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DIAGNOSIS AND TREATMENT OF ASTHMA IN CHILDHOOD: A PRACTALL CONSENSUS REPORT L. B. Bacharier, A. Boner, K.-H. Carlsen, P. A. Eigenmann, T. Frischer, M. Gçtz, P. J. Helms, J. Hunt, A. Liu, N. Papadopoulos, T. Platts-Mills, P. Pohunek, F. E. R. Simons, E. Valovirta, U. Wahn, J. Wildhaber – The European Pediatric Asthma Group Allergy 2008; 63: 5 The PRACTALL consensus report describes asthma in children as “repeated attacks of airway obstruction and intermittent symptoms of increased airway responsiveness to triggering factors, such as exercise, allergen exposure and viral infections”. DIAGNOSIS AND TREATMENT OF ASTHMA IN CHILDHOOD: A PRACTALL CONSENSUS REPORT L. B. Bacharier, A. Boner, K.-H. Carlsen, P. A. Eigenmann, T. Frischer, M. Gçtz, P. J. Helms, J. Hunt, A. Liu, N. Papadopoulos, T. Platts-Mills, P. Pohunek, F. E. R. Simons, E. Valovirta, U. Wahn, J. Wildhaber – The This European Pediatric Asthma Group more Allergydifficult 2008; 63: 5 definition becomes to apply confidently in infants and children of preschool age who present The PRACTALL consensus report describes asthma in with recurrent episodes of coughing children as “repeated attacks of airway obstruction and/or wheezing. and intermittent symptoms of increased airway responsiveness to triggering factors, such as exercise, allergen exposure and viral infections”. PRACTALL CONSENSUS REPORT: INCIDENCE AND PREVALENCE OF PEDIATRIC ASTHMA Incidence of pediatric wheezing 18 16 – Incidence (in %) 14 - 12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 Age (years) 9 10 11 12 13 PRACTALL CONSENSUS REPORT: INCIDENCE AND PREVALENCE OF PEDIATRIC ASTHMA Incidence of pediatric wheezing 18 16 – According to prospective birth cohort studies, up to 50% of all infants and children younger than 3 years will have at least 1 episode of wheezing. However, 60% of children with infantile wheeze will be healthy at school age. Incidence (in %) 14 - 12 10 8 6 4 2 0 1 2 3 4 5 6 7 8 Age (years) 9 10 11 12 13 PRACTALL CONSENSUS REPORT: INCIDENCE AND PREVALENCE OF PEDIATRIC ASTHMA * * * * * * * * * * * * * * * * * * * * * * * * * * * * A COMMUNITY-BASED STUDY OF EPIDEMIOLOGY OF ASTHMA Yunginger ARRD 1992, 146: 888 % females 4000 – males 3000 – From Jan 1, 1964 through Dec 31, 1983 Population-based computer-linked medical diagnosis 2000 – 1000 – 0 yrs <1 1-4 5-9 10-14 15-29 30-49 >50 A COMMUNITY-BASED STUDY OF EPIDEMIOLOGY OF ASTHMA Yunginger ARRD 1992, 146: 888 % females 4000 – males From Jan 1, 1964 Asthma shows its peak of incidence through Dec 31, 1983 in the first 1-4years of life Population-based and 80% of asthmacomputer-linked has its onset medical diagnosis before the age of 4 years. 3000 – 2000 – 1000 – 0 yrs <1 1-4 5-9 10-14 15-29 30-49 >50 PRACTALL CONSENSUS REPORT: WHEEZING PATTERNS Hypothetical peak prevalence for 3 different wheezing phenotypes PRACTALL CONSENSUS REPORT: WHEEZING PATTERNS 1.Transient (early) wheezing 2.Nonatopic wheezing 3.Persistent asthma 4.Severe intermittent wheezing PRACTALL CONSENSUS REPORT: ASTHMA PHENOTYPES No PRACTALL CONSENSUS REPORT: AGE AND ASTHMA PHENOTYPES Preschool children (ages 3 to 5 years) Virus-induced asthma > allergen-induced asthma > exercise induced asthma School children (ages 6 to 12 years) Allergen-induced asthma > virus-induced asthma > exercise induced asthma Adolescents (older than 12 years) Allergen-induced asthma > virus-induced asthma > exercise induced asthma PRACTALL CONSENSUS REPORT: ASTHMA PHENOTYPES 1) According to the PRACTALL consensus report, age and triggers can be used to define different phenotypes of disease. 2) These phenotypes are likely to be useful because they recognize the heterogeneity of childhood asthma. 3) Asthma phenotypes do not represent separate diseases, but are part of the “asthma syndrome”. PRACTALL CONSENSUS REPORT: ASTHMA PHENOTYPES Allergen-induced asthma 1) Allergen-induced asthma is more common in school-age children than in children of preschool age. 2) If a clinically relevant association between exposure and symptom occurrence is suspected, allergen-induced asthma is the likely diagnosis. 