1. Management of Asthma and COPD
W.S. Krell M.D.
Wayne State University

3. NIH Statement (1992, ‘97) Chronic inflammatory disorder
multiple cellular components, mediators
recurrent wheeze, shortness of breath, chest tightness, cough (pm & early am)
reversible airflow obstruction
secondary: hyperresponsiveness
Sub-basement membrane fibrosis

4. Treating Asthma Medications: Stepped therapy: start high, back down
long term or controller medications
quick relief medications
Stepped therapy: start high, back down
Asthma monitoring and action plans
Environmental controls

5. Overview of Medications
Controller medications
control inflammation
long duration bronchodilation
multiple medications
Quick relief medications
for intermittent or breakthrough symptoms

6. Controller Agents Inhaled corticosteroids Systemic corticosteroids
Long acting 2 agonists
Cromolyn and derivatives
Methylxanthines
Leukotriene Modifiers

7. Inhaled Corticosteroids
Control airway inflammation locally
Ideal: control asthma (high local potency); no side effects (low systemic effects)
fluticasone, budesonide ****
beclomethasone *
(triamcinolone, flunisolide)

8. Systemic Corticosteroids
May be needed initially
Side effect profile well known
Step down therapy
Alternatives: high dose inhaled corticosteroids; methotrexate; other immunosuppressive drugs; Omalizumab

9. Omalizumab (Xolair)
Recomb. DNA derived IgG - selectively binds human IgE
Indication: mod. to severe persistent asthma not controlled w/inhaled CS
IgE > 30, RAST A or skin tests +
Given SQ/ mo. or biweekly
Dose based on wt. and IgE level

10. Long acting ß2 Agonists Salmeterol Formoterol Prolonged duration
Potentiate steroid effects?
Should we be using them????????

11. Leukotriene Modifiers
Anti-inflammatory
Precursor step affected
Compliance may be better than MDIs
Few side effects

12. Other Controllers Cromolyn derivatives Methylxanthines Safe, effective
Less predictable, frequent dosing
Methylxanthines
Mechanism not fully understood
Therapeutic/Toxic ratio high
Multiple drug interactions

13. Quick Relief Medications
ß2 Agonists
Systemic corticosteroids

14. Exacerbation of Asthma
History: Sudden (exposure) vs gradual worsening vs viral infection vs non-compliance
Tachypnea, tachycardia
Accessory muscles
Wheezing, prolonged expiration, silent
Speaking ability compromised

15. ABGs - Asthma Respiratory alkalosis Normal PCO2 is worrisome
Rising PCO2 is near respiratory failure
Note: O2 doesn’t fall until late so pulse oximetry is not very sensitive

16. Emergency Management Nebulized albuterol x 3
Monitor exam, peak flows, ABGs
If no improvement, start IV corticosteroids and admit
DOSE?? (30 to 180 mg/day)
Asthma: CXR not likely helpful

17. Further Mgt of Asthma Continue bronchodilators Q 6 hour steroids
Hydration
Mucomyst may exacerbate
If failing: consider anticholinergics, theophylline, single isomer β2, Mg2+

18. Impending Respiratory Failure
Respiratory acidosis
Decreasing mental status
Asthma: PCO2 above 40 or rising despite therapy

19. Outpatient Asthma Management
Classify by severity
Step up and down number of medications based on symptoms and peak flows

20. Severity of Asthma Mild Intermittant: Mild persistent:
symptoms < 2X/wk
nights<2/month
Mild persistent:
> 2X/wk but < 1/day
Nights > 2/month

21. (cont.) Moderate: SEVERE: Daily symptoms Nights > 1/week
Continual symptoms
Frequent nighttime symptoms

22. Rules of 2 Sx > 2/week PM sx > 2 nights/month
> 2 rescue MDIs/year

23. Stepped Therapy Inhaled beta agonist Inhaled corticosteroid
Long acting beta agonist
Leukotriene modifiers
(Cromolyn derivatives)
(Theophyllines)
Systemic corticosteroids

25. Patient Education Avoid triggers Home monitoring
Proper inhaler techniques
Spacers
“Asthma Action Plan”

28. Compliance? Few patients continue to document
Always give them Action Plans
Simple in office questionnaire
validated in testing
Snap shot of asthma control

30. Asthma vs. COPD Sensitizing agent ↓ Inflammation CD4 T-lymphocytes
Eosinophils
Completely reversible
airflow limitation
Noxious agent ↓
Inflammation
CD8 T-lymphocytes
Macrophages, PMNs
Irreversible airflow limitation

31. Treating COPD Step up Long acting Anticholinergics
Long acting beta agonists
Short acting bronchodilators
(steroids: inhaled and oral)
Soon: Cilomalist?

