- Email: [email protected]
Alternaria Sensitiziation is Associated with Increased Airway Hyperresponsiveness and Sinusitis in Children with Severe Asthma
232
Real-world Effectiveness Of Asthma Step-up Options: Matched Comparison Of Extrafine Hydrofluoroalkanebeclometasone AND Inhaled Corticosteroid / Long-Acting Beta-Agonist D. B. Price1,2, R. Martin3, N. Barnes4, N. Roche5, A. J. Lee1, P. Dorinsky6, A. Burden2, J. von Ziegenweidt2, A. Chisholm2, E. V. Hillyer2, G. Colice7; 1 University of Aberdeen, Aberdeen, UNITED KINGDOM, 2Research in Real Life, Cambridge, UNITED KINGDOM, 3National Jewish Health, Denver, CO, 4London Chest Hospital, Barts and the London NHS Trust, London, UNITED KINGDOM, 5Hopital de l’Hotel-Dieu, Paris, FRANCE, 6Teva Pharmaceuticals, Horsham, PA, 7Washington Hospital Center and George Washington University School of Medicine, Washington, DC. RATIONALE: If inhaled corticosteroid (ICS) therapy fails to provide asthma control, guideline recommendations include increasing ICS dose or adding long-acting beta2-agonist (LABA). Extrafine hydrofluoroalkanebeclometasone dipropionate (EF HFA-BDP) has been shown to be highly effective in achieving asthma control. METHODS: This retrospective study using the UK General Practice Research Database compared real-world effectiveness of stepping-up therapy from ICS (budesonide, beclometasone, fluticasone) to (i) higher _50% increase) as EF HFA-BDP (n51065) or (ii) ICS/LABA dose ICS (> (no change in ICS dose or drug) (n51065). Patients (aged 4:-80 years) were matched (1:1) on key demographic and disease characteristics over 1 year pre-step-up: age, sex, asthma control status, reliever medication use, baseline ICS dose, and routine asthma consultations. Co-primary outcomes over 1 year were severe exacerbations (ATS/ERS definition) and asthma control (absence of: severe exacerbations; out-of-hours care; outpatient department attendance; antibiotics for lower respiratory infections). Secondary outcomes included treatment success (asthma control plus no additional therapy) and short-acting-beta2-agonist [SABA] usage. RESULTS: There were no statistically significant differences in odds of achieving asthma control: as compared with ICS/LABA Odds Ratio (OR)(95%CI) for EF HFA-BDP, 1.16(0.94-1.45) or in exacerbation rates, RR(95%CI), 0.88(0.69-1.11). Odds of achieving treatment success were significantly higher for EF HFA-BDP: OR(95%CI), 1.50(1.27-1.85). SABA daily dose range was marginally, but insignificantly higher for EF HFA-BDP (median[IQR], 164.4[82.2-328.8]mcg vs 164.4[54.8-328.8] mcg; p50.112). CONCLUSIONS: These real-world data suggest stepping-up therapy with an increased dose with EF HFA-BDP provides overall asthma control as effective as adding a LABA, indicating the importance of treating small and large airway inflammation in asthma.
233
Alternaria Sensitiziation is Associated with Increased Airway Hyperresponsiveness and Sinusitis in Children with Severe Asthma J. Shih, A. Fitzpatrick; Emory University, Atlanta, GA. RATIONALE: Although aeroallergen sensitization is a distinguishing feature of children with severe asthma, the specific role of aeroallergens in the modulation of asthma severity is not entirely understood. Given increased reports of Alternaria sensitization and asthma symptoms in adults and children, we determined whether Alternaria sensitization and associated clinical features differed between children with severe and mild-to-moderate asthma enrolled in the NHLBI Severe Asthma Research Program (SARP). METHODS: 187 children 6-17 years of age with physician diagnosed mild-to-moderate (n597) and severe (n590) asthma were included in this analysis. Alternaria sensitization was determined by skin prick testing (SPT). RESULTS: Overall, 28% (n553) of all children with asthma enrolled in SARP had a positive SPT to Alternaria. However, Alternaria sensitization was more prevalent in children with severe (37%, n533) versus mild-tomoderate (21%, n520) asthma (p<0.01, OR 2.2, 95% CI [1.2,4.3]). Within the group of children with severe asthma, lung function (FEV1% predicted), lung volumes, blood eosinophils, serum IgE, medication
requirements, and healthcare utilization did not differ according to Alternaria sensitization. However, children with severe asthma with Alternaria sensitization had increased airway hyperresponsiveness (0.75 6 0.91 PC20 mg/mL vs 3.3 6 4.8 PC20 mg/mL, p<0.01) and were more likely to report a history of acute/chronic sinusitis requiring antibiotic treatment (58% vs 42%, p<0.05). CONCLUSION: Alternaria sensitization is associated with increased airway hyperresponsiveness and sinusitis in children with severe asthma and may account for the increased symptom burden in this population. Routine evaluation of Alternaria sensitization may be useful in the clinical management of children with severe asthma.
