Asthma 20 second questionnaire

Asthma is a common respiratory disease characterized by chronic airway inflammation. Characteristic respiratory symptoms of asthma include wheezing, shortness of breath, chest tightness, and cough, as well as variable expiratory airflow limitation. Asthma symptoms vary over time and in intensity, and numerous triggers, such as exercise, allergen or irritant exposure, change in weather, or viral respiratory infections, have been identified.1 The prevalence of asthma continues to grow, with an estimated 7 million children and 18.7 million adults in the United States (U.S.) alone affected by this condition.2,3

Despite significant advances in both the availability and formulation of various inhaler medications and devices, as well as recognition of the importance of biomarkers in targeting treatment with systemic biologic agents, an estimated 3 to 10% of patients with asthma suffer from severe disease refractory to standard treatments.4,5 Individuals with severe or refractory asthma symptoms account for a significant portion of healthcare spending; although these patients account for a small minority of asthma cases, their care comprises 60% of the healthcare dollars spent on managing this condition.6

Advances in pharmacotherapy, including the advent and availability of targeted treatment options, coupled with improved understanding of the various asthma phenotypes, suggest that severe asthma management is possible. The availability of guideline evidence has helped to bring recognition to this asthma subtype and improve strategies for tailoring asthma treatment for this patient population. Research priorities, considering the high cost of biologic or targeted therapies for managing severe asthma, include identifying which asthma patient has the greatest likelihood of benefitting from these interventions in the management of their disease. Pharmacists have a critical role to play in the management of severe asthma, importantly, by helping to ensure proper medication use and technique for self-administering medication via the variety of inhaler devices that exist, by promoting medication adherence and encouraging continued daily use of therapies even in the absence of acute symptoms, as well as in making recommendations on the appropriate use of a step-wise approach, consistent with national guideline recommendations, in evaluating asthma phenotypes in order to guide add-on treatments.1,5

Pause and reflect:
In your practice, what are patient characteristics or clues that asthma may be poorly controlled?

In this monograph, the current state of severe asthma management, including emerging evidence regarding phenotypes and biomarkers, will be reviewed; the mechanisms of action of approved and emerging biologic therapies for the management of severe asthma will be explored, as well as the role of the pharmacist in achieving optimal asthma control.

Definition of Severe Asthma

Asthma severity exists on a spectrum of degree of control. While many patients’ asthma is controlled using traditional pharmacotherapy, including inhaler medications such as the inhaled corticosteroids (ICSs) short-and long-acting beta-agonists (SABAs and LABAs, respectively), and oral medication classes (e.g., leukotriene receptor antagonists, theophylline, systemic corticosteroids), a portion of patients will experience asthma that remains only partially controlled or uncontrolled despite standard treatment. Different definitions of severe asthma currently exist; according to the World Health Organization (WHO), severe asthma may be considered untreated, incorrectly treated, or difficult-to-treat (as a result of non-adherence, persistent triggers, or comorbidities).7 The consensus definition of the European Respiratory Society (ERS) and the American Thoracic Society (ATS) defines severe asthma as that, “which requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or remaining “uncontrolled” despite this therapy”.5 According to this definition, severe asthma is differentiated from difficult-to-treat or uncontrolled asthma; in the latter, patients’ symptoms remain uncontrolled for reasons other than the disease (e.g., due to improper inhaler technique, medication noncompliance, comorbidities, or allergen exposure) whereas severe asthma is a subset of difficult-to- control disease characterized by persisting symptoms despite high-doses of ICS or other controllers or that requires continued use of these treatments to remain well-controlled.1 Importantly, patients whose condition improves with appropriate diagnosis, treatment, and education on proper medication administration technique should not be confused with patients with severe or refractory asthma.5

Pause and reflect:
Can you think of patients who you interact with whose condition would qualify as severe asthma?

