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A long and winding road led to the discovery of immunoglobulin E (IgE) in 1966 and 1967. We are currently on a long and winding road to understand the immunologic basis of the clinical effects of the anti-IgE antibody omalizumab in asthma. It is possible that patients with asthma (as patients with chronic spontaneous urticaria) benefit in different immunologic ways from omalizumab treatment. This article reviews the history of IgE discovery and current concepts of anti-IgE therapy in asthma., Competing Interests: Interessenkonflikt: M. Lommatzsch erhielt Honorare für Beratungen und Vorträge von den Firmen ALK Abelló, Allergopharma, AstraZeneca, Bencard, Berlin-Chemie, Boehringer-Ingelheim, Boston Scientific, Chiesi, GSK, Janssen-Cilag, MSD, Mundipharma, Novartis, Nycomed/Takeda, Sanofi, TEVA, UCB. ML erhielt Forschungsförderung von der Deutschen Forschungsgemeinschaft (DFG), dem Land Mecklenburg-Vorpommern, GSK, AstraZeneca. K. Geißler hat Vortragshonorare von den Firmen AstraZeneca, Novartis und Teva erhalten. KG hat Forschungsförderung von den Firmen AstraZeneca und Teva erhalten. K.-C. Bergmann hat Vortrags- und Beraterhonorare von den Firmen AstraZeneca, ALK, Bencard, HAL, Lofarma, Novartis, Stallergenes und Teva erhalten. J. C. Virchow hat Vorträge gehalten und Honoraria erhalten von: AstraZeneca, Avontec, Bayer, Bencard, Bionorica, Boehringer-Ingelheim, Chiesi, Essex/Schering-Plough, GSK, Janssen-Cilag, Leti, MEDA, Merck, MSD, Mundipharma, Novartis, Nycomed/Altana, Pfizer, Revotar, Sanofi/Regeneron, Sandoz-Hexal, Stallergens, TEVA, UCB/Schwarz-Pharma, Zydus/Cadila und als Berater fungiert für: Avontec, Boehringer-Ingelheim, Chiesi, Essex/Schering-Plough, GSK, Janssen-Cilag, MEDA, MSD, Mundipharma, Novartis, Regeneron, Revotar, Roche, Sanofi-Aventis, Sanofi/Regeneron, Sandoz-Hexal, TEVA, UCB/Schwarz-Pharma. JCV hat Forschungsförderung erhalten von der Deutschen Forschungsgemeinschaft (DFG), dem Land Mecklenburg-Vorpommern, GSK, MSD., (© Georg Thieme Verlag KG Stuttgart · New York.)

Escouflaire antiasthmatic cigarettes and powders knew certain success during almost one century. The medical use of solanaceae with bronchodilator properties helped relieve numerous asthmatics. The Belgian pharmacist Charles Adolphe Escouflaire (1857-1909), pharmacist from the university of Leuven, Belgium, awarded his diploma in 1879. He created his antiasthmatic products in his pharmacy of Ath and established in 1885 a pharmaceutical laboratory. He registered trademarks under the brand name Zematone for its antiasthmatic cigarettes. His products will be rapidly known and sold all over the world. The discovery of a complete box of medical cigarettes in the Czech Republic allows us to evoke his products, the distributor F. S chnöbling in this country, the modes of display and uses. This article redraws the history of the laboratory under the direction of three generations of the Escouflaire family. The laboratory will expand after WWII with production factories in Baisieux and Blandain before definitely close in 1974.

This article presents many products used against asthma since half of 19th century, until they've been took off from the market, in 1992. Thoses products were used in fumigation or inhalation, without any complex machine. They were powders, impragnated papers, cigares an cigarets. They contained more often nitrates and Solanacées. An exemple of struggle between two specialities is studied: Cléry's powder against Exibard's powder.

This year is the 50th anniversary of the introduction into clinical use of the first modern inhaler for the management of asthma--the pressurised metered-dose inhaler (pMDI). The pMDI was initially used for the administration of the non-selective beta-agonists adrenaline and isoprenaline. However, the epidemic of asthma deaths which occurred in the 1960s led to these drugs being superseded by the selective short-acting beta-agonist salbutamol, and the first inhaled corticosteroid (ICS) beclomethasone. At the same time, sodium cromoglycate was introduced, to be administered via the first dry-powder inhaler--the Spinhaler--but owing to its relatively weak anti-inflammatory action its use is now very limited. Over the last 10 years, the long-acting beta-agonists (LABAs) have become an important add-on therapy for the management of asthma, and they are now often used with ICS in a single ICS/LABA combination inhaler.

