ERS Handbook of Paediatric Respiratory Medicine

handbook

Paediatric Respiratory Medicine

Editors Ernst Eber Fabio Midulla

handbook P aediatric R espir atory Medicine

The 18 chapters of the ERS Handbook of Paediatric Respiratory Medicine cover the whole spectrum of paediatric respiratory medicine, from anatomy and development to disease, rehabilitation and treatment. The Editors have brought together leading clinicians to produce a thorough and easy- to-read reference tool. The Handbook is structured

to accompany the paediatric HERMES syllabus, making it an essential resource for anyone interested in this field and an ideal educational training guide.

Ernst Eber is a Professor of Paediatrics and Head of the Respiratory and Allergic Disease Division in the Department of Paediatrics and Adolescence Medicine at the Medical University of Graz, and is also Head of the ERS Paediatric Assembly.

Fabio Midulla is an Assistant Professor and

Director of the Paediatric Emergency Department,

Policlinico Umberto I. “Sapienza” University of

Rome, and is Secretary of the ERS Paediatric

Assembly.

Paediatric Respiratory Medicine

1st Edition Editors Ernst Eber

and Fabio Midulla

handbook

PUBLISHED BY

THE EUROPEAN RESPIRATORY SOCIETY

CHIEF EDITORS

Ernst Eber (Graz, Austria) Fabio Midulla (Rome, Italy)

ERS STAFF

Matt Broadhead, Alyson Cann, Jonathan Hansen, Sarah Hill, Elin Reeves, Claire Turner

© 2013 European Respiratory Society Design by Claire Turner, 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: info@ersj.org.uk

ISBN 978-1-84984-038-5

Table of contents

Contributors xii

Preface xvii

Get more from this Handbook xviii

List of abbreviations xxix

Chapter 1 – Structure and function of the respiratory system

Anatomy and development of the respiratory system 1 Robert Dinwiddie

Applied respiratory physiology 11

Caroline Beardsmore and Monika Gappa

Immunology and defence mechanisms 19

Diana Rädler and Bianca Schaub

Environmental determinants of childhood respiratory health 29 and disease

Erik Melén and Matthew S. Perzanowski Chapter 2 – Respiratory signs and symptoms

History and physical examination 33

Michael B. Anthracopoulos, Kostas Douros and Kostas N. Priftis

Cough 44 Ahmad Kantar, Michael Shields, Fabio Cardinale and Anne B. Chang

Tachypnoea, dyspnoea, respiratory distress and chest pain 50 Josef Riedler

Snoring, hoarseness, stridor and wheezing 57

Kostas N. Priftis, Kostas Douros and Michael B. Anthracopoulos

Exercise intolerance 65

Kai-Håkon Carlsen

Chapter 3 – Pulmonary function testing and other diagnostic tests

Static and dynamic lung volumes 70

Oliver Fuchs

Respiratory mechanics 77 Oliver Fuchs

Reversibility, bronchial provocation testing and exercise testing 83 Kai-Håkon Carlsen

Blood gas assessment and oximetry 93

Paola Papoff, Fabio Midulla and Corrado Moretti

Exhaled nitric oxide, induced sputum and exhaled breath analysis 100 Johan C. de Jongste

Pulmonary function testing in infants and preschool children 107 Enrico Lombardi, Graham L. Hall and Claudia Calogero

Single- and multiple-breath washout techniques 113 Sophie Yammine and Philipp Latzin

Forced oscillation techniques 118

Shannon J. Simpson and Graham L. Hall

Polysomnography 122 Sedat Oktem and Refika Ersu

Chapter 4 – Airway endoscopy

Flexible bronchoscopy 132

Jacques de Blic

Bronchoalveolar lavage 140

Fabio Midulla, Raffaella Nenna and Ernst Eber

Bronchial brushing and bronchial and transbronchial biopsies 146 Petr Pohunek and Tamara Svobodová

Rigid and interventional endoscopy 151

Thomas Nicolai

General anaesthesia, conscious sedation and local anaesthesia 156

Jacques de Blic and Caroline Telion

Chapter 5 – Lung imaging

Conventional radiography 161

Meinrad Beer

Computed tomography 166

Harm A.W.M. Tiddens, Marcel van Straten and Pierluigi Ciet

Magnetic resonance imaging 176

Lucia Manganaro and Silvia Bernardo

Ultrasonography 183 Carolina Casini, Vincenzo Basile, Mariano Manzionna and

Roberto Copetti

Isotope imaging methods 189

Georg Berding

Interventional radiology 193

Efthymia Alexopoulou, Argyro Mazioti and Dimitrios Filippiadis Chapter 6 – Inhalation therapy

Aerosol therapy 198

Hettie M. Janssens

Chapter 7 – Acute and chronic lung infections

Epidemiology 207 Steve Turner

Microbiology testing and interpretation 214

Elpis Hatziagorou, Emmanuel Roilides and John Tsanakas

Immunisation against respiratory pathogens 221 Horst von Bernuth and Philippe Stock

Upper respiratory tract infections 227

Rossa Brugha, Chinedu Nwokoro and Jonathan Grigg

Community-acquired pneumonia 233

Mark L. Everard, Vanessa Craven and Patricia Fenton

Hospital-acquired pneumonia 242 Vanessa Craven, Patricia Fenton and Mark L. Everard

Lung involvement in immunodeficiency disorders 248 Rifat Chaudry and Paul Aurora

Non-CF bronchiectasis 253

Elif Dagli

Pleural infection, necrotising pneumonia and lung abscess 258 Fernando M. de Benedictis, Chiara Azzari and Filippo Bernardi

Bacterial bronchitis with chronic wet lung 266 Petr Pohunek and Tamara Svobodová

Chapter 8 – Tuberculosis

Pulmonary TB, latent TB, and in vivo and in vitro tests 270 Zorica Zivkovi c and James Paton

Extrapulmonary TB and TB in the immunocompromised host 284 Toyin Togun, Uzor Egere and Beate Kampmann

Chapter 9 – Bronchial asthma and wheezing disorders

Epidemiology and phenotypes of bronchial asthma and 293 wheezing disorders

Franca Rusconi, Ben D. Spycher and Claudia E. Kuehni

Genetic and environmental factors in bronchial asthma and 298 wheezing disorders

Oliver Fuchs and Erika von Mutius

Acute viral bronchiolitis 305

Fabio Midulla, Ambra Nicolai and Corrado Moretti

Preschool wheezing 310

Paul L.P. Brand, Annemie M. Boehmer, Anja A.P.H. Vaessen-Verberne

Bronchial asthma 316

Mariëlle Pijnenburg and Karin C. Lødrup Carlsen

Emerging therapeutic strategies 328 Giorgio Piacentini and Laura Tenero

Differential diagnosis of bronchial asthma 334 Giorgio Piacentini and Laura Tenero

Chapter 10 – Allergic disorders

Pathophysiology and epidemiology of allergic disorders 339 Karin C. Lødrup Carlsen

