Asthma-Pharmacotherapy Principles and Practice PDF

SECTION 2 RESPIRATORY DISORDERS 15 Asthma Lori Wilken and Amanda Eades LEARNING OBJ...

SECTION 2 RESPIRATORY DISORDERS 15 Asthma Lori Wilken and Amanda Eades LEARNING OBJECTIVES Upon completion of the chapter, the reader will be able to: 1. Describe the pathophysiology and clinical presentation of acute and chronic asthma. 2. List the treatment goals for asthma. 3. Identify environmental factors associated with worsening asthma control. 4. Discuss the factors to consider when choosing an inhaled drug delivery device for a patient. 5. Recommend an asthma medication regimen for an adult patient based on symptoms. 6. Compare the preferred asthma reliever and controller regimens for children, adolescents, and adults. 7. Describe the purpose of an individualized asthma action plan. INTRODUCTION exposure to tobacco smoke, air pollution, diet, and stress.10 Host A factors that increase risk of developing asthma include genes, sthma is a disorder of the airways characterized obesity, sex, and early growth characteristics including younger by chronic airway inflammation, bronchial gestational age, lower birth weight, and greater infant weight gain. hyperresponsiveness, and airflow obstruction. Patients with asthma typically present with respiratory symptoms such as wheezing, shortness of breath, chest tightness, and cough. PATHOPHYSIOLOGY These symptoms vary over time and in intensity, and worsening Asthma is characterized by airway narrowing and is often triggered by factors such as exercise, allergen exposure, inflammation primarily in medium-sized bronchi. A key patho- change in weather, or respiratory infections.1 Severity of chronic physiologic feature is airway hyperresponsiveness, which is asthma ranges from mild intermittent symptoms to severe and exaggerated narrowing of the airways in response to a trigger or disabling disease. Despite variability in the severity of chronic allergen such as cold air, strong odors, pollen, or dust. Airway asthma, all patients with asthma are at risk of acute severe exac- narrowing results from contraction of airway smooth muscle, erbations that may be life threatening. International guidelines increased mucus secretion, airway edema, and remodeling.1 emphasize the importance of treating underlying airway inflam- In recent years, the discovery of various asthma endotypes, or mation to control asthma and reduce asthma-associated risks.1–5 subtypes of asthma defined by a distinct pathobiological mecha- nism, has helped clinicians individualize treatment regimens to EPIDEMIOLOGY AND ETIOLOGY address a patient’s specific pathophysiology within a very het- Asthma is the most prevalent chronic disease of child- erogeneous disease.1 Two distinct molecular endotypes have hood, and it causes significant morbidity and mortality in both emerged involving a CD4+ T helper 2 (Th2) cell response: Th2 adults and children. About 262 million adults and children high and Th2 low inflammations. worldwide have asthma.6 In the United States, asthma affects 8% Th2 high inflammation asthma includes early-onset allergic of adults (20 million) and 7% of children (5.1 million).7 Asthma asthma, adult-onset eosinophilic nonallergic asthma, and exercise- is the primary diagnosis for 9.8 million physician office vis- induced asthma.11 In early-onset allergic asthma, environmental its, 1.6 million emergency department visits, and 3524 deaths allergens trigger the asthma; it commonly presents in child- annually.7 In 2019, 41.2% of persons with asthma reported having hood and is associated with family history of allergic disease one or more asthma attacks, indicating that nearly half of patients such as eczema, allergic rhinitis, or food or drug allergy.1 Air- with asthma are not optimally controlled.8 way inflammation is initiated by an inhaled allergen or trigger Asthma is also a significant economic burden. Annual per- such as dust, pollen, or animal dander inducing a Th2 response. person medical costs have been estimated to exceed $3000, with This leads to B-cell production of antigen-specific immuno- cost of medications amounting for about 56% of total medical globulin E (IgE), proinflammatory cytokines (eg, interleukin-5), expenditures. The total cost of asthma is estimated to be $81.9 and chemokines that recruit and activate eosinophils, neutro- billion, with 61% for medical costs and nearly 39% attributable to phils, and alveolar macrophages.2 Further exposure to the anti- absenteeism and mortality.9 gen results in cross-linking of cell-bound IgE in mast cells and It is believed that asthma originates primarily early in life basophils, causing release of preformed inflammatory mediators and involves a complex interaction of genetic and environmen- such as histamine, cysteinyl leukotrienes, and prostaglandin D2.1 tal factors such as allergens, occupational sensitizers, infections, Patients with Th2 high asthma typically respond well to inhaled 293 Chisholm_Ch015_p0293-0310.indd 293 11/10/21 12:26 PM  294  SECTION 2 | RESPIRATORY DISORDERS corticosteroids (ICS), monoclonal antibodies to IgE, and Th2- in this subset of asthma often demonstrate severe disease with a targeted therapeutics. poor response to ICS therapy. Adult-onset eosinophilic nonallergic asthma develops in adult- hood and has a severe onset with high levels of eosinophils in sputum and peripheral blood. These patients often have chronic CLINICAL PRESENTATION AND DIAGNOSIS sinusitis, nasal polyps, and asthma that is exacerbated by aspirin See accompanying box for the clinical presentation and diagno- (aspirin-exacerbated respiratory disease, AERD). ICS and IL-5 sis of asthma. Diagnosis is based on a detailed medical history, monoclonal antibodies are used to treat this endotype. physical examination of the upper respiratory tract and skin, and Patients with nonallergic, Th2 low asthma have severe, adult- measurement of expiratory airflow. The clinician determines if onset asthma. The sputum shows a high percentage of neutrophils episodic symptoms of airflow obstruction are present, whether instead of eosinophils. Th2 low asthma is commonly triggered by airflow obstruction is at least partially reversible, and that alterna- viral respiratory infections, air pollution, and cigarette smoke. tive diagnoses are excluded. Full pulmonary function tests should Obesity is also thought to worsen this type of asthma. Patients be performed at baseline in patients 5 years or older to rule out Clinical Presentation and Diagnosis of Asthma General Findings vital capacity) less than 80% (0.80) and a decrease in the Asthma presentation ranges from normal pulmonary function FEV1 to less than 80% (0.80) of the predicted value. with symptoms only during acute exacerbations to significantly Excessive airway variability is seen with: decreased pulmonary function with continuous symptoms of a. A positive bronchodilator test, defined as an increase daily coughing, wheezing, and shortness of breath. in greater than 200 mL and 12% (0.12) in the FEV1 from Acute asthma can present rapidly (within 3–6 hours), but baseline, 10 to 15 minutes after 200 to 400 mcg inhaled deterioration more commonly occurs over a longer period, albuterol or equivalent. For children, a positive test is even days or weeks. Acute asthma can be life threatening. defined as increase in the FEV1 greater than 12% (0.12) Family history, social history, precipitating factors, history of of the predicted value. exacerbations, and development of symptoms