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NSAID-Induced Asthma Attacks Does Not Correlate with Severity of Asthma Induced During Oral ASA Challenges
Abstracts S85
J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 1
The Severity of Historical ASA/NSAID-Induced Asthma Attacks Does Not Correlate with Severity of Asthma Induced During Oral ASA Challenges A. N. Williams, R. A. Simon, K. M. Woessner, D. D. Stevenson; Scripps Clinic, San Diego, CA. RATIONALE: Historical aspirin (ASA) or nonsteroidal antiinflammatory drug (NSAID)-induced reactions might provide predictive information about the severity of reactions in patients with aspirin exacerbated respiratory disease (AERD) undergoing oral ASA challenges (OAC). METHODS: The provoking doses, treatments, and treatment settings of the historical ASA/NSAID-induced asthma attacks was obtained from 210 consecutive patients with suspected AERD referred for OAC and ASA desensitization. RESULTS: Of 210 subjects, 147 (70%) reported seeking acute medical care for their historical ASA/NSAID-induced asthma attacks. Of these 147, 101 (69%) were treated in ERs and released and 46 (31%) required hospitalization. During OAC in these 147 subjects, 37 (25%) had a >20% decline and 14 (10%) had a >30% decline in FEV1 values. Of the 46 patients previously hospitalized for ASA/NSAID-induced asthma attacks, 15 (33%) had a >20% decline and 6 (13%) had a >30% decline in FEV1 during OAC. By contrast, of the 63 patients who treated their prior ASA/NSAID-induced reactions at home, 10 (16%) had a >20% decline and 5 (8%) had a >30% decline in FEV1 during OAC (p value NS for both). The average provoking doses of ASA were 550 mg for the historical reaction and 62 mg during OAC. CONCLUSIONS: The severity of the historical ASA/NSAID-induced asthma attack was not helpful in predicting asthma severity during OAC. Even though 70% of patients sought acute medical care for asthma attacks provoked by therapeutic doses of ASA/NSAID, a minority had clinically significant asthma during low-dose OAC. These data provide further reassurance regarding the safety of outpatient ASA desensitization. Funding: General Clinical Research Center, Scripps Clinic
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Serum TGF-b1 in Allergic Asthma W. Manuyakorn1, S. Benjaponpitak1, W. Kamchaisatian1, C. Setthaudom2, K. Atamasirikul2, C. Sasisakulporn3, C. Direkwattanachai1; 1 Division of Allergy/Immunology, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, THAILAND, 2Department of Pathology, Ramathibodi Hospital,Mahidol University, Bangkok, THAILAND, 3Research Center, Ramathibodi Hospital,Mahidol University, Bangkok, THAILAND. BACKGROUND: Asthma is a chronic inflammatory disease of the airway, leading to airway remodeling. TGF-b1 is a potent profibrotic and anti-inflammatory cytokine, which plays a significant role in the airway remodeling process. OBJECTIVE: To study serum TGF-b1 in different severity of allergic asthma and nonatopic healthy control. METHOD: 3 groups of allergic asthmatic patients, age 7-18 year, were recruited as to the asthma severity: mild intermittent asthma, moderate asthma and asthma in remission (no symptom of asthma and no inhaled corticosteroid use for at least 6 months). Serum TGF-b1 was measured by enzyme-linked immunosorbent assay. RESULT: Of the 31 patients recruited, 7 were mild steroid naı¨ve asthma, 12 were moderate asthma and 12 were asthma in remission. The mean serum TGF-b1 was significantly higher in mild steroid naı¨ve group (47.44 ng/mL) when compared to the asthma in remission group (35.93 ng/mL, p 5 0.014). The mean serum TGF-b1 in steroid treated groups was significantly lower than steroid naı¨ve group (37.29 ng/mL vs. 47.44 ng/mL, p 5 0.033). There was no significant difference among serum TGF-b1 in all asthmatic patient groups and control group. There was no correlation among serum TGF-b1 and other variables; age, FEV1 (%predicted), and duration of asthma. CONCLUSION: Serum TGF-b1 in allergic asthma was not different from nonatopic healthy control. Mild asthma with steroid naı¨ve group had the highest level of serum TGF-b1. Lower level of serum TGF-b1 in moderate
