Asthma

 

 

INTRODUCTION

Background: Asthma or hyperreactive airway disease is a very common clinical syndrome and is the most common cause of hospitalization for children in the United States. Despite recent advances in understanding the pathophysiology and treatment of asthma, it continues to have significant medical and economic impacts worldwide. In 1991, the National Asthma Education and Prevention Program Expert Panel from the US National Institutes of Health (NIH) issued its first report on the guidelines for the diagnosis and management of asthma. They defined asthma in the following manner:

 

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial responsiveness to a variety of stimuli.

The Expert Panel Report 2 was issued in 1997 and further refined effective asthma management based on the following 4 components: objective measures of lung function, environmental control measures, comprehensive pharmacologic therapy, and patient education.

Exercise-induced asthma (EIA) or exercise-induced bronchospasm is an asthma variant defined as a condition in which exercise or vigorous physical activity triggers acute bronchospasm in persons with heightened airway reactivity. It is observed primarily in persons who are asthmatic but can also be found in patients with atopy, allergic rhinitis, cystic fibrosis, and even in healthy persons. EIA is often a neglected diagnosis, and the underlying asthma may be silent in as many as 50% of patients, except with exercise.

 

Pathophysiology: The pathophysiology of asthma is complex and involves 3 components: airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present.

Some of the principal cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines. Other constituent airway cells, such as fibroblasts, endothelial cells, and epithelial cells, contribute to the chronicity of the disease. Other factors, such as adhesion molecules (eg, selectins, integrins), are critical in directing the inflammatory changes in the airway. Finally, cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway.

Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. The extent of reversibility of airway obstruction is based on structural changes in the airway due to long-standing inflammation. One feature of asthma is the exaggerated response to numerous stimuli. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

The pathogenesis of EIA is controversial. The disease is believed to be mediated by water loss from the airway, heat loss from the airway, or a combination of both. The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C. The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. Results from bronchoalveolar lavage studies have not demonstrated an increase in inflammatory mediators. These patients generally develop a refractory period, during which a second exercise challenge does not cause a significant degree of bronchoconstriction.

 

Frequency:

  • In the US: Asthma affects 5-10% of the population or an estimated 14-15 million persons, including 5 million children. The prevalence rate of EIA is 3-10% of the general population if persons who do not have asthma or allergy are excluded, but the rate increases to 12-15% of the general population if patients with asthma are included. The rate of exercise-induced symptoms in persons with asthma has been reported to vary from 40-90%.
  • Internationally: Asthma is common in industrialized nations such as Canada, England, Australia, Germany, and New Zealand, where much of the data have been collected. Recent trends suggest an increase in both the prevalence and morbidity of the disease, especially in children younger than 6 years. Factors that have been implicated include urbanization, air pollution, passive smoking, and change in exposure to environmental allergens.

Mortality/Morbidity:

  • The estimate of lost work and school time is approximately 100 million days of restricted activity. More than 1.8 million emergency department evaluations occur annually. The latest figures from the 1997 NIH report an estimated 500,000 hospitalizations and 5000 deaths annually. Mortality is primarily related to lung function, with an 8-fold increase in patients in the lowest quartile. Other factors that impact mortality include age older than 40 years, cigarette smoking greater than 20-pack years, blood eosinophilia, forced expiratory volume in one second (FEV1) of 40-69% predicted, and greater reversibility.
  • EIA has not been reported to cause death. Morbidity is associated with exercise limitation. This is observed most dramatically in elite athletes with high levels of exercise who may be limited by airway hyperreactivity.

Race:

  • Asthma occurs in persons of all races worldwide.
  • Although genetic factors are of major importance in determining a predisposition to the development of asthma, environmental factors play a greater role than racial factors in the onset of disease.

Sex:

  • Asthma predominantly occurs in boys in childhood, with a male-to-female ratio of 2:1 until puberty, when the male-to-female ratio becomes 1:1.
  • Asthma incidence is greater in females after puberty, and the majority of adult-onset cases diagnosed in persons older than 40 years occur in females.
  • Boys are more likely than girls to experience a decrease in symptoms by late adolescence.

Age:

  • Asthma incidence is increased in very young persons and very old persons because of airway responsiveness and lower levels of lung function. Two thirds of all asthma cases are diagnosed before the patient is aged 18 years. Approximately half of all children diagnosed with asthma have a decrease or disappearance of symptoms by early adulthood.
  • The diagnosis of EIA is made more often in children and young adults than in older adults and is related to high levels of physical activity. It can be observed in persons of any age based on the level of underlying airway reactivity and the level of physical exertion.

CLINICAL

History:

  • A detailed medical history should address the following factors:
    • Whether symptoms are attributable to asthma

       

    • Whether findings support the likelihood of asthma (eg, family history)

       

    • Asthma severity

       

    • Identification of possible precipitating factors
  • Symptoms
    • Cough

       

    • Wheezing

       

    • Shortness of breath

       

    • Chest tightness

       

    • Sputum production
  • Patterns of symptoms
    • Perennial versus seasonal

       

    • Continual versus episodic

       

    • Duration, severity, and frequency

       

    • Diurnal variations (nocturnal and early-morning awakenings)
  • Precipitating/aggravating factors 
    • Allergens

       

    • Occupation

       

    • Medications
  • Disease development
    • Age of onset

       

    • History of injury early in life due to infection or passive smoke exposure

       

    • Progress of disease

       

    • Current response to management

       

    • Comorbid conditions
  • Family history
    • Asthma

       

    • Allergy

       

    • Sinusitis

       

    • Rhinitis
  • Social history
    • Home characteristics

       

    • Smoking

       

    • Workplace or school characteristics

       

    • Educational level

       

    • Employment

       

    • Social support
  • Profile of typical exacerbation

     

  • Impact on patient and family
    • Emergency department visits, hospitalizations, intensive care unit (ICU) admissions, intubations

       

    • Missed days from work or school or activity limitation
  • Assessment of disease perception
    • Knowledge of asthma and treatment

       

    • Use of medications

       

    • Coping mechanisms

       

    • Family support

       

    • Economic resources
  • The clinical history for EIA is typical of asthma, with symptoms such as cough, wheezing, shortness of breath, and chest pain or tightness. Some individuals may also complain of sore throat or GI upset.
    • Symptoms are usually associated with exercise but may be related to exposure to cold air or other triggers, such as seasonal allergens, pollutants (eg, sulfur, nitrous oxide, ozone), or upper respiratory infections.