are important b. Excessive variability in twice-daily PEF over 2 weeks: components of an asthma diagnosis. average daily diurnal PEF variability >10% (0.10) for adults and >13% (0.13) for children. Symptoms c. Significant increase in lung function after 4 weeks of Patients usually complain of wheezing, shortness of breath, anti-inflammatory treatment. coughing (usually worse at night), and chest tightness. d. Positive exercise challenge test: fall in FEV1 greater Patients may be anxious and agitated. In acute severe than 10% (0.10) and more than 200 mL from baseline asthma, patients may be unable to communicate in for adults, and greater than 12% (0.12) predicted for complete sentences. children. Mental status changes (eg, confusion, irritability, agitation) e. Positive bronchial challenge test: after administration may indicate impending respiratory failure. of methacholine or histamine, a decrease in the FEV1 of The presence of precipitating factors (eg, smoke, mold, or 20% (0.20) at specified doses. viral illness) worsens symptoms. A white blood cell count with differential may show an Symptoms usually have a pattern (eg, worse at night, elevated absolute eosinophil count. seasonal symptoms). Elevated serum immunoglobulin E (IgE) levels may be Physical Exam present. Vital signs may reflect tachypnea, tachycardia, and hypoxemia. Immunoassays are serologic tests used to detect allergies On inspection, there may be hyperexpansion of the thorax in patients that may have sensitivities to molds, dust mites, and use of accessory muscles. pollen, and other triggers that worsen asthma control. The test is used when skin testing is not available or cannot be Auscultation of the lungs may detect end-expiratory used because it is a less sensitive test than skin testing. wheezes in mild exacerbations or wheezing throughout inspiration and expiration in severe exacerbations. Other Diagnostic Tests Bradycardia and absence of wheezing may indicate Arterial blood gases (to evaluate PCo2) should be obtained impending respiratory failure. for patients in severe distress, suspected hypoventilation, In acute asthma, patients may present with pulsus or when PEF or FEV1 is at least 30% less than the percent paradoxus, diaphoresis, and cyanosis. predicted after initial treatment. Pulse oximetry is performed at each visit to assess for Laboratory Tests hypoxemia. Spirometry may demonstrate airway limitation and excessive FeNO changes from baseline may indicate inflammation or airway variability. a response to an ICS. A normal value in adults is less than Airway limitation is demonstrated by a decrease in the FEV1/ 25 parts per billion (ppb). FVC (forced expiratory volume in the first second/forced Chisholm_Ch015_p0293-0310.indd 294 11/10/21 12:26 PM  CHAPTER 15 | ASTHMA  295 other disorders. Spirometry is the preferred method of measuring expiratory airflow for diagnosing asthma in persons older than Table 15–1 5 years; however, peak expiratory flow (PEF) meters may be used Nonpharmacologic Interventions to Improve Symptom in the absence of a spirometer. The medical history and physical Control in Patients With Asthma examination alone are not reliable for characterizing the status of lung impairment or excluding other diagnoses. Spirometry may Tobacco use1 Strongly encourage smokers to quit be normal when the patient is asymptomatic. In this situation, Advise parents/caregivers of children with asthma to not smoke methacholine bronchoprovocation test is used to clinically evalu- and not allow smoking in rooms or cars that children use ate airway hyperresponsiveness. Diagnostic tests to confirm aller- Physical activity1 gic asthma include allergy testing for environmental allergens, a If EIB, use a SABA or ICS–formoterol 5–20 minutes prior to white blood cell count to look for increased eosinophils, blood physical activity IgE antibody level, and occasionally measurements of fractional Encourage stretching and warm-up exercises prior to physical concentration of exhaled nitric oxide (FeNO). activity Occupational exposures1 Chronic Asthma Ask patients with adult-onset asthma about work history and Patients with chronic asthma should be assessed based other exposures on current symptom control as well as future risk of adverse Record when work-related exposures and symptoms occur, outcomes. Asthma control considers the frequency and severity when bronchodilator is needed, and peak airflow at work vs. of symptoms, use of short-acting β2-agonists (SABA) for quick home relief of symptoms, and impact on normal activity and quality of Use respiratory protective devices such as air-purifying masks to life. Future risk refers to the potential for future severe exacerba- help protect against noxious occupational inhalants Identify and eliminate occupational sensitizers and remove tions and asthma-related death, progressive loss of lung function sensitized patients from further exposure, if possible (adults) or reduced lung growth (children), and the occurrence of drug-related adverse effects.4 Asthma severity is determined Medications1 Ask about asthma before prescribing NSAIDs and advise patients by the level of treatment needed to achieve control of asthma to stop NSAIDs if asthma worsens after use symptoms. If β-blockers are indicated, choose cardioselective agents (eg, atenolol). Asthma is not an absolute contraindication to Acute Asthma β-blocker use, but consider the risk vs. benefit In acute asthma, symptoms of wheezing, coughing, and shortness Indoor allergens12 of breath increase. Most exacerbations can be treated at home, Mold: Dehumidifiers, removal of dampness in homes, and mold while some require hospitalization. The severity of the asthma abatement exacerbation does not depend upon the classification of the Rodents and/or cockroaches: Abatement and measures to block patient’s chronic asthma. Patients with intermittent asthma can infestation have life-threatening acute exacerbations. Dust mites: Dust-mite impermeable pillow and mattress covers, HEPA filter-equipped vacuum cleaner, carpet and curtain removal, and cleaning products TREATMENT Diet1 Desired Outcomes Avoid foods for which there is a confirmed allergy The goals of treatment for asthma are directed at maintain- Encourage weight reduction if overweight or obese ing long-term control of symptoms while minimizing adverse Avoid foods containing sulfites if they cause symptoms (eg, beer, wine, shrimp, dried fruit, processed potatoes) effects.1–5 Treatment goals are to: (a) achieve good control of asthma symptoms, (b) maintain normal or near-normal pul- Vaccinations13,14 monary function, (c) maintain normal activity levels, (d) meet Administer yearly influenza vaccine to patients with moderate- to-severe asthma patients’ and families’ expectations of satisfaction with asthma Follow CDC recommendations for administering the care, (e) prevent exacerbations of asthma and the need for emer- pneumococcal and COVID-19 vaccines gency department visits or hospitalizations, (f) prevent progres- Emotional stress1 sive loss of lung function, (g) provide optimal medications with Identify goals and strategies (eg, relaxation, breathing exercises) minimal or no adverse effects, and (h) minimize risk of asthma- to deal with emotional stress if it worsens asthma related death. Weather conditions1 Avoid strenuous outdoor activities during unfavorable weather Nonpharmacologic Therapy conditions Incorporating nonpharmacologic care and education is impor- Cover the nose and mouth with a scarf on