Table Of ContentClinical Handbook of
Interstitial Lung Disease
Clinical Handbook of
Interstitial Lung Disease
Edited by
Muhunthan Thillai
Cambridge Interstitial Lung Disease Unit
Royal Papworth Hospital, Cambridge, United Kingdom
David R Moller
Department of Medicine, Division of Pulmonary and
Critical Care Medicine, Johns Hopkins University School
of Medicine, Baltimore, Maryland, USA
Keith C Meyer
Department of Medicine, Division of Allergy, Pulmonary,
Critical Care and Sleep Medicine, University of Wisconsin School
of Medicine and Public Health, Madison, Wisconsin, USA
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We dedicate this book to our patients and research volunteers for their courage and support,
to our families and to our mentors.
Muhunthan Thillai dedicates this book to his mentor Donald Mitchell, to his wife Abi and to his family
Raj, Anushya, Kiruthikah, Krishnan and Ambika.
David Moller dedicates this book with love, to his wife Teresa and our family Stephanie, Christopher,
Ryan, Kristen and Avery.
Keith Meyer especially dedicates this book to all the patients who have trusted his guidance and given him
important lessons about coping with interstitial lung disease and to his wife, Emily Auerbach, and his
children and grandchildren.
Contents
Foreword ix
Contributors xi
Introduction xv
1 An overview of the classification and diagnosis of interstitial lung disease 1
Keith C Meyer
2 Histopathology of interstitial lung disease: A pattern-based approach 11
Angela M Takano, Junya Fukuoka and Kevin O Leslie
3 Using thoracic imaging to diagnose ILD 39
Maria Daniela Martin and Jeffrey P Kanne
4 Genetics and genomics of idiopathic pulmonary fibrosis 49
Susan K Mathai and David A Schwartz
5 Clinical evaluation of the patient with suspected ILD 65
Kaïssa de Boer and Joyce S Lee
6 Role of invasive testing in ILD diagnosis 83
J Scott Ferguson and Keith C Meyer
7 General principles of ILD diagnosis and management 95
Melissa Wickremasinghe, Richard J Hewitt and Athol Wells
8 Idiopathic pulmonary fibrosis: Epidemiology, natural history and pathophysiology 113
Zulma Yunt, Jeffrey J Swigris and Amy L Olson
9 Idiopathic pulmonary fibrosis: How should a confident diagnosis be made? 135
Bridget F Collins and Ganesh Raghu
10 Management of idiopathic pulmonary fibrosis 149
Damian AD Bruce-Hickman, Helen Garthwaite, Melissa Heightman and Bibek Gooptu
11 Hypersensitivity pneumonitis 189
Christine Fiddler and Helen Parfrey
12 Idiopathic interstitial pneumonias other than idiopathic pulmonary fibrosis 209
Toby M Maher
13 Eosinophilic interstitial lung disorders 221
Vincent Cottin and Claudia Valenzuela
14 Interstitial lung disease associated with connective tissue disorders 237
Deborah Assayag and Aryeh Fischer
15 Pulmonary sarcoidosis 257
David R Moller and Ling-Pei Ho
16 Sarcoidosis extra-pulmonary manifestations 271
Dominique Valeyre, Hilario Nunes, Florence Jeny, Matthieu Mahévas and Marc A Judson
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viii Contents
17 Smoking and interstitial lung disease 289
Joshua J Solomon and Kevin K Brown
18 Drug-induced and iatrogenic interstitial lung disease 311
Philippe Camus and Philippe Bonniaud
19 Occupation-related ILD 329
Traci Adams, Annyce S Mayer, Craig Glazer and Lisa A Maier
20 Pulmonary vasculitis and alveolar haemorrhage syndromes 345
Rebecca C Keith and Stephen K Frankel
21 Lymphangioleiomyomatosis and other cystic interstitial lung diseases 361
Amanda T Goodwin and William YC Chang
22 Pulmonary alveolar proteinosis 379
Cliff Morgan
23 Rare forms of interstitial lung disease 391
Jay H Ryu
24 Childhood ILD 409
Andrew Bush
25 Understanding the role of co-morbidities in interstitial lung diseases 429
Adrian Shifren, Tonya Russell, Adam L Anderson and Steven D Nathan
26 Lung transplantation for ILD 451
Henry Yung and Jasvir S Parmar
27 Diagnosis and management of critical illness in patients with interstitial lung disease 493
Teng Moua
Index 511
Foreword
The Clinical Handbook of Interstitial Lung Disease, patterns. Throughout the book, the pathogenetic
edited by Drs. Thillai, Moller, and Meyer, provides mechanisms are discussed in detail, including
a comprehensive, thoughtful, and in depth review genetic associations and polymorphisms and
of the complexity of interstitial lung disease (ILD), external factors (inhaled irritants or allergens,
with a broad perspective provided by 60 authors smoking, environmental factors) that may influ-
with expertise in ILD. The book is extensively ref- ence clinical expression and course of ILD. Over
erenced, and provides insights suited not only for the past 30 years, several genetic mutations have
trainees but for clinicians and academicians at all been implicated in familial and sporadic ILDs.
