1. ASTHMA MANAGEMENT and EDUCATION INITIATIVE
JOB CORPS
2005 National Health and Wellness Conference
Orlando, Florida
June 7, 2005
Gary Strokosch, MD
Region V Medical Consultant

2. Guidelines for the Diagnosis and Management of Asthma Update on Selected Topics
Expert Panel Report (EPR) – Update 2002
National Asthma Education and Prevention Program (NAEPP)
NIH Publication No
June 2003

3. PREVIOUS REPORTS
1997 Guidelines for the Diagnosis and Management of Asthma (EPR-2)
1991 National Asthma Education and Prevention Program’s (NAEPP) first report

4. AVAILABLE NAEPP PUBLICATIONS
(National Heart, Lung and Blood Institute)

5. OBJECTIVE
To give participants the tools to develop up-to-date individual management plans for JC students with asthma

6. SCOPE OF ASTHMA - I
11 million people reported having an asthma attack in 2000
More than 5% of all children under 19 report asthma attacks in 2000
In % of teens years of age have had asthma diagnosed

7. SCOPE OF ASTHMA - II 1999: 2 million ER visits
1999: 478,000 hospitalizations for asthma
1999: 4426 deaths from asthma
Mortality is 3 times higher in Black males than white males
Mortality is 2 ½ times higher in Black females than while females

8. 2002 UPDATE OUTLINE Overview of asthma Medication Updates
Steroids Efficacy & Safety
Combination Therapy
Antibiotics
Monitoring Issues
Written Plans for Management
Peak Flow Vs. Symptom Monitoring
Management

9. ----------------------note----------------------
DEFINITION
Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role.
note
The ability to synthesize IgE antibody to environmental allergens (i.e., atopy) remains a major risk factor in asthma pathogenesis.

10. NATURAL HISTORY OF PERSISTENT ASTHMA
The majority of children who wheeze before 3 years of age do not experience any more symptoms after 6 years of age.
A smaller group of children wheezing before 3 years of age go on to have persistent asthma.
A predictive index identified the following risk factors for developing persistent asthma

11. PREDICTIVE INDEX Major and Minor Risk Factors
Physician diagnosis of atopic dermatitis/eczema
- OR -
Parental history of asthma OR
Two out of three of the following asthma-associated phenotypes:
Peripheral blood eosinophilia (>4%)
Wheezing apart from colds
Physician-diagnosed allergic rhinitis

12. BIRTH COHORT FOLLOWED FOR 13 YEARS
76% of those diagnosed with asthma after 6 years of age had a positive predictive index
97% of those without a diagnosis of asthma after 6 years of age had a negative predictive index
(Castro-Rodriguez, et.al. 2000)

13. SPIROMETRY Recommends tests be done:
At the time of the initial assessment
After treatment is initiated and symptoms and PEF have stabilized
At least every 1-2 years

14. SYMPTOM CLASSIFICATION
Severe Persistent
Moderate Persistent
Mild Persistent
Mild Intermittent

15. SYMPTOM CLASSIFICATION
Severe Persistent
Day: continual
Night: frequent
Moderate Persistent
Day: daily
Night: >1/week
Mild Persistent
Day: >2/week (<1/day) [3-6/week]
Night: >2/month
Mild Intermittent
Day: 2/week
Night: 2/month

16. TARGET OF THERAPY - I
1) Acute symptoms of asthma usually arise from BRONCHOSPASM and require and respond to bronchodilator therapy.

17. TARGET OF THERAPY - II
2) Acute and chronic INFLAMMATION affects the airway caliber and airflow and also causes bronchial hyper responsiveness, resulting in susceptibility to bronchospasm. Therapy is with anti inflammatory drugs but may require weeks to achieve a successful response.

18. TARGET OF THERAPY - III
3) Some patients experience persistent airflow limitations and this REMODELING has NO current therapy.

19. INFLAMMATION
This inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and cough, particularly at night and in the early morning.

