Asthma: Diagnosis and Management

1. Asthma: Diagnosis and Management Rochelle M. Nolte, MD CDR USPHS

2. National Heart, Lung, and Blood Institute Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma 2007 Last report in 1997 with an update in 2002 More emphasis on monitoring control over time

3. Asthma: Working Definition Chronic inflammatory disorder of the airways in which many cells & cellular elements play a role: in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli. Reversibility of airflow limitation may be incomplete in some patients with asthma.

4. Asthma Airflow limitation is caused by a variety of changes in the airway: Bronchoconstriction Airway edema Airway hyperresponsiveness Airway remodeling

5. Asthma: Demographics Most common chronic condition in children #1 cause of school absenteeism Morbidity and mortality highly correlated with Poverty, urban air quality, indoor allergens, lack of patient education, and inadequate medical care About 5000 deaths annually

6. Asthma: Diagnosis Episodic sx of airflow obstruction or airway hyperresponsiveness Airflow obstruction is at least partially reversible Alternative diagnoses are excluded

7. Asthma: Diagnosis Detailed medical history Physical exam focusing on upper resp tract, chest, and skin Spirometry to demonstrate obstruction and assess reversibility (> 5 yrs of age) Increase of FEV1 of > 10-12% after a short-acting bronchodilator

8. Asthma: Diagnosis-History Symptoms (and symptom patterns) Precipitating and/or aggravating factors Development of disease and treatment Family and Social history History of exacerbations Impact on patient and family Patient�s and family�s perception of dx

9. Indicators to Consider Asthma Wheezing (expiratory) History of: Cough, especially nocturnal Recurrent wheeze, SOB, or chest tightness Symptoms worsen with: Exercise, viral infection, animals with hair, dust mites, mold, smoke, pollen, wx changes, strong emotional expressions, chemicals or dust, menstrual cycles

10. Importance of Spirometry Hx and PE are NOT reliable means of excluding other DX or of characterizing the status of lung impairment Objective assessment (spirometry) of pulmonary function is needed Peak flow meters are designed as monitoring, not diagnostic tools

11. Asthma: Differential Diagnoses Infants and Children Upper airway diseases Allergic rhinitis and sinusitis Large airway obstruction Tracheal or bronchial foreign body Vocal cord dysfunction Vascular rings or laryngeal webs Laryngotracheomalacia, tracheal stenosis Tumor or enlarged lymph nodes

12. Asthma: Differential Diagnoses Infants and Children Recurrent cough not due to asthma Aspiration from swallowing mechanism dysfunction or gastroesophageal reflux

13. Asthma: Differential Diagnoses Adults COPD Congestive heart failure Pulmonary embolus Mechanical obstruction of the airways Pulmonary infiltration with eosinophilia Cough secondary to drugs Vocal cord dysfunction

14. Asthma: Initial Assessment Once diagnosed, asthma must be characterized to guide therapy ID precipitating factors (LOE A) ID comorbidities (LOE B) Classify severity by: Impairment (LOE B) Risk (LOE C)

15. Asthma: Severity Impairment Frequency and intensity of symptoms and functional limitations the patient is experiencing or has recently experienced Risk The likelihood of either asthma exacerbations, progressive decline in lung function (or, for children, reduced lung growth)

16. Asthma: Impairment Symptoms Nighttime awakenings Need for SABA for quick relief of symptoms Work/school days missed Ability to engage in ADL�s and desired activity Quality-of-life issues Lung function measured by spirometry

17. Asthma: Risk of Adverse Events Exacerbations (acute or subacute) Progressive worsening SOB, cough, wheeze, and/or chest tightness Decreased expiratory airflow Any level of severity can have severe exacerbations �Intermittent asthma� replaces �Mild intermittent asthma�

18. Predictors of exacerbations Severe airflow obstruction (by spirometry) Persistent severe airflow obstruction >2 ED or hospitalizations in past year ICU or intubation in past 5 years Patients report feeling frightened Female, non-white, smoker, no ICS Depression, stress, attitudes about meds

19. Severity Classification Ages 0-4

20. Severity Classification Ages 0-4 Intermittent Impairment Symptoms: < 2 days/week Nighttime awakenings: None SABA < 2 days/week Interference with normal activity: None Risk Exacerbations: 0-1/year (needing systemic steroids)

