1. ASTHMA: MANAGEMENT AND PREVENTION IN CHILDREN Lecturer: prof. Galyna Pavlyshyn prof. Galyna Pavlyshyn

2. THE BURDEN OF ASTHMA Asthma is a problem worldwide, with an estimated 300 million affected individuals; The World Health Organization has estimated that 15 million disability-adjusted life years (DALYs) are lost annually due to asthma. Annual worldwide deaths from asthma have been estimated at 250,000 and mortality does not appear to correlate well with prevalence.

3. WHAT IS KNOWN ABOUT ASTHMA? Asthma is a major cause of chronic morbidity and mortality throughout the world; There is evidence that its prevalence has increased considerably over the past 20 years, especially in children.

4. Unfortunately…asthma is one of the most common chronic diseases worldwide. The prevalence of asthma symptoms in children varies from 1 to more than 30 percent in different populations and is increasing in most countries, especially among young children; Fortunately… asthma can be effectively treated and most patients can achieve good control of their disease. WHAT IS KNOWN ABOUT ASTHMA?

5. What is Asthma? Disease of chronic inflammatory disorder of the airways Disease of chronic inflammatory disorder of the airways Characterized by: Characterized by: –Airway inflammation –Airflow obstruction –Airway hyperresponsiveness http://health.allrefer.com/health/asthma-normal-versus-asthmatic-bronchiole.html Cookson W. Nature 1999; 402S: B5-11

6. A sthma is a chronic inflammatory disorder of the airways. The chronic inflammation is associated with airway hyperresponsiveness ; - airways become obstructed and airflow is limited (by bronchoconstriction, mucus plugs, increased inflammation) when they are exposed to various risk factors. Asthma causes recurring episodes of wheezing breathlessness chest tightness coughing particularly at night or in the early morning. DEFINITION OF ASTHMA

7. DEFINITION Asthma is a disorder defined by its clinical, physiological and pathological characteristics The predominant feature of the clinical history is episodic shortness of breath, particularly at night, often accompanied by cough. Wheezing defined on auscultation of the chest is the most common physical finding. The main physiological feature of asthma is episodic airway obstruction characterized by expiratory airflow limitation. The dominant pathological feature is airway inflammation, sometimes associated with airway structural changes.

8. Asthma is an inflammatory disorder of the airways, which involves several inflammatory cells and multiple mediators that result in characteristic pathophysiological changes: result in airway inflammation, which limits airflow from bronchospasm, mucosal edema, and mucus plugs. result in airway inflammation, which limits airflow from bronchospasm, mucosal edema, and mucus plugs. Although many of the mediators responsible : cytokines, chemokines, and growth factors Although many of the mediators responsible : cytokines, chemokines, and growth factors These factors are produced by: mast cells, lymphocytes, eosinophils, basophils, epithelial cells, dendritic cells, and smooth muscle cells. These factors are produced by: mast cells, lymphocytes, eosinophils, basophils, epithelial cells, dendritic cells, and smooth muscle cells. Pathophysiology

9. Two types of Th lymphocytes have been characterized: Two types of Th lymphocytes have been characterized: Th1 cells produce IL-2 and IFN-a, which are critical in cellular defense mechanisms in response to infection. Th2, in contrast, generates a family of cytokines (IL-4, -5, -6, -9, -13 ) that can mediate allergic inflammation. Airway inflammation in asthma may represent a loss of normal balance between two "opposing" populations of Th lymphocytes

10. Specific Pathophysiology With exposure to a trigger, a cascade of cellular responses result in: With exposure to a trigger, a cascade of cellular responses result in: –Increased mucus production –Mucosal swelling –Bronchial muscle contraction

11. Pathophysiology Early Acute - t Early Acute - these changes cause bronchial hyperresponsiveness and obstruction. Airway obstruction increases resistance to airflow and decreases expiratory flow. Impaired expiration causes hyperinflation distal to the obstruction and increases the work of breathing. Late Recurrence of symptoms appears in 4- 12 hours Late Asthma Response occurs in cases of significant allergen exposure. Recurrence of symptoms appears in 4- 12 hours after the initial attack due to persistent cellular activation. It can be more severe than the initial attack. Untreated inflammation can cause long term airway damage that is irreversible (airway remodeling).