In vivo and in vitro diagnostic tests in allergic disorders 345 Gunilla Hedlin

Anaphylaxis 349 Antonella Muraro

Allergic rhinitis 354

Michele Miraglia Del Giudice, Francesca Galdo and Salvatore Leonardi

Atopic dermatitis 363

Paolo Meglio, Elena Galli and Nunzia Maiello

Food allergy 370

Alessandro Fiocchi, Lamia Dahdah and Luigi Terracciano

Allergic bronchopulmonary aspergillosis 376

Andrew Bush

Specific immunotherapy, prevention measures and alternative treatment 383 Susanne Halken and Gunilla Hedlin

Chapter 11 – Cystic fibrosis

Genetics, pathophysiology and epidemiology of CF 390 Sabina Gallati

Screening and diagnosis of CF 397

Jürg Barben and Kevin Southern

CF lung disease 402

Nicolas Regamey and Jürg Barben

Extrapulmonary manifestations of CF 410 Anne Munck, Manfred Ballmann and Anders Lindblad

Emerging treatment strategies in CF 421

Melinda Solomon and Felix Ratjen

Prognosis, management and indications for lung transplantation in CF 427 Helen Spencer and Andrew Bush

Chapter 12 – Congenital malformations

Airway malformations 435

Ernst Eber and Andreas Pfleger

Thoracic malformations 445

Ashok Daya Ram, Jennifer Calvert and Sailesh Kotecha

Vascular malformations 452

Oliviero Sacco, Serena Panigada, Nicoletta Solari, Elena Ribera, Chiara Gardella, Silvia Rosina, Michele Ghezzi and Francesca Rizzo Chapter 13 – Bronchopulmonary dysplasia and chronic lung disease

Aetiology, pathogenesis, prevention and evidence-based 461 medical management

Robert I. Ross-Russell

Nutritional care 466

Kajsa Bohlin

Neurodevelopmental assessment and outcomes 469 Charles C. Roehr, Lex W. Doyle and Peter G. Davis

Long-term respiratory outcomes 472

Manuela Fortuna, Marco Filippone and Eugenio Baraldi Chapter 14 – Pleural, mediastinal and chest wall diseases

Pleural effusion, chylothorax, haemothorax and mediastinitis 477 Juan Antón-Pacheco, Carmen Lucas-Paredes and

Antonio Martinez-Gimeno

Pneumothorax and pneumomediastinum 485

Nicolaus Schwerk, Folke Brinkmann and Hartmut Grasemann

Neuromuscular disorders 492 Anita K. Simonds

Chest wall disorders 497

Daniel Trachsel, Carol-Claudius Hasler and Jürg Hammer

Chapter 15 – Sleep-related disorders

Physiology and pathophysiology of sleep 503

Sedat Oktem and Refika Ersu

OSAS and upper respiratory airway resistance syndrome 514 Maria Pia Villa and Silvia Miano

Central sleep apnoea and hypoventilation syndromes 521 Malin Rohdin and Hugo Lagercrantz

Impact of obesity on respiratory function 528 Andrea Bon, Martina Tubaro and Mario Canciani

Chapter 16 – Lung injury and respiratory failure

Lung injury 533

Andreas Schibler

Acute and chronic respiratory failure 538

Robert I. Ross-Russell and Colin Wallis

Home oxygen therapy, invasive ventilation and NIV, and home 545 ventilatory support

Brigitte Fauroux, Adriana Ramirez and Sonia Khirani Chapter 17 – Other respiratory diseases

Primary ciliary dyskinesia 551

Deborah Snijders, Serena Calgaro, Massimo Pifferi, Giovanni Rossi and Angelo Barbato

Gastro-oesophageal reflux-associated lung disease and 559 aspiration syndrome

Osvaldo Borelli, Efstratios Saliakellis, Fernanda Cristofori and

Keith J. Lindley

Foreign body aspiration 566 Iolo Doull

Bronchiolitis obliterans 570

Francesca Santamaria, Silvia Montella and Salvatore Cazzato

Plastic bronchitis 577

Bruce K. Rubin and William B. Moskowitz

Haemangiomas, lymphangiomas and papillomatosis 582 Thomas Nicolai

Interstitial lung diseases 587

Annick Clement, Guillaume Thouvenin, Harriet Corvol and Nadia Nathan Surfactant dysfunction and alveolar proteinosis 596 Armin Irnstetter, Carolin Kröner, Ralf Zarbock and Matthias Griese

Pulmonary vascular disorders 601

Andrea McKee and Andrew Bush

Eosinophilic lung diseases and hypersensitivity pneumonitis 610 Carlo Capristo, Giuseppina Campana, Francesca Galdo, Emilia Alterio

and Laura Perrone

Pulmonary haemorrhage 619

Robert Dinwiddie

Sickle cell disease 625

Tobias Ankermann

Lung and mediastinal tumours 630

Amalia Schiavetti

Systemic disorders with lung involvement 636

Andrew Bush

Lung transplantation and management of post-lung transplant patients 647

Paul Robinson and Paul Aurora

Chapter 18 – Rehabilitation in chronic respiratory diseases

Rehabilitation programmes and nutritional management 656 Andreas Jung

Prevention of indoor and outdoor pollution 662 Giuliana Ferrante, Velia Malizia, Roberta Antona and Stefania La Grutta

Respiratory physiotherapy 665

Beatrice Oberwaldner

Fitness-to-fly testing 670

Mary J. Sharp and Graham L. Hall

Sports medicine 673

Giancarlo Tancredi, Giovanna De Castro and Anna Maria Zicari

xii

Contributors

Emilia Alterio

Department of Pediatrics, Second University of Naples, Naples, Italy.

Efthtymia Alexopoulou 2nd Department of Radiology, University Hospital ATTIKON, Athens, Greece.

ealex64@hotmail.com Tobias Ankermann

Klinik für Allgemeine Pädiatrie Universitätsklinikum Schleswig- Holstein (UKSH), Kiel, Germany.

ankermann@pediatrics.uni-kiel.de Michael B. Anthracopoulos Respiratory Unit, Department of Paediatrics, University of Patras, Patras, Greece.

manthra@otenet.gr Roberta Antona

Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e Immunolo- gia Molecolare, Palermo, Italy.

roberta.antona@ibim.cnr.it Juan L. Antón-Pacheco

Pediatric Surgery, Hospital Universi- tario 12 de Octubre, Madrid, Spain.

janton.hdoc@salud.madrid.org

Paul Aurora

Great Ormond Street Hospital for Children, London, UK.

p.aurora@ucl.ac.uk Chiara Azzari

Department of Pediatrics, University of Florence, Mayer Children’s Hospital, Florence, Italy.

c.azzari@meyer.it Manfred Ballmann Department of Pediatric Pulmonology, Ruhr-University Bochum, Bochum, Germany.

m.ballmann@klinikum-bochum.de Eugenio Baraldi

Pediatric Pneumonolgy, University of Padova, Padova, Italy.

baraldi@pediatria.unipd.it Angelo Barbato

Department of Pediatrics, University of Padova, Italy.

barbato@pediatria.unipd.it Jürg Barben

Division of Respiratory Medicine, Children’s Hospital St. Gallen, St Gallen, Switzerland.

juerg.barben@kispisg.ch Chief Editors

Ernst Eber

Respiratory and Allergic Disease Division, Department of Paediatrics

and Adolescence, Medical University of Graz, Graz, Austria.

ernst.eber@medunigraz.at Authors

Fabio Midulla

Department of Paediatrics,

“Sapienza” University of Rome, Rome, Italy.

midulla@uniroma1.it

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Vincenzo Basile

Pediatric Department, Monopoli Hospital, Bari, Italy.

vinbasile67@libero.it Caroline Beardsmore

Department of Infection, Immunity and Inflammation (Child Health), University of Leicester, Leicester, UK.

csb@le.ac.uk Meinrad Beer

Department of Pediatric

Radiology, Medical University Graz, Graz, Austria.

meinrad.beer@medunigraz.at Georg Berding

Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.

berding.georg@mh-hannover.de Filippo Bernardi

Department of Pediatrics, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.

filippo.bernardi@unibo.it Silvia Bernardo

Radiological Oncological and Pathological Sciences, Umberto I Hospital, “Sapienza” University of Rome, Rome, Italy.

silviabernardo@live.it Annemie M. Boehmer

Department of Paediatrics, Maasstad Hospital, Rotterdam,

The Netherlands.

