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Tryptase in Induced Sputum of Asthmatics: A Clue for the Severity of Asthma
S210 Abstracts
805
Sensitivity And Specificity Of Inhaled Mannitol And Methacholine For Clinical Diagnosis Of Asthma S. L. Spector1, S. D. Anderson2, B. Charlton3, S. Nichols4, J. M. Weiler4; 1 California Allergy & Asthma Medical Group, Los Angeles, CA, 2Royal Prince Alfred Hospital, Sydney, AUSTRALIA, 3Pharmaxis, Sydney, AUSTRALIA, 4CompleWare, Iowa City, IA. RATIONALE: No previous large study has reported utility of bronchial provocation testing in patients with an equivocal diagnosis of asthma. METHODS: Subjects with symptoms suggesting asthma were enrolled in this multi-center study; those with >95% or < 5% likelihood of asthma or with current seasonal allergy were excluded. Subjects were assigned clinical diagnoses based on exercise challenge, history, physical examination, skin tests and FEV1 reversibility. No subject was taking inhaled corticosteroids. Methacholine and mannitol bronchial provocation tests were performed one week apart. Challenge was positive if methacholine PC20 16 mg/ml or mannitol PD15 635 mg. RESULTS: 375 subjects were assessed: ages 6-50 years (median 22); median FEV1 % predicted 93.3; mild asthma with mean NAEPPII asthma severity 1.2 (SD0.5); atopic 79%. 168 were mannitol positive and 156 methacholine positive. Sensitivity of mannitol and methacholine for diagnosis were 58.3% and 55.3%; specificity were 65.6% and 68.8%, respectively. Specificity and sensitivity for mannitol and methacholine were not significantly different; concordance between the two tests was 69.1%. Geometric Mean (95% CI) PD15 for mannitol was 158 mg (129,193) and PC20 methacholine was 2.12 mg/mL (1.70, 2.64). CONCLUSIONS: Diagnostic sensitivity and specificity were similar for mannitol and methacholine and concordance between the tests was high. Methacholine sensitivity for a clinical diagnosis of asthma was less than expected from previous studies in well defined populations.
806
MONDAY
Tryptase in Induced Sputum of Asthmatics: A Clue for the Severity of Asthma Y. W. Lee1, J. W. Park1, Y. S. Shin1, J. H. Kim2, C. S. Hong1; 1Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA, 2Allergy-Asthma Clinic, Severance Hospital, Yonsei Health System, Seoul, REPUBLIC OF KOREA. RATIONALE: Several reports had been suggested mast cells and tryptase in lower airways had important roles in asthma (BA) pathogenesis. We investigated the clinical aspects of tryptase in induced stputum (sTryptase) of asthmatics. METHODS: 100 asthmatics (M/F 5 41/59, mean 46.9 6 18.3 years) were prospectively enrolled. Tryptase and ECP in induced sputum supernatant were measured by ImmunoCAP system. Induced sputum analysis, total IgE, and total eosinophil counts (TEC) were also evaluated. Spirometry and methacholine challenge test were also done. Collected clinical data were statistically analyzed. RESULTS: Among the 100 asthmatics, sTryptase was detected in 34 cases (BA-Tp). BA-Tp were older than the sTryptase non-detected group (BATn) (54.2 6 16.0 vs. 43.1 6 18.4 years, p < 0.01). BA-Tp had higher BMI (24.7 6 3.1 vs. 23.2 6 3.2 kg/m2, p 5 0.023). BA-Tp showed higher eosinophil counts (29.5 6 25.5 vs. 9.0 6 16.0%, p < 0.001) and ECP levels (191.1 6 34.6 vs. 114.6 6 79.4 mcg/L, p < 0.001) in induced sputum. But TEC and serum total IgE levels were not different between two groups. BA-Tp had lower peak expiratory flow rate (357 6 95 vs. 407 6 101 L/ min, p 5 0.022), FEV1 (78.6 6 18.6 vs. 87.1 6 15.7%, p < 0.05) and FEV1/FVC (72.3 6 9.3 vs. 78.8 6 9.3%, p 5 0.001). There were no differences between groups in disease duration, quality of life score, and methacholine airway hyperresponsiveness. sTryptase detection rate (%) increased linearly according to the BA severity based on clinical features or treatment steps (GINA 2006, p < 0.01 for both). CONCLUSIONS: Asthmatics with sTryptase detection showed more severe airway eosinophilic inflammation and obstruction. These results suggested that sTryptase might have a significant role in the pathogenesis of BA and could be associated with disease severity.
