Asma - nuwere konsepte

1. Asma - nuwere konsepte Dr FCJ Bester Tel: 051 522 1907 Sell: 082 554 2799

2. Lesingskedule Definisie van Asma Patologie van Asma Diagnose van Asma Hantering van Asma NAEP protokol

3. Wat is Asma ? Chroniese inflammatoriese toestand Episodiese irriteerbaarheid Sx: Hoes en/of sputum en/of brongospasma Keer om spontaan of met medikasie

4. Kenmerke van asma in die afwesigheid van: Linker ventrikulêre versaking Infektiewe longsiekte Degeneratiewe longsiekte Pulmonale embolisme GERS Geïrriteerde lugweë

5. Snellerfaktore van Asma Infeksies - veral viraal Allergene - Huisstofmiet, swamme, Katepiteel, Honde epiteel, grasse Sigaretrook Koue lug Industriële irritante Spanning

6. Patologie van Asma

7. Patologie van Asma

8. Patologie van Asma

9. Diagnose van asma: Kliniese geskiedenis soos definisie Spirometrie: Fev 1 minder as 80% van voorspelde waarde. FEV1/VK minder as 65% > 12% verbetering na toediening van kortwerkende beta stimulant.

10. Diagnose van asma:

11. Hantering van Asma Non farmakologies farmakologies

12. Nonfarmakologies - Verminder allergeen blootstelling ventilasie van geboue Ioniseerders verhoed verkoue, griep, BLWI Spartaanse meubels Matrasse in die son Bad Kat elke week

13. Middels vir asma Aminofillien Oraal en intraveneus Beta stimulante Oraal, intraveneus, inhalasies, nebulisasies kortwerkend, langwerkend Steroïede Intraveneus, oraal, inhalasies, nebulisasies Leukotrien antagoniste

14. Aminofillien Swak brongodilatories - hoë dossise nodig Laer dosis wel anti-inflammatories Goedkoop Geneesmiddel interaksies Meer newe effekte as ander orale meds

15. Beta stimulante

16. Beta stimulante (agoniste) Effektief net voor oefening en blootstelling van bekende sneller Toleransie kan ontwikkel Geen effek op inflammatoriese kaskade Langtermyn beta stimulante potensieer Steroïede

17. Langwerkende beta agoniste Facet studie - formoterol het ‘n sinergistiese effek saam met steroiede

20. Verklaring vir sinergisme (Peter Barnes)

21. Steroïede Inhalasie steroïede die mees potente anti-inflammatoriese middel. Inhibeer Eosinofiele, limfosiete, mastselle. Mees koste effektiewe wyse om asma te kontrolleer. Dosis respons neem dramaties af bokant 800 µg/d met toename in newe effekte

22. Slide 6 Corticosteroids have demonstrated substantial clinical benefits in patients with asthma, including improved lung function, reduced symptoms, and decreased asthma exacerbations.6 For many patients, a low corticosteroid dose provides effective control with no adverse effects.7 However, the higher corticosteroid doses have variable effects on control of asthma; the dose-response relationship appears to be shallow as the dosage is increased (as shown in the graph).8,9 In contrast, the local and systemic side effects of corticosteroids are dose dependent.3,8 Systemic effects of higher doses of corticosteroids (>800–1000 µg/day in adults), which may result from direct absorption through the lung, can include growth delay in children, loss of bone mineral density after as little as one year of treatment, easy bruising, cataracts, and/or glaucoma.3,7-9 Current asthma treatment guidelines recommend use of the lowest possible corticosteroid dose necessary to achieve clinical control so as to avoid treatment-related side effects.3 Slide 6 Corticosteroids have demonstrated substantial clinical benefits in patients with asthma, including improved lung function, reduced symptoms, and decreased asthma exacerbations.6 For many patients, a low corticosteroid dose provides effective control with no adverse effects.7 However, the higher corticosteroid doses have variable effects on control of asthma; the dose-response relationship appears to be shallow as the dosage is increased (as shown in the graph).8,9 In contrast, the local and systemic side effects of corticosteroids are dose dependent.3,8 Systemic effects of higher doses of corticosteroids (>800–1000 µg/day in adults), which may result from direct absorption through the lung, can include growth delay in children, loss of bone mineral density after as little as one year of treatment, easy bruising, cataracts, and/or glaucoma.3,7-9 Current asthma treatment guidelines recommend use of the lowest possible corticosteroid dose necessary to achieve clinical control so as to avoid treatment-related side effects.3

23. Steroïede Begin met hoë dosis vir 4 tot 8 weke en verminder dan na 800 of minder Hoë dossise geassosieer met subkapsulêre katarakte en verhoogde oogdrukke Verminder Moniliase met spasieerder. Vroeë intervensie met steroïede en voldoende gebruik voorkom hermodulering en brongeale fibrose.