20. INFLAMMATION - I
Airway inflammation in asthma is found in patients with mild, moderate and severe disease.

21. INFLAMMATION – II Mild / Moderate Persistent Asthma
Inflammation of airway by inflammatory cells such as activated lymphocytes & eosinophils
Denudation of the epithelium
Deposition of collagen in the subbasement membrane area
Mast cell degranulation

22. INFLAMMATION – III Severe Persistent & Deaths from Asthma
Occlusion of bronchial lumen by mucous
Hyperplasia & hypertrophy of bronchial smooth muscle
Goblet cell hyperplasia

23. IgE PATHOGENESIS
IgE antibodies are synthesized to environmental allergens (atopy)
Synthesized IgE binds to mast cells and basophils via high-affinity IgE receptors
These cells are signaled to release preformed and newly generated mediators, including histamine & cysteinyl leukotrienes to rapidly contract airway smooth muscle
Mast cells also produce a variety of cytokines (pro-inflammatory proteins) including interleukin (IL 1,2,3,4 &5), granulocyte-macrophage colony-stimulating factor, interferon and tumor necrosis factor-α

24. ATOPY
Atopy is the genetic susceptibility to produce IgE ABs directed toward common environmental allergens, including house-dust mites, animal proteins, and fungi.
With the production of IgE ABs, mast cells and possibly other airway cells (e.g., lymphocytes) are sensitized and become activated when they encounter specific antigens.
Atopy has been found in 30 to 50% of the general population, therefore frequently found in the absence of asthma.
Atopy is one of the strongest predisposing factors in the development of asthma.

25. EOSINOPHIL PATHOGENESIS
Infiltration seen in all acute inflammation & many patients with chronic persistent asthma
The granules are the source of inflammatory mediators
Injure airway epithelium
Enhance bronchial responsiveness
Affect acetylcholine release
Release cysteinyl leukotrienes to contract airway smooth muscle
Eosinophils are produced & released from bone marrow via IL-5, migrate to airway via a number of factors

26. EOSINOPHIL PATHOGENESIS
Although its role in pathophysiology is less clear, it is affected by anti-inflammatory therapy.

27. ASTHMA MEDICATIONS Beta2-Agonists Corticosteroids
Leukotriene Modifiers
Methyl Xanthines
Cromolyn and Nedocromil
Anticholinergics

28. ASTHMA MEDICATIONS Beta2-Agonists Corticosteroids
Injected
Short-acting inhaled
Long-acting inhaled
Corticosteroids
Inhaled
Systemic (oral)
Leukotriene Modifiers
Methyl Xanthines
Cromolyn and Nedocromil
Anticholinergics

29. COMBINATION ASTHMA MEDICATIONS
Beta2-Agonists
Long-acting inhaled
Corticosteroids
Inhaled

30. ADVAIR 100/50, 250/50 & 500/50 Fluticasone DPI 100/250/500 mcg
Salmererol DPI 50 mcg

31. ASTHMA MEDICATIONS Beta2-Agonists Corticosteroids
Injected
Short-acting inhaled
Long-acting inhaled
Corticosteroids
Inhaled
Systemic (oral)
Leukotriene Modifiers
Methyl Xanthines
Cromolyn and Nedocromil
Anticholinergics

32. ASTHMA MEDICATIONS Beta2-Agonists Anticholinergics
Short-acting inhaled
Anticholinergics

33. COMBIVENT For Use In COPD
Ipratropium 18 mcg/puff MDI
Albuterol 90 mcg/puff MDI
Ipratropium 0.5 mg/3ml Nebulizer Solution
Albuterol 2.5 mg/3ml Nebulizer Solution

34. CORTICOSTEROID EFFICACY

35. Does chronic use of inhaled corticosteroids improve long-term outcomes with mild or moderate persistent asthma, in comparison to the following treatment?
PRN beta2-agonists?
Long-acting beta2-agonists?
Theophylline?
Cromolyn/Nedocromil?
Combinations of above drugs?

36. RESULT
Inhaled corticosteroids improve long-term outcomes with mild or moderate persistent asthma, compared to previously outlined treatments.

37. RECOMMENDATION
Inhaled corticosteroids are the preferred treatment for initiating therapy for persistent asthma.

38. CORTICOSTEROID SAFETY

39. What are the long term adverse effects of chronic inhaled corticosteroid use on the following outcomes?
Vertical Growth?
Bone Mineral Density?
Ocular Toxicity (posterior subcapsular cataract and glaucoma)?
Suppression of adrenal/pituitary axis?

40. RESULT
The use of corticosteroids at recommended doses does not have long-term, clinically significant, or irreversible effects on any of the outcomes reviewed.