J ALLERGY CLIN IMMUNOL FEBRUARY 2008
807
The Association Between Fractional Exhaled Nitric Oxide (FeNO) and Allergic Diseases and Asthma at Age Six Years in a High Risk Birth Cohort C. Virnig, D. J. Jackson, M. D. Evans, E. L. Anderson, L. E. Salazar, Sr, , D. F. DaSilva, R. Kelley, T. E. Pappas, K. A. Roberg, C. J. Tisler, R. E. Gangnon, J. E. Gern, R. F. Lemanske, Jr.; UW School of Medicine and Public Health Madison, WI. RATIONALE: To determine whether FeNO levels are associated with the development of eczema, allergic sensitization, elevated total IgE levels, and/or asthma. METHODS: The relationship between FeNO levels and the development of allergic diseases was evaluated in children enrolled in the COAST (Childhood Origins of ASThma) study. FeNO was measured at age six years using the NIOXÒ online technique (Aerocrine, AB, Stockholm, Sweden); values were determined from three maneuvers that were within 2.5 ppb or 10%. Skin prick testing was performed at 5 years, and both allergen-specific IgE and total IgE levels were obtained at age 6 years. Asthma and eczema were diagnosed at 6 years of age. RESULTS: 88% of children (199/227) successfully performed FeNO maneuvers at age six. There was no association between FeNO levels and active eczema (p 5 0.13). FeNO levels were higher in subjects with at least one positive skin prick test compared to patients without any positive tests (geometric mean 9.9 vs 7.3 ppb, p 5 0.005). A similar association was found between FeNO levels and a positive RAST test (geometric mean 10.9 vs 6.5 ppb, p < 0.0001). A positive correlation was demonstrated between FeNO levels and total IgE (r 5 0.40, p < 0.0001). FeNO levels were higher in subjects with asthma (geometric mean 10.1 vs 8.0 ppb, p 5 0.02); however, this association did not remain significant after adjusting for allergic sensitization in a multivariate model (p 5 0.33). CONCLUSIONS: Elevated FeNO levels at age six years are present in children with allergic sensitization and correlate with total IgE levels; eczema and asthma are not independently associated with increased FeNO. Funding: NIH grants M01 RR03186, R01 HL61879, and P01 HL70831
808
Abnormalities in Lung Function at Age 6 Years are Associated with Children Who Wheezed with Rhinovirus in Early Childhood E. L. Anderson1, M. D. Evans2, K. A. Roberg1, L. E. P. Salazar1, D. D. F. Da Silva1, T. E. Pappas1, C. J. Tisler1, R. A. Grabher1, R. E. Gangnon2, J. E. Gern1, R. F. Lemanske, Jr.1; 1University of Wisconsin Medical School and Public Health Madison, WI, 2University of Wisconsin Population Health Sciences Biostatistics and Medical Informatics, Madison, WI. RATIONALE: We previously reported that children who wheezed with rhinovirus (RV) in early childhood have decreased lung function at age 6 years. In this study, we tested the hypothesis that asthmatic children with a history of RV wheezing in infancy would have distinct patterns of lung function at age 6 years. METHODS: Nasal lavage samples were obtained from participants in the Childhood Origins of ASThma (COAST) project from birth to two years. Samples were analyzed (culture and PCR) for RV during acute respiratory illnesses. Spirometry using JaegerÒ Master Screen was performed at the 6 year scheduled visit. Lung function of children with asthma was then related to the presence or absence of rhinovirus wheezing in the first 2 years of life. RESULTS: Asthmatic children who wheezed with RV in the first two years of life (n 5 17) had lower FVC (median: 1.47 vs. 1.53, p 5 0.03), FEV1 (1.23 vs. 1.37, p 5 0.02), FEV0.5 (.88 vs. 1.06, p 5 0.02) and FEF25-75 (1.09 vs.1.36, p 5 0.03) than controls (nonasthmatic children who did not wheeze with RV (n 5 89). In contrast, asthmatic children who did not wheeze with RV (n 5 22) had similar FVC (1.53, p 5 0.70), FEV1 (1.37, p 5 .95), FEV 0.5 (1.03, p 5 0.83), and FEF25-75 (1.36, p 5 0.87) compared to controls. CONCLUSIONS: Asthmatic children with wheezing illnesses due to RV infections in early childhood are more likely to have impaired lung function at age 6 years than other asthmatic children. Funding: NIH grants M01 RR03186, R01 HL61879 and P01 HL70831
