9-05: Approach to Management Asthma

Asthma is a common disease, affecting approximately 8–10% of the population. It is slightly more common in male children (younger than 14 years) and in female adults. There is a genetic predisposition to asthma. Prevalence, hospitalizations, and fatal asthma have all increased in the United States over the past 20 years. Each year, approximately 10 million office visits, 1.8 million emergency department visits, and more than 3500 deaths in the United States are attributed to asthma. Hospitalization rates are highest among African-Americans and children, and death rates are consistently highest among African-Americans aged 15–24 years. The 2019 Global Initiative for Asthma (GINA) Report entitled Global Strategy for Asthma Management and Prevention is a comprehensive and practical resource that addresses asthma diagnosis, assessment, management and exacerbations.

Asthma is a chronic disorder of the airways characterized by variable airway obstruction, airway hyperresponsiveness, and airway inflammation. No single histopathologic feature is pathognomonic but common findings include airway inflammatory cell infiltration with eosinophils, neutrophils, and lymphocytes (especially T cells); goblet cell hyperplasia, sometimes plugging of small airways with mucus; collagen deposition beneath the basement membrane; hypertrophy of bronchial smooth muscle; airway edema; mast cell activation; and denudation of airway epithelium. IgE plays a central role in the pathogenesis of allergic asthma. Interleukin-5 is important in promoting eosinophilic inflammation.

Many clinical phenotypes of asthma have been identified. The most common is allergic asthma, which usually begins in childhood and is associated with other allergic diseases such as eczema, allergic rhinitis, or food allergy. Exposure of sensitive patients to inhaled allergens may cause symptoms immediately (immediate asthmatic response) or 4–6 hours after allergen exposure (late asthmatic response). Common allergens include house dust mites (often found in pillows, mattresses, upholstered furniture, carpets, and drapes), cockroaches, cat dander, and seasonal pollens. Substantially reducing exposure reduces pathologic findings and clinical symptoms. Nonallergic asthma is not associated with allergy. Late-onset adult asthma presents for the first time in adult life. Asthma with persistent airflow limitation is thought to be due to airway remodeling. Asthma with obesity refers to prominent respiratory symptoms in obese patients with little airway inflammation.

Nonspecific precipitants of asthma include upper respiratory tract infections, rhinosinusitis, postnasal drip, aspiration, gastroesophageal reflux, changes in the weather, stress, and exercise. Exposure to products of combustion (eg, from tobacco, methamphetamines, diesel fuel, and other agents) increases asthma symptoms and the need for medications and reduces lung function. Air pollution (increased air levels of respirable particles, ozone, SO₂, and NO₂) precipitates asthma symptoms and increases emergency department visits and hospitalizations. Selected individuals may experience asthma symptoms after exposure to aspirin (aspirin-exacerbated respiratory disease), nonsteroidal anti-inflammatory drugs, or tartrazine dyes. Other medications may precipitate asthma symptoms (see Table 9–24). Occupational asthma is triggered by various agents in the workplace and may occur weeks to years after initial exposure and sensitization. Women may experience catamenial asthma at predictable times during the menstrual cycle. Exercise-induced bronchoconstriction begins during exercise or within 3 minutes after its end, peaks within 10–15 minutes, and then resolves by 60 minutes. This phenomenon is thought to be a consequence of the airways’ warming and humidifying an increased volume of expired air during exercise. “Cardiac asthma” is wheezing precipitated by pulmonary edema in the setting of decompensated heart failure. Cough-variant asthma has cough instead of wheezing as the predominant symptom of bronchial hyperreactivity.

Symptoms and signs vary widely among patients as well as individually over time. General clinical findings in stable asthma patients and findings seen during asthma exacerbations are listed in Table 9–1.

A. Symptoms and Signs

Asthma is characterized by episodic wheezing, shortness of breath, chest tightness, and cough. Symptoms vary over time and in intensity and are often worse at night or in the early morning. Asthma symptoms may occur spontaneously or be precipitated or exacerbated by many different triggers, as discussed above. The following features decrease the likelihood that respiratory symptoms are due to asthma: isolated cough with no other symptoms, chronic sputum production, chest pain, shortness of breath with paresthesias.

Some physical examination findings increase the probability of asthma. Nasal mucosal swelling, increased secretions, and polyps are often seen in patients with allergic asthma. Eczema, atopic dermatitis, or other allergic skin disorders may also be present. Wheezing (AUDIO 9–5) or a prolonged expiratory phase during normal breathing correlates well with the presence of airflow obstruction; wheezing during forced expiration does not. Chest examination may be normal between exacerbations in patients with mild asthma. During severe asthma exacerbations, airflow may be too limited to produce wheezing, and the only diagnostic clue on auscultation may be globally reduced breath sounds with prolonged expiration (AUDIO 9–4). Hunched shoulders and use of accessory muscles of respiration suggest an increased work of breathing.

B. Laboratory Findings

Arterial blood gas (ABG) measurements may be normal during a mild asthma exacerbation, but respiratory alkalosis and an increase in the alveolar-arterial oxygen difference (A–a–DO₂) are common. During severe exacerbations, hypoxemia develops and the PaCO₂ returns to normal. The combination of an increased PaCO₂ and respiratory acidosis may indicate impending respiratory failure and the need for mechanical ventilation.

C. Pulmonary Function Testing

Clinicians correctly identify airflow obstruction on examination but have limited ability to gauge its severity or to predict whether it is reversible. The evaluation for asthma should therefore include spirometry (forced expiratory volume in 1 second [FEV₁], forced vital capacity [FVC], and FEV₁/FVC) before and after the administration of a short-acting bronchodilator (eFigure 9–3). These measurements help determine the presence and extent of airflow obstruction and whether it is immediately reversible. Airflow obstruction is indicated by a reduced FEV₁/FVC ratio. Significant reversibility of airflow obstruction is defined by an increase of 12% or more and 200 mL in FEV₁ or FVC after inhaling a short-acting bronchodilator. A positive bronchodilator response strongly supports the diagnosis of asthma but a lack of responsiveness in the pulmonary function laboratory does not preclude success in a clinical trial of bronchodilator therapy. Severe airflow obstruction results in significant air trapping, with an increase in residual volume and consequent reduction in FVC, resulting in a pattern that may mimic a restrictive ventilatory defect.

Bronchial provocation testing with inhaled histamine or methacholine may be useful when asthma is suspected but spirometry is nondiagnostic. Bronchial provocation is not recommended if the FEV₁ is less than 65% of predicted. A positive methacholine test is defined as a fall in the FEV₁ of 20% or more at exposure to a methacholine concentration of less than or equal to 8 mg/mL. A negative methacholine test has a negative predictive value for asthma of 95%. Exercise challenge testing may be useful in patients with symptoms of exercise-induced bronchospasm.

Peak expiratory flow (PEF) meters are handheld devices designed as personal monitoring tools. PEF monitoring can establish peak flow variability, quantify asthma severity, and provide both patient and clinician with objective measurements on which to base treatment decisions. There are conflicting data about whether measuring PEF improves asthma outcomes but doing so is recommended to help confirm the diagnosis of asthma, to improve asthma control in patients with poor perception of airflow obstruction, and to identify environmental and occupational causes of symptoms. Predicted values for PEF vary with age, height, and sex but are poorly standardized. Comparison with reference values is less helpful than comparison with the patient’s own baseline. PEF shows diurnal variation; it is generally lowest on first awakening and highest several hours before the midpoint of the waking day. PEF should be measured in the morning before the administration of a bronchodilator and in the afternoon after taking a bronchodilator. A 20% change in PEF values from morning to afternoon or from day to day suggests inadequately controlled asthma. PEF values less than 200 L/min indicate severe airflow obstruction.

D. Additional Testing

Routine chest radiographs in patients with asthma are usually normal or show only hyperinflation. Other findings may include bronchial wall thickening and diminished peripheral lung vascular shadows. Chest imaging is indicated when pneumonia, another disorder mimicking asthma, or a complication of asthma such as pneumothorax is suspected.

Skin testing or in vitro testing, including total serum IgE and allergen-specific IgE, to assess sensitivity to environmental allergens can identify atopy in patients with persistent asthma who may benefit from therapies directed at their allergic diathesis. Evaluations for paranasal sinus disease or gastroesophageal reflux should be considered in patients with persistent, severe, or refractory asthma symptoms. An absolute eosinophil count can identify patients eligible for anti–interleukin-5 therapy to manage eosinophilic airway disease.

Noninvasive assessment of underlying airway inflammation through measurement of eosinophilia in induced sputum, or fractional nitric oxide concentration in exhaled breath condensates (FeNO), offers the promise of improved diagnosis and treatment strategies. Adjusting corticosteroid dose to minimize sputum eosinophilia appears to reduce the frequency of exacerbations compared with conventional clinical management, but data are conflicting regarding the impact of FeNO on asthma outcomes.

Complications of asthma include exhaustion, dehydration, airway infection, and tussive syncope. Pneumothorax occurs but is rare. Acute hypercapnic and hypoxemic respiratory failure occurs in severe disease.

Patients who have atypical symptoms or poor response to therapy may have one of several conditions that mimic asthma. These disorders typically fall into: upper airway disorders, lower airway disorders, systemic vasculitides, cardiac disorders, and psychiatric disorders. Upper airway disorders that mimic asthma include vocal fold paralysis, vocal fold dysfunction syndrome, narrowing of the supraglottic airway, and laryngeal masses or dysfunction. Lower airway disorders include foreign body aspiration, tracheal masses or narrowing, tracheobronchomalacia, airway edema (eg, angioedema or inhalation injury), nonasthmatic chronic obstructive pulmonary disease (COPD) (chronic bronchitis or emphysema), bronchiectasis, allergic bronchopulmonary mycosis, cystic fibrosis, eosinophilic pneumonia, hypersensitivity pneumonitis, sarcoidosis, and bronchiolitis obliterans. A systemic vasculitis with pulmonary involvement may have an asthmatic component, such as eosinophilic granulomatosis with polyangitis. Cardiac disorders include heart failure and pulmonary hypertension. Psychiatric causes include conversion disorders (“functional” asthma), emotional laryngeal wheezing, or episodic laryngeal dyskinesis. Rarely, Münchausen syndrome or malingering may explain a patient’s complaints.

The 2019 GINA Report Global Strategy for Asthma Management and Prevention provides guidelines for the management of asthma and identifies five important aspects of chronic asthma management: (1) assessing asthma control and severity, (2) distinguishing between severe asthma and uncontrolled asthma, (3) personalized pharmacologic therapy for asthma, (4) treatment of modifiable risk factors and control of environmental factors, and (5) guided self-management education and skills training.

1. Assessing asthma control and severity

Asthma control is assessed by evaluating symptoms, activity limitations, and risk of future exacerbations. Asthma symptoms are assessed by asking patients about their past 4 weeks including frequency of symptoms (days per week), awakening from sleep, and frequency of short-acting beta-agonist (SABA) reliever use for relief of symptoms (Table 9–1). Future risk of exacerbations is increased by poor symptom control as well as several other risk factors: more than 1 exacerbation in the previous year, poor asthma medication adherence, incorrect inhaler technique, chronic sinusitis, and smoking. Asthma severity is evaluated retrospectively from the level of treatment needed to control symptoms and exacerbations. For example, a patient who requires Step 3 treatment to achieve control has moderate disease. Figure 9–1 describes the step therapy in a personalized asthma management plan. Typically, mild asthma responds to Step 1 or 2 treatments, moderate asthma, to Step 3 treatment, and severe asthma, to Step 4 or 5 treatments.

2. Severe vs uncontrolled asthma

It is important to distinguish between severe and uncontrolled asthma in patients who are using Step 4 or Step 5 treatments. The clinician must assess inhaler technique, medication adherence, comorbidities such as obstructive sleep apnea or gastroesophageal reflux disease (GERD), and ongoing exposure to allergens as causes of poor asthma control. If the patient still requires Step 4 or 5 therapy after these issues have been addressed, then the patient has severe asthma and should be referred to a pulmonary or asthma specialist.

3. Pharmacotherapy for asthma

The goals of pharmacologic therapy are to minimize chronic symptoms that interfere with normal activity (including exercise), to prevent recurrent exacerbations, to reduce or eliminate the need for emergency department visits or hospitalizations, and to maintain normal or near-normal pulmonary function. Personalized asthma management is a continuous cycle that involves assessment, treatment and review with the goals of symptom control and minimizing future risk. These goals should be met while providing therapeutic agents with the fewest adverse effects and while satisfying patients’ expectations of asthma care. Management should include stepping up therapy if asthma remains uncontrolled despite adherence and good inhaler technique, and stepping down to find the minimum effective therapeutic dose.

4. Treat modifiable risk factors and control environmental factors

Significant reduction in exposure to nonspecific airway irritants in all patients or to inhaled allergens in atopic patients may reduce symptoms and medication needs. Comorbid conditions that impair asthma management, such as smoking, rhinosinusitis, gastroesophageal reflux, obesity, and obstructive sleep apnea, should be identified and treated. Nonpharmacologic interventions include increasing physical activity and breathing exercises.

5. Guided asthma self-management education and skills training

Self-management includes self-monitoring of symptoms or peak flow, a written action plan and regular review of asthma control, treatment and skills with a health care professional.

A. Pharmacologic Agents

Asthma medications can be divided into three categories: (1) long-term controller medications (Table 9–2) used long-term to reduce airway inflammation, symptoms and risk of future exacerbations, (2) reliever medications (Table 9–3) used on an as-needed basis to relieve breakthrough symptoms, and (3) add-on therapies for severe asthma. Figure 9–1 shows a personalized management plan for asthma to control symptoms and minimize future risk.

Most asthma medications are administered by inhalation or by oral dosing. Inhalation of an appropriate agent results in a more rapid onset of pulmonary effects as well as fewer systemic effects compared with the oral dose required to achieve the same effect on the airways. Proper inhaler technique and the use of an inhalation chamber (a “spacer”) with metered-dose inhalers (MDIs) improve drug delivery to the lung and decrease oropharyngeal drug deposition. Nebulizer therapy is reserved for patients who are acutely ill and those who cannot use inhalers because of difficulties with coordination, understanding, or cooperation.

1. Inhaled corticosteroids

Inhaled corticosteroids are essential controller medications (Tables 9–3 and 9–4). Once the diagnosis of asthma is made, early initiation of inhaled corticosteroid therapy leads to a greater improvement in lung function than delayed therapy. Prescribing intermittent or daily controller inhaled corticosteroids at the start of asthma therapy conveys a message to patients that both symptom control and risk reduction are the mainstays of asthma treatment. The most important determinants of medication choice, device and dose are a patient’s symptoms and risk factors, along with practical issues (such as cost and delivery mechanism). Inhaled corticosteroid dosages are classified as low-, medium- and high-dose strengths in various published sources including GINA, but low-dose inhaled corticosteroid provides clinical benefit and is sufficient for most patients with asthma. Dosages for inhaled corticosteroids vary depending on the specific agent and delivery device (Table 9–4). For patients who require high-dose inhaled corticosteroids to achieve adequate symptom control, after 3 months of good control the dose of inhaled corticosteroid should be decreased to the lowest dose that preserves symptom control and minimizes exacerbation risk.

Concomitant use of a MDI and an inhalation chamber coupled with mouth washing after inhaled corticosteroid use decreases systemic absorption and local side effects (cough, dysphonia, oropharyngeal candidiasis). Dry powder inhalers (DPIs) are not used with an inhalation chamber. Systemic effects (adrenal suppression, osteoporosis, skin thinning, easy bruising, and cataracts) may occur with high-dose inhaled corticosteroid therapy. Combination inhalers with an inhaled corticosteroid and a long-acting beta-2-agonist (LABA) offer convenient treatment of asthma. The GINA report recommends low-dose inhaled corticosteroid/formoterol as its preferred agent due to clinical evidence but notes that its cost and availability in different countries must be taken into consideration. Budesonide/formoterol is listed as a World Health Organization essential medication.

2. Beta-adrenergic agonists

Beta-agonists are divided into SABAs and LABAs. SABAs, including albuterol, levalbuterol, bitolterol, pirbuterol, and terbutaline (Table 9–3), are mainstays of reliever or rescue therapy for asthma patients. There is no convincing evidence to support the use of one agent over another. All asthmatics should have immediate access to a SABA because they are the most effective bronchodilators during exacerbations and provide immediate relief of symptoms. Administration before exercise effectively prevents exercise-induced bronchoconstriction.