How is difficult-to-control asthma clinically distinguished from severe asthma?7
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Asthma is heterogeneous along its entire spectrum. This is especially evident in severe asthma, and substantial overlap exists among the different classifications of patients with uncontrolled and/or severe asthma. This makes it challenging to phenotype the disease. In addition, it is not currently known how factors such as obesity, tobacco smoke, environmental factors (e.g., air pollutants) comorbid conditions, including frequent respiratory infections, sinus disease, sleep apnea, and gastroesophageal reflux disease, impact asthma control in patients with severe asthma.5 Studies suggest that genetics may significantly contribute to the categorization of severe asthma as its own phenotype separate from mild or moderate asthma (Table 1).5,8

Table 1. Integration of factors, beginning with genetics, which may contribute to the ultimate phenotype of the severe asthma patient.5
Severe Asthma Phenotyping
Genes Gene expression Airway histology/Lung function The patient
Quality of life
Adapted from Chung KF, Wenzel SE, Brozek, JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-373.

Epidemiology and Current Trends in Severe Asthma

The lack of a consensus definition has rendered it difficult to capture the incidence of severe asthma on national health and disease surveys. While the prevalence of asthma in the U.S. population has been quantified, estimates on the incidence of severe asthma vary, with some evidence suggesting up to 10% of all asthmatic patients may suffer from severe disease.9 In order to more precisely evaluate the prevalence of severe disease, Hekking and colleagues conducted a descriptive observational study by analyzing pharmacy claims data from 65 pharmacy databases, representative of 500,500 inhabitants or 3% of the Dutch population, in the Netherlands.9 Data from adult patients (aged 18 years or older) with at least one prescription for an ICS during the 2011 study period were selected from the pharmacy registration databases; 6,519 adults were identified as receiving a high-dose ICS (≥ 1,000 mcg/day of fluticasone equivalent) plus a LABA or a medium-to high-dose ICS (500-1000 mcg/day fluticasone equivalent) plus chronic oral corticosteroids (two consecutive prescriptions for a three-month supply of ≥5 mg/day prednisone equivalent) and LABAs. Of these patients, a sample of 5,002 were identified to receive a questionnaire designed to capture demographic information, respiratory diagnoses, history of smoking, allergy triggers, childhood pulmonary disease, and medication adherence/nonadherence factors. Based on these data, patients with uncontrolled asthma, despite use of the high doses of inhalation medications, were classified as having difficult-to-control asthma. Patients with uncontrolled asthma, despite adherence to their inhalation medications and a correct inhalation technique, were extracted and labeled as severe refractory asthma.

The results of this database analysis were matched and compared with the Dutch population overall to calculate the prevalence of both difficult-to-control asthma and severe refractory asthma. The authors of this study determined that 0.68% of the adult population of the Netherlands were receiving high-intensity treatment for asthma, correlating with 17.4% of the total asthmatic population experiencing difficult-to-control asthma. Further analysis revealed that 20.5% of these individuals were adherent to inhaler medication regimens and demonstrated correct inhaler technique, leaving the authors to estimate a prevalence of severe refractory asthma in only 3.6% of all adults with asthma. The results of this analysis suggest that severe refractory asthma prevalence may, in fact, be overestimated; additional studies designed to evaluate the presence of severe asthma in a more diverse population are necessary to more completely evaluate the incidence of this condition. These data bring to light the issue of medication compliance, including proper inhalation technique and adherence to treatment, in order to distinguish difficult-to-treat from severe asthma in cases where asthma symptoms remain uncontrolled, and suggest that there is opportunity to improve the management of asthma of all types.9

Issues in Managed Care

As previously stated, the subset of patients with severe asthma account for a substantial amount of healthcare dollars and resources spent in asthma management. A recent retrospective analysis of a national (U.S.) administrative claims database has suggested that asthmatic patients with severe disease experiencing two or more exacerbations have a 2.1-fold greater use of controller medications compared with patients with persistent asthma, incur 2.9-fold higher adjusted asthma-related costs and 3-fold higher adjusted asthma medication costs, and have higher rates of healthcare utilization compared with persistent asthma cases.10 Other evaluations have suggested that the severe asthma phenotype necessitates more intensive pharmacotherapy, the need for management provided by an asthma specialist, and a more personalized treatment approach to optimize disease management and lessen the burden of cost of illness.11 Pharmacists, as we will discuss later in this monograph, thus have an opportunity to assume a larger and more active role in the care of these patients.

