Bronchial Asthma PDF

Chest Bronchial asthma  Definition: ❑ Bronchial asthma: is a heterogeneous disease usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheezing, shortness of breath, chest tightness, and coughing tha...

Chest Bronchial asthma  Definition: ❑ Bronchial asthma: is a heterogeneous disease usually characterized by chronic airway inflammation. It is defined by the history of respiratory symptoms such as wheezing, shortness of breath, chest tightness, and coughing that vary over time and in intensity together with variable expiratory airflow limitation (GINA 2022). ❑ Atopy: production of high amounts of IgE in response to environmental allergens. ❑ Airway hyperresponsiveness: condition in which the airways narrow too easily or too much in response to a provoking stimulus.  Risk factors: ❑ Host factors 1. Genetic predisposition: including genes predisposing to atopy and genes predisposing to airway hyper-responsiveness 2. Obesity: there is a correlation between higher BMI & risk of developing asthma. 3. Sex: childhood asthma is more prevalent in boys than in girls. More females than males develop asthma during puberty and thereafter ❑ Environmental factors 1. Indoor allergens: House dust, several organic and inorganic compounds, including fibers, mold spores, pollen grains, insects & insect feces, mammalian danders, mites & mite feces (the most common indoor allergen), animal allergens (cat, dogs, rodents), cockroach allergen, fungi, mold, yeasts 2. Outdoor allergens; pollens (trees, grasses), fungi (Alternaria), molds, yeasts 3. Indoor air pollution: cooking or heating with natural gas, cooking on wood, kerosene, building and furnishing with foam installations, glues, fireboard… 4. Outdoor air pollution: industrial smog (sulfur dioxide), photochemical smog (ozone and nitrogen oxides) and exposure to traffic 5. Occupational sensitizers: over 300 substances have been associated with occupational asthma including low or high-molecular-weight sensitizers 6. Tobacco smoke (passive and active smoking): Tobacco smoking is associated with increased severity, low response to treatment and difficult asthma control 7. Respiratory infections: particularly with respiratory viruses and Chlamydia. 8. Diet: cow's milk, soy protein, fishes, eggs, processed food, low antioxidants 9. Low socioeconomic status: dietary habits, passive smoking, allergen exposure. 1  Chest  Pathogenesis: ▪ Asthma is a chronic inflammatory disorder of the airways ▪ Inflammatory cells: mainly eosinophils, mast cells, CD4 T lymphocytes, ▪ Inflammatory mediators: chemokines, cytokines, histamine, prostaglandins, cysteinyl leukotreines, nitric oxide, platelet activating factor, bradykinines. ▪ Early-phase asthmatic response: results from the activation of mast cells (bearing allergen-specific IgE) that results in secretion of mediators. These mediators induce contraction of airway smooth muscle, mucus hypersecretion, airway edema (vasodilatation and microvascular leakage) and airway thickening ▪ Late-phase asthmatic response: involves increased airway responsiveness and bronchial inflammation (eosinophils, basophils, lymphocytes and monocytes are recruited into inflamed airways and have enhanced survival). Both central and peripheral airways are inflamed ❑ Intrinsic non-allergic asthma: patients with intrinsic asthma show: ▪ Negative skin tests, normal serum total IgE, normal specific IgE antibodies ▪ Have no clinical or family history of atopy ▪ Have nasal polyps and aspirin sensitivity, ▪ Its onset is often preceded by a history of respiratory virus infection and disproportionately affects females and older patients. ▪ The clinical course is more severe. ▪ Intrinsic asthma may represent a form of autoimmunity triggered by infection.  