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Asthma

Asthma. Ping-Wei Chen Dr. Sarah McPherson. Epidemiology. 8.4% adult prevalence in Canada (2000) Most common during childhood At least 12% Canadian children Prevalence increasing 1979 – 2.3 per cent 1988 – 4.9 per cent 1994 – 6.1 per cent Large economic burden

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Asthma

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  1. Asthma Ping-Wei Chen Dr. Sarah McPherson

  2. Epidemiology • 8.4% adult prevalence in Canada (2000) • Most common during childhood • At least 12% Canadian children • Prevalence increasing • 1979 – 2.3 per cent • 1988 – 4.9 per cent • 1994 – 6.1 per cent • Large economic burden • $12 billion spent on asthma (1993) • Estimated ¼ costs spent on acute asthma exacerbations

  3. Epidemiology • ED Visits • 146,000 ED Visits in Canada(1994) • 105,813 ED Visits in Alberta (Apr’99 – Mar’05) • Rowe B, et al. 2009 • Females • Aboriginal • Welfare/Government subsidized • CDC • Non-hispanic African Americans • Children 0-4 years old

  4. Pathophysiology • Bronchial Hyperreactivity • Bronchoconstriction response to various stimuli • Allergic Airway Inflammation • IgE mediated response to allergens • cell release of preformed mediators (histamine) • production of other cytokines (eg: prostaglandins, leukotrienes, ILs) • recruitment of other inflammatory cells Airway inflammation, Bronchoconstriction, Airway edema

  5. Pathophysiology • Eosinophils are the major effector cells • Release of preformed mediators (major basic protein, cationic protein, leukotrienes) • Production of inflammatory mediators (leukotrienes) • Neutrophils, Basophils, Macrophages have smaller role

  6. Pathology • Airway Remodelling • distinct to chronic asthma • airway edema/cellular infiltrates • epithelia damage • hypertrophy/hyperplasia smooth muscle layer • thickening of epithelial basement membrane • enlargement of mucus secreting apparatus • Diffuse Airway Involvement • large airways to airways <2mm in diameter

  7. Clinical Presentation • Cough, Dyspnea, Wheeze, Chest tightness • nocturnal worsening common • poor correlation of symptoms with airway obstruction (as per PFTs) • Difficulty with expiration > inspiration • a variable intrathoracic obstruction

  8. Clinical Presentation • Early Asthmatic Response • from release of preformed mediators • usually resolves within an hour • responds to mast cell stabilizers (β-agonists) • Late Asthmatic Response • result of cytokine generation and recruitment of inflammatory cells • clinically, 4-6 hours later • responds to anti-inflammatory therapy (corticosteroids, LT antagonists)

  9. Clinical Presentation • Gradual Onset • Mainly eosinophilic inflammation • Progression over hours to days • Less responsive to treatment • 80% deaths but preventable • Sudden Onset • Mainly neutrophilic • Progression <2 hours • massive allergen exposure/emotion • Rapid response to therapy

  10. Clinical Assessment

  11. Clinical Assessment • Clinical findings correlate poorly with severity of airway obstruction • Tachypnea (RR>40) • Accessory muscle use • Tachycardia (HR >120bpm) • Pulsus paradoxus • Upright position/inability to lie supine • Sweating • Difficulty finishing sentences • Cyanosis • Decreased LOC • “Quiet chest” Aldington S, Beasley R. Asthma exacerbations · 5: Assessment and management of severe asthma in adults in hospital. Thorax 2007;62:447-458.

  12. Lung Volumes

  13. Pulmonary Function Testing • Flow Rates • Forced Vital Capacity (FVC) • Forced Expiratory Volume in 1 second (FEV1) • Maximum Midexpiratory Flow Rate (MMFR) • “Normal” Standards/Predicted Values • Large numbers of non-smoking controls • Regression equations (age, height) • 95% confidence intervals VS >80% predicted

  14. Pulmonary Function Testing • Flow-Volume Loops

  15. Objective Measurements

  16. PEFR VS FEV1 • Aggarwal AN, Gupta D, Jindal SK. The relationship between FEV1 and peak expiratory flow in patients with airways obstruction is poor. Chest. 2006 Nov;130(5):1454-61. • Cross-sectional, retrospective study • 6,167 adult patients showing obstructive pattern on spirometry over a 6-year period • “we found that in patients with severe airway obstruction (FEV1 < 40% of predicted), PEF% overestimated FEV1 %, whereas exactly the opposite happened in patients with less severe airway obstruction”

  17. PEFR VS FEV1

  18. Diagnostic Strategies • Pulmonary Function Testing • Initially, then 30-60 mins after initial treatment • NOT indicated in initial assessment of life-threatening asthma exacerbation (Evidence D) National Asthma Education and Prevention Program: Expert Panel Report III. 2007

  19. Diagnostic Strategies • Arterial Blood Gas • Rarely indicated • Consider in: • Inability to obtain O2 sat • Severe distress • Perplexing clinical course/Non-response to treatment • If done: • PaCO2 usually low (normal to high – severe airflow restriction, impending respiratory failure)