Advances in Understanding Severe Asthma

The pathophysiology of asthma is complex, and many questions still exist regarding its etiology, particularly with regard to severe asthma. Although inflammatory mediators, including histamine, prostaglandins, leukotrienes, and others, have long been recognized as contributing to the underlying bronchoconstriction, airway inflammation, and symptoms characteristic of asthma, advances in recognition of novel inflammatory pathways and the contribution of specific immune cells to disease progression have recently been reported.

Etiology and Pathophysiology

Asthma pathogenesis involves the interaction of airway inflammation, variable airflow limitation, and bronchial hyperresponsiveness, mediated by immune response.12 The traditional approach to asthma classification included assessment of atopic status and classification of ‘allergic’ versus ‘non-allergic’ asthma, although recently cellular inflammation and sequestration have been recognized to additionally contribute to pathogenesis. The immune inflammation of asthma includes eosinophils and/or neutrophils, with four distinct subtypes of asthma now recognized based on the presence or absence of eosinophils and/or neutrophils.13 Most patients with severe asthma display both eosinophilic and neutrophilic inflammation, but there is great variability in the numbers of each when sputum is analyzed, with patients demonstrating anywhere from none to very high levels of either cell type. This can also vary substantially from month-to-month.5 Neutrophilic asthma may be more prevalent in severe asthma, and it may be less responsive to corticosteroid treatment than eosinophilic asthma.

It is becoming apparent that asthma can also be categorized based on the degree of type 2 T helper cell (Th2) inflammation. Type 2 inflammation is now recognized as an important disease marker and a distinct endotype, or subtype of this condition, while non-type 2 inflammatory versions of asthma may encompass several endotypes that are still under investigation.13 Additionally, several cytokine signaling pathways have been hypothesized to underlie the different types of severe asthma, although these pathways are yet to be fully described.8

Clinical and Mechanistic Differences Compared with Mild and Moderate Asthma

The Severe Asthma Research Program, a network sponsored by the National Heart Lung and Blood Institute of the National Institutes of Health, has been investigating the characteristics and pathophysiologic mechanisms underlying severe asthma relative to milder forms of the disease in both the U.S. and United Kingdom.14,15 In an evaluation of a cohort of 438 patients aged ≥12 years with asthma (204 severe, 70 moderate, 164 mild disease), patients with severe asthma were more likely to be older with a longer duration of illness (P<0.0001), and more likely to require urgent healthcare utilization, including increased numbers of Emergency Department visits, hospitalizations, and intensive care unit (ICU) stays over and within 12 months of the evaluation, or to experience co-morbid sinusitis and pneumonia (P≤0.0001). With regard to the presence of asthma symptoms, patients in the severe asthma group were more likely to experience daily cough (42%) and shortness of breath (47%), with more than 34% also reporting daily nighttime symptoms, chest tightness, and wheezing (P<0.0001).15 This compelling research underscores the impact of severe asthma on an individual’s overall health status and the dichotomy of disease that exists between more milder forms of asthma and severe illness.

Phenotypes and Biomarkers in Severe Asthma

Identification of the underlying immunologic mechanisms and pathophysiology contributing to severe, poorly-controlled asthma may ultimately improve the current understanding of the disease along with the ability to effectively deploy targeted therapies to improve symptomatic management and patient quality of life (Figure 1).16

Figure 1. Immunologic targets and agents (approved and in development) in severe asthma.16

Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease

Increasing interest in the evaluation of the heterogeneous nature of asthma, coupled with the correlation with clinical presentation, physiologic characteristics of disease, and health outcomes, has led researchers to investigate the identification of asthma phenotypes, clusters of demographic, clinical, and pathophysiological characteristics that define the disease and its subsets, beyond allergic or non-allergic disease (Table 2).5,17-18 There is limited evidence to suggest expansion of asthma phenotypes to include the patient’s age of onset, presence of atopy or atopic disease, exacerbation triggers, airway obstruction severity, and need for medication—factors which may be associated with an increased risk of poor asthma control.18,19 Consideration for phenotypic characteristics, along with disease severity and other patient- specific factors, must be considered in initiation and modification of an asthma management treatment plan.17,20 Correlating specific asthma phenotypes, including consideration for underlying pathophysiologic mechanisms and treatment response, may ultimately help clinicians select the best possible treatment approach for patients with severe asthma, while considering risks and costs attributed to expensive treatment options, particularly for patients with moderate to severe uncontrolled asthma who respond poorly to current therapies.18-19,21 Additional research into asthma phenotype delineation may provide better understanding of the risk factors and causes of asthma and help to guide cost-effective management of disease.