Types of asthma: There are 2 types of asthma Many patients have features of both types. ❑ Intrinsic or idiosyncratic asthma (nonallergic 50%) ▪ A bronchial reaction occurs secondary to nonimmunologic stimuli, such as infection, irritating inhalant, cold air, exercise, and emotional upset. ▪ The asthma attacks are severe, and prognosis is less favorable. ❑ Extrinsic (allergic, atopic) asthma (20% of asthmatics) ▪ Results from sensitization. Specific immunoglobulins (IgE class [type 1]) are produced, and total serum IgE concentration is elevated. ▪ There is a positive family history of allergic disease. ▪ Extrinsic asthma is precipitated by allergens. ▪ Other symptoms include allergic rhinitis, urticaria, and eczema. ▪ Prognosis is good. 2  Chest  Clinical picture: ❑ Symptoms: ▪ Asthma symptoms: episodic dyspnea, wheezing, cough and chest tightness. ▪ Diagnostic criteria: more than one asthma symptoms that tend to be variable over time & intensity, worse at night or early morning, triggered by exercise, allergen, irritants, cold air, viral infection, respond to anti-asthma therapy, ends spontaneously or after treatment. ▪ The attack may persist as asthma exacerbation (may be fatal or near fatal). ▪ In between attacks, the patient is clinically free except in chronic asthma. ▪ Seasonal variability, positive family history of asthma or allergy and history of atopic disease (allergic rhinitis, urticarial, eczema, hey fever, spring catarrh). ❑ Physical examination: ▪ Physical finding in patients with asthma is often normal. ▪ Auscultation: The most usual auscultatory finding is wheezing (usually diffuse, polyphonic, bilateral and particularly expiratory) associated with vesicular breathing and prolonged expiration. Wheeze may be palpated. ▪ In-between attacks chest examination may be normal. ▪ Acute exacerbation (acute severe asthma): tachypnea, tachycardia, pulsus paradoxus, cyanosis, signs of hyperinflation, diminished breath & heart sounds up-to silent chest, use of accessory muscles of respiration.  Investigations: ▪ Spirometry: normal or reversible airflow obstructive. ▪ Peak expiratory flow rate (PEFR): using portable flow-meter, decreased PEFR with diurnal variation of > 20% on ≥ 3 days in a week for 2 weeks is considered to be diagnostic of asthma. Regular home monitoring of PEF ▪ Bronchial provocation tests: to assess airway hyper-responsiveness to inhaled methacholine, histamine, mannitol or exercise challenge causing 20% decrease in FEV1. It is not recommended as it is rarely diagnostic & can result in life-threatening bronchospasm. ▪ Markers of allergic component: positive skin testing or high serum IgE. ▪ Markers of airway inflammation: sputum eosinophilia >2%, exhaled NO & CO. ▪ Other tests: CXR, blood tests, and more extensive lung function studies are used to exclude other conditions that may mimic asthma.  Prevention: 1. Prevention of allergic sensitization (development of atopy) prenatally and perinatally mostly by prevention of tobacco exposure, exclusive breast feeding, prevention of exposure to cat or other allergens 2. Prevention & control of asthma symptoms and exacerbation: by reduction of exposure to risk factors (smoking, environmental or occupational agents) 3. Treatment of risk factors and comorbidities as obesity, smoking, rhinitis, sinusitis, polyposis and GERD should be treated. 4. Influenza vaccination every year. 3  Chest  Medications for asthma:  Route of administration: inhaled, oral and parenteral (subcutaneous, IM or IV). ✓ Anticholinergic is only available as inhales. ✓ Theophyllines are not available by inhalation  Types of inhalation therapy: 1. Pressurized metered dose inhalers (pMDIs), pMDI with spacer, soft mist 2. Dry powder inhalers as aerolizers, breezhaler, turbohalers, discus, ellipta 3. Nebulizer  Advantages of inhalation therapy: 1. High concentrations can be delivered to the airways 2. Minimal systemic absorption and side effects. 3. Fast onset of action of bronchodilators.  Relievers (rescue medications): short acting β2 agonists (SABA), short acting anticholinergic (SAMA) or fast-acting LABA/ICS.  