cold or windy days tant for patients with asthma. Patient education begins at the Outdoor allergens1 time of diagnosis and should meet the individual patient’s needs. When pollen counts are high, remain indoors and keep windows Asthma management improves when patients are empowered to and doors closed assume an active role in their asthma management and provided If time is spent outdoors, shower afterward to remove allergens with the knowledge and skills to do so.1 It is also vital that all indi- on the skin viduals with asthma be assessed for sensitivity to common aller- Avoid being outdoors in areas of high pollution gens known to worsen asthma. This assessment should include CDC, Centers for Disease Control and Prevention; EIB, exercise- a detailed history of symptoms when exposed to allergens and/ induced bronchospasm; ICS, inhaled corticosteroid; NSAID, or skin testing for sensitivity. For those who are proven to have nonsteroidal anti-inflammatory drug; SABA, short-acting β2 sensitivity to allergens or other environmental triggers, mitiga- agonist. tion interventions may improve asthma control12 (Table 15–1). Chisholm_Ch015_p0293-0310.indd 295 11/10/21 12:26 PM  296  SECTION 2 | RESPIRATORY DISORDERS Patient Encounter Part 1 HPI: A 36-year-old woman presents to the clinic for a yearly emergency department visit in the past year for an asthma check-up. She has no acute health complaints other than exacerbation. She was treated with albuterol/ipratropium symptoms of seasonal allergies (sneezing, runny nose, watery inhalation solution and discharged with a prednisone eyes). She takes loratadine 10 mg as needed for allergy burst. symptoms and fluticasone nasal spray as needed for rhinitis. Allergic rhinitis She reports having mild allergy symptoms year around, but Nasal polyps symptoms are worst in the spring months. The patient has a history of asthma and has been prescribed an albuterol Obesity inhaler to use as needed for asthma symptoms. She cannot Family History: Has a sister who also has asthma. No other recall exactly how often she has used her albuterol inhaler in notable family history the past month but estimates “maybe 4 or 5 times. I usually Social History: Denies tobacco use; socially drinks (1–2 glasses need it about once a week.” She remembers needing it after of wine on the weekends); lives in a smoke-free home, but she participated in a walkathon event stating, “I finished the her mother smokes heavily; denies having any pets; patient walk, but I thought I was going to pass-out afterwards.” She is self-employed (owns a pastry shop in her town); home has also recalls needing to use albuterol when she was helping her hardwood floors throughout. She enjoys walking when it is mother clean out her basement and states, “That day I thought nice outside, but it aggravates her asthma. I was going to end up in the emergency room again.” She says she self-treated with several puffs of albuterol and took some Allergies: Pollen, ragweed, trees, grass, roaches, mold, sulfites, prednisone she had in her cabinet. Otherwise, she attributes dogs, and cats. No known medication allergies. the need for her inhaler to outdoor allergens. She denies any What environmental factors may affect the patient’s asthma nighttime awakenings due to asthma symptoms. control? PMH: What nonpharmacologic recommendations might decrease Mild, intermittent asthma diagnosed during childhood; the patient’s risk of future exacerbations? has never been hospitalized or intubated. She has had one What aspects of the patient’s past medical history are relevant? Pharmacologic Therapy drug particles to deposit in the lungs rather than in the mouth Treatment of chronic asthma involves avoidance of triggers and throat. This technique for DPI and BAI limits their use in known to precipitate or worsen asthma and use of long-term younger patients. Selection of the appropriate inhalation device control and quick-relief medications. Long-term control medica- depends on patient characteristics and medication accessibility. tions include ICS, inhaled long-acting β2-agonists (LABAs), oral leukotriene receptor antagonists (LTRAs), inhaled long-acting ▶▶ Maintenance Medications muscarinic antagonists (LAMA), and biologic agents. Quick- Inhaled Corticosteroids All adults and adoles- relief medications include SABAs, ICS–formoterol, short-acting cents with persistent asthma should receive an ICS-containing muscarinic antagonists (SAMAs), and short bursts of systemic treatment to control symptoms and reduce future risk of severe corticosteroids. exacerbations.1 It is recommended that patients who present with asthma symptoms at least 2 days each month be initiated on ▶▶ Drug Delivery Devices either daily low-dose ICS therapy along with a SABA as needed, Direct airway administration of asthma medications or low-dose ICS–formoterol to use as needed. through inhalation is the most efficient route and minimizes sys- Corticosteroids are the most potent anti-inflammatory agents temic adverse effects. Inhaled asthma medications are available in available for asthma treatment and are available in inhaled, oral, metered-dose inhalers (MDIs), dry powder inhalers (DPIs), slow and injectable dosage forms. They decrease airway inflammation, mist inhalers (SMIs), breath-actuated inhalers (BAI), and inhala- attenuate airway hyperresponsiveness, and minimize mucus pro- tion solutions for nebulization. Poor inhaler technique is com- duction and secretion. Corticosteroids also improve the response mon with inhaler devices and results in increased oropharyngeal to β2-agonists. ICS are more effective than LTRAs in improving deposition, leading to decreased efficacy and increased adverse lung function and preventing emergency department visits and effects. Use of a spacer is recommended with an MDI inhaler to hospitalizations due to asthma exacerbations.1,4 The primary decrease the need for coordination of actuation with inhalation, advantage of using ICS instead of systemic corticosteroids is tar- decrease oropharyngeal deposition, and increase pulmonary drug geted drug delivery to the lungs, which decreases the risk of sys- delivery.15,16 A spacer with a face mask may be used in younger temic adverse effects. Product selection is based on preference for patients who are unable to hold their breath after inhalation. A dosage form, delivery device, and cost. spacer with a face mask is not recommended for most adults Recommended doses of ICS are provided in Tables 15–2 and because the mask results in fewer drug particles being delivered 15–3. ICS have a flat dose–response curve; doubling the dose to the lungs. Using an MDI with a spacer also has faster medi- has a limited additional effect on asthma control.17 Cigarette cation delivery and is as effective as administration by nebuliza- smoking decreases the response to ICS, and smokers require tion. Although DPIs and BAIs have the benefit of not requiring higher doses of ICS than nonsmokers.18 Although some benefi- coordination of breath with the actuation of the inhaler, patients cial effect is seen within 12 hours of administration of an ICS, must demonstrate the ability to breathe quickly and deeply for the 2 weeks of therapy is necessary to see significant clinical effects. Chisholm_Ch015_p0293-0310.indd 296 11/10/21 12:26 PM  CHAPTER 15 | ASTHMA  297 Table 15–2 Estimated Comparative Daily Dosages for Inhaled Corticosteroids and Inhaled Corticosteroid–Long-Acting β2-Agonist Combinations for Asthma in Ages 12 Years and Older1 