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BRONCHIAL ASTHMA Department of Pediatrics Soochow University Affiliated Children’s Hospital 由于哮喘和束手 无策的医生而死 于维也纳 Exhausted by asthma and hopeless doctors in Vienna Ludwig Van Beethoven 1770-1827 哮喘名人录 Global Strategy for Asthma Management and Prevention Evidence Category Sources of Evidence A Randomized clinical trials Rich body of data B Randomized clinical trials Limited body of data C Non-randomized trials Observational studies D Panel judgment consensus Outline of this lecture Revised 2006 Definition and Overview Diagnosis and Classification Asthma Medications Asthma Management and Prevention Program Definition of Asthma A chronic inflammatory disorder of the airways Many cells and cellular elements play a role Chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing Widespread, variable, and often reversible airflow limitation Burden of Asthma Asthma is one of the most common chronic diseases worldwide with an estimated 300 million affected individuals Prevalence increasing in many countries, especially in children A major cause of school/work absence Burden of Asthma Health care expenditures very high Developed economies might expect to spend 1-2 percent of total health care expenditures on asthma. Developing economies likely to face increased demand Poorly controlled asthma is expensive; investment in prevention medication likely to yield cost savings in emergency care Asthma Prevalence and Mortality Source: Masoli M et al. Allergy 2004 In China, there are 30,000,000 asthmatic patients. Etiology Asthma is a multifactorial disorder,caused by a combination of genetic predisposition and environmental factors Asthma is one manifestation of atopy Asthma is belong to a multi-genetic inherited disorder In most asthmatic childhood characterized by raised serum IgE levels Eosinophilia Eczema Allergic rhinitis and conjunctivitis hay fever Risk Factors for Asthma Host factors: predispose individuals to, or protect them from, developing asthma Environmental factors: influence susceptibility to development of asthma in predisposed individuals, precipitate asthma exacerbations, and/or cause symptoms to persist Factors that Influence Asthma Development and Expression Host Factors Genetic - Atopy - Airway hyperresponsiveness Gender Obesity Environmental Factors Indoor allergens Outdoor allergens Occupational sensitizers Tobacco smoke Air Pollution Respiratory Infections Diet Factors that Exacerbate Asthma Allergens Respiratory infections Exercise and hyperventilation Weather changes Sulfur dioxide Food, additives, drugs Pathophysiology The airway chronic inflammation is “three S” Spasm –smooth muscle spasm Swelling—mucosal oedema Secretion—mucosal hypersecretion Pathophysiology SPASMA SWELLING SECRETION INFLAMMATORY CELL BHR Asthma Inflammation: Cells and Mediators Source: Peter J. Barnes, MD Mechanisms: Asthma Inflammation Source: Peter J. Barnes, MD Asthma Inflammation: Cells and Mediators Source: Peter J. Barnes, MD Airway inflammation Healthy person Asthmatic patient These lungs appear essentially normal, but are normal-appearing because they are the hyperinflated lungs of a patient who died with status asthmaticus Is it Asthma? 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 Asthma Diagnosis History and patterns of symptoms Measurements of lung function - Spirometry - Peak expiratory flow Measurement of airway responsiveness Measurements of allergic status to identify risk factors Extra measures may be required to diagnose asthma in children 5 years and younger and the elderly History Recurrent episodes of cough, wheeze and breathlessness A diagnosis of asthma in infants(under 1 year or 2 years) may be particularly difficult In the some children, a nocturnal cough may be the only symptom Asthma is a clinical diagnosis Examination Auscultation of the chest is usually normal Wheezing Crackles Differential diagnosis Acute bronchiolitis Pneumonia Foreign body aspiration Croup Cystic fibrosis Cardiac failure TB Sometime, the diagnosis is more difficult, special in infant Investigation X-ray PEFR(Peak Expiratory Flow Rate) Lung function Typical Spirometric (FEV1) Tracings Volume FEV1 Normal Subject Asthmatic (After Bronchodilator) Asthmatic (Before Bronchodilator) 1 2 3 4 Time (sec) 5 Note: Each FEV1 curve represents the highest of three repeat measurements Measuring Variability of Peak Expiratory Flow Measuring Airway Responsiveness Classification of Severity CLASSIFY SEVERITY Clinical Features Before Treatment Symptoms STEP 4 Severe Persistent STEP 3 Moderate Persistent STEP 2 Mild Persistent Nocturnal Symptoms Continuous Limited physical activity Frequent Daily Attacks affect activity > 1 time week > 1 time a week but < 1 time a day 