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 quantifye.g.,
mild-moderate-severe, scale 15
- Wheezing
- Cough (nonproductive or with copious
sputum)
- Shortness of breath
- Chest tightness (often confused with
angina pectoris)
- Desperate hunger for air with severe
attacks
Differential Diagnosis
- Upper airway obstruction
- Viral tracheobronchitis
- Chronic obstructive pulmonary disease
- Congestive heart failure
- Pulmonary embolism
- Churg-Strauss syndrome
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
Best
Therapy
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, 1.255.0 mg q. 48 hr p.r.n; exacerbation, 5
mg q. 2 hr
- Cost/mo: $30.0040.00
- Metered-dose inhaler (MDI), 84 ΅g/puff:
MDI as effective as nebulizer when
used with spacer
- Dose: maintenance, 24 puffs q. 6 hr p.r.n; exacerbation, 38 puffs q. 2
hr
- Dry-powder inhaler (DPI), 200 ΅g/capsule
- Dose: maintenance, 12 capsules q. 6 hr p.r.n; exacerbation, not
studied
- Levalbuterol
- Nebulizer, 0.63 mg/3 ml
- Dose: maintenance, 0.310.63 mg q. 68 hr
p.r.n.; exacerbation, 0.631.25 mg q. 68 hr p.r.n.
- Cost/mo: $110.00130.00
- Bitolterol
- Nebulizer, 2 mg/ml
- Dose: maintenance, 0.53.5 q. 48 hr
p.r.n.; exacerbation, not studied
- Cost/mo: price not available.
- MDI, 370 ΅g/puff
- Dose: maintenance, 24 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 ΅g/puff
- Dose: maintenance, 2 puffs q. 12 hr;
exacerbation, not recommended
- Cost/mo: $50.0070.00
- DPI, 50 ΅g/blister
- Dose: maintenance, 1 blister q. 12
hr
- Formoterol: faster onset of action than
salmeterol; may be used as a rescue bronchodilator
- DPI, 12 ΅g/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. 28 hr
- Cost/mo: $30.0035.00
- MDI, 18 ΅g/puff: as effective
as nebulizer when used with spacer
- Dose: maintenance, not recommended;
exacerbation, 38 puffs q. 34 hr
- Cost/mo: $30.0035.00
- Combined short-acting beta2 agonist and anticholinergic: use
when both are indicated
- MDI albuterol (90 ΅g/puff) + ipratropium
bromide (18 ΅g/puff)
- Dose: maintenance, not recommended;
exacerbation, 38 puffs q. 2 hr
- Cost/mo: $30.0040.00
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, 0.51.0 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, 2448 mg/day; maintenance, none or minimal
- Cost/mo: $9.0043.00
- Methylprednisolone, I.V.: usual I.V.
agent; oral therapy is as effective
- Dose: initial, 60125 mg q. 68 hr; maintenance, none
- Cost/day: $24.0027.00
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, 168504 ΅g; medium, 504840 ΅g;
high, > 840 ΅g
- 42 ΅g/puff: low, 412 puffs/day; medium,
1220 puffs/day; high, > 20 puffs/day
- Cost/mo: $30.0040.00
- Budesonide: DPI inhaler
- Dose: low, 200400 ΅g; medium, 400600 ΅g;
high, > 600 ΅g
- 220 ΅g/puff: low, 12 puffs/day; medium,
23 puffs/day; high, > 3 puffs/day
- Cost/mo: $30.0040.00
- Flunisolide:
- Dose: low, 5001,000 ΅g; medium, 1,0002,000
΅g; high, > 2,000 ΅g
- 42 ΅g/puff: low, 412 puffs/day; medium,
1220 puffs/day; high, > 20 puffs/day
- Cost/mo: $50.0060.00
- Fluticasone: also formulated in combination
with salmeterol in DPI
- Dose: low, 83264 ΅g; medium, 264660 ΅g;
high, > 660 ΅g
- 44 ΅g/puff: low, 24 puffs/day
- 110 ΅g/puff: low, 2 puffs/day; medium, 26
puffs/day; high, > 6 puffs/day
- 220 ΅g/puff: medium, 12 puffs/day; high,
> 3 puffs/day
- Cost/mo: $40.0050.00
- Triamcinolone: provided with spacer
- Dose: low, 4001,000 ΅g; medium, 1,0002,000
΅g; high, > 2,000 ΅g
- 100 ΅g/puff: low, 410 puffs/day; medium,
1020 puffs/day; high, > 20 puffs/day
- Cost/mo: $50.0059.00
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: $30.0040.00/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: $50.0060.00
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, 100200 mg b.i.d.; maintenance,
adjust to serum level 1020 ΅g/ml
- Cost: $10.0016.00
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: 150375 mg q. 24 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
Best References
Guidelines for the diagnosis and management of asthma update on selected
topics2002.
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
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