ASTHMA BASICS

-DR AJITH KUMAR M S

MBBS, MD RESPIRATORY MEDICINE
ASTHMA PHENOTYPES
1. Major Asthma Phenotypes(Inflammatory asthma phenotypes i.e.,
Based on type of inflammation and immune cell type)-
- Early onset allergic asthma
- Late onset eosinophillic asthma
- Late onset non eosinophilic asthma

2. Symptom based phenotypes- Exacerbation prone asthma, cough

variant asthma, obesity related asthma, asthma with persistent
airflow obstruction.
3. Trigger induced phenotypes- exercise induced asthma,
occupational asthma, seasonal asthma, aspirin exacerbated
respiratory disease.

4. Biomarker based phenotypes- eosinophilic asthma, neutrophilic

asthma, Paucigranulocytic asthma, mixed granulocytic asthma.

5. Treatment based- Steroid resistant asthma.

ASTHMA CLASSIFICATION BY SEVERITY(OLDER GINA
CLASSIFICATION)

• Intermittent asthma.
• Mild persistent asthma.
• Moderate persistent asthma. Terms obsolete in newer GINA
• Severe persistent asthma.
• Symptom duration- less than or equal to 2 days a week
• Nighttime awakening- less than or equal to 2 times a month
• SABA use for symptom control- less than or equal to 2 days a week
• Interference with normal activity- no interference
• Lung function- FEV1/FVC ratio- normal,FEV1 > 80% pred
Diurnal variation of PEF- <20%

• Intermittent asthma
• Symptom duration- more than 2 days a week but not daily
• Nighttime awakening- 3-4 times a month
• SABA use for symptom control- more than 2 days a week but not more than 1
time per day.
• Interference with normal activity- minor limitation
• Lung function- FEV1/FVC ratio- normal,FEV1 > 80% pred
Diurnal variation of PEF- 20- 30%

Mild persistent asthma

• Symptom duration- daily
• Nighttime awakening- >1 time per week
• SABA use for symptom control- daily
• Interference with normal activity- some limitation
• Lung function- FEV1/FVC ratio- reduced,FEV1 > 60%- 80% pred
Diurnal variation of PEF- >30%

• Moderate persistent asthma

• Symptom duration- Throughout the day
• Nighttime awakening- often 7 days a week
• SABA use for symptom control- several times a day
• Interference with normal activity- extreme limitation
• Lung function- FEV1/FVC ratio- reduced,FEV1 < 60% pred
Diurnal variation of PEF- >30%

• Severe persistent asthma

• The current definition of asthma severity is based on retrospective
assessment after at least 2-3 months of controller treatment, from
the treatment required to control symptoms and exacerbations.

• This definition is clinically useful for severe asthma as it identifies

patients whose asthma is relatively refractory to conventional high
dose ICS- LABA and who may benefit from additional treatment
such as biological therapy. It is important to distinguish between
severe asthma and uncontrolled asthma due to modifiable factors
such as incorrect inhaler technique or poor adherence.
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)

© Global Initiative for Asthma, www.ginasthma.org

DEFINATIONS-
• DIFFICULT TO TREAT ASTHMA

• THERAPY RESISTANT ASTHMA

• SEVERE ASTHMA
 DIFFICULT TO TREAT ASTHMA
• SYNONYMS- Chronic Severe Asthma
Difficult to control Asthma
Steroid Dependent Asthma
Brittle Asthma
Difficult Asthma

Definition- Uncontrolled Asthma despite of High intensity Asthma treatment

because of additional issues due to-Persistently poor adherence with
treatment.
Triggers.
Exposures.
Co morbidities.
Additional diagnosis or alternate diagnosis.
Therapy Resistant Asthma
• Synonym- Severe Refractory Asthma

• Definition- Uncontrolled Asthma despite of High intensity Asthma

treatment in whom alternate diagnosis excluded, Comorbidities
treated, Trigger factors removed, Compliance with treatment
checked but still have poor Asthma control or frequent(>=2/yr)
exacerbations despite the prescription of high intensity treatment
or can only maintain adequate control when taking systemic
corticosteroids and are thereby at risk of serious adverse effects of
treatment.
 SEVERE ASTHMA
• It comprises of both difficult to treat Asthma and therapy resistant Asthma