       

    • Initially, airway dilation is noted during exercise. If exercise extends beyond approximately 10 minutes, bronchoconstriction supervenes, resulting in asthma symptoms. If the exercise period is shorter, symptoms may develop up to 5-10 minutes after completion of exercise. A higher intensity level of exercise results in a more intense attack. Running produces more symptoms than walking.

       

    • Patients may note symptoms are related to seasonal changes or the ambient temperature and humidity in the environment in which a patient exercises. Cold dry air generally provokes more obstruction than warm humid air. Consequently, many athletes have good exercise tolerance in sports such as swimming. Athletes who are more physically fit may not notice the typical symptoms and may only complain of a reduced or more limited level of endurance.

       

    • Several modifiers in the history should prompt an evaluation for causes other than EIA. While patients may complain of typical obstructive symptoms, a history of a choking sensation with exercise, inspiratory wheezing, or stridor should prompt an evaluation for evidence of vocal cord dysfunction.

Physical:

  • General
    • Evidence of respiratory distress manifests as increased respiratory and cardiac rates, diaphoresis, and use of accessory muscles of respiration.
    • Marked weight loss or severe wasting may indicate severe emphysema.
  • Pulsus paradoxus: This is an exaggerated fall in systolic blood pressure during inspiration and may occur during an acute asthma exacerbation.
  • Depressed sensorium: This finding suggests a more severe asthma exacerbation with impending respiratory failure.
  • Chest examination
    • End-expiratory wheezing or a prolonged expiratory phase is found most commonly, although inspiratory wheezing can be heard.
    • Diminished breath sounds and chest hyperinflation may be observed during acute exacerbations.
    • The presence of inspiratory wheezing or stridor may prompt evaluation for an upper airway obstruction such as vocal cord dysfunction, vocal cord paralysis, thyroid enlargement, or soft tissue mass (eg, malignant tumor).
  • Upper airway
    • Look for evidence of erythematous or boggy turbinates or the presence of polyps from sinusitis, allergic rhinitis, or upper respiratory infection.
    • Any type of nasal obstruction may result in worsening of asthma or symptoms of EIA.
  • Skin: Observe for presence of atopic dermatitis/eczema or other manifestations of allergic skin conditions.

Causes:

  • Factors that can contribute to asthma or hyperreactive airway disease may include any of the following:
    • Environmental allergens
    • Viral respiratory infections
    • Exercise
    • Gastroesophageal reflux disease
    • Chronic sinusitis or rhinitis
    • Aspirin or nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity, sulfite sensitivity
    • Use of beta-adrenergic receptor blockers (including ophthalmic preparations)
    • Environmental pollutants, tobacco smoke
    • Occupational exposure
    • Emotional factors
  • Factors that contribute to EIA symptoms include the following:
    • Exposure to cold or dry air
    • Environmental pollutants (eg, sulfur, ozone)
    • Level of bronchial hyperreactivity
    • Chronicity of asthma and symptomatic control
    • Duration and intensity of exercise
    • Allergen exposure in atopic individuals
    • Coexisting respiratory infection

DIFFERENTIAL

Allergic and Environmental Asthma
Alpha1-Antitrypsin Deficiency
Chronic Obstructive Pulmonary Disease
Churg-Strauss Syndrome
Gastroesophageal Reflux Disease
Sarcoidosis
Vocal Cord Dysfunction


Other Problems to be Considered:

Allergic bronchopulmonary aspergillosis (ABPA)
Aspirin hypersensitivity
Viral respiratory infections
Occupational asthma
Congestive heart failure (cardiac asthma)
Other causes of upper airway obstruction


WORKUP

Lab Studies:

  • Laboratory studies are not routinely indicated for asthma but may be used to exclude other diagnoses.
  • Eosinophilia greater than 4% or 300-400/mm3 supports the diagnosis of asthma, but an absence of this finding is not exclusionary. Eosinophil counts greater than 8% may be observed in patients with concomitant atopic dermatitis, but this finding should prompt an evaluation for ABPA, Churg-Strauss syndrome, or eosinophilic pneumonia.
  • Total serum immunoglobulin E (IgE) levels greater than 100 IU are frequently observed in patients experiencing allergic reactions, but this finding is not specific for asthma and may be observed in patients with other conditions (eg, ABPA, Churg-Strauss syndrome). A normal total serum IgE level does not exclude the diagnosis of asthma.

Imaging Studies:

  • In most patients, chest radiography findings are normal or indicate hyperinflation. Findings may help rule out other pulmonary diseases such as ABPA or sarcoidosis, which can manifest with symptoms of reactive airway disease.
  • Sinus CT scan may be useful to help exclude acute or chronic sinusitis as a contributing factor. In patients with chronic sinus symptoms, a CT scan of the sinuses can also help rule out chronic sinus disease.

Other Tests:

  • Allergy skin testing is a useful adjunct in individuals with atopy. Results help guide indoor allergen mitigation or diagnose allergic rhinitis symptoms.
  • In patients with reflux symptoms and asthma, 24-hour pH monitoring can help determine if gastroesophageal reflux disease is a contributing factor.

