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This book gives an up-to-date analysis of the epidemiology of
asthma i n children and adults, the role of steroids in asthma
management and n ew and novel asthma therapies. Specific chapters
deal with the epidem iology of asthma mortality and of childhood
asthma, others discuss the advantages and drawbacks of the use of
b2-adenoreceptor agonists, cor ticosteroids, theophylline and new
generation phosphodiesterase inhibi tors in the treatment of
asthma. A new non-invasive method to assess a irway inflammation is
also presented as well as steroid-sparing therap ies in asthma. The
book addresses clinicians and basic scientists wit h an interest in
asthma epidemiology, steroids and future therapies. I t is also of
interest to clinical and no-clinical teachers in academic
disciplines relating to respiratory disease.
Continuing the Respiratory Pharmacology and Pharmacotherapy series,
this volume explores the pathophysiology and therapy of rhinitis.
The volume is introduced by a chapter describing the normal anatomy
and physiology of the nose and sinuses. Against this background the
contributing authors describe and discuss the immunological and
pathological changes which occur in rhinitis. The various causes
and the types of rhinitis - such as allergic, vasomotor, and
infectious - are discussed as are the treatments available
(pharmacotherapy, immunotherapy, surgery). The book concludes with
a description of the animal models of rhinitis which are now
available. This book will be of interest to bench scientists and
clinicians alike.
1. 1. Invasive versus Non-Invasive Clinical Measurements in
Medicine Clinical measurement has become an essential complement to
traditional physical diagnosis. An ideal clinical measurement
should be quantitative, have a high level of reliability and
accuracy, be safe, acceptable to the patient, easy to perform and
non-invasive. The latter demands that the technique should not
break the skin or the lining epithelium and should be devoid of
effects on the tissues of the body by the dissipation of energy or
the introduction of infection [1]. It is therefore logical that for
a given measurement, a non-invasive test will be preferred if it
provides the same information with the same accuracy and precision.
In the following sections, we will discuss the role of various
non-invasive or relatively non-invasive methods to assess airway
inflammation in asthma and concentrate on the only direct method of
induced sputum examination. 1. 2. Why Is Assessment of Airway
Inflammation Important in Asthma? Inflammation is a localized
protective response elicited by injury or destruc tion of tissues
which serves to destroy, dilute or wall off both the injurious
agent and the injured tissue [2]. The role of inflammation in
asthma was rec ognized long ago. In his textbook The Principles and
Practice of Medicine, in 1892, Sir William Osler described
"bronchial asthma . . . in many cases is a spe cial form of
inflammation of the smaller bronchioles . . .
Most studies on autonomic innervation of smooth muscle have focused
on the short-term mechanisms involved in neurotransmission in
physiological and pathophysiological conditions. However recent
obser vations of the long-term plasticity of this system, i. e. its
capacity for regeneration and for compensatory change in pattern of
innervation and expression of cotransmitters and receptors in
ageing, following surgery, trauma or in disease, have indicated
that an understanding of the mechanisms involved could influence
the design of therapeutic regimes. There is increasing evidence for
long-term communication between nerves and smooth muscle cells
during development and throughout adult life. To date, the trophic
interactions between nerves and airway musculature have attracted
little interest, consequently, much of the information presented
here is drawn from studies using other smooth muscles. However, the
questions posed about trophic interactions dur ing development
apply as much to airways smooth muscle neuroeffector systems as to
other autonomic neuroeffector systems. These are: i) How do
developing nerve fibres know where to go and how do they reach
their target sites? ii) What determines the density and pattern of
inner vation at reaching the effector? iii) How do the nerves
survive and maintain their position once established? iv) What
factors influence neurochemical differentiation such that
genetically multipotential neu rones are triggered to synthesize
one or combinations of neurotransmit ters? v) What influence do
nerves have on the structure, function and receptor expression of
their effector cells? vi) How do diseases interrupt these
processes? - see 1]."
