Table Of ContentAsthma Treatment
A Multidisciplinary Approach
NATO ASI Series
Advanced Science Institutes Series
A series presenting the results of activities sponsored by the NATO Science Committee,
which aims at the dissemination of advanced scientific and technological knowledge,
with a view to strengthening links between scientific communities.
The series is published by an international board of publishers in conjunction with the
NATO Scientific Affairs Division
A Life Sciences Plenum Publishing Corporation
B Physics New York and London
C Mathematical and Physical Sciences Kluwer Academic Publishers
D Behavioral and Social Sciences Dordrecht, Boston, and London
E Applied Sciences
F Computer and Systems Sciences Springer-Verlag
G Ecological Sciences Berlin, Heidelberg, New York, London,
H Cell Biology Paris, Tokyo, Hong Kong, and Barcelona
1 Global Environmental Change
Recent Volumes in this Series
Volume 224—Drug Epidemiology and Post-Marketing Surveillance
edited by Brian L. Strom and Giampaolo Velo
Volume 225—Computational Aspects of the Study of Biological Macromolecules
by Nuclear Magnetic Resonance Spectroscopy
edited by Jeffrey C. Hoch, Flemming M. Poulsen,
and Christina Redfield
Volume 226—Regulation of Chloroplast Biogenesis
edited by Joan H. Argyroudi-Akoyunoglou
Volume 227—Angiogenessi in Health and Disease
edited by Michael E. Maragoudakis, Pietro Gullino, and Peter I. Lelkes
Volume 228—Playback and Studies of Animal Communication
edited by Peter K. McGregor
Volume 229—Asthma Treatment—A Multidisciplinary Approach
edited by D. Olivieri, P. J. Barnes, S. S. Hurd, and G. C. Folco
Volume 230—Biological Control of Plant Diseases: Progress and Challenges
for the Future
edited by E. C. Tjamos, G. C. Papavizas, and R. J. Cook
Series A: Life Sciences
Asthma Treatment
A Multidisciplinary Approach
Edited by
D. Olivieri
University of Parma
Parma, Italy
P. J. Barnes
National Heart and Lung Institute
London, United Kingdom
S. S. Hurd
National Institutes of Health
Bethesda, Maryland
and
G. C. Folco
University of Milan
Milan, Italy
Springer Science+Business Media, LLC
Proceedings of a NATO Advanced Study Institute
on Asthma Treatment—A Multidisciplinary Approach,
held May 19-29, 1991,
in Erice, Sicily, Italy
NATO-PCO-DATA BASE
The electronic index to the NATO ASI Series provides full bibliographical references (with key-
words and/or abstracts) to more than 30,000 contributions from international scientists published
in all sections of the NATO ASI Series. Access to the NATO-PCO-DATA BASE is possible in two
ways:
—vai online FILE 128 (NATO-PCO-DATA BASE) hosted by ESRIN, Via Galileo Galilei, I-00044
Frascati, Italy.
Additional material to this book can be downloaded from http://extra.springer.com.
ISBN 978-1-4613-6525-9 ISBN 978-1-4615-3446-4 (eBook)
DOI 10.1007/978-1-4615-3446-4
© 1992 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1992
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
From the 19-29 May 1991 the NATO ASI Course PAsthma Treatment: A
P
Multidisciplinary Approach was held in Erice, on the rocky North West
Coast of Sicily, facing the ancient Phoenician shore of the African
Continent.
Sixty NATO sponsored participants arriving from many different European
Countries - Nato members and non - attended the course. Qualified
researchers from Europe and the United States held extensive lectures,
short meetings and small informal group discussions.
Erice is a magical place which draws together people from different
backgrounds and cultures under her Mediterrean charm, recreating the
ancient Greek openair discussion atmosphere.
And so, during the 10 days gathering, the extensive willingness of the
senior investigators and the laudable enthusiasm of the younger
participants was stimulated. All of the most recent findings in the
biology and the pharmacology of Asthma were discussed, initially behind
closed doors, to be unhurriedly continued along the alley ways of the
"Cittadella della Scienza", in Erice's small restaurants, and on her
deserted beaches.
