Childhood Asthma

1. Childhood Asthma 上海交通大学医学院附属新华医院 鲍一笑

2. 邓丽君 邓丽君 1953-1995（42岁） Died in Thailand due to acute asthma exacerbation

3. 贝多芬 1770-1827（57岁） Died in Vienna because there is no effectivetreatment for asthma

4. Introduction

5. 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.

6. Allergy Eosinophils cell infiltrate Corticosteroids as anti-inflammatory therapy Infection Neutrophils cell infiltrate Red swelling, hot and pain Antibiotics therapy Asthma is an inflammation indduced by allergy

7. The Role of Th2 Cytokines in Allergic Cascade

8. The balance of Th1 and Th2

9. Epidemiology Prevalence↑ Death rates↑ (per 10,0000 population) China 0.5-3.3% 36.7 worldwide0.1-32% 1.3 Shanghai 90：1.79% 00：4.52% Europe and north America10% Asia 5% The prevalence of asthma has been increasing since the early 1980s for all age, sex, and racial groups.

10. The death rate1979-2000

11. The current asthma prevalence 2003 in USA

12. Etiology

13. 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.

14. 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).

15. 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.

16. Inhalant Allergens Sensitization to inhalant allergens increases over time and is found in the majority of children with asthma.

17. Pollen

18. Mite

19. House Pet

20. Smoke Exposure to tobacco smoke, especially from the mother, is also a risk factor for asthma.

21. Food Allergen • Animal Protein Fishery,product,milk,meat,egg • Oil Crop and Nuts Peanuts • Fruit and Greengrocery • Grain • Food additive

22. Drug Allergen • Benzylpenicillin • Sulfonamides • Antipyretic analgesic • Anesthetic agent • Biological products Aspirin sensitivity is uncommon in children.

23. Contactant allergen • Para-phenylenediamine • Nickel sulphate • Mercurial • Plasticsproducts • Rubber goods • Essence

24. Pathogenesis • Genetic factors • Immunity factors • Psychological factors • Endocrine factors

25. Allergic inflammation allergen Excise、Wether Harmful gas DC、MC、B cell IL-4 IgE Th2 B cell Mast cell histamine,LT,PG,PAF ECF IL-5 Eos EAR LAR PAF,LT,MBP,ECP Airwayinflammation,Hyperresponsiveness,Airway contraction, bronchoconstriction, airway wall edema, mucus plug formation Airway remodeling Wheezing, Cough, Dyspnea,

26. Allergic inflammation

27. Pathologic features • Shedding of airway epithelium • Edema • Mucus plug formation • Mast cell activation • Collagen deposition beneath the basement membrane

28. Pathologic features Pathologic features Bronchospasm mucosal edema mucus plug formation

29. Changes of Airway Epithelium shedding of airway epithelium Asthma Normal

30. Specimen of Bronchial Mucosa • In the subject without asthma, the epithelium is intact; • there isno thickening of the sub-basement membrane, and there is nocellular infiltrate. A 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.

31. Clinical Manifestation

32. Symptoms • Precursory symptoms: • Rhinocnesmus • Sneezing • Nasal obstruction • Nasal discharge • Itching of eye • Dry cough

33. Symptoms • Wheezing is the most characteristic sign of asthma. • Patients may also have cough and shortness of breath.

34. 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

35. LaboratoryExamination • 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）

36. Pulmonary Function Test Lung Function Abnormalities in Asthma FEV1, forced expiratory volume in 1 sec; FVC, forced vital capacity.

37. Diagnosis

38. 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

39. 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） ≥5score 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

40. Classification of Asthma Severity 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.

41. Differential diagnosis • Viral bronchiolitis • Foreign body • Congenital laryngeal stridor • Tuberculosis of trachebronchial lymph nodes • Vascular malformation • Gastroesophageal Reflux

42. Treatment • To control airway inflammation. • To prevent asthmatic attack.

43. 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

44. 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.

45. The role ofGlucocorticosteroid

46. Inhalation therapy • Inhaled corticosteroids versus systemic corticosteroids : • The drug nonstop to bellows • Low doses • Rapid onset of action • High security • Effectiveness

47. Distribution of inhalation in lungs

48. 10 - 20 % To both lungs circulation biologicalactivity adverse effect Intestinal Absorption 80 - 90% swallow Inactivationdue to first pass effect Metabolic pathway of Inhaled corticosteroids

49. Inhaler

50. Nebulizing therapy an infants