Respiratory Medicine (2013)

(1)

handbook

Respiratory

Medicine

2nd Edition

Editors

Paolo Palange

Anita K. Simonds

handbook

R

espir

atory Medicine

The European Respiratory Society (ERS)

Handbook of Respiratory Medicine, now in

its second edition, is a concise, compact and

easy-to-read guide to each of the key areas in

respiratory medicine. Its 18 chapters, written

by clinicians and researchers at the forefront

of the field, explain the structure and function

of the respiratory system, its disorders and

how to treat them.

The Handbook is a must-have for anyone

who intends to remain up to date in the

field, and to have within arm’s reach a

reference that covers everything from the

basics to the latest developments in

respiratory medicine.

Paolo Palange is head of the Pulmonary

Function and Research Unit in the

Department of Clinical Medicine at the

Sapienza University of Rome, and is the

HERMES Director.

Anita Simonds is Consultant in Respiratory &

Sleep Medicine at NIHR Respiratory

Biomedical Research Unit,Royal Brompton &

Harefield NHS Trust, London,

and is the ERS School Chair.

(2)

Respiratory

Medicine

2nd Edition

Editors

Paolo Palange

and Anita K. Simonds

(3)

PUBLISHED BY

THE EUROPEAN RESPIRATORY SOCIETY

CHIEF EDITORS

Paolo Palange (Rome, Italy)

Anita K. Simonds (London, UK)

ERS STAFF

Alice Bartlett, Matt Broadhead, Neil Bullen, Alyson Cann, Jonathan Hansen,

Sarah Hill, Fiona Marks, Elin Reeves, David Sadler, Claire Turner

© 2013 European Respiratory Society

Design by Claire Turner and Lee Dodd, ERS

Typeset in China by Charlesworth Group

Printed by Charlesworth Press

All material is copyright to the European Respiratory Society.

It may not be reproduced in any way including electronically without the express

permission of the society.

CONTACT, PERMISSIONS AND SALES REQUESTS:

European Respiratory Society, 442 Glossop Road, Sheffield, S10 2PX, UK

Tel: +44 114 2672860 Fax: +44 114 2665064 e-mail: [email protected]

(4)

Contributors

xiv

Preface xxix

Get more from this Handbook

xxx

List of abbreviations

xxxi

Chapter 1 – Structure and function of the respiratory system

Genetics

1 Gernot Zissel

Molecular biology of the lung

7 Melanie Königshoff and Oliver Eickelberg

Anatomy of the respiratory system

13 Pallav L. Shah

Respiratory physiology

18 Susan A. Ward

Cytology of the lung

29 Venerino Poletti, Giovanni Poletti, Marco Chilosi and Bruno Murer

Immunology and defence mechanisms

39 Bruno Balbi, Davide Vallese, Alessandro Pitruzzella, Chiara Vicari and

Antonino Di Stefano

Chapter 2 – Signs and symptoms

Cough and sputum

45 Alyn H. Morice

Dyspnoea 51

(5)

Chest pain

59 Matthew Hind

Physical examination

61 Martyn R. Partridge

Chapter 3 – Pulmonary function testing

Static and dynamic lung volumes

66 Riccardo Pellegrino and Andrea Antonelli

Respiratory mechanics

72 Daniel Navajas and Ramon Farré

Gas transfer: T

LCO

_{and T}

LNO 77

J. Mike Hughes

Control of ventilation

82 Brian J. Whipp and Susan A. Ward

Arterial blood gas assessment

87 Paolo Palange, Alessandro Maria Ferazza and Josep Roca

Exercise testing

94 Paolo Palange and Paolo Onorati

Bronchial provocation testing

99 Kai-Håkon Carlsen

Sputum and exhaled breath analysis

103 Patrizia Pignatti, Andrea Zanini, Sabrina Della Patrona, Federico Gumiero,

Francesca Cherubino and Antonio Spanevello

(6)

Chapter 4 – Other diagnostic tests

Bronchoscopy 109

Pallav L. Shah

Bronchoalveolar lavage

114 Patricia L. Haslam

Fine-needle biopsy

122 Stefano Gasparini

Medical thoracoscopy/pleuroscopy

124 Robert Loddenkemper

Thoracentesis 128

Emilio Canalis and Mari Carmen Gilavert

Interventional pulmonology

131 Marc Noppen

Chapter 5 – Lung imaging

Chest X-ray and fluoroscopy

136 Walter De Wever

Lung CT and MRI

141 Johny A. Verschakelen

HRCT of the chest

146 Johny A. Verschakelen

Nuclear medicine of the lung

151

(7)

Transthoracic ultrasound

154 Florin von Groote-Bidlingmaier, Coenraad F.N. Koegelenberg and

Chris T. Bolliger

Chapter 6 – Lung injury and respiratory failure

Lung injury

159 Bernrd Schönhofer and Christian Karagiannidis

Respiratory failure

162 Nicolino Ambrosino and Fabio Guarracino

NIV in acute respiratory failure

166 Anita K. Simonds

Acute oxygen therapy

171 Anita K. Simonds

Assessment for anaesthesia/surgery

174 Macé M. Schuurmans, Chris T. Bolliger and Annette Boehler

Long-term ventilation

178 Anita K. Simonds

Chapter 7 – Respiratory Infections

Microbiology testing and interpretation

183 Magareta Ieven

Upper respiratory tract infections

190 Gernot Rohde

Infective exacerbations of COPD

194

(8)

Pneumonia 199

Mark Woodhead

Hospital-acquired pneumonia

203 Francesco Blasi

Opportunistic infections in the immunocompromised host

207 Thomas Fuehner, Mark Greer, Jens Gottlieb and Tobias Welte

Pneumonia in the immunocompromised host

211 Santiago Ewig

Pleural infection and lung abscess

215 Amelia Clive, Clare Hooper and Nick Maskell

Influenza, pandemics and SARS

222 Wei Shen Lim

Chapter 8 – Tuberculosis

Pulmonary tuberculosis

229 Giovanni Sotigu and Giovanni Battista Migliori

Extrapulmonary tuberculosis

241 Aik Bossink

Tuberculosis in the immunocompromised host

245 Martina Sester

Latent tuberculosis

248 Jean-Pierre Zellweger

Nontuberculous mycobacterial diseases

251

(9)

