Computed Tomography of Interstitial Lung Diseases 9383989505, 9789383989508

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COMPUTED TOMOGRAPHY of INTERSTITIAL LUNG DISEASES BHAVIN JANKHARIA

TREE LIFE MEDIA Publishing For Practice

(A division of Kothari Medical)

CT OF INTERSTITIAL LUNG DISEASES TREE LIFE MEDIA Publishing For Practice

(A division of Kothari Medical)

© 2019 Jankharia Publications Pvt. Ltd. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission of the copyright holder. Permission of the Publisher is required for all other derivative works, including compilations and translations. Medical knowledge is constantly changing. As new information becomes available, changes in treatment, procedures, equipment, and the use of drugs become necessary. The authors, editors, contributors, and the publishers have, as far as possible, taken care to ensure that the information given in this text is accurate and up-to-date. However, readers are strongly advised to confirm that the information, especially with regard to drug dose/ usage, complies with the current legislation and standard of practice. Opinions expressed in this book are those of the authors and do not necessarily reflect those of Kothari Medical Subscription Services Pvt. Ltd., the editors, or sponsors. TreeLife Media, Kothari Medical Subscription Services Pvt. Ltd. assumes no liability for any material published herein. Relevant permissions to use and build the content for the book are solely authors’ responsibility and the Publisher is not liable for the same. In case of any dispute, all legal matters to be settled under Mumbai’s jurisdiction only. Although all advertising material is expected to conform to ethical (medical) standards, inclusion in this publication does not constitute a guarantee or endorsement of the quality or value of such product or of the claims made of it by its manufacturer.

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Acknowledgements My father, Dr G. R. Jankharia, who has helped me navigated life without imposing himself. My mother, Mrs. Nalini Jankharia, who, in childhood, instilled in me the discipline that has helped get this book done. My wife, Bijal for being patient about everything and tolerating me. Dr Ravi Ramakantan, for being the mentor he is. Dr Jyotsna Joshi for all her silent help over the last 25 years that has fostered my expertise in chest radiology. All the chest physicians who I work with, without whose support, I wouldn’t have the case material that has gone into the book. Dr Ganesh Raghu, for agreeing to write a Foreword without batting an eyelid.

Preface This book is meant for radiology consultants looking at chest diseases, chest physicians who interpret CT scans for diffuse lung diseases and residents in radiology and chest medicine who want to learn how to interpret these diseases. I have been involved with chest radiology for the last 25 years. When the first Hi-Q scanner was installed in 1991 in Bombay Hospital, we became pretty much the first institution in the country doing HRCT scans for interstitial lung diseases. Spurred on and encouraged by committed and interested chest physicians, my team and I kept honing our skills as the years passed by. Our radiology centre now is a tertiary referral center for the imaging of patients with diffuse lung diseases as well as for opinions on scans done elsewhere. The first chapter sets out the current definitions. The second chapter, which to me is perhaps the most important of all, describes what a good CT study is and how to make out when a scan is suboptimal. The third chapter lists the various signs of fibrosing and non-fibrosing ILDs and explains why the distinction is important. The fourth chapter discusses the fibrosing ILDs. It incorporates the 2018 Fleischner Society and ERS/ ATS Guidelines for the diagnosis of idiopathic pulmonary fibrosis (IPF) and discusses the findings that allow differentiation of the various fibrosing ILDs. The fifth to eighth chapters discuss individual signs of non-fibrosing ILDs, such as ground glass attenuation, septal thickening, nodules and cystic ILDs. The ninth chapter is on unclassifiable ILDs and the rare pleuro-parenchymal fibroelastosis (PPFE) followed by the tenth chapter on diverse presentations that include connective tissue disease related ILDs, smoking related ILDs and those caused by iatrogenic etiologies such as chemotherapy and radiation. These are followed by a clinical and history examination form to aid radiologists and a format for structured reporting. This book is a treatise to help understand ILDs and provide a roadmap to interpret them well. There are more than 175 figures and images that will also help with pattern recognition, if stuck while making a diagnosis. I hope this book finds its way to the table of every radiologist interpreting chest CT scans and every chest physician who looks at patients with diffuse lung diseases.

Bhavin Jankharia

Foreword In the absence of infection and neoplasm, interstitial lung diseases (ILDs) are a heterogeneous group of acute and chronic bilateral lung diseases of known and unknown causes. While the liberal access to computed tomography (CT) scans of chest has surfaced an increased awareness of ILD – fibrotic and non fibrotic, the standard of care of management for patients manifesting with ILD, has evolved over the last few years and includes the CT scans of the chest as an essential diagnostic tool to evaluate patients. This is driven by the evidence accumulated over the last two decades and also because the distribution and patterns of the images surfaced by the high resolution CT (HRCT) scans of the chest are found to be distinct for specific ILD/interstitial pneumonia. Hence, the need for clinical evaluation of ILD patients with HRCT scans of chest as an essential component became evident in the first evidence based guidelines published in 2011 by the American thoracic society (ATS) as a joint ATS-European respiratory society (ERS), Japanese respiratory society (JRS) and the association of the Latin American thoracic society (ALAT) - the 2011 ATS-ERS-JRS-ALAT guideline for diagnosis and management of idiopathic pulmonary fibrosis (IPF). The recognition of the pattern of usual interstitial pneumonia (UIP) in HRCT eliminates the need for clarifying /confirming the UIP pattern in lung biopsy and this in itself is a milestone in the management of patients suspected to have IPF. Recognizing the UIP pattern in HRCT scans of chest is thus of paramount importance as then these patients do not need to be subjected to lung biopsy to clarify/confirm the diagnosis by histopathologic features of UIP. The recent 2018 evidence based guideline published as an update of the official document of the ATS – the 2011 ATS-ERS-JRS-ALAT guideline for diagnosis of IPF and the white paper consensus document of the Fleischner Society has revised and refined the criteria for the UIP patterns. Both documents emphasize the need for recognizing the UIP patterns and discussions with experts from multi disciplines and thus eliminate the need for histopathology diagnosis in patients suspected to have IPF and demonstrating the UIP pattern. The need for histopathology clarification of the diagnosis in patients who do not have the pattern of UIP and do not have contraindications to obtain lung biopsy with invasive diagnostic intervention such as bronchoscopy or thoracoscopy (the surgical lung biopsy) must be discussed by experts from multi disciplines – i.e., a multidisciplinary discussion (MDD) before and after obtaining the lung biopsy to ascertain the accurate diagnosis. The recent Fleischner ‘white paper’ and the 2018 ATS-ERS-JRS-ALAT evidence-based guidelines emphasize the need for MDD between expert pulmonologists, radiologists and pathologists familiar with ILD to facilitate an accurate diagnosis of specific idiopathic interstitial pneumonias (IIP), including IPF. MDD is particularly important for diagnosis of specific ILDs, such as IPF, that may be based on clinical characteristics and diagnostic patterns on HRCT images of the chest without surgical lung biopsy (SLB). With the increasing clinical utility of HRCT scans of the chest and utilizing the MDD, the need for histopathology in lung biopsy is decreasing worldwide. The diagnosis of hypersensitivity pneumonitis (HP), in particular, strongly relies on a high index of clinical suspicion, a thorough history to elicit environmental exposures known to be associated with HP as well as consistent HRCT imaging patterns. Ascertainment of diagnosis by histopathology in these cases would be ideal, but may not be essential for all patients with typical clinical and radiological features in a patient with known exposure to inducer/s and agents associated with HP. The need for evidence based clinical practice guideline for diagnosis of HP is long overdue and is anticipated that this will become available in the near future.

