II. Monitoring

  1. Pulse oximetry
  2. Timed walking of specific distances
  3. Spirometry
    1. Serial FEV1 Measurements are most significant value
    2. FEV1 <1 Liter indicates severe disease
    3. Poor prognosis if FEV1 <750 cc (<50% predicted)

III. Management: GOLD Criteria - Low Risk

  1. Low risk criteria
    1. Spirometry Mild to Moderate Severity (FEV1 >50% of predicted) AND
    2. One or none COPD exacerbation per year AND
    3. No hospitalizations
  2. Less Symptoms (GOLD A): mMRC Dyspnea Scale <2 or COPD Assessment Test <10
    1. First-choice (intermittent symptom management)
      1. Short-acting Beta Agonist (e.g. Albuterol) 2 puffs as needed up to every 6 hours OR
      2. Short-acting Anticholinergic (e.g. Ipratropium) as needed up to every 6 hours
    2. Second-choice
      1. Long-acting Beta Agonist (e.g. Salmeterol) OR
      2. Long-acting Anticholinergic (e.g. Tiotropium) OR
      3. Combined Short-acting Beta Agonist with short-acting Anticholinergic (e.g. Combivent)
    3. Other choices
      1. Theophylline
  3. More Symptoms (GOLD B): mMRC Dyspnea Scale 2 or COPD Assessment Test 10 or higher
    1. First-choice (long-acting symptom management)
      1. Long-acting Beta Agonist (e.g. Salmeterol) OR
      2. Long-acting Anticholinergic (e.g. Tiotropium)
    2. Second-choice
      1. Long-acting Beta Agonist (e.g. Salmeterol) AND
      2. Long-acting Anticholinergic (e.g. Tiotropium)
    3. Third-choice
      1. Short-acting Beta Agonist (e.g. Albuterol) 2 puffs as needed up to every 6 hours OR
      2. Short-acting Anticholinergic (e.g. Ipratropium) as needed up to every 6 hours
    4. Other choices
      1. Theophylline

IV. Management: GOLD Criteria -High Risk

  1. High risk criteria
    1. Spirometry Severe to Very Severe (FEV1 <50% of predicted) AND
    2. Two or more COPD exacerbation per year or one or more hospitalizations
  2. Less Symptoms (GOLD A): mMRC Dyspnea Scale <2 or COPD Assessment Test <10
    1. First-Choice
      1. Inhaled Corticosteroid (e.g. fluticasone or Flovent) AND
      2. Long acting beta agonist (e.g. Salmeterol or Serevent) or Long acting Anticholinergic (e.g. Tiotropium or Spiriva)
    2. Second-Choice
      1. Long-acting Beta Agonist (e.g. Salmeterol) AND
      2. Long-acting Anticholinergic (e.g. Tiotropium)
    3. Third-Choice
      1. Short-acting Beta Agonist (e.g. Albuterol) 2 puffs as needed up to every 6 hours OR
      2. Short-acting Anticholinergic (e.g. Ipratropium) as needed up to every 6 hours
    4. Other choices
      1. Phosphodiesterase-4 Inhibitor (e.g. roflumilast or Daliresp)
      2. Theophylline
  3. More Symptoms (GOLD B): mMRC Dyspnea Scale 2 or COPD Assessment Test 10 or higher
    1. First-Choice
      1. Inhaled Corticosteroid (e.g. fluticasone or Flovent) AND
      2. Long acting beta agonist (e.g. Salmeterol or Serevent) or Long acting Anticholinergic (e.g. Tiotropium or Spiriva)
    2. Second-Choice
      1. Inhaled Corticosteroid and Long-acting Beta Agonist (e.g. Salmeterol) AND Long-acting Anticholinergic (e.g. Tiotropium)
        1. Alternative: Anoro Ellipta (umeclidinium and vilanterol) once daily (released 2014)
      2. Add Phosphodiesterase-4 Inhibitor (e.g. roflumilast or Daliresp) to the first-choice regimen
    3. Third-Choice
      1. Short-acting Beta Agonist (e.g. Albuterol) 2 puffs as needed up to every 6 hours OR
      2. Short-acting Anticholinergic (e.g. Ipratropium) as needed up to every 6 hours
    4. Other choices
      1. Theophylline