Procedures:

  • Pulmonary function testing (spirometry)
    • Perform spirometry measurements before and after inhalation of a short-acting bronchodilator in all patients in whom the diagnosis of asthma is considered. Spirometry measures the forced vital capacity (FVC), the maximal amount of air expired from the point of maximal inhalation, and the FEV1. A reduced ratio of FEV1 to FVC, when compared to predicted values, demonstrates the presence of airway obstruction. Reversibility is demonstrated by an increase of 12% or 200 mL after administration of a short-acting bronchodilator.
    • The diagnosis of asthma cannot be based on spirometry findings alone because many other diseases are associated with obstructive spirometry indices.
    • As a preliminary evaluation for EIA, perform spirometry in all patients with exercise symptoms to determine if any baseline abnormalities (the presence of obstructive or restrictive indices) are present.
  • Methacholine or histamine challenge testing
    • Bronchoprovocation testing with either methacholine or histamine is useful when spirometry findings are normal or near normal, especially in patients with intermittent symptoms or exercise-induced symptoms. Bronchoprovocation testing helps determine if hyperreactive airways are present, and a negative test result usually excludes the diagnosis of asthma.
    • Trained individuals should perform this testing in an appropriate facility and in accordance with the guidelines of the American Thoracic Society published in 1999. Methacholine is administered in incremental doses up to a maximum dose of 16 mg/mL, and a 20% decrease in FEV1 is considered a positive test result for the presence of bronchial hyperresponsiveness. The presence of airflow obstruction with an FEV1 less than 65-70% at baseline is generally an indication to not perform the test.
  • Exercise testing
    • Exercise spirometry is the standard method for evaluating patients with EIA. Testing involves 6-10 minutes of strenuous exertion at 85-90% of predicted maximal heart rate and measurement of postexercise spirometry for 15-30 minutes. The defined cutoff for a positive test result is a 15% decrease in FEV1 postexercise.
    • Exercise testing may be accomplished in 3 different ways, using cycle ergometry, a standard treadmill test, or free running exercise. This method of testing is limited because laboratory conditions may not subject the patient to the usual conditions that trigger EIA symptoms, and results have a lower sensitivity compared to other methods.
  • Eucapnic hyperventilation
    • Eucapnic hyperventilation with either cold or dry air is an alternate method of bronchoprovocation testing.
    • It has been used to evaluate patients for EIA and has been shown to produce results similar to those of methacholine challenge testing.
  • Peak-flow monitoring
    • Peak-flow monitoring is designed for ongoing monitoring of patients with asthma because the test is simple to perform and results are a quantitative and reproducible measure of airflow obstruction.
    • It can be used for short-term monitoring, managing exacerbations, and daily long-term monitoring.
    • Results can be used to determine the severity of an exacerbation and to help guide therapeutic decisions.
    • Guidelines for the use of peak-flow meters are as follows:

       

      • Advise the patient to use the peak-flow meter upon awakening in the morning before using a bronchodilator.

         

      • Instruct the patient on how to establish a personal best peak expiratory flow (PEF).

         

      • Inform the patient that a peak flow of less than 80% of patient's personal best indicates a need for additional medication and a peak flow below 50% indicates severe exacerbation.

         

      • Advise the patient to use the same peak-flow meter over time.

TREATMENT

Medical Care: The long-term outpatient management of asthma should follow the stepwise therapy model based on the Global Initiative for Asthma guidelines. These recommendations were updated during the 1997 National Asthma Education and Prevention Program, the results of which were published by the NIH. Management should incorporate 4 treatment components: (1) objective measures of lung function, (2) environmental control measures, (3) comprehensive pharmacologic therapy, and (4) patient education. Classify the severity of asthma before treatment, based on symptom prevalence and measurement of lung function. Classification of severity and treatment options are shown below.

  • Step 1 - Intermittent
    • Intermittent symptoms occurring less than once a week

       

    • Brief exacerbations

       

    • Nocturnal symptoms occurring less than twice a month

       

    • Asymptomatic with normal lung function between exacerbations

       

    • No daily medication needed
    • FEV1 or PEF rate greater than 80%, with less than 20% variability
  • Step 2 - Mild persistent
    • Symptoms occurring more than once a week but less than once a day

       

    • Exacerbations affect activity and sleep

       

    • Nocturnal symptoms occurring more than twice a month

       

    • Either inhaled steroid (low dose) or cromolyn (adult: 2-4 puffs tid/qid; child: 1-2 puffs tid/qid) or nedocromil (adult: 2-4 puffs bid/qid; child: 1-2 puffs bid/qid); children usually begin with a trial of cromolyn or nedocromil
    • FEV1 or PEF rate greater than 80% predicted, with variability of 20-30%
  • Step 3 - Moderate persistent

     

    • Daily symptoms

       

    • Exacerbations affect activity and sleep

       

    • Nocturnal symptoms occurring more than once a week

       

    • Either anti-inflammatory; inhaled steroid (medium dose) or inhaled steroid (low-to-medium dose) and long-acting bronchodilator, especially for nighttimesymptoms (either long-acting inhaled beta2-agonist, adult: 2 puffs q12h, child: 1-2 puffs q12h, sustained-release theophylline, or long-acting beta2-agonist tablets); if needed, give inhaled steroids (medium-to-high dose)
    • FEV1 or PEF rate 60-80% of predicted, with variability greater than 30%
  • Step 4 - Severe persistent

     

    • Continuous symptoms

       

    • Frequent exacerbations

       

    • Frequent nocturnal asthma symptoms

       

    • Physical activities limited by asthma symptoms

       