The importance of proper technique of obtaining the optimal HRCT and obtaining the images in both inspiration and exhalation is emphasized in the 2018 guideline to increase the diagnostic yield of the HRCT scans of chest to recognize the patterns and distribution of the parenchymal abnormalities in patients with ILD. This is of utmost importance as the detection of significant air trapping in the HRCT images will increase the likelihood of the diagnosis of HP. Since the radiology pattern of UIP can be similar to patients with chronic HP and IPF, the presence of air trapping in HRCT can be overt if HRCT images are obtained in exhalation phase of respiration. The incidence and prevalence of ILDs varies among studies, which is likely due to differences in design as well as differential recognition and data collection. Geographic differences in disease burden must be taken into consideration and the challenge in diagnosing ILDs in patients residing and/or originating from endemic areas for mycobacterial tuberculosis infection is confounded by environmental and cultural factors. Despite the recognized image patterns on HRCT scan chest, the challenge in ascertaining an accurate diagnosis of ILD is more so in regions and countries where there is no standardized approach for evaluation and diagnosis of ILD. This is confounded by lack of resources and standardized health care, especially in tropical countries where the high incidence and prevalence of mycobacterial tuberculosis and post tuberculosis fibrosis, varying infections, tropical interstitial eosinophilia, occupational lung diseases and air pollution are evident. These factors need to be taken into consideration in evaluating patients with CT scans of chest for ILD in such endemic and geographical areas. In summary, evaluation of patients with ILD with HRCT scans of chest is an essential component of the diagnostic intervention for patients with ILD. This book of CT of Interstitial lung diseases written by Dr Bhavin Jankharia illustrated with ~ 180 images surfaces the importance in recognizing patterns of fibrotic and non fibrotic lung to the general radiologist and it is hoped that with this knowledge, an accurate diagnosis of a specific ILD will be made with the MDD that includes the interaction of the radiologist with the clinician confronted with the evaluation of patients with ILD and other experts; the need for histopathology of IIP/ILD, other than UIP will hopefully be minimized and decisions for invasive diagnostic interventions will be made wisely and judiciously. I anticipate that ongoing and future studies with advancing technology for high resolution imaging lungs, machine learning tools to recognize distinct HRCT patterns for diagnosis of specific ILD and for quantifying the extent of lung involvement with fibrosis and non fibrotic pattern will yield useful results and move the field of chest imaging further for accurate diagnosis of specific ILD beyond UIP and this includes prognostication and for assessing response to treatment. Ganesh Raghu, MD, FCCP, FACP Professor of Medicine & Lab Medicine (Adjunct), Division of Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, School of Medicine, University of Washington (UW), Campus Box 356175 Director, CENTER for Interstitial Lung Disease (ILD), UW Medicine, Director, ILD, Sarcoid and Pulmonary Fibrosis Program Co-Director, Scleroderma Clinic, UW Medicine, Seattle, WA 98195, USA

Foreword It is a privilege to write the foreword to the first edition of this book by Dr Bhavin Jankharia, one of the most gifted and brilliant radiologist in the country today. Interstitial lung diseases (ILDs) pose a challenge to the clinicians and radiologists alike. Since the advent of high resolution computed tomography (HRCT) the role of radiology in diagnosing and recognizing disease pattern has become crucial. Multidisciplinary diagnosis (MDD) comprising of pulmonologist, radiologist and pathologist is recommended for managing ILDs. In many cases, HRCT is sufficient to make a confident diagnosis obviating the need for lung biopsy. The radiologist with expertise in ILD is therefore indispensable in management of ILD. This book is a comprehensive compilation on the latest in HRCT in ILD. It is superbly illustrated and that makes it easy for students, physicians and practising radiologist to update themselves in mastering HRCT in ILD. I have been associated with Dr Jankharia for over two decades. His expertise in CT in general and HRCT in particular is unparalleled. He keeps abreast of the latest in the field, which benefits not only patients but also students for whom he arranges CMEs on a regular basis. All these years of experience and learning has translated into this book. I recommend this book for all physicians and radiologists who handle ILDs Students will benefit immensely from the information and illustrations provided painstakingly in the book. Jyotsna M. Joshi, MD Consultant Pulmonologist, Currae Hospital, Thane, India. Former Professor and Head, Department of Pulmonary Medicine, TN Medical College, BYL Nair Hospital, Mumbai, India

Foreword Through almost three decades, I have seen Bhavin mature in his technique, understanding and interpretation of images relating to interstitial lung diseases. Very often I have seen new and beautiful looking images and passionate interpretation. Through years of his close interactions with chest physicians, this has only grown more accurate and meaningful in patient management. Bhavin teaches this subject with an intensity born out of years of hard work - often with an original an algorithmic approach perfected to mathematical accuracy. He has come to believe that in a majority of patients with interstitial lung pathology, a  histological diagnosis is possible from CTs and that this can go a long way in alleviating those suffering from this crippling disease. The book by Weber and Muller has been the standard textbook to refer to for HRCT of the chest. But then you don’t see cows and bulls on the streets of Boston or San Francisco. You need to have someone who has seen the disease patterns in the towns and cities of our country to tell you how to approach and interpret images of diseases that are often peculiar to our country. What you hold in your hands is not a textbook; in fact, this is not even a book… not even a booklet. This little compendium of about 130 pages is a Walkthrough - a walkthrough that holds your hand and takes you through .. the need for knowing certain points in the patient’s history, the importance of perfect technique and a ‘divide and rule’ formula to arrive at the final - often histological diagnosis in a vast number of patients with interstitial lung diseases. Of course, all of this starts with the understanding of what is normal as seen on HRCT of the lung. I will sum all this up with this.. Get a copy of this book for yourself ; reading it you will get intimately familiar with the philosophy and understanding of a radiologist’s  approach to interstitial lung diseases as seen in our country. We have often heard the phrase ‘pour your heart out’… In this little Walkthrough on CT of Interstitial Lung Diseases, Bhavin has done - just that. He has attempted to promote the need for and the ability to accurately interpret radiology of interstitial lung diseases by every radiologist and chest physician. Residents in training should start their journey with this little compendium. It now seems to have become a habit with Bhavin. This is another book of his that you can finish in two hours on a flight ... and be much wiser. I promise you that! Ravi Ramakantan MD, DMRD Director, Department of Radiology, Kokilaben Dhirubhai Ambani Hospital, Mumbai, India

C HA P TE R 01

ILDs - Definition and Classification

1.1

 Definition

Interstitial lung diseases (ILDs) are a heterogeneous group of disorders that affect the interstitium, which is the space between the capillary basement membranes. Inflammation, infiltration, and fibrosis can affect the interstitial and the alveolar spaces at the same time. A recent review on ILDs describes them as a “family of ILDs characterized by cellular proliferation, interstitial inflammation, fibrosis or a combination of such findings within the alveolar wall that is not due to infection or cancer”.1 There are multiple conditions that can cause ILDs. 1.2

  Classification and Distribution

A good way to look at the causes is given in Table 1 by Poletti et al.2 TABLE : 01

ILD etiologies.

Exposure Related

CTD

Occupational Environmental Avocational Medication

Sclerderma RA Sjogren’s PM/DM

Sarcoidosis

Idiopathic

Miscellaneous LCH LAM Neurofibromatosis Eosinophillic pneumonia

CTD: connective tissue disease, LCH: Langerhans cell histiocytosis, LAM:  lymphangioleiomyomatosis, DM-PM: dermatopolymyositis.

Though the number of etiologies can go up to 200 depending on the textbooks and references one reads, the vast majority of ILDs are caused by a few conditions, a knowledge of which helps in getting a good perspective on ILDs and the way to approach them (Figs. 1–3). Figures 1 through 3 show that idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), connective tissue disease (CTD) related ILDs that include non-specific interstitial pneumonia (NSIP) and organizing pneumonia (OP) patterns and sarcoidosis are responsible for 80–85% of all ILDs. All the others account for less than 15–20% of ILDs that one will see in practice. A structured approach to ILDs (Fig. 4), will help narrow down the differential diagnosis to one of these four buckets and help identify those rarer and less common conditions as and when they occur.

