The Experts below are selected from a list of 186 Experts worldwide ranked by ideXlab platform
Carol R. Reinero - One of the best experts on this subject based on the ideXlab platform.
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Feline Asthma and heartworm disease clinical features diagnostics and therapeutics
Journal of Feline Medicine and Surgery, 2019Co-Authors: Sarah Garrity, Tekla M Leefowler, Carol R. ReineroAbstract:Practical relevance:For Feline practitioners, the cat with a cough or respiratory distress and thoracic radiographs with a bronchial or bronchointerstitial pattern suggests lower airway disease. Tw...
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Oral Probiotics Alter Healthy Feline Respiratory Microbiota.
Frontiers in Microbiology, 2017Co-Authors: Aida I. Vientós-plotts, Aaron C. Ericsson, Hansjörg Rindt, Carol R. ReineroAbstract:Probiotics have been advocated as a novel therapeutic approach to respiratory disease, but knowledge of how oral administration of probiotics influences the respiratory microbiota is needed. Using 16S rRNA amplicon sequencing of bacterial DNA our objective was to determine whether oral probiotics changed the composition of the upper and lower airway, rectal, and blood microbiota. We hypothesized that oral probiotics would modulate the respiratory microbiota in healthy cats, demonstrated by the detection and/or increased relative abundance of the probiotic bacterial species and altered composition of the microbial population in the respiratory tract. Six healthy young research cats had oropharyngeal (OP), bronchoalveolar lavage fluid (BALF), rectal, and blood samples collected at baseline and 4 weeks after receiving oral probiotics. 16S rRNA gene amplicon libraries were sequenced, and coverage, richness, and relative abundance of representative operational taxonomic units (OTUs) were determined. Hierarchical and principal component analyses (PCA) demonstrated relatedness of samples. Mean microbial richness significantly increased only in the upper and lower airways. The number of probiotic OTUs (out of 5 total) that significantly increased in relative abundance versus baseline was 5 in OP, 3 in BAL and 2 in feces. Using hierarchical clustering, BALF and blood samples grouped together after probiotic administration, and PERMANOVA supported that these two sites underwent significant changes in microbial composition. PERMANOVA revealed that OP and rectal samples had microbial population compositions that did not significantly change. These findings were visualized via PCA, which revealed distinct microbiomes in each site; samples clustered more tightly at baseline and had more variation after probiotic administration. This is the first study describing the effect of oral probiotics on the respiratory microbiota via detection of probiotic species in the airways. Finding bacterial species present in the oral probiotics in the upper and lower airways provides pilot data suggesting that oral probiotics could serve as a tool to target dysbiosis occurring in inflammatory airway diseases such as Feline Asthma, a disease in which cats serve as an important comparative and translational model for humans.
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Dynamic changes of the respiratory microbiota and its relationship to fecal and blood microbiota in healthy young cats.
PLOS ONE, 2017Co-Authors: Aida I. Vientós-plotts, Leah A Cohn, Megan E Grobman, Amber Graham, Aaron C. Ericsson, Hansjörg Rindt, Kaitlin Bishop, Carol R. ReineroAbstract:Advances in the field of metagenomics using culture-independent methods of microbial identification have allowed characterization of rich and diverse communities of bacteria in the lungs of healthy humans, mice, dogs, sheep and pigs. These data challenge the long held belief that the lungs are sterile and microbial colonization is synonymous with pathology. Studies in humans and animals demonstrate differences in the composition of airway microbiota in health versus disease suggesting respiratory dysbiosis occurs. Using 16S rRNA amplicon sequencing of DNA extracted from rectal and oropharyngeal (OP) swabs, bronchoalveolar lavage fluid (BALF), and blood, our objective was to characterize the fecal, OP, blood, and lower airway microbiota over time in healthy cats. This work in healthy cats, a species in which a respiratory microbiota has not yet been characterized, sets the stage for future studies in Feline Asthma in which cats serve as a comparative and translational model for humans. Fecal, OP and BALF samples were collected from six healthy research cats at day 0, week 2, and week 10; blood was collected at week 10. DNA was extracted, amplified via PCR, and sequenced using the Illumina MiSeq platform. Representative operational taxonomic units (OTUs) were identified and microbial richness and diversity were assessed. Principal component analysis (PCA) was used to visualize relatedness of samples and PERMANOVA was used to test for significant differences in microbial community composition. Fecal and OP swabs provided abundant DNA yielding a mean±SEM of 65,653±6,145 and 20,6323±4,360 sequences per sample, respectively while BALF and blood samples had lower coverage (1,489±430 and 269±18 sequences per sample, respectively). Oropharyngeal and fecal swabs were significantly richer than BALF (mean number OTUs 93, 88 and 36, respectively; p < 0.001) with no significant difference (p = 0.180) in richness between time points. PCA revealed site-specific microbial communities in the feces, and upper and lower airways. In comparison, blood had an apparent compositional similarity with BALF with regard to a few dominant taxa, but shared more OTUs with feces. Samples clustered more by time than by individual, with OP swabs having subjectively greater variation than other samples. In summary, healthy cats have a rich and distinct lower airway microbiome with dynamic bacterial populations. The microbiome is likely to be altered by factors such as age, environmental influences, and disease states. Further data are necessary to determine how the distinct Feline microbiomes from the upper and lower airways, feces and blood are established and evolve. These data are relevant for comparisons between healthy cats and cats with respiratory disease.
