Mark A. Giembycz – författare

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].

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.

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.

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 . . .

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.

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 . . .

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.

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.

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.