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Treatment of Children Asthma Dr. Fatemeh Behmanesh

Key elements to optimal asthma management

Assess severity The classification of asthma severity is based on the following parameters: Frequency of day time symptoms Frequency of might time symptoms Degree of air flow obstruction by spirometry or PEF variability

Asthma severity categorized as Mild intermittent Mild persistent Moderate persistent Sever persistent

Classification of Asthma Severity FOR ADULTS AND CHILDREN AGE > 5 YEARS WHO CAN USE A SPIROMETER OR PEAK FLOW METER CLASSIFICATION STEP DAYS WITH SYMPTOMS NIGHTS WITH SYMPTOMS FEV1 or PEF[*] % Predicted Normal PEF Variability (%) Severe persistent 4 Continual Frequent ≤60 >30 Moderate persistent 3 Daily >1/wk >60–<80 Mild persistent 2 >2/wk, but <1 time/day >2/mo ≥80 20–30 Mild intermittent 1 ≤2/wk <2/mo <20

Stepwise Approach for Managing Infants and Young Children (≤5 Yr of Age) with Acute or Chronic Asthma; Treatment     Classify Severity: Clinical Features Before Treatment Or Adequate Control Medications Required To Maintain Long-Term Control      Symptoms/Day Symptoms/Night Daily Medications Step 4 Severe persistent Step 3 Moderate persistent Step 2 Mild persistent Step 1 Mild intermittent    Continual Frequent    Daily >1 night/wk >2/Week but<1 /day >2 nights/mo  2days/wk 2nights/mo Preferred treatment High-dose inhaled corticosteroids AND Long-acting inhaled β2-agonists AND, if needed, Corticosteroid tablets or syrup long term (2 mg/kg/day, generally do not exceed 60 mg/day).(Make repeat attempts to reduce systemic corticosteroids and maintain control with high-dose inhaled corticosteroids.) Low-dose inhaled corticosteroids and long-acting inhaled β2-agonists OR Medium-dose inhaled corticosteroids. Alternative treatment Low-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. If needed (particularly in patients with recurring severe exacerbations): Medium-dose inhaled corticosteroids and long-acting β2-agonists. Medium-dose inhaled corticosteroids and either leukotriene receptor antagonist or theophylline. Low-dose inhaled corticosteroid (with nebulizer or MDI with holding chamber with or without face mask or DPI). Cromolyn (nebulizer is preferred or MDI with holding chamber) OR leukotriene receptor antagonist. No daily medication needed.  Quick Relief All Patients Bronchodilator as needed for symptoms. Intensity of treatment will depend on severity of exacerbation. Preferred treatment: Short-acting inhaled β2-agonists by nebulizer or face mask and space/holding chamber Alternative treatment: Oral β2-agonist With viral respiratory infection Bronchodilator q 4–6 hr up to 24 hr (longer with physician consult); in general, repeat no more than once every 6 wk Consider systemic corticosteroid if exacerbation is severe or patient has history of previous severe exacerbations Use of short-acting β2-agonists >2 times/wk in intermittent asthma (daily, or increasing use in persistent asthma) may indicate the need to initiate (increase) long-term-control therapy.

Treat all persistent asthma with anti-inflammatory controller medication. the type and amounts of daily controller medication are determined by asthma severity.

Three strikes rule: Symptom or uses quick-relif medication at least 3 times per week. Awakens at might due to asthma at least 3 times per months. Experiences asthma exacerbations at least 3 times per year. Or require short courses of systemic cortico-steroids at least 3 times a year. Patient should receive daily controller therapy

Controller therapy can be considered for children who present with frequent exacerbation At least 2 exacerbation occuring < 6 week apart

All levels of persistent asthma should be treated with daily medications include: ICS LABA Leukotriene modifiers Nonsteroidal anti-inflamatory agents Sustained – release theophylline Anti- IgE (omalizumab, Xolair) approved by add- on therapy for patients with moderate to sever allergic asthma. Most potent and effective medication is corticosteroids Acute (systemically) Chronic (inhalation)

ICS First line treatment for persistent asthma Reduce asthma symptoms Improve lung function Reduce AHR Reduce “rescue” medication use Reduce urgent care visits & hospitalization Lower the risk of death