12. Asthmatic Inflammation Normal Airway Mast Cells Alveolar macrophages Recruitment and activation of inflammatory cells Subacute/Chronic Inflammation Neural & vascular effects Late Asthmatic Response Early Asthmatic Response chemotactic factors cytokines Inhaled trigger

13. What are the Triggering Factors? Domestic dust Domestic dust mites mites Animal with fur Animal with fur Air pollution Air pollution Cockroaches Cockroaches Pollen Pollen Tobacco smoke Tobacco smoke Occupational irritants Occupational irritants

14. Triggering Factors Respiratory (viral) infections Respiratory (viral) infections Chemical irritants Chemical irritants Strong emotional expressions Strong emotional expressions Drugs ( aspirin, beta blockers) Drugs ( aspirin, beta blockers)

15. Potential Risk Factors Host factors Host factors –Genetic predisposition –Atopy –Airway hyperresponsiveness –Gender –Race/Ethnicity Environmental factors Environmental factors –Indoor allergens –Outdoor allergens –Occupational sensitizer Environmental factors Environmental factors –Tobacco smoke –Air pollution –Respiratory infections –Socioeconomic status –Family size –Diet and drugs –Obesity 1 Masoli M, et al. The Global Burden of Asthma: Executive Summary of the GINA Dissemination Committee Report. Allergy 2004; 59: 469-78.

16. DIAGNOSING ASTHMA - Not Easy CLINICAL DIAGNOSIS Clinical diagnosis supported by the certain historical, physical and laboratory findings Clinical diagnosis supported by the certain historical, physical and laboratory findings –History of episodic symptoms of airflow obstruction (breathlessness, wheezing, chest tightness and COUGH)-response to therapy! Episodic symptoms after an incidental allergen exposure; easonal variability of symptoms; Seasonal variability of symptoms; Positive family history of asthma Positive family history of asthma and atopic disease. and atopic disease.

18. DIAGNOSING ASTHMA Consider asthma if any of the following signs or symptoms are present: Frequent episodes of wheezing – more than once a month Activity-induced cough or wheeze Cough particularly at night during periods without viral infections Absence of seasonal variation in wheeze Symptoms that persist after age 3 The child’s colds repeatedly “go to the chest” or take more than 10 days to clear up Symptoms improve when asthma medication is given

19. DIAGNOSING ASTHMA Symptoms occur or worsen in the presence of: Animals with fur Aerosol chemicals Changes in temperature Domestic dust mites Drugs (aspirin, beta blockers) Exercise Pollen Respiratory (viral) infections Smoke Strong emotional expression

20. Dyspnea, airflow limitation (wheeze), hyperinflation are more likely to be present if patients are examined during symptomatic periods. Dyspnea, airflow limitation (wheeze), hyperinflation are more likely to be present if patients are examined during symptomatic periods. Physical signs reflecting severity: cyanosis, drowsiness, difficulty speaking, tachycardia, Physical signs reflecting severity: cyanosis, drowsiness, difficulty speaking, tachycardia, hyperinflated chest, hyperinflated chest, use of accessory muscles, use of accessory muscles, and intercostal recession. and intercostal recession. DIAGNOSING ASTHMA

21. Physical examination Physical examination - Respiratory rate; - Work of breathing; - Aeration - Degree of wheezing Suppotive data: Suppotive data: - Pulse oximetry (oxygen saturation); - PEFR – peak expiratory flow rate - Chest radiograph; DIAGNOSING ASTHMA

22. Pulse oximetry Pulse oximetry - Noninvasive and nonexpensive; - Can help to predict the need for hospitalization; - Obtain for moderately to severely ill children; - Supplement with oxygen if oxygen saturation < 92 % DIAGNOSING ASTHMA

23. Measurements of lung function Spirometry is the preferred method of measuring airflow limitation and its reversibility to establish a diagnosis of asthma. Forced expiratory volume in 1 second (FEV1) - Forced expiratory volume in 1 second (FEV1) - an increase in FEV1 of ≥ 12% (or ≥ 200 ml) after administration of a bronchodilator indicates reversible airflow limitation consistent with asthma.

24. Peak expiratory flow (PEF) measurements can be an important aid in both diagnosis and monitoring of asthma Measurements of lung function

25. The Peak Flow Meter

27. Effort dependent; Measures in airflow larger airways; Compare to personal best; May be useful in those > age 6 year ; Peak Expiratory Flow Rate

28. Measurements of lung function Peak expiratory flow (PEF) PEF measurements are ideally compared to the patient’s own previous best measurements using his/her own peak flow meter. An improvement of 60 L/min (or ≥ 20% of the pre-bronchodilator PEF) after inhalation of a bronchodilator, or diurnal variation in PEF of more than 20% (with twice-daily readings, more than 10%), suggests a diagnosis of asthma.

