Asthma

Definition
A chronic inflammatory disease of airways, characterized by increased responsiveness of the tracheobronchial tree to various stimuli o Bronchospasm, once thought to be the primary event in asthma, is now recognized as a secondary phenomenon caused by the underlying inflammatory process. Manifested physiologically by widespread narrowing of the air passages, and clinically by paroxysms of dyspnea, cough, chest tightness and wheezing Episodic disease, with acute exacerbations interspersed with symptom-free periods o Most attacks are short-lived, lasting minutes to hours, and can be managed relatively easily. o Less often, patients develop persistent disease necessitating aggressive therapy. o Status asthmaticus is the most severe form of asthma. Severe obstruction persists for days or weeks Can be life threatening

Epidemiology
Prevalence o Increasing in many parts of the world, but it is unclear whether this is due to an actual increase in incidence or to overall population growth o Worldwide: 300 million people o Affluent countries: Adults: 1012% Children: 15% o Developing countries: lower prevalence but may be rising due to increased urbanization Incidence in the U.S.

1011 million persons had acute attacks in 1998. 13.9 million outpatient visits o 2 million requests for urgent care o 423,000 hospitalizations o Total cost: >$6 billion Ethnic distribution
o o

More prevalent in minorities and inner-city AfricanAmerican and Hispanic populations Age
o

Risk Factors

All ages affected, but more prevalent in early life Peak age: 3 years o ~50% of cases develop before 10 years of age. o Another one-third of cases occur before 40 years of age. Sex o 2:1 male-to-female ratio in childhood o Sex ratio equalizes by 30 years of age.
o

First-degree relative with a history of asthma Personal or family history of atopy History of multiple respiratory infections during childhood Obesity[1] Other risk factors that may be implicated
o

Lower maternal age o Prematurity o Low birth weight o Inactivity o Acetaminophen consumption Breast feeding during infancy appears to reduce risk of childhood asthma.

Etiology
Airway hyperresponsiveness to both specific and nonspecific stimuli is the hallmark of asthma. o Etiology is unknown, but genetic susceptibility and airway inflammation are believed to play fundamental roles. o Cells thought to be important in the inflammatory response include mast cells, eosinophils, lymphocytes, and airway epithelial cells. Allergic (extrinsic) asthma o Associated with a personal and/or family history of allergic diseases, such as rhinitis, urticaria, or eczema o Immunoglobulin E (IgE) mediated o Precipitants

Dust mites (often found in pillows, mattresses, carpets and drapes) Cockroaches Animal dander, especially cats Seasonal pollens Idiosyncratic (intrinsic) asthma o No defined immunologic mechanism o Precipitants Upper respiratory infections

Exercise Gastroesophageal reflux (rarely causes asthma symptoms) Exposure to cold air Tobacco smoke Pollutants: ozone, nitrogen dioxide, sulfur dioxide Sulfites in food Emotional stress Pharmacologic agents Aspirin NSAIDs Tartrazine dyes -Adrenergic antagonists Dietary factors (controversial) Diets low in antioxidants (vitamin A, vitamin C, magnesium,selenium, omega-3 polyunsaturated fats) Diets high in sodium, omega-6 polyunsaturated fats Occupational asthma can be both allergic and nonallergic, with hundreds of precipitants having been identified.

Associated Conditions Symptoms & Signs

Classic symptom triad o Wheezing o Dyspnea o Cough Typical acute attack o Often occurs at night With occupational asthma, attacks may occur at work or after work. o Patients experience a sense of constriction in the chest, often with a nonproductive cough. o Respiration becomes audibly harsh. o Wheezing is first noted during expiration and then with inspiration as well. o Expiration becomes prolonged. o If attack is severe or prolonged, there may be loss of adventitial breath sounds. Wheezing becomes very high pitched.

