Almost 5 million children in the United States have asthma1 and it is the most common reason for admission to pediatric hospitals.2 Each year, asthma results in 10 million school absences,2 5500 deaths,3 and 500,000 hospitalizations.4,5 Appropriate asthma treatment prevents hospital admissions and emergency room visits, reduces the risk of death, and improves the quality of life for children with asthma.4,6,7 The hospitalist is ideally situated to have a major impact on asthma by treating its acute manifestations, by implementing effective long-term therapy where indicated, and by diagnosing and managing any comorbidity that accompanies and/or exacerbates asthma.
Asthma results from airway inflammation and smooth muscle dysfunction. It is defined by the National Heart Lung and Blood Institute (NHLBI) and World Health Organization (WHO) as:
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 cough, particularly at night and in the early morning. These symptoms are usually associated with widespread but variable airway obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli. Reversibility of airflow limitation may be incomplete in some patients with asthma.4
PATHOPHYSIOLOGY OF ASTHMA
The underlying cause of asthma is unknown and the course of pediatric asthma is dynamic. Early in the course of the disease, airway inflammation, bronchial hyperreactivity and loss of lung function are evident. Atopy and a family history of asthma are strongly correlated with asthma in childhood. Exposure to allergens activates mast cells and promotes inflammation and airway infiltration with neutrophils, eosinophils, and lymphocytes.8 Whatever the cause, the inflammation results in airway hyperresponsiveness, which causes bronchoconstriction, edema and mucus plugging, all of which contribute to bronchial obstruction. Chronically, collagen deposition below the epithelial basement membrane results in narrowing of the airway due to remodeling.
Asthma exacerbations are acute or subacute episodes of progressively worsening shortness of breath, cough, wheezing, and chest tightness, or some combination of these symptoms. Exacerbations are characterized by decreases in expiratory airflow that can be documented and quantified by measurement of lung function (spirometry or PEF). These objective measures more reliably indicate the severity of an exacerbation than does the severity of the symptoms. Status asthmaticus is continued or progressive airway obstruction despite bronchodilator therapy resulting in sustained or worsening respiratory distress.4
Acute asthma exacerbations can be triggered by infectious respiratory illness, environmental allergen or irritant exposure, exercise, cold air, or a combination of these. An asthma exacerbation involves either a slow onset of symptoms or a rapid decline in respiratory status. Persistent or acute allergen or irritant exposure promotes inflammation, bronchoconstriction, and airway hyperresponsiveness on an ongoing basis. Allergen exposure triggers a biphasic response. The “early response” occurs within minutes of allergen exposure resulting in rhinorrhea, sneezing, itching of the eyes and nose, and bronchospasm due to the release of histamine and other preformed mediators of inflammation. The “late-phase response” peaks 6 to 8 hours after allergen exposure with the development of eosinophilic inflammation and T-cell infiltration of the airway. During an asthma exacerbation due to allergen exposure, both phases must be treated with medications to treat the symptoms of the early phase as well as the resultant inflammation of the late phase.9
Viral infections cause asthma symptoms by promoting eosinophilic or neutrophilic airway inflammation.4 Viral-induced asthma exacerbations are common in children, and in fact, a majority of acute asthma admissions are associated with viral infections in children and adults, especially rhinovirus.10,11 The risk of an asthma exacerbation can be modified by a patient’s underlying inflammatory state and level of airway hyperreactivity. A patient with reduced airway inflammation due to adequate controller therapy is less likely to have a severe asthma flare when exposed to offending agents.
The presentation of acute asthma may vary, but all patients experience worsening airflow obstruction associated with respiratory distress. Patients often complain of shortness of breath, chest tightness, and wheezing. Some patients describe chest pain, cough, or fatigue. Caregivers may report observations of breathlessness, trouble speaking, decreased activity, retractions, rapid breathing, wheezing noises, or relentless cough.12
On physical examination, tachypnea is present, often accompanied by tachycardia. Pulse oximetry may reveal decreased oxygen saturation. There is evidence of increased respiratory effort, such as intercostal, supraclavicular, or subcostal retractions. Infants and young children may demonstrate nasal flaring or head bobbing. Paradoxical motion of the thoracoabdominal wall (i.e. expansion of the abdominal girth with inspiration) is another useful sign of increased work of breathing. Auscultation of the chest often reveals wheezing and a prolonged expiratory phase. Rales or crackles are often heard, and may shift in location over minutes to hours (“migratory atelectasis”). An assessment of air movement is determined by the loudness of breath sounds in various areas of the chest and may also vary over time. Patients with poor air movement may have minimal wheezing since the passage of air through the airway is what generates wheezing sounds. As air exchange improves, wheezing may become more pronounced. Conversely, patients with a deteriorating clinical course may have diminishing wheezing indicative of worsening air movement and perhaps respiratory insufficiency. Agitation or somnolence are worrisome signs and may indicate hypoxemia or hypercarbia with impending respiratory failure.
Some patients present without significant wheezing but with prominent cough as their manifestation of asthma, often referred to as “cough-variant” asthma. It is believed that the pathophysiology and response to treatment are similar to classic asthma.
Many conditions result in acute or chronic respiratory symptoms that mimic an asthma syndrome. Some of these conditions are discussed below.
Anatomical abnormalities should be considered in young children with frequent episodes of cough or wheeze. Inhaled foreign bodies are most common in toddler-aged children (see Chapter 145). These problems may present with cough, stridor, or wheeze. In all age groups, gastroesophageal reflux can mimic or contribute to underlying asthma13,14 (see Chapter 82). Cystic fibrosis is a genetic disorder that can also present with chronic cough or recurrent episodes of wheezing (see Chapter 144).
