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Persistence of Airflow Obstruction in Asthmatic Children
AB8 Abstracts
23
Impact of Asthma Exacerbations on Health Status in Patients with Severe Asthma
SATURDAY
Sarah Cockle1, Linda Nelsen2, Miriam Kimel3, Frank C. Albers, MD, PhD4, Paul Jones5; 1GlaxoSmithKline, Value Evidence and Outcomes, Stockley Park, United Kingdom, 2GlaxoSmithKline, King of Prussia, PA, 3Evidera, Bethesda, MD, 4GlaxoSmithKline, Research Triangle Park, NC, 5GlaxoSmithKline, Stockley Park, United Kingdom. RATIONALE: Asthma exacerbations constitute a considerable part of disease burden in patients with severe uncontrolled asthma. However, the impact of exacerbations is challenging to quantify. The St George’s Respiratory Questionnaire (SGRQ), a measure of health status in obstructive airway disease, was measured at baseline and end of treatment in a 32 week phase III clinical trial of mepolizumab for treatment of severe asthma with a history of exacerbations (MENSA). METHODS: In this post-hoc analysis, we examined the impact of exacerbations in 2 ways (1) baseline SGRQ scores by exacerbation history _2 compared with >2) and (2) change in SGRQ scores for subjects with and (< without exacerbations during treatment. All patients entering the trial had a history of at least two severe asthma exacerbations in the prior 12 months. _2 exacerbations, mean RESULTS: Among subjects with a history of < baseline SGRQ total score was 42.5 compared to 49.4 for those a history of >2 exacerbations (p<0.0001). Among patients not experiencing an exacerbation during the study, SGRQ total score at 32 weeks was 28.5 compared to 41.5 for subjects experiencing >1 exacerbations during study treatment (p<0.0001) with changes of -15.4 and -8.0, respectively. Similar patterns were observed for SGRQ domain scores. CONCLUSIONS: The observed differences in SGRQ total and domain scores for subjects with history of exacerbations at baseline or experiencing an exacerbation during the study substantially exceeded the accepted minimum clinically important difference of 4. These differences in SGRQ score demonstrate a substantial health impact of exacerbations. Funding: GSK (NCT01691521).
24
Persistence of Airflow Obstruction in Asthmatic Children
Lori Banka, DO1, Yang Lu, PhD2, Lyne G. Scott, MD3, Salima A. Thobani, MD4, Marilyn Li, MD5, Cindy Xi, MD6, Kenny Y. Kwong6; 1 LAC+USC Medical Center, Los Angeles, CA, 2Harbor-UCLA Medical Center, 3University of Southern California, CA, 4University of Southern California, Los Angeles, 5University of Southern California, 6LAC+USC Medical Center. RATIONALE: Chronic lung injury during early childhood may lead to abnormal lung function persisting into adolescence. This study endeavors to determine whether children with asthma who initially present with low lung function continue to have ongoing airflow obstruction despite optimal asthma treatment. METHODS: This is a 5 year retrospective study involving asthmatic children, aged 6 to 14 enrolled in a pediatric asthma disease management program (Breathmobile). Patients had at least 1 spirometric assessment per year and received asthma care in accordance with 2007 NHLBI-EPR-3 asthma guidelines. Patients were divided into 2 groups, one with mean FEV1 and FEV1/FVC < 80% predicted and the second group with these mean values > 80% predicted during the first year of treatment. Outcome was FEV1 and FEV1/FVC % predicted of these patients over subsequent 4 years. RESULTS: 621 patients were enrolled with 2711 visits. Mean age of patients was 9.3 years. 30%, 18%, 32% and 20% of patients had intermittent, mild, moderate and severe persistent asthma at initial evaluation. Patients with FEV1% and FEV1/FVC% <80% predicted during first year of enrollment was associated with increased odds ratio
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
of 19 (p<0.01) and 21 (p<0.01) of having respective values <80% predicted over subsequent 4 years. CONCLUSIONS: Airflow obstruction persists in asthma children with early lung functions despite optimal guideline based therapy.