V. Management: Stepped care of Dyspnea

  1. At risk: Stage 0 (Normal Pulmonary Function Tests)
    1. Chronic intermittent symptoms
    2. Eliminate exposures (e.g. Tobacco)
  2. Mild: Stage I (FEV1/FVC <0.7, FEV1>80%) - Intermittent symptoms management
    1. Short-acting Beta Agonist (e.g. Albuterol) 2 puffs as needed up to every 6 hours OR
    2. Short-acting Anticholinergic (e.g. Ipratropium) as needed up to every 6 hours
  3. Moderate: Stage II (FEV1/FVC <0.7, FEV1 50-80%)
    1. Add to Stage I management
    2. Long acting beta agonist (e.g. Salmeterol or Serevent) or Long acting Anticholinergic (e.g. Tiotropium or Spiriva)
    3. Patients benefit most during daytime active hours
      1. Consider dosing only in morning to save cost
      2. However, sleep is improved
  4. Severe: Stage III (FEV1/FVC <0.7, FEV1 30-50%)
    1. Add to Stage I and II management (short acting beta agonist and long acting beta agonist)
    2. Inhaled Corticosteroid (e.g. fluticasone or Flovent)
    3. Consider using both a long acting beta agonist and a long acting Anticholinergic
    4. Low-flow oxygen at night and with exertion
    5. Pulmonary rehabilitation
    6. Consider Systemic Bronchodilator
      1. Leukotriene Receptor Antagonist (e.g. Accolate)
      2. Theophylline (see efficacy below)
  5. Very severe: Stage IV (FEV1/FVC <0.7, FEV1 <30%)
    1. Add to Stage I, II and III management (short acting beta agonist, long acting beta agonist, Inhaled Corticosteroid)
    2. Continuous Low-flow oxygen
    3. Consider adding Phosphodiesterase-4 Inhibitor (e.g. roflumilast or Daliresp)
    4. Consider using both a long acting beta agonist and a long acting Anticholinergic
    5. Consider less efficacious methods for Dyspnea
      1. Buspirone as Anxiolytic agent
      2. Sustained release oral Morphine 20 mg daily
        1. Use with caution, studies are preliminary
        2. Abernethy (2003) BMJ 327:523-6
  6. Crisis Management
    1. See Acute Exacerbation of Chronic Bronchitis
    2. Beta agonist up to 6 to 8 puffs q1-2 hours
    3. Ipratropium Bromide up to 6 to 8 puffs q3-4 hours
    4. Systemic Corticosteroids for 5-10 days (see below)
    5. Theophylline (see efficacy below)
    6. BiPAP
    7. Oxygen therapy: Do not limit FIO2 in CO2 retainers
      1. Set O2 Sat goal of 88-91%
      2. Anticipate CO2 rise of 12 points
      3. Consider BiPap for pH < 7.25

VI. Management: Protocols

  1. Exacerbation Guidelines
    1. See Stepped Management as above
    2. See Antibiotic Use in COPD Exacerbation
    3. Do not define exacerbation severity by Spirometry
    4. Consider Chest XRay in hospitalized patients
    5. Prednisone 40 mg orally daily (5 day course is typical)
      1. Five day course of 40 mg daily is sufficient for most COPD exacerbations
        1. Leuppi (2013) JAMA 309(21):2223-31
      2. Ten day course reduces relapse rate after COPD evaluation in ER
        1. Aaron (2003) N Engl J Med 348:2618-25
    6. Avoid low efficacy therapies
      1. Mucolytic medications are not shown helpful
      2. Chest physiotherapy is not efficacious
      3. Theophylline not helpful in exacerbations
    7. References
      1. Snow (2001) Chest 119:1185-9
  2. Maintenance Guidelines
    1. Before Intervention
      1. Test Spirometry
      2. Review Patient's symptoms
    2. Initiate Trial of Intervention
    3. After Intervention
      1. Recheck Spirometry
      2. Were Patient's symptoms improved?

