Managing Asthma in Adults and Adolescents Materials

MANAGING ASTHMA IN ADULTS AND ADOLESCENTS

AMANDA MAYER, PharmD

Amanda Mayer is a graduate of the University of Montana, Skaggs School of Pharmacy. She has clinical experience working in inpatient mental health, which is her passion. She has also done fill-in work at retail pharmacies throughout her career. Amanda appreciates the wide variety of professional opportunities available to pharmacists. Amanda loves spending time with her family and spends most of her free time exploring new restaurants, hiking in the summer, and snowboarding and cross-country skiing in the winter.

Topic Overview

The Global Initiative for Asthma has published a Global Strategy for Asthma Management and Prevention that was updated in July 2023. Asthma is a global health problem that affects all age groups and requires ongoing medical management and education. Most patients can achieve good control of their asthma by following the updated guidelines, thereby avoiding serious asthma exacerbations. This enables them to avoid the need for reliever medications, permits them to be physically active and to have normal to near normal lung function. Treatment of asthma should be customized to each patient based on symptoms, risk factors, and effectiveness and availability of medication to the patient.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-23-161-H01-P

Pharmacy Technician  0669-0000-23-162-H01-T

Credits: 1 hour of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $4.99

Estimated time to complete activity: 1 hour, including Course Test and course evaluation

Release Date: September 25, 2023 Expiration Date: September 25, 2026

Target Audience: This educational activity is for pharmacists.

How to Earn Credit: From September 25, 2023, through September 25, 2026, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “educational activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

List diagnostic criteria and symptoms of asthma

Construct a standard asthma management plan

Describe mechanisms of action for medications used for the treatment of asthma

Identify initial treatment options for asthma management

Disclosures

The following individuals were involved in developing this activity: Amanda Mayer, PharmD, Jeff Goldberg, PharmD, BCPP, and Pamela Sardo, PharmD, BS. Pamela Sardo was an employee of Rhythm Pharmaceuticals until March 2022 and has no conflicts of interest or relationships regarding the subject matter discussed. There are no financial relationships relevant to this activity to report or disclose by any of the individuals involved in the development of this activity.

© RxCe.com LLC 2023: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.

Introduction

Asthma is a common global health problem that impacts a person’s ability to breathe. It affects persons of all age groups, and it can be serious, even fatal. Asthma management requires ongoing medical management and education. This includes controlling symptoms so the patient may maintain normal activity levels. Asthma management and education can help reduce asthma-related exacerbations and mortality. Pharmacists play an important role in ensuring proper inhaler technique as they are commonly the last healthcare providers encountered before asthma self-management is initiated.

What is Asthma

Asthma is a disease that is typically characterized by chronic airway inflammation.1 Individuals with asthma have a history of respiratory symptoms that may include wheezing, shortness of breath, chest tightness and cough, and variable expiratory airflow limitation.2 These symptoms may vary over time and in intensity, with airflow limitation potentially becoming persistent with disease progression. Environmental factors such as exercise, allergen or irritant exposure, change in weather, or viral respiratory infections can trigger asthma exacerbations.2 Asthma symptoms may be absent for weeks or months, with some symptoms and airflow limitation resolving spontaneously or with a quick response to medication. Some patients can experience exacerbations that may be life-threatening.1

Prevalence of Asthma

According to a 2021 survey by the Centers for Disease Control and Prevention (CDC), approximately 8%, or over 20 million adults, in the United States were classified as having current asthma, with 3,372 deaths in individuals over 18 years old attributed to asthma.3 In 2020, there were 716,117 adult visits to the emergency department, and 67,505 hospital inpatient stays due to asthma.3 Proper asthma education by healthcare professionals can help reduce the number of acute asthma attacks, emergency

department visits, and hospital stays. It can also help to increase the patient’s quality of life.1

Diagnosing Asthma

Symptoms that could trigger testing a patient for asthma include wheezing, shortness of breath, chest tightness, and cough. More than one type of respiratory symptom helps support the diagnosis of asthma.1 Features that support an asthma diagnosis include symptom variability over time and varying intensity, or symptoms that are often worse at night.2 Additional features include symptoms upon waking and asthma triggered by exercise, laughter, allergens, or cold air.2 Asthma is diagnosed based on a history of symptoms and should be documented based on bronchodilator reversibility testing.1 It should be noted that asthma symptoms often worsen with viral infections.2