Allergic conditions, such as rhinitis, urticaria, and eczema Gastroesophageal reflux

In extreme situations, mucus plugging and impending suffocation are signaled by:
o

Lessening or disappearance of wheezing Cough may become extremely ineffective. o Accessory muscles become visibly active, and a paradoxical pulse often develops. These 2 signs are very valuable in indicating the severity of the obstruction. o The end of an episode is frequently marked by a cough that produces thick, stringy mucus. Less typically, the patient may have intermittent episodes of nonproductive cough or exertional dyspnea. o Patients tend to have normal breath sounds but may wheeze after repeated forced exhalations. Patients with allergic asthma o Exposure to antigen typically produces an immediate response. o Airway obstruction develops in minutes and then resolves. o 3050% of patients have a second wave of bronchoconstriction, a "late reaction," 610 hours later. o In a minority, only a late reaction occurs. Patients with idiosyncratic asthma o Bronchospasm typically follows an upper respiratory infection. Other physical findings o Respiratory rate Increases with severity o Heart rate Increases with severity Relative bradycardia may develop with impending respiratory failure o Use of accessory respiratory muscles Increases with severity Paradoxical thoracoabdominal movement with impending respiratory failure o Pulsus paradoxus (normally < 10 mmHg) 1025 mmHg in moderate episode >25 mmHg in severe episode o Ear, nose, and throat examination Nasal polyps in patients with allergic asthma, cystic fibrosis, aspirinsensitivity o Skin

Eczema and atopic dermatitis in allergic patients

Differential Diagnosis
Recurrent pulmonary emboli o Can be very difficult to distinguish from asthma o Lung scans may not be diagnostic because of the ventilationperfusion abnormalities characteristic of asthma. o Chest CT is now preferred at many centers for the diagnosis of a pulmonary embolism. o Rarely, pulmonary angiography may be necessary. Upper airway obstruction by tumor or laryngeal edema o Typically presents with stridor, and harsh respiratory sounds can be localized to the trachea. o Diffuse wheezing throughout both lung fields is usually absent. o Indirect laryngoscopy or bronchoscopy may be required. Glottic dysfunction o Narrowing glottis during inspiration and expiration produces episodic attacks of severe airway obstruction. o Unlike asthma, arterial oxygen tension is well preserved. o Alveolararterial gradient for oxygen narrows during the episode but widens in lower airway obstruction. o Normal findings of glottic examination during symptoms exclude the diagnosis; normal findings during asymptomatic periods do not. Endobronchial disease (e.g., foreign-body aspiration, neoplasm, or bronchial stenosis) o Indicated by persistent wheezing localized to 1 area of the chest, in association with paroxysms of coughing Carcinoid tumors o Usually associated with stridor o Recurrent episodes of bronchospasm can occur. Chronic bronchitis or emphysema o No true symptom-free periods, history of chronic cough and sputum production as a background to acute attacks of wheezing Eosinophilic pneumonia, various chemical pneumonias, and exposures to insecticides and cholinergic drugs Acute left ventricular failure o Moist basilar rales, gallop rhythms, blood-tinged sputum, and other signs of heart failure

Diagnostic Approach
In any patient presenting with dyspnea, the first step must be to ascertain the severity of the compromise even before a specific diagnosis is made. o This can be accomplished quickly by:

Systemic vasculitis with pulmonary involvement Vocal cord dysfunction

Observation of the patients difficulty breathing (general appearance, ability to speak between breaths, use of accessory muscles, etc.) Obtaining vital signs, including pulsus paradoxus and oxygen saturation (which may be falsely elevated in a patient with tachypnea) Diagnosis of asthma is made by history and physical examination, with confirmation by pulmonary function tests. History o Course of previous attacks (e.g., need for hospitalization, steroid treatment) Previous intensive care unit admission or intubation: marker of severe disease and high-risk patient o Response to medications o If occupational exposure is suspected Ask about workplace and work history in detail. Specific contaminants? Availability and use of protective devices? Ventilation (dose of environmental agent influenced by intensity and physiologyventilation rate and depth) Do coworkers have similar complaints? Ask about every job; short-term exposures may be significant. Physical examination o Presence of wheezing, especially expiratory Absence of wheezing may signify poor airflow and impending respiratory failure. o Assessment of severity of airflow obstruction Increased respiratory rate, tachycardia, use of accessory muscles for breathing, and an elevated pulsus paradoxus are all helpful indicators of severity. Pulmonary function tests (see Diagnostic Procedures)