VII. Agents: Inhaled Bronchodilators

  1. Efficacy
    1. Spirometry improved 15% significant
    2. Symptom improvement also suggests benefit
    3. Use with spacer always due to lack of lung excursion
    4. Give prn unless jittery (precedes cardiotoxicity)
  2. Safety
    1. Low risk of precipitating major cardiovascular event
      1. Salpeter (2004) Chest 125:2309-21
  3. Agents
    1. Short-acting Beta Agonist for rescue
      1. Albuterol 2 puffs every 4-6 hours prn
        1. In crisis, may be used up to 6-8 puffs q1-2 hours
      2. Levalbuterol (Xopenex hfa) 2 puffs every 4-6 hours
      3. Pirbuterol (Maxair Autohaler) 1-2 pufss every 4-6 hours prn
    2. Long-acting Beta Agonist for maintenance
      1. Arformoterol (Brovana) 15 mcg twice daily
      2. Formoterol (Foradil) once twice daily
      3. Indacaterol (Arcapta) once daily
      4. Salmeterol (Serevent Discus) once twice daily
      5. Effective and safe (no increased vascular events)
      6. Ferguson (2003) Chest 123:1817-24

VIII. Agents: Inhaled Anticholinergics (e.g. Ipratropium Bromide)

  1. Precautions
    1. Variable data on risk of increased cardiovascular related mortality
      1. Exercise caution in comorbid cardiovascular disease
      2. Singh (2008) JAMA 300(12): 1439-50
      3. Ogale (2010) Chest 137(1): 13-9
  2. Efficacy
    1. Greater bronchodilation than Beta agonists in COPD
    2. Combined with beta agonist may offer additive effect
    3. No tachyphylaxis
    4. Decreases bronchoconstriction by inhibiting cGMP
  3. Preparations
    1. Short-acting agents
      1. Ipratropium Bromide (Atrovent) 2-3 puffs qid
        1. In crisis may be used up to 6 to 8 puffs q3-4 hours
      2. Ipratropium Bromide 500 ug vial nebulized qid
    2. Long-acting agents
      1. Aclidinium (Tudorza) once twice daily
      2. Tiotropium (Spiriva) once daily
    3. Combination agents
      1. Duoneb (Nebulized Ipratropium Bromide and Albuterol)
      2. Combivent (Ipratropium with Albuterol)
        1. Significant cost savings when combined
        2. Benayoun (2001) Chest 119:85-92
      3. Anoro Ellipta (umeclidinium and vilanterol)
        1. Long acting Anticholinergic (umeclidinum) and long acting beta agonist (vilanterol) once daily (2014 release in U.S.)

IX. Agents: Systemic Corticosteroids

  1. Short course Corticosteroids in severe exacerbation
    1. Increases FEV1 and shortens hospital stay
    2. Avoid use longer than 2 weeks
    3. Protocol (total of 10 day course at full strength)
      1. Solu-Medrol 1-2 mg/kg q6-12 hours IV for 3 days
        1. IV Corticosteroids are not more effective than oral Corticosteroids
      2. Prednisone 40 mg daily for 5 days
        1. Equivalent to 10-14 day courses (see above)
        2. Prolonged Prednisone tapers off over 2 weeks are not indicated in most cases
  2. Long-term Systemic Corticosteroids not often helpful
    1. Long-term Corticosteroid use is rarely indicated
    2. Beneficial effects seen in only 10-20% COPD patients
    3. Test to see if COPD patient Corticosteroid responsive
      1. Prednisone 40 mg PO for 10 days
      2. Alternative: Theophylline challenge
      3. Test PFTs before and after course
    4. Attempt to slowly discontinue Corticosteroids
      1. Decrease Corticosteroid dose by 5 mg per week
    5. Most patients tolerate taper without rebound
      1. No change in Spirometry
      2. No change in symptoms (e.g. Dyspnea)
    6. Stopping steroids often alleviates adverse effects
      1. Anticipate resolution of prior weight gain
    7. Risk of Osteoporosis with long-term steroid use
      1. See Corticosteroid Associated Osteoporosis
      2. Dubois (2002) Chest 121:1456-63
    8. References
      1. Rice (2000) Am J Respir Crit Care Med 162:174-8

