Update on Asthma Management

Tewodros Haile, MD,

Pulmonary & Critical Care Physician
 Outline of presentation
• Burden of asthma
• Definition & diagnosis
• Pathophysiology
• Assessment of asthma control
• Stepwise asthma management
• Case studies
 Burden of asthma
• Asthma is one of the most common chronic
diseases worldwide with an estimated 300
million affected individuals
• Prevalence is increasing in many countries,
especially in children
• Asthma is a major cause of school and work
absence
• Health care expenditure on asthma is very high
• Ethiopia: prevalence in children aged 13-14: 4.6%
Prevalence of asthma in children aged
13-14 years
Definition and diagnosis of
asthma
 Definition of asthma
Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation.

It is defined by the history of respiratory

symptoms such as wheeze, shortness of breath,
chest tightness and cough that vary over time
and in intensity, together with variable
expiratory airflow limitation.
 Asthma phenotypes
• Allergic asthma- eosinophilic air way
inflammation; respond well to ICS.
• Non-allergic asthma- neutrophilic, eosinophilic
or paucigranulocytic; repond less well to ICS.
• Late-onset asthma
• Asthma with fixed air flow limitation
• Asthma with obesity- little eosinophilic air way
inflammation
 Diagnosis of asthma
• The diagnosis of asthma should be based on:
– A history of characteristic symptom patterns
– Evidence of variable airflow limitation, from
bronchodilator reversibility testing or other tests
• Asthma is usually characterized by airway
inflammation and airway
hyperresponsiveness, but these are not
necessary or sufficient to make the diagnosis
of asthma.
 Diagnosis of asthma – symptoms
• Increased probability that symptoms are due to asthma if:
– More than one type of symptom (wheeze, shortness of breath, cough, chest
tightness)
– Symptoms often worse at night or in the early morning
– Symptoms vary over time and in intensity
– Symptoms are triggered by viral infections, exercise, allergen exposure, changes in
weather, laughter, irritants such as car exhaust fumes, smoke, or strong smells
• Decreased probability that symptoms are due to asthma if:
– Isolated cough with no other respiratory symptoms
– Chronic production of sputum
– Shortness of breath associated with dizziness, light-headedness or peripheral
tingling
– Chest pain
– Exercise-induced dyspnea with noisy inspiration (stridor)
 Diagnosis of asthma – physical examination

• Physical examination in people with asthma

– Often normal
– The most frequent finding is wheezing on auscultation, especially
on forced expiration
• Wheezing is also found in other conditions, for example:
– Respiratory infections
– COPD
– Upper airway dysfunction
– Endobronchial obstruction
– Inhaled foreign body
• Wheezing may be absent during severe asthma exacerbations
(‘silent chest’)
 Reevaluation of diagnosis in adults with
physician-diagnosed asthma
701
Mean age 51
67% female

181 (29.5%)
Asthma ruled out in 203
Continued to exhibit no
(33%)
symptoms or investigations
12 months later
suggestive of asthma

12 serious cardiorespiratory
diagnosis that had been mis-
diagnosed Less likely to have
undergone testing of
airflow limitation

Shawn D et al. JAMA 2017;317(3):269-279

 Diagnosis of asthma – variable airflow
limitation
• Confirm presence of airflow limitation
– Document that FEV1/FVC is reduced (at least once, when FEV 1 is low)
– FEV1/ FVC ratio is normally >0.75 – 0.80 in healthy adults, and
>0.90 in children
• Confirm variation in lung function is greater than in healthy individuals
– The greater the variation, or the more times variation is seen, the greater
probability that the diagnosis is asthma
– Excessive bronchodilator reversibility (adults: increase in FEV 1 >12% and >200mL;
children: increase >12% predicted)
– Excessive diurnal variability from 1-2 weeks’ twice-daily PEF monitoring (daily
amplitude x 100/daily mean, averaged)
– Significant increase in FEV1 or PEF after 4 weeks of controller treatment
– If initial testing is negative:
• Repeat when patient is symptomatic, or after withholding bronchodilators
• Refer for additional tests (especially children ≤5 years, or the elderly)
 Typical spirometric tracings
Volume Flow
Normal

FEV1
Asthma
(after BD)
Normal
Asthma
(before BD) Asthma
(after BD)

Asthma
(before BD)

1 2 3 4 5 6 Volume
Time (seconds)
Note: Each FEV1 represents the highest of
three reproducible measurements

GINA 2017 © Global Initiative for Asthma

 Patient with
respiratory symptoms
Are the symptoms typical of asthma?