When trying to make an initial diagnosis of asthma, practitioners should get a detailed history/examination of patients with respiratory symptoms that are typical of asthma.1 If the patient is not currently taking inhaled corticosteroid treatment and there is no clinical urgency to treat, practitioners should perform spirometry/PEF (peak expiratory flow) with a reversibility test. If the results of the spirometry/PEF test support the diagnosis, the patient should be treated for asthma.1 Testing a patient’s forced expiratory volume in

1 second (FEV1) is more reliable than using peak expiratory flow testing.4 Using spirometry to document excessive variability in lung function for adults includes a positive bronchodilator responsiveness (reversibility) test, which gives results of an increase in FEV1 of >12% and >200 mL when change is measured 10 to 15 minutes after administering 200 to 400 mcg of albuterol or equivalent medication, compared with pre-bronchodilator readings.1 Documented expiratory airflow limitation may be obtained at a time when FEV1 is reduced (during testing mentioned above), confirming that FEV1/FVC is also reduced below the lower limit of normal. If there is clinical urgency and spirometry testing cannot be done before treatment, patients should receive empiric initial treatment, response should be reviewed, and diagnostic testing should be done within 1 to 3 months.1 Physical examination in individuals with

asthma often appears normal, with the most frequent abnormality presenting as expiratory wheezing on auscultation, which may also be present in patients with other diagnoses.1

Ideally, patients would be tested before starting treatment for asthma; however, that is typically not what is seen in the community setting.1 Although it is common to encounter patients who have a diagnosis of asthma without a spirometry test, asthma diagnosis should be confirmed to avoid unnecessary treatment and over-treatment and to avoid missing other diagnoses.1

Differential diagnoses that may go undiagnosed and untreated in adults misdiagnosed with asthma include inducible laryngeal obstruction, hyperventilation due to dysfunctional breathing, or COPD. Additional conditions may include bronchiectasis, cardiac failure, medication-related cough, parenchymal lung disease, pulmonary embolism, central airway obstruction, tuberculosis, and pertussis.1

Assessment of Asthma

Assessing patients with asthma includes assessing asthma control, treatment issues (including inhaler technique and adherence), any comorbidities that could increase symptom burden or poor quality of life, and misdiagnosis of asthma.1 Asthma control includes symptom control and future risk of adverse outcomes and is the extent to which asthma can be observed in the patient or has been reduced or removed by treatment.5,6 Lung function (using FEV1 scores) is an important predictor of future risk. Lung function should be measured when treatment starts, after 3 to 6 months of treatment, and then from time to time. Assessment of symptom control includes asking a patient about symptoms in the past four-week period. Practitioners should inquire about the frequency of asthma symptoms, night waking due to asthma, activity limitations, and frequency of use of a short-acting beta- agonist reliever (not including a reliever taken before exercise). Prior to diagnosing a patient with severe asthma, the patient should be assessed for uncontrolled asthma.1

Poor inhaler techniques and adherence contribute to uncontrolled asthma.7-10 Additional issues may include multi-morbidities such as rhinosinusitis, GERD, obesity, obstructive sleep apnea, and ongoing exposure to sensitizing or irritant agents in the patient’s environment.10-12

Asthma severity is assessed during treatment based on the treatment intensity required to achieve good asthma control.6 Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype.6 Table 1 provides the current definitions of asthma severity.5,6,13

Table 1: Current Definitions of Asthma Severity

Definitions Using Retrospective Assessment

Research shows that asthma control can be achieved in most patients, but real-life asthma control is poor.10 Proper inhaler technique is essential. Pharmacists play an important role in ensuring proper inhaler technique as they are commonly the last healthcare providers encountered before asthma self-management is initiated. This can involve pharmacist-led interventions.10 Pharmacy technicians may play a role in treatment by recognizing via patient profiles that the patient has never received an inhaler before and can refer the patient to the pharmacist for counseling on proper inhaler technique before dispensing the medication.10