32. Exacerbation of COPD Viral or secondary bacterial infection
Non-compliance
Cor pulmonale
Tachypnea, tachycardia
Rhonchi, wheezes, prolonged expiration
Signs of right heart failure, pulmonary hypertension

33. Causes Infections (bacterial) Environmental (↑ pollution)
Unknown in 1/3

34. Management Increase bronchodilators
Systemic steroids (PO if possible) (A)
Shortens recovery time
Quicker return to baseline function
↓ risk of early exacerbation
10 day to 2 week course
Antibiotics (B)

35. Additional Management: COPD
Nebulized anticholinergics, β agonists
Antibiotics
Steroids
Manage other complications: pneumonia, pneumothorax, right heart failure
Oxygen to keep saturation near 90%

36. ABGs - COPD Pay more attention to pH, bicarb
PCO2 elevations more significant when acute
Expect increased (A-a)DO2
Hypoxia must be treated, despite fears of hypercarbia

37. Impending Respiratory Failure
Non Invasive Ventilation
Bi-level Positive Pressure
Increase inspiratory P to ↓ pCO2
Start expiratory P at 5-6 cm H2O and ↑ if needed for oxygenation
Evidence A for success

38. Management of COPD Smoking cessation Spirometry
Yearly influenza vaccine
Pneumovax
Antibiotics for exacerbations
Monitor rest and exercise oxygenation

39. Spirometry is KEY FEV1 FEV1/FVC Ratio
Screen based on exposure and symptoms
Follow at least yearly
Patients should KNOW THEIR NUMBERS

40. Spirograms

41. Classification STAGE FEV1/FVC FEV1 >70% > 80% + Symptoms I
>70%
> 80% + Symptoms I
< 70%
≥ 80% ± Symptoms II
≥ 50% but < 80% ± Sx
III
≥ 30% but < 50% ± Sx IV
< 30% or < 50% + chronic respiratory failure

42. Management: All Stages
Avoidance of noxious exposures
SMOKING CESSATION (Evidence: A)
Avoid occupational/environmental exposures (Evidence: B)
Vaccination
Influenza
Pneumovax

43. Smoking Cessation Strategies
Repeated counseling
Nicotine replacement agents
Buproprion, anxiolytics
This is the ONLY measure available proven to halt the decline in lung function
Evidence: A

45. COPD Outpatient SHORT ACTING BETA AGONISTS ANTICHOLINERGICS ****
Ipatropium
Tiotropium
LONG ACTING BETA AGONISTS
Theophyllines
Inhaled corticosteroids

46. Management: Stage I Short acting bronchodilator used PRN
Albuterol: beta 2 agonist
Ipatropium: M3 anticholinergic blocker
Both are effective
Albuterol has faster onset of action
Combination is additive for bronchodilation
Evidence: A

47. Management: Stage II Long acting bronchodilators
Long acting beta agonists
Long acting anticholinergic
Short acting bronchodilators PRN
Education
Inhaled corticosteroids if frequent exacerbations
Evidence: A

48. Long Acting Beta Agonists
Formoterol
Onset comparable to short acting agents
Duration: 12 hours
Salmeterol
Slower onset
Cautions re: use without inhaled steroids applies to asthmatics not COPD patients

49. Tiotropium Duration: 24 hours Blocks M1 and M3 receptors
Stop ipatropium (M3 only)
Few side effects (some caution with BPH)
Sustained improvement in FEV1

50. What about Theophylline?
Old drug, proven useful
If chosen, careful monitoring required
High toxic to therapeutic ratio
Multiple drug and food interactions
Aim for levels 8 – 12 mcg/mL

51. Cilomalist
Orally active PDE4 inhibitor  cAMP (inflam, bronchial reactivity)
Positives
Improved FEV1, reduced sx (SGRQ)
Negatives
Significant GI toxicity
Study done prior to release of tiotropium
Rennard, CHEST 2006

52. Inhaled Corticosteroids
If indicated, choose long acting agents
Fluticasone
Combination drug with salmeterol
Budesonide
Also available for use in nebulizer

53. More is better??? Combinations can produce benefits
Long acting agents are ALL expensive
Optimal combinations not known

54. Management: Stage III One or More Long acting Bronchodilators
Short acting bronchodilators PRN
Inhaled corticosteroids if frequent exacerbations
Pulmonary Rehabilitation
Evidence: A

55. Management: Stage IV Long acting bronchodilators
Short acting bronchodilators PRN
Inhaled corticosteroids
Education
Evaluate need for oxygen therapy
Nighttime non-invasive ventilation?
Consider surgical options

56. Surgical Options Lung transplantation Lung volume reduction surgery
Upper age limit: 60 years
Consider for younger patients without serious co-morbidities
Few last long enough to get transplanted
Lung volume reduction surgery
Consider if no serious co-morbidities
Improves diaphragmatic function

57. Resources NIH Asthma Guidelines: www.nhlbi.gov/guidelines/asthma/
Global Initiative for chronic obstructive lung disease:
Resource for asthma action plans, info: