This action might not be possible to undo. Are you sure you want to continue?
‘Asthma’ literally means ‘panting’ Asthma is a chronic inflammatory disorder of the airways These airways are hypersensitive to certain “triggers” in the environment Asthma cannot be cured but its symptoms can be controlled with proper environmental changes and medications
Conceptual model for the immunopathogenesis of asthma Phase 1. First exposure to allergens Exposure to an allergen Production of allergic antibodies (IgE’s) by immune system Phase 2.488 2 . No. 2002. LTD4. 31. LTE4) Leukotriene Basic granular protein o Hyperreactivity o o o o Bronchoconstriction Vasodilation Inflammation Edema o Bronchoconstriction o Vasodilation o Inflammation Epidemiology o More common in urban areas o Prevalence of asthma in adult population is 5.3% o Children suffer the most o About 7 million people including 4 million children are suffering from asthma in Bangladesh Ref: International Journal of Epidemiology. 2: 483 . Vol. Subsequent exposures to allergens Allergen + antibody (IgE) reaction on the surface of mast cells Immune cells rupture Histamine (LTC4.
of possible trigger factors- o Allergens (pollens. There are a no. moulds. animals) o Viral respiratory tract infections o Cold and dry air o Chemical irritants (industrial. laughter) Pathophysiology Asthma is a reversible airway disease with the following pathophysiological characteristics- o Airway hyperreactivity o Airway inflammation o Airflow obstruction Figure: Asthmatic airway 3 . household) o Drugs (aspirin.) o Exercise o Psychological stimuli (emotion. stress. house-dust mite. β adrenergic receptor blocker etc.Aetiology The specific abnormality of asthma is hyperreactivity of lungs to one or more stimuli.
It measures in liters. 4 . FEV1/FVC: This is the ratio of FEV1 to FVC. measured in litres. Any reduction indicates deterioration in lungs performance. measured in liters per second. Forced Expiratory Volume in 1 Second (FEV1): This is the amount of air that can be forcibly blow out in one second.Clinical manifestations Recurrent coughing Wheezing Chest tightness Shortness of breath Difficulty in sleeping Difficulty in breathing (dyspnea) Wake up at night because of coughing & chest tightness Investigation The two most common tools to measure lung function are: Spirometer Peak flow meter Forced Vital Capacity (FVC): This is the total amount of air that can be forcibly blow out after full inspiration.80%. In healthy adults this should be approximately 75 . Peak Expiratory Flow (PEF): This is the speed of the air moving out from the lungs at the beginning of the expiration.
but no more than one time per day o Nighttime symptoms occur greater than two times a month o Activity levels affected by the flare-ups o FEV1 or PEF is less than 80% of the predicted value. & the variation in PEF is 20-30% 5 . Mild intermittent: o Mild symptoms occurs in less than two times a week o Nighttime symptoms occur less than two times a month o Do not have problems in-between flare-ups o The variation in PEF is less than 20% 2. Mild persistent: o More than two times a week.Treatment There are basically three kinds of medicines: Quick relievers ■ Short-acting β2agonist ■ Anticholinergics ■ Short-acting theophylline ■ Systemic corticosteroids Protectors ■ Long-acting β2agonist ■ Sustained release theophylline ■ Sustained release salbutamol Controllers ■ ■ ■ ■ Corticosteroids Sodium cromoglycates Leukotriene antagonists Anti-IgE therapy Classification 1.
and PEF varies by more than 30% Step care management Treatment of chronic asthma can be given in a stepwise progression. Step 1: Inhaled short acting β2-agonist as needed Step 2: Standard dose inhaled corticosteroids + Step 1 Step 3: Increase dose of inhaled corticosteroids + Step 1 OR. according to the severity of the patient’s asthma symptoms.Classification 3. and others) 6 . Moderate persistent: o Asthma symptoms occurs once a day o Nocturnal symptoms occur more than once a week o Have to use inhaled short-acting β2-agonists every day o FEV1 and PEF values are 60-80% of the predicted values. and PEF varies by more than 30% 4. Step 2 + Inhaled long acting β2-agonist Step 4: High dose of inhaled corticosteroid + Inhaled long acting β2agonist + Step 1 Step 5: Step 4 + Oral therapy (oral steroids. Severe persistent: o Have continuous or frequent symptoms o Frequent nocturnal symptoms o Limited physical activity o FEV1 and PEF values are less than 60% of the predicted values.
