Mild Persistent Asthma: Characteristics, Treatment,
and Unmet Needs

Mild Persistent Asthma: Characteristics, Treatment, and Unmet Needs

Asthma is a chronic respiratory disease caused by inflammatory processes that result in airway obstruction and an overactive bronchial response following exercise or exposure to irritants and/or allergens.^1,2 The most common symptoms of asthma are wheezing, dyspnea, and cough.³ Asthma may also involve a significant reduction in lung function.⁴ In the United States, 25.7 million people or approximately 8% of the population had asthma (2010 estimates), with the number of cases growing annually from 2004 to 2010.⁵ The economic burden of asthma is considerable. From 2002 to 2007, the estimated total cost of asthma in the United States was $56 billion.⁶

Although asthma is a heterogeneous disease involving several phenotypes, endotypes, and multiple pathological processes, no clear association has been determined between phenotype and treatment response.¹ The disease is also categorized by severity, which is determined by an assessment of impairment and risk. Asthma severity is currently divided into 4 categories: intermittent, mild persistent, moderate persistent, and severe persistent (Table 1).²

Despite the seemingly innocuous classification, mild persistent asthma is an important health care problem that poses significant health risks; symptoms and airflow limitation may vary over time and in intensity.^1,2 The purpose of this newsletter is to discuss the risks and unmet needs associated with mild persistent asthma, the current guidelines for treating mild persistent asthma, and key strategies to educate patients about their disease.

Table 1. Classifying asthma severity

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; PEF, peak expiratory flow; SABA,
short-acting β₂ agonist.
Source: National Heart, Lung, and Blood Institute; National Institutes of Health; US Department of Health and Human Services.²

Mild Persistent Asthma: Symptoms and Differentiation From More Severe Persistent Asthma Types

Mild persistent asthma has been reported to account for 12% to 38% of asthma cases.⁷ The current National Asthma Education and Prevention Program (NAEPP) guidelines for the classification of mild persistent asthma are shown in Table 1.² It is important that symptoms of mild persistent asthma be identified and addressed early to prevent these cases from developing into more severe disease. Frequent wheezing in children is a risk factor for asthma persistence and increased severity in adulthood.⁸ Additional predictors for the development of severe persistent asthma include cigarette smoking; early impairment of FEV₁; high total immunoglobulin E serum levels; persistent, productive cough; and eosinophilia.^8-10

Although typically associated with more severe disease, asthma exacerbations (acute or subacute episodes of worsening shortness of breath, wheezing, coughing, and/or chest tightness) can also occur in patients with mild persistent asthma. Though they are considered to have normal lung function,² patients with mild persistent asthma experience exacerbations with a frequency of 0.12 to 0.77 episodes per patient-year.⁷ In fact, 20% to 22% of exacerbation episodes requiring emergency care occur in patients with mild persistent asthma.⁷ This is a concern, as having just 1 severe exacerbation per year has been linked to an annual decline in FEV₁ of 30.2 mL, suggesting that exacerbations could be a factor driving the transition from mild persistent asthma to more severe disease.¹¹ Moreover, an Australian retrospective study showed that one-third of deaths due to asthma-related complications occurred in patients with mild persistent asthma.¹² It is important to note that severe exacerbations can occur, for example, in response to a viral infection,¹³ regardless of whether symptoms are well controlled in patients with mild persistent asthma.^1,8 Given the serious consequences of exacerbations, a visit with a specialist is recommended following an exacerbation to ensure appropriate treatment.²

Treatment Options for Mild Persistent Asthma

The primary treatment goal for mild persistent asthma should be to provide symptom control and prevent disease progression, while minimizing the side effects of treatment. Table 1 details the key criteria that are used to assess a patient’s asthma severity before treatment. In patients with intermittent asthma, asthma control is typically maintained using relief medication, usually a SABA.²

Treatment of mild persistent asthma begins at step 2 (Table 1 and Figure 1) and includes low-dose ICS therapy plus a SABA as needed.² ICS therapy suppresses inflammation and can maintain lung function in patients with mild persistent asthma.¹⁴ Moreover, ICS therapy can reduce asthma symptoms,^15,16 reduce the need for rescue medication^16-18 and/or oral corticosteroid use,^15,17,18 decrease exacerbation frequency,¹⁹ and improve patients' quality of life.¹⁴ Other studies conducted in patients with mild persistent asthma have shown that ICS therapy, even when used solely on an as-needed basis,²⁰ was effective in reducing exacerbation rate and severity, asthma symptoms, the decline in pulmonary function, and the number of nocturnal awakenings.^21,22

When asthma control with ICS alone (at step 2) cannot be achieved or when impairment and risk measures on initial presentation place the patient in the moderate to severe persistent category, a fixed combination of ICS with a long-acting β₂-agonist (LABA) is recommended.² The addition of a LABA to daily ICS therapy can effectively reduce symptoms and improve lung function in patients with asthma. In some patients, higher-dose (approximately twofold) ICS may be preferable to initiating combination therapy with low-dose ICS.²² Leukotriene receptor antagonists are another option for patients with mild persistent asthma who do not achieve complete control; these agents also may be used in combination with ICS.²

