Treatment of Acute Asthma

1. Annual World CRITER Conference Treatment of Acute Asthma Brian H. Rowe, MD, MSc, CCFP(EM) Tier I CRC in Evidence-Based Emergency Medicine Associate Dean (Clinical Research), FoMD Professor, Department of Emergency Medicine University of Alberta

2. Conflicts • Support for the studies reported in this talk: • CIHR (ON); • Physician's Services Inc. (PSI) Foundation (ON); • Medical Services Inc. (MSI) Foundation (AB); • University of Alberta Hospital Foundation (AB) • Canadian Assoc. of Emergency Physicians (CAEP); • Emergency Health Services - RAC (ON); • Department of Emergency Medicine, U of Alberta; • Industry: drugs supplied AZ, GSK and partial study funding: GSK. • The presenter is not a paid employee or consultant for any sponsor except the University of Alberta.

3. Conclusions • ED visits are common; various treatment options. • In –ED: • SABA/SAAC; SCS; IV MgSO4, ICS and ? NIV. • Post-discharge: • SCS, ICS +/- LABA. • Follow-ups: • Delays common and methods of “connecting”patients to their PCPs is under-studied. • Delivery of non-drug treatments important.

4. Condensed version Give lots of steroids!

5. Asthma • Definition: relapsing chronic airway disease characterized by symptoms of dyspnea. • Pathophysiology: • Primary: Airway inflammation (heterogeneity); • Secondary: broncho-constriction (most symptoms); • Long-term: may produce inflammatory scarring and fixed obstruction. • Exacerbation causes: Many and variable (URI, noncompliance, occupational, environmental, etc). • Summary: treatment addresses primary inflammation and secondary bronchospasm.

6. ED Asthma • Asthma exacerbations are common ED presentations. • Exacerbations result in significant: • Costs to the health care system; • Impairments in quality of life for patients; • Lost time from work, school or activities. • Potential for serious sequelae: • Hospitalizations and complications; • Rarely - death.

7. A person visits an Alberta ED every 16 minutes with asthma. Presentation rates highest in boys. Regional (not shown) and SES variation. In 2004/05, welfare rates were 2.6 times higher and aboriginal were 2 times higher than employed workers. Alberta ED visits for asthma Rowe BH, et al. Chest. 2009

8. Summary • ED asthma visits in adults are declining (stable in children) but still common. • Admission rates variable (~ 9% AB; 20% USA). • Children present more frequently than adults, especially boys. • SES, regional, age and sex variation exists in ED presentations. • Variation in acute asthma care likely contributes to these statistics – can we do better?

9. “Phenotyping” acute asthma • Investigations to confirm diagnosis: • CXR/ABG – discouraged; • VBG – for pH and bicarbonate. • Biomarkers to measure severity: • Never: eNO, sputum cells, urine metabolome. • Our innovation: • History; • Physical (including VS and SaO2); • Airway measures: PEF>FEV1>>> FEV1/FVC

10. Can we really tell asthma from COPD? Spirometry-2 FEV1/FVC > 0.7 FEV1/FVC < 0.7 O‘Donnell DE, et al. CRJ 2008;15:1A-8A

11. Severity assessment (CAEP/CTS)

12. ED (simple) Approach

13. Finding the evidence 2013 Especially productive EM group: Cochrane Airways Group.

14. Cochrane in-ED asthma treatments: • Beneficial effect confirmed: • MDI + spacers vs nebulization (Cates); • Early systemic corticosteroids (Rowe); • Inhaled CS (Edmonds); • Anticholinergics (Plotnick); • Early systemic magnesium sulfate (Rowe). • Beneficial effect lacking: • Antibiotics (Graham); • Heliox (Rodrigo); • Aminophylline (Belda). • Insufficient evidence?: NIV. Hodder R, et al. Can Med Assoc J. 2010

15. In-ED Asthma • Inhaled SABA: • Recommends salbutamol. • Inhaled SAAC: • Recommends IB to reduce admission. • Systemic corticosteroids: • Recommends SCS to reduce admission. • Adjunctive care: • IV MgSO4, ICS, IM epinephrine, NIV? Hodder R, et al. Can Med Assoc J. 2010

16. Nebulizers vs MDI + Spacers? • Evidence: • Cochrane Review (high quality); • Wide search updated 2009; • Search identified 27 trials (2295 children and 614 adults) from ED and community settings. • Variable spacer devices (doesn't seem to make a difference) and doses (higher doses don’t seem to be more efficacious). • Outcomes sub-grouped into peds and adults.

