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ASTHMA IN CHILDREN: Diagnosis and Management Milagros S. Salvani-Bautista, MD Pediatric Pulmonologist OPERATIONAL DESCRIPTION: “ Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment” GINA: 2002,2006,2007 What Is Asthma ? What is known about Asthma? increasing PREVALENCE especially in children CHRONIC INFLAMMATORY DISORDER of the airways chronically inflamed airways are HYPERRESPONSIVE EPISODIC WHEEZING, BREATHLESSNESS, CHEST TIGHTNESS and COUGHING can be CONTROLLED PATTERNS OF RECURRENT WHEEZE IN PEDIATRIC PATIENTS 1. Transient wheezing 2. Non-atopic wheezing 3. Persistent asthma Tucson Children’s Respiratory Study JACI 2003; 111: 661-675 4. Severe, intermittent wheezing Bacharier. JACI 2007; 119: 604-610 PRESENTING FEATURES Wheeze Dry cough Breathlessness Noisy breathing DETAILED HISTORY AND PE Pattern of illness Severity/control Differential clues IS IT ASTHMA? Probably INVESTIGATE OR SEEK Causal factors Exacerbating factors Complications Comorbidity No Follow relevant course of action Seek specialist assistance Possibly DIFFERENTIAL DIAGNOSTIC TESTS &/or TRIALS OF ASTHMA THERAPY Asthma likely ASTHMA ACTION PLAN Poor response Good response Asthma unlikely DIAGNOSIS OF ASTHMA IN CHILDREN CLASSIFICATION OF ASTHMA SEVERITY GINA 2002 Intermittent Symptoms less than once a week Brief exacerbations Mild Persistent Symptoms more than once a week but less than once a day Exacerbations may affect activity and sleep Nocturnal symptoms not more than 2x/mo. Nocturnal symptoms more than 2x/mo. • FEV1 or PEF ≥ 80% predicted • FEV1 or PEF ≥ 80% predicted • PEF or FEV1 variability < 20% • PEF or FEV1 variability < 20 – 30% Moderate Persistent Symptoms daily Exacerbations may affect activity & sleep Nocturnal symptoms more than once a wk. Daily use of inhaled short-acting 2-agonist • FEV1 or PEF 60-80% predicted • PEF or FEV1 variability > 30% Severe Persistent Symptoms daily Frequent exacerbations Frequent nocturnal asthma symptoms Limitation of physical activities • FEV1 or PEF ≤ 60% predicted • PEF or FEV1 variability > 30% Level of Asthma Control Characteristic Controlled (All of the ff) Partly Controlled (Any measure present in any week) Daytime symptoms None (2x or </wk.) More than 2x/wk Limitations of activities None Any Nocturnal symptoms/ awakening None Any Need for reliever/rescue tx None (2x or less/week) More than 2x/ wk Lung function (PEF or FEV1)+ Normal <80% predicted or personal best (if known) Exacerbations None One or more/ yr* * Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate. + By definition, an exacerbation in any week makes that an uncontrolled asthma week. ╪ Lung function testing is not reliable for children 5 years and younger. Uncontrolled Three or more features of partly controlled asthma present in any week One in any wk╪ GINA 2006 ASTHMA MANAGEMENT: COMPONENTS OF THERAPY Assess and monitor asthma severity and asthma control Education for a partnership in care Control of environmental factors and co-morbid conditions that affect asthma Medications GINA ASTHMA GUIDELINES 2002, 2006, 2007 Medicines in Childhood Asthma Relievers Rapid-acting inhaled Beta (B)2 agonist Inhaled anticholinergics Short acting theophylline Short acting B2 agonist (SABA) Controllers Inhaled and systemic corticosteroids Leukotriene modifiers Long-acting B2 agonist (LABA) with Inhaled Corticosteroid ICS Sustained release theophyllines Cromones ACUTE ASTHMA EXACERBATION GINA 2002, 2006, 2007 Severity of Asthma Exacerbations….. MILD BreathlessWalking Talking Can lie flat MODERATE SEVERE At rest Infants – softer shorter cry Prefers sitting Infants- Stops feeding *Hunched forward Talks in Sentences Phrases Alertness May be agitated Usually agitated Usually agitated Respiratory Rate Increased Increased *Often >30/min RESPIRATORY ARREST IMMINENT Words GUIDE TO RATES OF BREATHING ASSOCIATED WITH RESPIRATORY DISTRESS IN AWAKE CHILDREN AGE NORMAL RATE > 2 months < 60/min 2-12 months < 50/min 1-5 years < 40/min 6-8 years < 30/min Bradypnea GINA 