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Part 1 book “High-Resolution CT of the lung” has contents: High-resolution CT techniques and normal anatomy, approach to HRCT diagnosis and findings of lung disease, high-resolution CT diagnosis of diffuse lung disease.
High-Resolution CT of the Lung #152201 Cust: LWW Au: Webb Pg No i DESIGN SERVICES OF #152201 Cust: LWW Au: Webb Pg No ii DESIGN SERVICES OF High-Resolution CT of the Lung FIFTH EDITION W Richard Webb, MD Professor Emeritus of Radiology and Biomedical Imaging Emeritus Member, Haile Debas Academy of Medical Educators University of California San Francisco San Francisco, California Nestor L Müller, MD, PhD Professor Emeritus of Radiology Department of Radiology, University of British Columbia Vancouver, British Columbia, Canada David P Naidich, MD, FACR, FAACP Professor of Radiology and Medicine New York University Langone Medical Center New York, New York #152201 Cust: LWW Au: Webb Pg No iii DESIGN SERVICES OF Senior Executive Editor: Jonathan W Pine, Jr Acquisitions Editor: Ryan Shaw Product Development Editor: Amy G Dinkel Production Project Manager: David Orzechowski Senior Manufacturing Coordinator: Beth Welsh Marketing Manager: Dan Dressler Senior Designer: Joan Wendt Production Service: S4Carlisle Publishing Services Copyright © 2015 Wolters Kluwer Health Two Commerce Square 2001 Market Street Philadelphia, PA 19103 USA LWW.com 4th edition © 2009 by LIPPINCOTT WILLIAMS & WILKINS, a WOLTERS KLUWER business All rights reserved This book is protected by copyright No part of this book may be reproduced in any form by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews Materials appearing in this book prepared by individuals as part of their official duties as U.S government employees are not covered by the above-mentioned copyright Printed in China Library of Congress Cataloging-in-Publication Data Webb, W Richard (Wayne Richard), 1945- author High-resolution CT of the lung / W Richard Webb, Nestor L Müller, David P Naidich — Fifth edition p ; cm Includes bibliographical references and index ISBN 978-1-4511-7601-8 (alk paper) I Müller, Nestor Luiz, 1948- , author II Naidich, David P., author III Title [DNLM: 1. Lung—radiography. 2. Tomography, X-Ray Computed. 3. Lung Diseases—pathology WF 600] RC734.T64 616.2’407572—dc23 2014003388 Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication Application of the information in a particular situation remains the professional responsibility of the practitioner The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with current recommendations and practice at the time of publication However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions This is particularly important when the recommended agent is a new or infrequently employed drug Some drugs and medical devices presented in the publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings It is the responsibility of the health care providers to ascertain the FDA status of each drug or device planned for use in their clinical practice To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320 International customers should call (301) 223-2300 Visit Lippincott Williams & Wilkins on the Internet: at LWW.com Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to pm, EST 10 #152201 Cust: LWW Au: Webb Pg No iv DESIGN SERVICES OF DEDICATION To my father, who encouraged my curiosity and taught me to figure things out ––WRW To my wife, Isabela, and my children—Alison, Phillip, and Noah Müller ––NLM To Jocelyn, whose constant love and support has always been my greatest inspiration ––DPN #152201 Cust: LWW Au: Webb Pg No v DESIGN SERVICES OF #152201 Cust: LWW Au: Webb Pg No vi DESIGN SERVICES OF Contributing Authors Brett M Elicker, MD Associate Professor of Clinical Radiology and Biomedical Imaging Chief, Cardiac and Pulmonary Imaging University of California San Francisco San Francisco, California Myrna C B Godoy, MD, PhD Assistant Professor of Radiology University of Texas MD Anderson Cancer Center Houston, Texas C Isabela S Müller, MD, PhD Department of Radiology Delfin Clinic Salvador, Bahia, Brazil vii #152201 Cust: LWW Au: Webb Pg No vii DESIGN SERVICES OF #152201 Cust: LWW Au: Webb Pg No viii DESIGN SERVICES OF Preface During the past 25 years, high-resolution CT (HRCT) has become established as an indispensable tool in the evaluation of patients with diffuse lung disease HRCT is now commonly used in clinical practice to detect and characterize a variety of lung abnormalities In the approximately years since our fourth edition was published, considerable progress has taken place