Asthma is a clinical syndrome characterized by episodic reversible airway obstruction, increased bronchial reactivity, and airway inflammation. Asthma results from complex interactions among inflammatory cells, their mediators, airway epithelium and smooth muscle, and the nervous system. In genetically susceptible individuals, these interactions can lead to symptoms of breathlessness, wheezing, cough, and chest tightness.
Risk factors for asthma include a family history of allergic disease, the presence of allergen-specific immunoglobulin E (IgE), viral respiratory illnesses, exposure to aeroallergens, obesity, and lower socioeconomic status.
Environmental exposure in sensitized individuals is a major inducer of airway inflammation, which is a hallmark finding in the asthmatic lung. Although triggers induce inflammation through different pathways, the resulting effects all lead to increased bronchial reactivity.
Exposure to dust mites within the first year of life is associated with later development of asthma and, possibly, atopy. Mite and cockroach antigens are common, and exposure and sensitization has been shown to increase asthma morbidity. Allergies trigger asthma attacks in 60-90% of children and in 50% of adults. Approximately 75-85% of patients with asthma have positive (immediate) skin test results. In children, this sensitization is associated with disease activity. The level of IgE is associated with the prevalence and severity of airway hyperresponsiveness (AHR) and asthma.
Although most people with asthma have aeroallergen-induced symptoms, some individuals manifest symptoms with nonallergic triggers. As many as 3-10% of people with asthma are sensitive to nonsteroidal anti-inflammatory drugs (NSAIDs). Approximately 5-10% of people with asthma have occupation- or industry-induced airway disease. Many individuals develop symptoms after viral respiratory tract infections.
Allergen avoidance and other environmental control efforts are feasible and effective. Symptoms, pulmonary function test findings, and AHR improve with avoidance of environmental allergens. Removing even one of many allergens can result in clinical improvement. However, patients frequently are not compliant with such measures.
The allergic response in the airway is the result of a complex interaction of mast cells, eosinophils, T lymphocytes, macrophages, dendritic cells, and neutrophils. Inhalation-challenge studies with allergens reveal an early allergic response (EAR), which occurs within minutes and peaks at 20 minutes following inhalation of the allergen. Clinically, the manifestations of the EAR in the airway include bronchial constriction, airway edema, and mucus plugging. These effects are the result of mast cell–derived mediators. Four to 10 hours later, one sees the late allergic response, which is characterized by infiltration of inflammatory cells into the airway and is most likely caused by cytokine-mediated recruitment and activation of lymphocytes and eosinophils.
Antigen-presenting cells (ie, macrophages, dendritic cells) in the airway capture, process, and present antigen to helper T cells, which, in turn, become activated and secrete cytokines. Helper T cells can be induced to develop into TH1 (ie, interferon-gamma, interleukin [IL]–2) or TH2 (ie, IL-4, IL-5, IL-9, IL-13). Allergens drive the cytokine pattern towards TH2, which promotes B-cell IgE production and eosinophil recruitment. Subsequently, IgE binds to the high-affinity receptor for IgE, Fc-epsilon-RI, on the surface of mast cells and, with subsequent exposure to the allergen, the IgE is cross-linked. This leads to degranulation of the mast cell. Preformed mast cell mediators, such as histamine and proteases, are released, leading to the EAR.
Newly formed mediators such as leukotriene C4 and prostaglandin D2 also contribute to the EAR. Proinflammatory cytokines (IL-3, IL-4, IL-5, tumor necrosis factor-alpha) are released from mast cells and are generated de novo after mast cell activation. These cytokines contribute to the late allergic response by attracting neutrophils and eosinophils. The eosinophils release major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase into the airway, causing epithelial denudation and exposure of nerve endings. The lymphocytes that are attracted to the airway continue to promote the inflammatory response by secreting cytokines and chemokines, which further potentiate the cellular infiltration into the airway. The ongoing inflammatory process eventually results in hypertrophy of smooth muscles, hyperplasia of mucous glands, thickening of basement membranes, and continuing cellular infiltration. These long-term changes of the airway, referred to
Prevalence is difficult to determine because definitions and survey methods vary, but it is likely increasing as a result of greater sensitization to common allergens and the redefinition of some nonatopic wheezing as asthma. From 1982-1992, the average age-adjusted prevalence rate increased 42% (from 34.7/1000 to 49.4/1000). Asthma may affect 31 million people, including 9.2 million children (7.2% of adults by self-report).
