- Email: [email protected]
Entire Course Monitoring and Evaluation of Asthma Attack Following Allergen Airway Challenge In A Rat Model
14
Identification of steroid response signature among patients with mild to moderate asthma using differential protein expression analysis.
16
Entire Course Monitoring and Evaluation of Asthma Attack Following Allergen Airway Challenge In A Rat Model
Tanvi Patel, MD1, Lata Kaphalia, MS, MEd, PhD2, and William J. Calhoun, MD2; 1UTMB, League City, TX, 2UTMB, Galveston, TX. RATIONALE: Asthma is a heterogeneous disorder with several phenotypes. We proposed to identify a unique steroid response signature in mildto-moderate asthmatics, and postulated that asthmatics without ICS (A-S) would express higher inflammatory cytokine levels, and asthmatics on ICS (A+S) would express protein patterns similar to normal (N) patients. METHODS: We enrolled 6 N, 6 A-S and 11 A+S patients. All patients underwent bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was analyzed for 22 cytokines using the Bio-Rad Bio-Plex Pro Assay. Each cytokine was expressed as a percentage of the mean for that cytokine. Analysis was performed using one-way ANOVA, using log-transformed data. RESULTS: Seven of 22 cytokines were detectable. Combined inflammatory cytokine expression decreased between N, A-S, and A+S groups (159%, 111%, 62%, respectively; p<.05), and combined anti-inflammatory cytokine expression did not differ. Compared to A-S, A+S patients expressed lower levels of IP-10 (85% vs. 71%, p5.037) and MIG (86% vs. 35%, p5.005). IL-8 expression varied between N, A-S and A+S patients (83%, 168%, 57%; p<.001). There were no statistically significant differences in IL-10, IL-1Ra, G-CSF or VGEF expression. CONCLUSIONS: Except for IL-8, pro-inflammatory cytokine expression was decreased in A-S and A+S, compared to the N group. IL-8, IP-10 and MIG were identified as steroid responsive cytokines, as their detection levels were reduced in the A+S compared to the A-S group. The explanation for lower cytokine levels in A-S and A+S subjects may suggest in vivo proteolysis, or other effect. This data suggests that protein expression patterns may recognize steroid responsive genes in asthma.
Xingdong Zhang, Jingjing Tao, and Chuan Qin; Chinese Academy of Medical Sciences, Beijing, China. RATIONALE: For airway measurement following specific allergen challenge, anesthetization and artificial ventilation were necessary with traditional method in rodent asthma models and it was hard to naturally record the entire course of asthma attack including early-(EAR) and latephase asthmatic responses (LAR). Ergo, a new asthma animal model to meet our research requirement is necessary. METHODS: Brown Norway rats were immunized subcutaneously with 0.01, 0.1, 1, and 10 mg of ovalbumin in saline and mixed with aluminum hydroxide (alum) on days 0 and 5. Sera were collected for specific IgE analyses. Airway challenge with aerosolized 5% ovalbumin was conducted in conscious rats on day 35. Airway measurement was performed with whole-body plethysmography and enhanced pause (a parameter from the expiratory phase) was recorded continuously for 16 hours (covering the entire period of asthma attack). RESULTS: Rats developed dose-dependent specific IgE and asthmatic responses following airway challenge. The group sensitized with 10 mg ovalbumin plus 100 mg alum steadily developed EAR and LAR. EAR developed immediately following challenge and ended within the first hour. LAR initiated 1 to 2 hours after challenge and lasted from 2 hours to 14 hours. The airway responses can be inhibited if animals were treated with dexamethasone before challenge. CONCLUSIONS: Entire course of asthma attack was successfully recorded in the conscious rat model especially LAR can be observed. This model may be a useful tool for asthma studies especially for evaluating or finding antiasthma drugs.