Medication Low Dose Medium Dose High Dose Beclomethasone HFA Redihaler 80 mcg: 1 inhalation twice 80 mcg: 2 inhalations twice daily 80 mcg: > 2 inhalations 80 mcg/inhalation daily twice daily Budesonide DPI Flexhaler 90 or 90 mcg: 2 inhalations twice 180 mcg: 2 inhalations twice daily 180 mcg: > 2 inhalations 180 mcg/inhalation daily twice daily 180 mcg: 1 inhalation twice daily Ciclesonide HFA MDI 80 or 80 mcg: 1 inhalation twice 160 mcg: 1 inhalation twice daily 160 mcg: > 1 inhalation 160 mcg/inhalation daily twice daily Fluticasone furoate DPI Ellipta 100 or 100 mcg: 1 inhalation daily 200 mcg: 1 inhalation 200 mcg/inhalation daily Fluticasone propionate DPI Respiclick 55 mcg: 1 inhalation twice 113 mcg: 1 inhalation twice daily 232 mcg: 1 inhalation and Digihaler 55, 113, or 232 mcg/ daily twice daily inhalation Fluticasone propionate HFA MDI 110 mcg: 1 inhalation twice 110 mcg: 2 inhalations twice daily 220 mcg: 2 inhalations 110 or 220 mcg/inhalation daily 220 mcg: 1 inhalation twice daily twice daily Fluticasone propionate DPI Diskus 100 mcg: 1 inhalation twice 100 mcg: 2 inhalations twice daily 250 mcg: 2 inhalations 100 or 250 mcg/inhalation daily 250 mcg: 1 inhalation twice daily twice daily Mometasone DPI Twisthaler 220 mcg: 1 inhalation twice 220 mcg: 2 inhalations daily in the 220 mcg: 2 inhalations 220 mcg/inhalation daily evening or 1 inhalation twice daily twice daily Mometasone HFA MDI 100 or 100 mcg: 1 inhalation twice 200 mcg: 1 inhalation twice daily 200 mcg: 2 inhalations 200 mcg/inhalation daily twice daily Combined ICS/LABA Fluticasone/Salmeterol DPI Diskus 100/50 mcg: 1 inhalation 250/50 mcg: 1 inhalation twice 500/50 mcg: 1 inhalation and Inhub 100/50 mcg, 250/50 mcg, twice daily daily twice daily 500/50 mcg Fluticasone/Salmeterol DPI Respiclick 55/14 mcg: 1 inhalation 113/14 mcg: 1 inhalation twice 232/14 mcg: 1 inhalation and Digihaler 55/14 mcg, twice daily daily twice daily 113/14 mcg, 232/14 mcg Fluticasone/Salmeterol HFA MDI 45/21 mcg: 2 inhalations 115/21 mcg: 2 inhalations twice 230/21 mcg: 2 inhalations 45/21 mcg, 115/21 mcg, twice daily daily twice daily 230/21 mcg Budesonide/Formoterol HFA MDI 80/4.5 mcg: 1 inhalation 160/4.5 mcg: 1 inhalation twice daily 160/4.5 mcg: 2 inhalations 80/4.5 mcg, 160/4.5 mcg twice daily twice daily Mometasone/Formoterol HFA MDI 100/5 mcg: 1 inhalation 200/5 mcg: 1 inhalation twice daily 200/5 mcg: 2 inhalations 100/5 mcg, 200/5 mcg twice daily twice daily Fluticasone furoate/Vilanterol DPI 100/25 mcg: 1 inhalation 200/25 mcg: 1 inhalation Ellipta 100/25 mcg, 200/25 mcg daily daily DPI, dry powder inhaler; HFA, hydrofluoroalkane; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; MDI, metered-dose inhaler. Longer treatment may be necessary to realize the full effects on in adults.21 An important drug interaction causing Cushing airway inflammation. syndrome and adrenal insufficiency occurs when potent inhib- Local adverse effects associated with ICS therapy include itors of CYP3A4 (eg, ritonavir, itraconazole, ketoconazole) are oral candidiasis, cough, and dysphonia. For most delivery administered with high doses of ICS; therefore, coadministra- devices, the majority of the drug is deposited in the mouth and tion should be avoided whenever possible.22 Poor adherence throat and swallowed. The incidence of local adverse effects to ICS treatment is common and contributes to uncontrolled can be reduced by using an MDI with a spacer and by hav- asthma.23 The cost, slow onset of action and concerns about ing the patient rinse the mouth with water and expectorate side effects are major deterrents to using these highly effective after use. Decreasing the dose reduces the incidence of hoarse- medications. ness. Systemic adverse effects, such as adrenal suppression and Considerable variability in response to ICS exists, with up to decreased bone mineral density, may also occur with long-term 40% of patients not responding to ICS. This lack of response may high doses of ICS. Growth suppression is a concern of some be related to functional glucocorticoid-induced transcript 1 gene parents whose children are prescribed an ICS. However, final (GLCCI1) variant in some patients with asthma.24 adult height is not thought to be affected by ICS use, but growth Systemic Corticosteroids Add-on low-dose oral corticoste- velocity is slightly reduced (by less than half a centimeter per roids (prednisone, prednisolone, methylprednisolone) are con- year), and height after 1 year of treatment is decreased by less sidered a last-line option for patients with severe, uncontrolled than 1 cm in children treated with low- and medium-dose asthma when all other add-on treatment options have been ICS.19,20 Risk of pneumonia is increased with higher ICS doses Chisholm_Ch015_p0293-0310.indd 297 11/10/21 12:26 PM  298  SECTION 2 | RESPIRATORY DISORDERS Table15–3 Estimated Comparative Daily Dosages for Inhaled Corticosteroids and Inhaled Corticosteroid—Long-Acting β2-Agonist Combinations for Asthma in Children < 12 Years Old1 Medication Low Dose Medium Dose High Dose Beclomethasone HFA BAI 5 years of age: 6–11 years of age: 6–11 years of age: 40 or 80 mcg/inhalation 40 mcg: 1 inhalation twice daily 80 mcg: 2 inhalations twice daily 80 mcg: > 2 inhalations twice 6–11 years of age: daily 40 mcg: 1–2 inhalations twice daily 80 mcg: 1 inhalation twice daily Budesonide DPI 90 or 6–11 years of age: 6–11 years of age: 6–11 years of age 180 mcg/inhalation 90 mcg: 1 inhalation twice daily 180 mcg: 1 inhalation twice daily 180 mcg: > 2 inhalations twice daily Budesonide inhalation suspension 0–4 years of age: 0.25 mg once or 0–4 years of age: 0.25–0.5 mg 0–4 years of age: > 0.5 mg twice for nebulization 0.25 mg/2 mL, twice daily twice daily daily 0.5 mg/2 mL, 1 mg/2 mL 5–11 years of age: 0.25 mg twice 5–11 years of age: 0.5 mg twice 5–11 years of age: 1 mg twice daily or 0.5 mg once daily daily daily Fluticasone propionate HFA MDI 4–11 years of age: 4–11 years of age: 6–11 years of age: 44, 110, or 220 mcg/inhalation 44 mcg: 1 inhalation twice daily 44 mcg: 2 inhalations twice daily 110 mcg: ≥ 1 inhalation twice daily1 Fluticasone propionate DPI 50 or 4–11 years of age: 4–11 years of age: 4–11 years of age: 100 mcg/inhalation 50 mcg: 1 inhalation twice daily 100 mcg: 1 inhalation twice daily 100 mcg: 1 inhalation twice daily Fluticasone furoate DPI 5–11 years of age: 50 mcg/inhalation 50 mcg: 1 inhalation daily Mometasone HFA MDI 50 mcg/ 5–11 years of age: 5–11 years old: 5–11 years old inhalation 50 mcg: 1 inhalation twice daily 50 mcg: 1 inhalation twice daily 50 mcg: 2 inhalations twice daily Mometasone DPI 110 mcg/ 4–11 years of age: inhalation 110 mcg: 1 inhalation daily in the evening Combined ICS/LABA Fluticasone/Salmeterol DPI 4–11 years of age: 100/50 mcg 100/50 mcg: 1 inhalation twice daily Budesonide/Formoterol HFA 6–11 years of age: MDI 80/4.5 mcg 80/4.5 mcg: 2 inhalations twice daily Mometasone/Formoterol HFA 5–11 years of age: MDI 50/5 mcg 50/5 mcg: 2 inhalations twice daily BAI, breath-actuated inhaler; DPI, dry powder inhaler; HFA, hydrofluoroalkane; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist; MDI, metered-dose inhaler. expended. Prior to considering addition of oral corticosteroids, containing LABAs includes a box warning against their use with- barriers to asthma control should be assessed (eg, poor inhaler out an ICS. The risk of increased severe asthma exacerbations technique, nonadherence to inhaled treatments, exposure to does not appear to be increased in adults