Asthma affects more than 100 million people worldwide. Some reports suggest asthma prevalence has peaked at 8-12%, perhaps because of improved management or because asthma has already been induced in the maximal number of genetically available individuals.
The classic history consists of wheeze, cough, and dyspnea. The predictive value of any single parameter is approximately 30% but is much higher when parameters are combined. Chest discomfort (eg, pain, tightness, congestion, inability to take a full breath) is also common. Some patients may have cough without other symptoms. Recurrent or refractory chest colds may also suggest the diagnosis.
Physical examination findings are often normal.
The etiology of asthma is likely multifactorial. Genetic factors may control individual predispositions to asthma and responses to medications. Genetics alone cannot account for the significant increases in prevalence, as genetic factors take several generations to develop, and asthma and atopy are not always co-inherited. Several environmental or lifestyle factors have been implicated.
Other Problems to be Considered
Children and young adults
Cystic fibrosis
Congenital cardiac anomalies
Pulmonary anomalies
Adults
Gastroesophageal reflux
Vocal cord dysfunction
Endobronchial lesion
Churg-Strauss syndrome (allergic angiitis and granulomatosis)
Allergic bronchopulmonary aspergillosis
Reactive airway dysfunction syndrome: This is a distinct entity caused by exposure to a single, large, inhaled agent leading to asthma symptoms within 24 hours and lasting 3 months or longer.
A 15% drop in FEV1 after 6 minutes of running or other exercise can be diagnostic of exercise-induced bronchospasm.
A 20% variation in the peak expiratory flow rate (PEFR) between high and low values is highly suggestive of asthma, but formal pulmonary function testing (as above) is recommended because the PEFR is extremely effort-dependent.
An asthma specialist can perform bronchoprovocation testing with exercise, histamine, methacholine, or eucapnic voluntary hyperventilation. The results from these tests have a very high negative predictive value and are useful for excluding the diagnosis of asthma. The authors most commonly use a challenge with increasing doses of inhaled methacholine. A 20% decline in FEV1 with a methacholine concentration of 8 mg/mL or less is considered a positive (abnormal) test result. This testing should be avoided during pregnancy because of the risk of precipitating an asthma attack and because methacholine is a class C drug.
Skin test findings have very high positive and negative predictive values; however, a negative test finding does not rule out the possibility that an allergen is having an impact on the patient’s asthma. Conversely, a positive test finding does not mean that a patient is exposed to an allergen or that he or she will react to it in a natural exposure.
Antihistamine medications, but not short courses of oral glucocorticoids at moderate doses, interfere with allergy skin testing.
Skin testing is performed with controls (eg, histamine and saline) to avoid false-positive (dermatographism) or false-negative results.
Identification of allergen triggers can assist in formulating an environmental control strategy.
An RAST may be used in place of skin testing if dermatologic disease is generalized, antihistamine or tricyclic antidepressant (TCA) use cannot be suspended (these will not interfere with RAST results), or skin testing is relatively contraindicated. However, skin testing is more specific, more sensitive, and usually less expensive than the RAST.
The diagnosis of asthma is not made histologically. However, autopsy and bronchoscopic biopsy findings include mucus plugging, inflammatory cell infiltrates and debris, vascular permeability, mucosal edema, and epithelial exfoliation. Remodeling, consisting of hypertrophy of smooth muscle, squamous and goblet cell metaplasia, mucous gland hypertrophy, and basement membrane thickening due to collagen and other matrix protein deposition, is present.
Sputum analysis results show creola bodies (ie, bronchial regenerative cells with nuclear atypia), Charcot-Leyden crystals (ie, residual product of eosinophils), and Curschmann spirals (ie, concentric layers of mucous and debris).
The National Asthma Education and Prevention Program, Expert Panel Report 2 (1997) from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes Health suggests the following stepwise approach to the diagnosis and treatment of adults and children older than 5 years. Updates were published in 2002. In addition, see Medication.