Viral infections often cause wheezing in childhood as well. Respiratory syncytial virus (RSV) is the most common cause of infantile bronchiolitis, but other respiratory viruses such as rhinovirus, parainfluenza virus, coronavirus, adenovirus, and influenza viruses are other common infectious agents.15 Viral bronchiolitis is associated with edema, bronchospasm, and increased mucus production of the smaller airway, features which overlap with asthma (see Chapter 100). As these respiratory viral infections are known to precipitate asthma exacerbations, it may be difficult to determine if the wheezing represents and isolated episode of bronchiolitis or an asthma exacerbation triggered by the respiratory illness.
Atypical respiratory infections with agents such as Mycoplasma, Chlamydia pneumoniae, Bordetella pertussis, or parapertussis can present with chronic cough. Coughing associated with these infections can persist for several months.
Functional disorders can coexist with or mimic asthma and include vocal cord dysfunction (VCD) and psychogenic cough. VCD usually presents in adolescence, with upper airway (laryngeal) inspiratory and/or expiratory stridor, which may be difficult to distinguish from lower airway wheezing. The diagnosis of VCD is confirmed by laryngoscopy demonstrating paradoxical adduction of the vocal cords seen during inspiration.16-19 Psychogenic cough is a habitual cough that can also persist for months, often occurring after an acute respiratory illness.20 Habitual cough has a characteristic sound described as barky or honking. The cough is exaggerated by stress or attention to the cough and will disappear with sleep.20 These features help distinguish this entity from cough-variant asthma. A key feature of VCD and psychogenic cough is the lack of response to asthma therapy.16-20 In addition, they are not associated with hypoxia.
In the United States, the NHLBI Guidelines for the Diagnosis and Management of Asthma (EPR-3) are available to guide clinicians through the diagnosis and management of chronic asthma. These guidelines are complementary to the material presented in this chapter (http://www.nhlbi.nih.gov/guidelines/asthma/).
The initial evaluation of a patient presenting with an asthma exacerbation should include the assessment of the acute respiratory symptoms, signs or symptoms of coexisting or precipitating conditions, and treatments initiated prior to presentation. History should be obtained regarding the characteristics of the patient’s asthma symptoms, the pattern and frequency of the symptoms, any precipitating or aggravating factors as well as features indicative of the severity and level of control of their asthma (Tables 141-1 and 141-2).4
TABLE 141-1Questions to Ask Patients Who Present with Wheezing ||Download (.pdf) TABLE 141-1 Questions to Ask Patients Who Present with Wheezing
|Types of Symptoms (Impairment) ||Cough |
|Shortness of breath |
|Chest tightness |
|Sputum production |
|Frequency of Symptoms (Impairment) ||Daily, weekly, none |
|Perennial, seasonally |
|Do they have a night cough? |
|Do they cough with activity? |
|How often do they use their albuterol? |
|Severity of Symptoms (Risk) ||How often do they have flares of their asthma? How many times in the last year? |
|How many times have they used oral steroids? How many times in the last year? |
|How many emergency room visits? |
|How many visits to the hospital? |
|Have they ever been in the ICU? |
TABLE 141-2Features That Place Patient at Risk for Death from Asthma ||Download (.pdf) TABLE 141-2 Features That Place Patient at Risk for Death from Asthma
Previous severe exacerbation (e.g. intubation or ICU admission for asthma)
Two or more hospitalizations for asthma in the past year
Three or more ED visits for asthma in the past year
Hospitalization of ED visit for asthma in the past month
Using >2 canisters of SABA per month
Difficulty perceiving asthma symptoms or severity of exacerbations
Low socioeconomic status or inner-city residence
Major psychosocial problems
Cardiovascular, other chronic lung, or chronic psychiatric disease
The physical examination provides clues to the severity of the current illness as well as the presence of comorbidities. Important physical parameters include respiratory rate, work of breathing, air entry, wheezing, and oxygen saturation. Work of breathing refers to the use of accessory muscles of respiration and also includes parameters such as nasal flaring, abdominal retractions, and depth of respiration.
During an asthma exacerbation, physical findings may vary and evolve with treatment or progression of the acute condition. A quiet or silent chest is a worrisome sign as poor movement of air can be associated with respiratory insufficiency or failure. Asymmetry of auscultatory findings may indicate other conditions. Unequal breath sounds can be found with pneumonia, effusion (especially in dependent regions of the lung), or atelectasis. Unilateral breath sounds may indicate an aspirated foreign body or a pneumothorax on the side with diminished breath sounds,4 and may be accompanied by hyperresonance on that side, especially if there is significant air trapping. Chest radiographs are typically not needed for patients with known asthma and a straightforward asthma exacerbation.21 Typical radiographic findings include hyperinflation, peribronchial thickening, and atelectasis (Figure 141-1). Chest radiographs may be helpful when there is concern for pneumonia, effusion, pneumothorax, pneumomediastinum, or foreign body aspiration.
Typical radiographic findings in a patient with an acute asthma exacerbation.
A classification system for the severity of an asthma exacerbation is provided in Table 141-3. Patients in mild distress typically have slightly increased respiratory rates, may not use accessory muscles of respiration, and have end-expiratory wheezes with good air entry. Patients in severe distress are working hard to breathe, with inspiratory and expiratory wheezes, and are often hypoxic. Signs of impending respiratory failure are provided in (Table 141-4). For infants and children under 5 years of age, clues to breathlessness include difficulty or reluctance to feed and changes in crying pattern (e.g. softer or shorter). Changes in vital signs in these younger patients must be interpreted in the context of normal values for the age of the patient. Interestingly, paradoxical thoracoabdominal movement, a sign associated with severe respiratory distress in older children, may be seen in young children and infants even in states of mild or moderate respiratory distress.
