Evidence Based Asthma Diagnosis and Management 2007 EPR CPG Update Henry A. Wojtczak, M.D....

Evidence Based Asthma Diagnosis and Management 2007 EPR CPG Update Henry A. Wojtczak, M.D. [email protected]

Learning Objectives Understand how to diagnosis and assess asthma Recognize the goals of asthma therapy Be able to recommend optimal treatment strategies for patients with asthma of varying severity Determine the optimal controller medications for patients with persistent asthma Understand the proposed changes to the NHLBI Asthma guideline for 2007 Identify the vital role the pharmacist plays in asthma disease management

The Literature on Asthma, as Indexed in PubMed (Last 5 Years) 22,135 citations under asthma 3301 English-language articles on search terms asthma & management 9 indexed journals with asthma in their name 80 clinical practice guidelines

http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf NAEPP Expert Panel Report 2 Issued, 1997 NIH Publication #97-4051 Updated in Selected Areas, 2002

Burden of Disease General Over 300 million asthmatics worldwide 1 20.5 million Americans have Asthma 2 Approximately 6.5 million children are affected 2 10.6 million individuals experienced an asthmatic episode during the previous 12 months Nearly 500,000 hospitalizations for asthma anualaly in the US 1.Allergy 2004 Global Burden of Asthma: 59; 469-478 2.National Center for Health Statistics. Raw Data from the National Health Interview Survey, US, (2005)

Burden of Disease Death Rate, 1979 to 1997 0.8 1 1.2 1.4 1.6 1.8 '79'80'81'82'83'84'85'86'87'88'89'90'91'92'93'94'95'96'97 Male + Female Male Female Deaths per 100,000 Population Year National Center for Health Statistics. Raw Data from the National Health Interview Survey, US, 1997-1998. (Analysis by the American Lung Association Best Practices Division, Using SPSS and SUDAAN software)

Definition, Pathophysiology, and Pathogenesis Asthma as a chronic inflammatory disorder of the airways Persistent structural changes in some patients Increasing importance of gene-by-environment interactions Strongest identifiable predisposing factor: atopy Viral infections as important precipitants of exacerbations and development of asthma

Current Understanding of Pathogenesis Development of asthma cannot be prevented in susceptible individuals Daily long-term control medication does not alter the underlying course of the disease

Clinical Presentation May present as any combination of the following symptoms: episodic wheezing, shortness of breath, or coughing paroxysms Patients will sometimes relate a history of frequent bronchitis or reactive airway disease. Often related to specific triggers (cold air, exercise,viral upper respiratory tract infections) Often have a personal or family history of atopic disorders (allergic rhinitis, asthma,eczema)

Diagnosing Asthma Asthma is, ultimately, a clinical diagnosis. Historical and objective data must be combined to arrive at the diagnosis. History Cough, recurrent wheeze, SOB. Note: Many patients may not note wheezing. Cough may be the primary presentation. Symptoms worsen with triggers such as allergen exposure, exercise, pollutants. Symptoms occur or worsen at night, resulting in awakening.

Diagnosing Asthma Physical exam wheezing is not always asthma asthma patients do not always wheeze, even during an exacerbation Improvement in the physical exam usually noted after bronchodilator treatment

Diagnosis Objective lung studies: In patients > 4 years old, spirometry is used to: Document airflow changes consistent with an obstructive lung disease such as asthma Document clinically suspected reversible* airways obstruction in patients. Some young patients (4-8 yo) will have difficulty producing reliable spirometry. *Reversible means that a bronchodilator such as albuterol decreases or reverses the airflow obstruction. (FEV1 or FVC increases 12%; see below)

Diagnosis Documenting reversible airflow obstruction is the most accurate method to diagnose asthma Since asthma is an episodic disease, the lack of reversibility during a healthy period does not rule out asthma There are 3 ways to document reversible obstruction. (1) Spirometry; pre- and post- inhaled bronchodilator therapy (eg, albuterol) (2) Spirometry before and after a course of systemic or inhaled steroids. (3) Bronchoprovocation studies

Spirometry Diagnosis Classically, see a low FEV 1 (amount of air expired in one second with maximal effort) with a decreased FEV 1 / FVC ratio in an asthmatic with active airflow limitation. To help confirm asthma, after a bronchodilator or a course of steroids, expect to see: Increase in FVC, FEV 1, or FEV 1 /FVC ratio of 12% from baseline; or an increase in FEF 25-75 of 30% from baseline In adults, an absolute increase of 200ml in FVC and FEV1 should also be seen Failure to see 12% increase or greater does not mean asthma is excluded.

