INTRODUCTION — The goals of asthma therapy for all degrees of disease severity are minimizing asthma symptoms, maximizing lung function, and preventing asthma exacerbations. A basic tenet of asthma therapy is that treatment intensity should be individualized to match the frequency and severity of asthmatic symptoms and the risk of exacerbations. For all persons with asthma, regardless of severity, effective communication, ongoing patient education, and regular reassessment of asthma control are crucial for long-term success.
The issues relating to the treatment of intermittent and persistent mild asthma in adults and adolescents will be discussed here, with an emphasis on pharmacologic therapy. The recommendations made in this review are based upon guidelines from the National Asthma Education and Prevention Program (NAEPP), including the "2020 Focused Updates to the Asthma Management Guidelines," and the Global Initiative for Asthma (GINA) [1-3]. An overview of the management of asthma, and reviews of the treatment of other severities of asthma, are presented separately. (See "An overview of asthma management" and "Treatment of moderate persistent asthma in adolescents and adults" and "Treatment of severe asthma in adolescents and adults".)
CLASSIFICATION OF ASTHMA — Mild asthma may be classified as intermittent or as mild persistent. Classification of asthma in general is determined by an assessment of current impairment (based on patient reported symptoms and measurement of lung function) and risk of future exacerbations (based on the number of serious exacerbations within the past year) [1]:
●Reported daytime and nighttime symptoms, and exercise limitation over the previous two to four weeks
●Current values of peak expiratory flow (PEF), or forced expiratory volume in one second (FEV1) and FEV1/forced vital capacity (FVC) (see "Peak expiratory flow monitoring in asthma" and "Office spirometry")
●Number of exacerbations requiring oral glucocorticoids in the previous year
The Global Initiative for Asthma (GINA) and the National Asthma Education and Prevention Program (NAEPP) use slightly different combinations and thresholds to describe asthma severity as summarized in the table (table 1) [2,3]. It is important to keep in mind that patients with intermittent or mild persistent asthma can have severe and life-threatening exacerbations, even if their symptoms are generally mild and infrequent.
●Intermittent asthma – Intermittent asthma is characterized by the following (table 1) [1]:
•Daytime asthma symptoms occurring two or fewer days per week
•Two or fewer nocturnal awakenings per month
•Use of short-acting beta-agonists (SABAs) to relieve symptoms no more than two days a week
•No interference with normal activities between exacerbations
•PEF or FEV1 measurements when asymptomatic that are consistently within the normal range (ie, >80 percent of predicted normal)
•FEV1/FVC ratio is normal (based upon age-adjusted values) when asymptomatic
•At the most, one exacerbation requiring oral glucocorticoids in the preceding year
If the patient has impairment that is greater than that described in any one of these categories, the severity of asthma should be categorized as more severe than intermittent asthma. However, a person using an inhaled bronchodilator preventively prior to exercise to avoid exercise-induced bronchoconstriction may also have intermittent asthma, even if exercising more than two days per week. (See "Exercise-induced bronchoconstriction".)
Others in whom periods of increased asthma symptoms arise only under certain infrequently occurring circumstances (eg, upon encountering a cat or during a viral respiratory tract infection) may also be considered to have intermittent asthma, even if they experience intense symptoms, provided that oral glucocorticoids are not required more than once per year (table 1) [1].
●Mild persistent asthma – Mild persistent asthma is characterized by PEF or FEV1 measurements within the normal range (≥80 percent of predicted normal), normal or near normal FEV1/FVC ratio, and the presence of any one of the following (table 1):
•Symptoms more than two days a week (although less than daily)
•Three to four nocturnal awakenings per month due to asthma (but not more than once weekly)
•Use of quick-relief bronchodilator to treat symptoms more than two days a week (but not daily)
•Minor interference with normal activities
•Two or more exacerbations requiring oral glucocorticoids per year
Inclusion of the criterion "two or more glucocorticoid-requiring exacerbations in the past year" is based on the observations that such patients have an increased risk of future exacerbations and antiinflammatory therapy reduces this risk. Thus, asthma experts advise use of medication strategies to reduce exacerbation risk, even in the absence of frequent asthma symptoms, nighttime awakenings, or impairment of normal activity level. (See 'Medications for mild persistent asthma' below.)
These criteria for judging asthma severity are appropriately applied to persons who, at the time of assessment, take no regular medications for control of their asthma. They are not applicable to persons with asthma already using regular controller medications. For persons already using regular controller therapy, asthma assessment is best made in terms of asthma control rather than asthma severity. (See "An overview of asthma management", section on 'Adjusting controller medication'.)
●Moderate persistent asthma – The presence of any of the following is considered an indication of moderate asthma severity (table 1):
•Daily symptoms of asthma.
•Nocturnal awakenings more than once per week.
•Daily need for quick-acting bronchodilator for symptom relief.
•More than just minor limitation in normal activity.
•FEV1 between 60 and 80 percent of predicted and an FEV1/FVC ratio less than the lower confidence interval for normal. Age-dependent normal ranges for FEV1/FVC are typically provided with computer-generated spirometry results, using 95% confidence intervals around the mean.
Patients with moderate persistent asthma require pharmacologic therapy beyond that recommended for mild asthma [1,3]. (See "Treatment of moderate persistent asthma in adolescents and adults".)
PATIENT EDUCATION — Nonpharmacologic interventions for intermittent and mild persistent asthma are essential components of management and include trigger avoidance and patient education.
Trigger avoidance — Elimination or avoidance of known triggers is a useful strategy to help control the disease. History taking is crucial in determining exposure to environmental allergens and irritants in the home, school, and/or workplace. This topic is reviewed in detail separately. (See "Trigger control to enhance asthma management" and "Allergen avoidance in the treatment of asthma and allergic rhinitis" and "Occupational asthma: Definitions, epidemiology, causes, and risk factors".)
Asthma action plan — Patient education is an ongoing process that is intended to create a partnership between the patient and provider in achieving and maintaining asthma control. In addition to educational materials, every patient with asthma should be provided with a personalized asthma action plan that gives detailed instructions about how to self-administer medications at baseline and during exacerbations (form 1). It is important for patients with mild asthma to understand that they are also at risk for severe, potentially life-threatening asthma attacks, like those with more severe forms of the disease. (See "Asthma education and self-management".)
Delivery of inhaled medication — Inhaler devices are the major method for delivery of medications for asthma, but their effectiveness depends on optimal use of the particular device. (See "The use of inhaler devices in adults".)
Short-acting beta-agonists (SABAs) are available in metered dose inhalers (MDIs), a dry powder inhaler (DPI), and in solution for nebulization (table 2). All current MDIs use hydrofluoroalkanes (HFAs) as a propellant, rather than chlorofluorocarbons, which were phased out by 2010.