asthma and asthma in remission may due to the effect of inhaled corticosteroid therapy. Funding: Ramathibodi Hospital, Mahidol University
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Systemic Autoimmunity Significance in Patients with Asthma I. Agache1, L. Duca1, M. Anghel2; 1Transylvania University Brasov, Faculty of Medicine, Brasov, ROMANIA, 2Brasov County Hospital, Brasov, ROMANIA. RATIONALE: T regulatory cell dysfunction was implicated in both asthma and autoimmune diseases. Clinical significance of systemic autoimmunity in asthma was not assessed. METHODS: 96 asthma patients (pts), mean age 53.06613.66 years, 68(70.83%) women, mean disease duration 13.21612.30 years, were ELISA appreciated for the presence of antinuclear antibodies - ANA and anti b2GPI autoantibodies, and by immune turbidimetry for serum b2 microglobulin (b2MG), circulating immune complexes (CIC) and cryoglobulins (CRG) in correlation with asthma severity (ATS criteria). For comparison ‘‘classic’’ features like atopy (skin prick test), total serum IgE (chemiluminiscence), sputum and blood eosinophilia (EO) were also assessed in relation with asthma severity. Statistics by multiple regression analysis and Spearman correlation test. RESULTS: 22(22.92%) pts. had severe asthma. Multiple regression analysis pointed out as independent risk factors for severe asthma sputum eosinophilia (T-value 5 3.4379523; p<0.001), blood eosinophilia (T-value 5 2.0587923, p 5 0.043), increased total serum IgE (T-value 5 2.2288375; p 5 0.029) and the presence of ANA (T-value 5 2.611779; p50.011). Spearman correlation test between asthma severity and: sputum eosinophilia 0.5049, p <0.001; blood eosinophilia 0.2009, p50.05; increased total serum IgE 0.3494, p<0.001; ANA 0.6629; p<0.001; anti b2GPI 0.3294, p50.001; b2MG 0.4156, p<0.001; CIC 0.3053, p50.002; CRG 0.4351, p<0.001. CONCLUSIONS: The presence of antinuclear antibodies is an independent risk factor for severe asthma. Asthma severity was strongly correlated with the presence of antinuclear antibodies, moderately correlated with the presence of anti b2GPI antibodies, increased serum levels of b2 microglobulin and cryoglobulins and weakly correlated with increased levels of circulating immune complexes. Systemic autoimmunity could thus contribute to asthma severity.
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Allergy, Serum IgE, and Lung Function in Children and Adolescents With Severe or Difficult-to-Treat Asthma T. Haselkorn1, S. J. Szefler2, F. E. R. Simons3, D. R. Mink4, B. E. Chipps5, D. A. Wong1, L. Borish6; 1Genentech, Inc., South San Francisco, CA, 2Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, 3Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, CANADA, 4Ovation Research Group, San Francisco, CA, 5Capital Allergy and Respiratory Disease Center, Sacramento, CA, 6University of Virginia Health Systems, Charlottesville, VA. RATIONALE: Little is known about the rate of allergy and allergic comorbidities in young patients with severe or difficult-to-treat asthma. METHODS: One thousand two hundred sixty-one patients from the TENOR observational study were stratified by baseline age group (6-8, 9-11, 12-14, 15-17 years). The chi-square test for categorical variables and ANOVA for continuous variables were used to identify significant differences in allergic measures among age groups, stratified by gender. RESULTS: Approximately two thirds of male and female patients had a history of allergic rhinitis; 14% and 25% had a history of atopic dermatitis (AD). The proportion of male patients with AD decreased with age (P<0.05). Among patients tested, there was a high prevalence of skin test positivity in patients of pulmonologists or allergists (87% and 95%); however, fewer patients of pulmonologists than allergists reported being skin tested. In general, rates for self-reported asthma triggers were higher in females than in males. Mean total serum IgE was higher in males than females across age groups; IgE was significantly different among age groups in males (P<0.01) and females (P<0.05). Patients with lower pre- and post- FEV1 had higher IgE levels.