60% predicted Asymptomatic and normal PEF between attacks Variability > 30% 60 - 80% predicted > 2 times a month Variability > 30% 80% predicted Variability 20 - 30% < 1 time a week STEP 1 Intermittent FEV1 or PEF 2 times a month 80% predicted Variability < 20% The presence of one feature of severity is sufficient to place patient in that category. Clinical Control of Asthma No (or minimal)* daytime symptoms No limitations of activity No nocturnal symptoms No (or minimal) need for rescue medication Normal lung function No exacerbations * Minimal = twice or less per week Levels of Asthma Control Characteristic Controlled Partly controlled (All of the following) (Any present in any week) Daytime symptoms None (2 or less / week) More than twice / week Limitations of activities None Any Nocturnal symptoms / awakening None Any Need for rescue / “reliever” treatment None (2 or less / week) More than twice / week Lung function (PEF or FEV1) Normal < 80% predicted or personal best (if known) on any day Exacerbation None One or more / year Uncontrolled 3 or more features of partly controlled asthma present in any week 1 in any week Asthma Management and Prevention Program: Five Components 1. Develop Patient/Doctor Partnership 2. Identify and Reduce Exposure to Risk Factors 3. Assess, Treat and Monitor Asthma 4. Manage Asthma Exacerbations 5. Special Considerations Revised 2006 Asthma Management and Prevention Program: Five Interrelated Components 1. Develop Patient/Doctor Partnership 2. Identify and Reduce Exposure to Risk Factors 3. Assess, Treat and Monitor Asthma 4. Manage Asthma Exacerbations 5. Special Considerations Asthma Management and Prevention Program Goals of Long-term Management Achieve and maintain control of symptoms Maintain normal activity levels, including exercise Maintain pulmonary function as close to normal levels as possible Prevent asthma exacerbations Avoid adverse effects from asthma medications Prevent asthma mortality Asthma Management and . Prevention Program Asthma can be effectively controlled in most patients by intervening to suppress and reverse inflammation as well as treating bronchoconstriction and related symptoms Early intervention to stop exposure to the risk factors that sensitized the airway may help improve the control of asthma and reduce medication needs. Asthma Management and Prevention Program Although there is no cure for asthma, appropriate management that includes a partnership between the physician and the patient/family most often results in the achievement of control Asthma Management and Prevention Program Component 1: Develop Patient/Doctor Partnership Guidelines on asthma management should be available but adapted and adopted for local use by local asthma planning teams Clear communication between health care professionals and asthma patients is key to enhancing compliance Asthma Management and Prevention Program Component 1: Develop Patient/Doctor Partnership Educate continually Include the family Provide information about asthma Provide training on self-management skills Emphasize a partnership among health care providers, the patient, and the patient’s family Asthma Management and Prevention Program Component 1: Develop Patient/Doctor Partnership Key factors to facilitate communication: Friendly demeanor Interactive dialogue Encouragement and praise Provide appropriate information Feedback and review Example Of Contents Of An Action Plan To Maintain Asthma Control Your Regular Treatment: 1. Each day take ___________________________ 2. Before exercise, take _____________________ WHEN TO INCREASE TREATMENT Assess your level of Asthma Control In the past week have you had: Daytime asthma symptoms more than 2 times ? No Yes Activity or exercise limited by asthma? No Yes Waking at night because of asthma? No Yes The need to use your [rescue medication] more than 2 times? No Yes If you are monitoring peak flow, peak flow less than________? No Yes If you answered YES to three or more of these questions, your asthma is uncontrolled and you may need to step up your treatment. HOW TO INCREASE TREATMENT STEP-UP your treatment as follows and assess improvement every day: ____________________________________________ [Write in next treatment step here] Maintain this treatment for _____________ days [specify number] WHEN TO CALL THE DOCTOR/CLINIC. Call your doctor/clinic: _______________ [provide phone numbers] If you don’t respond in _________ days [specify number] ______________________________ [optional lines for additional instruction] EMERGENCY/SEVERE LOSS OF CONTROL If you have severe shortness of breath, and can only speak in short sentences, If you are having a severe attack of asthma and are frightened, If you need your reliever medication more than every 4 hours and are not improving. 