1. ASTHMA

2. Objectives 1.Definition of asthma 2.Causes of asthma and risk factors 3.Diagnosis 4.Treatment 5.Acute exacerbation of asthma

3. Asthma Asthma Chronic disease of the airways that may cause WheezingBreathlessness Chest tightness Nighttime or early morning coughing Episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment.

4. Definition : Chronic lung disease characterized by:Chronic lung disease characterized by: –Airway narrowing that is reversible (± completely) either spontaneously or with treatment –Airway inflammation –Airway hyper-responsiveness to a variety of stimuli.

8. The Spirogram

9. Asthma Mortality Rates by Race United States: 1979-2005 White Black Source: Underlying Cause of Death; CDC National Center for Health Statistics * Age-adjusted to 2000 U.S. population ICD-9ICD-10 Other

10. Risk Factors for Developing Asthma: Genetic Characteristics The body’s predisposition to develop an antibody called immunoglobulin E (IgE) in response to exposure to environmental allergens

11. Environmental Facotors: Viral/Bacterial infections Chemical irritants: industrial, household Air pollution: CO, ozone Tobacco smoke Dust mite/cockroach allergens Animal dander, Exercise, cold air, emotion, stress Genetic Factors: Genetic alterations on chromosomes 5 and 11, and polymorphisms of IgE INFLAMMATION Airway Hyper-responsiveness Airflow Obstruction Asthma Symptoms

12. Environmental Factors : Biological Agents Sufficient evidence of causal relationshipSufficient evidence of causal relationship –House dust mite Sufficient evidence of associationSufficient evidence of association –None found Limited or suggestive evidence of associationLimited or suggestive evidence of association –Cockroach (among pre-school aged children) –Respiratory syncytial virus (RSV) Chemical Agents Sufficient evidence of causal relationshipSufficient evidence of causal relationship –None found Sufficient evidence of associationSufficient evidence of association –Environmental Tobacco Smoke (among pre-school aged children) Limited or suggestive evidence of associationLimited or suggestive evidence of association –None found

13. Diagnosing Asthma * Troublesome cough, particularly at night *Awakened by coughing *Coughing or wheezing after physical activity *Breathing problems during particular seasons *Coughing, wheezing, or chest tightness after allergen exposure *Colds that last more than 10 days *Relief when medication is used

14. Diagnosis of Asthma History of exercise or cold air participating dyspnea.History of exercise or cold air participating dyspnea. PFT using spirometry with ≥ 12% improvement in peak expiratory flow rate (PEFR) or peak expiratory volume in one second (FEV1) after bronchodilator administration helps in diagnosis.PFT using spirometry with ≥ 12% improvement in peak expiratory flow rate (PEFR) or peak expiratory volume in one second (FEV1) after bronchodilator administration helps in diagnosis. Skin prick tests to identify allergens.Skin prick tests to identify allergens.

15. Diagnosing Asthma: Spirometry T est lung function when diagnosing asthma

16. The Spirogram

19. Treatment of Asthma  Goals f oAsthma Management:  Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness at night, in the early morning, or after exertion ).  Maintain normal or near normal pulmonary function.  Maintain normal activity levels ( including exercise and other physical activity.  Prevent recurrent exacerbations of asthma and minimize the need for emergency department visits or hospitalizations.  Provide optimal pharmacotherapy with minimal or no adverse effects.  Meet patients ’ and families ’ expectations of and satisfaction with asthma care.

20. Pharmacological treatment of asthma

21. 1-Short-acting Inhaled  2 -agonists Short-acting inhaled  2 -agonists are the fastest acting and most effective therapies for the relief of acute asthma symptoms, including wheezing, dyspnea, and chest tightness.Short-acting inhaled  2 -agonists are the fastest acting and most effective therapies for the relief of acute asthma symptoms, including wheezing, dyspnea, and chest tightness.  2 -selective therapies (e.g., albuterol, pirbuterol, and terbutaline)  2 -selective therapies (e.g., albuterol, pirbuterol, and terbutaline) No clinical advantages among agents. Product selection decisions should be based on factors, including patient preference, cost of treatment, and availability of various choices for delivery of inhalation therapy.No clinical advantages among agents. Product selection decisions should be based on factors, including patient preference, cost of treatment, and availability of various choices for delivery of inhalation therapy.