    • Anti-inflammatory, inhaled steroid (high dose) and long-acting bronchodilator (either long-acting inhaled beta2-agonist, adult: 2 puffs q12h, child: 1-2 puffs q12h and sustained-release theophylline, or long-acting beta2-agonist tablets and steroid tablets or syrup long term); make repeated attempts to reduce systemic steroid and maintain control with high-dose inhaled steroid
    • FEV1 or PEF rate less than 60%, with variability greater than 30%

Consultations:

  • Refer any patient with difficulty controlling asthma to a pulmonologist or allergist to ensure proper stepwise management of asthma or for further evaluation to help rule out other diagnoses such as vocal cord dysfunction.
  • Refer patients to a pulmonologist for evaluation of symptoms consistent with EIA. These patients should undergo either exercise or bronchoprovocation testing to document evidence of airway hyperreactivity and response to exercise.
  • Refer patients to an otolaryngologist for treatment of nasal obstruction due to polyps, sinusitis, and allergic rhinitis or for diagnosis of upper airway disorders.
  • Refer patients to allergist or immunologist for skin testing to guide indoor allergen mitigation efforts and consideration of immunotherapy to treat seasonal allergic rhinitis. The use of immunotherapy for the treatment of asthma is controversial.

Diet:

  • No special diets are indicated.

Activity:

  • Activity is generally limited by the patients' ability to exercise and their response to medications. No specific limitations are recommended to patients with asthma, although they should avoid exposure to agents that may exacerbate their disease.
  • A significant number of patients with asthma also have EIA, and baseline control of their disease should be adequate to prevent exertional symptoms. The ability of patients with EIA to exercise is based on the level of exertion, degree of fitness, and the environment in which they exercise.
  • Many patients have fewer problems when exercising indoors or in a warm humid environment compared to outdoors or in a cold dry environment.

MEDICATIONS

Medications used for asthma are generally divided into 2 categories, quick relief (also called reliever medications) and long-term control (also called controller medications). Quick relief medications are used for the relief of acute asthma exacerbations and to prevent EIA symptoms. These medications include short-acting beta-agonists, anticholinergics (used for severe exacerbations), and systemic corticosteroids, which speed recovery from acute exacerbations. Long-term control medications include inhaled corticosteroids, cromolyn sodium, nedocromil, long-acting beta-agonists, methylxanthines, and leukotriene antagonists. Use of these medications by the stepwise approach is outlined in Medical Care

Other medications that have been used to reduce oral systemic corticosteroid dependence include cyclosporine, methotrexate, gold, intravenous immunoglobulin, dapsone, troleandomycin, and hydroxychloroquine. Their use in patients with asthma is extremely limited because of variable responses, adverse effects, and limited experience. Only an asthma specialist should administer these medications.

Omalizumab (Xolair) is a recombinant DNA-derived humanized IgG monoclonal antibody that binds selectively to human IgE on the surface of mast cells and basophils. The drug reduces mediator release, which promotes allergic response. Indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens, in whom symptoms are not controlled by inhaled corticosteroids. The dose (adults and children >12 y) is 150-375 mg SC q2-4wk (precise dose and frequency is established by serum IgE levels). The estimated annual cost is $12,000-15,000.

