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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Asthma</title><author><name sortKey="Heltzer, Meredith" sort="Heltzer, Meredith" uniqKey="Heltzer M" first="Meredith" last="Heltzer">Meredith Heltzer</name></author><author><name sortKey="Spergel, Jonathan M" sort="Spergel, Jonathan M" uniqKey="Spergel J" first="Jonathan M." last="Spergel">Jonathan M. Spergel</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">7152009</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152009</idno><idno type="RBID">PMC:7152009</idno><idno type="doi">10.1016/B978-032303004-5.50079-X</idno><idno type="pmid">NONE</idno><date when="2007">2007</date><idno type="wicri:Area/Pmc/Corpus">000221</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000221</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Asthma</title><author><name sortKey="Heltzer, Meredith" sort="Heltzer, Meredith" uniqKey="Heltzer M" first="Meredith" last="Heltzer">Meredith Heltzer</name></author><author><name sortKey="Spergel, Jonathan M" sort="Spergel, Jonathan M" uniqKey="Spergel J" first="Jonathan M." last="Spergel">Jonathan M. Spergel</name></author></analytic><series><title level="j">Comprehensive Pediatric Hospital Medicine</title><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="American Academy Of Allergy Asthma And Immunology Inc" uniqKey="American Academy Of Allergy Asthma And Immunology Inc">American Academy of Allergy, Asthma, and Immunology, Inc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lemanske, Rf" uniqKey="Lemanske R">RF Lemanske</name></author><author><name sortKey="Busse, Ww" uniqKey="Busse W">WW Busse</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Moss, Mh" uniqKey="Moss M">MH Moss</name></author><author><name sortKey="Gern, Je" uniqKey="Gern J">JE Gern</name></author><author><name sortKey="Lemanske, Rf" uniqKey="Lemanske R">RF Lemanske</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="National Heart Lung And Blood Institute National Asthma Education And Prevention Program" uniqKey="National Heart Lung And Blood Institute National Asthma Education And Prevention Program">National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="National Heart Lung And Blood Institute National Asthma Education And Prevention Program" uniqKey="National Heart Lung And Blood Institute National Asthma Education And Prevention Program">National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="National Heart Lung And Blood Institute National Asthma Education And Prevention Program" uniqKey="National Heart Lung And Blood Institute National Asthma Education And Prevention Program">National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="chapter-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Comprehensive Pediatric Hospital Medicine</journal-id><journal-title-group><journal-title>Comprehensive Pediatric Hospital Medicine</journal-title></journal-title-group></journal-meta><article-meta><article-id pub-id-type="pmc">7152009</article-id><article-id pub-id-type="publisher-id">B978-0-323-03004-5.50079-X</article-id><article-id pub-id-type="doi">10.1016/B978-032303004-5.50079-X</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Asthma</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Heltzer</surname><given-names>Meredith</given-names></name></contrib><contrib contrib-type="author" id="au2"><name><surname>Spergel</surname><given-names>Jonathan M.</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="editor"><name><surname>Zaoutis</surname><given-names>Lisa B.</given-names></name><degrees>MD, FAAP</degrees></contrib></contrib-group><aff>Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine</aff><aff>Chief, Section of Inpatient Services, Division of General Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania</aff><contrib-group><contrib contrib-type="editor"><name><surname>Chiang</surname><given-names>Vincent W.</given-names></name><degrees>MD, FAAP</degrees></contrib></contrib-group><aff>Assistant Professor of Pediatrics, Harvard Medical School</aff><aff>Chief, Inpatient Services, Children's Hospital Boston, Boston, Massachusetts</aff><pub-date pub-type="pmc-release"><day>15</day><month>5</month><year>2009</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><year>2007</year></pub-date><pub-date pub-type="epub"><day>15</day><month>5</month><year>2009</year></pub-date><fpage>463</fpage><lpage>481</lpage><permissions><copyright-statement>Copyright © 2007 Elsevier Inc. All rights reserved.</copyright-statement><copyright-year>2007</copyright-year><copyright-holder>Elsevier Inc.</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></article-meta></front><body><p id="para3">Almost 5 million children in the United States have asthma,<xref rid="bib7" ref-type="bibr"><sup>1</sup></xref> and it is the most common reason for admission to pediatric hospitals.<xref rid="bib8" ref-type="bibr"><sup>2</sup></xref> Each year, asthma results in 10 million school absences,<xref rid="bib8" ref-type="bibr"><sup>2</sup></xref> 5500 deaths,<xref rid="bib9" ref-type="bibr"><sup>3</sup></xref> and 500,000 hospitalizations.<xref rid="bib10" ref-type="bibr">4</xref>, <xref rid="bib11" ref-type="bibr">5</xref> Appropriate asthma treatment prevents hospital admissions and emergency room visits, reduces the risk for death, and improves the quality of life for children with asthma.<xref rid="bib10" ref-type="bibr">4</xref>, <xref rid="bib12" ref-type="bibr">6</xref>, <xref rid="bib13" ref-type="bibr">7</xref> The hospitalist is ideally situated to have a major impact on asthma by treating its acute manifestations, by implementing effective long-term therapy when indicated, and by diagnosing and managing any comorbidity that accompanies or exacerbates asthma (or both).</p><p id="para4">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 as follows:</p><p id="para5">“A chronic inflammatory disorder of the airways in which many cells play a role, in particular, mast cells, eosinophils, and T lymphocytes. 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.”<xref rid="bib10" ref-type="bibr"><sup>4</sup></xref></p><sec id="cesec1"><title>PATHOPHYSIOLOGY OF ASTHMA</title><p id="para6">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 infiltration of the airway with neutrophils, eosinophils, and lymphocytes.<xref rid="bib14" ref-type="bibr"><sup>8</sup></xref> Whatever the cause, the inflammation results in airway hyperresponsiveness, which causes bronchoconstriction, edema, and mucous plugging, all of which contribute to bronchial obstruction. Chronically, collagen deposition below the epithelial basement membrane results in narrowing of the airway secondary to remodeling</p></sec><sec id="cesec2"><title>ASTHMA EXACERBATIONS</title><p id="para7">An asthma exacerbation refers to an increase in a patient's respiratory symptoms above baseline as a result of increased airway obstruction. Status asthmaticus is continued or progressive airway obstruction despite bronchodilator therapy that results in sustained or worsening respiratory distress.<xref rid="bib10" ref-type="bibr"><sup>4</sup></xref></p><p id="para8">Acute asthma exacerbations can be triggered by infectious respiratory illness, exposure to environmental allergens or irritants, exercise, cold air, or a combination of these factors. 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 and results in rhinorrhea, sneezing, itching of the eyes and nose, and bronchospasm secondary to 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 exacerbation of asthma as a result of allergen exposure, both phases must be treated with medications to treat the symptoms of the early phase, as well as the subsequent inflammation of the late phase.<xref rid="bib15" ref-type="bibr"><sup>9</sup></xref></p><p id="para9">Viral infections cause asthma symptoms by promoting eosinophilic or neutrophilic airway inflammation.<xref rid="bib10" ref-type="bibr"><sup>4</sup></xref> 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.<xref rid="bib16" ref-type="bibr">10</xref>, <xref rid="bib17" ref-type="bibr">11</xref> The risk for exacerbation of asthma can be modified by a patient's underlying inflammatory state and level of airway hyperreactivity. A patient with reduced airway inflammation because of adequate controller therapy is less likely to have a severe asthma flare when exposed to offending agents.</p></sec><sec id="cesec3"><title>CLINICAL PRESENTATION</title><p id="para10">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.<xref rid="bib18" ref-type="bibr"><sup>12</sup></xref></p><p id="para11">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 abdominal girth with inspiration) is another useful sign of increased work of breathing. Auscultation of the chest frequently reveals wheezing and a prolonged expiratory phase. Rales or crackles are often heard and may shift in location over a period of minutes to hours (“migratory atelectasis”). 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 because 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 and somnolence are worrisome signs and may indicate hypoxemia or hypercapnia with impending respiratory failure.</p><p id="para12">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 that for classic asthma.</p></sec><sec id="cesec4"><title>DIFFERENTIAL DIAGNOSIS</title><p id="para13">Many conditions result in acute or chronic respiratory symptoms that mimic an asthma syndrome. Some of these conditions are discussed in the following text.</p><p id="para14">Anatomic abnormalities should be considered in young children with frequent episodes of cough or wheezing. Inhaled foreign bodies are most common in toddler-aged children (Chapter 79). These problems may manifest as cough, stridor, or wheezing. In all age groups, gastroesophageal reflux can mimic or contribute to underlying asthma (Chapter 101).<xref rid="bib19" ref-type="bibr">13</xref>, <xref rid="bib20" ref-type="bibr">14</xref> Cystic fibrosis is a genetic disorder that can also present with chronic cough or recurrent episodes of wheezing (Chapter 78).