Current drug therapy for asthma is highly effective and has evolved from naturally occurring substances through logical pharmaceutical developments. Pharmacology has played a critical role in asthma drug development and several key experimental observations have been published in this journal. Understanding the pharmacology of effective drug therapies has also taught us much about the underlying mechanisms of asthma. beta(2)-Adrenoceptor agonists are the most effective bronchodilators and evolved from catecholamines from the adrenal medulla, whereas corticosteroids, from the adrenal cortex, are by far the most effective controllers of the underlying inflammatory process in the airways. The current 'gold standard' of asthma therapy is a combination inhaler containing a long-acting beta(2)-agonist with a corticosteroid - an improved form of adrenal gland extract. Cromoglycate, derived from a plant product and theophylline, a dietary methyl xanthine, have also been extensively used in the therapy of asthma, but we still do not understand their molecular mechanisms. Pharmacology has played an important role in improving natural products to make effective long lasting and safe asthma therapies, but has so far been challenged to produce new classes of antiasthma therapy. The only novel class of antiasthma therapy introduced in the last 30 years are leukotriene antagonists, which are less effective than existing treatments. New, more specific, therapies targeted at specific cytokines are less effective than corticosteroids, whereas more effective therapies carry a risk of side effects that may not be acceptable. It seems likely that pharmacology, rather than molecular genetics, will remain the main approach to the further improvement of treatment for asthma.

Inhaled therapies have been used since ancient times and may have had their origins with the smoking of datura preparations in India 4,000 years ago. In the late 18th and in the 19th century, earthenware inhalers were popular for the inhalation of air drawn through infusions of plants and other ingredients. Atomizers and nebulizers were developed in the mid-1800s in France and were thought to be an outgrowth of the perfume industry as well as a response to the fashion of inhaling thermal waters at spas. Around the turn of the 20th century, combustible powders and cigarettes containing stramonium were popular for asthma and other lung complaints. Following the discovery of the utility of epinephrine for treating asthma, hand-bulb nebulizers were developed, as well as early compressor nebulizers. The marketing of the first pressurized metered-dose inhaler for epinephrine and isoproterenol, by Riker Laboratories in 1956, was a milestone in the development of inhaled drugs. There have been remarkable advances in the technology of devices and formulations for inhaled drugs in the past 50 years. These have been influenced greatly by scientific developments in several areas: theoretical modeling and indirect measures of lung deposition, particle sizing techniques and in vitro deposition studies, scintigraphic deposition studies, pharmacokinetics and pharmacodynamics, and the 1987 Montreal Protocol, which banned chlorofluorocarbon propellants. We are now in an era of rapid technologic progress in inhaled drug delivery and applications of aerosol science, with the use of the aerosolized route for drugs for systemic therapy and for gene replacement therapy, use of aerosolized antimicrobials and immunosuppressants, and interest in specific targeting of inhaled drugs.

There have been four types of drug treatment of asthma that have been used over the past 100 years. Belladonna alkaloids, derived from the thorn-apple plant were used in 1905, and chemically synthesized entities in this class are still in use today. Western medicine began to use adrenergic stimulants approximately 100 years ago, but they were likely used in Asian medicine long before that. Systemic treatment with corticosteroids was introduced into the treatment of asthma in the mid-20th century; inhaled corticosteroids have been in use for over 35 years. The last 40 years have also seen the development of the first targeted asthma treatments: cromones, antileukotrienes, and anti-IgE. As we learn more of the biology of asthma, we anticipate that more effective targeted asthma treatments will be developed.

Sodium cromoglycate, which was launched in 1968 by the British company Fisons for the treatment of allergies and asthma, was an absolute novelty in chemical, pharmacological as well as therapeutic respects. The khellin derivative meanwhile did not owe its discovery to the usual strategies for finding drugs. On the contrary, the protective effect of the substance was discovered in a self trial through systematic antigen-induced provocation tests of the medicinal doctor and allergic Roger Ernest Collingwood Altounyan (1922-1987). The only subsequently formed hypothesis of a mast cell stabilising effect of Sodium cromoglcycate did not prove to be valid for the search for similar or more effective substances. A further development of this drug class could not take place because of the lack of suitable pharmacological models.

Asthma is an inflammatory disorder in which the small airways of the lung play an important role. There is also evidence for the systemic nature of asthma. No current method adequately measures small airways function alone. Therefore, a combination of functional and clinical parameters should be used to ensure that patients with asthma are adequately treated with due consideration of the small airways. Previously therapeutic strategies have focused on bronchodilation and attenuation of airway inflammation. While early oral therapies had the advantage of reaching the small airways and treating the systemic aspect of asthma, they were associated with serious side-effects. Inhaled therapies were therefore developed to limit these effects. However, inhaled therapies have the disadvantage of limited penetration into the peripheral airways and an inability to treat the systemic component of asthma. They are also associated with local and systemic side-effects. The future for asthma treatment is likely to be a systemically administered medication with few side-effects targeting disease-specific mediators. The leukotriene receptor antagonists and anti-IgE monoclonal antibodies are examples of such therapies and the emergence of other new strategies is awaited.

For the 30 years between 1967 and 1997, pharmacologic therapy of asthma has consisted primarily of five classes of drugs, beta 2-agonists, anticholinergics, theophyllines, cromones, and corticosteroids. The first four of these classes of drugs have origins in herbal treatments going back 5000 or 6000 years. This article briefly reviews the history of asthma pharmacotherapy up to the late 1990s and outlines a current approach to the pharmacotherapy of asthma, which is but one component of an integrated overall approach to asthma treatment involving patient education and environmental control as well.

The common belief that reductive biological sciences--for example, molecular biology and cellular chemistry--will write the book of revelation of all future anti-asthma drugs is at variance with the demonstrated importance of discoveries in complex in vivo systems.