Opinion
Asthma – a need for a rethink?

https://doi.org/10.1016/S0165-6147(02)02022-9Get rights and content

Abstract

Asthma is a major medical problem but, despite decades of research, the mechanisms that underlie this condition remain elusive. Although the eosinophil has been regarded as a cell that is central to the pathogenesis of asthma, the failure to abrogate asthma symptoms by novel treatments that are designed to suppress the recruitment of eosinophils to the airways challenges this dogma. Our approach to understanding bronchial asthma needs to be broadened to include alterations in the function of afferent nerves that supply airways. Changes in the activity of these nerves offer a possible mechanism by which asthmatic subjects are uniquely responsive to a wide range of physiological and chemical stimuli. Here, we review the current status of asthma research.

Section snippets

The single-mediator hypothesis

Much of our current understanding of asthma is derived from studies of patients with allergic asthma because they are often well characterized and can be made to undergo controlled airway responses to inhaled allergens, including an infiltration of eosinophils into the airways [7]. The recognition that allergen-induced airway responses were associated with airway eosinophilia led to the hypothesis that allergy and eosinophils are central to the pathogenesis of asthma [8]. This led to the

The role of eosinophils

The discovery of T helper 2 (Th2) cells and their repertoire of cytokines, in particular IL-4 and IL-5, and the recognition that allergic asthmatics often had an imbalance between Th2 and Th1 cells [14] led to the development of the Th2 hypothesis of asthma. A wide range of approaches were developed to try to switch off this cell type and/or divert the immune system to a Th1 profile, as occurs in non-allergic individuals. Two such approaches were the development of a monoclonal antibody to IL-5

A case for afferent nerves?

Much of the initial work with capsaicin was conducted in tissues from guinea-pigs. Because capsaicin-induced contraction in smooth muscle from guinea-pig airways is associated with a pronounced fall in tissue levels of sensory neuropeptides [35], most investigators attributed the effects of capsaicin to depletion of sensory neuropeptides from C-fibres. In human bronchus [36], including bronchi from subjects with asthma [37], capsaicin produces only a modest contractile response at high

Concluding remarks

The past decade has witnessed a revolution in ‘new biology’ with the ability to identify and clone receptors and ion channels almost at will. This molecular revolution is widely reported as a scientific advance that should lead to a more rapid identification of drug targets for major diseases and thus to a faster introduction of novel drugs into clinical practice. However, in asthma, like most other diseases, we are still waiting for these promised new drugs. In a recent, sobering commentary,

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