Asthma

Mitchell H. Grayson, M.D., and Michael J. Holtzman, M.D.
Washington University School of Medicine, St. Louis

Definition/Key Clinical Features
Differential Diagnosis
Best Tests
Best Therapy
Best References

Definition/Key Clinical Features

• Airway inflammation, caused by various stimuli, that leads to reversible airway narrowing
• During periods of normal lung function, no abnormal physical findings
• Symptoms: always try to quantify—e.g., mild-moderate-severe, scale 1–5
  • Wheezing
  • Cough (nonproductive or with copious sputum)
  • Shortness of breath
  • Chest tightness (often confused with angina pectoris)
  • Desperate hunger for air with severe attacks
    

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Differential Diagnosis

• Upper airway obstruction
• Viral tracheobronchitis
• Chronic obstructive pulmonary disease
• Congestive heart failure
• Pulmonary embolism
• Churg-Strauss syndrome

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Best Tests

No single lab test can establish diagnosis; bronchodilator responsiveness provides supportive evidence

• Spirometry
  • > 12% increase in airflow (FEV₁ or FVC) after bronchodilator inhalation suggests asthma
  • Lacks sensitivity and specificity
  • False negatives occur during asymptomatic periods
  • False positives occur with chronic bronchitis, emphysema, or other diseases with chronic airflow obstruction
• Bronchoprovocation with methacholine
  • May be helpful if pulmonary function is normal
  • Abnormal response is > 20% decline in FEV₁ in response to 8 mg/ml or less of methacholine
  • Other provocative agents are cold, exercise, and histamines
• CXR may exclude alternative diagnoses; not recommended for screening or diagnosis
• CBC, sputum exam, IgE measurement, allergy skin test not useful in most cases

Red Flags

• Following factors suggest greater risk:
  • Advanced age
  • Greater airway reactivity
  • Previous use of mechanical ventilation
  • Long-term steroid therapy
  • Previous hospitalizations for asthma
  • Problems with compliance
  • Major psychiatric diagnoses
  • Use of major tranquilizers

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Emergency

• Assess oxygenation by pulse oximetry
• Increase O₂ sat to > 90%
• Measure arterial blood gas
• Rapidly evaluate for hypercapnia, pneumothorax, atelectasis, or pneumonia
• Administer short-acting beta₂ agonist by inhalation

Agents for Persistent Asthma

Bronchodilators for Asthma

• Inhaled short-acting beta₂ agonists: first-line p.r.n. therapy; no significant differences in efficacy among inhaled short-acting beta₂ agonists; dilute aerosols to minimum of 4 ml at gas flow of 6-8 L/min
  • Albuterol
    • Nebulizer, 5 mg/ml
      • Dose: maintenance, 1.25–5.0 mg q. 4–8 hr p.r.n; exacerbation, 5 mg q. 2 hr
      • Cost/mo: $30.00–40.00
    • Metered-dose inhaler (MDI), 84 µg/puff: MDI as effective as nebulizer when used with spacer
      • Dose: maintenance, 2–4 puffs q. 6 hr p.r.n; exacerbation, 3–8 puffs q. 2 hr
    • Dry-powder inhaler (DPI), 200 µg/capsule
      • Dose: maintenance, 1–2 capsules q. 6 hr p.r.n; exacerbation, not studied
  • Levalbuterol
    • Nebulizer, 0.63 mg/3 ml
      • Dose: maintenance, 0.31–0.63 mg q. 6–8 hr p.r.n.; exacerbation, 0.63–1.25 mg q. 6–8 hr p.r.n.
      • Cost/mo: $110.00–130.00
  • Bitolterol
    • Nebulizer, 2 mg/ml
      • Dose: maintenance, 0.5–3.5 q. 4–8 hr p.r.n.; exacerbation, not studied
      • Cost/mo: price not available.
    • MDI, 370 µg/puff
      • Dose: maintenance, 2–4 puffs q. 6 hr p.r.n.; exacerbation, not studied
      • Cost/mo: price not available.
• Inhaled long-acting beta₂ agonists: first-line scheduled bronchodilator therapy; must be used with inhaled glucocorticoids
  • Salmeterol: slower onset of action; not used as a rescue bronchodilator
    • MDI, 21 µg/puff
      • Dose: maintenance, 2 puffs q. 12 hr; exacerbation, not recommended
      • Cost/mo: $50.00–70.00
    • DPI, 50 µg/blister
      • Dose: maintenance, 1 blister q. 12 hr
  • Formoterol: faster onset of action than salmeterol; may be used as a rescue bronchodilator
    • DPI, 12 µg/capsule
      • Dose: maintenance, 1 capsule q. 12 hr; exacerbation, not recommended
      • Cost/mo: $80.00
• Inhaled anticholinergics: indicated in combination with inhaled short-acting beta₂ agonists for exacerbations
  • Ipratropium bromide
    • Nebulizer, 0.25 mg/ml; may mix with albuterol in same nebulizer
      • Dose: maintenance, not recommended; exacerbation, 0.5 mg q. 2–8 hr
      • Cost/mo: $30.00–35.00
    • MDI, 18 µg/puff: as effective as nebulizer when used with spacer
      • Dose: maintenance, not recommended; exacerbation, 3–8 puffs q. 3–4 hr
      • Cost/mo: $30.00–35.00
• Combined short-acting beta₂ agonist and anticholinergic: use when both are indicated
  • MDI albuterol (90 µg/puff) + ipratropium bromide (18 µg/puff)
    • Dose: maintenance, not recommended; exacerbation, 3–8 puffs q. 2 hr
    • Cost/mo: $30.00–40.00