in the understanding of diffuse lung diseases and the recognition of new entities and their nature, causes, and characteristics Without doubt, HRCT has played a fundamental role in contributing to this progress and has become essential to the diagnosis of a number of diffuse diseases This fifth edition continues what the three of us, independently, in conjunction, and with each other’s encouragement and support, began some 30 years ago The photograph of the three of us below was taken by a local resident at the 1989 Diagnostic Course in Davos, on a walk we took on the promenade above the Sweitzerhof on the day of our arrival, when as junior faculty, we were more than a little anxious about teaching along with such important and impressive chest radiologists as Fraser, Felson, Greenspan, Milne, Flowers, Heitzman, and many others At this meeting, we each spoke about the use of HRCT, which, at the time, was a little-known technique that was regarded with skepticism by many radiologists We learned from each other as we spoke, compared slides in the speaker-ready room, and gained confidence from our shared opinions At this meeting, we began thinking about a collaboration that would combine our experience and thoughts about this new modality and its potential uses Our first edition of this book was published in late 1991, with a grand total of 159 pages It was a quarter of an inch thick, and, to our knowledge, referenced every known paper on HRCT From our perspective, it was the most important thing we had ever done That is how things start Maybe that is the best way things should start It was certainly fun and rewarding for each of us And we three have stuck together over the years, out of our combined respect, admiration, friendship, and good humor Each one of us believes that we learned more from our collaboration than we taught In this edition, we have incorporated an update and review of numerous recent advances in the classification and understanding of diffuse lung diseases and their HRCT features Recent technical modifications in obtaining HRCT have also been reviewed, most notably the use of helical HRCT and dose-reduction techniques We hope the reader will find these changes and updates helpful As is our wont, we have reorganized our discussions into new sections and chapters, which we feel best presents the most important topics in HRCT diagnosis for reference and learning A new section has been added at the end of the book to provide a general review of HRCT, including an illustrated glossary of HRCT terms and a chapter providing a compilation of the common and typical appearances of the most common diffuse lung diseases encountered in clinical practice These sections are intended to provide an illustrated index to the detailed descriptions of diseases found elsewhere in the book It is with a great deal of pride that we complete our fifth edition of this book, which has occupied so much of our thoughts, efforts, and time over the years This task is accomplished in the hope that this book will encourage future generations of thoracic imagers to develop mutually productive relationships with friends and colleagues, in order to explore important questions in our understanding of the role of imaging in the assessment of thoracic disease To this end, we acknowledge the contributions of three esteemed colleagues, our former fellows, who have authored parts of this book Their efforts have greatly inspired our own enthusiasm for the considerable task of bringing this edition to fruition W Richard Webb Nestor L Müller David P Naidich ix #152201 Cust: LWW Au: Webb Pg No ix DESIGN SERVICES OF C hapter 12 Sarcoidosis A 327 B FIGU RE 12-29 A and B: Pulmonary sarcoidosis and findings of pulmonary fibrosis in a 32-year-old man HRCT at the level of the tracheal carina shows extensive irregular or nodular septal thickening (B, arrows), irregular interfaces, and traction bronchiectasis Posterior displacement of the upper lobe bronchi is an early sign of lung distortion Extensive bilateral ground-glass opacities correlated with increased 67Ga uptake, reflecting the presence of active inflammation Lymph Node Abnormalities HRCT demonstrates characteristic symmetric hilar and paratracheal lymphadenopathy in many patients, but lymph node enlargement need not be present in patients with extensive pulmonary abnormalities On CT, lymph node enlargement is often seen in other locations as well, including the anterior mediastinum (Fig 12-38A), internal mammary chain, posterior mediastinum, retrocrural regions, and axilla (26); it has been suggested that the presence of enlarged