ILDs - Definition and Classification

2

he r 10 ILD % S

nioses Pneumoco 10%

Ot

Sa rco 20 idos % is

Diagnosis

Idiopathic pulmonary fibrosis 20%

CTD -ILD 20%

Chronic hypersensitivity pneumonitis 20%

FIGURE : 01 

Approximate distribution of ILDs - adapted from the article by Lederer et al.1

Diagnosis

.

n..

co

mo

Others 6%

eu

Pn

Sa rc o 8% ido sis

HP 47% CTD-ILD 22%

IPF 14%

FIGURE : 02 

Distribution of ILDs in India as per the Jaipur registry data.3

3

ILDs - Definition and Classification Diagnosis

Others 21% HP 38% Sarcoidosis 7% CTD-ILD 9% IPF 25%

FIGURE : 03

Distribution of ILDs in 796 patients seen in our center over 18 months (internal data and presentation).

Diagnose ILD If fibrotic, is it IPF or chronic HP or sarcoidosis

Broadly differentiate fibrotic from non-fibrotic

If non-fibrotic, is it diffuse cystic or not. If not, is it HP or sarcoid

Does the patient have a known condition that produces ILDs (Smoker/Drugs/CTD)

FIGURE : 04 

A flowchart for radiologists and physicians using the CT scan as the take-off point.

Radiologists should have some basic clinical information (Page 135) that allows them to differentiate among the various ILDs while physicians should take a thorough history, examine the patient, and then order the appropriate tests required to come to a working diagnosis that along with the CT picture will allow a definite diagnosis or a short differential to be reached. A multi-disciplinary meeting on the lines of a tumor board is often superior at reaching a diagnosis and management plan, than an individual radiologist, pathologist, or physician.4 The distribution of ILDs will vary depending on the region, the type of practice, whether institutional (public or private hospital) or a private clinic. For example, a doctor practicing in Dhanbad is likely to see a larger number of patients with silicosis and coal-worker’s pneumoconiosis than a physician in an urban setting as in Mumbai, where again depending on the area, hypersensitivity pneumonitis may turn out to be the commonest ILD. In a hospital that has a strong rheumatology unit, the number of CTD-ILDs will be higher than in a place which is a tertiary referral center for sarcoidosis.

ILDs - Definition and Classification

4

1.3

  Classification of IIPs

The idiopathic interstitial pneumonias (IIPs), of which IPF is the commonest entity, have been reclassified in 2013 by the ATS/ERS committee5 as follows (Fig. 5): Major • • • • • •

Idiopathic pulmonary fibrosis (IPF) Idiopathic nonspecific interstitial pneumonia with fibrosis (NSIP) Respiratory bronchiolities interstitial ILD (RB–ILD) Desquamative interstitial pneumonia (DIP) Cryptogenic organizing pneumonia (COP) Acute interstitial pneumonia (AIP)

Rare •

Idiopathic lymphocytic interstitial pneumonia (LIP)

•

Idiopathic pleuroparenchymal fibroelastosis (PPFE)

Unclassifiable FIGURE : 05 

The 2013 ATS/ERS classification of the idiopathic interstitial pneumonias (IIPs).

The major IIPs can be further classified as per their pathophysiology (Table 2). In the rest of the book, we will see how to diagnose and characterize the various ILDs.

TABLE : 02

The major IIPs classified as per their clinical presentation.

Category

Clinico-Radialogic-Pathologic Diagnoses

Associated Radiologic and/or Pathologic Morphologic Patterns

Chronic Fibrosing IP

Idiopathic pulmonary fibrosis

Usual interstitial pneumonia

Idiopathic nonspecific interstitial pneumonia

Nonspecific interstitial pneumonia

Smoking-related IP

Respiratory bronchiolitis ILD

Respiratory bronchiolitis

Desquamative interstitial pneumonia

Desquamative interstitial pneumonia

Acute/subacute IP

Cryptogenic organizing pneumonia

Organizing pneumonia

Acute interstitial pneumonia

Diffuse alveolar damage

ILDs - Definition and Classification

References 1.  Lederer DJ, Martinez FJ. Idiopathic pulmonary fibrosis. N Engl J Med 2018;378:1811–23. 2. Poletti V, Ravaglia C, Buccioli M, Tantalocco P, Piciucchi S, Dubini A, et al. Idiopathic pulmonary fibrosis: Diagnosis and prognostic evaluation. Respiration 2013;86:5–12. 3. Singh S, Collins BF, Sharma BB, Joshi JM, Talwar D, Katiyar S, et al. Interstitial lung disease in India. Results of a prospective registry. Am J Respir Crit Care Med 2017;195:801–13. 4. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2018;198:e44–e68. 5. Travis WD, Costabel U, Hansell DM, King TE, Lynch DA, Nicholson AG, et al. An Official American Thoracic Society/European Respiratory Society Statement: Update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias. Am J Respir Crit Care Med 2013;188:733–48.

5

2.1

C HA P TE R 02

Scan Parameters, Quality and Presentation

 Introduction

A good quality scan is paramount to reporting ILDs.

It is imperative to have great quality scans to diagnose and characterize the various interstitial lung diseases (ILDs). Sadly, a large number of scans done in many centers and hospitals are suboptimal and these lead to improper or erroneous diagnoses and eventually management. Scans without supervision or protocol invariably are blurred either due to poor breath-hold (Fig. 1) or because of improper end inspiration. Expiratory images lead to over-exaggeration of disease and can create problems where none exist (Fig. 2). They can be identified by the gradient of increasing lung density especially in the lower lobes (Fig. 3) and the posterior concavity of the trachea (Fig. 4). A

FIGURE : 01

B

Blurred image due to absence of suspended respiration (breathing artifact) (A) with the corresponding non-blurred image (B) in suspended respiration.

Scan Parameters, Quality and Presentation

7

A

B

FIGURE : 02

A

FIGURE : 03

Expiratory image (A) suggests the presence of possible ground glass attenuation. Inspiratory image (B) at the same level shows no pathology.

B

Expiratory image (A) shows a gradient of increasing whiteness from non-dependent (anterior) to dependent (posterior) (arrow). Inspiratory image (B) at the same level shows no pathology and complete absence of a gradient. The presence of this gradient helps differentiate the increased density simulating ground glass attenuation from true ground glass attenuation.

Scan Parameters, Quality and Presentation

8

A

B

FIGURE : 04

Inspiratory image (A) shows a normal ovoid / round trachea. Expiratory image at the same level (B) shows a posterior concave trachea (red arrow)

The ideal thin section CT parameters for ILDs are as follows1–3: •  Slice thickness: 1 mm or less • Gap: Overlapping or contiguous scans, preferably overlapping, reconstructed at 0.5 mm intervals • Scan method: Volumetric scan, obtained caudo-cranial or cranio-caudal. Volumetric scans allow for better understanding of the disease patterns, and the subtle changes during follow-up.2 Differentiation of honeycombing from traction bronchiolectasis is also enhanced by the ability to obtain sagittal and coronal images from the volumetric data. •  Breathing:   End-inspiratory in suspended respiration.  Expiratory scans are also needed in most situations, to look for areas of air-trapping (Fig. 5). These may be sequential or volumetric.  It is a good idea to give commands manually rather than using the automatic scanner “voice”, after training the patient on how to achieve end-inspiratory and end-expiratory states.  



•  KV: 120 kV. Lower kV (100 kV) in thin individuals. •  mAs: As low as possible, but not low-dose scans. • Prone images: One prone set, either sequential or volumetric is of great value in separating gravity dependent densities from disease (Fig. 6) and often is of help in those who are unable to manage end-inspiration (Fig. 7). Very experienced centers or radiologists may keep prone imaging optional, especially if non-dependent areas are involved (Fig. 8), but more and more, prone scanning has become part of the standard protocol for the clarity these bring to the evaluation of the lung bases and the subpleural interstitium (Fig. 7). They may be restricted to the lower lobes, if need be. • Films: If films are given, then they should be documented in a 12:1 format with proper window settings (Fig. 9) and the windowing should be such that the pleural rib interface is visualised (Fig. 10). • Soft copy: Soft copy images on a CD or an USB must be given to every patient to enable review and to allow comparisons in the future.

9

Scan Parameters, Quality and Presentation

A

FIGURE : 05

FIGURE : 06

B

Inspiratory image (A) shows a “mosaic” pattern with alternating “white” and “black” areas. The expiratory image (B) shows widespread patchy areas of lobular air trapping. The “white” areas show a normal gradient and represent normal lung parenchyma.