receiving both a LABA environmental triggers). If systemic therapy is necessary, once- and ICS.27 daily or every-other-day therapy is used with repeated attempts to Salmeterol is available as a single-ingredient product and as a decrease the dose or discontinue the drug. Patients must be coun- fixed-ratio combination product containing an ICS. Formoterol is seled on potential adverse effects including weight gain, mood available in combination with ICS for asthma and as an inhalation disturbances, hypertension, impaired wound healing, adrenal solution for nebulization for COPD. Vilanterol is available only suppression, and decreased bone mineral density. in combination with ICS. Combination products may increase Long-Acting Inhaled β2-Agonists LABAs are frequently used adherence because of the need for fewer inhalers and inhalations. as add-on maintenance therapy for asthma that is not controlled The individual LABAs vary both in their onset and duration of on an ICS alone. Class benefits of LABAs when used as mainte- action. Vilanterol has the longest duration of action, allowing nance therapy in combination with an ICS include improved pul- for once-daily dosing, while salmeterol and formoterol must be monary function, increased symptom-free days, and decreased dosed every 12 hours. Salmeterol has a delayed onset of action need for SABA use. Adding a LABA to a low-dose ICS is at least compared to the other LABAs; both vilanterol and formoterol as effective in improving symptoms and decreasing asthma exac- have an onset of action of around 5 minutes, whereas salmeterol erbations as doubling the dose of an ICS or adding an LTRA to onset is around 15 minutes. ICS.25 Adding a LABA to ICS therapy also reduces the amount Long-Acting Muscarinic Antagonists (LAMAs) Muscarinic of ICS necessary for asthma control.5 LABAs should not be used antagonists inhibit the effects of acetylcholine on muscarinic as monotherapy for chronic asthma because there may be an receptors in the airways and protect against cholinergic-mediated increased risk of severe asthma exacerbations and asthma-related bronchoconstriction. Tiotropium bromide is an inhaled LAMA deaths when LABAs are used alone.26 Labeling for all drugs available as a slow-mist inhaler for asthma. It has an onset in Chisholm_Ch015_p0293-0310.indd 298 11/10/21 12:26 PM  CHAPTER 15 | ASTHMA  299 approximately 30 minutes and a duration longer than 24 hours. exacerbations, and increases asthma-related quality of life.34 The Tiotropium is used as a long-term controller medication in initial dose is based on the patient’s weight and baseline total patients at least 6 years of age with uncontrolled asthma already serum IgE concentration. See Table 15–4 for dosing recommen- taking an ICS or an ICS and LABA combination.28,29 Addition of dations. Subsequent IgE levels are not monitored. a LABA is preferred over adding a LAMA to patients who are The most common adverse effects of omalizumab are not adequately controlled on an ICS alone.12 Addition of tiotro- injection-site reactions (bruising, redness, pain, stinging, itching, pium to combined ICS-LABA therapy has been associated with and burning). Anaphylactic reactions are rare but may occur at improved asthma control and quality of life with no change in any time after medication administration. Monitoring the patient exacerbations. for an anaphylactic reaction for 2 hours after medication admin- Umeclidinium is another LAMA available as a three-drug com- istration is recommended for the first 3 months; thereafter, moni- bination with fluticasone and vilanterol for treatment of asthma toring time can be reduced to 30 minutes.35 It is also important in patients at least 18 years of age. This is currently the only once- to issue a prescription for subcutaneous epinephrine and educate daily single inhaler with triple therapy available for treatment of the patient on its use for anaphylactic reactions to omalizumab. asthma. In clinical trials, combination umeclidinium–fluticasone– Interleukin-5 (IL-5) and IL-5R (Receptor) Antagonist Monoclonal vilanterol showed statistically significant improvements in Antibody For patients with severe asthma exacerbations in FEV1 when compared to combination fluticasone–vilanterol.30 the past year and high blood eosinophil counts, starting a Muscarinic-antagonists may cause adverse effects such as urinary medication that decreases eosinophils improves asthma out- retention, dry mouth, headache, and upper respiratory tract infec- comes. Mepolizumab and reslizumab are monoclonal antibod- tions. Refer to Table 15–4 for LAMA dosing recommendations. ies that block the cytokine IL-5 from recruiting eosinophils. Leukotriene Receptor Antagonists The LTRAs are anti- Benralizumab is a monoclonal antibody that binds directly to inflammatory medications that either inhibit 5-lipoxygenase the IL-5 receptor alpha on eosinophils and destroys the cells. (zileuton) or competitively antagonize the effects of leukotriene All three medications decrease asthma exacerbations and D4 (montelukast, zafirlukast). These agents improve FEV1 and symptoms.36–38 Common side effects include nasopharyngitis, decrease asthma symptoms, SABA use, and asthma exacerba- headache, hypersensitivity reactions, and worsening asthma or tions. Although they offer the convenience of oral administra- upper respiratory tract infections. Long-term side effects are tion, they are significantly less effective than ICS.4,31 Combining unknown. See Table 15–4 for dosing. an LTRA with an ICS is not as effective as an ICS plus a LABA but Interleukin-4 (IL-4) Receptor Alpha Antagonist Monoclonal is considered steroid sparing.1,4 LTRAs are beneficial for asthma Antibody Dupilumab improves the symptoms of patients patients with allergic rhinitis, aspirin sensitivity, or exercise- with high IgE and eosinophil counts by inhibiting IL-4 and induced bronchospasm (EIB).1 IL-13 signaling in Th2 inflammation. Dupilumab decreases Montelukast has a boxed warning about serious mental health asthma exacerbations, oral corticosteroid dosing, and asthma side effects. All three LTRAs have reports of neuropsychiatric symptoms.39 The most common side effects are injection site events, such as sleep disorders, aggressive behavior, and suicide. pain and transient blood eosinophilia. Zileuton and zafirlukast are less commonly used because of the Macrolides Recent evidence indicates that azithromycin 500 mg risk of hepatotoxicity. Zileuton use requires liver function tests orally three times weekly decreases asthma exacerbations and prior to use, monthly for 3 months, every 3 months for the first improves quality of life for adults with asthma not controlled with year, and periodically thereafter. Zileuton and zafirlukast are a medium-to-high dose ICS and LABA.40 Results were similar metabolized through the CYP 2C9 hepatic pathway and have sig- in patients with both eosinophilic and noneosinophilic asthma. nificant drug interactions. Refer to Table 15–4 for LTRA dosing Potential benefits result from anti-inflammatory and not anti- recommendations. microbial properties. Screening for hearing impairment, cardiac Biologic Agents About 3.7% of patients with asthma have arrhythmias, and drug interactions is recommended prior to ini- severe, difficult to treat asthma requiring high doses of ICS and at tiating treatment. There is no clear evidence on how long azithro- least one other controller medication along with frequent bursts mycin should be continued, but a clear benefit was not