Asthma

Authors: Tokunbo Adeniyi MD, Katrin Takenaka, MD , McGovern Medical School at the University of Texas Health Science Center at Houston 

Editor: Al’ai Alvarez, MD (Assistant Professor), Stanford University; Palo Alto, CA

Original Author: Matt Tews; Medical College of Wisconsin; Milwaukee, WI

Original Editor: Scott Sherman, John H. Stroger Hospital; Chicago, IL

Update: November 2019

Case Study

A 29-year-old woman with history of asthma presents with cough and shortness of breath after a recent upper respiratory tract infection. She has been using her albuterol inhaler every 2-4 hours at home; however, she continues to wheeze and feel short of breath. She has never had to be admitted to the hospital for an asthma exacerbation, but she does tend to use her inhaler every few days when she feels short of breath or has wheezes. Triage vital signs include T 98.8F, BP 125/76, HR 115, RR 26, 93% oxygen saturation on room air. On exam, she is alert and able to speak in full sentences but noticeably tachypneic when talking.  Her pulmonary exam reveals bilateral end-expiratory wheezes with bilateral restricted air movement. She is not using her accessory muscles to breathe. 

Objectives

1. Describe the varying clinical presentations of an acute asthma exacerbation
2. Explain the clinical approach to a patient with an asthma exacerbation, including primary survey, diagnostic tests, and treatment 
3. Determine appropriate patient disposition depending on the severity of the exacerbation and response to emergency department (ED) treatment
   

Introduction

Asthma affects over 18 million adults and more than 6 million children in the US. Thus acute exacerbations are common ED presentations, accounting for 1.6 million visits per year in the US. Patients with acute asthma exacerbations present with symptoms ranging from cough and chest tightness to dyspnea and audible wheezes to respiratory failure. A common medical adage states that “not all that wheezes is asthma.” Several other conditions can mimic asthma, including chronic obstructive pulmonary disease (COPD), acute decompensated heart failure (ADHF), acute coronary syndrome, pulmonary embolism, pneumonia, pneumothorax, and airway foreign body. However, acute asthma can usually be diagnosed with a thorough history and physical exam.

Initial Actions and Primary Survey

When approaching a patient with an asthma exacerbation, a clinician needs to quickly evaluate the patient’s airway, breathing, and circulatory status; determine the severity of this episode; and decide whether the patient needs immediate airway support including intubation.  Factors such as vital signs (especially respiratory rate and pulse oximetry), signs of respiratory distress (such as ability to speak and use of accessory muscles), pulmonary exam (including wheezes and amount of air movement), and mental status are important components of this initial assessment/primary survey. Remember that lack of wheezing can be an ominous sign in a patient with respiratory distress and poor air movement. 

If the patient’s respiratory status allows, a history should be obtained, focusing on current symptoms, prior episodes, known precipitants, home asthma control regimen, medication compliance, and other comorbidities. Risk factors for death from asthma include prior intubation and/or ICU admission, recent ED visit or hospitalization for asthma, recent/last course of steroids, frequent asthma-related ED visits or admissions, frequent use of “rescue” short-acting beta agonists (SABAs) such as albuterol, and cardiopulmonary comorbidities. It is important to note that a lack of risk factors does not eliminate the risk of severe morbidity and mortality.

As mentioned above, the exam should focus on assessing the severity of disease and identifying signs of respiratory distress/failure. The clinician can use other portions of the exam to identify/exclude other causes of dyspnea (e.g., neck exam for jugular venous distention, cardiac exam for murmurs or gallops, extremity exam for peripheral pulses or edema). 

Depending on the severity of the current exacerbation, a patient may initially require continuous cardiac monitoring and/or pulse oximetry, supplemental oxygen, initiation of therapy with inhaled SABAs and anticholinergics, administration of steroids, use of non-invasive positive pressure ventilation (NIPPV), and/or rapid sequence induction (RSI) and intubation. 

Presentation

Asthma is a chronic inflammatory condition resulting in hyperresponsiveness to environmental and infectious exposures.  Airway smooth muscle obstruction, bronchospasm, and mucosal edema then ensue. An acute exacerbation is usually characterized by progressive cough, shortness of breath, chest tightness, and wheezing. 

Common triggers include infection (upper respiratory infection in adults, respiratory syncytial virus/parainfluenza in children), exposure to cold or dry environments, stress, physical exertion, or inhaled irritants (e.g., dust, cigarette smoke, air pollution). 

