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Childhood Asthma 上海交通大学医学院附属新华医院 鲍一笑 邓丽君 邓丽君 1953-1995(42岁) Died in Thailand due to acute asthma exacerbation 贝多芬 1770-1827(57岁) Died in Vienna because there is no effective treatment for asthma Introduction Definition Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements plays 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. Asthma is an inflammation indduced by allergy Allergy Infection Eosinophils cell infiltrate Neutrophils cell infiltrate Red swelling, hot and pain Corticosteroids as anti-inflammatory therapy Antibiotics therapy The Role of Th2 Cytokines in Allergic Cascade The balance of Th1 and Th2 Epidemiology Prevalence↑ Death rates↑ (per 10,0000 population) China worldwide Shanghai 90:1.79% 00:4.52% 0.5-3.3% 36.7 0.1-32% 1.3 Europe and north America10% Asia 5% The prevalence of asthma has been increasing since the early 1980s for all age, sex, and racial groups. The death rate1979-2000 The current asthma prevalence 2003 in USA Etiology Genetic Factor Epidemiology In asthma children, 30-40% have a family history of asthma, 50-60% have a family history of allergic disease. • Atopy is the strongest identifiable predisposing factor. An elevated IgE level is often found in the serum of allergic patients, because IgE is the primary antibody associated with allergic reactions. Related gene of Asthma More than 22 loci on 15 autosomal chromosomes have been linked to asthma. Gene associated with IgE Genetic variation in receptors for different asthma medications (polymorphisms in the β2-adrenergic receptor). Environmental Factor Respiratory Tract Infections(viral, bacterial, mycoplasma) Inhalant Allergen Others About 40% of infants and young children who have wheezing with viral infections in the first few years of life will have continuing asthma through childhood. Inhalant Allergens Animal dander Environmental tobacco smoke Indoor allergens Air pollutants Dust mites Cold air, dry air Cockroaches Exercise Molds Strong or noxious odors or fumes Pollens (trees, grasses, weeds) Crying, laughter, hyperventilation Sensitization to inhalant allergens increases over time and is found in the majority of children with asthma. Pollen Mite House Pet Smoke Exposure to tobacco smoke, especially from the mother, is also a risk factor for asthma. Food Allergen Animal Protein Fishery,product,milk,meat,egg Oil Crop and Nuts Peanuts Fruit and Greengrocery Grain Food additive Drug Allergen Benzylpenicillin Sulfonamides Antipyretic analgesic Anesthetic agent Biological products Aspirin sensitivity is uncommon in children. Contactant allergen • Para-phenylenediamine • Nickel sulphate • Mercurial • Plastics products • Rubber goods • Essence Pathogenesis Genetic factors Immunity factors Psychological factors Endocrine factors Allergic inflammation allergen Excise、Wether Harmful gas DC、MC、B cell IL-4 Th2 IgE B cell Mast cell ECF IL-5 histamine,LT,PG,PAF Eos PAF,LT,MBP,ECP LAR EAR Airwayinflammation,Hyperresponsiveness,Airway contraction, bronchoconstriction, airway wall edema, mucus plug formation Airway remodeling Wheezing, Cough, Dyspnea, Allergic inflammation Pathologic features Shedding of airway epithelium Edema Mucus plug formation Mast cell activation Collagen deposition beneath the basement membrane Pathologic features Bronchospasm mucosal edema mucus plug formation Changes of Airway Epithelium shedding of airway epithelium Normal Asthma Specimen of Bronchial Mucosa A • • In the subject without asthma, the epithelium is intact; there is no thickening of the subbasement membrane, and there is no cellular infiltrate. B In the patient with mild asthma, there is evidence of goblet-cell hyperplasia in the epithelial-cell lining. The sub-basement membrane is thickened, with collagen deposition in the submucosal area, and there is a cellular infiltrate. Clinical Manifestation Symptoms Precursory symptoms: Rhinocnesmus Sneezing Nasal obstruction Nasal discharge Itching of eye Dry cough Symptoms Wheezing is the most characteristic sign of asthma. Patients may also have cough and shortness of breath. Physical signs General signs: Cyanosis, Agitation and lethargy Chest auscultation: Prolongation of the expiratory phase and wheezing. As the obstruction becomes more severe, wheezes become more high pitched and breath sounds diminished. Chest Radiograph: Bilateral hyperinflation Others: Tachycardia and pulsus paradoxus severe obstruction: Flaring of nostrils, intercostal and suprasternal retractions, and use of accessory muscles of respiration Laboratory Examination Clumps of eosinophils on sputum smear and blood Chest radiograph: Bilateral hyperinflation Immunologic test (1) Allergen skin testing (2) Elevated total serum IgE levels (3) Abnormality of cytokines (IL-3、IL-4、IL-5) Pulmonary Function Test Lung Function Abnormalities in Asthma Spirometry (in clinic) Airflow limitation Low FEV1 (relative to percentage of predicted norms) FEV1/FVC ratio <0.80 Bronchodilator response (to inhaled β-agonist) Improvement in FEV1 ≥12% or ≥200 mL Exercise challenge Worsening in FEV1 ≥15% Daily peak flow or FEV 1 monitoring: Day to day and/or AM-to-PM variation ≥20% FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity. Diagnosis Diagnostic Criteria of Childhood Asthma Children older than 3 years, reccurent wheezing Prolongation of the expiratory phase and expiratory wheezing Improved after the use of inhaled bronchodilators Exclusion of other diseases which can also cause wheezing, dyspnea, and cough Diagnostic Criteria of Infant’s Asthma 1. Children younger than 3 years, more than three episodes of wheezing (2 score ) 2. Acute asthma exacerbation (1 score ) 3. Prolongation of the expiratory phase and wheezing can be heard on chest auscultation. (2 score ) 4. Allergic disease, such as allergic rhinitis and atopic dermatitis. (1 score ) 5. A family history of allergic disease (1 score ) ≥5 score to diagnose asthma。 ≤4 score or just two episodes of wheezing, to diagnose suspicious asthma or asthmatic bronchitis Wheezing decrease or disappear after use bronchodilators 2 score Classification of Asthma Severity symptoms Nighttime symptoms Lung function FEV1/PEF % predicted PEF variability Step1 Mild intermittent ≤2 times a week ≤2 times a month ≥80% <20% Step2 Mild persistent >2 times a week >2 times a month ≥80% 20%-30% Step3 Moderate persistent Daily symptoms >1 times a week 60%-80% >30% Step4 Severe persistent Continual symptoms Limited physical activity Frequent ≤60% >30% The presence of one of the features of severity is sufficient to place a patient in the category. An individual should be assigned to the most severe grade in which any features occurs. Differential diagnosis Viral bronchiolitis Foreign body Congenital laryngeal stridor Tuberculosis of trachebronchial lymph nodes Vascular malformation Gastroesophageal Reflux Treatment To control airway inflammation. To prevent asthmatic attack. General Measures Avoid exposure to sensitive allergens Give inactivated influenza vaccine Cure respiratory tract infections Avoid trigger factors Self-management education Regular follow-up PEFR monitoring physical exercise Glucocorticosteroid ICS therapy is recommended daily as the treatment of choice for all patients with persistent asthma. ICS therapy has been shown to reduce asthma symptoms, improve lung function, reduce AHR, reduce “rescue” medication use and, most important, reduce urgent care visits, hospitalizations. ICS therapy may lower the risk of death due to asthma. The role of Glucocorticosteroid Inhalation therapy Inhaled corticosteroids versus systemic corticosteroids : The drug nonstop to bellows Low doses Rapid onset of action High security Effectiveness Distribution of inhalation in lungs Metabolic pathway of Inhaled corticosteroids 10 - 20 % To both lungs circulation biological activity 80 - 90% swallow Intestinal Absorption Inactivation adverse effect due to first pass effect Inhaler Nebulizing therapy an infants Effect of long-term treatment with inhaled budesonide on adult height in children with asthma. patients use inhaled corticosteroids 180 Adult height (cm) 170 unimpaired child 160 150 140 Children with asthma who have received long-term treatment with budesonide attain normal adult height. 130 120 110 6岁 Pedersen,1999 8岁 10岁 12岁 14岁 16岁 Bronchodilators Short-acting inhaledβ-agonist (SABA) Give their rapid onset of action, effectiveness, and 4–6 hr duration of action. (albuterol, levalbuterol, terbutaline, pirbuterol) Long-acting inhaledβ-agonist (LABA) have a prolonged duration of effect of at least 12 hr. (salmeterol, formoterol) Adverse effect of long-term use of β-agonists Induce down regulation of the β2-receptor function. Aggravate airway inflammation and airway hyperreactivity. Overuse of β-agonists is associated with an increased risk of death or near-death episodes from asthma. Interaction between corticosteroids and β2-agonists Glucocorticoids β2-agonists β2-receptor + Hormone receptor + Anti-inflammatory effect Bronchiectasis effect • Corticosteroids may enhance Expression of β2-receptor β2-agonists may enhance Anti-inflammatory effect of Corticosteroids The addition of LABA to ICS to is superior to doubling the dose of ICS Other drugs Leukotriene receptor antagonists (LTRA). Aminophylline Sodium Cromoglicate Immunotherapy Specific immunotherapy —— hyposensitization therapy Nonspecific immunotherapy —— immunoloregulation therapy GINA • WHO issued Global initiative for asthma (GINA) in 1994. The aims were to set up standardization of asthmatic treatment. It works with health care professionals and public health officials around the world to reduce asthma prevalence, morbidity, and mortality. Stepwise Approach Summary Asthma is a chronic inflammatory condition of the lung airways resulting in episodic airflow obstruction. The inflammatory cell infiltrate is the main pathologic features includes eosinophils, lymphocytes, and neutrophils. Airway hyperresponsiveness to nonspecific stimuli is a hallmark of asthma. Wheezing, dry cough, and shortness of breath is the characteristic sign of asthma. Summary Asthma medications include long-term control medications combined with quick-relief medications. Antiinflammatory therapy is the core of modern treatment of asthma. Corticosteroids is the most effective antiinflammatory agent. Inhalation therapy is the main medication for asthma. Up to now, there is no radical treatment American Greg Louganis The greatest diver 美国跳水名将洛加尼斯 Jackie Joyner-Kersee She earned the gold medal of heptathlon in the 1992 Olympics. 美国田径全能乔伊娜 Thanks!