Bronchial hyperreactivity and Asthma

1. Bronchial hyperreactivity and Asthma Prof. Sevda Özdoğan MD, Chest Diseases

2. DEFINITION • Asthma is a chronic inflammatory disorder of the airways in which mast cells, eosinophils and T lymphocytes play a role. The chronic inflammation causes an associated bronchial hyperreactivity which leads to recurrent episodes of reversible airflow obstruction with wheesing, breathlesssness, chest tightness and coughing

3. PATHOGENESIS • Characteristics of the disease: • Chronic inflammation • BHR • Diffuse reversibl airway obstruction

4. Epidemiology • Asthma is one of the most common chronic diseases worldwide (300 million people) • Occurs in all countries but varies in prevalance • 5-10% of adult and 10-15% of children worldwide have asthma • General prevalance in our country is 7-14%

5. Personal predisposition+ Environmental factors INFLAMATION Bronchial hyperreactivity Airway wall remodeling Airflow limitation Symptoms

6. Personal predisposition • Genetic Factors: There is a good evidence that Asthma is a heritable disease • Probability of developing asthma in the a child is 20-30% if one parent has asthma; 70% if both the parents have asthma • Atopy:Production of abnormal amounts of IgE antibodies in response to contact with environmental allergens. It is an important host factor that predisposes to asthma • Multiple genes (ch 5,6,11,12,14) are involved in atophy and asthma susceptibility

7. Gender: Childhood asthma is more prevalant in boys but the prevalance of adult asthma becomes higher in females • Obesity: It is a risk factor for asthma (Leptin)

8. Environmental Factors • Prenatal • Smoking in pregnancy increases the child’s risk of developing asthma (Due to impaired bronchial development leading to narrow bronchi) • Intrauterin malnutrition • High antioxidants, vit E, zinc levels in maternal diet • Prenatal maternal stress • Prenatal antibiotic treatment • Emergency Cesarean section

9. Risk Factors in childhood • High allergen exposure (dust mite, cat, dog, fungi, cochroach etc) • Passive smoking • Respiratory infections (Chlamidia, RSV and severe viral respiratory infections impaire THtype 1 immunity and augment THtype 2 immunity) • Large family size (increased bacterial infections?)

10. Indoor allergens Dust mites Cochroach Fungi Pet Outdoor allergens Pollen Mold Allergens (Inhalation)

11. Risk Factors in childhood • High allergen exposure (dust mite, cat, dog, fungi, cochroach etc) • Passive smoking • Respiratory infections (Chlamidia, RSV and severe viral respiratory infections impaire THtype 1 immunity and augment THtype 2 immunity) • Large family size (increased bacterial infections?)

12. Tuberculosis, BCG vaccination, measles reduce the risk of allergy and asthma • Hygene Hypothesis: Improvement in hygiene and reduced recirculation of common infections (orofecal and foodborne microbes) is strongly associated with increasing prevelance of atopy and asthma • Other than breast feeding increase the risk of asthma (contriversial)

13. Adulthood(New onset asthma?; relaps of Childhood asthma?) • Air pollution? • Occupational pollutants and sensitizers • Industrial smog (sulfur dioxide, ozone, nitrogen, particulate material) • Animal proteins, poultry droppings, feathers,storage mites • Carpenters (wood dust) • Bakers (flour, amylase) • Food processing (Coffee bean dust, tea, meat tenderizer (papain) • Plastic industry (toluene diisocyanate, anhydrites etc) • Beauticians (persulfate) • Detergent, drug manufacturing (bacillus subtilis) • Hospital workers (Formaldehyde, gluteraldehyde, latex) • Certain drug treatment • Beta blockers • NSAID • Hormon replacement in women

15. Bronchial hyperreactivity (Airway hyperresponsiviness): A state in which the airways narrow too easily and too much in response to provoking stimuli as documented with measurements of lung function under controlled conditions. It is closely related to serum IgE levels and airway inflammation. Asymptomatic, nonspecific hyperreactivity is a risk factor for asthma

16. Clinical signs and symptoms • Asthma can be diagnosed on the basis of symptoms • Episodic breathlessness • Wheesing • Chest tightness • Cough (sometimes small thick sputum) • Seasonal variability of symptoms • Family history of asthma or atopic disease

17. Asthma • Allergic • Non allergic • Other

18. Allergic Asthma • The person should be sensitized by the allergen • A second challenge with the antigen in sensitized person, causes mast cell degranulation by forming a complex with the specific IgE molecules on the cell surface.

19. Early Asthmatic reaction: Begins in 3-5 min, resolves in 2-3 hr • Acute changes: • Bronchoconstruction • Mucous hypersecretion • Vasodilatation • Increased vascular permeability

20. Late asthmatic reaction begins in 4-6 hr, resolves in 24-48 hr *Mast cell degranulation are responsible from the acute changes and reaction where as eosinophyles are responsible from airway remodeling and chronic disease!