General Principles of Asthma Management

The long-term goals for asthma management include good symptom control, maintaining normal activity levels, minimizing future risk of asthma- related mortality, exacerbations, persistent airflow limitations, and side effects of treatment.1 Health literacy can affect treatment outcomes. Low health literacy has been associated with poorer management and worse asthma control.14 A patient may have specific goals they strive to meet regarding their asthma treatment that may differ or be more than is outlined by the conventional medical goals.1

Pharmacological and non-pharmacological treatments are adjusted continuously in control-based asthma management. A continuous cycle of assessment, treatment, and review of symptom control and patient preferences should be considered. Assessment may include confirmation of diagnosis, inhaler technique and adherence, patient preferences, medication adverse effects, and comorbidities. Adjustments can then be made.1

Mechanism of Action for Medications Used in Asthma Treatment

Table 2 contains basic information. Dosing and availability should be confirmed using specific package insert information.1,15-21

Table 2: Asthma Medications, Mechanisms of Action

MDI= Metered Dose Inhaler, DPI = Dry Powder Inhaler, SMI= Soft Mist Inhaler

Medications and Strategies for Asthma Symptom Control and Risk Reduction

Current Global Initiative for Asthma Global Strategy for Asthma Management and Prevention (GINA) guidelines do NOT recommend the

treatment of asthma with SABA alone.1 Examples of commonly used SABA include albuterol and levalbuterol. Adult and adolescent treatment options should include inhaled corticosteroids (ICS) to reduce the risk of serious exacerbations and asthma death. SABA-only treatment is associated with an increased risk of exacerbations, lower lung function, and asthma-related death. When SABAs are used regularly, they increase allergic responses, increase airway inflammation, and reduce the bronchodilator response to SABA when needed. Pharmacy staff can help screen for over-use of SABA, which is defined as more than three 200-dose canisters dispensed in a year.1

Asthma medications can be placed into two main categories: controller medications and reliever medications. Controller medications historically referred to medications containing ICS. These medications help to reduce airway inflammation, control symptoms, and reduce the risk of exacerbations and decline in lung function. Reliever medications are provided to all patients with asthma for as-needed relief of breakthrough symptoms. Reliever medications can be used during worsening asthma or exacerbations and are recommended for short-term prevention of exercise-induced bronchoconstriction (EIB). Anti-inflammatory reliever (AIR) refers to reliever inhalers that contain a low-dose ICS and a rapid-acting bronchodilator. Included in AIR treatments are budesonide-formoterol, beclometasone- formoterol, and ICS-salbutamol combinations.

Maintenance-and-reliever therapy (MART) is defined as a treatment regimen where a patient uses an ICS-formoterol inhaler every day as a maintenance dose and uses the same medication to relieve asthma symptoms on an as-needed basis. The only combination of therapies that can be used for MART are ICS-formoterol inhalers such as budesonide-formoterol and beclomethasone-formoterol, ICS with non-formoterol LABAs or ICS-SABA cannot be used for MART.1

Initial Asthma Treatment

Inhaled corticosteroid-containing treatment should be initiated when the diagnosis of asthma is made to help reduce the risk of severe exacerbations,

emergency department visits, and hospitalizations.22 If symptoms remain uncontrolled after 2 to 3 months of ICS-containing treatment, inhaler technique, adherence, and exposures should be addressed prior to considering any step up in treatment. There are two treatment tracks for ongoing asthma treatment. The key difference is the medications used for symptom relief. (See Table 3.) Track 1 is preferred, and the reliever is an as-needed low-dose ICS- formoterol. Track 2 consists of a reliever of an as-needed ICS-SABA.1

Table 3: Recommendations from GINA Guidelines1,23

* *Recommendations for patients >/=12 years old

‡ Anti-inflammatory reliever (AIR)