Treatment with daily low-dose inhaled glucocorticoids and short-acting inhaled bronchodilators as needed
Alternate daily therapy - Increase inhaled glucocorticoids (to medium dose) or low-to-medium–dose inhaled glucocorticoids and either a leukotriene modifier or theophylline
Leukotriene synthesis inhibitors, such as zileuton
Allergy immunotherapy for appropriately selected patients
Treatment with daily high-dose inhaled glucocorticoids and daily long-acting inhaled beta-agonist and short-acting bronchodilators as needed
The goals of treatment are to minimize symptoms, improve quality of life, decrease need for urgent care or hospitalizations, normalize pulmonary function test results, and decrease the inflammatory process that leads to airway remodeling. For this discussion, treatment is divided into pharmacotherapy, environmental control, allergen immunotherapy, antibodies against IgE, and education.
In emergency situations, nebulized magnesium sulfate during acute asthma attacks—when added to short-acting beta-2 agonists—may improve pulmonary function and reduce admissions, based on a limited number of studies.
All patients should receive assistance with quitting tobacco use. While smoking cessation is essential for a number of reasons, it particularly appears to increase corticosteroid responsiveness in patients with asthma.
All patients should receive an annual flu shot. A pneumococcal pneumonia vaccination is not required unless indicated based on age (ie, >65 y). Asthma symptoms do not increase after these shots because the antigens in the vaccinations are not alive.
Evaluating and treating patients for associated conditions (eg, rhinitis, GERD, sinusitis) can be important components of therapy. In one study, treating the GERD symptoms of patients with asthma with a proton pump inhibitor for 6 months reduced asthma exacerbations and improved quality of life but did not improve asthma symptoms or pulmonary function or reduce albuterol usage.
Allergen avoidance takes different forms depending on the specific allergen size and characteristic. Improvement in symptoms after avoidance of the allergen may take 1-6 months.
Efforts should focus on the home, where 30-60% of time is spent. Patients should clean and dust their homes regularly. If patients cannot avoid vacuuming, they should use a face mask or a double-bagged vacuum with a high-efficiency particulate air filter. Consideration can be given to moving to a higher floor in the house (less dust and mold) or different neighborhood (fewer cockroaches) if possible. Active smoking and exposure to passive smoke must be avoided. Room air ionizers have not been proven effective to help persons with chronic asthma and the generation of ozone by these machines may be harmful to some. Other factors related to the home include the following:
The cost may be $800 for the first year and then $170/y thereafter (1996 estimate). No direct comparisons with medical therapy have been made to allow a cost-benefit analysis.
Allergen immunotherapy should be considered if specific allergens have a proven relationship to symptoms; the individual is sensitized (ie, positive skin test or RAST findings); the allergen cannot be avoided and is present year-round (eg, industrial); or symptoms are poorly controlled with medical therapy, and a vaccine to the allergen is available. As discussed above, this treatment is especially useful if asthma is associated with allergic rhinitis.
Referral to an allergist is required. The patient must commit to a course of 3-5 years of therapy (although a trial of several months can be considered).
Precautions include serious adverse reactions (occurring in 1 per 30-500 people, usually within 30 min). The estimated crude annual death rate is 0.7 deaths per million population. Monitoring and resuscitation personnel and equipment are required. Also, allergen immunotherapy should be avoided if the patient is taking beta-blockers or is having an asthma exacerbation (ie, PEFR <70% of patient’s personal best) or has moderate or worse fixed obstruction. A major risk factor for immunotherapy-related fatalities includes uncontrolled asthma; therefore, appropriate caution should be exercised.
Dosing of allergen extracts is in bioequivalent allergy units (BAU), weight per volume (w/v), or protein nitrogen units (PNU), but "major allergen content" may be a more standardized and reliable method of dosing and characterizing allergen extracts.
Sublingual immunotherapy has been shown to improve allergic rhinitis symptoms, but effectiveness compared with the standard injection type is unclear. Sublingual immunotherapy and allergoids (modified or peptide-associated allergens) are not currently used in the United States.
Omalizumab (Xolair) was approved by the FDA in 2003 for adults and adolescents (>12 y) with moderate-to-severe persistent asthma who have a positive skin test result or in vitro reactivity to a perennial aeroallergen and whose symptoms are inadequately controlled with inhaled corticosteroids.