21. Severity Classification Ages 0-4 Mild Impairment Symptoms: > 2 days/week, but not daily Nighttime awakenings: 1-2 X q month SABA: > 2 days/week, but not daily Interference with normal activity: Minor Risk >2 exacerbations/6m, or >4 wheezing episodes in 12m lasting > 1 day and RF for persistent asthma

22. Severity Classification Ages 0-4 Moderate Impairment Symptoms: daily Nighttime awakenings: 3-4 X q month SABA: daily Interference with normal activity: Some limitation Risk >2 exacerbations/6m, or >4 wheezing episodes in 12m lasting > 1 day and RF for persistent asthma

23. Severity Classification Ages 0-4 Severe Impairment Symptoms: throughout the day Nighttime awakenings: >1 X q week SABA: several times per day Interference with normal activity: Extreme Risk >2 exacerbations/6m, or >4 wheezing episodes in 12m lasting > 1 day and RF for persistent asthma

24. Severity Classification Ages 5-11

25. Severity Classification Ages 5-11 Intermittent Impairment Symptoms: < 2 days/week Nighttime awakenings: < 2 X q month SABA < 2 days/week Interference with normal activity: None Lung function: FEV1 >80%; FEV1/FVC >85% Risk Exacerbations: 0-1/year (needing systemic steroids)

26. Severity Classification Ages 5-11 Mild Impairment Symptoms: > 2 days/week, but not daily Nighttime awakenings: >1Xq wk, but not nightly SABA: > 2 days/week, but not daily Interference with normal activity: Minor Lung function: FEV1 > 80%; FEV1/FVC > 80% Risk >2 in one year

27. Severity Classification Ages 5-11 Moderate Impairment Symptoms: daily Nighttime awakenings: >1Xq wk, but not nightly SABA: daily Interference with normal activity: Some limitation Lung function: FEV1 60-80%; FEV1/FVC 75-80% Risk >2 exacerbations/ year

28. Severity Classification Ages 5-11 Severe Impairment Symptoms: throughout the day Nighttime awakenings: Often 7 X q week SABA: several times per day Interference with normal activity: Extreme Lung function: FEV1 < 60%; FEV1/FVC <75% Risk >2 exacerbations/year

29. Classifying Severity Age > 12

30. Severity Classification Age > 12 Intermittent Impairment Symptoms: < 2 days/week Nighttime awakenings: < 2 X q month SABA < 2 days/week Interference with normal activity: None Lung function: FEV1 >80%; FEV1/FVC normal Risk Exacerbations: 0-1/year (needing systemic steroids)

31. Severity Classification Age > 12 Mild Impairment Symptoms: > 2 days/week, but not daily Nighttime awakenings: 3-4 X q month SABA: > 2 days/week, but not daily Interference with normal activity: Minor Lung function: FEV1 > 80%; FEV1/FVC normal Risk >2 in one year

32. Severity Classification Age > 12 Moderate Impairment Symptoms: daily Nighttime awakenings: >1Xq wk, but not nightly SABA: daily Interference with normal activity: Some limitation Lung function: FEV1 60-80%; FEV1/FVC 5% <nl Risk >2 exacerbations/ year

33. Severity Classification Age > 12 Severe Impairment Symptoms: throughout the day Nighttime awakenings: Often 7 X q week SABA: several times per day Interference with normal activity: Extreme Lung function: FEV1 < 60%; FEV1/FVC > 5% < nl Risk >2 exacerbations/year

34. Tx Goals: Achieve Control Reducing impairment Prevent chronic and troublesome symptoms Require infrequent (<2d q wk) use of SABA Maintain (near) �normal� pulmonary function Maintain normal activities (incl exercise) Meet patients� and families� expectations of and satisfaction with asthma care

35. Tx Goals: Achieve Control Reducing Risk Prevent recurrent exacerbations of asthma Minimize the need for ED and hospitalizations Prevent progressive loss of lung function For children, prevent reduced lung growth Provide optimal pharmacotherapy With minimal or no adverse effects

36. Periodic Assessment of Control Signs and symptoms of asthma Pulmonary function Quality of life and functional status History of asthma exacerbations Pharmacotherapy (adherence/side effects) Patient-provider communication Patient satisfaction