In track 1, where the reliever is as-needed low-dose ICS-formoterol, the patients use a single medication for reliever and for maintenance treatment if prescribed. GINA prefers this track due to evidence that an AIR using low- dose ICS-formoterol reduces the risk of severe exacerbations compared to using SABA as a reliever.1 In steps 3-5 of this track, a patient also takes ICS- formoterol as their daily maintenance treatment in what is referred to as Maintenance and Reliever Therapy (MART). Patients on this track receive initial treatment of as-needed-only low-dose ICS-formoterol if presenting infrequent asthma symptoms less than 4-5 days a week (Steps 1 and 2). Initial treatment of low-dose MART is preferred when a patient has troublesome asthma symptoms most days or because of waking due to asthma once a week or more (Step 3). Step 4 medium dose MART is initiated if severely uncontrolled asthma is observed or daily acute exacerbations occur. Step 4 may be needed for individuals waking with asthma once a week or more or in patients with impaired lung function. In Step 5 of treatment, if escalation to add-on LAMA is required, refer the patient for phenotypic assessment and consider high dose ICS-formoterol plus as-needed low dose formoterol.

In track 2, step 1 includes a patient taking the reliever when symptoms occur. Steps 2-5 include a SABA or combination ICS-SABA for symptom relief and maintenance of ICS-containing medication daily. This approach is used if Track 1 is not possible or if a patient’s asthma is stable with good adherence and no exacerbations on the current therapy. Track 2, Step 1 begins with low- dose ICS and SABA for infrequent (less than 2x/month) symptoms without risk factors for exacerbations. Low-dose maintenance ICS plus as-needed SABA is an initial treatment sometimes needed as Step 2. This occurs when a reliever is required 2+ times/month but less than 4-5 days/week (Step 2). Low-dose maintenance ICS-LABA plus as-needed SABA OR medium-dose ICS plus as-needed SABA is preferred when a patient has troublesome asthma symptoms most days or wakes due to asthma once a week or more (Step 3). In Step 4, initial medium- or high-dose maintenance ICS-LABA plus as-needed SABA or plus as-needed ICS-SABA is preferred. This happens when severely uncontrolled asthma is the initial presentation. Step 4 is also preferred if an acute exacerbation includes daily symptoms, waking with asthma once a week

or more, and impaired lung function. In Step 5 of treatment, add-on LAMA, refer for phenotypic assessment and consider high dose ICS-LABA plus as- needed SABA or ICS-SABA.

Patients who make it to step 5 of treatment include individuals with persistent symptoms or exacerbations despite correct inhaler technique and good adherence in Step 4. These individuals should be referred to specialists. It is important to optimize existing therapy and treat modifiable risk factors and comorbidities in these patients. Additional treatment options that may be considered in these patients may include combination high-dose ICS-LABA, add-on long-acting muscarinic antagonists, add-on azithromycin three times per week, add-on biologic therapy, sputum-guided treatment, add-on bronchial thermoplasty, and as a last resort, add-on low-dose OCS.

Reviewing Responses and Adjusting Treatment

Patients and treatment should be assessed regularly, with a follow-up appointment 1 to 3 months after starting treatment and every 3 to 12 months thereafter.1 If a patient experiences an exacerbation, they should receive a follow-up visit within 1 week.24 Symptom improvement and improvement in lung function can begin within days of initiating treatment with controller medication, with full benefits being reached after 3 to 4 months.25 Stepping up asthma treatment uses one of three methods: a day-to-day adjustment using AIR, short-term step-up for 1 to 2 weeks, or a sustained step up for at least 2 to 3 months.1 For each patient, asthma medication can be adjusted up or down in a “stepwise approach” to achieve good symptom control.1 The “stepwise approach” is used to decrease the risk of exacerbations, persistent airflow limitations, and medication side effects.1

Stepping-up Asthma Treatment

Patients with a reliever inhaler of budesonide-formoterol or beclometasone-formoterol, with or without a maintenance ICS-formoterol, would adjust day-to-day with an AIR.1 The patient would adjust the number of as-needed doses of ICS-formoterol daily depending on their daily symptoms. The short-term step-up option involves increasing the

maintenance ICS dose for 1 to 2 weeks as necessary, often during seasonal allergen exposure or viral infections.1 The short-term step-up option can be initiated by either the patient or health care provider based on the patient’s written asthma action plan.1 When patients use the sustained step-up option, they often have uncontrolled asthma on low-dose ICS-LABA therapy despite good adherence and correct technique. These patients may benefit from increasing the maintenance dose from low to medium for approximately 2 to