This is a humanized murine IgG antibody against the Fc component of the IgE antibody (the part that attaches to mast cell surfaces). Use of this antibody prevents IgE from binding directly to the mast cell surface, thereby preventing cell degranulation.
Therapy has been shown to decrease IgE antibody levels by 99% and cell receptor sites for IgE antibody by 97%. This decrease, in turn, is associated with reduced histamine production (90%), early-phase bronchospasm (40%), and late-phase bronchospasm (70%) and a decrease in the number, migration, and activity of eosinophils. levels drop quickly and remain low for at least a month.
Adverse effects are rare and include upper respiratory infection symptoms, headache, urticaria (2%) without anaphylaxis, and anaphylaxis (0.1%). Transient thrombocytopenia has also been noted but not in humans. Antibodies are formed against the anti-IgE antibody, but these do not appear to cause immune-complex deposition or other significant problems. To date, decreased IgE levels have not been shown to inhibit one’s ability to fight infection (including parasites). Registration trials raised a question of increased risk of malignancy, but this has not been seen in the postmarketing data.
Aside from avoiding known food allergens or additives, diet is not restricted.
Maintaining physical activity and exercise is essential to avoid deconditioning. Susceptible individuals should decrease outdoor activity during midday and afternoon when pollen counts are highest. A short-acting beta-2 agonist and/or cromolyn metered-dose inhaler (MDI) can be used 15-30 minutes before exercise if needed.
Anti-inflammatory medications (especially inhaled glucocorticosteroids) are now the mainstay of therapy and the single most effective therapy for adults with asthma. Anti-inflammatory medications are proven to improve lung function (ie, FEV1, AHR) and to decrease symptoms, exacerbation frequency, and the need for rescue inhalers.
Short-acting inhaled beta-2 agonists, as needed, are most effective for rapid relief of asthma symptoms. No benefit and some risk of developing tolerance occur with regular long-term use. These agents should still be available to the patient, even if he or she is using a long-acting beta-2 agonist (eg, salmeterol).
Of note, the list of medications that combine 2 drugs in a single delivery device in an effort to increase patient convenience and compliance is expanding. These include a combination of albuterol and ipratropium bromide (Combivent) and a combination of fluticasone and salmeterol (Advair). Another combination product, composed of formoterol and budesonide (Symbicort), may be approved in the United States within 2 years.
Glucocorticoids may increase cell beta-2 agonist receptors, which, in turn, may enhance the action of the combination products.
According to the 1998 Leukotriene Working Group, leukotriene pathway modifiers may be useful as first-line therapy for mild persistent asthma or as an add-on or glucocorticoid-sparing medication in others. These agents are less effective than glucocorticoid inhalers but tend to improve compliance because dosing is oral and once daily, and usage appears more reasonable for those unable or unwilling to take glucocorticoids. Leukotriene synthesis inhibitors montelukast, zafirlukast, and zileuton are available.
When adding to a medication regimen for asthma (referred to as stepping up therapy), consider adding LABA for persistent symptoms with impaired FEV1. Patients with symptoms but normal lung function (especially those with symptomatic allergic rhinitis) might benefit first from a leukotriene pathway modifier. Of course, some patients will ultimately be treated with both types of medications for optimum management.
Mast cell stabilizers can also be used. Cromolyn sodium (Intal) indirectly blocks calcium influx into mast cells, preventing inflammatory mediator release. Adults can use it in an MDI (2-4 puffs 3-4 times daily) or in a nebulized form (1 ampule 3-4 times daily). Because of its safety profile, this agent is often tried in children; however, it may take a month to work. The pediatric dose is 1-2 puffs via an MDI 3-4 times daily or 1 ampule via a nebulizer 3-4 times daily. Cromolyn sodium tends to work best in young and highly allergic patients.
Nedocromil (Tilade) has similar effects, although it is structurally distinct. The adult dose is 2-4 puffs via an MDI 2-3 times daily. The pediatric regimen is 1-2 puffs via an MDI 2-4 times daily. MDIs may be used with a spacer as necessary (mask if <2 y). Patients should activate the MDI while breathing in slowly, and then they should hold their breath for 10 seconds if possible.
