Bronchial asthma management

Definition and introduction to bronchial asthma - classification of bronchial asthma - pathophysiology and risk factors for bronchial asthma - diagnosis of bronchial asthma - clinical manifestations - investigations - management of bronchial asthma

1. Dr. Sameh Ahmad Muhamad abdelghany Lecturer Of Clinical Pharmacology Mansura Faculty of medicine Bronchial asthma Management

2. BRONCHIAL ASTHMA INTRODUCTION      CLASSIFICATION RISK FACTORS Diagnosis Treatment & Prevention CONTENTS

3. INTRODUCTION

4. Introduction Asthma is a chronic inflammatory disorder of the airways that is characterized: clinically by recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night/early morning. physiologically by widespread, reversible narrowing of the bronchial airways and a marked increase in bronchial responsiveness.

5. Introduction In 2015, 358 million people globally had asthma, up from 183 million in 1990. It caused about 397,100 deaths in 2015, most of which occurred in the developing world. Asthma was recognized as early as Ancient Egypt. The word "asthma" is from the Greek ἅσθμ α, ásthma, which means "panting".

6. CLASSFICATION

7. Classification A heterogenous disorder. Atopic /extrinsic /allergic ( 70%): Most common type Environmental agent: dust, pollen, food, animal dander Family history - present Serum IgE levels - increased Skin test with offending agent –wheal flare

8. Classification Non-atopic/ intrinsic /non-allergic( 30%) Triggered by respiratory tract infection Viruses - most common cause Family history uncommon IgE level normal No associated allergy Skin tests NEGATIVE Cause- hyperirritability of bronchial tree

9. Classification Drug induced asthma Several pharmacologic agents Aspirin sensitive asthma Increased bronchoconstrictor leukotrienes. sensitive to small doses of aspirin. Inhibits COX pathway, without affecting LPO pathway

10. Pathophysiology Chronic inflammation Airway Hyperresponsiveness

11. Pathophysiology Inflammation Chronic inflammatory state Involves respiratory mucosa from trachea to terminal bronchioles, predominantly in the bronchi. Activation of mast cell , infiltration of eosinophils & T-helper type 2 (Th2) lymphocytes

12. Pathophysiology Inflammation Exact cause of airway inflammation is unknown. Thought to be an interplay between endogenous and environmental factors. Endogenous factors Atopy Genetic predisposition to IgE mediated type I hypersensitivity The major risk factor for asthma Genetics

13. Pathophysiology Inflammation Environmental factors Viral infections : RSV, Mycoplasma, Chlamydia Air pollution Allergens :house dust mite

14. Pathophysiology Airway Hyperresponsiveness (AHR) The excessive bronchoconstrictor response to multiple inhaled triggers that would have no effect on normal airways. Characteristic physiologic abnormality of asthma.

15. Pathophysiology

16. Pathophysiology

17. RISK FACTORS

18. Risk factors Host factors: predispose individuals to, or protect them from, developing asthma Genetic Atopy Airway hyperresponsiveness Gender Obesity

19. Risk factors Environmental factors: influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist Indoor allergens , Outdoor allergens Occupational sensitizers Tobacco smoke , Air Pollution Respiratory Infections Diet

20. Triggers Asthma Triggers Allergens Virus Infections Drugs Exercise Food Air pollutants Physical factors GERD Stress Occupational factors

21. DIAGNOSIS

22. Clinical manifestations Symptoms Wheezing, dyspnea and cough. Variable – both spontaneously and with therapy. Symptoms worse at night. Nonproductive cough Limitation of activity

23. Clinical manifestations Signs ↑ respiratory rate, with use of accessory muscles Hyper-resonant percussion note Expiratory rhonchi No findings when asthma is under control or b/w attacks

24. Classification for asthma severity Grade Symptoms Night-time Symptoms Mild intermittent Symptoms ≤ 2 times/week ≤ 2 times/month Mild persistent Symptoms ≥ 2 times/week but ≤ 1/day ≥ 2 times/month Moderate persistent Daily Symptoms ≥ 1/week Severe persistent Continued Symptoms Limited physical activity Frequent

25. Clinical manifestations

26. Laboratory diagnosis Pulmonary function tests: Using Spirometry estimate degree of obstruction ↓FEV1, ↓FEV1/FVC, ↓PEF.