2002, 2006, 2007 Severity of Asthma Exacerbations….. MILD Accessory Muscles & Suprasternal Retraction Wheeze Pulses/min None Audible with stethoscope <100 MODERATE SEVERE Present Present Audible with stethoscope 100-120 RESPIRATORY ARREST IMMINENT Present Thoraco-abdominal Movement Audible w/o stethoscope >120 Absence of wheeze with decreased to absent breathe sounds Bradycardia GUIDE TO LIMITS OF NORMAL PULSE RATE IN CHILDREN Age Normal Limits Infants 2-12 months <160/min Preschool 1-2 years <120/min School Age 2-6 years <110/min GINA 2002,2006,2007 Severity of Asthma Exacerbations MILD MODERATE SEVERE May be present 10—20mm Hg Often present 20-40mm Hg Pulses Paradoxus Absent <10mm Hg PEF %predicted Or %personal best 80% 60-79% PaO2 RA Normal test NOT usually necessary 60mm Hg <60mmHg Possible Cyanosis PaCO2 45 mm Hg 45 mm Hg >45 mm Hg possible respiratory failure SaO2 RA 95% 90-94% <60% <90% Hypercapnea (hypoventilation) develops more rapidly in young children RESPIRATORY ARREST IMMINENT Absence suggests respiratory muscle fatigue GINA ASTHMA GUIDELINES: (2002, 2006,2007) Management of Asthma Exacerbation in Acute Care S1 Initial Assessment History, Physical Examination(auscultation, use of accessory muscles, HR, RR, PEF or FEV1, O2 saturation, ABG’s if patient in extremis) Initial Treatment Oxygen to achieve O2 saturation ≥90% (95% in children) Inhaled rapid β2-agonist continuously for one hour Systemic GCS, if no immediate response, or if patient recently took Oral GCS, of if episode is severe SEDATION is CONTRAINDICATED in the treatment of an exacerbation Reassess after 1 hour : PE, PEF, O2 saturation & other tests as needed Criteria for MODERATE Episode: • PEF 60-80% predicted/personal best • Physical exam: moderate symptoms, • Accessory muscle use Treatment: O2, Inhaled β2 agonist + anticholinergic every 60 min Oral GCS Continue treatment for 1-3 hours,provided There is improvement Criteria for SEVERE Episode: • History of risk factors for near fatal asthma • PEF < 60% predicted/personal best • PE: severe symptoms at rest, chest retraction NO improvement after initial treatment Treatment: O2, Inhaled β2 agonist + anticholinergic Systemic GCS IV Magnesium Continuation next slide GINA ASTHMA GUIDELINES: (2002, 2006,2007) Cont. (S2) Management of Asthma Exacerbation in Acute Care Reassess after 1 – 2 hours Good Response within 1-2 hours: Response sustained 60 minutes after last treatment PE normal: no distress PEF > 70% O2 saturation > 90% (95% in children) Incomplete Response within 1-2 hours: Risk Factors for near fatal asthma PE : mild to moderate signs PEF < 60% O2 saturation: NOT IMPROVING ADMIT to ACUTE CARE Setting • Oxygen • Inhaled β2-agonist ± anticholinergic • Systemic GCS • Intravenous Magnesium •Monitor PEF, O2 saturation, Pulse Improved: Criteria for Discharging Home PEF > 60% predicted / personal best Sustained on oral/inhaled medications HOME TREATMENT: • Continue inhaled β2 agonist •Consider in most cases, oral GCS •Consider adding a combination inhaler •Patient education: take medicine correctly review action plan close medical check up Poor Response within 1-2 hours: Risk factors fro near fatal asthma PE : symptoms severe, drowsiness, confusion PEF : < 30% PCO2 : > 45mmHg PO2: < 60mmHg ADMIT to INTENSIVE Care • Oxygen • Inhaled β2agonist+anticholinergic • IV GCS •Consider IV β2 agonist • Consider IV theophylline • Possible intubation • mechanical ventilation Reassess at Intervals Improved Poor Response: • Admit to intensive Care Incomplete response in 6-12 hours • Consider admission to Intensive Care •If No improvement within hours Inhaled β2-agonists are the mainstay of therapy in acute asthma. However, once response to the initial β2-agonists is minimal, incomplete or poor … COMBINATION of INHALED β2-AGONIST and INHALED ANTICHOLINERGIC is RECOMMENDED GINA ASTHMA GUIDELINES: 2002 Recommended Medications by Level of Severity: Children All Steps: In addition to daily controller therapy, rapid-acting inhaled β2 agonist* should be taken as needed to relieve symptoms, but