Scene 1

Global Initiative for Asthma (GINA) What’s new in GINA 2020?

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.

Scene 2

Advise patients with asthma to continue taking their prescribed asthma medications, particularly  inhaled corticosteroids  (ICS), and oral corticosteroids (OCS) if prescribed  Asthma medications should be continued as usual. Stopping ICS often leads to potentially dangerous worsening of asthma  For patients with severe asthma: continue biologic therapy, and do not suddenly stop OCS if prescribed  Make sure that all patients have a  written asthma action plan  with instructions about: Increasing controller and reliever medication when asthma worsens  Taking a short course of OCS  for severe  asthma exacerbations When to seek medical help  See the GINA 2020 report for more information about treatment options for asthma action plans.  Avoid   nebulizers  where possible Nebulizers increase the risk of disseminating virus to other patients AND to health care professionals Pressurized metered dose inhaler via a spacer is the preferred treatment during severe exacerbations , with a mouthpiece or tightly fitting face mask if required

COVID-19 and asthma  (as at April 3, 2020)

Scene 3

Avoid spirometry  in patients with confirmed/suspected COVID-19 Spirometry can disseminate viral particles and expose staff and patients to risk of infection While community transmission of the virus is occurring in your region, postpone spirometry and peak flow measurement within health care facilities unless there is an urgent need Follow contact and droplet precautions Follow strict infection control procedures  if aerosol-generating procedures are needed For example: nebulization, oxygen therapy (including with nasal prongs), sputum induction, manual ventilation, non-invasive ventilation and intubation World Health Organization (WHO) infection control recommendations are found here:  www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125 Follow local health advice  about hygiene strategies and use of personal protective equipment, as new information becomes available in your country or region

COVID-19 and asthma  (as at March 30, 2020)

Scene 4

Information for health professionals World Health Organization (WHO) recommendations for infection control www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125   Centers for Disease Control and Prevention (CDC)  www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html , Information for patients CDC:  https://www.cdc.gov/coronavirus/2019-ncov/index.html . Information for health systems www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance Follow local health advice about hygiene strategies and use of personal protective equipment as new information becomes available in your country or region

Other resources for COVID-19  (as at March 30, 2020)

Scene 5

The GINA report is not a guideline, but an integrated evidence-based strategy focusing on translation into clinical practice Recommendations are framed, not as answers to isolated PICOT questions, but as part of an integrated strategy, in relation to: The GINA goals of preventing asthma deaths and exacerbations, as well as  improving symptom control Current understanding of underlying disease processes Human  behavior  (of health professionals and patients/carers) Implementation in clinical practice Global variation in populations, health systems and medication access

Scene 6

A reminder – the key change in GINA 2019

@ERSpublications
GINA no longer recommends treating adults/adolescents with asthma with short-acting
bmnchodilators alone. Instead, they should receive symptom-driven (in mild asthma) or a daily
corticosteroid-containing inhaler, to reduce risk of severe exacerbations. http://bit_Iy/310LLzE
Cite this article as: Reddel 1-1K. FitzGerald JM, Bateman ED, et al. GINA 2019: a fundamental change in
asthma management. Ear Respir / 2019: 53: 1901046 [https:!/doi org'101183/13993003.01046-2019'

Scene 7

Patients with apparently mild asthma are at risk of serious adverse events 30–37% of adults with acute asthma 16% of patients with near-fatal asthma 15–20% of adults dying of asthma Exacerbation triggers are variable (viruses, pollens, pollution, poor adherence) Inhaled SABA has been first-line treatment for asthma for 50 years This dates from an era when asthma was thought to be a disease of bronchoconstriction Patient satisfaction with, and reliance on, SABA treatment is reinforced by its rapid relief of symptoms, its prominence in ED and hospital management of exacerbations, and low cost Patients commonly believe that  “My reliever gives me control over my asthma” , so they often don’t see the need for additional treatment

Background to changes in 2019 - the risks of ‘mild’ asthma

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

Scene 8

Background to changes in 2019 - the risks of SABA-only treatment

Regular or frequent use of SABA is associated with adverse effects b -receptor downregulation, decreased  bronchoprotection , rebound hyperresponsiveness, decreased bronchodilator response  ( Hancox , Respir Med 2000) Increased allergic response, and increased eosinophilic airway inflammation   (Aldridge, AJRCCM 2000) Higher use of SABA is associated with adverse clinical outcomes Dispensing of ≥3 canisters per year (average 1.7 puffs/day) is associated with higher  risk of emergency department presentations  (Stanford, AAAI 2012) Dispensing of ≥12 canisters per year is associated with higher   risk of  death   ( Suissa , AJRCCM 1994)