3 months. If there is no response after the 2- to 3-month period, the guidelines recommend decreasing the treatment to the previous level, and alternative treatments or referrals should be considered.1

Stepping-down Asthma Treatment

If a patient has well-controlled asthma that has been maintained for 2 to 3 months, treatment can often be reduced without loss of asthma control.1 Positive outcomes that may be seen when stepping down treatment include helping to minimize treatment costs and minimize the potential for side effects. A goal of stepping down in treatment is for patients to continue maintenance treatment and decrease the need for as-needed treatment. Patients who are well controlled on maintenance low-dose ICS with an as- needed SABA can be alternatively recommended to switch to as-needed low- dose ICS-formoterol.1 As far as the timing of step-down therapy, current evidence is in favor of stepping down ICS doses by 25 to 50% at three-month intervals.26 The GINA guidelines include a very thorough table of step-down options for provider reference, including current step, current medication, and dose, options for stepping down, as well as the level of evidence for suggested treatment.1 Patients who have a history that includes exacerbations, emergency department visits within the previous 12 months, and a low baseline FEV1 are at higher risk of exacerbation after a step-down in therapy.1 Treatment that is stepped down too far or too quickly may increase the risk of exacerbation.27 Before starting step-down therapy, the patient should receive a written asthma action plan and instructions for returning to previous treatment in case stepping down the medication treatment worsens the patient’s asthma symptoms.1

Treating Modifiable Risk Factors

Treating modifiable risk factors can help reduce exacerbation risk when asthma medications are optimized.1 Factors that may increase the risk of exacerbations include medications, medical conditions, exposures, psychosocial, lung function, type 2 inflammatory markers, and exacerbation history.1 A patient who has high SABA use, defined as more than 3 of the 200- dose canisters used per year, has an increased risk of mortality. Other medication-related concerns include inadequate ICS, poor adherence, poor inhaler technique, frequent oral corticosteroid use, and long-term, high-dose, and/or potent ICS. The CYP450 inhibitors ritonavir, ketoconazole, and itraconazole may increase systemic exposure to some types of ICS and LABAs, so drug interactions should be screened.1 Medical conditions such as obesity, chronic rhinosinusitis, GERD, confirmed food allergy, and pregnancy may increase risks of exacerbations. Lung function concerns include low FEV1 (especially if <60% predicted) and high bronchodilator responsiveness. Examples of type 2 inflammatory markers that increase the risk of exacerbations are higher blood eosinophils and elevated fractional concentrations of exhaled nitrous oxide (FeNO) in adults with allergic asthma who are taking ICS. Patients intubated or in intensive care due to asthma exacerbations are also at increased risk.1

Risk factors for developing persistent airflow limitation include preterm birth, low birth weight and greater infant weight, and chronic mucus hypersecretion.1 Risk factors also include lack of ICS treatment in patients with a history of severe exacerbation, tobacco smoke, and noxious chemicals. Occupational or domestic exposures, low initial FEV1, and sputum or blood eosinophilia are also risk factors.1

Smoking cessation of the patient/family members should be encouraged and patients who are exposed to tobacco smoke or e-cigarettes may need to consider higher dose ICS if asthma is poorly controlled. Patients should be encouraged to quit smoking or vaping at each appointment, if applicable.1 Individuals with asthma should avoid environmental smoke exposure. There

is an increased risk of asthma and lower respiratory infections in children exposed to smoking while their mothers were pregnant.1

Strategies for weight reduction are suggested for patients who are obese, and asthma symptoms should be distinguished from symptoms due to deconditioning, mechanical restriction, and sleep apnea.1 Regular physical activity should be encouraged and advice about the prevention of exercise- induced bronchoconstriction with regular ICS should be provided.1 Breathing exercises are a way to help supplement conventional asthma management strategies; however, they do not improve lung function or reduce exacerbation risk. These breathing exercises and/or relaxation exercises have been reported to improve symptoms and quality of life.28