Table 2. Asthma phenotypes and characteristics
Asthma Phenotype Characteristics
  • Diagnosis is based on sensitization and clinical correlations (e.g., perennial with sensitization exposure, seasonal symptoms, symptoms with exposure to allergens)
  • More likely in males
  • Often associated with family history of allergy
  • Negative reaction to seasonal/perennial allergens
  • Characterized by normal or low IgE levels
  • More severe than allergic asthma and less responsive to steroids
Aspirin-exacerbated respiratory disease
  • Proven asthmatic response to aspirin or other NSAIDs
  • More likely in females; typical onset between ages 30 and 34
  • Respiratory tract infection causes or exacerbates asthma
  • May be associated with viral infection, chlamydia, or mycoplasma
  • Bronchoconstriction occurring shortly after exercise heightened susceptibility for up to four hours
  • Usually reversed with standard SABA therapy
  • Estimated 20% of the general population affected
Pre-asthma wheezing in infants
  • Episodic (viral) wheeze
  • Multi-trigger wheezing
  • Episodic wheeze can occur when infant is suffering from a viral infection
  • Multi-trigger wheeze can occur regardless of acute viral infection
Exacerbation-prone asthma
  • Most costly asthma phenotype
  • May be associated with: low FEV1; history of pneumonia; early age of onset; NSAID-exacerbated airway disease; worsening asthma symptoms during menstruation
Asthma-associated with apparent irreversible or fixed airflow limitation
  • FEV1/FVC ratio below the lower limit of normal for age and FEV­­1 <90% despite corticosteroid use and after use of a short-acting bronchodilator
Eosinophilic and Neutrophilic asthma Eosinophilic
  • Eosinophilic inflammation associated with poor asthma control, increased bronchodilator response, lower lung function, and exacerbations in ICS treated patients
  • Requires evaluation of sputum for presence of eosinophils
  • Associated with nasal polyps, later onset of disease, and lower BMI
  • Less well-defined than eosinophilic asthma
  • More likely to occur in severe, older asthmatics
  • Increase with increasing asthma severity and corticosteroid use
  • May respond better to macrolide antibiotics
Abbreviations: BMI = body mass index; FEV1 = forced expiratory volume in one second; FEC = forced vital capacity; IgE = immunoglobulin E; NSAID = nonsteroidal anti-inflammatory drugs
Adapted from references 18,19

Pause and reflect:
How might you identify patients falling into the various asthma phenotypes?

Evolving Therapies in Severe Asthma

Therapeutic Targets in Severe Asthma

Although one of the hallmarks of severe asthma is corticosteroid insensitivity with a persistent lack of control despite corticosteroid treatment, the treatment of severe asthma still relies heavily on a “one size fits all” approach, utilizing ICSs and bronchodilators. Several new pharmacologic therapies have recently received approval for severe asthma, and therapies reserved for other pulmonary conditions, like chronic obstructive pulmonary disease (COPD), may have utility in severe asthma as well. As an example, the role of the use of long acting muscarinic antagonists (LAMAs) is well-established in guidelines for managing COPD, but emerging data from key clinical trials suggest that LAMAs may also confer enhanced bronchodilator effects and improved control when used in addition to ICS or in conjunction with LABAs in asthma management.22

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Rationale for Use of Specific and Emerging Interventions

The high level of unmet need in severe asthma and research breakthroughs surrounding the role of inflammatory cytokines in asthma pathophysiology have spurred the development of multiple cytokine-inhibiting agents with various targets, including immunoglobulin E (IgE), Th2, and eosinophil-driven phenotypes, that are expected to be used in selected asthma populations based on biomarker evaluation.

