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Asthma Definition
Asthma
is a clinical syndrome of unknown etiology characterized by three distinct components: 1- recurrent episodes of airway obstruction that resolve spontaneously or as a result of treatment 2- airway hyperresponsiveness = exaggerated bronchoconstrictor responses to stimuli that have little or no effect in nonasthmatic subjects 3- inflammation of the airways
Asthma Prevalence:
One of the most common chronic disease, affects
approximately 300 million people worldwide The greatest increases in asthma prevalence have occurred in countries that have recently adopted an industrialized lifestyle All ages , predominantly early life with a peak age of 3 years Adults: 10-12% population Children 15% population 2:1 male/female preponderance in childhood but by adulthood the sex ratio has equalized
Asthma Types
Indoor allergens Outdoor allergens Occupational sensitizers Passive smoking Respiratory infections Air pollution Socioeconomic factors Family size
The 2007 Expert Panel Report 3 (EPR-3) of the National Asthma Education and Prevention Program (NAEPP) noted several key changes in pathophysiology of asthma:
The critical role of inflammation + considerable variability in the pattern of inflammation => phenotypic differences that may influence treatment responses
Current asthma treatment with anti-inflammatory therapy does not appear to prevent progression of the underlying disease severity
Asthma Pathophysiology
The
mast cells, eosinophils, epithelial cells, macrophages and activated T lymphocytes Structural cells of the airways including fibroblasts, endothelial cells, and epithelial cells, contribute to the chronicity of the disease Other factors such as cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway.
Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.
of normal balance between two "opposing" populations of Th lymphocytes (Th1 and Th2)
Chronic Asthma
Chronic inflammation of the airways is associated
with increased bronchial hyperresponsiveness and bronhospasm and typical symptoms after exposure to allergens, environmental irritants, viruses, cold air, or exercise In chronic asthma, airflow limitation may be only partially reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and subepithelial fibrosis) that occurs with chronic untreated disease
Asthma
Asthma Triggers
Allergens Upper respiratory tract viral infections Exercise and hyperventilation Cold air Sulfur dioxide and irritant gases Drugs (-blockers, aspirin) Stress Irritants (household sprays, paint fumes)
Asthma Diagnosis
Lung
Function Tests Simple spirometry confirms airflow limitation with a reduced FEV1,FEV1/FVC ratio and PEF Reversibility is demonstrated by a >12% and 200-mL increase in FEV1 15 minutes after inhaling a shortacting bronchodilator Measurements of PEF twice daily may confirm the diurnal variation in airflow obstruction Flow-volume loops show reduced peak flow and reduced maximum expiratory flow
Asthma Diagnosis
Airway Hyperresponsiveness can be measured by:
Methacholine or histamine challenge calculate the provocative concentration that reduces FEV1 by 20% rarely useful in clinical practice can be used in the differential diagnosis of chronic cough or in case of normal pulmonary function tests Exercise testing may demonstrate the postexercise bronchoconstriction if there is a history of EIA Allergen challenge rarely necessary to identify specific occupational agents
Asthma Diagnosis
Chest Radiography is usually normal hyperinflated lungs in severe patients pneumothorax in exacerbations pneumonia or eosinophilic infiltrates in
Asthma Diagnosis
Exhaled Nitric Oxide is now used as a
noninvasive test to measure eosinophilic airway inflammation the typically high-levels in asthma are reduced by ICS, so this may be a test of compliance with therapy Skin Prick Tests to common inhalant allergens are positive in allergic asthma and negative in intrinsic asthma
Asthma - Treatment
Table 254-2 Aims of Asthma Therapy
Minimal (ideally no) chronic symptoms, including nocturnal Minimal (infrequent) exacerbations No emergency visits Minimal (ideally no) use of a required 2-agonist
Asthma Treatment
The main drugs used for asthma can be divided in two categories: bronchodilators give rapid relief of symptoms through relaxation of airway smooth muscle controllers inhibit the underlying inflammatory process
Relaxation of airway smooth muscle (proximal and distal airways) Inhibition of mast cell mediator release Inhibition of plasma exudation and airway edema Increased mucociliary clearance Increased mucus secretion Decreased cough No effect on chronic inflammation
-2-adrenergic agonists
usually
3-6 hours duration of action Rapid onset of bronchodilation used as needed for symptom relief Increased use of SABAs indicates that asthma is not controlled Used in preventing EIA
Over 12 hours duration of action Given twice daily by inhalation Used in combination (fixed combination inhalers) with ICS, because alone they do not control the underlying inflammation Added to ICS they reduce exacerbations, improve asthma control at lower doses of corticosteroids
-2-adrenergic agonists
Side
Effects: Muscle tremor and palpitations especially in elderly patients Small potassium fall as a result of increased uptake by skeletal muscle cells but does not usually cause clinical problems Safety: Association between asthma mortality and the use of LABAs is related to the lack of use of concomitant ICS, as the LABAs fails in control the underlying inflammation