Normal ( red) vs. Asthma (black) Flow Volume Loop

PFT Sheet

Precipitating / Sustaining Factors for Asthma Allergen exposure Allergic Rhinitis Exercise Viral URIs Rhinosinusitis GERD Cigarette smoke Environmental exposures (eg, pollution, fumes)

Viral Respiratory Infections The vast majority (~80%) of acute asthma exacerbations are secondary to viruses Most common agent is rhinovirus Mechanism is poorly understood Most plausible is that existing airway inflammation is up-regulated Frequent hand washing and routine influenza vaccination can prevent viral-induced asthma exacerbations

Allergen Exposure/Allergic Rhinitis Estimated that 50% or so of asthmatics are atopic. In these individuals, allergens are believed to be a major driving factor in chronic inflammation. Most significant indoor allergens are dust mite, cat and cockroach. Outdoor allergens can also prompt airway inflammation. Allergy skin testing or RAST can help identify which allergens are important in individual patients Allergen avoidance may result in disease improvement. Control of the atopic response with long acting antihistamines, inhaled nasal steroids or leukotriene inhibitors can help decrease asthma symptoms that are allergen related

Exercise-Induced Bronchospasm Probably a subset of asthma, rather than a distinct clinical entity. Classically, see worst symptoms and airway obstruction 5 to 10 minutes after exercise. Those with symptoms exclusively during exercise are probably mild asthmatics who only get symptoms at the extremes of exertion. Possibly due to cool, dry air inspiration that results in drying/irritation of bronchial mucosa. Typically pre-treatment with short acting beta agonist prior to exercise limits the symptoms from exercise induced asthma, as does exercise conditioning. Consider alternative diagnoses such as vocal cord dysfunction especially if symptoms not improved by bronchodilator pre- treatment

Gastroesophageal Reflux (GER) and Asthma GER has been proposed by many authors as a chronic and acute driving factor for asthma, likely via a vagal reflex. In studies, perfusion of acid into the esophagus leads to an increase in cough response and increased airways hyperresponsiveness. Studies show medical treatment with a proton pump inhibitors can improve asthma symptom control, but not objective lung studies (eg. PEF, FEV 1 ). studies suggest up to 70% improvement in symptoms. Fundoplication may provide even better results than medical management.

Rhinosinusitis and Asthma National Heart Lung and Blood Institute (NHLBI) Asthma CPG recognizes that chronic rhinosinusitis can contribute to asthmatic inflammation and poor disease control. 50-80% of asthmatics have chronic rhinitis By an unknown mechanism (neural?), inflammation of the nose and sinuses appears to drive or worsen asthma in some individuals. Curing the sinus/nasal disease often markedly improves the asthma (ie: inhaled nasal corticosteroid, sinus polyp surgery, long term antihistamines).

Asthma: Making the Diagnosis Differences from 1997 & 2002 guidelines Emphasis on spirometry Preference over peak flow for diagnosis Inclusion of FEV 6 as well as FVC Recommended in children > age 4

Asthma: Making the Diagnosis Differences from 1997 & 2002 guidelines Consideration of alternative diagnoses Vocal cord dysfunction Cough variant asthma Gastroesophageal reflux disease Obstructive sleep apnea Allergic bronchopulmonary aspergillosis

NHLBI National Asthma Education and Prevention Program Expert Panel Guidelines for the Diagnosis and Management of Asthma (EPR-3) Due Summer 2007 (Draft for Comment by Stakeholding Groups, January 2007)

Key Differences From 1997 Guideline The critical role of inflammation has been further substantiated, but evidence is emerging for considerable variability in the pattern of inflammation, thus indicating phenotypic differences that may influence treatment responses. Gene-by-environmental interactions are important to the development and expression of asthma. Of the environmental factors, allergic reactions remain important. Evidence also suggests a key and expanding role for viral respiratory infections in these processes.

