Bronchiolitis: A Schematic Diagnostic Approach with Radiologic-pathologic Correlation
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1 Bronchiolitis: A Schematic Diagnostic Approach with Radiologic-pathologic Correlation Mariana Benegas Urteaga 1, MD; M Sanchez 1, MD; J Ramirez 2, MD; D Barnes 1, MD; T de Caralt 1, MD; R J Perea 1, MD Departments of 1 Radiology and 2 Pathology Hospital Clínic- Barcelona, Spain
2 Objectives To show the classification of bronchiolitis with radio-pathological correlation To provide an easy and schematic diagnostic approach, based on HRCT findings and relevant clinical information To emphasize the role of post-processing techniques: MIP, MinIP and densitometric evaluation
3 Understanding where is the problem: normal anatomy Centrilobular region 1 cm Centrilobular artery Lobular bronchiole Poligonal shape * * Lobular artery * A normal bronchiole accompanies a pulmonary artery * and shows a thin rim of smooth muscle and a thin layer of surrounding connective tissue within its wall Pulmonary vein Interlobular septa sometimes visible The secondary pulmonary lobule is the smallest unit of lung that is delineated by connective tissue septa and measure from 1 to 2,5 cm
4 Bronchioles Small airways that do not contain cartilage and mucous glands in their walls Internal diameter of 2 mm or less Bronchioles cannot be seen on CT Diseased bronchioles with dilated lumen or thickened walls can be visuallized on CT Lobular bronchiole Terminal bronchiole Alveolar ducts Alveoli Membranous bronchiole Respiratory bronchiole S E C O N D A R Y P U L M O N A R Y L O B U L E
5 Bronchiolitis- Small Airways Diseases Bronchiolitis or small airways diseases is a generic term used clinically to describe various inflammatory diseases of the bronchioles. Means an inflammation of the bronchiolar wall usually centered in and around the membranous and terminal bronchioles Relatively common diseases Symptoms and chest Rx are nonspecific Confusing terminology There are multiple classifications Etiologic Classification Pathological Classification CT Classification Lobular bronchiole Membranous bronchioles Terminal bronchiole TC is the imaging technique of choice for suspected bronchiolitis Respiratory bronchiole
6 Classifications of Bronchiolitis Primary bronchiolar disorders Respiratory bronchiolitis Acute bronchiolitis Constrictive bronchiolitis (Obliterative bronchiolitis) Follicular bronchiolitis Diffuse panbronchiolitis Mineral dust airway disease Bronchiolar involvement in interstitial lung diseases Hypersensitivity pneumonitis Respiratory bronchiolitis associated interstitial lung disease/desquamative interstitial pneumonia Organizing pneumonia Other interstitial lung disease: Sarcoidosis, Pulmonary Langerhans cell histiocytosis, idiopathic pulmonary fibrosis Bronchiolar involvement in large airway diseases Chronic bronchitis, Bronchiectasis, Asthma Ryu JH, Myers JL, Swensen SJ. Bronchiolar disorders. Am J Respir Crit Care Med Dec 1;168(11): Review.