15
17
Impact of Environmental Factors on Recurrent Asthma Exacerbations among Inner-CIty Schoolchildren from the Pittsburgh Region
Deborah A. Gentile, MD1, Nicole Sossong2, Tricia Morphew3, Albert Presto4, and Jennifer Elliott5; 1Allegheny Singer Research Institute, Pittsburgh, PA, 2Allegheny Singer Research Institute, Pittsburgh, 3Morphew Consulting, Seattle, 4Carnegie Mellon University, Pittsburgh, 5Duquense University, Pittsburgh. RATIONALE: Pediatric asthma is a public health concern in the inner-city of Pittsburgh. The purpose of this study was to determine factors influencing the occurrence of repeated episodes of asthma among Pittsburgh school-children. METHODS: This study was approved by the Allegheny Singer Research Institute IRB. Informed consent/assent was obtained from all subjects prior to participation. Students aged 4-13 years with asthma were enrolled from fifteen Pittsburgh schools. Parents were surveyed using an abbreviated, validated survey to assess asthma control. Relationships between potential contributing factors were explored using logistic regression analyses. RESULTS: 166 subjects were enrolled (53.6% African American, 48.8% female, 64.8% public insurance, and mean+/- age 9.2+/-1.8 years). 59.6% had repeated episodes of asthma in the prior year. NO2 exposure was the only unadjusted factor that influenced odds of repeated asthma exacerbations (OR51.35 per one unit increase; P<.05). Adjusted analysis showed that influence of NO2 exposure on odds of repeated asthma exacerbations became a significant factor after 9 years of age (OR51.72, P<.05 in children age 10; P>.05 in children <59 years). Chronic stress corresponded to 6 times higher odds of repeated exacerbations (OR56.10, P<.05), among children with private insurance and lower than average NOx exposure. CONCLUSIONS: Results indicate a high rate of repeated exacerbations of asthma among school children from the inner-city of Pittsburgh. Identified contributors to uncontrolled disease include outdoor air pollution, chronic stress in those not on public health insurance nor exposed to higher than average NOx levels. Future studies need to focus on improving asthma outcomes in at-risk populations.
Does Bioaerosol Exposure Increase the Risk of Pediatric Asthma?
Nadia Thura1, Eugene Hershorin, MD1, Lourdes Forster, MD1, Sumitha Khatri, MD2, and Naresh Kumar, PhD3; 1University of Miami Miller School of Medicine, Miami, FL, 2Respiratory Institute, Clevaland Clinic, Clevaland, 3University of Miami Miller School of Medicine, Department of Public Health Sciences, Miami, FL. RATIONALE: Miami, FL has high levels of year-round bioaerosols in the form of indoor molds and outdoor pollens. Elevated exposure to bioaerosols can sensitize subjects with predisposition for developing allergies and/or asthma, especially those unexposed previously. We hypothesize that migrants, especially those from higher latitudes, are at a greater risk of developing allergies and asthma after migrating to Miami. METHODS: An online survey designed with Qualtrics software was administered using iPads in two general pediatric clinics at the University of Miami. The survey includes questions on demographics, migration status, past diagnosis and symptoms of asthma or other allergic respiratory disease, medications, and environmental factors such as exposure to secondhand smoke, pets, and other indoor allergen sources. RESULTS: A total of 109 (; 70%) of 162 parents/guardians who were approached participated in the survey. Twenty percent (22 of 109) of children had physician-diagnosed asthma, and 31% of children without an asthma diagnosis reported wheezing in the past. Therefore, diagnosed and possible undiagnosed pediatric asthma prevalence was as high as 45%. Among 109 subjects, 11 were migrants. Although the prevalence of physician-diagnosed asthma among migrants and nonmigrants was not significantly different, 27% of migrant children (3 of 11) had physician-diagnosed asthma as compared to 20% (19 of 98) of non-migrants. CONCLUSIONS: While the small sample size limits the ability to draw certain conclusions, this research provides important findings concerning the sensitization to bioaerosols in the context of migration to Miami and management of pediatric asthma.