Until 2015, the anti-IgE antibody omalizumab was the only approved biologic agent for severe persistent asthma. Its use is limited to patients with moderate-to-severe persistent asthma with a positive allergy skin test or in whom laboratory testing demonstrates sensitivity to a perennial allergen, such as mold or pollen. Dosing of omalizumab is determined according to pre-treatment serum IgE levels.23 While no comprehensive evidence for the use of omalizumab in severe refractory asthma exists thus far, current late-stage trials demonstrate reduced disease severity, inflammation, and airway remodeling, as well as long-term stable conditions (n=6 years).24,25 Omalizumab may be particularly useful for treating the overlapping phenotype of severe allergic asthma and COPD.26

Evidence showed that treatments targeting interleukin-5 (IL-5), a potent chemoattractant for eosinophils, were effective in patients with eosinophilia. This discovery led to the identification of eosinophils, particularly blood eosinophils, as a Type 2 biomarker predictive of treatment responses in patients with severe asthma.27,28 At present, Type 2 biomarkers include periostin, fractional exhaled nitric oxide (FeNO), and presence of sputum or blood eosinophils. Trials of Type 2-targeted therapy have shown promise in asthmatic patients with disease characterized by Type 2 inflammation; however, in a recent review, Fajt et al. pointed out that additional research is necessary regarding the utility of these agents for patients with severe disease who do not show evidence of Type 2 inflammation.16 Mepolizumab and reslizumab, anti-IL-5 monoclonal antibodies, are indicated for the treatment of severe eosinophilic asthma poorly controlled with conventional therapy. Other anti-IL-5 monoclonal antibodies are being evaluated in severe asthma including benralizumab, which has demonstrated significantly reduced annual exacerbation rates for patients with high eosinophil levels.29,30

Studies of anti-IL-13 monoclonal antibodies (lebrikuzimab, tralokinumab, dupilumab) confirm that IL-13 (and perhaps IL-4) are key players in cytokine airway inflammation and hyper-responsiveness in asthma and in moderate-to-severe asthmatics with evidence for Type 2 inflammation. Further studies are necessary to determine whether one approach (e.g., inhibition of IL-13 vs. IL-4) is superior to the other and which patients are likely to garner the best response to these treatments as compared to those therapies targeting IL-5.16

A summary of severe asthma phenotypes and biomarkers and therapies likely to be beneficial in those conditions is available in Table 3.5 The emerging biologic therapies may help to personalize treatment for severe asthma and enhance outcomes among patients suffering from this disease. Dr. Bernard Kinane, chief of the pediatric pulmonary unit at Massachusetts General Hospital, notes that physicians have seen improvements in disease management with monthly in-office administration of biologics, since asthma self-care—including inhaler technique for use and frequency of administration—can be cumbersome compared with the administration of intermittent subcutaneous injections provided by the healthcare provider in-office.31 The advent and availability of novel pharmacologic agents targeting specific inflammatory markers likely to be present in subsets of patients with severe asthma necessitated that pharmacists be familiar with these emerging biologic therapies and their mechanisms of action to effectively educate patients in their communities who are using these therapies.

Table 3. Potential phenotype-targeted therapies for severe asthma7
Characteristic Associations Targeted Treatments
Severe allergic asthma Blood and sputum eosinophils, high serum IgE, high FeNO Anti-IgE (adults and children)
Anti-IL-4/IL-13, anti-IL-4 receptor
Eosinophilic asthma Blood and sputum eosinophils, recurrent exacerbations, high FeNO Anti-IL-5, anti-IL4/IL-13, anti-IL-4 receptor
Neutrophilic asthma Corticosteroid insensitivity, bacterial infections Anti-IL-8, CXCR2 antagonists, anti-LTB4 (adults and children), macrolides (adults and children)
Chronic airflow obstruction Airway wall remodeling as increased airway wall thickness Anti-IL-13, bronchial thermoplasty
Recurrent exacerbations Sputum eosinophils in sputum, reduced response to ICS and/or OCS Anti-IL-5, anti IgE (adults and children)
Corticosteroid insensitivity Increased neutrophils in sputum P38 MAPK inhibitors, theophylline (adults and children), macrolides (adults and children)
FeNO, exhaled nitric oxide fraction; IL, interleukin; LTB4, leukotriene B$; ICS, inhaled corticosteroid; MAPK, mitogen-activated protein kinase; Neutrophilic asthma is rare in children
Adapted from Chung KF, Wenzel Se, Brozek, JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-373.