internal mammary and paracardiac lymph nodes, while often seen in sarcoid, should raise the possibility of lymphoma (84) Lymph node calcification is not uncommon, and when present, is often hazy, feathery, or eggshell-like in appearance (Fig 12-38A), in distinction to the densely calcified lymph nodes typically seen in tuberculosis (Fig 12-38B) HRCT may be useful in detecting hilar lymphadenopathy in lungs distorted by fibrosis (Fig 12-38C) Enlarged nodes due to sarcoidosis rarely cause significant compression of critical mediastinal structures such as the central pulmonary arteries, the superior vena cava or the esophagus Thoracic Complications of Sarcoidosis A number of specific complications are known to occur in patients with sarcoidosis, for which imaging may play an important diagnostic role (48) These include infection with mycetoma formation in pre-existing cavities, bronchostenosis and/or bronchomalacia resulting in central A FIGU RE 12-30 Sarcoidosis with fibrosis Coronal HRCT section shows a typical appearance of marked architectural distortion with traction bronchiectasis (arrows) primarily involving the parahilar upper lobes Note that the lung apices are lucent despite upper lobe volume loss and bilateral hilar retraction In this case, perilymphatic nodules are also seen Focal diaphragmatic retraction (arrowheads) is another sign of upper lobe volume loss B FIGU RE 12-31 A and B: Sarcoidosis with fibrosis Noncontiguous 1-mm HRCT through the right lower lung field shows the classic appearance of peribronchial fibrotic masses with marked architectural distortion, traction bronchiectasis, and focal emphysema Note that although the distribution of these findings primarily affecting the lower lung zones is atypical, there is evidence of perilymphatic nodules consistent with the diagnosis of sarcoidosis 328 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease C FIGU RE 12-33 (Continued) FIGU RE 12-32 Pulmonary sarcoidosis and findings of pulmonary fibrosis in a 32-year-old man HRCT at the level of the tracheal carina shows extensive irregular or nodular septal thickening (arrows), irregular interfaces, and traction bronchiectasis Posterior displacement of the upper lobe bronchi is an early sign of lung distortion Extensive bilateral ground-glass opacities correlated with increased67 Ga uptake airway obstruction, pulmonary vascular involvement with pulmonary hypertension (PH), pleural disease, and, more rarely, necrotizing angiitis More often, patients with sarcoid develop pseudocavities representing bullae or cystic bronchiectasis typically seen in patients with extensive fibrosis (33,86) (Figs 12-34 and 12-35) True cavities are more often multiple and may be either thin or thick walled in appearance In the absence of a known etiology, differential most importantly includes potential infectious etiologies, especially tuberculosis (Fig. 12-39), or saprophytic fungal infections with Cystic and Cavitary Disease True cavitary sarcoidosis is rare and has been reported to be the result of either ischemic necrosis of angiitis (85) A A B B FIGU RE 12-33 Extensive pulmonary fibrosis due to sarcoidosis A: In the upper lobes, fibrous masses associated with traction bronchiectasis and posterior displacement of bronchi are visible (white arrows) B: At a lower level, a fibrous mass (white arrow) is visible on the left Subpleural bullae (black arrows) reflect adjacent fibrosis C: Near the lung base, small areas of subpleural honeycombing (arrows) are visible FIGU RE 12-34 Sarcoidosis with fibrosis A and B: Sequential sections through the carina and subcarinal space, respectively, show typical findings of lung fibrosis with marked architectural distortion, traction bronchiectasis, and thickening of bronchovascular bundles Note that there is also evidence of cystic bronchiectasis, as well as apparent cavitation (B) Differentiation between severe cystic bronchiectasis and cavitation may be difficult, especially in the setting of extensive lung scarring There is also evidence of pleural thickening on the right side, a finding usually seen only in association with extensive underlying lung disease C: Coronal reconstruction through the carina shows the global extent of these findings to good advantage Apical pleural thickening is visible C hapter 12 Sarcoidosis 329 mycetoma formation, typically due to Aspergillus species (Fig 12-37) (26,33,46,86) Although often asymptomatic, superimposed fungal infection may lead to recurrent episodes of hemoptysis, sometimes severe and requiring bronchial artery embolization or surgical resection for control Fatality rates as