NO
YES

Detailed history/examination
for asthma
History/examination supports
asthma diagnosis?
Further history and tests for
NO alternative diagnoses
Clinical urgency, and
YES Alternative diagnosis confirmed?
other diagnoses unlikely

Perform spirometry/PEF
with reversibility test
Results support asthma diagnosis?

Repeat on another
NO
occasion or arrange
NO
YES other tests
Confirms asthma diagnosis?

Empiric treatment with YES NO YE

ICS and prn SABA S

Review response
Consider trial of treatment for
Diagnostic testing most likely diagnosis, or refer
within 1-3 months for further investigations

Treat for ASTHMA Treat for alternative diagnosis

© Global Initiative for Asthma

Pathogenes
is of
asthma
Asthma occurs as a result
of the interaction of
genetic susceptibility and
the environment

Environmental factors can

be intrinsic or extrinsic:
Intrinsic (non-atopic)
Initiated by infections,
drugs, pollutants,
chemical irritants
Extrinsic (atopic,
allergic)
Allergens: food,
pollen, dust, etc.
 Asthma and its pathology
Inhaled allergens

Epithelial cells
CCL11

SCF
Mast cell

TSLP
Histamine, cysteinyl
leukotrienes and CCL17 and Dendritic
prostaglandin D2 IL-9 CCL22 cell
CCR4
Smooth
muscle cell IgE

IL-13 TH2 cell TReg cells?

Bronchoconstriction Antibody
IL-4 IL-5
production CCR3

Eosinophil

Eosinophilic inflammation
B cell

Global Initiative for Asthma. Revised 2015. Available from http://www.ginasthma.org/local/uploads/files/GINA_Report_2015.pdf

Figure adapted from Barnes P. Nat Rev Immunol 2008;8:183–92.
Disease
pathology Asthma
Bronchoconstrictio involves
n inflammati
on of the
Excess Mucus airways
secretion
Bronchial edema
Inflammatory cell
infiltration
airway thickening
( remodeling)
 Targeting inflammation with ICS
• ICS have a regulatory effect on genes encoding pro- or anti-inflammatory
proteins via interaction with glucocorticoid receptors

Corticosteroids Inflammatory cells Structural cells

(high-dose) Eosinophil Epithelial cell
↓ Numbers
(apoptosis) ↓ Cytokines
↓ Mediators
T-lymphocyte
Anti-inflammatory ↓ Cytokines Endothelial cell
protein GR
Mast cell ↓ Leak
CORTICOSTEROIDS
GRE Airway smooth muscle
SRC-1 ↓ Numbers
CBP ↑ 2-receptors
Macrophage ↓ Cytokines
PCAF HAT
mRNA ↓ Cytokines
Mucus gland
Acetylation
Anti-inflammatory Dendritic cell
gene ↓ Mucus
↓ Numbers
(SLPI) secretion
↑ Gene Gene
transcription repression

Figures reproduced from Barnes P et al. Ann Intern Med 2003;139:359–70.

 Assessment of asthma
1. Asthma control - two domains
– Assess symptom control over the last 4 weeks
– Assess risk factors for poor outcomes, including low lung function
2. Treatment issues
– Check inhaler technique and adherence
– Ask about side-effects
– Does the patient have a written asthma action plan?
– What are the patient’s attitudes and goals for their asthma?
3. Comorbidities
– Think of rhinosinusitis, GERD, obesity, obstructive sleep apnea,
depression, anxiety
– These may contribute to symptoms and poor quality of life
 Case 1:
• SA, 43 year old, goes for a routine asthma consultation:

• Daytime symptoms > twice a week

• Nocturnal awakenings

• In recent weeks used rescue medication 2/3 times a

week
• She is regularly taking LABA/ medium dose ICS and
salbutamol as needed
• What is her asthma control?
 Is her asthma controlled?
Controlled Partly controlled Uncontrolled
Characteristic (Any present in any week)
(All of the following)

Twice or less More than

Daytime symptoms
per week twice per week
Limitations of 3 or more
None Any
activities features of
partly
Nocturnal symptoms controlled
None Any
/ awakening asthma
present in
Need for rescue / Twice or less More than any week
“reliever” treatment per week twice per week

www.ginasthma.org
 What is asthma control?
As defined by the Global Initiative for Asthma (GINA), 2017?