Diagnostic Testing

The ED diagnosis of acute asthma is usually made by thorough history taking and physical examination. Diagnostic testing is often unnecessary unless the diagnosis is uncertain or a complication is suspected. Furthermore, testing should not delay the initiation of treatment. 

Laboratory testing:  A complete blood count may be obtained if infection is suspected; however, its usefulness is limited as the white blood cell count may be elevated in acute asthma without any underlying infection. For patients who take theophylline, a level may be drawn although it would not help determine further management. A basic metabolic panel may be helpful in patients with kidney disease, those on diuretics, or those who will require multiple doses of SABAs (as beta agonists can lower potassium levels by shifting it intracellularly). 

Blood gas: Although blood gases are unnecessary in most patients with an asthma exacerbation, they can provide useful information in those who remain hypoxic despite supplemental oxygen, are unresponsive to initial therapy, or are in severe respiratory distress. Blood gases are used to assess for hypoxia, hypo-/hypercarbia, and acidosis. Hypocarbia and respiratory alkalosis are expected findings in tachypneic patients while normal or elevated pCO2 levels and metabolic acidosis are markers of impending respiratory failure. Although blood gas results can aid in identifying respiratory failure, they should be used in conjunction with a patient’s clinical status to determine the need for intubation. While venous and arterial blood gases are equivalent in their ability to assess pCO2 and pH, venous blood gases are less painful to obtain and, therefore, may be preferred unless accurate pO2 levels are necessary. 

Chest radiography: Chest x-ray (CXR) is not routinely indicated for patients with acute asthma. In most cases, the CXR is normal or shows hyperinflation or atelectasis, and the results would not affect any therapeutic decisions. It can aid in identifying/excluding alternative diagnoses such as pulmonary edema or pneumonia. Additionally, it can be useful if a complication such as pneumothorax or pneumomediastinum is suspected.

Peak flow measurements: These can be useful bedside tests to aid in the assessment of disease severity and response to treatment as well as in final disposition decisions They are measured using a peak expiratory flow rate (PEFR) meter or a handheld spirometry machine that determines the forced expiratory volume in one second (FEV1). Both devices measure velocity of air flow and degree of airway obstruction. Although these devices are simple and inexpensive to use, they are effort dependent. As a result, they may have limited utility in pediatric patients and others who are unable to perform the test. If used, serial measurements should be obtained (e.g., upon initial presentation and 1 hour after each SABA treatment). Measurements during an acute exacerbation can be compared to a patient’s baseline, if known. Normal predicted peak flow rates are based on age, gender, and height. Tables of normal predicted peak flow rates are easily available online. Peak flow measurements should only be used in conjunction with other indicators of clinical status to make therapeutic and disposition decisions.

Treatment

Therapy is determined by the severity of the exacerbation based on vital signs, work of breathing, and PEF (peak expiratory flow) or FEV1 (forced expiratory volume 1 sec). Mild exacerbations are characterized by normal vital signs (including pulse oximetry > 90%), mild wheezes and minimal work of breathing, and PEF or FEV1 > 70% of predicted. Patients with moderate exacerbations demonstrate an elevated heart rate and respiratory rate with pulse oximetry > 90%, increased work of breathing, and PEF or FEV1 40-69% of predicted. Those with severe acute asthma present with abnormal vital signs including pulse oximetry < 90%, significantly increased work of breathing, altered mentation, and PEF or FEV1 < 40% of predicted. 

The goals of treatment of acute asthma include: 

• Correction of significant hypoxemia
• Rapid reversal of airflow obstruction
• Reduction of the likelihood of relapse 

Patient with mild to moderate exacerbations may only require inhaled SABAs and ipratropium and steroids while those with severe exacerbations may also benefit from IV magnesium. Those in more severe distress may need NIPPV or intubation.

Individual treatment options are discussed below.

β2-adrenergic agonists: SABAs (most commonly albuterol) are first line therapy for acute asthma. They can be delivered via nebulizer or metered-dose inhaler (MDI) plus spacer. MDIs with spacers are as effective as nebulizers although MDIs without spacers require more supervision to ensure proper usage. Nebulized albuterol is usually given 2.5-5 mg every 20 minutes for up to 3 doses, followed by 2.5-10 mg every 1-4 hours as needed. Continuous nebulized albuterol may be used in patients with severe exacerbations. The dose of “continuous” albuterol is 10-15 mg/hr (0.5 mg/kg/hr in children). Onset is 5-15 minutes with peak effect within 2 hours. Adverse effects may include tremor and tachycardia. Additionally mild hypokalemia may occur due to potassium being shifted intracellularly.

