The current concept of asthma severity is based on ‘difficulty to treat’
The current concept of asthma severity, recommended by an ATS/ERS Task Force38,84 and included in most asthma guidelines, is that asthma severity should be assessed retrospectively from how difficult the patient’s asthma is to treat. This is reflected by the level of treatment required to control the patient’s symptoms and exacerbations, i.e., after at least several months of treatment.38,84,175 This definition is mainly relevant to, and useful for, severe asthma.
By this definition:
- severe asthma is defined as asthma that remains uncontrolled despite optimized treatment with high-dose ICS- LABA, or that requires high-dose ICS-LABA to prevent it from becoming uncontrolled. Severe asthma must be distinguished from asthma that is difficult to treat due to inadequate or inappropriate treatment, or persistent problems with adherence or comorbidities such as chronic rhinosinusitis or obesity,175 as they need very different treatment compared with if asthma is relatively refractory to high-dose ICS-LABA or even oral corticosteroids
(OCS).175 See Box 2-4 (p.47) for how to distinguish difficult-to-treat asthma from severe asthma, and Section 8 (p.139) for more detail about assessment, referral and treatment in this population.
- moderate asthma is asthma that is well controlled with Step 3 or Step 4 treatment e.g., with low- or medium-dose ICS LABA in either treatment track
- mild asthma is asthma that is well controlled with low-intensity treatment, i.e., as needed low-dose ICS-formoterol, or low-dose ICS plus as-needed SABA.
The utility of this retrospective definition of asthma severity is limited by the fact that it cannot be assessed unless good asthma control has been achieved and treatment stepped down to find the patient’s minimum effective dose at which their asthma remains well controlled (Box 4-13, p.102), or unless asthma remains uncontrolled despite at least several months of optimized maximal therapy.
The terms ‘severe asthma’ and ‘mild asthma’ are often used with different meanings than this
In the community and in primary care, the terms ‘severe’ or ‘mild’ asthma are more commonly based on the frequency or severity of symptoms or exacerbations, irrespective of treatment. For example, asthma is commonly called ‘severe’ if patients have frequent or troublesome asthma symptoms, regardless of their treatment, and ‘mild asthma’ is commonly used if patients do not have daily symptoms or if symptoms are quickly relieved.
In epidemiological studies and clinical trials, asthma is often classified as ‘mild’, ‘moderate’ or ‘severe’ based only on the prescribed treatment by GINA or BTS Step, regardless of patients’ level of asthma control. This assumes that the prescribed treatment was appropriate for the patient’s needs, but asthma is often under-treated or over-treated.
Most clinical trials of biologic therapy enroll patients with asthma that is uncontrolled despite taking medium- or high- dose ICS-LABA, but contributory factors such as incorrect inhaler technique, poor adherence, or comorbidities are rarely assessed and treated before the patient’s eligibility for enrolment is considered.176,177 Some clinical trial participants may therefore have ‘difficult-to-treat’, rather than severe asthma.
Some guidelines 178,179 also retain another, older, classification of asthma severity based on symptom and SABA frequency, night waking, lung function and exacerbations before ICS-containing treatment is started.38,84 This classification also distinguishes between ‘intermittent’ and ‘mild persistent’ asthma, but this historical distinction was arbitrary: it was not evidence-based, but was based on an untested assumption that patients with symptoms
≤2 days/week were not at risk and would not benefit from ICS, so should be treated with SABA alone. However, it is now known that patients with so-called ‘intermittent’ asthma can have severe or fatal exacerbations,180,181 and that their risk is substantially reduced by ICS-containing treatment compared with SABA alone.182-184 Although this symptom-based classification is stated to apply to patients not on ICS-containing treatment,178,179 it is often used for patients taking these medications. This can cause confusion, as a patient’s asthma may be classified differently, and they may be prescribed different treatment, depending on which definition the clinician or healthcare system uses.
For low-resource countries without access to effective medications such as ICS, the World Health Organization definition of severe asthma185 includes a category of ‘untreated severe asthma’. This category corresponds to uncontrolled asthma in patients not taking any ICS-containing treatment.
