymal lung diseases Also known as interstitial lung disease Heterogeneous group of nonneoplastic disorders resulting from damage by varying patterns of inflammation and fibrosis Interstitium primary site of injury Airspaces, peripheral airways and vessels
3 Liebow and Carrington (1969) History Previous Classifications of IIP Katzenstein (1995) Müller and Colby (1997) Usual interstitial pneumonia Usual interstitial pneumonia Usual interstitial pneumonia Desquamative interstitial pneumonia Bronchiolitis obliterans interstitial pneumonia and DAD Lymphoid interstitial pneumonia Giant cell interstitial pneumonia DIP/RB-ILD Acute interstitial pneumonia Nonspecific interstitial pneumonia Desquamative interstitial pneumonia BOOP Acute interstitial pneumonia Nonspecific interstitial pneumonia
4 Idiopathic Interstitial Pneumonias In 2002 American Thoracic Society (ATS) and European Respiratory Society (ERS) published a new classification of IIPs Defines clinical-radiologic-pathologic patterns In their idiopathic form, IIPs rare diseases Classification is based on histologic criteria that is associated with a characteristic CT pattern
5 Diffuse Parenchymal Lung Disease DPLD known cause e.g. drugs, collagen vascular disease Idiopathic Interstitial Pneumonias Granulomatous DPLD e.g. sarcoidosis Other forms DPLD e.g. LAM, HX, etc
6 Diffuse Parenchymal Lung Disease DPLD known cause e.g. drugs, collagen vascular disease Idiopathic Interstitial Pneumonias Granulomatous DPLD e.g. sarcoidosis Other forms DPLD e.g. LAM, HX, etc Idiopathic Pulmonary Fibrosis IIP other than IPF Desquamative Interstitial Pneumonia Respiratory Bronchiolitis Interstitial Lung Disease Acute Interstitial Pneumonia Cryptogenic Organizing Pneumonia Nonspecific Interstitial Pneumonia Lymphocytic Interstitial Pneumonia
7 Idiopathic Pulmonary Fibrosis Distinct type chronic fibrosing interstitial pneumonia of unknown cause Associated with histologic pattern of UIP To diagnose IPF: exclusion other cause (drugs, exposure, CVD) abnormal radiographs and HRCT abnormal pulmonary function studies (restriction) Definite diagnosis requires sx lung biopsy
8 Idiopathic Pulmonary Fibrosis Clinical Onset of symptoms is gradually Dyspnea is most prominent symptom Nonproductive cough usual and paroxysmal Age: 50 yr and slightly more common males Digital clubbing and velcro crackles bibasilar In late stages there are right heart failure and peripheral edema Survival: yr
9 Idiopathic Pulmonary Fibrosis BAL Excess of neutrophils and eosinophils When eosinophils >20% eosinophilic lung disease Lymphocytosis above 15% should alert to an alternative diagnosis (NSIP, COP, sarcoid, hypersensitivity pneumonitis or other granulomatous disease)
10 Idiopathic Pulmonary Fibrosis Histology Architectural destruction, fibrosis with honeycombing, fibroblastic foci (patchy) Alternate normal and abnormal areas Interstitial inflammation consists of alveolar septal infiltrate of lymphocytes, plasma cells and histiocytes Fibrotic zones show temporal heterogeneity Honeycomb areas show cysts filled w mucin
11 Idiopathic Pulmonary Fibrosis Radiologic Features Chest x-ray may be normal Commonest abnormality peripheral reticular opacity in lung bases and honeycombing CT: subpleural reticular opacities, honeycombing traction bronchiectasis and GGO bibasilar and peripheral often patchy distribution temporal heterogeneity
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15 Trio of Signs Apicobasal gradient Subpleural reticular opacities Macrocystic honeycombing with traction bronchiectasis
16 Trio of Signs Apicobasal gradient Subpleural reticular opacities Macrocystic honeycombing with traction bronchiectasis
17 ATS/ERS Criteria for Diagnosis in Absence of Surgical Lung Biopsy Am. J. Resp. Crit. Care Med. 2002;165:
18 Idiopathic Pulmonary Fibrosis Differential Diagnosis CT pattern of IPF can be indistinguishable from UIP due to asbestosis and collagen vascular disease Hypersensitivity pneumonitis should be considered if micronodules are seen or there is sparing of lung bases Sarcoidosis should be suspected if cysts are large or peribronchovascular nodules are present
19 Nonspecific Interstitial Pneumonia Some pts with IID do not fit into any welldefined histologic patterns Katzenstein & Fiorelli used this term in1994 NSIP is divided into 2 subtypes: cellular: interstitial inflammation fibrosing: inflammation and fibrosis
20 Nonspecific Interstitial Pneumonia Clinical Better prognosis w almost complete recovery Age of onset 40 and 50 yr, M=F No association with smoking Duration symptoms mo Breathlessness, cough, fatigue, weight loss Finger clubbing in 10%-35% Crackles initially basal, may be widespread
21 Nonspecific Interstitial Pneumonia BAL Increase percentage of lymphocytes in about 50% of the cases Increase neutrophils and eosinophils Presence of lymphocytes strengthens the suspicion of NISP
