Assess symptom control from asthma-related symptom frequency, night waking and activity limitation, and, for patients using short-acting β2-agonist (SABA) reliever, the frequency of SABA use (Fig. 1). Other symptom control tools include the Asthma Control Test7 and the Asthma Control Questionnaire (preferably the five-item version).8

Fig. 1.

Global Initiative for Asthma assessment of asthma control in adults, adolescents, and children 6–11 years. For a version of this figure with full reference citations, please see Box 2–2 in Ref. 4. P450 inhibitors include cytochrome P450 inhibitors such as ritonavir, ketoconazole, and itraconazole. *Based on SABA (as-needed ICS–formoterol reliever not included); excludes reliever taken before exercise. For children 6–11 years, see also Box 2–3 in Ref. 4. For specific risk reduction strategies, see Box 3–8 in Ref. 4. †“Independent” risk factors are those that are significant after adjustment for the level of symptom control. Reproduced by permission from Ref. 4 (Box 2–2). BD=bronchodilator; FeNO=fractional exhaled nitric oxide; GERD=gastroesophageal reflux disease; ICS=inhaled corticosteroid; OCS=oral corticosteroid; SABA=short-acting β2-agonist.

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Rationale: Historically, the frequency of SABA reliever use (≤2 or >2d/wk) was included in the composite assessment of symptom control. This distinction was arbitrary and was based on the assumption that if a SABA was used on >2 days in a week, the patient needed to start controller therapy or increase the dose. However, if a patient uses as-needed ICS–formoterol as their reliever on average >2d/wk, this is already providing additional controller therapy, so further dose escalation may not be needed. Therefore, use of ICS–formoterol reliever ≤2 versus >2d/wk is not included in the composite assessment of symptom control. Instead, the average frequency of ICS–formoterol use over the past 4 weeks should be assessed separately when the patient's maintenance controller dose is reviewed.

Assess every patient's risk of exacerbations, even when symptom control is good. Although patients with poor symptom control are more likely to have exacerbations, patients with few or no symptoms can still have severe or even fatal exacerbations, including with external triggers such as viral respiratory infections.9 Factors that increase a patient's risk of exacerbations even if they have few symptoms include one or more exacerbations in the previous year, overuse of SABA (e.g., ≥3×200-dose albuterol [salbutamol] canisters per year [i.e., average more than daily use]), inadequate ICS use (undertreatment, poor adherence, incorrect inhaler technique), some comorbidities (including obesity, chronic rhinosinusitis, gastroesophageal reflux, confirmed food allergy), a low FEV1, a high blood eosinophil count in patients with type 2 inflammation, and major psychological or socioeconomic problems. Also assess risk factors for persistent airflow limitation and medication side effects (Fig. 1).

Record lung function at diagnosis, 3–6 months after starting treatment, and then periodically (e.g., at least once every 1–2 yr; more often in at-risk patients and those with severe asthma) to identify progressive decline. Lung function at individual visits is of limited use for guiding treatment because of its large (up to 20%) visit-to-visit variation.10 Investigate further if there are few symptoms but impaired lung function is present, which may indicate poor perception11 or long-term adaptation, or if there are frequent symptoms despite good lung function, which may indicate an alternative cause for the symptoms (Box 1–5 in Ref. 4).

By consensus,6 asthma severity is assessed retrospectively, after at least 2–3 months of treatment, from the level of treatment required to control symptoms and exacerbations. GINA does not distinguish between so-called “intermittent” and “mild persistent” asthma because this historical distinction was arbitrary, with no evidence of a difference in the treatment response. Severe asthma is asthma that remains uncontrolled despite optimized treatment with high-dose ICS–LABA or that requires such treatment to prevent it from becoming uncontrolled.12 It is important to distinguish between severe asthma and difficult-to-treat asthma (i.e., asthma that may be uncontrolled because of other factors, such as incorrect inhaler technique, poor adherence, and comorbidities such as obesity and environmental exposures).13

