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Reactivity to common allergens in spontaneous feline asthma
S26
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 2002
1 With T Cell Responses to MycoplasmaPneumoniae(MP) in Patients ChronicAsthma
9 Reactivityto CommonAllergens in SpontaneousFeline Asthma Keigo Kurata*, Kenichi Masuda*, Masahiro Sakaguchi§, Koichi Ohno*. Hajime Tsujimoto* *University of Tokyo, Tokyo, Japan §National Institute of Infectious Diseases, Tokyo, Japan It has been thought that an appropriate animal model for human asthma is necessary to evaluate efficacy of novel therapy such as immunotherapy with CpG oligodeoxynucleotides and DNA vaccine. Feline asthma is a chronic inflammatory airway syndrome characterized by recurrent respiratory symptoms such as coughing and wheezing. Increasing opacity of bronchial walls is a typical finding in thoracic radiography of cats with asthma. In contrast to asthma in humans, an association with sensitization to aeroallergen in feline asthma has been unclear. The objective of this study was to determine whether cats with asthma were sensitive to aeroallergens. Intradermal testing, in vitro serum allergen-specific IgE testing, and lymphocyte blastogenic responses were used in 9 cats diagnosed as feline asthma based on clinical symptoms, radiographic findings and therapeutic responses to corticosteroids. Seven of the 9 cats showed positive reactions to common allergens such as house dust mite (Dermatophagoidesfarinae and D. pteronyssinus), weeds (ragweed, yellow dock, etc), trees (oak, elm, etc), grasses (orchard grass, timothy grass, etc), arthropods, fungi (Aspergillus spp., Alternaria spp., etc), and foods (egg, corn, etc) in either intradermal testing or IgE testing. Of these allergens, the allergens showing agreement of positive results between intradermal tesing and IgE tesing were house dust mite (7 cats), fungi (1) and foods (1). Two cats were negative to any allergens examined in intradermal testing and IgE testing. In blastogenic responses of peripheral blood mononuclear cells from the cats showing positive reactions to house dust mite, 4 of the 7 cats showed positive reactions to both D. farinae and D. pteronyssinus with stimulation indices (S.1.) from 2,0 to 9.8. Two of the 7 cats showed positive reaction to only D. farinae with S.I. of 2.0. These results indicate that sensitization to aeroallergens can be, in part, associated with the pathogenesis of feline asthma similar to that in human patients with asthma. House dust mite can be considered as a common allergen causing allergic reactions in respiratory organs in cats. From the similarities to human asthma, feline asthma is considered as a useful animal model of asthma in terms of development of a novel immunotherapy. Supported by a grant from the Ministry of Education, Science, Sports and Culture.
f~ The Neurokinin-1 Receptor Is Crucial for the Development of Nonatopic Asthma
2U
Hanneke P Van der Kleij*, Aletta D Kraneveld*, Frank A Redegeld*, Norma P Gerard§, Olivier Morteau§, Frans P Nijkamp* *Faculty of Pharmacy, Utrecht University, Utrecht, Netherlands §Harvard Medical School, Boston, MA Mast cell activation, hronchoconstriction, inflammation and airway hyperreactivity are prominent features of dinitrofluorobenzene (DNFB)induced hypersensitivity reactions in the mouse airways, a murine model for nonatopic asthma. We studied the role of neurokinin receptors in the development of nonatopic asthma using specific NK- 1 (RP67580) or NK-2 (SR48968) receptor antagonists and genetically NK-1 receptor-deficient animals. NK- 1 receptor blockade strongly reduced the DNFB-induced tracheal hyperreactivity and the accumulation of neutrophils and mononuclear cells in the BAL fluid in DNFB-sensitized mice at 48 hrs after DNS challenge. Treatment with the NK-2 receptor antagonist did not prevent the development of tracheal hyperreactivity or cellular accumulation in the airways. The role for the NK- 1 receptor was further confirmed in NK- 1 receptor knockout mice. In earlier studies, we have shown that mast cells played a crucial role in the development of nonatopic asthma. Although mast cell activation may be induced by stimulation of neurokinin receptors, we did not find an inhibitory effect of the NK receptor antagonists or genetic absence of NK- 1 receptors on the release of mast cell protease in serum of asthmatic animals. In conclusion, present study shows that, distal from mast cell activation, the NK- 1 receptor is crucial for the development of tracheal hyperreactivity and pulmonary leukocyte accumulation in nonatopic asthma. Sponsored by a research grant of the Netherlands Asthma Foundation (NAF94.34).