Using a spacer or holding the inhaler 2 inches from the mouth may improve delivery. The recent change from chlorofluorocarbon to hydrofluoroalkane propellants with smaller particle size may help deliver more medication. The only reliable way to determine if the inhaler is empty is to count the number of doses. Patients should rinse their mouths with water and spit after glucocorticoid inhaler use to prevent oral thrush and dysphonia. An alcohol-containing mouthwash may be more effective than water.
Breath-actuated inhalers are easier to use for less-coordinated individuals. A dry-powder inhaler (DPI) allows rapid inhalation. These devices also often have built-in dose counters.
Consider recommending a nebulizer if the patient is younger than 2 years or is unable to use an MDI or DPI because of cough, severe dyspnea, or poor coordination.
Additionally, recombinant DNA-derived humanized immunoglobulin G monoclonal antibodies to IgE are now available to treat moderate-to-severe persistent asthma in patients who react to perennial allergens and whose symptoms are not controlled by inhaled corticosteroids.
Provide immediate relief of bronchospasm. Preferentially (but not exclusively) bind beta2-adrenergic receptors, resulting in conversion of ATP to cyclic AMP, relaxation of bronchial smooth muscle, and decreased release of inflammatory mediators. Anticholinergic agent ipratropium is included here because it has an additive beneficial effect when given with bronchodilators in acute, severe asthma.
| Drug Name | Albuterol (Proventil, Ventolin, Airet) |
|---|---|
| Description | Beta-agonist. Relaxes bronchial smooth muscle by action on beta-2 receptors with little effect on cardiac muscle contractility. |
| Adult Dose | 4 mg PO q12h; not to exceed 32 mg/d MDI: 1-2 puffs q4-6h prn; not to exceed 12 puffs/d Nebulizer: 2.5 mg tid/qid |
| Pediatric Dose | PO <12 years: 0.3-0.6 mg/kg/d, not to exceed 8 mg/d >12 years: Administer as in adults MDI <4 years: Not established >4 years: Administer as in adults Nebulizer 2-12 years: 0.1-0.15 mg/kg/dose, not to exceed 2.5 mg tid/qid prn >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; used regularly during pregnancy; can cause paradoxical bronchospasm; increasing need for this rescue medication may indicate clinical destabilization that requires medical reevaluation |
| Drug Name | Ipratropium (Atrovent) |
|---|---|
| Description | DOC for beta-2 agonist-induced bronchospasm. Chemically related to atropine and has antisecretory properties. Inhibits vagally mediated reflexes by increasing cyclic GMP, causing local bronchial smooth muscle dilation. Not effective for exercise-induced symptoms. Additive to, but slower than, effects of beta-2 agonists. |
| Adult Dose | Nebulizer: 1 U dose vial (500 mcg) q30min for 3 doses, then q2-4h prn MDI: 4-8 puffs prn initially; not to exceed 12 puffs/d |
| Pediatric Dose | Nebulizer: 250 mcg q20min for 3 doses, then q2-4h prn MDI: 4-8 puffs prn initially; not to exceed 6 puffs/d |
| Contraindications | Documented hypersensitivity |
| Interactions | Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol may increase effects |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Not indicated for acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction |
| Drug Name | Bitolterol (Tornalate); Pirbuterol (Maxair) |
|---|---|
| Description | Stimulates beta-2 receptors directly to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance. |
| Adult Dose | Bitolterol: 2 puffs q8h prn Pirbuterol: 1-2 puffs q4-6h prn |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; tachycardia resulting from cardiac arrhythmia |
| Interactions | Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; can cause paradoxical bronchospasm; increased need for this rescue medication may indicate clinical destabilization that requires medical reevaluation |
| Drug Name | Metaproterenol (Alupent, Metaprel) |
|---|---|
| Description | Relaxes bronchial smooth muscle by action on beta2-adrenergic receptors with little effect on cardiac muscle contractility. Generally not recommended because of excessive cardiac stimulation, especially in high doses. |
| Adult Dose | MDI: 2-3 puffs q3-4h prn Nebulizer: 0.01 mg/kg; not to exceed 0.3 mL of 5% solution q4h prn PO: 20 mg tid/qid |
| Pediatric Dose | <6 years: 2 mg/kg/d PO 6-9 years: 10 mg PO tid/qid >9 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders; can cause paradoxical bronchospasm; increased need for this rescue medication may indicate clinical destabilization that requires medical reevaluation |
| Drug Name | Terbutaline (Brethaire, Brethine, Bricanyl) |
|---|---|
| Description | Acts directly on beta-2 receptors to relax bronchial smooth muscle, relieving bronchospasm and reducing airway resistance. |
| Adult Dose | MDI: 2 puffs q4-6h prn SC: 0.25 mg PO: 5 mg tid |