3) The risk of acquiring atopy and allergic asthma continues during adolescence. PRACTALL CONSENSUS REPORT: ASTHMA PHENOTYPES 1) 2) 3) 4) Exercise-induced asthma Exercise-induced asthma can be a unique phenotype in children aged 3 to 5 years. It may be the primary clinical manifestation in patients with mild intermittent disease (ie, isolated exercise-induced asthma). Patients with isolated exercise-induced asthma are free of symptoms for extended periods in the absence of triggers. Asthma symptoms in isolated EIA are frequently reported in association with viral infections of the upper respiratory tract, though. PREVALENCE OF EXERCISE-INDUCED ASTHMA IN CHILDREN In the general population is between 6% and 13%. Among adolescent athletes EIA estimates reach 12%. EIA is found in up to 90% of asthmatics and in up to 40% of patients with allergic rhinitis. EIA is usually more prevalent in children than in adults, most likely because children are physically more active. PREVALENCE OF EXERCISE-INDUCED ASTHMA IN CHILDREN In the general population is between 6% and 13%. Among adolescent athletes EIA estimates reach 12%. It is very likely that EIA go EIA is found inmay up tofrequently 90% of asthmatics and in undiagnosed. up to 40% of patients with allergic rhinitis. EIA is usually more prevalent in children than in adults, most likely because children are physically more active. DETERMINANTS OF AND RISK FACTORS FOR EXERCISE-INDUCED ASTHMA 1) It is estimated that 91% of individuals with EIA have a history of asthma or allergy, making it the premier risk factor for EIA. 2) A child’s response to exercise may change markedly from day to day. 3) Response depends on the mode of exercise (eg, treadmill running, biking on ergometer, swimming), environmental conditions, and the child’s airway responsiveness that in turn may be affected by viral infections, exposure to allergens, and the current use of medications. DETERMINANTS OF AND RISK FACTORS FOR EXERCISE-INDUCED ASTHMA 4) The severity of bronchospasm in EIA is believed to be related to the level of ventilation, to heat and water loss from the respiratory tree, and the rate of airway rewarming and rehydration after exercise. 5) Reduction of the temperature and humidity of the inspired air enhances bronchoconstriction caused by isocapnic hyperventilation. PRACTALL CONSENSUS REPORT: ASTHMA PHENOTYPES Virus-induced asthma 1) Viral infections are the most common trigger of wheezing in preschool children and are still very frequent among school-age children. 2) If symptoms are usually preceded by a cold, are transient and disappear completely between episodes, virus-induced asthma is the most likely diagnosis according to the consensus report. PRACTALL CONSENSUS REPORT: PATHOPHYSIOLOGY Interactions between airway tissue damage in early life caused by viral infections and inhalant allergens in asthma etiology. PRACTALL CONSENSUS REPORT: PATHOPHYSIOLOGY Interactions between airway tissue damage in early life caused by viral infections and inhalant allergens in asthma etiology. Low TH1 competence during infancy is associated with increased risk for respiratory infection and respiratory allergy. PRACTALL CONSENSUS REPORT: DIAGNOSIS 1.Asthma should be suspected in any infant with recurrent wheezing and coughing episodes. 2.Diagnosis is often only possible through long-term follow-up, observations of the child´s response to bronchodilator and/or anti-inflammatory treatment and consideration of the extensive differential diagnoses. TO DIAGNOSE ASTHMA IN INFANTS THINK OF THE “3R” Reactivity Reversibility Recurrence There should be an identifiable trigger usually a viral infection Airways obstruction is reversible with bronchodilators Usually more than 3 episodes Finder Curr. Probl. Pediatr. 