levels with an interest in ILD. Initial epidemiological studies identified muta-
More than 200 ILDs have been identified, and tions in surfactant C and A proteins, and sub-
a logical approach requires the analysis of clinical, sequent studies identified a variety of genetic
radiographic, and histological patterns that may abnormalities (e.g., telomerase mutations, poly-
establish a precise and definitive diagnosis. The morphisms of MUC5B prometer gene, etc.).
first few chapters provide an overview of the evolv- Differences in the function of specific genetic loci
ing classification schema of ILD, the disparate affecting host defense, cell adhesion, and DNA
histological patterns of ILD, the use of thoracic may be central to the pathogenesis and clinical
imaging [particularly high-resolution thin-sec- expression of idiopathic pulmonary fibrosis (IPF)
tion computed tomographic scanning (HRCT)] to and other ILDs. Investigations using peripheral
diagnose and follow ILDs, and clinical evaluation blood mononuclear cell (PBMC) or alveolar epi-
of patients with suspected ILD. These initial chap- thelial cells in IPF and other ILDs suggest that
ters, as well as those that follow, are replete with specific genetic profiles may be critical to the evo-
superb color photomicrographs and HRCT scans lution of the disease process, resulting in a rapid
to illustrate the salient findings of these various or slow disease progression, with associated dif-
ILDs. The major patterns (both radiographic and ferences in survival. A better understanding of
histologic) are discussed, including: acute and genetic risk factors for IPF and other ILDs may
chronic lung injury; airway-centered (bronchiolo- lead to improved phenotyping of disease and more
centric); alveolar filling (e.g., alveolar hemorrhage, targeted therapies.
pulmonary alveolar proteinosis, organising pneu- Clinical approach to ILD includes careful occu-
monia); nodular patterns (e.g., sarcoidosis, granu- pational history, exposures (drugs, inhaled anti-
lomatosis with polyangiitis, silicosis, Langerhans gens), demographics (age, gender), in addition to
cell histiocytosis (LCH), infections, malignancy); physical exam and radiographic tests. Blood tests
cystic patterns [(e.g., lymphangioleiomyomatosis may be critical to identify specific causes of ILD
(LAM), LCH, lymphocytic interstitial pneumonia such as connective tissue disease (CTD) or hyper-
(LIP)]; and mixed patterns. Further, the salient sensitivity pneumonia (HP). The role of invasive
features of the idiopathic interstitial pneumonias techniques including bronchoscopy with bron-
(IIPs) are illustrated and discussed, with in-depth choalveolar lavage (BAL), endobronchial ultra-
discussion of usual interstitial pneumonia (UIP) sound-guided biopsies (EBUS), and surgical lung
and nonspecific interstitial pneumonia (NSIP) biopsy are discussed. Several authors emphasize the
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