Rationale: This definition of asthma severity works well at the severe end of the spectrum but is less useful for describing mild asthma (see Topics Requiring Further Research). For example, patients with infrequent or no interval symptoms can still have severe exacerbations. This risk is reduced to a similar extent by either daily ICS treatment14,15 or by ICS–formoterol taken only for symptom relief,15 and the baseline symptom frequency does not predict the need for daily ICS.15,16

Assess not only symptom control and lung function but also the individual's modifiable risk factors and comorbidities (also called “treatable traits”)17 and patient/parent goals and preferences. Check adherence and inhaler technique frequently. Poor symptom control is associated with a much higher risk of exacerbations, but patients with apparently mild asthma or with good symptom control can still have severe or life-threatening exacerbations.9,14,18

Treatment adjustment includes not only changes in the asthma medication dose or type but also multidisciplinary management of modifiable risk factors and comorbidities (Section 3D in Ref. 4) and nonpharmacological strategies such as smoking cessation and avoidance of indoor/outdoor air pollution (Box 3–9 in Ref. 4).

For all patients, provide regular training in inhaler techniques and asthma self-management, including self-monitoring of symptoms and/or PEF, and a written asthma action plan19 (Section 3C in Ref. 4). Encourage adherence with controller medication, even when symptoms are infrequent. Consider stepping down treatment when good control has been maintained for 2–3 months (Box 3–7 in Ref. 4).

Arrange regular medical review to identify modifiable risk factors, optimize care, and minimize the risk of exacerbations; review at least yearly (more often in patients with moderate or severe asthma), after an exacerbation, and after a treatment change. Review clinical outcomes and side effects, patient/parent/caregiver satisfaction, inhaler technique and self-management skills. Ensure the patient/caregiver has an up-to-date written asthma action plan.

Rationale: The GINA strategy (Fig. 2) considers not only patient characteristics that may predict a clinically important difference in treatment response but also medication access, the patient's preferences, and practical issues of cost, ability to use the inhaler, and likely adherence. The extent to which asthma treatment can be individualized according to patient characteristics or phenotype depends on the health system, the clinical context, evidence about the magnitude of potential difference in outcomes, cost, and available resources.

Since 2019, GINA has recommended against SABA-only treatment of asthma in adults and adolescents after consideration of its risks and the evidence for a safer alternative.28 Instead, to reduce the risk of serious exacerbations and control symptoms, all adults and adolescents with asthma should receive ICS-containing treatment, either regularly or, in mild asthma, as needed to relieve symptoms.28 ICS is now also recommended for all children 6–11 years with asthma, either regularly or, in mild asthma, whenever SABA is taken for symptom relief.

Rationale: Although SABA is inexpensive and relieves symptoms quickly, treatment of asthma with SABA alone is associated with increased risk of asthma-related death22 and of urgent asthma-related health care,20 even in patients with so-called intermittent asthma.29 Overuse of SABAs (≥3×200-dose albuterol canisters per year) is associated with incrementally increasing risk of asthma exacerbations and mortality, including in patients treated with SABA alone.22 Regular use of SABA, even 2–4 times per day for 1–2 weeks, is associated with β2-receptor downregulation, loss of bronchodilator response, increased airway hyperresponsiveness, and increased airway inflammation.30,31 Importantly, from a cognitive and behavioral perspective, starting treatment with SABA alone trains the patient to regard it as their main asthma treatment, increasing the challenges for adherence with any subsequent advice to take ICS every day even when asymptomatic.

By contrast, in mild asthma, as-needed ICS–formoterol decreases the risk of severe exacerbations requiring oral corticosteroid (OCS) by ≥60% compared with SABA alone,15,21 including in patients without elevated type 2 inflammatory markers,15,32 with a very small average daily ICS dose.15,16,21,33 Starting treatment with as-needed ICS–formoterol in patients with mild asthma addresses both symptom relief and risk reduction without the need for daily maintenance treatment.

There are five levels of treatment (Steps 1–5; Fig. 3), with two “tracks,” depending on the choice of reliever: ICS–formoterol (Track 1, preferred) or SABA (Track 2, alternative). Treatment may be stepped up or down within a track by using the same reliever at each step or may be switched between tracks.

