Determinants of the bronchodilation response to salbutamol on histamine-induced bronchoconstriction.

Assessment of the bronchodilation response to short-acting beta2-adrenoreceptor agonists on pharmacologically induced bronchoconstriction has often been used to investigate airway smooth muscle beta2-adrenoreceptor function. However, little is known about factors affecting this response. In the present study, the bronchodilation response to 0.2 mg of salbutamol on histamine-induced bronchoconstriction was assessed in 101 steroid-naïve asthmatic subjects. The associations of the response with a wide range of challenge procedure-related variables, clinical asthma severity indicators, and blood markers of airway inflammation were investigated. The response was re-assessed after 6 and 12 weeks' therapy with inhaled budesonide. Baseline FEV1, final histamine concentration, and the maximal fall in FEV1 explained 35-59% of the total variation in the response to salbutamol, depending on the index chosen to express the response. Serum concentration of myeloperoxidase, an index of neutrophilic inflammation, was associated with a poor response. The preceding week daily PEF variation, rescue bronchodilator use, severity of asthmatic symptoms, blood eosinophil count, and serum eosinophilic cationic protein and eosinophilic protein X concentrations were not associated with the response. The salbutamol response seemed to diminish during budesonide treatment but when adjusted by the challenge procedure-related variables the treatment effect vanished. In conclusion, the bronchodilation response to salbutamol on histamine-induced bronchoconstriction is largely determined by challenge procedure-related variables. It seems to be unrelated to the clinical severity of asthma and is not affected by treatment with inhaled corticosteroids. Neutrophilic airway inflammation may be associated with a poor response.

Use of multiple peptides containing T cell epitopes is a feasible approach for peptide-based immunotherapy in Can f 1 allergy.

We have previously shown that the major dog allergen Can f 1 contains seven T cell epitope regions, none of which was preferentially recognized. To identify the immune characteristics of Can f 1 epitopes and to verify their suitability for peptide-based allergen immunotherapy, short-term T cell lines were generated with epitope-containing peptides from peripheral blood mononuclear cells of Can f 1 skinprick test-positive allergic and healthy control subjects. The lines were examined for their proliferative capacity and cytokine production upon stimulation with the allergen peptide, a homologous peptide from human tear lipocalin (TL) and Can f 1 and TL proteins. Can f 1 peptides induced proliferation of T cells and gave rise to T cell lines with comparable efficiencies. In particular, the T cell lines of allergic subjects induced with p33-48 and p107-122 favoured the production of interferon-gamma and interleukin-10, respectively. A greater number of Can f 1-specific T cell lines were generated from allergic than from healthy individuals. Two p107-122-induced Can f 1-specific T cell lines also reacted to a homologous peptide of human TL. Our results suggest that several T cell epitope-containing peptides should be used in combination for specific immunotherapy in Can f 1 allergy.