Estimated Comparative Daily Dosages for Inhaled Corticosteroids DRUG LOW DAILY DOSE MEDIUM DAILY DOSE HIGH DAILY DOSE Adult Child[*] Beclomethasone CFC 42 or 84 μg/puff 168–504 μg 84–336 μg 504–840 μg 336–672 μg >840 μg >672 μg Beclomethasone HFA 40 or 80 μg/puff 80–240 μg 80–160 μg 240–840 μg 160–320 μg >480 μg >320 μg Budesonide DPI 200 μg/inhalation 200–600 μg 200–400 μg 600–1,200 μg 400–800 μg >1,200 μg >800 μg Inhalation suspension for nebulization (child dose) 0.5 μg 1.0 μg 2.0 μg Flunisolide 250 μg/puff 500–1,000 μg 500–750 μg 1,000–2,000 μg 1,000–1,250 μg >2,000 μg >1,250 μg Fluticasone MDI: 44, 110, or 220 μg/puff 88–264 μg 88–176 μg 264–660 μg 175–440 μg >660 μg >440 μg DPI: 50, 100, or 250 μg/inhalation 100–300 μg 100–200 μg 300–600 μg >600 μg >400 μg Triamcinolone acetonide 100 μg/puff 400–1,000 μg 800–1,200 μg * Children ≤ 12 years of age

Leukotrience pathway modifiers Two classes of leukotrene modifiers: Inhibitors of leukotriene synthesis: zileuton Leukotriene receptor antagonists: Montelukast Zafirlukast

Zileuton: Not upproved for children < 12 year 4 times daily Elevated liver function enzymes Montelukast Approved for children 1 year One daily Zafirlukast Approved in children  5 year Twic daily

Leukotriene modifiers are considered alternative controllers for mild persistent asthma

Sustained- Release Theophylline Considered on alternative monotherapy controller agent for older children and adults with mild persistent asthma. No longer considered a first line agent for small children

LABA Daily controller medication Not as monotherapy for persistent asthma Add- on agent for patients suboptimally controlled on ICS therapy alone Salmetrol For moterol In patients with nocturnal asthma Low dose ICS with LABA for moderate persistent asthma in older children and adult High dose ICS + LABA for sever persistent asthma

Non-steroidal Anti- Inflammatory Agents Cromolyn and nedocromil Non- corticosteroid anti- inflammatory Reduce exercise- induced bronchospasm For mild persistent asthma Adminstered frequently 2-4 times/day Not nearly as effective daily contoller as ICS

Anti IgE (omalizumal) Humanized monoclonal antibody that binds IgE FDA approved for patients > 12 year old For moderate to sever asthma For Patients with inadequate disease control with ICS or oral corticosteroids Every 2-4 week

Step-up, step up- Down Approach Initiating higher-level controller therapy Step down after good asthma control Decrease ICS dose about 25% every 2-3 months If control is not maintained, step up, review patient medication technique Adherence Environment

Quick – Reliever medications Rescue medications: Short acting inhaled -agonist Inhaled antichilinergics Short course systemic corticosteriods For management of acute asthma

SABA Rapid onset of action 4-6 hr duration of action First choice for acute asthma symptom For preventing exercise induced bronchospasm It is helpful to monitor the frequency of SABA Use At least 1 MDI/Month Indicate Inadequate Asthma Control Al least 3 MDI/ year

Anticholinergic Agents Ipratropium bromide Tretament of acute sever asthma Combination with SABA Improve lung function Reduce the rate of hospitalization MDI, Nebulizer formulation Approved by FDA for children > 12 year of age

Management acute asthma The home The emergency department The hospital

Home Management Home treatment based on changes in PEF values Green zone Yellow zone Red zone In children too young or otherwise incapable of performing PFT, sing & symptoms to be evaluated: (e.g., color changes, respiratory rate, location/extent of retractions, duration of inspiratory/ expiratory phases, presence or absence of cough/wheezing)

…Home Management Note signs and symptoms: Degrees of cough, breatlessness, wheeze and chest tightness, corrolate imperfectly with severity of exacebration. Accessory muscle use and suprasternal retraction suggest severed exacebration. If PEF<50% predicted: initial treatment Inhaled short-acting β2 agonist: up to three treatment of 2-4 puff 20-min intervales by MDI MDI + Spacer device DPI Hand nebulizer

