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Global Initiative for Asthma (GINA)�What’s new in GINA 2022?

This slide set is restricted for academic and educational purposes only. No additions or changes may be made to slides. Use of the slide set or of individual slides for commercial or promotional purposes requires approval from GINA.

© Global Initiative for Asthma

GINA Global Strategy for Asthma �Management and Prevention

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The Global Initiative for Asthma (GINA)

  • GINA was established by the WHO and NHLBI in 1993
    • To increase awareness about asthma
    • To improve asthma prevention and management through a coordinated worldwide effort
    • GINA is independent, funded only by the sale and licensing of its reports and figures
  • The GINA report is a global evidence-based strategy that can be adapted for local health systems and medicine availability
    • ~500,000 copies of GINA reports downloaded each year from 100 countries
    • Practical focus: multiple flow-charts and tables
  • The GINA strategy report is updated every year
    • Twice-yearly cumulative review of new evidence across the whole asthma strategy
    • The Science Committee reviews published GRADE reviews, when available
    • Careful attention is paid to clinical relevance of study designs and generalizability of populations
    • Extensive external review before publication
  • For detailed description of GINA methodology, see www.ginasthma.com/aboutus/methodology

​

© Global Initiative for Asthma, www.ginasthma.org

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Diagnosis of asthma

  • The diagnosis of asthma is based on a history of variable respiratory symptoms and demonstration of variable expiratory airflow limitation
    • Test before treating, wherever possible
    • Symptoms, variability in lung function, and airway hyperresponsiveness are decreased by ICS, so it is often more difficult to confirm the diagnosis after controller treatment is started
  • The flow-chart (Box 1-1) has been updated in 2022 to emphasize the different approach for initial diagnosis compared with confirming the diagnosis in patients taking controller treatment
    • Diagnostic approaches for patients taking controller treatment are in Boxes 1-3 and 1-4
  • At a global level, spirometry before and after bronchodilator is the most useful initial investigation
    • Optimize the conditions for testing, if possible (e.g. when symptomatic, and after withholding bronchodilators)
    • In patients on controller treatment, more than one test is often needed
  • GINA will review GRADE evidence from ERS Task Force on diagnosis of asthma (Louis et al, ERJ 2022)

​

© Global Initiative for Asthma, www.ginasthma.org

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Diagnosis of asthma

GINA 2022, Box 1-1

© Global Initiative for Asthma, www.ginasthma.org

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Diagnosis in patients already on controller treatment

GINA 2022, Box 1-3

© Global Initiative for Asthma, www.ginasthma.org

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Diagnosis of asthma in low- and middle-income countries

  • Asthma is often under-diagnosed
    • Differential diagnosis often includes other endemic respiratory disease, e.g. tuberculosis, HIV/AIDS-associated lung disease, parasitic or fungal lung diseases
    • A syndromic approach is often used for diagnosis
  • GINA recommends confirmation of asthma diagnosis with lung function testing, whenever possible, before commencing long-term treatment
    • Spirometry-based testing if available
    • Peak expiratory flow (PEF)
      • >20% increase in PEF, 15 minutes after 2 puffs of salbutamol = asthma likely (WHO-PEN)
      • Improvement of symptoms and PEF after 4 weeks ICS treatment
  • Access to affordable diagnostic equipment and skills training needs to be substantially scaled up in low- and middle-income countries

​

© Global Initiative for Asthma, www.ginasthma.org

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GINA treatment figure for adults and adolescents (≥12 years)

  • Treatment options are shown in two tracks
    • This was necessary to clarify how to step treatment up and down with the same reliever
  • Track 1, with low dose ICS-formoterol as the reliever, is the preferred strategy
    • Preferred because of the evidence that using ICS-formoterol as reliever reduces the risk of exacerbations compared with using a SABA reliever, with similar symptom control and lung function
  • Track 2, with SABA as the reliever, is an ‘alternative’ (non-preferred) strategy
    • Less effective than Track 1 for reducing severe exacerbations
    • Use Track 2 if Track 1 is not possible; can also consider Track 2 if a patient has good adherence with their controller, and has had no exacerbations in the last 12 months
    • Before considering a regimen with SABA reliever, consider whether the patient is likely to continue to be adherent with daily controller – if not, they will be exposed to the risks of SABA-only treatment
  • “Other controller options”
    • These have limited indications, or less evidence for efficacy and/or safety than Track 1 or 2 options
  • Step 5
    • A new class of biologic therapy has been added (anti-TSLP)
    • A prompt added about the GINA severe asthma guide

​

© Global Initiative for Asthma, www.ginasthma.org

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Low dose ICS whenever SABA taken, or daily LTRA, or add HDM SLIT

Medium dose ICS, or add LTRA, or add HDM SLIT

Add LAMA or LTRA or HDM SLIT, or switch to high dose ICS

Add azithromycin (adults) or LTRA. As last resort consider adding low dose OCS but consider side-effects

RELIEVER: As-needed short-acting beta2-agonist

STEP 1

Take ICS whenever SABA taken

STEP 2

Low dose maintenance ICS

STEP 3

Low dose maintenance ICS-LABA

STEP 4

Medium/high

dose maintenance ICS-LABA

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-LABA, ± anti-IgE,

anti-IL5/5R, anti-IL4R, anti-TSLP

RELIEVER: As-needed low-dose ICS-formoterol

STEPS 1 – 2

As-needed low dose ICS-formoterol

STEP 3

Low dose maintenance ICS-formoterol

STEP 4

Medium dose maintenance ICS-formoterol

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-formoterol,

± anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP

Treatment of modifiable risk factors and comorbidities

Non-pharmacological strategies

Asthma medications (adjust down/up/between tracks) Education & skills training

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

Symptoms Exacerbations Side-effects Lung function

Patient satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence Patient preferences and goals

CONTROLLER and

PREFERRED RELIEVER

(Track 1). Using ICS-formoterol as reliever reduces the risk of exacerbations compared with using a SABA reliever

Other controller options for either track (limited indications, or less evidence for efficacy or safety)

CONTROLLER and

ALTERNATIVE RELIEVER

(Track 2). Before considering a regimen with SABA reliever, check if the patient is likely to be adherent with daily controller