A

B

C

D

Supine image (A) shows dependent densities (red arrow) that disappear on the prone image (B) suggesting gravity dependent densities. In another patient with scleroderma, the supine image (C) shows densities (red arrow) that are persistent on the prone image (red arrow in D) suggesting scleroderma related ILD.

Scan Parameters, Quality and Presentation

10

A

B

E FIGURE : 07

D Prone imaging in a patient who is unable to manage end-inspiration. Axial supine expiratory image (A) shows reticular opacities that are difficult to further evaluate. Note the slit like trachea (B). The sagittal supine expiratory image (C) also shows “crowding” of the reticular opacities. The axial prone image (D) is also in partial inspiration, but shows the traction bronchiolectasis much better as does the sagittal prone image (E), allowing a confident diagnosis of a probable usual interstitial pneumonia (UIP) pattern, to be made.

A

FIGURE : 08

C

B

This patient has dependent disease in (A), but also reticular lesions in the non-dependent segments (red arrow in A). This itself may obviate the need for a prone image. The prone image (B) shows the reticular lesions in the right middle lobe (red arrow in B) to now be “dependent” but “real” - the reticular lesions in the posterior basal segment continue to be seen (blue arrow in B) and as in Fig. 7, are much better appreciated than in the supine image. This suggests that even in experienced centers, it may be a good idea to obtain prone images in every patient without triaging.

Scan Parameters, Quality and Presentation

FIGURE : 09

11

This is the format for filming. Not more than 12 images on 1. Single lung images, as used to be done in the past, are no longer required.

Scan Parameters, Quality and Presentation

12

A

B

FIGURE : 10

The window setting in A is suboptimal. It is too narrow as compared to the correct setting in B, where the lung-pleura-rib interface is well visualized (red arrow in B).

References 1. ACR–STR Practice Parameter for the Performance of High-Resolution Computed Tomography (HRCT) of the Lungs in Adults. https://www.acr.org/~/media/ACR/Documents/PGTS/guidelines/ HRCT_Lungs.pdf 2. Lynch DA, Sverzellati N, Travis WD, Brown KK, Colby TV, Galvin JR, et al. Diagnostic criteria for idiopathic pulmonary fibrosis: A Fleischner Society White Paper. Lancet Respir Med 2018;6:138–53. 3. Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, et al. Diagnosis of idiopathic pulmonary fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med 2018;198:e44–e68.

3.1

C HA P TE R 03

The Bare Essentials - ILD Signs

 Introduction

By definition, interstitial lung diseases (ILDs) are diffuse and bilateral. They may be asymmetric and heterogeneous on occasion. However, all bilateral, diffuse disease is not an ILD and an attempt should be made to rule out conditions like metastases, infection, emphysema, bronchiectasis and similar conditions that also present bilaterally. It is important to understand the various signs of ILDs seen on a CT scan. While traditional teaching focusses on an understanding of lesions in relation to the secondary pulmonary lobule, in practice, pattern recognition of the various ILD signs is perhaps a better way to learn and understand how to identify and then stratify the various ILDs. The basic signs of an ILD singly or in combination include the following: 1 2 3 4 5 6 7 8

Honeycombing (Fig. 1) Traction bronchiectasis/bronchiolectasis (Fig. 2) Reticular opacities (Fig. 3) Septal thickening (Fig. 4) Ground glass attenuation (Fig. 5) Consolidation (Fig. 6) Nodules (Fig. 7) Cystic interstitial lung disease (Fig. 8)

The Bare Essentials - ILD Signs

14

FIGURE : 01

A

FIGURE : 02

Honeycombing. Layered cysts stacked one upon the other with shared walls without subpleural sparing (arrows).

B

Traction bronchiectasis/bronchiolectasis. Traction bronchiectasis/bronchiolectasis occurs due to fibrosis. Proximal traction bronchiectasis (red arrow in A) and distal traction bronchiolectasis (red arrow in B).

The Bare Essentials - ILD Signs

15

FIGURE : 03

Reticular opacities. Reticular opacities (arrows) due to interlobular interstitial thickening, without significant traction bronchiectasis/bronchiolectasis and without honeycombing.

FIGURE : 04

Septal thickening. Septal thickening in the right lower lobe (arrow).This represents thickening of the interlobular septae and may occur due to fluid, cells or lymph.

16

The Bare Essentials - ILD Signs

FIGURE : 05

Ground glass attenuation. Ill-defined opacities (red arrow) not obscuring the underlying vessels defines the presence of ground-glass attenuation.

FIGURE : 06

Consolidation. Ill-defined consolidation obscuring underlying vessels with associated ground-glass attenuation as well.

The Bare Essentials - ILD Signs

A

17

B

FIGURE : 07

Nodules. Ill-defined bronchocentric (centrilobular) nodules (red arrow in A) and well-defined, discrete, perivascular (arrowhead) and fissural (arrow) nodules (B).

FIGURE : 08

Cystic interstitial lung disease. Well-defined cysts with walls, randomly distributed throughout the lung parenchyma.

The Bare Essentials - ILD Signs

18

3.2

  Fibrosing vs. Non-Fibrosing ILDs

ILDs can broadly be classified into fibrosing and non-fibrosing ILDs. With the new treatment options (pirfenidone and nintedanib) for idiopathic pulmonary fibrosis (IPF), the current work-up of all ILDs is essentially focussed on ensuring we do not miss a diagnosis of IPF and other potentially treatable conditions among both the fibrosing and especially the non-fibrosing ILDs. Fibrosing ILDs have the following features: 1 Honeycombing 2 Traction bronchiectasis/bronchiolectasis 3 Reticular opacities 4 Distortion of architecture 5 Volume loss Non-fibrosing ILDs are characterized by the following: 1 Ground glass attenuation and consolidation 2 Discrete and ill-defined nodules 3 Septal thickening Overlaps occur especially when there is ongoing inflammation and fibrosis at the same time or when there is an acute exacerbation of the disease on a background of fibrosis. Cystic interstitial lung diseases may or may not be associated with fibrosis. 3.2.1

  Fibrosing ILDs

The fibrosing ILD patterns are the following 1 Usual interstitial pneumonia (UIP) - IPF is the most common etiology 2 Non-specific interstitial pneumonia (NSIP) 3 Chronic hypersensitivity pneumonitis (chronic HP) 4 Chronic pulmonary sarcoidosis 5 The end-stage of any prior insult (e.g. acute lung injury, sarcoidosis, etc) 6 Pneumoconiosis 3.2.2

  Non-Fibrosing ILDs

The non-fibrosing ILDs include the following. Many of them may progress to a fibrosing ILD, too.  1 Hypersensitivity pneumonitis (HP)  2 Sarcoidosis  3 Desquamative interstitial pneumonitis (DIP)  4 Respiratory bronchiolitis - ILD (RB-ILD)  5 Lymphangitis carcinomatosis  6 Acute interstitial pneumonitis (AIP)  7 Organising pneumonia (OP)

The Bare Essentials - ILD Signs

 8 Pulmonary alveolar proteinosis  9 Cystic lung diseases 10 Pneumoconiosis There are also mimics that include 1 Pulmonary edema 2 Miliary tuberculosis

19

4.1

C HA P TE R 04

Fibrosing ILDs: IPF and non-IPF Conditions   Diagnosis of a Fibrosing ILD

As mentioned in Chapter 3, fibrosing ILDs are diagnosed by the presence of reticular opacities, honeycombing and/or traction bronchiectasis/bronchiolectasis, which may secondarily cause distortion of architecture and volume loss. 4.2

  Characterization

of a Fibrosing ILD

Once a fibrosing ILD is diagnosed, the next step is to differentiate between idiopathic pulmonary fibrosis (IPF) and a non-IPF etiology. To do this, it is important to understand the new Fleischner Society guidelines1 and the ATS/ERS criteria,2 both published in 2018 (Table 1). TABLE : 01

Distribution

Features

Fleischner Society1 and ARS/ETS2 criteria for the diagnosis of idiopathic pulmonary fibrosis (IPF) Typical UIP Pattern