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intravenous adipose derived mesenchymal stem cell therapy for the treatment of Feline Asthma a pilot study
Journal of Feline Medicine and Surgery, 2016Co-Authors: Julie E Trzil, Tracy L Webb, Cheehoon Chang, Jessica M Quimby, John R Dodam, Isabelle Masseau, Carol R. ReineroAbstract:Objectives The aim of this study was to evaluate the feasibility and efficacy of serially administered adipose-derived mesenchymal stem cells (MSCs) in an experimental Feline Asthma model. Methods Allergic Asthma was acutely induced with Bermuda grass allergen in six purpose-bred cats. Five intravenous infusions of allogeneic MSCs (n = 4; MSC-treated) or saline (n = 2; placebo-treated) were administered over the first 130 days after Asthma induction. Infusions contained 2 × 106, 4 × 106, 4.7 × 106, 1 × 107 and 1 × 107 cryopreserved MSCs/cat. For thoracic imaging additional cats were enrolled as control groups: four untreated, experimentally Asthmatic cats (combined with placebo-treated cats), and six healthy, non-Asthmatic cats. Outcome measures included airway eosinophilia, pulmonary mechanics, thoracic computed tomography and several immunologic assays. Results Cats were assessed for 9 months after treatment. At early points, airway eosinophil percentage was not affected by MSC administration (post-treatment average of days 12, 26, 47, 108 and 133 in MSC-treated cats was 41 ± 15% and in placebo-treated cats it was 34 ± 16%). By month 9, eosinophil percentages in all MSC-treated cats decreased to normal reference intervals (MSC-treated 6%; placebo-treated 20%; normal Conclusions and relevance MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced Asthmatic cats. Results warrant additional investigation of MSC therapy for Asthma in cats.
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chronic neurokinin 1 receptor antagonism fails to ameliorate clinical signs airway hyper responsiveness or airway eosinophilia in an experimental model of Feline Asthma
Journal of Feline Medicine and Surgery, 2016Co-Authors: Megan E Grobman, John R Dodam, Hilton Outi, Amber Graham, Carol R. ReineroAbstract:ObjectivesFeline allergic Asthma is a common chronic lower airway disease characterized by clinical signs attributed to eosinophilic inflammation, airway hyper-responsiveness (AHR) and airway remodeling. Tachykinins released from sensory nerves and immune cells bind neurokinin-1 (NK-1) receptors in the lung. The resultant neurogenic airway inflammation has been implicated in Asthma pathogenesis. In mouse models and spontaneous human Asthma, NK receptor antagonists reduce bronchospasm and inflammation. We hypothesized that chronic administration of maropitant, an NK-1 receptor antagonist, would decrease clinical signs of Asthma, AHR and eosinophilic inflammation in experimentally Asthmatic cats.MethodsCats (n = 6) induced to have Asthma using Bermuda grass allergen (BGA) were enrolled in a randomized, prospective, placebo-controlled crossover design study. Cats received either oral maropitant (2 mg/kg) or placebo q48h for 4 weeks; following a 2 week washout, cats were crossed-over to the alternate treatmen...
John R Dodam - One of the best experts on this subject based on the ideXlab platform.