| Pediatric Dose | <12 years: Not established 12-15 years: 2.5 mg PO tid >15 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; tachycardia resulting from cardiac arrhythmias |
| Interactions | Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilation; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Through intracellular shunting, may decrease serum potassium levels, which can produce adverse cardiovascular effects; decrease is usually transient and may not require supplementation |
| Drug Name | Salmeterol (Serevent) |
|---|---|
| Description | Long-acting bronchodilator - works by relaxing smooth muscles of bronchioles and relieving bronchospasms. Effect may also facilitate expectoration. Inhaler does not replace anti-inflammatory medications but can be added to decrease rescue inhaler use. Evening dose may be useful for nocturnal symptoms. SR PO albuterol has greater systemic sympathomimetic adverse effects and is considered an alternate therapy only. WARNING: Data from a large placebo-controlled US study (SMART trial) that compared the safety of salmeterol or placebo added to usual asthma therapy showed a small but significant increase in asthma-related deaths in patients receiving salmeterol (13 deaths out of 13,176 patients treated for 28 weeks) versus those on placebo (3 of 13,179). |
| Adult Dose | PO: 4 mg q12h MDI: 2 puffs (or 1 blister pack) q12h |
| Pediatric Dose | PO: 0.3-0.6 mg/kg/d; not to exceed 8 mg MDI: 1-2 puffs (or 1 blister pack) q12h |
| Contraindications | Documented hypersensitivity; angina, tachycardia, and cardiac arrhythmia associated with tachycardia |
| Interactions | Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia due to diuretics may worsen |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Not indicated to treat acute asthmatic symptoms; sympathomimetic responses (tremor, tachycardia) can occur and may be significant in some patients with cardiovascular disease; onset of action can be delayed (does not preclude need for short-acting bronchodilators) |
| Drug Name | Theophylline (Theo-24, Theolair, Theo-Dur, Slo-bid) |
|---|---|
| Description | Structurally classified as a methylxanthine, it acts as a bronchodilator. Potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation. For bronchodilation, near toxic (>20 mg/dL) levels are usually required. Less effective than glucocorticoids but may be glucocorticoid-sparing agent. Routine drug level monitoring required (goal: 5-15 mcg/mL). |
| Adult Dose | 10 mg/kg/d (not to exceed 300 mg) PO initially; not to exceed 800 mg/d maintenance |
| Pediatric Dose | <1 year: 0.2 (times age in wk) plus 5 (estimated in mg/kg/d) maximum PO >1 year: 16 mg/kg/d PO; not to exceed 400 mg/d; alternatively, 10 mg/kg/d IV |
| Contraindications | Documented hypersensitivity; uncontrolled arrhythmia; peptic ulcers; hyperthyroidism; uncontrolled seizure disorders |
| Interactions | Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects Effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in peptic ulcer, hypertension, tachyarrhythmia, hyperthyroidism, and compromised cardiac function; do not inject IV solution >25 mg/min; patients diagnosed with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance |
Recombinant, DNA-derived agents inhibit IgE binding to the high-affinity IgE receptor on mast cells and basophils, causing a decrease in release of mediators of the allergic response.
| Drug Name | Omalizumab (Xolair) |
|---|---|
| Description | Recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE receptor on surface of mast cells and basophils. By inhibiting IgE binding, release of mediators of allergic response is inhibited. Indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens in whom symptoms are not controlled by inhaled corticosteroids. |
| Adult Dose | 150-375 mg SC q2-4wk; inject slowly over 5-10 seconds due to viscosity; not to exceed 150 mg/injection site Precise dose and frequency established by serum total IgE level (IU/mL) |
| Pediatric Dose | <12 years: Not established >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Not effective to treat acute asthma; do not abruptly discontinue inhaled corticosteroids when initiating omalizumab; malignancy rate among treated patients (0.5%) was numerically higher than among control patients (0.2%); malignancies varied, and further long-term observation needed to fully assess risk; may cause injection-site reaction |
Maintenance medications that decrease inflammatory mediators to limit airway remodeling. Must be taken regularly to be beneficial. Do not relieve acute bronchospasm; short-acting bronchodilators must be available. The multiple formulations are not equivalent on a per-dose or per-mcg basis. Inhaled corticosteroids are one of the most important developments in asthma management because they decrease inflammation. Proven to improve lung function (ie, FEV1, airway hyperactivity) and decrease symptoms, exacerbation frequency, and need for rescue inhalers. Dose ranges as recommended by NHLBI.