should not be taken more than 3 to 4 times a day. PERSISTENT INTERMITTENT MILD Daily Controller • None Medications necessary Other Treatment Options MODERATE SEVERE • IGCS 100-400mcg BUD IGCS 400-800µg BUD • IGCS >800µg BUD PLUS one or more of the following: • Sustainedrelease Theophylline, •IGCS< 800µg BUD PLUS Sustained released theophylline OR • Sustainedrelease theophylline OR • Cromone, OR • Leukotriene modifier • IGCS <800µg BUD •PLUS LABA OR • IGCS >800µg OR •IGCS <800mcg PLUS • Leukotriene modifier • Long Acting Inhaled β-2 agonist • Leukotriene modifier • Oral glucocortico steroid In all steps: Once control of asthma is achieved and maintained for at least 3months, a gradual reduction of the maintenance therapy should be tried in order to identify the minimum therapy required to maintain control REDUCE LEVEL OF CONTROL TREATMENT OF ACTION maintain and find lowest controlling step partly controlled consider stepping up to gain control INCREASE controlled uncontrolled exacerbation step up until controlled treat as exacerbation GINA Guidelines 2006 REDUCE TREATMENT STEPS INCREASE STEP STEP STEP STEP STEP 1 2 3 4 5 GINA 2006 Asthma Medications As needed: RELIEVER BRONCHODILATORS Short acting β2-Agonists Anticholinergics (inhaled) Short acting Theophyllines Daily: CONTROLLER ANTI-INFLAMMATORY Corticosteroids (inhaled and systemic) Leukotriene modifier Long acting β2 agonists Sustained release theophyllines GINA 2006 Inhaled Corticosteroids Most effective long-term control for persistent asthma Small risk for adverse events at recommended dosage Benefits of daily use Reduction of asthma symptoms frequency of exacerbations airway inflammation airway responsiveness asthma mortality Improvement of lung function quality of life Estimated Equipotent Doses of Inhaled Glucocorticosteroids for Children Drug Low Daily Dose (µg) Medium Daily Dose (µg) High Daily Dose (µg) Beclomethasone dipropionate 100-200 >200-400 >400 Budesonide* 100-200 >200-400 >400 Budesonide-Neb Inhalation Susp. 250-500 >500-1000 >1000 80-160 >160-320 >320 Flunisolide 500-750 >750-1250 >1250 Fluticasone 100-200 >200-500 >500 Mometasone furoate* 100-200 >200-400 >400 Triamcinolone acetonide 400-800 >800-1200 >1200 Ciclesonide* GINA 2006 COMPARISON OF PHARMACOKINETICS & PHARMACODYNAMIC PARAMETERS OF ICS PARAMETERS BDP/BMP BUD FP LIPOPHILICITY Mod/high Low High PROTEIN BINDING:FREE FRACTION T1/2, hr 87:13 88:12 90:10 0.5/2.7 2.8 7.8 Vd, Li 20/424 183 318 Clearance, L/h 15/120 84 69 TECHNIQUES FOR BALANCING SAFETY AND EFFICACY OF ICS Selection and use of ICS 1. Select safest ICS drug 2. Use minimum effective dose 3. Dose in AM when once daily dosing 4. If control is poor, add another controller rather than double dose of ICS 5. To maximize ICS delivery to lung, consider: 6. CFC vs HFA propellant formulation pMDI vs DPI formulation Use of spacer device Patient technique Rinse mouth of ICS and discard TECHNIQUES FOR BALANCING SAFETY AND EFFICACY OF ICS Use of ICS – sparing strategies Reduce allergens and smoke Inoculate with influenza vaccine Diagnose and treat rhinosinusitis or GERD Use add-on therapies Monitor growth at all ICS doses Monitor eyes and bone mineral density when using > 1600 ug/day ICS Consider first line alternatives to ICS for mild persistent asthma SYSTEMIC SIDE EFFECTS OF ICS THERAPY IN CHILDREN EVIDENCE GRADE EFFECT ON CONCLUSION A, B, C GROWTH Potential to decrease growth velocity. Effects are small, non-progressive, reversible A BONE MINERAL DENSITY No serious adverse effects A, C CATARACTS GLAUCOMA No significant effects on incidence of subcapsular cataracts or glaucoma A, C HPA AXIS FUNCTION Rare individuals may be susceptible to ICS effects on HPA axis even on conventional doses LEUKOTRIENE MODIFIERS Mechanisms 5-LO inhibitors (zileuton) CysLT 1 receptor antagonists (montelukast, pranlukast, zafirlukast) Indications • • • • Alternative treatment in mild persistent asthma Aspirin-sensitive asthma Add-on therapy, but less effective than LABA Concomitant asthma with allergic rhinitis LEUKOTRIENE