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Chronic inflammatory disease of airways Increased responsiveness of tracheobronchial tree Multiplicity of stimuli Episodic disease Narrowing of airways (acutely and gradually), relieved spontaneously or after therapy.
Risk Factors (for development of asthma) INFLAMMATIONAirwayHyperresponsiveness Airflow Obstruction Risk Factors Symptoms (for exacerbations)
Asthma is one of the most common chronic diseases worldwide —160 million patients suffer from asthma Prevalence increasing in many countries, especially in children — 1~4% in adult, 3~5% in children in China A major cause of school/work absence An overall increase in severity of asthma increases the pool of patients at risk for death
Worldwide Variation in Prevalence ofAsthma SymptomsInternational Study ofAsthma and Allergies inChildren (ISAAC)Lancet 1998;351:1225
Environmental Genetic factors factors MixedAtopic factors Non-asthma atopic/idiosyncratic asthma Early onset Late onset
Gross overdistention of lungs, non-collapsible Gelatinous plugs of exudate in bronchial branches, down to terminal bronchioles Hypertrophy of bronchial smooth muscle Hyperplasia of mucosal & submucosal blood vessels Mucosal oedema Thickening of basement membrane Eosinophilic infiltrates in the bronchial walls
History and patterns of symptoms Physical examination Measurements of lung function Measurements of allergic status to identify risk factors
Recurrent episodes of wheezing Troublesome cough at night Cough or wheeze after exercise Cough, wheeze or chest tightness after exposure to airborne allergens or pollutants Colds ―go to the chest‖ or take more than 10 days to clear
Lung function tests- FEV1/FVC ratio (<70%or normal), PEFR Bronchodilator test- reversibility (>15% improvement in FEV1) CXR Sputum (thick, with eosinophils + Charcots- Leyden crystals), blood (IgE levels, eosinophilia) Allergy tests- skin, inhalants, catecholamines etc.
Asthma COPDcannot be fully prevented can be prevented can be fully controlled cannot be fully reversed does not progress is progressive
COPD and Asthma are different diseases! Asthma COPD Allergic Small airway inflammation of COPD narrowing airways & & Asthma Bronchospasm Hyper- (15%) & responsiveness Airway collapse Bronchospasm Maintain Control inflammation bronchodilatation with ICS with regularMinimal bronchodilator bronchodilator
History COPD AsthmaSmoker or ex- Nearly always VariablesmokerOnset Usually > 40 Most < 30 years yearsBreathlessness Gradual and Paroxysmal progressiveChronic cough Common Infrequentwith sputum
To effectively controll asthma by…A. Suppressing and reversing inflammationB. Treating bronchoconstriction and related symptoms
Life-threatening medical emergencies Treatment is often most safely undertaken in a hospital or hospital-based emergency department
Initial Assessment History, Physical Examination, PEF or FEV1 Initial Therapy Bronchodilators; O2 if neededGood Response Incomplete/Poor Response Respiratory FailureObserve for at Add Systemic Glucocorticosteroids least 1 hour Good Response Poor Response If Stable, Discharge to Discharge Admit to Hospital Admit to ICU Home
Goals of Long-term Management Achieve and maintain control of symptoms Prevent asthma episodes or attacks Maintain pulmonary function as close to normal levels as possible Maintain normal activity levels, including exercise Avoid adverse effects from asthma medications Prevent development of irreversible airflow limitation Prevent asthma mortality
Uncontrolled Controlled (mild Partly controlled (moderate- Characteristic intermittent) (mild persistent) severe (All of the following) (Any present in any week) persistent) None (2 or less / More thanDaytime symptoms week) twice / week Limitations of 3 or more None Any features of activities partly Nocturnal controlled symptoms / None Any asthma awakening present in Need for rescue / None (2 or less / More than any week“reliever” treatment week) twice / week < 80% predicted or Lung function Normal personal best (if (PEF or FEV1) known) on any day Exacerbation None One or more / year 1 in any week