TABLE 141-3Clinical Classification of Severity for Asthma Exacerbation in Patients ≥5 Years of Age ||Download (.pdf) TABLE 141-3 Clinical Classification of Severity for Asthma Exacerbation in Patients ≥5 Years of Age
|Exacerbation Severity ||Mild ||Moderate ||Severe ||Subset: Respiratory Arrest Imminent |
| Breathlessness ||While walking ||While talking (infants: softer, shorter cry; difficulty feeding) ||While at rest (infants: stop feeding) || |
| Positioning ||Can lie down ||Prefers sitting ||Sits upright || |
| Speaks in ||Sentences ||Phrases ||Words || |
| Alertness ||May be agitated ||Usually agitated ||Usually agitated ||Drowsy or confused |
|Signs || || || || |
| Respiratory rate ||Increased ||Increased ||Often >30/min || |
| Use of accessory muscles, suprasternal retractions ||Usually not ||Commonly ||Usually ||Paradoxical thoracoabdominal movement |
| Wheeze ||Moderate, often only end expiratory ||Loud; throughout exhalation ||Usually loud, throughout inhalation and exhalation ||Absence of wheeze |
| Pulse/min ||<100 ||100-120 ||>120 ||Tachycardia or bradycardia |
| Pulsus paradoxus ||Absent (<10 mm Hg) ||May be present (10-25 mm Hg) ||Often present (>25 mm Hg for an adult, 20-40 mm Hg for a child) ||Absence suggests respiratory muscle fatigue |
|Functional Assessment || || || || |
| PEF % predicted or % personal best ||>70% ||40% to 69% or response lasts <2 hours ||<40% predicted or personal best ||<25% Note: PEF test may not be needed for severe attacks |
| PaO2 (on room air) ||Normal (test not usually necessary) ||>60 mm Hg (test not usually necessary) ||<60 mm Hg, possible cyanosis || |
| And/or PaCO2 ||<42 mm Hg ||<42 mm Hg ||>42 mm Hg, possible respiratory failure || |
| SaO2 % (on room air) at sea level ||>95% ||90% to 95% ||<90% || |
TABLE 141-4Indicators of Impending Respiratory Failure ||Download (.pdf) TABLE 141-4 Indicators of Impending Respiratory Failure
|Poor air movement or silent chest in combination with increased respiratory effort, bradypnea, or disorganized breathing pattern |
|Inability to speak |
|Increasing pulsus paradoxus or decreasing pulsus paradoxus in an exhausted patient |
|PCO2 > 42 mm Hg |
|Inability to lie supine |
|Deteriorating mental status, lethargy, or agitation |
|Respiratory or cardiac arrest |
Objective measures of acute asthma include pulmonary function testing, pulse oximetry, and arterial blood gases. Patients with asthma exacerbations are at risk for hypoxemia. As a result, patients require frequent monitoring to ensure adequate oxygenation. During a severe exacerbation, continuous pulse oximetry is recommended whereas intermittent oximetry may be acceptable as the clinical course improves.
Arterial blood gases are typically performed in critically ill patients and those with clinical deterioration or signs of respiratory insufficiency or failure. Arterial blood gases may reveal hypoxemia due to ventilation-perfusion mismatch and respiratory alkalosis with hypocapnia due to hyperventilation. A normal or elevated partial pressure of carbon dioxide (PaCO2) may be the harbinger of respiratory failure22 and may be associated with a decreased blood pH due to respiratory acidosis. In addition, lactic acidosis is a particularly concerning finding in status asthmaticus and patients with lactic acidosis are also at high risk of respiratory failure.
Pulmonary function tests can be used to assess lung function even during an asthma exacerbation. Spirometric indices such as the measurement of the forced expiratory volume at 1 second (FEV1), or peak expiratory flow rate (PEFR) are most useful to assess the severity of asthma. However, since spirometry is often not readily available in the emergency setting, PEFR can be used instead. The hand-held peak flow meter measures PEFR, and normal values have been established according to age, gender, and height23 (Table 141-5). PEFR provides a measure of large airway flow by measuring the rate of airflow in liters per minute. As a flare or asthma exacerbation worsens, PEFR typically becomes lower than baseline and may reflect the severity of the exacerbation. In patients presenting to an emergency room with an asthma exacerbation, the FEV1 is typically 30% to 35% of normal,24 and the PEFR is less than 50% of normal.
TABLE 141-5Predicted Average Peak Expiratory Flow (Liters per Minute) in Normal Children and Adolescents23 ||Download (.pdf) TABLE 141-5 Predicted Average Peak Expiratory Flow (Liters per Minute) in Normal Children and Adolescents23
|Height ||Males & Females ||Height ||Males & Females ||Height ||Males & Females |
|(in) ||(cm) ||(in) ||(cm) ||(in) ||(cm) |
|43 ||109 ||147 ||51 ||130 ||254 ||59 ||150 ||360 |
|44 ||112 ||160 ||52 ||132 ||267 ||60 ||152 ||373 |
|45 ||114 ||173 ||53 ||135 ||280 ||61 ||155 ||387 |
|46 ||117 ||187 ||54 ||137 ||293 ||62 ||157 ||400 |
|47 ||119 ||200 ||55 ||140 ||307 ||63 ||160 ||413 |
|48 ||122 ||214 ||56 ||142 ||320 ||64 ||162 ||427 |
|49 ||124 ||227 ||57 ||145 ||334 ||65 ||165 ||440 |
|50 ||127 ||240 ||58 ||147 ||347 ||66 ||168 ||454 |
Monitoring PEFR can also assist in tapering medication during the recovery phase of an acute hospitalization. The PEFR is effort- and technique-dependent and therefore, reliability remains a concern. It should be used in conjunction the other parameters of severity for assessments.
