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Bronchial Asthma Ayman A Hamid Farghaly MD FCCP 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 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 Remodeling Environment Normal Airway Function Repair Remodeling Smooth muscle hypertrophy/hyper plasia Matrix deposition Angiogenesis Epithelial and goblet cell phenotype alterations Genetic predispositi on Asthma Injury Genetic predisposition for remodeling 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 Asthma Prevalence and Mortality 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 Genetics of Asthma While it is generally agreed that there is a major hereditary contribution to the etiology of asthma, the inheritance patterns are complex, and asthma cannot be simply classified as having an autosomal-dominant, recessive, or sex-linked mode of inheritance. Genetics & Asthma .. Chromosomes 2q, 3p, 5q, 6p, 12q, 13q, 19q, and 21q are likely to contain genes for allergy and asthma. Factors that Exacerbate Asthma Allergens Respiratory infections Exercise and hyperventilation Weather changes Sulfur dioxide Food additives , drugs 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 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 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 Nonatopic Asthma Patients who have none of the typical features of atopy. Older . Intrinsic asthma may involve activation by an as-yet-unidentified antigen. Putative nonallergic antigens that may cause such reactions include viral antigens or inappropriately recognized “self-antigens.” 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 (All of the following) Partly controlled (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 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 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 Education 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 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 Factors Involved in Non-Adherence Medication Usage Difficulties associated with inhalers Complicated regimens Fears about, or actual side effects Cost Distance to pharmacies Non-Medication Factors Misunderstanding/lack of information Fears about side-effects Inappropriate expectations Underestimation of severity Attitudes toward ill health Cultural factors Poor communication 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 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 Systemic glucocorticosteroids 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 >320 Flunisolide 500-1000 500-750 >1000-2000 >750-1250 >2000 >1250 Fluticasone 100-250 100-200 >250-500 >200-500 >500 >500 Mometasone furoate 200-400 100-200 > 400-800 >200-400 >800-1200 Triamcinolone acetonide 400-1000 400-800 >1000-2000 >800-1200 >2000 >400 >1200 Component 4: Asthma Management and Prevention Program Reliever Medications Rapid-acting inhaled β2-agonists 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 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) 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 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 Bronchial Thermoplasty 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 Neutrophilic inflammation in asthma The release of IL-8 and GRO-α from airway epithelial cells may be stimulated by viral infection. Allergens may stimulate dendritic cells to release IL-23, activating Th17 cells to release TNF-α. This enhances inflammation and stimulates the release of IL-8 and GRO-α, which recruit neutrophils into the airways. These release further IL-8 plus transforming growth factorβ (TGF-β), which activates fibroblasts to cause fibrosis, and neutrophil elastase and matrix metalloproteinase (MMP)-9 which stimulate mucus hypersecretion from goblet cells. Neutrophils & Asthma Is asthma a Neutrophilic disease? Asthmatic patients who show an increased neutrophil count in the airways tend to be older, and have an overall increase in the total number of inflammatory cells compared to patients with an eosinophilic pattern of asthma. They are also more likely to be female and non-atopic. An increased neutrophil count is also found in the induced sputum of patients with asthma who smoke, and sputum neutrophils are also increased in asthmatic patients during exacerbations, which are mostly due to infections of the upper respiratory tract. In children with asthma, a marked increase in neutrophils is also seen in induced sputum during exacerbations. An increase in neutrophil numbers is now a recognised feature in patients with asthma, particularly in those with more severe disease, and in exacerbations. The increase in neutrophil numbers is likely to be a contributing factor to loss of asthma control, indicating that there may be a therapeutic benefit to targeting neutrophils. Neutrophil asthma appears to be poorly responsive to corticosteroids even when given at high doses, suggesting that other therapies may be needed. LABA have recently been shown to reduce neutrophilic inflammation in asthma, an effect that may be mediated via inhibition of IL-8 or other related chemokines. This provides a rationale for the use of combination inhalers in asthma treatment, Asthma & Pregnancy Asthma is one of the most common conditions that can complicate a pregnancy, and the question whether the asthma itself or the medications used to treat it have any negative effects on the unborn baby or infant has become increasingly urgent. Asthma in itself does not increase the risk of having a premature birth. but taking steroid tablets or theophylline does. No increased risk was seen with taking inhaled corticosteroids. The risk of low birth weight or size increases with the severity of the asthma symptoms, regardless of the medication. The recommended is a more active treatment of pregnant women with mild or moderate asthma, Add steroid tablets only if the asthma gets considerably worse.