Show initial airflow obstruction and reversibility with bronchodilator inhalation The most useful measures are peak flow and forced expiratory volume in 1 second (FEV1) evaluated as a percent of predicted normal values. These can be obtained quickly and easily at the bedside. o Bronchoprovocation test may be required if wheezing or airflow obstruction is not initially demonstrated.
o

Laboratory Tests
Complete blood count may show eosinophilia. Serum IgE level o Elevated in allergic asthma o Normal in idiosyncratic asthma o Marked elevations may suggest allergic bronchopulmonary aspergillosis. Sputum examination o Eosinophilia o Curschmanns spirals (casts of small airways) o CharcotLeyden crystals o Presence of large numbers of neutrophils suggests bronchial infection. Arterial blood gas o Rarely required o May show hypoxemia during a severe attack o Hypocarbia and respiratory alkalosis may also be present. o Normal or elevated arterial partial pressure of carbon dioxide suggests severe respiratory muscle fatigue or airways obstruction and impending respiratory failure. o Metabolic acidosis is another indicator of impending respiratory collapse. o Arterial blood gas abnormalities are helpful when present, but are insensitive indicators of severe disease. Electrocardiogram o May show reversible changes of right axis deviation, P pulmonale, right bundle branch block, or right ventricular hypertrophy with repolarization abnormalities

Imaging

Chest radiography
o

Not always necessary

Important when complicating infection or pneumothorax is a consideration o May show hyperinflation or patchy infiltrates due to atelectasis behind plugged airways
o

Diagnostic Procedures
Pulmonary function tests o Support the clinical diagnosis by demonstrating reversible airway obstruction. o Reversibility is defined as a 15% increase in FEV1 after 2 puffs of a -adrenergic agonist. o Helpful in judging severity of airway obstruction and for following response to treatment o More reliable than clinical examination or patients subjective symptoms o Findings in asthma Forced vital capacity (FVC); FEV1; maximum, mid-, and peak expiratory flow rate; and FEV1/FVC ratio are all decreased. Residual volume and total lung capacity are increased. Diffusing capacity of the lung for carbon dioxide is usually normal or slightly increased. An FEV1 of < 25% predicted or < 0.75 L after administration of a bronchodilator indicates severe disease. Bronchoprovocation test o May be required when spirometry results are normal and no wheezing is present o Heightened airway responsiveness is found when the patient is challenged with: Histamine Methacholine Isocapnic hyperventilation of cold air Skin tests o Positive wheal-and-flare reactions can be demonstrated to various allergens in patients with allergic asthma. Findings do not necessarily correlate with the intrapulmonary events. o A significant number of asthmatic patients have negative allergic histories and do not react to skin tests with specific allergens.

Classification

Asthma is quantified by severity. o As severity will vary over time, so will the patients classification.

The purpose of classification is to enable the clinician to optimize therapy as quickly as possible. The 4 major classes are: o Mild, intermittent Symptoms occur 2 or fewer times per week. Asymptomatic between attacks Exacerbations are brief (hours to at most days) and of varying intensity. Nocturnal symptoms are rare, less than twice a month. The FEV1 is greater than 80% predicted during episodes. o Mild, persistent Symptoms occur more than 2 times a week but less than once a day. Exacerbations may affect normal activity. Nocturnal symptoms occur more than twice a month. FEV1 is greater than 80% predicted during episodes. o Moderate, persistent Symptoms occur daily. Exacerbations occur more than twice a week and may last days. Exacerbations affect normal activity. Nocturnal symptoms occur more than twice a month. FEV1 is between 60% and 80% during episodes. o Severe, persistent Symptoms are continual. Physical activity is limited. Exacerbations are frequent. Nocturnal symptoms are frequent. FEV1 is always abnormal and less than 60% predicted during episodes.

