The Pediatric Lung PDF
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I Respiratory Pharmacology and Pharmacotherapy Series Editors: Dr. David Raeburn Dr. Mark A Giembycz Discovery Biology Department of Thoracic Medicine Rhone-Poulenc Rorer Ltd National Heart and Lung Institute Dagenham Research Centre Imperial College of Science, Technology and Medicine Dagenham London SW3 6L Y Essex RM 10 7XS England England rhe Pediatric Lung Edited by R. W. Wilmott Springer Basel AG Editor: Robert W. Wilmott, M.D. Director, Pulmonary Medicine, Allergy, and Clinical Immunology The Hubert and Dorothy Campbell Professor of Pediatric Pulmonology Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati, OH 45229-3039 USA Library of Congress Cataloging-in-Publication Data A CIP catalogue record for this book is available from the library of Congress, Washington D.C., USA Deutsche Bibliothek Cataloging-in-Publication Data The pediatric lung / ed by R. W. Wilmott. - Basel; Boston: Berlin: Birkhauser, 1997 (Respiratory pharmacology and pharmacotherapy) Basic mechanisms and clinical perspectives. - 1997 ISBN 978-3-0348-9845-4 ISBN 978-3-0348-8960-5 (eBook) DOI 10.1007/978-3-0348-8960-5 The publisher and editors cannot assume any legal responsibility for information on drug dosage and admini stration contained in this publication. The respective user must check its accuracy by consulting other sources of reference in each individual case. The use of registered names, trademarks, etc. in this publication, even if not identified as such, does not imply that they are exempt from the relevant protective laws and regulations or free for general use. This work is subject to copyright. AII rights are reserved, whether the whole or part of the material is con cerned, specifically the rights of translation, reprinting, re-use of illustrations, recitation, broadcasting, repro duction on microfilms or in other ways, and storage in data banks. For any kind of use the permission of the copyright holder must be obtained. © 1997 Springer Basel AG Originally published by Birkhauser Verlag in 1997 Printed on acid-free paper produced from chlorine-free pulp. TCF = Cover design: Markus Etterich ISBN 978-3-0348-9845-4 987654321 Contents List of Contributors VII Introduction . . . . IX 1. Aerosol Delivery Systems in Children S. G. Devadason and P. N. Le Souej . 1 2. Nedocromil Sodium in Children P. Konig . ........... . ............... 27 3. Corticosteroids in Pediatric Asthma H A. Wojtczak and J. S. Wagener . . . . . . . .. 41 4. Viral Pneumonia and Antiviral Therapy in Children MA. Fiedler and J. M Stark .. . . . . . . . . . . .... 83 5. Anti-inflammatory Therapies for Chronic Lung Diseases in Children R.S.Amin andA.HAssa'ad ................... 113 6. Treatment of Acute Life-Threatening Asthma in Children M Kattan and J.M Hojsak ................ 137 7. Mucoactive Agents: Old and New B.K. Rubin, R.P. Tomkiewicz and M King ............ 155 8. Aerosol Therapies for Cystic Fibrosis C. E. Harris and R. W. Wilmott .... 181 9. Surfactant Replacement Therapies in Children D. A. Evans and J. A. Whitsett . . . . . . . . . 199 10. Gene Therapy for Cystic Fibrosis Lung Disease B. C. Trapnell . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 11. New Therapies for Asthma C. M Kercsmar and J. C. Carl ...... 259 12. The Physiology and Pathophysiology of Nitric Oxide in the Lung C. SzabO and A. L. Salzman . . . . . . . . . . . . . . . . . . . . 279 13. Pharmacological Strategies for the Treatment of the Basic Defect in Cystic Fibrosis B. Wainwright, P. Lovelock and C. Wainwright . 311 Index ..................... . 