Preventers - anti-inflammatory Relievers - short acting bronchodilators that provide rapid relief of symptoms Controllers - sustained bronchodilator action with unproven or mild anti-inflammatory action
Classification of drugs used in the maintenance treatment of asthma PREVENTERS CONTROLLERS RELIEVERS Anti-inflammatory Sustained broncho- For quick relief of action to prevent dilator action but weak symptoms and use in asthma attacks or unproven anti- acute attacks as p.r.n. inflammatory effect dose onlyInhaled Long-acting ß2 Short-acting ß2corticosteroids agonists agonists Beclomethasone Salmeterol Salbutamol Budesonide Formoterol Fenoterol Fluticasone Methylxanthines Terbutaline Flunisolide Hexoprenaline Triamcinolone Sustained-release Orciprenaline theophyllinesOral Anti-cholinergicscorticosteroids Leukotriene IpratropiumPrednisone receptor Short-actingPrednisolone antagonists** theophyllinesMethylprednisolone Montelukast Zafirlukast ** Provisional categorisation pending further data
A convenient and reliable multi-dose device New propellant is HFA (ozone-friendly) Rapidly moving, short- duration plume Impaction of spray in oropharynx likely Evaporating spray feels cold 70% of dose lodges in pharynx and much may be swallowed, 15 -20% in lung
Remove mouthpiece cap Shake inhaler (suspensions only) Breathe out Place actuator mouthpiece between lips Fire while breathing in slowly and deeply Continue to inhale Hold breath (for 10 sec)
CRUCIAL ERRORS Firing device at or after end of inhalation Stopping inhalation / inhaling through nose (―cold Freon‖ effect) Bizarre errors (e.g. not removing mouthpiece cap) NON-CRUCIAL ERRORS Firing device before start of inhalation Fast inhalation No breath-hold / short breath-hold Failure to shake inhaler (suspensions only)
Useful for small children (used with snug-fitting face mask) Useful in improving inhaled steroid deposition in those with difficulty co- ordinating firing of pMDI during or before inhalation Shake inhaler (suspensions only) Insert pMDI into spacer Breathe out Fire while (or before) breathing in slowly and deeply Continue to inhale Hold breath (for 10 sec) Repeat with second puff
Remove cover (device-specific) Prepare device / load dose (device-specific) Pierce capsule (single-dose devices only) Breathe out gently Place mouthpiece between lips Inhale deeply and quickly* Breath-hold (device-specific) Replace cover and store in dry cool environment
Montelukast - SingulairZafirlukast - AccolateAdvantages:• Unique mode of action• Anti-inflammatory – no bronchodilator effect• Very simple dosing: taken by mouth; single dose strength for children, another foradults• Safe• Use: – Add to inhaled corticosteroids – Monotherapy in mild allergic asthma (children)Disadvantages:• Poor efficacy (not better than theophylline for most endpoints especially in adults( More useful in children)• Expensive !
DISADVANTAGESADVANTAGES Bulky, inconvenient Easy to use correctly once Electricity supply usually needed prepared: relaxed tidal Preparation and assembly a problem, breathing especially for the elderly? Convenient way of Long treatment times delivering high doses Patients find them Cleaning / contamination issues reassuring Expensive Dose control possible in Patients rely on them instead of using sophisticated devices controller medications No propellants needed Their use can delay patients presenting to emergency departments and lead to asthma deaths (false sense of security) They are air and not oxygen-driven, so do not correct hypoxia
Reasons for poorpatient adherence to treatment Misunderstanding about need for both long-term preventive and quick-relief medications Difficulty with inhaler devices Fear of side effects or addiction Cost of medication Dislike of medication
Follow-upAt regular visits (every one to six months): Monitor asthma control – Review symptoms – Measure lung function – Assess compliance Modify the treatment plan – Reinforce compliance – Adjust medications
Kasper et-al. Harrison’s Principles of Internal Medicine, 16th edition: 2005; McGraw-Hill, New York, USA: pp1508-1516 Zhiwen Zhu. Pulmonary & Critical Care Medicine, 1st Affiliated Hospital of Sun Yat-Sen University, China