Patients may need help distinguishing between symptoms of anxiety and asthma.1 Advice about the management of panic attacks may be necessary, and mental health assessments should be done if needed. Patients exposed to occupational or domestic irritants should be removed from exposure as soon as possible.1 Examples of indoor allergens include house dust mites, furred pets, pest rodents, cockroaches, and fungi. A review of work history and other exposures to irritant gasses or particles should be done in patients with adult-onset asthma. The avoidance of food allergies and education on anaphylaxis action plan and injectable epinephrine is important for those with a confirmed food allergy. The most cost-effective ICS-based regimen should be considered to help patients with socioeconomic concerns.1

Referral for specialist care is recommended if there is difficulty confirming the diagnosis of asthma or suspected occupational asthma or persistent or severely uncontrolled asthma is identified. Refer if frequent exacerbations occur, risk factors for asthma-related death are identified, and risk of significant treatment side-effects, or complications or sub-types of asthma are suspected.1

Education and Skills Training

Patients with asthma are most successful with the proper education and skill training. Patients may interact with many healthcare providers to successfully manage asthma.1 Pharmacy staff can play a key role in the education of patients on inhaler devices as well as helping providers pick the most cost-effective option for each patient. Proper inhaler technique can achieve a high medication concentration in the airways, which helps with the onset of action and decreases systemic adverse effects that may be seen with systemic medication delivery.1 Increased risk of exacerbations, poor asthma control, and increased adverse effects are associated with poor inhaler technique.7

Checking and correcting inhaler technique is a quick and easy way to help improve asthma control.1 This should be done by physical demonstration to a healthcare provider and is crucial for patients with poor symptom control or a history of exacerbations. When choosing an inhaler, the preferred medication, available devices, patient skills, and cost should all be considered. If there are multiple options available, patients can be encouraged to participate in the choice of inhalers. Spacers can help improve the delivery of medication when using a pressurized metered dose inhaler.1 Spacers can also be helpful to reduce the potential side effects of inhaled corticosteroids, such as dysphonia and oral candidiasis. Physical barriers, such as arthritis, may affect the use of inhalers, and avoiding multiple different inhaler types can help to avoid confusion in patients. When educating a patient on inhaler technique, it is helpful to have a placebo inhaler available for proper demonstration.1

Strategies to help identify poor adherence include checking the date of the last prescription or the date on the inhaler or dispensing records.1 Understanding a patient’s beliefs and concerns about asthma and medications can help healthcare providers understand their medication-taking behaviors. Medication/regimen factors that contribute to poor adherence include difficulties using the device, a burdensome regimen/dosing schedule, and multiple different inhalers.1 Unintentional factors that may affect adherence

include misunderstanding instructions, forgetfulness, absence of a daily routine, and cost. Intentional causes of poor adherence may include the perception that the patient does not need treatment, denial or anger about a diagnosis or treatment. Poor adherence may also occur due to inappropriate expectations, side effect concerns, dissatisfaction with health care providers, stigmatization, cultural or religious issues, and cost.1

Asthma self-management may look different in each patient.1 The key components of self-management education include self-monitoring of symptoms and/or peak flow, a written asthma plan that helps recognize and respond to worsening asthma, and a regular review of asthma control, treatment, and skills by a healthcare provider.1

Difficult-to-treat and Severe Asthma

Severe and difficult-to-treat asthma can lead to physical, mental, emotional, social, and economic burdens to the patients.1 These patients may commonly experience shortness of breath, wheezing, chest tightness, and cough that may affect their day-to-day activities, including sleep. When asthma does not improve in response to optimized treatment, patients should be referred to specialized care. Patients who continue to have symptoms or exacerbations with high-dose ICS use should have the clinical or inflammatory phenotype assessed to help guide add-on treatment.1