</p><p id="para15">Viral infections often cause wheezing in childhood as well. Respiratory syncytial virus is the most common cause of infantile bronchiolitis, but other respiratory viruses such as rhinovirus, parainfluenza virus, coronavirus, adenovirus, and influenza viruses are also common infectious agents.<xref rid="bib21" ref-type="bibr"><sup>15</sup></xref> Viral bronchiolitis is associated with edema, bronchospasm, and increased mucus production of the smaller airways, features that overlap with asthma (Chapter 66). Because these respiratory viral infections are known to precipitate asthma exacerbations, it may be difficult to determine whether the wheezing represents an isolated episode of bronchiolitis or an asthma exacerbation triggered by the respiratory virus.</p><p id="para16">Atypical respiratory infections with agents such as <italic>Mycoplasma</italic>, <italic>Chlamydia pneumoniae</italic>, and <italic>Bordetella pertussis</italic> or <italic>parapertussis</italic> can present with chronic cough. Coughing associated with these infections can persist for several months.</p><p id="para17">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 or expiratory stridor, or both, 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 during inspiration.<xref rid="bib22" ref-type="bibr">16</xref>, <xref rid="bib23" ref-type="bibr">17</xref>, <xref rid="bib24" ref-type="bibr">18</xref>, <xref rid="bib25" ref-type="bibr">19</xref> Psychogenic cough is a habitual cough that can also persist for months, and it often occurs after an acute respiratory illness.<xref rid="bib26" ref-type="bibr"><sup>20</sup></xref> Habitual cough has a characteristic sound described as barky or honking. The cough is exaggerated by stress or attention to the cough and disappears with sleep.<xref rid="bib26" ref-type="bibr"><sup>20</sup></xref> These features help distinguish this entity from cough-variant asthma. A key feature of VCD and psychogenic cough is lack of response to asthma therapy.<xref rid="bib22" ref-type="bibr">16</xref>, <xref rid="bib23" ref-type="bibr">17</xref>, <xref rid="bib24" ref-type="bibr">18</xref>, <xref rid="bib25" ref-type="bibr">19</xref>, <xref rid="bib26" ref-type="bibr">20</xref> In addition, they are not associated with hypoxia.</p></sec><sec id="cesec5"><title>EVALUATION</title><p id="para18">The initial evaluation of a patient presenting with an asthma exacerbation should include assessment of the acute respiratory symptoms, signs or symptoms of coexisting or precipitating conditions, and treatments initiated before presentation. A history should be obtained of the characteristics of the patient's asthma symptoms, the pattern and frequency of the symptoms, and any precipitating or aggravating factors, as well as features indicative of the severity and level of control of the asthma (<xref rid="cetable1" ref-type="table">Table 75-1</xref>, <xref rid="cetable2" ref-type="table">Table 75-2</xref>).<xref rid="bib10" ref-type="bibr"><sup>4</sup></xref><table-wrap position="float" id="cetable1"><label>Table 75-1</label><caption><p>Questions to Ask Patients Who Present with Wheezing</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left"><bold>Types of Symptoms</bold><break></break>Cough<break></break>Wheeze<break></break>Shortness of breath<break></break>Chest tightness<break></break>Sputum production</td></tr><tr><td align="left"><bold>Frequency of Symptoms</bold><break></break>Daily, weekly, none<break></break>Perennial, seasonally<break></break>Do they have a night cough?<break></break>Do they cough with activity?<break></break>How often do they use their albuterol?</td></tr><tr><td align="left"><bold>Severity of Symptoms</bold><break></break>How often do they have flares of their asthma?<break></break>How many times in the last year?<break></break>How many times have they used oral steroids?<break></break>How many times in the last year?<break></break>How many emergency room visits?<break></break>How many visits to the hospital?<break></break>Have they ever been in the intensive care unit?</td></tr></tbody></table></table-wrap><table-wrap position="float" id="cetable2"><label>Table 75-2</label><caption><p>Features That Place Patient at Risk for Severe Asthma</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left">History of respiratory failure with asthma</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td align="left">Recent or multiple emergency department visits or hospitalizations (<6 months)</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td align="left">Daily oral steroid use at the time of exacerbations</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td align="left">Comorbid psychosocial conditions that interfere with administration of medications</td></tr></tbody></table></table-wrap></p><p id="para19">The physical examination provides clues to the severity of the current illness, as well as the presence of comorbid conditions. Important physical parameters include the respiratory rate, work of breathing, air entry, wheezing, and oxygen saturation. Work of breathing refers to the use of accessory muscles of respiration and involves nasal flaring, abdominal retractions, and depth of respiration.</p><p id="para20">During an exacerbation of asthma, physical findings may vary and evolve with treatment or progression of the acute condition. A quiet or silent chest is a worrisome sign because 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, pleural effusion (especially in dependent regions of the lung), or atelectasis. Unilateral breath sounds may indicate an aspirated foreign body or pneumothorax on the side with diminished breath sounds<xref rid="bib10" ref-type="bibr"><sup>4</sup></xref> and may be accompanied by hyperresonance on that side, especially if significant air trapping is present.</p><p id="para21">Chest radiographs are not typically needed for patients with known asthma and a straightforward asthma exacerbation.<xref rid="bib27" ref-type="bibr"><sup>21</sup></xref> Typical radiographic findings include hyperinflation, peribronchial thickening, and atelectasis (<xref rid="f1" ref-type="fig">Fig. 75-1</xref>). Chest radiographs may be helpful when there is concern for pneumonia, pleural effusion, pneumothorax, pneumomediastinum, or foreign body aspiration.<fig id="f1"><label>Figure 75-1</label><caption><p>Typical radiographic findings of hyperinflation and peribronchial thickening in a patient with an acute asthma exacerbation. Flattening of the diaphragms is prominent in both the anteroposterior (A) and lateral (B) view. The lateral view demonstrates a widened anteroposterior diameter and increased prominence of the retrocardiac space.</p></caption><graphic xlink:href="gr1"></graphic></fig></p><p id="para22">A classification system for determining the severity of an asthma exacerbation in children 5 years of age or older is provided in <xref rid="cetable3" ref-type="table">Table 75-3</xref>. 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 wheezing, and are often hypoxic. Signs of impending respiratory failure are provided in <xref rid="cetable4" ref-type="table">Table 75-4</xref>. For infants and children younger than 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 range. 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-wrap position="float" id="cetable3"><label>Table 75-3</label><caption><p>Clinical Classification of Severity for Asthma Exacerbation</p></caption><table frame="hsides" rules="groups"><thead><tr><th><hr></hr></th><th colspan="4" align="center"><sc>Severity of Exacerbation</sc><hr></hr></th></tr><tr><th></th><th align="left" valign="bottom"><italic>Mild</italic></th><th align="left" valign="bottom"><italic>Moderate</italic></th><th align="left" valign="bottom"><italic>Severe</italic></th><th align="left"><italic>Impending Respiratory Failure</italic></th></tr></thead><tbody><tr><td><bold>Symptoms</bold></td><td></td><td></td><td></td><td></td></tr><tr><td>Breathlessness</td><td>While walking</td><td>While talking (infants: softer, shorter cry; difficulty feeding)</td><td>While at rest (infants: stop feeding)</td><td></td></tr><tr><td>Positioning</td><td>Can lie down</td><td>Prefers sitting</td><td>Sits upright</td><td></td></tr><tr><td>Speaks in</td><td>Sentences</td><td>Phrases</td><td>Words</td><td></td></tr><tr><td>Alertness</td><td>May be agitated</td><td>Usually agitated</td><td>Usually agitated</td><td>Drowsy or confused</td></tr><tr><td><bold>Signs</bold></td><td></td><td></td><td></td><td></td></tr><tr><td>Respiratory rate</td><td>Increased</td><td>Increased</td><td>Often >30/min</td><td></td></tr><tr><td>Use of accessory muscles, suprasternal retractions</td><td>Usually not</td><td>Commonly</td><td>Usually</td><td>Paradoxical thoracoabdominal movement</td></tr><tr><td>Wheezing</td><td>Moderate, often only end expiratory</td><td>Loud, throughout exhalation</td><td>Usually loud, throughout inhalation and exhalation</td><td>Absence of wheezing</td></tr><tr><td>Pulse/min</td><td><100</td><td>100-120</td><td>>120</td><td>Tachycardia or bradycardia</td></tr><tr><td>Pulsus paradoxus</td><td align="center">Absent (<10 mm Hg)</td><td>May be present (10-25 mm Hg)</td><td>Often present (>25 mm Hg for an adult, 20-40 mm Hg for a child)</td><td>Absence suggests respiratory muscle fatigue</td></tr><tr><td><bold>Functional Assessment</bold></td><td></td><td></td><td></td><td></td></tr><tr><td>PEF, % predicted or % personal best</td><td>80%</td><td>∼50%-80%</td><td><50% of predicted or personal best</td><td></td></tr><tr><td>PaO<sub>2</sub> (on room air)</td><td>Normal (test not usually necessary)</td><td>>60 mm Hg (test not usually necessary)</td><td><60 mm Hg, possible cyanosis</td><td></td></tr><tr><td>And/or PaCO<sub>2</sub></td><td><42 mm Hg</td><td><42 mm Hg</td><td>>42 mm Hg, possible respiratory failure</td><td></td></tr><tr><td>SaO<sub>2</sub> (on room air) at sea level</td><td>>95%</td><td>91%-95%</td><td><91 %</td><td></td></tr></tbody></table><table-wrap-foot><fn><p>Asthma exacerbation usually includes several parameters, but not necessarily all. These parameters serve only as general guidelines because many have not been systemically studied.