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intravenous adipose derived mesenchymal stem cell therapy for the treatment of Feline Asthma a pilot study
Journal of Feline Medicine and Surgery, 2016Co-Authors: Julie E Trzil, Tracy L Webb, Cheehoon Chang, Jessica M Quimby, John R Dodam, Isabelle Masseau, Carol R. ReineroAbstract:Objectives The aim of this study was to evaluate the feasibility and efficacy of serially administered adipose-derived mesenchymal stem cells (MSCs) in an experimental Feline Asthma model. Methods Allergic Asthma was acutely induced with Bermuda grass allergen in six purpose-bred cats. Five intravenous infusions of allogeneic MSCs (n = 4; MSC-treated) or saline (n = 2; placebo-treated) were administered over the first 130 days after Asthma induction. Infusions contained 2 × 106, 4 × 106, 4.7 × 106, 1 × 107 and 1 × 107 cryopreserved MSCs/cat. For thoracic imaging additional cats were enrolled as control groups: four untreated, experimentally Asthmatic cats (combined with placebo-treated cats), and six healthy, non-Asthmatic cats. Outcome measures included airway eosinophilia, pulmonary mechanics, thoracic computed tomography and several immunologic assays. Results Cats were assessed for 9 months after treatment. At early points, airway eosinophil percentage was not affected by MSC administration (post-treatment average of days 12, 26, 47, 108 and 133 in MSC-treated cats was 41 ± 15% and in placebo-treated cats it was 34 ± 16%). By month 9, eosinophil percentages in all MSC-treated cats decreased to normal reference intervals (MSC-treated 6%; placebo-treated 20%; normal Conclusions and relevance MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced Asthmatic cats. Results warrant additional investigation of MSC therapy for Asthma in cats.
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chronic neurokinin 1 receptor antagonism fails to ameliorate clinical signs airway hyper responsiveness or airway eosinophilia in an experimental model of Feline Asthma
Journal of Feline Medicine and Surgery, 2016Co-Authors: Megan E Grobman, John R Dodam, Hilton Outi, Amber Graham, Carol R. ReineroAbstract:ObjectivesFeline allergic Asthma is a common chronic lower airway disease characterized by clinical signs attributed to eosinophilic inflammation, airway hyper-responsiveness (AHR) and airway remodeling. Tachykinins released from sensory nerves and immune cells bind neurokinin-1 (NK-1) receptors in the lung. The resultant neurogenic airway inflammation has been implicated in Asthma pathogenesis. In mouse models and spontaneous human Asthma, NK receptor antagonists reduce bronchospasm and inflammation. We hypothesized that chronic administration of maropitant, an NK-1 receptor antagonist, would decrease clinical signs of Asthma, AHR and eosinophilic inflammation in experimentally Asthmatic cats.MethodsCats (n = 6) induced to have Asthma using Bermuda grass allergen (BGA) were enrolled in a randomized, prospective, placebo-controlled crossover design study. Cats received either oral maropitant (2 mg/kg) or placebo q48h for 4 weeks; following a 2 week washout, cats were crossed-over to the alternate treatmen...
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acute neurokinin 1 receptor antagonism fails to dampen airflow limitation or airway eosinophilia in an experimental model of Feline Asthma
Journal of Feline Medicine and Surgery, 2016Co-Authors: Megan E Grobman, John R Dodam, Stacy Krumme, Hilton Outi, Carol R. ReineroAbstract:ObjectivesFeline allergic Asthma is a chronic inflammatory disorder of the lower airways that may manifest with acute, life-threatening clinical signs. Tachykinins released from sensory nerves and ...
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the trpv1 receptor agonist capsaicin is an ineffective bronchoprovocant in an experimental model of Feline Asthma
Journal of Feline Medicine and Surgery, 2015Co-Authors: Megan E Grobman, John R Dodam, Stacy Krumme, Carol R. ReineroAbstract:ObjectivesAirway hyper-responsiveness (AHR), a key feature of Feline Asthma, can be measured using bronchoprovocation testing. Limitations of both direct and indirect bronchoprovocants evaluated to...
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COMPARISON OF LUNG ATTENUATION AND HETEROGENEITY BETWEEN CATS WITH EXPERIMENTALLY INDUCED ALLERGIC Asthma, NATURALLY OCCURRING Asthma AND NORMAL CATS.