29. Note Peak Flow Numbers Keeping a peak flow diary will help you predict and prevent asthma attacksKeeping a peak flow diary will help you predict and prevent asthma attacks Record peak flow numbers daily, every morning before taking control medicine(s)Record peak flow numbers daily, every morning before taking control medicine(s) Watch for trends in symptomsWatch for trends in symptoms Diary cards to record symptoms and PEF (in children older than 5 years )

30. Measurements of lung function Other diagnostic considerations in children include: Allergy skin tests, The measurement of specific IgE in serum, which can help in the identification of risk factors so that appropriate environmental control measures can be recommended.

31. Classification of Asthma Mild Intermittent Asthma Mild Intermittent Asthma - - Symptoms less than once a week - - Brief exacerbations - - Nocturnal symptoms not more than twice a month - - FEV1 or PEF ≥ 80% predicted - - PEF or FEV1 variability < 20% Mild Persistent Asthma Mild Persistent Asthma - - Symptoms more than once a week but less than once a day - - Exacerbations may affect activity and sleep - - Nocturnal symptoms more than twice a month - - FEV1 or PEF ≥ 80% predicted - - PEF or FEV1 variability < 20 – 30% Traditionally, the degree of symptoms, airflow limitation, and lung function variability have allowed asthma to be classified by severity (Intermittent, Mild Persistent, Moderate Persistent, Severe Persistent)

32. Traditionally, the degree of symptoms, airflow limitation, and lung function variability have allowed asthma to be classified by severity (Intermittent, Mild Persistent, Moderate Persistent, Severe Persistent)

33. Classification of Asthma Moderate Persistent Asthma Moderate Persistent Asthma Symptoms daily Exacerbations may affect activity and sleep Nocturnal symptoms more than once a week Daily use of inhaled SABA (short-acting 2- agonist) FEV1 or PEF 60-80% predicted PEF or FEV1 variability > 30% Severe Persistent Asthma Severe Persistent Asthma Symptoms daily Frequent exacerbations Frequent nocturnal asthma symptoms Limitation of physical activities FEV1 or PEF ≤ 60% predicted PEF or FEV1 variability > 30%

35. Severity of Asthma Exacerbations MildModerateSevere Talks in sentencesTalks in phrasesTalks in single words Breathlessness walking Breathlessness with talking/feeding Breathlessness in rest Normal mental status Mildly anxiousAnxious Mild tachypneaModerate tachypneaSevere tachypnea End expiratory wheeze Loud expiratory wheeze Inspiratory and expiratory wheezing Good aerationFair aerationPoor aeration Oxygen saturation > 95 % Oxygen saturation 90-95 % Oxygen saturation < 90 % PEFR > 70%PEFR = 40-69 %PEFR < 40%

36. Exacerbations of asthma (asthma attacks) are episodes of a progressive increase in shortness of breath, cough, wheezing, chest tightness, or a combination of these symptoms The attack is severe : The patient is breathless at rest, is hunched forward, talks in words rather than sentences (infant stops feeding), agitated, drowsy or confused, has bradycardia, or a respiratory rate greater than 30/min Wheeze is loud or absent Pulse is greater than: - 160/min for infants - 120/min for children 1-2 years - 110/min for children 2-8 years PEF is less than 60 percent of predicted or personal best even after initial treatment The child is exhausted.

37. TREATMENT Asthma Medications TREATMENT Asthma Medications Bronchodilators (Sympathomimetics) Bronchodilators (Sympathomimetics) Bronchodilators (Anticholinergics) Bronchodilators (Anticholinergics) Inhaled Corticosteroids Inhaled Corticosteroids Biologic Response Modifiers (Monoclonal Antibodies) Biologic Response Modifiers (Monoclonal Antibodies) Leukotriene Receptor Antagonists Leukotriene Receptor Antagonists Mast Cell Stabilizers Mast Cell Stabilizers Methylxanthene Derivatives Methylxanthene Derivatives

38. Bronchodilator, beta2-agonists (Sympathomimetics) Short acting beta agonists – SABA Short acting beta agonists – SABA Albuterol, Ventolin, Salbutamol (400 mcg), Proventil,Terbutaline, Long-acting - Sereven (24 mcg), Long-acting - Sereven (24 mcg), Foradil, Salmeterol Foradil, Salmeterol