BoehmerA@maasstadziekenhuis.nl

Kajsa Bohlin

Neonatal intensive Care, Karolinska Institutet, Karolinska University Hospital

Huddinge, Stockholm, Sweden.

kajsa.bohlin@ki.se Andrea Bon

Pediatric Department, University of Udine, Udine, Italy.

gandale@gmail.com Osvaldo Borrelli

Department of Paediatric Gastroenterology, Division of Neurogastroenterology and Motility, Great Ormond Street Hospital for Children, ICH University College of London, London, UK.

osvaldo.borrelli@gosh.nhs.uk Paul L.P. Brand

Princess Amalia Children’s Clinic, Isala Klinieken, Zwolle,

The Netherlands.

p.l.p.brand@isala.nl Folke Brinkmann

Department of Pediatrics, Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.

brinkmann.folke@mh-hannover.de Rossa Brugha

Centre for Paediatrics, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

r.brugha@qmul.ac.uk

Andrew Bush

Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK.

A.Bush@rbht.nhs.uk Claudia Calogero

Respiratory Medicine, Anna Meyer, University Hospital for Children, Florence, Italy.

c.calogero@meyer.it Serena Calgaro

Department of Pediatrics, University of Padova, Padova, Italy.

serena.calgaro@studenti.unipd.it Jennifer Calvert

Department of Neonatal Medicine, University Hospital of Wales, Cardiff and Vale LHB, Cardiff, UK.

Giuseppina Campana

Department of Pediatrics, Second University of Naples, Naples, Italy.

Mario Canciani

Pediatric Department, Azienda Ospedaliero, Universitaria di Udine, Udine, Italy.

canciani.mario@aoud.sanita.fvg.it Carlo Capristo

Department of Pediatrics, Second University of Naples, Naples, Italy.

carlo.capristo@unina2.it

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Fabio Cardinale

Department of Pediatric Allergy and Pulmonology, Paediatric Hospital Giovanni XXIII, University of Bari, Bari, Italy.

fabiocardinale@libero.it Kai-Håkon Carlsen

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

k.h.carlsen@medisin.uio.no Carolina Casini

Pediatric Department, Sant’Andrea Hospital, Rome, Italy.

carolinacasini@libero.it Salvatore Cazzato

Dept of Pediatrics, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.

salvatore_cazzato@aosp.bo.it Anne B. Chang

Respiratory Medicine, Royal Children’s Hospital, Brisbane, Australia.

annechang@ausdoctors.net Rifat Chaudry

Great Ormond Street Hospital for Children, London, UK.

r.chaudry@gosh.nhs.uk Pierluigi Ciet

Radiology and Pediatric

Pulmonology, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands.

p.ciet@erasmusmc.nl

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Annick Clement

Paediatric Pulmonary Department, Reference Centre for Rare Lung Diseases, AP-HP, Hôpital Trousseau, INSERM UMR S-938, Université Pierre et Marie Curie, Paris, France.

annick.clement@trs.aphp.fr Roberto Copetti

Latisana General Hospital, Latisana, Italy.

robcopet@tin.it Harriet Corvol

Paediatric Pulmonary Department, Reference Centre for Rare Lung Diseases, AP-HP, Hôpital Trousseau, INSERM UMR S-938, Université Pierre et Marie Curie, Paris, France.

harriet.corvol@trs.aphp.fr Vanessa Craven

Department of Respiratory Medicine and Microbiology, Sheffield

Children’s Hospital, Sheffield, UK.

valgar@doctors.org.uk Fernanda Cristofori

Pediatrics Department, University of Bari, Bari, Italy.

fernandacristofori@gmail.com Elif Dagli

Pediatric Pulmonology, Marmara University, Istanbul, Turkey.

elifzdagli@gmail.com Lamia Dahdah

Division of Allergy, Department of Pediatrics, Pediatric Hospital Bambino Gesù, Rome, Italy.

lamia.dahdah@opbg.net

Peter G. Davis

Department of Newborn Research, The Royal Women’s Hospital, Melbourne, Australia.

pgd@unimelb.edu.au Ashok Daya Ram

Department of Paediatric Surgery, Birmingham Children’s Hospital, Birmingham, UK.

ashokdram@hotmail.com Fernando M. de Benedictis Department of Mother and Child Health, Salesi University Children’s Hospital, Ancona, Italy.

debenedictis@ospedaliriuniti.

marche.it Jacques de Blic

Université Paris Descartes, Assistance Publique des Hôpitaux de Paris, Hôpital Necker Enfants Malades, Service de Pneumologie et Allergologie Pédiatriques Paris, France.

j.deblic@nck.aphp.fr Giovanna De Castro Department of Paediatrics,

“Sapienza” University of Rome, Rome, Italy.

giovanna.decastro@uniroma1.it Johan C. de Jongste

Dept of Pediatrics/Respiratory Medicine, Erasmus Medical Center, Sophia Childrens’ Hospital,

Rotterdam, The Netherlands.

j.c.dejongste@erasmusmc.nl

Robert Dinwiddie

Portex Unit, Institute of Child Health, London, UK.

rdinwiddie@doctors.org.uk Iolo Doull

Department of Paediatric Respiratory Medicine, Children’s Hospital for Wales, Cardiff, UK.

doullij@cf.ac.uk Kostas Douros

Respiratory Unit, 3rd Department of Paediatrics, “Attikon” Hospital, University of Athens, Athens, Greece.

costasdouros@gmail.com Lex W. Doyle

Department of Obstetrics and Gynaecology, The University of Melbourne, Melbourne, Australia.

lwd@unimelb.edu.au Uzor Egere

Vaccinology Theme, Medical Research Council (MRC) Unit, The Gambia, Africa.

uegere@mrc.gm Refika Ersu

Division of Pediatric Pulmonology, Marmara University, Istanbul, Turkey.

rersu@yahoo.com Mark L. Everard

School of Paediatrics and Child Health, University of Western Australia, Princess Margaret Hospital, Subiaco, Australia.

mark.everard@uwa.edu.au

xvi

Brigitte Fauroux

AP-HP, Hopital Armand Trousseau, Pediatric Pulmonary Department, INSERM U 955, Université Pierre et Marie Curie, Paris, France.

brigitte.fauroux@trs.aphp.fr Patricia Fenton

Department of Respiratory Medicine and Microbiology, Sheffield

Children’s Hospital, Sheffield, UK.