25
Characteristics That Distinguish Difficult-to-Control Asthma in Inner-City Children
Jacqueline A. Pongracic, MD, FAAAAI1, Rebecca A. Zabel, MS2, Denise C. Babineau, PhD2, Edward M. Zoratti, MD, FAAAAI3, George T. O’Connor, MD4, Robert A. Wood, MD, FAAAAI5, Gurjit K. Khurana Hershey, MD, PhD, FAAAAI6, Carolyn Kercsmar, MD7, Rebecca S. Gruchalla, MD, PhD, FAAAAI8, Meyer Kattan, MD9, Stephen J. Teach, MD10, Samuel J. Arbes, Jr2, William W. Busse, MD, FAAAAI11, Peter J. Gergen, MD, MPH12, Alkis Togias, MD, FAAAAI13, Cynthia Visness, PhD, MPH2, Andrew H. Liu, MD, FAAAAI14,15; 1Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 2Rho Federal Systems Division Inc., Chapel Hill, NC, 3Henry Ford Health System, Detroit, MI, 4Boston University School of Medicine, Boston, MA, 5 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, 6Cincinnati Children’s Hospital, Cincinnati, OH, 7Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 8 UT Southwestern Medical Center, Dallas, TX, 9College of Physicians and Surgeons, Columbia University, New York, NY, 10Children’s National Health System, Washington, DC, 11University of Wisconsin School of Medicine and Public Health, Madison, WI, 12AAIB/DAIT/NIH, Bethesda, MD, 13NIAID/NIH, Bethesda, MD, 14Children’s Hospital Colorado, Aurora, CO, 15National Jewish Health, Denver, CO. RATIONALE: Because a significant proportion of inner-city children are only partially responsive to guidelines-directed asthma therapy, we sought to identify the clinical characteristics that distinguish difficult-to-control asthma. METHODS: The Inner City Asthma Consortium enrolled children aged 6-17 years with asthma. After baseline assessment, participants had bi-monthly guidelines-based asthma management visits over one year. Difficult-to-control asthma (DCA) versus Easy-to-control asthma (ECA) were defined as daily controller therapy with inhaled fluticasone >500mcg +/-LABA versus <100mcg assigned on at least 4 visits, respectively. Forty-one baseline variables were used to compare DCA and ECA using univariate analyses. A variable selection algorithm was used to determine the most relevant features of DCA versus ECA. Generalized additive mixed-effects models were used to describe seasonal variation of symptoms, lung function, and exacerbations. RESULTS: Of the 619 participants, 40.9% had DCA and 37.5% had ECA. DCA was characterized by persistently low lung function, more frequent exacerbations in the spring and fall as well as greater daytime and nocturnal symptoms in the fall and winter. Of the 41 variables, FEV1 bronchodilator reversibility (BDR) was the most important characteristic distinguishing DCA. The other dominant features of DCA, in order of importance, included: FEV1/FVC ratio, rhinitis medication score, FEV1 % predicted, rhinitis symptom score, mold sensitization, and total serum IgE. CONCLUSIONS: The phenotypic characteristics of DCA in inner-city children include seasonal loss of asthma control, BDR, persistently low lung function, rhinitis severity and atopy. These findings suggest that baseline assessment of BDR and allergy-related factors, including rhinitis, may predict future DCA.
23
Impact of Asthma Exacerbations on Health Status in Patients with Severe Asthma
SATURDAY
Sarah Cockle1, Linda Nelsen2, Miriam Kimel3, Frank C. Albers, MD, PhD4, Paul Jones5; 1GlaxoSmithKline, Value Evidence and Outcomes, Stockley Park, United Kingdom, 2GlaxoSmithKline, King of Prussia, PA, 3Evidera, Bethesda, MD, 4GlaxoSmithKline, Research Triangle Park, NC, 5GlaxoSmithKline, Stockley Park, United Kingdom. RATIONALE: Asthma exacerbations constitute a considerable part of disease burden in patients with severe uncontrolled asthma. However, the impact of exacerbations is challenging to quantify. The St George’s Respiratory Questionnaire (SGRQ), a measure of health status in obstructive airway disease, was measured at baseline and end of treatment in a 32 week phase III clinical trial of mepolizumab for treatment of severe asthma with a history of exacerbations (MENSA). METHODS: In this post-hoc analysis, we examined the impact of exacerbations in 2 ways (1) baseline SGRQ scores by exacerbation history _2 compared with >2) and (2) change in SGRQ scores for subjects with and (< without exacerbations during treatment. All patients entering the trial had a history of at least two severe asthma exacerbations in the prior 12 months. _2 exacerbations, mean RESULTS: Among subjects with a history of < baseline SGRQ total score was 42.5 compared to 49.4 for those a history of >2 exacerbations (p<0.0001). Among patients not experiencing an exacerbation during the study, SGRQ total score at 32 weeks was 28.5 compared to 41.5 for subjects experiencing >1 exacerbations during study treatment (p<0.0001) with changes of -15.4 and -8.0, respectively. Similar patterns were observed for SGRQ domain scores. CONCLUSIONS: The observed differences in SGRQ total and domain scores for subjects with history of exacerbations at baseline or experiencing an exacerbation during the study substantially exceeded the accepted minimum clinically important difference of 4. These differences in SGRQ score demonstrate a substantial health impact of exacerbations. Funding: GSK (NCT01691521).