• ERS/ATS Definition-
Asthma that requires treatment with-
High dose ICS +One additional controller(ICS-LABA/LT Modifier)
+/-
Oral corticosteroids >6 m/yr
+
Atleast one of this occurs/would occur if treatment is reduced-
a)Asthma Control Test <20 or Asthma Control Questionnare >1.5
b)Atleast 2 exacerbations in last 12 months.
c)Atleast 1 exacerbation treated in hospital or requiring mechanical
ventilation in last 12 months
d)FEV1 <80% Predicted
SEVERE ASTHMA PHENOTYPES
• Exacerbation prone asthma
• Asthma with fixed airflow obstruction
• Steroid dependent asthma
• Persistent eosinophilic severe asthma
• Non eosinophilic severe asthma
GINA 2022 GUIDELINES
 STARTING TREATMENT
in adults and adolescents with a diagnosis of asthma
Track 1 is preferred if the patient is likely to be poorly adherent with daily controller
ICS-containing therapy is recommended even if symptoms are infrequent, as it
reduces the risk of severe exacerbations and need for OCS. Daily symptoms, Short course OCS
or waking with may also be needed
asthma once a for patients presenting
Symptoms most week or more, with severely
days, or waking and low lung uncontrolled asthma
Symptoms less with asthma once function
FIRST ST ART than 4–5 days a a week or more
ASSESS: H ERE week ST EP 5
IF: ST EP 4 Add-on LAMA
ST EP 3 Medium dose Refer for phenotypic
maintenance assessment ± anti-IgE,
CONT ROLLER and ST EPS 1 – 2 Low dose
ICS-formoterol anti-IL5/5R, anti-IL4R
• Confirm diagnosis PREFERRED RELIEVER maintenance
As-needed low dose ICS-formoterol Consider high dose ICS-
(Track 1). Using ICS-formoterol ICS-formoterol
• Symptom control formoterol
as reliever reduces the risk of
and modifiable risk
exacerbations compared with
factors, including RELIEVER: As-needed low-dose ICS-formoterol
lung function using a SABA reliever

• Comorbidities
• Inhaler technique Short course OCS
Daily symptoms,
and adherence or waking with may also be needed
• Patient preferences asthma once a for patients presenting
and goals Symptoms most week or more, with severely
days, or waking and low lung uncontrolled asthma
ST ART Symptoms twice
with asthma once
a month or more, function
H ERE Symptoms less but less than 4–5 a week or more
IF: than twice days a week ST EP 5
a month
ST EP 4 Add-on LAMA
CONT ROLLER and ST EP 3 Medium/high dose Refer for phenotypic
ALT ERNAT IVE maintenance ICS- assessment ± anti-IgE,
ST EP 2 Low dose
anti-IL5/5R, anti-IL4R
RELIEVER LABA
ST EP 1 Low dose
maintenance
Consider high dose
(Track 2). Before considering ICS-LABA
Take ICS whenever maintenance ICS ICS-LABA
a regimen with SABA reliever, SABA taken
check if the patient is likely
to be adherent with daily RELIEVER: As-needed short-acting β2-agonist
controller therapy

GINA 2021, Box 3-4Bi © Global Initiative for Asthma, www.ginasthma.org

 Confirmation of diagnosis if necessary
Adults & Symptom control & modifiable
adolescents 12+ risk factors (including lung function)
Comorbidities
years
Personalized asthma management Inhaler technique & adherence
Patient preferences and goals
Assess, Adjust, Review for
individual patient needs
Symptoms
Exacerbations
Side-effects
Treatment of modifiable risk factors
Lung function and comorbidities
Patient satisfaction Non-pharmacological strategies
Asthma medications (adjust down/up/between tracks)
Education & skills training
STEP 5
STEP 4 Add-on LAMA
STEP 3 Medium dose Refer for phenotypic
maintenance assessment ± anti-IgE,
CONTROLLER and STEPS 1 – 2 Low dose
maintenance ICS-formoterol anti-IL5/5R, anti-IL4R
PREFERRED RELIEVER As-needed low dose ICS-formoterol
ICS-formoterol Consider high dose ICS-
(Track 1). Using ICS-formoterol
formoterol
as reliever reduces the risk of
exacerbations compared with
RELIEVER: As-needed low-dose ICS-formoterol
using a SABA reliever