seen until of oral corticosteroids or daily use of oral corticosteroids.32,33 after 3 months of treatment. Treatment for at least 6 months is These patients have poor symptom control despite good adher- recommended.1 ence to medications and appropriate inhaler technique. Bio- logic agents target Th2 inflammation, allowing for reduction ▶▶ Reliever Medications or discontinuation in corticosteroid use, fewer asthma exacer- Short-Acting Inhaled B2-Agonists SABAs such as albuterol bations, and improved lung function. Assessing inflammatory (known as salbutamol outside the United States) reverse acute markers such as IgE, blood eosinophils, and FeNO help identify airway obstruction caused by bronchoconstriction and block the appropriateness of an individual biologic agent. the early-phase response to antigen in an asthma exacerbation. Anti-IgE Monoclonal Antibody Omalizumab is a recombinant They also increase mucociliary clearance and stabilize mast-cell humanized monoclonal anti-IgE antibody that inhibits bind- membranes. Due to their rapid onset of action for reversing bron- ing of IgE to receptors on mast cells and basophils, resulting in choconstriction, inhaled SABAs have been considered the cor- inhibition of inflammatory mediator release and attenuation of nerstone of therapy for acute asthma exacerbations. More recent the early- and late-phase allergic response. Omalizumab is indi- evidence shows that SABA use without an ICS increases the risk cated for patients with moderate-to-severe persistent asthma of asthma-related death, urgent asthma-related healthcare, and whose symptoms are not controlled by ICS and who have a posi- reduced lung function.41 Based on these findings, SABAs may tive skin test or in vitro reactivity to aeroallergens and elevated still be used to manage acute asthma symptoms, but guidelines IgE (30–700 IU/mL [kIU/L] for patients age 12 and older or recommend that an ICS be given concomitantly in patients age 30–1300 IU/mL [kIU/L] for ages 6–11 years). Omalizumab sig- 6 years and older.1 Scheduled SABA use decreases the duration of nificantly decreases ICS use, reduces the number and length of bronchodilation provided by the SABA and is not recommended. Chisholm_Ch015_p0293-0310.indd 299 11/10/21 12:26 PM 300  SECTION 2 | RESPIRATORY DISORDERS Table 15–4 Usual Doses of Long-Term Control Medications in Asthmaa Medication Dosage Form Ages 0–11 Years Adults and Children > 12 Years Inhaled Corticosteroids (see Tables 15–2 and 15–3) Inhaled Corticosteroids/Long-Acting β2-Agonists (see Tables 15–2 and 15–3) Long-Acting β2-Agonists Salmeterol DPI 50 mcg/blister Ages 0–3 years: N/A One inhalation every 12 hours Ages 4–11 years: One inhalation every 12 hours Long-Acting Muscarinic Agents Tiotropium SMI 1.25 mcg/actuation Ages 0–5: N/A Two inhalations once daily Ages 6–11: Two inhalations of 1.25 mcg once daily Inhaled Corticosteroid/Long-Acting β2-Agonists/Long-Acting Muscarinic Fluticasone/ DPI 100/62.5/25 mcg/actuation or N/A Age 12-17: N/A Umeclidinium/ 200/62.5/25 mcg/actuation Age 18 and older: One inhalation daily Vilanterol Leukotriene Modifiers Montelukast 4 mg or 5 mg chewable tablets Ages 1–5 years: 4 mg at bedtime Ages 12–14 years: 5 mg at bedtime 4 mg granule packets Ages 6–11 years: 5 mg at bedtime Ages 15 and older: 10 mg at bedtime 10 mg tablet Zafirlukast 10 or 20 mg tablets Ages 0–4 years: N/A 20 mg twice daily Ages 5–11 years: 10 mg twice daily Zileuton 600 mg extended-release tablet N/A: only approved for those Extended-release tablets: 1200 mg twice daily after 600 mg immediate-release tablet 12 years of age and older morning and evening meals Immediate-release tablets: 600 mg four times daily Anti-IgE Monoclonal Antibody Omalizumab Injection: 75 mg/0.5 mL and Ages 0–5: N/A 150–375 mg SC every 2–4 weeks, depending on 150 mg/mL solution in Ages 6–11: 75–375 mg SC every body weight and pretreatment serum IgE level; prefilled syringe and 150 mg 2–4 weeks, depending on body see dosing chartb powder in single-dose vial for weight and pretreatment serum reconstitution IgE level; see dosing chartb Interleukin-5 and Interleukin-5 Receptor Antagonist Monoclonal Antibodies Mepolizumab Injection: 100 mg/mL, single- Age 0-5: N/A 100 mg SC once every 4 weeks; suggested AEC dose, prefilled autoinjector or Ages 6-11: 40 mg SC once every ≥150–300 cells/μL (0.15 × 109–0.3 × 109/L) prefilled syringe and 100 mg 4 weeks powder for reconstitution Reslizumab Injection: 100 mg/10 mL vial N/A Ages 12-17: N/A Ages 18 and older: 3 mg/kg IV infusion over 20–50 minutes every 4 weeks; suggested AEC ≥ 400 cells/μL (0.4 × 109/L) Benralizumab Injection, 30 mg/mL prefilled N/A 30 mg SC every 4 weeks for the first 3 doses, syringe and single-dose followed by once every 8 weeks; suggested autoinjector pen AEC > 300 cells/μL (0.3 × 109/L) Interleukin-4 Receptor Alpha Antagonist Monoclonal Antibody Dupilumab Injection: 200 mg/1.14 mL N/A 400 mg SC, followed by 200 mg SC every other and 300 mg/2 mL prefilled week; suggested AEC >150 cells/μL (0.15 × 109/L) syringe; 300 mg/2 mL and or FeNO ≥ 25 ppb 200 mg/1.14 mL solution in a OR prefilled pen 600 mg SC, followed by 300 mg SC every other week for patients on OCS or also having atopic dermatitis and asthma a Dosages are provided for products that have been approved by the US FDA or have sufficient clinical trial safety and efficacy data in the appropriate age ranges to support their use. b XOLAIR (omalizumab) Dosing for Allergic Asthma, CIU & Nasal Polyps (xolairhcp.com). AEC, absolute eosinophil count; DPI, dry powder inhaler; FeNO fraction of exhaled nitric oxide ppb parts per billion; IgE, immunoglobulin E; IV, intravenous; N/A, safety and efficacy not established; OCS, oral corticosteroid; SC, subcutaneous; SMI, slow mist inhaler. Inhaled SABAs have an onset in less than 5 minutes and a dura- the pure R-enantiomer of albuterol (referred to as R-salbutamol tion of action of 4 to 6 hours. Albuterol is the most commonly outside the United States), is available as an MDI and an inhala- used inhaled SABA and is available as an MDI, breath-actuated tion solution for nebulization. Levalbuterol has similar efficacy DPI, and an inhalation solution for nebulization. Levalbuterol, to albuterol and is purported to have fewer side effects; however,  CHAPTER 15 | ASTHMA  301 Table 15–5 Usual Dosages for Reliever Medications for Asthma in Home Settinga,b Adults and Children 12 Years Medications Dosage Form Children 0–11 Years of Age and Older Inhaled SABA Albuterol HFA MDI (inhalation suspension) 0–11 years: 2–6 inhalations every 4–6 hours as 2 inhalations every 4–6 hours as 90 mcg/inhalation, 200 needed1 needed actuations/canister Albuterol DPI (inhalation powder) Not approved for 30/min or > 150 bpm (4–5 years) ≤ 5 years of age Accessory muscles in use O2 saturation < 92% (0.92) Give inhaled SABA + ipratropium bromide in ED Pulse rate > 120 bpm Marked subcostal and/or setting; no benefit from adding ipratropium to O2 saturation (on air) < 90% (0.90) subglottic retractions SABA once hospitalized PEF < 50% predicted or personal Oxygen to maintain saturation 93%–95% (0.93– best 0.95) for adults; 94%–98% (0.94–0.98) for children; > 95% (0.95) during pregnancy Oral or IV systemic corticosteroids; oral preferred if possible Consider IV magnesiuma Epinephrine indicated only if exacerbation is associated with anaphylaxis and angioedema Subset: Life Too dyspneic to speak Unable to speak or drink Transfer to ICU Threatening Drowsiness Central cyanosis While waiting, start SABA + ipratropium