Treatment Approach
Emergencies

Identify life-threatening airway obstruction. o Presence of a paradoxical pulse, use of accessory muscles, and marked hyperinflation of the thorax signify severe airways obstruction. o Failure of these signs to remit promptly after aggressive therapy mandates frequent monitoring of:

Arterial blood gases Peak expiratory flow rate (PEFR) or FEV1 If at presentation the PEFR or FEV1 is 20% of that predicted and does not double after 1 hour of intensive therapy o Patient is likely to require intensive treatment, including systemic glucocorticoids and inpatient treatment. o If the clinical signs of a paradoxical pulse and accessory muscle use are diminishing and/or the PEFR is increasing No need to change medications or doses Patient needs to be followed closely. o If the PEFR decreases by > 20% of its previous value or if the magnitude of the pulsus paradoxicus is increasing Serial measures of arterial blood gases are required. Reconsider the therapeutic methods being used. o If the patient has hypocarbia, continue the current approach. If the arterial partial pressure of carbon dioxide is within the normal range or is elevated o Patient should be monitored in an intensive care setting. o Therapy should be intensified to reverse or arrest the patients respiratory failure. Failure of PEFR to improve to 70% of baseline with emergency treatment suggests need for hospitalization, with the final decision made on the basis of individual factors (e.g., symptoms, history).

Chronic stable asthma

Goals
General: a stable, asymptomatic state with the best pulmonary function possible using the least medication Specific

Minimal or absent chronic symptoms or exacerbations o No limitation on activities o No absences from school or work
o

Maintenance of normal or near-normal pulmonary functions o Minimal use of short-acting 2-agonists (less than once daily, < 1 canister/month) o Minimal or absent adverse effects from medications A primary step is educating patients. o Patients should monitor PEFR regularly at home and at work. o Asthma triggers should be avoided. Assess severity of the illness and monitor with objective measures of lung function. o Disappearance of subjective symptoms or wheezing in an acute attack should not be used as the end point for therapy. Plan for both long-term management and treatment of exacerbations.
o

Stepwise pharmacologic approach of the National Asthma Education and Prevention Program
Step 1: mild, intermittent o No daily medication needed o Short acting inhaled 2-agonist or glucocorticoid used as needed during exacerbations only Step 2: mild, persistent

Low-dose inhaled glucocorticoids taken daily in lowest dose necessary to control symptoms o Short acting 2-agonists used as needed for exacerbations o Alternative treatments (listed alphabetically): cromolyn, leukotriene modifier, nedocromil, or sustained-release theophylline (serum concentration target of 515 g/mL) Step 3: moderate, persistent
o

Low- to medium-dose inhaled glucocorticoids often combined with long-acting inhaled 2-agonists (salmeterol, albuterol sustained-release tablets) are used daily. o Alternative treatment: leukotriene modifier or theophylline instead of 2-agonists o Short acting 2-agonsts are again used for exacerbations. Step 4: severe, persistent o Moderate to high-dose inhaled glucocorticoids and long-acting inhaled 2-agonists are used daily and
o

If needed, glucocorticoid tablets or syrup long term (generally not exceeding 60 mg/d) Make repeated attempts to reduce systemic glucocorticoids and maintain control with high-dose inhaled glucocorticoids. o Short acting 2-agonists are again used for exacerbations. Failure to respond quickly may necessitate hospitalization.
o

Quick relief for all patients

Short-acting bronchodilator: 24 puffs inhaled 2agonists (e.g., albuterol,terbutaline, pirbuterol) as needed for symptoms Intensity of treatment will depend on the severity of exacerbation. o Up to 3 treatments at 20-minute intervals or a single nebulizer treatment as needed o A course of systemic glucocorticoids may be needed. Use of short-acting 2-agonists > 2 times a week in intermittent asthma (daily, or increasing use in persistent asthma) may indicate need to initiate or increase longterm control.

