The traditional definition of asthma is based on clinical symptoms in the presende of reversible airflow limitation. This definition is very broad and likely can encompass many entities. Therefore, it is not surprising that asthma is increasing recognized as a syndrome of syndromes, as opposed to a single disease. Over the years, numerous attempts at categorizing these phenotypes have been proposed, however, likely due to the overlap among the syndromes and the lack of specific biomarkers for each syndrome, the definition of asthma phenotypes continues to evolve. General categories for asthma phenotypes include those based on clinical characteristics, those based on types of inflammation identified and those based on triggers for the symptoms. These phenotypes are perhaps easier to define in patients with more symptomatic disease, such that much of the recent work identifying phenotypes has focused on patients with more severe disease. Whether severity of asthma also can be considered a phenotype of asthma is controversial, however, among moderate to severe asthmatics, the broadest general categorization is based on disease that is highly labile, with frequent exacerbations and a range of airflow limitation, as compared to a phenotype which may have fewer or even absent exacerbations, but continuous lower level symptoms and more severe and perhaps fixed airflow limitation. A further clinical distinction can be made on the basis of age at onset with early onset asthmatics more likely to represent a more homogeneous group with a strong allergic component, while later onset asthma can be extremely heterogeneous. Currently, 3 different inflammatory phenotypes have been defined, including eosinophilic, non-eosinophilic (neutrophilic) and paucigranulocytic. Of these, the eosinophilic phenotype is the most well defined and has been associated with a more symptomatic disease with frequent exacerbations, greater reversibility and airway hyperresponsiveness. Interestingly, there may be dfifferences between eosinophilic early onset asthma and eosinophilic late onset asthma, with early onset eosinophilic asthma associated with the highest risk for extremely severe asthma exacerbations. Noneosinophilic/ neutrophilic asthma has been associated with a lower FEV1, but less wheezing/chest tightness. Finally, the association of phenotypes with triggers, such as allergic, aspirin and hormonal also has been described. Allergic asthma is more likely to be seen in childhood onset asthma, while aspirin sensitive asthma is more commonly seen in later onset disease. However, allergic bronchopulmonary aspergillosis is more likely to be seen in association with late onset asthma. In our present understanding of this area, there remains considerable overlap among the groups, with an eosinophilic asthmatic, in the face of corticosteroid treatment, more likely to be severe and exacerbating and at least in adults, likely to have gotten the disease in adult hood. Further work is necessary to more specifically identify asthma phenotypes, likely incorporating definitions from each of these areas. This broader approach should allow better biomarker identification, more precise genetic evaluation and, eventually better and more effective treatment in a targeted population.
Full conference title:
3rd Advances Against Aspergillosis
- AAA 3rd (2008)