Laboratory diagnosis of mycobacterial infections

255 Claudio Piersimoni

Chapter 9 – Airway diseases

Chronic rhinitis

261 Arnaud Bourdin and Pascal Chanez

Asthma 264

Bianca Beghé, Leonardo M. Fabbri and Paul O’Byrne

Vocal cord dysfunction

274 Adel H. Mansur

Bronchitis 279

Gernot Rohde

Gastro-oesophageal reflux

281 Lieven Dupont

COPD and emphysema

287 Eleni G. Tzortaki and Nikolaos M. Siafakas

Exacerbations of COPD

293 Alexander J. Mackay and Jadwiga A. Wedzicha

Extrapulmonary effects of COPD

300 Yvonne Nussbaumer-Ochsner and Klaus F. Rabe

Pharmacology of asthma and COPD

304 Peter J. Barnes

Bronchiectasis 311

(10)

Cystic fibrosis

315 Andrew Bush and Jane C. Davies

Chapter 10 – Occupational and environmental lung

Work-related and occupational asthma

327 Eleftherios Zervas and Mina Gaga

Respiratory diseases caused by acute inhalation of gases, vapours and dusts

332 Benoit Nemery

Hypersensitivity pneumonitis

337 Torben Sigsgaard and Anna Rask-Andersen

Pneumoconiosis 341

Allan F. Henderson

Indoor and outdoor pollution

345 Giovanni Viegi, Marzia Simoni, Sara Maio, Sonia Cerrai, Giuseppe Sarno and

Sandra Baldacci

Smoking-related diseases

352 Yves Martinet and Nathalie Wirth

Treatment of tobacco dependence

357 Luke Clancy and Zubair Kabir

High-altitude disease

361 Yvonne Nussbaumer-Ochsner and Konrad E. Bloch

Diving-related diseases

366

(11)

Radiation-induced lung disease

369 Robert P. Coppes and Peter van Luijk

Chapter 11 – Interstitial lung disease

HRCT in the diagnosis of interstitial lung diseases

371 Giovanni Della Casa, Stefania Cerri, Paolo Spagnolo, Pietro Torricelli and

Luca Richeldi

Sarcoidosis 382

Ulrich Costabel

Idiopathic interstitial pneumonias

386 Dario Olivieri, Sara Chiesa and Panagiota Tzani

Eosinophilic diseases

395 Andrew Menzies-Gow

Drug-induced respiratory disease

399 Philippe Camus and Philippe Bonniaud

Chapter 12 – Pulmonary vascular diseases

Pulmonary embolism

411 Massimo Pistolesi

Pulmonary vasculitis

417 Georgios Margaritopoulos and Athol U. Wells

Pulmonary hypertension

422

(12)

Chapter 13 – Pleural, mediastinal and chest wall diseases

Pleural effusion

428 Robert Loddenkemper

Pneumothorax and pneumomediastinum

432 Paul Schneider

Mediastinitis 439

Pierre-Emmanuel Falcoz, Nicola Santelmo and Gilbert Massard

Neuromuscular disorders

443 Andrea Vianello

Chest wall disorders

448 Pierre-Emmanuel Falcoz, Nicola Santelmo and Gilbert Massard

Chapter 14 – Thoracic tumours

Pathology and molecular biology of lung cancer

451 Sylvie Lantuéjoul, Lénaïg Mescam-Mancini, Barbara Burroni and

Anne McLeer-Florin

Lung cancer: diagnosis and staging

455 Johan Vansteenkiste, Sofie Derijcke and Inge Hantson

Chemotherapy and molecular biological therapy

460 Amanda Tufman and Rudolf M. Huber

Surgical treatment for lung cancer

466 Gilbert Massard, Nicola Santelmo and Pierre-Emmanuel Falcoz

Radiotherapy for lung cancer

472

(13)

Metastatic tumours

477 Elisabeth Quoix

Pleural and chest wall tumours

482 Arnaud Scherpereel

Mediastinal tumours

489 Paul E. Van Schil, Patrick Lauwers and Jeroen M. Hendriks

Chapter 15 – Sleep-related disorders

Obstructive sleep apnoea/hypopnoea syndrome

491 Wilfried De Backer

Central sleep apnoea

498 Konrad E. Bloch and Thomas Brack

Hypoventilation syndromes

503 Jean-François Muir

Chapter 16 – Immunodeficiency/orphan lung disorders

Pulmonary diseases in primary immunodeficiency syndromes

509 Federica Pulvirenti, Cinzia Milito, Maria Anna Digiulio and Isabella Quinti

HIV-related disease

513 Marc C.I. Lipman and Rob F. Miller

Graft versus host diseases

521 Federica Pulvirenti, Cinzia Milito, Maria Anna Digiulio and Isabella Quinti

Amyloidosis 526

(14)

Pulmonary alveolar proteinosis

529 Maurizio Luisetti

Adult pulmonary Langerhans’ cell histiocytosis

532 Vincent Cottin, Romain Lazor and Jean-François Cordier

Lymphangioleiomyomatosis 535

Vincent Cottin, Romain Lazor and Jean-François Cordier

Chapter 17 – Pulmonary rehabilitation

Respiratory physiotherapy

539 Julia Bott

Pulmonary rehabilitation

543 Thierry Troosters, Hans Van Remoortel, Daniel Langer, Marc Decramer and

Rik Gosselink

Palliative care

552 Sylvia Hartl

Chapter 18 - Epidemiology

Measuring the occurrence and causation of respiratory diseases

554 Riccardo Pistelli and Isabella Annesi-Maesano

(15)

xiv

Contributors

Nicolino Ambrosino

Cardio-Thoracic Dept

University Hospital

Pisa, Italy

Isabella Annesi-Maesano

Université Pierre et Marie Curie –

Paris 6

Medical School Saint-Antoine

UMR S 707: EPAR

Paris, France

Andrea Antonelli

Allergologia e Fisiopatologia

Respiratoria, ASO S. Croce e Carle

Cuneo, Italy

Bruno Balbi

Fondazione Salvatore Maugeri

IRCCS

Veruno, Italy

Sandra Baldacci

Pulmonary Environmental

Epidemiology Unit, Institute of

Clinical Physiology National Research

Council

Pisa, Italy

Peter J. Barnes

National Heart and Lung Institute

Imperial College

London, UK

Bianca Beghé

Section of Respiratory Diseases

Department of Oncology

Haematology and Respiratory

Diseases

University Policlinic of Modena

University of Modena and Reggio

Emilia

Modena, Italy

Francesco Blasi

Respiratory Medicine Section

Dipartimento Toraco-Polmonare e

Cardiocircolatorio

Università degli Studi di Milano and

IRCCS Fondazione Cà Granda

Milan, Italy

Konrad E. Bloch

Pulmonary Division

University Hospital of Zurich

Zurich, Switzerland

Chief Editors

Paolo Palange

Department of Public Health and

Infectious Diseases

Sapienza University of Rome

Rome, Italy

Authors

Anita K. Simonds

NIHR Respiratory Disease Biomedical

Research Unit

Royal Brompton and Harefield NHS

Foundation Trust

London, UK

(16)

xv

Annette Boehler

University Hospital of Zurich

Zurich, Switzerland

Chris T. Bolliger

†

Philippe Bonniaud

Department of Pulmonary Medicine

and Intensive Care

CHU Dijon

Dijon, France

Aik Bossink

Diakonessenhuis

Utrecht, the Netherlands

Julia Bott

Virgin Care

Chertsey, UK

Arnaud Bourdin

Department of Respiratory Disease

CHU Arnaud de Villeneuve

Montpellier, France

Thomas Brack

Cantonal Hospital Glarus

Glarus, Switzerland

Barbara Burroni

Département de Pathologie

Pôle de Biologie et de Pathologie

Centre Hospitalier Universitaire A.