Scene 9

Since 2007, GINA has been actively seeking interventions for mild asthma to reduce the risk of asthma-related exacerbations and death to provide consistent messaging about the goals of asthma treatment, including prevention of exacerbations, across the spectrum of asthma severity  to avoid establishing patient reliance on SABA early in the course of the disease GINA emphasized poor adherence as a modifiable risk factor for exacerbations  When the reliever is SABA, poor adherence with maintenance controller exposes the patient to risks of SABA-only treatment GINA members repeatedly sought funding for RCTs of as-needed ICS-formoterol  for risk reduction in mild asthma Eventually culminated in 2014 with the initiation of the SYGMA studies, published in 2018  (O’Byrne  NEJMed  2018; Bateman  NEJMed  2018)

The 12-year history behind changes in GINA 2019

Scene 10

For safety, GINA no longer recommends SABA-only treatment for Step 1 This decision was based on evidence that SABA-only treatment increases the risk of severe exacerbations, and that adding any ICS significantly reduces the risk GINA now recommends that all adults and adolescents with asthma should receive  ICS-containing controller treatment, to reduce the risk of serious exacerbations The ICS can be delivered by regular daily treatment or, in mild asthma, by as-needed low dose ICS-formoterol This is a population-level risk reduction strategy Other examples: statins, anti-hypertensives Individual patients may not necessarily experience (or be aware of) short-term clinical benefit The aim is to reduce the probability of serious adverse outcomes at a population level

GINA 2019 – landmark changes in asthma management

Scene 11

Personalized asthma management: Assess – Adjust – Review response NOT just medications, NOT one-size-fits-all No changes from 2019 in preferred and ‘other’ treatment options Additional supporting evidence for recommendations in Steps 1 and 2 Some formatting changes for clarity Separate figures for adults/adolescents, children 6–11 years and children ≤5 years For children ≤5 years, see Chapter 6 of main GINA report

Scene 12

A screenshot of a cell phone

Description automatically generated

Scene 13

ICS-formoterol is the preferred reliever for patients prescribed maintenance and reliever therapy. For other  ICS-LABAs, the reliever  is SABA

Scene 14

Two additional RCTs of as-needed low dose budesonide-formoterol in mild asthma 12-month studies, open-label, no twice-daily placebo, i.e. the way it would be used in real life Novel START  (Beasley et al, NEJM 2019, n=668)  and   PRACTICAL  (Hardy et al, Lancet 2019,  independent study, n=885) Significant reduction in severe exacerbations vs SABA alone, and vs maintenance ICS, with small or no difference in symptom control, and lower average ICS dose Patients in RCTs of this regimen in mild asthma now total n=9,565 Both of these studies included inflammatory markers FeNO  was significantly reduced by as-needed ICS-formoterol (with average 3-5 doses per week)  Reduction in risk of severe exacerbations with as-needed ICS-formoterol was independent of baseline characteristics, including blood eosinophils and exhaled nitric oxide An additional RCT of taking ICS whenever SABA is taken (separate inhalers) ASIST, in African-American children 6-17 years with mild asthma, compared with  physician-adjusted treatment  (Sumino et al, JACI in  Pract  2019, n=206)

Scene 15

Scene 16

Initial asthma treatment – where to start?

Should all patients start at Step 1?  Table about initial treatment since 2014, but not widely known New figures created (two versions)

Scene 17

Scene 18

Scene 19

Scene 20

Scene 21

As-needed low dose budesonide-formoterol  Prescribed in maintenance and reliever therapy (Steps 3–5), or as-needed only (Steps 1–2),  or within an asthma action plan From product information, the maximum recommended total in one day is 72 mcg formoterol  (12 inhalations of budesonide-formoterol  Turbuhaler  200/6 mcg)  As-needed low dose beclometasone-formoterol  Prescribed in maintenance and reliever therapy (Steps 3–5), or within an asthma action plan From product information, the maximum recommended total in one day is 48 mcg formoterol  (6 inhalations of beclometasone-formoterol pMDI100/6 mcg)

As-needed ICS-formoterol – maximum daily dose?