Pause and reflect:
What are some therapeutic options that you might consider for patients with severe asthma today and in the future?

Current Standards of Care for Severe Asthma

While a number of different professional organizations and societies have developed clinical guidelines that summarize the state of the evidence to help guide clinicians to improved, evidence-based asthma care, there exists one comprehensive guideline for severe asthma management, developed by the American Thoracic Society (ATS) and European Respiratory Society (ERS), and a segment of the Global Initiative for Asthma (GINA) 2017 document devoted to this subset of disease.1,5

International ERS/ATS Guidelines

The ERS and ATS have worked collaboratively to develop a number of clinical practice guidelines, research statements, technical standards, and other reports related to the international management of pulmonary diseases. The development of the consensus guidelines on the definition, evaluation and treatment for severe asthma reflect this joint effort.5 Beyond establishing a consensus definition for severe asthma, this guidance document delineates pathophysiology as well as the role of phenotypes and specific biomarkers in the evaluation and for severe asthma. It also underscores the role of established asthma therapies as well as the utility of biomarkers in guiding therapy for individuals with severe asthma.5

2017 GINA Strategy

The 2017 update to the Global Strategy for Asthma Management and Prevention reflects the findings of the GINA committee, who convene twice annually to evaluate best practice and emerging evidence. This document is updated annually to guide practice changes in asthma management and translate clinical research into practice as quickly as possible. While the document is divided into three segments (adults, adolescents, and children six years and older; children age five years or younger; clinical practice translation), the discussion of severe asthma management falls under the segment devoted to ‘treating to control symptoms and minimize future risk’ in adults, adolescents, and children six and older.1

According to GINA recommendations, a four-step approach to investigating the cause of refractory or severe symptoms should occur:

1) Confirmation of the asthma diagnosis, including the consideration of other respiratory diseases like COPD or recurrent infections, that could result in persistent symptoms;

2) Evaluation of comorbidities that can worsen asthma control or exacerbate symptoms, including those mentioned previously;

3) Assessment of medication compliance, including validating inhaler technique and evaluating medication adherence, as both of these conditions represent the most common reasons for inadequate asthma control; and

4) Investigation for persistent exposure to triggers, including tobacco smoke, allergens, or other toxins.1

Upon evaluation and correction of these features, a step-wise approach to managing severe asthma is provided, which includes:1

  • Optimization of bronchodilator (LABA/LAMA) dose.
  • Judicious use of daily low-dose maintenance systemic corticosteroid therapy.
  • Use of add-on controller medications, including LAMAs, theophylline, or leukotriene receptor antagonists.
  • Sputum-guided treatment and evaluation for pharmacotherapy guided by the absence or presence of sputum eosinophils.
  • Phenotype-guided add-on therapy, including the use of omalizumab for elevated IgE levels or anti-IL-5 therapy with mepolizumab or resilumab for severe eosinophilic disease.
  • Consideration for nonpharmacologic interventions, such as bronchial thermoplasty, high-altitude treatment, or psychological interventions, although the place in therapy for these treatments has not been established.

Figure 2 depicts the GINA cycle of asthma care, an approach to managing all severities of asthma. Key aspects of the model include reliance on communication in order to engage the patient as a partner in their care; consideration of population-based and patient-specific factors in informing treatment decisions; adjustment of medications in a step-wise approach; and provision of an asthma action plan, informing patients how to troubleshoot and respond to acute changes in their condition.1

Figure 2. The GINA Cycle of Asthma Care1
fig 2

Used with permission from the Global Initiative for Asthma. Available from

Although the majority of patients with asthma can be managed successfully in the primary care setting, for those patients with severe or refractory disease, evaluation by an asthma specialist to further investigate causes and pathophysiologic characteristics and optimize a treatment plan for these individuals should be considered.1

Pause and reflect:
What are the key aspects of the approach to severe asthma management underscored by the GINA guidelines? What changes do you need to consider making yourself or advocating for with other healthcare professionals to ensure your patients are receiving care that is in line with these guidelines?