For any inhaled medication to be effective, it needs to reach the intrathoracic airways. Proper inhalation technique is difficult for many patients, especially with MDIs. Each time a new device is introduced, the technique needs to be reviewed in detail. Proper inhaler techniques are described in the tables (table 3 and table 4 and table 5). Patients should be shown the device dose counter, present on most SABA inhalers, so that they will know when the inhaler is approaching empty. MDIs should be primed before first-time use and again if the canister has not been used for several days to weeks (depending on MDI product). Priming involves spraying one or more puffs of medication into the surrounding air because of the possibility that a submaximal amount of medication might be contained in the initial spray.
Besides coaching in proper technique and repeated reinforcement, use of a valved holding chamber or "spacer" can help to optimize medication delivery from MDIs and therefore effectiveness (table 4). Available spacers include Aerochamber, Optichamber, Ellipse, Vortex, and others. (See "The use of inhaler devices in adults", section on 'Teaching inhaler use skills'.)
A dry-powder formulation of albuterol is available in the United States (eg, ProAir RespiClick) and elsewhere. Inhalational technique may be easier for some patients with the DPI device because medication is only released during inhalation, so that patients do not need to coordinate timing of their inhalation with release of the dose (table 5). The DPI device does not require priming and should not be used with a valved holding chamber ("spacer"). The dry-powder formulation of albuterol is also available with an electronic recording system and smart-device application ("Digihaler"), allowing measurement of inspiratory airflow at the time of actuation and an electronic record of frequency and timing of use.
Additional details about the use and cleaning of the various inhaler devices are provided separately. (See "The use of inhaler devices in adults".)
GOALS OF PHARMACOTHERAPY — The primary goals of treatment are relief of patient symptoms, prevention of acute asthmatic attacks, and improved quality of life. Evidence is lacking to support the concept that therapy alters the natural history of asthma (ie, the risk of progressive loss of lung function over time, as occurs in a subset of asthmatic patients).
●Irreversible airflow obstruction – Asthma is associated with chronic airway inflammation that, even in the absence of cigarette smoking, can progress over time to cause permanent structural changes in the airway wall associated with irreversible airflow obstruction. However, in some patients, the airway inflammation can persist into old age without permanent change in lung function. The development of irreversible airways obstruction appears to occur most often in those with longstanding, severe disease or a history of recurrent severe asthma exacerbations [1,4]. It may also result from impaired lung growth during childhood among those with a history of childhood asthma [5]. (See "Natural history of asthma".)
It would clearly be preferable to identify those patients who are destined to progress to permanent pulmonary impairment and intervene early to prevent progression to irreversible airflow obstruction. Unfortunately, the ability to predict the progression of mild asthma in this way is lacking at present. No epidemiologic studies have been performed that provide long-term physiologic (lung function) and histologic follow-up of a large cohort of adults with mild asthma [6,7].
One small clinical trial in adults found that delayed initiation (after two years) of antiinflammatory therapy (ie, inhaled glucocorticoids) appeared to be less beneficial than treatment begun closer to the initial diagnosis of asthma [8,9]. This observation suggested that inhaled glucocorticoids (commonly called inhaled corticosteroids or simply "inhaled steroids") might help prevent the changes in lung function that occur in some patients over time. However, several subsequent studies found that inhaled glucocorticoids do not prevent disease progression or abnormalities in lung function [10-12]. Thus, in the absence of evidence that long-term treatment can prevent the development of irreversible airflow obstruction, as may develop in a subset of patients with asthma, the primary goals of treatment remain focused on ameliorating patient symptoms and preventing asthmatic attacks.
●Small airways dysfunction – Peripheral airways inflammation and narrowing are present in asthma of all degrees of severity and may persist when asthma is asymptomatic and expiratory flow as measured by forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) is normal. It has been suggested that reductions in expiratory flow in the midportion of the vital capacity (forced expiratory flow between 25 and 75 percent of the vital capacity, FEF25-75, previously called the maximal mid-expiratory flow) reflect small airway dysfunction and can detect persistent peripheral obstruction despite a normal FEV1 or PEF. However, we would emphasize the following observations:
•A reduced FEF25-75 with a normal FEV1 is not specific for small airways obstruction and may be found in healthy individuals.
•Normalization of the FEF25-75 is not a recommended goal of asthma therapy and may lead to overtreatment.
•No therapies specifically targeting peripheral airways have led to improved asthma outcomes compared with traditional therapies. (See "Office spirometry", section on 'Other flow measures'.)
●Role of chronic airway inflammation in intermittent and mild asthma – Individuals with intermittent and mild persistent asthma (like all people with asthma) have airway hyperresponsiveness manifesting as airway smooth muscle constriction that occurs too readily and to too great a degree (compared with normal); and they have chronic airway inflammation that is often, although not always, eosinophil-predominant. The latter (chronic airway inflammation) contributes to the former (airway hyperresponsiveness). Suppression of chronic airway inflammation in asthma, such as with inhaled glucocorticoids, can lessen (but not eliminate) bronchial hyperresponsiveness. As we say to our patients, use of controller medications can make your breathing tubes less "twitchy."
It has been the practice over the last several decades to use the distinction between intermittent asthma and mild persistent asthma as a dividing line, distinguishing patients who could be treated with as-needed bronchodilators only (intermittent asthma) and those whose burden of asthma was sufficiently greater that their chronic airway inflammation should also be treated with a controller (antiinflammatory) medication (persistent asthma). Creating a category of intermittent asthma served to address: the observation that some patients have asthma symptoms only a few times per year and have never experienced a serious asthma attack; and the reality that a recommendation for daily administration of antiinflammatory therapy, such as inhaled glucocorticoids, comes with financial and potentially psychological burdens along with risk of medication side effects. Consequently, it has been felt that when symptoms are minor and rare, lung function mostly normal, and asthma attacks infrequent (that is, intermittent asthma), the persistent airway inflammation underlying the disease could go untreated.
More recently, the international experts in asthma research and management who develop the guidelines for the Global Initiative for Asthma (GINA) have challenged this approach, as outlined in the GINA 2019 and subsequent guidelines [3]. They note that some persons with asthma, categorized as intermittent, suffer preventable asthma attacks severe enough to lead to hospitalization, respiratory failure, and even death. They observe that the frequency of use of a short-acting beta-agonist (SABA) bronchodilator can easily increase in persons with intermittent asthma from "no more than two days per week" to much more frequent self-administration without triggering intervention by a medical provider, and they offer treatment options for persons with intermittent asthma that address chronic airway inflammation but do not require daily administration of inhaled glucocorticoids.
Both the traditional approach to treatment of intermittent and mild persistent asthma [1] and the newer strategies proposed by guidelines from GINA and the National Asthma Education and Prevention Program (NAEPP) are discussed below [2,3].
MEDICATIONS FOR INTERMITTENT ASTHMA — All patients with asthma should have immediate access to an inhaled bronchodilator with a rapid onset of action for prompt relief of asthma symptoms (eg, albuterol, levalbuterol, combination formoterol-low dose glucocorticoid). The following sections describe the rationale for making a selection among the potential agents (table 6).
