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Future directions in asthma management Expert Rev. Clin. Immunol. 4(6), 647–648 (2008)
William J Calhoun, MD Sealy and Smith Distinguished Chair in Internal Medicine, Vice Chair for Research, University of Texas Medical Branch, Galveston, TX, USA Tel.: +1 409 772 2482 Fax: +1 409 772 9532 william.calhoun@ utmb.edu
www.expert-reviews.com
“The word asthma amalgamates numerous different pathogenic and mechanistic pathways, genetic susceptibilities, environmental and microbial exposures, gender, age and other factors...”
This special issue of Expert Review of Clinical Immunology is focused on asthma, a disorder of global importance and impact. Asthma is a syndromic disorder; the word asthma, as used clinically, amalgamates numerous different pathogenic and mechanistic pathways, genetic susceptibilities, environmental and microbial exposures, gender, age and other factors, into a clinical syndrome of variable airway obstruction, airway hyperresponsiveness and airway inflammation. The purpose of this issue is to bring much-needed attention to this common and sometimes fatal disease by summarizing current diagnostic and therapeutic strategies, exploring the boundaries of our concepts of asthma pathogenesis and treatments outlining the promise of new techniques and technologies, and providing scholarly synthesis of our understandings of immune mechanisms and their role in accentuating disease, as they interplay with existing comorbidities, environmental sensitivities and allergen exposures. Michael Schatz, a past president of the prestigious American Academy of Allergy, Asthma and Immunology, was a member of the 2007 National Asthma Education and Prevention Program (NAEPP) Expert Panel that produced the scholarly, authoritative, evidence-based and extensive 2007 NAEPP guidelines [1] . He has written a clear and very readable summary as a Special Report, which highlights critical new concepts and novel management approaches now recommended by the Expert Panel and supported by scientific evidence. Important to this readership, Michael Schatz’s
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summary is informed and enhanced by his first-hand knowledge of the internal debates and controversies that always accompany a summative recommendation of this magnitude. This issue contains three thought-provoking perspectives, each of which examines the evidence surrounding an area of controversy in asthma. Menachem Rottem explores the question of the possible association between early childhood vaccinations and the development of asthma, and exacerbations thereof. Clearly, answers to this question have very important publichealth ramifications, both in developed countries and in the developing world. His message that the risk–benefit ratio of vaccinations strongly favors vaccination is an important one for healthcare practitioners and patients to hear. An important controversy in the management of childhood asthma is the question of whether or not inhaled steroids alone are adequate for the treatment of childhood asthma exacerbations. Although avoiding the potential and real complications of oral steroid therapy is a laudable goal addressed using this approach, the contravening concern is whether inhaled steroids alone provide acceptable and adequate treatment for asthma exacerbations. Benjamin Volovitz reviews the relevant literature and adds practical guidelines for treating exacerbations via the inhaled route. Concluding this set of perspectives, Sue Adams addresses the largely unexplored, and often dismissed, asthma management strategies labeled ‘complementary’ or ‘alternative’. These two labels
© 2008 Expert Reviews Ltd
ISSN 1744-666X
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are not synonymous, connoting subtle but important philosophic differences for the role of more standard allopathic approaches. Because these therapies may be quite widely used in certain sociocultural groups, it is important for healthcare providers to be aware of this field. Finally, this issue contains seven state-of-the-art reviews that point the way to the future of asthma diagnostics, pathogenic concepts and clinical therapeutics. The advent of ‘-omics’ has fundamentally changed the nature of scientific investigations, by combining high-throughput analyses of nucleic acids, proteins and metabolites (derived from individuals with and without disease) with advanced bioinformatics and biostatistics. These approaches, although initially disdained by some as descriptive and exploratory, have proven to be invaluable for new pathway discovery, hypothesis generation and proof-of-concept testing. Functional genomics, proteomics and metabolomics have each brought the promise of new