22 Nonspecific Interstitial Pneumonia Histology Histologic features do not fit the histologic pattern of UIP, OP, DAD, DIP, LIP Varying degrees of alveolar inflammation or fibrosis At cellular end there is mild/moderate interstitial chronic inflammation (L and PC) At fibrosing end there is dense interstitial fibrosis and connective tissue is temporally homogeneous
23 Nonspecific Interstitial Pneumonia Radiologic Features Plain: bilateral pulmonary infiltrates lower lung zones patchy parenchymal opacities interstitial abnormalities CT: GG bilateral, symmetrical, subpleural reticular opacities with scattered micronodules traction bronchiectasis honeycombing and consolidation are infrequent
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26 Nonspecific Interstitial Pneumonia Differential Diagnosis Idiopathic interstitial fibrosis (IPF) Hypersensitivity pneumonitis Organizing pneumonia (OP) Desquamative interstitial pneumonia (DIP)
27 Cryptogenic Organizing Pneumonia Described by Davison in 1983 In 1985 Epler used the term BOOP COP is preferred because conveys essential features and avoid confusion with BO (airway) Features are organization within alveolar ducts and alveoli with or without organization within bronchioles It is included in IIP because idiopathic nature
28 Cryptogenic Organizing Pneumonia Clinical Equal sex distribution, mean age 55 y/o Nonsmokers outnumber smokers by 2:1 Illness of short duration (3 mo) Cough may be productive, dyspnea, sweats, chills, weight loss, fever Crackles are localized or widespread ESR, C reactive protein, neutrophilia Patients recover on administration of steroids
29 Cryptogenic Organizing Pneumonia BAL Increase lymphocytes up to 40% total cells Increase neutrophils and eosinophils If prominent increase of eosinophils should raise the consideration of eosinophilic pneumonia
30 Cryptogenic Organizing Pneumonia Histology Organizing pneumonia involving alveolar ducts and alveoli with or without intrabronchial polyps Majority of changes center on small airways Associated interstitial inflammatory infiltrate and increase in alveolar macrophages Relative preservation lung architecture
31 Cryptogenic Organizing Pneumonia Radiologic Features Chest radiograph: consolidation areas uni or bilateral, patchy small nodular opacities 10%-50% large nodular opacities (>1cm) 15% normal lung volumes 75% reduced lung volumes 25%
32 Cryptogenic Organizing Pneumonia Radiologic Features CT: airspace consolidation in 90% subpleural or peribronchial in up to 50% lower lung zones more frequent GG attenuation 60% multiple large nodules 15% nodules irregular borders, air bronchogram pleural effusion is rare
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37 Cryptogenic Organizing Pneumonia Differential Diagnosis Consolidation: alveolar cell Ca, lymphoma, sarcoidosis, infection, vasculitis Subpleural consolidation: eosinophilic pneumonia Multiple large masses: metastases, infection, lymphoma Combination of GG and cysts should suggest either LIP or DIP
38 Acute Interstitial Pneumonia Rapidly progressive Described as organizing form of DAD Indistinguishable from ARDS Also known as Hamman Rich
39 Acute Interstitial Pneumonia Clinical No sex predominance, mean age 50 y/o No association with smoking Myalgias, arthralgias, fever, chills, malaise, dyspnea Pulmonary function tests show restrictive pattern Mortality rate 50% between 1 or 2 months of onset
40 Acute Interstitial Pneumonia BAL Increased total cells Hemorrhage Neutrophils Occasionally lymphocytes
41 Acute Interstitial Pneumonia Histology Exudative phase: edema, hyaline membrane, interstitial acute inflammation Proliferative phase: type II pneumocyte hyperplasia Organizing phase: loose organizing fibrosis within alveolar septa May progress to end-stage fibrosis
42 Acute Interstitial Pneumonia Radiographic Features Chest radiograph: bilateral airspace opacification with air bronchograms patchy with sparing costophrenic angles as disease progresses lungs become more consolidated volume near normal
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44 Acute Interstitial Pneumonia Radiographic Features CT: GG attenuation, bronchial dilatation, architectural distorsion in exudative phase GG bilateral, patchy, consolidation in dependent areas in organizing phase distorsion bronchovascular bundles and traction bronchiectasis cysts and lucent areas common in late stages of AIP
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46 Acute Interstitial Pneumonia Differential Diagnosis ARDS (asymmetric distribution) Infection (P jiroveci) Edema, hemorrhage Alveolar proteinosis Bronchioloalveolar cell carcinoma DIP