• When asthma is well-controlled, patients can

 Avoid troublesome symptoms during the day and night
 Need little or no reliever medication
 Have productive, physically active lives
 Have normal or near-normal lung function
 Avoid serious asthma flare-ups (also called exacerbations,
or severe attacks)
Overall asthma control
• GINA guidelines state that control of asthma involves both current control and
longer-term components, referred to as ‘future risk’ 1

GINA, Global initiative for asthma; ICS, inhaled corticosteroid; LABA, long-acting β2-agonist.

1. GINA, Global strategy for asthma management and prevention, 2012. Available at: http://
www.ginasthma.org/uploads/users/files/GINA_Report_2012.pdf; 2. Bateman ED et al. J Allergy Clin Immunol 2010; 125: 600–8.
 How do we measure asthma control ?

• History
• Prescription review
• Questionnaires
• Objective measures
 How to assess asthma control in practice?
Simple tools that both healthcare providers and patients can use.
- Asthma Control Questionnaire (ACQ)
• 7-item questionnaire. Based upon day/night-time symptoms, daily activities, rescue
bronchodilator

- Royal College of Physicians (RCP)

• 3 questions based upon day/night-time symptoms and daily activities

- Asthma Control Test (ACT)

• Validated instrument. 5 questions based upon day/night-time symptoms, rescue
bronchodilator use and daily activities.

- Control of Allergic Rhinitis and Asthma Test (CARAT)

• Validated instrument. 4 questions on rhinitis + 6 on asthma. Available in several
languages

Juniper et al ERJ 1999;14:902-7, Br Med J 1990;301:651-653, Nathan J Allergy Clin Immun, 2004:113:59-65
Page 27 - © IPCRG 2013
Page 28 - © IPCRG 2013
 GINA assessment of asthma control

A. Symptom control Level of asthma symptom control

Well- Partly Uncontrolled
In the past 4 weeks, has the patient had:
controlled controlled
• Daytime asthma symptoms more
than twice a week?

Yes No
• Any night waking due to asthma?

Yes No None of 1-2 of 3-4 of

• Reliever needed for symptoms* these these these
more than twice a week?

Yes No
• Any activity limitation due to asthma?

Yes No
B. Risk factors for poor asthma outcomes
• Assess risk factors at diagnosis and periodically
• Measure FEV at start of treatment, after 3 to 6 months of treatment to record
GINA 2017 Box 2-2B (1/4) 1
the patient’s
© Global Initiative for Asthma
 Assessment of risk factors for poor asthma
outcomes
Risk factors for exacerbations include:
• Ever intubated for asthma
• Uncontrolled asthma symptoms
• Having ≥1 exacerbation in last 12 months
• Low FEV1 (measure lung function at start of treatment, at 3-6 months
to assess personal best, and periodically thereafter)
• Incorrect inhaler technique and/or poor adherence
• Smoking
• Elevated FeNO in adults with allergic asthma
• Obesity, pregnancy, blood eosinophilia

Risk factors for fixed airflow limitation include:

• No ICS treatment, smoking, occupational exposure, mucus
hypersecretion, blood eosinophilia
Risk factors for medication side-effects include:
• Frequent oral steroids, high dose/potent ICS, P450 inhibitors
GINA 2017, Box 2-2B (4/4) © Global Initiative for Asthma
Asthma Control

45% asthmatics have uncontrolled asthma (GINA defined)

84% of those patients believe they are controlled

70% of those patients do not believe their asthma to be

serious!
Price D et al. Asthma control and management in 8,000 European patients:
the REcognise Asthma and LInk to Symptoms and Experience (REALISE)
survey. NPJ Prim Care Respir Med 2014;24:14009
Results: Types of Asthma Medications, TASH