27. Laboratory diagnosis CXR : hyperinflation,emphysema Arterial blood-gas analysis hypoxia & hypocarbia Skin hypersensitivity test Sputum & blood eosinophilia Elevated serum IgE levels

28. TREATMENT

29. Management Non-Pharmacological Pharmacological

30. Non-Pharmacological Reduce exposure to indoor allergens Avoid tobacco smoke Avoid vehicle emission Identify irritants in the workplace Explore role of infections on asthma development, especially in children and young infants

31. Non-Pharmacological Influenza Vaccination should be provided to patients with asthma when vaccination of the general population is advised routine influenza vaccination of children and adults with asthma does not appear to protect them from asthma exacerbations or improve asthma control

32. Pharmacological treatment Classification of drugs Bronchodilators : rapid relief, by relaxation of airway smooth muscle β2 Agonists Anticholinergic Agents Methylxanthines Controllers : inhibit the inflammatory process Glucocorticoids Leukotrienes pathway inhibitors Cromones Anti-IgE therapy

33. Pharmacological treatment β2 Agonists in asthma Potent bronchodilators. Usually given by inhalation route. Effects: Relaxation of airway smooth muscle Inhibition of mast cell mediator release Reduction in plasma exudation Increased mucociliary transport Inhibition of sensory nerve activation No effect on airway inflammation

34. Pharmacological treatment β2 Agonists in asthma Short-Acting β2 Agonists E.g salbutamol , terbutaline Convenient,rapid onset,without significant systemic side effect Bronchodil . of choice in acute severe asthma Used for symptomatic relief Only treatment required for mild, intermittent asthma. Use >2 times a week indicates need of a regular controller therapy.

35. Pharmacological treatment β2 Agonists in asthma Long-Acting β2 Agonists E.g salmeterol, formoterol Duration of action - >12 hrs. Used in combination with inhaled corticosteroid therapy. Improve asthma control and reduce frequency of exacerbations. Should not be used as monotherapy (increased mortality). Not effective for acute bronchospasm.

36. Pharmacological treatment Anticholinergic agents E.g Ipratropium bromide, tiotropium. Prevent cholinergic nerve induced bronchoconstriction. Less effective than β2 agonists. Response varies with existing vagal tone. Use in asthma Intolerance to inhaled β2 agonist. Status asthmaticus –additive effect with β2 agonist

37. Pharmacological treatment Anticholinergic agents Ipratropium: slow,bitter taste precipitate glaucoma paradoxical bronchoconstriction Tiotropium: longer acting, approved for treatment of COPD. Dryness of mouth

38. Pharmacological treatment Methylxanthines Medium potency bronchodilator E.g Theophylline, theobromine, caffeine Recently interest has declined in this class of drugs: Side effects Need for plasma drug levels Pharmacokinetics Availability of other effective drugs Still widely used drugs especially in developing countries due to their lower cost.

39. Pharmacological treatment Methylxanthines Adverse effects Anorexia, nausea, vomiting, abdominal discomfort headache, and anxiety Seizures or arrhythmias Diuresis Doxyphylline long acting,oral

40. Pharmacological treatment Corticosteroids in asthma Effective drugs for treatment of asthma. Development of inhaled corticosteroids is a major advance in asthma therapy. Used prophylactically as a controller therapy. Reduce the need for rescue β2 agonist. Benefit starts in 1week but continues up to several months. If asthma not controlled at low dose of ICS then addition of long acting β2 agonist is more effective than doubling steroid dose.