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J ALLERGY CLIN IMMUNOL VOLUME 119, NUMBER 1
The Severity of Historical ASA/NSAID-Induced Asthma Attacks Does Not Correlate with Severity of Asthma Induced During Oral ASA Challenges A. N. Williams, R. A. Simon, K. M. Woessner, D. D. Stevenson; Scripps Clinic, San Diego, CA. RATIONALE: Historical aspirin (ASA) or nonsteroidal antiinflammatory drug (NSAID)-induced reactions might provide predictive information about the severity of reactions in patients with aspirin exacerbated respiratory disease (AERD) undergoing oral ASA challenges (OAC). METHODS: The provoking doses, treatments, and treatment settings of the historical ASA/NSAID-induced asthma attacks was obtained from 210 consecutive patients with suspected AERD referred for OAC and ASA desensitization. RESULTS: Of 210 subjects, 147 (70%) reported seeking acute medical care for their historical ASA/NSAID-induced asthma attacks. Of these 147, 101 (69%) were treated in ERs and released and 46 (31%) required hospitalization. During OAC in these 147 subjects, 37 (25%) had a >20% decline and 14 (10%) had a >30% decline in FEV1 values. Of the 46 patients previously hospitalized for ASA/NSAID-induced asthma attacks, 15 (33%) had a >20% decline and 6 (13%) had a >30% decline in FEV1 during OAC. By contrast, of the 63 patients who treated their prior ASA/NSAID-induced reactions at home, 10 (16%) had a >20% decline and 5 (8%) had a >30% decline in FEV1 during OAC (p value NS for both). The average provoking doses of ASA were 550 mg for the historical reaction and 62 mg during OAC. CONCLUSIONS: The severity of the historical ASA/NSAID-induced asthma attack was not helpful in predicting asthma severity during OAC. Even though 70% of patients sought acute medical care for asthma attacks provoked by therapeutic doses of ASA/NSAID, a minority had clinically significant asthma during low-dose OAC. These data provide further reassurance regarding the safety of outpatient ASA desensitization. Funding: General Clinical Research Center, Scripps Clinic
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Serum TGF-b1 in Allergic Asthma W. Manuyakorn1, S. Benjaponpitak1, W. Kamchaisatian1, C. Setthaudom2, K. Atamasirikul2, C. Sasisakulporn3, C. Direkwattanachai1; 1 Division of Allergy/Immunology, Department of Pediatrics, Ramathibodi Hospital, Mahidol University, Bangkok, THAILAND, 2Department of Pathology, Ramathibodi Hospital,Mahidol University, Bangkok, THAILAND, 3Research Center, Ramathibodi Hospital,Mahidol University, Bangkok, THAILAND. BACKGROUND: Asthma is a chronic inflammatory disease of the airway, leading to airway remodeling. TGF-b1 is a potent profibrotic and anti-inflammatory cytokine, which plays a significant role in the airway remodeling process. OBJECTIVE: To study serum TGF-b1 in different severity of allergic asthma and nonatopic healthy control. METHOD: 3 groups of allergic asthmatic patients, age 7-18 year, were recruited as to the asthma severity: mild intermittent asthma, moderate asthma and asthma in remission (no symptom of asthma and no inhaled corticosteroid use for at least 6 months). Serum TGF-b1 was measured by enzyme-linked immunosorbent assay. RESULT: Of the 31 patients recruited, 7 were mild steroid naı¨ve asthma, 12 were moderate asthma and 12 were asthma in remission. The mean serum TGF-b1 was significantly higher in mild steroid naı¨ve group (47.44 ng/mL) when compared to the asthma in remission group (35.93 ng/mL, p 5 0.014). The mean serum TGF-b1 in steroid treated groups was significantly lower than steroid naı¨ve group (37.29 ng/mL vs. 47.44 ng/mL, p 5 0.033). There was no significant difference among serum TGF-b1 in all asthmatic patient groups and control group. There was no correlation among serum TGF-b1 and other variables; age, FEV1 (%predicted), and duration of asthma. CONCLUSION: Serum TGF-b1 in allergic asthma was not different from nonatopic healthy control. Mild asthma with steroid naı¨ve group had the highest level of serum TGF-b1. Lower level of serum TGF-b1 in moderate