Veterinary Radiology & Ultrasound, 2015Co-Authors: Isabelle Masseau, John R Dodam, Leah A Cohn, Alina Banuelos, Carol R. ReineroAbstract:Airway remodeling is a prominent feature of Feline allergic Asthma but requires biopsy for characterization. Computed tomography (CT) has appeal as a minimally invasive diagnostic test. The purpose of this prospective case–control study was to compare indices of airway remodeling between cats with experimentally induced, spontaneousAsthmaandhealthyunaffectedcatsusingCT.Wehypothesizedthatexperimentalandspontaneous Feline Asthma would have similar CT airway remodeling characteristics and that these would be significantly different in healthy cats. Experimentally induced Asthmatic research cats (n = 5), spontaneously Asthmatic pet cats (n = 6), and healthy research cats (n = 5) were scanned unrestrained using a 64-detector row CT scanner. Inspiratory breath-hold CT scans were also performed in experimentally induced Asthmatic and healthy cats. Mean ± extent variation of lung attenuation for each cat was determined using an airway inspector software program and CT images were scored for lung heterogeneity by a board-certified veterinary radiologist who was unaware of cat group status. Groups were compared using one-way ANOVA (unrestrained scans) and the Student’s t-test (anesthetized scans) with significance defined as P < 0.10. Experimentally Asthmatic and spontaneously Asthmatic cats had significantly (P = 0.028 and P = 0.073, respectively) increased lung attenuation compared to healthy cats. Heterogeneity scores were higher in experimentally induced Asthmatic cat than in healthy cats. Objective quantification of lung heterogeneity and lung volume did not differ among the three groups (P = 0.311, P = 0.181, respectively). Findings supported our hypothesis. Inspiratory breathhold anesthetized CT scans facilitated discrimination between Asthmatic and healthy cats in comparison to unrestrained CT scans. C � 2015 American College of Veterinary Radiology.
Julie E Trzil - One of the best experts on this subject based on the ideXlab platform.
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Feline Asthma diagnostic and treatment update
Veterinary Clinics of North America-small Animal Practice, 2019Co-Authors: Julie E TrzilAbstract:: Asthma is an important allergic lower-airway disease in cats affecting approximately 1% to 5% of the pet cat population. New diagnostics are being developed to help better differentiate Asthma from other lower-airway diseases and improve monitoring. In addition, new treatments are being developed to help in refractory cases or in those cases in which traditional therapeutics are contraindicated. This article discusses potential pitfalls in the diagnosis of Asthma. In addition, current literature investigating new diagnostic tests and therapies for Feline Asthma is reviewed.
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intravenous adipose derived mesenchymal stem cell therapy for the treatment of Feline Asthma a pilot study
Journal of Feline Medicine and Surgery, 2016Co-Authors: Julie E Trzil, Tracy L Webb, Cheehoon Chang, Jessica M Quimby, John R Dodam, Isabelle Masseau, Carol R. ReineroAbstract:Objectives The aim of this study was to evaluate the feasibility and efficacy of serially administered adipose-derived mesenchymal stem cells (MSCs) in an experimental Feline Asthma model. Methods Allergic Asthma was acutely induced with Bermuda grass allergen in six purpose-bred cats. Five intravenous infusions of allogeneic MSCs (n = 4; MSC-treated) or saline (n = 2; placebo-treated) were administered over the first 130 days after Asthma induction. Infusions contained 2 × 106, 4 × 106, 4.7 × 106, 1 × 107 and 1 × 107 cryopreserved MSCs/cat. For thoracic imaging additional cats were enrolled as control groups: four untreated, experimentally Asthmatic cats (combined with placebo-treated cats), and six healthy, non-Asthmatic cats. Outcome measures included airway eosinophilia, pulmonary mechanics, thoracic computed tomography and several immunologic assays. Results Cats were assessed for 9 months after treatment. At early points, airway eosinophil percentage was not affected by MSC administration (post-treatment average of days 12, 26, 47, 108 and 133 in MSC-treated cats was 41 ± 15% and in placebo-treated cats it was 34 ± 16%). By month 9, eosinophil percentages in all MSC-treated cats decreased to normal reference intervals (MSC-treated 6%; placebo-treated 20%; normal Conclusions and relevance MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced Asthmatic cats. Results warrant additional investigation of MSC therapy for Asthma in cats.
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long term evaluation of mesenchymal stem cell therapy in a Feline model of chronic allergic Asthma
Clinical & Experimental Allergy, 2014Co-Authors: Julie E Trzil, Tracy L Webb, Cheehoon Chang, Jessica M Quimby, John R Dodam, Leah A Cohn, Isabelle Masseau, Carol R. ReineroAbstract:SummaryBackground Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodelling in murine models of acutely induced Asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic Feline Asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, AHR, and remodelling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental Feline allergic Asthma. Methods Cats with chronic, experimentally induced Asthma received six intravenous infusions of MSCs (0.36–2.5 × 10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for 1 year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia, pulmonary mechanics and clinical scoring to assess AHR, and thoracic computed tomographic (CT) scans to assess structural changes (airway remodelling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA P = 0.0311; BWT P = 0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic Feline Asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodelling by month 8, although the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodelling in chronic Asthma.
