# Presentation: 055998

## 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**

## Guidelines for the Diagnosis and Management of Asthma--------------------------------------Update on Selected Topics  - 2002 -

- Expert Panel Report (EPR) – Update 2002
- National Asthma Education and Prevention Program (NAEPP)
- NIH Publication No. 02-5074
- June 2003

## PREVIOUS REPORTS

- _1997_ Guidelines for the Diagnosis and Management of Asthma (EPR-2)
- _1991_ National Asthma Education and Prevention Program’s (NAEPP) first report

## AVAILABLE NAEPP PUBLICATIONS

- _[http://www.](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[nhlbi](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[.](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[gov](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[.](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[nhlbi](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[/](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[nhlbi](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[.](http://www.nhlbi.gov.nhlbi/nhlbi.htm)__[htm](http://www.nhlbi.gov.nhlbi/nhlbi.htm)_
- (National Heart, Lung and Blood Institute)

## OBJECTIVE

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

## 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 2003 14.7% of teens 12-17 years of age have had asthma diagnosed

## 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 1⁄2 times higher in Black females than while _females_

## 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

## 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.

## 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

## 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

## 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)

## 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

## SYMPTOM CLASSIFICATION

- _Severe Persistent_
- _Moderate Persistent_
- _Mild Persistent_
- _Mild Intermittent_

## 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

## TARGET OF THERAPY - I

- 1) Acute symptoms of asthma usually arise from _BRONCHOSPASM_ and require and respond to bronchodilator therapy.

## 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.

## TARGET OF THERAPY - III

- 3) Some patients experience persistent airflow limitations and this _REMODELING_ has NO current therapy.

## INFLAMMATION

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

## INFLAMMATION - I

- Airway inflammation in asthma is found in patients with _mild_, _moderate_ and _severe_ disease.

## 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

## INFLAMMATION – IIISevere Persistent & Deaths from Asthma

- Occlusion of bronchial lumen by mucous
- Hyperplasia & hypertrophy of bronchial smooth muscle
- Goblet cell hyperplasia

## 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

## 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.

## 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

## EOSINOPHIL PATHOGENESIS

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

## ASTHMA MEDICATIONS

- Beta2-Agonists
- Corticosteroids
- Leukotriene Modifiers
- Methyl Xanthines
- Cromolyn and Nedocromil
- Anticholinergics

## ASTHMA MEDICATIONS

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

## COMBINATIONASTHMA MEDICATIONS

- Beta2-Agonists
- Long-acting inhaled
- Corticosteroids
- Inhaled

## ADVAIR100/50, 250/50 & 500/50

- Fluticasone DPI 100/250/500 mcg
- Salmererol DPI 50 mcg

## ASTHMA MEDICATIONS

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

## ASTHMA MEDICATIONS

- Beta2-Agonists
- Short-acting inhaled
- Anticholinergics

## 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

## CORTICOSTEROID EFFICACY

## 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?

## RESULT

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

## RECOMMENDATION

- Inhaled corticosteroids are the _preferred treatment for initiating therapy for persistent asthma_.

## CORTICOSTEROID SAFETY

## 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?

## RESULT

- The use of corticosteroids at recommended doses _does not have long-term, clinically significant, or irreversible effects on any of the outcomes reviewed_.

## 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.

## 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.

## 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.

## 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.

## OVERALLRECOMMENDATION

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

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

## QUESTION

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

## ANSWER

- Strong evidence consistently indicates that long-acting inhaled _beta__2__-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.

## RECOMMENDATION

- The preferred treatment for adults and children older than 5 years of age is the _addition of long-acting inhaled beta__2__-agonists_ to low-to-medium doses of inhaled corticosteroids (not as a substitute).

## “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.

## USE OF ANTIBIOTICS TO TREAT ASTHMA EXACERBATIONS

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

## 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.

## 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.

## 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.

## WRITTEN ACTION PLANS COMPARED TO MEDICAL MANAGEMENT ALONE

## QUESTION

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

## 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.

## 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.

## 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

## PEAK FLOW-BASED COMPARED TOSYMPTOM-BASED WRITTEN ACTION PLANS

## QUESTION

- Compared to a written action plan based on symptoms, does use of a written action plan based on _peak flow monitoring_ improve outcomes?

## 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.

## 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.

## MANAGEMENT

## 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

## 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

## SYMPTOM CLASSIFICATION

- _Severe Persistent_	Step 4		PEF/FEV1 <60%
- Day: continual
- Night: frequent
- _Moderate Persistent_	Step 3		PEF/FEV1 60-80%
- 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

## SYMPTOM CLASSIFICATION

- _Severe Persistent_	Step 4		PEF/FEV1 <60%
- Day: continual				Variability >30%
- Night: frequent
- _Moderate Persistent_	Step 3		PEF/FEV1 60-80%
- 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

## DAILY MEDICATIONSPreferred Treatment:

- Step 4
- High-dose inhaled corticosteroids, AND
- Long-acting beta2-agonists
- Step 3
- Low-to-medium dose inhaled corticosteroids, AND
- Long-acting beta2-agonists
- Step 2
- Low-dose inhaled corticosteroids
- Step 1
- No daily medication needed

## QUICK RELIEFTREATMENT

- Short-acting bronchodilator inhaler
- Nebulizer treatment with bronchodilator
- Course of systemic corticosteroids

## 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

## 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_.

## 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)

## 2004 PERRY POINTTWO ORAL STEROIDS

- Prednisone tablets, 20 mg (prednisone)
- Dexamethasone tablets, 4 mg (Decadron)

## PROPELLENTS

_**CFC: chlorofluorocarbons**_
- 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

## SEVERAL WEBPAGESREGARDING ASTHMA

- _[www.chestnet.org](http://www.chestnet.org/)_
- American College of Physicians
- _[www.whatsasthma.org](http://www.whatsasthma.org/)_ (many links)
- Neomedicus and Merck
- _[www.lungusa.org](http://www.lungusa.org/)_
- American Lung Association

## PERSONAL COMMENTS

## 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

## 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

## 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

## 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

## CROMOLYN & NEDOCROMIL

- Cromolyn is available as Intal
- Nedocromil is available as Tilade
- 				Not commonly used

## LEUKOTRIENE MODIFIERS

- Used as adjunctive therapy for asthma
- Oral treatment available
- Simultaneously treats allergic rhinits

## 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

## METHYLXANTHINES

- Theophylline used very little now and requires blood level monitoring

## 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

## 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

## 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 Beta__2__-Agonists_: Formoterol (Foradil) can be given BID in place of Serevent

## 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

## 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