Pharmacists’ Role in Severe Asthma

Regardless of the severity of asthma a patient may be experiencing, there are fundamental issues related to patient care and assurance of safe and effective medication use that should be employed by the pharmacist as initial steps in evaluating disease and medication compliance.

Barriers to Achieving Optimal Asthma Control in Patients with Severe Asthma

Four common barriers affect asthma control and must be considered in the evaluation of the individual with difficult-to-control or severe asthma subtypes, including:1

  1. Poor inhaler technique
  2. Poor adherence
  3. Misdiagnosis
  4. Comorbidities and complicating conditions

While numerous reasons for inadequate asthma control exist for patients with difficult-to- control or severe asthma, by far the most common reasons for inadequate asthma control across asthma disease severity includes improper inhaler technique and suboptimal adherence to medications.1 Patients with asthma may:

  • fail to differentiate between inhaler devices or to recognize the importance of daily maintenance inhaler use compared with short-acting rescue bronchodilators needed for treating acute shortness of breath;
  • receive conflicting evidence from different healthcare providers, leaving them confused as to the optimal approach;
  • have low health literacy whereby they may not understand the education provided to them; experience cultural conflict resulting in clinician mistrust; or
  • experience other barriers contributing to medication noncompliance or misuse.

These barriers represent opportunities, which we will discuss further in the next section, for pharmacists to be aware of and to intervene in order to help optimize asthma control.

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Pause and reflect:
How does low health literacy influence the provision of effective asthma management?

The Pharmacist’s Role in Addressing Barriers in Severe Asthma Management

One of the contributing factors resulting in difficult-to-treat asthma is nonadherence to prescribed treatments, principally ICS therapy.32 A recent survey of patients with difficult asthma found that suboptimal rates of adherence among the treatment population ranged from 62.4% to 85.7%, and that only 29.2% of patients demonstrated full adherence; poor adherence rates lead to poor outcomes for patients with difficult-to-control disease.33 Additionally, a patient’s perception of asthma control may differ substantially from their true or actual control, suggesting that patients are unlikely to proactively seek intervention and support from healthcare professionals due to perceived achievement of optimal control.34 While promoting medication adherence is a primary function of clinicians when managing patients with asthma, achieving compliance mandates considerable commitment, time, and effort on the part of the care provider.35

Currently, asthma is = routinely managed in the ambulatory care setting by primary care providers, although gaps in quality of care, including inadequate provision of written asthma action plans, lack of guideline-compliant practices, and suboptimal patient outcomes, have been identified. A lack of routine asthma visits by patients limits primary care providers’ opportunities for education and chronic disease management; clinicians practicing in primary care report that they only see asthma patients when they are experiencing an acute exacerbation and not for routine asthma management and evaluation.34Additionally, even under specialist’s care, a majority of patients with asthma may continue to experience symptoms which limit daily activities and exacerbations of disease.36

Pharmacists have extensive training in pharmacotherapy and patient counseling, are readily available to the public, and have access to individual patient drug-usage data. Thus they are well positioned to improve adherence to asthma medication and patient quality of life through direct intervention.36,37-38 Growing evidence exists that community pharmacists may play a potentially beneficial role in reducing the burden of asthma, but that they are an under- utilized resource.34 Substantial barriers exist to the effective implementation of pharmacists into comprehensive asthma care, but pharmacists have a high level of desire to expand their roles in asthma management; 70% of pharmacists want more interaction with other healthcare providers regarding care of patients with asthma, and pharmacists perceive their roles in asthma management as tied to patient self-management and asthma control.39

