Asthma

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 (Apr99 Mar05)
• 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 lt2mm 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 gt 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 (ß-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 lt2 hours
• massive allergen exposure/emotion
• Rapid response to therapy

10
Clinical Assessment
Risk Factors for Death from Asthma
Sudden, severe onset
gt2 asthma hospitalizations in previous year
gt3 asthma-related ED visits in previous year
Hospitalization or ED visit in previous month
gt2 canisters ß-agonist use in previous month
Recent/current systemic corticosteroid use
Previous ICU admission for asthma
Previous intubation for asthma
Cormorbidities
Severe psychiatric or psychosocial issues
Illicit drug use
Poor perception of severity of airway obstruction
11
Clinical Assessment

• Clinical findings correlate poorly with severity
  of airway obstruction
• Tachypnea (RRgt40)
• Accessory muscle use
• Tachycardia (HR gt120bpm)
• 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 200762447-458.
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 gt80 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
  Nov130(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 lt 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)

Symptoms/Signs Initial PEF (or FEV1)
Mild Dyspnea only with activity 70
Moderate Dyspnea interferes/limits usual activity 40 - 69
Severe Dyspnea at rest interferes with conversation lt40
Life-Threatening Too dyspneic to speak perspiring lt25
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 gt50

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 gt90 in all patients,
• gt95 in pregnant or CV comorbid patients
• Short-Acting ß-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 lt30 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 ß2 -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.
  200643321-331
• 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 lt1hr after
  presentation
• Reduced hospital admissions (NNT 8)
• NNT 5 when baseline admission rate gt40
  (iesevere 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 ß-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 (N2, OR 0.48 95 CI 0.1 to 2.4)
• Tremor (N4, OR 0.82 95 CI 0.45 to 1.48)
• Headache (N2, 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 110,000 solution over 5 mins
• 1µg-20µg/min infusion if response to bolus
• SC for inability to inhale
• 0.2mL-0.5mL 11000 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.
  20007(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. 19952118-23
• 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 ß-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 ß-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 ß-agonist
• Epinephrine
• Magnesium
• Heliox
• Leukotriene inhibitors
• NIPPV
• Intubation

48
Disposition

• Good Response PFTs gt70
• Home
• Incomplete Response PFTs gt50 but lt70
• Individualized decision
• ?severe cough, wheeze, SOB, lack of self care
  ?admit
• ?Risk factors for death from asthma ? admit
• Poor Response PFTs lt50
• 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 370741-750.
51
Pathophysiology

• progressive disease state associated with an
  abnormal inflammatory response in the lungs
  characterized by airflow limitation that is not
  fully reversible

52
Pathophysiology

• Airway inflammation central to COPD
• An imbalance of proteases/anti-proteases favoring
  destruction of lung parenchyma
• Neutrophil, macrophage, CD8 lymphocyte
  predominance

53
Pathophysiology

• Chronic Bronchitis
• Progressive airway scarring/narrowing
• Increased number of mucus secreting goblet cells
• Impaired mucociliary clearance response
• Emphysema
• Destruction of lung parenchyma
• Small airway closure due to loss of radial
  connective tissue support

54
Pathophysiology
55
Pathophysiology
56
Comorbidities

• Cardiac MI, CHF, HTN, cor pulmonale, arrythmias
• Pulmonary PE, pulmonary HTN, pneumonia, cancer
• MSK cachexia, muscle wasting, osteoporosis
• GI GERD
• Metabolic diabetes, dyslipidemia
• Hematologic polycythemia

57
Clinical Presentation

• Acute exacerbation is defined as (at least) 1 of
  the 3
• Increasing dyspnea
• Increasing cough
• Increasing sputum production/change in
  character/purulence

58
Investigations?

• PFTs?
• ABG?
• Blood Tests?
• Chest X-Ray?
• Sputum examination?
• Cardiac monitoring?
• Oxygen therapy?

59
Diagnostic Strategies

• Pulmonary Function Testing
• Post-bronchdilator FEV1/FVC lt0.7 (non-reversible)
• Less helpful acutely
• Arterial Blood Gas
• Rarely indicated
• Consider in
• Inability to obtain O2 sat/low O2 sat
• Severe exacerbations
• Hospital admission
• Prior to NIPPV
• Follow with pulse oximetry

60
Diagnostic Strategies

• Blood Tests
• Not routinely indicated
• CBC
• Polycythemia
• ?WBC (stress response/steroids)
• Theophylline level
• CXRay
• Recommended (Level of evidence 2B)
• Changes management in 16 to 21 of patients
• Rules out comorbidities

ODonnell et al. 2007. Can Respir J. Vol 14.
Suppl B.
61
Diagnostic Strategies

• Sputum Examination
• Poor correlation with sputum cultures
• Role in AECOPD undefined (level of evidence 3C)
• Consider in
• Very poor lung function
• Frequent exacerbations
• Abx treatment in past 3 months

ODonnell et al. 2007. Can Respir J. Vol 14.
Suppl B.
62
Diagnostic Strategies

• Cardiac Monitoring
• Detection of arrhythmias
• Atrial arrhythmias most common (A.fib, MAT)
• ECG
• Screen for cardiac causes of dyspnea
• Right atrial enlargement, Right axis deviation,
  Right ventricular hypertrophy

63
Management

• Oxygen therapy
• Titrate to approximately 90 O2 sat
• Concerns?
• Hypoxic respiratory drive
• Removal of hypoxic pulmonary vasoconstriction
• Haldane Effect

64
Case

• 54yo male with 50 pack year smoking hx
• 2 week hx of increasing SOB and productive cough
• Med Hx I take puffersa blue and white one
• Vitals 37.3oC, RR 32, 110bpm, 148/92, 91 RAO2
• Obese, crackles at bases, bilateral pitting
  edema, JVP??