Levalbuterol is another SABA that can be used to treat acute asthma. However, it does not provide any clinical advantage over albuterol and is more costly. 

Although important in maintenance therapy, long-acting beta agonists (e.g., salmeterol) do not have a place in acute exacerbations. 

Anticholinergic agents (ipratropium): Inhaled ipratropium is used in moderate to severe exacerbations. Studies have shown that combining ipratropium with SABAs provides an advantage over using it as a single agent. Due to its anticholinergic effects, it may inhibit airway secretions. It can be combined with albuterol in a nebulized form (Duoneb) or in an MDI (Combivent). It is administered as 500 microgram (2.5 mL) every 20 minutes up to 3 doses, followed by 2.5 mL every 6 hours as needed. There is no apparent benefit beyond 3 back-to-back treatments.

Corticosteroids: These are another fundamental component of acute asthma treatment. They are administered to reduce airway inflammation and obstruction as well as to decrease the rate of relapse. Early steroid administration is correlated with decreased rates of hospitalization, perhaps in part due to the delayed onset of action (4-6 hours). Steroids may be given orally or intravenously (IV) with equal efficacy.  In general, the oral form is preferred unless a patient’s clinical condition warrants IV administration (e.g., inability to swallow or tolerate oral medications, severe respiratory distress). All steroids can produce similar side effects (i.e., hyperglycemia, hypertension, decrease in potassium, fluid retention, and even mood symptoms) although short courses of steroids convey little risk of serious adverse events. 

Common oral steroids include prednisone, methylprednisolone, prednisolone, and dexamethasone. Dexamethasone, hydrocortisone and methylprednisolone are frequently encountered IV forms. The optimal dosage and duration of therapy is somewhat controversial although prednisone 40-80 mg/day orally or methylprednisolone 40-80 mg/day IV are common. The initial dose is usually followed by a 3-10 day “burst” of continued steroids depending on the severity of the exacerbation.  Dexamethasone can be administered once in the ED and once in the next 1-2 days with equivalent effect to a 3-5 day burst of prednisone. 

Although inhaled corticosteroids are not recommended for acute asthma, they are useful to help prevent acute exacerbations. While they are not currently recommended in an acute asthma exacerbation, they should be considered in patients with frequent exacerbations or frequent need to use SABAs.

Epinephrine: The beta-agonist activity of epinephrine causes bronchodilation. It is useful as an adjunct therapy in severe acute asthma, especially if not responsive to initial treatment with SABAs. Although epinephrine can be administered intramuscularly (IM) or subcutaneously (SC), studies have shown that IM epinephrine provides faster and more consistent delivery of medication than SC. The adult and pediatric doses of 1:1000 are 0.3-0.5 mg of 1:1000 IM and 0.01 mg/kg (up to 0.3-0.5 mg) IM, every 20 minutes for up to 3 doses.

Magnesium: Although magnesium sulfate has shown some benefit in severe asthma exacerbations, the literature does not support its routine use, especially in mild to moderate flares.  It appears to work through relaxation of the smooth muscles in the airways. The usual dose is 2 gm IV over 20 minutes, and must be given with continuous albuterol nebulization.

Heliox: This is a helium-oxygen mixture (most commonly 80:20 or 70:30) and may be used as adjunctive therapy in severe exacerbations. Because helium is less dense than oxygen, it can travel through smaller airways with more laminar flow, resulting in increased oxygen or inhaled medication delivery. In turn, this is thought to decrease the work of breathing. Hypoxic patients may not tolerate heliox in light of its lower oxygen concentration. 

Agents without routine benefit in acute asthma: Antibiotics should be reserved for patients with evidence of bacterial infection as routine antibiotic dosing provides no therapeutic benefits. 

Theophylline is not recommended in the treatment of acute asthma as it does not provide any additional clinical benefit and is associated with adverse effects such as tremors, nausea, anxiety, and tachydysrhythmia. If a patient is already taking theophylline, a serum level should be measured since the drug has a narrow therapeutic index.

Non-invasive positive pressure ventilation: NIPPV can be helpful in severe acute asthma by decreasing the work of breathing and improving recruitment of alveoli. Another theory is that positive pressure helps push albuterol in the periphery, and thus further help with opening of the smaller airways. Although the use of NIPPV in acute asthma appears promising, further study is needed to determine its optimal role in acute asthma management. 

Intubation: Mechanical ventilation may be required in patients with severe asthma exacerbations and respiratory failure (including hypoxia and/or hypercarbia despite intervention)/arrest, respiratory fatigue, or altered mentation. It is important to remember that mechanical ventilation is not used in isolation but in conjunction with the other above-mentioned therapies. Ketamine may be useful as an induction agent due to its bronchodilatory effects, although anticipate increase in secretions in using this induction agent. Consider using glycopyrrolate. Managing an intubated asthmatic presents several challenges because mechanically-ventilated asthmatics can develop high lung pressures due to breath-stacking. This may result in barotrauma, pneumothorax or hypotension (due to decreased venous return). Permissive hypercapnia and prolonged expiratory phase in mechanical ventilation may help avoid this pitfall.

Disposition: The decision to discharge or admit a patient with acute asthma is based on their clinical course in the ED, response to treatment, and ability to access outpatient medications and obtain outpatient follow-up. Patients with persistent tachypnea, increased work of breathing, hypoxia, and/or PEF or FEV1 < 70% of predicted should be considered for hospitalization. It is important to recognize the transient hypoxia immediately after treatment with albuterol. This should improve upon brief observation. Persistent hypoxia is concerning. 

If patients are deemed safe for discharge, they should go home with appropriate follow-up and a written asthma action plan, including instructions on the appropriate use of medications, and removal of any environmental precipitants. They should also have access to SABAs and receive a prescription for continued steroids (most commonly a steroid “burst” as described above). 

Pearls and Pitfalls

• “Not all that wheezes is asthma, and not all asthma wheezes.” The differential diagnoses for acute asthma includes COPD, ADHF, acute coronary syndrome, pulmonary embolism, pneumonia, pneumothorax, and airway foreign body. Furthermore, patients with severe asthma may not move enough air to be able to produce wheeze.
• Acute asthma is a clinical diagnosis, and laboratory tests and adjunctive studies are not routinely required unless there is a diagnostic dilemma or a complication is suspected
• Objective measures of lung function such as PEF and FEV1 can be useful bedside tests to aid in the assessment of disease severity and response to treatment as well as in final disposition decisions
• Mainstays of treatment include SABAs and corticosteroids. Concurrent inhaled ipratropium may provide additional benefit.  Consider early administration of steroids as they have a delayed onset of action. 
• Adjunctive therapy for severe exacerbations may include magnesium sulfate, epinephrine, heliox, and/or NIPPV.
• Most patients can be managed medically. Consider intubation if the patient is in respiratory arrest or if the patient has impending respiratory failure and has failed other therapies. If intubation is necessary, permissive hypercapnia may help avoid the complications of barotrauma and hypotension.

Case Study

The patient receives 3 rounds of nebulized albuterol and ipratropium as well as 50 mg of oral prednisone . Initially she remains tachypneic although her work of breathing improves and pulse oximetry is 94% on room air.  On re-evaluation, she has persistent wheezing, so additional albuterol nebulizer treatments are ordered. After 5 hours in the ED, she has occasional scattered wheezing, a normal respiratory rate, and 98% room air saturation.  She is able to ambulate in the ED without any respiratory distress or hypoxia. She is discharged home with a refill for her albuterol MDI, a prescription for 5 additional days of oral prednisone, a written action plan, and follow up with her primary care physician.

References

Camargo CA, Rachelefsky G, Schatz M. Managing Asthma Exacerbations in the Emergency Department: summary of the National Asthma Education and Prevention Program Expert Panel Report 3 guidelines for the management of asthma exacerbations. Proc Am Thorac Soc. 2009; 6: 357-66. (PMID: 19675345)

Hodder R, Lougheed D, Rowe  BH, FitzGerald JM, Kaplan AG, McIvor A. Management of Acute Asthma in Adults in the Emergency Department: Nonventilatory Management. CMAJ. 2010; 182: E55-E67. (PMID: 19858243)

Rodrigo GJ, Rodrigo C, Hall JB., Acute Asthma in Adults. Chest. 2004; 125:1081-1102. (PMID: 15006973)

Schauer SG, Cuenca PJ, Johnson JJ, Ramirez S. Management of Acute Asthma in the Emergency Department. Emerg Med Pract. 2013;15:1-28. (PMID: 24040898)