22. 2-Long-acting Inhaled  2 -agonists Currently, Formoterol and salmeterol are the only long- acting inhaled  2 -agonists available in the United StatesCurrently, Formoterol and salmeterol are the only long- acting inhaled  2 -agonists available in the United States Causing bronchodilation by relaxing the smooth muscle in the airwayCausing bronchodilation by relaxing the smooth muscle in the airway Monotherapy of LABA chronic use in the absence of inhaled corticosteroids is not recommendedMonotherapy of LABA chronic use in the absence of inhaled corticosteroids is not recommended Studies in adults and children with asthma have shown that LABA monotherapy increases in the frequency of asthma exacerbationsStudies in adults and children with asthma have shown that LABA monotherapy increases in the frequency of asthma exacerbations

23. Combination Salmeterol and Fluticasone : Advantages of combining salmeterol with an inhaled fluticasone improves lung functions, improves symptoms. Advantages of combining salmeterol with an inhaled fluticasone improves lung functions, improves symptoms.

24. 3-Leukotriene Modifiers Montelukast and zafirlukast Montelukast and zafirlukast Leukotriene modifiers prevent the action of leukotrienes in the body. Leukotrienes are released from mast cells, basophils and eosinophils. The release of leukotrienes causes airway constriction, increased mucus production, swelling and inflammation in the lungs. This presents as wheezing, shortness of breath in asthmaLeukotriene modifiers prevent the action of leukotrienes in the body. Leukotrienes are released from mast cells, basophils and eosinophils. The release of leukotrienes causes airway constriction, increased mucus production, swelling and inflammation in the lungs. This presents as wheezing, shortness of breath in asthma These agents should be considered as alternatives to inhaled corticosteroids and other treatments for patients 12 years old and older with mild asthmaThese agents should be considered as alternatives to inhaled corticosteroids and other treatments for patients 12 years old and older with mild asthma

25. Leukotriene Modifiers cont Zafirlukast 10 mg 2 times/day is now approved by the FDA for asthma management in children 7-11 years of age. Zafirlukast 10 mg 2 times/day is now approved by the FDA for asthma management in children 7-11 years of age. Montelukast 10 mg/day is indicated for treating asthma in patients 15 years and older, children ages 6-14 years at 5 mg/day. and 2-5 years at 4mg/day.Montelukast 10 mg/day is indicated for treating asthma in patients 15 years and older, children ages 6-14 years at 5 mg/day. and 2-5 years at 4mg/day. Both Zafirlukast and montelukast are effective as monotherapy in asthma.Both Zafirlukast and montelukast are effective as monotherapy in asthma.

26. Corticosteroids are the most potent and effective therapy currently available for treating asthma. Corticosteroids are the most potent and effective therapy currently available for treating asthma. Topical used reduce the systemic exposure to these agents by reducing absorption through the gastrointestinal tract. Topical used reduce the systemic exposure to these agents by reducing absorption through the gastrointestinal tract. Children should use spacer devices when using inhaled corticosteroid. Children should use spacer devices when using inhaled corticosteroid. ICSs suppress inflammation in the lungs and are recommended for prophylactic treatment of asthma.ICSs suppress inflammation in the lungs and are recommended for prophylactic treatment of asthma. 4- Inhaled Corticosteroids:

27. HIGHMEDIUM LOW DOSE AdultChildAdultChildAdultChild >840>480>1.200Unknown>672>320>800>1.000504-840240-480600-1.200Unknown336-672160-320400-800 500- 1.000 168 -504 80 -240 200 -600 Unknown84-336 80 -160 200-400 250 -500 Beclomethasone dipropionateCFC-MDI (42& 84μg/MD) HFA-MDI (40& 80μg/MD) Budesonide DPI( 200 μg/MD) NEB( 200 & 500 μg/amp)

