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Severe asthma: Lessons from the Severe Asthma Research Program

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Severe asthma affects only a small percentage of the asthma population. However, these patients remain poorly understood and difficult to treat. Because the numbers are relatively small (10% or less of the asthma population), a network approach with shared protocols, samples, and data provides a unique opportunity to recruit the numbers of subjects necessary to perform adequately powered studies. The Severe Asthma Network (Severe Asthma Research Program) was established by the National Heart, Lung, and Blood Institute in 2001 to advance collectively the study of severe asthma to determine factors that differentiated these patients or subjects from those with milder asthma. Nearly 800 subjects have been recruited in less than 4 years to begin to address these differences. Future studies will specifically evaluate the role of inflammatory/oxidative processes, infection, genetics, and the distal lung in the pathogenesis of severe asthma.

Section snippets

The need for networking to address severe asthma mechanisms

Severe asthma represents approximately 10% of all subjects with asthma. This subset of patients has greater morbidity and a disproportionate need for health care support compared with the less severe subset.6 The frequency of severe asthma makes study of this group difficult, because a single center is unlikely to have a sufficient number of subjects for evaluation. However, given both the clinical and economic importance of this asthma phenotype and the lack of established animal models, the

Defining severe asthma

The definition of asthma, per se, remains clinically and physiologically based, dependent on appropriate symptoms and the presence of reversible airflow limitation. This general definition allows for the capture of numerous syndromes able to meet such criteria. This general definition of asthma makes precise definitions of severe asthma even more difficult. Guidelines for the Diagnosis and Management of Asthma9 and the Global Initiative on Asthma10 classify asthma severity on the basis of

Risk factors for severe asthma

As noted, the commonality of definition of severe asthma across centers allows for uniform analysis of epidemiologic and pathologic factors associated with and possibly contributory to severe asthma. In the initial SARP database, many clinical factors were found to be associated with severe asthma. Although many had been associated with severe asthma in the past, some factors that might have been predicted to associate with severe asthma, such as a lower bronchodilator response and

SARP and severe asthma phenotypes

Because SARP consists of such a large database of subjects, in addition to overall predictive elements for severe asthma, risk factors for the development of phenotypes of severe asthma (ie, frequent exacerbators, low FEV1) can be addressed. In an abstract presented in 2005, risk factors for the development of severe (intensive care unit or intubation) exacerbations were also analyzed.20 The risk factors were somewhat different from those for severe asthma, in general. Although FEV1 (%

SARP Approaches to understanding the pathobiology of severe asthma

Although each of the 8 initial sites had a specific hypothesis and aims, the utility of the network is to provide access to samples and data that enhance the power to address questions that may require more than the numbers of subjects available at a given site. The initial areas of interest for the SARP sites are shown in Fig 2. In general terms, these included the role of genetics and the environment (specifically respiratory viruses) on the development of inflammation (specifically

Bronchoscopic, imaging, and genetic studies

Bronchoscopic studies of subjects with severe asthma have been performed only in limited sites and with limited safety data available. One of the primary tasks of SARP was to confirm that it was possible to sample the lungs safely in subjects with severe asthma compared with subjects with less severe disease. To confirm the safety of bronchoscopy in the severe asthma population, rigorous standards were developed for the performance of bronchoscopy across sites. To date, the safety of

Conclusion

Severe asthma remains poorly understood. It is likely that some of the reasons for this lack of information relate to the multiple phenotypes that contribute to this overall population of patients with asthma. The presence of networks such as SARP (and others in Europe) will provide both the numbers of subjects and the depth of analysis required to elucidate the pathobiologic and genetic mechanisms behind these phenotypes and eventually to improve their treatment.

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  • Cited by (0)

    (Supported by an unrestricted educational grant from Genentech, Inc. and Novartis Pharmaceuticals Corporation)

    Series editors: William T. Shearer, MD, PhD, Lanny J. Rosenwasser, MD, and Bruce S. Bochner, MD

    Disclosure of potential conflict of interest: W. W. Busse has consulting arrangements with Schering, Genentech/Novartis, Isis, GlaxoSmithKline, Altana, Wyeth, Pfizer, Dynavax, Centocor, and Merck; has received grant support from Novartis, Dynavax, Wyeth, Centocor, GlaxoSmithKline, and Astellas; and is on the speakers' bureau for Novartis, Dynavax, Wyeth, Centocor, GlaxoSmithKline, and Astellas. S. E. Wenzel has declared that she has no conflict of interest.

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