Add-on treatments for severe asthma may include LAMA, leukotriene receptor antagonist (LTRA), low-dose azithromycin, and biologic agents.1 Although OCS were previously a mainstay of severe asthma treatment, maintenance low-dose OCS are considered a last resort option due to serious long-term side effects. Adverse effects of long-term or frequent OCS include obesity, diabetes, osteoporosis and fragility fractures, hypertension and adrenal suppression, cataracts, depression, and anxiety.1 Patients who take short-term OCS therapy may have sleep disturbances and an increased risk of infection, fracture, and thromboembolism.29-31

The majority of individuals with severe asthma are found to have Type

2 inflammation.1 Characteristics of Type 2 inflammation include elevated eosinophils or increased FeNO and may include atopy and elevated Immunoglobulin E (IgE). Non-Type 2 inflammation typically produces increased neutrophils. Type 2 inflammation should be considered if a patient is taking high-dose ICS or daily OCS but presents with blood eosinophils

≥150/µl, FeNO ≥20 ppb, sputum eosinophils ≥2%, and/or asthma that is clinically allergen-driven. Oral corticosteroids may suppress these biomarkers of Type 2 inflammation, so testing should be performed before starting OCS if possible. These tests are not the same as criteria eligibility for Type 2- targeted biologic therapy; however, they are sufficient for initial assessment.1

Biologic therapy use remains minimal due to high cost and availability.1 Non-biologic options should be considered first in patients with evidence of Type 2 inflammation. If adherence is good, an option is to consider increasing the ICS dose for 3 to 6 months and then review again. Add-on non-biologic treatment for specific Type 2 clinical phenotypes may also be considered. If biological therapy is not available or affordable, providers may consider high- dose ICS-LABA therapy if not already used, add-on of LAMA, LRTA, low-dose azithromycin, low-dose OCS as a last resort, discontinuing ineffective add-on therapies and continuing to optimize treatment by assessing technique and adherence. When biologic treatment is available to a patient, the following should be considered: whether the patient meets insurance eligibility criteria, comorbidities, predictors of response, cost, dosing frequency, delivery route, and patient preferences are met.1

Add-on anti-IgE therapy for severe allergic asthma, omalizumab, may be given by subcutaneous injection every 2 to 4 weeks.1 Eligibility includes sensitization to inhaled allergens on skin prick testing or specific IgE, total serum IgE, and body weight within the local dosing range, and more than a specified number (may vary depending on insurance) of exacerbations within the last year. Omalizumab binds to free IgE and reduces the amount of free IgE, which down-regulates receptor expression.1

Add-on anti-IL5 or Anti IL5R therapy for severe eosinophilic asthma includes the subcutaneous injections of mepolizumab and benralizumab, and reslizumab as an intravenous infusion.1 Mepolizumab and reslizumab bind to circulating IL-5, and benralizumab binds to the IL-5 receptor alpha subunit, which leads to apoptosis of eosinophils. To meet eligibility for these therapies, there must be more than a specified number of severe exacerbations in the last year and blood eosinophils above the locally specified level (may vary, typically ≥150 or 300/µl). Criteria will vary by payer.1

Dupilumab is an anti-IL4Rɑ for severe eosinophilic/Type 2 asthma or patients who require maintenance OCS.1 It is given by subcutaneous injection. Dipilumab binds to interleukin-4 (IL-4) receptor alpha and blocks IL-4 and IL-

13 signaling. Potential predictors of a good response to dupilumab include higher blood eosinophils and FeNO.1

Epithelial cytokines (e.g., thymic stromal lymphopoietin (TSLP)) are released in response to triggers, initiating a cascade of immune responses that drive clinical features of asthma.1 Add-on anti-TSLP therapy for severe asthma includes tezepelumab by subcutaneous injection. Tezepelumab binds to circulating TSLP, which is a bronchial epithelial cell-derived alarmin that is implicated in multiple downstream processes in asthma pathophysiology. Anti- TSLP therapy may also be considered in patients with no elevated T2 markers.1

There are currently no well-defined criteria for a good response with Type 2-targeted therapy.1 If the response is unclear after 4 months, an extension of 6 to 12 months may be considered. The response may include reduced exacerbations, greater symptom control, lung function, reduced treatment intensity, and patient satisfaction. If there is no apparent response, biologic therapy should be discontinued, or switching to a trial of a different Type 2-targeted therapy may be considered.1