1. Take 2 to 4 puffs ___________ [reliever medication] 2. Take ____mg of ____________ [oral glucocorticosteroid] 3. Seek medical help: Go to _____________________; Address___________________ Phone: _______________________ 4. Continue to use your _________[reliever medication] until you are able to get medical help. Asthma Management and Prevention Program Factors Involved in Non-Adherence Medication Usage Non-Medication Factors Difficulties associated with inhalers Misunderstanding/lack Complicated regimens Fears Fears about, or actual side effects Inappropriate Cost Distance to pharmacies of information about side-effects expectations Underestimation Attitudes Cultural Poor of severity toward ill health factors communication Asthma Management and Prevention Program Component 2: Identify and Reduce Exposure to Risk Factors Measures to prevent the development of asthma, and asthma exacerbations by avoiding or reducing exposure to risk factors should be implemented wherever possible. Asthma exacerbations may be caused by a variety of risk factors – allergens, viral infections, pollutants and drugs. Reducing exposure to some categories of risk factors improves the control of asthma and reduces medications needs. Asthma Management and Prevention Program Component 2: Identify and Reduce Exposure to Risk Factors Reduce exposure to indoor allergens Avoid tobacco smoke Avoid vehicle emission Identify irritants in the workplace Explore role of infections on asthma development, especially in children and young infants Asthma Management and Prevention Program Influenza Vaccination Influenza vaccination should be provided to patients with asthma when vaccination of the general population is advised However, routine influenza vaccination of children and adults with asthma does not appear to protect them from asthma exacerbations or improve asthma control Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma The goal of asthma treatment, to achieve and maintain clinical control, can be achieved in a majority of patients with a pharmacologic intervention strategy developed in partnership between the patient/family and the health care professional Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma Depending on level of asthma control, the patient is assigned to one of five treatment steps Treatment is adjusted in a continuous cycle driven by changes in asthma control status. The cycle involves: - Assessing Asthma Control - Treating to Achieve Control - Monitoring to Maintain Control Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma A stepwise approach to pharmacological therapy is recommended The aim is to accomplish the goals of therapy with the least possible medication Although in many countries traditional methods of healing are used, their efficacy has not yet been established and their use can therefore not be recommended Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma The choice of treatment should be guided by: Level of asthma control Current treatment Pharmacological properties and availability of the various forms of asthma treatment Economic considerations Cultural preferences and differing health care systems need to be considered Levels of Asthma Control Partly controlled Characteristic Controlled Daytime symptoms None (2 or less / week) More than twice / week Limitations of activities None Any Nocturnal symptoms / awakening None Any Need for rescue / “reliever” treatment None (2 or less / week) More than twice / week Lung function (PEF or FEV1) Normal < 80% predicted or personal best (if known) on any day Exacerbation None (Any present in any week) One or more / year Uncontrolled 3 or more features of partly controlled asthma present in any week 1 in any week Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma The choice of treatment should be guided by: Level of asthma control Current treatment Pharmacological properties and availability of the various forms of asthma treatment Economic considerations Cultural preferences and differing health care systems need to be considered Component 4: Asthma Management and Prevention Program Controller Medications Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β2-agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral β2-agonists Anti-IgE Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age Drug Low Daily Dose (g) > 5 y Age < 5 y Medium Daily Dose (g) > 5 y Age < 5 y Beclomethasone 200-500 100-200 >500-1000 >200-400 Budesonide 200-600 100-200 600-1000 >200-400 Budesonide-Neb Inhalation Suspension Ciclesonide 250-500 80 – 160 High Daily Dose (g) > 5 y Age < 5 y >1000 >1000 >500-1000 >400 >400 >1000 80-160 >160-320 >160-320 >320-1280 >750-1250 >2000 >1250 >200-500 >500 >500 Flunisolide 