  20. Diagnostic Strategies • Pulse oximetry • Useful to assess both severity and improvement with treatment • Boychuk R. et al. Correlation of initial emergency department pulse oximetry values in asthma severity classes (steps) with the risk of hospitalization. Am J Emerg Med. 2006; 24(1)48-52. • “The presenting OSAT is the dominant initial predictor of hospitalization”

  21. Diagnostic Strategies • Blood Tests • Rarely indicated • CBC: • ↑WBC (stress response/steroids/epinephrine) • Theophylline level • CXRay • Not routinely indicated • Consider in: suspected complicating process • Pneumonia, PTX, pneumomediastinum, CHF, lobar atelectasis

  22. Diagnostic Strategies • Cardiac Monitoring • Not routinely indicated • indicated for: • severe hypoxemia • comorbid patients • Age >50

  23. Case • 23yo female • 1 week hx of increasing SOB, wheezing, nocturnal cough • Med Hx: asthma • Meds: ventolin, symbicort • Vitals: 36.7oC, 115bpm, RR36, 102/70, 93% RAO2 • Short sentences, SCM use • Moderate A/E bilat, expiratory wheezes

  24. Management • Oxygen therapy • O2 sats >90% in all patients, • >95% in pregnant or CV comorbid patients • Short-Acting β-agonist (Evidence A) • Ventolin • MDI/spacer: 4-8 puffs q20mins X 3, then q1-4 hours PRN • Nebulizer: 2.5mg-5mg q20mins X 3, then q1-4 hours PRN • Continuous Neb: 10mg-15mg/hour • IV: 4µg/kg for 2-5 mins, then 0.1µg -0.2µg/kg/min National Asthma Education and Prevention Program: Expert Panel Report III. 2007

  25. MDI versus Nebulizer • No significant difference • Hospital admission rate (RR 0.97, 95% CI 0.63 to 1.49) • Time spent in ED (MD 0.02 hours, 95% CI -0.4 to 0.44) • PEFR/FEV1 • FEV1 <30% predicted (MD -1.6% predicted, CI -7.69 to 4.49)

  26. MDI versus Nebulizer • No significant difference • Number of participants given steroids • Change in respiratory rate • Pulse rate

  27. MDI versus Nebulizer Dolovich et al. 2005. • “Both the nebulizer and MDI with spacer/holding chamber are appropriate for the delivery of short-acting β2 -agonists in the ED. Quality of evidence: good”

  28. Management • Ipratropium Bromide (Evidence A) • MDI/spacer: 4-8 puffs q20mins X 3, then as needed • Nebulizer: 0.25mg - 0.5mg q20mins X3, then as needed

  29. Management • 32 RCTs (16 adult, 16 peds) • 3611 patients • Results: • Decreased hospital admission (RR 0.68, 95% CI 0.53-0.86) • NNT = 14 • Larger decrease in: most severe asthma, treatment with multiple doses • Increased PEFR (WMD -44.18, 95% CI -57.72 to -30.84) • Larger increase in treatment with muiltiple doses

  30. Management • Corticosteroids • Oral • Prednisone 40mg-60mg q6-8h until improved, then OD X 5-10 days • IV • Methylprednisolone 60mg-125mg q6-8h until improved • Hydrocortisone 200mg-500mg q6-8h until improved • Fiel SB. et al. Systemic corticosteroid therapy in acute asthma exacerbations. J Asthma. 2006;43:321-331 • “no clear evidence supports any one route of systemic corticosteroid administration over another”

  31. Management • Corticosteroids • 12 studies, 863 patients • Administration of IV/IM/PO steroids <1hr after presentation • Reduced hospital admissions (NNT =8); • NNT = 5 when baseline admission rate >40% (ie:severe asthma) • Improved PEFR (persistent heterogeneity) • SMD 0.54; 95% CI 0.01 to 1.1

  32. Management • Corticosteroids • 6 studies, 374 patients • PO/IM corticosteroids on discharge following acute exacerbation of asthma • Fewer relapses to addition care at 7-10 days (RR 0.38, 95% CI 0.20 to 0.74, NNT = 9) • Fewer relapse requiring hospitalizations (RR 0.35, 95% CI 0.13 to 0.95) • Decreased use of β-agonist (MD -3.3 use/day, 95% CI -5.6 to -1.0)

  33. Management • Corticosteroids • Side effects: • Reporting uncommon • “similar in frequency”, “rare” • Nausea (N=2, OR 0.48; 95% CI 0.1 to 2.4) • Tremor (N=4, OR 0.82; 95% CI 0.45 to 1.48) • Headache (N=2, OR 1.04; 95% CI 0.01 to 1.1)

  34. Case • 30yo male transferred from Brooks Hospital • Week long hx of increasing SOB, wheezing, nocturnal cough • Med Hx: asthma (always worse in spring) • Meds: Ventolin, Symbicort, Singulair • Vitals: 37.2oC, RR48, 122bpm, 130/86, 90% on 10L O2 by mask • Sitting upright, anxious, SCM/SS indrawing • Poor A/E, intermittent wheezing