41. LINEAR GROWTH
Growth reduction my occur from inadequate control of any chronic disease.
Although low/medium doses may have the potential of decreased growth velocity, the effects are small, nonprogressive and may be reversible.
When high doses are needed, the use of adjunctive therapy should be initiated in order to reduce the steroid dose.
Children and adolescents taking steroids by any route should be monitored for growth interference.

42. BONE MINERAL DENSITY
A small, dose-dependent reduction in BMD may be associated with inhaled corticosteroid use in patients older than 18 years of age, but the clinical significance of these findings is not clear.

43. CATARACTS / GLAUCOMA
In children, no significant effects are seen with low-to-medium doses. However, high (>2000 mg) cumulative lifetime doses of inhaled corticosteroids may increase slightly the prevalence of cataracts in two studies of adult and elderly patients.

44. HPA AXIS FUNCTION
Available evidence indicates that, on average, children may experience only clinically insignificant, if any, effects of low-to-medium dose of inhaled corticosteroids. Rare individuals may be more susceptible to their effects even at conventional doses.

45. OVERALL RECOMMENDATION
Inhaled corticosteroids are the preferred treatment for initiating therapy for persistent asthma.

46. COMBINATION THERAPY: ADDITION OF OTHER LONG-TERM-CONTROL MEDICATIONS TO INHALED CORTICOSTEROIDS

47. QUESTION
In patients with moderate persistent asthma who are receiving inhaled corticosteroids, does addition of another long-term-control agent improve outcomes?

48. ANSWER
Strong evidence consistently indicates that long-acting inhaled beta2-agonists added to low-to-medium inhaled corticosteroids improve outcomes.
Adding a leukotriene modifier or theophylline to inhaled corticosteroids also improves outcomes, but the evidence is not as substantial.

49. RECOMMENDATION
The preferred treatment for adults and children older than 5 years of age is the addition of long-acting inhaled beta2-agonists to low-to-medium doses of inhaled corticosteroids (not as a substitute).

50. “JUST DOUBLE THE DOSE”
Studies of adults in which the dose of inhaled corticosteroids was at least doubled consistently demonstrate improved outcomes when their asthma was not controlled with low-to-medium-doses of inhaled steroids, but these results are consistently less effective than adding a long-acting inhaled beta2-agonist.

51. USE OF ANTIBIOTICS TO TREAT ASTHMA EXACERBATIONS

52. DOES ROUTINELY ADDING ANTIBIOTICS TO STANDARD CARE IMPROVE THE OUTCOMES OF TREATMENT FOR ACUTE EXACERBATION OF ASTHMA?

53. NOTES ON COMORBID INFECTION
Most asthma exacerbations are associated with infection by a respiratory virus, especially rhinovirus.
Only a small percentage of exacerbations are associated with infection by an atypical bacterium, like Mycoplasma pneumoniae or Chlamydia pneumoniae.
It is widely believed that coincident bacterial sinusitis contributes to asthma exacerbations.
Airway obstruction due to mucus plugging possibly predisposes patients to bacterial infection of non-draining regions of the lungs.
Viral and bacterial infections are both associated with neutrophilic inflammation of the upper and lower airways.

54. MORE NOTES ON COMORBID INFECTION
Low-grade fever may accompany viral respiratory infections.
Sputum discoloration (from PMNs) may accompany viral respiratory infections.
Sputum of patients with uncomplicated asthma exacerbations commonly contains high numbers of PMNs.

55. UNCHANGED RECOMMENDATION (Same as EPR-2)
Therefore, antibiotics are not recommended for the treatment of acute asthma exacerbations except as needed for comorbid conditions – e.g., for the patients with fever and purulent sputum, evidence of pneumonia, or suspected bacterial sinusitis.

56. WRITTEN ACTION PLANS COMPARED TO MEDICAL MANAGEMENT ALONE

57. QUESTION
Compared to medical management alone, does the use of a written asthma action plan improve outcomes?

58. SUMMARY ANSWER TO THE QUESTION
Data are insufficient to support or refute the benefits of using written asthma action plans compared to medical management alone.

59. UNCHANGED RECOMMENDATION (Same as EPR-2)
Use of written action plans as part of an overall effort to educate patients in self-management is recommended, especially for patients with moderate or severe persistent asthma and patients with a history of severe exacerbations.

