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Evaluation of Pulmonary Function in Children with Eosinophilic Bronchitis
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Evaluation of Pulmonary Function in Children with Eosinophilic Bronchitis J. Choi, H. Jee, K. Kim, Y. Park, B. Choi, M. Sohn, K. Kim; Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA. RATIONALE: Eosinophilic Bronchitis (EB) is recognized as asthma-like eosinophilic inflammation, but it is different from asthma in terms of a lack of airway hyperresponsiveness. Pulmonary function test (PFT) is used for asthmatic children to diagnose and monitor the disease, but not for children with EB. So both spirometry and IOS (impulse oscillometry) were used for children with EB to assess their pulmonary function at the pre-/postinhalation of bronchodilator (BD) and reversibility. METHODS: The subjects were children aged between 4 to 14 years: 71 with asthma, 51 with EB, 61 controls. At the pre-/post-inhalation of bronchodilator, we measured separately spirometry parameters (FVC, FEV1, PEF, MMEF) and IOS parameters (Resistence at 5 Hz [R5], R10, R20, R35, Average reactance [AX], X5). RESULTS: PreBD FEV1, preBD PEF and preBD MMEF of spirometry parameters in children with EB and controls were higher than in children with asthma (P < .001). However bronchodilator response of FEV1 (delta [d] FEV1) was significantly lower in children with EB and controls compared with asthmatic children (P 5.014). PreAX and preX5 of IOS parameters showed lower in both children with EB and controls than asthmatic children (P < .001), but there was no difference in bronchodilator response (dAX and dX5). Asthmatic children in the pre-and post-inhalation of bronchodilator showed higher in AX, X5, R5, R10, R20, R35 and dAX compared with controls (P < .05), but no difference between controls and children with EB. CONCLUSIONS: Asthmatic children showed a decrease in pulmonary function, but children with EB showed normal pulmonary function on spirometry and IOS.
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Comparison of Asthma Phenotypic Characteristics to Exhaled Nitric Oxide: Observations from the ACE Trial C. A. Sorkness1, G. Bloomberg2, A. Calatroni3, M. Curry3, P. Gergen4, C. Kercsmar5, J. Kim6, W. Neaville7, S. Steinbach8; 1University of Wisconsin Madison School of Pharmacy, Madison, WI, 2Washington University School of Medicine & St. Louis Children’s Hospital, St. Louis, MO, 3 Rho Inc., Chapel Hill, NC, 4NIAID Division of Allergy, Immunology and Transplantation, Bethesda, MD, 5Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 6Northwestern University Feinberg School of Medicine, Chicago, IL, 7University of Texas Southwestern Medical Center, Dallas, TX, 8Boston University School of Medicine, Boston, MA. RATIONALE: Exhaled nitric oxide (FeNO), a noninvasive biomarker for airway inflammation often elevated in asthmatics, may be influenced by phenotypic characteristics specific to inner-city residents. METHODS: FeNO, asthma history, asthma control measures, atopy measures, and pulmonary function tests were collected on 546 inner-city residents aged 12-20 enrolling in the Asthma Control Evaluation (ACE) Trial; all participants had persistent uncontrolled asthma. Relationships between baseline FeNO and phenotypic characteristics were determined, using Pearson correlation coefficients. RESULTS: Median FeNO was 31.7 ppb (IQR 14.1-65.1); mean FEV1 was 92.1 6 16.6% predicted and mean FEV1/FVC was 77.8 6 9.4%. Maximum symptom days self-reported over the prior 2 weeks averaged 5.6 6 4.6 days. The mean ACTÒ score over the last month was 18.2 6 4.2. Median total IgE was 262 kU/L (IQR 100-658). Participants averaged 4.8 6 3.4 positive skin tests (14 tested), led by sensitivity to roach, cat, mold, and mite. Correlation coefficients for associations with FeNO were: 0.46 for total IgE (p < 0.001); 0.38 for number of positive skin tests (p < 0.001); -0.21 for FEV1 (p < 0.001); -0.32 for FEV1/FVC (p < 0.001); 0.01 for maximum symptom days (NS); and -0.05 for ACT (NS). The correlation coefficients for asthma-related health care use in the prior year were also weak and not significant. CONCLUSIONS: FeNO was best correlated with measures of atopy, and only modestly with lung function, in this highly allergic cohort. These data