Probable UIP Pattern

Indeterminate for UIP

Consistent with non-IPF Diagnosis1 Alternative Diagnosis2

Basal predominant

Basal predominant

Variable and diffuse1

Upper lung or mid lung

Subpleural predominant

Subpleural predominant

Subpleural and basal predominant2

Peribronchovascular / perilymphatic predominance with subpleural sparing

Heterogeneous

Heterogeneous

Honeycombing

Honeycombing is absent

Subtle reticulation, may have early GGO or distortion2

Cysts, marked mosaic attenuation, predominant ground glass, profuse micronodules, centrilobular nodules, nodules, consolidation2

Reticular pattern with peripheral traction bronchiectasis / bronchiolectasis

Reticular pattern with peripheral traction bronchiectasis / bronchiolectasis

CT features and/ or distribution that do not suggest any specific etiology (truly “indeterminate”)2

Lobular air trapping on expiration1

21

Fibrosing ILDs: IPF and non-IPF Conditions

Absence of features to suggest alternative diagnosis

Absence of features to suggest alternative diagnosis

Pleural plaques (asbestosis), dilated esophagus (scleroderma), distal clavicular erosions (RA), extensive nodal enlargement (consider other etiologies), pleural effusions, thickening (consider CTD / drugs)2

Evidence of fibrosis with some inconspicuous features suggestive of a non UIP pattern1

May have mild ground glass2 Where there is no reference, the findings are common. Findings or comments unique to only one of the guidelines are referenced. CTD: connective tissue disease, RA: rheumatoid arthritis, UIP: usual interstitial pneumonia, IPF: idiopathic pulmonary fibrosis.

4.3

  IPF

As seen in the new 2018 classification systems,1,2 the diagnosis of IPF is made, when either a typical UIP or a probable UIP pattern is diagnosed on a CT scan in the correct clinical context. Both, a typical UIP pattern and a probable UIP pattern are characterized by the presence of reticular opacities and traction bronchiectasis with subpleural basal involvement and the absence of any other finding. The only additional finding that distinguishes one from the other is the presence of honeycombing, which defines the typical UIP pattern and is absent in the probable UIP pattern (Fig. 1). Once either UIP pattern has been diagnosed, it is suggestive of IPF in the correct clinical setting and in the absence of a definite etiology. If the patient is young or there is a definite etiology such as connective tissue disease (CTD), asbestosis, etc then the UIP pattern, either typical or probable, would represent that etiology related UIP pattern, e.g. CTD ILD with a UIP pattern.

Fibrosing ILD Reticular opacities Traction Bronchiectasis/bronchiolectasis Subpleural basal predominant

+

Honeycombing

-

Typical UIP pattern

Probable UIP pattern

IPF if no etiology and correct age

Another etiology - UIP pattern. E.g., CTD, asbestos, etc

FIGURE : 01

Schematic for diagnosing a typical or probable UIP pattern and the implications.

Fibrosing ILDs: IPF and non-IPF Conditions

22

4.3.1   Traction

Bronchiectasis/Bronchiolectasis

Traction bronchiectasis/bronchiolectasis, is therefore, the defining feature of a fibrosing ILD and a UIP pattern, when present along with reticular opacities and a sub-pleural basal predominance and distribution (Fig. 2).

FIGURE : 02

Traction bronchiectasis (arrow in lingula) and traction bronchiolectasis (arrow in lower lobe) with reticular opacities in a 72-years old patient with a probable UIP pattern and IPF.

Traction bronchiectasis/bronchiolectasis is defined as irregular bronchial or bronchiolar dilatation due to retractile pulmonary fibrosis,3 basically presenting as cystic spaces without shared walls.4 When the distal bronchioles in the last 2 cm of the lungs are involved, the term traction bronchiolectasis is used. It is important to differentiate focal traction bronchiectasis that may occur following a focal insult like an infection (Fig. 3), from that occurring as part of an ILD.

Fibrosing ILDs: IPF and non-IPF Conditions

FIGURE : 03

23

Focal traction bronchiectasis (arrows) as part of post-infectious residual lesions in a patient treated for tuberculosis.

When we see a diffuse ILD with reticular opacities and traction bronchiectasis/bronchiolectasis and without honeycombing, if there is subpleural basal predominance, it implies a probable UIP pattern (Fig. 4).

A

B

C FIGURE : 04

(A-C): IPF. This patient has subpleural reticular opacities. The traction bronchiolectasis in the lower and upper lobes (arrows) confirms the presence of a fibrosing ILD and is suggestive of the probable UIP pattern.

Fibrosing ILDs: IPF and non-IPF Conditions

24

Since traction bronchiectasis / bronchiolectasis can occur as part of any fibrosing ILD, it is also seen in non-IPF or indeterminate for UIP (only in the Fleischner Society criteria) settings, which we will discuss a little later in the chapter (Fig. 5).

A FIGURE : 05

B (A,B): Traction bronchiectasis/bronchiolectasis (arrows) as a manifestation of fibrosis in a 79-years old woman with a non-IPF pattern (indeterminate for UIP as per Fleischner Society criteria), with upper and mid-zone predominance of reticular opacities and an axial distribution pattern. The exact diagnosis could not be established.

4.3.2   Honeycombing

If the traction bronchiectasis / bronchiolectasis is accompanied by honeycombing (Fig. 6),5 defined as the presence of subpleural cysts with shared walls that are stacked one upon the other, then it implies the typical UIP pattern, when there is subpleural basal predominance and no other finding.

Fibrosing ILDs: IPF and non-IPF Conditions

FIGURE : 06

25

Honeycombing. Layered cysts stacked one upon the other with shared walls without subpleural sparing (arrows). Note the traction bronchiectasis as well (arrowhead on the right). This implies the typical UIP pattern given the subpleural basal predominance and the absence of other findings.

In cases of doubt, these findings are often better appreciated on sagittal images (Fig. 7).

A

B FIGURE : 07

The axial image (A) shows honeycombing. However the sagittal image (B) shows the subpleural distribution better and in subtle cases can be of invaluable help.

Fibrosing ILDs: IPF and non-IPF Conditions

26

Apart from the ability to help with the diagnosis of IPF, the mere presence of honeycombing in the setting of any form of fibrosing ILD generally implies a poor prognosis and reduced survival equivalent to IPF, even if the eventual diagnosis is a non-IPF fibrosing ILD.6,7 It is therefore important to differentiate honeycombing from other mimics. Some authors8 also classify honeycombing into macrocystic, microcytic and mixed subtypes, which occur variably in different fibrosing ILDs, though in practice, sub-classifying patterns of honeycombing does not seem to make much of a difference. Mimics and Differentials 1. Bronchiectasis (Fig. 8): The “cysts” are dilated bronchi that extend from the hilum to the periphery, and perhaps the easiest to diagnose and differentiate from honeycombing. 2. Centrilobular emphysema (Fig. 9): The “cysts” are centrilobular lucencies without walls. 3. Cystic interstitial lung disease (Fig. 10): These are cysts with walls that are randomly distributed throughout the lung parenchyma. 4. Paraseptal cysts (Fig. 11): Peripheral single layer of cysts, typically in the upper lobes, usually seen in smokers or those with biomass fuel exposure. 5. Non-specific reparative cysts (Fig. 12): These are randomly seen, without areas of fibrosis, often nondependent in cases of post-adult respiratory distress syndrome (ARDS) fibrosis. 6. Traction bronchiectasis/bronchiolectasis (Fig. 13): It can sometimes be a challenge differentiating traction bronchiectasis / bronchiolectasis from honeycombing. It is important to develop this art because that implies the difference between a typical UIP and a probable UIP pattern, though more and more, since both UIP patterns imply IPF, it may not be so relevant as far as the diagnosis is concerned, though the prognosis may differ, the presence of honeycombing as noted earlier, implying a worse prognosis.

A FIGURE : 08

B Bronchiectasis. Axial (A) image shows typical honeycombing while the axial (B) image shows classic bronchiectasis (arrow).