40. Bronchodilators (Anticholinergics) Ipratropium Ipratropium

41. Inhaled Corticosteroids Beclamethasone Flunisolide Beclamethasone Flunisolide Triamcinalone Budesonide Triamcinalone Budesonide Pulmicort Turbuhaler or Respules Pulmicort Turbuhaler or Respules

42. Leukotriene Receptor Antagonists - Leukotriene modifier Zafirlukast (Accolate) Zafirlukast (Accolate) 5-11 years: 10 mg >12 years: 20 mg 5-11 years: 10 mg >12 years: 20 mg Montelukast (Singulair) Montelukast (Singulair) 12-23 months: 1 packet of 4 mg oral granules 2-6 years: 4 mg 6-14 years: 5 mg >14 years: 10 mg 12-23 months: 1 packet of 4 mg oral granules 2-6 years: 4 mg 6-14 years: 5 mg >14 years: 10 mg

43. Biologic Response Modifiers (Monoclonal Antibodies) Omalizumab Omalizumab

44. Mast cell stabilizers Cromolyn sodium (Intal), Cromolyn sodium (Intal), nedocromil sodium (Tilade) nedocromil sodium (Tilade)

45. Methylxanthines Theophylline - 10 mg/kg sustained- release tablets and capsules; not to exceed 300 mg/d Theophylline - 10 mg/kg sustained- release tablets and capsules; not to exceed 300 mg/d Euphylline 4-5 mg/kg/day Euphylline 4-5 mg/kg/day

46. Select Medications Two types of medication help control asthma Two types of medication help control asthma - Reliever medications that work quickly to treat attacks or relieve symptoms: - Reliever medications that work quickly to treat attacks or relieve symptoms: SABA (  2 -agonists) and anticholinergic agents, systemic corticosteroids. - Controller medications that keep symptoms and attacks from starting systemic corticosteroids;

47. Frequent SABA are the standard of care Frequent SABA are the standard of care Use of NEB or MDI-S are each reasonable Use of NEB or MDI-S are each reasonable Most will require just 1-2 treatment Most will require just 1-2 treatment Those who are SABA unresponsive may benefit from systemic corticosteroids Those who are SABA unresponsive may benefit from systemic corticosteroids Most will be discharged home Most will be discharged home TREATMENT MILD ASTHMA

49. MDI-Space, Holding-chamber MDI

51. NEB

52. Management Moderate Asthma No improvement Marked improvement Hospitalize Slight improvement Albuterol NEB or MDI-S Albuterol NEB or MDI-S Prednisone 2 mg/kg/d IM or NEB Prednisone 2 mg/kg/d IM or NEB Atrovent Atrovent↓ Disposition Discharge home Continue albuterol every 30-45 min Continue albuterol every 30-45 min

53. Management Severe Asthma Monitor pulse, RR, oxygen saturation Monitor pulse, RR, oxygen saturation↓ Supplemental oxygen 0.15mg/kg Albuterol by nebulization Atrovent Good response Continue with approach to moderate asthma Poor response Terbutaline or epinephrine IM Methylprednisolone 1-2 mg/kg IV Albuterol |NEB 50-75 mg/kg IV Magnesii sulfate

54. Acute severe asthmatic episode (status asthmaticus) –Treatment goals are the following: Correction of significant hypoxemia with supplemental oxygen: In severe cases, alveolar hypoventilation requires mechanically assisted ventilation. Correction of significant hypoxemia with supplemental oxygen: In severe cases, alveolar hypoventilation requires mechanically assisted ventilation. Rapid reversal of airflow obstruction by using repeated or continuous administration of an inhaled beta2-agonist; Rapid reversal of airflow obstruction by using repeated or continuous administration of an inhaled beta2-agonist; Early administration of systemic corticosteroids ( oral prednisone or intravenous methylprednisolone) is suggested in children with asthma that fails to respond promptly and completely to inhaled beta2-agonists. Early administration of systemic corticosteroids ( oral prednisone or intravenous methylprednisolone) is suggested in children with asthma that fails to respond promptly and completely to inhaled beta2-agonists. Reduction in the likelihood of recurrence of severe airflow obstruction by intensifying therapy: Often, a short course of systemic corticosteroids is helpful. Reduction in the likelihood of recurrence of severe airflow obstruction by intensifying therapy: Often, a short course of systemic corticosteroids is helpful.