patricia.fenton@sch.nhs.uk Giuliana Ferrante

Consiglio Nazionale delle Ricerche, Dipartimento di Scienze per la Promozione della Salute e Materno Infantile, University of Palermo, Palermo, Italy.

giuliana.ferrante@unipa.it Dimitrios Filippiadis

2nd Deaprtment of Radiology, University Hospital ATTIKON, Athens, Greece.

dfilippiadis@yahoo.gr Marco Filippone

Department of Pediatrics, University of Padova, Padova, Italy.

filippone@pediatria.unipd.it Alessandro Fiocchi

Division of Allergy, Dept of Pediatrics, Pediatric Hospital Bambino Gesù, Rome, Italy.

allerg@tin.it

xvii

Manuela Fortuna

Pediatric Pneumonolgy, University of Padova, Padova, Italy.

fortuna.manuela@alice.it Oliver Fuchs

Division of Paediatric Allergology, University Children’s Hospital, Ludwig-Maximilians-University, Munich, Germany.

oliver.fuchs@med.lmu.de Francesca Galdo

Department of Pediatrics, Second University of Naples, Naples, Italy.

Sabina Gallati

Division of Human Genetics, Departments of Paediatrics and Clinical Research, Inselspital, University of Bern, Bern, Switzerland.

sabina.gallati@insel.ch Elena Galli

Department of Pediatric Allergy, Research Centre, San Pietro Hospital - Fatebenefratelli, Rome, Italy.

galli.elena@fbfrm.it Monica Gappa

Children’s Hospital and Research Insitute for the Prevention of

Allergies and Respiratory Diseases in Children, Marien-Hospital Wesel GmbH, Wesel, Germany.

Monika.gappa@prohomine.de

Chiara Gardella

Dept of Pulmonary Disease, G.

Gaslini Institute, Genoa, Italy.

chiaragardella@hotmail.com Michele Ghezzi

Pulmonary Disease Department, G. Gaslini Institute, Genoa, Italy.

Hartmut Grasemann

Division of Respiratory Medicine, Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada.

hartmut.grasemann@sickkids.ca Matthias Griese

Hauner Childrens’ Hospital, University of Munich, Germany.

matthias.griese@med.uni- muenchen.de

Jonathan Grigg

Paediatric Respiratory and Environmental Medicine Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

j.grigg@qmul.ac.uk Susanne Halken

Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense,

Denmark.

Susanne.Halken@rsyd.dk

Graham L. Hall

Paediatric Respiratory Physiology , Telethon Institute for Child Health Research, Perth, Australia.

grahamh@ichr.uwa.edu.au Jürg Hammer

Paediatric Intensive Care and Pulmonology, University-Children’s Hospital Basel, Basel, Germany.

juerg.hammer@unibas.ch Carol-Claudius Hasler

Paediatric Orthopaedics, University Children’s Hospital UKBB, Basel, Switzerland.

carolclaudius.hasler@ukbb.ch Elpis Hatziagorou

Peadiatric Respiratory Unit, 3rd Paediatric Dept, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.

elpcon@otenet.gr Gunilla Hedlin

Astrid Lindgren Children’s

Hospital, Department of Women’s and Children’s Health and Centre for Allergy Research, Karolinska

Institutet, Stockholm, Sweden.

Gunilla.Hedlin@ki.se Armin Irnstetter

Pneumology Dept, University of Munich, Dr. von Haunersches Kinderspital, Munich, Germany.

armin.irnstetter@med.uni- muenchen.de

xviii

Hettie M. Janssens

Department of Paediatric Respiratory Medicine, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam, The Netherlands.

H.Janssens@erasmusmc.nl Andreas Jung

Children`s University Hospital Zurich, Division of Respiratory Medicine, Zurich, Switzerland.

andreas.jung@kipsi.uzh.ch Beate Kampmann

Vaccinology Theme, Medical Research Council (MRC) Unit, The Gambia, Africa.

bkampmann@mrc.gm Ahmad Kantar

Department of Paediatrics, Institutes of Bergamo Hospitals, Bergamo, Italy.

kantar@tin.it Sonia Khirani

A.A.O. Ospedali Riuniti di Bergamo, U.S.C. Pneumologia, Bergamo, Italy.

sonia_khirani@yahoo.fr Sailesh Kotecha

Department of Child Health, School of Medicine, Cardiff University, University Hospital of Wales, Cardiff, UK.

kotechas@cardiff.ac.uk Carolin Kröner

Pediatrics Dept, University of Munich, Munich, Germany.

Carolin.Kroener@med.uni-

muenchen.de

xix

Claudia E. Kuehni

Division of International and Environmental Health, Institute of Social and Preventive Medicine, University of Bern, Switzerland.

kuehni@ispm.unibe.ch Stefania La Grutta

Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e

Immunologia Molecolare, Palermo, Italy.

stefania.lagrutta@ibim.cnr.it Hugo Lagercrantz

Neonatal Research Unit, Department of Woman and Child Health,

Karolinska Institutet, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.

hugo.lagercrantz@ki.se Philipp Latzin

Division of Respiratory Medicine, Department of Paediatrics, University Children’s Hospital of Bern, Bern, Switzerland.

philipp.latzin@insel.ch Salvatore Leonardi

Department of Pediatrics, University of Catania, Catania, Italy.

leonardi@unict.it Anders Lindblad

Dept of Pediatrics, Queen Silvias Hospital, Gothenburg University, Gothenburg, Sweden.

anders.lindblad@vgregion.se

Keith J. Lindley

Great Ormond Street Hospital, London, UK.

k.lindley@ucl.ac.uk Karin C. Lødrup Carlsen

Department of Paediatrics, Women and Children’s Division, Oslo University Hospital, Oslo, Norway.

k.c.l.carlsen@medisin.uio.no Enrico Lombardi

Paediatric Pulmonary Unit, Anna Meyer Paediatric University Hospital, Florence, Italy.

e.lombardi@meyer.it Carmen Luna-Paredes

Hospital Universitario 12 de Octubre, Madrid, Spain.

lunalavin1@yahoo.es Nunzia Maiello

Department of Women, Children and General and Specialized Surgery, Second University of Naples, Naples, Italy.

nunzia.maiello@unina2.it Velia Malizia

Consiglio Nazionale delle Ricerche, Istituto di Biomedicina e

Immunologia Molecolare, Palermo, Italy.

velia.malizia@ibim.cnr.it Lucia Manganaro

Department of Radiological Sciences, Umberto I Hospital, “Sapienza”

University of Rome, Rome, Italy.

lucia.manganaro@uniroma1.it

Mariano Manzionna

Pediatric Department, Monopoli Hospital, Bari, Italy.

mariano.manzionna@alice.it Antonio Martinez-Gimeno Division of Respiratory Medicine, Hospital Universitario 12 de Octubre, Madrid, Spain.

amgimeno@gmail.com Argyro Mazioti

Department of Radiology, General Hospital of Larissa, Larissa, Greece.

argyromazioti@yahoo.gr Andrea Mckee

Paediatric Respiratory Medicine, Royal Brompton Hospital, London, UK.

a.mckee@rbht.nhs.uk Paolo Meglio

Department of Pediatric Allergy, Research Centre, San Pietro Hospital - Fatebenefratelli, Rome, Italy.