See GINA

severe asthma guide

© Global Initiative for Asthma, www.ginasthma.org

GINA 2022, Box 3-5A

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Low dose ICS whenever SABA taken, or daily LTRA, or add HDM SLIT

Medium dose ICS, or add LTRA, or add HDM SLIT

Add LAMA or LTRA or HDM SLIT, or switch to high dose ICS

Add azithromycin (adults) or LTRA. As last resort consider adding low dose OCS but consider side-effects

RELIEVER: As-needed short-acting beta2-agonist

STEP 1

Take ICS whenever SABA taken

STEP 2

Low dose maintenance ICS

STEP 3

Low dose maintenance ICS-LABA

STEP 4

Medium/high

dose maintenance ICS-LABA

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-LABA, ± anti-IgE,

anti-IL5/5R, anti-IL4R, anti-TSLP

RELIEVER: As-needed low-dose ICS-formoterol

STEPS 1 – 2

As-needed low dose ICS-formoterol

STEP 3

Low dose maintenance ICS-formoterol

STEP 4

Medium dose maintenance ICS-formoterol

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-formoterol,

± anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP

Treatment of modifiable risk factors and comorbidities

Non-pharmacological strategies

Asthma medications (adjust down/up/between tracks) Education & skills training

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

Symptoms Exacerbations Side-effects Lung function

Patient satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence Patient preferences and goals

CONTROLLER and

PREFERRED RELIEVER

(Track 1). Using ICS-formoterol as reliever reduces the risk of exacerbations compared with using a SABA reliever

Other controller options for either track (limited indications, or less evidence for efficacy or safety)

CONTROLLER and

ALTERNATIVE RELIEVER

(Track 2). Before considering a regimen with SABA reliever, check if the patient is likely to be adherent with daily controller

See GINA

severe asthma guide

Symptoms Exacerbations Side-effects Lung function

Patient satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence Patient preferences and goals

Treatment of modifiable risk factors and comorbidities

Non-pharmacological strategies

Asthma medications (adjust down/up/between tracks) Education & skills training

© Global Initiative for Asthma, www.ginasthma.org

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

GINA 2022, Box 3-5A, 1/4

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Low dose ICS whenever SABA taken, or daily LTRA, or add HDM SLIT

Medium dose ICS, or add LTRA, or add HDM SLIT

Add LAMA or LTRA or HDM SLIT, or switch to high dose ICS

Add azithromycin (adults) or LTRA. As last resort consider adding low dose OCS but consider side-effects

RELIEVER: As-needed short-acting beta2-agonist

STEP 1

Take ICS whenever SABA taken

STEP 2

Low dose maintenance ICS

STEP 3

Low dose maintenance ICS-LABA

STEP 4

Medium/high

dose maintenance ICS-LABA

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-LABA, ± anti-IgE,

anti-IL5/5R, anti-IL4R, anti-TSLP

RELIEVER: As-needed low-dose ICS-formoterol

STEPS 1 – 2

As-needed low dose ICS-formoterol

STEP 3

Low dose maintenance ICS-formoterol

STEP 4

Medium dose maintenance ICS-formoterol

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-formoterol,

± anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP

Treatment of modifiable risk factors and comorbidities

Non-pharmacological strategies

Asthma medications (adjust down/up/between tracks) Education & skills training

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

Symptoms Exacerbations Side-effects Lung function

Patient satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence Patient preferences and goals

CONTROLLER and

PREFERRED RELIEVER

(Track 1). Using ICS-formoterol as reliever reduces the risk of exacerbations compared with using a SABA reliever

Other controller options for either track (limited indications, or less evidence for efficacy or safety)

CONTROLLER and

ALTERNATIVE RELIEVER

(Track 2). Before considering a regimen with SABA reliever, check if the patient is likely to be adherent with daily controller

See GINA

severe asthma guide

RELIEVER: As-needed low-dose ICS-formoterol

CONTROLLER and

PREFERRED RELIEVER

(Track 1). Using ICS-formoterol as reliever reduces the risk of exacerbations compared with using a SABA reliever

STEPS 1 – 2

As-needed low dose ICS-formoterol

STEP 3

Low dose maintenance ICS-formoterol

STEP 4

Medium dose maintenance ICS-formoterol

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-formoterol,

± anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP

© Global Initiative for Asthma, www.ginasthma.org

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

GINA 2022, Box 3-5A, 2/4

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Low dose ICS whenever SABA taken, or daily LTRA, or add HDM SLIT

Medium dose ICS, or add LTRA, or add HDM SLIT

Add LAMA or LTRA or HDM SLIT, or switch to high dose ICS

Add azithromycin (adults) or LTRA. As last resort consider adding low dose OCS but consider side-effects

RELIEVER: As-needed short-acting beta2-agonist

STEP 1

Take ICS whenever SABA taken

STEP 2

Low dose maintenance ICS

STEP 3

Low dose maintenance ICS-LABA

STEP 4

Medium/high

dose maintenance ICS-LABA

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-LABA, ± anti-IgE,

anti-IL5/5R, anti-IL4R, anti-TSLP

RELIEVER: As-needed low-dose ICS-formoterol

STEPS 1 – 2

As-needed low dose ICS-formoterol

STEP 3

Low dose maintenance ICS-formoterol

STEP 4

Medium dose maintenance ICS-formoterol

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-formoterol,

± anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP

Treatment of modifiable risk factors and comorbidities

Non-pharmacological strategies

Asthma medications (adjust down/up/between tracks) Education & skills training

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

Symptoms Exacerbations Side-effects Lung function

Patient satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence Patient preferences and goals

CONTROLLER and

PREFERRED RELIEVER

(Track 1). Using ICS-formoterol as reliever reduces the risk of exacerbations compared with using a SABA reliever

Other controller options for either track (limited indications, or less evidence for efficacy or safety)

CONTROLLER and

ALTERNATIVE RELIEVER

(Track 2). Before considering a regimen with SABA reliever, check if the patient is likely to be adherent with daily controller