In our opinion, the advantage of treating intermittent asthma with a combination budesonide-formoterol inhaler taken as needed is its proven reduction in asthma attacks, including severe attacks leading to emergency department visits and hospitalizations. The disadvantages are the reliance on a single branded inhaler, potentially not available to many patients because of cost and health insurance policies; the aversion of some patients to using any medication containing a glucocorticoid; and potential glucocorticoid-associated side effects, including oral candidiasis and dysphonia. With all glucocorticoid-containing metered dose inhalers (MDIs), we advise use of a spacer and mouth-rinsing after each use, advice that is harder to follow when a budesonide-formoterol MDI is carried for as-needed relief as carrying a spacer can be cumbersome and facilities for mouth-rinsing are not always available.
Short-acting beta-agonists for quick relief — The traditional strategy for intermittent asthma (for several decades) has been to prescribe a short-acting beta-agonist (SABA) as needed for relief of symptoms of cough, chest tightness, shortness of breath, or wheeze (table 6) [1,2]. Although sometimes referred to as an "emergency inhaler," it should be made clear that patients do not need to wait for a medical emergency to use their quick-acting bronchodilator inhaler. The SABA can also be used preventively, 5 to 20 minutes prior to exposure to a known trigger of their asthma, such as exercise or exertion in cold air. This remains our preferred strategy and the preference of the National Asthma Education and Prevention Program (NAEPP) 2020 Focused Updates [2].
The inhaled SABAs (eg, albuterol and levalbuterol in the United States; salbutamol and levosalbutamol in other parts of the world, albeit the exact same drugs, respectively) have a rapid onset of action (within five minutes), an intermediate duration of effect (approximately four to six hours), and relative beta-2 selectivity (table 2).
Side effects are generally mild and reflect sympathomimetic stimulation, including a “racy” feeling, jitteriness, and tachycardia. In those who are particularly sensitive to these side effects, we advise using half the usual dose (1 inhalation of medication rather than 2), mouth rinsing and spitting after dosing to minimize oral systemic absorption, and on rare occasion a short-acting muscarinic antagonist (ipratropium) rather than a SABA.
Levalbuterol is the R-enantiomer of albuterol, purified from the racemic mixture of R- and S-enantiomers that constitute albuterol. It is available as a liquid for nebulization and as a MDI. Each MDI actuation contains 45 mcg of levalbuterol (compared with 90 mcg per actuation of albuterol). Its onset, duration of action, and side effect profiles are comparable to albuterol. It had been hoped that levalbuterol might cause fewer stimulatory side effects than albuterol, but this difference has not been demonstrated with certainty.
Combination low-dose glucocorticoid-formoterol used as needed — The Global Initiative for Asthma (GINA) prefers the strategy of using a combination low-dose glucocorticoid-formoterol inhaler for as needed relief of asthma symptoms (off-label use in the United States) in patients with intermittent asthma (table 6) [3]. Formoterol has a rapid onset of action comparable to albuterol (within three to five minutes), in addition to being long-acting (up to 12 hours of bronchodilation). Although traditionally used as maintenance therapy for asthma (together with an inhaled glucocorticoid), its rapid onset of action makes it appropriate for quick symptom relief. Use of formoterol in combination with an inhaled glucocorticoid treats both airway smooth muscle constriction and underlying airway inflammation; the more symptomatic the patient and the more frequent the use of the combination inhaler, the greater the dose of glucocorticoids delivered to the airways to suppress the inflammation. This strategy has been referred to as "antiinflammatory rescue."
●Dosing – When used for quick relief of asthma symptoms, the dose of budesonide-formoterol (HFA 80 mcg-4.5 mcg or 160 mcg-4.5 mcg/inhalation or dry powder inhaler [DPI] 100 mcg-6 mcg or 200 mcg-6 mcg/inhalation, not available in the United States) is 1 inhalation, when needed for symptom relief (off-label in the United States) [13]. For persistent symptoms, 2 inhalations can be given every 20 minutes up to a total of 6 inhalations. The maximum daily dose of the formoterol component is 12 inhalations (54 mcg).
●Efficacy – Evidence in support of this approach comes from randomized trials comparing low-dose budesonide plus formoterol taken as needed versus albuterol taken as needed, performed in a mixture of patients with intermittent and mild persistent asthma. The results, described in more detail below, demonstrated fewer asthma attacks and fewer severe attacks in the group randomized to combination budesonide plus formoterol taken as needed, without an increase in adverse events. As a result, this approach may be particularly beneficial for persons with intermittent asthma who have experienced or are at risk for repeated or severe asthma attacks. (See 'Efficacy' below.)
●Other combination inhalers – Beclomethasone-formoterol (available outside of the United States) and mometasone-formoterol may have comparable effects to budesonide-formoterol, but evidence is less robust.
Short-acting beta-agonist with inhaled glucocorticoid — A potential alternative for intermittent asthma is use of a combination inhaler with low-dose glucocorticoid plus a SABA, such as albuterol, used as-needed [2,3]. This "symptom-driven" approach appears more effective than as-needed albuterol alone, although data are more limited than for combination glucocorticoid-formoterol inhalers, and combination glucocorticoid-albuterol inhalers are not available in many parts of the world (including the United States).
MEDICATIONS FOR MILD PERSISTENT ASTHMA — Patients with mild persistent asthma (see 'Classification of asthma' above) are considered to have a burden of disease activity and risk of asthma exacerbations for which as-needed bronchodilator therapy alone is inadequate [1,2,13]. By adding regular antiinflammatory therapy, the frequency of symptoms generally decreases, airway hyperresponsiveness lessens, lung function improves, and the risk of asthmatic attacks decreases. Inhaled glucocorticoids, which target the underlying airway inflammation of asthma, are part of the first-line treatment of persistent asthma of all degrees of severity, beginning with low-dose glucocorticoids in mild asthma.
Daily use of a low dose of an inhaled glucocorticoid has been recommended for treatment of mild persistent asthma for approximately 30 years (traditional strategy) [1]. A major shortcoming of this approach is poor patient adherence, with fewer than 50 percent of patients renewing their prescribed inhaled glucocorticoid on a regular basis. Among the barriers to regular use are the cost, patient fear of medication dependence and long-term side effects, common adverse effects (including thrush and dysphonia), and lack of any immediate symptomatic improvement after each dose. Alternative approaches have been tested, including the first-choice recommendation of the Global Initiative for Asthma (GINA) since 2019 [3], which advises symptom-guided ("as needed") use of a combination low-dose glucocorticoid and a fast-acting long-acting beta-agonist (LABA) inhaler. This strategy and other novel approaches are discussed in the following sections.
Approach — National and international guidelines advise use of inhaled glucocorticoids as preferred therapy in patients with mild persistent asthma, but they differ in the specific medication choices and dosing strategies (table 6) [1,2,13]. The differences in approach are in part related to local regulatory approval and availability of medications.