7 Pathological Classification Cellular bronchiolitis Infectious bronchiolitis Hypersensivity pneumonitis Follicular bronchiolitis Panbronchiolitis Respiratory bronchiolitis/rb-ild Constrictive bronchiolitis Secondary (associated with infections, drugs, collagen, vascular diseases, transplantation) Idiopatic Bronchiolitis obliterans with intraluminal polips Idiopatic or Secondary Now is considered an idiopatic interstitial pneumonia (COP)
8 Cellular bronchiolitis Cellular inflammation of the bronchiolar wall and intraluminal exudates Constrictive bronchiolitis Peribronchiolar fibrosis with extrinsic compression and obliteration of the airway Bronchiolitis obliterans with intraluminal polips Polipoid intraluminal plugs of proliferating fibroblasts within alveolar ducts and spaces
9 How can I recognize a bronchiolitis on CT? DIRECT SIGNS Direct visualization of the diseased bronchioles INDIRECTS SIGNS Changes in the lung parenchyma distal to the obstruction of the bronchiolar lumen Tree-in-bud opacities Poorly defined centrilobular nodules Bronchiolectasis Mosaic attenuation Air trapping Bronchiolar wall thickening and occupation of the bronchiolar lumen (fluid, mucus, pus) Peribronchiolar inflammation Bronchiolar dilatation C E L L U L A R C O N S T R I C T I V E
10 Direct Signs Lobular bronchioles are usually not directly visible on CT because its wall is too thin But they can become visible at the center of the secondary lobule when there is increased soft tissue in or around the bronchioles Tree-in-bud opacities: resembles a budding tree Centrilobular noduls and V or Y- shaped branching linear opacities Dilatation and impactation of centrilobular bronchioles by pus or mucus (the branches) associated of peribronchiolar inflammation or fibrosis (the buds). It is almost due to INFECTION NOT specific to the type of infection Bacterial and mycobacterial are most frequent BRONCHIECTASIS or bronchial wall thickening may be present depending on the cause or duration of the infection
11 Direct Signs: tree-in-bud opacities Tree-in-bud opacities is generally taken to mean that infection is present. Describe this finding only when you are sure that is present. The use of MIP has been proved to increase the number of bronchiolar centrilobular opacities compared with single thin-section CT scan in patients with infectious or inflammatory bronchiolitis Rémy Jardin M et al. Spiral CT of the Chest. Springer-Verlag 1996
12 Vascular tree-in bud Tumor emboli Tumoral thrombotic microangio pathy Franquet et al. AJR 2002;179(4):897-9 Differential diagnosis of the tree-in-bud pattern Infections Infectious variants Bacterial, mycobacterial, fungal, viral infections Cystic fibrosis, Ciliary disorders, Immunodeficiency, Panbronchiolitis, Allergic bronchopulmonary aspergillosis Cortesy Dra Eva Castañer SDI UDIAT 44 year-old patient without medical history Clinically PE suspected without evidence in angioct The patient died 2 days after admission Autopsy: pulmonary tumor thrombotic microangiopathy Noninfectious bronchiolar diseases Vascular abnormalities Perilymphatic diseases Invasive mucinous adenocarcinoma, Follicular bronchiolitis, Aspiration Talcosis, Intravascular metastases Sarcoidosis
13 Direct Signs: centrilobular nodules Poorly defined Centrilobular nodules of ground glass opacity Differential diagnosis of centrilobullar nodules Hypersensitivity pneumonitis Respiratory bronchiolitis Respiratory bronchiolitis with interstitial lung disease Follicular bronchiolitis Inflammatory cellular or fibrosis surrounding the centrilobular bronchiole. Impactation of bronchiole is tipically absent. Tend to be fairly homogeneous in size Pneumoconioses Collagen vascular diseases Atypical infections
14 Direct Signs: Bronchiolectasis BRONCHIOLECTASIS may be air filled or filled with secretions. Luminal impactation + wall thickening Tree-in-bud opacities Probably an infection Commonly are associated with large airways abnormalities Dilated bronchioles visualized in the peripheral 1 to 2 cm of the lung wich is not normal