support the role of FeNO, a non-invasive measure of airway inflammation, as an important dimension of asthma control. Funding: NIAID
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Reduced Adult Airway Function after Wheezing Early in Life ˚ mark1, B. Alm1, P. M. G. Wennergren1, E. Gokso¨r1, M. A Gustafsson2; 1Department of Pediatrics, Go¨teborg University, Go¨teborg, SWEDEN, 2Department of Pediatric Clinical Physiology, Go¨teborg University, Go¨teborg, SWEDEN. RATIONALE: Wheezing during viral infections is common in infants and young children. Do these children have reduced airway function in early adulthood, and if so, what accounts for this? To analyze this we have compared airway function in early adulthood in subjects with wheezing in infancy with age-matched controls. METHODS: Asthma development has been prospectively studied in 101 children hospitalised due to wheezing before the age of two. The cohort was re-investigated at age 17-20 years and tested with spirometry and for bronchial hyper-responsiveness and allergic sensitisation. An age-matched population (n 5 294) was used for comparison. RESULTS: The cohort had a significantly lower FEV1/FVC ratio and MEF50, both pre- and post-bronchodilation, compared with the controls, p < 0.01. The reduction in airway function was most evident in current asthmatic female subjects, but a reduced pre-bronchodilation FEV1/FVC ratio was also seen in symptom-free cohort subjects, p 5 0.03. In the multivariate analysis, female gender was the most prominent independent risk factor for reduced airway function in early adulthood, pre-bronchodilation OR 4.0 (1.4-11.3) and post-bronchodilation OR 8.8 (1.8-42.0). In addition, a history of early wheezing, i.e. belonging to the cohort, was an independent risk factor for reduced pre-bronchodilation airway function, OR 3.3 (1.3-8.7). Furthermore, there was an association between current bronchial hyper-responsiveness and an increased risk of reduced airway function post-bronchodilation, OR 7.3 (2.0-26.6). CONCLUSIONS: Reduced airway function in early adulthood was found in subjects with wheezing early in life, compared with age-matched controls. The reduction was most prominent in females with current asthma. Funding: Go¨teborg University
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Salivary Cytokine amd Pathogen Detection in Patients with Asthma P. J. Wexler1, F. F. Little1, J. S. Brody1, W. L. Siqueira2, E. J. Helmerhorst2, F. G. Oppenheim2, T. Bilcharz3, R. Hayman3, D. R. Walt3; 1Pulmonary Center, Boston University Medical Center, Boston, MA, 2Boston University Graduate School of Dental Medicine, Boston, MA, 3Tufts University, Medford, MA. RATIONALE: There are similarities in the inflammatory immune response in the upper (sinus, nasal) and lower (bronchial) airways of atopic asthmatics. We hypothesize that due to the direct anatomic relation with the mouth, cytokine concentrations of the airway will be reflected in saliva. Salivary analysis of cytokines and pathogens could offer noninvasive rapid diagnostic information on contributors to asthma control deterioration. METHODS: Whole saliva was collected from 20 healthy volunteers and 20 asthmatics in varying states of control. Patients all underwent a detailed history and physical exam focused on asthma control (asthmatics) and dental health. Salivary cytokines were measured by ELISA and microsphere-based multiplex array. The presence of common respiratory viral pathogens was detected by PCR amplification of salivary pellet DNA. RESULTS: Compared to healthy controls, VEGF, RANTES/CCL5, IL-6, and TIMP-1, but not eotaxin-3/CCL26, were elevated in asthmatic saliva. As a group, 13/20 asthmatics had one or two respiratory viruses detected by PCR; of which six had typical viral URTI symptoms. The prevalence of viral detection was not different between stable and uncontrolled asthmatics. CONCLUSION: Inflammatory proteins and viral pathogens known to be expressed in the asthmatic airway can be detected in whole saliva. Specific salivary (and/or nasal lavage) cytokine and pathogen profiles from a multianalyte array may distinguish varied causes of deteriorated asthma control. Funding: NIH/NIDCR, U01-DE017788
