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Asthma in Children-Step Care PowerPoint Presentation

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Description : Check out this medical presentation on Pediatrics, which is titled "Asthma in Children: Step Care", to know about recent studies that impact the approach to asthma therapy, summarize key findings that differentiate treatment in children, and learn methods to select therapy to optimize effect and minimize adverse effects.

Tags : Pediatrics, Asthma, Children, Step Care, asthma therapy

Published on : Aug 03, 2021 | Views : 866 | Downloads : 8

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Slide 1-

Asthma in Children: Step Care Stanley J. Szefler, MD Helen Wohlberg and Herman Lambert Chair in Pharmacokinetics, Head, Pediatric Clinic Pharmacology, National Jewish Health & Professor of Pediatrics and Pharmacology, University of Colorado School of Medicine
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Learning Objectives • To review recent studies that impact the approach to asthma therapy. • To summarize key findings that differentiate treatment in children. • To indicate methods to select therapy to optimize effect and minimize adverse effects.
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Disclosure Advisory Board for Boehringer Ingelheim, Genentech, GlaxoSmithKline and Merck Consultant for Genentech Investigator for GlaxoSmithKline Grant support: NHLBI Childhood Asthma Management Program, Asthma Clinical Research Network, Childhood Asthma Research and Education Network and AsthmaNet
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Disclosure Grant support (continued): NIAID Inner City Asthma Consortium NIEHS/EPA Childhood and Environmental Health Center Grant CDPHE Colorado Cardiovascular, Cancer and Pulmonary Disease Program Caring for Colorado Foundation, GlaxoSmithKline Health Outcomes Program.
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Primary Goal of Therapy: Achieving and Maintaining Asthma Control • Primary goal of asthma therapy is to enable a patient to achieve and maintain control over their asthma - Eliminate impairments including symptoms, functional limitations, poor quality of life, and other manifestations of asthma - Reduce risk of exacerbations, ED visits, and hospitalizations • Treatment goals are identical for all levels of asthma severity NHLBI. National Asthma Education and Prevention Program. Full report of the Expert Panel: Guidelines for the Diagnosis and Management of Asthma (EPR-3). Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed August 31, 2007.
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Pediatric Population • NAEPP defined three age groups - 12 years and above - 5 to 11 years of age - Less than 5 years of age • Treatment goals are identical for all age groups • Treatment steps vary by age due to available studies and disease presentation. NHLBI. National Asthma Education and Prevention Program. Full report of the Expert Panel: Guidelines for the Diagnosis and Management of Asthma (EPR-3). Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed August 31, 2007.
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Assessing Asthma Control and Adjusting Therapy in Youths 12 Years of Age and Adults
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Stepwise Approach for Managing Asthma in Youths >12 Years of Age and Adults
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Approaches to Personalizing Asthma Management • Early intervention strategies – Who? What treatment? What outcomes? • Biomarkers – Which ones? What application? • Combination therapy – How soon? What type? • Genetics/epigenetics – Are we there yet? • Immunomodulators – benefit-risk?
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EPR-3 Recommendations:Step-Up Therapy Intermittent Asthma Persistent Asthma Step 1 Step 2 Step 3 Step 4 Step 5 Step 6 Preferred: Low-dose ICS Alternative: Either cromolyn, LTRA, nedocromil, or theophylline
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CARE Network CLIC Study Timeline Assessment/ Characterization Mt Treatment Phase FP Mt FP FP FP Mt Mt Consent Asthma Hx eNO PFTs BD response Biomarkers Genetics Diary and PFM Review diary eNO PFTs Methacholine Skin testing Visit 1 2 3 4 5 6 Week -1 0 4 8 12 16 Review diary eNO PFTs Randomization
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CLIC Primary Outcome: FEV1 Response FEV1 % Change with FP FEV1 % Change with Mt Mt alone n=6 (5%) Neither n=69 (55%) FP alone n=29 (23%) Both n=22 (17%) Line of identity Concordance Correlation 0.55 (0.43, 0.65) >7.5% Mt Response >7.5% FP Response Ref. Szefler SJ and CARE Network. JACI 2005;115:233-42. -50 -40 -30 -20 -10 0 10 20 30 40 50 -50 -40 -30 -20 -10 0 10 20 30 40 50
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CLIC FEV1 Response ≥ 7.5%:Odds Ratio Ref. Szefler SJ and the CARE Network. J Allergy Clin Immunol 2005;115:233-42.
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CLIC Differential Response Analysis Higher bronchodilator use Greater response to bronchodilator Higher exhaled nitric oxide Higher serum eosinophilic cationic protein Lower pre-bronchodilator FEV1 percent predicted Lower FEV1/FVC Lower methacholine PC20 Greater response to fluticasone over montelukast for increased FEV1 was associated with: Ref. Szefler SJ and the CARE Network. J Allergy Clin Immunol 2005;115:233-42.