Michallon

INSERM U 823 – Institut A. Bonniot

Université J. Fourier

Grenoble, France

Andrew Bush

Imperial College and Royal Brompton

Hospital

London, UK

Philippe Camus

Department of Pulmonary Medicine

and Intensive Care

CHU Dijon

Dijon, France

Emilio Canalis

Thoracic Surgery Service

Hospital Universitari Joan XXIII

IISPV

URV

Tarragona, Spain

Kai-Håkon Carlsen

Institute of Clinical Medicine,

University of Oslo

Dept of Paediatrics, Oslo University

Hospital

Norwegian School of Sport Science

Oslo, Norway

(17)

Sonia Cerrai

Pulmonary Environmental

Epidemiology Unit

Institute of Clinical Physiology

National Research Council

Pisa, Italy

Stefania Cerri

Centre for Rare Lung Disease

Dept of Medical and Surgical

Sciences

University of Modena and Reggio

Emilia

Modena, Italy

Pascal Chanez

Service de Pneumo-Allergologie et

Laboratoire d’Immunologie INSERM

U600

Université de la Méditerranée

AP-HM

Marseille, France

Francesca Cherubino

Pneumology Unit, Fondazione

Salvatore Maugeri

IRCCS

Tradate, Italy

Sara Chiesa

Department of Clinical and

Experimental Medicine

University of Parma

Parma, Italy

Marco Chilosi

Department of Pathology

Università di Verona

Veronica, Italy

Luke Clancy

TobaccoFree Research Institute

Ireland

Dublin, Ireland

Amelia Clive

North Bristol Lung Centre

University of Bristol

Bristol, UK

Robert P. Coppes

Depts of Cell Biology and Radiation

Oncology

University Medical Center Groningen

University of Groningen

Groningen, the Netherlands

Jean-François Cordier

Department of Respiratory Diseases

CHU de Lyon

Lyon, France

Ulrich Costabel

Dept of Pneumology and Allergy

Ruhrlandklinik

Essen

Germany

Vincent Cottin

Department of Respiratory Diseases

CHU de Lyon

Lyon, France

Jane C. Davies

Imperial College and Royal Brompton

Hospital

London, UK

Wilfried De Backer

Dept of Pulmonary Medicine

University of Antwerp

Antwerp, Belgium

Marc Decramer

Respiratory Rehabilitation and

Respiratory Division

University Hospital Leuven

Leuven, Belgium

Giovanni Della Casa

Division of Radiology

Dept of Diagnostic and Imaging

Services

University of Modena and Reggio

Emilia

Modena, Italy

Sabrina Della Patrona

Pneumology Unit

Fondazione Salvatore Maugeri

IRCCS

Tradate, Italy

Sofie Derijcke

Respiratory Oncology Unit

Dept of Pulmonology

University Hospital Leuven

Leuven, Belgium

Walter De Wever

University Hospitals Leuven

Leuven, Belgium

Maria Anna Digiulio

Dept of Clinical Medicine

Reference Centre for Primary

Immunodeficiencies

Sapienza University of Rome

Rome, Italy

Antonino Di Stefano

Fondazione Salvatore Maugeri

IRCCS

Veruno, Italy

Lieven Dupont

Department of Respiratory Medicine

University Hospital Gasthuisberg

KU Leuven

Leuven, Belgium

Oliver Eickelberg

Comprehensive Pneumology Center,

Ludwig-Maximilians-University and

Helmholtz Zentrum München

Munich, Germany

Santiago Ewig

Thoraxzentrum Ruhrgebiet

Kliniken für Pneumologie und

Infektiologie

Evangelisches Krankenhaus Herne

und Augusta-Kranken-Anstalt

Bochum

Bochum, Germany

Leonardo M. Fabbri

Section of Respiratory Diseases

Department of Oncology

Haematology and Respiratory

Diseases

University Policlinic of Modena

University of Modena and Reggio

Emilia

Modena, Italy

Pierre-Emmanuel Falcoz

Université Louis Pasteur and

Hôpitaux Universitaires de

Strasbourg

Strasbourg, France

Ramon Farré

Unitat de Biofisica i Bioenginyeria,

Facultat de Medicina, Universitat de

Barcelona

CIBER Enfermedades Respiratorias

Institut de Investigacions

Biomèdiques August Pi Sunyer

Barcelona, Spain

Alessandro Maria Ferrazza

Dept of Public Health and Infectious

Diseases

Sapienza University of Rome

Rome, Italy

Thomas Fuehner

Dept of Respiratory Medicine

Hanover Medical School

Hanover, Germany

Mina Gaga

Asthma Centre and 7th Respiratory

Medicine Dept

Athens Chest Hospital

Athens, Greece

Stefano Gasparini

Pulmonary Diseases Unit

Dept of Immunoallergic and

Respiratory Diseases

Azienda Ospedaliero-Universitaria

“Ospedali Riuniti”

Ancona, Italy

Mari Carmen Gilavert

Intensive Care Unit

Hospital Universitari Joan XXIII

IISPV

URV

Tarragona, Spain

Rik Gosselink

Faculty of Kinesiology and

Rehabilitation Sciences

Dept of Rehabilitation Sciences

Katholieke Universiteit Leuven

Leuven, Belgium

(20)

xix

Jens Gottlieb

Dept of Respiratory Medicine

Hanover Medical School

Hanover, Germany

Mark Greer

Dept of Respiratory Medicine

Hanover Medical School

Hanover, Germany

Fabio Guarracino

Cardio-Thoracic Dept

University Hospital

Pisa, Italy

Federico Gumiero

Department of Clinical and

Experimental Medicine

University of Insubria

Varese, Italy

Inge Hantson

Respiratory Oncology Unit

Dept of Pulmonology

University Hospital Leuven

Leuven, Belgium

Sylvia Hartl

Dept of Respiratory and Critical Care

Otto Wagner Hospital

Vienna, Austria

Patricia L. Haslam

National Heart and Lung Institute

and Royal Brompton Hospital

Imperial College

London, UK

Allan F. Henderson

Norfolk and Norwich University

Hospital

Norwich, UK

Jeroen M. Hendriks

Department of Thoracic and Vascular

Surgery

Antwerp University Hospital

Antwerp, Belgium

Matthew Hind

Royal Brompton Hospital

London, UK

Clare Hooper

Worcestershire Royal Hospital

Worcester, UK

Rudolf M. Huber

Division of Respiratory Medicine

and Thoracic Oncology, Hospitals

of Ludwig-Maximilians-University –

Campus Innenstadt, and Thoracic

Oncology Centre of Munich

Munich, Germany

J. Mike Hughes

National Heart and Lung Institute

Imperial College

London, UK

(21)