24. Steroïede

25. Eikosanoïed metabolisme

26. Sisteiniel Leukotriene

27. Sisteiniel Leukotriene

28. Slide 10 Both the early- and late-phase asthmatic responses are characterized by allergen-induced release of cysteinyl leukotrienes from inflammatory cells, such as mast cells, eosinophils, basophils, macrophages, and monocytes.18-20 The effects of cysteinyl leukotrienes (LTC4, LTD4, and LTE4) relevant to the pathophysiology of asthma include the following: • Eosinophil recruitment, an important event in the development of the chronic inflammatory response in asthma.18,20 • Edema, caused by increased microvascular permeability with  exudation of plasma into the airway wall and lumen.21 • Increased secretion of mucus, which interacts with plasma protein  and cell debris to form mucous plugs.21 • Bronchoconstriction, mediated by the contractile effects of cysteinyl  leukotrienes on the smooth muscle within airway walls.21 Cysteinyl  leukotrienes may also contribute to airway smooth-muscle  hypertrophy.18 Slide 10 Both the early- and late-phase asthmatic responses are characterized by allergen-induced release of cysteinyl leukotrienes from inflammatory cells, such as mast cells, eosinophils, basophils, macrophages, and monocytes.18-20 The effects of cysteinyl leukotrienes (LTC4, LTD4, and LTE4) relevant to the pathophysiology of asthma include the following: • Eosinophil recruitment, an important event in the development of the chronic inflammatory response in asthma.18,20 • Edema, caused by increased microvascular permeability with exudation of plasma into the airway wall and lumen.21 • Increased secretion of mucus, which interacts with plasma protein and cell debris to form mucous plugs.21 • Bronchoconstriction, mediated by the contractile effects of cysteinyl leukotrienes on the smooth muscle within airway walls.21 Cysteinyl leukotrienes may also contribute to airway smooth-muscle hypertrophy.18

29. Slide 21 After 12 weeks of therapy, the addition of montelukast to inhaled beclomethasone resulted in significant improvements versus beclomethasone alone in the primary study endpoints of change in FEV1 (p<0.001 ) and daytime asthma symptom scores (p=0.041). Whereas morning FEV1 decreased by 0.02 L in the beclomethasone group, this parameter increased by 0.14 L in the additivity group. Daytime symptom scores decreased (improved) by 0.02 in the beclomethasone group, compared with a decrease of 0.13 in the additivity group.32 Slide 21 After 12 weeks of therapy, the addition of montelukast to inhaled beclomethasone resulted in significant improvements versus beclomethasone alone in the primary study endpoints of change in FEV1 (p<0.001 ) and daytime asthma symptom scores (p=0.041). Whereas morning FEV1 decreased by 0.02 L in the beclomethasone group, this parameter increased by 0.14 L in the additivity group. Daytime symptom scores decreased (improved) by 0.02 in the beclomethasone group, compared with a decrease of 0.13 in the additivity group.32

30. Slide 22 The addition of montelukast to inhaled beclomethasone resulted in improved asthma control, compared with beclomethasone alone, as shown by substantial reductions in the secondary endpoints of days with asthma exacerbations (25% decrease in least-square mean; p=0.041) and asthma attacks (48% decrease in least-square mean; p=0.055) in the additivity group.32 Slide 22 The addition of montelukast to inhaled beclomethasone resulted in improved asthma control, compared with beclomethasone alone, as shown by substantial reductions in the secondary endpoints of days with asthma exacerbations (25% decrease in least-square mean; p=0.041) and asthma attacks (48% decrease in least-square mean; p=0.055) in the additivity group.32

31. Leukotrien antagoniste Montelukast (10 mg/d) en Zafirlukast (20 mg bd) Respons toon variasie agv genetiese variasie in 5-lipooksigenase Additiewe effek saam met Steroïed inhalasies Montelukast vanaf 6 jaar geregistreer (5 mg/d)

32. Leukotrien antagoniste Werk binne die eerste 24 uur. Montelukast inhibeer nie Sitochroom P450 nie Newe effekte vergelykbaar met placebo Aangedui as tweede linie terapie Vervang nie inhalasie steroïede nie. Kan Churg Strauss sindroom ontlok

33. Leukotrien antagoniste Effektief by aspirien allergie Effektief by oefenings geïnduseerde asma Effektief by hooikoors Moontlik ook vir urtikaria en ekseem.

35. Trapmodel benadering tot ASMA Stap 1: Intermitterend Sporadies, lig Stap 2: Gereelde aanvalle Stap 3: Daagliks Stap 4: Betekenisvol Stap 5: Steroïed afhanklik.

36. Trapmodel benadering tot ASMA Stap 1: Intermitterend Sporadies, lig

37. Trapmodel benadering tot ASMA Stap 1: Intermitterend Sporadies, lig Stap 2: Gereelde aanvalle

38. Trapmodel benadering tot ASMA Stap 1: Intermitterend Sporadies, lig Stap 2: Gereelde aanvalle Stap 3: Daagliks

39. Trapmodel benadering tot ASMA Stap 1: Intermitterend Sporadies, lig Stap 2: Gereelde aanvalle Stap 3: Daagliks Stap 4: Betekenisvol

40. Trapmodel benadering tot ASMA Stap 1: Intermitterend Sporadies, lig Stap 2: Gereelde aanvalle Stap 3: Daagliks Stap 4: Betekenisvol Stap 5: Steroïed afhanklik.