Patients with coexisting conditions

Examples: heart disease, pregnancy Treatment does not differ materially from that outlined above. Inhaled 2-selective and anti-inflammatory agents are the mainstay. Use the lowest doses of adrenergics that produce the desired effects.

Occupational asthma
Specific Treatments
Emergencies Aerosolized 2-agonists are the primary therapy for acute episodes. o 3 doses given every 20 minutes by handheld nebulizer, then a single dose every 2 hours until the attack subsides o Some studies suggest that continuous nebulized 2-agonists may be more effective than intermittent treatment, especially in severe acute exacerbations.

Therapy follows usual guidelines.

Treatment with albuterol administered by jet nebulizer, metered-dose inhaler (MDI), or dry powder inhaler (DPI) all provide equal resolution in acute situations when doses are matched. o Optimum cumulative dose of albuterol is 510 mg. Systemic glucocorticoids o Prednisone (1 mg/kg PO once daily) or SoluMedrol (125 mg IV every 6 hours) o No difference between oral and intravenous administration in moderate exacerbations o Intravenous therapy is preferred in severe exacerbations. Theophylline may speed resolution after the first hour in 510% of patients. Magnesium (as magnesium sulfate) o A smooth musclecell relaxant; may also reduce inflammatory bronchoconstriction through actions on mast cells o Several small randomized, controlled trials support use of magnesium (2 g IV) in acute severe asthma exacerbations. o Especially useful if the response to inhaled 2agonist in appropriate dose is inadequate
o

Adrenergic stimulants
Dilate the airways, decrease release of mediators, and improve mucociliary transport Short-acting -adrenergic agonists o The resorcinols (e.g., fenoterol) and saligenins (e.g., albuterol) are highly selective for the respiratory tract and devoid of significant cardiac effects except at high doses. o Are active by all routes of administration o May last 46 hours o Major side effect is tremor. o Inhalation is the preferred route of administration. Allows maximal bronchodilation with fewer side effects o In treating episodes of severe asthma, intravenous administration offers no advantage over the inhaled route. o Safety Association between asthma mortality and the amount of short-acting -adrenergic agonists used

Increased use of rescue short-acting adrenergic agonists reflects poor asthma control, which is a risk factor for asthma death.
o

Methylxanthines
Used rarely in acute situations, infrequently in chronic cases Serum monitoring is important (target serum concentration of 515 g/mL at steady state). Theophylline and its various salts are medium-potency bronchodilators with questionable anti-inflammatory properties. o Liquids, sustained-release tablets, and capsules o Starting dose for adults: 10 mg/kg daily Dose required to achieve desired level varies widely from patient to patient owing to differences in drug metabolism. o Clearance decreases with age, congestive heart failure, liver disease, pneumonia, viral infection and vaccination, high-carbohydrate diet, and concurrent use of erythromycin and other macrolide antibiotics; quinolone antibiotics; and troleandomycin, allopurinol, cimetidine, andpropranolol, zileuton, zafirlukast. o Clearance increases with use of cigarettes, marijuana, phenobarbital,phenytoin, or any other drug capable of inducing hepatic microsomal enzymes; highprotein, low-carbohydrate diet; barbecued meat; and childhood. Adjust dose on the basis of the clinical response, with the aid of serumtheophylline measurements. Single-dose administration in the evening o Reduces nocturnal symptoms o Helps keep patients symptom-free during the day For maintenance therapy, usually given once or twice daily Minimal evidence for additional benefit when used with optimal doses of -adrenergic stimulants May decrease inflammation, but as with the long-acting 2-agonists, the effect is not large and clinical impact is undefined. Side effects: nervousness, nausea, vomiting, anorexia, and headache o At plasma levels > 30 g/mL, there is a risk of seizures and cardiac arrhythmias.