SATURDAY
Abstracts AB5
J ALLERGY CLIN IMMUNOL VOLUME 139, NUMBER 2
Identification of steroid response signature among patients with mild to moderate asthma using differential protein expression analysis.
16
Entire Course Monitoring and Evaluation of Asthma Attack Following Allergen Airway Challenge In A Rat Model
Tanvi Patel, MD1, Lata Kaphalia, MS, MEd, PhD2, and William J. Calhoun, MD2; 1UTMB, League City, TX, 2UTMB, Galveston, TX. RATIONALE: Asthma is a heterogeneous disorder with several phenotypes. We proposed to identify a unique steroid response signature in mildto-moderate asthmatics, and postulated that asthmatics without ICS (A-S) would express higher inflammatory cytokine levels, and asthmatics on ICS (A+S) would express protein patterns similar to normal (N) patients. METHODS: We enrolled 6 N, 6 A-S and 11 A+S patients. All patients underwent bronchoscopy with bronchoalveolar lavage (BAL). BAL fluid was analyzed for 22 cytokines using the Bio-Rad Bio-Plex Pro Assay. Each cytokine was expressed as a percentage of the mean for that cytokine. Analysis was performed using one-way ANOVA, using log-transformed data. RESULTS: Seven of 22 cytokines were detectable. Combined inflammatory cytokine expression decreased between N, A-S, and A+S groups (159%, 111%, 62%, respectively; p<.05), and combined anti-inflammatory cytokine expression did not differ. Compared to A-S, A+S patients expressed lower levels of IP-10 (85% vs. 71%, p5.037) and MIG (86% vs. 35%, p5.005). IL-8 expression varied between N, A-S and A+S patients (83%, 168%, 57%; p<.001). There were no statistically significant differences in IL-10, IL-1Ra, G-CSF or VGEF expression. CONCLUSIONS: Except for IL-8, pro-inflammatory cytokine expression was decreased in A-S and A+S, compared to the N group. IL-8, IP-10 and MIG were identified as steroid responsive cytokines, as their detection levels were reduced in the A+S compared to the A-S group. The explanation for lower cytokine levels in A-S and A+S subjects may suggest in vivo proteolysis, or other effect. This data suggests that protein expression patterns may recognize steroid responsive genes in asthma.
Xingdong Zhang, Jingjing Tao, and Chuan Qin; Chinese Academy of Medical Sciences, Beijing, China. RATIONALE: For airway measurement following specific allergen challenge, anesthetization and artificial ventilation were necessary with traditional method in rodent asthma models and it was hard to naturally record the entire course of asthma attack including early-(EAR) and latephase asthmatic responses (LAR). Ergo, a new asthma animal model to meet our research requirement is necessary. METHODS: Brown Norway rats were immunized subcutaneously with 0.01, 0.1, 1, and 10 mg of ovalbumin in saline and mixed with aluminum hydroxide (alum) on days 0 and 5. Sera were collected for specific IgE analyses. Airway challenge with aerosolized 5% ovalbumin was conducted in conscious rats on day 35. Airway measurement was performed with whole-body plethysmography and enhanced pause (a parameter from the expiratory phase) was recorded continuously for 16 hours (covering the entire period of asthma attack). RESULTS: Rats developed dose-dependent specific IgE and asthmatic responses following airway challenge. The group sensitized with 10 mg ovalbumin plus 100 mg alum steadily developed EAR and LAR. EAR developed immediately following challenge and ended within the first hour. LAR initiated 1 to 2 hours after challenge and lasted from 2 hours to 14 hours. The airway responses can be inhibited if animals were treated with dexamethasone before challenge. CONCLUSIONS: Entire course of asthma attack was successfully recorded in the conscious rat model especially LAR can be observed. This model may be a useful tool for asthma studies especially for evaluating or finding antiasthma drugs.
