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Severe asthma can be divided into four phenotypes based on the time of onset and responsiveness to treatment with corticosteroids. Patients with the early onset form occurring in childhood have more obvious immune involvement, but relatively better lung function than the late onset form occurring in adolescence or adulthood. With a less clear aetiology of late onset severe asthma, it will be more difficult to establish novel treatments for this type of the severe asthmatic population. Moreover, the classification of severe asthma indicates a dependence on high dose corticosteroid administration or even a degree of insensitivity to corticosteroids. The following section briefly describes the state of the art of the technologies utilized in P3AGI for understanding and treating AA.

Imaging: so far, several targets have been utilized to study inflammatory processes in asthma including:
  • Eosinophil cationic protein
  • Exhaled nitric oxide
  • Serum tryptase
  • Exhaled breath condensate
Other biomarkers used in imaging of inflammation principally monitor key proteins involved in inflammatory pathways by means of specific targeted probes (e.g. Lymph node glycoprotein, apoptotic cells in hyperplastic synovia), inducible probes (e.g. Cathepsin B, L and S and plasmin), and the tracking and monitoring of lymphocytes, leucocytes and macrophages.

Genomics and bioinformatics: CBM has state of the art genomics facilities including microarray platforms such as Illumina and Affymetrix as well as next generation sequencing capacity with access to Illumina Solexa 1G sequencers. DNA microarrays are an extremely powerful technique for the simultaneous measurement of the expression of thousands of genes. Such studies can quickly yield a genome-wide description of RNA levels in a given cell or tissue at a given point in time, or a genetic characterization of a tissue's response to treatment. We will integrate conventional microarray technology with the use of next-generation sequencing for the identification of small non-coding RNAs. Samples will be obtained by laser cell microdissection, in order to utilize only specific cell types of importance to the AA intrinsic processes.

Experimental models of AA: although there are several models of AA in use, very few models recapitulate the important clinical problem of severe and steroid-resistant asthma. We present two models to address this problem. One is a model of relapsing remitting allergic asthma developed by MUW. The lungs of animals recovered from one episode of allergic asthma maintain inflammatory infiltrates which respond to aerosol challenge with antigen at any time during their lifetime. Moreover, treatment with steroids, either inhaled or systemic, only reduces inflammation and additional disease parameters by half. We consider this a model of severe steroid-resistant allergic asthma. The second model is derived by transferring PBMCs from humans with severe steroid-resistant allergic asthma into SCID mice. These chimeric mice will develop disease that recapitulates the patients.

Novel compounds for the treatment of AA:
The compounds used for the medication are:
  • Long-term asthma control medication (taken regularly to control chronic symptoms and prevent asthma attacks, i.e. inhaled corticosteroids)
  • Quick-relief medication (Taken as needed for rapid, short-term relief of symptoms, i.e. oral and intravenous corticosteroids)
  • Medication for allergy-induced asthma (Taken regularly or as needed to reduce your body's sensitivity to a particular allergen, i.e. antihistamines, decongestants)
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The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7 (2007-2013)) under grant no. 230739