</p></fn></table-wrap-foot><attrib>Adapted from Moss MH, Gern JE, Lemanske RF Jr: Asthma in infancy and childhood. In Adkinson NF Jr, Yunginger JW, Busse WW, et al (eds): Middleton's Allergy Principles and Practice, 6th ed. Philadelphia, CV Mosby, 2003. Available at <ext-link ext-link-type="uri" xlink:href="http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.p107" id="interref1"><italic>http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.p107</italic></ext-link>.</attrib></table-wrap><table-wrap position="float" id="cetable4"><label>Table 75-4</label><caption><p>Indicators of Impending Respiratory Failure</p></caption><table frame="hsides" rules="groups"><tbody><tr><td>Poor air movement or silent chest in combination with increased respiratory effort, decreased respiratory rate, or disorganized breathing pattern</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td>Inability to speak</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td>Inability to lie supine</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td>Deteriorating mental status, lethargy, or agitation</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td>Diaphoresis</td></tr><tr><td colspan="1"><hr></hr></td></tr><tr><td>Respiratory or cardiac arrest</td></tr></tbody></table></table-wrap></p><p id="para23">Objective measures for evaluation of acute asthma include pulmonary function testing, pulse oximetry, and arterial blood gases. Patients with exacerbations of asthma are at risk for hypoxemia. As a result, patients require frequent monitoring to ensure adequate oxygenation. Continuous pulse oximetry is recommended during a severe exacerbation, whereas intermittent oximetry may be acceptable as the clinical course improves.</p><p id="para24">Arterial blood gas parameters are typically obtained in critically ill patients and those with clinical deterioration or signs of respiratory insufficiency or failure. Arterial blood gases may reveal hypoxemia from ventilation-perfusion mismatch and respiratory alkalosis with hypocapnia secondary to hyperventilation. A normal or elevated partial pressure of carbon dioxide (Paco<sub>2</sub>) may be the harbinger of respiratory failure<xref rid="bib28" ref-type="bibr"><sup>22</sup></xref> and may be associated with decreased blood pH because of respiratory acidosis.</p><p id="para25">Pulmonary function tests can be used to assess lung function even during an asthma exacerbation. Spirometric indices such as forced expiratory volume in 1 second (FEV<sub>1</sub>) or the peak expiratory flow rate (PEFR) are most useful to assess the severity of asthma. However, because spirometry is often not readily available in the acute care setting, PEFR can be used instead. The hand-held peak flowmeter measures PEFR, and normal values have been established according to age, gender, and height<xref rid="bib29" ref-type="bibr"><sup>23</sup></xref> (<xref rid="cetable5" ref-type="table">Table 75-5</xref>). 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, FEV<sub>1</sub> is typically 30% to 35% of normal<xref rid="bib30" ref-type="bibr"><sup>24</sup></xref> and PEFR is less than 50% of normal. Monitoring PEFR can also assist in tapering medication during the recovery phase of an acute hospitalization. PEFR is effort and technique dependent, and therefore reliability remains a concern. It should be used in conjunction with other parameters of severity for assessment of patients (see Chapter 80).<table-wrap position="float" id="cetable5"><label>Table 75-5</label><caption><p>Predicted Average Peak Expiratory Flow (L/min): Normal Children and Adolescents</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="2" align="center"><sc>Height</sc><hr></hr></th><th><hr></hr></th><th colspan="2" align="center"><sc>Height</sc><hr></hr></th><th><hr></hr></th><th colspan="2" align="center"><sc>Height</sc><hr></hr></th><th><hr></hr></th></tr><tr><th align="left"><italic>in</italic></th><th align="left"><italic>cm</italic></th><th>Males and Females</th><th align="left"><italic>in</italic></th><th align="left"><italic>cm</italic></th><th>Males and Females</th><th align="left"><italic>in</italic></th><th align="left"><italic>cm</italic></th><th>Males and Females</th></tr></thead><tbody><tr><td>43</td><td>109</td><td align="center">147</td><td>51</td><td>130</td><td align="center">254</td><td>59</td><td>150</td><td align="center">360</td></tr><tr><td colspan="9"><hr></hr></td></tr><tr><td>44</td><td>112</td><td align="center">160</td><td>52</td><td>132</td><td align="center">267</td><td>60</td><td>152</td><td align="center">373</td></tr><tr><td colspan="9"><hr></hr></td></tr><tr><td>45</td><td>114</td><td align="center">173</td><td>53</td><td>135</td><td align="center">280</td><td>61</td><td>155</td><td align="center">387</td></tr><tr><td colspan="9"><hr></hr></td></tr><tr><td>46</td><td>117</td><td align="center">187</td><td>54</td><td>137</td><td align="center">293</td><td>62</td><td>157</td><td align="center">400</td></tr><tr><td colspan="9"><hr></hr></td></tr><tr><td>47</td><td>119</td><td align="center">200</td><td>55</td><td>140</td><td align="center">307</td><td>63</td><td>160</td><td align="center">413</td></tr><tr><td colspan="9"><hr></hr></td></tr><tr><td>48</td><td>122</td><td align="center">214</td><td>56</td><td>142</td><td align="center">320</td><td>64</td><td>162</td><td align="center">427</td></tr><tr><td colspan="9"><hr></hr></td></tr><tr><td>49</td><td>124</td><td align="center">227</td><td>57</td><td>145</td><td align="center">334</td><td>65</td><td>165</td><td align="center">440</td></tr><tr><td colspan="9"><hr></hr></td></tr><tr><td>50</td><td>127</td><td align="center">240</td><td>58</td><td>147</td><td align="center">347</td><td>66</td><td>168</td><td align="center">454</td></tr></tbody></table><table-wrap-foot><fn><p>This table is a guideline. National Heart, Lung, and Blood Institute guidelines suggest using a personal best as baseline values.</p></fn></table-wrap-foot><attrib>From Polgar G, Promahcat V: Pulmonary Function Testing in Children. Techniques and Standards. Philadelphia, WB Saunders, 1971.</attrib></table-wrap></p></sec><sec id="cesec6"><title>TREATMENT</title><p id="para26">Exacerbations of asthma are treated with a combination of supportive therapy and pharmacologic interventions. Treatment is tailored to the severity of symptoms and adjusted according to the patient's 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 saturation in a safe range. This range is widely debated, but most agree that levels greater than 91% are needed, and many target levels to greater than 93% to 95%.</p><sec id="cesec7"><title>Adrenergic Agonists</title><p id="para27">This class of medications works by stimulating the β<sub>2</sub>-adrenergic receptor and causing activation of adenyl cyclase, which increases the production of cyclic 3′,5-adenosine monophosphate (cAMP). This increase in cAMP, depending on the site of stimulation, results in relaxation of bronchial smooth muscle, stimulation of skeletal and cardiac muscle, and inhibition of the release of inflammatory mediators through stabilization of the mast cell membrane. Albuterol is one of the short-acting β<sub>2</sub>-adrenergic agents used as first-line therapy for an acute asthma exacerbation because of its ability to rapidly 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.<xref rid="bib31" ref-type="bibr">25</xref>, <xref rid="bib32" ref-type="bibr">26</xref>, <xref rid="bib33" ref-type="bibr">27</xref> 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 <xref rid="cetable6" ref-type="table">Table 75-6</xref>.<table-wrap position="float" id="cetable6"><label>Table 75-6</label><caption><p>Dosages of Bronchodilators Commonly Used for Asthma Exacerbations</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Medications</th><th align="left">Adult Dose</th><th align="left">Child Dose</th><th align="left">Onset of Action</th><th align="left">Duration</th><th align="left">Comments</th></tr></thead><tbody><tr><td colspan="2"><bold>Inhaled Short-Acting β<sub>2</sub>-Agonists</bold></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Albuterol nebulizer<break></break> 5.0 mg/mL<break></break> 2.5 mg/3 mL<break></break> 1.25 mg/3 mL<break></break> 0.63 mg/3 mL</td><td align="left">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/hr continuously</td><td align="left">0.15 mg/kg (minimum dose, 2.5 mg) every 20 minutes for 3 doses, then 0.15-0.3 mg/kg up to 10 mg every 1-4 hours as needed or 0.5 mg/kg/hr by continuous nebulization</td><td align="left">15 minutes</td><td align="left">3-4 hours</td><td align="left">Only selective β<sub>2</sub>-agonists are recommended.<break></break>For optimal delivery, dilute aerosols to minimum of 4 mL at gas flow rates of 6-8 L/min</td></tr><tr><td align="left">Albuterol via MDI<break></break> 90 μg/puff</td><td align="left">2-8 puffs every 20 minutes up to 4 hours, then every 1-4 hours as needed</td><td align="left">2-8 puffs every 20 minutes for 3 doses, then every 1-4 hours inhalation maneuver. A spacer or holding chamber should be used</td><td align="left">15 minutes</td><td align="left">3-4 hours</td><td align="left">As effective as nebulized therapy if patient is able to coordinate</td></tr><tr><td align="left">Levalbuterol via nebulizer<break></break> 0.31 mg/3 mL<break></break> 0.63 mg/3 mL<break></break> 1.25 mg/3 mL</td><td align="left">Adults: 0.63 mg 3 times/day, may be increased to 1.25 mg</td><td align="left">Children 6-11 years: 0.31 mg 3 times/day every 6-8 hours<break></break>Children >12 years: 0.63 mg 3 times/day, may be increased to 1.25 mg</td><td align="left">15 minutes</td><td align="left">5-6 hours</td><td align="left">0.63 mg of levalbuterol is equivalent to 1.25 mg of racemic albuterol in both efficacy and side effects</td></tr><tr><td align="left">Levalbuterol via MDI</td><td align="left">1-2 puffs every 4-6 hours as needed</td><td align="left">1-2 puffs every 4-6 hours as needed</td><td align="left">5-10 minutes</td><td align="left">3-6 hours</td><td align="left">Children 2-11 years: in a randomized, double-blind, single-dose, crossover study, doses ranging from 0.16 to 1.25 mg were used safely with clinically significant improvements in pulmonary function test values</td></tr><tr><td align="left"><bold>Anticholinergics</bold></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td align="left">Ipratropium bromide Nebulizer solution<break></break> (0.25 mg/mL)</td><td align="left">0.5 mg every 30 minutes for 3 doses, then every 2-4 hours as needed</td><td align="left">0.25 mg every 20 minutes for 3 doses, then every 2-4 hours</td><td align="left">1-3 minutes</td><td align="left">3-6 hours</td><td align="left">May mix in same nebulizer with albuterol. Should not be used as first-line therapy.