Several recent studies highlight the gaps that exist in the utilization of pharmacists as part of a comprehensive asthma management team. The interactions between pharmacists and primary care providers, according to one study, continues to consist of routine dispensing functions, rather than as a collaborative, shared decision-making relationship, despite evidence that suggests such a model improves health outcomes and reduces gaps in medication adherence, patient drug knowledge, and suboptimal prescribing procedures.40 Additionally, patients may routinely decline to involve their community pharmacist in their asthma care. Although patients who had established relationships with their pharmacists reported high satisfaction rates with their pharmacist’s proactive role in medication and disease management, most patients disregarded their pharmacists as part of the care team, citing a lack of recognition or established relationship and comfort in understanding of their disease and medications.37 Several studies have shown that the patient creates a significant barrier to the extension of pharmacists’ roles in counseling.39 Increasing the quality and quantity of patient interactions with pharmacists may promote patient trust in pharmacists and help pharmacists to more fully participate as members in the asthma care team, thereby enhancing patient outcomes.40 Pharmacists additionally require training, support, tools, and strategies to overcome these barriers.39 Expansion of interprofessional education and training for pharmacists and primary care providers regarding the collaborative roles of each are also of vital importance.41

Pause and reflect:
What barriers or challenges have you encountered in pharmacist-lead disease management? What other chronic diseases, beside asthma, does pharmacy intervention contribute to optimization of outcomes? Can you apply lessons learned with other diseases to the management of severe asthma?

Pharmacist Strategies to Support Patient Self-management and Improve Asthma Control

Optimizing asthma management, particularly for patients with difficult-to-treat or severe diseases, necessitates clinical vigilance and judgment, in addition to awareness of best practice recommendations and incorporation of current evidence into clinical practice. By interacting with providers and patients alike, pharmacists serve as a critical conduit in disease management by:

  • relaying relevant information to the care provider that may suggest the need for therapy escalation or referral,
  • providing education on inhaler technique and proper use, management of medication adverse effects, and
  • offering disease state counseling that can result in reduced healthcare costs and improved asthma control to the patient.

In this role, it is essential that pharmacists keep abreast of updates in asthma management, especially severe asthma management, as therapies continue to evolve and treatment becomes more personalized. Ultimately, the pharmacist serves a critical role in the management of asthma, and their ability to educate patients and providers may result in improvement in patients' symptoms, pulmonary function, and functional health status.

References (All accessed as of December 1, 2017)

  1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2017. Global Initiative for Asthma (GINA). Available from 2017.
  2. Asthma's impact on the nation. Centers for Disease Control and Prevention website. Available from
  3. Centers for Disease Control and Prevention. National Surveillance of Asthma: United States, 2001-2010. November 2012. Vital and Health Statistics, series 3, number 35. DHHS Publication No. (PHS) 2013-1419.
  4. Hekking PP, Wener RR, Amelink M, et al. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135:896-902.
  5. Chung KF, Wenzel SE, Brozek, JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343-373.
  6. Sadatsafavi M, Lynd L, Marra C, et al. Direct healthcare costs associated with asthma in British Columbia. Can Respir J. 2010;17:74-80. 
  7. Bousquet J, Mantzouranis E, Cruz AA, et al. Uniform definition of asthma severity, control, and exacerbations: Document presented for the World Health Organization consultation on severe asthma. J Allergy Clin Immunol. 2010;126:926–938. 
  8. Poon AH, Hamid Q. Severe Asthma: Have We Made Progress? Ann Am Thorac Soc. 2016;13 Suppl 1:S68-77.
  9. Hekking PP, Wener RR, Amelink M, et al. The prevalence of severe refractory asthma. J Allergy Clin Immunol. 2015;135:896-902.
  10. Chastek B, Korrer S, Nagar SP, et al. Economic burden of illness among patients with severe asthma in a managed care setting. J Manag Care Spec Pharm. 2016;22:848-861.
  11. Zeiger RS, Schatz M, Dalal AA, et al. Utilization and Costs of Severe Uncontrolled Asthma in a Managed-Care Setting. J Allergy Clin Immunol Pract. 2016;4:120-129.e3.
  12. Colice GL, Ostrom NK, Geller DE, et al. The CHOICE survey: high rates of persistent and uncontrolled asthma in the United States. Ann Allergy Asthma Immunol. 2012;108(3):157-162. 
  13. Robinson D, Humbert M, Buhl R, et al. Revisiting Type 2-high and Type 2-low airway inflammation in asthma: current knowledge and therapeutic implications. Clin Exp Allergy. 2017;47(2):161-175. 
  14. Severe Asthma Research Program, National Health, Lung & Blood Institute. Available from
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