1. ASTHMA

2. INTRODUCTION Asthma is a disorder of the respiratory system that leads to episodic difficulty in breathing. It is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells,eosinophils,T lymphocytes, macrophages, neutrophils and epithelial cells. In susceptible individuals this inflammation causes recurrent episodes of wheezing,breathlessness,chest tightness and coughing. These are usually associates with variable airflow obstruction that is often reversible.

3. AETIOLOGY The specific abnormality underlying asthma is hyper reactivity of the lungs to one or more stimuli. This can also occur in certain patients with chronic bronchitis and allergic rhinitis but usually to a lesser extent. One of the most common trigger factors is the allergen found in the house dust mite. Allergens Pollens,moulds,house dust mite, animals Industrial chemicals Isocyanate containing paints, epoxy resins,aluminium,hair sprays.

4. Cont… Drugs Aspirin, ibuprofen and other prostaglandin synthetase inhibitors, beta blockers. Foods nuts, fish, sea food, dairy products, food colouring Other industrial chemicals Wood or grain dust, cotton dust, cigarette etc Miscellaneous Cold, exercise, hyperventilation,viral respiratory tract infections, emotion or stress

5. PATHOPHYSIOLOGY Mast cell components are released as a result of an IgE antibody reaction on the surface of the cell. The mast cell releases histamine and other mediators of inflammation. Eg- leukotrienes, prostaglandins, bradykinin, and various chemotactic agents that attract eosinophils and neutrophils. Histamine triggers rapid bronchoconstriction where as leukotrienes such as LTC 4, LTD 4,and LTE 4 constrict at a slower rate. The chemotactic agents cause infiltration of the macrophages into the lumen of airways.

6. Cont.. Macrophages release prostaglandins,thromboxane and platelet- activating factor(PAF). PAF causes bronchial hyperreactivity and respiratory capillaries to leak plasma which increases mucosal oedema. Eosinophils release various inflammatory mediators such as LTC 4 and PAF. In asthma hypertrophy of bronchial glands and goblet cells occurs that produce mucus. It plugs the airways. Mucociliary clearance is also decreased due to inflammation of epithelial cells. This can result bronchoconstriction

7. T-lymphocyte activation leads to release of cytokines from type 2 T- helper (TH2) cells that mediate allergic inflammation (interleukin [IL]- 4, IL-5, and IL-13). Conversely, type 1 T-helper (TH1) cells produce IL-2 and interferon- γ that are essential for cellular defense mechanisms. Allergic asthmatic inflammation may result from an imbalance between TH1 and TH2 cells. Bronchial epithelial cells participate in inflammation by releasing eicosanoids, peptidases, matrix proteins, cytokines, and nitric oxide. Epithelial shedding results in heightened airway responsiveness, altered permeability of the airway mucosa, depletion of epithelial- derived relaxant factors, and loss of enzymes responsible for degrading inflammatory neuropeptides.

8. CLINICAL MANIFESTATIONS Persistent cough Recurrent episodes of difficulty in breathing associates with wheezing Chest tightness Shortness of breath Abnormal lung function Acute severe asthma Breathlessness at rest, Breath sounds diminished Cardiac stress Low arterial oxygen tension Increased breath rate Increased pulse rate, tachypnea, tachycardia

9. DIAGNOSIS Lung function assessment by using spirometer The most useful test for abnormalities in airway function is FEV 1 (Forced Expiratory Volume) and another volume that is commonly measured is FVC(Forced Vital Capacity). It is reported as FEV 1 /FVC ratio. It is a reproducible measure of the capabilities of the lungs.

10. Cont.. Peak flow meter measures PEFR(Peak Expiratory Flow Rate) It is used to assess the improvement or deterioration in the disease as well as the effectiveness of the treatment. Test for PaO 2 and PaCO 2.

11. TREATMENT Therapeutic goals  Reducing inflammation  Increasing bronchodilation  Restoration of normal airways function  Prevention of severe acute attacks  Avoidance of recognized trigger factors

12. CHRONIC ASTHMA The pharmacological management of asthma depends upon the frequency and severity of patient’s symptoms. I.Sympathomimetics β 2 adrenergic receptor stimulation activates adenyl cyclase, which produce an increase in intracellular cAMP. This cause relaxation of bronchial smooth muscles and bronchodilation Short acting agents Salbutamol 2-4mg oral Inh. 100-200µg 3-4 times daily Terbutaline 5mg oral Long acting agents Inh. Salmeterol 25µg bid Inh. Formeterol 12-24µg bid

13. Cont.. ADR head ache tachycardia peripheral vasodilation nervousness

14. Cont.. II. Methyl xanthines Produce bronchodilation by inhibition of phosphodiesterase and inhibition of calcium ion influx into smooth muscles Theophylline Aminophylline ADR tachycardia gastro intestinal disturbances insomnia seizures palpitation

15. Cont.. III. Anticholinergics These agents produce bronchodilation by inhibiting cholinergic receptors in larger airways Slow acting agents Ipratropium bromide 80µg 4 times daily Long acting agents Tiotropium bromide ADR dry mouth urinary retention blurred vision constipation

16. Cont.. IV.Anti-inflammatory agents Inhalational Beclomethasone Budesonide Systemic Prednisolone Hydrocortisone Decrease mucous production Inhibition of release of proteolytic enzymes from leukocytes Inhibition of prostaglandins

17. Cont.. Prednisolone-40-60mg Inh. Beclomethasone 100-400µg in 2 div doses Inh. Budesonide 200-800µg in 2 div doses Inh. Fluticasone 200-500µg in 2 div doses ADR Inhaled corticosteroids hoarseness oral candidasis adrenal suppression

18. Cont.. oral corticosteroids Cushing syndrome osteoporosis Precipitation diabetes peptic ulceration

19. Leukotriene antagonists : montelukast, zafirlukast. Used in combination with corticosteroids. Find importance in aspirin induced asthma, due to role of leukotrienes in this form of asthma. ADR : upper respiratory tract infections, diarrhoea, headache.

20. ACUTE SEVERE ASTHMA The management of acute asthma depends on the severity of the attack and its response to treatment as well as an appreciation of the patient’s past medication history and present treatment. Features of acute severe asthma PEF ≤ 50% of predicted or best Can’t complete sentences in one breath Respirations ≥ 25 breath/min Pulse > 110 beats/min

21. Cont.. Immediate management of acute severe asthma Oxygen 40-60% Nebulizer Salbutamol 5 mg or terbutaline 10 mg Prednisolone tablets 40-60 mg or intravenous hydrocortisone 200 mg or both if very ill. If life threatening features are present such as cyanosis, bradycardia, confusion, unconsciousness intravenous bronchodilators can be used. Intravenous aminophylline –bolus dose of 250 mg over 30 min. Salbutamol 200 µg over 10 min if patient is already taking oral theophylline

22. PATIENT COUNSELING Understand the patient about their diseases condition. Educate the patient about the action of each medicines and correct use of inhalational devices. Self management plan. Avoid allergens. Educate the patient about aim of the treatment and the possible side effects.