Effects: are related to plasma concentrations(rarely observed at plasma concentration <10mg/L) nausea , vomiting and headache (most common) diuresis and palpitations cardiac arrhythmias and epileptic seizures (at high doses)
High-protein, low-carbohydrate diet Barbecued meat Childhood Decreased Clearance Enzyme inhibition (cimetidine, erythromycin, ciprofloxacin, allopurinol, zileuton, zafirlukast) Congestive heart failure Liver disease Pneumonia Viral infection and vaccination High carbohydrate diet Old age
side effects: truncal obesity, bruising, osteoporosis, diabetes, hypertension, gastric ulceration, proximal myopathy, depression and cataracts
Asthma-Controller Therapies
Antileukotrienes:
montelukast, zafirlukast are given orally once or twice daily added to low doses of ICS Cromones: -cromolyn sodium, nedocromil sodium have short duration of action (at least 4 times daily by inhalation) so they have little benefit in the long-term control of asthma -very safe and were popular in the treatment of childhood asthma (now ICS are preferred)
Asthma- Treatment
Steroid-Sparing
Therapies: methotrexate, cyclosporin A, azathioprine, gold, and IV gamma globulin reduce the requirement for OCS in patients with sever asthma and serious side effects with OCS no long-term benefit and high risk of side effects
Asthma- Treatment
Anti-IgE:omalizumab
reduce the number of severe asthma exacerbations and improve asthma control very expensive and is only suitable for highly selected patients who are not controlled on maximal doses of inhaler therapy given as a subcutaneous injection every 24 weeks for 3 - 4 months
by face mask oxygen saturation >90% SABAs unsatisfactory response add inhaled anticholinergic In patients who are refractory to inhaled therapies slow infusion of aminophylline (monitor blood levels) Prophylactic intubation in case of impending respiratory failure (Pco2 normal or rises) Respiratory failure intubation and mechanical ventilation. NO sedatives (may depress ventilation). AB only if there are signs of pneumonia
Refractory Asthma
Approximately 5% of asthmatics Factors that cause poor control asthma: noncompliance with medication (particularly ICS) compliance may be improved by giving ICS as a combination with LABA that relieves symptoms Exposure to high ambient levels of allergens or unidentified occupational agents Sever rhinosinusitis,GOR, infection with Mycoplasma pneumoniae, Chlamydophyla pneumoniae, hyper- and hypothyroidism Drugs such as: beta-adrenergic blockers, aspirin and COX inhibitors
brittle asthma describes patients with asthma who maintained a wide variation in peak expiratory flow (PEF) despite high doses of inhaled steroids Type 1 brittle asthma: characterised by a maintained wide PEF variability (>40% diurnal variation for >50% of the time over a period of at least 150 days) despite considerable medical therapy including a dose of inhaled steroids of at least 1500g of beclomethasone (or equivalent) Type 2 brittle asthma: characterised by sudden acute attacks occurring in less than three hours without an obvious trigger on a background of apparent normal airway function or well controlled asthma
Special Considerations
Aspirin-Sensitive
Asthma 1-5% of asthmatics becomes worse with aspirin and other COX inhibitors Is usually preceded by perennial rhinitis and nasal polyps Aspirin even in small doses provokes rhinorrhea, conjunctival irritation, facial flushing and wheezing Treatment: - ICS, antileukotrienes - aspirin desensitization
Special Considerations
Asthma
in the Elderly Is more difficult to treat due to the side effects of drugs, the comorbidities which are more frequent at this age group and interactions with drugs such as -2-blockers,COX inhibitors, agents that may affect the theophylline clearance Pregnancy Its important to maintain good control of asthma during pregnancy May be safe treat with SABAs, ICS and theophylline There are less safety informations about drugs such as: LABAs, antileukotrienes, and anti-IgE If an OCS is needed it is better to use prednisone
Special Considerations
Cigarette Smoking Approximately 20% of asthmatics are smokers This patients have more severe disease, more frequent hospital admissions, faster decline in lung function and a higher risk of death Smoking interferes with the anti-inflammatory actions of corticosteroids smokers needs higher doses for asthma control Smoking cessation improves lung function and reduces the steroid resistance
Special Considerations
Surgery
Well-controlled asthma has no contraindication to anesthesia and intubation Patients treated with OCS will have adrenal suppression and should be treated with an increased dose of OCS immediately prior surgery Patients with FEV1<80% of their normal levels should be given OCS before surgery High-maintenance doses of steroids may be a contraindication to surgery because of increased risks of infection and delayed wound healing
Special Considerations
Bronchopulmonary Aspergillosis (BPA) Is a hypersensitivity lung disease due to bronchial
colonization by Aspergillus fumigatus that occurs in susceptible patients with asthma BPA is characterized by: Chest radiographic infiltrates particularly in the upper lobes Allergy prick skin to A. fumigatus always positive Serum Aspergillus precipitins low or undectable Central bronchiectasis Fibrotic stage may be associated with honeycombing Treatment with : OCS, oral antifungal itraconazole