Inhaled SABA therapy is as effective as oral or parenteral beta-agonist therapy in relaxing airway smooth muscle and improving acute asthma and offers the advantages of rapid onset of action (less than 5 minutes) with fewer systemic side effects. Beta-2-selective agents may produce less cardiac stimulation than those with mixed beta-1 and beta-2 activities, although clinical trials have not consistently demonstrated this finding. Repetitive administration produces incremental bronchodilation. One or two inhalations of a SABA from an MDI are usually sufficient for mild to moderate symptoms. Severe exacerbations frequently require higher doses: 6–12 puffs every 30–60 minutes of albuterol by MDI with an inhalation chamber or 2.5 mg by nebulizer provide equivalent bronchodilation. Administration by nebulization does not offer more effective delivery than MDIs used correctly but does provide higher doses. With most SABAs, the recommended dose by nebulizer for acute asthma (albuterol, 2.5 mg) is 25–30 times that delivered by a single activation of the MDI (albuterol, 0.09 mg). This difference suggests that standard dosing of inhalations from an MDI may be insufficient in the setting of an acute exacerbation. Independent of dose, nebulizer therapy may be more effective in patients who are unable to coordinate inhalation of medication from an MDI because of age, agitation, or severity of the exacerbation.

GINA does not recommend SABA-only treatment of asthma in adults or adolescents and does not recommend scheduled daily use of SABAs. Although SABA is effective as a quick relief medication, patients who are treated with SABA alone are at increased risk for asthma-related death and urgent healthcare even if their symptoms are controlled. Increased use (more than one canister a month) or lack of expected effect indicates diminished asthma control and the need for additional long-term controller therapy.

LABAs provide bronchodilation for up to 12 hours after a single dose. Salmeterol, formoterol, and olodaterol are LABAs available for asthma in the United States. In combination with an inhaled corticosteroid they are indicated for long-term prevention of asthma symptoms (including nocturnal symptoms) and for prevention of exercise-induced bronchospasm. LABAs should not be used as monotherapy because they have no anti-inflammatory effect and because monotherapy has been associated with a small but statistically significant increased risk of severe or fatal asthma attacks in two large studies. Combination inhalers containing formoterol and low-dose budesonide are the preferred option because of a large study in mild asthma that showed a 64% reduction in severe exacerbations compared with SABA-only treatment, and two large studies in mild asthma that showed noninferiority for severe exacerbations compared to low-dose inhaled corticosteroid alone.

3. Systemic corticosteroids

Systemic corticosteroids (oral prednisone or prednisolone or parenteral methylprednisolone) are most effective in achieving prompt control of asthma during acute exacerbations. Systemic corticosteroids are effective as primary treatments for patients with moderate to severe asthma exacerbations and for patients with exacerbations that do not respond promptly and completely to inhaled SABA therapy. These medications speed the resolution of airflow obstruction and reduce the rate of relapse. Delays in administering corticosteroids may result in progressive impairment. Therefore, patients with moderate to severe asthma should be prescribed oral corticosteroids so they are available for early, at-home administration. The minimal effective dose of systemic corticosteroids for asthma patients has not been identified. Outpatient prednisone “burst” therapy is 0.5–1 mg/kg/day (typically 40–60 mg) in 1–2 doses for 3–10 days. Severe exacerbations requiring hospitalization typically require 1 mg/kg of prednisone or methylprednisolone every 6–12 hours for 48 hours or until the FEV₁ (or PEF rate) returns to 50% of predicted (or 50% of baseline). The dose is then decreased to 0.5 mg/kg/day until the PEF reaches 70% of predicted or personal best. No clear advantage has been found for higher doses of corticosteroids. It may be prudent to administer corticosteroids intravenously to critically ill patients to avoid concerns about altered gastrointestinal absorption.

In patients with refractory, poorly controlled asthma, systemic corticosteroids may be required for the long-term suppression of symptoms. Repeated efforts should be made to reduce the dose to the minimum needed to control symptoms. Alternate-day treatment is preferred to daily treatment. Concurrent treatment with calcium supplements and vitamin D should be initiated to prevent corticosteroid-induced bone mineral loss with long-term administration. Bone mineral density testing after 3 or more months of cumulative systemic corticosteroid exposure can guide the use of bisphosphonates for treatment of steroid-induced osteoporosis. Rapid discontinuation of systemic corticosteroids after long-term use may precipitate adrenal insufficiency.