SATURDAY
Abstracts S5
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2
Evaluation of Pulmonary Function in Children with Eosinophilic Bronchitis J. Choi, H. Jee, K. Kim, Y. Park, B. Choi, M. Sohn, K. Kim; Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, REPUBLIC OF KOREA. RATIONALE: Eosinophilic Bronchitis (EB) is recognized as asthma-like eosinophilic inflammation, but it is different from asthma in terms of a lack of airway hyperresponsiveness. Pulmonary function test (PFT) is used for asthmatic children to diagnose and monitor the disease, but not for children with EB. So both spirometry and IOS (impulse oscillometry) were used for children with EB to assess their pulmonary function at the pre-/postinhalation of bronchodilator (BD) and reversibility. METHODS: The subjects were children aged between 4 to 14 years: 71 with asthma, 51 with EB, 61 controls. At the pre-/post-inhalation of bronchodilator, we measured separately spirometry parameters (FVC, FEV1, PEF, MMEF) and IOS parameters (Resistence at 5 Hz [R5], R10, R20, R35, Average reactance [AX], X5). RESULTS: PreBD FEV1, preBD PEF and preBD MMEF of spirometry parameters in children with EB and controls were higher than in children with asthma (P < .001). However bronchodilator response of FEV1 (delta [d] FEV1) was significantly lower in children with EB and controls compared with asthmatic children (P 5.014). PreAX and preX5 of IOS parameters showed lower in both children with EB and controls than asthmatic children (P < .001), but there was no difference in bronchodilator response (dAX and dX5). Asthmatic children in the pre-and post-inhalation of bronchodilator showed higher in AX, X5, R5, R10, R20, R35 and dAX compared with controls (P < .05), but no difference between controls and children with EB. CONCLUSIONS: Asthmatic children showed a decrease in pulmonary function, but children with EB showed normal pulmonary function on spirometry and IOS.
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Comparison of Asthma Phenotypic Characteristics to Exhaled Nitric Oxide: Observations from the ACE Trial C. A. Sorkness1, G. Bloomberg2, A. Calatroni3, M. Curry3, P. Gergen4, C. Kercsmar5, J. Kim6, W. Neaville7, S. Steinbach8; 1University of Wisconsin Madison School of Pharmacy, Madison, WI, 2Washington University School of Medicine & St. Louis Children’s Hospital, St. Louis, MO, 3 Rho Inc., Chapel Hill, NC, 4NIAID Division of Allergy, Immunology and Transplantation, Bethesda, MD, 5Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 6Northwestern University Feinberg School of Medicine, Chicago, IL, 7University of Texas Southwestern Medical Center, Dallas, TX, 8Boston University School of Medicine, Boston, MA. RATIONALE: Exhaled nitric oxide (FeNO), a noninvasive biomarker for airway inflammation often elevated in asthmatics, may be influenced by phenotypic characteristics specific to inner-city residents. METHODS: FeNO, asthma history, asthma control measures, atopy measures, and pulmonary function tests were collected on 546 inner-city residents aged 12-20 enrolling in the Asthma Control Evaluation (ACE) Trial; all participants had persistent uncontrolled asthma. Relationships between baseline FeNO and phenotypic characteristics were determined, using Pearson correlation coefficients. RESULTS: Median FeNO was 31.7 ppb (IQR 14.1-65.1); mean FEV1 was 92.1 6 16.6% predicted and mean FEV1/FVC was 77.8 6 9.4%. Maximum symptom days self-reported over the prior 2 weeks averaged 5.6 6 4.6 days. The mean ACTÒ score over the last month was 18.2 6 4.2. Median total IgE was 262 kU/L (IQR 100-658). Participants averaged 4.8 6 3.4 positive skin tests (14 tested), led by sensitivity to roach, cat, mold, and mite. Correlation coefficients for associations with FeNO were: 0.46 for total IgE (p < 0.001); 0.38 for number of positive skin tests (p < 0.001); -0.21 for FEV1 (p < 0.001); -0.32 for FEV1/FVC (p < 0.001); 0.01 for maximum symptom days (NS); and -0.05 for ACT (NS). The correlation coefficients for asthma-related health care use in the prior year were also weak and not significant. CONCLUSIONS: FeNO was best correlated with measures of atopy, and only modestly with lung function, in this highly allergic cohort. These data