high as 50% have been reported in these cases, usually as a result of severe underlying lung disease rather than infection (87) Cavitation of nodules or masses may also be seen in patients with necrotizing sarcoid granulomatosis (33) This rare entity, in fact, represents a systemic disease first described by Liebow (88), and is characterized by sarcoid-like granulomas and vasculitis associated with variable degrees of necrosis CT features reported in this entity include diffuse infiltrates, bilateral nodules, and solitary nodules, with intrathoracic adenopathy present in a minority of cases (37) C FIGU RE 12-34 (Continued) A C Bronchostenosis Bronchostenosis may result from extrinsic compression by adjacent enlarged or fibrotic hilar lymph nodes, distortion of lung parenchyma due to extensive fibrosis resulting in severe airway angulation, or direct granulomatous inflammation or subsequent fibrosis of the bronchial B FIGU RE 12-35 Sarcoidosis with cystic disease, bronchiectasis, or honeycombing A and B: HRCT through the upper lobes show evidence of extensive honeycombing or cystic disease associated with bronchiectasis C: Coronal reconstruction shows the apical distribution of disease Note that although there is mild basilar honeycombing on the right side, this pattern of predominant upper lobe/ apical disease is inconsistent with most other causes of lung fibrosis, in particular, IPF 330 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease FIGU RE 12-36 Prone HRCT in a patient who has end-stage sarcoidosis B manifested by upper lobe honeycombing FIGU RE 12-37 End-stage sarcoidosis with upper lobe fibrous masses, adjacent emphysema, and a mycetoma (arrow) C FIGU RE 12-38 (Continued) A FIGU RE 12-38 Lymph node abnormalities in sarcoidosis A: Unenhanced CT at the level of the aorta shows the typical appearance of amorphous or hazy nodal calcifications in sarcoidosis In this case, note that there are enlarged pretracheal, prevascular mediastinal, and left internal mammary lymph nodes (arrow) B: An image through the upper abdomen in the same patient as in A showing a cluster of enlarged retroperitoneal nodes CT may be of value by identifying disease in atypical locations prior to attempted biopsy C: Coronal reconstructed HRCT shows mediastinal lymph node calcification in a patient with extensive parenchymal disease and fibrosis wall (Figs 12-21 and 12-22) (68–70) It is typically associated with respiratory symptoms, including cough, dyspnea, wheezing, and hemoptysis In one study of 18 patients with documented bronchial stenoses, therapeutic response was most efficacious when initiated less than months from the onset of symptoms (68) In a similar study of 11 patients presenting with airway obstruction, defined as FEV1/FVC less than 70%, due to documented endobronchial granulomas, Lavergne et al (69) showed improvement in (72%) and normalization of respiratory function in 4, with prompt initiation of therapy Pulmonary Hypertension Although rare, another important complication seen in patients with sarcoidosis is PH Variably defined as mean pulmonary arterial pressure of 25 to 40 mm Hg, PH has been reported to occur in 5% to 12% of cases (7,89) Proposed mechanisms include direct granulomatous C hapter 12 Sarcoidosis A B C D 331 FIGU RE 12-39 A–D: Sequential sections through the upper lobes show perilymphatic nodules associated with thick-walled cavities in the right lung In the absence of extensive fibrosis or coalescent nodules, this appearance should raise the suspicion of a superimposed infectious process, in this case proven active TB infiltration of vessel walls with obliteration of the pulmonary vascular bed and marked vasoconstriction due to advanced lung disease CT findings suggestive of PH are described in detail in Chapter 22 and include a pulmonary artery diameter greater than 29 mm, a segmental artery-to-bronchus ratio greater than in three of four lobes, and a main pulmonary artery to aorta diameter ratio greater than (90,91) Although absence of these signs does not preclude the diagnosis of PH, CT may still be of value by first suggesting this diagnosis In a prospective study of 246 consecutive patients with sarcoidosis evaluated by Doppler echocardiography, 12 (5.7%) proved to have PH defined as mean pulmonary arterial pressure greater than 40 mm Hg (92) Radiographic and HRCT findings in of these patients were compared with those in 122 patients without PH Although all patients with PH had radiographic evidence of advanced disease and a marked decrease in pulmonary functional parameters, there was no significant correlation with either the