15 Indirect signs Mosaic attenuation: visualized on inspiratory CT Air trapping: is an indirect sign of obstructive small airways disease that is accentuated on expiratory CT * * * * Expiratory CT is the key When mosaic attenuation/air trapping is the only or predominant finding the differential diagnosis is quite limited Inspiration Expiration Differential Diagnosis of isolated Mosaic Attenuation Asthma Hypersensitivity pneumonitis Constrictive bronchiolitis Vascular diseases (CTEPH, vasculitis)
16 Indirect signs MinIP: increase the contrast between areas of normal lung attenuation and areas of lung hyppoattenuation facilitating the depiction of mosaic pattern. Improve the detection of air trapping. Fotheringhan el al. JCAT 1999;23: Wiltram et al. JThoracImaging 20002;7:47-52 Quantitative assessment of air trapping -860 HU -950 HU (expiration)= air trapping Quantitative expiratory CT with LLL air trapping Chabat et al. J CAT 2000;24: Matsuoka et al.ajr 2008; 190:
17 Interpretation of air trapping Inspiration Expiration Air trapping with normal inspiratory CT - Constrictive bronchiolitis - Asthma - Smokers - Hypersensitivity pneumonitis - Sarcoidosis Interpretation of expiratory CT is complicated: in approximately 50% of asymptomatic subjects lobular areas of air trapping may be depicted on expiratory CT in dependent portions of the lung. Increase with age (1) and should be ignored in the absence of physiologic evidence of airway obstruction (2) (1)Lee et al. Radiology 2000;214: (2)Tanaka el al. Radiology 2003;227:
18 Mosaic Attenuation Pattern Decrease in size of pulmonary vessels Uniform size vessels No air trapping Air trapping No air trapping Vascular disease Obstructive disease Infiltrative disease Chronic PE Airways disease Ground-glass
19 CT Patterns of Small Airways Disease CT Findings Pathophysiology Common diseases Tree-in-bud Pattern Centrilobular nodules of ground-glass opacity Mosaic pattern/air trapping Infectious mucoid impactation of bronchioles Peribronchial inflammation or fibrosis Bronchiolar narrowing or occlusion Endobronchial infections Aspiration Hypersensitivity pneumonitis Respiratory bronchiolitis Follicular bronchiolitis Atypical infections Pneumoconiosis Constrictive bronchiolitis Hypersensitivity pneumonitis C E L L U L A R CONSTRICTIVE
20 What do they have in common? Tree-in-bud Pattern + Centrilobular Nodules A Cellular Bronchiolitis B more Frequent Infectious Bronchiolitis C D
21 How do they differ? 35-year-old Immunocompetent Clinical Presentation Medical history Other CT findings 50-year-old ACUTE Immunocompromised (neutropenic) Bronchiectasis Viral infection CHRONIC Airway-invasive Aspergillosis Cavitation Nontuberculous Mycobacterial infection 70-year-old Immunocompetent women Tuberculosis 80-year-old Immunocompetent
22 Infectious Bronchiolitis Cellular Bronchiolitis CMV Mycobacterium abscessus Pseudomonas aeruginosa Mycobacterium avium-intracellulare Haemophilus influenzae Lady Windermere Syndrome -MAC and M. kansasii -lingula and middle lobe -Bronchiectasis -Elderly women -Chronic cough
23 Infectious Bronchiolitis- Aspergillosis Airway-Invasive Aspergillosis 1/3 of invasive aspergillosis Immunocompromised neutropenic patients Traqueobronchitis Bronchiolitis Bronchopneu monia Aspergillus deep to the airway basement membrane Buckingham et al. Eur Radiol 2003;13: * Allergic bronchopulmonary aspergillosis (ABPA) - Asthmatic - Large airways findings (bronchiectasis and bronchial impactation) (black asterisk) - Tree-in-bud may also be present (red arrow)
24 Cellular Bronchiolitis- Follicular Bronchiolitis Tree-in-bud +/- centrilobular nodules of ground glass opacity 30-year-old women with Sjogren s disease and respiratory symptoms Associated with collagen vascular diseases, particularly rheumatoid arthritis, Sjogren syndrome and immunocompromised patients Cellular bronchiolitis with lymphoid follicle formation in relationto the bronchiole FB and lymphoid interstitial pneumonia represent a spectrum of the same disease Pipavath et al.ajr 2005;185: A Fig A:Florid hyperplasia of peribronchiolar lymphoid follicles with compression and narrrowing of airways lumen
25 Cellular Bronchiolitis- Hypersensitivity Pneumonitis Centrilobular nodules pattern Young woman with dyspnea Represent a reaction to inhaled organic antigens Airways abnormalities most evident in the subacute stage Chronic Hypersensitivity Pneumonitis: Air trapping with mosaic attenuation pattern associated Increased with intensity fibrosis of inflammation around the airway Silva et al.ajr 2007; 188: Air trapping in lower lobes Centrilobular nodules of ground-glass opacity are usually diffuse, poorly defined and with symmetric distribution Areas of mosaic attenuation due to air trapping are frequent Small granulomas are seen adyacent to a bronchiole
