An Update on Severe Asthma
Severe asthma - determinants and treatment
Prof.Dr. K.F. Rabe
Leiden University Medical Center
"The term severe refractory asthma (SRA) in adults applies to patients who remain difficult to control despite extensive reevaluation of diagnosis and management following an observational period of at least 6 months by a specialist. Factors that influence asthma control should be recognized and adequately addressed prior to confirming the diagnosis of SRA."
This citation from a recent report on severe asthma in adults summarizes some of the relevant aspects of the presentation. The definition of the disease is based on clinical parameters and the management is directly influenced by risk factors and determinants that very individually influence the course of the disease. The estimate for the prevalence lies between 5 and 10% of the population with asthma and by now a number of risk factors have been identified. Tobacco smoking, female gender, and obesity are some of the determinants that have been described although the precise contribution is not always certain. There is good evidence that severe asthma can be described by various phenotypes and for clinical practice it seems advisable to differentiate individuals that have a more rapid decline in lung function from those that present with frequent exacerbations. For those patients with frequent exacerbations respiratory viruses seem to play an important role as well as allergen exposure and occupational sensitizes. Furthermore, trigger factors such as nonsteroidal anti-inflammatory drugs are important for a subset of individuals with severe asthma. Patients with a rapid decline in lung function appear to have a different risk factor profile with persistent (eosinophilic) inflammation, persistence of inflammation of the upper airways, and structural changes of the lungs. The common abnormality lies in a poor corticosteroid response which is likely to be multi-factorial and is still insufficiently understood.
The management of severe asthma relies nevertheless on the use of inhaled corticosteroids and bronchodilators and a limited number of studies have addressed the use of high doses corticosteroids above those routinely recommended. Leukotriene receptor antagonists are included in several guidelines although their benefit is questionable. Alternative immunesuppressive therapies have been disappointing so far and there is an urgent need for alternative pharmacological developments. There is limited data available on the use of anti-TNF therapies for severe asthma and large scale trials are now underway. The monoclonal antibody omalizumab has demonstrated efficacy in this patient group.
Given the complexity of the disease the role of non-pharmacological strategies including education and instructions in medication use need to be stressed. Severe asthma is undoubtedly frequently associated with a range of co-morbid conditions and the management strategies need to include pharmacological and non-pharmacological approaches. Finally, clinical trials in the future should be performed in well phenotyped patients since severe asthma is likely not a homogeneous entity and the role of allergic sensitization, the onset of the disease, and the clinical course vary greatly between patient populations which will inevitably reflect on the efficacy of novel interventions.
- Chanez P, Wenzel SE, Anderson GP, Anto JM, Bel EHD, Boulet LP, Brightling CE, Busse WW, Castro M, Dahlen B, Dahlen SE, Fabbri LM, Holgate ST, Humbert M, Gag M, Joos GF, Lely B, Rabe KF, Sterk PJ, Wilson SJ, Vachier I. Severe asthma in adults: what are the important questions? J Allergy Clin Immunol 2007;119(6):1337-1348.
- Bel EH. Clinical phenotypes of asthma. Curr Opin Pulm Med 2004;10:44-50.
- Chung K, Godard P, Adelroth E, Ayres J, Barnes N, Barnes P, et al. Difficult/therapy resistant asthma: the need for an integrated approach to define clinical phenotypes, evaluate risk factors, understand pathophysiology and find novel therapies. ERS Task Force on Difficult/ Therapy-Resistant Asthma. Eur Respir J 1999;13:1198-208.
- American Thoracic Society. Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med 2000;162:2341-51.
- ENFUMOSA Study Group. The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma. Eur Respir J 2003;22:470-7.
- Wenzel S, Szefler SJ. Managing severe asthma. J Allergy Clin Immunol 2006;117:508-11.