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Asthma
chronic inflammatory disorder of the airways infiltration of mast cells, eosinophils and lymphocytes wheeze, cough, chest tightness and shortness of breath
Mast cell
Neutrophil Eosinophil
Subepithelial fibrosis Plasma leak Oedema Sensory nerve activation Cholinergic reflex Bronchoconstriction Hypertrophy / hyperplasia
Barnes PJ
Inflammatory processes
Barnes PJ
Epidemiology / pathology
Pathophysiology
chemical mediators
Nonuniform ventilation
atelectasis
hyperinflation
Decreased complicance
Increased work of breathing
Decreased surfactant
Pulmoary vasoconstriction
acidosis
Alveolar hypoventilation
Pco2 Po2
Contributing Factors
respiratory infections small size at birth diet air pollution smoking
Hereditary/genes
Causal Factors
indoor allergens
passive active
outdoor allergens
occupational sensitisers
flour / grain dust (bakery) paint, glue or plastic fumes soldering flux natural rubber latex
wood dust
Clinical manifestations
The onset of an asthma exacerbation
may be acute or insidious during younger childhood. Acute episodes are most often caused exposure to irritants or allergens. Exacerbation precipitated by viral respiratory infections are slower in onset.
dyspnea with prolonged expiration and use of accessory muscles of respiration, cyanosis, hyperinflation of the chest, tachycardia. Wheezing may be absent in extreme respiratory distress, only after bronchodilator treatment wheeze can occur again.
Laboratory evaluation
Asthma:
diagnosis
Asthma diagnosis
history and pattern of symptoms physical examination measurements of lung function evaluation of allergic status
Is it asthma?
cough wheeze
breathlessness
chest tightness
symptoms occur or worsen at night or after exposure to trigger colds go to the chest or take >10 days to clear
aerosol chemicals
drugs (NSAIDs, -blockers)
The best of three PEF measurements is compared with the normal predicted for that individual based on age, height and sex.
PEF curves
PEF (L / min)
Day
Morning Evening Diagnosis
Clinical exacerbation
PEF
Exacerbation
Days
An acute severe attack of asthma refers to the onset of symptoms severe enough to require emergency treatment
STEP 4
Severe persistent
Continuous Limited physical activity Daily Use b2-agonist daily Attacks affect activity >1 time a week but <1 time a day <1 time a week Asymptomatic and normal PEF between attacks
Frequent
STEP 3
Moderate persistent
STEP 2
Mild persistent
STEP 1
Intermittent
no emergency visits
no need for quick relief (as needed) 2-agonist normal physical activity including exercise
Treatment strategy
identify and avoid triggers that make asthma worse achieve control by selecting appropriate medication treat asthma attacks promptly and effectively
Pharmacological therapy
Relievers
Controllers
inhaled corticosteroids inhaled long-acting 2agonists inhaled cromones oral anti-leukotrienes oral theophyllines oral corticosteroids
RELIEVERS MEDICATION
Quick relief medicine or rescue medicine. Rapid acting bronchodilators that act to relieve bronchoconstriction.
ROUTE OF ADMINISTRATION
INHALATION
Pressurized metered dose inhalers ( MDI) MDI-plus-spacer Breath actuated MDI Dry powder inhalers Nebulised
ORAL
PARENTERAL
Use intermittently to control episodes of bronchoconstriction Use only on impending asthma attack/during asthma attack
Mechanism of action: Bronchodilator Enhance mucociliary clearance Modulate mediators release from mast cells and basophils Example : Inhaled : Salmeterol , formeterol Oral : Bambuterol Salbutamol SR Terbutaline SR Clenbuterol
CONTROLLER MEDICATIONS
Are medications taken daily on a long term basis that are useful in getting and keeping persistent asthma under control. Prophylactic, preventive or maintenance medications Include
Inhaled glucocorticosteroids Systemic glucocorticosteroids Theophylline Long acting inhaled b2 agonist Long acting oral b2 agonist Leukotriene modifiers
GLUCOCORTICOSTEROIDS
Mechanisms of action :
Reduced airway inflammation Efficacy in improving lung function, decreasing airways hyperresponsiveness, reducing symptoms, reducing frequency and severity of exacerbations and improving quality of life.
