1. Asthma

2. Asthma and COPD mortality Mathers, PLos Med 2006

3. Prevalence of astma (A) and asthmatic symptoms (B) between 1965 and 2005 in children and young adults

4. Asthma morbidity in Hungary 2013, OKTPI incidence prevalence

5. Medical history of D.B. 30-year-old woman, school teacher Complaints for 20 years: periods of S.O.B., particularly in the August-October period, but also during exercise (tennis), cold air exposure (skie) or under stress (exams). Severity changes considerably time to time, with frequent attacks of wheezing, between attacks no complaints Never smoked Mother also had asthma

6. Acute admission Severe attack which responded poorly to BD drugs and inhaled CS. Exhausted, dehydrated, very anxious On examination: dyspneic, orthopneic, accessory muscles of respiration were active Lungs hyperinflated, musical rhonchi in all areas HR: 110/min with pulsus paradoxus Sputum scant and viscid

7. Asthma - an inflammatory disorder of the airways, characterized by periodic attacks of wheezing, shortness of breath, chest tightness, and coughing, tipically during the night and early morning. - a condition characterized by recurrent attacks of bronchoconstriction and excessive mucus production, in response to a variety of factors. - the attacks releave spontaneously or by bronchodilators - chronic inflammation results in bronchial hyperreactivity

8. Use os releaver, symptom increases Asthma control decreases time Exacerbation allergenes, viruses cold weather, exercise Asthma – variable nature

9. Prevalence 3-5% of adults and 7-10% of children. *Half of the people with asthma develop it before age 10 and most develop it before age 30. Asthma symptoms can decrease over time, especially in children. Concomittant diseases Many people with bronchial asthma have an individual and/or family history of allergies such as hay fever (allergic rhinitis) or eczema. Others have no history of allergies or evidence of allergic problems.

10. Phenotypes Wenzel, Lancet 2006

11. House dust mite (Dermatophagoides pteronyssimus)

12. Inflammatory cells Mast cell eosinophil Th2 basophil neutrophil platelet Structural cells Epithel Smooth muscle Endothel Fibroblast Nerves Mediators Histamin Leukotrienes Prostanoids PAF Kinins Adenosin Endothelins NO Cytokines Chemokines Growth factors Effects Brochospasm Plasma exsudation Mucus secretion AHR Structural changes

13. Etiology * In sensitive individuals, asthma symptoms can be triggered by inhaled allergens (allergy triggers) such as pet dander, dust mites, cockroach allergens, pollens. * Asthma symptoms can also be triggered by respiratory infections, exercise, cold air, tobacco smoke and other pollutants, stress, food or drug allergies. * Aspirin and other non-steroidal anti-inflammatory medications (NSAID) provoke asthma in some patients.

14. Johnston & Sears, Thorax 2006 „The September epidemic” (Ontario, Canada, 2001-2004)

15. Eosinophil Mast cell Allergen Th2 cell MODERN VIEW OF ASTHMA Vasodilatation New vessels Plasma leak Oedema Neutrophil Mucus hypersecretion hyperplasia Mucus plug Macrophage Bronchoconstriction Hypertrophy/hyperplasia Cholinergic reflex Epithelial shedding Subepithelial fibrosis Sensory nerve activation Nerve activation

16. Inflammatory and immune cells involved in asthma

19. Typical pathologic features: epithel shedding + basement membrane thickening After ICS Before ICS

20. Effect of inhaled steroid in asthma Laitinen LA, et al. J Allergy Clin Immunol 1992;90(1):32-42

21. Infect theory Th1 – Th2 imbalance

23. Asztma and COPD 1.

24. COPD Asthma Differences in airway obstruction

25. Asztma and COPD 2

26. Characteristics

27. Symptoms 1. *Most people with asthma have periodic wheezing attacks separated by symptom-free periods. *Some asthmatics have chronic shortness of breath with episodes of increased shortness of breath. *Asthma attacks can last minutes to days, and can become dangerous if the airflow becomes severely restricted

28. Symptoms 2. Cough, Wheezing, Dyspnoe - usually begins suddenly - episodic - may be worse at night or in early morning - aggravated by exposure to cold air, by exercise, by reflux - resolves spontaneously or by bronchodilators - cough with or without sputum (dyscrinia) - breathing that requires increased work - intercostal retractions - abnormal breathing pattern: exhalation (breathing out) more than twice as long as inspiration (breathing in)

29. Dyscrinia

30. Symptoms 3. Emergency symptoms * extremely difficult breathing *bluish color to the lips and face *severe anxiety *rapid pulse (pulsus paradoxus) *sweating *decreased level of consciousness (severe drowsiness or confusion) during an asthma attack

31. Signs and tests Listening to the chest (auscultation) during an episode reveals wheezing. Lung sounds are usually normal between episodes. Tests may include: *pulmonary function tests *chest X-ray *allergy testing by skin testing or serum tests (IgE) *arterial blood gas *eosinophil count

32. Diagnostics -Lung function 1. - Between the attacks: may be normal - During the attacks: obstruction (PEF, FEV 1 decreased) - Patients with - normal lung function: provocation test - obstruction: pharmacodynamic test

33. Metacholin provocation test bronchial hyperreactivity

34. Fractional metacholin provocation bronchial hyperreactivity

38. Pharmacodynamic test reversible obstruction

39. Provocation test *Specific provocation-allergen challenge (rarely done, can be dangeorus) inhalation causes prompt and sign. bronchoconstriction *rapid decline in FEV1: lasts: 15 min.- 1 hour *=early asthmatic reaction (EAR)=early phase response *After this phase resolves (spontaneously or with  -agonist), the FEV1 reaches a level to the pre-chall. baseline. *6-24 hours after exposure to the allergen bronchoconstriction can be developed=late asthmatic response (LAR). The decline in FEV1 may be less severe. *Aspecific provocation (histamin, metacholin): *Exercise test – 6-8 min run, pre/post LF Pharmacodynamic test:baseline obstr.lung function resolved in 15 min due to inh. bronchodilatator Lung function 2.