Mode of action • • • • Relax airway smooth muscle Modulate mediator release from inflammatory cells Enhance mucociliary clearance Decrease vascular permeability Long-acting β2agonist Long-acting inhaled β2agonist (Salmeterol.Short-acting β2agonist Selective inhaled β2 adrenoreceptor agonists (Salbutamol. Formoterol) used when Standard introductory doses of inhaled glucocorticoids fail to achieve the control of asthma before raising the dose of inhaled glucocorticoids Protection required against asthma attack specially during night (nocturnal asthma) and exercise • Same as short-acting β2agonist • Effects persists for at least 12 hours Mode of action 7 . Terbutalin) are the mainstay of the management of asthma.
Fig: β2-Adrenoreceptor agonist signaling pathways Methylxanthines Only theophylline is clinically used as second-line bronchodilator. as well as. Mode of action • • • The bronchodilator effect may be related to phosphodiesterase (PDE) inhibition Excites the phrenic nerve which increase the activity of diaphragm. It is given with β-agonists for severe airflow obstruction. acts as anti-inflammatory Adenosine receptor antagonism (inhibit mediator release from mast cells) 8 .
Agonist Agonist Receptor Theophylline Receptor Adenyl cyclase PDE3.4 PDE5 Guanylyl cyclase ATP cAMP AMP GMP cGMP GTP PKA PKG Inflammatory cell inhibition Bronchodilatation Fig: Role of theophylline in Asthma Anticholinergics Prevent the action of acetylcholine. Commonly used anticholinergics are Ipratropium bromide and Oxitropium bromide Mode of action • • • Inhibit the action of acetylcholine at muscarinic receptors Block the increase of GMP which causes constriction Block reflex bronchoconstriction caused by inhaled irritants 9 .
mediators Fig: Role of anticholinergics in Asthma Fig: Role of sympathomimetic agents in Asthma 10 .CNS Vagus nerve Parasympathetic nerve ACh Parasympathetic ganglion Anticholinergics ACh Irritant receptors Airway epithelium ACh Submucosal gland Inflammatory cell Airway irritants.
Anti-Inflammatory medications Anti-inflammatory medicines (Beclomethasone. Fluticasone) reduce airway inflammation. Budesonide. Mode of action • • • • Modulate cytokine and chemokine production Inhibit eicosanoid synthesis Markedly inhibit the accumulation of leucocytes in lung tissue Decrease vascular permeability Sodium Cromoglycates Commonly used Sodium Cromoglycates are – Cromolyn Sodium and Nedocromil Sodium They are used as prophylaxis in- o Allergic asthma in children o Exercise induced asthma Mode of action Stabilizes mast cells 11 .
Mode of action: o Omalizumab binds tightly to free IgE in the circulation to form Omalizumab-IgE complexes o Omalizumab-IgE complexes cannot bind to IgE receptors on inflammatory cells.Leukotriene antagonists Leukotriene is a powerful bronchoconstrictor and vasodilator. Montelucast Mode of action: Selective competitive antagonist for leukotriene-receptor Leukotriene-Synthesis inhibitors: Zileuton Mode of action: Zileuton is a potent and selective inhibitor of 5lipoxygenase activity and thus inhibit the formation of leukotriene Anti-IgE therapy Omalizumab is the first “biological drug” approved for the treatment of asthma. thereby preventing the allergic reaction at a very early step in the process 12 . Leukotriene antagonists are of two types- Leukotriene-Receptor antagonists: Zafirlucast.
This action might not be possible to undo. Are you sure you want to continue?
We've moved you to where you read on your other device.
Get the full title to continue reading from where you left off, or restart the preview.