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update on Feline Asthma
Veterinary Clinics of North America-small Animal Practice, 2014Co-Authors: Julie E Trzil, Carol R. ReineroAbstract:This article provides an overview of recent advances in the diagnosis and treatment of Feline Asthma. The authors discuss the potential pitfalls in the diagnosis of Feline Asthma. In addition, current literature investigating new therapies for the treatment of Feline Asthma is reviewed.
Leah A Cohn - One of the best experts on this subject based on the ideXlab platform.
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Dynamic changes of the respiratory microbiota and its relationship to fecal and blood microbiota in healthy young cats.
PLOS ONE, 2017Co-Authors: Aida I. Vientós-plotts, Leah A Cohn, Megan E Grobman, Amber Graham, Aaron C. Ericsson, Hansjörg Rindt, Kaitlin Bishop, Carol R. ReineroAbstract:Advances in the field of metagenomics using culture-independent methods of microbial identification have allowed characterization of rich and diverse communities of bacteria in the lungs of healthy humans, mice, dogs, sheep and pigs. These data challenge the long held belief that the lungs are sterile and microbial colonization is synonymous with pathology. Studies in humans and animals demonstrate differences in the composition of airway microbiota in health versus disease suggesting respiratory dysbiosis occurs. Using 16S rRNA amplicon sequencing of DNA extracted from rectal and oropharyngeal (OP) swabs, bronchoalveolar lavage fluid (BALF), and blood, our objective was to characterize the fecal, OP, blood, and lower airway microbiota over time in healthy cats. This work in healthy cats, a species in which a respiratory microbiota has not yet been characterized, sets the stage for future studies in Feline Asthma in which cats serve as a comparative and translational model for humans. Fecal, OP and BALF samples were collected from six healthy research cats at day 0, week 2, and week 10; blood was collected at week 10. DNA was extracted, amplified via PCR, and sequenced using the Illumina MiSeq platform. Representative operational taxonomic units (OTUs) were identified and microbial richness and diversity were assessed. Principal component analysis (PCA) was used to visualize relatedness of samples and PERMANOVA was used to test for significant differences in microbial community composition. Fecal and OP swabs provided abundant DNA yielding a mean±SEM of 65,653±6,145 and 20,6323±4,360 sequences per sample, respectively while BALF and blood samples had lower coverage (1,489±430 and 269±18 sequences per sample, respectively). Oropharyngeal and fecal swabs were significantly richer than BALF (mean number OTUs 93, 88 and 36, respectively; p < 0.001) with no significant difference (p = 0.180) in richness between time points. PCA revealed site-specific microbial communities in the feces, and upper and lower airways. In comparison, blood had an apparent compositional similarity with BALF with regard to a few dominant taxa, but shared more OTUs with feces. Samples clustered more by time than by individual, with OP swabs having subjectively greater variation than other samples. In summary, healthy cats have a rich and distinct lower airway microbiome with dynamic bacterial populations. The microbiome is likely to be altered by factors such as age, environmental influences, and disease states. Further data are necessary to determine how the distinct Feline microbiomes from the upper and lower airways, feces and blood are established and evolve. These data are relevant for comparisons between healthy cats and cats with respiratory disease.
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COMPARISON OF LUNG ATTENUATION AND HETEROGENEITY BETWEEN CATS WITH EXPERIMENTALLY INDUCED ALLERGIC Asthma, NATURALLY OCCURRING Asthma AND NORMAL CATS.