Scene 22

Frequency of SABA use is included in symptom control assessment Higher SABA use is associated with worse outcomes, even in patients taking ICS Our current view is that frequency of ICS-formoterol use should not be included in symptom control assessment, particularly in patients not taking maintenance ICS The as-needed ICS-formoterol is providing the patient’s controller therapy Further data awaited: this issue will be reviewed again next year

BOX 2-2. GINA assessment Of asthma control in adults,
adolescents and children 6—11 years
A. Asthma symptom control
Level Of asthma symptom control
In the past 4 weeks, has the patient had:
Daytime asthma symptoms more than W,'ice/week9
Any night waking due to asthma?
Reliever (SABA) for symptoms more than Wice"week?'
Any activity limitation due to asthma?
Well
Partly
Uncontrolled
controlled controlled
yesa NOO
Yeso Noo
Yesa Noo
Yesa Noo
None
of these
1-2
Of these
Of these

Scene 23

Low, medium and high doses of different ICS

NOT a table of equivalence Suggested total daily doses for ‘low’, ‘medium’ and ‘high’ dose treatment options Based on available studies (very few) and product information Does NOT imply potency equivalence Doses may be country-specific depending on local availability, regulatory labelling and clinical guidelines Clinical relevance Low dose ICS provides most of the clinical benefit of ICS for  most patients  with asthma However, ICS responsiveness varies between patients, so some patients may need medium dose ICS if their asthma is uncontrolled despite good adherence and correct technique  High dose ICS (in combination with LABA or separately) is needed by very few patients Its long-term use is associated with an increased risk of local and systemic side-effects, which must be balanced against the potential benefits

Scene 24

Low, medium and high ICS doses: adults/adolescents

Adults and adolescents (12 years and older)
Inhaled corticosteroid
Beclometasone dipropionate (pMDl, standard particle,
Beclometasone dipropionate (pMDl, extrafine particle•,
Budesonide (DPI)
Ciclesonide (pMDl, extrafine particle•, HFA)
Fluticasone furoate (DPI)
Fluticasone propionate (DPI)
Fluticasone propionate (pMDl, standard particle, HFA)
Mometasone furoate (DPI)
Mometasone furoate (PMDI, Standard particle. HFA)
Total daily ICS dose (mcg)
HFA)
Low
200-500
100-200
200—m
80-160
100-250
100-250
100
Medium
>500-1000
>200-400
>160-320
>250-500
>250-500
200-400
High
>1000
>400
>800
>320
>500
>500
>400

DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant;  pMDI : pressurized metered dose inhaler (non-CFC); * see product information

This is NOT a table of equivalence. These are suggested total daily doses for the ‘low’, ‘medium’ and ‘high’ dose treatment options with different ICS.

Scene 25

Low, medium and high ICS doses: children 6-11 years

Children 6—11 years
Inhaled corticosteroid
Beclometasone dipropionate (pMDl, standard particle,
3eclometasone dipropionate (pMDl, extrafine particle* ,
Budesonide (DPI)
Budesonide (nebules)
Ciclesonide (pMDl, extrafne particle•, HFA)
Fluticasone furoate (DPI)
Fluticasone propionate (DPI)
Fluticasone propionate (pMDl, standard particle, HFA)
Mometasone furoate (pMDl, standard particle, HFA)
Total daily ICS dose (mcg)
100-200
50-100
100-200
250-500
80
50
50-100
50-100
100
Medium
>200-400
>100-200
>200-400
>500-1000
>80-160
>100-200
>100-200
High
>400
>200
>1000
> 160
>200
>200
200

Scene 26

Low, medium and high ICS doses: children 5 years and younger

Inhaled corticosteroid
BOP (pMDl, standard particle, HFA)
BOP (PMDI, extraflne particle, HFA)
Budesonide nebulized
Fluticasone propionate (pMDl, standard particle, HFA)
Fluticasone furoate (DPI)
Mometasone furoate (pMDl, standard particle, HFA)
Ciclesonide (pMDl, extrafine particle. HFA)
Low total daily dose (mcg)
(age-group with adequate safety and effectiveness data)
100 (ages 5 years and older)
50 (ages 5 years and older)
500 (ages 1 year and older)
50 (ages 4 years and older)
Not sufficiently studied in children 5 years and younger)
100 (ages 5 years and Older)
Not sufficiently studied in children 5 years and younger

BDP: beclometasone dipropionate; DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant;  pMDI : pressurized metered dose inhaler (non-CFC)

This is NOT a table of equivalence. These are suggested total daily doses for the  ‘low’ dose treatment options with different ICS.