The texts collected here are testimony to the high quality of the
investigators contributions as well as their far reaching interests.
I think that a Director of such a Course would be adequatly satisfied
by merely considering the enthusiasm and high level involvement of every
participant. He could not have been more satisfied after having considered
the proceedings summerizing the scientific content of the meeting.
Prof. Dario Olivieri
Director of the Course
v
CONTENTS
Histopathology of Bronchial Asthma and the Effects of Treatment 1
P.K. Jeffery
Neural Control of Airways 9
P.J. Barnes
Airway Neuropeptides 21
P.J. Barnes
Potential Role of Mast Cell Proteases in Asthma 51
J.A. Nadel
Human Mast Cells, Basophils and Their Mediators 63
v. Casolaro, C. Stellato, G. de Crescenzo, M. Triggiani
and G. Marone
Platelets and Asthma 81
J. Morley, K. Hoshiko and I.D. Chapman
The Maximal Bronchoconstriction Induced by Methacholine is not
Altered by Platelet Activating Factor 89
S. Bellofiore, G.O. Di Maria, N. Ciancio, F.L.M. Ricciardolo,
M. Rinaldo, N. Sapienza and A. Mistretta
Leukotrienes and Asthma 93
J. Rokach, M. Barth, T. Bach, M. Belley, E. Champion, C. Chan,
L. Charette, S. Charleson, R.N. DeHaven, D. Denis, R. Dixon,
G. Eiermann, D. Ethier, J. Evans, A.W. Ford-Hutchinson,
R. Fortin, A. Foster, R. Frenette, J.Y. Gauthier, J. Gillard,
Y. Girard, Y. Guidon, P. Hamel, S. Hopple, J. Humes, L. Hupe,
T.R. Jones, S. Leger, C. Leveille, A., Lord, S. Luell, P. Masson,
C.S. McFarlane, D.E. McIntyre, J. Metzger, R. Meurer, D. Miller,
H. E. Morton, E. Opas, S. Pacholok, L. Peterson, H. Piechuta,
S.S. Pong, D. Riendeau, C. Rouzer, H. Williams, R. Young,
c. Yoakim, and R. Zamboni
Plasma Exudation in Asthma and its Pharmacological Control 105
c.G.A. Persson
vii
Synthesis and Regulation of IgE in Asthma 117
G. Del Prete
Modulation of Mediator Release from Human Fct'RI+ Cells 131
A. Genovese, G. Spadaro, A. Ciccarelli, A. de Paulis, R. Cirillo
and G. Marone
Osmotic and Ionic Factors in Bronchial Responsiveness 145
S. Bianco, M. Robuschi, A. Vaghi, G. Gambaro, S. Spagnotto,
M.G. Pieroni, R. Metella Refini and P. Sestini
Airway Responsiveness, Late-Phase Response, and Inflammation in
Allergic Asthma 155
V. Brusasco, E. Crimi and G.A. Rossi
Injury and Repair of the Airway Epithelium in Asthma 161
S.1. Rennard, K.A. Rickard, D.J. Romberger, J.D. Beckmann,
O. Sacco, M. Kawamoto and J.R. Spurzem
Bronchoalveolar Lavage: Its Application in Asthma 171
S.I. Rennard and K. Rickard
Bronchial Asthma and Pulmonary Gas Exchange 183
R. Rodriguez-Roisin
Allergen Inhalation Increases Cough Sensitivity in Subjects with
Allergic Asthma 189
N. Ciancio, S. Bellofiore, F.L.M. Ricciardolo, S. Privitera,
P. Inglese, A. Mistretta and G.U. Di Maria
Asthma Management 193
A.E. Tattersfield
The National Asthma Education Program 207
S.S. Hurd and R. Fulwood
Management of Asthmatic Children 215
K.F. Kerrebijn
Inhaled Corticosteroids in the Long Term Treatment of Asthma
and COPD 231
A. Foresi and D. Olivieri
Sympathomimetics and Xanthines ln the Treatment of Asthma 237
G. Joos and R.A. Pauwels
Protective Effect of Furosemide, Administered Using a Pressurized
Metered Dose Inhaler and a Spacer Device, on the Bronchial
Obstructive Response to Ultrasonically Nebulized Distilled
Water 257
P. Sestini, M. Robuschi, A. Vaghi, G. Gambaro, S. Spagnotto,
M.G. Pieroni, R. Metella Refini and S. Bianco
viii
Frusemide Inhalation Prevents Immunological Mediator Release and
Respiratory Changes in Guinea-pig 261
