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.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 ½ 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

----------------------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.

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

ASTHMA MEDICATIONS Beta2-Agonists Anticholinergics 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 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.

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).

“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 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 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

SEVERAL WEBPAGES REGARDING ASTHMA www.chestnet.org American College of Physicians www.whatsasthma.org (many links) Neomedicus and Merck 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 Beta2-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