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CLIC Conclusions Children with lower pulmonary function or higher levels of markers associated with allergic inflammation should receive ICS therapy. Children without these indicators could receive a therapeutic trial of either ICS or LTRA. How does the asthma-related phenotype influence the choice of medication selected to improve pulmonary function? Ref. Szefler SJ and the CARE Network. J Allergy Clin Immunol 2005;115:233-42.
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Follow-up Study LTE4/FENO ratios were associated with a greater response to montelukast than FP for FEV1 and for asthma control days. Children with high LTE4/FENO ratios were likely to be younger and female and exhibit lower levels of atopic markers and methacholine reactivity. Can we predict who would have a better response to montelukast over ICS? Ref. Rabinovitch N and the CARE Network. J Allergy Clin Immunol 2010;126:545-51 and 959-61.
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EPR-3 Recommendations Intermittent Asthma Persistent Asthma Step 1 Step 2 Step 3 Step 4 Step 5 Step 6
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BADGER Protocol: Overview Period 1 Period 2 Period 3 Run-in period on 1xICS to demonstrate lack of control 16 weeks 16 weeks 16 weeks Run-in Period 2-8 weeks Randomization Three Treatment Period, Double blind, 3 way cross-over 2.5 x ICS = fluticasone DPI 250 µg BID 1xICS+LABA = fluticasone/salmeterol DPI 100/50 BID 1xICS+LTRA = fluticasone DPI 100 µg BID + montelukast 1xICS = fluticasone DPI 100 µg BID 2.5 x ICS or 1x ICS + LABA or 1 x ICS + LTRA 2.5 x ICS or 1x ICS + LABA or 1 x ICS + LTRA 2.5 x ICS or 1x ICS + LABA or 1 x ICS + LTRA Evaluation Period Evaluation Period Evaluation Period
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LABA ICS Primary Outcome: Probability of BEST Response Based on Composite Outcome* LTRA *Ref. Lemanske RF and CARE Network. NEJM 2010;362:975-985. LABA step-up was more than 1.5 times as likely to produce the best response (p = 0.002) (p = 0.004)
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BADGER Study: Conclusions • Significant variability in treatment response was noted at the Step-3 level. • LABA step-up therapy was more than 1.5 times as likely to produce the best response. Many children demonstrated a best response to either step-up ICS or LTRA. Several characteristics, such as baseline ACT®, eczema, and race could be useful in selecting medication treatment for best response. Ref. Lemanske RF and CARE Network. NEJM 2010;362:975-985.
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Summary Points • Inhaled corticosteroids are the preferred long-term controller therapy at Step 2 level. • At Step 3 Level, LABA step-up therapy was more than 1.5 times as likely to produce the best response. LTRA are alternative choices for Step 2 long-term controller and supplementary Step 3. Variable response can occur at either Step 2 or Step 3 therapy and alternative treatments may be selected within each Step before stepping up therapy.
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Inner-City Anti-IgE Therapy for Asthma (ICATA) Published by Busse et al, New Eng J Med 2011;364:1005-1015 A Randomized Trial to Evaluate the Impact of the Addition of Omalizumab to Guidelines Based Therapy of Inner-City Children and Adolescents with Asthma
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Enrollment characteristics 6 to 20 years of age with a diagnosis of persistent asthma Allergy to a perennial allergen Inner-city resident At recruitment, participants had uncontrolled asthma Weight and total serum IgE levels were suitable for omalizumab dosing
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Study Design Enrollment (4 weeks) Asthma control assessed Using a Guidelines-based algorithm, treatment was begun or adjusted to achieve asthma control Randomization and treatment (60 weeks) Following an adjustment of asthma medications during enrollment, participants were randomized to receive omalizumab or placebo every 2 to 4 weeks for 60 weeks
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The effect of omalizumab on exacerbations
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Effect of Omalizumab on Asthma Exacerbations
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Asthma Management Utilize asthma characteristics, biomarkers, and genetics to “profile” asthma severity and prognosis. Select medications based on driving factors of disease presentation and predictors of response. Monitor response and assess reasons for treatment failure. Develop proactive approach and adjust therapy accordingly. Individualized or “Personalized” Approach
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Where Do We Go From Here? Improve process of asthma management to apply step-care approach Identify alternative biomarker for Step 3 Assess “step-up” treatment strategies to improve control and reduce exacerbations Environment control measures Reduce impact of viral infection Immune-based therapy to reduce impact of allergen-induced inflammation. Possibilities to improve asthma control
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Future Approaches to Improving Asthma Management • Genetics • Early intervention • Immunomodulators • Biomarkers • Combination therapy