4. Anticholinergics

Anticholinergic agents reverse vagally mediated bronchospasm but not allergen- or exercise-induced bronchospasm. They may decrease mucous gland hypersecretion. Both short-acting muscarinic agents (SAMAs) and long-acting muscarinic agents (LAMAs) are available. Ipratropium bromide, a SAMA, is less effective than SABA for relief of acute bronchospasm, but it is the inhaled drug of choice for patients with intolerance to SABA or with bronchospasm due to beta-blocker medications. Ipratropium bromide reduces the rate of hospital admissions when added to inhaled SABAs in patients with moderate to severe asthma exacerbations. Although LAMAs have long been the cornerstone of therapy for COPD, their role in asthma continues to evolve. Studies have shown that the addition of tiotropium to medium-dose inhaled corticosteroid and salmeterol improves lung function and reduces the frequency of asthma exacerbations.

5. Leukotriene modifiers

Leukotrienes are potent mediators that contribute to airway obstruction and asthma symptoms by contracting airway smooth muscle, increasing vascular permeability and mucous secretion, and attracting and activating airway inflammatory cells. Zileuton is a 5-lipoxygenase inhibitor that decreases leukotriene production, and zafirlukast and montelukast are cysteinyl leukotriene receptor antagonists. In randomized controlled trials (RCTs), these agents caused modest improvements in lung function and reductions in asthma symptoms and lessened the need for SABA rescue therapy. These agents are less effective than inhaled corticosteroid for exacerbation reduction but may be considered as alternatives in patients with asthma who are unable to take inhaled corticosteroid or have undesirable side effects.

6. Phosphodiesterase inhibitor

Theophylline provides mild bronchodilation in asthmatic patients. It also has anti-inflammatory and immunomodulatory properties, enhances mucociliary clearance, and strengthens diaphragmatic contractility. Sustained-release theophylline preparations are effective in controlling nocturnal symptoms and as added therapy in patients with moderate or severe persistent asthma whose symptoms are inadequately controlled by inhaled corticosteroids. Low-dose sustained-release theophylline is included as a less effective option in Step 3 treatment. Neither theophylline nor aminophylline is recommended for therapy of acute asthma exacerbations.

Theophylline has a notably narrow therapeutic-toxic range. At therapeutic doses, potential adverse effects include insomnia, aggravation of dyspepsia and gastroesophageal reflux, and urination difficulties in men with prostatic hyperplasia. Dose-related toxicities include nausea, vomiting, tachyarrhythmias, headache, seizures, hyperglycemia, and hypokalemia. Theophylline serum levels are highly variable due to many factors that alter drug absorption, significant individual differences in metabolism, and multiple drug-drug interactions. Therefore, serum concentrations need to be monitored closely.

Theophylline and its intravenous formulation, aminophylline, are not recommended for therapy of asthma exacerbations. Aminophylline has clearly been shown to be less effective than SABAs when used as single-drug therapy for acute asthma; it adds little except toxicity to the acute bronchodilator effects achieved by nebulized metaproterenol alone. Patients with exacerbations who are currently taking theophylline should have its serum concentration measured to exclude theophylline toxicity.

7. Mediator inhibitors

Cromolyn sodium and nedocromil are long-term control medications that prevent asthma symptoms and improve airway function in patients with mild persistent or exercise-induced asthma. These agents modulate mast cell mediator release and eosinophil recruitment and inhibit both early and late asthmatic responses to allergen challenge and exercise-induced bronchospasm. The clinical response to these agents is less predictable than to inhaled corticosteroids. Both agents have excellent safety profiles.

8. Monoclonal antibody agents

Asthmatic patients who require monoclonal antibody therapies should be evaluated by either a pulmonologist or allergist experienced in their use. Omalizumab is a recombinant antibody that binds IgE without activating mast cells. In clinical trials in patients with moderate to severe asthma and elevated serum IgE levels, omalizumab reduced the need for corticosteroids. Reslizumab, mepolizumab, and benralizumab are interleukin-5 antagonist monoclonal antibodies (anti IL-5/5R) approved for the treatment of severe asthma with peripheral blood eosinophilia that has not responded to standard treatments. Dupilumab is a self-administered monoclonal antibody (anti-IL-4R) that inhibits overactive signalling of interleukin-4 and interleukin-13.