Donald YM Leung *, Gail H Cassell§, Johnny Gutierrez*, Richard J Martin*. Monica Kraft* *National Jewish Medical and Research Center, Denver. CO §University of Alabama, Birmingham, AL Recent studies have demonstrated a potential association between chronic asthma and the presence of airway MP in a subset of patients. To date, this association has been based on PCR reactivity for MP, as cultures have been negative and there has been a lack of antibody response to MP. In the current study, we defined T cell responses to MP. In vitro studies were initially carried out to examine T cell proliferative responses and T cell repertoire stimulated by MP in peripheral blood mononuclear cells (PBMC) of 12 asthmatics who previously had MP in their airways detected by PCR. MP induced T cell proliferation in all 12 asthmatics as measured by 3H-thymidine incorporation (mean cpm=29,931+9656 incorporated after MP vs 460+55 in the absence ofMP; p<0.0l). PBMC stimulated with MP or anti-CD3 were stained with monoclonal antibodies against the T cell receptor (TCR) B V chains B V2, 3, 5.1, 5.2, 6.7, 7, 8, 9, 11,12, 13.1, 13.2, 14, 16, 17, 20, 21.3, 22 and 23. TCR BV5.2 and 23 were the only TCRBVs that demonstrated a significant expansion after in vitro stimulation with MP, as compared to anti-CD3 (p<0.05). To examine the potential in vivo role of MP in chronic asthma, we examined 4 TCRBVs in the bronchoalveolar lavage (BAL) T cells vs PBMC in 4 asthmatics known to be PCR reactive for MP in their airways vs 5 asthmatics without MP in their airways. We found that patients with MP in their airways as compared to PBMC had a significant increase in CD4+ T cells (but not CDS+ T cells) expressing TCRBV5.2 (p<0.01), but a decrease in TCRBV23 (p<0.05). These changes were not observed in TCRBV2 or TCRBV8 CD4 or CD8 T cells. In conclusion, asthmatics with MP in their airways exhibit evidence of a local T cell response to Mycoplasma Pneumoniae.
22
Acoustic Analysis of Cough Sounds in Asthma
Jaclvn A Smith*, Yen Ha Hiew§, Bart3' M Cheetham§, John E Earis~,, Ashley A Woodcock* *Wythenshawe Hospital, Manchester, UK §University of Manchester, Manchester, UK YUniversity Hospital Aintree, Liverpool, UK We have compared spontaneous coughs in asthma (n=8) with cryptogenic fibrosing alveolitis (n=9) using overnight cough recording. Audio editing software and a computer algorithm are used to identify and analyse the cough sounds in the time and frequency domains. Cough in asthma has a different frequency distribution (as analysed by Fast Fourier Transformation) than cough in cryptogenic fibrosing alveolitis and voluntary coughs in normal subjects. In particular, immediately after the initial explosive event (glottic opening) most asthmatics have a high frequency periodic component to the waveform (range 350-800Hz), absent in other coughs. The frequency of these periodic waves varies both within and between individuals. Some individuals who do not have the periodic component at the start of the night develop them in the early hours of the morning. A similar periodic pattern can be re-produced in normal subjects by coughing from mid to low lung volumes (i.e. 50% and 25% of forced vital capacity). It appears this periodic waveform is due to wheezing.
Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 2002
1 With T Cell Responses to MycoplasmaPneumoniae(MP) in Patients ChronicAsthma
9 Reactivityto CommonAllergens in SpontaneousFeline Asthma Keigo Kurata*, Kenichi Masuda*, Masahiro Sakaguchi§, Koichi Ohno*. Hajime Tsujimoto* *University of Tokyo, Tokyo, Japan §National Institute of Infectious Diseases, Tokyo, Japan It has been thought that an appropriate animal model for human asthma is necessary to evaluate efficacy of novel therapy such as immunotherapy with CpG oligodeoxynucleotides and DNA vaccine. Feline asthma is a chronic inflammatory airway syndrome characterized by recurrent respiratory symptoms such as coughing and wheezing. Increasing opacity of bronchial walls is a typical finding in thoracic radiography of cats with asthma. In contrast to asthma in humans, an association with sensitization to aeroallergen in feline asthma has been unclear. The objective of this study was to determine whether cats with asthma were sensitive to aeroallergens. Intradermal testing, in vitro serum allergen-specific IgE testing, and lymphocyte blastogenic responses were used in 9 cats diagnosed as feline asthma based on clinical symptoms, radiographic findings and therapeutic responses to corticosteroids. Seven of the 9 cats showed positive reactions to common allergens such as house dust mite (Dermatophagoidesfarinae and D. pteronyssinus), weeds (ragweed, yellow dock, etc), trees (oak, elm, etc), grasses (orchard grass, timothy grass, etc), arthropods, fungi (Aspergillus spp., Alternaria spp., etc), and foods (egg, corn, etc) in either intradermal testing or IgE testing. Of these allergens, the allergens showing agreement of positive results between intradermal tesing and IgE tesing were house dust mite (7 cats), fungi (1) and foods (1). Two cats were negative to any allergens examined in intradermal testing and IgE testing. In blastogenic responses of peripheral blood mononuclear cells from the cats showing positive reactions to house dust mite, 4 of the 7 cats showed positive reactions to both D. farinae and D. pteronyssinus with stimulation indices (S.1.) from 2,0 to 9.8. Two of the 7 cats showed positive reaction to only D. farinae with S.I. of 2.0. These results indicate that sensitization to aeroallergens can be, in part, associated with the pathogenesis of feline asthma similar to that in human patients with asthma. House dust mite can be considered as a common allergen causing allergic reactions in respiratory organs in cats. From the similarities to human asthma, feline asthma is considered as a useful animal model of asthma in terms of development of a novel immunotherapy. Supported by a grant from the Ministry of Education, Science, Sports and Culture.
f~ The Neurokinin-1 Receptor Is Crucial for the Development of Nonatopic Asthma
2U
Hanneke P Van der Kleij*, Aletta D Kraneveld*, Frank A Redegeld*, Norma P Gerard§, Olivier Morteau§, Frans P Nijkamp* *Faculty of Pharmacy, Utrecht University, Utrecht, Netherlands §Harvard Medical School, Boston, MA Mast cell activation, hronchoconstriction, inflammation and airway hyperreactivity are prominent features of dinitrofluorobenzene (DNFB)induced hypersensitivity reactions in the mouse airways, a murine model for nonatopic asthma. We studied the role of neurokinin receptors in the development of nonatopic asthma using specific NK- 1 (RP67580) or NK-2 (SR48968) receptor antagonists and genetically NK-1 receptor-deficient animals. NK- 1 receptor blockade strongly reduced the DNFB-induced tracheal hyperreactivity and the accumulation of neutrophils and mononuclear cells in the BAL fluid in DNFB-sensitized mice at 48 hrs after DNS challenge. Treatment with the NK-2 receptor antagonist did not prevent the development of tracheal hyperreactivity or cellular accumulation in the airways. The role for the NK- 1 receptor was further confirmed in NK- 1 receptor knockout mice. In earlier studies, we have shown that mast cells played a crucial role in the development of nonatopic asthma. Although mast cell activation may be induced by stimulation of neurokinin receptors, we did not find an inhibitory effect of the NK receptor antagonists or genetic absence of NK- 1 receptors on the release of mast cell protease in serum of asthmatic animals. In conclusion, present study shows that, distal from mast cell activation, the NK- 1 receptor is crucial for the development of tracheal hyperreactivity and pulmonary leukocyte accumulation in nonatopic asthma. Sponsored by a research grant of the Netherlands Asthma Foundation (NAF94.34).