●National Asthma Education and Prevention Program (NAEPP) preferred – Regular (daily) treatment with separate low-dose inhaled glucocorticoid and short-acting beta-agonist (SABA) reliever as needed [2]. This remains the most common approach to treating mild persistent asthma in the United States. (See 'Daily low-dose inhaled glucocorticoids' below.)
●GINA preferred – As-needed use of a combination inhaler that contains low-dose glucocorticoid and the fast-acting LABA formoterol (off-label in the United States) [3]. This is the same as GINA-recommended step one management of intermittent asthma. (See 'Combination inhaled glucocorticoid plus formoterol as needed' below and 'Combination low-dose glucocorticoid-formoterol used as needed' above.)
●NAEPP and GINA alternative – Low-dose inhaled glucocorticoid taken whenever SABA reliever is used (separate or combination inhalers, off-label; combination inhalers not available in the United States) [2,3]. (See 'Inhaled glucocorticoid and short-acting beta-agonist together when needed' below.)
Regular use of an oral leukotriene receptor antagonist (LTRA) is an alternative option for mild persistent asthma, with a SABA taken as needed. This approach is not as effective in controlling symptoms and preventing asthma attacks as daily low-dose inhaled glucocorticoids. (See 'Alternative choice leukotriene-modifying agents' below.)
Historically, other alternatives to low-dose glucocorticoids have included the long-acting oral bronchodilator theophylline and inhaled cromoglycates (cromolyn and nedocromil), although use of these agents is limited due to frequent side effects and an increased risk of serious adverse consequences (theophylline) or limited availability in the United States (cromoglycates); neither of these options is recommended [1-3]. (See 'Medications that are avoided or rarely used' below.)
Daily low-dose inhaled glucocorticoids — Inhaled glucocorticoids are recommended for the treatment of persistent asthma of all degrees of severity according to national and international guidelines (table 6) [1-3]. Daily use of an inhaled glucocorticoid with a SABA for quick relief remains the preferred treatment recommendation for mild persistent asthma in the 2020 Focused Updates of the National Asthma Education and Prevention Program (NAEPP) [2] and is an alternative strategy in the GINA guidelines [3]. (See "An overview of asthma management".)
●Patient education – When using daily inhaled glucocorticoid and a separate SABA for symptom relief, patient education is crucial to convey an understanding of the distinct roles of the two different inhalers: the inhaled glucocorticoid is to be taken every day but has no immediate symptomatic benefit; the SABA provides immediate symptom relief and should be kept on-hand at all times, but it is to be used only as needed when symptoms develop (or prior to exercise). (See 'Asthma action plan' above.)
●Inhaler technique – The prescription of an inhaled glucocorticoid should be accompanied by review of proper inhaler technique, reassurance as to the long-term safety of low-dose glucocorticoids, instructions about rinsing the mouth after use to minimize the risk of oral candidiasis, and preferably use of a valved holding chamber ("spacer") when the inhaled glucocorticoid is administered via a metered dose inhaler (MDI). A major advantage from the use of a valved holding chamber with inhaled glucocorticoid by MDI is reduced medication deposition on the oropharynx, thereby reducing both systemic absorption and the risks of oropharyngeal candidiasis and dysphonia. Beneficial effects from addition of an inhaled glucocorticoid may take up to two weeks to observe and in some patients may not reach their maximum for several months. (See 'Delivery of inhaled medication' above.)
Initial dosing — The initial dose of inhaled glucocorticoids for mild persistent asthma should be in the low-dose range, corresponding to step two treatment [1,2]. The usual starting dose and the different types of inhaled glucocorticoids are shown in the low-dose column in the table (table 7).
Among the low-dose inhaled glucocorticoids, mometasone is approved for once-daily dosing. The other inhaled glucocorticoids have traditionally been administered twice daily, although it is likely that they can be used once daily in many patients with mild asthma, which might improve compliance [14,15].
More evidence supports the safety of budesonide during pregnancy than is available for the other inhaled glucocorticoids. (See "Management of asthma during pregnancy".)
Inhaled glucocorticoids are available via MDI, breath-actuated MDI, dry powder inhaler (DPI), and as a solution (budesonide) for nebulization (table 7). Use of a valved holding chamber ("spacer") is recommended for MDI glucocorticoids in order to maximize medication delivery to the bronchi and to minimize oropharyngeal deposition; "spacers" are not used with DPIs or breath-actuated MDIs. (See 'Delivery of inhaled medication' above and "The use of inhaler devices in adults".)
Adverse effects — Oral candidiasis and dysphonia (hoarse voice) may occur with the use of low-dose inhaled glucocorticoids, but long-term adverse effects are rare. The local and systemic side effects of inhaled glucocorticoids, as well as strategies for minimizing them, are discussed in detail separately. (See "Major side effects of inhaled glucocorticoids" and "Clinical features and evaluation of glucocorticoid-induced osteoporosis".)
Efficacy — Regular treatment with inhaled glucocorticoids reduces the frequency of symptoms (and the need for inhaled bronchodilators), improves the overall quality of life, and decreases the risk of serious exacerbations for patients with asthma [16-23]. In addition, by reducing airway inflammation, this therapy may reduce bronchial hyperresponsiveness, thereby ameliorating the exaggerated sensitivity to any and all triggers of asthma [16]. Representative studies demonstrating the efficacy of inhaled glucocorticoids include the following [16-22,24]:
●A multicenter, double-blind trial randomly assigned over 7000 patients with mild persistent asthma to treatment with low-dose inhaled budesonide (400 mcg once daily) or placebo for three years [17]. Early initiation of budesonide was associated with a lower risk of a severe asthma exacerbation during the study period (3.2 percent) compared with placebo (5.5 percent; hazard ratio 0.56, 95% CI 0.45-0.71). Patients who were treated with budesonide demonstrated better pulmonary function and experienced fewer days with symptoms [17,25].
●A second trial randomly assigned 103 patients with recent-onset mild asthma to either high-dose budesonide (600 mcg twice daily) or terbutaline (375 mcg twice daily) [18]. At one- and two-year follow-up, budesonide therapy was associated with a greater increase in morning peak expiratory flow (PEF) (32.8 versus 4.8 L/min with terbutaline), fewer asthma symptoms, and decreased need for supplemental dosing of the SABA.
Not all patients with asthma are responsive to inhaled glucocorticoid therapy. Studies suggest that up to 35 to 40 percent of patients may not experience improvements in asthma control, forced expiratory volume in one second (FEV1), or bronchial responsiveness [26-28]. The possibility that the degree of airway eosinophilic inflammation might influence responses to inhaled glucocorticoids was examined in a randomized, crossover trial that included 295 adolescents and adults with mild persistent asthma [28]. Among subjects with <2 percent sputum eosinophils (73 percent), the proportion with improved asthma control (composite of symptom diary, Asthma Control Test, and FEV1) during 12 weeks of inhaled mometasone was roughly comparable to the proportion responding to 12 weeks of tiotropium (57 and 60 percent, respectively) and only modestly better than the proportion responding to placebo (40 to 43 percent). Of note, the differences in responses were largely based on changes in FEV1, which would bias the results in favor of a bronchodilating medication such as tiotropium. Subjects with high sputum eosinophilia (≥2 percent eosinophils), in contrast, were substantially more likely to benefit from mometasone than placebo (74 versus 26 percent) but were not more likely to respond to tiotropium than placebo. More long-term trials are needed to confirm these findings before recommending a change in practice.
