Asthma in Pediatrics GINA guidelines.pptx

Latest GINA guidelines

1. Asthma and Recent GINA guidelines Department of Pediatrics Dr DY Patil Medical College and Hospital

2. OVERVIEW DEFINITION ETIOPATHOGENESIS CLINICAL PRESENTATION DIAGNOSTIC CRITERIA MANAGEMENT RECENT ADVANCES

3. Definition Heterogenous disease, characterized by chronic airway inflammation Associated with airway hyperresponsiveness and airway inflammation Defined by history of respiratory symptoms- wheeze, shortness of breath, chest tightness and cough These symptoms vary over time and in intensity together with variable expiratory airflow limitation and are associated with environmental/ biological and genetic risk factors

4. Epidemiology- World wide Prevalence % of asthma is different in all countries depending upon the geographical location, environmental factors and lifestyle changes Approximately 334 million people around the world are affected 14% Children and a round 8.6% of young adults (aged 18-45 years) suffer from this condition Global Asthma Network

5. Etiopathogenesis Combination of environmental exposures, inherent biologic and genetic susceptibilities have been implicated immune responses to common airway exposures (respiratory viruses, allergens, pollutants) can stimulate prolonged pathogenic inflammation and aberrant repair of injured airway tissues Airway inflammation, edema, basement membrane thickening, sub-epithelial collagen deposition, smooth muscle and mucous gland hypertrophy and mucus hypersecretion- leads to airway obstruction Subsequently lung dysfunction (airway hyperresponsiveness, reduced airflow) and airway remodelling happens

6. Environment Allergens Infections Microbes Pollutants Stress Biological and genetic risk Immune Lung Repair Innate and adaptive immune development (Atopy) Lower airways inflammation Respiratory viral infections Aeroallergens pollutants Aberrant repair Persistent inflammation Airway hyperresponsiveness Remodeling ASTHMA AGE Etiopathogenesis

7. Clinical Presentation Symptoms Cough- Chronic, intermittent + dry in nature Cough variant asthma Early morning or nocturnal worsening of cough or following physical exertion is classical Acute exacerbation- Shortness of breath, chest tightness or chest pain Limitation of physical activities, general fatigue

8. Clinical Presentation B. Examination/ Signs Expiratory wheeze and Prolonged exhalation – Auscultation Decreased breath sounds Severe exacerbations- Labored breathing, respiratory distress– manifesting in the form of inspiratory and expiratory wheezing, poor air entry, retractions- suprasternal, sternal and intercoastal, nasal flaring and accessory respiratory muscle use

9. Asthma Phenotypes : Allergic asthma- Most easily recognized type. Associated with past/ family history of allergic disease- eczema, allergic rhinitis, or food or drug inflammation. They usually respond well to inhaled corticosteroid treatment Non-allergic Asthma : Cellular profile may be neutrophilic or contain few inflammatory cells (paucigranulocytic) Adult onset (late onset) Asthma : Asthma seen for the first time in adult life, non-allergic and are relatively refractory to corticosteroid treatment

10. Asthma Phenotypes : Occupational asthma : Asthma due to exposures at work space Asthma with persistent airflow limitation : long standing asthma  airflow limitation which is persistent or incompletely reversible. This is attributed to airway wall remodeling. Asthma with obesity : Obese people have prominent respiratory symptoms and eosinophilic airway inflammation GLOBAL INITIATIVE FOR ASTHMA (GINA 2023 UPDATE)

11. Asthma severity – GINA Update 2023 Current concept of asthma severity is based on “Difficulty to treat” Mild asthma : Asthma well controlled with low intensity treatment i.e ; as needed low dose ICS-formoterol or low dose ICS + as needed SABA Moderate Asthma : Asthma well controlled with low or medium dose ICS-LABA Severe asthma : Asthma remains uncontrolled despite optimized treatment with high dose ICS-LABA or that requires high dose ICS-LABA to prevent it from becoming uncontrolled . GLOBAL INITIATIVE FOR ASTHMA (GINA 2023 UPDATE)