37. Periodic Assessment of Control Assessment of the pt�s sx hx should incl: Daytime asthma symptoms Nocturnal awakening 2ndary to asthma Frequency of use of SABA for relief Inability or difficulty performing normal activities because of asthma symptoms

38. Periodic Assessment of Control Quality of Life Assessment Work or school missed Reduction in usual activities Disturbances in sleep Any change in caregivers� activities due to a child�s asthma Only moderately correlated with clinical assessment

39. Periodic Assessment of Control Clinician assessment and patient self-assessment are primary methods for monitoring asthma Spirometry is recommended (LOE B) Initial assessment After tx started and sx have stabilized Progressive or prolonged loss of control At least q1-2 years (LOE D)

40. Periodic Assessment of Control Provide a written action plan (LOE B) Self-monitoring is important to the effective self-management of asthma (LOE A) Peak flow monitoring and symptom monitoring show similar benefits

41. Periodic Assessment of Control Pt�s should be taught to recognize symptom patterns indicating inadequate asthma control and the need for additional therapy (LOE A) Consider peak flow monitoring for: Severe persistent asthma or exacerbations (B) Poor perceivers of airway obstruction (D) To monitor response to treatment (B)

42. Assessing Control in Ages 0-4

43. Assessing Control in Ages 0-4 Well Controlled Impairment Symptoms: <2 days/week Nighttime awakenings: None Interference with normal activity: None SABA: <2 days/week Risk Exacerbations: 0-1/year Treatment-related adverse effects

44. Assessing Control in Ages 0-4 Not Well Controlled Impairment Symptoms: >2 days/week Nighttime awakenings: > 1 X q month Interference with normal activity: Some SABA: >2 days/week Risk Exacerbations: 2-3/year Treatment-related adverse effects

45. Assessing Control in Ages 0-4 Very Poorly Controlled Impairment Symptoms: Throughout the day Nighttime awakenings: > 1 X q week Interference with normal activity: Extreme SABA: Several times q day Risk Exacerbations: >3/year Treatment-related adverse effects

46. Assessing Control in Ages 5-11

47. Assessing Control in Ages 5-11 Well Controlled Impairment Symptoms: <2 days/week Nighttime awakenings: <1 X q month Interference with normal activity: None SABA: <2 days/week Lung function: FEV1 > 80%; FEV1/FVC > 80% Risk Exacerbations: 0-1/year Reduction in lung growth Treatment-related adverse effects

48. Assessing Control in Ages 5-11 Not Well Controlled Impairment Symptoms: >2 d/wk or multiple times on <2d/wk Nighttime awakenings: > 2 X q month Interference with normal activity: Some SABA: >2 days/week Lung function: FEV1 60-80%; FEV1/FVC 75-80% Risk Exacerbations: >2/year Reduction in lung growth Treatment-related adverse effects

49. Assessing Control in Ages 5-11 Very Poorly Controlled Impairment Symptoms: Throughout the day Nighttime awakenings: >2 X q week Interference with normal activity: Extreme SABA: Several times q day Lung function: FEV1 <60%; FEV1/FVC < 75% Risk Exacerbations: >2/year Reduction in lung growth Treatment-related adverse effects

50. Assessing Control in Ages > 12

51. Asthma Therapy Assessment Questionnaire (ATAQ)

52. Asthma Control Test (ACT)

53. Assessing Control in Ages >12 Well Controlled Impairment Symptoms: <2 days/week Nighttime awakenings: <2 X q month Interference with normal activity: None SABA: <2 days/week Lung function: FEV1 > 80% predicted Validated Questionnaires ATAQ: Zero ACQ: <0.75 ACT: >20

54. Assessing Control in Ages >12 Well Controlled Risk Exacerbations: 0-1/year Consider severity and interval since last exacerbation Progressive loss of lung function Evaluation requires long-term follow-up care Treatment-related adverse effects Do not correlate to specific levels of control, however: Should be considered in the overall assessment of risk

55. Assessing Control in Ages > 12 Not Well Controlled Impairment Symptoms: >2 day q week Nighttime awakenings: 1-3 X q week Interference with normal activity: Some SABA: >2 days/week Lung function: FEV1 60-80% of predicted Validated Questionnaires ATAQ: 1-2 ACQ: >1.5 ACT: 16-19