15
17
Impact of Environmental Factors on Recurrent Asthma Exacerbations among Inner-CIty Schoolchildren from the Pittsburgh Region
Deborah A. Gentile, MD1, Nicole Sossong2, Tricia Morphew3, Albert Presto4, and Jennifer Elliott5; 1Allegheny Singer Research Institute, Pittsburgh, PA, 2Allegheny Singer Research Institute, Pittsburgh, 3Morphew Consulting, Seattle, 4Carnegie Mellon University, Pittsburgh, 5Duquense University, Pittsburgh. RATIONALE: Pediatric asthma is a public health concern in the inner-city of Pittsburgh. The purpose of this study was to determine factors influencing the occurrence of repeated episodes of asthma among Pittsburgh school-children. METHODS: This study was approved by the Allegheny Singer Research Institute IRB. Informed consent/assent was obtained from all subjects prior to participation. Students aged 4-13 years with asthma were enrolled from fifteen Pittsburgh schools. Parents were surveyed using an abbreviated, validated survey to assess asthma control. Relationships between potential contributing factors were explored using logistic regression analyses. RESULTS: 166 subjects were enrolled (53.6% African American, 48.8% female, 64.8% public insurance, and mean+/- age 9.2+/-1.8 years). 59.6% had repeated episodes of asthma in the prior year. NO2 exposure was the only unadjusted factor that influenced odds of repeated asthma exacerbations (OR51.35 per one unit increase; P<.05). Adjusted analysis showed that influence of NO2 exposure on odds of repeated asthma exacerbations became a significant factor after 9 years of age (OR51.72, P<.05 in children age 10; P>.05 in children <59 years). Chronic stress corresponded to 6 times higher odds of repeated exacerbations (OR56.10, P<.05), among children with private insurance and lower than average NOx exposure. CONCLUSIONS: Results indicate a high rate of repeated exacerbations of asthma among school children from the inner-city of Pittsburgh. Identified contributors to uncontrolled disease include outdoor air pollution, chronic stress in those not on public health insurance nor exposed to higher than average NOx levels. Future studies need to focus on improving asthma outcomes in at-risk populations.
Does Bioaerosol Exposure Increase the Risk of Pediatric Asthma?
Nadia Thura1, Eugene Hershorin, MD1, Lourdes Forster, MD1, Sumitha Khatri, MD2, and Naresh Kumar, PhD3; 1University of Miami Miller School of Medicine, Miami, FL, 2Respiratory Institute, Clevaland Clinic, Clevaland, 3University of Miami Miller School of Medicine, Department of Public Health Sciences, Miami, FL. RATIONALE: Miami, FL has high levels of year-round bioaerosols in the form of indoor molds and outdoor pollens. Elevated exposure to bioaerosols can sensitize subjects with predisposition for developing allergies and/or asthma, especially those unexposed previously. We hypothesize that migrants, especially those from higher latitudes, are at a greater risk of developing allergies and asthma after migrating to Miami. METHODS: An online survey designed with Qualtrics software was administered using iPads in two general pediatric clinics at the University of Miami. The survey includes questions on demographics, migration status, past diagnosis and symptoms of asthma or other allergic respiratory disease, medications, and environmental factors such as exposure to secondhand smoke, pets, and other indoor allergen sources. RESULTS: A total of 109 (; 70%) of 162 parents/guardians who were approached participated in the survey. Twenty percent (22 of 109) of children had physician-diagnosed asthma, and 31% of children without an asthma diagnosis reported wheezing in the past. Therefore, diagnosed and possible undiagnosed pediatric asthma prevalence was as high as 45%. Among 109 subjects, 11 were migrants. Although the prevalence of physician-diagnosed asthma among migrants and nonmigrants was not significantly different, 27% of migrant children (3 of 11) had physician-diagnosed asthma as compared to 20% (19 of 98) of non-migrants. CONCLUSIONS: While the small sample size limits the ability to draw certain conclusions, this research provides important findings concerning the sensitization to bioaerosols in the context of migration to Miami and management of pediatric asthma.
SATURDAY
Abstracts AB5
J ALLERGY CLIN IMMUNOL VOLUME 139, NUMBER 2