paolo.meglio@tiscali.it Erik Melén

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

erik.melen@ki.se Silvia Miano

“Sapienza” University of Rome, Rome, Italy.

silvia.miano@gmail.com Michele Miraglia del Giudice Department of Pediatrics, Second University of Naples, Naples, Italy.

michele.miraglia@unina2.it

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Silvia Montella

Department of Pediatrics, Federico II University, Naples, Italy.

amina2004@virgilio.it Corrado Moretti

Department of Paediatrics Emer- gency and Intensive Care, “Sapienza”

University of Rome, Rome, Italy.

corrado.moretti@uniroma1.it William B. Moskowitz

Department of Pediatrics, The Children’s Hospital of Richmond at VCU, Richmond, VA, USA.

moskowit@hsc.vcu.edu Anne Munck

Paediatric CF Centre Gastrointesti- nal and Pulmonology Department, Robert Debré University Hospital, Paris-Diderot AP-HP, Paris, France.

anne.munck@rdb.ap-hop-paris.fr Antonella Muraro

Food Allergy Centre, Department of Women and Child Health, University of Padua, Padua, Italy.

muraro@pediatria.unipd.it Nadia Nathan

Paediatric Pulmonary Department, Reference Centre for Rare Lung Diseases, AP-HP, Hôpital Trousseau, INSERM UMR S-938, Université Pierre et Marie Curie, Paris, France.

nadia.nathan@trs.aphp.fr Raffaella Nenna

Department of Paediatrics,

“Sapienza” University of Rome, Rome, Italy.

raffaella.nenna@uniroma1.it

xxi

Ambra Nicolai

Department of Paediatrics, University of Rome, Rome, Italy.

ambra10.nic@gmail.com Thomas Nicolai

University Kinderklinik, Munich, Germany.

tnicolai@med.uni-muenchen.de Chinedu Nwokoro

Centre for Paediatrics, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

c.nwokoro@qmul.ac.uk Beatrice Oberwaldner Klinische Abteilung für

Pulmonologie und Allergologie,Univ.

Klinik für Kinder-und

Jugendheilkunde, Graz, Austria.

beatrice.oberwaldner@klinikum- graz.at

Sedat Oktem

Istanbul Medipol University, Division of Pediatric Pulmonology, Istanbul, Turkey.

sedatoktem@hotmail.com Serena Panigada

Pediatric Pulmonary and Allergy Unit, Istituto Giannina Gaslini, Genoa, Italy.

serenapanigada@ospedale-gaslini.

ge.it

Paola Papoff

PICU, Policlinico Umberto I,

“Sapienza” University of Rome, Rome, Italy.

p.papoff@libero.it James Paton

Royal Hospital for Sick Children, Glasgow, UK.

james.paton@glasgow.ac.uk Laura Perrone

Department of Pediatrics, Second University of Naples, Naples, Italy.

laura.perrone@unina2.it Matthew S. Perzanowski

Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.

mp2217@columbia.edu Andreas Pfleger

Respiratory and Allergic Disease Division, Department of Paediatrics and Adolescence Medicine, Medical University of Graz, Graz, Austria.

andreas.pfleger@meduni-graz.at Maria Pia Villa

Dept of Pediatrics, University Hospital, Rome, Italy.

mariapia.villa@uniroma1.it Giorgio Piacentini

Department of Pediatrics, University of Verona, Verona, Italy.

giorgio.piacentini@univr.it

Massimo Pifferi

Department of Pediatrics, University of Pisa, Pisa, Italy.

m.pifferi@med.unipi.it Mariëlle Pijnenburg

Department of Paediatrics/Paediatric Respiratory Medicine, Rotterdam The Netherlands.

m.pijnenburg@erasmusmc.nl Petr Pohunek

Paediatric Pulmonology,

University Hospital Motol, Prague, Czech Republic.

petr.pohunek@LFMotol.cuni.cz Kostas N. Priftis

Respiratory Unit, 3rd Department of Paediatrics, “Attikon” Hospital, University of Athens, Athens, Greece.

kpriftis@otenet.gr Diana Rädler

Pulmonary Dept, University Children´s Hospital, Munich,

Germany.

diana.raedler@med.uni-muenchen.de Adriana Ramirez

ADEP ASSISTANCE, Suresnes, France.

a.ramirez@adepassistance.fr Felix Ratjen

Hospital for Sick Children, Toronto, Canada.

felix.ratjen@sickkids.ca

xxii

Nicolas Regamey

Division of Respiratory Medicine, Department of Paediatrics, Inselspital and University of Bern, Bern,

Switzerland

Nicolas.Regamey@insel.ch Elena Ribera

Pulmonary Disease Department, G. Galini Institute, Genoa, Italy.

Josef Riedler

Children’s Hospital Schwarzach, Salzburg, Austria.

josef.riedler@kh-schwarzach.at Francesca Rizzo

Pulmonary Disease Department, G. Galini Institute, Genoa, Italy.

Paul Robinson

Dept of Respiratory Medicine, Children’s Hospital at Westmead, Westmead, Australia.

paul.robinson1@health.nsw.gov.au Charles C. Roehr

Dept of Neonatology, Charité Berlin, Berlin, Germany.

christoph.roehr@charite.de Malin Rohdin

Neonatal Research Unit, Department of Woman and Child Health,

Karolinska Institutet, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden.

malin.rohdin@ki.se

xxiii

Emmanuel Roilides

Peadiatric Respiratory Unit, 3rd Paediatric Dept, Aristotle University of Thessaloniki, Hippokration

Hospital, Thessaloniki, Greece.

roilides@gmail.com Silvia Rosina Giovanni Rossi

Pulmonary and Allergy Units, Giannina Gaslini Institute, Genova, Italy.

giovannirossi@ospedale-gaslini.ge.it Robert I. Ross-Russell

Department of Paediatrics,

Addenbrooke’s Hospital, Cambridge, UK.

robert.ross-russell@addenbrookes.

nhs.uk Bruce K. Rubin

Children’s Hospital of Richmond at VCU, Richmond, VA, USA.

brubin@vcu.edu Franca Rusconi

Epidemiology Unit, Anna Meyer, Children’s Hospital, Florence, Italy.

f.rusconi@meyer.it Oliviero Sacco

Pulmonary Disease Department, G. Gaslini Institute, Genoa, Italy.

olivierosacco@ospedale-gaslini.ge.it Efstratios Saliakellis

Great Ormond Street Hospital, London, UK.

efstratios.saliakellis@gosh.nhs.uk

Francesca Santamaria

Department of Paediatrics, Federico II University, Naples, Italy.

santamar@unina.it Bianca Schaub

University Children’s Hospital Munich, Munich, Germany.

Bianca.Schaub@med.uni-muenchen.de

Amalia Schiavetti

Department of Paediatrics,

“Sapienza” University of Rome, Rome, Italy.

amalia.schiavetti@uniroma1.it Andreas Schibler

Paediatric Critical Care Research Group, Paediatric Intensive Care Unit, Mater Children’s Hospital, Brisbane, Australia.

andreas.schibler@mater.org.au Nicolaus Schwerk

Department of Pediatrics , Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany.

schwerk.nicolaus@mh-hannover.de Mary Sharp

Neonatology Clinical Care Unit, King Edward Memorial Hospital for Women, Perth, Australia.