56. Assessing Control in Ages >12 Not Well Controlled Risk Exacerbations: > 2/year Consider severity and interval since last exacerbation Progressive loss of lung function Evaluation requires long-term follow-up care Treatment-related adverse effects Do not correlate to specific levels of control, however: Should be considered in the overall assessment of risk

57. Assessing Control in Ages > 12 Very Poorly Controlled Impairment Symptoms: Throughout the day Nighttime awakenings: > 4 X q week Interference with normal activity: Extreme SABA: Several times q day Lung function: FEV1 <60% predicted Validated Questionnaires ATAQ: 3-4 ACQ: N/A ACT: < 15

58. Assessing Control in Ages >12 Very Poorly Controlled Risk Exacerbations: > 2/year Consider severity and interval since last exacerbation Progressive loss of lung function Evaluation requires long-term follow-up care Treatment-related adverse effects Do not correlate to specific levels of control, however: Should be considered in the overall assessment of risk

59. Environmental Factors Exposure of patients who have asthma to allergens (LOE A) or irritants to which they are sensitive has been shown to increase asthma symptoms and precipitate asthma exacerbations.

60. Environmental Factors Clinician should evaluate the role of potential allergens (especially indoor) in patient�s with persistent asthma (LOE A) Patient history of exposure and exacerbations Skin testing or in vitro testing

61. Chronic Comorbid Conditions Allergic Bronchopulmonary Aspergillosis Suspect in asthma patients with: h/o pulmonary infiltrates IgE sensitivity to Aspergillus on allergy test Corticosteroid dependence Treatment improves control of asthma (LOE A)

62. Chronic Comorbid Conditions Control of chronic conditions improves control of asthma GERD (LOE B) Obesity (LOE B) OSA (LOE D) Rhinitis/Sinusitis (LOE B) Chronic Stress/Depression (LOE D)

63. Medications Long-term control medications Inhaled corticosteroids Cromolyn sodium and nedocromil Immunomodulators Leukotriene modifiers Long-acting beta-agonists Methylxanthines

64. Medications Quick-relief medications Anticholinergics Short-acting beta-agonists Systemic corticosteroids

65. Inhaled Corticosteroids Block late-phase reaction to allergen, reduce airway hyperrepsonsiveness, and inhibit inflammatory cell migration and activation Most potent and effective anti-inflammatory medication currently available (LOE A)

66. Inhaled Corticosteroids Reduce severity of symptoms Improve asthma control and QOL Improve PEF and spirometry Decrease hyperresponsiveness Prevent exacerbations Reduce systemic corticosteroids, ED care, hospitalizations, and death

67. Inhaled Corticosteroids Should be used to control asthma sx and improve QOL Should NOT be initiated or prolonged for the purpose of changing the natural hx of disease (LOE A) Evidence does not support that early intervention with ICS will alter underlying severity or progression of disease

68. Long-acting beta-agonists LABA�s are not to be used as monotherapy for long-term control of asthma (LOE A) LABA�s are used in combo w/ ICS�s for long-term control & prevention of sx in moderate or severe asthma (LOE A for age >12) (LOE B for 5-11) LABA�s are preferred tx to combine w/ICS

69. Leukotriene modifiers Leukotriene Receptor Antagonists (LTRA�s) Montelukast (for > 1year of age) Zafirlukast (for > 7 years of age) Alternative, but not preferred tx for persistent asthma (LOE A) 5-lipoxygenase pathway inhibitor Zileuton (for >12 years of age)

70. Cromolyn and nedocromil Mast cell stabilizers Alternative, but not preferred tx in mild persistent asthma (LOE A)

71. Immunomodulators Omalixumab (anti-IgE) Monoclonal antibody that prevents binding of IgE to receptors on basophils and mast cells Adjunctive tx for age >12 w/ allergies (LOE B) Clinicians must be prepared to ID and tx anaphylaxis

72. Methylxanthines Theophylline (sustained-release) Mild to moderate bronchodilator Alternative, not preferred adjuctive tx with ICS (LOE A) May have anti-inflammatory effect Must monitor serum theophylline levels