Controllers (maintenance): inhaled corticosteroids, leukotriene modifiers, long acting β2 (inhaled and oral) agonists, sustained released theophylline, cromones, anti- IgE, anti-IL5/5R, anti-IL4R, systemic corticosteroids and oral anti-allergic compounds ❑ Bronchodilators:  Sympathomimetics: ▪ Mechanisms of bronchodilator action: activates adenyl cyclase, facilitating the conversion of ATP to cyclic AMP resulting in relaxation of bronchial smooth muscle. Other potentially beneficial non-bronchodilator effects include enhances mucociliary clearance, decrease vascular permeability, and may modulate mediator release from mast cells and basophils. ▪ They are subdivided into non-selective (isoprenaline) and selective β2 agonists (including short-acting as salbutamol, terbutaline & fenoterol and long-acting as formoterol, salmetrol, indacaterol, vilanterol, olodaterol) ▪ Main side effects: tremor, restlessness, tachycardia, hypokalemia, hypomagnesemia, hyperglycemia, tachyphylaxis  Anticholinergics: ▪ Mechanisms of bronchodilator action: competitive antagonists of acetylcholine at muscarinic receptor. ▪ They are subdivided into short-acting (ipratropium bromide) and long-acting (tiotropium bromide). They are given only by inhalation only. ▪ Main side effects: headache, flushed skin, blurred vision, tachycardia, palpitations, urinary retention, drying of mucous secretions 4 Chest  Thiophyllines: ▪ Mechanisms of bronchodilator action: inhibit phosphodiesterases (the antagonism of adenosine receptors) thereby retarding the hydrolysis and breakdown of cyclic AMP and cyclic GMP ▪ They are given only by all methods of administration except inhalation. ▪ Main side effects: nausea, vomiting, CNS stimulation, headache, tachycardia, SVT, seizures, hematemesis, hyperglycemia, hypokalemia. Theophylline has a narrow therapeutic index. Xanthines undergo metabolism by cyt P450 in the liver with multiple drug interaction. ❑ Anti-inflammatory: 1. Steroids: the main anti-inflammatory drugs. ICS is a corner stone drug ▪ Mechanisms of action: gene modulating effects, inhibition of arachidonic acid cascade, inhibition of histamine release, reduction of capillary permeability, reduction of circulating eosinophils, basophils, monocytes & lymphocytes, increased sensitivity of β2-adrenergic receptors to both endogenous catecholamines & administered β2-agonists and inhibit the growth of fibroblasts ▪ Systemic: short-acting (prednisolone, hydrocortisone dexamethazone) and long-acting (methylprednisolone, triamcinolone betamethazone). ▪ Inhaled CS: beclomethasone dipripionate, budesonide, fluticasone and ciclisonide. ▪ Main side effects: Inhaled: oral candidiasis, hoarseness. Systemic: cushing effects, growth retardation, osteoporosis, hypertension, cataracts, glucose intolerance, skin thinning, myopathy, euphoria, depression. 2. Leukotriene modifiers: given orally, include cysLT1 receptor antagonists as montelucast, zafirlucast and 5-lipo-oxygenase antagonists as zileuten 3. Anti-Ig E: SC omalizumab for severe asthma (sensitization in skin-prick test or specific or total serum IgE, or exacerbations in last year) 4. Anti-IL 5/IL5R: SC mepolizumab, IV reslizumab for severe eosinophilic asthma (exacerbations in last year, blood eosinophil ≥ 150 or ≥ 300/ul) 5. Anti-4R: SC dupilumab for severe eosinophilic asthma (exacerbations in last year, blood eosinophil ≥ 300/ul, or FeNo ≥ 25 ppb) 6. Mast cell stabilizers: as sodium cromoglicate and ketotifen (not used) 7. Non-sedating anti-histaminic: in asthma associated with allergic rhinitis 5  Chest  Assessing Asthma Control: ▪ First assess: confirm diagnosis, modifiable risk factors, comorbidities and inhaler technique and adherence ▪ Treat modifiable risk factors & comorbidities as smoking, obesity, anxiety ▪ Advice nonpharmacological therapies as physical activities, weight loss ▪ Consider adding sublingual immunotherapy in allergic asthma ▪ Consider step up if uncontrolled symptoms, exacerbation or risk, but first check diagnosis, inhaler technique and adherence ▪ Consider step down if symptom controlled for 3 months 6  Chest Management of asthma exacerbations  Definition: ▪ Acute or subacute worsening in symptoms and lung function from the patient usual status that is sufficient to require change in treatment.  Severity of exacerbations: ▪ The severity of asthma exacerbations may range from mild to life threatening. ▪ Features of life-threatening attacks are severe dyspnea, bradycardia, central cyanosis, confusion, drowsiness, silent chest, paradoxical thoraco-abdominal movement & disturbed ABG (PaCO2>50mmHg, PaO2