The patient’s view of asthma severity
Patients may perceive their asthma as severe if they have intense or frequent symptoms, but this does not necessarily indicate underlying severe disease, as symptoms and lung function can rapidly become well controlled with commencement of ICS-containing treatment, or improved inhaler technique or adherence.38,84 Likewise, patients often perceive their asthma as mild if they have symptoms that are easily relieved by SABA, or that are infrequent.38,84 Of concern, patients often interpret the term ‘mild asthma’ to mean that they are not at risk of severe exacerbations and do not need to take ICS-containing treatment. This is often described as patients ‘underestimating’ their asthma severity, but instead it reflects their different interpretation of the words ‘severity’ and ‘mild’ compared with the academic usage of these terms.38,84
How useful is the current retrospective definition of asthma severity?
The retrospective definition of severe asthma based on ‘difficulty to treat’ has been widely accepted in guidelines and in specialist clinical practice. It has obvious clinical utility as it identifies patients who, because of their burden of disease and incomplete response to optimized conventional ICS-based treatment, may benefit from referral to a
respiratory physician (if available) for further investigation, phenotyping, and consideration of additional treatment such as biologic therapy (See Section 8, p.139). It is appropriate to classify asthma as ‘difficult-to-treat’ rather than severe if there are modifiable factors such as incorrect inhaler technique, poor adherence or untreated comorbidities, because asthma may become well controlled when such issues are addressed.38,84,175
By contrast, the clinical utility of the retrospective definition of mild asthma is much less clear. There is substantial variation in opinions about the specific criteria that should be used, for example whether FEV1 should be ≥80% predicted in order for asthma to be considered ‘mild’, and whether the occurrence of any exacerbation precludes a patient’s asthma being classified as ‘mild’ for the next 12 months.186 There are too few studies of the underlying pathology to discern whether isolated exacerbations necessarily imply greater inherent severity, especially given the contribution of external triggers such as viral infections or allergen exposure to sporadic exacerbations.
Further, by this definition, asthma can be classified as ‘mild’ only after several months of ICS-containing treatment, and only if asthma is well controlled on low-dose ICS or as-needed low-dose ICS-formoterol, so this definition clearly cannot be applied to patients with uncontrolled or partly controlled symptoms who are taking SABA.
Finally, retrospective classification of asthma as mild appears of little value in deciding on future treatment. In addition, in the studies of as-needed ICS-formoterol, baseline patient characteristics such as daily reliever use, lower lung function or history of exacerbations (or even baseline blood eosinophils or FeNO) did not identify patients who should instead be treated with daily ICS.187,188 Instead, decisions about ongoing treatment should be based upon the large evidence base about the efficacy and effectiveness of as-needed ICS-formoterol or daily ICS, together with an individualized assessment of the patient’s symptom control, exacerbation risk, predictors of response, and patient preferences (see Box 3-3, p.53).
However, the most urgent problem with the term ‘mild asthma’, regardless of how it is defined, is that it encourages complacency, since both patients and clinicians often interpret ‘mild asthma’ to mean that the patient is at low risk and does not need ICS-containing treatment. However, up to 30% of asthma exacerbations and deaths occur in people with infrequent symptoms, for example, less than weekly or only on strenuous exercise.180,181
Interim advice about asthma severity descriptors
For clinical practice
GINA continues to support the current definition of severe asthma as asthma that remains uncontrolled despite optimized treatment with high-dose ICS-LABA, or that requires high-dose ICS-LABA or biologic therapy to prevent it from becoming uncontrolled. GINA also maintains the clinically important distinction between difficult-to-treat and severe asthma. See Box 2-4 (p.47) and Section 8 (p.139) for more detail about assessment and management of difficult-to-treat and severe asthma. For patients who have had a good asthma response to biologic therapy, it may be helpful for administrative reasons to describe their asthma as, e.g., ‘severe eosinophilic asthma, well controlled on [therapy]’, to indicate that the biologic therapy is needed to maintain their improved status. For discussion about the related concept of asthma remission on treatment, see p.50.
We suggest that in clinical practice, the term ‘mild asthma’ should generally be avoided if possible, because of the common but mistaken assumption by patients and clinicians that it equates to low risk, and that ICS treatment is not needed. Instead, assess each patient’s symptom control and risk factors on their current treatment (Box 2-1, p.36), as well as multimorbidity and patient goals and preferences. Explain that patients with infrequent or mild asthma symptoms can still have severe or fatal exacerbations if treated with SABA alone,180,181 and that this risk is reduced by half to two-thirds with low-dose ICS or with as-needed low-dose ICS formoterol.182,183 Ensure that you prescribe ICS- containing therapy to reduce the patient’s risk of severe exacerbations (Box 4-3, p.74), and treat any modifiable risk factors or comorbidities using pharmacologic or non-pharmacologic strategies (see Box 3-5, p.55 and Box 3-6, p.57).