805
Sensitivity And Specificity Of Inhaled Mannitol And Methacholine For Clinical Diagnosis Of Asthma S. L. Spector1, S. D. Anderson2, B. Charlton3, S. Nichols4, J. M. Weiler4; 1 California Allergy & Asthma Medical Group, Los Angeles, CA, 2Royal Prince Alfred Hospital, Sydney, AUSTRALIA, 3Pharmaxis, Sydney, AUSTRALIA, 4CompleWare, Iowa City, IA. RATIONALE: No previous large study has reported utility of bronchial provocation testing in patients with an equivocal diagnosis of asthma. METHODS: Subjects with symptoms suggesting asthma were enrolled in this multi-center study; those with >95% or < 5% likelihood of asthma or with current seasonal allergy were excluded. Subjects were assigned clinical diagnoses based on exercise challenge, history, physical examination, skin tests and FEV1 reversibility. No subject was taking inhaled corticosteroids. Methacholine and mannitol bronchial provocation tests were performed one week apart. Challenge was positive if methacholine PC20 16 mg/ml or mannitol PD15 635 mg. RESULTS: 375 subjects were assessed: ages 6-50 years (median 22); median FEV1 % predicted 93.3; mild asthma with mean NAEPPII asthma severity 1.2 (SD0.5); atopic 79%. 168 were mannitol positive and 156 methacholine positive. Sensitivity of mannitol and methacholine for diagnosis were 58.3% and 55.3%; specificity were 65.6% and 68.8%, respectively. Specificity and sensitivity for mannitol and methacholine were not significantly different; concordance between the two tests was 69.1%. Geometric Mean (95% CI) PD15 for mannitol was 158 mg (129,193) and PC20 methacholine was 2.12 mg/mL (1.70, 2.64). CONCLUSIONS: Diagnostic sensitivity and specificity were similar for mannitol and methacholine and concordance between the tests was high. Methacholine sensitivity for a clinical diagnosis of asthma was less than expected from previous studies in well defined populations.
806
MONDAY
Tryptase in Induced Sputum of Asthmatics: A Clue for the Severity of Asthma Y. W. Lee1, J. W. Park1, Y. S. Shin1, J. H. Kim2, C. S. Hong1; 1Division of Allergy and Immunology, Department of Internal Medicine, Institute of Allergy, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA, 2Allergy-Asthma Clinic, Severance Hospital, Yonsei Health System, Seoul, REPUBLIC OF KOREA. RATIONALE: Several reports had been suggested mast cells and tryptase in lower airways had important roles in asthma (BA) pathogenesis. We investigated the clinical aspects of tryptase in induced stputum (sTryptase) of asthmatics. METHODS: 100 asthmatics (M/F 5 41/59, mean 46.9 6 18.3 years) were prospectively enrolled. Tryptase and ECP in induced sputum supernatant were measured by ImmunoCAP system. Induced sputum analysis, total IgE, and total eosinophil counts (TEC) were also evaluated. Spirometry and methacholine challenge test were also done. Collected clinical data were statistically analyzed. RESULTS: Among the 100 asthmatics, sTryptase was detected in 34 cases (BA-Tp). BA-Tp were older than the sTryptase non-detected group (BATn) (54.2 6 16.0 vs. 43.1 6 18.4 years, p < 0.01). BA-Tp had higher BMI (24.7 6 3.1 vs. 23.2 6 3.2 kg/m2, p 5 0.023). BA-Tp showed higher eosinophil counts (29.5 6 25.5 vs. 9.0 6 16.0%, p < 0.001) and ECP levels (191.1 6 34.6 vs. 114.6 6 79.4 mcg/L, p < 0.001) in induced sputum. But TEC and serum total IgE levels were not different between two groups. BA-Tp had lower peak expiratory flow rate (357 6 95 vs. 407 6 101 L/ min, p 5 0.022), FEV1 (78.6 6 18.6 vs. 87.1 6 15.7%, p < 0.05) and FEV1/FVC (72.3 6 9.3 vs. 78.8 6 9.3%, p 5 0.001). There were no differences between groups in disease duration, quality of life score, and methacholine airway hyperresponsiveness. sTryptase detection rate (%) increased linearly according to the BA severity based on clinical features or treatment steps (GINA 2006, p < 0.01 for both). CONCLUSIONS: Asthmatics with sTryptase detection showed more severe airway eosinophilic inflammation and obstruction. These results suggested that sTryptase might have a significant role in the pathogenesis of BA and could be associated with disease severity.