See GINA

severe asthma guide

RELIEVER: As-needed short-acting beta2-agonist

STEP 1

Take ICS whenever SABA taken

STEP 2

Low dose maintenance ICS

STEP 3

Low dose maintenance ICS-LABA

STEP 4

Medium/high

dose maintenance ICS-LABA

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-LABA, ± anti-IgE,

anti-IL5/5R, anti-IL4R, anti-TSLP

CONTROLLER and

ALTERNATIVE RELIEVER

(Track 2). Before considering a regimen with SABA reliever, check if the patient is likely to be adherent with daily controller

© Global Initiative for Asthma, www.ginasthma.org

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

GINA 2022, Box 3-5A, 3/4

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Low dose ICS whenever SABA taken, or daily LTRA, or add HDM SLIT

Medium dose ICS, or add LTRA, or add HDM SLIT

Add LAMA or LTRA or HDM SLIT, or switch to high dose ICS

Add azithromycin (adults) or LTRA. As last resort consider adding low dose OCS but consider side-effects

RELIEVER: As-needed short-acting beta2-agonist

STEP 1

Take ICS whenever SABA taken

STEP 2

Low dose maintenance ICS

STEP 3

Low dose maintenance ICS-LABA

STEP 4

Medium/high

dose maintenance ICS-LABA

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-LABA, ± anti-IgE,

anti-IL5/5R, anti-IL4R, anti-TSLP

RELIEVER: As-needed low-dose ICS-formoterol

STEPS 1 – 2

As-needed low dose ICS-formoterol

STEP 3

Low dose maintenance ICS-formoterol

STEP 4

Medium dose maintenance ICS-formoterol

STEP 5

Add-on LAMA

Refer for assessment of phenotype. Consider high dose maintenance ICS-formoterol,

± anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP

Treatment of modifiable risk factors and comorbidities

Non-pharmacological strategies

Asthma medications (adjust down/up/between tracks) Education & skills training

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

Symptoms Exacerbations Side-effects Lung function

Patient satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence Patient preferences and goals

CONTROLLER and

PREFERRED RELIEVER

(Track 1). Using ICS-formoterol as reliever reduces the risk of exacerbations compared with using a SABA reliever

Other controller options for either track (limited indications, or less evidence for efficacy or safety)

CONTROLLER and

ALTERNATIVE RELIEVER

(Track 2). Before considering a regimen with SABA reliever, check if the patient is likely to be adherent with daily controller

See GINA

severe asthma guide

Other controller options for either track (limited indications, or less evidence for efficacy or safety)

Low dose ICS whenever SABA taken, or daily LTRA, or add HDM SLIT

Medium dose ICS, or add LTRA, or add HDM SLIT

Add LAMA or LTRA or HDM SLIT, or switch to high dose ICS

Add azithromycin (adults) or LTRA. As last resort consider adding low dose OCS but consider side-effects

© Global Initiative for Asthma, www.ginasthma.org

Adults & adolescents 12+ years

Personalized asthma management

Assess, Adjust, Review

for individual patient needs

GINA 2022, Box 3-5A, 4/4

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Background - the risks of ‘mild’ asthma

  • Patients with apparently mild asthma are still at risk of serious adverse events
    • 30–37% of adults with acute asthma
    • 16% of patients with near-fatal asthma
    • 15–27% of adults dying of asthma
  • Exacerbation triggers are unpredictable (viruses, pollens, pollution, poor adherence)
  • Even 4–5 lifetime OCS courses increase the risk of osteoporosis, diabetes, cataract (Price et al, J Asthma Allerg 2018)

​

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had symptoms less than weekly in previous 3 months (Dusser, Allergy 2007; Bergstrom, 2008)

SABA: short-acting beta2-agonist

© Global Initiative for Asthma, www.ginasthma.org

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Why not treat with SABA alone?

  • Inhaled SABA has been first-line treatment for asthma for 50 years
    • Asthma was thought to be a disease of bronchoconstriction
    • Role of SABA reinforced by rapid relief of symptoms and low cost
  • Regular use of SABA, even for 1–2 weeks, is associated with increased AHR, reduced bronchodilator effect, increased allergic response, increased eosinophils (e.g. Hancox, 2000; Aldridge, 2000)
    • Can lead to a vicious cycle encouraging overuse
    • Over-use of SABA associated with 🡩 exacerbations and �🡩 mortality (e.g. Suissa 1994, Nwaru 2020)
  • Starting treatment with SABA trains the patient to �regard it as their primary asthma treatment
  • The only previous option was daily ICS even when �no symptoms, but adherence is extremely poor
  • GINA changed its recommendation once evidence for �a safe and effective alternative was available

​

© Global Initiative for Asthma, www.ginasthma.org

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As-needed low dose ICS-formoterol in mild asthma (n=9,565)

COMPARED WITH AS-NEEDED SABA

  • The risk of severe exacerbations was reduced by 60–64% (SYGMA 1, Novel START)

COMPARED WITH MAINTENANCE LOW DOSE ICS

  • The risk of severe exacerbations was similar (SYGMA 1 & 2), or lower (Novel START, PRACTICAL)
  • Small differences in other asthma outcomes, favoring maintenance ICS, but all were less than the minimal clinically important difference
    • ACQ-5 mean difference 0.15 (MCID 0.5)
    • FEV1 mean difference ~54 mL
    • FeNO mean difference ~10ppb (Novel START, PRACTICAL)
    • No evidence of progressive worsening over 12 months
  • In Novel START and PRACTICAL, outcomes were independent of baseline features including blood eosinophils, FeNO, lung function, and exacerbation history
  • Average ICS dose was ~50–100mcg budesonide/day

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*Budesonide-formoterol 200/6 mcg, 1 inhalation as needed for symptom relief

O’Byrne et al, NEJM 2018

© Global Initiative for Asthma, www.ginasthma.org

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New evidence for as-needed ICS-formoterol in mild asthma

  • Meta-analysis of all four RCTs, n=9,565�(Crossingham, Cochrane 2021)
    • 55% reduction in severe exacerbations compared with SABA alone
    • Similar risk of severe exacerbations as with daily ICS + as-needed SABA

© Global Initiative for Asthma, www.ginasthma.org

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New evidence for as-needed ICS-formoterol in mild asthma

  • Meta-analysis of four all RCTs, n=9,565�(Crossingham, Cochrane 2021)
    • 55% reduction in severe exacerbations compared with SABA alone
    • Similar risk of severe exacerbations as with daily ICS + as-needed SABA
    • ED visits or hospitalizations
      • 65% lower than with SABA alone
      • 37% lower than with daily ICS