Marc Humbert

Université Paris-Sud

INSERM U999

Assistance Publique-Hôpitaux de

Paris

Service de Pneumologie

Hôpital Bicêtre

Paris, France

Magareta Ieven

Laboratory of Medical Microbiology,

University Hospital Antwerp,and

Dept of Medical Microbiology,

Vaccine and Infectious Disease

Institute, Faculty of Medicine,

University of Antwerp

Antwerp, Belgium

Zubair Kabir

TobaccoFree Research Institute

Ireland

Dublin, Ireland

Christian Karagiannidis

Abteilung für Pneumologie und

Internistische Intensivmedizin

Krankenhaus Oststadt-Heidehaus

Klinikum Region Hannover

Hanover, Germany

Coenraad F.N. Koegelenberg

Division of Pulmonology

Dept of Medicine

University of Stellenbosch and

Tygerberg Academic Hospital

Cape Town, South Africa

Melanie Königshoff

Comprehensive Pneumology Center

Ludwig-Maximilians-University and

Helmholtz Zentrum München

Munich, Germany

Helen J. Lachmann

UK National Amyloidosis Centre

Division of Medicine

University College London Medical

School

London, UK

Daniel Langer

Faculty of Kinesiology and

Rehabilitation Sciences

Dept of Rehabilitation Sciences

Katholieke Universiteit Leuven

Leuven, Belgium

Sylvie Lantuéjoul

Département de Pathologie

Pôle de Biologie et de Pathologie

Centre Hospitalier Universitaire A.

Michallon

INSERM U 823-Institut A.

Bonniot-Université J. Fourier

Grenoble, France

Patrick Lauwers

Dept of Thoracic and Vascular

Surgery

Antwerp University Hospital

Antwerp, Belgium

(22)

xxi

Pierantonio Laveneziana

Equipe de Recherche ER 10 UPMC

Laboratoire de Physio-Pathologie

Respiratoire

Faculté de Médecine Pierre et Marie

Curie

Université Pierre et Marie Curie

(Paris VI)

Paris, France

Romain Lazor

Interstitial and Rare Lung Disease

Unit

Lausanne University Hospital

Lausanne, Switzerland

Wei Shen Lim

Respiratory Medicine

Nottingham University Hospitals

NHS Trust

Nottingham, UK

Marc C.I. Lipman

University College London Medical

School and Royal Free London NHS

Foundation Trust

London, UK

Robert Loddenkemper

Dept of Pneumology II

Lungenklinik Heckeshorn

HELIOS Klinikum Emil von Behring

Berlin, Germany

Maurizio Luisetti

University of Pavia

SC Pneumologia

Dip. di Medicina Molecolare

IRCCS Policlinico San Matteo

Pavia, Italy

Alexander J. Mackay

Academic Unit of Respiratory

Medicine

UCL Medical School

London, UK

Sara Maio

Pulmonary Environmental

Epidemiology Unit

Institute of Clinical Physiology

National Research Council

Pisa, Italy

Adel H. Mansur

Birmingham Heartlands Hospital

Birmingham, UK

Georgios Margaritopoulos

Interstitial Lung Disease Unit

Royal Brompton Hospital

London, UK

Yves Martinet

University of Nancy Henri Poincaré

Nancy, France

(23)

Nick Maskell

North Bristol Lung Centre

University of Bristol

Bristol, UK

Gilbert Massard

Dept of Thoracic Surgery

Hôpitaux Universitaires de

Strasbourg

Strasbourg, France

Anne McLeer-Florin

Plateforme de Génétique Moléculaire

des Cancers

Pôle de Biologie et de Pathologie

Centre Hospitalier Universitaire A.

Michallon

INSERM U 823-Institut A.

Bonniot-Université J. Fourier

Grenoble, France

Andrew Menzies-Gow

Royal Brompton and Harefield NHS

Foundation Trust

London, UK

Lénaïg Mescam-Mancini

Département de Pathologie et

Plateforme de Génétique Moléculaire

des Cancers

Pôle de Biologie et de Pathologie

Centre Hospitalier Universitaire A.

Michallon

INSERM U 823-Institut A.

Bonniot-Université J. Fourier

Grenoble, France

Giovanni Battista Migliori

WHO Collaborating Centre for TB

and Lung Diseases

Fondazione S. Maugeri

Care and Research Institute

Tradate, Italy

Cinzia Milito

Dept of Molecular Medicine

Reference Centre for Primary

Immunodeficiencies

Sapienza University of Rome

Rome, Italy

Rob F. Miller

University College London Medical

School, and London School of

Hygiene and Tropical Medicine

London, UK

Marc Miravitlles

Pneumology Dept

Hospital Universitari Vall d’Hebron

Barcelona, Spain

Luigi Moretti

Dept of Radiation Oncology

Institut Jules Bordet

Université Libre de Bruxelles

Brussels, Belgium

Alyn H. Morice

Hull York Medical School

University of Hull

Hull, UK

(24)

xxiii

Jean-François Muir

Respiratory Dept and Respiratory

Intensive Care Unit

Rouen University Hospital

Rouen, France

Bruno Murer

Surgical Pathology Unit

Department of Clinical Pathology

Ospedale dell’Angelo

Venice, Italy

Daniel Navajas

Unitat de Biofisica i Bioenginyeria,

Facultat de Medicina, Universitat

de Barcelona, CIBER Enfermedades

Respiratorias, and Institut de

Bioenginyeria de Catalunya

Barcelona, Spain

Benoit Nemery

Research Unit of Lung Toxicology,

Occupational, Environmental and

Insurance Medicine

KU Leuven

Leuven, Belgium

Marc Noppen

University Hospital Brussels

Brussels, Belgium

Yvonne Nussbaumer-Ochsner

University Hospital Zurich

Zurich, Switzerland

Dario Olivieri

Department of Clinical and

Experimental Medicine

University of Parma

Parma, Italy

Paolo Onorati

Department of Public Health and

Infectious Diseases

Sapienza University of Rome

Rome, Italy

Antonio Palla

Cardiothoracic and Vascular Dept

University of Pisa

Pisa, Italy

Martyn R. Partridge

Imperial College, London, UK and

Lee Kong Chian School of Medicine,

Singapore

Riccardo Pellegrino

Allergologia e Fisiopatologia

Respiratoria

ASO S. Croce e Carle

Cuneo, Italy

Claudio Piersimoni

Regional Reference Mycobacteriology

Unit

Clinical Pathology Laboratory

Azienda Ospedaliera-Universitaria

Ospedali Riuniti

Ancona, Italy

c.piersimoni@ospedaliriuniti.