In some studies, patients with mild asthma who smoke cigarettes appear relatively resistant to the effects of low-dose inhaled glucocorticoids, although this has not been confirmed in all studies [29-32]. The optimal choice of medications for treating asthma in patients who continue to smoke has not been determined.
Combination inhaled glucocorticoid plus formoterol as needed — The recommendation for as-needed use of combination inhaled glucocorticoid-formoterol (off-label in the United States) is based on randomized trials that found this strategy to be more effective than daily inhaled glucocorticoid (plus a SABA as needed) in preventing severe attacks requiring systemic steroids, while at the same time reducing the annualized dose of inhaled glucocorticoids. (See 'Efficacy' below.)
Additional advantages to this approach include: no need for daily medication and use of a single inhaler rather than two separate devices. On the other hand, in these studies daily inhaled glucocorticoids were equally effective in preventing asthma attacks in general (when including attacks not considered severe) and somewhat more effective than combination budesonide-formoterol taken as needed in improving patient-reported symptoms.
Adverse medication effects were no more common with this use of the glucocorticoid-formoterol combination than daily inhaled glucocorticoid.
Dosing and devices — Published literature on the as-needed use of an inhaled glucocorticoid combined with a fast-acting LABA has largely been limited to the DPI of budesonide-formoterol (200 mcg-6 mcg/inhalation, taken 1 inhalation as needed), a preparation not available in the United States. Comparable dosing would be achieved with combined budesonide-formoterol by MDI, 160 mcg-4.5 mcg/inhalation, taken 1 inhalation as needed; or combined budesonide-formoterol by MDI, 80 mcg-4.5 mcg/inhalation, taken 2 inhalations as needed. While this dosing is off-label, it is supported by international guidelines and clinical trials [3]. (See 'Efficacy' below.)
Another inhaled glucocorticoid, mometasone, has also been paired with formoterol (mometasone-formoterol DPI, 110 mcg-5 mcg, and MDI, 100 mcg-5 mcg). Mometasone is considered a more potent glucocorticoid than budesonide. Although studies are lacking for symptom-guided mometasone-formoterol in mild persistent asthma, we would anticipate comparable results to budesonide-formoterol if used at a dose of 1 inhalation, as needed.
Similarly, a low-dose beclomethasone-formoterol (100 mcg-6 mcg) combination inhaler is available in Europe and other countries outside the United States for maintenance therapy. It is an alternative to low-dose budesonide-formoterol as-needed, although clinical trial data for as-needed usage of beclomethasone-formoterol are less robust than for budesonide-formoterol [3,33]. To match budesonide-formoterol dosing, it would be used at a dose of 1 inhalation, as needed (off-label).
Safety and adverse effects — In late 2017, the US Food and Drug Administration (FDA) removed the previous "boxed warning" for combination LABA-glucocorticoid inhalers after their review of four large clinical safety trials that together examined the safety and efficacy of combination LABA-glucocorticoid inhalers compared with inhaled glucocorticoids alone in more than 40,000 subjects [34]. The FDA concluded that, when used in combination with an inhaled glucocorticoid, LABAs do not significantly increase the risk of serious asthma-related side effects. It should be noted that these safety data were derived from studies of LABA-glucocorticoid combination inhalers taken on a regular basis. Monotherapy with a LABA should not be used for asthma. (See 'Medications that are avoided or rarely used' below and "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Long-term maintenance therapy with LABAs'.)
Potential, minor side effects of the LABAs include headache, muscle cramps, and sympathomimetic stimulation, including a low risk of tachyarrhythmias.
Adverse effects of inhaled glucocorticoids are discussed separately. (See "Major side effects of inhaled glucocorticoids".)
Efficacy — Several trials and systematic reviews have examined whether patients with mild persistent asthma might be managed with combination inhalers containing both a glucocorticoid and a fast-acting LABA, used as-needed for symptom relief, rather than an inhaled glucocorticoid on a prescribed daily schedule, with a SABA for "rescue" therapy [35-43].
●In the open-label Novel START trial, 668 adults with intermittent or mild persistent asthma were randomly assigned to one of three groups: albuterol as needed, budesonide (200 mcg) 1 inhalation twice daily plus albuterol as needed, or combination budesonide-formoterol (200 mcg-6 mcg) 1 inhalation as needed [41]. After 52 weeks, the annualized exacerbation rate among subjects who received budesonide-formoterol was lower than that of the albuterol group (19 versus 40 percent; relative rate [RR] 0.49, 95% CI 0.33-0.72) and comparable with the budesonide group (RR 1.12, 95% CI 0.70-1.79). Severe exacerbations occurred less often with budesonide-formoterol used as needed, compared with either of the other two groups. However, regular use of budesonide was superior to as-needed budesonide-formoterol for control of asthma symptoms. Mean adherence to twice-daily budesonide was 56 percent.
●The randomized SYGMA1 trial assigned 3836 participants with mild asthma, age 12 years and older, to one of three groups: twice-daily placebo plus inhaled terbutaline as needed; twice-daily placebo plus budesonide-formoterol (200 mcg budesonide, 6 mcg formoterol) as needed; or budesonide 200 mcg twice daily plus terbutaline as needed [39]. After 52 weeks, the mean percentage of weeks with well-controlled asthma per patient with as-needed budesonide–formoterol was inferior to budesonide maintenance (odds ratio 0.64, 95% CI 0.57-0.73) but superior to terbutaline as needed. The annual rate of severe exacerbations (requiring systemic glucocorticoids) was similar between the two budesonide treatment groups (6 percent for budesonide-formoterol versus 6.9 percent for budesonide alone; RR 0.83, 95% CI 0.59-1.16). The median daily dose of inhaled glucocorticoid in the budesonide-formoterol group was 17 percent of the dose in the twice-daily budesonide group.
●The separate SYGMA 2 trial compared budesonide-formoterol (200 mcg-6 mcg), as needed, with budesonide (200 mcg) twice daily, as maintenance, in 4176 participants with mild asthma who were 12 years of age or older [40]. After 52 weeks, budesonide-formoterol was noninferior to daily budesonide for severe exacerbations (10.4 versus 10.6 percent; annualized RR 0.97, with upper side of 95% confidence limit of 1.16). The time to first exacerbation was also similar between the groups, but symptom control (Asthma Control Questionnaire-5) favored budesonide maintenance.