Figure 1. Stepwise approach for the management of asthma according to NAEPP

Management of Mild Persistent Asthma

The management of mild persistent asthma involves numerous challenges, including accurate diagnosis,¹ adequate and consistent treatment,⁷ and possible prevention.^1,7 Patients with mild persistent asthma may have poor adherence to maintenance medication regimens due to mild symptoms.¹⁴ In addition, mild persistent asthma is likely underdiagnosed by primary care clinicians,⁸ and patients with mild persistent asthma may also be less likely to receive preventative care compared with patients with more severe persistent asthma. Furthermore, poor disease management planning can result in missed follow-up visits and inadequate patient education regarding the administration of medication, including proper inhaler use, as well as failure of the patient to recognize new or worsening symptoms.²³

It is evident that greater focus on diagnosing mild persistent asthma, symptom recognition, and preventing the occurrence of uncontrolled symptoms is necessary in patients with mild persistent asthma.⁸ Patient education should be a cornerstone of asthma management, regardless of disease severity. An essential element of such education is a disease management plan that has been discussed and agreed on by the HCP and patient.¹⁴ This should include education concerning asthma pathophysiology and instructions that help patients detect the early warning signs of asthma exacerbations, action steps to help mitigate the severity of exacerbations at their onset,¹⁴ and reference material such as the asthma action plan (Figure 2) that may be helpful for patients during moments requiring rapid decision making.²⁴ Education on proper inhaler technique is crucial as well.¹⁴ Poor inhaler technique is one of the most common problems associated with inadequate asthma control, and it can be addressed through proper patient education.¹ Self-management for those periods between HCP visits should also be discussed with patients. Evidence suggests that a self-management program, in combination with regular visits to an HCP, can result in fewer hospital and emergency room visits, lower rates of missed work or school, and increased patient quality of life, compared with HCP visits alone.¹⁴

Figure 2. American Academy of Allergy, Asthma & Immunology Asthma action plan

Patient adherence to the disease management program is another key to achieving good asthma control.^1,25 In fact, a systematic review including patients with asthma of all severities found that 24% of exacerbations and 60% of asthma-related hospitalizations were attributed to poor adherence.²⁶ Mild or infrequent symptoms associated with mild persistent asthma may be largely responsible for poor adherence; patients with mild symptoms may not follow up with their HCPs as readily as those with severe symptoms.²⁷ Education regarding disease management can improve patient adherence.²⁸ Notably, good medication adherence has been associated with better lung function, reduced inflammation, fewer hospitalizations, and reduced oral corticosteroid use and mortality.²⁶ Therefore, it is important to encourage patients with mild persistent asthma to seek medical attention when necessary and follow the maintenance plan laid out by their HCP.

A patient-provider interview may not always be sufficient to identify and correct poor medication adherence.²⁵ Several strategies and tools can be used to improve adherence and improve patient accountability for maintaining a good medication regimen.²⁵ Self-reporting may be the best method for adherence monitoring²⁹; therefore, encouraging strategies such as patient diaries and questionnaires should promote adherence. In addition, new sensors have been developed for inhalers to provide feedback for patients and could potentially detect environmental allergens, such as weed pollen or mold, that trigger symptom worsening.³⁰ A telemedicine-based application for smart devices has been shown to promote patient attentiveness and improve symptom reporting by a median of 85.6% in a population of patients with chronic obstructive pulmonary disease (COPD); most had severe or very severe COPD.³¹ In addition, new adherence monitors have been developed to fit inhalers and provide feedback on the user’s inhaler technique in a real-time fashion.³²

 Table 2. Assessing asthma control and corresponding therapy modification

*ACQ values of 0.76-1.4 are indeterminate regarding well-controlled asthma.
Abbreviations: ACQ, the Asthma Control Questionnaire; ACT, Asthma Control Test; ATAQ, Asthma Therapy Assessment Questionnaire;
EIB, exercise-induced bronchoconstriction; FEV₁, forced expiratory volume in 1 second; N/A, not available.
Source: National Heart, Lung, and Blood Institute; National Institutes of Health; US Department of Health and Human Services.²

Conclusions
Mild persistent asthma accounts for the largest proportion of total asthma cases. Symptoms related to mild persistent asthma may not result in patients seeking medical attention. However, if left untreated, even mild persistent asthma can result in exacerbations, which in turn can lead to emergency room visits, hospitalizations, and disease progression. Treatment with ICS is recommended for mild persistent asthma to suppress airway inflammation and decrease symptoms. Rescue medication (eg, SABA) should be used as-needed to address acute symptoms.

Despite the availability of effective medication, uncontrolled mild persistent asthma persists. Patient education and cooperation with HCPs are essential to improving control of asthma. Efforts to increase adherence through health care management plans would also be beneficial in decreasing the rate of uncontrolled symptoms and exacerbations in patients with mild persistent asthma.

References

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