marche.it

(25)

Patrizia Pignatti

Allergy and Immunology Unit

Fondazione Salvatore Maugeri

IRCCS

Pavia, Italy

Massimo Pistolesi

Section of Respiratory Medicine

Dept of Experimental and Clinical

Medicine

University of Florence

Florence, Italy

Riccardo Pistelli

Catholic University

Columbus Hospital

Rome, Italy

Alessandro Pitruzzella

Fondazione Salvatore Maugeri

IRCCS

Veruno, Italy

Giovanni Poletti

Hematology Laboratory Area Vasta

Romagna

Pievesestina, Italy

Venerino Poletti

Department of Diseases of the

Thorax

Ospedale GB Morgagni

Forlì, Italy

Federica Pulvirenti

Dept of Clinical Medicine

Reference Centre for Primary

Immunodeficiencies

Sapienza University of Rome

Rome, Italy

Isabella Quinti

Dept of Molecular Medicine

Reference Centre for Primary

Immunodeficiencies

Sapienza University of Rome

Rome, Italy

Elisabeth Quoix

University of Strasbourg

University Hospital

Strasbourg, France

Klaus F. Rabe

Centre for Pneumology and Thoracic

Surgery

Grosshansdorf Hospital

Grosshansdorf, Germany

Anna Rask-Anderson

Uppsala University

Uppsala, Sweden

Luca Richeldi

Centre for Rare Lung Disease

Dept of Medical and Surgical

Sciences

University of Modena and Reggio

Emilia

Modena, Italy

(26)

xxv

Josep Roca

Hospital Clinic

IDIBAPS

CIBERES

University of Barcelona

Barcelona, Spain

Gernot Rohde

Dept of Respiratory Medicine

Maastricht University Medical Centre

Maastricht, the Netherlands

Nicola Santelmo

Université de Strasbourg and

Hôpitaux Universitaires de

Strasbourg

Strasbourg, France

Giuseppe Sarno

Pulmonary Environmental

Epidemiology Unit

Institute of Clinical Physiology

National Research Council

Pisa, Italy

Giorgio Scano

Dept of Internal Medicine

Section of Immunology and

Respiratory Medicine

University of Florence

Florence, Italy

Arnaud Scherpereel

Faculté de Médecine, Université de

Lille Nord de France, CHRU de Lille,

and INSERM unit 1019, CIIL, Institut

Pasteur de Lille

Lille, France

Paul Schneider

DRK Kliniken Berlin

Thoracic Surgery

Berlin, Germany

Bernd Schönhofer

Abteilung für Pneumologie und

Internistische Intensivmedizin

Krankenhaus Oststadt-Heidehaus

Klinikum Region Hannover

Hanover, Germany

Macé M. Schuurmans

University Hospital

Zurich, Switzerland

Martina Sester

Dept of Transplant and Infection

Immunology

Institute of Virology

University of the Saarland

Homburg, Germany

Pallav L. Shah

Royal Brompton Hospital

London, UK

Nikolaos M. Siafakas

Dept of Thoracic Medicine

Medical School

University of Crete

Heraklion, Greece

Torben Sigsgaard

Aarhus University

Aarhus, Denmark

Marzia Simoni

Pulmonary Environmental

Epidemiology Unit

Institute of Clinical Physiology

National Research Council

Pisa, Italy

Gérald Simonneau

National Reference Center for

Pulmonary Hypertension Hôpital

Antoine Béclère

Paris, France

France

Giovanni Sotgiu

Epidemiology and Medical Statistics

Unit

Department of Biomedical Sciences,

University of Sassari

Sassari, Italy

Paolo Spagnolo

Centre for Rare Lung Disease

Dept of Medical and Surgical

Sciences

University of Modena and Reggio

Emilia

Modena, Italy

Antonio Spanevello

Pneumology Unit, Fondazione

Sal-vatore Maugeri, IRCCS Tradate, and

Dept of Clinical and

Experimental Medicine, University of

Insubria, Varese, Italy

Nick ten Hacken

University Medical Center Groningen

Groningen, the Netherlands

Einar Thorsen

University of Bergen

Bergen, Norway

Pietro Torricelli

Division of Radiology

Dept of Diagnostic and Imaging

Services

University of Modena and Reggio

Emilia

Modena, Italy

Thierry Troosters

Respiratory Rehabilitation and

Respiratory division, University

Hospital Leuven, and Faculty of

Kinesiology and Rehabilitation

Sciences, Dept of Rehabilitation

Sciences, KU Leuven

Leuven, Belgium

Amanda Tufman

Division of Respiratory Medicine

and Thoracic Oncology, Hospitals of

Ludwig-Maximilians-University, and

Thoracic Oncology Centre of Munich

Munich, Germany

Panagiota Tzani

Department of Experimental and

Clinical Medicine

University of Parma

Parma, Italy

(28)