47 Respiratory Bronchiolitis-Associated Interstitial Lung Disease Clinical manisfestation of ILD Associated with pathologic lesion of respiratory bronchiolitis RB is histopathologic lesion found in cigarette smokers characterized by intralumenal macrophages within respiratory bronchioles Asymptomatic, rarely presents as ILD Frequently associat centrilobular emphysema
48 Respiratory Bronchiolitis-Associated Interstitial Lung Disease Clinical Dyspnea, cough and hypoxemia 4 th 5 th decades Smokers >30 pack-years M:F 2:1 Improve after cessation of smoking
49 Respiratory Bronchiolitis-Associated Interstitial Lung Disease BAL Alveolar macrophages with golden, brown or black pigmented inclusion Absence of these cells should alert to an alternative diagnosis Modest increase in neutrophils may also be present
50 Respiratory Bronchiolitis-Associated Interstitial Lung Disease Histology Changes are patchy and have bronchiolocentric distribution Pigmented macrophages in respiratory bronchioles, alveolar ducts and peribronchial alveoli Mild peribronchiolar fibrosis Type II pneumocyte hyperplasia Centrilobular emphysema
51 Respiratory Bronchiolitis-Associated Interstitial Lung Disease Radiographic Features Chest radiograph: thickening of walls central or peripheral bronchi (75%) GG (60%) chest x-ray normal in 14%
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53 Respiratory Bronchiolitis-Associated CT: Interstitial Lung Disease Radiographic Features centrilobular nodules GG thickening walls central/peripheral airways hypoattenuation areas represent air trapping
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56 Respiratory Bronchiolitis-Associated Interstitial Lung Disease Differential Diagnosis Hypersensitivity pneumonitis DIP (GG more extensive, less poorly defined, centrilobular nodules are uncommon) NSIP
57 Desquamative Interstitial Pneumonia Name originated from the belief that dominant histologic feature was desquamation However now is recognized to be intra-alveolar macrophage accumulation Condition may represent the end of a spectrum of RB-ILD (similar pathology) Associated with cigarette smoke Proper name alveolar macrophage pneumonia
58 Desquamative Interstitial Pneumonia Clinical Affects primarily cigarette smokers M:F 2:1 4 th 5 th decades Patients improve with smoking cessation Survival rate 70% after 10 years Dyspnea and dry cough Decrease DL CO
59 Desquamative Interstitial Pneumonia BAL Intra-alveolar macrophages with granules of smokers pigment Also increase in neutrophils, eosinophils and lymphocytes
60 Desquamative Interstitial Pneumonia Histology Diffuse involvement by macrophage accumulations within airspaces Thickening alveolar septa by plasma cells and eosinophils Intralumenal macrophages contain dusty brown pigment
61 Desquamative Interstitial Pneumonia Radiologic Features Chest radiograph: normal in 3%-22% widespread GGO, peripheral, lower zones CT: GG lower zones, peripheral, patchy irregular linear opacities, reticular pattern honeycombing (30%), limited in extent
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64 Desquamative Interstitial Pneumonia Differential Diagnosis Respiratory brochiolitis associated interstitial lung disease Acute or subacute hypersensitivity pneumonitis Sarcoidosis Infections (P jiroveci)
65 Lymphoid Interstitial Pneumonia Term introduced by Liebow and Carrington in 1969 Considered as preneoplastic disease Incidence of idiopathic LIP is low and its existence is doubted by some
66 Lymphoid Interstitial Pneumonia Clinical Clinical presentation remains poorly defined More common in women Any age but most typically in 5 th decade Cough, fever, weight loss, CP, arthralgia Crackles and lymphadenopathy Associated RA, SLE, Sjögren, Hashimoto Idiopathic LIP rarely progresses to fibrosis Corticosteroids improve symptoms
67 Lymphoid Interstitial Pneumonia BAL BAL fluid shows lymphocytes
68 Lymphoid Interstitial Pneumonia Histology Infiltrate of lymphocytes, plasma cells and histiocytes Associated with type II cell hyperplasia and a mild increase in alveolar macrophages Lymphoid follicles in pulmonary lymphatics
69 Lymphoid Interstitial Pneumonia Radiologic Features Chest radiograph: two patterns basilar with alveolar component diffuse with associated honeycombing CT: ground glass is dominant cysts or honeycombing can also be seen reticular abnormality in 50% nodules and widespread consolidation
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72 Mueller-Mang C. et al. RadioGraphics 2007;27:
73 Mueller-Mang C. et al. RadioGraphics 2007;27:
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75 Mueller-Mang C. et al. RadioGraphics 2007;27:
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78 Mueller-Mang C. et al. RadioGraphics 2007;27:
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80 Thank you!!
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