500-1000 500-750 >1000-2000 Fluticasone 100-250 100-200 >250-500 Mometasone furoate 200-400 100-200 > 400-800 >200-400 >800-1200 Triamcinolone acetonide 400-1000 400-800 >1000-2000 >800-1200 >2000 >320 >400 >1200 Component 4: Asthma Management and Prevention Program Reliever Medications inhaled β2-agonists Rapid-acting Systemic glucocorticosteroids Anticholinergics Theophylline Short-acting oral β2-agonists Component 4: Asthma Management and Prevention Program Allergen-specific Immunotherapy Greatest benefit of specific immunotherapy using allergen extracts has been obtained in the treatment of allergic rhinitis The role of specific immunotherapy in asthma is limited Specific immunotherapy should be considered only after strict environmental avoidance and pharmacologic intervention, including inhaled glucocorticosteroids, have failed to control asthma Perform only by trained physician REDUCE LEVEL OF CONTROL TREATMENT OF ACTION maintain and find lowest controlling step partly controlled consider stepping up to gain control INCREASE controlled uncontrolled exacerbation step up until controlled treat as exacerbation REDUCE INCREASE TREATMENT STEPS STEP STEP STEP STEP STEP 1 2 3 4 5 Treating to Achieve Asthma Control Step 1 – As-needed reliever medication Patients with occasional daytime symptoms of short duration A rapid-acting inhaled β2-agonist is the recommended reliever treatment (Evidence A) When symptoms are more frequent, and/or worsen periodically, patients require regular controller treatment (step 2 or higher) Treating to Achieve Asthma Control Step 2 – Reliever medication plus a single controller A low-dose inhaled glucocorticosteroid is recommended as the initial controller treatment for patients of all ages (Evidence A) Alternative controller medications include leukotriene modifiers (Evidence A) appropriate for patients unable/unwilling to use inhaled glucocorticosteroids Treating to Achieve Asthma Control Step 3 – Reliever medication plus one or two controllers For adults and adolescents, combine a low-dose inhaled glucocorticosteroid with an inhaled longacting β2-agonist either in a combination inhaler device or as separate components (Evidence A) Inhaled long-acting β2-agonist must not be used as monotherapy For children, increase to a medium-dose inhaled glucocorticosteroid (Evidence A) Treating to Achieve Asthma Control Additional Step 3 Options for Adolescents and Adults Increase to medium-dose inhaled glucocorticosteroid (Evidence A) Low-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A) Low-dose sustained-release theophylline (Evidence B) Treating to Achieve Asthma Control Step 4 – Reliever medication plus two or more controllers Selection of treatment at Step 4 depends on prior selections at Steps 2 and 3 Where possible, patients not controlled on Step 3 treatments should be referred to a health professional with expertise in the management of asthma Treating to Achieve Asthma Control Step 4 – Reliever medication plus two or more controllers Medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β2-agonist (Evidence A) Medium- or high-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A) Low-dose sustained-release theophylline added to medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β2-agonist (Evidence B) Treating to Achieve Asthma Control Step 5 – Reliever medication plus additional controller options Addition of oral glucocorticosteroids to other controller medications may be effective (Evidence D) but is associated with severe side effects (Evidence A) Addition of anti-IgE treatment to other controller medications improves control of allergic asthma when control has not been achieved on other medications (Evidence A) Treating to Maintain Asthma Control When control as been achieved, ongoing monitoring is essential to: - maintain control - establish lowest step/dose treatment Asthma control should be monitored by the health care professional and by the patient Treating to Maintain Asthma Control Stepping down treatment when asthma is controlled When controlled on medium- to high-dose inhaled glucocorticosteroids: 50% dose reduction at 3 month intervals (Evidence B) When controlled on low-dose inhaled glucocorticosteroids: switch to once-daily dosing (Evidence A) Treating to Maintain Asthma Control Stepping down treatment when asthma is controlled When controlled on combination inhaled glucocorticosteroids and long-acting inhaled β2agonist, reduce dose of inhaled glucocorticosteroid by 50% while continuing the long-acting β2-agonist (Evidence B) If control is maintained, reduce to low-dose inhaled glucocorticosteroids and stop longacting β2-agonist (Evidence D) Treating to Maintain Asthma Control Stepping up treatment in response to loss of control