Fibrosing ILDs: IPF and non-IPF Conditions

B

A FIGURE : 09

A FIGURE : 10

27

Centrilobular emphysema. Axial (A) image shows typical honeycombing while the axial (B) image shows classic centrilobular emphysema (arrows).

B Cystic interstitial lung disease. Axial (A) image shows typical honeycombing while the axial (B) image shows cystic interstitial lung disease (arrow).

Fibrosing ILDs: IPF and non-IPF Conditions

28

A

B

FIGURE : 11

A FIGURE : 12

Paraseptal cysts. Axial (A) image shows typical honeycombing while the axial (B) image shows paraseptal cysts/emphysema (arrow) in a smoker.

B Non-specific / reparative cysts. Axial (A) image shows typical honeycombing while the axial (B) image shows non-specific cysts without shared walls (arrow) within an area of fibrosis.

Fibrosing ILDs: IPF and non-IPF Conditions

29

A

B FIGURE : 13

C Traction bronchiectasis. Axial (A) image shows typical honeycombing while the axial (B) image shows dilated bronchioles of traction bronchiectasis simulating honeycombing. Sagittal (C) image shows the traction bronchiectasis (arrow) exquisitely.

4.3.3   Typical

and Probable UIP Patterns

4.3.3.1   Typical UIP Pattern

To reiterate, a typical UIP pattern needs the following criteria (Fig. 14). 1. 2. 3. 4.

Reticular opacities with traction bronchiectasis Honeycombing Subpleural basal predominance Absence of other findings

The typical UIP pattern (Fig. 14) however occurs in only 1/3rd of patients with IPF.9 Two-thirds of IPF patients have other patterns that include the “probable UIP”, the “indeterminate for UIP” and sometimes the non-IPF patterns as well.

Fibrosing ILDs: IPF and non-IPF Conditions

30

A

B

FIGURE : 14

4.3.3.2

Typical UIP pattern. Honeycombing is seen with lower lobe subpleural predominance, with some upper lobe involvement as well, without any other finding like ground-glass or air-trapping or nodules.

Probable UIP Pattern

In the absence of honeycombing a diagnosis of UIP/IPF can be made if the following findings are present, as initially described by Gruden et al5 under the heading “UIP without honeycombing” (Fig. 15). 1. 2. 3. 4. 5. 6. 7.

Reticular opacities Traction bronchiectasis Subpleural basal predominance Absence of other findings Heterogeneous appearance Some upper lobe involvement Non-segmental and crossing fissures

This “UIP without honeycombing” pattern, is pretty much now the “probable UIP pattern” as defined by the Fleischner Society and the ARS/ETS guidelines.

Fibrosing ILDs: IPF and non-IPF Conditions

31

A

B FIGURE : 15 UIP without honeycombing / Probable UIP pattern. Traction bronchiolectasis defines this pattern

with lower lobe subpleural predominance, non-segmental, crossing fissures with upper lobe involvement as well, with absence of honeycombing and other features.

The Fleischner Society and ARS/ETS guidelines for the “probable UIP pattern”1,2 (Fig. 16) are as follows: 1. Reticular opacities with traction bronchiectasis 2. Absent honeycombing 3. Absence of other findings 4. Basal, subpleural predominance. Often heterogeneous.

A

B FIGURE : 16

Probable UIP pattern. Axial images through the mid zone (A) and lower lobes (B) show reticular opacities (arrow in A) with traction bronchiolectasis (arrow in B) with absence of honeycombing and absence of other findings with subpleural, heterogeneous distribution.

Fibrosing ILDs: IPF and non-IPF Conditions

32

4.3.4

Idiopathic Pulmonary Fibrosis (IPF) and other UIP Etiologies

A typical or probable UIP pattern in the absence of an etiology and in the typical clinical setting is highly suggestive of IPF and obviates the need for a biopsy. 4.3.4.1

Clinical Diagnostic Criteria for IPF

The following criteria make a diagnosis of IPF likely4 1. Age > 60 2. Male 3. Former or current smoker 4. Absence of other clinical conditions or features that may cause a fibrosing ILD, such as those listed below. In addition, the recent 2018 guidelines2 also mention these criteria. 1. Moderate to severe traction bronchiectasis/bronchiolectasis (defined as mild traction bronchiectasis/ bronchiolectasis) in four or more lobes including the lingula as a lobe, or moderate to severe traction bronchiectasis/bronchiolectasis in two or more lobes) in a man over age 50 or in a woman over 60 2. Extensive reticulation (>30%) on HRCT and age >70. However, before we label someone as IPF, the following causes of a UIP pattern need to be excluded. 4.3.4.2

4.3.4.2.1

Other Conditions with the UIP Pattern, Typical or Probable Connective tissue diseases (CTDs)

All of the defined connective tissue disease can present with the UIP pattern, though of these, RA is the one disease where the UIP pattern is the commonest (Fig. 17). Scleroderma is another CTD that commonly presents with the UIP pattern (Fig. 18). A recent publication by Chung et al10 has described 3 signs that may help differentiate CTD-UIP from UIP-IPF. These are the: A. Anterior upper lobe sign (Fig. 19) B. Exuberant honeycombing sign (Fig. 19), and C. Straight-edge sign (Fig. 39) (see section on NSIP). Another recently described sign is the “four corners” sign (Fig. 20) specifically to differentiate scleroderma ILD from IPF, also described in Chapter 10.11 These need further validation.

Fibrosing ILDs: IPF and non-IPF Conditions

A

33

B

FIGURE : 17

RA-UIP. Axial images (A, B). This 65-years old smoker with RA shows a UIP pattern, though without significant honeycombing (arrow in A), with centrilobular emphysema (arrow in B).

FIGURE : 18

Scleroderma-UIP. Axial image shows classic honeycombing (arrow) in this 33-years old lady with scleroderma. Note the esophageal dilatation (arrowhead).

Fibrosing ILDs: IPF and non-IPF Conditions

34

A

B FIGURE : 19

Axial image (A) in a patient with RA UIP shows exuberant honeycombing (arrow). In another patient with scleroderma UIP (B), the anterior upper lobe (arrow) sign is seen.

Fibrosing ILDs: IPF and non-IPF Conditions

35

A

B FIGURE : 20

4.3.4.2.2

C Scleroderma ILD - UIP pattern showing the “four-corners” sign.20 Axial (A) image through the upper lobes shows anterolateral fibrosis and honeycombing (arrows), with typical posterosuperior lesions on a more inferior axial (B) image (arrowheads). The sagittal (C) image shows this well. There is more disease also seen more inferiorly, which is known in these patients.

Asbestosis

Asbestos exposure leads to the UIP pattern commonly (Fig 21).

A FIGURE : 21

B

Asbestosis-UIP. Axial contrast-enhanced image (A) shows the calcified pleural plaques in this 66-years old man who worked in a brake-lining factor with a UIP pattern without honeycombing but with extensive traction bronchiectasis (arrow in B).

Fibrosing ILDs: IPF and non-IPF Conditions

36

4.3.4.2.3

Familial & Syndromes

The UIP pattern occurs with familial IPF (FPF), but bizarre patterns are known in all familial and congenital conditions These present with the UIP pattern, typically in younger individuals, though unusual patterns are known.1 A. Dyskeratosis congenita (Fig. 22) B. Hermansky Pudlak syndrome (Fig. 23)

B

A FIGURE : 22

C Dyskeratosis congenita. This is a short telomere syndrome. This 32-years old man shows a UIP pattern with extensive disease on the sagittal (A) image. The photographs of the foot (B) and the tongue and face (C) show the typical features of this condition. This patient died of acute exacerbation 2 months after the CT scan. Courtesy: Dr. Jyotsna Joshi, Mumbai

Fibrosing ILDs: IPF and non-IPF Conditions

A FIGURE : 23

4.3.4.2.4

37

B Hermansky Pudlak syndrome. Sagittal (A) image shows a fibrosing ILD with honeycombing in the upper lobes and ground glass attenuation in the lower lobes. This would now be classified as a non-IPF pattern and unusual presentations like this are known.4 The photograph (B) shows the typical oculo-cutaneous albinism. With permission from the patient Courtesy: Dr. Vijai Kumar, Hyderabad

Combined Pulmonary Fibrosis with Emphysema (CPFE) (Fig. 24).12

In smokers, a combination of upper lobe emphysema and a lower lobe UIP pattern is often labelled, combined pulmonary fibrosis with emphysema (CPFE). These patients typically have different PFT patterns and a survival profile that is different from both emphysema as well as IPF.