GLUCOCORTICOSTEROID
Side effects Local effects oropharyngeal candidiasis, dysphonia, upper airway irritation
Systemic adverse effects depends on the dose and potency of glucocrticosteroids , absorption in the gut, first past effect of liver.
Systemic adverse effects include : skin thinning, easy bruising, cataract, obesity, adrenal suppression, hypertension, diabetes and myopathy.
METHYLXANTHINES
GIT Symptoms nausea, vomiting CVS Symptoms tachycardia, arrhythmias Drug interaction : Erythromycin, cimetidine and rifampicin
Anti-cholinergics
Inhaled ipratropium bromide. Mechanism of action : Bronchodilator. Efficacy : Bronchodilator actions are less potent than those of inhaled 2-agonists, slower onset of action which peaks 30 60 min. Side-effect : Dry mouth.
LEUKOTRIENE MODULATORS
MECHANISM OF ACTION :
Patient education essential at every step Reduce therapy if controlled for at least 3 months Continue monitoring
Avoid or control triggers STEP 1: INTERMITTENT CONTROLLER: none RELIEVER Inhaled 2agonist p.r.n.
Step 1
Step 1: Intermittent asthma
Controller
Reliever
Inhaled b2-agonist prn (not more than 3x a week) Inhaled b2-agonist or cromone prior to exercise or allergen exposure
None required
Step 2
Step 2: Mild persistent asthma
Controller
Daily inhaled corticosteroid (200-500 mg), cromone, sustained release theophylline, or anti-leukotriene
Reliever
Inhaled b2-agonist prn (but less than 3-4 times per day)
If still not controlled, particularly nocturnal symptoms, increase inhaled steroid (500-800 mg) or add long-acting bronchodilator
Step 3
Step 3: Moderate persistent asthma
Controller
Daily inhaled corticosteroid > 500 mg Daily long-acting bronchodilator Consider anti-leukotriene
Reliever
Inhaled b2-agonist prn (but less than 3-4 times per day)
A long-acting inhaled 2-agonist is the first choice add on therapy to inhaled steroids
Step 4
Step 4: Severe persistent asthma
Controller
Daily inhaled corticosteroid 800-2000 mg Daily long-acting bronchodilator Daily / alternate day oral corticosteroid
Reliever
Inhaled b2-agonist prn (but less than 3-4 times per day)
Patients with severe persistent asthma are often poorly controlled despite using combinations of all available controller medications.
Summary guidelines
gain control step up if control is not achieved and sustained step down if control is sustained for at least 3 months review treatment every 3-6 months
A total of 825 adult patients with moderate-tosevere asthma were randomised into 4 treatment groups based on bid doses as follows : - budesonide 100 ug bid + placebo - budesonide 100 ug bid + formorterol 9 ug bid - budesonide 400 ug bid + placebo - budesonide 400 ug bid + formorterol 9 ug bid
0.5
10
L / min
Months
12
Conclusion
Co-formulated products are generally less expensive than giving the two constituents separately.
Management of asthma during pregnancy should be aggressive. Cooperation between the resp. physician and obstetrcian throughout pregnancy for women with severe asthma.
Beta2 agonists. There is no evidence of a teratogenic risk. Ipratopium bromide / Sodium cromoglycate. Safe for use during pregnancy. Salmeterol/formoterol. Have not been tested extensively in pregnant women.
Theophyllines. May aggravate the nausea and gastroesophageal reflux. May cause transient neonatal tachycardia and irritability. Inhaled corticosteroids. Has good safety profile in pregnancy. Anti-leukotrienes. No data is available on the use of this agent in pregnant women.
Oral corticosteroids. Sometimes necessary for severe asthma but usually only for short periods. An increased risk of cleft palate has been reported in animals given huge doses. Breastfeeding. Should be continued in women with asthma. In general, asthma medications are safe during pregnancy and lactation and the benefits outweigh any potential risks to the fetus and baby.