17. Nebulizers vs MDI + Spacers? Cates CA, et al. CL 2010. Outcome: admissions.

18. Nebulizers vs MDI + Spacers? Cates CA, et al. CL 2010. Outcome: LOS in ED.

19. Nebulizers vs MDI + Spacers? Cates CA, CL 2010. Outcome: Rise in pulse rate (% baseline).

20. Summary • SARS and H1N1 have changed care. • MDI + spacer conclusion: • Children - superiority proven; • Adults – no differences vs. equivalence. • Patients with life threatening asthma exacerbations were excluded from the studies, so the results cannot be assumed to apply to this group. • Continuous nebulization may be an effective option (Camargo).

21. In-ED Asthma • Inhaled SABA: • Recommends salbutamol. • Inhaled SAAC: • Recommends IB to reduce admission. • Systemic corticosteroids: • Recommends SCS to reduce admission. • Adjunctive care: • IV MgSO4, ICS, IM epinephrine, NIV? Hodder R, et al. Can Med Assoc J. 2010

22. Anticholinergics (ipratropium bromide) • During the ED stay • P: 2189 patients, > 18 years of age; • D: 7 high quality RCTs; • I: single/multiple IB compared to placebo; • O: 26% reduction to hospital (RR = 0.74; 95% CI: 0.60 to 0.89, with a NNT = 9); • O: increase in early FEV1: m: large with both single (RR = 0.69) and multiple (RR = 0.76). • Summary: use often and early.

23. IB + SABA in the ED

24. In-ED Asthma • Inhaled SABA: • Recommends salbutamol. • Inhaled SAAC: • Recommends IB to reduce admission. • Systemic corticosteroids: • Recommends SCS to reduceadmission. • Adjunctive care: • IV MgSO4, ICS, IM epinephrine, NIV? Hodder R, et al. Can Med Assoc J. 2010

25. During the ED stay Mainstay of ED asthma treatment. CAEP AIR study: 96% SABA (3); 85% SAAC (3); 78% of ED patients received SCS. What’s the evidence? Systemic Corticosteroids Rowe BH, et al. Acad Emerg Med 2008; 15:709–717

26. Systemic CS to prevent admission • During the ED stay • P: 863 patients (435 corticosteroids; 428 placebo); • D: 12 variable quality RCTs; • I: systemic CS compared to “SOC”; • O: reduction in admissions (RR = 0.75; 95% CI: 0.64, 0.85; NNT = 8); • O: earlier treatment, earlier effects observed. • Summary: use often and early. Rowe BH, et al. Cochrane Library, Version 1. 2007

27. SCS - admissions Rowe BH, et al. Cochrane Library, Version 1. 2007

28. In-ED Asthma • Inhaled SABA: • Recommends salbutamol. • Inhaled SAAC: • Recommends IB to reduce admission. • Systemic corticosteroids: • Recommends SCS reduces admission. • Adjunctive care: • IV MgSO4, ICS, IM epinephrine, NIV? Hodder R, et al. Can Med Assoc J. 2010

29. Magnesium • Mechanism: • Cofactor in cellular activity; • Direct bronchodilator; • Perhaps anti-inflammatory agent. • Systematic review of RCTs: • High quality; • 11 trials involving ~900 patients. • Safe, inexpensive, sensible/easy to use, readily available.

30. In-ED use of MgSO4 (admissions) Rowe BH, et al. Cochrane Library, Version 1. 2007

31. ICS • Mechanism: • Local anti-inflammatory; • Vasoactive effects; • Similar to croup. • Systematic review of RCTs: • High quality; • 7 trials involving ~500 patients. • HD needed; safe and readily available.

32. In-ED use of ICS (admissions) Edmonds M, et al. CDSR. 2009 (Issue 1)

33. NIV? • Cochrane review (Ram F, et al; CDSR. 2005 (Issue 2): • 1 included trial (Soroksky 2003; 33 patients treated for 3 hours). • Showed benefit with NIV when compared to usual medical care alone: • ↓ Hospitalisation – HR: 0.28 (95% CI: 0.09, 0.84); • Discharged from ED - HR: 2.26 (95% CI: 1.03, 4.97); •  % predicted FEV1 - WMD: 13.80 (95% CI: 2.3, 25); •  % predictedFVC, PEFR. • Question: who might benefit?