…Home Management After 1 hour Good response Incomplete response Poor response

Good Response (Mild Episode) PFE>80% predicted No wheezing or shortness of breath Response to β2 agonist sustained for 4 hours May continue β2 agonist every 3-4h for 24-48h For patients on inhaled corticosteroids, double dose for 7-10 days and contact clinician

Incomplete Response (Moderate Episode) PEF 50%-80% predicted Persistent wheezing and shortness of breath Add oral corticosteroid Continue β2 agonist Contact clinician urgently (this day)

Poor Response (Sever Episode) PEF<50% predicted Marked wheezing 8 shortness of breath Add oral corticosteroid Repeat β2 agonist immediately Call your doctor Proceed to emergency department

Office or Emergency Department Management A brief history of the events leading up to the exacerbation and the medications used both chronically and acutely to treat Physical examination: RR, PR, Pluse oximetry, use of accessory muscle, air flow, wheezing, (1÷E), verbalization, puls paradoxus. Studies: PEF, FEV1, ABG Routine CXRnot nessary unless complication (e.g., pneumothorax, pneumomediastinum, aspiration)

Respiratory arrest imminent Intubate and mechanically ventilate with 100% O2. Nebulized β2 agonist and anticholinergic IV corticosteroid. Admit to ICU Continuous monitoring Intensive asthma management

… Respiratory arrest imminent Improved Admit to hospital ward O2 to maintain good saturation Nebulized β2 agnoist +/- anticholinergic PO or IV corticoesteroid Monitor vital signs, O2 saturation, FEV1 or PEF

… Respiratory arrest imminent Improved Discharge to home Continue home treatment with inhaled β2 agonist Consider need for oral corticosteroids or controller medication Educate patient in medication use and action plans Arrange follow-up

Emergency department management Give nebulized albuterol with o2 at 6 liters flow, 2.5mg per dose q 20min. O2 to achieve saturation>90% Give corticosteroid po or IV if FEV1 or PEF<50% Or If the patient was recently receiving corticosteroids If the patient in historically a high risk patient

Reassess Physical examination: RR, HR, Pulse oximetry, use of accessory muscles, airflow, wheezing, (1÷E) verbalization, pulsus paradoxus Studies; PEF, FEV1 Mild exacerbation Moderate exacerbation Sever exacerbation

Mild Exacerbation FEV1 or PEF>80% Good response Maintained without repeated treatments during ER PE: Normal Discharge to home Continue home treatment with inhaled β2 agonist Consider need for oral corticosteroids or controller medication E ducat patient in medication use and action plus Arrange follow up

Moderate Exacerbation FEV1 or PEF>50% but <80% In complete response to treatment PE: RR, Wheezing present, mild to moderate accessory muscle use, O2 satiration 91-95% 1:E<1:2 PP=10-25mmHg

… Moderate Exacerbation Admit to Hospital Ward 02 up to 02 sat >95% Nebulized β2 agonist +/- anticholinergic Po or IV corticosteroid Monitor vital signs, 02 saturation, FEV1 or PEF

… Moderate Exacerbation Improved Discharge to home Continue home treatment with inhaled β2 agonist Consider need for oral corticosteroid or controller medication Educate patient in medications and action plan Arrange follow up

Sever Exacerbatis FEV1 or PEF<50% Poor response to treatment PE: RR, Wheezing present, poor airflow Moderate-sever accessory muscle use, 02 sat<91% PP>25mmHg Admit to ICU Continuous monitoring Intensive asthma management

… Sever Exacerbatis Improved Admit to hospital ward O2 to maintain good saturation Nebulized β2 agnoist +/- anticholinergic PO or IV corticoesteroid Monitor vital signs, O2 saturation, FEV1 or PEF

… Sever Exacerbatis Improved Discharge to home Continue home treatment with inhaled β2 agonist Consider need for oral corticosteroids or controller medication Educate patient in medication use and action plans Arrange follow-up

Short-acting 2 agonist Therapy of EIA Useful prophylactic approaches Class Drug Dose inhaled Time delay Duration Long- acting 2 agonist Salmeterol 1 inhalation DPI 20 min 8-10 hr Short-acting 2 agonist Albuterol 2 puffs MDI 15 min 3-4 hr Antileukotriene Montelukast 10 mg orally 30 min 8-10 hr Mast cell stabilizers Cromolyn 1.5-2 hr Duration of protection may decrease with regularly scheduled use