Drug Category: Bronchodilators -- Provide symptomatic relief of bronchospasm due to acute asthma exacerbation (short-acting agents) or long-term control of symptoms (long-acting agents). Also used as the primary medication for prophylaxis of EIA. A metered-dose inhaler (MDI) can be used for administration.
Drug Name
 Albuterol (Ventolin, Proventil) -- Beta-agonist for bronchospasm. Relaxes bronchial smooth muscle by action on beta-2 receptors, with little effect on cardiac muscle contractility.
Adult Dose PO: 2-4 mg/dose divided tid/qid; not to exceed 32 mg/d
MDI: 1-2 puffs q4-6h; not to exceed 12 puffs/d; may use 2-4 puffs q20min for 3 doses to treat an acute exacerbation; a tube spacer is recommended unless the patient can demonstrate excellent technique without it
Nebulizer: Dilute 0.5 mL (2.5 mg) 0.5% inhalation solution in 1-2.5 mL of NS; administer 2.5-5 mg q4-6h, diluted in 2-5 mL sterile saline or water
Pediatric Dose PO
2-5 years: 0.1-0.2 mg/kg/dose divided tid; not to exceed 12 mg/d
5-12 years: 2 mg/dose divided tid/qid; not to exceed 24 mg/d
>12 years: Administer as in adults
MDI
<12 years: 1-2 puffs qid with tube spacer
>12 years: Administer as in adults
Nebulizer
<5 years: Dilute 0.25-0.5 mL (1.25-2.5 mg) 0.5% inhalation solution in 1-2.5 mL of NS and administer q4-6h in divided doses
>5 years: Administer as in adults
Contraindications Documented hypersensitivity
Interactions Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; 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
Drug Name
 Metaproterenol (Alupent, Metaprel) -- Beta-2 adrenergic agonist that relaxes bronchial smooth muscle with little effect on heart rate.
Adult Dose MDI: 2 puffs q4-6h prn
Nebulizer: 0.3 mL 5% solution diluted in 2.5 mL 0.45% or 0.9% NS, nebulized over 5-15 min q4h
Pediatric Dose MDI
Not recommended
PO
6-9 years or <60 lb: 10 mg tid/qid
>9 years or >60 lb: Administer as in adults
Nebulizer
<12 years: Not recommended
>12 years: 0.1-0.2 mL 5% solution diluted in 3 mL 0.45% or 0.9% NS over 5-15 min q4h
Contraindications Documented hypersensitivity; arrhythmia associated with tachycardia
Interactions Decreases effect of beta-receptor blockers; increases toxicity of MAOIs, TCAs, and sympathomimetics
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in hypertension, cardiovascular disease, CHF, hyperthyroidism, diabetes, and seizures; not recommended during breastfeeding; adverse reactions include tachycardia, headache, nervousness, dizziness, tremor, GI upset, hypertension, paradoxical bronchospasm, and cough
Drug Name
 Salmeterol (Serevent) -- Can relieve bronchospasms by relaxing the smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis. Effect also may facilitate expectoration.
Adverse effects are more likely to occur when administered at high or more frequent doses than recommended; incidence of adverse effects is higher. Regular use in patients with EIA associated with smaller decrease in FEV1 during exercise.
Adult Dose MDI: 2 puffs (42 mcg) bid
Diskus: 1 puff (50 mcg) bid
Pediatric Dose 4-12 years: 1 puff (50 mcg) q12h
>12 years: Administer as in adults
Contraindications Documented hypersensitivity; angina, tachycardia, and cardiac arrhythmias 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 resulting from diuretics may worsen when coadministered
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Not indicated to treat acute asthmatic symptoms
Drug Name
 Ipratropium (Atrovent) -- Decreases vagal tone in the airways through antagonism of muscarinic receptors and inhibition of vagally mediated reflexes. Chemically related to atropine. Has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Only 50% of patients who are asthmatic bronchodilate with ipratropium and, to a lesser degree, with beta-adrenergic agonists. Used primarily in conjunction with beta-agonists for severe exacerbations. No additive or synergistic effects observed with long-term treatment of asthma.
Adult Dose Nebulizer: 1-dose vial (500 mcg) q2h for acute exacerbations
MDI: 2 puffs qid; not to exceed 12 puffs/d
Pediatric Dose Nebulizer: 250 mcg tid
MDI: 1-2 puffs tid; not to exceed 6 puffs/d
Contraindications Documented hypersensitivity
Interactions Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol increases 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; eye pain or blurred vision may occur if sprayed in eyes
Drug Name
 Theophylline (Slo-bid, Theo-Dur, Uniphyl) -- Mild-to-moderate bronchodilator used as an adjuvant in the treatment of stable asthma and prevention of nocturnal asthma symptoms. Potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation.
Adult Dose 5-8 mg/kg/d initially to maintain concentration in the range of 5-15 mcg/mL; 5.6 mg/kg loading dose (based on aminophylline) IV over 20 min, followed by maintenance infusion of 0.1-1.1 mg/kg/h
Pediatric Dose 6 weeks to 6 months: 0.5 mg/kg/h loading dose IV in first 12 h (based on aminophylline), followed by maintenance infusion of 12 mg/kg/d thereafter; may administer continuous infusion by dividing total daily dose by 24 h
6 months to 1 year: 0.6-0.7 mg/kg/h, loading dose IV in first 12 h, followed by maintenance infusion of 15 mg/kg/d; may administer as continuous infusion, as above
>1 year: Administer as in adults
Contraindications Documented hypersensitivity; uncontrolled arrhythmias, peptic ulcers, hyperthyroidism, and 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, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution >25 mg/min; patients with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance; signs of toxicity include nausea, vomiting, tremors, nervousness, ventricular arrhythmias, and seizures
Drug Category: Leukotriene receptor antagonists -- Direct antagonist of mediators responsible for airway inflammation in asthma. Used for prophylaxis of EIA and long-term treatment of asthma as alternative to low doses of inhaled corticosteroids.
Drug Name
 Montelukast (Singulair) -- Selective and competitive receptor antagonist of leukotriene D4 and E4, components of slow-reacting substance of anaphylaxis.
Indicated for treatment of stable, mild, persistent asthma or prophylaxis for EIA.
Adult Dose 10 mg PO qhs
Pediatric Dose <6 years: Not established
6-14 years: 5 mg PO qd
>14 years: Administer as in adults
Contraindications Documented hypersensitivity
Interactions None reported
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Not indicated for treatment of acute asthma exacerbations; systemic eosinophilia and vasculitis consistent with Churg-Strauss syndrome rarely reported
Drug Name
 Zafirlukast (Accolate) -- Selective and competitive receptor antagonist of leukotriene D4 and E4, components of slow-reacting substance of anaphylaxis. Indicated for treatment of stable, mild, persistent asthma or prophylaxis for EIA.
Adult Dose 20 mg PO bid; must be taken 30 min prior to breakfast and supper
Pediatric Dose <12 years: Not established
>12 years: Administer as in adults
Contraindications Documented hypersensitivity
Interactions Increases half-life of warfarin; erythromycin and theophylline decrease serum levels