Key Differences From 1997 Guideline The onset of asthma for most patients begins early in life with the pattern of disease persistence determined by early, recognizable risk factors including atopic disease, recurrent wheezing, and a parental history of asthma. Current asthma treatment with anti-inflammatory therapy does not appear to prevent disease progression

Assessment The key elements of assessment and monitoring are refined to include the separate, but related, concepts of Severity Control Responsiveness to treatment

Severity Classification Classifying severity is emphasized for initiating therapy; assessing control is emphasized for monitoring and adjusting therapy. Asthma severity and control are defined in terms of two domains Impairment Risk

Severity Classification Severity classification is defined in terms of two domainsimpairment and riskto emphasize the need to consider separately asthmas effects on Quality of life and functional capacity on an ongoing basis (i.e., in the present) The risks that asthma presents for adverse events in the future, such as exacerbations and progressive loss of pulmonary function. These domains of asthma may respond differentially to treatment.

Severity Classification New parameters for pulmonary function measuresFEV1/FVChave been added to classify severity for children. The severity classification for chronic asthma changed the category of mild intermittent to intermittent in order to emphasize that even patients who have intermittent asthma can have severe exacerbations.

Diagnosis Information on vocal cord dysfunction (VCD) and cough variant asthma as an alternative diagnosis has been added. Reference has been added to updated information in another component on comorbid conditions that may complicate diagnosis and treatment of asthma (e.g., allergic bronchopulmonary aspergillosis (ABPA), obstructive sleep apnea (OSA), and GERD).

Control Evidence strengthens recommendations that reducing exposure to inhalant indoor allergens can improve asthma control and notes that a multifaceted approach is required; single steps to reduce exposure are generally ineffective. Formaldehyde and volatile organic compounds (VOCs) have been implicated as potential risk factors for asthma and wheezing. Evidence shows that influenza vaccine, while having other benefits, does not appear to reduce either the frequency or severity of asthma exacerbations during the influenza season. The section has been expanded to include discussion of ABPA, obesity, OSA, and stress as chronic comorbid conditions that may interfere with asthma management, in addition to rhinitis, sinusitis, and gastroesophageal reflux.

Patient Education Emphasis on the many potential points of care and sites available in which to provide asthma education, including review of new evidence regarding the efficacy of asthma self management education outside the usual office setting. Greater emphasis on the two aspects of the asthma action plan(1) daily management, and (2) early recognition of and actions for handling exacerbations. Use of the terminology asthma action plan encompasses both aspects. This change addresses confusion over the previous guidelines use of different terms for asthma management plans. One term is now used. New sections on the impact of cultural and ethnic factors and health literacy that affect delivery of asthma self- management education.

Provider Education New section with review of system-based interventions to improve the quality of asthma care, to support clinical decision-making, and to enhance clinical information systems Review of tested programs that use effective strategies to provide clinician education in asthma care, e.g., multidimensional approaches, interactive formats, and practice-based case studies

Medications Information about asthma medications has been updated based on review of evidence published since 1997. This updated report (EPR3) continues to emphasize that the most effective medications for long-term therapy are those shown to have anti-inflammatory effects. New medicationsimmunomodulatorsare available for long-term control and prevention of symptoms. New data on the safety of LABAs are discussed, and the position of LABA in therapy has been revised (see text). The most significant difference is that for youths 12 years of age and adults whose asthma is not controlled on low-dose ICS, the option of increasing the dose of ICS should be given equal weight to the option of adding LABA to low-dose ICS. The estimated clinical comparability of different ICS preparations has been updated. The significant role of ICSs in asthma therapy continues to be supported.