Asthma exacerbations are treated with a combination of supportive therapy and pharmacological interventions. Treatment is tailored to the severity of the symptoms and adjusted based on response to therapy. Adequate hydration should be established and maintained either orally or with intravenous fluids. Physiologic monitoring should include vital signs and pulse oximetry. Oxygen supplementation is provided to maintain oxygen saturations in a safe range. This range is widely debated, but most agree that levels >90% are needed, and many target levels >93% to 95%.
This class of medications works by stimulating the β2-adrenergic receptor causing activation of adenylate cyclase, which increases the production of cyclic 3’5-adenosine monophosphate (cAMP). This increase in cAMP depending on the site of stimulation results in bronchial smooth relaxation, skeletal muscle and cardiac muscle stimulation, and inhibition of the release of inflammatory mediators via stabilization of the mast cell membrane. Albuterol is one of the short-acting β2-adrenergic agents used as first-line therapy for an acute asthma exacerbation, and this class of agents is used first line due to their ability to rapidly and reliably open the airways. Albuterol can be administered by nebulizer, either continuously or intermittently, or by metered-dose inhaler (MDI) with a spacer device. Studies have compared the amount of medication delivered to the lungs when given by MDI with spacer versus nebulizer.25-27 The two modes are considered equivalent if the patient can use proper technique with the MDI-spacer method of delivery. Dosing information is provided in Table 141-6.
TABLE 141-6Dosages of Bronchodilators Commonly Used for Asthma Exacerbations ||Download (.pdf) TABLE 141-6 Dosages of Bronchodilators Commonly Used for Asthma Exacerbations
|Medications ||Adult Dose ||Child Dose (<12 yrs of age) ||Onset of Action ||Duration ||Comments |
Inhaled Short-Acting β-2 Agonists
2.5 mg/3 ml
1.25 mg/3 ml
0.63 mg/3 ml
2.5-5.0 mg every 20 minutes for 3 doses then 2.5-10 mg every 1-4 hours as needed or 10-15 mg/hour continuously
0.15 mg/kg (minimum dose 2.5 mg) every 20 minutes for 3 doses then 0.1-5 to 0.3 mg/kg up to 10 mg every 1-4 hours as needed, or 0. mg/kg/hour by continuous nebulization
|15 minutes ||3-4 hours || |
Only selective β-2 agonists are recommended. For optimal delivery, dilute aerosols to minimum of 4 mL at gas flow of 6-8 L/min.
As effective as nebulized therapy if patient is able to coordinate.
|4-8 puffs every 20 minutes up to 4 hours, then every 1-4 hours as needed || |
4-8 puffs every 20 minutes for 3 doses, then every 1-4 hours inhalation maneuver
Use VHC; add mask in children <4 years
(0.63 mg/3 ml, 1.25 mg/0.5 ml
1.25 mg/3 ml)
|1.25-2.5 mg every 20 minutes for 3 doses, then 1.25-5 mg every 1-4 hours as needed ||0.075 mg/kg (minimum dose 1.25 mg) every 20 minutes for 3 doses, then 0.075-0.15 mg/kg up to 5 mg every 1-4 hours as needed || |
Levalbuterol administered in one-half the mg dose of albuterol provides comparable efficacy and safety. Has not been evaluated by continuous nebulization.
MDI has not been studied in severe asthma exacerbations.
metered- dose inhaler
|See albuterol MDI dose ||See albuterol MDI dose |
Ipratropium bromide nebulizer solution (0.25 mg/ml)
0.5 mg every 20 minutes for 3 doses then as needed
0.25-0.5 mg every 20 minutes for 3 doses, then as needed
Peak 60-90 minutes
Duration 3-6 hours
May mix in same nebulizer with albuterol. Should not be used as first-line therapy, should be added to SABA therapy for severe exacerbations. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized. Should use with VHC and face mask for children <4 years. Studies have examined ipratropium bromide MDI for up to 3 hours.
|MDI (18 mcg/puff) ||8 puffs as needed up to 3 hours ||4-8 puffs as needed up to 3 hours |
Paradoxical and transient worsening of hypoxia due to increased ventilation-perfusion mismatching can be seen with the administration of albuterol and the other β2-adrenergic agents. This class of medication causes increased cardiac output which leads to increased perfusion of unventilated lung.28 Other side effects include sinus tachycardia, tremor, palpitations, headache, agitation, and ventricular irritability (e.g. ventricular premature contractions, ventricular tachycardia). In addition, frequent or continuous dosing with adrenergic agents can lead to hypokalemia, therefore patients receiving such treatment should have serum potassium levels checked periodically. Non-selective adrenergic agents (e.g. epinephrine) can also cause transient hyperglycemia and elevations in neutrophil counts due to demargination.