asthma and asthma in remission may due to the effect of inhaled corticosteroid therapy. Funding: Ramathibodi Hospital, Mahidol University
334
Systemic Autoimmunity Significance in Patients with Asthma I. Agache1, L. Duca1, M. Anghel2; 1Transylvania University Brasov, Faculty of Medicine, Brasov, ROMANIA, 2Brasov County Hospital, Brasov, ROMANIA. RATIONALE: T regulatory cell dysfunction was implicated in both asthma and autoimmune diseases. Clinical significance of systemic autoimmunity in asthma was not assessed. METHODS: 96 asthma patients (pts), mean age 53.06613.66 years, 68(70.83%) women, mean disease duration 13.21612.30 years, were ELISA appreciated for the presence of antinuclear antibodies - ANA and anti b2GPI autoantibodies, and by immune turbidimetry for serum b2 microglobulin (b2MG), circulating immune complexes (CIC) and cryoglobulins (CRG) in correlation with asthma severity (ATS criteria). For comparison ‘‘classic’’ features like atopy (skin prick test), total serum IgE (chemiluminiscence), sputum and blood eosinophilia (EO) were also assessed in relation with asthma severity. Statistics by multiple regression analysis and Spearman correlation test. RESULTS: 22(22.92%) pts. had severe asthma. Multiple regression analysis pointed out as independent risk factors for severe asthma sputum eosinophilia (T-value 5 3.4379523; p<0.001), blood eosinophilia (T-value 5 2.0587923, p 5 0.043), increased total serum IgE (T-value 5 2.2288375; p 5 0.029) and the presence of ANA (T-value 5 2.611779; p50.011). Spearman correlation test between asthma severity and: sputum eosinophilia 0.5049, p <0.001; blood eosinophilia 0.2009, p50.05; increased total serum IgE 0.3494, p<0.001; ANA 0.6629; p<0.001; anti b2GPI 0.3294, p50.001; b2MG 0.4156, p<0.001; CIC 0.3053, p50.002; CRG 0.4351, p<0.001. CONCLUSIONS: The presence of antinuclear antibodies is an independent risk factor for severe asthma. Asthma severity was strongly correlated with the presence of antinuclear antibodies, moderately correlated with the presence of anti b2GPI antibodies, increased serum levels of b2 microglobulin and cryoglobulins and weakly correlated with increased levels of circulating immune complexes. Systemic autoimmunity could thus contribute to asthma severity.
335
Allergy, Serum IgE, and Lung Function in Children and Adolescents With Severe or Difficult-to-Treat Asthma T. Haselkorn1, S. J. Szefler2, F. E. R. Simons3, D. R. Mink4, B. E. Chipps5, D. A. Wong1, L. Borish6; 1Genentech, Inc., South San Francisco, CA, 2Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO, 3Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, CANADA, 4Ovation Research Group, San Francisco, CA, 5Capital Allergy and Respiratory Disease Center, Sacramento, CA, 6University of Virginia Health Systems, Charlottesville, VA. RATIONALE: Little is known about the rate of allergy and allergic comorbidities in young patients with severe or difficult-to-treat asthma. METHODS: One thousand two hundred sixty-one patients from the TENOR observational study were stratified by baseline age group (6-8, 9-11, 12-14, 15-17 years). The chi-square test for categorical variables and ANOVA for continuous variables were used to identify significant differences in allergic measures among age groups, stratified by gender. RESULTS: Approximately two thirds of male and female patients had a history of allergic rhinitis; 14% and 25% had a history of atopic dermatitis (AD). The proportion of male patients with AD decreased with age (P<0.05). Among patients tested, there was a high prevalence of skin test positivity in patients of pulmonologists or allergists (87% and 95%); however, fewer patients of pulmonologists than allergists reported being skin tested. In general, rates for self-reported asthma triggers were higher in females than in males. Mean total serum IgE was higher in males than females across age groups; IgE was significantly different among age groups in males (P<0.01) and females (P<0.05). Patients with lower pre- and post- FEV1 had higher IgE levels.
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