Veterinary Radiology & Ultrasound, 2015Co-Authors: Isabelle Masseau, John R Dodam, Leah A Cohn, Alina Banuelos, Carol R. ReineroAbstract:Airway remodeling is a prominent feature of Feline allergic Asthma but requires biopsy for characterization. Computed tomography (CT) has appeal as a minimally invasive diagnostic test. The purpose of this prospective case–control study was to compare indices of airway remodeling between cats with experimentally induced, spontaneousAsthmaandhealthyunaffectedcatsusingCT.Wehypothesizedthatexperimentalandspontaneous Feline Asthma would have similar CT airway remodeling characteristics and that these would be significantly different in healthy cats. Experimentally induced Asthmatic research cats (n = 5), spontaneously Asthmatic pet cats (n = 6), and healthy research cats (n = 5) were scanned unrestrained using a 64-detector row CT scanner. Inspiratory breath-hold CT scans were also performed in experimentally induced Asthmatic and healthy cats. Mean ± extent variation of lung attenuation for each cat was determined using an airway inspector software program and CT images were scored for lung heterogeneity by a board-certified veterinary radiologist who was unaware of cat group status. Groups were compared using one-way ANOVA (unrestrained scans) and the Student’s t-test (anesthetized scans) with significance defined as P < 0.10. Experimentally Asthmatic and spontaneously Asthmatic cats had significantly (P = 0.028 and P = 0.073, respectively) increased lung attenuation compared to healthy cats. Heterogeneity scores were higher in experimentally induced Asthmatic cat than in healthy cats. Objective quantification of lung heterogeneity and lung volume did not differ among the three groups (P = 0.311, P = 0.181, respectively). Findings supported our hypothesis. Inspiratory breathhold anesthetized CT scans facilitated discrimination between Asthmatic and healthy cats in comparison to unrestrained CT scans. C � 2015 American College of Veterinary Radiology.
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long term evaluation of mesenchymal stem cell therapy in a Feline model of chronic allergic Asthma
Clinical & Experimental Allergy, 2014Co-Authors: Julie E Trzil, Tracy L Webb, Cheehoon Chang, Jessica M Quimby, John R Dodam, Leah A Cohn, Isabelle Masseau, Carol R. ReineroAbstract:SummaryBackground Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodelling in murine models of acutely induced Asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic Feline Asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, AHR, and remodelling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental Feline allergic Asthma. Methods Cats with chronic, experimentally induced Asthma received six intravenous infusions of MSCs (0.36–2.5 × 10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for 1 year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia, pulmonary mechanics and clinical scoring to assess AHR, and thoracic computed tomographic (CT) scans to assess structural changes (airway remodelling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA P = 0.0311; BWT P = 0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic Feline Asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodelling by month 8, although the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodelling in chronic Asthma.
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neonatal aerosol exposure to bermuda grass allergen prevents subsequent induction of experimental allergic Feline Asthma evidence for establishing early immunologic tolerance
Veterinary Immunology and Immunopathology, 2014Co-Authors: Meera C Heller, Leah A Cohn, Tekla M Leefowler, Carol R. ReineroAbstract:Allergic Asthma is increasing in industrialized countries, especially in children. Rodent and human studies suggest an opportunity to “prevent” Asthma in the perinatal period. The aims of this study were to create a more “natural” model of Feline Asthma by exposing offspring of Asthmatic queens to Bermuda grass allergen (BGA) by inhalation only, and to investigate maternal–fetal–infant interactions in the development of Asthma. Kittens from Asthmatic queens were divided into four groups: maternal exposure to aerosolized BGA during the third trimester, neonatal exposure to aerosolized BGA in the first three months of life, both maternal and neonatal exposure, or saline control. Kittens failing to achieve an Asthmatic phenotype based on bronchoalveolar lavage fluid (BALF) analysis by 6 months underwent traditional sensitization: adjuvanted allergen injection, intranasal allergen, and aerosol challenges. BALF was collected at 3, 4 and 6 months, and after sensitization at 8 months, and analyzed for eosinophil counts and BGA-specific IgG and IgA. Intradermal testing (IDT) was performed at 6 and 7 months. At six months none of the kittens had airway eosinophilia, BGA-specific IgG or IgA, and were non-responsive to IDT. After sensitization, kittens receiving neonatal aerosolization failed to develop airway eosinophilia as seen in the controls. Kittens exposed to BGA aerosols, either in-utero or neonatally, continued to lack IDT response. Chronic exposure to BGA aerosols failed to induce Asthma in kittens, and instead tolerized the kittens to BGA. This is the first evidence that neonatal intervention could potentially “prevent” allergic Asthma in cats.