Mary.Sharp@health.wa.gov.au Michael Shields

Department of Child Health, Queen’s University of Belfast, Belfast, UK.

m.shields@qub.ac.uk

xxiv

Anita K. Simonds

NIHR Respiratory Biomedical Research Unit, Royal Brompton &

Harefield NHS Foundation Trust, London UK.

A.Simonds@rbht.nhs.uk Shannon J. Simpson

Paediatric Respiratory Physiology, Telethon Institute for Child Health Research, University of Western Australia, Perth, Australia.

shannons@ichr.uwa.edu.au Deborah Snijders

Department of Pediatrics, University of Padova, Padova, Italy.

olanda76@gmail.com Nicoletta Solari

Pulmonary Disease Department, G. Gaslini Institute, Genoa, Italy.

Melinda Solomon

Hospital for Sick Children, Toronto, Canada.

melinda.solomon@sickkids.ca Kevin Southern

Institute of Child Health, University of Liverpool, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK.

kwsouth@liverpool.ac.uk Helen Spencer

Great Ormond Street Hospital, London, UK.

helen.spencer@gosh.nhs.uk

Ben D. Spycher

Division of International and Environmental Health, Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.

bspycher@ispm.unibe.ch Philippe Stock

Charité Kinderklinik mit Schwerpunkt Pneumologie und Immunologie Labor Berlin – Fachbereich Allergologie, Berlin, Germany.

philippe.stock@charite.de Tamara Svobodová

Paediatric Respiratory Division, University Hospital Motol, Prague, Czech Republic.

tamara.svobodova@lfmotol.cuni.cz Giancarlo Tancredi

Department of Paediatrics,

“Sapienza” University of Rome, Rome, Italy.

giancarlo.tancredi@uniroma1.it Caroline Telion

Département d’anesthesie,

Assistance Publique des Hôpitaux de Paris, Hôpital Universitaire Necker Enfants Malades, Paris, France.

caroline.telion@nck.aphp.fr Laura Tenero

Clinica Pediatrica,

Pediatria Verona, Verona, Italy.

lauratenero@hotmail.com Luigi Terracciano

Melloni Paediatria, Melloni University Hospital, Milan, Italy. terrycom1957@

gmail.com

xxv

Guillaume Thouvenin

Paediatric Pulmonary Department, Reference Centre for Rare Lung Diseases, AP-HP, Hôpital Trousseau, INSERM UMR S-938, Université Pierre et Marie Curie, Paris, France.

guillaume.thouvenin@trs.aphp.fr Harm A.W.M. Tiddens

Pediatric pulmonology, Erasmus Medical Center, Sophia Children’s Hospital, Rotterdam,

The Netherlands.

h.tiddens@erasmusmc.nl Toyin Togun

Vaccinology Theme, Medical Research Council (MRC) Unit, The Gambia, Africa.

ttogun@mrc.gm Daniel Trachsel

Paediatric Intensive Care and Pulmonology, University-Children’s Hospital Basel, Basel, Switzerland.

daniel.trachsel@ukbb.ch JohnTsanakas

Peadiatric Respiratory Unit, 3rd Paediatric Dept, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki, Greece.

tsanakasj@ath.forhnet.gr Martina Tubaro

Pediatric Department, University of Trieste, Trieste, Italy.

martina.tubaro@gmail.com

Steve Turner

Child Health, Royal Aberdeen Children’s Hospital, Aberdeen, UK.

s.w.turner@abdn.ac.uk Anja A.P.H. Vaessen-Verberne Department of Paediatrics, Amphia Hospital, Breda, The Netherlands.

AVaessen-Verberne@amphia.nl Horst von Bernuth

Pediatric Pneumology and

Immunology, Charité Berlin, Berlin, Germany.

Horst.von-Bernuth@charite.de Marcel van Straten

Department of Radiology, Erasmus MC, Rotterdam, The Netherlands.

marcel.vanstraten@erasmusmc.nl Erika von Mutius

University Children’s Hospital, Ludwig Maximilians-University, Munich, Germany.

erika.von.mutius@med.uni- muenchen.de

Colin Wallis

Respiratory Unit, Great Ormond Street Hospital, London, UK.

Colin.Wallis@gosh.nhs.uk Sophie Yammine

Pediatric Pulmonology Dept, University of Bern, Bern, Switzerland.

sophie.yammine@insel.ch

xxvi

Ralf Zarbock

Pediatrics Dept, University of Munich, Munich, Germany.

Ralf.Zarbock@med.uni-muenchen.de Anna Maria Zicari

Department of Paediatrics,

“Sapienza” University of Rome, Rome, Italy.

annamaria.zicari@uniroma1.it

Zorica Zivkovic

Medical Center Dr Dragisa Misovic, Hospital for Lung Diseases and Tuberculosis, Belgrade, Serbia.

zoricazivkovic@beotel.net

xxvii

Preface

The dissemination of knowledge, and medical and public education constitute a fundamental objective of the ERS mission; and the ERS School aims to provide excellence in respiratory medicine education. In 2005, the ERS School started the very ambitious HERMES (Harmonised Education in Respiratory Medicine for European Specialists) project. Since then, seven HERMES Task Forces have formed to standardise training and education within different specialties of respiratory medicine. To support the implementation of various educational activities, the ERS has produced a series of Handbooks as educational tools, with the ERS Handbook of Respiratory Medicine being the first textbook to be launched in 2010.

Starting in 2007, the Paediatric Respiratory Medicine Task Force, using a formal consensus process and working with numerous experts throughout Europe, developed a HERMES syllabus (description of the competencies required) and a HERMES curriculum (description of how competencies should be taught, learned and assessed), as well as a voluntary European examination in paediatric respiratory medicine. With the paediatric HERMES project now well underway, it is an opportune time to publish an ERS Handbook of Paediatric Respiratory Medicine to provide a comprehensive update for specialists within this field of respiratory medicine. The content of this Handbook follows the HERMES syllabus and curriculum to provide a compact, state-of-the-art textbook, with each of the sections prepared by senior specialists and clinical experts in the field.

We hope that this Handbook will not only inform our trainees but also provide an easily accessible and comprehensive update for colleagues at all levels of seniority across paediatric respiratory medicine. Thus, this educational tool is intended to make a significant contribution to increasing the standards of training in paediatric respiratory medicine throughout Europe and, ultimately, to improving the care of children with respiratory disease.

We are indebted to the ERS School Committee and to the ERS staff who so thoroughly and thoughtfully curated this Handbook, and last, but not least, to all the contributors who have shared their knowledge and experience with the readers.

Ernst Eber and Fabio Midulla Chief Editors

“Tell me and I forget.

Teach me and I remember.

Involve me and I learn.”

Benjamin Franklin

xxviii

Get more from this Handbook

Also available from the ERS

Go to erm.erjsournals.com to view the table of contents for each Monograph To buy a copy of these Monographs please visit ersbookshop.com

Paediatric Asthma

Edited by Kai-Håkon Carlsen and Jorrit Gerritsen

EUROPEAN RESPIRATORY

EUROPEAN RESPIRATORY N U M B E R 5 6 / J U N E 2 0 1 2

Paediatric Lung Function

Edited by U. Frey and P.J.F.M. Merkus Monograph 47, March 2010

EUROPEAN RESPIRATORY SOCIETY

EUROPEAN RESPIRATORY MONOGRAPH

By buying the ERS Handbook of Paediatric 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 the inside of the front cover. 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.