Medications Recommendations for managing asthma in children 04 and 511 years of age are presented separately from recommendations for managing asthma in youths >12 years of age and adults. Treatment decisions for initiating long-term- control therapy are based on classifying severity (considering both the impairment and risk domains) and selecting a corresponding step for treatment. Recommendations on when to initiate therapy in children 04 years of age have been revised

Medications Treatment decisions for adjusting therapy and maintaining control are based on assessing the level of asthma control (considering separately asthmas effects on quality of life and functional capacity on an ongoing basis (i.e., in the present) and the risks it presents for adverse events in the future, such as exacerbations and progressive reduction in lung growth or lung function.

Medications Stepwise approach to managing asthma has been expanded to include six steps of care to simplify the actions within each step. For example, previous guidelines had several progressive actions within step 3, whereas the current guidelines separate the actions into different steps. Treatment options within the steps have been revised, especially: For patients not well controlled on low-dose inhaled corticosteroid (ICS), increasing the dose of ICSs to medium dose is recommended before adding adjunctive therapy in the 04 years age group; for other age groups (children 511 years of age and youths 12 years of age and adults), increasing the dose of ICS to medium dose or adding adjunctive therapy to a low dose of ICS are considered as equal options. Evidence for the selection of adjunctive therapy is limited in children under 12 years of age; recommendations vary according to the assessment of impairment or risk. Steps 56 for youths 12 years of age and adults include consideration of omalizumab. Managing special situations has been expanded to include racial and ethnic disparities.

Exacerbation Management For the assessment of exacerbations, the current update (EPR3): simplifies classification of severity of asthma exacerbations. Reinstates the 1991 cut points of forced expiratory volume in 1 second (FEV1) or peak expiratory flow (PEF) to indicate the goal for discharge from urgent care (70 percent predicted FEV1 or PEF); patients for whom response to therapy is incomplete and who usually require continued treatment in the ED (4069 percent predicted); and the exacerbation severity level where adjunct therapies may be considered (

Short-Acting Beta Agonists (SABA) in Asthma Most effective agents available for acute bronchospasm Use of > 1 canister/month indicates inadequate asthma control Regularly-scheduled, daily, chronic use of SABAs is NOT recommended

Relative Risk of Hospitalization in the United States Donahue et al. JAMA. 1997;277:887-891. Prescriptions per person-year Relative Risk None1-22-33-55-88+0-1 2 -agonists Total ICS 0 1 2 3 4 5 6 7 8 Age 0-17 Age 18-44 Age 45+ Total Age 0-17 Age 18-44 Age 45+

Pharmacologic Therapy: Differences from the Old Guidelines Emphasis on agents with anti-inflammatory properties for long-term control Revision of position of LABAs in long-term control scheme: more priority for increased doses of ICS as option Addition of immunomodulators for long-term control

SMART (Salmeterol Multicenter Asthma Research Trial) Study* Randomized, placebo-controlled, double-blind study of adding salmeterol to usual therapy for asthma (26,355 patients) Terminated early because of increases in respiratory- and asthma-related deaths and life-threatening experiences in salmeterol group These adverse events were more frequent in African- American patients, especially if not also taking inhaled corticosteroids *Nelson HS et al, Chest 2006;129:15-26

SMART (Salmeterol Multicenter Asthma Research Trial) Study* African-American patients in study Comprised 18% of total study patients Had lower baseline lung function Utilized more urgent health care services Fewer of them were using ICS ? worse asthma and worse management FDA required Black Box warning on all LABAs as result of these findings *Nelson HS et al, Chest 2006;129:15-26

If Persistent Asthma Not Adequately Controlled with Low-Dose ICS* GINA: Add LABA (ie, use combination rx) rather than ICS dose New NAEPP Guideline (1/07 draft): ICS dose alone is acceptable alternative in light of SMART Study findings *Moore WC, Peters SP. AJRCCM 2007;175:649-654

Anticholinergics in Asthma In the emergency treatment of acute severe asthma, ipratropium has beneficial effects when added to SABAs.* There is no evidence for benefit from either ipratropium or tiotropium in stable asthma. Neither drug is FDA approved for use in asthma. *Meta-analysis: Rodrigo GJ et al, Thorax 2005;60:740-746

Step Therapy Age 0-4 years

Step Therapy Age 5-11 years

Step Therapy Age 12 years +

Asthma Therapy Goals of asthma therapy- Prevent symptoms that limit activity and/or result in missed school/work days. Avoid hospitalizations/ER visits. Avoid asthma deaths (3,000 - 5,000/year). Prevent unchecked inflammation (poorly perceived PFT abnormalities) that can lead to airway remodeling and irreversible damage.