234
Disconnect Between Sputum Neutrophilia and Indices of Mucosal Inflammation in Severe Asthma J. R. Arron1, D. F. Choy1, S. Audusseau2, Q. Hamid2, J. M. Harris1; BOBCAT Study Group1. 1Genentech, Inc., South San Francisco, CA, 2 McGill University, Montreal, QC, CANADA. RATIONALE: Phenotypic heterogeneity in severe asthma has been described in terms of the nature and intensity of granulocytic inflammation in the airways, but few studies have directly compared various methods of airway sampling. We sought to examine the relationships between mediators of inflammation in endobronchial biopsies, induced sputum, and peripheral blood in a large cohort of severe asthmatics. _1.5 despite METHODS: Severe asthmatics (N567), defined by ACQ> _1000 micrograms/day treatment with high dose inhaled corticosteroids (> fluticasone equivalent), were assessed in an observational study in which induced sputum, endobronchial biopsies, and peripheral blood were collected. Cell counts and inflammatory cytokines were measured by immunohistochemistry. RESULTS: In induced sputum, there was a negative correlation between the proportions of eosinophils and neutrophils. However, in endobronchial biopsy tissue there was a strong positive correlation between eosinophil and neutrophil counts. Eosinophil and neutrophil counts and multiple other markers of inflammation in biopsies as determined by immunohistochemistry were significantly intercorrelated (p<0.05), including TSLP, IL25, IL33, IL17A, and IL17F. While sputum and tissue eosinophils were both positively correlated with serum periostin, sputum neutrophil percentage was negatively correlated while tissue neutrophil counts showed a trend toward positive correlation with serum periostin. None of these measures was significantly correlated with lung function or asthma control within this severe asthma cohort. CONCLUSIONS: Of multiple indices of asthmatic airway inflammation, most metrics were positively intercorrelated with the exception of sputum neutrophil percentage. Definitions of subphenotypes of severe asthma as determined solely by sputum granulocyte proportions may misrepresent the pathophysiology present in bronchial tissue.
SATURDAY
Abstracts AB61
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2
Real-world Effectiveness Of Asthma Step-up Options: Matched Comparison Of Extrafine Hydrofluoroalkanebeclometasone AND Inhaled Corticosteroid / Long-Acting Beta-Agonist D. B. Price1,2, R. Martin3, N. Barnes4, N. Roche5, A. J. Lee1, P. Dorinsky6, A. Burden2, J. von Ziegenweidt2, A. Chisholm2, E. V. Hillyer2, G. Colice7; 1 University of Aberdeen, Aberdeen, UNITED KINGDOM, 2Research in Real Life, Cambridge, UNITED KINGDOM, 3National Jewish Health, Denver, CO, 4London Chest Hospital, Barts and the London NHS Trust, London, UNITED KINGDOM, 5Hopital de l’Hotel-Dieu, Paris, FRANCE, 6Teva Pharmaceuticals, Horsham, PA, 7Washington Hospital Center and George Washington University School of Medicine, Washington, DC. RATIONALE: If inhaled corticosteroid (ICS) therapy fails to provide asthma control, guideline recommendations include increasing ICS dose or adding long-acting beta2-agonist (LABA). Extrafine hydrofluoroalkanebeclometasone dipropionate (EF HFA-BDP) has been shown to be highly effective in achieving asthma control. METHODS: This retrospective study using the UK General Practice Research Database compared real-world effectiveness of stepping-up therapy from ICS (budesonide, beclometasone, fluticasone) to (i) higher _50% increase) as EF HFA-BDP (n51065) or (ii) ICS/LABA dose ICS (> (no change in ICS dose or drug) (n51065). Patients (aged 4:-80 years) were matched (1:1) on key demographic and disease characteristics over 1 year pre-step-up: age, sex, asthma control status, reliever medication use, baseline ICS dose, and routine asthma consultations. Co-primary outcomes over 1 year were severe exacerbations (ATS/ERS definition) and asthma control (absence of: severe exacerbations; out-of-hours care; outpatient department attendance; antibiotics for lower respiratory infections). Secondary outcomes included treatment success (asthma control plus no additional therapy) and short-acting-beta2-agonist [SABA] usage. RESULTS: There were no statistically significant differences in odds of achieving asthma control: as compared with ICS/LABA Odds Ratio (OR)(95%CI) for EF HFA-BDP, 1.16(0.94-1.45) or in exacerbation rates, RR(95%CI), 0.88(0.69-1.11). Odds of achieving treatment success were significantly higher for EF HFA-BDP: OR(95%CI), 1.50(1.27-1.85). SABA daily dose range was marginally, but insignificantly higher for EF HFA-BDP (median[IQR], 164.4[82.2-328.8]mcg vs 164.4[54.8-328.8] mcg; p50.112). CONCLUSIONS: These real-world data suggest stepping-up therapy with an increased dose with EF HFA-BDP provides overall asthma control as effective as adding a LABA, indicating the importance of treating small and large airway inflammation in asthma.