55. Asthma attacks require prompt treatment Oxygen is given at health centers or hospitals if the patient is hypoxemic Inhaled rapid-acting b2-agonists in adequate doses are essential Oral glucocorticosteroids (0.5 to 1 mg of prednisolone/kg or equivalent during a 24-hour period) introduced early in the course of a moderate or severe attack help to reverse the inflammation and speed recovery. Methylxanthines are not recommended if used in addition to high doses of inhaled 2-agonists. However, theophylline can be used if inhaled 2-agonists are not available.

56. Controller Medications Inhaled corticosteroids - ICS Inhaled corticosteroids - ICS Systemic corticosteroids - SCS Systemic corticosteroids - SCS Leukotriene modifiers Leukotriene modifiers Sodium cromoglycate (cromolyn sodium) Sodium cromoglycate (cromolyn sodium) Nedocromil sodium Nedocromil sodium Methylxanthines Methylxanthines Long-acting inhaled  2-agonists, Long-acting inhaled  2-agonists, Long-acting oral  2-agonists. Long-acting oral  2-agonists.

57. When asthma is controlled, patients can: Prevent most attacks Avoid troublesome symptoms night and day Use little or no relieve medication Have productive, physically active lives Have (near) normal lung function Avoid serious attack The goal of asthma care

58. is to achieve and maintain control of the clinical manifestations of the disease for prolonged periods; it is important to recognize that asthma severity involves both the severity of the underlying disease and its responsiveness to treatment; For ongoing management of asthma, classification of asthma by level of control is more relevant and useful;

59. Classification of asthma by level of control is more relevant and useful Levels of Asthma Control CharacteristicControlled (All of the following) Partly Controlled - Any measure present in any week Uncontrolled ExacerbationsNoneOne or more/yearOne in any week Three or more features of partly controlled asthma present in any Week Daytime symptoms None (twice or less/week) More than twice/week Limitations of activities NoneAny Nocturnal symp- toms/awakening NoneAny Need for reliever /rescue treatment None (twice or less/week) More than twice/week Lung function (PEF or FEV1) Normal< 80% predicted or personal best (if known)

60. intermittent asthma –Long-term control: Usually, no daily medication is needed. –Quick relief : Short-acting bronchodilators (SABA) in the form of inhaled beta2-agonists should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists more than 2 times a week may indicate the need to initiate long-term control therapy.

61. Mild persistent asthma Long-term control: Anti-inflammatory treatment in the form of low-dose inhaled corticosteroids or nonsteroidal agents (cromolyn, nedocromil) is preferred. Long-term control: Anti-inflammatory treatment in the form of low-dose inhaled corticosteroids or nonsteroidal agents (cromolyn, nedocromil) is preferred. –Some evidence suggests that leukotriene antagonists may be useful as first-line therapy in children. Quick relief: Short-acting bronchodilators in the form of inhaled beta2-agonists (SABA) should be used as needed for symptom control. Use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.

62. Moderate persistent asthma –Long-term control: Daily anti-inflammatory treatment in the form of inhaled corticosteroids (medium dose) is preferred. Otherwise, low- or medium-dose inhaled corticosteroids combined with a long- acting bronchodilator or leukotriene antagonist can be used, especially for the control of nocturnal or exercise-induced asthmatic symptoms. Daily anti-inflammatory treatment in the form of inhaled corticosteroids (medium dose) is preferred. Otherwise, low- or medium-dose inhaled corticosteroids combined with a long- acting bronchodilator or leukotriene antagonist can be used, especially for the control of nocturnal or exercise-induced asthmatic symptoms. –Quick relief: Short-acting bronchodilators in the form of inhaled beta2- agonists (SABA) should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy. Short-acting bronchodilators in the form of inhaled beta2- agonists (SABA) should be used as needed for symptom control. The use of short-acting inhaled beta2-agonists on a daily basis or increasing use indicates the need for additional long-term therapy.

63. Severe persistent asthma Long-term control Daily anti-inflammatory treatment in the form of inhaled corticosteroids (high dose) is preferred. Other medications, such as a long-acting bronchodilator, leukotriene antagonist or theophylline, can be added. Daily anti-inflammatory treatment in the form of inhaled corticosteroids (high dose) is preferred. Other medications, such as a long-acting bronchodilator, leukotriene antagonist or theophylline, can be added. Quick relief : Short-acting bronchodilators in the form of inhaled beta2-agonists or ipratropium bromid should be used as needed for symptom control systemic corticosteroids.

65. Asthma is not a cause for shame. Olympic athletes, famous leaders, other celebrities, and ordinary people live successful lives with asthma. Managing Asthma