Dept.Pulmonology, University of Szeged, Deszk, Hungary

1. Attila Somfay Dept.Pulmonology, University of Szeged, Deszk, Hungary 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 Prevalence Incidence 290 201 15 836 14 629 290 422 OKTPI, 2016

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 viscous

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

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. Asthma phenotypes Wenzel, Nature Med 2012

11. Symptom – inflammation relationship Haldar, AJRCCM 2008

12. House dust mite (Dermatophagoides pteronyssimus)

13. 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

14. 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.

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

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

17. Inflammatory and immune cells involved in asthma

18. Infect theory Th1 – Th2 imbalance

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. Asztma and COPD 2

22. Clinical characteristics of asthma

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

24. 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, byreflux - 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)

25. Dyscrinia

26. 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

27. 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

28. Diagnostics -Lung function 1. - Between the attacks: may be normal - During the attacks: obstruction (PEF, FEV1 decreased) - Patients with - normal lung function:provocation test -obstruction:pharmacodynamic test

29. Metacholin provocation testbronchial hyperreactivity

31. Pharmacodynamic testreversible obstruction

32. Lung function 2. Provocation test *Specific provocation-allergen challenge (rarely done, can be dangeorus – anaphylaxis, suffocation) inhalationcauses 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 spirometry Pharmacodynamic test:baseline obstr.lung function, resolved in 15 min due to inh. bronchodilator (salbutamol)

33. 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) Differencial diagnostics I. Respiratory Non-respiratory

34. Differencial diagnostics II. • X-ray (chest, sinuses) • Oesophageal pH monitoring • Bronchoscopy • Echocardiography • CT angiography, V/Q scan

35. Asthma diff. dg.1./A COPD Farmacodynamic test: prae post FVC: 2,00 (47%)- 1,89 (44%) FEV1: 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

36. Asthma diff. dg.1./B COPD/Emphysema Lung function FVC: 3,05 86% FEV1:1,03 37% VC:3,56 96% FRC:5,93 171% RV: 4,27 173% RV/TLC%: 55% DLCO: 1,6 20% 68 years old man Blood gas analysis pH: 7,42 pO2: 66,6 Hgmm pCO2:37,2 Hgmm Sat: 93%

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

38. Asthma diff.dg 3.Heart failure

39. Asthma severity

40. Treatment 1. Controllers (Anti-inflammatory) - ICS, inhaled corticosteroid: (budenosid, fluticasone, beclomethason, ciclesonide) - leukotriene inhibitors (montelukast, zafirlukast, pranlukast) - LABA(long acting beta-2 agonists) – salmeterol, formoterol – only with ICS - xantin derivates (teophllin)

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

42. GINA 2015 : treatment decrease increase

43. A kontroll elérésének lehetőségei GINA 2015

44. Severity of asthma exacerbations I.

45. Severity of asthma exacerbations II.

46. Severity of asthma exacerbations III.

47. Treatment of acute exacerbation + O2