28. HIGHMEDIUM LOW DOSE AdultChildAdultChildAdultChild >2.000>660>2.000>1.250>440>1.200 1.000- 2.000 264-660 750- 1.250 176-440 800- 1.200 500-1.00088-264400-1.000 500 -750 88 -176 400 -800 FlonisolidCFC-MDI (250 μg/MD) Fluticasone propionate CFC-MDI (44,110,220 μg/MD) Triamcinolone acetonide CFC-MDI (100 μg/MD)

30. Receptor-bindingAffinityInhaled Bioavailability (%) T ½ (hrs) InhaledCorticosteroid1.83.613.59.4183922253816-301.63.6UK2.014.4FlunisolideTriamcinoloneBeclomethasoneBudesonideFluticasone

31. Nebulizer Budesonide Inhalation Suspension : First inhaled corticosteroid product available for inhalation by nebulizer. Two dosage strengths are available in 2 ml single-dose ampules, 0.25 mg and 0.5 mg.First inhaled corticosteroid product available for inhalation by nebulizer. Two dosage strengths are available in 2 ml single-dose ampules, 0.25 mg and 0.5 mg. The recommended starting dose depends on previous corticosteroids therapy; 0.5 mg/day is suggested for patients on previous inhaled asthma therapy, and 1 mg/day is recommended for patients on oral corticosteroids.The recommended starting dose depends on previous corticosteroids therapy; 0.5 mg/day is suggested for patients on previous inhaled asthma therapy, and 1 mg/day is recommended for patients on oral corticosteroids.

32. New therapies 3- Formoterol: 3- Formoterol: is a long-acting inhaled  2 -agonist with a duration of effect similar to that of salmeterol.is a long-acting inhaled  2 -agonist with a duration of effect similar to that of salmeterol. The faster onset of effect for formoterol, less than 5 minutes, is an advantage that distinguishes it from salmeterol ( the onset of which is about 20 minutes ). ”

33. (1) Environmental control and education (2) Short-acting  2-agonist on demand SubclinicalIntermittentPersistent Symptom characteristics Very mildMildModerate Moderately severe severe Severity of asthma Inhaled glucocorticosteroid (daily dose ) Additionaltherapy + Prednisone low medium High 3

34. DisadvantagesAdvantagesDevice Requires water-soluble drug. Significant drug wasted (residual volume) Numerous factors can affect delivery Device variability ( brand to brand, lt to lot ) Inconvenient, bulky, costly, and time consuming Requires electrical power source Nebulizer must be kept clean ( potential for infection) costly Simple to use (requires minimal coordination) can be used in mechanically ventialated patients Nebulizer

35. DisadvantagesAdvantagesDevice Requires significant coordination Requires minimal time for treatments Small, portable Can be used in mechanically ventilated patients. Reduce coordination required. Improve pulmonary drug deposition. Reduces risk for adverse effects. Metered- dose inhaler MDI + spacer

36. DusadvantagesAdvantagesDevice Children+obstructed pt may not generate adequate inspiratory flow. Increase cough. Increase cough. Cannot be used in mechanically ventilated pt. Potential of drug aggregation. Increase oropharyngeal drug deposition and systemic absorption. Minimal coordination. Improve pulmonary drug deposition. Lactose excipients. Dry powder inhaler.

37. Acute Asthma Exacerbation

38. Levels of severity of acute asthma exacerbations Near fatal asthma Raised PaCO 2 and/or requiring mechanical ventilation with raised inflation pressures Although there are no universally agreed diagnostic criteria for NFA, it is typically associated with the presence of hypercapnia, acidemia, altered state of consciousness and the development of cardiorespiratory arrest requiring endotracheal intubation and mechanical ventilation

39. Levels of severity of acute asthma exacerbations Near fatal asthma Raised PaCO 2 and/or requiring mechanical ventilation with raised inflation pressures Life threatening asthma Any one of the following in a patient with severe asthma: PEF <33% best or predicted PEF <33% best or predicted SpO 2 <92% SpO 2 <92% PaO 2 <60 mmgh PaO 2 <60 mmgh normal PaCO 2 (34 – 45 mmgh) normal PaCO 2 (34 – 45 mmgh) silent chest silent chest cyanosis cyanosis feeble respiratory effort feeble respiratory effort bradycardia bradycardia dysrhythmia dysrhythmia hypotension hypotension exhaustion exhaustion confusion confusion coma coma