Albuterol is actually a racemic mixture of R-albuterol and S-albuterol, with a 50:50 ratio of these two stereoisomers. Levalbuterol (Xopenex™) is made up of the R-isomer, which is felt to be the active component of the racemic product. However, the vast majority of clinical studies and in vitro pharmacology data have shown no significant differences for cardiopulmonary side effects and tremor when comparing racemic to R-isomer albuterol or bronchodilator effects.29-31 Three studies found differences in rates of admission from emergency department and bronchodilation,29,30,32 while two studies found improvement with levalbuterol with decreased rates of admission from an emergency department using levalbuterol versus racemic albuterol33 or improved bronchodilation.34 Overall, in these authors’ consideration, levalbuterol does not offer any significant advantage over racemic albuterol in the treatment of asthma.
Terbutaline, a selective β2-adrenergic agonist, and epinephrine, a non-selective adrenergic agonist, are used in asthmatics not responding to albuterol and corticosteroids, or who are deteriorating. These medications are given by subcutaneous injection or intravenous infusion. Bronchodilation is seen within 5 minutes of administration and can persist for 3 to 4 hours.35,36 Terbutaline can also be given by continuous IV infusion starting with a bolus and titrating the dose to the desired effect. Dosing of β2-adrenergic and bronchodilator agonists are shown in Tables 141-6 and 141-7.
TABLE 141-7Systemic Bronchodilators for Acute Asthma Exacerbations ||Download (.pdf) TABLE 141-7 Systemic Bronchodilators for Acute Asthma Exacerbations
|Medications ||Adult Dose ||Child Dose ||Onset of Action ||Duration ||Comments |
1:1000 (1 mg/ml)
0.3-0.5 mg every 20 minutes for 3 doses subcutaneous
Loading dose: Loading dose: 2-10 mcg/kg, followed by continuous infusion of 0.08-0.4 mcg/kg/minute; titrate dose by clinical response up to 6 mcg/kg/minute
0.01 mg/kg up to 0.3-0.5 mg every 20 minutes for 3 doses subcutaneously
No proven advantage of systemic therapy over aerosol.
0.25 mg every 20 minutes for 3 doses subcutaneous
Loading dose 2-10 mcg/kg followed by continuous infusion of 0.08-0.4 mcg/kg/min, titrate dose by clinical response up to 6 mcg/kg/min
0.01mg/kg every 20 minutes for doses then every 2-6 hours as need subcutaneously
Loading dose 2-10 mcg/kg followed by continuous infusion of 0.08-0.4 mcg/kg/min, titrate dose by clinical response up to 6 mcg/kg/min
| || || |
Corticosteroids are indicated in the initial treatment of status asthmaticus. They are potent anti-inflammatory medications that have been shown to hasten recovery, prevent recurrence,37-41 and prevent hospitalizations.42 Due to their mechanism of action, the effect of corticosteroids is not immediate. Steroids bind to the intracytoplasmic glucocorticoid receptor and translocate to the nucleus thereby affecting RNA transcription in both a positive and negative fashion through the transcription factors NF-κB and AP-1. In general, corticosteroids lead to downregulation of inflammatory cytokines. Corticosteroids also activate histone deacetylase that inhibits DNA transcription.43 This change in transcription leads to increased numbers of β2-adrenegeric receptors at the cell surface and decreases in airway inflammation and mucous secretion. It can take several hours to reverse airway inflammation and benefits are typically seen within 4 hours after corticosteroids are given.38,39,44 Studies comparing oral and IV corticosteroids have found no significant differences in efficacy.45,46 Oral steroids are typically preferred since IV access is not required.45,47 Dosing of corticosteroids are shown in Table 141-8.
TABLE 141-8Systemic Corticosteroids in the Setting of Asthma Exacerbations ||Download (.pdf) TABLE 141-8 Systemic Corticosteroids in the Setting of Asthma Exacerbations
|Medication ||Adult Dose ||Child Dose (< or = 12 yrs of age) ||Onset of Action ||Duration ||Comments |
40-80 mg/day in 1 or 2 divided doses until PEF reaches 70% of predicted or personal best
1-2 mg/kg in 2 divided doses (maximum = 60 mg/day) until PEF 70% of predicted or personal best
| || |
For outpatient burst for 3-10 days:
Adult: use 40-60 mg in single or 2 divided doses
Children: use 1-2 mg/kg/day with maximum of 60 mg/day.
Inhaled Anticholinergic Agents
Anticholinergic agents work by competitively inhibiting the neurotransmitter acetylcholine at the muscarinic junction to relieve cholinergic mediated bronchoconstriction. Nebulized atropine is associated with significant systemic absorption but anticholinergic medications such as ipratropium bromide, have fewer side effects and less systemic absorption.48
The use of inhaled ipratropium in the initial phase of treatment has been shown to be effective in reducing the need for hospitalization. A few studies have found no benefit compared to β-agonists alone, while others have a slight advantage in 1 to 3 doses in the initial phase of acute asthma exacerbation.49 The role of ipratropium for hospitalized patients is less clear.50
Combined administration of anticholinergic and β2-agonist medications increases bronchodilation although some controversy about this persists.51,52 Despite this, many institutions use a combination of β2-agonists and anticholinergic medications during the initial phase of acute asthma exacerbations. Studies examining the use of anticholinergic medications as monotherapy have also been controversial. Dosing is listed in Table 141-6.
If initiation of the above standard therapies does not improve the level of respiratory distress or if symptoms progress, additional interventions may be necessary. The clinical experience and expertise available at the particular institution should be considered in the decisions. Safe transfer to a facility able to provide critical care management should be anticipated and arrangements should be expedited.
Magnesium sulfate has been studied as a bronchodilator in severe asthma with conflicting results.53-56 Magnesium is thought to inhibit mast cell degranulation and increase bronchial dilatation due to a decrease in calcium uptake by bronchial smooth muscle.57 Its use is considered when the patient fails to improve or worsens despite treatment with continuous inhaled β2-agonist, systemic corticosteroids, and inhaled anticholinergic agents.
