Asthma

1. Asthma Michelle Harkins, MD University of New Mexico Pulmonary and Critical Care Project Echo

3. Asthma and School Absences • Asthma is one of the leading causes of school absenteeism. • In 2003, an estimated 12.8 million school days were missed due to asthma among the more than 4 million children who reported at least one asthma attack in the preceding year. • 39% reported receiving an asthma management plan Akinbami LJ. The State of Childhood Asthma (pdf 365K), United States, 1980-2005. Advance data from Vital and Health Statistics: no 381, Revised December 29, 2006. Hyattsville, MD: National Center for Health Statistics, 2006

5. Asthma in New Mexico • 204,292 adults have had an asthma dx • 68.8K under age 17 • # of days missed by NM School children for asthma? • Estimated cost of treating asthma in those under 18 is $3.2 billion per year (Weiss KB, Sullivan SD, Lytle SD) • 30-40 deaths/year from asthma • Mortality decreased from 3.1/100,000 in 1993 to 1.5/100,000 in 2004 • >65 years at greatest risk • Dept. of Health Statistics, 2007, BRFSS

8. 14.9* 23.3 33.1 16.8* 46.7 46.7 41.5 41.5 13.6* 13.6* 7.6* 25.5 14.2 13.2 49.2 49.2 28.7* 28.7* 26.8 23.4 42.9* 42.9* 27.7 27.7 9.0* 10.1* 15.5* 7.9* 0.0* 0.0* 0.0* 0.0* 56.5 38.2 9.5 10.3 22.5 22.5 35.1 35.1 39.2 39.2 11.1 13.7 12.0 15.3 41.8 41.8 16.5 14.9 19.0* 17.8* 135.6 135.6 17.7* 14.9 14.9 19.4 62.2 62.2 8.0* 8.0* 4.5* 4.5* 9.1* 6.6* 21.8 21.8 18.2 13.3 22.2 22.2 63.3 64.7 103.2 103.2 20.6* 22.7* 17.7* 17.7* 14.8* 6.2* 13.9* 5.8* 50.9 42.9 104.2 104.2 144.0 144.0 0.0 – 10.1 14.8* 14.8* 9.2* 13.7* 37.0 37.0 10.2 – 14.2 15.1 35.4 63.9 63.9 14.3 – 23.3 69.1 69.1 6.3* 10.5* 11.3* 11.6 77.9 23.4 – 77.9 60.4 60.4 118.2 76.3 76.3 10.9 11.4 80.1 80.1 23.7 46.5 11.5 11.7 37.9 37.9 95.3 95.3 75.4 75.4 24.5 26.1 15.6* 26.2* 24.0* 24.0* Asthma Hospitalization Rates (Age<15), New Mexico 2006-2008 STATE RATE: 20.1 Rates per 10,000 population. * Rates based of fewer than 20 cases should be interpreted with caution. SOURCE: NMHPC.

9. What is Asthma? • A chronic inflammatory disease of the airways • The majority of asthma diagnosed in childhood • Common Symptoms: • Cough-may be only at night • Wheezing • Chest Tightness • Shortness of breath • Mucus (phlegm production)

10. Features of Asthma • Intermittent wheezing, chest tightness, cough—times when there are no symptoms • Bronchial hyperresponsiveness-”twitchy” airways • Airway inflammation • Airway obstruction - initially reversible • gradual decline in lung function • Peak Flow variability

11. All that wheezes is not asthma... • Bronchiolitis: RSV • Aspiration (micro versus foreign body) • vocal cord dysfunction, laryngeal dysfunction • Competitive athletes • 35% of “severe asthma” referred to specialty clinics • CF • Tracheal malacia

12. Vocal Cord Dysfunction • VCD can mimic asthma, but it is a distinct disorder • VCD may coexist with asthma • Asthma medications typically do little, if anything, to relieve VCD symptoms • Variable flattening of the inspiratory flow volume loop on spirometry is strongly suggestive of VCD • Diagnosis of VCD is from indirect or direct vocal cord visualization during an episode, during which abnormal adduction can be documented • VCD should be considered in patients with difficult-to-treat, atypical asthma and in elite athletes who have exercise related breathlessness unresponsive to asthma medication Guidelines for the Diagnosis and Management of Asthma NHLBI NAEPP EPR 3November, 2007