If a patient has no evidence of Type 2 inflammation, inhaler technique and other factors should be evaluated and corrected if needed.1 Trials of add- on treatment such as LAMA, low-dose azithromycin, Anti-IL4Rɑ if taking OCS, and Anti-TSLP, and low-dose OCS as a last resort may be considered.1

Summary

Asthma affects all age groups and requires ongoing medical management and education. Adherence and proper inhaler technique are a large source of treatment issues and should be addressed as soon as patients start having treatment issues. Several available medication options may be considered with a stepwise approach to help guide treatment. Cost and difficulty using the inhaler device are two common issues that may decrease successful asthma management. The GINA guidelines and the 2020 Focused updates to the Asthma Management Guidelines provide good information with tables and charts that can help healthcare providers optimize treatment in patients.

Research shows that asthma control can be achieved in most patients, but real-life asthma control is poor. Proper inhaler technique is essential. Pharmacists play an important role in ensuring proper inhaler technique as they are commonly the last healthcare providers encountered before asthma self-management is initiated. This can involve pharmacist-led interventions. Pharmacy technicians may play a role in treatment by recognizing via patient profiles that the patient has never received an inhaler before and can refer the patient to the pharmacist for counseling on proper inhaler technique before dispensing the medication.

Course Test

Which of the following is NOT true about asthma?

Common symptoms include wheezing, shortness of breath, chest tightness, cough, and variable expiratory airflow limitation.

Asthma treatment and education do not need common reassessment and evaluation.

Environmental factors such as exercise, allergen or irritant exposure, change in weather, or viral respiratory infections can trigger asthma.

Symptoms of asthma may be absent for weeks or months at a time in some individuals.

True or False: Testing a patient’s peak expiratory flow (PEF) is more reliable than testing a patient’s forced expiratory volume in 1 second (FEV1).

True

False

If clinical urgency for treatment is present and spirometry testing cannot be done before treatment, patients should

receive empiric initial treatment, response should be reviewed, and diagnostic testing should be done within 1 to 3 months.

receive initial treatment with no further diagnostic testing suggested.

avoid treatment until diagnostic testing can be done, even in the presence of an exacerbation.

receive empiric initial treatment, with follow-up diagnostic testing done 12 months after treatment initiation.

Issues that may contribute to uncontrolled asthma include

poor inhaler technique and medication adherence.

multi-morbidities such as rhinitis, GERD, obesity, and obstructive sleep apnea.

ongoing exposure to irritant agents in the patient’s environment.

All of the above

Which of the following is NOT a goal of asthma management?

Maintaining normal daily activity levels

Minimize risk of asthma-related mortality and exacerbations

Obtaining the highest dosing regimen possible

Minimize future risk of persistent airflow limitations

Which of the following is NOT an inhaled corticosteroid (ICS)?

Albuterol

Beclomethasone

Budesonide

Mometasone

Which of the following is true about asthma treatment?

Oral corticosteroids are the preferred treatment in difficult-to-treat and severe asthma.

Short-acting beta-agonists (SABA) are recommended as monotherapy in patients with asthma.

Anti-inflammatory reliever (AIR) refers to reliever inhalers that contain a low-dose ICS and a rapid-acting bronchodilator.

Step-up in treatment may be done without evaluating inhaler technique, adherence, or exposures.

Which of the following is NOT an ICS-LABA combination?

Budesonide/Formoterol

Ipratropium/Albuterol

Fluticasone/Salmeterol

Mometasone/Formoterol

If a patient has had well-controlled asthma maintained for 2 to 3 months, treatment

can often be reduced without losing asthma control.

the maintenance dose should be increased from low to medium.

the patient should use the step-up option to increase maintenance.

of comorbidities should be suspended.

Which of the following can help with asthma treatment adherence and decrease asthma exacerbations?

Asthma self-management is the same for all patients.

Realizing that a patient’s beliefs and concerns about asthma and its medications should not impact the treatment plan.

Deprescribing medication devices if the patient did not properly use the device

Screening for poor adherence by checking the date of the last prescription and dispensing records

References

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