Asthma Therapy Goals Obvious triggers of airway inflammation should be treated and/or avoided if possible. Allergen avoidance may be useful adjunct to meds (for identified indoor allergens). Treat allergic rhinitis, sinusitis, GER. Full physical activity should be encouraged.

Intermittent Intermittent NHLBI Asthma CPG states that patients may be treated with prn bronchodilators alone as long as all of the following are true: Symptoms continue to occur two or less times weekly Nighttime symptoms (awakenings) are occurring less than twice monthly Rescue BD use < 2/ week Normal Spirometry No interference with normal activity < 1 exacerbation yearly

Mild Persistent These are patients with symptoms more than twice weekly (but not daily) who have normal baseline spirometry. Require Long-Term Controller (ICS)!!! The vast majority of experts and clinicians use inhaled steroids as the treatment of choice for first line therapy in persistent asthma. If one is considering not using inhaled steroids as the first line agent, there should be a compelling reason for that decision.

Mild Persistent Using leukotriene modifiers (eg, Accolate, Singulair) mono-therapy as a LTC is discouraged. Low dose inhaled steroids (e.g., fluticiasone (Flovent) 44 mcg/puff, 2 puffs BID) are usually sufficient in this group. Patients should be instructed to rinse mouth after use to avoid thrush and dysphonia. If not controlled with the above, the patient is most likely a moderate persistent asthmatic.

Moderate Persistent These are patients with daily symptoms, or baseline FEV 1 60-80% predicted. Three treatment choices Going from low to medium dose ICS (eg, fluticasone 110 mcg/puff, 2 puffs bid) (preferred) OR Add a long-acting bronchodilator (eg, salmeterol) to low-dose ICS Less attractive alternative: Add an anti-leukotriene agent (eg, montelukast) to low- dose ICS

Moderate Persistent A change in the recent NHLBI Asthma CPG : For Moderate Persistent asthma, increasing ICS from low-dose to medium dose is preferred over adding LABA or LTRA.

Meta-analysis Clinic FEV 1 at 6 Months Favors increasing ICS Ind Greening Woolcock Kelsen Murray Kalberg Condemi van Noord (LD) van Noord (HD) Vermetten Fixed effects Random effects Treatment difference (L) Favors adding salmeterol -0.250.000.25-0.500.50 Adapted from Shrewsbury et al. Br Med J. 2000;320:1368-1373.

Meta-analysis Mean Percentage of Symptom-Free Days at 6 Months -10010304020 Ind Greening Woolcock Kelsen Murray Kalberg Condemi van Noord (LD) van Noord (HD) Vermetten Fixed effects Random effects Treatment difference (%) Favors adding salmeterol -30-20-40 Favors increasing ICS Adapted from Shrewsbury et al. Br Med J. 2000;320:1368-1373.

Run-in FP 100 mcg inhalation powder BID FP 100 mcg BID + MON 10 mg QHS (n=225) 3 weeks12 weeks FP/SP DISKUS 100/50 BID (n=222) Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095. FP/SAL DISKUS 100/50 vs FP 100 mcg + Montelukast 10 mg Study Design Patients: 15 years of age Baseline FEV 1 50%-80% of predicted Symptomatic on ICS MON, montelukast

FP/SAL DISKUS 100/50 vs. LTRA: AM PEFR Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095. Baseline AM PEF: FP/Sal DISKUS 100/50 = 398 L/min; FP + MON = 392 L/min. *P 0.001 vs FP + MON at Endpoint. Mean Change from Baseline in AM PEF (L/min) Day Endpoint (last evaluable measurement) FP/SAL DISKUS 100/50 BID FP 100 mcg BID + MON 10 mg QD * 714212835Baseline42495663707784