21. Questions to consider in diagnosis of asthma • Has the patient had an attack or recurrent attacks of wheesing? • Does the patient have a troublesome cough at night? • Does the patient have wheese, chest tightness or cough after exposure to airborne allergens or pollutants? • Does the patients colds “go to the chest” or take more than 10 days to clear up? • Are symptoms improved by appropiate antiasthma treatment?

22. Physical examination • Normal (Does not exclude asthma!!) • Wheesing on oscultation (Dyspnea, wheesing, hyperinflation are more likely to be present during symptomatic periods) • Wheesing can be absent in severe asthma (silent chest) • Cyanosis • Drowsiness • Difficulty in speaking • Tachicardia • Hyperinflated chest • Accesory muscle activation with intercostal recession

23. Diagnosis • Measurements of lung function (PFT) • Spirometry (FEV1/FVC<75%) • Peak expiratory flow • Reversibility test (early and late) • PEF diurnal variation monitoring • Simple exercise test (6 min) • Nonspecific bronchoprovocation tests (PD20) (measurement of hyperreactivity)

24. Chest x-ray (important in differential diagnosis) • Sputum or nasal smear eosinophyls • Creola bodies • Curshmann spirales • Measurement of allergic status • Skin testing • Specific Ig E in serum (A positive test does not mean allergic asthma so must be confirmed by history of exposure)

27. Factors that precipitate asthma exacerbations (Triggers) • Allergens (indoor and outdoor) • Respiratory infections (RSV, Influensa) • Exercise and hyperventilation • Cold air, weather changes • Foods, additives and drugs • Irritant gases (air polution, smoking) • Extreme emotional expression • Occupational agents • Pschological stress • Gastroesophageal reflux • Chronic rhinosinusitis

28. Acetylsalicylic acid NSAI Beta blockers Contrast agents Cocaine Heroin Dipyridamol Hydrocortisone Beclomethasone inh Pentamidine inh Protamine Vinblastine Mitomycin IL-2 Drugs or agents associated with induction of bronchospasm

29. Different Diagnostic Groups • Asthma in Elderly (differentiation from cardiac asthma, drug effects, changes in the perception of symptoms, difficulty in performing PFT, false positive reversibility) • Occupational Asthma • Cough variant asthma • Exercise induced asthma • Samter syndrome • Asthma in pregnancy

30. Occupational Asthma • Small molecular weight chemicals: isocyanates, platinum salts,metals • High molecular weight: Complex plant and animal biological products. • Diagnosis requires • a defined occupational history, exposure to sentisizing agents, • absence of asthma symptoms before beginning employement, • A documented relationship between development of symptoms at the workplace and the reduction on withdrawal from the workplace

31. Exercise Induced asthma • Some patients have asthma symptoms only during exercise • The symptoms begin in 5-10 min after beginning the exercise (Sometimes at the end of the exercise) and continue afterwards • Cooling and rewarming of the airway mucosa and changes in the osmolarity of the mucus are the probable cause

32. Cough variant asthma • These patients have chronic cough as the only symptom • Frequently at night • ACE inh drug use, GER, PND or chronic sinusitis should be excluded • Documentation of variability in lung function or airway hyperresponsiviness, sputum eosinophylia are important

33. Asthma in pregnancy • Asthma symptoms may reduce in 1/3 of pregnant asthmatics • May stay stable in 1/3 • May increase in 1/3

35. Treatment Goals in Athma • Prevent asthma attacks • Achieve and maintain control of symptoms • Maintain pulmonary function as close to normal levels as possible • Maintain normal activity levels, including exercise (Increase life quality) • Avoid adverse effects of medication • Prevent development of irreversibl airflow limitation • Prevent asthma mortality

36. Treatment program • Educate patients to develop a partnership in asthma management • Assess and monitor asthma severity • Avoid or control asthma triggers • Establish individual medication plans • Establish plans for managing exacerbations • Provide regular follow-up care

37. Classification of asthma

38. Controllers: Inhaled corticosteroids (systemic steroids) Chromones Long acting bronchodilators (beta agonist) Methylxantines (Theophyline) Leukotriene modifiers New drugs: Anti IgE (Omeluzimab) Relievers:quick relief medicine or resque medicine Short acting beta2 agonist Sistemic corticosteroids Theophylline Anticholinergics Asthma medications

40. Advantages of Inhaled forms • Drug is delivered directly to the targed • Quick effect • Small doses • Negligable systemic absorbtion • Less side effects

41. Breathlesness Speaking Agitation Accesory muscle activity Wheesing Respir Rate Pulse Pulsus paradoksus PEF PaO2 PaCO2 SaO2 Oscultation Mild attack Walking Sentences - - Mild < 20 < 100 < 10 mmHg > %80 Normal < 45 mmHg > %95 End ekspiratory wheese Moderate Talking Few words + + Severe 20-30 100-120 10-25 mmHg %60-80 > 60 mmHg < 45 mmHg %91-95 generalised (Full eksp) Severe Rest (Ortopnea) Word + + Severe > 30 > 120 > 25 mmHg < %60 < 60 mmHg > 45 mmHg < %90 Expiratory and inspiratory

42. THANKS