Fig. 3.

Personalized management for adults and adolescents to control symptoms and minimize risk. For ICS doses, see Box 3–6 in Ref. 4. Reproduced by permission from Ref. 4 (Box 3–5A). HDM=house dust mite; ICS=inhaled corticosteroid; LABA=long-acting β2-agonist; LAMA=long-acting muscarinic antagonist; LTRA=leukotriene receptor antagonist; OCS=oral corticosteroid; SABA=short-acting β2-agonist; SLIT=sublingual immunotherapy.

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Within Track 1, the reliever is as-needed, low-dose ICS–formoterol. This means that when a patient at any treatment step has asthma symptoms, they take low-dose ICS–formoterol for symptom relief. In Steps 1–2, this also provides the patient's controller therapy and reduces severe exacerbation risk,15,16,21,33 without daily maintenance treatment. This is distinguished from maintenance-and-reliever therapy (MART) in Steps 3–5, where patients take ICS–formoterol both as daily maintenance treatment and, as needed, for symptom relief (Table 1).

Track 2, with SABA reliever, is suggested where ICS–formoterol is not available or is not preferred by a patient at low risk of exacerbations (including having no exacerbations in the past year). Before prescribing therapy with SABA reliever, consider if the patient is likely to be poorly adherent with ICS controller therapy, as this increases the risk of exacerbations.

In Fig. 3, additional or alternative treatments with less evidence for safety, efficacy, and/or effectiveness are shown as “other controller options.”

Rationale: GINA introduced two tracks into the 2021 treatment figure for adults and adolescents (Fig. 3 and Box 3–5A in Ref. 4) to clarify:

• •

  How to step treatment up or down within the different reliever options (ICS–formoterol or SABA).

• •

  That SABA is the recommended reliever for patients prescribed maintenance nonformoterol ICS–LABA.

The Track 1 approach is preferred overall because it reduces the risk of severe exacerbations compared with using a SABA reliever, with similar symptom control and lung function, and it integrates messaging about the importance of both symptom control and risk reduction across all treatment steps, including Step 1. The figure also summarizes the main considerations for choosing ICS–formoterol or SABA as the reliever and reinforces the key elements of personalized asthma treatment.

Treatment steps for children are shown in Fig. 4 (Box 3–5B in Ref. 4). In Step 1, for children with initial symptoms less than twice per month, taking ICS whenever SABA is taken for symptom relief is preferred over regular ICS or as-needed SABA alone. Regular, low-dose ICS with as-needed SABA is recommended in Step 2 for most children with asthma, but attention must be paid to adherence.

Fig. 4.

Personalized management for children 6–11 years to control symptoms and minimize future risk. For ICS doses for children, see Box 3–6 in Ref. 4. For MART doses, see Table E2 and the downloadable resource in the online supplement, Appendix A. Reproduced by permission from Ref. 4 (Box 3–5B). BUD-FORM=budesonide–formoterol; ICS=inhaled corticosteroid; LABA=long-acting β2-agonist; LTRA=leukotriene receptor antagonist; MART=maintenance-and-reliever therapy; OCS=oral corticosteroid; SABA=short-acting β2-agonist.

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In Step 3, options include low-dose ICS–LABA, medium-dose ICS, or very-low-dose budesonide–formoterol MART.52 In Step 4, options include medium-dose ICS–LABA53 or low-dose MART (Table 1; Table E2 and downloadable resource in the online supplement, Appendix A). For all children at Step 4, consider referral for expert advice. In children, before stepping up, consider trying other controller options at the same step.