presence of lymph node enlargement or the finding of thickened bronchovascular bundles (in the absence of lung fibrosis) This led the investigators to conclude that the likely mechanism of PH in sarcoidosis is the presence of lung fibrosis causing obliteration of the pulmonary arterial bed rather than extrinsic compression of pulmonary arteries (Figs 18-13 and 23-13) (92) Similar findings have been reported by Sulica et al (93); they found that PH in sarcoidosis is associated with a higher prevalence of stage disease More recently, in a cross-sectional study of 313 consecutive patients with biopsy-proven sarcoidosis evaluated with cardiac magnetic resonance imaging (MRI) and Doppler echocardiography, 37 (11.8%) were found to have pulmonary artery hypertension with pulmonary arterial systolic pressure greater than 40 mm Hg Compared with patients without PH, those with PH were significantly older and had greater lung function impairment PH proved to be secondary to either pulmonary fibrosis, left ventricular diastolic dysfunction due to cardiac sarcoidosis, or other comorbidities in the majority of cases In patients without pulmonary fibrosis, a reduced carbon monoxide diffusing capacity (DLCO) was associated with the presence of PH (89) Pleural Disease Pleural abnormalities can be demonstrated in 5% to 10% of cases with radiographic evidence of sarcoidosis (Fig. 12-34) Small to moderate-size effusions are typical and usually clear spontaneously in to 3 months (33) 332 s e c t i o n III High-Resolution CT Diagnosis of Diffuse Lung Disease In one study of 61 consecutive patients with documented sarcoidosis, evaluated with CT, 25 (41%) had evidence of pleural disease, including 20 with pleural thickening and with effusions, compared with only (11%) with pleural abnormalities identified on plain chest radiographs (40) Although pleural thickening was commonly noted in association with restrictive pulmonary function tests (PFTs), this did not prove significant when adjusted for the presence of parenchymal fibrosis Extrapulmonary and Extranodal Manifestations of Sarcoidosis Extrapulmonary and extranodal abnormalities are sometimes visible in patients with sarcoidosis on CT obtained for assessment of the lungs or mediastinum These include abnormalities of the musculoskeletal system, liver and spleen, and heart Musculoskeletal abnormalities may be more common than previously believed In one study of 56 MRI scans obtained in 40 patients with documented sarcoidosis and unexplained musculoskeletal complaints, 42% proved to have bone lesions, in particular, large bone or axial skeletal lesions, whereas 17% had abnormal joints and 22% had soft-tissue lesions (Fig 12-40) (94) Skeletal abnormalities are not commonly visible on HRCT CT findings in patients with splenic and hepatic involvement have been described, and although more easily FIGU RE 12-40 Musculoskeletal disease T2-weighted coned down view oblique sagittal image of the left humerus shows numerous high signal foci in the proximal humeral shaft In this case, identical lesions were also preset in the contralateral right shoulder, leading to an erroneous initial diagnosis of metastatic tumor despite previously documented sarcoidosis The true incidence of soft tissue and bony abnormalities in patients, especially with advanced disease, is likely underdiagnosed (Case courtesy of Sandra Moore, MD, New York University-Langone Medical Center, New York.) FIGU RE 12-41 Sarcoid spleen Multiple low-attenuation lesions are visible on this contrast-enhanced CT This appearance is typical of sarcoidosis seen on contrast-enhanced CT, may be visible on HRCT studies as well Low-attenuation hepatic or splenic nodules may be seen, isolated or innumerable, and ranging in size from mm to cm These are found more often in the spleen than in the liver (Fig 12-41) (95) and have been reported to occur in up to 70% of autopsy studies Hepatic and splenic involvement occurs with a distinctly higher frequency in African American patients, with cirrhosis and liver failure only rarely occurring (3) Cardiac sarcoidosis is diagnosed clinically in less than 5% of cases, although it has been reported to be present at autopsy in up to 25% of patients with systemic involvement (96,97) It carries a particularly poor prognosis It is most often manifested by a cardiac tachyarrhythmia, often requiring the placement of an implantable defibrillator device to obviate sudden death resulting from ventricular fibrillation Rarely, if ever, diagnosed using CT (98), the diagnosis of cardiac sarcoidosis can be suggested in patients with pulmonary sarcoidosis and cardiac