​

© Global Initiative for Asthma, www.ginasthma.org

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New evidence for as-needed ICS-formoterol in mild asthma

  • Meta-analysis of four all RCTs, n=9,565�(Crossingham, Cochrane 2021)
    • 55% reduction in severe exacerbations compared with SABA alone
    • Similar risk of severe exacerbations as with daily ICS + as-needed SABA
    • ED visits or hospitalizations
      • 65% lower than with SABA alone
      • 37% lower than with daily ICS
  • Analysis by previous treatment
    • Patients taking SABA alone had lower risk of severe exacerbations with as-needed �ICS-formoterol compared with daily ICS + as-needed SABA (Bateman, Annals ATS 2021; Beasley, NEJMed 2019)

Bateman 2021

Beasley 2019

© Global Initiative for Asthma, www.ginasthma.org

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Other changes in medication recommendations for ≥12 years

  • Long-acting muscarinic antagonists (LAMA) should not be used as monotherapy for asthma �(i.e. without ICS) because of increased risk of severe exacerbations (Baan, Pulm Pharmacol Ther 2021)
  • Adding LAMA to ICS-LABA: GRADE review and meta-analysis (Kim, JAMA 2021) confirms previous findings
    • Small increase in lung function (mean difference 0.08 L)
    • No clinically important benefits for symptoms or quality of life 🡪 don’t prescribe for dyspnea
    • Modest overall reduction in exacerbations compared with ICS-LABA (risk ratio 0.83 [0.77, 0.90])

​

​

​

​

​

​

​

    • Patients with exacerbations should receive at least medium dose ICS-LABA before considering add-on LAMA
  • Chromone pMDIs (sodium cromoglycate, nedocromil sodium) have been discontinued globally

​

​

© Global Initiative for Asthma, www.ginasthma.org

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Management of asthma in low- and middle-income countries

  • 96% of asthma deaths are in low- and middle-income countries (LMIC) (Meghji, Lancet 2021)
    • Much of this burden is avoidable, especially with ICS (e.g. Comaru, Respir Med 2016)
    • Barriers include lack of access to essential medications, and prioritization of acute care over chronic care by health systems (Mortimer, ERJ 2022)
  • Lack of access to affordable quality-assured inhaled medications (Stolbrink, review for WHO 2022)
    • Oral bronchodilators have slow onset of action and more side-effects than inhaled
    • OCS are associated with serious cumulative adverse effects (e.g. sepsis, cataract, osteoporosis) even with occasional courses (Price, J Asthma Allerg 2018)
  • GINA supports the initiative by IUATLD towards a World Health Assembly Resolution on equitable access to affordable care for asthma, including inhaled medicines
    • In the meantime, if Track 1 is not available due to lack of access or affordability, Track 2 treatment may be preferable, although less effective in reducing exacerbations
    • If Track 2 options also not available, taking ICS whenever SABA is taken may be preferable to LTRA or maintenance OCS because of concerns about efficacy and/or safety
    • Greatest overall benefit at a population level would be from increasing access to ICS-formoterol

© Global Initiative for Asthma, www.ginasthma.org

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Short GINA guide for difficult-to-treat and severe asthma in adults and adolescents, 2022

  • Full size rather than ‘pocket’ size; easier to read
  • Updated decision tree for assessment of adults and adolescents with difficult-to-treat asthma
    • Sections 1–4: primary or specialist care
    • Sections 5–8: specialist care
    • Sections 9–10: ongoing collaborative care with patient, GP, specialist, other health professionals
  • Decision tree and text are also included in full GINA report (Chapter 3E)
  • Slide set on GINA website

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© Global Initiative for Asthma, www.ginasthma.org

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Key changes to GINA severe asthma guide in 2022

  • Additional investigations
    • Consider screening for adrenal insufficiency if patient is on maintenance OCS or high dose ICS-LABA
    • For patients with eosinophils ≥300/µl, investigate for non-asthma causes including Strongyloides (often asymptomatic), before considering biologic therapy
    • For patients with hypereosinophilia, e.g. ≥1500/µl, investigate for conditions such as EGPA
  • Assessment of inflammatory phenotype
    • If blood eosinophils or FeNO not elevated, repeat up to 3 times, at least 1–2 weeks after stopping OCS, or on lowest possible OCS dose
  • Treatment options for patients with no evidence of Type 2 inflammation on repeated testing
    • Consider add-on treatment with LAMA or low-dose azithromycin if not already tried
    • Can also consider anti-IL4R* (if on maintenance OCS) or anti-TSLP* (but insufficient evidence with maintenance OCS)
  • Consider maintenance OCS only as last resort, because of serious cumulative adverse effects

*Check local eligibility criteria for specific biologic therapies

© Global Initiative for Asthma, www.ginasthma.org

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Key changes to GINA severe asthma guide in 2022 (continued)

  • Anti-IL4R* (dupilumab) for severe eosinophilic/Type 2 asthma
    • Not suggested if blood eosinophils (current or historic) >1500/µl
    • Dupilumab now also approved for children ≥6 years with severe eosinophilic/Type 2 asthma, not on maintenance OCS (Bacharier, NEJMed 2021)
  • Anti-TSLP* (tezepelumab) now approved for severe asthma (age ≥12 years)
    • Greater clinical benefit with higher blood eosinophils and/or higher FeNO
    • Insufficient evidence in patients taking maintenance OCS

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*Check local eligibility criteria for specific biologic therapies; TSLP: thymic stromal lymphopoietin

Class

Name

Age*

Asthma indication*

Other indications*

Anti-IgE

Omalizumab (SC)

≥6 years

Severe allergic asthma

Nasal polyposis, chronic spontaneous urticaria

Anti-IL5

​

Anti-IL5R

Mepolizumab (SC)

Reslizumab (IV)

Benralizumab (SC)

≥6 years

≥18 years

≥12 years

Severe eosinophilic/Type 2 asthma

Mepolizumab: EGPA, CRSwNP, hypereosinophilic syndrome

Anti-IL4R

Dupilumab (SC)