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oral glucocorticoids diminish the efficacy of allergen specific immunotherapy in experimental Feline Asthma
Veterinary Journal, 2013Co-Authors: Cheehoon Chang, Leah A Cohn, Amy E Declue, Carol R. ReineroAbstract:Abstract Allergen-specific rush immunotherapy (RIT) shows promise in treating Asthma; however, pet cats will likely require at least initial concurrent glucocorticoids (GCs) to control serious clinical signs. How the immunosuppressive effects of GCs would impact RIT in cats is unknown. The hypothesis of this study was that oral, but not inhaled GCs will diminish the efficacy of RIT in experimental Feline Asthma. Cats (n = 6/group) were sensitized using Bermuda grass allergen (BGA) and randomized to receive BGA-specific RIT for 9 months with an oral GC (prednisolone 10 mg daily), inhaled GC (fluticasone 220 μg twice daily), or placebo administered for the first 6 months. Bronchoalveolar lavage fluid (BALF) percent eosinophils and other immunological assays were performed. Eosinophilic airway inflammation was suppressed in all groups at month 6 of RIT (group mean ± SD, 5 ± 2%, 13 ± 4%, and 7 ± 2% for oral GC, inhaled GC, and placebo, respectively; P = 0.291). BALF percent eosinophils significantly increased over time only in oral GC/RIT cats between months 6 and 9 (P = 0.031). Placebo/RIT cats had significant decreases over time in BGA-specific serum IgE (P = 0.031). Concentration of interleukin (IL)-5 in BALF significantly increased over time in inhaled GC/RIT cats (P = 0.031). No significant differences were found between groups at month 6 or over time in each group for BGA-specific lymphocyte blastogenesis, percent blood T regulatory cells, or number of IL-10-producing cells. Given the significant increase of airway eosinophilia over time in RIT cats initially treated with an oral GC, inhaled GCs might be better for dampening eosinophilic inflammation until RIT normalizes the dysregulated immune system.
Cheehoon Chang - One of the best experts on this subject based on the ideXlab platform.
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intravenous adipose derived mesenchymal stem cell therapy for the treatment of Feline Asthma a pilot study
Journal of Feline Medicine and Surgery, 2016Co-Authors: Julie E Trzil, Tracy L Webb, Cheehoon Chang, Jessica M Quimby, John R Dodam, Isabelle Masseau, Carol R. ReineroAbstract:Objectives The aim of this study was to evaluate the feasibility and efficacy of serially administered adipose-derived mesenchymal stem cells (MSCs) in an experimental Feline Asthma model. Methods Allergic Asthma was acutely induced with Bermuda grass allergen in six purpose-bred cats. Five intravenous infusions of allogeneic MSCs (n = 4; MSC-treated) or saline (n = 2; placebo-treated) were administered over the first 130 days after Asthma induction. Infusions contained 2 × 106, 4 × 106, 4.7 × 106, 1 × 107 and 1 × 107 cryopreserved MSCs/cat. For thoracic imaging additional cats were enrolled as control groups: four untreated, experimentally Asthmatic cats (combined with placebo-treated cats), and six healthy, non-Asthmatic cats. Outcome measures included airway eosinophilia, pulmonary mechanics, thoracic computed tomography and several immunologic assays. Results Cats were assessed for 9 months after treatment. At early points, airway eosinophil percentage was not affected by MSC administration (post-treatment average of days 12, 26, 47, 108 and 133 in MSC-treated cats was 41 ± 15% and in placebo-treated cats it was 34 ± 16%). By month 9, eosinophil percentages in all MSC-treated cats decreased to normal reference intervals (MSC-treated 6%; placebo-treated 20%; normal Conclusions and relevance MSCs may have a delayed effect in reducing airway inflammation, airway hyper-responsiveness and remodeling in experimentally induced Asthmatic cats. Results warrant additional investigation of MSC therapy for Asthma in cats.