FP/SAL Discus vs. MON 10: Rescue Albuterol Use Nelson et al. J Allergy Clin Immunol. 2000;106:1088-1095. Baseline albuterol use (puffs/day): ADVAIR DISKUS 100/50 = 3.77; FP + MON = 3.73. *P=0.004 vs FP + MON at Endpoint. Mean Change from Baseline in Rescue Albuterol Use (puffs/day) Endpoint Week * FP/SP DISKUS 100/50 BID FP 100 mcg BID + MON 10 mg QD 12345Baseline6879101211 No significant difference between treatments was observed for the Overall Daytime Symptom Score. Statistical significance was not achieved in the replicate study for median percentage of rescue-free nights.

FP/SAL DISKUS 100/50 vs. FP/MON 10 mg FEV 1 Changes Baseline FEV 1 : ADVAIR DISKUS 100/50 = 2.38 L; FP + MON = 2.39 L. *P

Usual Pediatric Doses (mcg) for Inhaled Corticosteroids Drug Low MediumHigh BDP(42 ug/p) 84-336 336-672 > 672 FLUN(250 ug/p) 500-750 1,000-1,250 >1,250 TAM(100 ug/p) 400-800 800-1,200 >1,200 FP(44/110/220/p) 88-176 176-440 >440 BUD(200ug) 100-200 200-400 >400 BDP- Beclomethasone dipropriate, Flun- Flunisolide, BUD- Budesonide TAM- Triamcinolone, FP-Fluticasone proprionate,

Which Asthma Patients Should Be Referred to an Asthma Specialist? History of life-threatening exacerbation Treatment goals not met after 3-6 months Atypical Sx/signs, or uncertain diagnosis Significant comorbidities VCD, sinusitis, polyps, ABPA, GERD, COPD Additional diagnostic testing indicated

Which Asthma Patients Should Be Referred to an Asthma Specialist? Consideration for immunotherapy Requirement for step 4 care or higher Hospitalization for asthma Requirement for 2 steroid courses in 1 yr Suspected occupational/environmental contribution Psychiatric/psychosocial/family problems

Expert Panel Recommendations for Elements of Each Follow-up Visit Ask patients what concerns they have about their asthma and what they especially want addressed during the visit? Review the short-term goals agreed on in the initial visit. Review the written action plan. Continue teaching and reinforcing key educational messages. Give patients brief, written materials.

Pharmacists Role in a Comprehensive Asthma Disease Management Program Provide patient focused education on medication efficacy and side effects Review and instruct on optimal delivery Pharmacy database review to identify poor adherence to refills and B 2 abuse

Pharmacists Role in a Comprehensive Asthma Disease Management Program Educate patients about asthma medications. Instruct patients about the proper techniques for inhaling medications. Monitor medication use and refill intervals to help identify patients with poorly controlled asthma. Encourage patients purchasing OTC asthma inhalers or tablets to seek medical care Help patients use peak flow meters appropriately. Help patients discharged from the hospital understand their asthma management plan.

NMCSD Pediatric Asthma Hospitalization Rate vs. Healthy People 2000 and 2010 Benchmarks Year Pediatric Asthma Admissions / 10,000 0 5 10 15 20 25 30 35 40 45 1996199719981999200020012002 NMCSD HP 2000 HP 2010 20032004 20052006

ED Visits Fiscal Year NMCSD Emergency Department Pediatric Asthma Visits 0 100 200 300 400 500 600 1999200020012002 E.D Asthma Visits 2003 2004 20052006

Net Savings 97-03- $4,087,500 Naval Medical Center San Diego Pediatric Asthma Inpatient Cost Savings Compared to Fiscal Year 1996

Evidence Based Asthma Diagnosis and Management 2007 EPR CPG Update Henry A. Wojtczak, M.D....

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Transcript of Evidence Based Asthma Diagnosis and Management 2007 EPR CPG Update Henry A. Wojtczak, M.D....