B. Desensitization

Immunotherapy for specific allergens may be considered in selected asthma patients who have exacerbations when exposed to allergens to which they are sensitive and when unresponsive to environmental control measures or other therapies. Studies show a reduction in asthma symptoms in patients treated with single-allergen immunotherapy. Because of the risk of immunotherapy-induced bronchoconstriction, it should be administered only in a setting where such complications can be immediately treated.

C. Vaccination

Adult patients aged 19–64 with asthma should receive the 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23) and annual influenza vaccinations. Inactive vaccines (Pneumovax) are associated with few side effects. However, the use of the intranasal live attenuated influenza vaccine may be associated with asthma exacerbations in young children.

GINA asthma treatment algorithms begin with an assessment of the severity of a patient’s baseline asthma. Adjustments to that algorithm follow a stepwise approach based on a careful assessment of asthma control. Educating patients to recognize symptoms of an exacerbation and to use their action plan are important aspects of asthma management. Symptoms of exacerbations include progressive breathlessness, increasing chest tightness, decreased peak flow, and lack of improvement after SABA therapy (Table 9–5). Most instances of uncontrolled asthma are mild and can be managed successfully by patients at home with self-management plans. More severe exacerbations require evaluation and management in a primary care office (Figure 9–2) or emergency department setting (Figure 9–3).

A. Mild to Moderate Exacerbations

Mild asthma exacerbations are characterized by only minor changes in airway function (PEF greater than 60% of best) with minimal symptoms and signs of airway dysfunction. Many such patients respond quickly and fully to an inhaled SABA alone. However, an inhaled SABA may need to be continued at increased doses, eg, every 3–4 hours for 24–48 hours. Patients may also require a short-term increase in inhaled corticosteroid to four times the usual dose. In patients not improving after 48 hours, a 5- to 7-day course of oral corticosteroids (eg, prednisone 0.5–1.0 mg/kg/day) may be necessary.

The principal goals for treating moderate asthma exacerbations are correcting hypoxemia, reversing airflow obstruction, and reducing the likelihood of obstruction recurrence. Early intervention may lessen the severity and shorten the duration of an exacerbation. Airflow obstruction is treated with continuous administration of an inhaled SABA and the early administration of systemic corticosteroids. Systemic corticosteroids should be given to patients who have a peak flow less than 70% of baseline or who do not respond to several treatments of SABA. Serial measurements of lung function to quantify the severity of airflow obstruction and its response to treatment are useful. The improvement in FEV₁ after 30–60 minutes of treatment correlates significantly with the severity of the asthma exacerbation. Serial measurement of airflow in the emergency department may reduce the rate of hospital admissions for asthma exacerbations. Post-exacerbation care planning is important. All patients, regardless of severity, should be provided with (1) necessary medications and taught how to use them, (2) instruction in self-assessment, (3) a follow-up appointment, and (4) an action plan for managing recurrence.

B. Severe Exacerbations

Severe exacerbations of asthma can be life-threatening, so treatment should be started immediately. All patients with a severe exacerbation should immediately receive oxygen, high doses of an inhaled SABA, and systemic corticosteroids. A brief history pertinent to the exacerbation can be completed while such treatment is being initiated. More detailed assessments, including laboratory studies, usually add little early on and so should be postponed until after therapy is instituted. Early initiation of oxygen therapy is paramount because asphyxia is a common cause of asthma deaths. Supplemental oxygen should be given to maintain an SaO₂ greater than 90% or a PaO₂ greater than 60 mm Hg. Oxygen-induced hypoventilation is extremely rare in asthmatic patients, and concern for hypercapnia should never delay correction of hypoxemia.

Frequent high-dose delivery of an inhaled SABA is indicated and usually well tolerated in severe airway obstruction. At least three MDI or nebulizer treatments should be given in the first hour of therapy. Some studies suggest that continuous therapy is more effective than intermittent administration of these agents, but there is no clear consensus as long as similar doses are administered. After the first hour, the frequency of administration varies according to improvements in airflow and symptoms and occurrence of side effects. Ipratropium bromide reduces the rate of hospital admissions when added to inhaled SABAs in patients with moderate to severe asthma exacerbations.