| Drug Name | Beclomethasone (Beclovent, Vanceril) |
|---|---|
| Description | Inhibits bronchoconstriction, produces direct smooth muscle relaxation, decreases number and activity of inflammatory cells, and decreases airway hyperresponsiveness. |
| Adult Dose | Low dose: 2-6 puffs (84-mcg MDI) or 4-12 puffs (42-mcg MDI) Medium dose: 6-10 puffs (84-mcg MDI) or 12-20 puffs (42-mcg MDI) High dose: >10 puffs (84-mcg MDI) or >20 puffs (42-mcg MDI) |
| Pediatric Dose | Low dose: 1-4 puffs (84-mcg MDI) or 2-8 puffs (42-mcg MDI) Medium dose: 4-8 puffs (84-mcg MDI) or 8-16 puffs (42-mcg MDI) High dose: >8 puffs (84-mcg MDI) or >16 puffs (42-mcg MDI) |
| Contraindications | Documented hypersensitivity; bronchospasm, status asthmaticus, other types of acute episodes of asthma |
| Interactions | Coadministration with ketoconazole may increase plasma levels but does not appear to be clinically significant |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Not for acute attack; weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur (taper medication slowly if these changes occur); adverse effects include dysphonia and oral thrush (minimize by rinsing mouth); long-term high-dose use may cause osteoporosis, adrenal suppression, or growth impairment; universally safer than PO steroids and are necessary to avoid permanent lung damage in some patients with asthma |
| Drug Name | Budesonide (Pulmicort Respules, Pulmicort Turbuhaler, Rhinocort Aqua Intranasal) |
|---|---|
| Description | Inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease number and activity of inflammatory cells, which, in turn, decreases airway hyperresponsiveness. |
| Adult Dose | DPI Low dose: 200-600 mcg Medium dose: 600-1200 mcg High dose: 1200 mcg |
| Pediatric Dose | Inhalation suspension for children Low dose: 0.5 mg Medium dose: 1 mg High dose: 2 mg |
| Contraindications | Documented hypersensitivity; bronchospasm, status asthmaticus, other types of acute episodes of asthma |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur (taper medication slowly if these changes occur); adverse effects include dysphonia and oral thrush (minimize by rinsing mouth); long-term high-dose use may cause osteoporosis, adrenal suppression, or growth impairment; universally safer than PO steroids and are necessary to avoid permanent lung damage in some patients with asthma |
| Drug Name | Flunisolide (AeroBid) |
|---|---|
| Description | Inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease number and activity of inflammatory cells, which, in turn, decreases airway hyperresponsiveness. |
| Adult Dose | Low dose: 2-4 puffs Medium dose: 4-8 puffs High dose: >8 puffs |
| Pediatric Dose | Low dose: 2-3 puffs Medium dose: 4-5 puffs High dose: >5 puffs |
| Contraindications | Documented hypersensitivity: bronchospasm, status asthmaticus, other types of acute episodes of asthma |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur (taper medication slowly if these changes occur); adverse effects include dysphonia and oral thrush (minimize by rinsing mouth); long-term high-dose use may cause osteoporosis, adrenal suppression, or growth impairment; universally safer than PO steroids and are necessary to avoid permanent lung damage in some patients with asthma |
| Drug Name | Fluticasone (Flovent) |
|---|---|
| Description | Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary-adrenocortical axis inhibitory potency when applied topically. |
| Adult Dose | MDI Low dose: 88-264 mcg Medium dose: 264-660 mcg High dose: >660 mcg DPI Low dose: 100-300 mcg Medium dose: 300-600 mcg High dose: >600 mcg |
| Pediatric Dose | MDI Low dose: 88-176 mcg Medium dose: 176-440 mcg High dose: >440 mcg DPI Low dose: 100-200 mcg Medium dose: 200-400 mcg High dose: >400 mcg |
| Contraindications | Documented hypersensitivity; bronchospasm, status asthmaticus, other types of acute episodes of asthma |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur (taper medication slowly if these changes occur); adverse effects include dysphonia and oral thrush (minimize by rinsing mouth); long-term high-dose use may cause osteoporosis, adrenal suppression, or growth impairment; universally safer than PO steroids and are necessary to avoid permanent lung damage in some patients with asthma |