bromide, Confusion Silent chest IV corticosteroids, and O2 to maintain saturation Silent chest Confusion 93%–95% (0.93–0.95) for adults; 94%–98% (0.94– Central cyanosis 0.98) for children; > 95% (0.95) during pregnancy Pulse rate > 200 bpm Prepare patient for intubation PEF < 25% predicted or personal Consider IV magnesiuma best Epinephrine indicated only if exacerbation is associated with anaphylaxis and angioedema a Intravenous magnesium sulfate is not recommended for routine use in asthma exacerbations; however, it reduces hospital admissions in some patients, including adults with FEV1 < 25%–30% predicted at presentation; adults and children who fail to respond to initial treatment and have persistent hypoxemia; and children whose FEV1 fails to reach 60% predicted after 1 hour of care. The role of magnesium sulfate is not established for children ages 5 years and younger but may be considered as an adjuvant to standard treatment in children 2 years or age and older with severe asthma. bpm, beats per minute; ED, emergency department; FEV1, forced expiratory volume in first second; ICU, intensive care unit; MDI, metered-dose inhaler; O2, oxygen; PEF, peak expiratory flow; SABA, short-acting β2-agonist. Data obtained from Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021. Available from: www.ginasthma.org. Asthma control is assessed by evaluating symptoms of worsen- established over a 2- to 3-week period when the patient is receiving ing asthma and/or monitoring PEF. Early signs of deterioration optimal treatment.4 Subsequent PEF measurements are evaluated include increasing nocturnal symptoms, increasing use of reliever in relation to their variability from the patient’s best PEF mea- medication, or symptoms that do not respond to increased use surement. PEF measurements in the range of 80% to 100% of per- of reliever medication. Providing patients with a prescription for sonal best (green zone) indicate that current therapy is acceptable. oral corticosteroids to use on an as-needed basis at the onset of an A PEF in the range of 50% to 79% of personal best (yellow zone) asthma exacerbation is part of asthma self-management. indicates an impending exacerbation, and therapy is intensified Measurement of PEF is considered for patients with moderate- with reliever therapy, possibly oral corticosteroids, and a call to to-severe persistent asthma, poor perception of worsening asthma the physician. A PEF less than 50% (red zone) signals a medical or airflow obstruction, and those with an unexplained response alert; patients use their reliever medications immediately, take to environmental or occupational exposures.4 PEF measurements oral corticosteroids, and go to the emergency department. PEF are not necessary for a patient to receive an asthma action plan; measurements alone should not be used to determine the sever- the plan can be based on symptoms only. PEF is measured daily ity of airflow limitation. Measurements can be falsely elevated in the morning upon waking or when asthma symptoms worsen. or decreased with poor technique, such as coughing into the meter For PEF-based action plans, the patient’s personal best PEF is or insufficient patient effort. Smaller airways may become inflamed  306  SECTION 2 | RESPIRATORY DISORDERS Patient Encounter Part 3 CC: “One minute I felt fine and then I just couldn’t breathe.” Neuro/Psych: Grossly normal, normal affect HPI: Patient presented to ED with complaints of worsening Asthma Control Test: 15 out of 25 (goal above 20); 3 months shortness of breath not relieved by use of albuterol 4 prior to today’s visit ACT: 23 inhalations every 20 minutes. Symptoms began this morning PEFR: 350 L/min best. 210 L/min in ED today while she was visiting with her mother and worsened despite use of albuterol MDI. It became difficult for her to speak in full FeNO: 50 ppb at last visit sentences, so her husband brought her to the emergency Review of RAST testing: Pollen, ragweed, trees, grass, roaches, department. She was treated with albuterol–ipratropium mold, dogs, and cats inhalation solution and started on oral prednisone 40 mg daily. Spirometry from 1 month ago: Supplemental oxygen was given because O2 saturation was 92% (0.92) upon arrival. O2 saturation now improved to 98% Measured % Predicted (0.98) on room air. Patient is feeling better and is able to speak FVC (L) 3.87 112.73 in full sentences. Patient states that her asthma symptoms have FEV1 (L) 3.10 75.09 been worse lately because she has been spending a lot of time FEV1/FVC (%) 80 – outside gardening. She’s been using her albuterol inhaler 3 to 4 TLC (L) 5.93 92.47 days a week after being outdoors for extended periods. DLCO (mL/min/mm Hg) 29.31 143.09 ROS: Summary: Normal FEV1/FVC. FVC is normal and FEV1 is decreased. General: no fever/chills, night sweats; + obesity There is a response to inhaled bronchodilator (not shown in the table). The TLC and diffusing capacity are normal. ENT: + allergic rhinitis, + nasal congestion, + postnasal drip, occasional mouth breathing Labs: Respiratory: + shortness of breath, no cough Na 141 mEq/L (mmol/L) WBC 9.6 × 103 cells/μL The reminder of the ROS is noncontributory. (9.6 × 109/L) K 3.6 mEq/L (mmol/L) Absolute eosinophil count PE: 400 cells/μL (0.4 × 109/L) VS: Temp 36.3°C, BP 138/84 mm Hg, Pulse 90 bpm, Cl 104 mEq/L (mmol/L) Hgb 15.4 g/dL (154 g/L; RR 20 breaths/min, Sao2 98% (0.98), Ht 162 cm, Wt 85 kg, BMI 9.56 mmol/L) 32.4 kg/m2 CO2 30 mEq/L (mmol/L) Hct 43.9% (0.439) Anion gap 7 Plt 216 × 103 cells/μL Gen: NAD (216 ×109/L) Eyes: PERRL, EOMI Ca 9.3 mg/dL (2.33 mmol/L) IgE 90 IU/mL (kIU/L) Scr 0.92 mg/dL (81 μmol/L) Aspergillus antibody: none HEENT: OP clear, septal spur with deviation to the left noted, detected TMs clear eGFR 106 mL/min/1.73 m2 Lungs: + slight wheezing at both bases What therapeutic regimens are available for this patient? CV: RRR no m/r/g Provide this patient with an asthma action plan. Abd: Soft, NT/ND Recommend monitoring and follow-up for this patient. Skin: No rash/hives, + hyperpigmented cheeks during severe exacerbations, and the PEF is unable to detect this, Monitor use of reliever medications to help determine asthma possibly causing a patient to be discharged from the hospital with control and if a step-up in therapy is warranted. an unresolved exacerbation. Use the PEF meter as a tool along Determine the frequency of patient exacerbations. Frequent with assessing the patient’s symptoms for best care. It is important exacerbations, unscheduled clinic visits, emergency department to advise patients who use peak flow meters as a monitoring tool visits, and hospitalizations due to asthma may indicate the need to treat asthma symptoms in accordance with their asthma action to reassess the patient’s asthma regimen and environment. plan even if the PEF does not indicate airflow impairment. Measure lung function using office spirometry yearly in patients older than 5 years. OUTCOME EVALUATION Identify environmental factors triggering asthma exacerbations Chronic Asthma and provide trigger avoidance recommendations. Perform medication reconciliation to identify discrepancies Assess onset, duration, and timing of subjective symptoms in medications prescribed and used by the patient and to such as wheezing, shortness of breath, chest tightness, cough, determine drug and disease state interactions. nocturnal awakenings, and activity level. Use validated questionnaires (such as the Asthma Control Test, Asthma Assess adherence to medications and inhaler technique