Many factors may influence the release of neurotransmitters from
airway nerves 1]. This is likely to be important in physiological
control of airway functions and may be particularly relevant in
airway diseases, such as asthma and chronic obstructive pulmonary
disease (COPD). Neural elements in airways interact in a complex
manner and the activation of certain neural pathways may profoundly
influence the release of transmitters from other neural pathways.
Similarly inflamma tory mediators released from inflammatory cells
in the airways may also modulate neurotransmitter release. There
are marked differences be tween species in airway innervation and
in neuromodulatory effects and, wherever possible, studies in human
airways have been emphasised, although information on
neuromodulation in human airways is some what limited at present.
Release of neurotransmitters from nerve terminals occurs via a Ca2+
dependent secretion evoked by a nerve action potential, but may
also be evoked experimentally by a high extracellular K +
concentration which directly depolarises the nerve terminal
membrane. Modulation refers to the alteration of neurotransmitter
release, which may either be increased (facilitation) or reduced
(inhibition) by the action of a particular agent, thus changing the
magnitude of the neurally-mediated response. Such agents would
normally act on receptors on the nerve terminal which are referred
to as pre-junctional (or presynaptic) receptors, in contrast to
post-junctional (or post-synaptic) receptors located on the target
cells which are influenced by that particular transmitter."
Continuing the Respiratory Pharmacology and Pharmacotherapy series,
this volume explores the pathophysiology and therapy of rhinitis.
The volume is introduced by a chapter describing the normal anatomy
and physiology of the nose and sinuses. Against this background the
contributing authors describe and discuss the immunological and
pathological changes which occur in rhinitis. The various causes
and the types of rhinitis - such as allergic, vasomotor, and
infectious - are discussed as are the treatments available
(pharmacotherapy, immunotherapy, surgery). The book concludes with
a description of the animal models of rhinitis which are now
available. This book will be of interest to bench scientists and
clinicians alike.
Building on the existing titles in the "Airways Smooth Muscle"
sub-series, the sixth volume explores physiological and
pharmacological processes in the lung in vivo. The various animal
models available for studying the bronchospasm and inflammation
associated with human asthma are thoroughly reviewed by
internationally recognised scientists. Specific chapters focus on
the problems of administering drugs to animal airways, the
mechanics of assessing lung function in the models, and describe in
detail the species used, from rodents to primates. The use of
genetically altered animals, an area of particular interest to
molecular biologists, is also considered in depth. This up-to-date
and extensively referenced work will prove invaluable to
pharmacologists, physiologists and other biological scientists at
all levels in academia and in the pharmaceutical industry.
Building on the existing titles in the "Airways Smooth Muscle"
sub-series, the sixth volume explores physiological and
pharmacological processes in the lung in vivo. The various animal
models available for studying the bronchospasm and inflammation
associated with human asthma are thoroughly reviewed by
internationally recognised scientists. Specific chapters focus on
the problems of administering drugs to animal airways, the
mechanics of assessing lung function in the models, and describe in
detail the species used, from rodents to primates. The use of
genetically altered animals, an area of particular interest to
molecular biologists, is also considered in depth. This up-to-date
and extensively referenced work will prove invaluable to
pharmacologists, physiologists and other biological scientists at
all levels in academia and in the pharmaceutical industry.
Building on the existing titles in the "Airways Smooth Muscle"
sub-series, the sixth volume explores physiological and
pharmacological processes in the lung in vivo. The various animal
models available for studying the bronchospasm and inflammation
associated with human asthma are thoroughly reviewed by
internationally recognised scientists. Specific chapters focus on
the problems of administering drugs to animal airways, the
mechanics of assessing lung function in the models, and describe in
detail the species used, from rodents to primates. The use of
genetically altered animals, an area of particular interest to
molecular biologists, is also considered in depth. This up-to-date
and extensively referenced work will prove invaluable to
pharmacologists, physiologists and other biological scientists at
all levels in academia and in the pharmaceutical industry.
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