support the role of FeNO, a non-invasive measure of airway inflammation, as an important dimension of asthma control. Funding: NIAID
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Reduced Adult Airway Function after Wheezing Early in Life ˚ mark1, B. Alm1, P. M. G. Wennergren1, E. Gokso¨r1, M. A Gustafsson2; 1Department of Pediatrics, Go¨teborg University, Go¨teborg, SWEDEN, 2Department of Pediatric Clinical Physiology, Go¨teborg University, Go¨teborg, SWEDEN. RATIONALE: Wheezing during viral infections is common in infants and young children. Do these children have reduced airway function in early adulthood, and if so, what accounts for this? To analyze this we have compared airway function in early adulthood in subjects with wheezing in infancy with age-matched controls. METHODS: Asthma development has been prospectively studied in 101 children hospitalised due to wheezing before the age of two. The cohort was re-investigated at age 17-20 years and tested with spirometry and for bronchial hyper-responsiveness and allergic sensitisation. An age-matched population (n 5 294) was used for comparison. RESULTS: The cohort had a significantly lower FEV1/FVC ratio and MEF50, both pre- and post-bronchodilation, compared with the controls, p < 0.01. The reduction in airway function was most evident in current asthmatic female subjects, but a reduced pre-bronchodilation FEV1/FVC ratio was also seen in symptom-free cohort subjects, p 5 0.03. In the multivariate analysis, female gender was the most prominent independent risk factor for reduced airway function in early adulthood, pre-bronchodilation OR 4.0 (1.4-11.3) and post-bronchodilation OR 8.8 (1.8-42.0). In addition, a history of early wheezing, i.e. belonging to the cohort, was an independent risk factor for reduced pre-bronchodilation airway function, OR 3.3 (1.3-8.7). Furthermore, there was an association between current bronchial hyper-responsiveness and an increased risk of reduced airway function post-bronchodilation, OR 7.3 (2.0-26.6). CONCLUSIONS: Reduced airway function in early adulthood was found in subjects with wheezing early in life, compared with age-matched controls. The reduction was most prominent in females with current asthma. Funding: Go¨teborg University
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Salivary Cytokine amd Pathogen Detection in Patients with Asthma P. J. Wexler1, F. F. Little1, J. S. Brody1, W. L. Siqueira2, E. J. Helmerhorst2, F. G. Oppenheim2, T. Bilcharz3, R. Hayman3, D. R. Walt3; 1Pulmonary Center, Boston University Medical Center, Boston, MA, 2Boston University Graduate School of Dental Medicine, Boston, MA, 3Tufts University, Medford, MA. RATIONALE: There are similarities in the inflammatory immune response in the upper (sinus, nasal) and lower (bronchial) airways of atopic asthmatics. We hypothesize that due to the direct anatomic relation with the mouth, cytokine concentrations of the airway will be reflected in saliva. Salivary analysis of cytokines and pathogens could offer noninvasive rapid diagnostic information on contributors to asthma control deterioration. METHODS: Whole saliva was collected from 20 healthy volunteers and 20 asthmatics in varying states of control. Patients all underwent a detailed history and physical exam focused on asthma control (asthmatics) and dental health. Salivary cytokines were measured by ELISA and microsphere-based multiplex array. The presence of common respiratory viral pathogens was detected by PCR amplification of salivary pellet DNA. RESULTS: Compared to healthy controls, VEGF, RANTES/CCL5, IL-6, and TIMP-1, but not eotaxin-3/CCL26, were elevated in asthmatic saliva. As a group, 13/20 asthmatics had one or two respiratory viruses detected by PCR; of which six had typical viral URTI symptoms. The prevalence of viral detection was not different between stable and uncontrolled asthmatics. CONCLUSION: Inflammatory proteins and viral pathogens known to be expressed in the asthmatic airway can be detected in whole saliva. Specific salivary (and/or nasal lavage) cytokine and pathogen profiles from a multianalyte array may distinguish varied causes of deteriorated asthma control. Funding: NIH/NIDCR, U01-DE017788
SATURDAY
Abstracts S5
J ALLERGY CLIN IMMUNOL VOLUME 121, NUMBER 2