Rapid-onset, short-acting or long-acting inhaled β2-agonist bronchodilators provide temporary relief. Need for repeated dosing over more than one/two days signals need for possible increase in controller therapy Treating to Maintain Asthma Control Stepping up treatment in response to loss of control Use of a combination rapid and long-acting inhaled β2-agonist (e.g., formoterol) and an inhaled glucocorticosteroid (e.g., budesonide) in a single inhaler both as a controller and reliever is effecting in maintaining a high level of asthma control and reduces exacerbations (Evidence A) Doubling the dose of inhaled glucocorticosteroids is not effective, and is not recommended (Evidence A) Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger Childhood and adult asthma share the same underlying mechanisms. However, because of processes of growth and development, effects of asthma treatments in children differ from those in adults. Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger Many asthma medications (e.g. glucocorticosteroids, β2- agonists, theophylline) are metabolized faster in children than in adults, and younger children tend to metabolize medications faster than older children Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger Long-term treatment with inhaled glucocorticosteroids has not been shown to be associated with any increase in osteoporosis or bone fracture Studies including a total of over 3,500 children treated for periods of 1 – 13 years have found no sustained adverse effect of inhaled glucocorticosteroids on growth Asthma Management and Prevention Program Component 3: Assess, Treat and Monitor Asthma – Children 5 Years and Younger Rapid-acting inhaled β2-agonists are the most effective reliever therapy for children These medications are the most effective bronchodilators available and are the treatment of choice for acute asthma symptoms Asthma Management and Prevention Program Component 4: Manage Asthma Exacerbations Exacerbations of asthma are episodes of progressive increase in shortness of breath, cough, wheezing, or chest tightness Exacerbations are characterized by decreases in expiratory airflow that can be quantified and monitored by measurement of lung function (FEV1 or PEF) Severe exacerbations are potentially life-threatening and treatment requires close supervision Asthma Management and Prevention Program Component 4: Manage Asthma Exacerbations Treatment of exacerbations depends on: The patient Experience of the health care professional Therapies that are the most effective for the particular patient Availability of medications Emergency facilities Asthma Management and Prevention Program Component 4: Manage Asthma Exacerbations Primary therapies for exacerbations: Repetitive administration of rapid-acting inhaled β2agonist Early introduction of systemic glucocorticosteroids Oxygen supplementation Closely monitor response to treatment with serial measures of lung function Asthma Management and Prevention Program Special Considerations Special considerations are required to manage asthma in relation to: Pregnancy Surgery Rhinitis, sinusitis, and nasal polyps Occupational asthma Respiratory infections Gastroesophageal reflux Aspirin-induced asthma Anaphylaxis and Asthma Asthma Management and Prevention Program: Summary Asthma can be effectively controlled in most patients by intervening to suppress and reverse inflammation as well as treating bronchoconstriction and related symptoms Although there is no cure for asthma, appropriate management that includes a partnership between the physician and the patient/family most often results in the achievement of control Asthma Management and Prevention Program: Summary A stepwise approach to pharmacologic therapy is recommended. The aim is to accomplish the goals of therapy with the least possible medication The availability of varying forms of treatment, cultural preferences, and differing health care systems need to be considered Acute severe asthma Respiratory rate over 50 breaths/min Pulse over 140 beats/min Use of accessory muscles Too breathless to talk Life-threatening feature Cyanosis Silent chest(insufficient airflow to generate wheeze) Exhaustion:poor respiratory effort Agitation, diminished consciousness Peak flow meter PARI Spacer Turbuhaler 思考题 Write short notes on the following: 1. The management of a 5-year-old girl referred with recurrent wheeze and nocturnal cough who has a strong family history of atopy and allergy. 2. The important features of an asthma inhaler device prior to prescribing such a device for an 8-year girl. 3. The management of the respiratory system in 12-year-old child with severe cystic fibrosis. (answer in text P70) Thank you Scenes of Children’s Hospital of Soochow University