Fibrosing ILDs: IPF and non-IPF Conditions

38

A

B

FIGURE : 24

CPFE. Axial (A) image through the upper lobe shows centrilobular emphysema (A), while a UIP pattern is seen in the axial (B) image through the lower lobe.

Hence, all of these conditions have to excluded before labelling a patient as IPF. Occasionally, a patient may present with an unusual finding that may suggest the likelihood of IPF over other conditions. One of those is diffuse pulmonary ossification (DPO) 4.3.4.3

Diffuse Pulmonary Ossification (Fig. 25)

Significant pulmonary ossification in the areas of fibrosis in a fibrosing ILD, best appreciated on the soft tissue images has been described to have a prevalence of around 18% and is supposed to be more common in IPF than other types of fibrosing ILDs.13 This finding however needs further validation.

Fibrosing ILDs: IPF and non-IPF Conditions

39

A

B

FIGURE : 25

4.4

Prone axial images through the lower lobes in lung (A) and soft tissue (B) windows of a fibrosing ILD that has a probable UIP pattern suggestive of IPF shows extensive diffuse pulmonary ossification (arrows) within the areas of fibrosis.

Consistent with Non-IPF Diagnosis / Alternative Diagnosis

If the fibrosing ILD is associated with atypical distribution or other associated findings, then the likelihood of a non-IPF etiology is high. The two commonest conditions are chronic hypersensitivity pneumonitis and chronic pulmonary sarcoidosis. These are the typical findings. 1. Upper lobe or mid-lung predominant fibrosis; peribronchovascular predominance with subpleural sparing 2. Any of the following • Predominant consolidation • Extensive pure ground-glass opacity • Extensive mosaic attenuation with air trapping

Fibrosing ILDs: IPF and non-IPF Conditions

40

• Diffuse nodules or • Cysts Chronic hypersensitivity pneumonitis (HP) (Figs. 26, 27) is perhaps the commonest entity that presents with this pattern,14 though in highly selected patient populations, IPF may still be a possibility.15 In the Indian setting, since HP is the commonest ILD seen in practice (Table 2), chronic HP should be strongly considered when atypical patterns are seen especially with upper lobe predominant fibrosis, ground-glass attenuation and patchy air-trapping (Figs. 26, 27). TABLE : 02

The Indian Registry Data16 Indian Registry Data

N = 1084

2012–2015

HRCT / MDT - 100% Bx-81 (7.43%)

Diagnosis

Number

Percentage

HP

513

47.3

IPF

148

13.7

CTD-ILD

151

13.9

92

8.5

NSIP Sarcoidosis

85

7.8

Pneumoconiosis

33

3.0

Others

62

5.7

Also see Chapter 1, Figure 3.

A

B

D C FIGURE : 26

Consistent with non-IPF. Chronic hypersensitivity pneumonitis (HP). Axial (A) image through the upper lobes shows bronchocentric fibrosis (arrow) with patchy air trapping (arrow) and mosaic attenuation on the expiratory image (B), with traction bronchiectasis and a mosaic pattern in the lower lobes (C). The sagittal image (D) shows the distribution of disease in the left lung with no significant zonal predominance.

Fibrosing ILDs: IPF and non-IPF Conditions

41

A

B

FIGURE : 27

Consistent with non-IPF. Chronic hypersensitivity pneumonitis (HP). The axial image in inspiration (A) shows a reticular pathology with mild traction bronchiolectasis that is difficult to further characterise. The expiratory image (B) shows classic mosaic attenuation with lobular areas of air trapping (arrow), findings that suggest an alternate diagnosis like chronic HP, which was then confirmed on clinical grounds.

Many other conditions can also present with “consistent with non-IPF” criteria including chronic sarcoidosis (Figs. 28, 29) and fibrosis following acute events such as adult respiratory distress syndrome (ARDS) (Fig. 30) and organising pneumonia (OP) (Fig. 31) as well as in patients with chronic pneumoconiosis such as silicosis (Fig. 32).

Fibrosing ILDs: IPF and non-IPF Conditions

42

A

Consistent with non-IPF. Chronic sarcoidosis. Axial (A) and coronal (B) images show a fibrosing ILD with traction bronchiectasis but with a peri-bronchovascular distribution (arrows) without zonal predominance in a patient known to have sarcoidosis for over 10 years.

FIGURE : 28

FIGURE : 29

B

A

B

C

D Consistent with non-IPF. Chronic sarcoidosis. 52-year old lady with gradually progressive breathlessness. Axial (A) image through the bases shows a fibrosing ILD with traction bronchiectasis and reticular opacities (arrow). The axial (B) image more superiorly shows an axial distribution pattern (arrow). The coronal (C, D) images show fissural nodules (arrow in C) and perivascular nodules (arrow in D). A trans-bronchial lung biopsy showed non-caseating granulomas helping to confirm the diagnosis.

43

Fibrosing ILDs: IPF and non-IPF Conditions

A

B

C FIGURE : 30

Consistent with non-IPF. Post adult respiratory distress syndrome (ARDS). Axial mid lobe (A), lower lobe (B) and coronal (C) images show a fibrosing ILD with traction bronchiectasis and honeycombing with anterior non-dependent lesions (arrow in A) and subpleural sparing (arrow in B), in a patient who recovered from an episode of ARDS 5 years prior.

A

C FIGURE : 31

B

Consistent with non-IPF. Post organising pneumonia (OP) fibrosis. Axial (A) and coronal (B) images show a fibrosing ILD with areas of ground glass and patchy mosaic and upper lobe predominance. This 46-years old man had one episode of organising pneumonia 20 years ago, as seen on an old axial CT (C), that was successfully treated at the time.

Fibrosing ILDs: IPF and non-IPF Conditions

44

A

C

B

FIGURE : 32

4.5

Consistent with non-IPF. Silicosis. Axial (A) and sagittal (B) images in this patient with silica exposure shows areas of mid-lung fibrosis (arrows), which is disordered and patchy. Note the nodes with egg-shell calcification (arrows) in the soft tissue axial image (C).

Indeterminate for UIP

This is a new bucket and the one bucket where there are are differences in the definition given by both societies (Table 1). The ATS/ERS2 criteria (Fig. 33) mention 1. Subtle reticulation with perhaps some ground glass (early UIP pattern) 2. Subpleural basal predominance 3. CT features and/or distribution that do not suggest any specific diagnosis (“truly indeterminate”) The Fleischner Society1 criteria (Fig. 34) mention 1. Variable or diffuse distribution 2. Evidence of fibrosis with some inconspicuous features suggestive of a non-IPF pattern These are essentially confusing terms by themselves.

Fibrosing ILDs: IPF and non-IPF Conditions

45

A

B FIGURE : 33

C Indeterminate for UIP. Axial supine (A) and prone (B) and sagittal (C) images show subtle reticular opacities with basal subpleural predominance (arrows), but without traction bronchiolectasis or any other sign. This is a 72-year-old lady with minimal symptoms.

A

B FIGURE : 34

Indeterminate for UIP. Axial (A) and sagittal (B) images show a diffuse ILD without zonal predominance with fibrosis (extensive traction bronchiectasis) without honeycombing with subpleural and central distribution. Ground-glass areas are seen in the upper lobes. Based on her earlier scan and clinical features, a multi-disciplinary meeting labeled her as idiopathic pulmonary fibrosis, since she was not in a situation to undergo a biopsy.However, the findings are essentially “indeterminate”.

46

Fibrosing ILDs: IPF and non-IPF Conditions

In practice though, the best use of the term “indeterminate for UIP” is in truly indeterminate situations, where the radiologist or physician or even the multi-disciplinary meeting actually says “I/we don’t know”. In most instances, it also means that the patient will likely require a biopsy (Fig. 35).