G. Rossoni, F. Berti, G. zuccari, A. Buschi, M. Robuschi,
L.M. Villa and O. Caratozzolo
Pharmacological Profile of CR 2039 CDizolast) a New Agent for the
Treatment of Allergic Diseases 273
L. Revel, F. Ferrari and F. Makovec
Effect of Betaxolol on Bronchial Responsiveness in Mild Asthmatic
Subjects with Chronic Glaucoma: A pilot Study 279
A. Chetta, S.A. Gandolfi, A. Foresi, M. Del Donno, D. Moretti
and D. Olivieri
Mast Cells and Eosinophils in Bronchial Asthma 285
A. Pesci, G. Bertorelli and D. Olivieri
Index 295
ix
HISTOPATHOLOGY OF BRONCHIAL ASTHMA AND THE EFFECTS OF 'rREA'rMEN'r
Peter K.Jeffery
Department of Lung Pathology
National Heart &Lung Institute
Royal Brompton Hospital, U.K.
ABSTRACT
Asthma is a complex condition with an imprecise definition. The
airways in fatal asthma are occluded by tenacious plugs consisting of a
mixture of exudate and mucus. There is fragility of airway surface
epithelium and thickening of the subepithelial reticular layer (referred
to as the epithelial "basement membrane" by light microscopy). Bronchial
vessel dilatation, congestion and oedema, hypertrophy of bronchial smooth
muscle and mucus-secreting submucosal glands together with an inflammatory
cell infiltrate contribute to thickening of the airway wall. An
inflammatory cell infiltrate, comprising lymphocytes and 'activated'
(EG2+) eosinophils with release of granular content in the latter, are
features of fatal asthma and also of relatively mild stable atopic,
intrinsic and occupational forms of asthma. Whilst widespread mast cell
degranulation (apparent by a reduction in their number) is found in fatal
asthma, it is not a feature of mild stable disease as evidenced by studies
of the numbers of tryptase positive mast cells and by morphometry of cells
examined by electron microscopy. Release of cytokines, particularly IL-5,
by lymphocytes, favour selective eosinophil adhesion to endothelium and
their differentiation, survival and activation in the mucosa. Short term
treatment of atopic asthmatics with inhaled corticosteroid reduces the
numbers of mast cells, eosinophils and the extent of eosinophil
degranulation. However, neither short-term nor long-term corticosteroid
treatment reduces the thickening of reticular basement membrane.
INTRODUCTION
Asthma is not considered to be a single disease entity but is probably
a complex of conditions all of which have in common airflow limitation.
The limitation to airflow is usually variable over short periods of time
and reversible spontaneously or with treatment, albeit an important
underlying (chronic) irreversible component may persist between episodes
of acute attacks [I]. Extrinsic, intrinsic and occupational forms are often
recognized but thus far can not be distinguished by the pathologist.
BRONCHIAL FLUIDS ~ BLOOD
Examination of sputa and airway fluids obtained at bronchial or
broncho-alveolar lavage (BAL) provide useful information. Corkscrew-shaped
twists of condensed mucus (Curshmann's spirals), clusters of surface airway
epithelial cells (Creola bodies), and the presence of Charcot-Leyden
crystals (composed of eosinophil cell membrane and granular
lysophospholipase) together with eosinophils and metachromatic cells are
characteristic features of asthmatic sputa [2,3]. BAL in mild (atopic)
asthma demonstrates the presence of sloughed epithelial cells and of
eosinophils and their secreted products (eg eosinophil cationic protein and
AsthmaTreatment-AMultidisciplinaryApproach
EditedbyD.Olivierietal.,PlenumPress,NewYork, 1992