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.

European Respiratory Monograph 56:

Paediatric Asthma covers all aspects of paediatric asthma from birth through to the start of adulthood. It considers diagnostic problems in relation to the many phenotypes of asthma, covers the treatment of both mild-to-moderate and severe asthma, and discusses asthma exacerbations as well as exercise- induced asthma. The issue provides an update on the pathophysiology of asthma, the role of bacterial and viral infections, and the impact of environmental factors, allergy, genetics and epigenetics.

European Respiratory Monograph 47: Paediatric Lung Function offers a comprehensive review of the lung function techniques that are currently available in paediatric pulmonology.

This field is developing rapidly and equipment and software can tell us more than ever about respiratory physiology in health and disease in children with various lung disorders.

The issue provides a state-of-the-art review of the techniques, with a special focus on the clinical applications and usefulness in diagnosing and treating children with chronic lung disease.

xxix

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

FEV

1

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

V'

^E

Minute ventilation

Anatomy and development of the respiratory system

Robert Dinwiddie

Anatomy of the lower respiratory tract The lower respiratory tract consists of the trachea, hila of the lungs, large bronchial airways, small airways and alveoli. The larynx lies at the junction of the upper and lower respiratory tract and since it is a frequent source of pathology in children its anatomy will also be described. The mediastinum contains the heart and its related cardiac structures:

N

_thymus,

N

_trachea,

N

thoracic lymph nodes,

N

thoracic duct,

N

vagus nerves,

N

recurrent laryngeal nerves,

N

autonomic nerve plexus.

Another important structure which passes through the thoraxviathe mediastinum is the oesophagus.

Larynx The larynx can be divided into three areas (fig. 1):

N

supraglottis,

N

_glottis,

N

subglottis.

It extends from the tip of the epiglottis to the lower border of the cricoid cartilage. In the neonatal period it lies at the level of cervical vertebrae C2–C3 and in adults at the level of C3–C6. It contains major cartilaginous structures including the epiglottic, thyroid and cricoid cartilages, and the paired arytenoid cartilages. The vocal apparatus is muscular and consists of the false vocal cords (vestibular folds) and the true vocal cords (folds). The true vocal cords are drawn together by adduction of the arytenoid cartilages. The larynx is bounded on each side by the aryepiglottic folds. These lie between the lateral borders of the epiglottis anteriorly and the upper edge of the arytenoid cartilages, which join posteriorly to form the interarytenoid cartilage. The larynx is chiefly innervated by branches of the vagus nerves. The subglottic area is supplied by the recurrent laryngeal nerves which also arise from the vagal nervous system. These supply the vocal cords and damage to them can result in unilateral or bilateral vocal cord paralysis.

Hila Each hilum forms the root of the lung joining it to the heart and the trachea.

Structures that pass through this area on each side include the major bronchus, pulmonary artery, superior and inferior pulmonary veins, bronchial artery and vein, vagus nerves, pulmonary autonomic nerves and lymphatic vessels. Lymph nodes within each hilum are often directly involved in Key points

N

The anatomy of the thorax can be divided into the lungs, heart, mediastinum, pleura, diaphragm and chest wall.

N

The lungs can be further subdivided into the trachea, bronchi, hila, lobes and preacinar and acinar regions.

N

The mediastinum contains the thymus, the heart and its associated structures, thoracic lymphatics, sympathetic and parasympathetic nerves and the oesophagus.

disease processes spreading systemically from the lung parenchyme.

Trachea and bronchi The trachea is made up of anterolateral cartilaginous rings and a fibro-muscular posterior wall. The trachea divides into the right and left main bronchi (fig. 2). The right main bronchus is more vertically orientated than the left resulting in a greater percentage of inhaled foreign bodies entering that side. The right main bronchus gives off the right upper lobe bronchus and continues as the bronchus intermedius. This divides into the right middle and lower lobe bronchi. The right upper lobe bronchus divides into three segmental bronchi: apical, posterior and anterior. The right middle lobe bronchus divides into two: the medial and lateral segments of the middle lobe. The right lower lobe bronchus gives off a superior

segmental branch and then medial, lateral, anterior and posterior segments. Segmental bronchi are particularly important to recognise during bronchoscopy. The left main bronchus divides into the left upper and lower lobe bronchi. The left upper lobe bronchus gives off the superior division supplying the apical, anterior and posterior branches of the left upper lobe. The inferior division of the left upper lobe supplies the superior and inferior segments of the lingua.

The left lower lobe bronchus then descends laterally to give off a posteriorly located apical segment of the left lower lobe and then the antero-medial, lateral and posterior basal segmental bronchi. After dividing into segmental bronchi the airways further subdivide into subsegmental bronchi and then, from generation seventeen onwards,

become bronchioles before finally becoming a terminal bronchiole (table 1).

The portion of the respiratory tree from the trachea down to the terminal bronchioles is known as the preacinar region. The acinar region comprises the gas exchanging units and includes seven further branches of the distal lung made up of the respiratory bronchioles, alveolar ducts and the alveolar sacs.

The blood supply to the trachea and bronchi is principallyviathe bronchial arteries and the intercostal arteries, which ariseviathe systemic circulation from the aorta. The upper trachea is supplied by branches of the inferior thyroid arteries.

The venous drainage from the trachea returnsviathe inferior thyroid venous plexus. The tracheal nerve supply isvia the vagus nerves, the recurrent laryngeal nerves, supplying parasympathetic fibres and sympathetic nerves arising from the upper ganglia of the sympathetic trunks.

Vestibular fold (false cord) Epiglottis

Trachea Interarytenoid cartilage Aryepiglottic fold Vocal cord (fold)

Figure 1. Laryngeal anatomy as seen from above.

Figure 2. The trachea and bronchi.ßP.L. Shah.

Pulmonary vasculature and lymphatic drainage The pulmonary artery carries deoxygenated blood to the lungs, thereafter subdividing and eventually becoming alveolar capillaries. Oxygenated blood then returnsviathe pulmonary capillary and venous circulation to the left atrium. The pulmonary arteries lie anterior to the carina and main bronchi. Each artery then enters the lungviathe hilum. There are two pulmonary veins on each side (superior and inferior) that pass in front of and below the adjacent pulmonary artery and major bronchus.

The lymphatic drainage of the lungs, pleurae and mediastinum isviavisceral lymph nodes. These are arranged along the bifurcation of the trachea, major bronchi and peripheral bronchi. Further nodes are situated in the mediastinum. The output of most of these vessels is into a

bronchomediastinal trunk on each side of the trachea. Another major lymphatic vessel in the chest is the thoracic duct. This starts in the abdomen and enters the chest on the right side through the aortic hiatus of the diaphragm. It then ascends close to the

aorta, subsequently crossing to the left side and runs alongside the oesophagus. It ends in the neck where it enters the left internal jugular vein. The right bronchomediastinal lymphatic trunk joins the right lymphatic duct and enters the venous circulation at the junction of the subclavian and internal jugular veins. Leakage of fluid from the thoracic duct is the primary cause of chylothorax in the paediatric age group.