xxvii

Eleni G. Tzortzaki

Dept of Thoracic Medicine

Medical School

University of Crete

Heraklion, Greece

Davide Vallese

Fondazione Salvatore Maugeri

IRCCS

Veruno, Italy

Paul Van Houtte

Dept of Radiation Oncology

Institut Jules Bordet

Université Libre de Bruxelles

Brussels, Belgium

Peter van Luijk

University Medical Center Groningen

University of Groningen

Groningen, the Netherlands

Hans Van Remoortel

Faculty of Kinesiology and

Rehabilitation Sciences

Dept of Rehabilitation Sciences

KU Leuven

Leuven, Belgium

be

Paul E. Van Schil

Dept of Thoracic and Vascular

Surgery

Antwerp University Hospital

Antwerp, Belgium

Johan Vansteenkiste

Respiratory Oncology Unit

Dept of Pulmonology

University Hospital Leuven

Leuven, Belgium

Johny A. Verschakelen

University Hospitals Leuven

Leuven, Belgium

Andrea Vianello

Respiratory Pathophysiology and

Intensive Care Division

University City Hospital of Padua

Padua, Italy

Chiara Vicari

Fondazione Salvatore Maugeri

IRCCS

Veruno, Italy

Giovanni Viegi

Pulmonary Environmental

Epidemiology Unit, Institute of

Clinical Physiology, National

Research Council, Pisa and

A. Monroy Institute of Biomedicine

and Molecular Immunology, National

Research Council, Palermo, Italy

Duccio Volterrani

Nuclear Medicine

University of Pisa

Pisa, Italy

Florian von Groote-Bidlingmaier

Division of Pulmonology

Dept of Medicine

University of Stellenbosch and

Tygerberg Academic Hospital

Cape Town, South Africa

Susan A. Ward

Human Bio-Energetics Research

Centre

Crickhowell, UK

Jadwiga A. Wedzicha

Academic Unit of Respiratory

Medicine

University College London

London, UK

Athol U. Wells

Interstitial Lung Disease Unit

Royal Brompton Hospital

London, UK

Tobias Welte

Dept of Respiratory Medicine

Hannover Medical School

Hanover, Germany

Brian J. Whipp

†

Nathalie Wirth

University of Nancy Henri Poincaré

Nancy, France

Mark Woodhead

Dept of Respiratory Medicine

Manchester Royal Infirmary

Manchester, UK

Andrea Zanini

Pneumology Unit, Fondazione

Salvatore Maugeri, IRCCS, Tradate,

Italy and Dept of Clinical and

Experimental Medicine, University of

Insubria, Varese, Italy

Jean-Pierre Zellweger

Swiss Lung Association

Berne, Switzerland

Eleftherios Zervas

7th Pulmonary Dept

Athens Chest Hospital

Athens, Greece

Gernot Zissel

Dept of Pneumology

University Medical Centre Freiburg

Freiburg, Germany

(30)

xxix

Preface

Eight years ago, the ERS School started a very ambitious project to harmonise

education in respiratory medicine for European specialists (HERMES). A

preliminary survey among 29 European countries showed considerable

variation in postgraduate training. Based on these findings, the ERS School

developed a range of consensus documents: a core syllabus describing the

competencies required, a curriculum of recommendations indicating how

competencies should be taught and learned, an accreditation methodology

for training centres, and a voluntary European examination to assess whether

specialists have acquired the knowledge-based component of competence. The

Handbook, together with a vast array of educational material, such as lectures,

articles published in Breathe and the European Respiratory Monograph, and other

lectures and courses, all available on the ERS School website, together comprise

an unrivalled educational resource for anyone preparing for the European

Examination in Adult Respiratory Medicine.

The first edition of the ERS Handbook of Respiratory Medicine was published

in 2010 with the aim of providing state-of-the-art summaries in all areas of

respiratory medicine. This second edition of the Handbook has been extensively

peer review and revisited, and includes new sections on

• cytology of the lung

• HRCT of the chest

• long-term

ventilation

• opportunistic infections in the immunocompromised host

• the pharmacology of asthma and COPD

• HRCT in the diagnosis of interstitial lung disease

• pathology and molecular biology of lung cancer

• palliative

care

The Handbook is a comprehensive, easily accessible source of the essentials

of respiratory medicine for senior medical staff requiring revalidation, and

nursing and allied healthcare professionals at all levels who wish to keep

their knowledge up to date. All readers can be assured that as they set sail to

manage patients across the spectrum of respiratory disorders, they are armed

with the best information, access to multiple-choice questions to check their

knowledge, and a source guide for more in-depth study.

We are particularly indebted to the ERS School Committee, the ERS Publications

Office who curated the entire contents of the Handbook, and all the

contributors.

Paolo Palange, Anita K. Simonds

Chief Editors

‘To study the phenomenon of disease without books is to sail an uncharted sea, while to study books without patients is not to go to sea at all.’ ‘Too many men slip early out of the habit of studious reading, and yet that is essential.’ William Osler

(31)

By buying the ERS Handbook of Respiratory Medicine, you also gain access to the

electronic version of the book, as well as an accredited online CME test.

To log in, simply visit

www.ersnet.org/handbook

and enter the unique code

printed on inside of the

front cover of the book.

Once logged in, you’ll

be able to download the

entire book in PDF or

EPUB format, to read on

your computer or mobile

device.

ERS Handbook: Self-Assessment in Respiratory Medicine

Edited by Konrad E. Bloch, Paolo Palange and

Anita K. Simonds

Self-Assessment in Respiratory Medicine is an invaluable

tool for any practitioner of adult respiratory medicine.

The 111 multiple-choice questions cover the full breadth

of the specialty, using clinical vignettes that test not only

readers’ knowledge but their ability to apply it in daily

practice.

xxx

Get more from this Handbook

Also available from the ERS

You’ll also be able to take the online CME test. This handbook has been accredited

by the European Board for Accreditation in Pneumology (EBAP) for 18 CME

credits.

To buy a copy of this Handbook for €50 (€40 for ERS members) plus postage,

please contact [email protected]

(32)

xxxi

List of abbreviations

(C)HF

(Congestive) heart failure

AHI

Apnoea–hypopnoea

index

AIDS

Acquired immunodeficiency syndrome

BMI

Body mass index

CF

Cystic

fibrosis

COPD

Chronic obstructive pulmonary disease

CPAP

Continuous positive airway pressure

CT

Computed

tomography

ECG

Electrocardiogram

ENT

Ear, nose and throat

FEV1

Forced expiratory volume in 1 s

FVC

Forced vital capacity

Hb

Haemoglobin

HIV

Human immunodeficiency virus

HRCT

High-resolution computed tomography

K

CO

Transfer coefficient of the lung for carbon monoxide

MRI

Magnetic resonance imaging

NIV

Noninvasive

ventilation

OSA(S)

Obstructive sleep apnoea (syndrome)

P

aCO2

Arterial carbon dioxide tension

P

aO

₂

Arterial oxygen tension

PCR

Polymerase chain reaction

P

tcCO2

Transcutaneous carbon dioxide tension

S

aO

₂

Arterial oxygen saturation

S

pO

₂

Arterial oxygen saturation measured by pulse oximetry

TB

Tuberculosis

TLC

Total lung capacity

T

LCO

Transfer factor for the lung for carbon monoxide

(33)

Genetics

Gernot Zissel

Genetics addresses the composition, function and transmission of inherited entities (genes) summing up to the genome of an individual. Generally, the term ‘gene’ is understood as a unit coding for a single RNA that gives rise to a single and specific protein. However, due to alternative splicing, one gene may code for different proteins. There are also genes not coding for proteins but for catalytic RNAs (tRNA, rRNA) or regulatory RNAs (microRNA (miRNA)). The genotype is the specific composition of genes of an individual that influences its phenotype. However, in contrast to the genotype, which is simply inherited, a phenotype is shaped by epigenetic phenomena, environment, climate, nutrition and other external factors.