Anti-inflammatory Agents for Asthma

Systemic Glucocorticoids

• Prednisone: usual oral agent; q.d. initially, then wean off, if possible, or switch to q.o.d.
  • Dose: initial, 0.5–1.0 mg/kg/day; maintenance, none or minimal
  • Cost/mo: $5.00
• Methylprednisolone, oral: less commonly used oral agent; q.d. initially, then wean off, if possible, or switch to q.o.d.
  • Dose: initial, 24–48 mg/day; maintenance, none or minimal
  • Cost/mo: $9.00–43.00
• Methylprednisolone, I.V.: usual I.V. agent; oral therapy is as effective
  • Dose: initial, 60–125 mg q. 6–8 hr; maintenance, none
  • Cost/day: $24.00–27.00

Inhaled Glucocorticoids: first choice of anti-inflammatory agents; various inhaled glucocorticoid agents differ in potency

• Beclomethasone: available in hydrofluroalkane (HFA) MDI, possibly improving effectiveness
  • Dose: low, 168–504 µg; medium, 504–840 µg; high, > 840 µg
    • 42 µg/puff: low, 4–12 puffs/day; medium, 12–20 puffs/day; high, > 20 puffs/day
  • Cost/mo: $30.00–40.00
• Budesonide: DPI inhaler
  • Dose: low, 200–400 µg; medium, 400–600 µg; high, > 600 µg
    • 220 µg/puff: low, 1–2 puffs/day; medium, 2–3 puffs/day; high, > 3 puffs/day
  • Cost/mo: $30.00–40.00
• Flunisolide:
  • Dose: low, 500–1,000 µg; medium, 1,000–2,000 µg; high, > 2,000 µg
    • 42 µg/puff: low, 4–12 puffs/day; medium, 12–20 puffs/day; high, > 20 puffs/day
  • Cost/mo: $50.00–60.00
• Fluticasone: also formulated in combination with salmeterol in DPI
  • Dose: low, 83–264 µg; medium, 264–660 µg; high, > 660 µg
    • 44 µg/puff: low, 2–4 puffs/day
    • 110 µg/puff: low, 2 puffs/day; medium, 2–6 puffs/day; high, > 6 puffs/day
    • 220 µg/puff: medium, 1–2 puffs/day; high, > 3 puffs/day
  • Cost/mo: $40.00–50.00
• Triamcinolone: provided with spacer
  • Dose: low, 400–1,000 µg; medium, 1,000–2,000 µg; high, > 2,000 µg
    • 100 µg/puff: low, 4–10 puffs/day; medium, 10–20 puffs/day; high, > 20 puffs/day
  • Cost/mo: $50.00–59.00

Cromolyn Sodium: much less potent than inhaled glucocorticoids; used more often in children; no steroid side effects

• Dose: initial, 2 puffs q.i.d.; maintenance, 2 puffs q.i.d.
• Cost/mo: $30.00–40.00/canister

Nedocromil: much less potent than inhaled glucocorticoids; no steroid side effects

• Dose: initial, 2 puffs q.i.d.; maintenance, 2 puffs q.i.d.
• Cost/mo: $50.00–60.00

Leukotriene Modifiers: less effective than inhaled glucocorticoids; help with associated allergic rhinitis; use for aspirin-sensitive patients

• Montelukast: first choice of leukotriene modifiers; note q.h.s. dosing; no lab monitoring or restrictions related to meals
  • Dose: 10 mg q.h.s.
  • Cost/mo: $95.00
• Zafirlukast: should be taken at least 1 hr before or 2 hr after meals
  • Dose: 20 mg b.i.d.
  • Cost/mo: $86.00
• Zileuton: must monitor LFTs
  • Dose: 600 mg q.i.d.
  • Cost/mo: $250.00

Theophylline: relatively weak bronchodilator; should be used only when all other agents are optimized; significant toxicity, must monitor levels

• Dose: initial, 100–200 mg b.i.d.; maintenance, adjust to serum level 10–20 µg/ml
• Cost: $10.00–16.00

Other Anti-inflammatory Agents

• Omalizumab: used only as add-on therapy in severe persistent asthma; given S.C., dosage based on IgE levels and body mass
• Dose, initial: 150–375 mg q. 2–4 wk; maintenance, same
• Cost/mo: $1,000
• Methotrexate: efficacy controversial; toxic drug, must monitor blood counts and LFTs closely; should be given only by asthma expert
  • Dose: 7.5 mg/wk (adjust to effect; maximum, 25 mg/wk)
  • Cost/mo: $32.00

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Best References

Guidelines for the diagnosis and management of asthma update on selected topics—2002.
National Asthma Education and Prevention Program. J Allergy Clin Immunol 110:S141, 2002 [PMID 12542074]

Holtzman MJ, et al: Proc Am Thorac Soc 2:132, 2005 [PMID 16113481]

Israel E, et al: Lancet 364:1505, 2004 [PMID 15500895]

Pearlman DS: J Allergy Clin Immunol 116:1206, 2005 [PMID 16337447]

Salpeter SR, et al: Chest 125:2309, 2004 [PMID: 15189956]

Vigo PG, Grayson MH: Immunol Allergy Clin North Am 25:191, 2005 [PMID 15579371]

December 2006