≥6 years

Severe eosinophilic/Type 2 asthma, or maintenance OCS

Moderate-severe atopic dermatitis, CRSwNP

Anti-TSLP

Tezepelumab (SC)

≥12 years

Severe asthma

​

© Global Initiative for Asthma, www.ginasthma.org

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© Global Initiative for Asthma 2022, www.ginasthma.org

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© Global Initiative for Asthma 2022, www.ginasthma.org

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© Global Initiative for Asthma 2022, www.ginasthma.org

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© Global Initiative for Asthma 2022, www.ginasthma.org

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Changes to treatment figure in children 6–11 years (Box 3-5B)

  • “Other controller options” clarified
    • These therapies may have limited indications, or less evidence about efficacy and/or safety than the “preferred” treatment options
  • Step 5:
    • Anti-IL4R (dupilumab) now approved for children with severe eosinophilic/Type 2 asthma (not on maintenance OCS)
    • Consider maintenance OCS only as last resort

​

​

© Global Initiative for Asthma, www.ginasthma.org

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Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

*Very low dose: BUD-FORM 100/6 mcg

†Low dose: BUD-FORM 200/6 mcg (metered doses).

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Children 6-11 years

Personalized asthma management:

Assess, Adjust, Review

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

Add tiotropium or add LTRA

Low dose ICS + LTRA

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

Box 3-5B © Global Initiative for Asthma 2022, www.ginasthma.org

30 of 52

Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

*Very low dose: BUD-FORM 100/6 mcg

†Low dose: BUD-FORM 200/6 mcg (metered doses).

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

Add tiotropium or add LTRA

Low dose ICS + LTRA

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

Children 6-11 years

Personalized asthma management:

Assess, Adjust, Review

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

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31 of 52

Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

*Very low dose: BUD-FORM 100/6 mcg

†Low dose: BUD-FORM 200/6 mcg (metered doses).

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

Add tiotropium or add LTRA

Low dose ICS + LTRA

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

Children 6-11 years

Personalized asthma management:

Assess, Adjust, Review

RELIEVER

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

STEP 3

STEP 4

STEP 5

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Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

*Very low dose: BUD-FORM 100/6 mcg

†Low dose: BUD-FORM 200/6 mcg (metered doses).

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

Add tiotropium or add LTRA

Low dose ICS + LTRA

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

Children 6-11 years

Personalized asthma management:

Assess, Adjust, Review

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 3

STEP 4

STEP 5

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

RELIEVER

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

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Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

*Very low dose: BUD-FORM 100/6 mcg

†Low dose: BUD-FORM 200/6 mcg (metered doses).

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

Add tiotropium or add LTRA

Low dose ICS + LTRA

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

Children 6-11 years

Personalized asthma management:

Assess, Adjust, Review

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 4

STEP 5

STEP 2

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

Low dose ICS + LTRA

RELIEVER

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

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Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

*Very low dose: BUD-FORM 100/6 mcg

†Low dose: BUD-FORM 200/6 mcg (metered doses).

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

Add tiotropium or add LTRA

Low dose ICS + LTRA

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

Children 6-11 years

Personalized asthma management:

Assess, Adjust, Review

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 5

STEP 2

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

Add tiotropium or add LTRA

STEP 3

RELIEVER

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

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Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

*Very low dose: BUD-FORM 100/6 mcg

†Low dose: BUD-FORM 200/6 mcg (metered doses).

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

STEP 1

Low dose ICS taken whenever SABA taken

Consider daily low dose ICS

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for children)

Daily leukotriene receptor antagonist (LTRA), or low dose ICS taken whenever SABA taken

STEP 3

Low dose ICS- LABA, OR medium dose ICS, OR

very low dose* ICS-formoterol maintenance and reliever (MART)

STEP 4

Medium dose ICS-LABA,

OR low dose† ICS-formoterol maintenance and reliever therapy (MART).

Refer for expert advice

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

Add tiotropium or add LTRA

Low dose ICS + LTRA

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

Symptoms Exacerbations Side-effects Lung function

Child and parent satisfaction

Confirmation of diagnosis if necessary Symptom control & modifiable

risk factors (see Box 2-2B)

Comorbidities

Inhaler technique & adherence

Child and parent preferences and goals

Treatment of modifiable risk factors & comorbidities

Non-pharmacological strategies

Asthma medications (adjust down or up) Education & skills training

Children 6-11 years

Personalized asthma management:

Assess, Adjust, Review

PREFERRED CONTROLLER

to prevent exacerbations and control symptoms

Other controller options (limited indications, or less evidence for efficacy or safety)

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 2

STEP 3

Add-on anti-IL5 or, as last resort, consider add-on

low dose OCS, but consider side-effects

STEP 5

Refer for phenotypic assessment

± higher dose ICS-LABA or

add-on therapy,

e.g. anti-IgE, anti-IL4R

STEP 4

RELIEVER

As-needed short-acting beta2-agonist (or ICS-formoterol reliever in MART in Steps 3 and 4)

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Changes to treatment figure in children 5 years and younger (Box 6-5)

  • Management of wheezing episodes in pre-school children with no (or few) interval symptoms
    • Intermittent short course ICS added to Step 1 for consistency with the existing text (Chapter 6, part C)
    • Only consider this option if confident it will be used appropriately, because of the risk of side-effects

​

© Global Initiative for Asthma, www.ginasthma.org

37 of 52

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

STEP 1

Children 5 years and younger

Personalized asthma management:

Assess, Adjust, Review response

Asthma medication options: Adjust treatment up and down for individual child’s needs

Infrequent viral wheezing and no or few interval symptoms

Asthma diagnosis, and asthma not well-controlled on low dose ICS

Asthma not well-controlled on double ICS

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

As-needed short-acting beta2-agonist

Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur frequently, e.g. ≥3 per year. Give diagnostic trial for 3 months. Consider specialist referral.

Symptom pattern consistent with asthma, and asthma symptoms not well-controlled or ≥3 exacerbations per year.