Systemic corticosteroids are administered as detailed above. Intravenous magnesium sulfate (2 g intravenously over 20 minutes) is not recommended for routine use in asthma exacerbations. However, a 2-g infusion over 20 minutes may reduce hospitalization rates in acute severe asthma (FEV₁ less than 25% of predicted on presentation or failure to respond to initial treatment).

Mucolytic agents (eg, acetylcysteine, potassium iodide) may worsen cough or airflow obstruction. Anxiolytic and hypnotic drugs are generally contraindicated in severe asthma exacerbations because of their potential respiratory depressant effects.

Multiple studies suggest that infections with viruses (rhinovirus) and bacteria (Mycoplasma pneumoniae, Chlamydophila pneumoniae) predispose to acute exacerbations of asthma and may underlie chronic, severe asthma. The use of empiric antibiotics is, however, not recommended in routine asthma exacerbations because there is no consistent evidence to support improved clinical outcomes. Antibiotics should be considered when there is a high likelihood of acute bacterial respiratory tract infection, such as when patients have fever or purulent sputum and evidence of pneumonia or bacterial sinusitis.

In the emergency department setting, repeat assessment of patients with severe exacerbations should be done after the initial dose of an inhaled SABA and again after 3 doses of an inhaled SABA (60–90 minutes after initiating treatment). The response to initial treatment is a better predictor of the need for hospitalization than is the severity of the exacerbation on presentation. The decision to hospitalize a patient should be based on the duration and severity of symptoms, severity of airflow obstruction, ABG results (if available), course and severity of prior exacerbations, medication use at the time of the exacerbation, access to medical care and medications, adequacy of social support and home conditions, and presence of psychiatric illness. In general, discharge to home is appropriate if the PEF or FEV₁ has returned to 60% or more of predicted or personal best and if symptoms are minimal or absent. Patients with a rapid response to treatment should be observed for 30 minutes after the most recent dose of bronchodilator to ensure stability of response before discharge.

In the intensive care setting, a small subset of patients will not respond to treatment and will progress to impending respiratory failure due to a combination of worsening airflow obstruction and respiratory muscle fatigue (see Figure 9–3 and Table 9–5). Since such patients can deteriorate rapidly, they must be monitored in a critical care setting. Intubation of an acutely ill asthma patient is technically difficult and is best done semi-electively before the crisis of a respiratory arrest. At the time of intubation, the patient’s intravascular volume should be closely monitored because hypotension commonly follows the administration of sedative medications and the initiation of positive-pressure ventilation; these patients are often dehydrated due to poor recent oral intake and high insensible losses.

The main goals of mechanical ventilation are to ensure adequate oxygenation and to avoid barotrauma. Controlled hypoventilation with permissive hypercapnia is often required to limit airway pressures. Frequent high-dose delivery of inhaled SABAs should be continued along with anti-inflammatory agents as discussed above. Many questions remain regarding the optimal delivery of inhaled SABAs to intubated, mechanically ventilated patients. Further studies are needed to determine the comparative efficacy of MDIs and nebulizers, optimal ventilator settings to use during drug delivery, ideal site along the ventilator circuit for introduction of the delivery system, and maximal acceptable drug doses. Unconventional therapies such as helium-oxygen mixtures and inhalational anesthetic agents are of unclear benefit but may be appropriate in selected patients.

• Atypical presentation or uncertain diagnosis of asthma, particularly if additional diagnostic testing is required (bronchoprovocation challenge, allergy skin testing, rhinoscopy, consideration of occupational exposure).

• Complicating comorbid problems, such as rhinosinusitis, tobacco use, multiple environmental allergies, suspected allergic bronchopulmonary mycosis.

• Occupational asthma.

• Uncontrolled symptoms despite a moderate-dose inhaled corticosteroid and a LABA.

• Patient not meeting goals of asthma therapy after 3–6 months of treatment.

• Frequent asthma-related healthcare utilization.

• More than two courses of oral prednisone therapy in the past 12 months.

• Any life-threatening asthma exacerbation or exacerbation requiring hospitalization in the past 12 months.

• Presence of social or psychological issues interfering with asthma management.