abnormalities, when other etiologies of heart disease are absent CT findings may include cardiomegaly, pericardial effusion, and left ventricular aneurysm (98) Thallium (201TL) single-photon emission CT, 18-fluoro-deoxy-glucose positron emission tomography (18FDG-PET) scanning, or gadolinium-enhanced MRI typically show lesions involving the interventricular septum and the free left ventricular lateral wall (Figs 12-42 and 12-43) (31,99) The use of one of these imaging studies appears to be appropriate if cardiac symptoms are present In one study of 101 patients with sarcoidosis, 16 of 19 presenting with cardiac symptoms proved to have cardiac sarcoidosis, with patients requiring a pacemaker; in distinction, only of 82 asymptomatic patients in this study proved to have abnormal cardiac imaging findings (99) On the basis of these findings, routine screening of patients with known or suspected sarcoidosis, to diagnose occult cardiac involvement, does not appear justifiable As recently reported by Teirstein et al in a retrospective C hapter 12 Sarcoidosis A FDG-PET B T2-weighted CMR C Late Gadolinium Enhancement CMR D Fused PET/CMR 333 FIGU RE 12-42 Cardiac involvement assessed by 18FDG-PET and MR A: 18FDG-PET image showing foci of increased myocardial activity in a patient with proved sarcoidosis B: T2-weighted contrast enhanced C: Late post-gadolinium-enhanced images show foci of decreased signal intensity (arrows) corresponding to the same areas shown in A D: Fused 18FDG-PET/MR imaging demonstrating precise co-registration between 18FDG-PET and MR (Case courtesy of Kent Friedman, MD, New York University-Langone Medical Center, New York.) evaluation of 188 18FDG-PET scans performed in 137 patients with documented sarcoid, no cardiac involvement was identified (100) UTILITY OF HIGH-RESOLUTION COMPUTED TOMOGRAPHY High-Resolution Computed TomographyPulmonary Function Correlations Most investigators believe that HRCT has a very limited role in assessing or predicting pulmonary function in patients who have sarcoidosis (101) Although CT provides a superior assessment of disease pattern, extent, and distribution in patients with sarcoidosis, it is controversial whether it correlates better than chest radiographs with clinical and functional impairment (101) In a review of 27 patients with sarcoidosis, Müller et al (44) demonstrated that CT and radiographic assessment of disease extent had similar correlations with the severity of dyspnea (r = 0.61 and 0.58, respectively; p < 0.001), total lung capacity (TLC) (r = −0.54 and −0.62, respectively; p < 0.01), and gas transfer as assessed by DLCO (r = −0.62 and −0.52, respectively; p 0.49) than the radiographic scores (all r < 0.15) Similarly, Drent et al (102) found that HRCT abnormalities, but not the chest radiographic stage, were strongly associated with functional parameters in patients with sarcoidosis Scores for the extent of various HRCT findings, particularly those associated with fibrosis (i.e., thickening or irregularity of the peribronchovascular interstitium, linear opacities, and nodules) and the total HRCT score, correlated with the FEV1, FVC, DLCO, arterial oxygen tension at maximal exercise (all p < 0.05), and alveolar-arterial oxygen difference at maximal exercise (p < 0.001) The presence of consolidation, groundglass opacity, and lymph node enlargement did not show a significant correlation with function (102) Remy-Jardin et al (45) also reported low, but statistically significant correlations between the HRCT extent of various findings of sarcoidosis (with the exception of nodules) and PFT results The best correlations were between the overall extent of abnormalities seen on HRCT and FVC (r = −0.40), FEV1 (r = −0.37), TLC (r = −0.48), and DLCO (r = −0.49; all p < 0.0001) Specific HRCT findings having the best correlations with PFTs were consolidation, ground-glass opacity, and lung distortion, although these correlations were generally low Carrington (20) suggested that poor correlation between the radiographic severity of disease and the functional impairment in patients who have sarcoidosis may be due to the fact that the nodular lesions, although easily seen and quantitated, cause minimal dysfunction This situation is similar to that seen in patients who have silicosis, in whom the severity of interstitial fibrosis rather than the number or size of nodules is responsible for impaired function (20) In the study by Müller et al (44), patients who had predominantly irregular reticular opacities had more severe dyspnea and lower lung volumes than patients who had predominantly nodular opacities (p