Inhaled glucocorticoid and short-acting beta-agonist together when needed — This approach mimics the as-needed use of an inhaled glucocorticoid plus the LABA, formoterol, described above, substituting a more conventional SABA, such as albuterol, for the long-acting formoterol [35,44-46]. The 2020 Focused Updates of the NAEPP embraced the as-needed use of an inhaled glucocorticoid and SABA as a potential therapy for mild persistent asthma, although at present in the United States this strategy requires that two separate inhalers be available at all times, to be used one after the other when symptoms occur [2]. Such a strategy poses considerable concern regarding patient adherence.
Availability — While not available in the United States, combination glucocorticoid-SABA inhalers (eg, beclomethasone-albuterol) have been utilized elsewhere for control of mild persistent asthma. Patients can obtain quick-relief from the SABA and simultaneously receive an antiinflammatory inhaled glucocorticoid. The more often they have symptoms requiring quick relief, the more antiinflammatory therapy they receive [44]. However, the optimal dose of inhaled glucocorticoids administered using this approach has not been determined.
Efficacy — While data are limited, the strategy of using inhaled glucocorticoid plus albuterol for symptom relief as needed may have similar efficacy to daily inhaled glucocorticoid with intermittent albuterol as needed. In a 44-week trial (TREXA), 843 children and adolescents were randomly assigned to one of four groups: maintenance beclomethasone 40 mcg twice daily with rescue beclomethasone 40 mcg taken with each inhalation of albuterol; beclomethasone 40 mcg twice daily with albuterol for rescue; daily placebo with combination beclomethasone and albuterol as rescue; and daily placebo with albuterol as rescue [45]. The frequency of exacerbations was lower in all groups containing beclomethasone as maintenance or reliever, compared with the group taking albuterol alone for rescue.
Alternative choice leukotriene-modifying agents — LTRAs are considered alternative treatment choices for mild persistent asthma (table 6 and table 8) [1,3]. Despite the convenience of these agents (oral, once or twice daily), inhaled glucocorticoids remain the preferred option when initiating long-term controller therapy in mild persistent asthma because of their greater and more consistent efficacy, according to national and international guidelines [1-3]. (See "Antileukotriene agents in the management of asthma".)
Patient selection — Responders and nonresponders to the antileukotriene agents can be best distinguished on the basis of a therapeutic trial. Failure to improve after approximately a month of therapy constitutes a negative response. There is no evidence to suggest that the presence of atopic asthma (that is, asthma with clear allergic sensitivities) responds more favorably to LTRAs than non-atopic asthma. (See 'Efficacy' below and "Antileukotriene agents in the management of asthma".)
Antileukotriene agents may prove helpful in these specific settings:
●Among patients with both mild persistent asthma and allergic rhinitis, use of an LTRA may simultaneously treat both processes. LTRAs are effective in the treatment of seasonal and perennial allergic rhinitis, with an efficacy comparable to second-generation antihistamines, but substantially inferior to intranasal glucocorticoids. (See "Pharmacotherapy of allergic rhinitis", section on 'Therapies requiring caution'.)
●When exercise-induced bronchospasm is a prominent feature, an LTRA can be used to prevent exercise-induced symptoms. Chronic use of LTRAs for prevention of exercise-induced bronchoconstriction is not associated with loss of bronchoprotective effect over time (tachyphylaxis), something that can be seen with LABAs [47]. (See "Exercise-induced bronchoconstriction", section on 'Prolonged or recurrent exercise'.)
●Patients with asthma and aspirin-exacerbated respiratory disease over-produce leukotrienes at baseline as well as in response to ingestion of aspirin or any nonsteroidal antiinflammatory drug (NSAID). Use of a leukotriene modifier in this context makes biologic sense and may improve overall asthma control. It does not make ingestion of aspirin or NSAIDs safe for these patients. (See "Aspirin-exacerbated respiratory disease".)
Availability and dosing — The LTRAs in use in the United States are zafirlukast and montelukast (table 8).
●Zafirlukast (Accolate) – In adolescents and adults, the dosing for zafirlukast is 20 mg administered twice daily. Absorption is optimized by ingestion of the medication on an empty stomach. Zafirlukast is metabolized in the liver by CYP2C9. The only significant drug interaction is with warfarin, resulting in an increase in the prothrombin time.
●Montelukast (Singulair) – The dose of montelukast in adolescents and adults is 10 mg once daily [48]. Montelukast has a boxed warning from the FDA about potential behavior and mood-related changes and should be used with particular caution in patients with mental health issues, especially preexisting depression. No significant drug interactions have been reported. In most clinical trials, montelukast was administered in the evening; however, there is no clinical evidence that favors evening versus morning dosing. For patients who struggle to swallow tablets, a chewable tablet formulation is available.
Zileuton, which inhibits 5-lipoxygenase and thus production of leukotrienes B4, C4, D4, and E4, is generally reserved for more severe asthma due to a greater frequency of adverse effects. (See "Treatment of severe asthma in adolescents and adults", section on 'Antileukotriene agents'.)
Dosing and adverse effects of LTRAs are discussed separately. (See "Antileukotriene agents in the management of asthma", section on 'Adverse effects'.)
Efficacy — Clinical trials in patients with mild to moderate asthma have demonstrated that zafirlukast and montelukast induce persistent bronchodilation and improve symptoms [49,50]. In addition, these drugs decrease the need for rescue use of SABA inhalers and, in some studies, protect against acute asthmatic exacerbations requiring oral glucocorticoids. Relative to inhaled medications, adherence is high with oral medications administered only once or twice daily [51].
The leukotriene-modifying agents, however, are generally less effective than inhaled glucocorticoids [27,52,53]. As an example, one randomized trial of 451 patients found that those treated with low-dose inhaled fluticasone had significantly greater improvements in lung function and number of symptom-free days and less use of rescue medications than patients treated with zafirlukast [52]. On the other hand, when the greater efficacy of inhaled glucocorticoids is balanced against the greater compliance with oral medication, the two types of medications appear to achieve similar outcomes in "real-world" practice [54].
It appears that some people with asthma respond well to the leukotriene-blocking drugs, whereas others do not. These differences likely relate to variability among patients in the relative contribution of leukotriene over-expression to the pathogenesis of their asthma. Tests to identify patients who are "over-expressers" of leukotrienes are not clinically available, although individuals with aspirin-exacerbated respiratory disease (ie, asthma made acutely worse by ingestion of aspirin or NSAIDs) typically make excess amounts of leukotrienes and may benefit from an LTRA. The role of antileukotriene therapy in aspirin-exacerbated respiratory disease is discussed separately. (See "Aspirin-exacerbated respiratory disease", section on 'Leukotriene-modifying agents'.)