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for pre-school children)

STEP 3

Double ‘low dose’ ICS

Low dose ICS + LTRA Consider specialist referral

STEP 4

Continue controller & refer for specialist assessment

Add LTRA, or increase ICS frequency, or add intermittent ICS

Daily leukotriene receptor antagonist (LTRA), or intermittent short course of ICS at onset of respiratory illness

Symptoms Exacerbations Side-effects Parent satisfaction

Exclude alternative diagnoses Symptom control & modifiable risk factors

Comorbidities

Inhaler technique & adherence Parent preferences and goals

Treat modifiable risk factors and comorbidities

Non-pharmacological strategies Asthma medications

Education & skills training

Consider intermittent short course ICS at onset of viral illness

Box 6-5 © Global Initiative for Asthma 2022, www.ginasthma.org

38 of 52

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

Infrequent viral wheezing and no or few interval symptoms

Asthma diagnosis, and asthma not well-controlled on low dose ICS

Asthma not well-controlled on double ICS

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

As-needed short-acting beta2-agonist

Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur frequently, e.g. ≥3 per year. Give diagnostic trial for 3 months. Consider specialist referral.

Symptom pattern consistent with asthma, and asthma symptoms not well-controlled or ≥3 exacerbations per year.

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for pre-school children)

STEP 3

Double ‘low dose’ ICS

Low dose ICS + LTRA Consider specialist referral

STEP 4

Continue controller & refer for specialist assessment

Add LTRA, or increase ICS frequency, or add intermittent ICS

Daily leukotriene receptor antagonist (LTRA), or intermittent short course of ICS at onset of respiratory illness

Symptoms Exacerbations Side-effects Parent satisfaction

Exclude alternative diagnoses Symptom control & modifiable risk factors

Comorbidities

Inhaler technique & adherence Parent preferences and goals

Treat modifiable risk factors and comorbidities

Non-pharmacological strategies Asthma medications

Education & skills training

Consider intermittent short course ICS at onset of viral illness

Children 5 years and younger

Personalized asthma management:

Assess, Adjust, Review response

Symptoms Exacerbations Side-effects Parent satisfaction

Exclude alternative diagnoses Symptom control & modifiable risk factors

Comorbidities

Inhaler technique & adherence Parent preferences and goals

Treat modifiable risk factors and comorbidities

Non-pharmacological strategies Asthma medications

Education & skills training

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39 of 52

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

Infrequent viral wheezing and no or few interval symptoms

Asthma diagnosis, and asthma not well-controlled on low dose ICS

Asthma not well-controlled on double ICS

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

As-needed short-acting beta2-agonist

Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur frequently, e.g. ≥3 per year. Give diagnostic trial for 3 months. Consider specialist referral.

Symptom pattern consistent with asthma, and asthma symptoms not well-controlled or ≥3 exacerbations per year.

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for pre-school children)

STEP 3

Double ‘low dose’ ICS

Low dose ICS + LTRA Consider specialist referral

STEP 4

Continue controller & refer for specialist assessment

Add LTRA, or increase ICS frequency, or add intermittent ICS

Daily leukotriene receptor antagonist (LTRA), or intermittent short course of ICS at onset of respiratory illness

Symptoms Exacerbations Side-effects Parent satisfaction

Exclude alternative diagnoses Symptom control & modifiable risk factors

Comorbidities

Inhaler technique & adherence Parent preferences and goals

Treat modifiable risk factors and comorbidities

Non-pharmacological strategies Asthma medications

Education & skills training

Consider intermittent short course ICS at onset of viral illness

Children 5 years and younger

Personalized asthma management:

Assess, Adjust, Review response

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

Asthma medication options: Adjust treatment up and down for individual child’s needs

Infrequent viral wheezing and no or few interval symptoms

As-needed short-acting beta2-agonist

STEP 2

STEP 3

STEP 4

Consider intermittent short course ICS at onset of viral illness

STEP 1

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40 of 52

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

Infrequent viral wheezing and no or few interval symptoms

Asthma diagnosis, and asthma not well-controlled on low dose ICS

Asthma not well-controlled on double ICS

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

As-needed short-acting beta2-agonist

Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur frequently, e.g. ≥3 per year. Give diagnostic trial for 3 months. Consider specialist referral.

Symptom pattern consistent with asthma, and asthma symptoms not well-controlled or ≥3 exacerbations per year.

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for pre-school children)

STEP 3

Double ‘low dose’ ICS

Low dose ICS + LTRA Consider specialist referral

STEP 4

Continue controller & refer for specialist assessment

Add LTRA, or increase ICS frequency, or add intermittent ICS

Daily leukotriene receptor antagonist (LTRA), or intermittent short course of ICS at onset of respiratory illness

Symptoms Exacerbations Side-effects Parent satisfaction

Exclude alternative diagnoses Symptom control & modifiable risk factors

Comorbidities

Inhaler technique & adherence Parent preferences and goals

Treat modifiable risk factors and comorbidities

Non-pharmacological strategies Asthma medications

Education & skills training

Consider intermittent short course ICS at onset of viral illness

Children 5 years and younger

Personalized asthma management:

Assess, Adjust, Review response

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

Asthma medication options: Adjust treatment up and down for individual child’s needs

STEP 3

STEP 4

Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur frequently, e.g. ≥3 per year. Give diagnostic trial for 3 months. Consider specialist referral.

Symptom pattern consistent with asthma, and asthma symptoms not well-controlled or ≥3 exacerbations per year.

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for pre-school children)

Daily leukotriene receptor antagonist (LTRA), or intermittent short course of ICS at onset of respiratory illness

STEP 1

As-needed short-acting beta2-agonist

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41 of 52

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

Infrequent viral wheezing and no or few interval symptoms

Asthma diagnosis, and asthma not well-controlled on low dose ICS

Asthma not well-controlled on double ICS

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

As-needed short-acting beta2-agonist

Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur frequently, e.g. ≥3 per year. Give diagnostic trial for 3 months. Consider specialist referral.

Symptom pattern consistent with asthma, and asthma symptoms not well-controlled or ≥3 exacerbations per year.