‘Mild asthma’ is a retrospective label, so it cannot be used to decide which treatment patients should receive. Advice has been provided in Section 4 about which patients are suitable for low intensity treatment (Step 1 and 2).
For health professional education
The term ‘apparently mild asthma’ may be useful to highlight the discordance between symptoms and risk, i.e., that patients with infrequent or mild symptoms, who might therefore appear to have mild asthma, can still have severe or fatal exacerbations. However, ‘apparently mild asthma’ in English can easily be mistranslated into some languages as
‘obviously mild asthma’, which is the opposite of the intended meaning. Alternative phrases include ‘asthma that seems to be mild’.
Regardless of the term used, explain that ‘asthma control’ tools such as ACQ and ACT assess only one domain of asthma control, and only over a short period of time (see Assessing asthma symptom control, p.38), and that patients with infrequent interval symptoms are over-represented in studies of severe, near-fatal and fatal asthma exacerbations.180,181 Always emphasize the need for and benefit from ICS-containing treatment in patients with asthma, regardless of their symptom frequency or severity, and even if they have no obvious additional risk factors.
For epidemiologic studies
If clinical details are not available, describe the prescribed (or dispensed) treatment, without imputing severity,
e.g., ‘patients prescribed SABA with no ICS’ rather than ‘mild asthma’. Since treatment options change over time, and may differ between guidelines, state the actual treatment class, rather than a treatment Step (e.g., ‘low-dose maintenance-and-reliever therapy with ICS-formoterol’ rather than ‘Step 3 treatment’).
For clinical trials
Describe the patient population by their level of asthma control and treatment, e.g., ‘patients with uncontrolled asthma despite medium-dose ICS-LABA plus as-needed SABA’ rather than ‘moderate asthma’.
Further discussion is clearly needed
Given the importance of mild asthma and the discordance between its current academic definition and the various ways that the term is used in clinical practice, GINA is continuing to discuss these issues with a wide range of stakeholders. The aim is to obtain agreement among patients, health professionals, researchers, industry and regulators about the implications for clinical practice and clinical research of current knowledge about asthma pathophysiology and treatment,38,84 and whether/how the term ‘mild asthma’ should be used in the future. Pending the outcomes of this discussion, no change has been made to use of the term ‘mild asthma’ elsewhere in this GINA Strategy Report.
HOW TO DISTINGUISH BETWEEN UNCONTROLLED ASTHMA AND SEVERE ASTHMA
Although good symptom control and minimal exacerbations can usually be achieved with ICS-containing treatment, some patients will not achieve one or both of these goals even with a long period of high-dose therapy.160,175 In some patients this is due to truly refractory severe asthma, but in many others, it is due to incorrect inhaler technique, poor adherence, over-use of SABA, comorbidities, persistent environmental exposures, or psychosocial factors.
It is important to distinguish between severe asthma and uncontrolled asthma, because lack of asthma control is a much more common reason for persistent symptoms and exacerbations, and may be more easily improved. Box 2-4 (p.47) shows the initial steps that can be carried out in primary care to identify common causes of uncontrolled asthma. More details are given in Section 8 (p.139) about investigation and management of difficult-to-treat and severe asthma, including referral to a respiratory physician or severe asthma clinic where possible, and use of add-on treatment including biologic therapy.
The most common problems that need to be excluded before making a diagnosis of severe asthma are:
- Poor inhaler technique (up to 80% of community patients)91 (Box 5-2, p.110)
- Poor medication adherence189,190 (Box 5-3, p.112)
- Incorrect diagnosis of asthma, with symptoms due to alternative conditions such as inducible laryngeal obstruction, cardiac failure or lack of fitness (Box 1-3, p.27)
- Multimorbidity such as rhinosinusitis, GERD, obesity and obstructive sleep apnea93,191 (Section 6, p.117)
- Ongoing exposure to sensitizing or irritant agents in the home or work environment, including tobacco smoke.