233
Alternaria Sensitiziation is Associated with Increased Airway Hyperresponsiveness and Sinusitis in Children with Severe Asthma J. Shih, A. Fitzpatrick; Emory University, Atlanta, GA. RATIONALE: Although aeroallergen sensitization is a distinguishing feature of children with severe asthma, the specific role of aeroallergens in the modulation of asthma severity is not entirely understood. Given increased reports of Alternaria sensitization and asthma symptoms in adults and children, we determined whether Alternaria sensitization and associated clinical features differed between children with severe and mild-to-moderate asthma enrolled in the NHLBI Severe Asthma Research Program (SARP). METHODS: 187 children 6-17 years of age with physician diagnosed mild-to-moderate (n597) and severe (n590) asthma were included in this analysis. Alternaria sensitization was determined by skin prick testing (SPT). RESULTS: Overall, 28% (n553) of all children with asthma enrolled in SARP had a positive SPT to Alternaria. However, Alternaria sensitization was more prevalent in children with severe (37%, n533) versus mild-tomoderate (21%, n520) asthma (p<0.01, OR 2.2, 95% CI [1.2,4.3]). Within the group of children with severe asthma, lung function (FEV1% predicted), lung volumes, blood eosinophils, serum IgE, medication
requirements, and healthcare utilization did not differ according to Alternaria sensitization. However, children with severe asthma with Alternaria sensitization had increased airway hyperresponsiveness (0.75 6 0.91 PC20 mg/mL vs 3.3 6 4.8 PC20 mg/mL, p<0.01) and were more likely to report a history of acute/chronic sinusitis requiring antibiotic treatment (58% vs 42%, p<0.05). CONCLUSION: Alternaria sensitization is associated with increased airway hyperresponsiveness and sinusitis in children with severe asthma and may account for the increased symptom burden in this population. Routine evaluation of Alternaria sensitization may be useful in the clinical management of children with severe asthma.
234
Disconnect Between Sputum Neutrophilia and Indices of Mucosal Inflammation in Severe Asthma J. R. Arron1, D. F. Choy1, S. Audusseau2, Q. Hamid2, J. M. Harris1; BOBCAT Study Group1. 1Genentech, Inc., South San Francisco, CA, 2 McGill University, Montreal, QC, CANADA. RATIONALE: Phenotypic heterogeneity in severe asthma has been described in terms of the nature and intensity of granulocytic inflammation in the airways, but few studies have directly compared various methods of airway sampling. We sought to examine the relationships between mediators of inflammation in endobronchial biopsies, induced sputum, and peripheral blood in a large cohort of severe asthmatics. _1.5 despite METHODS: Severe asthmatics (N567), defined by ACQ> _1000 micrograms/day treatment with high dose inhaled corticosteroids (> fluticasone equivalent), were assessed in an observational study in which induced sputum, endobronchial biopsies, and peripheral blood were collected. Cell counts and inflammatory cytokines were measured by immunohistochemistry. RESULTS: In induced sputum, there was a negative correlation between the proportions of eosinophils and neutrophils. However, in endobronchial biopsy tissue there was a strong positive correlation between eosinophil and neutrophil counts. Eosinophil and neutrophil counts and multiple other markers of inflammation in biopsies as determined by immunohistochemistry were significantly intercorrelated (p<0.05), including TSLP, IL25, IL33, IL17A, and IL17F. While sputum and tissue eosinophils were both positively correlated with serum periostin, sputum neutrophil percentage was negatively correlated while tissue neutrophil counts showed a trend toward positive correlation with serum periostin. None of these measures was significantly correlated with lung function or asthma control within this severe asthma cohort. CONCLUSIONS: Of multiple indices of asthmatic airway inflammation, most metrics were positively intercorrelated with the exception of sputum neutrophil percentage. Definitions of subphenotypes of severe asthma as determined solely by sputum granulocyte proportions may misrepresent the pathophysiology present in bronchial tissue.
SATURDAY
Abstracts AB61
J ALLERGY CLIN IMMUNOL VOLUME 129, NUMBER 2