พญ.มุกดา หวังวีรวงศ์ หัวหน้าหน่วยโรคภูมิแพ้ สถาบันสุขภาพเด็กแห่งชาติมหาราชินี

1. ชมรมโรคระบบหายใจและเวชบำบัดวิกฤตในเด็กแห่งประเทศไทยชมรมโรคระบบหายใจและเวชบำบัดวิกฤตในเด็กแห่งประเทศไทย ร่วมกับ ยูโรดรัก ลาบอราทอรีส์ พญ.มุกดา หวังวีรวงศ์ หัวหน้าหน่วยโรคภูมิแพ้ สถาบันสุขภาพเด็กแห่งชาติมหาราชินี

2. Clinical Asthma Control (GINA 2006) • No (twice or less/week) daytime symptoms • No limitation of daily activities, including exercise • No nocturnal symptoms or awakening because of asthma • No (twice or less/week) need for reliever treatment • Normal or near-normal lung function results • No exacerbations

3. Asthma management program Component 1. Develop patient/doctor partnership Component 2. Identify and reduce exposure to risk factors Component 3. Assess, treat, and monitor asthma Component 4. Manage asthma exacerbations Component 5. Special Considerations

4. * 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 is not a reliable test for children 5 years and younger

5. Asthma Control Test Score 1 Score 2 Score 3 Score 4 Score 5

6. Asthma Control Test

7. Childhood Asthma Control Test Score 0 Score 1 Score 2 Score 3

8. Children Asthma Control Test Score 0 Score 1 Score 2 Score 3 Score 4 Score 5

9. Childhood Asthma Score

10. Management Approach Based On ControlFor Children Older Than 5 Years, Adolescents and Adults(GINA 2006) Level Control Treatment Action Reduce Increase Reduce Increase Treatment Steps

11. Step 1 Step 2 Step 3 Step 4 Step 5 *ICS = Inhaled glucocorticosteroids ** = Receptor antagonist or synthesis inhibitors

12. The first 3 drugs used for asthma control(N = 171) RH / PH SH Total OR (95% CI) P Drug N (%) Drug N (%) Drug N (%) 1 LB2 39/88 LB2 37/83 LB2 76/171 0.99 (0.52-1.89) 0.973 (44.32) (44.58) (44.44) 2 IS 34/88 IS 31/83 IS 65/171 1.06 (0.54-2.05) 0.862 (38.64)(37.35) (38.01) 3 THEO 8/88 THEO 13/83 THEO 21/171 0.54 (0.19-1.49) 0.191 (9.09) (15.66) (12.28) RH = Regional hospital PH = Provincial hospital SH = Small hospital Vangveeravong M.Thai Pediatr J 2005; 12(1);25-32.

13. The first 3 drugs used for asthma control by different kinds of doctors(N= 172) Ped NG Others (O) Ped : NG + O Drug N (%) Drug N (%) Drug N (%)OR (95% CI) P Drug 1 IS 13/20 LB2 43/95 LB2 27/57 0.29 (0.07-0.97) 0.027 LB2 (65.0) (45.26) (47.37) 2 LB2 4/20 IS 36/95 IS 18/57 3.37 (1.16-10.02) 0.011 IS (20.0) (37.89)(31.57) 3 KETO 3/20 THEO 10/95 THEO 12/57 0.00 (0.00-1.31) 0.068 THEO (15.0) (10.53) (21.05) Undefined 0.000 KETO Ped = Pediatricians NG = Newly graduated doctors Vangveeravong M.Thai Pediatr J 2005; 12(1);25-32.

14. O H H N O O N O XANTHINE CH2 N H3C O N N N DOXOPHYLLINE H N O O H N H3C N CH3 N THEOPHYLLINE N O N CH3

15. Methylxanthinespostulated mechanism of action AC PDE-4 c’APM ATP 5’AMP Increased cyclic AMP level by inhibiting phosphodiesterase-4 (PDE-4) (-) (+) β2-agonists Xanthines Bronchodilatation

16. Bronchodilating actions • Inhibit C’ nucleotide phosphodiesterase (PDEs) • Antagonize receptor-mediated actions of adenosine Adenosine - bronchoconstriction - potentiate immunologically induced mediator release from human lung mast cells

17. Bronchoprotective actions • Reduction of airway responsiveness to “specific” challenges with allergen Hendeles et al. J Allergy Clin Immuno 1995; 95:505. • Against non-specific stimuli - exercise Pollock et al. Pediatrics 1977;60:840. - fog Allegra. Eur J Respir Dis 1980;61(S),106:41. - SO2 Koenig et al. J Allergy Clin Immunol 1992; 89:789.

18. Anti-inflammatory actions • Inhibition of LTs release from the airways Rabe et al. Am J Crit Care Med1995;151(S):338 abstract • Attenuation of the effects of LTD4 at its receptors Howell. J Pharmacol ExpTher 1990; 225:1108 • Blockade of adenosine-induced mediator release in mast cells Welton&Simko. Biochem Pharmacol 1980; 29:1085 • Attenuation of late phase airway obstruction in airway response to histamine, in allergics Hendeles. JACI 1995; 95 :505.

19. Anti-inflammatory actions • Decrease of the allergen induced migration of eosinophils into the airway mucosa Sullivan et al. Lancet1994;343: 1006. • Restoration of corticosteroid responsiveness by activation of histone deacetylase (HDAC) and consequent suppression of inflammation Cosio et al. J Exp Med 2004. • Decrease of microvascular leakage of plasma into the airway Erjefalt & Persson. Acta Physiol Scand 1986; 128:653 • Decrease of neutrophils and LTB4 at nights in asthmatics Kraft et al. Am J Crit Care Med 1996; 154 :1505.

20. Pulmonary system • Relax airway smooth muscles Rabe et al. Am Rev Respir Dis1993; 147(S):A 184, abstract. • Relax smooth musles in pulmonary arteries Hendeles & Weinberger. New Engl J Med 1996; 334:1380. • Reduce decrease in lung function at night in asthmatics Kraft et al. Am J Crit Care Med 1996; 154:1505.

21. Pulmonary system • Decrease fatigue in diaphragmatic muscles Merciano et al. New Engl J Med 1984 ; 311:349. • Increase mucociliary clearance Cotromanes et al. Chest1985; 88:194. • Block (centrally-acting) decrease in ventilation during hypoxia Easton & Anthonisen. J Appl Physio1998; 64:1445.