12. Modified Asthma Predictive Index ( mAPI ) Modified Asthma Predictive Index ( mAPI ) For children under 3 years of age with all of the following 4 wheezing exacerbations in past year, with 1 physician-confirmed episode Plus one major criteria or 2 minor criteria Major criteria – 1 of the following Parental history Physician diagnosed atopic dermatitis (eczema) Allergic sensitization to aeroallergen (dust mite, cat, dog, mold, grass, tress, weeds) Minor criteria – 2 of the following Allergic sensitization to food milk, egg or peanut (positive skin or blood test) Wheezing unrelated to colds Blood eosinophilia ≥ 4% of WBC Positive index: 76% risk of asthma during school years Negative index: 95% chance of not having asthma during school years

13. Allergy Skin Test at Dept of Pediatrics

14. Assessment of severity of acute exacerbation of Asthma The Severity of asthma exacerbations can be estimated by using few scoring systems : Becker’s asthma severity score Pulmonary severity score for acute severe asthma – IAP PRAM Score ( Pediatric respiratory assessment measure )

15. Pulmonary severity score – IAP SCORE RESPIRATORY RATE /MIN Wheezing Accessory muscle use < 6 years > 6 years < 30 <20 None No apparent activity 1 30-40 21-35 Terminal expiration with stethoscope Increase use 2 41-50 36-50 Entire expiration with stethoscope Apparent increased 3 > 50 <50 Inspiration + expiration without stethoscope Maximum activity Interpretation: Score 0-3: Mild asthma ; Score 4-6: Moderate asthma ; Score > 6 : Severe Asthma If wheezing is absent (due to minimal airflow) score =3

16. Clinical signs – Acute severe and Life threating asthma Acute severe asthma Red flag signs – Life threatening Asthma Sp02 < 92% and / or PEF 33-50% Sp02 < 92% and / or PEF 33-50% Cannot complete sentences in single breath Hypotension and / or Bradycardia Breathless on feeding Fatigue/ exhaustion with increased use of accessory muscles Pulse rate > 125 (>5 years) and > 140 (2-5 years)/ min Silent chest Respiratory rate > 30 (> 5 years) and > 40 (2-5 years)/ min Poor respiratory efforts/Dyspnea Cyanosis Confusion/ altered sensorium Spo2- oxygen saturation; PEF- peak expiratory flow

17. Diagnosis Past/family h/o allergy, allergen sensitization Allergy Skin test Spirometry Impulse Oscillometry PEFR Fractional Exhaled Nitric oxide

18. Pulmonary Function tests A. Spirometry : Low FEV1 (relative to % of predicted norms) FEV1/FVC ratio < 0.90 B. Bronchodilator response to assess reversibility of airflow inflammation : Determined by an increase in FEV1 > 12% or predicted FEV1 > 10% , 15 mins after inhalation of SABA (200 – 400 mcg salbutamol) Withhold SABA 4 hrs prior, twice daily LABA 24 hrs prior and once daily LABA 36 hrs C. Exercise Challenge: Worsening in FEV 1 ≥ 12% D. Daily peak expiratory flow (PEF) or FEV1 monitoring: day-to-day / AM to PM variation ≥ 13% after 2 weeks and > 20% after 4 weeks

19. PEFR (Peak Expiratory Flow Rate) PEFR = {(Height – 100) * 5 } + 100 Diurnal PEFR variability = Day’s highest – Day’s lowest * 100 Mean of day’s highest and lowest This is averaged over one week and variability calculated How do we check PEFR of the patient? When do you think PEFR is lowest and when highest?