Rationale: The addition of as-needed concomitant ICS+SABA as an antiinflammatory reliever in Step 1 for children was based on evidence from two studies in which children and adolescents were stepped down from maintenance ICS to as-needed ICS plus SABA in separate inhalers44,45 and because of likely nonadherence with daily ICS by children with infrequent symptoms. For Step 2, there is much more evidence for the safety and effectiveness of maintenance low-dose ICS, but in the real world, ICS adherence is extremely low. In Step 3, MART with very-low-dose ICS–formoterol52 was previously recommended in the GINA report text and for consistency is now also included in the figure (Box 3–5B in Ref. 4 and Fig. 4). For Step 4, doubling the MART maintenance dose to 100/6μg (delivered dose of 80/4.5μg) by instructing the patient to take one inhalation twice daily (still “low dose”) was included by consensus, given the variation in ICS responsiveness between patients (Table 1; Table E2 and downloadable resource in the online supplement, Appendix A).

Difficult-to-treat asthma is asthma that is uncontrolled despite medium- or high-dose ICS–LABA treatment or that requires high-dose ICS–LABA treatment to maintain good symptom control and reduce exacerbations.

Severe asthma is asthma that is uncontrolled despite good adherence with optimized high-dose ICS–LABA therapy and management of contributory factors or that worsens when high-dose treatment is decreased. Approximately 3–10% of people with asthma have severe asthma.12,59

Assess all patients with difficult-to-treat asthma to confirm the diagnosis of asthma and to identify and manage factors that commonly contribute to symptoms, poor quality of life, and/or exacerbations. For patients with persistent symptoms and/or exacerbations despite high-dose ICS–LABA, assess the clinical and inflammatory phenotype, as this may guide the selection of add-on treatment. Refer for expert advice if asthma does not improve in response to optimizing Step 4 or 5 treatment (or earlier, if needed).

Refer patients to support services, where available, to help them deal with the heavy physical, emotional, social and financial burden of severe asthma and its treatment.60

In Step 5, recommended add-on options include long-acting muscarinic antagonist (LAMA) (tiotropium ≥6 yr, triple therapy with ICS–LABA–LAMA ≥18 yr). Adding LAMA provided modest improvement in lung function but not symptom control, and exacerbations were reduced in some studies.61–65 Step 4 MART with ICS–formoterol should be tried before considering add-on LAMA; as-needed ICS–formoterol can be continued as the reliever for patients prescribed ICS–formoterol–LAMA, but for patients prescribed an ICS–LABA–LAMA with nonformoterol LABA, the appropriate reliever is SABA. After specialist referral, add-on, low-dose azithromycin is another option for reducing exacerbations, but risks of antibiotic resistance and prolongation of the corrected QT interval (QTc) on electrocardiography must be considered.66 Sputum-guided adjustment of the ICS dose improves outcomes in moderate-to-severe asthma67 but is not widely available, and the optimal frequency of sputum assessment is not known.

With add-on biologic therapies for severe eosinophilic asthma (benralizumab, dupilumab, mepolizumab, reslizumab) and severe allergic asthma (dupilumab, omalizumab) the main benefits are substantial reduction in severe exacerbations and reduced OCS exposure.68 No head-to-head studies are available, but typical eligibility criteria for each class, and predictors of good response, are found in the GINA pocket guide decision Tree.13

Maintenance OCS treatment should be avoided, wherever possible, because of its serious long-term side effects.40,69

At follow-up, assess the response to any add-on treatment, stop ineffective treatments, and consider other options. For patients who respond to add-on therapy, reevaluate the need for other therapies every 3–4 months, but do not completely stop ICS.

Continue to optimize patient care in collaboration with primary care and consider the patient's social and emotional needs. Arrange multidisciplinary team care for severe asthma, if available. Invite patients with severe asthma to enroll in a registry or clinical trial, if available and relevant, to help fill evidence gaps, including comparison of biologic therapy options and positioning of bronchial thermoplasty.68

As part of asthma self-management, provide all patients with a written asthma action plan appropriate for their level of asthma control and health literacy, so they know how to recognize and respond to worsening asthma.19 State when and how to change reliever and controller medications, use OCS if appropriate, and access medical care if symptoms fail to respond to treatment. Base the action plan on changes in symptoms or (only in adults) PEF.19

Advise patients who have a history of rapid deterioration to go to an acute care facility or see their doctor immediately if their asthma starts to worsen.