discovery, and each, in turn, may ultimately be proven to be predictive of therapeutic responses (pharmacogenomics) or clinical severity (protein–molecular phenot yping) [2] . Vicki Clifton and Annette Osei-Kuman review the ways in which proteomics data have informed the field of asthma and outline some of the future promises of this technology. Four reviews focus on the more clinical aspects of asthma management. Gustavo Rodrigo comprehensively reviews the current information on the rationale, safety and efficacy of inhaled steroids delivered as rescue therapy for acute severe asthma. Although severe asthma makes up only 5–12% of all asthma cases, there is a disproportionate use of healthcare and financial resources by patients at this end of the severity spectrum, so more effective therapy is sorely needed for severe asthma [3] . Mike Thomas and David Price consider the effect of common and treatable existing comorbidities on asthma (many of which can lead to a refractory asthma or severe asthma phenotype), and the potential and demonstrated effects of appropriately managing these comorbidities, on underlying asthma. Richard Leigh discusses a set of novel options for asthma management – the class of agents that are produced by genetic engineering and recombinant DNA techniques, are protein in character, generally parenterally administered, have exquisite selectivity for a particularly pathway and are collectively known as ‘biologicals’, short-hand for biologic response modifiers. It is important to understand in this context that ‘biologic’ is the adjective for ‘response modifier’, rather than ‘biologic response’ being the adjective for ‘modifier’; essentially, all current smallmolecule pharmaceuticals ‘modify’ a ‘biologic response’ but are not, in this connotation, ‘biologic response modifiers’. Many of these agents have a very strong scientific rationale behind their References 1
National Asthma Education and Prevention Program. Expert Panel Report 3: guidelines for the diagnosis and management of asthma. J. Allergy Clin. Immunol. 120, S93–S138 (2007).
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use, biologic plausibility and pathway relevance; however, clinical effectiveness has often been less dramatic than expected; a paradox that has not been entirely resolved. Santiago Quirce and Joaquin Sastre outline the current understanding of the pathogenesis and management of occupational asthma, a subset of asthma that is often misdiagnosed, or in which the contribution of occupational triggers is overlooked altogether.
“…this special focus issue of Expert Review of Clinical Immunology addresses clinical, basic and translational science related to the pathogenesis and management of asthma.” Lastly, and importantly, two reviews offer new insight regarding the interplay of innate and acquired immune mechanisms in the pathogenesis of asthma. Alberto Tedeschi reviews the relationships between autoimmunity, allergic inflammation and clinical expression of asthma, an area that is of considerable scientific interest, yet about which relatively little has been written. Moreover, there are potentially important implications of these relationships for more accurately defining clinical phenotypes of asthma. Steve Georas reviews the critically important interface between innate immunity and dendritic cells, and explores the clinical and immunologic implications of these interactions for adaptive immunity. The interplay between innate immune pattern-recognition receptors and pathways that regulate acquired immunity is now being exploited for clinical benefit. Arguably, these mechanisms have the most profound implications for the primary prevention of allergic diseases; Steve Georas’ synthesis and insights appreciably supplement our collective understanding of asthma pathogenesis. In summary, this special focus issue of Expert Review of Clinical Immunology addresses clinical, basic and translational science related to the pathogenesis and management of asthma. It is topical, scholarly, clinically relevant and thought provoking. The editors trust that this information will be of use to readers, of value to asthma scientists and of benefit to patients who suffer from this common disorder. Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.
Brasier AR, Victor S, Boetticher GD et al. Molecular phenotyping of severe asthma using pattern recognition of bronchoalveolar lavage-derived cytokines. J. Allergy Clin. Immunol. 121, 30–37 (2008).
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Moore WC, Bleecker ER, Curran-Everett D et al. Characterization of the severe asthma phenotype by the NHLBI’s severe asthma research program. J. Allergy Clin. Immunol. 119, 405–413 (2007).
Expert Rev. Clin. Immunol. 4(6), (2008)