<break></break>Should be added to β<sub>2</sub>-agonist therapy</td></tr><tr><td align="left"> MDI (18 μg/puff)</td><td align="left">2-8 puffs as needed</td><td align="left">4-8 puffs as needed</td><td align="left">1-3 minutes</td><td align="left">3-6 hours</td><td align="left">Dose in MDI is low and has not been studied in asthma exacerbations</td></tr></tbody></table><table-wrap-foot><fn><p>MDI, metered-dose inhaler.</p></fn></table-wrap-foot><attrib>Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report II: Guidelines for the Diagnosis and Management of Asthma (NIH Publication No. 96-4051). Bethesda, MD, U.S. Department of Health and Human Services, National Institutes of Health, 1997, 2002.</attrib></table-wrap></p><p id="para28">Paradoxical and transient worsening of hypoxia because of increased ventilation-perfusion mismatching can be seen with the administration of albuterol. The medication causes increased cardiac output, which leads to increased perfusion of unventilated lung.<xref rid="bib34" ref-type="bibr"><sup>28</sup></xref> Other side effects include sinus tachycardia, tremor, palpitations, headache, agitation, and ventricular irritability (e.g., ventricular premature contractions, ventricular tachycardia). In addition, because frequent or continuous dosing with adrenergic agents can lead to hypokalemia, patients receiving such treatment should have serum potassium levels checked periodically. Nonselective adrenergic agents (e.g., epinephrine) can also cause transient hyperglycemia and elevations in the neutrophil count as a result of demargination.</p><p id="para29">Albuterol is actually a racemic mixture of <italic>R</italic>-albuterol and <italic>S</italic>-albuterol, with a 50:50 ratio of these two stereoisomers. Levalbuterol (Xopenex) is made up of the <italic>R</italic>-isomer, which is thought to be the active component of the racemic product. However, <italic>S</italic>-albuterol has been found to have some bronchoconstrictive activity in select studies, but not in others, and demonstrates activation of eosinophils in vitro. In addition, <italic>S</italic>-albuterol is cleared much less rapidly, which can cause buildup of this isomer in vivo as opposed to the <italic>L</italic>-isomer. However, the vast majority of clinical studies and in vitro pharmacology data have shown no significant differences in cardiopulmonary side effects and tremor when comparing racemic with <italic>R</italic>-isomer albuterol.<xref rid="bib35" ref-type="bibr">29</xref>, <xref rid="bib36" ref-type="bibr">30</xref>, <xref rid="bib37" ref-type="bibr">31</xref> One study found decreased rates of admission from an emergency department with the use of levalbuterol versus racemic albuterol.<xref rid="bib38" ref-type="bibr"><sup>32</sup></xref> Another study showed improved bronchodilation,<xref rid="bib39" ref-type="bibr"><sup>33</sup></xref> but these findings have not been confirmed in other studies.<xref rid="bib35" ref-type="bibr">29</xref>, <xref rid="bib36" ref-type="bibr">30</xref>, <xref rid="bib40" ref-type="bibr">34</xref></p><p id="para30">Terbutaline, a selective β<sub>2</sub>-adrenergic agonist, and epinephrine, a nonselective adrenergic agonist, are used in asthmatics not responding to albuterol and corticosteroids or those 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.<xref rid="bib41" ref-type="bibr">35</xref>, <xref rid="bib42" ref-type="bibr">36</xref> Terbutaline can also be given via continuous intravenous infusion by starting with a bolus and titrating the dose to the desired effect.</p><p id="para31">Dosing of β<sub>2</sub>-adrenergic agonists and other bronchodilators is shown in <xref rid="cetable6" ref-type="table">Table 75-6</xref>, <xref rid="cetable7" ref-type="table">Table 75-7</xref>.<table-wrap position="float" id="cetable7"><label>Table 75-7</label><caption><p>Systemic (Injected) Bronchodilators for Acute Asthma Exacerbations</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="bottom">Medications</th><th align="left" valign="bottom">Adult Dose</th><th align="left" valign="bottom">Child Dose</th><th align="left" valign="bottom">Onset of Action</th><th align="left" valign="bottom">Duration</th><th align="left" valign="bottom">Comments</th></tr></thead><tbody><tr><td colspan="6"><bold>ß<sub>2</sub>-Agonists</bold></td></tr><tr><td align="left">Epinephrine 1 : 1000 (1 mg/mL) by IV infusion</td><td align="left">0.3-0.5 mg every 20 minutes for 3 doses<break></break>SC Loading dose: 2-10 μg/kg, followed by continuous infusion of 0.08-0.4 μg/kg/ min; titrate dose by clinical response up to 6 μg/kg/min</td><td align="left">0.01 mg/kg up to 0.3-0.5 mg every 20 minutes for 3 doses SC</td><td align="left">1-3 minutes</td><td align="left">30 minutes</td><td align="left">No proven advantage of systemic therapy over aerosol</td></tr><tr><td align="left">Terbutaline (1 mg/mL) by IV infusion</td><td align="left">0.25 mg every 20 minutes for 3 doses SC<break></break>Loading dose: 2-10 μg/kg followed by continuous infusion of 0.08-0.4 μg/kg/min; titrate dose by clinical response up to 6 μg/kg/min</td><td align="left">0.01 mg/kg every 20 minutes for 3 doses, then every 2-6 hours as needed SC<break></break>Loading dose: 2-10 μg/kg followed by continuous infusion of 0.08-0.4 μg/kg/min; titrate dose by clinical response up to 6 μg/kg/min</td><td align="left">SC: 6-15 minutes</td><td align="left">SC: 1.5-4 hours</td><td></td></tr></tbody></table></table-wrap></p></sec><sec id="cesec8"><title>Corticosteroids</title><p id="para32">Corticosteroids are indicated for the initial treatment of status asthmaticus. They are potent anti-inflammatory medications that have been shown to hasten recovery, prevent recurrence,<xref rid="bib43" ref-type="bibr">37</xref>, <xref rid="bib44" ref-type="bibr">38</xref>, <xref rid="bib45" ref-type="bibr">39</xref>, <xref rid="bib46" ref-type="bibr">40</xref>, <xref rid="bib47" ref-type="bibr">41</xref> and prevent hospitalizations.<xref rid="bib48" ref-type="bibr"><sup>42</sup></xref> Because of their mechanism of action, the effect of corticosteroids is not immediate. Steroids bind to the intracytoplasmic glucocorticoid receptor and translocate to the nucleus, where they effect RNA transcription in both positive and negative fashion through the transcription factors NF-κB and AP-1. In general, steroids lead to down-regulation of inflammatory cytokines. Corticosteroids also activate histone deacetylase, which inhibits DNA transcription.<xref rid="bib49" ref-type="bibr"><sup>43</sup></xref> This change in transcription leads to increased expression of the β<sub>2</sub>-adrenergic receptor and decreases in airway inflammation and mucus secretion. It can take several hours to reverse airway inflammation, and benefits are typically seen within 4 hours after the administration of corticosteroids.<xref rid="bib44" ref-type="bibr">38</xref>, <xref rid="bib45" ref-type="bibr">39</xref>, <xref rid="bib50" ref-type="bibr">44</xref> Studies comparing oral and intravenous corticosteroids have found no significant differences in efficacy.<xref rid="bib51" ref-type="bibr">45</xref>, <xref rid="bib52" ref-type="bibr">46</xref> Oral steroids are typically preferred because intravenous access is not required.<xref rid="bib51" ref-type="bibr">45</xref>, <xref rid="bib53" ref-type="bibr">47</xref> Suggested dosing of corticosteroids is provided in <xref rid="cetable8" ref-type="table">Table 75-8</xref>.<table-wrap position="float" id="cetable8"><label>Table 75-8</label><caption><p>Systemic Corticosteroids in the Setting of Asthma Exacerbations</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="bottom">Medication</th><th align="left" valign="bottom">Adult Dose</th><th align="left">Child Dose (≤ 12 Years Old)</th><th align="left">Onset of Action</th><th align="left" valign="bottom">Duration</th><th align="left" valign="bottom">Comments</th></tr></thead><tbody><tr><td align="left">Oral—prednisone/ prednisolone<break></break>IV— methylprednisolone</td><td align="left">120-180 mg/day in 3-4 divided doses for 48 hours, then 60-80 mg/day until PEF reaches 70% of predicted or personal best</td><td align="left">1 mg/kg every 6 hours for 48 hours, then 1-2 mg/kg/day (maximum, 60 mg/ day) in 2 divided doses until PEF is 70% of predicted or personal best</td><td align="left">1-4 hours (variable)<break></break><break></break>1-4 hours (variable)</td><td align="left">12-36 hours</td><td align="left">For outpatient burst for 3-10 days:<list list-type="simple" id="celist1"><list-item id="celistitem1"><p id="para1">Adult: use 40-60 mg in single or 2 divided doses</p></list-item><list-item id="celistitem2"><p id="para2">Children: use 1-2 mg/kg/ day with maximum of 60 mg/day</p></list-item></list></td></tr><tr><td colspan="6"><hr></hr></td></tr><tr><td align="left">IM methylprednisolone 40 mg/mL 80 mg/mL</td><td align="left">240 mg IM once</td><td align="left">7.5 mg/kg IM once</td><td align="left">1-4 hours (variable)</td><td align="left">36-72 hours</td><td align="left">IM should be used in place of a short burst of oral steroids in patients who are vomiting or if adherence is a problem</td></tr></tbody></table><table-wrap-foot><fn><p>PEF, peak expiratory flow.