20. Spirometry- Spirometric flow volume loops Role of peak expiratory flow (PEF) in asthma

21. 1.Recurrent viral respiratory tract infections 7. Bronchiectasis causes 13.Vascular ring 2.GERD 8.Bronchioloitis obliterans 14. TEF 3.Nasal foreign body 9.Hypersensitvity pneumonitis 15. Immune deficiency 4.Pertusis 10.Congenital heart disease 16. Endobronchial tumor 5.Persistent bacterial bronchitis 11.Cystic fibrosis 17. Chronic bronchitis 6.Tracheomalacia 12. Primary ciliary dyskinesia 18. Vocal cord dysfunction Differentials : All that wheezes is not Asthma

22. Management Education of Parents and caregivers Identification and Avoidance of triggers Treating comorbid conditions Regular assessment and Monitoring

23. Pharmacotherapy Asthma severity Step at which treatment to be initiated Achieve early and rapid control Reassess disease control regularly Step up therapy when control not achieved (1-3 months) and step down therapy when control is good in 3 months

24. Asthma management Cycle- GINA update 2023 Confirmation of diagnosis Symptom control Risk factors comorbidities Inhaler techniques Treatment of modifiable risk factors Non-pharmacological strategies Asthma medications Education and skills training Symptoms Exacerbations Side effects Lung function Comorbidities Patient/caregiver satisfaction

25. Asthma – classification- Symptom control In the past 4 weeks , does the child have : A. Daytime symptoms more than twice a week ? B. Limitation of activity ? C. SABA (Short acting beta-agonist) reliever medication needed > twice a week ? D. Any night awakening or night coughing due to asthma ? Well controlled Asthma Partly controlled Asthma Uncontrolled Asthma None of the above 1-2 of these -- Yes 3-4 of these--Yes

26. Risk factors for Exacerbations Medication : High SABA use, inadequate dose, incorrect technique, adherence issues Co morbidities : Obesity, Allergic Rhinitis, Chronic Rhinosinusitis, GERD, Food allergy, Anxiety, Depression, Obstructive Sleep Apnea Exposure : Smoking, Pollution, Irritants Psychosocial Low FEV1 < 60 % Type 2 inflammation History of mechanical ventilation in past

27. Management GINA update 2023 Asthma management according to GINA has been categorized by age group Age - 0-5 years Age- 6-11 years Age - > 12 years (Adolescents and adults)

28. Children 5 years and younger Infrequent wheezing and no or few interval symptoms Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur often eg ., > 3 per year Symptom pattern consistent with asthma and asthma symptoms not well controlled or ≥ 3 exacerbations per year Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures Asthma diagnosis, not well-controlled on low dose ICS Asthma not well controlled on double ICS Consider this step for children with As-needed short acting beta-agonist Reliever ICS-intermittent short course at onset of viral illness Daily leukotriene receptor antagonist (LTRA), or Intermittent short course ICS at onset of respiratory illness Low dose ICS + LTRA Consider specialist Add LTRA, or ↑ ICS frequency Add intermittent ICS Other controller options (Insufficient evidence for daily controller) Daily low dose inhaled corticosteroid (ICS) Double low dose ICS Continue controller and refer specialist Preferred controller choice STEP 1 STEP 2 STEP 3 STEP 4

29. Low daily doses – ICS for children 5 years and younger BDP: Beclometasone dipropionate; HFA:Hydrofloroalkanes

30. Children 6-11 years Symptoms < twice a month Symptoms twice a month or more, but less than daily Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures Symptoms most days/ waking with asthma once a week or more Symptoms most days/ waking with asthma once a week or more/ low lung function Consider this step for children with As-needed SABA (or low dose ICS-formoterol reliever for MART in steps 3 and 4) Reliever Daily low dose ICS Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken Low dose ICS + LTRA Add LTRA, or Add tiotropium Other controller options Low dose ICS taken whenever SABA Daily low dose inhaled corticosteroid (ICS) Low dose ICS-LABA Or Ver low dose ICS-Formoterol (MART) Medium dose ICS-LABA or Low dose ICS-Formoterol (MART) Refer Specialist Preferred controller choice STEP 1 STEP 2 STEP 3 STEP 4 As last resort- OCS-low dose* Refer for phenotypic assessment ± Higher dose ICS-LABA or add on therapy Eg : anti- IgE , anti-IL4R, anti-IL5 STEP 5