Donald YM Leung *, Gail H Cassell§, Johnny Gutierrez*, Richard J Martin*. Monica Kraft* *National Jewish Medical and Research Center, Denver. CO §University of Alabama, Birmingham, AL Recent studies have demonstrated a potential association between chronic asthma and the presence of airway MP in a subset of patients. To date, this association has been based on PCR reactivity for MP, as cultures have been negative and there has been a lack of antibody response to MP. In the current study, we defined T cell responses to MP. In vitro studies were initially carried out to examine T cell proliferative responses and T cell repertoire stimulated by MP in peripheral blood mononuclear cells (PBMC) of 12 asthmatics who previously had MP in their airways detected by PCR. MP induced T cell proliferation in all 12 asthmatics as measured by 3H-thymidine incorporation (mean cpm=29,931+9656 incorporated after MP vs 460+55 in the absence ofMP; p<0.0l). PBMC stimulated with MP or anti-CD3 were stained with monoclonal antibodies against the T cell receptor (TCR) B V chains B V2, 3, 5.1, 5.2, 6.7, 7, 8, 9, 11,12, 13.1, 13.2, 14, 16, 17, 20, 21.3, 22 and 23. TCR BV5.2 and 23 were the only TCRBVs that demonstrated a significant expansion after in vitro stimulation with MP, as compared to anti-CD3 (p<0.05). To examine the potential in vivo role of MP in chronic asthma, we examined 4 TCRBVs in the bronchoalveolar lavage (BAL) T cells vs PBMC in 4 asthmatics known to be PCR reactive for MP in their airways vs 5 asthmatics without MP in their airways. We found that patients with MP in their airways as compared to PBMC had a significant increase in CD4+ T cells (but not CDS+ T cells) expressing TCRBV5.2 (p<0.01), but a decrease in TCRBV23 (p<0.05). These changes were not observed in TCRBV2 or TCRBV8 CD4 or CD8 T cells. In conclusion, asthmatics with MP in their airways exhibit evidence of a local T cell response to Mycoplasma Pneumoniae.
22
Acoustic Analysis of Cough Sounds in Asthma
Jaclvn A Smith*, Yen Ha Hiew§, Bart3' M Cheetham§, John E Earis~,, Ashley A Woodcock* *Wythenshawe Hospital, Manchester, UK §University of Manchester, Manchester, UK YUniversity Hospital Aintree, Liverpool, UK We have compared spontaneous coughs in asthma (n=8) with cryptogenic fibrosing alveolitis (n=9) using overnight cough recording. Audio editing software and a computer algorithm are used to identify and analyse the cough sounds in the time and frequency domains. Cough in asthma has a different frequency distribution (as analysed by Fast Fourier Transformation) than cough in cryptogenic fibrosing alveolitis and voluntary coughs in normal subjects. In particular, immediately after the initial explosive event (glottic opening) most asthmatics have a high frequency periodic component to the waveform (range 350-800Hz), absent in other coughs. The frequency of these periodic waves varies both within and between individuals. Some individuals who do not have the periodic component at the start of the night develop them in the early hours of the morning. A similar periodic pattern can be re-produced in normal subjects by coughing from mid to low lung volumes (i.e. 50% and 25% of forced vital capacity). It appears this periodic waveform is due to wheezing.