</p></fn></table-wrap-foot><attrib>Adapted From National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report II: Guidelines for the Diagnosis and Management of Asthma (NIH Publication No. 96-4051). Bethesda, MD, U.S. Department of Health and Human Services, National Institutes of Health, 1997. Available at <ext-link ext-link-type="uri" xlink:href="http://www.nhlbi.nih.gov/guidelines/asthma/asthmafullrpt.pdf" id="interref2"><italic>http://www.nhlbi.nih.gov/guidelines/asthma/asthmafullrpt.pdf</italic></ext-link>.</attrib></table-wrap></p></sec><sec id="cesec9"><title>Inhaled Anticholinergic Agents</title><p id="para33">Anticholinergic agents work by competitively inhibiting acetylcholine at the muscarinic junction to relieve the 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.<xref rid="bib54" ref-type="bibr"><sup>48</sup></xref></p><p id="para34">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 in comparison to β<sub>2</sub>-agonists alone, whereas others have shown a slight advantage of one to three doses in the initial phase of an acute asthma exacerbation.<xref rid="bib55" ref-type="bibr"><sup>49</sup></xref> The role of ipratropium in hospitalized patients is less clear, but an initial study did not show clinical benefit.<xref rid="bib56" ref-type="bibr"><sup>50</sup></xref></p><p id="para35">Combined administration of anticholinergic and β<sub>2</sub>-agonist medications increases bronchodilation, although some controversy about this effect persists.<xref rid="bib55" ref-type="bibr">49</xref>, <xref rid="bib56" ref-type="bibr">50</xref> Nonetheless, many institutions use a combination of β<sub>2</sub>-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 <xref rid="cetable6" ref-type="table">Table 75-6</xref>.</p></sec><sec id="cesec10"><title>Nonstandard Therapies</title><p id="para36">If initiation of the aforementioned 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 such decisions. Safe transfer to a facility able to provide critical care management should be anticipated, and arrangements should be expedited.</p><sec id="cesec11"><title>Magnesium Sulfate</title><p id="para37">Magnesium sulfate has been studied as a bronchodilator in severe asthma, with conflicting results.<xref rid="bib57" ref-type="bibr">51</xref>, <xref rid="bib58" ref-type="bibr">52</xref>, <xref rid="bib59" ref-type="bibr">53</xref>, <xref rid="bib60" ref-type="bibr">54</xref> Magnesium is thought to inhibit mast cell degranulation and increase bronchial dilation because of a decrease in calcium uptake by bronchial smooth muscle.<xref rid="bib61" ref-type="bibr"><sup>55</sup></xref> Its use is considered when a patient fails to improve or worsens despite treatment with continuous inhaled β<sub>2</sub>-agonists, systemic corticosteroids, and inhaled anticholinergic agents.</p></sec><sec id="cesec12"><title>Methylxanthines</title><p id="para38">Intravenous methylxanthines, such as aminophylline, were commonly used in the past to manage asthma exacerbations because of their ability to act directly on β-adrenergic receptors and relax bronchial smooth muscle. Concern regarding the toxicity and efficacy of this class of medication and the availability of newer agents have limited its use. Methylxanthines may help prevent acute airway hyperresponsiveness but do not appear to produce these effects chronically.<xref rid="bib62" ref-type="bibr">56</xref>, <xref rid="bib63" ref-type="bibr">57</xref>, <xref rid="bib64" ref-type="bibr">58</xref> However, life-threatening events such as cardiac arrhythmia and seizures are associated with toxic levels of theophylline (>30 μg/mL). As a result, methylxanthines are recommended only as adjunctive therapy with close monitoring of serum concentrations and cardiac monitoring.</p><p id="para39">Studies examining the use of intravenous methylxanthines in children and adults with severe asthma have shown mixed benefit.<xref rid="bib65" ref-type="bibr">59</xref>, <xref rid="bib66" ref-type="bibr">60</xref>, <xref rid="bib67" ref-type="bibr">61</xref>, <xref rid="bib68" ref-type="bibr">62</xref>, <xref rid="bib69" ref-type="bibr">63</xref>, <xref rid="bib70" ref-type="bibr">64</xref> A recent Cochrane review found that theophylline in addition to β<sub>2</sub>-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.<xref rid="bib71" ref-type="bibr"><sup>65</sup></xref></p><p id="para40">Aminophylline requires a loading dose followed by a continuous infusion to reach and maintain a therapeutic level (see <xref rid="cetable9" ref-type="fig">Table 75-9</xref>). Dosing is titrated according to serum level, clinical efficacy, and side effects.<fig id="cetable9"><label>Table 75-9</label><caption><p>Nonstandard Therapies for Exacerbations of Asthma</p><p>Rights were not granted to include this table in electronic media. Please refer to the printed book.</p></caption><graphic xlink:href="table75-9"></graphic></fig></p></sec><sec id="cesec13"><title>Heliox</title><p id="para41">Heliox is a mixture of helium and oxygen used for inhalation. This agent is thought to improve airflow by creating gas with similar viscosity to air but with lower density, which in turn can increase ventilation and decrease work of breathing.<xref rid="bib72" ref-type="bibr">66</xref>, <xref rid="bib73" ref-type="bibr">67</xref>, <xref rid="bib74" ref-type="bibr">68</xref> Heliox is indicated in patients with a refractory exacerbation of asthma in whom respiratory failure is impending. Patients with high oxygen requirements may not be able to tolerate heliox because they need a higher Fio<sub>2</sub> than a helium-oxygen mixture can provide. Heliox can also lower body temperature because of the high thermal conductivity of the mixture. Therefore, patients need to have their temperature monitored closely.</p><p id="para42">Dosing of nonstandard therapies is shown in <xref rid="cetable9" ref-type="fig">Table 75-9</xref>, and adverse effects of medication are listed in <xref rid="cetable10" ref-type="table">Table 75-10</xref>.<table-wrap position="float" id="cetable10"><label>Table 75-10</label><caption><p>Common Side Effects of Pharmacologic Therapies</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Side Effect</th><th align="left">Possible Causative Agent</th><th align="left">Comment</th></tr></thead><tbody><tr><td align="left">Hypokalemia</td><td align="left">Adrenergic agonists</td><td align="left">Patients using prolonged hourly or continuous inhaled therapy or intravenous therapy should have serum potassium levels monitored</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Tremor/agitation</td><td align="left">Adrenergic agonists</td><td align="left">Dose dependent</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Hypertension</td><td align="left">Corticosteroids, adrenergic agonists</td><td align="left">May require reduction of dose, discontinuation of therapy, or addition of antihypertensive medication</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Tachycardia, palpitations, ventricular premature contractions</td><td align="left">Adrenergic agonists, aminophylline, theophylline</td><td align="left">Usually dose dependent. Serum levels of methylxanthines should be monitored. The risk is increased with hypoxemia or acidemia</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Hyperglycemia/glucosuria</td><td align="left">Corticosteroids, adrenergic agonists</td><td align="left">Resolves with completion or discontinuation of therapy</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Emotional lability</td><td align="left">Corticosteroids</td><td align="left">Resolves with completion or discontinuation of therapy</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Hyperphagia</td><td align="left">Corticosteroids</td><td align="left">Resolves with completion or discontinuation of therapy</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Seizure</td><td align="left">Theophylline, aminophylline</td><td align="left">Serum levels of methylxanthines should be monitored. Risk is increased in the presence of acidosis</td></tr><tr><td colspan="3"><hr></hr></td></tr><tr><td align="left">Elevated peripheral neutrophil count</td><td align="left">Corticosteroids, adrenergic agonists (in particular, epinephrine)</td><td align="left">May interfere with utility of the white blood count in assessing for infection</td></tr></tbody></table></table-wrap></p></sec></sec><sec id="cesec14"><title>Initial Treatment</title><p id="para43">The initial therapy for status asthmaticus has been outlined by the NHLBI guidelines (<xref rid="f2" ref-type="fig">Fig. 75-2</xref>). In brief, patients are first treated with inhaled β<sub>2</sub>-adrenergic agonists (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 with significant improvement after these initial interventions may not require hospitalization.<fig id="f2"><label>Figure 75-2</label><caption><p>NHLBI hospital assessment and management of acute exacerbation. PEF, peak expiratory flow; FEV<sub>1</sub>, forced expiratory volume in 1 second.</p></caption><graphic xlink:href="gr2"></graphic><attrib>Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report II: Guidelines for the Diagnosis and Management of Asthma [NIH Publication No. 96-4051]. Bethesda, MD, U.S. Department of Health and Human Services, National Institutes of Health, 1997.</attrib><permissions><copyright-statement>© 2007 </copyright-statement><copyright-year>2007</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></fig></p><p id="para44">Hospitalization is recommended for patients who continue to have moderately severe or severe symptoms after initial intervention. Treatment with inhaled albuterol (either every 1 to 2 hours by nebulizer or MDI with spacer or delivered continuously by nebulizer) and corticosteroid therapy (orally or, if not tolerated, intravenously) should be continued. Continuation of inhaled anticholinergic agents may be considered, although their benefit remains unproven.