STEP 5
STEP 4 Add-on LAMA
STEP 3 Medium/high Refer for phenotypic
dose maintenance assessment ± anti-IgE,
CONTROLLER and STEP 2 Low dose
STEP 1 maintenance ICS-LABA anti-IL5/5R, anti-IL4R
ALTERNATIVE RELIEVER Low dose Consider high dose ICS-
Take ICS whenever ICS-LABA
(Track 2). Before considering a maintenance ICS LABA
SABA taken
regimen with SABA reliever,
check if the patient is likely to be RELIEVER: As-needed short-acting β2-agonist
adherent with daily controller

Low dose ICS whenever Medium dose ICS, or Add LAMA or LTRA or Add azithromycin (adults)
Other controller options SABA taken, or daily add LTRA, or add HDM SLIT, or switch to or LTRA; add low dose
for either track LTRA, or add HDM SLIT HDM SLIT high dose ICS OCS but consider side-
effects

GINA 2021, Box 3-5A © Global Initiative for Asthma, www.ginasthma.org

 Children 6-11 years Confirmation of diagnosis if necessary
Symptom control & modifiable
risk factors (see Box 2-2B)
Comorbidities
Inhaler technique & adherence
Personalized asthma management:
Child and parent preferences and goals
Assess, Adjust, Review

Symptoms
Exacerbations
Side-effects
Lung function Treatment of modifiable risk factors
Child and parent & comorbidities
satisfaction Non-pharmacological strategies STEP 5
Asthma medications (adjust down or up)
Education & skills training Refer for
phenotypic
Asthma medication options: assessment
STEP 4
Adjust treatment up and down for ± higher dose
individual child’s needs Medium dose ICS-LABA or
STEP 3
ICS-LABA, add-on therapy,
STEP 2 Low dose ICS- OR low dose† e.g. anti-IgE,
PREFERRED STEP 1 LABA, OR medium ICS-formoterol
Daily low dose inhaled corticosteroid (ICS) anti-IL4R
CONTROLLER dose ICS, OR maintenance
Low dose ICS (see table of ICS dose ranges for children)
to prevent exacerbations very low dose* and reliever
and control symptoms taken whenever
ICS-formoterol therapy (MART).
SABA taken
maintenance and Refer for expert
reliever (MART) advice

Other controller options
(limited indications, or
less evidence for efficacy
or safety)
Consider daily Daily leukotriene receptor antagonist (LTRA), or Low dose Add tiotropium Add-on anti-IL5
low dose ICS low dose ICS taken whenever SABA taken ICS + LTRA or add LTRA or, as last resort,
consider add-on
low dose OCS, but
consider side-effects

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

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

†Low dose: BUD-FORM 200/6 mcg (metered doses).
Box 3-5B © Global Initiative for Asthma 2022, www.ginasthma.org
 Children 5 years and younger Exclude alternative diagnoses
Symptom control & modifiable
risk factors
Comorbidities
Inhaler technique & adherence
Personalized asthma management:
Parent preferences and goals
Assess, Adjust, Review response

Symptoms
Exacerbations
Side-effects
Parent satisfaction
Treat modifiable risk factors
and comorbidities
Non-pharmacological strategies
Asthma medications
Asthma medication options: Education & skills training
STEP 4
Adjust treatment up and down for
individual child’s needs STEP 3 Continue
STEP 2 controller & refer
Double ‘low for specialist
STEP 1
PREFERRED Daily low dose inhaled corticosteroid (ICS) dose’ ICS assessment
CONTROLLER (see table of ICS dose ranges for pre-school children)
CHOICE