| Drug Name | Triamcinolone (Azmacort) |
|---|---|
| Description | Decreases inflammation by suppressing migration of PMN leukocytes and reversing capillary permeability. |
| Adult Dose | Low dose: 4-10 puffs Medium dose: 10-20 puffs High dose: >20 puffs |
| Pediatric Dose | Low dose: 4-8 puffs Medium dose: 8-12 puffs High dose: >12 puffs |
| Contraindications | Documented hypersensitivity, bronchospasm, status asthmaticus, other types of acute episodes of asthma |
| Interactions | Coadministration with barbiturates, phenytoin, and rifampin decreases effects |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur (taper medication slowly if these changes occur); adverse effects include dysphonia and oral thrush (minimize by rinsing mouth); long-term high-dose use may cause osteoporosis, adrenal suppression, or growth impairment; universally safer than PO steroids and are necessary to avoid permanent lung damage in some patients with asthma |
| Drug Name | Prednisone (Deltasone, Orasone) |
|---|---|
| Description | Immunosuppressant for treatment of autoimmune disorders. May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Goal is lowest dose and shortest duration effective for disease control. Conversion: methylprednisolone (Medrol) dose equal to four fifths of desired prednisone dose. Prednisolone (Prelone, Pediapred) dose equal to prednisone dose. |
| Adult Dose | 40-60 mg/d PO for 3-10 d as burst; 5-60 mg/d PO qd or qod for long-term use prn for disease control; divided doses (20 mg tid) are more effective than 60 mg qd but are also associated with more adverse effects |
| Pediatric Dose | 1-2 mg/kg/d PO for 3-10 d as burst; not to exceed 60 mg/d; 0.25-2 mg/kg qd or qod for long-term use prn for disease control |
| Contraindications | Documented hypersensitivity; peptic ulcer disease, hepatic dysfunction; viral infection, connective tissue infections, fungal or tubercular skin infections; GI disease |
| Interactions | Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Category C for methylprednisolone and prednisolone; abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, weight gain, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur; qod therapy lessens adverse effects |
Consist of leukotriene receptor antagonists (eg, zafirlukast and montelukast) and synthesis inhibitors (eg, zileuton).
| Drug Name | Zafirlukast (Accolate), montelukast (Singulair), zileuton (Zyflo) |
|---|---|
| Description | Leukotriene pathway inhibitors. Not for use in acute episodes of asthma. |
| Adult Dose | Zafirlukast: 20 mg PO bid Montelukast: 10 mg PO qd Zileuton: 600 mg PO qid |
| Pediatric Dose | <12 years (zafirlukast and zileuton): Not established >6 years (montelukast): 5 mg PO qd |
| Contraindications | Documented hypersensitivity |
| Interactions | Warfarin and theophylline levels must be followed closely if coadministered with zafirlukast or zileuton; do not take with food |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Category C for zileuton; association with Churg-Strauss vasculitis (zileuton), although may be unrelated and only reflect coincidental corticosteroid withdrawal; monitor liver enzymes; not a bronchodilator; have appropriate rescue medication available |
A reduced FEV1 or PEFR to less than 50% of the patient’s personal best, normocapnia or hypercapnia, severe symptoms, or mental status changes warrants admission to an ICU.
If the patient responds to therapy, examination findings are normal 1 hour after the last medication dose, and the FEV1 or PEFR is greater than 70% of patient’s personal best, consider discharging the patient home on therapy to include oral steroids and scheduling a follow-up visit within 1 week.
Systemic glucocorticoids may increase the risk of preeclampsia and decreased birth weight but should be used if asthma exacerbation is severe because untreated asthma bears its own risks on the pregnancy.