Action plan recommendations for responding to worsening asthma depend on the patient's usual therapy. Patients prescribed as-needed ICS–formoterol as their reliever, either alone or in MART, should increase their as-needed doses as symptoms increase. Those on a maintenance ICS-containing controller should increase to a high dose temporarily (e.g., for 1–2 wk) (Box 4–2 in Ref. 4).

Rationale: In a systematic review of self-management studies, action plans in which the ICS dose was at least doubled were associated with improved asthma outcomes and reduced healthcare use.71 In some studies in adults and adolescents19,72 and preschool children,73 short-term, higher-dose ICS reduced progression to a severe exacerbation, and some found less impact on serum cortisol than with OCS,74,75 but cost may be an issue. Given the shape of the ICS dose–response curve, the benefit of increasing maintenance ICS when asthma worsens may be greater when background adherence is lower. The timing of an increased ICS dose may be important: studies in adults in which the ICS dose was doubled 5–7 days after symptoms worsened found no reduction in severe exacerbations.76,77 In contrast, in MART, taking reliever doses of ICS–formoterol as soon as asthma symptoms occur, reduces the risk of progression to severe exacerbation.24,25

Assess exacerbation severity from the patient's mental state, degree of dyspnea, vital signs, oxygen saturation, and lung function (PEF or spirometry) while starting treatment with repeated administration of SABA (in most patients, by pressurized metered-dose inhaler and spacer) and controlled flow oxygen (sufficient flow to maintain oxygen saturation at 93–95% for adults; 94–98% for children 6–11 yr), if available (Fig. 5). Controlled oxygen therapy is associated with lower mortality and better outcomes than high-concentration (100%) oxygen therapy.78–80

Fig. 5.

Management of asthma exacerbations in primary care (adults, adolescents, children 6–11 yr). SABA doses are for albuterol. Reproduced by permission from Ref. 4 (Box 4–3). PEF=peak expiratory flow; pMDI=pressurized metered-dose inhaler; SABA=short-acting β2-agonist.

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Arrange immediate transfer to an acute care facility if there are signs of severe exacerbation, or to intensive care, particularly if the patient is drowsy, confused, or has a silent chest. During transfer, give inhaled SABA and ipratropium bromide, controlled oxygen, and systemic corticosteroids.

Repeated administration of albuterol (up to 4–10 puffs every 20min for the first hour) is effective for rapidly reversing airflow limitation.81 Avoid nebulization except for life-threatening asthma; delivery of rapid-acting β2-agonist via a pressurized metered-dose inhaler and spacer or via a dry-powder inhaler is as effective in patients with moderately severe acute asthma81,82 and avoids the risk of disseminating infectious particles. Current evidence does not support the routine use of intravenous β2-agonists in patients with severe asthma exacerbations.83

Start OCS early after presentation. For adults, give prednisolone 40–50mg/d (or equivalent) for 5–7 days. For children, give prednisolone 1–2mg/kg (maximum, 40mg) for 3–5 days. Tapering is not needed if administered for <2 weeks.

Review response of symptoms, vital signs, oxygen saturation and lung function after 1h (or earlier if worsening). Give ipratropium bromide only for severe exacerbations. Consider intravenous magnesium sulfate for patients with severe exacerbations not responding to initial treatment.

Do not routinely request chest radiography or routinely prescribe antibiotics for asthma exacerbations.

The decision on whether to hospitalize should be based on the patient's clinical status, lung function, response to treatment, recent and past history of exacerbations, social support, and ability to manage at home.

Rationale: Currently, inhaled albuterol is the usual bronchodilator in acute asthma management. Similar efficacy and safety of formoterol in the ED have been reported.84 In one study, high-dose budesonide–formoterol had similar efficacy and safety to SABA in ED patients.85

Before the patient goes home, arrange ongoing treatment. This should include starting ICS-containing controller treatment, preferably ICS–formoterol as MART (Table 1; Table E2 and downloadable resource in the online supplement, Appendix A) to reduce the risk of another exacerbation, or stepping up the dose of existing maintenance treatment for 2–4 weeks. Advise patients to use reliever medication as needed, not regularly. Patients prescribed ICS–formoterol as their reliever should return to this after an ED presentation.