Anticholinergics

Drugs such as ipratropium bromide o Free of major side effects

Of particular benefit for patients with coexistent heart disease, in whom the use of methylxanthines and -adrenergic stimulants is undesirable Major disadvantages o Slow to act (6090 minutes may be required before peak bronchodilation achieved) o Of only modest potency
o

Long-term controller medications

Inhaled glucocorticoids
Drugs of choice in the long-term control of asthma o The combination of an inhaled steroid and a longacting -agonist (see below) seems particularly efficacious in patients with mild to moderate disease. Controls inflammation, facilitates long-term prevention of symptoms, reduces need for glucocorticoids taken as a tablet or syrup, minimizes acute exacerbations, and prevents hospitalizations No fixed dose works for all patients. There is no convincing reason to prefer one inhaled steroid to another. Inhaled steroids can take 1 week to produce improvements. o In rapidly deteriorating situations, prescribe oral preparations and initiate inhaled drugs as the dose of the former is reduced. o In less emergent circumstances, increase the quantity of inhaled drug up to 22.5 times the recommended starting doses. Side effects increase in proportion to the dose-time product. o Thrush and dysphonia o Increased systemic absorption that accompanies larger doses of inhaled steroids can cause adrenal suppression, cataract formation, decreased growth in children, interference with bone metabolism, and purpura. Specific agents
o

Beclomethasone: 42 g/puff Low dose: 412 puffs Medium dose: 1012 puffs High dose: >20 puffs Budesonide: 200 g/dose Low dose: 12 inhalations

Medium dose: 23 inhalations High dose: >3 inhalations Flunisolide: 250 g/dose Low dose: 24 puffs Medium dose: 48 puffs High dose: >8 puffs Fluticasone MDI: 44, 110, 220 g/puff o Low dose: 26 puffs (44 g) or 2 puffs (110 g) o Medium dose: 26 puffs (110 g) o High dose: >6 puffs (110 g) Daily permissible intake: 50, 100, 250 g/puff o Low dose: 26 inhalations (50 g) o Medium dose: 36 inhalations (100 g) o High dose: >6 inhalations (100 g) Triamcinolone: 100 g/puff Low dose: 410 puffs Medium dose: 1020 puffs High dose: >20 puffs

Systemic glucocorticoids
The most potent and most effective anti-inflammatory medications available Most beneficial o In acute illness, when severe airway obstruction is not resolving or is worsening despite intense optimal bronchodilator therapy o In chronic disease, when there has been failure of a previously optimal regimen and frequent recurrences of symptoms of increasing severity Prevent relapse after acute exacerbations when given for a 5- to 10-day "burst" at 4060 mg/d PO

Tapering the dose is not necessary. When continued steroid therapy is needed: o Institute an alternate-day schedule to minimize side effects Particularly important in children because continuous glucocorticoid administration interrupts growth Specific agents o Methylprednisolone Adults: 7.560 mg/d PO in a single dose in the morning or every other day as needed for control
o

Prednisolone Adults: Short-course "burst" to achieve control: 4060 mg/d PO as a single dose or 2 divided doses for 310 days Prednisone Adults: 40-60 mg/d PO

Long-acting -adrenergic agonists

Provide sustained effects for 912 hours Often used together with inhaled glucocorticoids Particularly helpful for such conditions as nocturnal and exercise-induced asthma Salmeterol o MDI: 21 g/puff; adult dose, 2 puffs every 12 hours o DPI: 50 g/blister; adult dose, 1 blister every 12 hours Formoterol o DPI: 12 g/single-use capsule; adult dose, 1 capsule every 12 hours Long-acting inhaled 2-agonists should not be used for symptom relief or for exacerbations. o Relatively slow onset of action (~30 minutes) Long half-life means that administration of extra doses can cause cumulative side effects. Safety o Slight excess in mortality associated with the use of long-acting -adrenergic agonists is related to the lack of use of concomitant inhaled corticosteroids (ICS), as the long-acting -adrenergic agonist therapy does not deal with the underlying inflammation Always use an ICS when long-acting adrenergic agonists are given.