Intravenous methylxanthines, such as aminophylline, were commonly used in the past to manage asthma exacerbations due to their ability to act directly on β-adrenergic receptors and relax bronchial smooth muscle. Methylxanthines can prevent acute airway hyperresponsiveness but do not appear to have effects chronically.58-60 Studies examining the use of intravenous methylxanthines in children and adults with severe asthma have shown mixed benefits.61-66 A recent Cochrane Review found that theophylline in addition to β2-agonists and glucocorticoids (with or without anticholinergics) improves lung function within 6 hours of treatment. However, there is no apparent reduction in symptoms, number of nebulized treatments and length of hospital stay.67
Concerns regarding toxicity and efficacy of this class of medication and the availability of newer agents limit its use. Life-threatening events such as cardiac arrhythmia and seizures are associated with toxic levels of theophylline (>30 μg/mL).
Heliox is a mixture of helium and oxygen used for inhalation. This agent is thought to improve airflow by creating a gas with a similar viscosity to air but with a lower density, which in turn can increase ventilation and decrease work of breathing.68-70 Heliox is indicated in patients with a refractory asthma exacerbation and whom respiratory failure is impending. Patients with high oxygen requirements may not be able to tolerate heliox because they need a higher Fi02 than a helium-oxygen mixture can provide. Heliox can also lower body temperature due to the high thermal conductivity of the mixture, patients need to have their temperature monitored closely.
Medication adverse effects are listed in Table 141-9.
TABLE 141-9Common Side Effects of Pharmacologic Therapies ||Download (.pdf) TABLE 141-9 Common Side Effects of Pharmacologic Therapies
|Side Effect ||Possible Causative Agent ||Comment |
|Hypokalemia ||Adrenergic agonists ||Patients on prolonged hourly or continuous inhaled therapy, or intravenous therapy should have serum potassium levels monitored |
|Tremor/Agitation ||Adrenergic agonists ||Dose-dependent |
|Hypertension ||Corticosteroids, adrenergic agonists ||May require reduction of dose, discontinuation of therapy, or addition of antihypertensive medication |
|Tachycardia, Palpitations, VPCs ||Adrenergic agonists, aminophylline, theophylline || |
Usually dose-dependent Serum levels of methylxanthines should be monitored
The risk is increased with hypoxemia or acidemia
|Hyperglycemia/Glucosuria ||Corticosteroids, adrenergic agonists ||Resolves with completion or discontinuation of therapy |
|Emotional Lability ||Corticosteroids ||Resolves with completion or discontinuation of therapy |
|Hyperphagia ||Corticosteroids ||Resolves with completion or discontinuation of therapy |
|Seizure ||Theophylline, aminophylline || |
Serum levels of methylxanthines should be monitored
Risk is increased in the presence of acidosis
|Elevated Peripheral Neutrophil Count ||Corticosteroids, adrenergic agonists (in particular epinephrine) ||May interfere with utility of the white blood count in assessing for infection |
The initial therapy of status asthmaticus has been outlined by the NHLBI guidelines (Figure 141-2). In brief, patients are first treated with short-acting inhaled β2-adrenergic agonists (SABA) (e.g. inhaled albuterol), corticosteroids either orally or intravenously and, if needed, oxygen. Inhaled anticholinergics, such as ipratropium bromide, may be added for patients who do not demonstrate prompt improvement. Patients who demonstrate significant improvement after these initial interventions may not require hospitalizations.
Management of asthma exacerbations: emergency department and hospital-based care. (Source: National, Heart, Lung, and Blood Institute; National Institutes of Health; US Department of Health and Human Services.)
Patients with moderately severe symptoms who are stable or are showing signs of improvement and patients with severe symptoms who are demonstrating clear signs of improvement should be hospitalized and treated with inhaled albuterol, either every 1 to 2 hours by nebulizer or MDI-spacer, or delivered continuously via nebulizer. Corticosteroid therapy is continued orally, or if not tolerated, intravenously. Continuation of inhaled anticholinergic agents may be considered, though their benefit remains unproven.
If patients continue to deteriorate, they must be monitored for respiratory insufficiency and failure. Signs of impending respiratory failure are provided in Table 141-4. An arterial blood gas can be used to confirm the condition and should reveal decreased pH, elevated partial pressure of carbon dioxide (PaCO2), and an increased alveolar-arterial oxygen gradient. Pulse oximetry remains a poor monitoring device for early detection of respiratory failure. Oxygen saturation is initially maintained despite a significant degree of hypoventilation, and the addition of supplemental oxygen would further obscure evidence of respiratory failure from this device. Patients with impending respiratory failure often need mechanical ventilatory support either invasively with endotracheal intubation or noninvasively with bilevel positive airway pressure administered via a mask.
TAPERING HOSPITAL THERAPY
After patients are stabilized and demonstrate improvement, the therapies can be gradually reduced and withdrawn. Ongoing assessments of clinical parameters are performed which include respiratory rate, work of breathing, auscultatory findings, and requirement for supplemental oxygen. If the patient remains comfortable with minimal signs of respiratory distress, the dosing of inhaled β-agonists is decreased. For patients on continuous inhaled β-agonist therapy, the dose may be reduced and then subsequently transitioned to intermittent treatments, usually every 2 hours. As the patient continues to improve, the interval between treatments can be extended further. Similarly, the amount of supplemental oxygen is titrated to maintain oxygen saturations above the desired level, and eventually discontinued. Systemic corticosteroids are continued throughout the exacerbation and maintained for several days after discharge from the hospital. If inhaled anticholinergic agents have been instituted, they are usually discontinued when albuterol begins to be tapered.