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for pre-school children)

STEP 3

Double ‘low dose’ ICS

Low dose ICS + LTRA Consider specialist referral

STEP 4

Continue controller & refer for specialist assessment

Add LTRA, or increase ICS frequency, or add intermittent ICS

Daily leukotriene receptor antagonist (LTRA), or intermittent short course of ICS at onset of respiratory illness

Symptoms Exacerbations Side-effects Parent satisfaction

Exclude alternative diagnoses Symptom control & modifiable risk factors

Comorbidities

Inhaler technique & adherence Parent preferences and goals

Treat modifiable risk factors and comorbidities

Non-pharmacological strategies Asthma medications

Education & skills training

Consider intermittent short course ICS at onset of viral illness

Children 5 years and younger

Personalized asthma management:

Assess, Adjust, Review response

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

Asthma medication options: Adjust treatment up and down for individual child’s needs

As-needed short-acting beta2-agonist

STEP 2

STEP 4

STEP 1

Asthma diagnosis, and asthma not well-controlled on low dose ICS

STEP 3

Double ‘low dose’ ICS

Low dose ICS + LTRA Consider specialist referral

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PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

STEP 1

Asthma medication options: Adjust treatment up and down for individual child’s needs

Infrequent viral wheezing and no or few interval symptoms

Asthma diagnosis, and asthma not well-controlled on low dose ICS

Asthma not well-controlled on double ICS

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

As-needed short-acting beta2-agonist

Symptom pattern not consistent with asthma but wheezing episodes requiring SABA occur frequently, e.g. ≥3 per year. Give diagnostic trial for 3 months. Consider specialist referral.

Symptom pattern consistent with asthma, and asthma symptoms not well-controlled or ≥3 exacerbations per year.

STEP 2

Daily low dose inhaled corticosteroid (ICS)

(see table of ICS dose ranges for pre-school children)

STEP 3

Double ‘low dose’ ICS

Low dose ICS + LTRA Consider specialist referral

STEP 4

Continue controller & refer for specialist assessment

Add LTRA, or increase ICS frequency, or add intermittent ICS

Daily leukotriene receptor antagonist (LTRA), or intermittent short course of ICS at onset of respiratory illness

Symptoms Exacerbations Side-effects Parent satisfaction

Exclude alternative diagnoses Symptom control & modifiable risk factors

Comorbidities

Inhaler technique & adherence Parent preferences and goals

Treat modifiable risk factors and comorbidities

Non-pharmacological strategies Asthma medications

Education & skills training

Consider intermittent short course ICS at onset of viral illness

Children 5 years and younger

Personalized asthma management:

Assess, Adjust, Review response

Before stepping up, check for alternative diagnosis, check inhaler skills, review adherence and exposures

PREFERRED CONTROLLER CHOICE

Other controller options (limited indications, or less evidence for efficacy or safety)

RELIEVER

CONSIDER THIS STEP FOR

CHILDREN WITH:

Asthma medication options: Adjust treatment up and down for individual child’s needs

As-needed short-acting beta2-agonist

STEP 2

STEP 1

STEP 3

Asthma not well-controlled on double ICS

STEP 4

Continue controller & refer for specialist assessment

Add LTRA, or increase ICS frequency, or add intermittent ICS

Box 6-5, 5/5 © Global Initiative for Asthma 2022, www.ginasthma.org

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Definition of asthma severity and mild asthma

  • By the ATS/ERS Task Force definition, asthma severity is assessed retrospectively from the treatment required to control the patient’s asthma, i.e. after at least several months of treatment (Taylor, ERJ 2008; Reddel, AJRCCM 2009)
    • By this definition, asthma severity can be assessed only when treatment has been optimized and asthma is well-controlled, except for patients taking high dose ICS-LABA
  • Severe asthma is 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 (Chung, ERJ 2014)
    • This definition is widely accepted, and has clinical utility
    • Severe asthma is distinguished from ‘difficult-to-treat’ asthma that is difficult to treat because of problems such as poor adherence, incorrect inhaler technique and comorbidities
  • Mild asthma is currently defined as asthma that is well controlled on low dose ICS or as-needed-only ICS-formoterol
    • The utility and relevance of this definition is much less clear
    • The term ‘mild asthma’ is often interpreted very differently
    • Patients and clinicians often assume that ‘mild asthma’ means no risk and no need for controller treatment
    • BUT: up to 30% asthma deaths are in patients with infrequent symptoms (Dusser, Allergy 2007; Bergstrom, Respir Med 2008)

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© Global Initiative for Asthma, www.ginasthma.org

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Interim advice about asthma severity descriptors

  1. Severe asthma: GINA continues to support the current definitions of severe asthma, and difficult-to-treat asthma
  2. ‘Mild asthma’: GINA suggests that this term should generally be avoided in clinical practice if possible, because it is used and interpreted in different ways
    • If used, emphasize importance of ICS-containing treatment to reduce risk of severe or fatal exacerbations
  3. For population-level observational studies: report the controller and reliever treatment not the ‘Step’, and don’t impute severity
    • e.g. ‘patients prescribed low dose ICS-LABA with as-needed SABA’, not ‘Step 3 patients’ and not ‘moderate asthma’
  4. For clinical trials: describe the included patients by their asthma control and treatment (controller and reliever), and don’t impute severity
  5. GINA proposes holding a stakeholder discussion about the definition of mild asthma, to obtain agreement about the implications for clinical practice and clinical research of the changes in knowledge about asthma pathophysiology and treatment since the current definition of asthma severity was published

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© Global Initiative for Asthma, www.ginasthma.org

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Other changes or clarifications in GINA 2022

  • “Written” asthma action plans
    • Handwritten, printed, digital or pictorial instructions about what to do when asthma gets worse
    • Not just verbal instructions!
  • Acute asthma in healthcare settings
    • At present, salbutamol (albuterol) is the usual bronchodilator in acute asthma management
    • Formoterol has similar efficacy and safety in ED studies (Rodrigo, Ann Allerg Asthma Immunol, 2010)
    • One study showed high dose budesonide-formoterol had similar efficacy and safety as SABA (Balanag, Pulm Pharmacol Ther 2006)
    • Patients admitted to hospital for an asthma exacerbation should continue, or commence, ICS-containing therapy
  • Air filters can reduce fine particle exposure, but no consistent effect on asthma outcomes (Park, Allergy Asthma Immunol Res 2021)
  • Use of e-cigarettes is associated with increased risk of respiratory symptoms and asthma exacerbations (Cho, PLoSOne 2016; Wills, ERJ 2021)

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© Global Initiative for Asthma, www.ginasthma.org