Combined medications

Glucocorticosteroid/2-agonist o Adds convenience and effectiveness in the care of chronic asthma o Tends to work best in patients with milder disease o Fluticasone/salmeterol DPI: 250 g/50 g Adult dose: 1 inhalation bid; dose depends on severity of asthma o Budesonide/formoterol MDI: 80 g/4.5 g; 160 g/4.5 g Adult dose: 2 inhalations bid; dose depends on severity of asthma

Mast cellstabilizing agents

Block the acute obstructive effects of exposure to antigen, industrial chemicals, exercise, or cold air Prevent release of chemical mediators of anaphylaxis Most effective in atopic patients with seasonal disease or perennial airway stimulation Need not be used continuously; protection can be obtained by taking the drug 1520 minutes before contact with a precipitant. Specific agents
o

Cromolyn MDI: 1 mg/puff; adult dose: 24 puffs tid or qid o A therapeutic trial of 2 puffs 4 times daily for 46 weeks is frequently necessary before the beneficial effects are seen. Nebulizer: 20 mg/ampule; adult dose: 1 ampule tid or qid Nedocromil MDI: 1.75 mg/puff; adult dose: 24 puffs bid to qid

Leukotriene modifiers
Not uniformly effective in all patients with asthma (< 50% responders) o If no improvement is seen after 1 month, treatment can be discontinued. Leukotriene blockers have been associated with uncovering of ChurgStrauss syndrome. Specific agents
o

Zileuton The only 5-lipoxygenase synthesis inhibitor available in the U.S. o Reduces asthma morbidity, provides protection against exercise-induced asthma, diminishes nocturnal symptoms o Limited effectiveness against allergens o Hepatic enzyme levels can be elevated after its use; there are significant interactions with other drugs metabolized in the liver. 300- or 600-mg tablet Adults: 2400 mg/d (tablets given qid) Montelukast Leukotriene D4 receptor antagonist

Longer acting than zileuton; has same therapeutic profile 4- or 5-mg chewable tablet, 10-mg tablet Adults: 10 mg at bedtime Zafirlukast Leukotriene D4 receptor antagonist Longer acting than zileuton; has same therapeutic profile 10- or 20-mg tablet Adults: 40 mg/d, as 20-mg tablet bid

Anti IgE
A blocking antibody that neutralizes circulating IgE without binding to cell-bound IgE; it thus inhibits IgEmediated reactions. Reduces the number of exacerbations in patients with severe asthma and may improve asthma control Very expensive Suitable only for highly selected patients who are not controlled on maximal doses of inhaler therapy and have a circulating IgE within a specified range o Omalizumab Give 34 month trial of therapy to show objective benefit. Subcutaneous injection every 24 weeks No significant side effects

Miscellaneous agents Opiates, sedatives, and tranquilizers should be absolutely avoided in the acutely ill patient with asthma. Expectorants and mucolytic agents do not add significantly to treatment. Little evidence that intravenous fluids hasten recovery in acute asthma Desensitization or immunotherapy has limited scientific support and minimal clinical effectiveness.

Monitoring
Once control is reached and sustained for several weeks, a step-down reduction in therapy should be undertaken. o Goal is to find the minimum amount of medication required to keep the patient well. o Begin with dose reduction of glucocorticosteroid. Medication adjustments should be based on objective changes in lung function (PEFR at home and/or the FEV1 in the office) as well as on symptoms. o Review treatment every 12 months.