A

B FIGURE : 35

Indeterminate for UIP. Axial images show a reticular pattern (arrow in A) without significant traction bronchiolectasis in this 61 years old patient with a gradually progressive 2-years history of breathlessness and other other supportive clinical findings. Note the subtle groundglass (arrow in B). A VATS guided lung biopsy showed hypersensitivity pneumonitis.

Some of these patients, however if not biopsied, on follow-up may demonstrate a transition to a typical UIP or probable UIP pattern (Figs. 36, 37).

Fibrosing ILDs: IPF and non-IPF Conditions

D

C

B

A

47

FIGURE : 36

Indeterminate for UIP to IPF over 4 years. Axial (A-D) images from Mar 2013 (A), Sep 2014 (B), Jan 2016 (C) and Oct 2017 (D). At first presentation in Mar 2013, reasonably symmetric reticular opacities are seen that may now retrospectively suggest an “indeterminate for UIP pattern”. In 2013, it was labeled as “possible UIP, but cannot be differentiated from NSIP”, in this 46-years old man with no history of CTD or any other systemic abnormality. There is progressive increase in the fibrosis, till in Oct 2017, there is distinct honeycombing and traction bronchiectasis without subpleural sparing that suggests typical UIP / IPF.

FIGURE : 37

Indeterminate for UIP to IPF over 12 years. In 2006, there are subtle reticular opacities. At that time, this 62-years old lady was labeled to have a non-specific interstitial pneumonia (NSIP) pattern. Today, in the absence of CTD and other etiologies, we would call it “indeterminate for UIP”. Seven years later, in 2013, traction bronchiolectasis can be seen in the lung bases with progression, suggesting a “probable UIP pattern” as per the new guidelines. Five more years later, in 2018, there is frank honeycombing in the lung bases, suggesting a typical UIP pattern and likely IPF in this now 74-years old lady.

48

Fibrosing ILDs: IPF and non-IPF Conditions

4.6

Non-Specific Interstitial Pneumonia (NSIP) Pattern

The NSIP pattern is a distinct clinicopathologic entity17 that may occur both as an idiopathic condition or as part of other conditions like connective tissue and collagen vascular diseases. It is often described to have cellular (more ground-glass areas) and fibrotic patterns and it is mainly the fibrotic pattern that causes diagnostic challenges with IPF (Fig. 38), especially the probable UIP pattern, predominantly in settings where an obvious etiology like connective tissue disease has not yet been established and where typical subpleural sparing is not appreciated.

A

B FIGURE : 38

NSIP. Axial (A) and sagittal (B) images. This is a fibrosing ILD with traction bronchiectasis. However note the subpleural sparing (arrows in A and B) and ground-glass attenuation (arrowhead in B), typical of NSIP.

NSIP typically occurs in younger patients (60), the more UIP is likely compared to NSIP. Follow-up also helps if a biopsy has not been done. In NSIP, the pathology can regress especially if there is a significant cellular, inflammatory component that responds to treatment (Fig. 41). UIP is not known to regress. Also in some patients with lung-dominant CTD, the CTD manifests a few years later, thus confirming the NSIP diagnosis, especially if a biopsy has not been performed.

Fibrosing ILDs: IPF and non-IPF Conditions

50

A

FIGURE : 41

B

NSIP over two years. Axial image (A) shows a fibrotic ILD with traction bronchiolectasis (arrowhead) with ground-glass attenuation in a patient with scleroderma. Two years later the axial image (B) shows regression of the ground-glass, which was likely the cellular component with a stable fibrotic component.

Interstitial Pneumonia with Auto-immune Features Often in younger patients, the CT picture or the biopsy may suggest an NSIP pattern with a clinical or laboratory hint of a possible auto-immune condition, though a definite diagnosis of a CTD is not possible. These patients are now, from a research perspective, labelled to have interstitial pneumonia with auto-immune features (IPAF).22 This replaces the earlier terms such as lung-dominant CTD, undifferentiated CTD, etc. 4.7

IPF and Other Fibrosing ILD Complications

Patients with IPF and other similar fibrosing ILDs are at risk for many complications that include 1. Acute exacerbation 2. Infection 3. Cancer 4.7.1

Acute exacerbation (Fig. 42)

Patients with acute exacerbation present clinically with increasing dyspnea, acute or subacute in onset. New GGA or GGA superimposed on the fibrosis suggests acute exacerbation. These may be symmetric or asymmetric. Extent, distribution and pattern of disease have a bearing on prognosis, though mortality often approaches 50%.23

Fibrosing ILDs: IPF and non-IPF Conditions

A FIGURE : 42

4.7.2

51

B Acute exacerbation. Sagittal (A) and axial (B) images in a patient with a classic UIP pattern show patchy areas of GGA (arrows) suggestive of acute exacerbation in the appropriate clinical setting.

Infection

Many patients present with frank areas of consolidation or focal opacities. Typically when lesions or areas that are denser than just ground glass are seen in acute exacerbation, they suggest the presence of superimposed infection (Fig. 43). In a country like India, the possibility of tuberculosis (Fig. 44) should always be considered. Rarely, one of the honeycomb cysts may get affected by chronic cavitary pulmonary aspergillosis (Fig. 45).24

A

B FIGURE : 43

Infection. Axial images through the upper (A) and lower (B) lobes in a patient with a classic UIP pattern and clinical findings of acute exacerbation show denser opacities and areas of pneumonic consolidation (arrows) that suggest superimposed infection.

Fibrosing ILDs: IPF and non-IPF Conditions

52

FIGURE : 44

Tuberculosis. Axial image shows a focal opacity in the left lower lobe in this patient with IPF. A CT guided biopsy confirmed the diagnosis of tuberculosis.

A

B

FIGURE : 45

4.7.3

Chronic cavitary pulmonary aspergillosis (CCPA) Axial image shows a focal opacity in the left lower lobe in this patient with IPF. A CT guided biopsy confirmed the diagnosis of CCPA.

Lung cancer (Figs. 46, 47).

There is an increased incidence of malignancy in patients with IPF, with a typical incidence of 10%, diagnosed either at presentation (Fig. 46) or on follow-up (Fig. 47), within the first three years.25 These typically present as small new nodules or focal opacities on a background of fibrosis. On follow-up scans they appear as small round to ovoid new nodules at the interface between fibrotic cysts and normal lung or subpleurally amidst the fibrotic/honeycomb cysts.26

Fibrosing ILDs: IPF and non-IPF Conditions

53

A biopsy typically then confirms the diagnosis. All attempts should be made in patients on regular follow-up to pick-up subtle changes in density that would allow these lesions to be picked up earlier.

A FIGURE : 46

B Lung cancer. Axial images 18 months apart show the development of a new nodule (arrow in B) in the anterior segment of the left upper lobe, which on biopsy was an adenocarcinoma.

A FIGURE : 47

B

Lung cancer. Axial (A) image shows a focal subsolid opacity (arrow) in the superior segment of the right lower lobe in a patient with idiopathic pulmonary fibrosis, the fibrosis well seen in the sagittal (B) image as a probable UIP pattern. Biopsy showed invasive mucinous adenocarcinoma with lepidic spread.

Fibrosing ILDs: IPF and non-IPF Conditions

54

4.8

Summary

The approach to a fibrosing ILD can be summarized in a simpler manner (Fig. 48). Fibrosing ILD

IPF

Non-IPF

Indeterminate

Chronic HP Chronic Sarcoidosis Others (less common)

Likely will need a bx

Typical or probable UIP pattern with a typical clinical scenario, after ruling out a possible etiology for these patterns, such as CTD, asbestosis, etc

FIGURE : 48

Simplified understanding of the approach to a fibrosing ILD.

When we see a fibrosing ILD, we have to essentially figure out whether this is 1. IPF, 2. Non-IPF, or 3. Indeterminate IPF is diagnosed when we see a “typical” or “probable” UIP pattern in a patient with a typical clinical profile, above the age of 60, preferably 70, male and with a smoking history, with no other etiologic factors that would account for the cause of the UIP pattern. In younger patients (