65
Management

• Bronchodilators
• Improve airway function/reduce hyperinflation
  (Evidence 2A
• 9 RCTs, update Oct 2005
• No difference
• Short acting ß-agonists versus anticholinergic
  agents
• WMD -0.0, 95CI -0.19 to 0.19
• Combination therapy versus individual agent
  (Evidence 3C)
• WMD -0.05, 95 CI -0.14 to 0.05

66
Management

• Corticosteroids
• Moderate/Severe AECOPD (Evidence 1A)
• dose/duration/type needs to be individualized
• 10 to 14 days recommended (ODonnell et al.
  2007)
• Cochrane Review Walters et al. 2009
• 10 RCTs, 1051 patients
• Fewer treatment failures within 30 days (NNT
  10)
• Decreased duration hospitalization
• MD -1.22 95 CI -2.26 to -0.18
• Improved FEV1, breathlessness, blood gas values
• No effect on mortality
• Increased adverse events (NNH 6)

67
Management

• Antibiotics
• Beneficial in treatment of more severe
  exacerbations
• 3/3 Increasing dyspnea, Increasing cough,
  Increasing sputum production/change in
  character/purulence
• Sputum purulence
• Need for mechanical ventilation

68
Management

• Antibiotics
• Puhan et al. 2007
• 13 RCTs, 1557 patients
• No reduction in treatment failures in mild/mod
  exacerbations (OR 1.09, 95 CI 0.75 to 1.59)
• Reduced treatment failures in severe
  exacerbations (OR 0.25, 95 CI 0.16 to 0.39),
  NNT 4
• Reduced mortality in severe exacerbations (OR
  0.20, 95 CI 0.06 to 0.62), NNT 14
• More adverse events in Abx treated group
• Mostly mild GI symptoms

69
Management

• Which Antibiotics?
• Dimopoulos et al. 2007. Comparison of first-line
  with second-line antibiotics for acute
  exacerbations of chronic bronchitis. Chest
  132447-455
• More treatment failures with 1st line Abx VS 2nd
  line Abx (OR 0.51, 95 CI 0.34 to 0.75)
• No differences in adverse effects

70
Management

• Which Antibiotics?

71
Management

• What antibiotics?

72
Case

• 55yo male with 60 pack year smoking hx
• 1 week of increasing SOB, productive cough
• Med Hx HTN, dyslipidemia, OSA
• Meds Ventolin, Symbicort
• Vitals 37.4oC, RR 44, 126bpm, 148/92, 86 RAO2
• Sitting upright, accessory muscle use ,
  IthinkImgonnadie

73
Management

• Methylxanthines
• Not recommended in AECOPD
• Cochrane Review Barr et al. 2003
• 4 RCTs, 169 patients
• No difference FEV1
• No difference hospital admissions/length of stay
• No difference relapses
• Increased adverse effects with methylxanthine
• Nausea/Vomiting (OR 4.6, 95 CI 1.7 to 12.6)
• Tremor (OR 1.8, 95 CI 0.7 to 4.6)
• Palpitations/Arrhythmias (OR 4.1, 95 CI 0.9 to
  19.6)
• MI (one case!)

74
Management

• Heliox
• Insufficient evidence to support use in AECOPD
• Cochrane Review Rodrigo et al. 2001
• 2 RCTs, 66 patients
• No clinical outocomes reported
• Improved peak inspiratory flow rate
• Decreased PaCO2
• Decreased dyspnea scores

75
Management

• Respiratory Stimulants
• Doxapram
• Not currently recommended in AECOPD
• Cochrane Review Greenstone et al. 2002
• 3 RCTs
• Improved blood gas exchange in first few hours of
  treatment, but NIPPV may be more effective

76
Disposition
Admission Criteria in AECOPD
Significant worsening of symptoms from baseline
Inadequate response of symptoms to ED management
Significant comorbidities
Worsening hypoxia/hypercarbia from baseline (or both)
Inability to cope at home/Insufficient home resources
77
Questions?
78
Writing the Orders

• Ventolin
• 10 puffs q15-20 mins MDI X 3, then q30-60mins
• 5mg q15-20mins Neb X3, then q30-60 mins
• Atrovent
• 10 puffs q15-20 mins MDI X 3, then q30-60mins
• 0.5mg q15-20mins Neb X 3, then as needed
• Epinephrine
• 0.3mg - 0.5mg IM, then infusion