41. Pharmacological treatment Corticosteroids in asthma Effects: Broad anti-inflammatory effects: Marked inhibition of infiltration of airways by inflammatory cells. Modulation of cytokine and chemokine production Inhibition of eicosanoid synthesis Decreased vascular permeability. Potentiate effect of β2 agonist.

42. Pharmacological treatment Corticosteroids in asthma Inhaled corticosteroids( ICS) Use of β2 Agonists >2 times a week indicates need of a ICS E.g Beclomethasone , Budesonide , Fluticasone

43. Pharmacological treatment Corticosteroids in asthma Inhaled corticosteroids( ICS) Adverse effects: Oropharyngeal candidiasis, dysphonia Decreased bone mineral density. Skin thinning, purpura Growth retardation in children

44. Pharmacological treatment Corticosteroids in asthma Systemic steroids in asthma Indication Acute exacerbation(lung function <30% predicted) Chronic severe asthma A 5-10 day course of prednisolone 30-45mg/d is used. 1% of patients may require regular maintenance therapy.

45. Pharmacological treatment Leukotrienes pathway inhibitors Inhibition of 5-lipoxygenase, thereby preventing leukotriene synthesis. Zileuton. Inhibition of the binding of LTD4 to its receptor on target tissues, thereby preventing its action. E.g Zafirlukast, montelukast. Oral route. Adverse effects Liver toxicity vasculitis with eosinophilia

46. Pharmacological treatment Leukotrienes pathway inhibitors They are less effective than ICSs in controlling asthma Use in asthma Patients unable to manipulate inhaler devices. Aspirin induced asthma. Mild asthma – alternative to ICS. Moderate to severe asthma – may allow reduction of ICS dose

47. Pharmacological treatment Cromones E.g Cromolyn sodium & nedocromil sodium On chronic use (four times daily) reduce the overall level of bronchial reactivity. have no effect on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm; they are only of value when taken prophylactically. Inhalation route

48. Pharmacological treatment Cromones May act by stabilization of Mast cells with inhibition of mediator release Uses Asthma - Prevention of asthmatic attacks in mild to moderate asthma Adverse effects Well tolerated drugs Minor side effects- throat irritation, cough, and mouth dryness, rarely, chest tightness, and wheezing

49. Pharmacological treatment Anti- IgE therapy : Omalizumab recombinant humanized monoclonal antibody targeted against IgE . Action: IgE bound to omalizumab cannot bind to IgE receptors on mast cells and basophils, thereby preventing the allergic reaction at a very early step in the process.

50. Pharmacological treatment Anti- IgE therapy : Use in asthma Persons >12 years of age with moderate-to-severe persistent asthma. Omalizumab is not an acute bronchodilator and should not be used as a rescue medication or as a treatment of status asthmaticus. Expensive drug Has to be given under direct medical supervision due to the risk of anaphylaxis

51. Status asthmaticus (severe acute asthma) Severe airway obstruction Symptoms persist despite initial standard acute asthma therapy. Severe dyspnea & unproductive cough Sweating , central cyanosis ,tachycardia

52. Status asthmaticus (severe acute asthma) Treatment of Status asthmaticus High conc. of oxygen through facemask Nebulised salbutamol in oxygen given immediately Ipratopium bromide + salbutamol nebulised in oxygen,who don’t respond within 15-30 min

53. Status asthmaticus (severe acute asthma) Treatment of Status asthmaticus Terbutaline s.c. or i.v. excessive coughing or too weak to inspire adequately. Hydrocortisone hemisuccinate i.v. , followed by infusion. Endotracheal intubation & mechanical ventilation if above ttt fails

54. Prophylaxis Preservation of the environment, healthy life-style (smoking cessation, physical training) – are the basis of primary asthma prophylaxis. These measures in combination with adequate drug therapy are effective for secondary prophylaxis.

55. thanks For Watching