</p><p id="para45">If patients continue to deteriorate, they must be monitored for respiratory insufficiency and failure. An arterial blood gas measurement can be used to confirm the condition and should reveal decreased pH, elevated partial pressure of carbon dioxide (Paco<sub>2</sub>), 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 (Chapter 66). Patients with impending respiratory failure often need mechanical ventilatory support.</p></sec><sec id="cesec15"><title>Tapering Hospital Therapy</title><p id="para46">After patients are stabilized and demonstrate improvement, therapies can be gradually reduced and withdrawn. Ongoing assessment of clinical parameters is performed, including the 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<sub>2</sub>-agonists is decreased. For patients receiving continuous inhaled β<sub>2</sub>-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. Similarly, the amount of supplemental oxygen is titrated to maintain oxygen saturation 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.</p><p id="para47">Many hospitals use clinical pathways, which are tools that detail a sequence of assessments and treatments for patients with various conditions.<xref rid="bib75" ref-type="bibr"><sup>69</sup></xref> Studies have shown that asthma clinical pathways shorten hospitalization and decrease the need for readmission for up to 2 weeks after discharge.<xref rid="bib76" ref-type="bibr">70</xref>, <xref rid="bib77" ref-type="bibr">71</xref> An asthma clinical pathway allows multiple caregivers, including nurses, respiratory therapists, and doctors, to modify treatment based on structured assessments. The NHLBI guidelines (see <xref rid="f2" ref-type="fig">Fig. 75-2</xref>) 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.</p><p id="para48">PEFR measurements may be useful to determine readiness for reduction in medication. If PEFR is at least 70% of baseline before a bronchodilator treatment (see <xref rid="cetable5" ref-type="table">Table 75-5</xref>), it is appropriate to space the frequency of the β<sub>2</sub>-adrenergic agonist treatments. Technique and effort will affect measurement of PEFR; therefore, it should be used in conjunction with other clinical indicators of improvement.</p></sec><sec id="cesec16"><title>Therapy after Discharge Home</title><p id="para49">Patients should be sent home on a regimen of oral corticosteroids, the duration of which depends on 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, a prolonged course of corticosteroids will be required, followed by tapering doses. A taper is prescribed to prevent relapse of symptoms, as well as to prevent an addisonian crisis from adrenal suppression. The risk for an addisonian crisis is hypothetical and has not been demonstrated in any study.<xref rid="bib78" ref-type="bibr">72</xref>, <xref rid="bib79" ref-type="bibr">73</xref>, <xref rid="bib80" ref-type="bibr">74</xref> In addition, patients receiving their second course of steroids in a month should undergo prolonged tapering as well. A typical taper involves keeping the patient at a full daily dose of corticosteroids until stable clinical status is achieved 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, hospitalization offers an opportunity to assess the overall treatment regimen. Patients should be evaluated according to the NHLBI guidelines shown in <xref rid="cetable11" ref-type="table">Table 75-11A</xref>, <xref rid="cetable12" ref-type="table">Table 75-11B</xref>and need their outpatient preventive treatment stepped up. Specific drug choices are outlined in <xref rid="cetable13" ref-type="table">Table 75-12</xref>, <xref rid="cetable14" ref-type="table">Table 75-13</xref>, <xref rid="cetable15" ref-type="table">Table 75-14</xref>.<table-wrap position="float" id="cetable11"><label>Table 75-11A</label><caption><p>Stepwise Approach for Managing Infants and Young Children (5 Years and Younger) with Acute or Chronic Asthma</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left"><inline-graphic xlink:href="fx1.gif"></inline-graphic></td></tr></tbody></table><table-wrap-foot><fn><p>DPI, dry powder inhaler.</p></fn></table-wrap-foot><attrib>Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program: Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics (NIH Publication No. 02-5075). Bethesda, MD, US Department of Health and Human Services, National Institutes of Health, 2002. Available at <ext-link ext-link-type="uri" xlink:href="http://www.nhlbi.nih.gov/guidelines/asthma/execsumm.pdf" id="interref3">http://www.nhlbi.nih.gov/guidelines/asthma/execsumm.pdf</ext-link>.</attrib><permissions><copyright-statement>© 2007 </copyright-statement><copyright-year>2007</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></table-wrap><table-wrap position="float" id="cetable12"><label>Table 75-11B</label><caption><p>Stepwise Approach for Managing Asthma in Adults and Children Older Than 5 Years: Treatment</p></caption><table frame="hsides" rules="groups"><tbody><tr><td align="left"><inline-graphic xlink:href="fx2.gif"></inline-graphic></td></tr></tbody></table><attrib>Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program: Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics (NIH Publication No. 02-5075). Bethesda, MD, US Department of Health and Human Services, National Institutes of Health, 2002. Available at <ext-link ext-link-type="uri" xlink:href="http://www.nhlbi.nih.gov/guidelines/asthma/execsumm.pdf" id="interref4">http://www.nhlbi.nih.gov/guidelines/asthma/execsumm.pdf</ext-link>.</attrib><permissions><copyright-statement>© 2007 </copyright-statement><copyright-year>2007</copyright-year><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></table-wrap><table-wrap position="float" id="cetable13"><label>Table 75-12</label><caption><p>Preferred Treatment of Asthma According to Severity</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Severity</th><th align="left">Preferred Treatment</th><th align="left">Alternative Treatments</th><th align="left">Comments</th></tr></thead><tbody><tr><td align="left">Intermittent</td><td align="left">No daily medication needed</td><td></td><td align="left">Severe exacerbations may occur, separated by long periods of no symptoms. Treat with a course of systemic corticosteroids</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Mild persistent</td><td align="left">Low-dose inhaled corticosteroid</td><td align="left">Cromolyn<break></break>Leukotriene modifier<break></break>Nedocromil<break></break>Sustained-release theophylline (level, 5-15 μg/mL)</td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Moderate persistent</td><td align="left">Low- to medium-dose inhaled corticosteroid <italic>and</italic> long-acting inhaled ß<sub>2</sub>-agonist</td><td align="left">Increased inhaled corticosteroid within medium-dose range <italic>or</italic> low- to medium-dose inhaled corticosteroid and either a leukotriene modifier or theophylline</td><td align="left">If exacerbations occur despite daily medication, increase the inhaled corticosteroid and add a long-acting inhaled ß<sub>2</sub>-agonist</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Severe persistent</td><td align="left">High-dose inhaled corticosteroids and long-acting inhaled ß<sub>2</sub>-agonists</td><td></td><td></td></tr></tbody></table><attrib>Adapted from Bacharier LB, Strunk RC: Asthma in older children. In Leung DYM, Sampson HA, Gehr RS, Szefler SJ (eds): Pediatric Allergy: Principles and Practice. Philadelphia, CV Mosby, 2003, p 416.</attrib></table-wrap><table-wrap position="float" id="cetable14"><label>Table 75-13</label><caption><p>Usual Dosages for Long-Term Control Medications</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Medication</th><th align="left">Dosage Form</th><th align="left">Adult Dose</th><th align="left">Child Dose</th></tr></thead><tbody><tr><td colspan="4"><bold>Inhaled Corticosteroids (see estimated daily dosages for inhaled corticosteroids)</bold><break></break><bold>Systemic Corticosteroids</bold></td></tr><tr><td align="left">Methylprednisolone<break></break>Prednisolone</td><td align="left">2-, 4-, 8-, 6-, 32-mg tablets<break></break>5-mg tablets<break></break>5 mg/5 mL, 15 mg/5 mL</td><td align="left">7.5-60 mg daily in a single dose in AM or qod as needed for control</td><td align="left">0.25-2 mg/kg daily as single dose in AM or qod as needed for control</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Prednisone</td><td align="left">1-, 2.5-, 5-, 10-, 20-, 50-mg tablets<break></break>5 mg/mL, 5 mg/5 mL</td><td align="left">Short-course “burst” to achieve control: 40-60 mg/day as single or 2 divided doses for 3-10 days</td><td align="left">Short-course “burst”: 1-2 mg/kg/day, maximum of 60 mg/day, for 3-10 days</td></tr><tr><td colspan="4"><bold>Long-Acting Inhaled ß<sub>2</sub>-Agonists (should not be used for symptom relief or for exacerbation; use with inhaled corticosteroids)</bold></td></tr><tr><td align="left">Salmeterol<break></break><break></break>Formoterol</td><td align="left">MDI: 21 μg/puff<break></break>DPI: 50 μg/blister<break></break>DPI: 12 μg/single-use capsule</td><td align="left">2 puffs q12h<break></break>1 blister q12h<break></break>1 capsule q12h</td><td align="left">1-2 puffs q12h<break></break>1 blister q12h<break></break>1 capsule q12h</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td colspan="4" align="left"><bold>Combined Medication</bold></td></tr><tr><td align="left">Fluticasone/salmeterol</td><td align="left">DPI: 100, 250, or 500 μg/50 μg</td><td align="left">1 inhalation bid; dose depends on severity of asthma</td><td align="left">1 inhalation bid; dose depends on severity of asthma</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td colspan="4"><bold>Cromolyn and Nedocromil</bold></td></tr><tr><td align="left">Cromolyn<break></break><break></break>Nedocromil</td><td align="left">MDI: 1 mg/puff<break></break>Nebulizer: 20 mg/ampule<break></break>MDI: 1.75 mg/puff</td><td align="left">2-4 puffs tid-qid<break></break>1 ampule tid-qid<break></break>2-4 puffs bid-qid</td><td align="left">1-2 puffs tid-qid<break></break>1 ampule tid-qid<break></break>1-2 puffs bid-tid</td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td colspan="4" align="left"><bold>Leukotriene Modifiers</bold></td></tr><tr><td align="left">Montelukast<break></break><break></break><break></break>Zafirlukast<break></break>Zileuton</td><td align="left">4- or 5-mg chewable tablet<break></break>10-mg tablet<break></break>10- or 20-mg tablet<break></break>300- or 600-mg tablet</td><td align="left">10 mg qhs<break></break><break></break>40 mg daily (20-mg tablet bid)<break></break>2400 mg daily (give tablets qid)</td><td align="left">4 mg qhs (2-5 yr)<break></break>5 mg qhs (6-14 yr)<break></break>10 mg qhs (>14yr)<break></break>20 mg daily (7-11 yr) (10-mg tablet bid)</td></tr><tr><td colspan="4"><bold>Methylxanthines (serum monitoring is important [serum concentration of 5-15 μ g/mL at steady state])</bold></td></tr><tr><td align="left">Theophylline</td><td align="left">Liquids, sustained-release tablets, and capsules</td><td align="left">Starting dose, 10 mg/kg/day up to 300 mg max; usual max, 800 mg/day</td><td align="left">Starting dose, 10 mg/kg/day; usual usual max:<break></break><1 yr of age: 0.2 (age in wk) + 5 = mg/kg/day<break></break>≥1 yr of age: 16 mg/kg/day</td></tr></tbody></table><table-wrap-foot><fn><p>DPI, dry powder inhaler; MDI, metered-dose inhaler.