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Elevations of liver enzymes occur rarely, but routine LFT monitoring not required; systemic eosinophilia and vasculitis consistent with Churg-Strauss syndrome also rarely reported; not indicated for treatment of acute asthma exacerbations
Drug Category: Corticosteroids -- Highly potent agents that are the primary DOC for treatment of chronic asthma and prevention of acute asthma exacerbations. Numerous inhaled corticosteroids are used for asthma and include beclomethasone (Beclovent, Vanceril), budesonide (Pulmicort Turbuhaler), flunisolide (AeroBid), fluticasone (Flovent), and triamcinolone (Azmacort).
Drug Name
 Fluticasone (Flovent) -- Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.
Adult Dose 44-mcg MDI: 2 puffs bid for mild persistent asthma
110- to 220-mcg MDI: 2 puffs bid for moderate-to-severe persistent asthma
Pediatric Dose 44-mcg MDI: 2 puffs bid
Contraindications Documented hypersensitivity; viral, fungal, and bacterial skin infections
Interactions None reported
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Not indicated to treat acute asthma exacerbation or status asthmaticus; prolonged use may increase systemic absorption and may cause Cushing syndrome, reversible HPA axis suppression, hyperglycemia, and glycosuria; localized infections of the pharynx due to Candida albicans (5%) may occur; rare presentation of systemic eosinophilic conditions consistent with Churg-Strauss syndrome reported
Drug Name
 Triamcinolone (Azmacort) -- Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.
Adult Dose 2 puffs tid/qid or 4 puffs bid; not to exceed 4 puffs qid for mild persistent or easily controlled moderately severe asthma
Pediatric Dose 6-12 years: 1-2 puffs tid/qid or 2-4 puffs bid; not to exceed 3 puffs qid
Contraindications Documented hypersensitivity; fungal, viral, and bacterial skin infections
Interactions Coadministration with barbiturates, phenytoin, and rifampin decreases effects
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Not indicated to treat acute asthma exacerbation or status asthmaticus; symptoms of adrenal insufficiency due to suppression of HPA axis may occur when being withdrawn from systemically active corticosteroids; small number of patients may develop hypercortisolism and adrenal suppression; localized infections of the pharynx due to Candida albicans (5%) reported
Drug Name
 Beclomethasone (Vanceril, Beclovent, QVAR) -- Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.
Adult Dose 2 puffs (84 mcg) tid/qid; alternatively, 4 puffs (168 mcg) bid
Severe asthma: 12-16 puffs (504-672 mcg)/d; adjust dose downward to response; not to exceed 20 puffs (840 mcg)/d
QVAR: 80 and 160 mcg/puff
Pediatric Dose <6 years: Not established
6-12 years: 1-2 puffs (42-84 mcg) tid/qid to response; alternatively, 4 puffs (168 mcg) bid; not to exceed 10 puffs (420 mcg)/d
Contraindications Documented hypersensitivity; bronchospasm, status asthmaticus, and 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 Symptoms of adrenal insufficiency due to suppression of the HPA axis may occur when being withdrawn from systemically active corticosteroids; small number of patients may develop hypercortisolism and adrenal suppression (weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur); localized infections of the pharynx due to Candida albicans (5%) reported
Drug Name
 Prednisone (Deltasone, Orasone, Meticorten) -- Systemic steroidal anti-inflammatory medication. Used primarily for moderate-to-severe asthma exacerbations to speed recovery and prevent late-phase response. May be used long-term to control severe asthma.
Adult Dose 5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric Dose 1-2 mg/kg PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Contraindications Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and 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 B - Usually safe but benefits must outweigh the risks.
Precautions Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use
Drug Name
 Budesonide (Pulmicort Turbuhaler, Rhinocort) -- 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 200-400 mcg via PO inhalation twice initially; may increase to 800 mcg bid
Pediatric Dose 200 mcg via PO inhalation twice initially; may increase to 400 mcg bid
Contraindications Documented hypersensitivity; bronchospasm, status asthmaticus, and other types of acute episodes of asthma
Interactions Coadministration with ketoconazole may increase plasma levels but does not appear to be clinically significant
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Coughing, upper respiratory tract infection, and bronchitis may occur
Drug Category: Mast cell stabilizers -- Prevent the release of mediators from mast cells, which results in airway inflammation and bronchospasm. Indicated for maintenance therapy of mild-to-moderate asthma or prophylaxis for EIA.
Drug Name
 Cromolyn (Intal) -- Inhibits degranulation of sensitized mast cells following exposure to specific antigens. Attenuates bronchospasm caused by exercise, cold air, aspirin, and environmental pollutants.
Adult Dose Chronic asthma: 2 puffs qid
EIA: 2 puffs 15-60 min prior to exercise or exposure
Pediatric Dose <12 years: Not established
>12 years: Administer as in adults
Contraindications Documented hypersensitivity; severe renal or hepatic impairment
Interactions None reported
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Do not use in patients with severe renal or hepatic impairment; caution when withdrawing because symptoms may recur
Drug Name
 Nedocromil (Tilade) -- Inhibits activation and release of mediators of variety of inflammatory cell types associated with asthma, to include eosinophils, mast cells, neutrophils, and others.
Adult Dose 2 puffs qid (14 mg/d)
Pediatric Dose <6 years: Not established
>6 years: Administer as in adults
Contraindications Documented hypersensitivity
Interactions None reported
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Must be used on regular basis to achieve therapeutic benefit; not indicated to treat acute bronchospasm
Drug Category: 5-Lipoxygenase inhibitors -- Inhibit the formation of leukotrienes. Leukotrienes activate receptors that may be responsible for events leading to the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with inflammatory reactions.
Drug Name
 Zileuton (Zyflo) -- Inhibits leukotriene formation, which, in turn, decreases neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, capillary permeability, and smooth muscle contractions.
Adult Dose 600 mg PO pc and hs
Pediatric Dose Not established
Contraindications Documented hypersensitivity; active liver disease or transaminase elevation greater than or equal to 3 times upper limit of normal
Interactions Increases toxicity of propranolol, warfarin, and theophylline
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Caution in liver disease; elevation of liver function test findings may occur; not indicated for reversal of acute asthma attacks