333 Contributors Raouf S. Amin, Division of Pulmonary Medicine, Allergy and Clinical Immunology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA Amal H. Ass'ad, Division of Pulmonary Medicine, Allergy and Clinical Immunology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA John C. Carl, Case Western Reserve University, Department of Pedia trics, Pediatric Pulmonology, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA Sunalene G. Devadason, Department of Paediatrics, University of Western Australia, and Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, WA 6001, Australia Daniel A. Evans, Division of Pulmonary Medicine, Allergy and Clinical Immunology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA Michael A. Fiedler, Division of Pulmonary Medicine, Allergy and Clini cal Immunology, Children's Hospital Medical Center, Cincinnati: Ohio 45229-3039, USA Christopher E. Harris, Division of Pulmonary Medicine, Allergy and Clinical Immunology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA Joanne M. Hojsak, Department of Pediatrics, Pediatric Pulmonology and Critical Care Division, Mount Sinai School of Medicine, New York, New York 10029, USA Meyer Kattan, Department of Pediatrics, Pediatric Pulmonology and Critical Care Division, Mount Sinai School of Medicine, New York, New York 10029, USA Carolyn M. Kercsmar, Case Western Reserve University, Department of Pediatrics, Pediatric Pulmonology, Rainbow Babies and Children's Hospital, Cleveland, Ohio 44106, USA Malcolm King, University of Alberta, Edmonton, Canada Peter Konig, Department of Child Health, University of Missouri, Columbia, Missouri 65212, USA Peter N. Le Souef, Department of Paediatrics, University of Western Australia, and Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, WA 6001, Australia Paul Lovelock, Centre for Molecular and Cellular Biology, The University of Queensland, St. Lucia 4072, Queensland, Australia Bruce K. Rubin, Allergy and Respirtory Medicine, Department of Pedia trics, Brenner Children's Hospital, Winston-Salem, North Carolina 27157-1081. USA VIII Contributors Andrew L. Salzman, Division of Critical Care, Children's Hospital Medi cal Center, Cincinnati, Ohio 45229-3039, USA James M. Stark, Division of Pulmonary Medicine, Allergy and Clini cal Immunology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA Csaba Szabo, Division of Critical Care, Children's Hospital Medical Cen ter, Cincinnati, Ohio 45229-3039, USA Robert P. Tomkiewicz, St. Louis University School of Medicine, St. Louis, Missouri 63104-1095, USA Bruce C. Trapnell, Department of Virology, Genetic Therapy Inc., and Department of Medicine, Georgetown University Medical Center, Washington D.C. 20007, USA Jeffrey S. Wagener, Department of Pediatrics, The Children's Hospital and University of Colorado Health Sciences Center, Denver, Colorado 80216, USA Brandon Wainwright, Centre for Molecular and Cellular Biology, The Uni versity of Queensland, St. Lucia, Queensland 4072, Australia Jeffrey A. Whitsett, Divisions of Pulmonary Biology and Neonatology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA Claire Wainwright, Department of Respiratory Medicine, Royal Children's Hospital, Herston 4001, Australia Robert W Wilmott, Division of Pulmonary Medicine, Allergy and Clini cal Immunology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA Henry A. Wojtczak, Department of Pediatrics, The Children's Hospital and University of Colorado Health Sciences Center, Denver, Colorado 80216, USA Introduction This volume in the Respiratory Pharmacology and Pharmacotherapy series is the first one dedicated to the topic of the pediatric lung. When thinking about this volume, I was faced with the dilemma of whether to take one subject, such as cystic fibrosis, and deal with it in depth or whether to take several topics and to give them a less exhaustive treatment. The final book is a compromise: I have tried to identify authors who would summar ize the newest developments in pediatric pulmonology, while providing an appropriate level of detail and, at the same time, cover a comprehensive range of diseases from asthma to cystic fibrosis to the acute respiratory distress