Genes are transcribed to RNA and subsequently translated into proteins. Genes do not code for ‘diseases’. Every genetic disease is based on an altered or missing protein. Because we are all equipped with a double set of

chromosomes, in the vast majority of cases, a dysfunctional gene is corrected by its counterpart with normal function. A deficiency occurs only when the respective gene is dysfunctional on both

chromosomes, or the gene product is either missing or does not perform its task. Diseases caused by the alteration of a single gene with relevance for pulmonologists are CF and a1-proteinase inhibitor (PI) deficiency (formerly a1-antitrypsin (AT) deficiency). In other diseases such a clear-cut relationship between a gene and a disease is not evident, although facts, such as geographical distribution or familial clusters, indicate a genetic background. This is the case in asthma, sarcoidosis, pulmonary fibrosis and primary pulmonary hypertension. Table 1 shows examples of mutated genes involved in respiratory disorders.

There are also numbers of gene variations that are regarded as neutral variations of the human gene pool. These variations are not harmfulper se, but together with distinct external stimuli they foster the development of certain diseases. Glutamine at position 69 in the human leukocyte antigen (HLA)-DPB1 gene does not cause an illness; however, when in contact with beryllium dust, carriers of Glu69+ HLA-DPB1 are at an increased risk of developing chronic beryllium disease (CBD). Up to 97% of CBD patients are Glu69+ HLA-DPB1 positive. Another example is the lack of functional

Key points

N

_{A few respiratory diseases, such as CF} and a1-Pi deficiency, are single-gene conditions.

N

_{A large range of respiratory diseases,} including asthma, COPD, sarcoidosis, IPF and primary pulmonary

hypertension, may have a genetic background.

N

_{Non-harmful gene variants can} nonetheless confer susceptibility to conditions such as chronic beryllium disease.

N

_{The role of epigenetic regulatory} mechanisms in respiratory disease is likely to be very significant.

(34)

receptors for interferon-c or interleukin-12. In these cases the individuals grow up normally and reach adolescence; however, after the BCG (Bacillus Calmette–Gue´rin) vaccination or when they encounter environmental mycobacteria (e.g. Mycobacterium fortuitum, Mycobacterium chelonae), these individuals develop severe and sometimes fatal disease.

Epigenetics and regulatory genes

The genome is not a static blueprint of the phenotype as it was regarded in the past. Several mechanisms of genetic regulation, epigenetics and regulatory genes, have been discovered in recent years. The term epigenetics describes a wide field of DNA and histone modifications that contribute to the regulation of gene transcription. One of these modifications is the methylation of the nucleobase cytosine. Cytosine is methylated only in CG ‘islands’; single cytosines are not methylated. Cytosine methylation inhibits binding of RNA polymerases to the gene,

which is subsequently not translated. Cytosine methylation is important in promoter silencing and inactivation of the X chromosome.

Histone modifications are an additional form of epigenetic regulation. Histones are protein spheres that bind DNA. There are four different histones, two of each histone together with the bound DNA build a nucleosome, the core of a chromosome. Histones can be modified, mainly by acetylation, methylation and various other mechanisms. Generally, acetylation of histones opens the nucleosome structure and the gene becomes accessible for transcription. In contrast, histone methylation leads to the accumulation of additional histone proteins in turn leading to a compacted nucleosome and

subsequently inhibiting gene transcription. The miRNAs are short, highly conserved, noncoding RNAs that bind to

39-untranslated regions (39-UTR) of mRNAs. Table 1. Examples of mutated genes involved in respiratory disorders

Disease Gene Gene product Mutation(s)

CF CFTR Cystic fibrosis transmembrane conductance regulator

.1500 Emphysema SERPINA1 Serpin peptidase inhibitor,

clade A (a-1 antiproteinase, antitrypsin)

SNP G-342A .90% of cases

Chronic beryllium disease

HLA-DPB1 Histocompatibility antigen, DP(W2) b-chain

Glutamine at position 69

Sarcoidosis BTNL2 Butyrophilin-like 2 rs2076530 SNP G-11084A causing premature stop codon ANXA11 Annexin A11 rs1049550 SNP CRT, arginine

to cysteine

TNF TNF SNP G-308A

TLR TLR SNPs in variousTLR genes

influence disease course

Cancer c-Myc Promoter translocation

Ras Family of GTPases Various SNPs induce permanent activation EGFR Epidermal growth factor

receptor

Deletions, SNPs leading to over expression and permanent activation

(35)

Incomplete binding leads to silencing and complete binding to degradation of the RNA. In fact, miRNAs are powerful regulators. Activation of transcription factors, such as nuclear factor (NF)-kB leads to the transcription of a variety of immune mediator genes. Simultaneous activation of miRNAs suppresses certain mediators, giving rise to a specific pattern of mediator activation. miRNAs are of strong

importance in cancer and pulmonary fibrosis; however, one might expect that transcriptional regulation by miRNAs is also important in other diseases. The pattern of miRNAs expressed in several diseases and tumours is highly specific and might be used as a biomarker.

Genetics in CF

CF is caused by the dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a chloride channel. However, although in all CF patients the CFTR is dysfunctional, there are .1 500 different mutations known to affect CFTR and lead to a dysfunctional chloride channel. CF inheritance follows an autosomal recessive heredity,i.e. the disease becomes manifest only when CFTR genes on both chromosomes are mutated, albeit not necessarily by the same mutation. The most common defect is the deletion of a phenylalanine at position 508 (DF508), which is responsible for up to 70% of all CF cases. Interestingly, there is a marked difference in the frequency of this disease in different populations. It is most common in Caucasians (1:2000 being highest in Scotland and the Faroe Islands (1:500)) but lower in descendants from Africa (1:15 000); and lowest in Asians (1:30 000). CFTR mutations can be grouped into classes based on their functional consequences on the CFTR within the cell: CFTR is either not synthesised, inadequately processed, not regulated, shows abnormal conductance, discloses partially defective production or shows accelerated degradation.

Genetics of proteinase inhibitors

The PI a1-antitrypsin belongs to a family of serine PIs (serpins) and blocks serine

proteases, such as neutrophil elastase, cathepsin G and proteinase 3, all released by neutrophils and is, therefore, renamed as a1-PI. The lack of a1-PI leads to an incomplete or absent containment of proteinases resulting in severe organ damage (e.g. emphysema), mostly in the lung.

There are several known mutations in the a1-PI gene, such as base substitutions, in-frame deletions, in-frame-shift mutations and exon deletions. More than 90% of cases are caused by single amino acid exchange at position 342 (glycine to lysine), which is called Z mutation. The Z mutation results in a structural alteration that inhibits post-translational modifications and secretion. Patients bearing the Z allele demonstrate ,15% of the normal a1-PI level in serum, which additionally seems to be non-functional.