1999; 29: 65 PRACTALL CONSENSUS REPORT: CASE HISTORY In all children, ask about: Wheezing and/or coughing. Specific triggers, such as exposure to passive smoke or cold air, pets, humidity, mold and dampness, respiratory infections, exercise/activity, coughing after laughing or crying. Altered sleep patterns (ie, awakening, night cough, sleep apnea). Number of exacerbations in the past year. Nasal symptoms, including runny nose, itching, sneezing, and blocking. PRACTALL CONSENSUS REPORT: CASE HISTORY In infants (younger than 2 yrs), ask about: Noisy breathing or vomiting associated with cough. Retractions of the chest. Difficulty with feeding (eg, grunting sounds, poor sucking. Changes in respiratory rate. PRACTALL CONSENSUS REPORT: CASE HISTORY In children (older than 2 yrs), ask about: Shortness of breath (day or night). Fatigue (eg, decrease in play activity compared with peers, increased irritability. Avoidance of other activities, such as sleep out or visit to friends with pets. Complaints about not feeling well. Poor school performance or school absences. Reduced frequency or intensity of physical activity (eg, in sports or gym classes). Specific triggers (eg, sports, exercise/activity.) PRACTALL CONSENSUS REPORT: CASE HISTORY In children (older than 2 yrs), ask about: Shortness of breath (day or night). Fatigue (eg, decrease in play activity compared with peers, increased irritability. Avoidance of other activities, such as sleep out or visit to should also be asked if friendsAdolescents with pets. they well. smoke. Complaints about not feeling Poor school performance or school absences. Reduced frequency or intensity of physical activity (eg, in sports or gym classes). Specific triggers (eg, sports, exercise/activity.) PHYSICAL EXAMINATION Listening to forced expiration and a nasal examination Key .. clinical signs suggesting an atopic phenotype include: atopic eczema or dermatitis dry skin dark rings under the eyes (allergic shiners) irritated conjunctivae persistent edema of the nasal mucosa, nasal discharge, allergic salut and allergic crease on the bridge of the nose. ASSESSING LUNG FUNCTION FEV1 FEV1/FVC FEF25-75 ASSESSING LUNG FUNCTION FEV1 An increase in (FEV1) of FEV1/FVC >12%suggests a significant bronchodilation. FEF25-75 OTHER TESTS a) Exercise testing b) Exhaled nitric oxide c) Eosinophil counting d) Measures of bronchial hyperresponsiveness e) Skin Prick Tests f) Serum specific IgE OTHER TESTS a) Exercise testing b) Exhaled nitric oxide In vitro testing for allergen-specific IgE doescounting not provide more accurate c) Eosinophil results than skin prick testing but d) Measures bronchial hyperresponsiveness may beof useful if skin prick testing cannot be performed. e) Skin Prick Tests f) Serum specific IgE DIFFERENTIAL DIAGNOSIS AND COMORBIDITIES Aspiration of a foreign body. Cystic fibrosis. Structural abnormalities. Aggravating factors, such as gastroesophageal reflux and rhinitis, must be excluded. PRACTALL CONSENSUS REPORT: PHARMACOLOGIC MANAGEMENT OF PEDIATRIC ASTHMA Goals of pharmacotherapy Control of symptoms. Prevention of exacerbations. To allow the child to maintain normal activities. Without producing possible adverse medication side effects. DEFINING AND EVALUATING ASTHMA CONTROL Asthma is well controlled when all of the following are achieved and maintained: Daytime symptoms twice or less per week No limitations of activities because of asthma. Night-time symptoms 0 to 1 per month (0-2 per month if child is 12 years or older). Reliever/rescue medication use is twice or less per week. Normal lung function (if able to measure). 