Allergen immunotherapy — In the 2020 Focused Updates to the Asthma Management Guidelines, subcutaneous immunotherapy (SCIT) was conditionally recommended as adjunctive therapy for persons with persistent allergic asthma [2]. Emphasis was placed on careful patient selection, including a history of asthma triggered by allergic exposures and documentation of allergen sensitization by blood or skin testing. Advantages of SCIT (following optimal pharmacotherapeutic management) might include improved asthma control, the ability to reduce asthma medications, and the potential to alter the underlying severity of asthma over time (immunomodulation). The risks of SCIT include allergic reactions to the subcutaneously administered allergens, including potentially life-threatening anaphylactic reactions. (See "Subcutaneous immunotherapy (SCIT) for allergic rhinoconjunctivitis and asthma: Indications and efficacy".)
Other strategies — Other strategies have proven effective in the treatment of mild persistent asthma but do not have sufficient evidence to support widespread adoption and have not been recommended in asthma management guidelines. They include the following two approaches:
Intermittent high-dose inhaled glucocorticoid — Patients with mild persistent asthma and by definition a low burden of symptoms may prefer not to take an inhaled glucocorticoid every day throughout the year. It is possible that use of regular (that is, daily) inhaled glucocorticoid therapy for 10 to 14 days at the onset of asthma symptoms or in circumstances when one might anticipate the development of symptoms (eg, at the beginning of an upper respiratory tract infection) might provide protection from attacks as effectively as year-round, daily administration. This strategy was examined in a randomized trial of 225 patients with mild persistent asthma who were treated with a brief course of high doses of budesonide (800 mcg twice daily for 10 days for increased symptom frequency) and, if necessary, a brief course of oral glucocorticoids for exacerbations while taking one of three daily therapies in addition to albuterol as needed: budesonide 200 mcg inhaled twice daily; oral zafirlukast 20 mg twice daily (a LTRA), or placebo (that is, the group utilizing only intermittent high-dose inhaled glucocorticoid) [35]. After one year, there were no differences between the groups in the rate of severe exacerbations, need for oral glucocorticoids, quality of life, or pulmonary function, suggesting that intermittent courses of inhaled glucocorticoid might be sufficient for selected patients with mild asthma, although more symptom-free days were reported in the group taking daily budesonide. The dose of inhaled steroids used intermittently was equivalent to budesonide DPI 180 mcg/puff, 4 puffs twice daily.
Once-daily combination inhaled glucocorticoid plus long-acting beta-agonist — In mild asthma, once-daily administration of combined inhaled glucocorticoid and LABA may suffice to achieve good control. As an example, in a randomized trial of 500 patients with mild persistent asthma, once-daily administration of combined low-dose fluticasone (100 mcg daily) plus salmeterol proved equally as effective as twice-daily inhaled fluticasone (200 mcg daily) and superior to the LTRA, montelukast, for the 16 weeks of the trial [55]. In these studies, a SABA inhaler was used as needed for quick relief of symptoms. A potential advantage of combining a long-acting bronchodilator with an inhaled glucocorticoid is that symptomatic benefit is typically experienced with each dose (unlike an inhaled glucocorticoid alone), potentially improving long-term compliance.
MEDICATIONS THAT ARE AVOIDED OR RARELY USED
Medications to avoid:
●Monotherapy with a long-acting beta-agonist – National and international guidelines and the US Food and Drug Administration (FDA) recommend not using long-acting beta-agonists (LABAs) as monotherapy for asthma, despite their classification as long-term controllers [1,3,34]. (See "Beta agonists in asthma: Acute administration and prophylactic use", section on 'Evidence against LABA monotherapy'.)
LABAs without concomitant antiinflammatory therapy have been associated with an increased risk of respiratory failure and death due to asthma [56]. In addition, monotherapy with LABAs has been shown to be inferior to monotherapy with inhaled glucocorticoids. In the salmeterol or inhaled corticosteroids trial of the Asthma Clinical Research Network, patients whose asthma was well-controlled on moderate doses of inhaled glucocorticoids were randomly assigned to continue the inhaled glucocorticoid or to switch to twice-daily salmeterol [57]. Although the two groups achieved similar peak flow values, the frequency of treatment failures (primarily exacerbations requiring an intensification of treatment) was significantly greater in the group receiving salmeterol alone.
●Racemic epinephrine – The FDA has approved the short-acting bronchodilator, inhaled racemic epinephrine, for nonprescription sale. We join a number of professional societies (such as the American Thoracic Society and the American Academy of Allergy, Asthma, and Immunology) in discouraging its use. We find the short-acting selective beta-2 agonists to be more effective, longer acting, and safer.
●Oral beta agonists – Oral beta agonists (eg, albuterol in liquid or tablet formulation, terbutaline tablets) generally do not make good alternative bronchodilators for mild asthma. They take longer to begin to work, achieve less bronchodilation, and are associated with more side effects than when the same medication is delivered by inhalation [58,59].
Rarely used medications:
●Ipratropium – Inhaled ipratropium (Atrovent) is a muscarinic antagonist that has a slower onset of action (15 to 20 minutes) and achieves significantly less bronchodilation in asthma than inhaled short-acting beta-agonists (SABAs). Its use is not recommended except in very special circumstances (eg, tachyarrhythmias due to inhaled beta agonists or concomitant use of monoamine oxidase inhibitors). A systematic review concluded that, except in the setting of acute, severe asthmatic attacks, combination therapy with ipratropium and SABAs is not superior to SABAs alone in adults with asthma [60].
●Theophylline – Sustained-release theophylline is a long-acting bronchodilator that was widely used in the past as a controller medication for persistent asthma. It is now rarely used because its antiinflammatory properties are at best modest, side effects are common, blood levels must be monitored in order to avoid toxicity, and more effective long-acting bronchodilators are now available.
The risk of serious, potentially life-threatening toxicity plus availability of alternative long-acting inhaled bronchodilators have led to the dramatic decline in use of theophylline. The dosing and proper administration of theophylline in asthma is presented in more detail elsewhere. (See "Theophylline use in asthma".)
●Cromoglycates – Cromolyn and nedocromil are alternative medications for prevention of exercise-induced bronchoconstriction or prevention of asthma symptoms caused by predictable allergic exposures (eg, visiting a home with a cat), but availability is limited (table 9). Neither cromolyn nor nedocromil is available as a metered dose inhaler (MDI) in the United States or Canada. The only remaining formulation for asthma in the United States is the solution of cromolyn for nebulization. Hydrofluoroalkane (HFA)-based and dry powder inhaler (DPI) formulations for cromolyn and nedocromil are available in many other countries.
These agents prevent bronchospasm through mast-cell stabilizing and other properties, but they do not have acute-bronchodilator activity. A disadvantage to their use as a long-term controller medication is the need for dosing three to four times daily. (See "The use of chromones (cromoglycates) in the treatment of asthma".)
Two inhalations of either cromolyn or nedocromil, taken approximately 10 to 20 minutes prior to exercise or other trigger exposure, have been shown to be effective preventive treatment against exercise-induced bronchoconstriction in blinded, placebo-controlled studies [61,62]. These medications provide additive protection when used in combination with an inhaled beta agonist prior to exercise [63].