at Therapy Assessment Questionnaire, or Asthma Control every visit and always ensure adherence and proper technique Questionnaire) to objectively document control. before stepping up therapy. Chisholm_Ch015_p0293-0310.indd 306 11/10/21 12:26 PM  CHAPTER 15 | ASTHMA  307 Patient Care Process: Chronic Asthma Collect Information: Assess inhaler technique. Identify any barriers that inhibit the Perform a medication history for use of prescription and patient from using their inhaler correctly. nonprescription medications and dietary supplements. Determine if the patient needs the influenza, COVID-19 and Identify allergies to medications and other substances. pneumococcal vaccines. Review previous full pulmonary function tests, RAST, CBC, IgE Assess the patient’s readiness to stop using tobacco or levels, and chemistry panel. marijuana. Assess patient’s peak flow measurement (if applicable). Develop a Care Plan: Collect current asthma control using validated questionnaire Document the patient’s specific goals for asthma control. (eg, ACT or c-ACT) results. If the patient is not controlled, before adding medications or Document current height, weight, blood pressure, heart rate, increasing dosing, make sure the patient is using the current and pulse oximetry. inhalers correctly and is willing to use the inhalers. Auscultate the lungs for wheezing. Look in the mouth for If asthma is not controlled and patient is adherent to their signs of oral candidiasis if on ICS. asthma medications and using them correctly, consider a Identify asthma exacerbations since the last visit, including step up in therapy. emergency room visits or hospitalizations, or use of oral Identify patient preference, ability to pay, and insurance corticosteroid bursts. coverage for MDI, DPI, SMI, BAI, or nebulization. Ask about tobacco use and exposure to secondhand smoke If the patient is controlled and has been on the current (tobacco or marijuana). regimen for 3 months or longer, consider discontinuing or Ask the patient to demonstrate inhaler use. Ask when the lowering the dose of controller medications. inhaler is used, how many times in the past week the inhaler Implement the Care Plan: was used, and when the inhaler was last refilled. Educate the patient about changes in drug therapy, Identify the number of missed days of school or work medication administration, potential new adverse effects, because of asthma. and how to manage and report adverse effects that may Ask about patient (or caregiver) goals and satisfaction with occur. asthma control. Review patient’s technique with inhalers. Use physical Collect diet and exercise information and use of SABA or demonstration with placebo inhalers, standardized checklists, reliever before exercise. pictures, and videos of inhalers (http://use-inhalers.com/). Identify comorbid conditions that may affect asthma control Provide an updated medication list with indication and use including gastroesophageal reflux disease (GERD), allergic of each inhaler device. rhinitis, sleep apnea, anxiety, and depression. Provide an updated asthma action plan with medication Assess the Information: changes. Evaluate medication side effects (rapid heart rate, jitteriness, Review environmental asthma triggers and avoidance plans. bad taste, cough, dysphonia, lack of efficacy). Administer and update vaccinations. Verify medication adherence. Examine the patient’s inhaler Discuss diet and exercise (using SABA or ICS–formoterol prior for the number of doses remaining. Call the dispensing to exercise if needed). pharmacy to determine fill history of inhalers. Refill all asthma-related medications, including medications Determine whether the patient is taking any medications to treat allergic rhinitis and GERD. (including prescription, OTC, or supplements) that may cause cough or worsen asthma control. Follow-up: Monitor and Evaluate: Determine if patient’s asthma medications are appropriate Schedule follow-up physician visits depending on asthma based on spirometry results, exacerbation history, and control (3–6 months). current asthma control. Check spirometry yearly. Identify changes in home, work, or school environment that Review adherence and inhaler technique at every visit. may contribute to worsening asthma symptoms. Update asthma action plan yearly or with each medication Assess for worsening in comorbid conditions that may change. contribute to worsening asthma symptoms. Monitor ACT quarterly. Identify factors that may be affecting medication adherence Monitor medication refill history. including side effects, cost issues, formulary issues, and unclear understanding of purpose of inhalers. Evaluate asthma-related hospitalizations, emergency department visits, and oral corticosteroid use. 308  SECTION 2 | RESPIRATORY DISORDERS Assess the patient’s understanding of the indication for long- 2. National Institute for Health and Care Excellence. Asthma: term controller medication and identify adverse events, cost Diagnosis Monitoring and Chronic Asthma Management. NICE issues, and need for refills. Guideline (NG80). February 2020. Available at www.nice.org.uk/ guidance/ng80. Review and update the asthma action plan and provide the 3. Global Initiative for Asthma (GINA). Asthma, COPD and Asthma- patient with a written copy of the plan. COPD Overlap Syndrome (ACOS), 2015. Available at http:// Update the patient’s immunization status and provide an goldcopd.org/asthma-copd-asthma-copd-overlap-syndrome. annual influenza vaccination. 4. NHLBI National Asthma Education and Prevention Program, Expert Panel Report-3. Guidelines for the diagnosis and Acute Asthma management of asthma. NIH Publication No. 07-4051. Bethesda, In addition to the outcomes measured for chronic asthma, acute MD: U.S. Department of Health and Human Services; 2007. Available from: http://www.ncbi.nlm.nih.gov/books/NBK7232/. asthma monitoring also includes the following: Accessed Sept. 1, 2020. Assess asthma symptoms and measure the PEF. The goal is 5. Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS improved asthma symptoms and a PEF measurement greater guidelines on definition, evaluation and treatment of severe than 70% of the patient’s personal best peak flow after the first asthma. Eur Respir J. 2014;43(2):343–373. three doses of an inhaled SABA or reliever. Spirometry is not 6. World Health Organization. Asthma Fact Sheet No. 307. World usually conducted in the emergency department. Health Organization; May 3, 2021. Available from: http://www Check respiratory rate and measure oxygenation using pulse.who.int/mediacentre/factsheets/fs307/en/index.html. Accessed oximetry and provide oxygen via nasal cannula if needed. The June 25, 2021. goal oxygen saturation is 93% to 95% (0.90–0.95) in adults 7. Centers for Disease Control and Prevention: Asthma Fast Stats [Internet]. 2021 April 14 [cited 2021 June 25]. Available from: and 94% to 98% (0.94–0.98) in children, pregnant women, https://www.cdc.gov/nchs/fastats/asthma.htm and patients with coexisting cardiovascular disease. 8. Centers for Disease Control and Prevention: Asthma Data and Obtain a pCO2 measurement via arterial blood gases in Surveillance [Internet]. 2021 March 30 [cited 2021 June 25]. patients with severe asthma exacerbations. An increased pCO2 Available from: https://www.cdc.gov/asthma/most_recent_ indicates the potential for respiratory failure. national_asthma_data.htm. Monitor serum potassium for hypokalemia upon admission 9. 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