60. WRITTEN ACTION PLANS SHOULD:
Enhance clinician-patient communication
Meet the medical needs of the student
Have a format that facilitates the student’s understanding and ability to take appropriate action
Be explicit
Be an algorithm of procedures to take
Contain steps to take if treatment is ineffective or an emergency arises
Contain contact information for securing urgent care
Be periodically reviewed and revised as needed

61. PEAK FLOW-BASED COMPARED TO SYMPTOM-BASED WRITTEN ACTION PLANS

62. QUESTION
Compared to a written action plan based on symptoms, does use of a written action plan based on peak flow monitoring improve outcomes?

63. SUMMARY ANSWER TO THE QUESTION
Evidence neither supports nor refutes the benefits of written action plans based on peak flow monitoring compared to symptom-based plans in improving health care utilization, symptoms, or lung function.
However, patient preferences and circumstances may warrant choosing peak flow monitoring.

64. PEAK FLOW MONITORING TRADITIONAL RECOMMENDATIONS
Peak flow monitoring can be used for short-term monitoring, managing exacerbations, and daily long-term monitoring.
When used in these ways, the patient’s measured personal best is the most appropriate reference value.
Daily long-term monitoring should be limited to moderate and severe persistent asthma.

65. MANAGEMENT

66. SYMPTOM CLASSIFICATION
Severe Persistent
Day: continual
Night: frequent
Moderate Persistent
Day: daily
Night: >1/week
Mild Persistent
Day: >2/week (<1/day) [3-6/week]
Night: >2/month
Mild Intermittent
Day: 2/week
Night: 2/month

67. SYMPTOM CLASSIFICATION
Severe Persistent Step 4
Day: continual
Night: frequent
Moderate Persistent Step 3
Day: daily
Night: >1/week
Mild Persistent Step 2
Day: >2/week (<1/day) [3-6/week]
Night: >2/month
Mild Intermittent Step 1
Day: 2/week
Night: 2/month

68. SYMPTOM CLASSIFICATION
Severe Persistent Step 4 PEF/FEV1 <60%
Day: continual
Night: frequent
Moderate Persistent Step 3 PEF/FEV %
Day: daily
Night: >1/week
Mild Persistent Step 2 PEF/FEV1 >80%
Day: >2/week (<1/day) [3-6/week]
Night: >2/month
Mild Intermittent Step 1 PEF/FEV1 >80%
Day: 2/week
Night: 2/month

69. SYMPTOM CLASSIFICATION
Severe Persistent Step 4 PEF/FEV1 <60%
Day: continual Variability >30%
Night: frequent
Moderate Persistent Step 3 PEF/FEV %
Day: daily Variability >30%
Night: >1/week
Mild Persistent Step 2 PEF/FEV1 >80%
Day: >2/week (<1/day) [3-6/week] Variability 20-30%
Night: >2/month
Mild Intermittent Step 1 PEF/FEV1 >80%
Day: 2/week Variability <20%
Night: 2/month

70. DAILY MEDICATIONS Preferred Treatment:
Step 4
High-dose inhaled corticosteroids, AND
Long-acting beta2-agonists
Step 3
Low-to-medium dose inhaled corticosteroids, AND
Step 2
Low-dose inhaled corticosteroids
Step 1
No daily medication needed

71. QUICK RELIEF TREATMENT
Short-acting bronchodilator inhaler
Nebulizer treatment with bronchodilator
Course of systemic corticosteroids

72. NOTES ON TREATMENT Classify patients to their most severe step
Gain control ASAP, then step down to the least medication needed for control
Minimize use of short acting inhaled beta2-agonist
Provide education on self-management and controlling environment
Refer to asthma specialist if it is difficult to control asthma or if step 3 or 4 is required

73. STEPPING
STEP DOWN: Review treatment every 1 to 6 months; a gradual stepwise reduction in treatment may be possible.
STEP UP: If control is not maintained, consider step up. First, review patient medication technique, adherence and environmental control.