MODIFIERS CHILDREN OLDER THAN 5 YRS. Clinical benefit at all levels of severity, but, generally less that that of low-dose ICS Partial protection against EIA As add-on treatment CHILDREN 5 YRS. AND YOUNGER In addition to above, it reduces viral- induced asthma exacerbation in children 2-5 yrs with a history of intermittent asthma. GINA 2006 LONG-ACTING INHALED B2-AGONISTS Monotherapy should be avoided Most effective when combined with ICS, preferably in a fixed combination inhaler May be used to prevent exercise-induced bronchospasm Regular use of rapid acting B2-agonists, in both short and long acting forms, may lead to relative refractoriness to B2-agonists THEOPHYLLINES Effective as monotherapy and as add-on treatment to ICS or oral steroids, but efficacy is less than that of low-dose ICS Anti-inflammatory function noted at low dose of less than 10 mkd As add-on therapy, theophylline is less effective than LABA Side effects: GI, arrhythmias, seizures, drug interactions CROMONES: Na CROMOGLYCATE AND NEDOCROMIL Na Limited role in long term treatment of asthma in children Can attenuate bronchospasm induced by exercise or cold air Side effect: Uncommon, cough and sore throat ANTI-IgE TREATMENT (Omalizumab) Addition to other controller medications has been shown to improve control of allergic asthma (Evidence A) Manage Exacerbations Do not underestimate the severity of an attack Patient should seek medical help if: The attack is severe The response to the initial bronchodilator treatment is not prompt There is no improvement within 2-6 hours There is further deterioration Manage Exacerbations Asthma Attack requires prompt treatment: Inhaled rapid acting B2-agonists Oral glucocorticosteroids Oxygen (to achieve SaO2 of 95%) Combination B2-agonist/anticholinergic therapy Therapies not recommended: Sedatives Mucolytics Chest physical therapy Manage Exacerbations Do not underestimate the severity of an attack Patient should seek medical help if: The attack is severe The response to the initial bronchodilator treatment is not prompt There is no improvement within 2-6 hours There is further deterioration Bronchodilators : Mechanism of Action RELIEVER MEDICATIONS RAPID ACTING INHALED B2-AGONISTS Most effective bronchodilator Preferred treatment for acute asthma Inhaled route is preferred Protection against exercise-induced bronchoconstriction Oral therapy is rarely needed and reserved for young children who cannot use inhaled therapy RELIEVER MEDICATIONS ANTICHOLINERGICS Inhaled anticholinergics are not recommended for long term management of asthma inchildren Comparative Pharmacokinetics of Nebulized Salbutamol and Ipratropium Parameters Onset of bronchodilation Peak effect Duration of effect Salbutamol Ipratropium within 5 mins. within 15-30 minutes 1-2 hours 1-2 hours 3-4 hours 5-7 hours http://www.medscape.com/druginfo/monograph REFERRAL to an Asthma Specialist (NAEP EPR 3 Report) Difficulties achieving or maintaining control of asthma Patient required > 2 bursts of oral steroids in 1 year or has an exacerbation requiring hospitalization Step 4 care or higher is required (Step 3 care or higher for 0-4 years) If immunotherapy or omalizumab is considered or if additional testing is indicated SUMMARY Asthma is a serious chronic inflammatory disease of the airways Controller medication – primarily inhaled corticosteroids – is the cornerstone of asthma management Essential components of successful asthma management include Pharmacotherapy Allergen avoidance Patient education Use of a standardized diagnostic questionnaire, use of an asthma control test SUMMARY • ALLERGEN AVOIDANCE is recommended when there is sensitization and a clear association between allergen exposure and symptoms. • ALLERGY TESTING (at all ages) to confirm the possible contribution of allergens to asthma exacerbation • EXERCISE SHOULD NOT BE AVOIDED: Asthmatic children should be encouraged to participate in sports, with efficient control of asthma inflammation and symptoms. 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