X. Agents: Inhaled Corticosteroids

  1. Fluticasone with Salmeterol (Advair Diskus)
    1. Significant benefit compared with either agent alone
    2. Resulted in symptom control and sustained for >1 year
    3. No significant adverse effects seen in studies
    4. Calverly (2003) Lancet 361:449-56
    5. Hanania (2003) Chest 124:834-43
  2. Possible impact on exacerbations and quality of life
    1. Consider in patients with FEV1 < 1.5 Liters (<50%)
    2. Consider if frequent exacerbations
    3. Consider trial for 6-18 weeks
      1. Check PFTs before and after course
  3. Pulmonary Function Tests do not reflect benefit
    1. Minimal impact on lung function
    2. No impact on rate of lung function decline
  4. Adverse effects may outweigh benefits
    1. Mild effects: Bruising, Dysphonia, Candidiasis
    2. Serious effects: Osteoporosis, Cataracts
    3. Agents are expensive (many are over $100 per month)

XI. Agents: Systemic Bronchodilators

  1. Leukotriene Receptor Antagonist (e.g. Accolate)
    1. Rarely used in COPD
    2. Some prior data showed efficacy when cobined with Bronchodilator
  2. Theophylline 10-15 mg/kg to drug level 10-12 ug/ml
    1. Recent guidelines do not recommend in exacerbation
    2. Several serious drug interactions (e.g. Quinolones)
      1. Review interactions at every medication change
    3. Efficacy in stable COPD
      1. Weak Bronchodilator
        1. Weaker than Beta agonists (e.g. Albuterol)
        2. Weaker than Anticholinergics (e.g. Atrovent)
      2. Improves respiratory Muscle Strength and endurance
      3. Improves mucociliary clearance
      4. Increases central respiratory drive
      5. May lead to symptomatic improvement
      6. Associated with reduced hospitalization rate
      7. Appears synergistic with long-acting Bronchodilator
        1. ZuWallack (2001) Chest 119:1661

XII. Agents: Home Oxygen

  1. Indications
    1. Stable clinical Status
    2. No end-organ dysfunction: PaO2 < 55 mmHg or O2 < 88%
    3. End Organ changes: PaO2 < 59 mmHg or O2 < 90%
      1. Cor Pulmonale or right Heart Failure
      2. P-pulmonale on EKG
      3. Polycythemia present (Hematocrit >55%)
  2. Documentation
    1. O2 Sat measured at rest or
    2. O2 Sat after 6 minute ambulation
      1. Document with and without oxygen
  3. Benefits
    1. Home Oxygen use only beneficial if >18 hours/day
    2. Increases life span in COPD by 6-7 years
    3. Goal to keep Oxygen Saturation >90%
  4. Adjuncts
    1. Consider Continuous Positive Airway Pressure (CPAP)

XIII. Agents: Surgical Interventions

  1. Lung transplantation
  2. Lung Volume reduction surgery
    1. Improves 5 year survival in severe COPD with heterogeneous distribution of Emphysema and upper lobe predominance
      1. Improved quality of life if BODE Index >5
      2. Sanchez (2010) J Thorac Cardiovasc Surg 140(3): 564-72
    2. Worse prognosis (increased 30 day mortality) if FEV1 <20% predicted, low DLCO or homogenous Emphysema
      1. (2001) N Engl J Med 345(15): 1075-83

XIV. Agents: Other Interventions

  1. Influenza Vaccine yearly
  2. Intranasal Steroid (Helps reduce airway phlegm)
  3. Regularly scheduled mucolytics (e.g. Guaifenesin)
    1. Reduces days of illness per month by 1/2 day
    2. Doubles chance of being free of exacerbations
    3. Poole (2001) BMJ 322:1-6
  4. N-Acetylcysteine for prevention of COPD Exacerbation
    1. Dose: 600-1200 mg/day in divided dosing
    2. Decramer (2005) Lancet 365(9470):1552-60
  5. Beta Blockers
    1. Despite prior relative contraindication in COPD, cardioselective Beta Blockers (e.g. Metoprolol, bisoprolol) improve COPD status
    2. Associated with decreased COPD exacerbations and increased survival
    3. Farland (2013) Ann Pharmacother 47(5):651-6

XV. Resources

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