0 to 1 exacerbations in the last year. RELIEVER MEDICATIONS The consensus report stresses that reliever medications are taken as needed for immediate relief of acute symptoms and before exercise to prevent exercise-induced bronchospasm. a) Short-acting ß-2 agonists b) Ipratropium bromide CONTROLLER MEDICATIONS: (Inhaled corticosteroids - Leukotriene receptor antagonists Long-acting beta-agonists) According to the consensus report, controller medications decrease the swelling and inflammation in the airways and may reduce mucous buildup. Medications for long-term control should be taken daily to help maintain control of asthma and prevent exacerbations. The main goal of regular controller therapy is to reduce bronchial inflammation. ALGORITHM OF PREVENTIVE PHARMACOLOGIC TREATMENT FOR ASTHMA IN CHILDREN >2 YEARS OF AGE (PRACTALL GUIDELINES) Bacharier Allergy 2008; 63: 5 ASTHMA TREATMENT IN CHILDREN AGED 0 TO 2 YEARS A diagnosis of asthma should be considered if more than 3 episodes of reversible bronchial obstruction have been documented within the previous 6 months. Intermittent Leukotriene ß2 agonists are the first choice. Receptor Antagonists (LTRAs) have been shown to reduce asthmatic episodes in children aged 2 to 5 years, and there is some evidence that they may be beneficial in children 2 years and younger. ASTHMA TREATMENT IN CHILDREN AGED 0 TO 2 YEARS A daily controller therapy with LTRAs for viral-induced asthma (long- or short-term treatment) should be considered. Nebulized or inhaled (metered-dose inhaler [MDI] and spacer) corticosteroids can be used as daily controller therapy for persistent asthma, especially if severe or requiring frequent oral corticosteroid therapy. ASTHMA TREATMENT IN CHILDREN AGED 0 TO 2 YEARS Evidence of atopy/allergy lowers the threshold for use of ICS and they may be used as first-line treatment in such cases. Use of oral corticosteroids (eg, 1-2 mg/kg prednisone) for 3 to 5 days during acute and frequently recurrent obstructive episodes is considered. MANAGEMENT OF ACUTE ASTHMA EPISODES Inhaled short-acting ß2 agonists (spacer): Two to four puffs (200 µg salbutamol equivalent) every 10 to 20 minutes for up to 1 hour. Children who have not improved should be referred to a hospital. Nebulized ß2 agonists: 2.5 to 5 mg salbutamol equivalent can be repeated every 20 to 30 minutes. Ipratropium bromide: This should be mixed with a nebulized ß2 agonist solution at 250 µg/dose and given every 20 to 30 minutes. MANAGEMENT OF ACUTE ASTHMA EPISODES High-flow O2 (if available) to ensure normal oxygenation. Oral and IV glucocorticosteroids are of similar efficacy. Steroid tablets are preferable to inhaled steroids. A dose of 1 or 2 mg/kg prednisone or prednisolone should be given; treatment for up to 3 days is usually sufficient. LISTS COMMON ALLERGENS AND POTENTIAL AVOIDANCE STRATEGIES Allergen Avoidance measure Comments Pets Remove pet and clean home, especially carpets and upholstered surfaces. Encourage schools to ban pets Allergen levels will typically take up to 6 months after removal of the pet from the household to fall enough to reduce asthmatic reactions. However, there is very little evidence that not having a pet will decrease the risk of sensitization. LISTS COMMON ALLERGENS AND POTENTIAL AVOIDANCE STRATEGIES Dust mites Avoidance measure Wash bedding and clothing in hot water every 1–2 weeks at >56°C. Freeze stuffed toys once per week. Encase mattress, pillows and quilts in impermeable covers. Use dehumidifying device and ventilate room regularly. LISTS COMMON ALLERGENS AND POTENTIAL AVOIDANCE STRATEGIES Cockroaches Avoidance measure Clean home. Use professional Encase mattress pest control. and pillows in impermeable covers. LISTS COMMON ALLERGENS AND POTENTIAL AVOIDANCE STRATEGIES Mold Avoidance measure Wash moldy surfaces with weak bleach solution. Use dehumidifying equipment. Fix leaks. Remove carpets. Use High Efficiency Particle Arrestor filtration. IMMUNOTHERAPY A.Subcutaneous immunotherapy has been shown to be effective in allergic asthma. B.Efficacy in young children younger than 5 years is less well documented for sublingual immunotherapy. C.Anti-IgE antibodies. Omalizumab licensed for children 12 years and older with severe, allergic asthma and proven IgE-mediated sensitivity to inhaled allergens is administered via subcutaneous