74. 2004 PERRY POINT FIVE ASTHMA MEDICATIONS www.jobcorpshealth.com
Albuterol inhalation aerosol (albuterol)
Fluticasone propionate oral inhaler (Flovent)
Triamcinolone acetonide inhalation aerosol (Azmacort)
Salmeterol xinafoate oral inhaler (Serevent)
Montelukast sodium tablets, 10 mg (Singulair)

75. 2004 PERRY POINT TWO ORAL STEROIDS
Prednisone tablets, 20 mg (prednisone)
Dexamethasone tablets, 4 mg (Decadron)

76. PROPELLENTS CFC: chlorofluorocarbons HFA: hydrofluoroalkane
Safe to inhale but damaging to the earth’s ozone layer
MDIs with CFC are being phased out
HFA: hydrofluoroalkane
Safe for the environment and the patient
Delivers nearly twice as much medication to the patient

77. SEVERAL WEBPAGES REGARDING ASTHMA
American College of Physicians
(many links)
Neomedicus and Merck
American Lung Association

78. PERSONAL COMMENTS

79. ORAL CORTICOSTEROIDS Only prednisone needed for PO use
Once per day about equivalent to BID
May stop med abruptly after ~5 days
Used almost exclusively for quick relief, not for supplementing (long term) inhaled steroids or long acting beta2-agonists in step 4

80. INHALED STEROIDS COMMON PRACTICES
Beclomethasone (Beclovent) not in common use in some medical centers
Budesonide (Pulmicort) ~20% absorbed, but used mostly in nebulizer for children
Flunisolide (Aerobid) not used much
Fluticasone (Flovent) ~1% absorbed, commonly used & available in 3 strengths
Triamcinolone acetonide (Azmacort) not in common use in some medical centers

81. LONG ACTING BETA2-AGONISTS
Salmeterol (Serevent) off market (CFC)
Fixed dose of salmeterol now only available in combination with 3 strengths of fluticasone as Advair (100/50, 250/50 & 500/50)
Formoterol (Foradil) available

82. FORMOTEROL Available as Foradil
It is both short acting and long acting
12 mcg of Foradil is equivalent to 50 mcg of salmeterol (Serevent)
Provided as 12 mcg capsules to be used in aerolizer (not PO) every 12 hours

83. CROMOLYN & NEDOCROMIL Cromolyn is available as Intal
Nedocromil is available as Tilade
Not commonly used

84. LEUKOTRIENE MODIFIERS
Used as adjunctive therapy for asthma
Oral treatment available
Simultaneously treats allergic rhinits

85. LEUKOTRIENE MODIFIERS
Leukotriene Receptor Antagonists (LTRAs)
Montelukast is available as Singulair prescribed as one 10 mg tablet per day
Zafirlukast is available as Accolate prescribed as 20 mg tablet BID
5-Lipoxygenase Inhibitors
Zileuton is available as Zyflo prescribed as 600 mg QID

86. METHYLXANTHINES
Theophylline used very little now and requires blood level monitoring

87. QUICK RELIEF Albuterol inhaler commonly used
Pirbuterol (Maxair) is also useful and also available as an Autohaler, a breath activated inhaler, easier and more reliable to use
Albuterol nebulizer solution is available, usually given as 2.5 mg/3ml (0.083%) for teens and young adults
Ipratropium (anticholinergic) (Atrovent) useful for beta2 receptor resistance to albuterol
Anticholinergic + albuterol generally used for COPD
Injectable beta2-agonists too short acting

88. SUGGESTED MINIMAL STOCK
Albuterol inhaler
Albuterol nebulizer solution 2.5 mg/3cc
Prednisone 20 mg tabs
Advair (fluticasone + salmeterol) DPI in 100/50 & 250/50 doses
Flovent (fluticasone) MDI 44,110 & 220 mcg/puff OR DPI 50, 100 & 250 mcg/puff

89. TWO POSSIBLE ADDITIONS
Quick Relief: Pirbuterol (Maxair) is also useful and also available as an Autohaler, a breath activated inhaler, easier and more reliable to use
Quick Relief and Long Acting Beta2-Agonists: Formoterol (Foradil) can be given BID in place of Serevent

90. COMMENTS ABOUT PEAK FLOW METERS
Comparable to careful monitoring of signs and symptoms in managing asthma
Inexpensive / disposable mouthpieces
Can be used with “personal best” or predicted average PEF (liters per minute)
Daily use reserved for most severe patients, but adherence drops off quickly
Very subject to effort, in contrast to FEV1

91. OTHERS Pulse oximetry – most useful in emergency rooms
Spirometry – useful to detect degree of obstruction and if it can clear with bronchodilators and or steroids
Asthma specialists – useful for step 3 and/or step 4 patients or difficulty with management