73. Quick-relief medications Short-acting beta-agonists (SABA) Systemic corticosteroids Anticholinergics

74. Short-acting beta-agonists Bronchodilators that relax smooth muscle Therapy of choice for relief of acute symptoms and prevention of Exercise Induced Bronchospasm (EIB) (LOE A) Regularly scheduled, daily, chronic use of SABA�s is NOT recommended!!! (LOE A)

75. Systemic Corticosteroids Although not short acting, used for moderate and severe exacerbations as adjucunt to SABA�s to speed recovery and prevent recurrence of exacerbations (LOE A)

76. Anticholinergics Inhibit muscarinic cholinergic receptors Reduce intrinsic vagal tone of airway Ipratropium bromide provides added benefit to SABA�s in moderate-severe exacerbations

77. Long-term mngt of asthma Reduce impairment Prevent chronic/troublesome symptoms Infrequent (<2/wk) use of inhaled SABA Maintain (near) normal pulmonary function Maintain normal activity levels Meet patient and family expectations

78. Long-term mngt of asthma Reduce risk Prevent recurrent exacerbations/ED visits Prevent loss of lung function/lung growth Avoid adverse effects of medications Ensure that quick-relief medications are available (LOE A)

79. Long-term mngt of asthma Stepwise approach recommended (LOE A) Type, amount, and scheduling of meds Severity for initiating therapy (LOE A) Control for adjusting therapy (LOE A) Persistent asthma is most effectively controlled w/daily long-term anti-inflammatory medication (LOE A)

80. Long-term mngt of asthma Goal is to maintain control with least amount of medication (LOE A) Education of patients is essential for achieving optimal pharmacologic therapy (LOE A) Therapeutic strategies should be considered in concert with clinician-patient partnership strategies

81. Long-term mngt of asthma Pt�s should be advised to avoid/control Allergens (LOE A) Irritants (LOE B) Comorbid conditions (LOE B)

82. Initiating long-term therapy Ages 0-4 >4 episodes of wheezing/yr that: (LOE A) Last > one day and affect sleep Occur in patients with risk factors for asthma: Parental history of asthma Physician diagnosis of atopic dermatitis Evidence of sensitization to aeroallergens Or 2 of the following: sensitization to foods, > 4% periph blood eosinophilia, or wheezing apart from colds

86. Initiating long-term therapy Ages 5-11 Daily long-term control tx should be initiated in children with persistent asthma ICS�s are the preferred tx for initiating long-term control tx in all children (LOE A) ICS�s are safe, even w/long-term use (LOE A) Potential albeit small risk of delayed growth from ICS�s is well balanced by their effectiveness (LOE A)

90. Stepwise approach for > 12 Step One SABA prn to tx sx (< 2/week) SABA before exercise for EIB Manage exacerbations SABA q4-6h for up to 24h Consider systemic steroids if mod/severe Consider long-term tx if exacerbation q 6 weeks Detailed written action plan for exacerbations

91. Stepwise approach for > 12 Step Two Low dose ICS is preferred tx (LOE A) Alternates (not preferred) LTRA Cromolyn Nedocromil Sustained release theophylline Insufficient evidence to recommend + LABA

92. Stepwise approach for > 12 Step Three Assess environmental factors (LOE A) Review inhaler technique and compliance (B) Add LABA to low-dose ICS (LOE A) Increase ICS to medium-dose (LOE A) Alternates to above (not preferred) Add LTRA, theophylline, or zileuton to ICS

93. Stepwise approach for > 12 Step Four Increase ICS to medium dose & add LABA (A) Alternate (not preferred) Add LTRA or theo or zileuton to med-dose ICS

94. Stepwise approach for > 12 Step Five High-dose ICS and LABA preferred (LOE B) Omalizumab for patient�s with relevant allergy Dust mites, cockroach, cat, or dog (LOE B) Clinicians must be able to assess and treat for anaphylaxis after injection Must educate patient and family on identifying and treating anaphylaxis with auto-injectors and seeking immediate medical treatment

95. Stepwise approach for > 12 Step Six Add oral corticosteroids to step five therapy (and I�d personally consult with a specialist if this hasn�t been done already���)

99. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm

100. Questions?