31. A. Before starting initial controller treatment: Record evidence for diagnosis of asthma, if possible Record child’s level of symptom control and risk factors and lung function Choose suitable inhaler and ensure usage correctly Schedule an appointment for follow up visit B. After starting initial controller treatment: Review child’s response after 2-3 months or earlier depending on clinical urgency Step down treatment once good control has been maintained for 3 months For Children 6-11 years

32. For 12 years +(Adolescents) : Treatment plan includes two treatment tracks Key difference – Medication used for symptom relief The reliever is as-needed low dose ICS-Formoterol The reliever is as needed SABA or as needed ICS-SABA Track 1 Track 2 Preferred by GINA 2023 Alternative approach, if track 1 is not possible Track 1 preferred as extensive evidence shows use of low dose ICS-Formoterol (AIR-anti-inflammatory reliever; AIR) reduces the risk of severe exacerbations compared with SABA as reliever, with symptom control

33. Preferred Controller and Reliever Reliever: As needed low dose ICS-Formoterol As needed only low dose ICS-Formoterol Low dose maintenance ICS-Formoterol Medium dose maintenance ICS-formoterol Add on LAMA Refer for phenotypic assessment ± biologic therapy Consider high dose ICS-formoterol STEP 1-2 STEP 3 STEP 4 STEP 5 Track 1 Alternative Controller and Reliever Reliever: As needed low dose ICS-Formoterol Take ICS whenever SABA taken Low dose maintenance ICS-LABA Medium/high dose maintenance ICS-LABA Add on LAMA Refer for phenotypic assessment ± biologic therapy Consider high dose ICS-LABA STEP 1 STEP 3 STEP 4 STEP 5 Track 2 Low dose maintenance ICS STEP 2 Note : Before considering SABA reliever regimen, check if the patient is likely to adhere to daily controller treatment Symptoms less than 4-5 day a week Symptoms most days/ waking with asthma once a week or more Daily symptoms/waking with asthma once a week or more / low lung function Note: Short course Oral corticosteroids – may be needed with severely uncontrolled asthma Symptoms less than twice a month Symptoms twice a month or more but less than 4-5 days a week Symptoms most days/ waking with asthma once a week or more Daily symptoms/waking with asthma once a week or more and low lung function Note: Short course Oral corticosteroids – may be needed with severely uncontrolled asthma

34. Inhaled corticosteroid-Doses :

35. What’s new in GINA 2023 Terminologies: “Controller” has been replaced by “maintenance treatment “ or “ICS containing treatment” “Anti inflammatory reliever” reflects its dual purpose : ICS SABA MART: Maintenance and Reliever therapy: ICS Formoterol 2. Comments added to ASSESS—ADJUST---REVIEW 3. Addition of as needed ICS- SABA for adults and adolescents instead of SABA alone 4. Mepolizumab (Anti IL 5 ) for severe eosinophilic asthma (for >6 yrs ) 5. Addition of environmental considerations for inhaler choice 6. Updated advice on mild asthma

36. 7. Pertusis added as a differential 8. Importance of Asthma Questionnaires and control tools 9. Digital intervention for adherence 10. Importance of physical activity 11. Outdoor air pollution 12. Fragility fractures due to high Oral Corticosteroids use

37. Key changes to GINA severe asthma guide in 2023 Additional investigations Consider screening for adrenal insufficiency if patient is on maintenance OCS or high dose ICS-LABA For patients with eosinophils ≥300/µl, investigate for non-asthma causes including Strongyloides (often asymptomatic), before considering biologic therapy For patients with hyper eosinophilia, e.g. ≥1500/µl, investigate for conditions such as EGPA Assessment of inflammatory phenotype If blood eosinophils or FeNO not elevated, repeat up to 3 times, at least 1–2 weeks after stopping OCS, or on lowest possible OCS dose