FOLLOW-UP

Further Inpatient Care:

  • The initial assessment of acute asthma exacerbations should focus on several key areas.
    • Perform a functional assessment of airway obstruction with measurement of FEV1 or PEF initially and to assess the patient’s response to treatment.

       

    • Assess the adequacy of arterial oxygen saturation in patients with severe distress.

       

    • Obtain a brief history, to include symptoms, onset of exacerbation, medications, prior emergency department visits, and hospitalizations (including intubations).
    • Perform a physical examination to assess the severity of exacerbation, overall patient status, presence of other diseases or complications, and to rule out upper airway obstruction.
    • Laboratory studies should be considered based on the status of the patient. These and other studies may include arterial blood gas measurement, complete blood cell count, serum theophylline level (if indicated), chest radiograph to assess for complications, and electrocardiograms in patients older than 50 years.
  • Once the initial assessment is completed, base treatment on the severity of exacerbation.
    • Supplemental oxygen should be used in most patients to maintain saturations greater than 90%.
    • Inhaled short-acting beta-agonists are the initial treatment.

       

      • Repetitive or continuous administration

         

      • In the emergency department, 3 treatments every 20-30 minutes as initial therapy

         

      • High-dose (6-12 puffs) beta-agonist by MDI or nebulizer therapy (Nebulizer is most effective with more severe exacerbations.)
    • Consider inhaled ipratropium bromide in patients with severe exacerbations.

       

    • Administer systemic corticosteroids early in the course of disease in patients with an incomplete response to beta-agonists. Oral administration is equivalent in efficacy to intravenous administration. Steroids speed resolution of airway obstruction and prevent a late-phase response.

       

    • Methylxanthines (theophylline) can be considered in patients with severe exacerbations, but their use is controversial.

       

    • Antibiotics should be reserved for patients with fever and purulent sputum or other evidence of pneumonia or sinusitis.

       

    • Aggressive hydration is not recommended for adults.

       

    • Chest physiotherapy, mucolytics, and sedation are not recommended.
  • Indications for hospitalization are based on findings from the repeat assessment of a patient after the patient receives 3 doses of an inhaled bronchodilator. Base the decision on the (1) duration and severity of symptoms, (2) severity of airflow obstruction, (3) course and severity of prior exacerbations, (4) medication use and access to medications, (5) adequacy of support and home conditions, and (6) presence of psychiatric illness.

     

  • In certain situations, admit the patient to the ICU for close observation and monitoring.
    • Rapidly worsening asthma or lack of response to initial therapy in the emergency department is an indication for ICU admission.

       

    • If patients have confusion, drowsiness, signs of impeding respiratory arrest, or loss of consciousness, they should be admitted to the ICU.

       

    • Impending respiratory arrest, as indicated by hypoxemia (PO2 <60 mm Hg) despite supplemental oxygen and/or hypercarbia with PCO2 greater than 45 mm Hg, should prompt ICU admission.

       

    • If intubation is required because of continued deterioration of the patient’s condition despite optimal treatment, admit the patient to the ICU.

Further Outpatient Care:

  • For all patients with asthma, monitoring should be performed on a continual basis based on the following parameters, which helps in the overall management of the disease:
    • Monitoring signs and symptoms of asthma: Patients should be taught to recognize inadequate asthma control, and providers should assess control at each visit.
    • Monitoring pulmonary function: Perform spirometry and peak-flow monitoring regularly.
    • Monitoring quality of life and functional status: Inquire about missed work or school days, reduction in activities, sleep disturbances, or change in caregiver activities.
    • Monitoring history of asthma exacerbations: Determine if patients are monitoring themselves to detect exacerbations and if these exacerbations are self-treated or treated by health care providers.
    • Monitoring pharmacotherapy: Ensure compliance with medications and usage of short-acting beta-agonists.
    • Monitoring patient-provider communication and patient satisfaction

In/Out Patient Meds:

  • The pharmacologic treatment of asthma is based on stepwise therapy. Medications should be added or deleted as the frequency and severity of the patient's symptoms change.

     

  • Step 1: Intermittent asthma is present.
    • A controller medication is not needed.

       

    • The reliever medication is a short-acting beta-agonist as needed for symptoms.
  • Step 2: Mild persistent asthma is present.

     

    • The controller medication is an inhaled corticosteroid (200-500 mcg), cromolyn, nedocromil, or a leukotriene antagonist. If needed, increase the dose of corticosteroid and add a long-acting beta-agonist or sustained-release theophylline, especially for nocturnal symptoms.

       

    • The reliever medication is a short-acting beta-agonist as needed for symptoms.
  • Step 3: Moderate persistent asthma is present.
    • The controller medication is an inhaled corticosteroid (800-2000 mcg) and a long-acting bronchodilator (either beta-agonist or sustained-release theophylline).

       

    • The reliever medication is a short-acting beta-agonist as needed for symptoms.
  • Step 4: Severe persistent asthma is present.
    • The controller medication is an inhaled corticosteroid (800-2000 mcg), a long-acting bronchodilator (beta-agonist and/or theophylline), and long-term oral corticosteroid therapy.

       

    • The reliever medication is a short-acting beta-agonist as needed for symptoms.
  • In patients with EIA, the primary aim of therapy is prophylaxis to prevent acute episodes.
    • A warmup period of 15 minutes is recommended prior to a scheduled exercise event and has been shown to have a duration of effect as long as 40 minutes. This approach is not helpful for unscheduled events, prolonged exercise, or elite athletes.

       

    • One of the primary treatments is to ensure good control of underlying asthma.

       

    • For isolated EIA without underlying asthma, regularly scheduled medications are not indicated. Prophylaxis in the form of inhaled medications administered 15-30 minutes prior to exercise is usually required.
  • The most commonly used medications are short-acting beta-agonists such as albuterol. Sodium cromolyn and nedocromil used 30 minutes prior to exercise have also been effective. The use of long-acting beta-agonists such as salmeterol (at least 90 min before exercise) can be effective for repetitive exercise. Newer agents such as the leukotriene antagonists, inhaled heparin, and inhaled furosemide have demonstrated an ability to prevent exercise-induced bronchospasm. No role exists for inhaled corticosteroids in the treatment of EIA except to control underlying asthma.