Scene 27

FDA boxed warning in March 2020 about risk of serious neuropsychiatric events, including suicidality, with montelukast Includes suicidality in adults and adolescents Nightmares and  behavioral  problems in children  Before prescribing montelukast, health professionals should consider its benefits and risks, and patients should be counselled about the risk of neuropsychiatric events

FDA requires Boxed Warning about serious
mental health side effects for asthma and allergy
drug montelukast (Singulair); advises restricting
use for allergic rhinitis
Risks may include suicidal thoughts or actions

Scene 28

School-based programs that included asthma self-management are associated with improved asthma outcomes  ( Kneale  et al, Thorax 2019) Fewer emergency department visits Fewer hospitalizations Fewer days of reduced activity  Severe eosinophilic asthma in children aged 6-11 years Mepolizumab approved by European Medicines Agency for this age-group (already approved for 12 years and older) Efficacy data are limited to one small uncontrolled open-label study  (Gupta et al, JACI 2019) Children aged 5 years and younger Assessment of severe exacerbations updated: respiratory rate >40/min added; pulse rate criteria modified; sub-glottic/sub-sternal retractions removed as too subjective

Scene 29

Pocket guide v2.0 published April 2019 A practical guide for primary and specialist care Includes a decision tree about assessment and management of adults and adolescents with uncontrolled asthma or exacerbations despite Step 4-5 treatment Includes strategies for clinical settings in which biologic therapy is not available or affordable Content also included in full GINA 2020 report Aim is to produce a similar pocket guide for children in 2020

DIFFICULT-TO-TREAT &
SEVERE ASTHMA
in adolescent and
ült patients
Diagnosis and Management

Scene 30

SPECIALIST CARE: SEVERE ASTHMA CLINIC IF AVAILABLE
Assess and treat severe asthma phenotypes cont'd
Continue to optimize management as in section 3 (including inhaler technique, adherence,
Consider add-on biologic Type 2
targeted treatments
• Consider add-on Type
2-targeted biologic for
patients with exacerbations
or poor symptom control
on high dose ICS-LABA,
who:e
- nave eosinophilic or
allergic biomarkers, or
- need maintenance OCS
• consider local payer
eligibility criteria
and predictors of
response when choosing
between available
therapies
• Also consider cost, dosing
frequency, route (SC or
IV), patient preference
Which biologic
iS appropnate to
start first?
Anti.lgE
Is the patient eligible for anti-lgE
ror severe auergjc asthma?
• sensitization on Skin prjCk testing or specific IgEC5
o
• Total serum lgE and weight within dosage range
• Exacerbations in last yearC
no
Anti-iL51 Anti-lL5R
Is the patient eligible for anti-lL5/anti-lL5R
tor severe eosinophilic asthma ?
• Exacerbations in last yeare
• Blood eosinophils 23004110
no
Anti-lL4R
IS tne patient ror anti-IL4R
. for severe eosinophilic asthma?
• Exacerbations in last year
comorbidities)
What factors may predict good
astnma response to anti-lgE?
• BIOOd eosinophils 2260/1-11 ++
• FeNO 220 ppb +
• Allergen-driven symptoms +
• Childhood-onset asthma +
What factors may predict good
asthma response to anti-lL5'5R?
• Higher blood eosinophils +++
• More exacerbations in
previous year
• Adult-onset of asthma ++
• Nasal polyposis ++
What factors may predjct good
asthma response to anti-lL4R?
• Higner blood eosinophils +++
• Higher FeN0 +++
Anti-lL4R may also be used to treat
• Moderate/severe atopic dermatitis
• Nasal polyposis
Choose one
it eligible;
trial for at least
4 months and
assess response
Extend trial to
6-12 montns
asthma
response ?
STOP add-on
Good response
to T2-targeted
therapy
o
• Blood eosinophils 2150/pl or FeNO 225 ppb
- or because of need for maintenance OCSO ?
Eligible for none?
Return to section 6a
Consider switching
to a different Type
2-targeted therapy,
if eligible
Little/no response
to T2•targeted
therapy