The gene frequency of the Z allele is rather common in Europe, with up to 4% of the population being heterozygotic. However, the frequency declines to ,1% in southern Europe. The lowest frequency is found in African–Americans (0.4%).

Genetics in interstitial lung diseases

There is some indication that interstitial lung diseases, such as sarcoidosis, CBD or idiopathic pulmonary fibrosis (IPF), are based on a specific genetic background. Familial clusters are seen in sarcoidosis and IPF. In Europe, sarcoidosis frequency increases from South to North. This might also be a matter of climate, as the same distribution is seen in Japan. However, the Swedish population encounters the highest prevalence in Europe (55–64 per 100 000). In contrast, in the Finnish population living at the same latitude, the prevalence is just half of the Swedish (28 per 100 000). This difference points to a strong genetic background in the pathogenesis of sarcoidosis.

An inherited pre-disposition for sarcoidosis is also indicated by an increased risk of sarcoidosis in close relatives of patients. The percentage of

(36)

patients with a positive family history ranges from 2.7% in Spain to 17% in African–Americans. Analysis of familial sarcoidosis suggests that multiple small or moderate genetic effects cause a

predisposition for sarcoidosis.

Genes of high interest are the HLA class II antigens. Although some of these linkages are largely dependent on the population investigated, several associations seem to be preserved,e.g. HLA-DRB1*03

associates with spontaneous resolution and mild disease, as demonstrated in Swedish, Polish, Croatian and Czech populations.

Using different methods, a variety of candidate genes were identified and found to be associated with the susceptibility or the natural course of the disease. This included genes for co-stimulatory molecules (e.g. butyrophilin-like 2

(BTNL2)), genes involved in cell cycle (e.g. annexin A11 (ANXA11)), and genes involved in immune regulation (e.g. CD40), mediators (e.g. tumour necrosis factor (TNF)-a (TNFA2) or Toll-like receptors (TLR)). These genes may alter the reactivity of the respective cells to external stimuli which subsequently initiate an inadequate immune response.

Angiotensin-converting enzyme (ACE) is often used in the diagnosis and clinical monitoring of sarcoidosis. However, serum levels of ACE (sACE) are highly variable, which impairs the clinical use of ACE as a marker. The variability of sACE is based on a deletion/insertion in intron 16 of the ACE gene. The homozygote deletion variant is associated with higher sACE, whereas homozygote insertion is associated with lower levels.

Heterozygotes exhibit intermediate values. Therefore, in populations of Caucasian origin, the knowledge of the zygosity of the deletion/insertion variants allows the application of genotype-corrected

reference values of sACE, which leads to an improvement of the clinical application of this marker. However, this is not

applicable in populations of African origin; the ACE gene in these populations is much

more polymorphic and sACE levels are not linked with the deletion/insertion

polymorphism.

Familial pulmonary fibrosis is frequently linked with two mutations in the surfactant protein C (SP-C) gene resulting either in a splice deletion of exon 4 in a SP-C variant that cannot be processed and accumulates as pro-SP-C in the cell causing cell stress and apoptosis. The pathological pattern of fibrosis is in both forms consistent with non-specific interstitial pneumonitis in younger patients and usual interstitial pneumonia in the elderly. A recent report points to a mutation in the telomerase reverse transcriptase (TERT) causing short ends in the telomeres and bone marrow hypocellularity. But also mutations in genes regulating cell cycle like TP53 and CDKN1A are found to influence survival times in IPF.

Genetics in asthma

There is a plethora of work related to the genetics of asthma. The idea of a genetic basis for asthma is supported by the fact that there are familial clusters of asthma and differences of asthma frequency in different populations (highest at the South Atlantic island Tristan da Cunha affecting .20% of the population). However, no single gene is responsible for the development or the clinical course of asthma; instead, several genes are regarded as risk genes for developing asthma. The gene products of these genes are involved in T-cell activation, cytokine release and balance, epithelial function and repair or smooth muscle contractility. Again, new genes involved in asthma susceptibility might be expected.

Nevertheless, although there are

predisposing genes in asthma, the influence of lifestyle on the development of asthma is also evident. There is a clear increase in asthma incidences in developing countries. Therefore, asthma might be an elucidating example for the complex genotype/ phenotype relationship.

Respiratory Medicine (2013)

handbook

Respiratory

Medicine

2nd Edition

Editors

Paolo Palange

Anita K. Simonds

handbook

R

espir

atory Medicine

The European Respiratory Society (ERS)

Handbook of Respiratory Medicine, now in

its second edition, is a concise, compact and

easy-to-read guide to each of the key areas in

respiratory medicine. Its 18 chapters, written

by clinicians and researchers at the forefront

of the field, explain the structure and function

of the respiratory system, its disorders and

how to treat them.

The Handbook is a must-have for anyone

who intends to remain up to date in the

field, and to have within arm’s reach a

reference that covers everything from the

basics to the latest developments in

respiratory medicine.

Paolo Palange is head of the Pulmonary

Function and Research Unit in the

Department of Clinical Medicine at the

Sapienza University of Rome, and is the

HERMES Director.

Anita Simonds is Consultant in Respiratory &

Sleep Medicine at NIHR Respiratory

Biomedical Research Unit,Royal Brompton &

Harefield NHS Trust, London,

and is the ERS School Chair.

Respiratory

Medicine

2nd Edition

Editors

Paolo Palange

and Anita K. Simonds

PUBLISHED BY

THE EUROPEAN RESPIRATORY SOCIETY

CHIEF EDITORS

Paolo Palange (Rome, Italy)

Anita K. Simonds (London, UK)

ERS STAFF

Alice Bartlett, Matt Broadhead, Neil Bullen, Alyson Cann, Jonathan Hansen,

Sarah Hill, Fiona Marks, Elin Reeves, David Sadler, Claire Turner

© 2013 European Respiratory Society

Design by Claire Turner and Lee Dodd, ERS

Typeset in China by Charlesworth Group

Printed by Charlesworth Press

All material is copyright to the European Respiratory Society.

It may not be reproduced in any way including electronically without the express

permission of the society.

CONTACT, PERMISSIONS AND SALES REQUESTS:

European Respiratory Society, 442 Glossop Road, Sheffield, S10 2PX, UK

Tel: +44 114 2672860 Fax: +44 114 2665064 e-mail: [email protected]

Table of contents

Contributors

xiv

Preface xxix

Get more from this Handbook

xxx

List of abbreviations

xxxi

Chapter 1 – Structure and function of the respiratory system

Genetics

1

Gernot Zissel

Molecular biology of the lung

7

Melanie Königshoff and Oliver Eickelberg

Anatomy of the respiratory system

13

Pallav L. Shah

Respiratory physiology

_{and T}