38. Treatment options for patients with no evidence of Type 2 inflammation on repeated testing Consider add-on treatment with LAMA or low-dose azithromycin if not already tried Consider maintenance OCS only as last resort, because of serious cumulative adverse effects Type 2 : Blood eosinophils > 150/ microl FeNO > 20 ppb Sputum eosinophils > 2 % Asthma is clinically allergen driven

39. New in Biologics Anti-IL4R* (dupilumab) for severe eosinophilic/Type 2 asthma Now suggested if blood eosinophils (current or historic) >150/µl Dupilumab now also approved for children ≥6 years with severe eosinophilic/Type 2 asthma, not on maintenance OCS Anti-TSLP* (tezepelumab) now approved for severe asthma (age ≥12 years) The greater clinical benefit with higher blood eosinophils and/or higher FeNO Insufficient evidence in patients taking maintenance OCS TSLP: thymic stromal lymphopoietin

40. Class Name Age* Asthma indication* Other indications* Anti-IgE Omalizumab (SC) ≥6 years Severe allergic asthma Nasal polyposis, chronic spontaneous urticaria Anti-IL5 Anti-IL5R Mepolizumab (SC) Reslizumab (IV) Benralizumab (SC) ≥6 years ≥18 years ≥12 years Severe eosinophilic/Type 2 asthma Mepolizumab: EGPA, CRSwNP , hypereosinophilic syndrome Anti-IL4R Dupilumab (SC) ≥6 years Severe eosinophilic/Type 2 asthma, or maintenance OCS Moderate-severe atopic dermatitis, CRSwNP Anti-TSLP Tezepelumab (SC) ≥12 years Severe asthma

41. Allergen Immunotherapy Also called as immune teaching, it’s a process of tolerance induction to specific allergens Respective allergens are introduced in the body through various routes in minimal concentration and dose is gradually increased. Targets coversion of allergic Th2 to non allergic Th1 pathway Indications: Allergic rhinitis Allergic asthma Insect hypersensitivity Subcutaneous vs Sublingual Immunotherapy Increase in IgG4 levels and decrease in IgE levels Duration of treatment : 3 – 5 yrs

42. Drug delivery systems MDI-Metered dose inhaler (Age > 12) MDI with Spacer (Age >4 years) MDI with spacer and face mask (Age <4 years) Dry powder inhaler Nebulizer

43. Management -GINA update 2023 AGE Preferred device Alternative device 0-3 years Pressurized metered dose inhaler + Spacer+ Face mask Nebulizer with face mask 4-12 years Pressurized metered dose inhaler + Spacer Nebulizer with mouth piece or face mask

44. 1. A 8 years old female child with history of dry cough, shortness of breath, chest tightness on and off for 2 months, more during early morning. She had waking at night ≥ once a week . On examination, bilateral wheeze was present with equal air entry. PFT showed low lung function Case scenario: Child belongs to which step ? Management ?

45. References Jindal SK, Aggarwal AN, Gupta D, et al. Indian study on epidemiology of asthma, respiratory symptoms and chronic bronchitis in adults (INSEARCH). Int J Tuberc Lung Dis 2012; 16: 1270–1277. GBD Compare. Viz Hub. (2021, June 30). https://vizhub.healthdata.org/gbd-compare 21 st edition NELSON-Textbook of Pediatrics Third Edition of the PG Textbook of Pediatrics ; Piyush Gupta Global Asthma Network Global Initiative For Asthma (Gina 2023 Update) National asthma Education and Prevention program

46. Pediatric Asthma and Allergy OPD Every Tuesday 10 am to 1 pm Doctors on board: Dr Vineeta Pande (Professor and Head of Unit) Dr Richa (Assistant Professor) Services offered: Allergy Skin test Spirometry PEFR Testing Education and counselling for caregivers Diagnosis and treatment of Allergic diseases Allergen Immunotherapy

47. Thank you for patient listening