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  • Review Article
  • Published:

New drugs for asthma

Nature Reviews Drug Discovery volume 3, pages 831–844 (2004)Cite this article

Key Points

  • Asthma is one of the major growth areas in therapeutics and many new drugs are currently in development.

  • These drugs include improvements of existing classes of drugs, notably once-daily inhaled β2 adrenoceptor agonists and corticosteroids with an improved safety profile.

  • New classes of drug are based on a better understanding of the complex pathophysiology of asthma and include inhibitors of specific mediators, cytokines and chemokines.

  • Several new classes of drug are targeted at signal-transduction pathways and transcription factors that regulate the expression of inflammatory genes and the immune mechanisms that underlie allergic inflammation.

  • A major challenge is to develop drugs that are as effective as existing inhaled treatments and are effective by oral administration, but without significant side effects.

  • No treatments are curative, but it is possible that in the future vaccination approaches and immunoregulators could provide long-term control of asthma.

Abstract

Asthma is a major and increasing global health problem and, despite major advances in therapy, many patients' symptoms are not adequately controlled. Treatment with combination inhalers, which contain a corticosteroid and long-acting β2 adrenoceptor agonist, is the most effective current therapy. There is therefore a search for new therapies, particularly safe and effective oral treatments and those that are more efficacious in severe asthma. New therapies in development include mediator antagonists and inhibitors of cytokines, although these therapies might be too specific to be very effective. New anti-inflammatory therapies include corticosteroids and inhibitors of phosphodiesterase-4, p38 mitogen-activated protein kinase and nuclear factor-κB. The prospects for a curative treatment are on the horizon.

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Figure 1: The pathophysiology of asthma.
Figure 2: Molecular mechanisms of action of bronchodilators.
Figure 3: There are several strategies for inhibiting pro-inflammatory cytokines in asthma.
Figure 4: Inhibition of eosinophilic inflammation.
Figure 5: Effects of blocking interleukin-13 in asthma.
Figure 6: Chemokine receptor antagonists in asthma.
Figure 7: Phosphodiesterase-4 inhibitors have a broad spectrum of anti-inflammatory effects in asthma.
Figure 8: Strategies to inhibit the allergic response underlying asthma.

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Authors and Affiliations

  1. National Heart and Lung Institute, Imperial College Faculty of Medicine, Dovehouse Street, London, SW3 6LY, UK

    Peter J. Barnes

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P.J.B. receives research funding from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis and Scios for research into asthma and chronic obstructive pulmonary disease.

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DATABASES

Entrez Gene

A1 receptor

A2A receptor

A2B receptor

ANP

CCR3

CRTH2

CTLA4

CysLT1 receptor

CXCR4

ET1

ETA receptor

ETB receptor

FLAP

GATA3

glucocorticoid receptor

ICAM1

ICOS

IKK2

IL-1

IL-1ra

IL-4

IL-4 receptor

IL-5

IL-5 receptor

IL-10

IL-12

IL-13

IL-13 receptor α1

IL-18

iNOS

LTB4 receptor

mast-cell tryptase

NF-κB

P2Y2 receptor

PAR2

PDE4

STAT6

TACE

VCAM1

VIP

OMIM

Chronic obstructive pulmonary disease

Crohn's disease

psoriasis

rheumatoid arthritis

FURTHER INFORMATION

Encyclopedia of Life Sciences

Adrenergic receptors

allergens

asthma

asthma and atopy

Peter Barnes' webpage

Asthma UK

American Lung Association

American Academy of Asthma, Allergy and Immunology

National Heart, Lung and Blood Institute Asthma Fact Sheet

World Health Organization Health Topics — Asthma

Glossary

TH2 CELL

T helper 2 lymhocytes that predominate in asthma and which are characterized by the production of interleukins 4, 5, 9 and 13.

CYTOKINE

A small protein mediator that acts as a communicator between cells.

BRONCHODILATOR

A drug that relaxes airway smooth muscle and provides immediate relief from asthma symptoms.

AIRWAY HYPERRESPONSIVENESS

(AHR). Exaggerated airway-narrowing response to many environmental triggers, such as allergen and exercise, which is characteristic of asthma. It is normally measured by histamine or methacholine challenge.

CHEMOKINE

A small protein mediator that acts as a chemoattractant for inflammatory cells through the activation of chemokine receptors that have the typical structure of G-protein-coupled receptors.

PHOSPHODIESTERASES

(PDE). Enzymes that break down cyclic nucleotides in the cell. More than 12 families are now known, but the PDE4 family is prominent in inflammatory cells that are important in asthma.

CELL-ADHESION MOLECULES

Cell-surface proteins that are involved in the interaction between inflammatory and immune cells and structural cells, such as endothelial or epithelial cells.

CO-STIMULATORY MOLECULES

Surface proteins on antigen-presenting cells and T lymphocytes that enhance the interaction between the T-cell receptor and the major histocompatibility complex.

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Barnes, P. New drugs for asthma. Nat Rev Drug Discov 3, 831–844 (2004). https://doi.org/10.1038/nrd1524

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