injection every 2 to 4 weeks, depending on patient weight and total serum IgE level. NON-PHARMACOLOGICAL MANAGEMENT OF ALLERGEN-INDUCED ASTHM Prevention Primary prevention: Elimination of any risk or etiological factor before it causes sensitization. Secondary prevention: Diagnosis and therapy at the earliest point in disease development. Tertiary prevention: Limitation of disease effect NON-PHARMACOLOGICAL MANAGEMENT OF ALLERGEN-INDUCED ASTHM Avoidance of allergens Exposure Typical - to allergens leads to sensitization. avoidable allergens include: pets, dust mites, mold, cockroaches,and foods. NON-PHARMACOLOGICAL MANAGEMENT OF ALLERGEN-INDUCED ASTHMA Avoidance of triggers Avoidance of triggers should be part of the general strategy for asthma management. Key avoidable triggers are tobacco smoke, other irritants, and some allergens. Tobacco smoke should be eliminated from the environment of all children. Infections and stress should be avoided. Physical exercise, although a possible trigger itself, should be encouraged when appropriate. PHARMACOLOGIC MANAGEMENT OF ALLERGEN-INDUCED ASTHMA Controller Therapy: Inhaled corticosteroids A first-line treatment for persistent asthma. Should be introduced as initial maintenance treatment when asthma control is inadequate. Atopy and poor lung function can predict favorable response. If control is inadequate on low dose, identify reasons. If indicated, an increased ICS dose or additional therapy with LTRAs or LABAs should be considered. Effect in older children disappears as soon as treatment is discontinued. New evidence does not support a disease-modifying role after cessation of treatment in preschool children. PHARMACOLOGIC MANAGEMENT OF ALLERGEN-INDUCED ASTHMA Controller Therapy: Leukotriene receptor antagonists Alternative first-line treatment for persistent asthma. Evidence supports LTRA as initial controller therapy for mild asthma in children with allergic asthma. Younger age (younger than 10 years) and high levels of urinary leukotrienes can predict favorable response. Therapy for patients who cannot or will not use ICS. Useful also as add-on therapy to ICS: Different and complementary mechanisms of action. Suggested for viral-induced asthma in young children. Benefit shown in children as young as 6 months. May be particularly useful if the patient has concomitant rhinitis. PHARMACOLOGIC MANAGEMENT OF ALLERGEN-INDUCED ASTHMA Controller Add-on therapy: Long-acting ß-agonists to ICS for partially controlled/uncontrolled asthma. Efficacy not as well documented in children. Use should be restricted to add-on therapy to ICS, when indicated. Combination LABA/ICS therapies may be licensed for use in children older than 4 or 5 years. IMMUNOTHERAPY Combination of immunotherapy with other therapies allows a broad therapeutic approach that addresses the pathophysiologic mechanism of allergy. Early intervention with immunotherapy may prevent the progression from monosensitization to polysensitization. Subcutaneous immunotherapy has been shown to be effective in allergic asthma in some patients. Effective sublingual immunotherapy may be an attractive alternative to injection. Injection immunotherapy should only be performed in a proper environment. ANTI IGE ANTIBODIES Benefit-to-risk ratio of this relatively new agent is being defined. Licensed for children 12 years of age and older with severe, allergic asthma and proven IgE-mediated sensitivity to inhaled allergens PRACTALL CONSENSUS REPORT: EDUCATION Asthma education is an integral part of asthma management: Identification and avoidance of triggers. Understanding the uses of prescribed medications, and the importance of compliance and monitoring. Proper use of inhalation devices. PRACTALL CONSENSUS REPORT: MONITORING Physical examination should include regular assessment of the child´s height and weight, along with respiratory signs and symptoms. Lung function measurement. The nasal airway should also be assessed.