Mediastinum The mediastinum is divided into superior, anterior, middle and posterior portions. It contains the thymus, which develops from the third branchial pouch and has two lobes located in the superior and anterior mediastinum. Its principle function is the programming of thymocytes.

Thymocytes, which originate from bone marrow, mature into T-lymphocytes and have major immune functions, especially in relation to resistance to infection and the development of atopic status and allergy. T- helper (Th)-1 lymphocytes form part of the cellular immune system and are principally involved in the response to infection. Th-2 lymphocytes are part of the humoral immune system mainly involved in allergic Table 1. Anatomical subdivisions of the lung

Trachea

Right main bronchus Left main bronchus

Segmental bronchi right Segmental bronchi left

Right upper lobe: Left upper lobe:

Apical Apical

Posterior Posterior

Anterior Anterior

Right middle lobe: Left middle lobe:

Lateral Superior

Medial Inferior

Right lower lobe: Left lower lobe:

Superior (apical) Apical

Medial basal Antero-medial basal

Anterior basal Lateral basal

Lateral basal Posterior basal

Posterior basal

responses resulting in atopy and allergy- related diseases including anaphylaxis, asthma and allergic rhinitis.

The thymus gland is proportionately largest in infancy and early childhood; by

adolescence it has begun to atrophy and greatly decreases in size.

Mediastinal lymph nodes are located in the pre-tracheal, paratracheal and subcarinal areas, as well as adjacent to the oesophagus.

Diaphragm The diaphragm is the principal muscle of respiration in childhood. It consists of a fibro-muscular sheet of tissue that separates the thorax from the abdomen.

It is comprised of a central membranous tendon to which the muscles of the diaphragm are attached. These comprise muscles arising from the xiphoid process of the lower sternum, the lower six costal cartilages and the upper two to three lumbar vertebrae. Diaphragmatic muscles are more easily fatigued in infancy because they contain a smaller proportion of fatigue- resistant muscle fibres than in later life. The diaphragm is perforated by a number of hiatal openings through which important structures pass from the thorax to the abdomen. These include the oesophagus (oesophageal hiatus), the aorta (aortic hiatus) and the inferior vena cava (vena caval hiatus). The diaphragm is supplied by the right and left phrenic nerves arising through the cervical vertebrae C3, C4 and C5.

Chest wall The chest wall includes the ribs and the intercostal muscles. The ribs initially develop as cartilage. The chest wall functions as a pump which performs the respiratory movements driving respiration itself. In the fetus the ribs are almost at right angles to the vertebral column and the muscles of the diaphragm are arranged more horizontally than in later life. Chest movements are therefore less efficient in early life than later life when the child adopts a more upright posture. The cartilaginous nature of the ribs also makes the chest wall less stiff, thus, resulting in the potential for paradoxical movements and indrawing of the thoracic cage during inspiration,

especially in preterm infants. Intercostal muscles are also less active during rapid eye movement (REM) sleep which lasts twice as long in infancy as in later life. As the child matures and spends more time awake and in the vertical position, gravity acts on the ribs and intercostal muscles pulling them downwards. The chest also becomes less circular in shape and more ovoid, particularly in the preschool years. The rib cage becomes increasingly calcified with age and consequently stiffer which improves its mechanical efficiency.

Development of the lungs

Lung development starts very early in fetal life, just before 28 days of gestation, as an endodermal outgrowth of the fetal gut called the ventral diverticulum. Although almost all of the lung structure is in place by the time of birth the process continues throughout childhood into adolescence.

Intrauterine lung development Lung developmentin uterois divided into four periods.

N

Embryonic: 3rd to 7th week of gestation.

N

Pseudoglandular: 7th to 17th week.

N

Canalicular: 17th to 27th week.

N

Alveolar period: from 27th week to term.

Embryonic period (3–7 weeks): During this period the initial lung bud develops as an endodermal groove from the fetal foregut (respiratory diverticulum). The lining of the larynx, trachea, major airways and alveoli is endodermal in origin. The thyroid, cricoid and arytenoid cartilages and their associated muscles, originating from the mesoderm of the fourth and sixth branchial arches, also develop during this period. The developing tracheobronchial tree then subdivides into the major bronchi, lobar bronchi and peripheral airways. Other locally developing mesodermal tissues influence this

branching pattern. At the end of this period the major subdivisions of lung anatomy have already formed and although the associated blood supply is not fully developed each lung bud is suppliedviathe pulmonary trunk, which appears at 5 weeks gestation from the sixth bronchial arch and divides into right and left branches. Each

lung bud is also connected to the evolving left atrium by a pulmonary vein. The associated capillaries begin their

development in the adjacent mesenchyme.

Pseudoglandular period (7–17 weeks): During this period there is further rapid branching of the airways. By 16 weeks the terminal bronchioles have developed and airway columnar and cuboidal lining cells have appeared. Fetal lung fluid develops and is propelled through the airways by fetal breathing movements first seen at around 10 weeks of gestation with important consequences for volume expansion of the fluid-filled lungs. Other specialised tissues develop including the cilia from 6 weeks, which becomes fully developed, including in the trachea, by 18 weeks. Cartilage and lymph vessels develop from 10 weeks onwards. These spread peripherally through the developing lungs. Goblet cells, mucus glands and airway muscles also first appear at this time and continue their development throughout prenatal and post-natal life. The main pulmonary arteries and veins develop further; the right pulmonary artery arises from the proximal part of the sixth right branchial arch following which the distal part degenerates. The left pulmonary artery arises from the sixth left aortic arch which gives off the main artery and then continues

as the arterial duct (ductus arteriosus) and remains patent until the early period of adaptation to post-natal life. Bronchial arteries also develop directly from the aorta.

The more distal preacinar arteries develop and are fully present by 16 weeks.

Canalicular period (17–27 weeks): At this stage the lungs develop their distal architecture. The peripheral airways elongate and the epithelial lining cells become cuboidal in shape in the lower airway generations. Mesodermal tissue thins out and the pulmonary microcirculation matures. Terminal bronchioles, respiratory bronchioles and distal alveolar sacs develop rapidly. The acinus, which forms the distal gas exchange unit of the lung, develops its final structure by 24 weeks; immediately before this time thin-walled saccules appear to develop into individual alveoli. The most peripheral pulmonary vascular structures develop as intimately associated alveolar capillary units to form a blood–gas barrier sufficient to maintain extrauterine life even at this gestation (fig. 3).

The alveolar lining cells subdivide into two types: Type I and Type II. Each is

histologically distinguished by 24 weeks gestation. Type I (gas exchanging) cells occupy 95% of the alveolar lining. Primary surfactant production occurs in Type II cells.

Trachea Major bronchi

Bronchioli

Terminal Respiratory Ducts Sac Alveoli

3 3 3

bronchi

10–15 8–10 Airway

generations

Preacinus^# Acinus^¶

1 1

Segmental/

subsegmental

Figure 3. Anatomy of the tracheobronchial tree.^#: this region comprises the conducting portion including trachea, bronchi and bronchioli to terminal bronchioles;^": this region comprises a gas exchanging unit (with alveoli) and includes respiratory bronchioli, alveolar ducts and alveolar sacs. Reproduced from Dinwiddie (1997), with permission from the publisher.