An Overview of Asthma Management Steven Weinberger, MD, FACP Deputy Executive Vice President

1. An Overview of Asthma Management Steven Weinberger, MD, FACP Deputy Executive Vice President Senior Vice President for Medical Education and Publishing American College of Physicians Adjunct Professor of Medicine University of Pennsylvania School of Medicine Senior Lecturer on Medicine Harvard Medical School

2. Outline • Focus on diagnosis and treatment • Summary of selected points from latest guideline • Additional points about new and/or controversial areas • Will concentrate on longer-term management rather than acute exacerbations

3. Published Asthma Guideline (U.S.) • National Asthma Education and Prevention Program, National Institutes of Health. Guidelines for the Diagnosis and Treatment of Asthma • Expert Panel Report 3 (2007) • www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm

4. Establishing the Diagnosis • Partially or fully reversible episodes of airflow obstruction and airway hyperresponsiveness • Documentation of episodic airflow obstruction (measured by FEV1) • At least partial bronchodilator responsiveness (>12% and >200 mL increase in FEV1 from baseline after short-acting β-agonist) • Alternative if baseline FEV1 normal: Hyperresponsiveness to bronchoprovocation challenge (positive methacholine test: PC20 < 8mg/ml); sensitive but not specific

5. Disorders Mimicking Asthma • Postnasal drip – can also worsen asthma • Gastroesophageal reflux – can also worsen asthma • Paradoxical vocal cord motion • Typically with inspiratory stridor • Oxygen saturation normal • Diagnose by visualizing vocal cords • Congestive heart failure (“cardiac asthma”) • Cystic fibrosis • Alpha-1-antitrypsin deficiency • Post-viral airway hyperreactivity

6. Disorders Associated with Asthma • Churg-Strauss syndrome – with vasculitis, pulmonary infiltrates • Allergic bronchopulmonary aspergillosis – with pulmonary infiltrates, proximal bronchiectasis • “Samter’s triad” – with nasal polyposis and aspirin sensitivity • Chronic eosinophilic pneumonia – often with peripheral pulmonary infiltrates

7. Allergic bronchopulmonary aspergillosis

8. Chronic eosinophilic pneumonia

9. Management Distinctions • Severity • The intrinsic intensity of the disease process • Assessing asthma severity guides initiation of therapy • Control • The degree to which the manifestations of asthma are minimized by therapeutic interventions and the goals of therapy are met • Assessing and monitoring control guides the adjustment of therapy From NAEPP, 2007

10. Classifying Asthma Severity* *Used for patients not taking long-term control medications (From NAEPP, 2007)

11. General Treatment of Asthma • Standard of treatment is a step-wise approach • Important principle is use of anti-inflammatory controller medication for more than intermittent disease • Self-management education plans are important • Patients should be instructed about technique for use of inhalers and peak expiratory flow rate monitors, and should be observed

12. Adjusting Asthma Control Well controlled: continue current rx.; consider step down if controlled >3 months Not well controlled: step up by 1 step Very poorly controlled: consider short course of oral steroids; step up 1-2 steps *Predicted or personal best (From NAEPP, 2007)

13. Step-Based Therapy of Asthma SABA = short-acting β-agonist; LABA = long-acting β-agonist; ICS = inhaled corticosteroids; Oral CS = oral corticosteroids; LD = low-dose; MD = medium-dose; HD = high-dose

14. Self-Management Plans • Benefits • Reduce emergency room visits and hospitalization • Improve pulmonary function • Patients should have a written action plan • No clear evidence whether action plan should be based on peak expiratory flow rate (PEFR) or on symptoms • Consensus recommendation to use PEFR monitoring for moderate or severe persistent asthma

15. Miscellaneous Points About Treatment • Adding antibiotics to standard care does not improve outcomes in acute exacerbations • Dosage of oral steroids in acute exacerbation (Cochrane Database Syst Rev 2000; 2:CD001740) – no clear advantage of high dose methylprednisolone (>360 mg/24 hrs.) over low dose (<80 mg/24 hrs.), though use of higher-dose steroids remains common • Response to leukotriene modifiers varies from patient to patient – probably depends upon genetic factors controlling 5-lipoxygenase expression

16. Recent Important Treatment Articles • Despite frequent asymptomatic gastroesophageal reflux in poorly controlled asthma, treatment with PPI does not improve asthma control (N Engl J Med 2009; 360:1487) • Investigational monoclonal antibody (mepolizumab) against interleukin-5 decreased frequency of exacerbations in patients with refractory eosinophilic asthma and recurrent severe exacerbations (N Engl J Med 2009; 360:973 and 985)

17. What About Long-Acting -Agonists? • Do LABA worsen disease control, and are they associated with increased mortality? • Meta-analysis (Ann Intern Med. 2006; 144:904-12): LABA associated with  exacerbations requiring hospitalization and  risk for asthma-related deaths • Other meta-analyses: no increase in risk of LABA in patients on inhaled steroids (Cochrane Rev. 2009: CD006922 and Am J Respir Crit Care Med 2008; 178:1009) • Conclusion: LABA in asthma should not be used in the absence of inhaled steroids

18. Value of Anti-IgE Therapy? • Omalizumab = recombinant humanized IgG1 monoclonal anti-IgE antibody • Cochrane review (2006): decreases need for inhaled steroids; decreases exacerbations • Issues • What is clinical value of ability to reduce inhaled steroid dose? • Value relative to other treatments (e.g., LT inhibitors)? • Risk of anaphylaxis (rare) • Cost of rx. - $4000-20,000/year • Utility and indications remain unclear Strunk and Bloomberg. N Engl J Med. 2006;354:2689

19. Exhaled Nitric Oxide: A Future Advance in Monitoring? • Exhaled nitric oxide (NO) correlates with eosinophilic airway inflammation • Could measurement of exhaled NO guide use of inhaled corticosteroids? • Conflicting results • Positive study (N Engl J Med. 2005; 352:2163): can significantly reduce maintenance doses of inhaled steroids without compromising control • Negative studies (Am J Respir Crit Care Med 2007; 176:231; Lancet 2008; 372:1065): did not  inhaled steroids or improve control

20. Bronchial Thermoplasty: A Future Advance in Treatment? • Technique: apply radiofrequency energy to airway wall, which heats tissue • Rationale: reduces mass of airway smooth muscle • N Engl J Med. 2007; 356:1327-37: fewer exacerbations, improved morning PEFR, and asthma control in treated group • No change in airway responsiveness or FEV1 • Am J Respir Crit Care Med. 2010; 181:116-24: improved asthma-related quality of life and decreased severe exacerbations

21. Conclusions • Spirometric demonstration of reversible airflow obstruction is key to the diagnosis • It is important to be aware of other disorders that can mimic or complicate asthma • The stepwise approach to managing asthma is continually being refined • Newer methods of monitoring airway inflammation and treating based on disease mechanisms may become clinically applicable in the future