  35. Management • Epinephrine • IV for severe/nonresponsive: • 200µg-1000µg 1:10,000 solution over 5 mins • 1µg-20µg/min infusion if response to bolus • SC for inability to inhale • 0.2mL-0.5mL 1:1000 solution q20mins X 3 doses maximum

  36. Management • Epinephrine • Not a lot of evidence for efficacy… • Plint A. et al. The efficacy of nebulized racemic epinephrine in children with acute asthma: a randomized, double blind trial. Acad Emerg Med. 2000;7(10):1097-1103 • Prospective, randomized, double-blind study • 121 patients • Primary Outcome: Pulmonary Index Score (PIS) • Secondary Outcomes: change in O2 sat, length of ED stay, return visits • No difference: change in PIS, O2 sat, O2 requirement, ED stay length, hospital admissions, length of hospital stay

  37. Management • Epinephrine • Not a lot of evidence for efficacy… • Abroug F. et al. A controlled trial of nebulized salbutamol and adrenaline in acute severe asthma. Intensive Care Med. 1995;21:18-23 • Prospective, randomized, double-blind study • 22 ICU patients • Primary outcome: PEFR • No statistical difference in PEFR, HR, PaCO2, cardiac rhythm • Effect of Salbutamol on ↓RR greater

  38. Management • Magnesium • IV: 2g-3g over 5-10mins • Side effects: hypotension, respiratory depression, N/V, flushing • Indicated in severe asthma • Cochrane Review: Rowe et al. 2000 • 7 trials, 665 patients • Pooled study results show no significant difference • In severe subgroup: • Decreased hospital admissions (OR 0.10, 95% CI 0.04 to 0.27)

  39. Management • Magnesium: Nebulized VS Intravenous • Cochrane Review: Blitz et al. 2005 • No difference in rate of hospitalization • No difference in pulmonary function tests • In severe subgroup: • PFTs improved (SMD 0.55; 95% CI 0.12 to 0.98)

  40. Management • Methylxanthines • Not recommended (Evidence A) • National Asthma Education and Prevention Program: Expert Panel Report III. 2007 • Cochrane Review: Parameswaran et al. 2000 • No statistical signficance airflow outcomes • More palpitations/arrhythmias

  41. Management • Heliox • 60%-80% helium + 20%-40% oxygen • Consider heliox-driven β-agonist nebulization • Life-threatening exacerbation • Patients who remain severe after 1 hr intensive conventional therapy • Cochrane Review: Rodrigo et al. 2006 • 10 trials, 544 patients • No significant difference in PFTs, admissions to hospital • Significant difference in PFT (N = 3, SMD 0.61; 95% CI 0.21 to 1.00)

  42. Management • Leukotriene Receptor Antagonists • Zafirlukast: 160mg PO once • Montelukast: 7mg-14mg IV once • Camargo et al. 2003 • Randomized, double-blind, pilot study • 194 patients • 7mg or 14 mg Montelukast IV versus placebo

  43. Management

  44. Management • Camargo et al. 2003 • Results • Improved FEV1 at 10 mins, up to 2 hours • Fewer β-agonist nebulizations • No effect: • Hospitalizations • Unscheduled, asthma related visits to ED • Doctor visits • Need for rescue corticosteroids in 14 days after discharge

  45. Management • Leukotriene Receptor Antagonists • National Asthma Education and Prevention Program: Expert Panel Report III. 2007 • Evidence D • “Intravenous LRTAs could provide another pathway to rapid bronchodilation during impending respiratory failure”

  46. Management • Antibiotics • National Asthma Education and Prevention Program: Expert Panel Report III. 2007 • “not generally recommended for the treatment of acute asthma exacerbations except as needed for comorbid conditions” (Evidence B) • Fever, purulent sputum, pneumonia • Cochrane Review: Graham et al. 2001 (update 2005) • 2 studies, 97 patients • “not enough evidence on whether antibiotics given to people with acute asthma (without evidence of infection) is effective”

  47. Status Asthmaticus • Severe bronchospasm that does not respond to aggressive therapies within 30-60 mins • “Throw everything at it” • IV β-agonist • Epinephrine • Magnesium • Heliox • Leukotriene inhibitors • NIPPV • Intubation

  48. Disposition • Good Response – PFTs >70% • Home • Incomplete Response – PFTs >50% but <70% • Individualized decision • ?severe cough, wheeze, SOB, lack of self care admit • ?Risk factors for death from asthma  admit • Poor Response – PFTs <50% • Admit

  49. Chronic Obstructive Pulmonary Disease

  50. Epidemiology • Prevalence in Canada (GOLD Stage ≥2) • Men 9.3%, Women 7.3% (2007) • Increasing prevalence with age • Pooled OR 1.94, 95% CI 1.80 to 2.10 per 10 years of life • Significant economic burden Buist et al. 2007. Lancet; 370:741-750.

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