Bronchial Asthma: Overview, Control & Pathogenesis

Bronchial Asthma Overview

• Bronchial asthma is an allergic condition marked by reversible airway obstruction
• This obstruction results from bronchoconstriction, mucosal edema, cellular infiltration, and viscid secretions
• Asthma is clinically evident through dyspnea, coughing, and wheezing

Control of Bronchial Smooth Muscle Tone

• Bronchial smooth muscle tone is controlled by parasympathetic and sympathetic mechanisms
• Parasympathetic nerves supply bronchial muscles and contain muscarinic M3 receptors
• Stimulation of M3 receptors leads to bronchoconstriction and increased mucus secretion
• Abundant beta-2 adrenoceptors exist, producing bronchodilation

Pathogenesis of Bronchial Asthma

• Bronchial asthma pathogenesis involves allergic hypersensitivity and autonomic disturbances
• Exposure to an allergen causes sensitization through the generation of specific IgE
• IgE binds to mast cells
• Re-exposure to the same antigen leads to an antigen-antibody (Ag-Ab) interaction
• This results in mast cell degranulation and release of mediators like histamine, serotonin, kinins, prostaglandin, and angiot
• Resting bronchospasm activity from vagal input must be balanced with circulating catecholamines
• Disturbing this balance, such as with beta-blockers, can cause bronchospasm in susceptible individuals

Management of Bronchial Asthma

• Management includes treatments for acute attacks and preventative measures in between attacks

Drug Therapy for Bronchial Asthma

• Drug therapy involves bronchodilators, anti-inflammatory drugs, and supportive treatments

Bronchodilators: Sympathomimetics

• Beta-agonists are bronchodilators, with non-selective types being adrenaline and isoprenaline
• Selective beta-2 agonists include short-acting (salbutamol, terbutaline) and long-acting (salmeterol, formeterol) options
• Selective beta-2 agonists are favored because the lack the serious side effects associated with non-selective beta-agonists, such as palpitation, tachycardia, and arrhythmias
• Salbutamol selectively stimulates beta-2 adrenergic receptors and has a more selective action on the bronchi
• It also has a weaker action on the cardiovascular system and a more prolonged duration of action than isoprenaline
• Salbutamol can be administered orally or via inhalation
• Selective beta-2 receptor stimulants may cause tremors of skeletal muscles, more so with oral preparations; inhalation reduces this effect
• All selective beta-2 agonists, in high doses, can produce cardiovascular effects

Bronchodilators: Methylxanthines

• Methylxanthines like theophylline and aminophylline are effective bronchodilators, especially in severe acute asthma
• Theophylline inhibits phosphodiesterase, increases intracellular cAMP, and redistributes intracellular calcium ions
• Methylxanthines block adenosine receptors and stabilizes mast cell membranes to prevent mediator release
• For acute attacks, aminophylline is given at 250 mg slowly IV or by IV infusion
• Theophylline is used orally or rectally for prophylaxis
• Intravenous administration of aminophylline should be slow to prevent cardiac arrhythmias
• Theophylline oral preparations are contraindicated in peptic ulcer, and all methylxanthine preperations are contraindicated in epilepsy

Bronchodilators: Muscarinic Receptor Antagonists

• Atropine blocks muscarinic receptors in bronchial muscle but is ineffective in asthma
• This is because it causes excessive sputum dryness (difficult to expectorate), impairs ciliated bronchial epithelium, and causes systemic adverse effects
• Ipratropium bromide provides a more selective bronchodilator effect
• Ipratropium bromide has a lesser action on sputum viscosity, does not affect ciliated bronchial epithelium, and causes minimal systemic effects

Anti-Inflammatory Drugs: Corticosteroids

• Corticosteroids possess anti-inflammatory and anti-allergic properties
• Corticosteroids facilitate lipocortin synthesis
• Lipocortin diminishes phospholipase A2 activity and reduces arachidonic acid, PGs, and leukotrienes
• Corticosteroids reduce antibody formation, inhibit antigen-antibody reactions, stabilize mast cell membranes, reduce capillary permeability, and reduce mucosal edema
• Corticosteroids treat severe acute attacks, are used between attacks and treat status asthmaticus
• Corticosteroid inhalation preparations include beclomethasone, betamethasone, triamcinolone, budesonide, or fluticasone
• Parenteral corticosteroids include hydrocortisone sodium hemisuccinate (IV or IV infusion) and dexamethasone (IV or IV infusion)
• ACTH (IV or IM/day) is favored in children because it does not produce adrenal suppression or growth retardation
• Oral forms include prednisolone, dexamethasone, and betamethasone

Cortocosteroids: Adverse Effects

• Inhalation therapy may cause oral moniliasis which can be treated with nystatin lozenge
• It may also cause dysphonia due to weakness of adductor muscle of the cord (myopathy)
• Systemic adverse effects include adrenocortical suppression, hypothalamo-pituitary suppression, Cushing's syndrome
• Systemic adverse effects also include hypokalemia, hyperglycemia, salt and water retention, weight gain, hypertension and cataracts

Bronchial Asthma Prophylaxis (Between Attacks)

• Preventative drugs reduce or stop the frequency of attacks
• Include bronchodilators, adrenal steroids, mast cell stabilizers, leukotriene blockers, and Omalizumab

Bronchial Asthma Prophylaxis: Bronchodilators

• Selective beta-2 agonists, non-selective beta agonists, ephedrine, and methylxanthines

Bronchial Asthma Prophylaxis: Adrenal Steroids

• Prednisolone and beclomethasone dipropionate

Bronchial Asthma Prophylaxis: Mast Cell Stabilizers

• Disodium cromoglycate and ketotifen are included as mast cell stabilizers
• Mast cell stabilizers possibly block calcium flow into the mast cell, which prevents the release of allergic mediators like histamine and leukotrienes
• Ketotifen provides additional antihistaminic effects on H1 receptors
• Disodium cromoglycate may cause cough, a sense of suffocation, and dryness of the mouth
• Ketotifen might cause drowsiness

Bronchial Asthma Prophylaxis: Leukotriene Blockers

• Leukotriene receptor antagonists such as Montelukast and zafirlukast (orally)
• 5-lipoxygenase inhibitors such as zileuton (orally), which acts by decreasing leukotriene synthesis
• These all serve as prophylaxis of bronchial asthma
• Zileuton causes liver toxicity more frequently and systemic vasculitis is a rare adverse effect

Bronchial Asthma Prophylaxis: Omalizumab

• Omalizumab selectively binds to human IgE
• This inhibits IgE binding to its receptor on mast cells and basophils, inhibiting the release of inflammatory mediators
• Omalizumab it is used in patients resistant to conventional therapy, namely beta-2 agonists and inhaled corticosteroids
• The use of Omalizumab is limited by its high cost