10.50%

ICS
32.20% 58.30% No ICS
ICS/LABA
 Results: Asthma Control, TASH

Well Controlled, 24%

Uncontrolled, 53%
Partially Controlled, 23%
 Assessing asthma severity
• How?
– Asthma severity is assessed retrospectively from the level of treatment
required to control symptoms and exacerbations
• When?
– Assess asthma severity after patient has been on controller treatment for
several months
– Severity is not static – it may change over months or years, or as different
treatments become available
• Categories of asthma severity
– Mild asthma: well-controlled with Steps 1 or 2 (as-needed SABA or low
dose ICS)
– Moderate asthma: well-controlled with Step 3 (low-dose ICS/LABA)
– Severe asthma: requires Step 4/5 (moderate or high dose ICS/LABA ± add-
on), or remains uncontrolled despite this treatment
 Goals of asthma management
• Asthma can be effectively treated.
• The long-term goals of asthma management are
1. Symptom control: to achieve good control of
symptoms and maintain normal activity levels
2. Risk reduction: to minimize future risk of
exacerbations, fixed airflow limitation and
medication side-effects
• Achieving these goals requires a partnership
between patient and their health care providers.
 Case 2
• 19 yo male with asthma since age 5
• Presents with EIA and year round nasal congestion
• Denies daytime symptoms
• Night time symptoms 2 times per month
• Uses SABA pre-exercise
• Never used any other type of inhaler
• He has moderate limitation on ability to exercise
• No ER visits or Hospitalizations
• What would you do now?
 Case 2
What would you do now?
a. Start a LABA
b. Start a low dose ICS
c. Start a high dose of ICS with LABA
d. Start a low dose of ICS with a LABA
 Initial controller treatment for adults,
adolescents and children 6–11 years
• Start controller treatment early
– For best outcomes, initiate controller treatment as early as possible after making
the diagnosis of asthma
• Indications for regular low-dose ICS - any of:
– Asthma symptoms more than twice a month
– Waking due to asthma more than once a month
– Any asthma symptoms plus any risk factors for exacerbations
• Consider starting at a higher step if:
– Troublesome asthma symptoms on most days
– Waking from asthma once or more a week, especially if any risk factors for
exacerbations
• If initial asthma presentation is with an exacerbation:
– Give a short course of oral steroids and start regular controller treatment (e.g. high
dose ICS or medium dose ICS/LABA, then step down)
 Stepwise approach to control asthma symptoms
and reduce risk UPDATED
2017
Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference

Symptoms
Exacerbations
Asthma medications
Side-effects
Non-pharmacological strategies
Patient satisfaction
Treat modifiable risk factors
Lung function

STEP 5

STEP 4

PREFERRED STEP 3 Refer for

STEP 1 STEP 2
CONTROLLER add-on
CHOICE treatment
Med/high e.g.
ICS/LABA tiotropium,*
Low dose anti-IgE,
anti-IL5*
Low dose ICS ICS/LABA**

Other Med/high dose ICS Add tiotropium* Add low dose

Consider low Leukotriene receptor antagonists (LTRA)
controller dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS
options (or + theoph*) + LTRA OCS
(or + theoph*)

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol#

• Provide guided self-management education (self-monitoring + written action plan + regular review)
REMEMBER
TO... • Treat modifiable risk factors and comorbidities, e.g. smoking, obesity, anxiety
• Advise about non-pharmacological therapies and strategies, e.g. physical activity, weight loss, avoidance of
sensitizers where appropriate
• Consider stepping up if … uncontrolled symptoms, exacerbations or risks, but check diagnosis, inhaler
technique and adherence first
• Consider adding SLIT in adult HDM-sensitive patients with allergic rhinitis who have exacerbations despite
ICS treatment, provided FEV1 is >70% predicted
• Consider stepping down if … symptoms controlled for 3 months + low risk for exacerbations.
Ceasing ICS is not advised.

GINA 2017, Box 3-5 (1/8) © Global Initiative for Asthma

 Step 2 – low-dose controller + as-needed
inhaled SABA

STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2 add-on
CONTROLLER treatment
CHOICE e.g.
Med/high tiotropium,*
anti-IgE,
ICS/LABA anti-IL5*
Low dose
Low dose ICS ICS/LABA**

Other Consider low Med/high dose ICS Add tiotropium* Add low
Leukotriene receptor antagonists (LTRA)
controller Low dose ICS+LTRA High dose ICS dose OCS
dose ICS Low dose theophylline*
options (or + theoph*) + LTRA
(or + theoph*)

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol#

*Not for children <12 years

**For children 6-11 years, the preferred Step 3 treatment is medium dose ICS
#For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy
 Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations
GINA 2017, Box 3-5, Step 2
 Case 2
• FVC was 90%, FEV-1 was 80% and his ratio was 85%
• CXR was normal
• Skin tests were positive for house dust mites
• Prescribed a low dose of inhaled steroid
• Started on nasal steroid
• Albuterol as needed
• Prednisone for severe asthma
• Educated on technique, adherence, acute asthma
action plan and mite avoidance
 Case 2
• Returns in 3 month
• He has been using his ICS regularly
• Denies nighttime, daytime symptoms, or exercise related
symptoms
• His QOL is good.
• Albuterol in the last week has been pre-exercise only.
• He used prednisone three times for asthma attacks over the
past 12 weeks
• FEV-1 was 80% with a ratio of 83%
• What is his asthma control?
• What would you do?
 Case 2
What is his asthma control?
• A. Well controlled asthma
• B. Partly controlled asthma
• C. Very poorly controlled
 Case 2
What would you do?
a. Increase to a high dose ICS
b. Low dose ICS/LABA
c. Add a short acting anticholingeric
d. Add Zileutin (a lipo-oxygenase inhibitor)
 Step 3 – one or two controllers +
as-needed inhaled reliever
STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2 add-on
CONTROLLER treatment
CHOICE e.g.
Med/high tiotropium,*
anti-IgE,
ICS/LABA anti-IL5*
Low dose
Low dose ICS ICS/LABA**