24
Persistence of Airflow Obstruction in Asthmatic Children
Lori Banka, DO1, Yang Lu, PhD2, Lyne G. Scott, MD3, Salima A. Thobani, MD4, Marilyn Li, MD5, Cindy Xi, MD6, Kenny Y. Kwong6; 1 LAC+USC Medical Center, Los Angeles, CA, 2Harbor-UCLA Medical Center, 3University of Southern California, CA, 4University of Southern California, Los Angeles, 5University of Southern California, 6LAC+USC Medical Center. RATIONALE: Chronic lung injury during early childhood may lead to abnormal lung function persisting into adolescence. This study endeavors to determine whether children with asthma who initially present with low lung function continue to have ongoing airflow obstruction despite optimal asthma treatment. METHODS: This is a 5 year retrospective study involving asthmatic children, aged 6 to 14 enrolled in a pediatric asthma disease management program (Breathmobile). Patients had at least 1 spirometric assessment per year and received asthma care in accordance with 2007 NHLBI-EPR-3 asthma guidelines. Patients were divided into 2 groups, one with mean FEV1 and FEV1/FVC < 80% predicted and the second group with these mean values > 80% predicted during the first year of treatment. Outcome was FEV1 and FEV1/FVC % predicted of these patients over subsequent 4 years. RESULTS: 621 patients were enrolled with 2711 visits. Mean age of patients was 9.3 years. 30%, 18%, 32% and 20% of patients had intermittent, mild, moderate and severe persistent asthma at initial evaluation. Patients with FEV1% and FEV1/FVC% <80% predicted during first year of enrollment was associated with increased odds ratio
J ALLERGY CLIN IMMUNOL FEBRUARY 2016
of 19 (p<0.01) and 21 (p<0.01) of having respective values <80% predicted over subsequent 4 years. CONCLUSIONS: Airflow obstruction persists in asthma children with early lung functions despite optimal guideline based therapy.
25
Characteristics That Distinguish Difficult-to-Control Asthma in Inner-City Children
Jacqueline A. Pongracic, MD, FAAAAI1, Rebecca A. Zabel, MS2, Denise C. Babineau, PhD2, Edward M. Zoratti, MD, FAAAAI3, George T. O’Connor, MD4, Robert A. Wood, MD, FAAAAI5, Gurjit K. Khurana Hershey, MD, PhD, FAAAAI6, Carolyn Kercsmar, MD7, Rebecca S. Gruchalla, MD, PhD, FAAAAI8, Meyer Kattan, MD9, Stephen J. Teach, MD10, Samuel J. Arbes, Jr2, William W. Busse, MD, FAAAAI11, Peter J. Gergen, MD, MPH12, Alkis Togias, MD, FAAAAI13, Cynthia Visness, PhD, MPH2, Andrew H. Liu, MD, FAAAAI14,15; 1Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL, 2Rho Federal Systems Division Inc., Chapel Hill, NC, 3Henry Ford Health System, Detroit, MI, 4Boston University School of Medicine, Boston, MA, 5 Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, 6Cincinnati Children’s Hospital, Cincinnati, OH, 7Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 8 UT Southwestern Medical Center, Dallas, TX, 9College of Physicians and Surgeons, Columbia University, New York, NY, 10Children’s National Health System, Washington, DC, 11University of Wisconsin School of Medicine and Public Health, Madison, WI, 12AAIB/DAIT/NIH, Bethesda, MD, 13NIAID/NIH, Bethesda, MD, 14Children’s Hospital Colorado, Aurora, CO, 15National Jewish Health, Denver, CO. RATIONALE: Because a significant proportion of inner-city children are only partially responsive to guidelines-directed asthma therapy, we sought to identify the clinical characteristics that distinguish difficult-to-control asthma. METHODS: The Inner City Asthma Consortium enrolled children aged 6-17 years with asthma. After baseline assessment, participants had bi-monthly guidelines-based asthma management visits over one year. Difficult-to-control asthma (DCA) versus Easy-to-control asthma (ECA) were defined as daily controller therapy with inhaled fluticasone >500mcg +/-LABA versus <100mcg assigned on at least 4 visits, respectively. Forty-one baseline variables were used to compare DCA and ECA using univariate analyses. A variable selection algorithm was used to determine the most relevant features of DCA versus ECA. Generalized additive mixed-effects models were used to describe seasonal variation of symptoms, lung function, and exacerbations. RESULTS: Of the 619 participants, 40.9% had DCA and 37.5% had ECA. DCA was characterized by persistently low lung function, more frequent exacerbations in the spring and fall as well as greater daytime and nocturnal symptoms in the fall and winter. Of the 41 variables, FEV1 bronchodilator reversibility (BDR) was the most important characteristic distinguishing DCA. The other dominant features of DCA, in order of importance, included: FEV1/FVC ratio, rhinitis medication score, FEV1 % predicted, rhinitis symptom score, mold sensitization, and total serum IgE. CONCLUSIONS: The phenotypic characteristics of DCA in inner-city children include seasonal loss of asthma control, BDR, persistently low lung function, rhinitis severity and atopy. These findings suggest that baseline assessment of BDR and allergy-related factors, including rhinitis, may predict future DCA.