syndrome in children. The chapter on aerosol delivery systems in children by Drs. Devadason and Le Souef is of general interest and provides data that is applicable to many respiratory diseases. Current therapy for asthma is reviewed in detail in a series of chapters. There is a chapter on the place ofn edocromil sodium in the treatment of pediatric asthma by Dr. Konig, a review of new agents for asthma by Drs. Kercsmar and Carl, a chapter on corticosteroids in pediatric asthma by Drs. Wojtczak and Wagener, and a discussion of the management of acute life-threatening asthma by Drs. Kattan and Hojsak. General topics include the use of mucoactive agents, reviewed by Drs. Rubin, Tomkiewicz, and King, a review of the role of nitric oxide in the lung by Drs. CzabO and Salzman, a description of the place of anti-inflam matory therapies for chronic lung disease in children by Drs. Amin and Assa'ad, and a chapter on surfactant replacement therapy in children by Drs. Evans and Whitsett. A topic dear to my heart is the treatment of cystic fibrosis, and this is covered comprehensively. Anti-inflammatory therapy for cystic fibrosis is reviewed by Drs. Amin and Assa'ad, and aerosol therapies for cystic fibrosis are summarized in a chapter by Dr. Harris and myself. The hottest areas in cystic fibrosis research are gene therapy, and pharmacological agents to activate CFTR. The current status of gene therapy for cystic fibro sis lung disease is reviewed by Dr. Trapnell, and the current pharmacologic strategies to increase CFTR expression and function in cystic fibrosis are reviewed by Dr. Wainwright. Finally, no book of this type would be complete without coverage of the pharmacology of viral infections in children, these being so common and severe in impact, and this is covered in a chapter on viral pneumonia and antiviral therapy by my Cincinnati colleagues, Drs. Stark and Fiedler. In summary, I have tried to review what is new in the treatment of children's lung diseases and to cover the more common of the pediatric respiratory disorders in a way that will be useful for the clinician, and with enough detail to be of value to the clinical researcher. x Introduction I thank Linda Dixon, the administrative coordinator of our department, for her help with editing the book and preparing the final manuscripts. I am indebted to Elizabeth Beckett and Petra Gerlach at Birkhauser Publishing Ltd. for their encouragement and support and to Dr. David Raeburn and Dr. Mark Giembycz for inviting me to be the editor of this volume. Robert W. Wilmott The Pediatric lung ed. by R. W. Wilmott © 1997 Birkhauser Verlag Basel/Switzerland CHAPTER 1 Aerosol Delivery Systems in Children * Sunalene G. Devadason and Peter N. Le souer Department of Paediatrics, University of Western Australia, and Department of Respiratory Medicine, Princess Margaret Hospitalfor Children, Perth, Western Australia, Australia I Introduction 1.1 Advantages of Aerosols for Drug Delivery 2 Principles of Aerosol Delivery 2.1 Physical Mechanisms of Deposition 2.1.1 Inertial Impaction 2.1.2 Sedimentation 2.1.3 Diffusion 2.1.4 Electrostatic Attraction 3 Assessment Techniques 3.1 Generation 3.1.1 Particle Size Distribution, 3.1.2 Total Drug Output 3.2 Delivery 3.3 Deposition 4 Problems with Aerosol Delivery to Infants and Children 4.1 Advice Given to Parents 4.2 Route ofInhalation 4.3 Small Tidal Volume and Inspiratory Flow 5 Dosage Considerations 5.1 Calculating Dose 5.2 Minimising Systemic Dose from Inhaled Drugs 6 Methods of Delivery 6.1 Pressurised Metered Dose Inhalers (PMDIs) 6.2 Dry Powder Inhalers (DPIs) 6.3 Nebulisers 7 Recommendations 7.1 General 7.2 Devices 7.2.1 Pressurised Metered Dose Inhalers 7.2.2 Pressurised Metered Dose Inhalers/Spacers 7.2.3 Dry Powder Inhalers 7.2.4 Nebulisers 8 The Ideal Delivery System References * Author for correspondence.
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