40. COPD Large airway obstruction –Foreign body –Tumor Pulmonary embolism Eosinophil pneumonia Chronic cough –Bronchitis simplex –Sinusitis –Tracheitis –Dyskinesis CHF Gastroesophageal reflux (GERD) Chronic cough –Drug-induced (ACE inhibitor,  -blocker) RespiratoryNon-respiratory Differencial diagnostics I.

41. Differencial diagnostics II. X-ray (chest, sinuses) Rhinoscopia Oesophageal pH monitoring Bronchoscopy Echocardiography Lung scintigraphy (V/Q scan)

42. Asthma diff. dg.1./A COPD Farmacodynamic test: praepost FVC: 2,00 (47%)- 1,89 (44%) FEV 1 : 0,93 (28%)- 0,88 (26%) FRC:5,29 (150%)- 5,09 (144%) RV: 4,65 (201%)- 4,57 (198%) Raw: 6,01-6,19 (<2,24) Irreversible obstructive pulmonary disease 61 years old man

43. Blood gas analysis pH: 7,42 pO 2 : 66,6 Hgmm pCO 2 :37,2 Hgmm Sat: 93% Lung function FVC: 3,05 86% FEV 1 :1,03 37% VC:3,56 96% FRC:5,93 171% RV: 4,27 173% RV/TLC%: 55% DLCO: 1,6 20% Asthma diff. dg.1./B COPD/ Emphysema 68 years old man

44. Asthma diff.dg 2. Tumor of big airway

45. Asthma diff.dg 3.Heart failure

46. Asthma severity Sympotms Day Night Exercise capacity Lung function (FEV 1 or PEF) IV. Chronic severe Folyamatos, naponta többször folyamatos gyakori Folyamatosan korlátozott FEV 1  60% PEF variability  30% III. Chronic moderate Minden nap napi tünetek  agonista  1 hét minden nap Panaszok idején fizikai terhelhetőség  FEV 1  60-80 % PEF variability  30% II. Chronic mild Hetente többször, de nem minden nap  1/hét, de  1/nap  2/hó Nagyobb fizikai terhelés köhögést és bronchospazmust provokál FEV 1  80% PEF variability  30% I. Epizodic Havonta többször, de nem minden héten  1 hét, a rohamok között  2/hó tünetmentesség PEF normál Hosszabb futás köhögést és bronchospazmust provokál FEV 1  80% PEF variability  20%

47. Treatment 1. 1. Controllers (Anti-inflammatory) *ICS, inhaled corticosteroid: (budenosid, fluticasone, beclomethason, ciclesonide) *oral or intravenous corticosteroids (prednisone, methylprednisolone, hydrocortisone) *leukotriene inhibitors (montelukast, zafirlukast, pranlukast) *LABA(long acting beta-2 agonists) – salmeterol, formoterol

48. Treatment 2. 2. Releavers (bronchodilators ) *beta-2 agonist: - short-acting (SABA): inhaled (salbutamol, terbutalin, formoterol) *aminophylline or theophylline (I.v) *anticholinergics (ipratropium)

49. 1. step2. step3. step4. step5. step p.r.n. SABA Choose one Copmbine one or more Combine one or more Preventive treatment ICS low doseICS low dose + LABA ICS moderate or high dose + LABA oral corticosteroid (small dose) antileukotriensICS moderate or high dose antileukotriens Anti IgE ICS low dose + antileukotrien theophyllin ICS low dose + theophyllin, antileukotrien GINA 2009 : treatment decreaseincrease

50. Normal Milde BHR Moderate BHR Severe BHR PC 20 Change in hyperreactivity Metacholin (mg/ml) FEV 1 decrease (%) ICS (400 μg BDP, 2 mo) Barnes ML, Allergy 2007

51. Severity of asthma exacerbations I. MildModerateSevereResp.arrest dyspneaWalking Can lie down Talking Prefers sitting At rest Hunched forward Talks insentencesphraseswords alertnessUsually agitated Usually agiteted Drowsy or confused Respirator y rate Increased >30/min

52. Severity of asthma exacerbations II. MildModerateSevereResp.arrest Accesory muscles notusually Paradox thoraco- abdominal movement wheezemoderateloudUsually loud Abscence of wheeze Pulse rate<100100-120>120bradycardi a Pulsus paradoxus Absent <10mmHg 10-25 mmHg >25mmHgAbscence musc.fatig.

53. Severity of asthma exacerbations III. MildModerateSevereResp.arrest PEF>80%60-80%<60% PaO2>60mmHg<60mmHg PaCO2<45mmHg>45mmHg SaO2>95%91-95%<90%

54. Treatment of acute exacerbation