</p></fn></table-wrap-foot><attrib>Modified from National Heart, Lung, and Blood Institute, Executive Summary of NAEPP Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics (NIH Publication No. 02-5075). Bethesda, MD, US Department of Health and Human Services, National Institutes of Health, 2002.</attrib></table-wrap><table-wrap position="float" id="cetable15"><label>Table 75-14</label><caption><p>Estimated Comparative Daily Dosages for Inhaled Corticosteroids</p></caption><table frame="hsides" rules="groups"><thead><tr><th></th><th colspan="2" align="center"><sc>Low Daily Dose</sc></th><th colspan="2" align="center"><sc>Medium Daily Dose</sc></th><th colspan="2" align="center"><sc>High Daily Dose</sc></th></tr><tr><th align="left">Drug</th><th align="left"><italic>Adult</italic></th><th align="left"><italic>Child</italic><xref rid="cetablefn3" ref-type="table-fn">*</xref></th><th align="left"><italic>Adult</italic></th><th align="left"><italic>Child</italic><xref rid="cetablefn3" ref-type="table-fn">*</xref></th><th align="left"><italic>Adult</italic></th><th align="left"><italic>Child</italic><xref rid="cetablefn3" ref-type="table-fn">*</xref></th></tr></thead><tbody><tr><td align="left">Beclomethasone HFA 40 or 80 μg/puff</td><td align="left">80-240 μg</td><td align="left">80-160 μg</td><td align="left">240-480 μg</td><td align="left">160-320 μg</td><td align="left">>480 μg</td><td align="left">>320 μg</td></tr><tr><td colspan="7"><hr></hr></td></tr><tr><td align="left">Budesonide DPI 200 μg/inhalation</td><td align="left">200-600 μg</td><td align="left">200-400 μg</td><td align="left">600-1200 μg</td><td align="left">400-800 μg</td><td align="left">>1200 μg</td><td align="left">>800 μg</td></tr><tr><td colspan="7"><hr></hr></td></tr><tr><td align="left">Budesonide inhalation suspension for nebulization (child dose)</td><td></td><td align="left">0.5 mg</td><td></td><td align="left">1.0 mg</td><td></td><td align="left">2.0 mg</td></tr><tr><td colspan="7"><hr></hr></td></tr><tr><td align="left">Flunisolide 250μg/puff</td><td align="left">500-1000 μg</td><td align="left">500-750 μg</td><td align="left">1000-2000 μg</td><td align="left">1000-1250 μg</td><td align="left">>2000 μg</td><td align="left">>1250 μg</td></tr><tr><td colspan="7"><hr></hr></td></tr><tr><td align="left">Fluticasone MDI: 44, 110, or 220 μg/puff DPI: 50, 100, or 250 μg/inhalation</td><td align="left">88-264 μg 100-300 μg</td><td align="left">88-176 μg 100-200 μg</td><td align="left">264-660 μg 300-600 μg</td><td align="left">176-440 μg 200-400 μg</td><td align="left">>660 μg >600 μg</td><td align="left">>440 μg >400 μg</td></tr><tr><td colspan="7"><hr></hr></td></tr><tr><td align="left">Trlamcinolone acetonide 100 μg/puff</td><td align="left">400-1000 μg</td><td align="left">400-800 μg</td><td align="left">1000-2000 μg</td><td align="left">800-1200 μg</td><td align="left">>2000 μg</td><td align="left">>1200 μg</td></tr></tbody></table><table-wrap-foot><fn><p>DPI, dry powder inhaler.</p></fn></table-wrap-foot><table-wrap-foot><fn id="cetablefn3"><label>*</label><p id="cenotep3">Children ≤12 years of age.</p></fn></table-wrap-foot><attrib>Modified from National Heart, Lung, and Blood Institute: Executive Summary of NAEPP Expert Panel Report: Guidelines for the Diagnosis and Management of Asthma: Update on Selected Topics (NIH Publication No. 02-5075). Bethesda, MD, US Department of Health and Human Services, National Institutes of Health, 2002.</attrib></table-wrap></p></sec></sec><sec id="cesec17"><title>CONSULTATION</title><p id="para50">Outpatient referral to an asthma specialist (e.g., pulmonologist, allergist) is associated with reduced rates of emergency department visits<xref rid="bib81" ref-type="bibr"><sup>75</sup></xref> and is recommended for patients with the following scenarios<xref rid="bib82" ref-type="bibr">76</xref>, <xref rid="bib83" ref-type="bibr">77</xref>, <xref rid="bib84" ref-type="bibr">78</xref>:<list list-type="simple" id="celist2"><list-item id="celistitem3"><label>•</label><p id="para51">Life-threatening asthma requiring admission to intensive care or a step-down unit</p></list-item><list-item id="celistitem4"><label>•</label><p id="para52">Severe persistent asthma in a patient who has required a prolonged course of steroids or multiple courses of corticosteroids in 1 year</p></list-item><list-item id="celistitem5"><label>•</label><p id="para53">Not meeting the goals of asthma therapy or not responding to treatment so that additional testing can be performed if necessary</p></list-item></list></p><p id="para54">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 in transition after discharge. Critical care physicians should be contacted for all patients who may need management in an intensive care setting.</p></sec><sec id="cesec18"><title>ADMISSION CRITERIA</title><p id="para55">Admission to the hospital is individualized and based on many factors. Hospitalization should be considered in patients with the following:<list list-type="simple" id="celist3"><list-item id="celistitem6"><label>•</label><p id="para56">Poor response to initial treatment</p></list-item><list-item id="celistitem7"><label>•</label><p id="para57">Oxygen saturation less than 92% on room air</p></list-item><list-item id="celistitem8"><label>•</label><p id="para58">Severe asthma with a relapsing course despite prolonged corticosteroid therapy</p></list-item><list-item id="celistitem9"><label>•</label><p id="para59">Previous emergency visits during the current period of exacerbation</p></list-item><list-item id="celistitem10"><label>•</label><p id="para60">Concern for noncompliance</p></list-item></list></p><p id="para61">Admission to an intensive care unit would be appropriate for patients with the following:<list list-type="simple" id="celist4"><list-item id="celistitem11"><label>•</label><p id="para62">Life-threatening or severe asthma that is unresponsive to initial therapy</p></list-item><list-item id="celistitem12"><label>•</label><p id="para63">Inability to maintain oxygen saturation greater than 92% with supplemental oxygen</p></list-item><list-item id="celistitem13"><label>•</label><p id="para64">Evidence of impending respiratory failure</p></list-item><list-item id="celistitem14"><label>•</label><p id="para65">Inability to provide adequate monitoring outside an intensive care setting<xref rid="bib85" ref-type="bibr"><sup>79</sup></xref></p></list-item></list></p></sec><sec id="cesec19"><title>DISCHARGE CRITERIA</title><p id="para66">Patients are ready to go home when they have been successfully weaned to albuterol treatments every 4 to 6 hours. Before receiving a treatment, they should be able to breathe comfortably during ambulation or speaking. Wheezing may persist on examination, but it 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, patients should leave with a plan of action for management of subsequent asthma exacerbations. Efforts should be coordinated with the primary care clinician and, if involved, the asthma specialist.</p><p id="para67">Before discharge, it is important to consider the environment to which the patient will return. Preventive management plans should be reviewed with the family, including identification of any potential comorbid conditions and triggers present in the environment. <xref rid="cetable16" ref-type="table">Table 75-15</xref>highlights a discharge checklist that was created by the NHLBI panel.<table-wrap position="float" id="cetable16"><label>Table 75-15</label><caption><p>Hospital Discharge Checklist for Patients with Asthma Exacerbations</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" valign="bottom">Intervention</th><th align="left" valign="bottom">Dose/Timing</th><th align="left" valign="bottom">Education/Advice</th><th align="left">MD/RN Initials</th></tr></thead><tbody><tr><td align="left">Inhaled medications (MDI + spacer/holding chamber)<break></break> Beta<sub>2</sub>-agonist<break></break><break></break> Corticosteroids</td><td align="left">Select agent, dose, and frequency (e.g., albuterol)<break></break>2-6 puffs q 3-4 hr prn<break></break>Medium dose</td><td align="left">Teach purpose<break></break>Teach technique<break></break>Emphasize need for spacer/holding chamber<break></break>Check patient technique</td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Oral medications</td><td align="left">Select agent, dose, and frequency (e.g., prednisone 20 mg bid for 3-10 days)</td><td align="left">Teach purpose<break></break>Teach side effects</td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Peak flow meter</td><td align="left">Measure AM and PM. PFF and record best of three tries each time</td><td align="left">Teach purpose<break></break>Teach technique<break></break>Distribute peak flow diary</td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Follow-up visit</td><td align="left">Make appointment for follow-up care with primary clinician or asthma specialist</td><td align="left">Advise patient (or caregiver) of date, time, and location of appointment within 7 days of hospital discharge</td><td></td></tr><tr><td colspan="4"><hr></hr></td></tr><tr><td align="left">Action plan</td><td align="left">Before or at discharge</td><td align="left">Instruct patient (or caregiver) on simple plan for actions to be taken when symptoms, signs, and PEF values suggest recurrent airflow obstruction</td><td></td></tr></tbody></table><attrib>Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report II: Guidelines for the Diagnosis and Management of Asthma (NIH Publication No. 96-4051). Bethesda, MD, US Department of Health and Human Services, National Institutes of Health, 1997.