14. Spirometry and Flow Volume Loops Reversible airflow obstruction VCD possible Normal FEV1 4.36 (100%) FVC 5.04 (108%) FEV1 / FVC .86 FEF25-75 4.77 (108%) FEF50 / FIF50 0.84 2.27  2.71 (16%) 3.20  3.58 (11%) .71  .76 (6%) 1.63  2.13 (23%) 0.38  0.30 3.65 (99%) 3.71 (96%) .98 6.15 (155%) 4.33

15. Pathophysiology of Asthma

16. Epithelial Damage in Asthma Normal Asthmatic Jeffery P. In: Asthma, Academic Press 1998.

17. Asthma Pathophysiology Smooth Muscle Dysfunction Airway Inflammation • Inflammatory cell infiltration/activation • Mucosal edema • Cellular proliferation • Epithelial damage • Basement membrane thickening • Bronchoconstriction • Bronchial hyperreactivity • Hypertrophy/hyperplasia • Inflammatory mediator release Symptoms/Exacerbations

18. Bronchospasm caused by activity Distinct from environmental induced asthma Does not cause swelling, inflammation or mucous production Can be avoided by giving medication prior to activity and by warming up and cooling down Exercise Induced Asthma

19. Bronchospasm caused by activity Some activity more likely than others to trigger it Cold environment: skiing, ice hockey Heavy exertion: Soccer, long distance running Exercising when you have a viral cold Exercise Induced Asthma

20. Symptoms include Coughing Wheezing Chest tightness Symptoms may begin during activity and peak in severity 10-20 minutes after stopping Can spontaneously resolve 20-30 minutes after its onset Exercise Induced Asthma

21. Epidemiology • Prevalence 7-20% of the general population • 80% of patients with asthma have some degree of EIB • Exercise is not a risk factor for asthma, rather a trigger • ?Exercise may help prevent onset of asthma in children • Decrease in physical activity may play a role in increased in asthma prevalence • JACI 2005 Lucas SR, Platts-Mills TA

22. Pathogenesis • Minute ventilation rises w exercise (Vt x RR) • Large volume of relatively cool, dry air inhaled during vigorous activity changes airway physiology. • Inflammatory mediators released • Leukotrienes LTC4 and LTD4, histamine, IL-8 • Th2-lymphocytes are activated: express CD23 • Eosinophils activated and increased in most

23. Clinical Manifestations • Patients with EIB have initial bronchodilation during 6-8 minutes of exercise • Followed by bronchoconstriction starting 3 minutes AFTER exercise, peak 10-15 min. • Resolves after 30-60 minutes • Refractory period where repeat exercise causes less bronchoconstriction • Hoarseness or stridor may suggest VCD instead.

24. Time Course of Exercise Induced Bronchoconstriction

25. Diagnosis • Clinical history of asthma and typical asthma symptoms after exercise, no testing needed • Exercise challenge test: cycle or treadmill for 4-8 minutes until HR 85% of predicted maximum • Fall in FEV1 by 15% is diagnostic • Baseline, then 3, 5, 10, 15 and 30 minutes post exercise • Peak Flows pre and post less accurate but have been used

26. Dyspnea with Exercise • If no history of asthma and pre-medication doesn’t help think about other diagnoses: • VCD or central airway obstruction • Deconditioning • Tracheal malacia • Cardiac causes • Other lung disease

27. Management • Increasing fitness: decreases minute ventilation needs with exercise • Less severe if inspired air is warmer, more humid (Evidence Class C) • Scarf or mask if cold weather • Warm-up period before exercise • Good asthma control: EIB more frequent in patients with poorly controlled disease (Class A) • Check for asthma control • Treating appropriately will reduce frequency and severity of EIB

28. Pharmacotherapy • Inhaled Beta agonists • Short and long acting • Cromoglycates • Inhaled Steroids • Leukotriene modifying agents • Avoid oral agents: theophylline or beta agonists

29. Non-pharmacotherapy • Fish oil supplementation was protective for EIB in elite athletes • Diet rich in Omega-3 fatty acids • Randomized double blind crossover study of 16 patients tx for 3 weeks with fish oil vs. placebo • 3.2 gm eicosapentaenoic acid, 2gm docohexaenoic acid • Pre and post exercise measurements of lung function, induced sputum, leukotrienes and cytokines • Fish oil diet decreased EIB, Sx and improved lung function, less bronchodilators needed • Mickleborough et al, Chest 2006