Deterrence/Prevention:

  • Another component of the treatment of asthma is the control of factors contributing to asthma severity.
  • Exposure to irritants or allergens has been shown to increase asthma symptoms and cause exacerbations. Clinicians should evaluate patients with persistent asthma for allergen exposures and sensitivity to seasonal allergens. Skin testing results should be used to assess sensitivity to perennial indoor allergens, and any positive results should be evaluated in context of the patient's medical history.
  • All patients with asthma should be advised to avoid exposure to allergens to which they are sensitive, especially in the setting of occupational asthma. Other factors may include the following:
    • Environmental tobacco smoke
    • Exertion during high levels of air pollution
    • Use of beta-blockers
    • Avoidance of aspirin and other NSAIDs if the patient is sensitive
    • Avoidance of sulfites or other food items/additives to which the patient may be sensitive

Complications:

  • The most common complications of asthma include pneumonia, pneumothorax or pneumomediastinum, and respiratory failure requiring intubation in severe exacerbations.
  • Risk factors for death from asthma include the following:
    • Past history of sudden severe exacerbations, history of prior intubation, or ICU admission
    • Two or more hospitalizations or 3 or more emergency department visits in the past year; hospitalization or emergency department visit in the past month
    • Use of more than 2 beta-agonist canisters per month
    • Current use of systemic corticosteroids or recent taper
    • Comorbidity from cardiovascular disease
    • Psychosocial, psychiatric, or illicit drug use problems
    • Low socioeconomic status or urban residence
  • Complications associated with most medications used for asthma are relatively rare. However, in those patients requiring long-term corticosteroid use, complications may include osteoporosis, immunosuppression, cataracts, myopathy, weight gain, addisonian crisis, thinning of skin, easy bruising, avascular necrosis, diabetes, and psychiatric disorders.

Prognosis:

  • Approximately half the children diagnosed with asthma in childhood outgrow their disease by late adolescence or early adulthood and require no further treatment.
  • Patients with poorly controlled asthma develop chronic changes over time, ie, with airway remodeling. This can lead to chronic symptoms and a significant irreversible component to their disease.
  • Many patients who develop asthma at an older age also tend to have chronic symptoms.

Patient Education:

  • The Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma emphasizes the need for patient education about asthma and the establishment of a partnership between patient and clinician in the management of the disease. The key points of education include the following:
    • Integrate patient education into every aspect of asthma care.
    • All members of the health care team, including nurses, pharmacists, and respiratory therapists, provide education.
    • Clinicians teach patients asthma self-management based on basic asthma facts, self-monitoring techniques, the role of medications, inhaler use, and environmental control measures.
    • Develop treatment goals for the patient and family.
    • Develop a written, individualized, daily self-management plan.
    • Encourage adherence by patient.

MISCELLANEOUS

Medical/Legal Pitfalls:

  • The most important factor in the diagnosis of asthma is to recognize exacerbating factors or other diagnoses that may affect the treatment of the disease.
    • Sinusitis: Of patients with asthma, 50% have concurrent sinus disease. Sinusitis is the most important exacerbating factor for asthma symptoms. Either acute infectious sinus disease or chronic inflammation may contribute to worsening airway symptoms. Treatment of nasal and sinus inflammation reduces airway reactivity.
    • Gastroesophageal reflux disease: Treatment with proton pump inhibitors, antacids, or propulsive agents may improve asthma symptoms or unexplained chronic cough. Treatment of asthma with agents such as theophylline may lower esophageal sphincter tone and induce gastroesophageal reflux disease symptoms.
    • Respiratory infections: Viral respiratory infections have not been shown to cause asthma but can aggravate chronic asthma symptoms or induce symptoms in patients with allergic rhinitis.
    • Aspirin-induced asthma: The triad of asthma, aspirin sensitivity, and nasal polyps affects 5-10% of patients with asthma. It can also occur with other NSAIDs and is caused by an increase in eosinophils and cysteinyl leukotrienes after exposure. Primary treatment is avoidance of these medications, but leukotriene antagonists have shown promise in treatment, allowing these patients to take daily aspirin for cardiac or rheumatic disease.
    • Vocal cord dysfunction: Inspiratory closure of the vocal cords may mimic asthma. Patients with symptoms of inspiratory wheezing or those whose asthma is refractory to standard therapy should be evaluated for evidence of vocal cord dysfunction. Usually, the diagnosis can be made based on direct laryngoscopy findings, but only during symptomatic periods. The presence of flattening of the inspiratory limb of the flow volume loops may also suggest this disorder.
    • Occupational asthma: Pay careful attention to the occupational history of the patient. Those patients with a history of asthma who report worsening of symptoms during the week and improvement during the weekends should be evaluated for an occupational exposure.

Special Concerns:

  • Nocturnal asthma
    • A large percentage of patients with asthma experience nocturnal symptoms once or twice a month. Some patients only experience symptoms at night and have normal pulmonary function in the daytime. This is due, in part, to the exaggerated response to the normal circadian variation in airflow.
    • Bronchoconstriction is highest between the hours of 4:00 am and 6:00 pm (the highest morbidity and mortality from asthma is observed during this time). These patients may have a more significant decrease in cortisol levels or increased vagal tone at night. Studies also show an increase in inflammation compared to controls and to patients with daytime asthma.
    • Inhaled corticosteroids and long-acting theophyllines have demonstrated the most benefit. Long-acting beta-agonists and leukotriene antagonists have also been shown to improve symptoms.
  • Pregnancy
    • The most important issue in the treatment of asthma during pregnancy is to maintain sufficient lung function and an adequate oxygen supply to the fetus.
    • With the exception of alpha-adrenergic compounds other than pseudoephedrine and some antihistamines, most drugs used to treat asthma and allergic rhinitis have not been shown to increase risk to the mother or fetus. The NIH stated that albuterol, cromolyn, beclomethasone, budesonide, prednisone, and theophylline, when clinically indicated, are considered appropriate for the treatment of asthma in pregnancy.
    • Poorly controlled asthma can result in low birth weight, increased prematurity, and increased perinatal mortality.
  • Surgery
    • Complications associated with surgery include acute bronchoconstriction resulting from intubation, impaired cough, hypoxemia, hypercapnia, atelectasis, respiratory infection, and exposure to latex.

       

    • The likelihood of these complications occurring depends on the severity of underlying asthma.