</attrib></table-wrap></p></sec><sec id="cesec20"><title>PREVENTION</title><p id="para68">Educating the family about the pathogenesis of asthma, triggers, and medications is crucial for preventing exacerbations and admissions to the hospital. A patient who requires frequent admissions needs to have the treatment plan reassessed and be evaluated for comorbid conditions. Assessment of adherence to therapy and review of relevant drug delivery systems are important as well. 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.<xref rid="bib86" ref-type="bibr"><sup>80</sup></xref> In addition, other factors, including gastroesophageal reflux, sinusitis, and others that might exacerbate asthma, should be explored and eliminated if possible (<xref rid="cetable17" ref-type="table">Table 75-16</xref>). If an allergic component is being considered, further evaluation can be arranged and environmental control measures recommended. Both passive and active cigarette smoking significantly increases the risk for asthma and worsens asthma symptoms.<xref rid="bib87" ref-type="bibr">81</xref>, <xref rid="bib88" ref-type="bibr">82</xref>, <xref rid="bib89" ref-type="bibr">83</xref>, <xref rid="bib90" ref-type="bibr">84</xref>, <xref rid="bib91" ref-type="bibr">85</xref>, <xref rid="bib92" ref-type="bibr">86</xref>, <xref rid="bib93" ref-type="bibr">87</xref>, <xref rid="bib94" ref-type="bibr">88</xref> As a result, no smoking should be permitted around asthmatics or in their home or family car. Physicians should provide assistance for caregivers to quit smoking.<table-wrap position="float" id="cetable17"><label>Table 75-16</label><caption><p>Exacerbating Factors for Asthma and Control Measures</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left">Factors That Worsen Asthma Severity</th><th align="left" valign="bottom">Control Measures</th></tr></thead><tbody><tr><td align="left">Animal dander</td><td align="left">Remove the animal from the environment<break></break>At a minimum, remove the pet from the bedroom</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">House dust mites</td><td align="left">Encase mattress and pillows in an allergen-impermeable cover<break></break>Wash bedding in hot water weekly at >130° F<break></break>Remove carpets from the bedroom</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Cockroaches</td><td align="left">Exterminate!<break></break>Do not leave garbage and food exposed</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Pollen</td><td align="left">During pollen season, stay indoors with windows closed, especially in the afternoon</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Mold</td><td align="left">Fix leaks, eliminate water sources<break></break>Clean moldy surfaces</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Cigarette/tobacco smoke</td><td align="left">Encourage family members and caregivers to smoke outside and cease smoking</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Sinusitis</td><td align="left">Promote sinus drainage<break></break>Antibiotic therapy when appropriate</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Gastroesophageal reflux</td><td align="left">No eating 3 hr before bedtime<break></break>Elevate head of bed 6-8 inches<break></break>Appropriate medications: H<sub>2</sub> receptor antagonist</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Medications</td><td align="left">No beta-blockers<break></break>Aspirin and NSAIDs in combination with severe persistent asthma, nasal polyps, and aspirin sensitivity increase the risk for a reaction</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Viral infections</td><td align="left">Annual influenza vaccination</td></tr><tr><td colspan="2"><hr></hr></td></tr><tr><td align="left">Irritants</td><td align="left">Decrease exposure to wood-burning stoves, fireplaces, unvented stoves or heaters, perfumes, cleaning agents, sprays</td></tr></tbody></table><table-wrap-foot><fn><p>NSAIDs, nonsteroidal anti-inflammatory medications.</p></fn></table-wrap-foot><attrib>Adapted from National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Expert Panel II: Guidelines for the Diagnosis and Management of Asthma (NIH Publication No. 96-4051). Bethesda, MD, US Department of Health and Human Services, National Institute of Health, 1997.</attrib></table-wrap></p><p id="para69">Appropriate preventive 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 between hospital admission for asthma and the use of daily inhaled corticosteroids. Suggested doses and regimens have been established through national and worldwide collaboration between primary physicians, allergists, pulmonologists, and others. An example is seen in <xref rid="cetable13" ref-type="table">Table 75-12</xref>, <xref rid="cetable14" ref-type="table">Table 75-13</xref>, <xref rid="cetable15" ref-type="table">Table 75-14</xref>.</p><p id="para70">Peak flowmeters can be helpful in managing asthma, if used appropriately.<xref rid="bib95" ref-type="bibr"><sup>89</sup></xref> However, studies comparing peak flow monitoring with symptom recognition show no benefit of peak flow–based action plans over those based on symptoms alone.<xref rid="bib95" ref-type="bibr">89</xref>, <xref rid="bib96" ref-type="bibr">90</xref>, <xref rid="bib97" ref-type="bibr">91</xref> Peak flowmeters have numeric indicators that allow the creation of green, yellow, and red zones (see <xref rid="cetable5" ref-type="table">Table 75-5</xref>). Green represents the “good” or “all clear” zone and is 80% to 100% of a child's personal best. The yellow zone is 50% to 80% of the personal best and indicates a time when the family should be “cautious” because the child may be having or is at risk for asthma symptoms. Asthma reliever medications should be started and contact with the physician considered. The red zone is indicated by a PEFR less than 50% of normal; it is cause for concern and requires a visit to the emergency room or a call to the doctor.<xref rid="bib10" ref-type="bibr"><sup>4</sup></xref> Peak flow monitoring is typically helpful for children who are not good at recognizing symptoms of asthma. Current NHLBI guidelines recommend either a symptom-based or peak flow–based management plan.</p><p id="para71">Additional sources of support for families can include the Asthma and Allergy Foundation of America and Mothers of Asthmatics.</p><p id="para72"><boxed-text id="cetextbox1"><caption><title>IN A NUTSHELL</title></caption><p id="para73"><list list-type="simple" id="celist5"><list-item id="celistitem15"><label>•</label><p id="para74">Asthma is a chronic disorder that results in airway inflammation and smooth muscle dysfunction and is manifested as recurrent episodes of wheezing, breathlessness, and chest tightness.</p></list-item><list-item id="celistitem16"><label>•</label><p id="para75">Exacerbations can be triggered by a variety of stimuli, including respiratory infections, exposure to allergens or irritants, exercise, and cold air.</p></list-item><list-item id="celistitem17"><label>•</label><p id="para76">Treatment of flares must be directed at decreasing airway inflammation and relieving bronchospasm while providing supportive care.</p></list-item><list-item id="celistitem18"><label>•</label><p id="para77">The mainstay of pharmacologic therapy includes inhaled short-acting β<sub>2</sub>-adrenergic agonist therapy and systemic corticosteroids. Supportive care includes supplemental oxygen if needed and maintenance of hydration.</p></list-item><list-item id="celistitem19"><label>•</label><p id="para78">Many of the pharmacologic agents have significant side effects, and therefore appropriate monitoring is required.</p></list-item><list-item id="celistitem20"><label>•</label><p id="para79">Patients with severe symptoms or those with moderately severe symptoms that fail to improve after initial therapy are candidates for admission to an intensive care setting.</p></list-item><list-item id="celistitem21"><label>•</label><p id="para80">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.</p></list-item></list></p></boxed-text></p><p id="para81"><boxed-text id="cetextbox2"><caption><title>ON THE HORIZON</title></caption><p id="para82"><list list-type="simple" id="celist6"><list-item id="celistitem22"><label>•</label><p id="para83">Asthma is a chronic inflammatory disease that affects 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. An example of one of these drugs is omalizumab, a recombinant humanized anti-IgE antibody. This drug binds circulating free IgE and consequently reduces the level of free IgE in the bloodstream and prevents it from binding to mast cell membrane receptors, thus curtailing the early and late asthmatic responses. Omalizumab has been found to reduce symptoms, exacerbations,<xref rid="bib98" ref-type="bibr"><sup>92</sup></xref> and the use of corticosteroids.</p></list-item><list-item id="celistitem23"><label>•</label><p id="para84">New NHLBI Expert Panel guidelines on the diagnosis and treatment of asthma are expected in late 2006 or early 2007. 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