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long term evaluation of mesenchymal stem cell therapy in a Feline model of chronic allergic Asthma
Clinical & Experimental Allergy, 2014Co-Authors: Julie E Trzil, Tracy L Webb, Cheehoon Chang, Jessica M Quimby, John R Dodam, Leah A Cohn, Isabelle Masseau, Carol R. ReineroAbstract:SummaryBackground Mesenchymal stem cells (MSCs) decrease airway eosinophilia, airway hyperresponsiveness (AHR), and remodelling in murine models of acutely induced Asthma. We hypothesized that MSCs would diminish these hallmark features in a chronic Feline Asthma model. Objective To document effects of allogeneic, adipose-derived MSCs on airway inflammation, AHR, and remodelling over time and investigate mechanisms by which MSCs alter local and systemic immunologic responses in chronic experimental Feline allergic Asthma. Methods Cats with chronic, experimentally induced Asthma received six intravenous infusions of MSCs (0.36–2.5 × 10E7 MSCs/infusion) or placebo bimonthly at the time of study enrollment. Cats were evaluated at baseline and longitudinally for 1 year. Outcome measures included: bronchoalveolar lavage fluid cytology to assess airway eosinophilia, pulmonary mechanics and clinical scoring to assess AHR, and thoracic computed tomographic (CT) scans to assess structural changes (airway remodelling). CT scans were evaluated using a scoring system for lung attenuation (LA) and bronchial wall thickening (BWT). To assess mechanisms of MSC action, immunologic assays including allergen-specific IgE, cellular IL-10 production, and allergen-specific lymphocyte proliferation were performed. Results There were no differences between treatment groups or over time with respect to airway eosinophilia or AHR. However, significantly lower LA and BWT scores were noted in CT images of MSC-treated animals compared to placebo-treated cats at month 8 of the study (LA P = 0.0311; BWT P = 0.0489). No differences were noted between groups in the immunologic assays. Conclusions and Clinical Relevance When administered after development of chronic allergic Feline Asthma, MSCs failed to reduce airway inflammation and AHR. However, repeated administration of MSCs at the start of study did reduce computed tomographic measures of airway remodelling by month 8, although the effect was not sustained at month 12. Further study of MSC therapy including repeated MSC administration is warranted to assess impact on remodelling in chronic Asthma.
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oral glucocorticoids diminish the efficacy of allergen specific immunotherapy in experimental Feline Asthma
Veterinary Journal, 2013Co-Authors: Cheehoon Chang, Leah A Cohn, Amy E Declue, Carol R. ReineroAbstract:Abstract Allergen-specific rush immunotherapy (RIT) shows promise in treating Asthma; however, pet cats will likely require at least initial concurrent glucocorticoids (GCs) to control serious clinical signs. How the immunosuppressive effects of GCs would impact RIT in cats is unknown. The hypothesis of this study was that oral, but not inhaled GCs will diminish the efficacy of RIT in experimental Feline Asthma. Cats (n = 6/group) were sensitized using Bermuda grass allergen (BGA) and randomized to receive BGA-specific RIT for 9 months with an oral GC (prednisolone 10 mg daily), inhaled GC (fluticasone 220 μg twice daily), or placebo administered for the first 6 months. Bronchoalveolar lavage fluid (BALF) percent eosinophils and other immunological assays were performed. Eosinophilic airway inflammation was suppressed in all groups at month 6 of RIT (group mean ± SD, 5 ± 2%, 13 ± 4%, and 7 ± 2% for oral GC, inhaled GC, and placebo, respectively; P = 0.291). BALF percent eosinophils significantly increased over time only in oral GC/RIT cats between months 6 and 9 (P = 0.031). Placebo/RIT cats had significant decreases over time in BGA-specific serum IgE (P = 0.031). Concentration of interleukin (IL)-5 in BALF significantly increased over time in inhaled GC/RIT cats (P = 0.031). No significant differences were found between groups at month 6 or over time in each group for BGA-specific lymphocyte blastogenesis, percent blood T regulatory cells, or number of IL-10-producing cells. Given the significant increase of airway eosinophilia over time in RIT cats initially treated with an oral GC, inhaled GCs might be better for dampening eosinophilic inflammation until RIT normalizes the dysregulated immune system.
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beneficial cross protection of allergen specific immunotherapy on airway eosinophilia using unrelated or a partial repertoire of allergen s implicated in experimental Feline Asthma
Veterinary Journal, 2012Co-Authors: Carol R. Reinero, Cheehoon Chang, Leah A Cohn, Tekla M Leefowler, Amy E DeclueAbstract:Abstract The study hypothesis was that in experimentally Asthmatic cats rush immunotherapy (RIT) using allergens not completely matched with sensitizing allergen(s) would at least partially attenuate the Asthmatic phenotype and modulate the aberrant immune response. In phase I, cats sensitized to Bermuda grass allergen (BGA), house dust mite allergen (HDMA) or placebo received BGA RIT. In phase II, cats dually sensitized to BGA and HDMA received RIT using BGA, HDMA or placebo. Efficacy of RIT was assessed using percentage bronchoalveolar lavage fluid (BALF) eosinophils. Additionally, a variety of immunologic assays were performed. Eosinophilic airway inflammation significantly decreased over time in Asthmatic cats given RIT using sensitizing allergen or unrelated allergen (P