LONG-TERM MANAGEMENT — The patient's level of asthma control should be assessed at each medical visit [1,3]. Assessments of control should be based upon the interim clinical history (for which validated questionnaires such as the Asthma Control Test and Asthma Control Questionnaire are available), current pulmonary function, and the patient's level of risk of future asthma exacerbations. Good asthma control, the goal of asthma management, is defined using the same criteria that define intermittent asthma: daytime asthma symptoms occurring two or fewer days per week; two or fewer nocturnal awakenings per month; use of short-acting beta-agonists (SABAs) to relieve symptoms no more than two days a week; no interference with normal activities between exacerbations; absence of airflow obstruction when asymptomatic; and at the most, one exacerbation requiring oral glucocorticoids in the preceding year. The concept of asthma control is presented in more detail separately and is summarized in the table (table 10). (See "An overview of asthma management", section on 'Adjusting controller medication'.)
Stepping up therapy — If the patient's asthma is not well controlled by initial therapy, then medication technique and adherence, along with trigger avoidance, should be reviewed in detail. Addressing complicating medical conditions, such as chronic rhinosinusitis, gastroesophageal reflux, obesity, and of course cigarette smoking, may also lead to improved asthma control. If poor asthma control persists despite these interventions, the patient's therapy should be "stepped up" to the next level (table 6) [1,3]. The patient should be reevaluated in two to six weeks following a change in therapy.
Stepping down therapy — In general, the importance of stepping down asthma therapy is greatest in patients with moderate and severe persistent asthma, where reducing moderate and high doses of inhaled glucocorticoids, when possible, is desirable. Although less important in intermittent and mild persistent asthma, stepping down therapy still has the potential benefit of reducing the overall drug exposure over the course of a lifetime. Some patients have asthma that is best categorized as intermittent during parts of the year and persistent during others. Such patients may alternate between step one and step two therapy (table 6) [1,3]. In mild asthma, this may mean regular use of inhaled glucocorticoids only during periods of increased asthmatic symptoms, or a trial of a low-dose glucocorticoid-formoterol inhaler taken as needed (off label).
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in adolescents and adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or email these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basic topics (see "Patient education: Medicines for asthma (The Basics)" and "Patient education: Inhaled corticosteroid medicines (The Basics)")
●Beyond the Basics topics (see "Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)" and "Patient education: Trigger avoidance in asthma (Beyond the Basics)" and "Patient education: How to use a peak flow meter (Beyond the Basics)" and "Patient education: Inhaler techniques in adults (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Classification – Mild asthma may be classified as intermittent or as mild persistent. Criteria for intermittent asthma and mild persistent asthma differ in the frequency of daily and nocturnal symptoms and the number of exacerbations requiring oral glucocorticoids per year (table 1). Both are characterized by normal or near normal lung function between exacerbations. (See 'Classification of asthma' above.)
●Goals of care – A basic tenet of asthma therapy is that treatment should be individualized to match the frequency and severity of asthmatic symptoms and the risk of future exacerbations. It is important to keep in mind that patients with intermittent or mild persistent asthma can have severe and life-threatening exacerbations, even if their symptoms are generally mild and infrequent. (See 'Introduction' above and 'Classification of asthma' above.)
It is not possible to predict the course of chronic mild asthma in individual patients. A small minority of patients with mild asthma may worsen and develop irreversible airways obstruction over time, although most will not. The factors predisposing to this outcome are unknown, and antiinflammatory therapies have not been definitively shown to be protective. As a result, the primary goals of treatment are relief of symptoms and prevention of acute attacks, rather than the long-term preservation of lung function. (See 'Goals of pharmacotherapy' above.)
●Asthma triggers – An essential part of asthma management is identification and avoidance of asthma triggers (with the exception of exercise). History taking is crucial in determining exposure to environmental allergens and irritants in the home and/or workplace. Allergy skin testing or immunoassays for antigen-specific immunoglobulin E in the blood can then supplement the history by identifying sensitivity to common aeroallergens. (See 'Trigger avoidance' above and "Trigger control to enhance asthma management" and "Allergen avoidance in the treatment of asthma and allergic rhinitis".)
●Immediate access to inhaled bronchodilator – All patients with asthma should have immediate access to an inhaled bronchodilator with a rapid onset of action (table 6). (See 'Medications for intermittent asthma' above.)
●Bronchodilator inhaler for intermittent asthma – When selecting a rapid-onset bronchodilator for patients with intermittent asthma, we suggest using a short-acting beta-agonist (SABA; eg, albuterol or levalbuterol), as needed for treatment of symptoms (table 2) (Grade 2C). A reasonable alternative, especially for patients at risk of serious asthma exacerbation, is a combination low-dose glucocorticoid-formoterol inhaler (eg, budesonide-formoterol 160 mcg-4.5 mcg), used 1 inhalation as needed for asthma symptoms (off-label) (table 6). Formoterol has a rapid onset of action comparable to albuterol. In agreement with recommendations in the Focused Updates 2020 of the National Asthma Education and Prevention Program (NAEPP), we prefer the SABA as needed option based on its long history of use, potentially wider availability, and avoidance of potential adverse effects of inhaled glucocorticoids. (See 'Medications for intermittent asthma' above.)
●Controller medication for mild persistent asthma – For patients with mild persistent asthma, we recommend using a regimen that includes a low-dose inhaled glucocorticoid (table 6) (Grade 1B). We suggest regular (daily) use of a low-dose inhaled glucocorticoid or a combination glucocorticoid-long-acting beta-agonist (LABA) inhaler, rather than as-needed use of a combination budesonide-formoterol inhaler (off-label) (table 7 and table 11) (Grade 2B). While the latter option appears to be equally effective in reducing the frequency and severity of exacerbations, overall symptom control is somewhat less effective. (See 'Medications for mild persistent asthma' above.)
As an alternative for mild persistent asthma, an oral leukotriene receptor antagonist (LTRA) can be prescribed for daily use, along with as-needed use of a SABA for symptom relief (table 8). Patients failing to improve with leukotriene modifying therapy should be switched to an inhaled glucocorticoid regimen. (See 'Alternative choice leukotriene-modifying agents' above.)
●Monitoring asthma and adjusting therapy – The patient's asthma control should be reassessed at each visit for asthma care (table 10). Return visits should also allow for ongoing patient/family education. (See 'Long-term management' above.)
Therapy should be stepped up if asthma is not well controlled and stepped down if symptoms have been well controlled over a period of months (table 6). For mild persistent asthma, stepping down therapy might mean finding the lowest dose of an inhaled glucocorticoid that maintains good asthma control, using the inhaled glucocorticoid intermittently during periods of increased symptoms, or changing to as-needed use of a combination budesonide-formoterol inhaler (off-label). Patients should be reevaluated in two to six weeks when therapy has been adjusted. (See 'Long-term management' above.)