34. Treatment after discharge Preventing relapses

35. Alberta data - Relapse to ED ~6.4% individuals had a repeat ED visit at 7 days.

36. Alberta Data - next MD visit ~35% had at least one (non-ED) follow-up visit within 7 days for any reason; time to first F/U = 19 days (95% CI: 18 to 21).

37. Follow-up Relapse occurs following discharge and other evidence suggests treatment plays a role. Guidelines recommend follow-up for reassessment and educational reinforcement. Follow-up after ED remains less than ideal and so ED MDs need to ensure patients are covered during the sub-acute phase.

38. Cochrane post-ED asthma treatments: Beneficial effect confirmed: Early PO corticosteroids (Rowe); Inhaled CS (Edmonds); Non-pharmacological approaches: Action plans and regular follow-up (multiple). Beneficial effect lacking: Antibiotics (Graham); Non-pharmacological approaches; Nutritional supplementation. Insufficient evidence: LABA, LKTs. Hodder R, et al. Can Med Assoc J. 2010

39. Post-ED asthma approach • Systemic corticosteroids: • Recommends SCS to reduce relapse. • Inhaled corticosteroids: • Recommends ICS to reduce relapse. • Adjunctive care: • Close follow-up, asthma education, smoking cessation, immunizations, AAP. Hodder R, et al. Can Med Assoc J. 2010

40. Cochrane Review • Following the ED stay: • D: Randomized controlled trials (7; quality RCTs); • P: acute asthma discharged (374 pts, all ages); • I: “SCS” (oral/IM) for 7-10 days; • C: vs “standard care”; • O: reduction in relapse (RR: 0.39; NNT: 5); • O: reduction in use of beta-agonists (2/day). Rowe BH, et al. CDSR. 2005 (Issue 1)

41. Systemic CS: preventing relapses

42. Summary • Unless contra-indicated, systemic corticosteroids should be prescribed for acute asthma at discharge. • IM corticosteroids as effective as oral agents (advantage: compliance; disadvantage: injection pain/bruising). • Tapering corticosteroids, not generally felt to be necessary (several trials to support this).

43. Post-ED asthma approach • Systemic corticosteroids (SCS): • Recommends SCS to reduce relapse. • Inhaled corticosteroids: • Recommends ICS to reduce relapse. • Adjunctive care: • Close follow-up, asthma education, smoking cessation, immunizations, AAP. Hodder R, et al. Can Med Assoc J. 2010

44. Flow chart – CS + ICS vs CS alone Emergency Department discharge  Budesonide 1600ug/day X 4 weeks Emergency DepartmentTreatment SABA 2 puffs QID + Prednisone 50 mg OD R Placebo Turbuhaler/day X 4 weeks SABA 2 puffs QID + Prednisone 50 mg OD Visit: 1 Telephone Clinic Visit Week: 0 10-14 days 4 weeks Rowe BH, et al. JAMA 1999

45. Relapse Rowe BH, et al. JAMA 1999

46. ICS • Following the ED visit: • D: 3 RCTs ~ 900 patients; • P: patients discharged from ED, all ages; • I: ICS for 7-21 days; • C: +/- oral prednisone + -agonists; • O: relapse to additional care; • Comparisons: • Primary: ICS + CS vs CS.

47. ICS + CS vs CS Evidence Edmonds ML, et al. Cochrane Library 2007

48. Post-ED asthma approach • Systemic corticosteroids: • Recommends SCS to reduce relapse. • Inhaled corticosteroids: • Recommends ICS to reduce relapse. • Adjunctive care: • LABA?, close follow-up, asthma education, smoking cessation, immunizations, AAP. Hodder R, et al. Can Med Assoc J. 2010

49. Flow chart - ICS vs ICS/LABA Emergency Department discharge  Fluticasone 1000ug/day X 4 weeks Emergency DepartmentTreatment SABA 2 puffs QID + Prednisone 50 mg OD R Fluticasone 1000ug/Salmeterol per day X 4 weeks SABA 2 puffs QID + Prednisone 50 mg OD Visit: 1 Telephone Telephone Week: 0 10-14 days 4 weeks Rowe BH, et al Acad Emerg Med 2007; 14:833-40.

50. Relapse