Many hospitals use clinical pathways, which are tools that detail a sequence of assessments and treatments for patients with various conditions.71 Studies have shown that asthma clinical pathways shorten hospitalization and decrease the need for readmission for up to 2 weeks after discharge.72,73 An asthma clinical pathway allows multiple caregivers, including nurses, respiratory therapists, and doctors to modify treatment based on structured assessments. The NHLBI guidelines (Figure 141-2) outline specific criteria that can be used to determine a patient’s severity and frequency of therapy. It also provides criteria to assist in weaning treatments.
PEFR measurements may be useful to determine readiness for reduction in medication. If the PEFR is at least 70% of baseline prior to a bronchodilator treatment (Table 141-5), it is appropriate to space the frequency of the β2-adrenergic agonist treatments. Technique and effort will affect the PEFR measurement, therefore it should be used in conjunction with other clinical indicators of improvement.
THERAPY AFTER DISCHARGE TO HOME
Patients should be sent home on oral corticosteroids, the duration of which depends upon the length and severity of illness and the patient’s frequency of exacerbations. In general, an isolated exacerbation is treated with oral corticosteroids for 5 days. However, if a patient was admitted to the hospital for an extended period, they will require a prolonged course of corticosteroids and then tapering doses. A taper is prescribed to prevent a relapse of symptoms as well as to prevent an Addisonian crisis from adrenal suppression. The risk of Addisonian crisis is hypothetical and has not been shown in any study.74-76 In addition, patients receiving their second course of steroids in a month should receive a prolonged taper as well. A typical taper involves keeping the patient at a full daily dose of corticosteroids until they achieve stable clinical status and then decreasing the dose by 30% to 50% daily. Patients who required admission to the hospital may not have been on an adequate treatment plan thus the hospitalization offers the opportunity to assess the overall treatment regimen. Patients should be evaluated according to the NHLBI guidelines and, if indicated, have their outpatient preventive treatment adjusted to the appropriate level of asthma control and disease severity. Specific drug choices are outlined in Table 141-6.
ADMISSION AND DISCHARGE CRITERIA
Admission to the hospital is individualized and is based on many factors. Hospitalization should be considered in patients with
Poor response to initial treatment
Oxygen saturation <92% on room air
Severe asthma with relapsing course despite prolonged corticosteroid therapy
Prior emergency visits during current flare
Concern for nonadherence
Admission to an intensive care unit would be appropriate for patients with
Life-threatening or severe asthma that is unresponsive to initial therapy
Inability to maintain oxygen saturations >92% with supplemental oxygen
Evidence of impending respiratory failure
Inability to provide adequate monitoring outside of an intensive care setting77
A patient is ready to go home when they have been successfully weaned to albuterol treatments every 4 to 6 hours. Prior to receiving a treatment, they should be able to breathe comfortably during ambulation or speaking. Wheezing may persist on examination but this should not be audible without a stethoscope. A plan of care should include ongoing management of the current acute exacerbation and transition to maintenance therapy. Additionally, the patient should leave with a plan of action, or asthma action plan, for management of subsequent asthma exacerbations. Efforts should be coordinated with the primary care clinician, and, if involved, the asthma specialist.
Prior to discharge, it is important to consider the environment to which the patient will return. The preventive management plans should be reviewed with the family which would include identifying any potential comorbidities and triggers present in the environment. Table 141-10 highlights a discharge checklist that was created by the NHLBI panel.
TABLE 141-10Checklist for Hospital Discharge of Patients Who Have Asthma ||Download (.pdf) TABLE 141-10 Checklist for Hospital Discharge of Patients Who Have Asthma
|Intervention ||Dose/Timing ||Education/Advice ||MD/RN Initials |
Inhaled medications (e.g. MDI with valved holding chamber (VHC or spacer); nebulizer)
Select agent, dose, and frequency (e.g. albuterol)
2-6 puffs every 3-4 hours as needed
| || |
|Oral medications ||Select agent, dose, and frequency (e.g. prednisone 50 mg qd for 5 days) || |
Teach side effects
|Peak flow meter ||For selected patients: measure AM and PM PEF, and record best of 3 tries each time || || |
|Follow-up visit ||Make appointment for follow-up care with primary clinician or asthma specialist ||Advise patient (or caregiver) of date, time, and location of appointment, ideally within 7 days of hospital discharge || |
|Action plan ||Before or at discharge ||Instruct patient (or caregiver) on simple plan for actions to be taken when symptoms, signs, or PEF values suggest airflow obstruction || |
Outpatient referral to an asthma specialist (e.g. pulmonologist, allergist) is associated with reduced rates of emergency department visits78 and is recommended for patients with the following scenarios.4
Patient has had a life-threatening asthma exacerbation.
Patient is not meeting goals of asthma therapy after 3 to 6 months of treatment. Earlier referral or consultation is appropriate if physician concludes patient is unresponsive to therapy.
Signs and symptoms are atypical, or there are problems in differential diagnosis.
Patient requires step 4 care or higher (step 3 for children 0–4 years of age). Consider referral if patient requires step 3 care (step 2 for children 0 to 4 years of age).
Patient has required more than 2 bursts of oral corticosteroids in 1 year or has an exacerbation requiring hospitalization.
Asthma specialists may be available to assist in the management of an acute asthma exacerbation as needed. Involving the specialist during a hospitalization may assist with transition after discharge. Critical care physicians should be contacted for all patients who may need management in an intensive care setting.