Arrange early follow-up after any exacerbation, regardless of where it was managed:

• •

  Review the patient's symptom control and risk factors for further exacerbations.

• •

  Prescribe/continue ICS-containing controller therapy (preferably MART with ICS–formoterol) to reduce the risk of further exacerbations. If already taking controller therapy, continue increased doses for 2–4 weeks.

• •

  Provide a written asthma action plan and, where relevant, advice about avoiding exacerbation triggers.

• •

  Check inhaler technique and adherence.

Asthma outcomes after an ED presentation for acute asthma are significantly improved by comprehensive intervention programs that include optimal controller management, inhaler technique, and elements of self-management education (self-monitoring, written action plan, and regular review).86,87

Referral for expert advice should be considered for patients who have been hospitalized for asthma or who have repeat presentations to acute care settings. Follow-up by a specialist is associated with fewer subsequent ED visits or hospitalizations and better asthma control.87

Recurrent wheezing occurs in a large proportion of children 5 years and younger, typically with viral respiratory infections. Recognizing when this is the initial presentation of asthma is difficult. In young children with a history of wheezing, a diagnosis of asthma is more likely if they have any of the following:

• •

  Wheezing or coughing that occurs with exercise, laughing, or crying, particularly in the absence of an apparent respiratory infection.

• •

  Allergic sensitization, eczema, allergic rhinitis or food allergy, or asthma in first-degree relatives.

• •

  Clinical improvement during 2–3 months of controller treatment and worsening after cessation.

It is particularly important in this age group to consider and exclude alternative causes of wheeze, cough, and breathlessness (Box 6–3 in Ref. 4).

Important indications for referral of children ≤5 years for further diagnostic investigations include neonatal/very early onset of symptoms, failure to thrive, continuous wheezing, symptoms not associated with typical triggers (e.g., viral respiratory infections), or associated with vomiting, focal lung or cardiovascular signs, finger clubbing, hypoxemia outside the context of viral illness, or failure to respond to asthma medications.

The goals of asthma management in young children are to achieve good control of symptoms and maintain normal activity levels and to minimize the risk of asthma exacerbations, impaired lung development, and medication side effects.

Wheezing episodes in young children should be treated initially with inhaled SABA, regardless of whether the diagnosis of asthma has been made. However, SABAs are generally ineffective for initial episodes of wheeze in children younger than 1 year with infectious bronchiolitis.

A trial of controller therapy (e.g., for 3 mo) should be given if the symptom pattern suggests asthma, alternative diagnoses have been excluded, and respiratory symptoms are uncontrolled and/or wheezing episodes are frequent or severe (Fig. 6). The response to treatment should be reviewed before deciding whether to continue it. If the response is absent or incomplete, reconsider alternative diagnoses.

Fig. 6.

Personalized management of asthma in children 5 years and younger. Reproduced by permission from Ref. 4 (Box 6–5). ICS=inhaled corticosteroid; LTRA=leukotriene receptor antagonist; SABA=short-acting β2-agonist.

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It is important to discuss controller treatment choices with the child's parent/caregiver to explain the relative benefits and risks of treatment and the importance of maintaining normal activity levels for their child's physical and social development.

The choice of inhaler device should be based on the child's age and capability. The preferred device is a pressurized metered-dose inhaler and spacer, with a face mask for children younger than 3 years and a mouthpiece for most aged 3–5 years. Children should be switched from a face mask to a mouthpiece as soon as they can demonstrate good technique.

Review the need for asthma treatment frequently, as asthma-like symptoms remit in many young children or may be markedly seasonal. Measure the child's height at least once every year.

Early symptoms of exacerbations in young children may include increased symptoms, increased coughing (especially at night), lethargy or reduced exercise tolerance, impaired daily activities including feeding, and a poor response to reliever medication.