Other controller options Consider intermittent Daily leukotriene receptor antagonist (LTRA), or Low dose ICS + LTRA Add LTRA, or increase
(limited indications, or short course ICS at intermittent short course of ICS at onset of Consider specialist ICS frequency, or add
less evidence for efficacy onset of viral illness respiratory illness referral intermittent ICS
or safety)

RELIEVER As-needed short-acting beta2-agonist

CONSIDER
THIS STEP FOR Infrequent viral Symptom pattern not consistent with asthma but wheezing Asthma diagnosis, and Asthma not
CHILDREN WITH: wheezing and no episodes requiring SABA occur frequently, e.g. ≥3 per year. asthma not well-controlled well-controlled
or few interval Give diagnostic trial for 3 months. Consider specialist referral. on low dose ICS on double ICS
symptoms Symptom pattern consistent with asthma, and asthma Before stepping up, check for alternative diagnosis,
symptoms not well-controlled or ≥3 exacerbations per year. check inhaler skills, review adherence and exposures

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

 STARTING TREATMENT
in adults and adolescents 12+ years with a diagnosis of asthma

FIRST ASSESS: IF: START WITH: TRACK 1 OR TRACK 2

(preferred)
Medium dose Short course OCS may
Daily symptoms, waking at Medium/high also be needed for patients
night once a week or more YES ICS-formoterol STEP 4
Confirmation dose ICS-LABA presenting with severely
of diagnosis and low lung function? maintenance and
+ as-needed SABA uncontrolled asthma
reliever (MART)

NO
Symptom control
& modifiable risk
factors (including Low dose
Symptoms most days, or Low dose
lung function) ICS-formoterol
waking at night once a YES ICS-LABA STEP 3
week or more? maintenance and
+ as-needed SABA
reliever (MART)

Comorbidities NO

Symptoms twice a As-needed low dose Low dose ICS

YES STEP 2 As-needed ICS-formoterol
month or more? ICS-formoterol + as-needed SABA
Inhaler technique is preferred if the patient is
& adherence likely to be poorly adherent
with daily ICS
ICS-containing therapy
is recommended even
NO
if
symptoms are infrequent,
Patient preferences Take low dose as it reduces the risk of
& goals As-needed low dose
ICS whenever STEP 1 severe exacerbations
ICS-formoterol
SABA is taken and need for OCS.

GINA 2021, Box 3-4Bii © Global Initiative for Asthma, www.ginasthma.org

GINA Track 1 (preferred): the reliever is low dose ICS-formoterol

 Why is this preferred for adults and adolescents?

 Because using low dose ICS-formoterol as reliever reduces the risk of severe exacerbations
compared with regimens with SABA as reliever, with similar symptom control
 How is it used?
 When a patient at any treatment step has asthma symptoms, they use low dose ICS-formoterol in a
single inhaler for symptom relief
 In Steps 3–5, patients also take ICS-formoterol as their daily controller treatment. Together, this is called
‘maintenance and reliever therapy’ or ‘MART’
 When should it not be used?
 ICS-formoterol should not be used as the reliever in patients prescribed a different ICS-LABA for their
controller therapy

ICS: inhaled corticosteroids; SABA: short-acting beta2-agonist

© Global Initiative for Asthma, www.ginasthma.org
GINA Track 2 (alternative): the reliever is SABA

 When should this be used?

 This is an alternative approach for adults and adolescents if Track 1 is not possible, or is not
preferred by a patient with no exacerbations on their current therapy
 How is it used?
 In Step 1, the patient takes a SABA and a low dose ICS together for symptom relief when
symptoms occur, in a combination inhaler, or with the ICS taken right after the SABA
 In Steps 2–5, the patient takes ICS-containing controller medication regularly every day, and uses a
SABA (alone) for symptom relief
 When should it not be used?
 Before prescribing a regimen with SABA reliever, consider whether the patient is likely to be adherent
with their prescribed ICS-containing controller therapy. If they are poorly adherent, they will be at higher
risk of exacerbations