When a patients asthma is destabilizing, frequent assessments are required. o Important to gain control as quickly as possible, then step down to the least medication necessary. o Before increasing treatment, review the patients inhaler technique, adherence to therapeutic recommendations, and environment control. In patients taking theophylline, monitor serum levels. o Goal: 515 g/mL at steady state o Risk of toxicity, including cardiac arrhythmias and seizure at levels > 20 g/mL In patients requiring oral corticosteroid treatment for maintenance o Monitor bone density. o Institute preventive treatment if bone density is low.

Calcium and vitamin D Bisphosphonates Estrogen (postmenopausal women)

Complications
Patients who smoke or have other comorbid stimuli may develop irreversible changes in lung function. Spontaneous pneumothorax and/or pneumomediastinum occur rarely. Status asthmaticus Respiratory failure Mortality o The most recent figures for the U.S. indicate < 6000 deaths per year among ~10 million patients at risk. o Death rates appear to be increasing in inner-city areas where there is limited availability of health care. o Only 0.090.25% of admissions to hospital are at risk of an untoward event. o Major risk factors for asthma deaths Poorly controlled disease with frequent use of bronchodilator inhalers Lack of corticosteroid therapy Previous admission to the hospital with nearfatal asthma Particularly good prognosis for those whose disease is mild and develops in childhood

Prognosis

The proportion of children who still have asthma 7 10 years after the initial diagnosis varies from 2678% (average, 46%). o Only 619% continue to have severe disease. Cigarette smoking and asthma o More severe disease o More frequent hospitalizations o Faster decline in lung function o Higher risk of death from asthma Even when untreated, persons with asthma do not continuously move from mild to severe disease with time. o Clinical course is characterized by exacerbations and remissions. o Some studies suggest:
o

Spontaneous remissions occur in approximately 20% of those who develop the disease as adults. ~40% can be expected to experience improvement, with less frequent and severe attacks, as they grow older.

Prevention

ICD-9-CM

There is no known primary prevention for asthma. In patients with known disease o Asthma triggers, including tobacco smoke and other precipitants (see Etiology), should be avoided or controlled. o Plans should be made for both long-term management and treatment of exacerbations. o Regular follow-up care is mandatory.

493.__ Asthma, (type of asthma specified with fourth digit, degree of severity specified with fifth digit) 493.90 Asthma, unspecified (type of asthma), unspecified (degree of severity)

See Also

Allergic Rhinitis Anaphylaxis Chronic Obstructive Lung Disease Pulmonary Function Tests Professionals o Information for professionals American Academy of Allergy Asthma & Immunology o Clinical Trials ClinicalTrials.gov

Internet Sites

Patients o Asthma MedlinePlus o Homepage Asthma and Allergy Foundation of America

References
1. Beuther DA, Sutherland ER: Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med 175:661, 2007 [PMID:17234901]

General Bibliography
Arshad SH: Primary prevention of asthma and allergy. J Allergy Clin Immunol 116:3, 2005 [PMID:15990764] Cabana MD, Le TT: Challenges in asthma patient education. J Allergy Clin Immunol 115:1225, 2005 [PMID:15940138] Currie GP et al: Recent developments in asthma management. BMJ330:585, 2005 [PMID:15761000] Dolovich MB et al: Device selection and outcomes of aerosol therapy: Evidence-based guidelines: American College of Chest Physicians/American College of Asthma, Allergy, and Immunology. Chest 127:335, 2005 [PMID:15654001] Hall JB: Concise review: Contemporary management of status asthmaticus. New York: McGrawHill, www.harrisonsonline.com Heaney LG, Robinson DS: Severe asthma treatment: need for characterising patients. Lancet 365:974, 2005 Mar 12-18 [PMID:15767000] Szczeklik A, Stevenson DD: Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol111:913, 2003 [PMID:12743549] Tarlo SM, Liss GM: Occupational asthma: an approach to diagnosis and management. CMAJ 168:867, 2003 [PMID:12668547] Togias A: Rhinitis and asthma: evidence for respiratory system integration.J Allergy Clin Immunol 111:1171, 2003 [PMID:12789212] This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 248, Asthma by PJ Barnes.