26 Cellular Bronchiolitis- Respiratory Bronchiolitis Smoker with dyspnea Ill-defined centrilobular nodules Air trapping Increased numbers of pigmented macrophages within a bronchiolar lumen and surrounding alveoli, with associated non specific chronic inflammation and fibrosis in peribronchiolar alveolar walls Smoking-related disease with Desquamative interstitial pneumonia (spectrum of the same pathological process) Common finding in smokers, often asymptomatic Ill-defined centrilobular nodules of ground-glass opacity, often indistinguishable from HP Air trapping Predominance in upper lobes Emphysema may develop
27 Constrictive Bronchiolitis- Indirect Signs Causes of Constrictive Bronchiolitis Post-viral infection - Childhood viral infection (adenovirus, respiratory syncytial virus) - Adults and children (Mycoplasma, Pneumocystis jirovecii in AIDS, endobronchial spread of tuberculosis) Transplant-related bronchiolitis - Graft vs. Host disease - Chronic rejection in heart-lung or lung transplant Connective tissue disease (Rheumatoid arthritis, Sjogren) Drug toxicity (penicillamine, gold, cocaine) Neuroendocrine Cell Hyperplasia and multiple carcinoid tumorlets Inflammatory bowel diseases Inhalationl injury (nitrogen dioxide, sulfur dioxide, amonia)
28 Postinfectious Bronchiolitis- Swyer-James-McLeod s Syndrome Classically described as Unilateral Constrictive bronchiolitis in chest x ray On CT we can observe this type of bronchiolitis segmental, lobar, uni o bilateral. Focal areas of decreased lung opacity with sharp margins Decreased lung volume and reduction in the size of pulmonary artery branches Bronchial wall thickening and bronchiectasis
29 Transplant-related bronchiolitis Hematopoietic cell trasplantation Allogeneic Associated with graft-versus-host disease 6 months to 2 years after. Incidence 6-26% Imaging findings and symptoms are identical to those found with BO after lung transplantation Incidence 50-70% after 5 years BO vs Bronchiolitis Obliterans Syndrome (BOS) CT: Air trapping Mosaic attenuation pattern Bronchiectasis Bronchial wall thickening
30 Bronchiolitis obliterans INSPIRATION EXPIRATION
31 Neuroendocrine cell hyperplasia 40 year-old woman with Sjogren Syndrome and nonspecific respiratory symptoms A C B C Fig A and B: MinIP shows heterogeneos lung density with sharply demarcated regions of decreased lung attenuation compatible with mosaic attenuation pattern Fig C and D: small scattered pulmonary nodules
32 Neuroendocrine cell hyperplasia Intraepithelial nodules of neuroendocrine cells with tumourlets Association with carcinoide tumour Asymptomatics- dyspnea CT: Mosaic attenuation pattern +/- nodules Davies et al.thorax 2007;62: Lee et al. JCAT 2002;26;180.84
33 Criado E et al.pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics Oct;30(6): Constrictive Bronchiolitis Sarcoidosis Air trapping at expiratory CT Granulomas in the bronchiolar wall
34 Algorithm for the interpretation of bronchiolitis 1- CT Pattern Direct Signs Indirect Signs Tree-in-bud Centrilobular nodules Air Trapping Mosaic attenuation pattern Cellular/Inflammatory Bronchiolitis Constrictive Bronchiolitis 2-Clinical Presentation 3-Clinical Information Infection Acute Chronic Immunocompetent Immunocompromised patient Hypersensitivity Pneumonitis Respiratory bronchiolitis Follicular bronchiolitis Inhaled organic antigens, smoker, collagen vascular disease -Transplant -Prior infections -Drugs -Toxic fume exposure
35 Conclusions Small airways diseases have a quite broad clinical diagnosis The diagnosis of bronchiolitis is often suggested by CT findings There is a correlation between radiographic signs and the different pathological types of bronchiolitis The recognition of the CT pattern associated with the clinical information allows the formulation of a focused differential diagnosis The radiological reports may not only be descriptive but has to refined the diagnosis helping the clinicians to choose the therapeutic options
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