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GINA guidance about �COVID-19 and asthma��Updated 30 April 2022

www.ginasthma.org

© Global Initiative for Asthma

GINA Global Strategy for Asthma �Management and Prevention

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COVID-19 and asthma

  • Are people with asthma at increased risk of COVID-19, or severe COVID-19?
    • People with asthma do not appear to be at increased risk of acquiring COVID-19, and systematic reviews have not shown an increased risk of severe COVID-19 in people with well-controlled, mild-to-moderate asthma
  • Are people with asthma at increased risk of COVID-19-related death?
    • Overall, studies to date indicate that people with well-controlled asthma are not at increased risk of COVID-19-related death (Williamson, Nature 2020; Liu et al JACI IP 2021) and in one meta-analysis, mortality appeared to be lower than in people without asthma (Hou, JACI IP 2021).
    • However, the risk of COVID-19 death was increased in people who had recently needed OCS for their asthma (Williamson, Nature 2020; Shi, Lancet RM 2022) and in hospitalized patients with severe asthma (Bloom, Lancet RM 2021).
  • What are the implications for asthma management?
    • It is important to continue good asthma management (as described in the GINA report), with strategies to maintain good symptom control, reduce the risk of severe exacerbations and minimise the need for OCS
  • Have there been more asthma exacerbations during the pandemic?
    • No: in 2020–21, many countries saw a decrease in asthma exacerbations and influenza-related illness
    • The reasons are not precisely known, but may be due to public health measures such as handwashing, masks and social/physical distancing that reduced the incidence of other respiratory infections, including influenza (Davies, Thorax 2021)

Updated 30 April 2022

© Global Initiative for Asthma, www.ginasthma.org

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COVID-19 and asthma medications

  • Advise patients to continue taking their prescribed asthma medications, particularly inhaled corticosteroids
    • For patients with severe asthma, continue biologic therapy or OCS if prescribed
  • Are inhaled corticosteroids (ICS) protective in COVID-19?
    • In one study of hospitalized patients aged ≥50 years with COVID-19, ICS use in those with asthma was associated with lower mortality than in patients without an underlying respiratory condition (Bloom, Lancet RM 2021)
  • Make sure that all patients have a written asthma action plan, advising them to:
    • Increase controller and reliever medication when asthma worsens (see GINA report Box 4-2)
    • Take a short course of OCS when appropriate for severe asthma exacerbations
  • When COVID-19 is confirmed or suspected, or local risk is moderate or high, avoid nebulizers where possible, to reduce the risk of spreading virus to health professionals and other patients/family
    • For bronchodilator administration, pressurized metered dose inhaler via a spacer is preferred except for acute severe asthma
    • Add a mouthpiece or mask to the spacer if required

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Updated 30 April 2022

© Global Initiative for Asthma, www.ginasthma.org

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COVID-19 and asthma – infection control

  • In healthcare facilities, follow local COVID-19 testing recommendations and infection control procedures if spirometry or peak flow measurement is needed (e.g. Virant, JACI in Practice 2022)
    • Use of an in-line filter minimizes the risk of transmission during spirometry, but many patients cough after performing spirometry; coach the patient to stay on the mouthpiece if they feel the need to cough
    • If spirometry is not available due to local infection control restrictions, and information about lung function is needed, consider asking patients to monitor lung function at home
  • Follow local infection control procedures if other aerosol-generating procedures are needed
    • Nebulization, oxygen therapy (including nasal prongs), sputum induction, manual ventilation, non-invasive ventilation and intubation
  • Follow local health advice about hygiene strategies and use of personal protective equipment, as new information becomes available in your country or region

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Updated 30 April 2022

© Global Initiative for Asthma, www.ginasthma.org

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COVID-19 vaccines and asthma

  • Have COVID-19 vaccines been studied in people with asthma?
    • Yes. Many types of COVID-19 vaccines have been studied and are being used worldwide
  • Are COVID-19 vaccines safe in people with allergies?
    • In general, allergic reactions to vaccines are rare
    • Patients with a history of severe allergic reaction to a COVID-19 vaccine ingredient (e.g. polyethylene glycol for Pfizer/BioNTech or Moderna, or polysorbate 80 for AstraZeneca or J&J/Janssen), should receive a different COVID-19 vaccine. More details from ACIP are here
    • People with allergies to food, insect venom or other medications can safely receive COVID-19 vaccines
    • As always, patients should speak to their healthcare provider if they have concerns
    • Follow local advice about monitoring patients after COVID-19 vaccination
  • Usual vaccine precautions apply, for example:
    • Ask if the patient has a history of allergy to any components of the vaccine
    • If the patient has a fever or another infection, delay vaccination until they are well
  • Based on the risks and benefits, and with the above precautions, GINA recommends people with asthma should be up to date with COVID-19 vaccination (including booster doses, if available)

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Updated 30 April 2022

© Global Initiative for Asthma, www.ginasthma.org

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COVID-19 vaccines and asthma

  • COVID-19 vaccination and biologic therapy
    • We suggest that the first dose of asthma biologic therapy and COVID-19 vaccine should not be given on the same day, so that adverse effects of either can be more easily distinguished
  • Influenza vaccination
    • Remind people with asthma to have an annual influenza vaccination
    • CDC now recommends that influenza vaccine and COVID-19 vaccine can be given on the same day
  • After COVID-19 vaccination
    • Current advice from the United States Centers for Disease Control and Prevention (CDC) is that where there is substantial transmission of COVID-19, people will be better protected, even if they are fully vaccinated, if they wear a mask in indoor public settings; this will also reduce risk to others. Further details are here
  • GINA will update advice about COVID-19 and asthma as new data become available

Updated 30 April 2022

© Global Initiative for Asthma, www.ginasthma.org

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Topics to be addressed in future GINA reports

(Some were delayed from 2021 by COVID-19)

  • Allergen immunotherapy for asthma
  • Diagnosis, assessment and management of asthma in children 5 years and younger
  • Further discussion about the definition of mild asthma, and assessment of symptom control
  • Use of digital tools and communication in asthma management
  • A pocket guide on management of severe asthma in children 6–11 years is in development
  • Advice about COVID-19 and asthma will be updated as relevant new information emerges

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  • We will be seeking your feedback on how to improve GINA resources

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© Global Initiative for Asthma, www.ginasthma.org