J ALLERGY CLIN IMMUNOL FEBRUARY 2008
807
The Association Between Fractional Exhaled Nitric Oxide (FeNO) and Allergic Diseases and Asthma at Age Six Years in a High Risk Birth Cohort C. Virnig, D. J. Jackson, M. D. Evans, E. L. Anderson, L. E. Salazar, Sr, , D. F. DaSilva, R. Kelley, T. E. Pappas, K. A. Roberg, C. J. Tisler, R. E. Gangnon, J. E. Gern, R. F. Lemanske, Jr.; UW School of Medicine and Public Health Madison, WI. RATIONALE: To determine whether FeNO levels are associated with the development of eczema, allergic sensitization, elevated total IgE levels, and/or asthma. METHODS: The relationship between FeNO levels and the development of allergic diseases was evaluated in children enrolled in the COAST (Childhood Origins of ASThma) study. FeNO was measured at age six years using the NIOXÒ online technique (Aerocrine, AB, Stockholm, Sweden); values were determined from three maneuvers that were within 2.5 ppb or 10%. Skin prick testing was performed at 5 years, and both allergen-specific IgE and total IgE levels were obtained at age 6 years. Asthma and eczema were diagnosed at 6 years of age. RESULTS: 88% of children (199/227) successfully performed FeNO maneuvers at age six. There was no association between FeNO levels and active eczema (p 5 0.13). FeNO levels were higher in subjects with at least one positive skin prick test compared to patients without any positive tests (geometric mean 9.9 vs 7.3 ppb, p 5 0.005). A similar association was found between FeNO levels and a positive RAST test (geometric mean 10.9 vs 6.5 ppb, p < 0.0001). A positive correlation was demonstrated between FeNO levels and total IgE (r 5 0.40, p < 0.0001). FeNO levels were higher in subjects with asthma (geometric mean 10.1 vs 8.0 ppb, p 5 0.02); however, this association did not remain significant after adjusting for allergic sensitization in a multivariate model (p 5 0.33). CONCLUSIONS: Elevated FeNO levels at age six years are present in children with allergic sensitization and correlate with total IgE levels; eczema and asthma are not independently associated with increased FeNO. Funding: NIH grants M01 RR03186, R01 HL61879, and P01 HL70831
808
Abnormalities in Lung Function at Age 6 Years are Associated with Children Who Wheezed with Rhinovirus in Early Childhood E. L. Anderson1, M. D. Evans2, K. A. Roberg1, L. E. P. Salazar1, D. D. F. Da Silva1, T. E. Pappas1, C. J. Tisler1, R. A. Grabher1, R. E. Gangnon2, J. E. Gern1, R. F. Lemanske, Jr.1; 1University of Wisconsin Medical School and Public Health Madison, WI, 2University of Wisconsin Population Health Sciences Biostatistics and Medical Informatics, Madison, WI. RATIONALE: We previously reported that children who wheezed with rhinovirus (RV) in early childhood have decreased lung function at age 6 years. In this study, we tested the hypothesis that asthmatic children with a history of RV wheezing in infancy would have distinct patterns of lung function at age 6 years. METHODS: Nasal lavage samples were obtained from participants in the Childhood Origins of ASThma (COAST) project from birth to two years. Samples were analyzed (culture and PCR) for RV during acute respiratory illnesses. Spirometry using JaegerÒ Master Screen was performed at the 6 year scheduled visit. Lung function of children with asthma was then related to the presence or absence of rhinovirus wheezing in the first 2 years of life. RESULTS: Asthmatic children who wheezed with RV in the first two years of life (n 5 17) had lower FVC (median: 1.47 vs. 1.53, p 5 0.03), FEV1 (1.23 vs. 1.37, p 5 0.02), FEV0.5 (.88 vs. 1.06, p 5 0.02) and FEF25-75 (1.09 vs.1.36, p 5 0.03) than controls (nonasthmatic children who did not wheeze with RV (n 5 89). In contrast, asthmatic children who did not wheeze with RV (n 5 22) had similar FVC (1.53, p 5 0.70), FEV1 (1.37, p 5 .95), FEV 0.5 (1.03, p 5 0.83), and FEF25-75 (1.36, p 5 0.87) compared to controls. CONCLUSIONS: Asthmatic children with wheezing illnesses due to RV infections in early childhood are more likely to have impaired lung function at age 6 years than other asthmatic children. Funding: NIH grants M01 RR03186, R01 HL61879 and P01 HL70831