ICS: inhaled corticosteroids; SABA: short-acting beta2-agonist

© Global Initiative for Asthma, www.ginasthma.org
Maintenance and reliever therapy (MART) in Steps 3–5
 Maintenance and reliever therapy (MART) with ICS-formoterol reliever reduces the risk
of severe exacerbations compared with regimens with SABA reliever
 Compared with same dose or higher dose ICS-LABA, in patients with history of severe
exacerbations (Sobieraj, JAMA 2018)
 Compared with conventional best practice, in broad populations (Cates, Cochrane 2013, Demoly
Respir Med 2009)
 Maintenance and reliever therapy (MART) in Step 4
 ICS responsiveness varies, and some patients whose asthma is uncontrolled on MART with low dose
ICS-formoterol despite good adherence and correct inhaler technique may benefit from increasing the
total daily maintenance dose to medium
 Maintenance and reliever therapy (MART) in Step 5
 There is no direct evidence about initiating MART in patients receiving add-on treatment such as LAMA
or biologic therapy, but if a patient is already taking MART, switching them to conventional ICS-LABA
plus as-needed SABA may increase the risk of exacerbations
ICS: inhaled corticosteroids; LABA: long-acting beta2-agonist; OCS: oral corticosteroids; SABA: short-acting beta2-agonist

© Global Initiative for Asthma, www.ginasthma.org

Add-on long-acting muscarinic antagonists (LAMA)

 Step 5 recommendations for add-on LAMA have been expanded to include combination ICS-
LABA-LAMA, if asthma is persistently uncontrolled despite ICS-LABA
 Add-on tiotropium in separate inhaler (ages ≥6 years)
 Triple combinations (ages ≥ 18 years): beclometasone-formoterol-glycopyrronium; fluticasone
furoate-vilanterol-umeclidinium; mometasone-indacaterol-glycopyrronium
 Lung function:
 Adding LAMA to medium or high dose ICS-LABA modestly improves lung function (Evidence A) but
not symptoms
 Severe exacerbations
 In some studies, add-on LAMA modestly increased the time to severe exacerbation requiring OCS
(Evidence B)
 For patients with exacerbations, it is important to ensure that the patient receives sufficient ICS,
i.e. at least medium dose ICS-LABA, before considering adding a LAMA

ICS: inhaled corticosteroids; LABA: long-acting beta2-agonist; LAMA: long-acting muscarinic antagonist; OCS: oral corticosteroids
© Global Initiative for Asthma, www.ginasthma.org
Add-on azithromycin

 Add-on azithromycin three days a week has been confirmed as an option for
consideration after specialist referral
 Significantly reduces exacerbations in patients taking high dose ICS-LABA
 Significantly reduces exacerbations in patients with eosinophilic or non-eosinophilic asthma
 No specific evidence published for azithromycin in patients taking medium dose ICS-LABA
(Hiles et al, ERJ 2019)
 Before considering add-on azithromycin
 Check sputum for atypical mycobacteria
 Check ECG for long QTc (and re-check after a month of treatment)
 Consider the risk of increasing antimicrobial resistance (population or personal)

ICS: inhaled corticosteroids; LABA: long-acting beta2-agonist

© Global Initiative for Asthma, www.ginasthma.org
Add-on biologic therapy for severe Type 2 asthma

 When assessing eligibility, repeat blood eosinophils if low at first assessment

 One study found that 65% patients on medium or high dose ICS-LABA shifted their eosinophil
category during 12 months’ follow-up (Lugogo et al, Ann Allergy Asthma Immunol 2020)
 Additional indications for these therapies in Europe and/or USA have been listed
 Omalizumab: chronic idiopathic urticaria, nasal polyposis
 Mepolizumab: hypereosinophilic syndrome, eosinophilic granulomatosis with polyangiitis (EGPA)
 Benralizumab: no additional indications at present
 Dupilumab: chronic rhinosinusitis with nasal polyposis (CRSwNP); atopic dermatitis
 Check local regulatory approvals and eligibility criteria

ICS: inhaled corticosteroids; LABA: long-acting beta2-agonist

© Global Initiative for Asthma, www.ginasthma.org