40. Levels of severity of acute asthma exacerbations Near fatal asthma Raised PaCO 2 and/or requiring mechanical ventilation with raised inflation pressures Life threatening asthma Any one of the following in a patient with severe asthma: PEF <33% best or predicted PEF <33% best or predicted SpO 2 <92% SpO 2 <92% PaO2 <60 mmgh PaO2 <60 mmgh normal PaCO2 (34 – 45 mmgh) normal PaCO2 (34 – 45 mmgh) silent chest silent chest cyanosis cyanosis feeble respiratory effort feeble respiratory effort bradycardia bradycardia dysrhythmia dysrhythmia hypotension hypotension exhaustion exhaustion confusion confusion coma coma Acute severe asthma Any one of: PEF 33-50% best or predicted PEF 33-50% best or predicted respiratory rate  25/min respiratory rate  25/min heart rate  110/min heart rate  110/min inability to complete sentences in one breath inability to complete sentences in one breath

41. Levels of severity of acute asthma exacerbations Near fatal asthma Raised PaCO 2 and/or requiring mechanical ventilation with raised inflation pressures Life threatening asthma Any one of the following in a patient with severe asthma: PEF <33% best or predicted PEF <33% best or predicted SpO 2 <92% SpO 2 <92% PaO2 <60 mmgh PaO2 <60 mmgh normal PaCO2 (34 – 45 mmgh) normal PaCO2 (34 – 45 mmgh) silent chest silent chest cyanosis cyanosis feeble respiratory effort feeble respiratory effort bradycardia bradycardia dysrhythmia dysrhythmia hypotension hypotension exhaustion exhaustion confusion confusion coma coma Acute severe asthma Any one of: PEF 33-50% best or predicted PEF 33-50% best or predicted respiratory rate  25/min respiratory rate  25/min heart rate  110/min heart rate  110/min inability to complete sentences in one breath inability to complete sentences in one breath Moderate asthma exacerbation Increasing symptoms Increasing symptoms PEF >50-75% best or predicted PEF >50-75% best or predicted No features of acute severe asthma No features of acute severe asthma

42. Levels of severity of acute asthma exacerbations Near fatal asthma Raised PaCO 2 and/or requiring mechanical ventilation with raised inflation pressures Life threatening asthma Any one of the following in a patient with severe asthma: PEF <33% best or predicted PEF <33% best or predicted SpO 2 <92% SpO 2 <92% PaO2 <60 mmgh PaO2 <60 mmgh normal PaCO2 (34 – 45 mmgh) normal PaCO2 (34 – 45 mmgh) silent chest silent chest cyanosis cyanosis feeble respiratory effort feeble respiratory effort bradycardia bradycardia dysrhythmia dysrhythmia hypotension hypotension exhaustion exhaustion confusion confusion coma coma Acute severe asthma Any one of: PEF 33-50% best or predicted PEF 33-50% best or predicted respiratory rate  25/min respiratory rate  25/min heart rate  110/min heart rate  110/min inability to complete sentences in one breath inability to complete sentences in one breath Moderate asthma exacerbation Increasing symptoms Increasing symptoms PEF >50-75% best or predicted PEF >50-75% best or predicted No features of acute severe asthma No features of acute severe asthma Brittle asthma Type 1: wide PEF variability (>40% diurnal variation for >50% of the time over a period >150 days) despite intense therapy Type 1: wide PEF variability (>40% diurnal variation for >50% of the time over a period >150 days) despite intense therapy Type 2: sudden severe attacks on a background of apparently well-controlled asthma Type 2: sudden severe attacks on a background of apparently well-controlled asthma

43. Management of Asthma Exacerbations: Home Treatment

49. Management of acute severe asthma PEF >75% predicted Time Measure PEF and arterial saturations PEF >75% best or predicted: mild 5 min Give usual bronchodilator 15-30 min Clinically stable AND PEF >75% 60 min 120 min POTENTIAL DISCHARGE