Educating the family about the pathogenesis of asthma, triggers, and medications is crucial to preventing exacerbations and admissions to the hospital. A patient that requires frequent admissions needs to have their treatment plan reassessed and be evaluated for comorbid conditions. In addition, others factors including gastroesophageal reflux, sinusitis, and others that might exacerbate asthma should be explored and eliminated if possible (Table 141-11). For children experiencing symptoms on a daily basis, there are certain controllable environmental factors such as exposure to allergens and cigarette smoke that can cause symptoms and contribute to asthma exacerbations.79 If an allergic component is considered, further evaluation can be arranged and environmental control measures recommended. Both passive and active cigarette smoking significantly increase the risk of asthma and worsen asthma symptoms.80-87 As a result, no smoking should be permitted around an asthmatic or in their home or family car. Physicians should provide assistance for caregivers to quit smoking.
TABLE 141-11Factors That Worsen Asthma Severity and Control Measures ||Download (.pdf) TABLE 141-11 Factors That Worsen Asthma Severity and Control Measures
|Factors That Worsen Asthma Severity ||Control Measures |
|Animal dander || |
Remove animal from the environment
At minimum, remove animal from the bedroom
|House dust mites || |
Encase mattress and pillows in an allergen impermeable cover
Wash bedding in hot water weekly >130°F
Remove carpets from the bedroom
|Cockroaches || |
Do not leave garbage and food exposed
|Pollens ||During pollen season, stay indoors with windows closed, especially in the late afternoon |
|Molds || |
Fix leaks, eliminate water sources
Clean moldy surfaces
|Cigarette/Tobacco smoke ||Encourage family members and caregivers to smoke outside |
|Sinusitis || |
Promote sinus drainage
Antibiotic therapy when appropriate
|Gastroesophageal reflux || |
No eating 3 hours before bedtime
Elevate head of bed 6-8 inches
Appropriate medications: Histamine-2 antagonist
|Medications || |
Avoid aspirin and NSAIDS in patients with severe persistent asthma, nasal polyps, and aspirin sensitivity
|Viral infections ||Annual influenza vaccination |
|Irritants ||Decrease exposure to wood-burning stoves, fireplaces, unvented stores or heaters, perfumes, cleaning agents, sprays |
An assessment of adherence to therapy and review of relevant drug delivery systems is important as well. Appropriate preventative medications based on daily symptoms and frequency of exacerbations should be maintained on a daily basis. These medications are essential for the prevention of asthma flares. Multiple studies have shown a strong negative correlation with the use of asthma admission and daily inhaled corticosteroids, that is, daily corticosteroids reduce asthma admissions. Suggested doses and regiments have been established in national and worldwide collaborations between pediatricians, allergists, pulmonologists, internists, and others. In 2007, the Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma was published by the NHLBI. The revised guidelines focus greatly on assessment of asthma severity based on two stratospheres, including risk and impairment. The risk domain includes frequency and severity of exacerbations and the occurrence of treatment-related adverse effects. The impairment domain is multifactorial and assesses symptoms, SABA use, pulmonary function, and uses validated questionnaires. For each patient, the more severe of these two categories dictates the level of preventive medications a patient requires and a consideration for reduction of controller therapy can be considered after at least 3 months of good control of asthma.4
Additional sources of support for families can include the Asthma and Allergy Network Mothers of Asthmatics, www.breatherville.org, and the Asthma and Allergy Foundation of America, www.aafa.org.
Asthma is a chronic inflammatory disease affecting many Americans and researchers are actively investigating new drugs and therapies to improve the quality of life of asthmatics. Drugs that modify the immune response are currently under active investigation.
Omalizumab, a recombinant humanized anti-immunoglobulin E (IgE) antibody, is an immunomodulator which is now utilized as adjunctive therapy in steps 5 or 6 care for patients with allergies and severe persistent asthma that is inadequately controlled with the combination of high-dose ICS and LABA. Omalizumab is approved for 6 and up and a new monoclonal antibody therapy is also available. Mepolizumab (Nucala) is available for severe eosinophilic asthma. This drug binds circulating free IgE, reducing the level of free IgE in the bloodstream and preventing it from binding to mast cell membrane receptors. This leads to a decrease in the release of mediators in response to allergen exposure. Omalizumab also decreases FceRI expression on basophils and airway submucosal cells.88,89 Omalizumab has been found to reduce symptoms, exacerbations,90 and the use of corticosteroids. In patients who have severe persistent asthma, omalizumab results in clinically relevant improvements in quality-of-life scores.91
Asthma is a chronic disorder that results in airway inflammation and smooth muscle dysfunction and manifests as recurrent episodes of wheezing, breathlessness, and chest tightness.
Exacerbations can be triggered by a variety of stimuli including respiratory infections, exposure allergens or irritants, exercise, or cold.
Treatment of flares must be directed at decreasing airway inflammation and relieving bronchospasms while providing supportive care.
The mainstay of pharmacologic therapy includes inhaled short acting β2-adrenergic agonist therapy and systemic corticosteroids. Supportive care includes supplemental oxygen if needed and maintenance of hydration.
Many of the pharmacologic agents have significant side effects and therefore appropriate monitoring is required.
Patients with severe symptoms or those with moderately severe symptoms that fail to demonstrate improvement on initial therapy are candidates for admission to an intensive care setting.
At the time of discharge, patients should have a clear plan for ongoing treatment of the acute exacerbation and transition to maintenance therapy. In addition, an action plan for subsequent exacerbations should be in place.
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