Scene 31

Also called ‘asthma-COPD overlap’ or ‘ asthma+COPD ’ NOT a single disease, but a descriptive label for patients commonly seen in clinical practice  Asthma and COPD are heterogeneous and overlapping conditions  The definitions of asthma and COPD are not mutually exclusive Each includes several phenotypes that are likely to have different underlying mechanisms  There is increasing interest in the potential for precision treatment However, the labels ‘asthma’ and ‘COPD’ are still clinically important, as evidence supports safety-based differences in treatment recommendations Asthma:  never  treat with bronchodilators alone (risk of death, hospitalization, severe exacerbations) COPD:  start  treatment with LABA and/or LAMA without ICS Patients with diagnoses of both asthma and COPD are more likely to die or be hospitalized if treated with LABA vs ICS-LABA  (Gershon et al, JAMA 2014;  Kendzerska  et al, Annals ATS 2019) High dose ICS may be needed for severe asthma, but should not be used in COPD (risk of pneumonia) Chapter 5 has been rewritten for clinical utility, focusing on clinical recognition and  safe initial treatment

Patients with features of asthma and COPD

Scene 32

A screenshot of a social media post

Description automatically generated

Scene 33

Acute asthma References to ‘high flow oxygen’ have been corrected to ‘high concentration oxygen’ Role of trained lay health workers in asthma education has been emphasized Improved outcomes compared with usual care including increased symptom-free days, reduced healthcare utilization, improved adherence, inhaler technique, symptom control and quality of life  Factors contributing to development of asthma Obesity may be a risk factor for developing asthma  (Deng et al,  Pediatr   Obes  2019) ,  but not vice versa  (Xu et al, Int J Epidemiol 2019)   13% of global asthma incidence in children may be attributable to traffic-related air pollution  ( Achakulwisut  et al, Lancet Plan Health 2019)

Scene 34

The GINA report is a global strategy document Regulatory approvals and submissions differ from country to country Many recommendations are ‘off-label’ in various countries, particularly for paediatrics The term ‘off-label’ is no longer used in the GINA report or slides  For new therapies  Regulatory agencies often receive more safety data than are in peer-reviewed literature GINA makes recommendations based on the best available evidence, after approval by at least one major regulatory agency (e.g. EMA, FDA)  For existing medications with evidence for new regimens or populations If satisfied with evidence for safety and effectiveness, GINA may consider making  recommendations that are not covered by a regulatory indication in any country at the time Examples: long-term macrolides for moderate-severe asthma (2018); as-needed ICS-formoterol, or taking ICS whenever SABA is taken, for mild asthma (2019)  When assessing and treating patients Use your own professional judgment Take into account local and national guidelines and payer eligibility criteria, and licensed drug doses

Scene 35

Global Initiative for Asthma (GINA)
What's new in GINA 2020?

Scene 0

 Avoid spirometry  in patients with confirmed/suspected COVID-19 Spirometry can disseminate viral particles and expose staff and patients to risk of infection While community transmission of the virus is occurring in your region, postpone spirometry and peak flow measurement within health care facilities unless there is an urgent need Follow contact and droplet precautions Follow strict infection control procedures  if aerosol-generating procedures are needed For example: nebulization, oxygen therapy (including with nasal prongs), sputum induction, manual ventilation, non-invasive ventilation and intubation World Health Organization (WHO) infection control recommendations are found here:  www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125 Follow local health advice  about hygiene strategies and use of personal protective equipment, as new information becomes available in your country or region

slide3-hotlink2

 Information for health professionals World Health Organization (WHO) recommendations for infection control www.who.int/publications-detail/infection-prevention-and-control-during-health-care-when-novel-coronavirus-(ncov)-infection-is-suspected-20200125   Centers for Disease Control and Prevention (CDC)  www.cdc.gov/coronavirus/2019-nCoV/hcp/index.html , Information for patients CDC:  https://www.cdc.gov/coronavirus/2019-ncov/index.html . Information for health systems www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance Follow local health advice about hygiene strategies and use of personal protective equipment as new information becomes available in your country or region 

Global Initiative for Asthma (GINA) What's new in GINA 2020?