30. Beta agonists • 2 puffs albuterol HFA 10 minutes prior • More severe asthma may need higher dosing • LABAs: Salmeterol or Formoterol have been used but not advised as daily monotherapy for EIB. • Intermittant beta agonist is preferred and more effective and will prevent EIB >80%. • Regularly scheduled albuterol INCREASES EIB and has decreased response to therapy. • Hancox Am JRRCM 2002,; Inman Am JRCCM 1996

31. Cromoglycates • Prophylactic cromolyn 2-4 puffs 15-20 minutes prior • Mast cell stabilizer • In high performance athletes or exercise under extreme conditions: combining 4 puffs with 4 puffs beta agonists likely more effective than either drug alone.

32. Inhaled Steroids • Improves hyperresponsiveness over weeks to months and will help in the long run if poor asthma control is the cause of EIB. • Important to assess for asthma symptoms outside of exercise when controller therapy is warranted.

33. Anti-leukotriene agents • Decreases urinary leukotrienes after exercise • Protection from EIB by 2 hours after a dose and post exercise recovery is accelerated. • Not effective in all patients • Probably better than long acting beta agonists over time but not better than short acting. • Decreases EIB by 50% compared to placebo • May be beneficial for those with unpredictable exercise patterns that cause symptoms.

34. Break through symptoms • 2-4 puffs of inhaled beta-agonists • Cromolyn not effective

35. Competitive Athletes • Need for disclosure of medications to organization • File Therapeutic Use Exception during competitions • World Anti-Doping Agency lists beta agonists, inhaled steroids as prohibited • Reference Line is 1–800–233–0393

36. Schools • Teachers and coaches should be notified of children with asthma • Students are encouraged to be active • May need to take medications prior to activity

37. Use bronchodilator 10-15 minutes before onset of activity Do warm-up/cool down exercises Check ozone/allergy warnings Never encourage a child to “tough it out” Prevention of Exercise InducedAsthma

38. The Four Components of Asthma Management • Measures of assessment and monitoring • Objective tests, physical exam, history • Severity and control of asthma • Education for a partnership in asthma care • Control of environmental factors and comorbid conditions that affect asthma • Pharmacologic therapy

43. Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 care or higher is required.Consider consultation at step 3. IntermittentAsthma Step 6 Preferred: High-doseICS + LABA + oral corticosteroid AND Consider Omalizumab for patients who have allergies Step up if needed (first, check adherence, environmental control, and comorbid conditions) Step down if possible (and asthma is well controlled at least3 months) Step 5 Preferred: High-dose ICS + LABA AND Consider Omalizumab for patients who have allergies ≥ 12 years old Step 4 Preferred: Medium-dose ICS + LABA Alternative: Medium-dose ICS + either LTRA, Theophylline, or Zileuton Step 3 Preferred: Medium-dose ICS OR Low-doseICS + LABA Alternative: Low-dose ICS + either LTRA, Theophylline, or Zileuton Step 2 Preferred: Low-dose ICS Alternative: Cromolyn,Nedocromil, LTRA, orTheophylline Step 1 Preferred: SABA PRN Assess control Patient Education and Environmental Control at Each Step Steps 2-4: Consider SQ allergen immunotherapy for allergic patients • Quick-Relief Medication for All Patients • SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of systemic oral corticosteroids may be needed. • Use of beta2-agonist >2 days a week for symptom control (not prevention of EIB) indicates inadequate control and the need to step up treatment.

44. Pharmacotherapy in Asthma • Short acting beta-2 agonists • Albuterol, levalbuterol • Long acting beta-2 agonists • Salmeterol, Formoterol • Inhaled corticosteroids—fluticasone, budesonide, mometasone, ciclesonide, beclomethasone, flunisolide, triamcinolone • Leukotriene modifiers • Combination inhalers • ICS/LABA • Theophylline • Oral steroids for exacerbations

45. Barnes et.al 1998 Asthma Basic Mechanisms and Clinical Management

46. Not all Spacers are created equal

47. One Way Valves