Other Consider low Med/high dose ICS Add tiotropium* Add low
Leukotriene receptor antagonists (LTRA)
controller dose OCS
dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS
options (or + theoph*) + LTRA
(or + theoph*)

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol#

*Not for children <12 years

**For children 6-11 years, the preferred Step 3 treatment is medium dose ICS
#For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy
 Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations
GINA 2017, Box 3-5, Step 3 (6/8) © Global Initiative for Asthma
Combination treatment improves symptoms
and lung function
Salmeterol/BDP Higher dose BDP
35
n=144
n=162
30 n=142
Change in PEF (L/min)

25 † n=137
‡ n=159
* †
20 †
n=208
15 ‡ n=136

n=135
10 n=149
n=156
5 n=126

n=195
0

0 1 5 9 13 17 21
Weeks of treatment
*P<0.05; †P<0.01; ‡P<0.001.
Adapted from Greening AP et al. Lancet 1994; 344:219–24
 Combination treatment: reduces
exacerbation risk
• The addition of LABA to ICS significantly reduces the risk of exacerbations

Mild exacerbations Severe exacerbations

40 1 p = 0.01

Estimated annual exacerbation rate

p < 0.001
0.9
Estimated annual exacerbation rate

35
0.8
30

(no./patient/yr)
0.7
p < 0.001
(no./patient/yr)

25 0.6
p = 0.01
20 0.5

15 *
0.4 *
0.3
10
0.2
5 0.1

0 0
BUD 200 μg/d BUD/FORM BUD 800 μg/d BUD/FORM BUD 200 μg/d BUD/FORM BUD 800 μg/d BUD/FORM
+ PBO 200/24 μg/d + PBO 800/24 μg/d + PBO 200/24 μg/d + PBO 800/24 μg/d

*p < 0.001 higher vs lower-dose BUD.

BUD, budesonide; FORM, formoterol; PBO, placebo. Adapted from Pauwels RA et al. N Engl J Med 1997;337:1405–11.
 62-78% of patients were well controlled with optimal
treatment with ICS/LABA
Well-controlled asthma Uncontrolled asthma
100%
Proportion of patients

80%

60% 78%
70% 75%
P=0.003 P<0.001
vs FP 60% vs FP 62%
40% P<0.001
47% vs FP

20%

0%
FP SFC FP SFC FP SFC
ICS use in No prior ICS ≤500 μg BDP >500 to ≤1000 μg BDP
previous N=1098 or equivalent or equivalent
6 months: N=1163 N=1155
BDP, beclometasone dipropionate; FP, fluticasone propionate; GINA, Global Initiative for Asthma; GOAL, Gaining Optimal Asthma Control; ICS, inhaled corticosteroid;
LABA, long-acting β2-agonist; SFC, salmeterol/fluticasone propionate combination

Bateman E, et al. Am J Respir Crit Care Med 2004;170:836-844.

 Case 3
• AK, 18 year old female asthmatic presented
with exacerbations despite other therapies, the
risk of exacerbation is reduced with
• A. maintenance controller treatment plus as-
needed SABA
• B. Low dose ICS/ formoterol as both
maintenance and reliever
• C. LTRA
• D. high dose ICS
FACET: Profile of symptoms and reliever use
preceding exacerbations

Tattersfield A, et al. Am J Respir Crit Care Med 1999; 160:594-599

 Timely increase inhaled steroid dose
Profile of 425 severe exacerbations* in 242 patients

100 Window of opportunity Night-time symptoms

to increase Relief inhaler use
anti-inflammatory?
% Change from day –14

80

60
THEORETICAL
40

20

–15 –10 –5 0 5 10 15
Days before and after an exacerbation
 COMPASS: Study Design

Seretide 25/125 µg 2 inhalations bd maintenance + terbutaline as reliever

(n=1,123)

Run-in
Regular ICS ≥ Symbicort 320/9 µg 1 inhalation bd as maintenance + terbutaline as reliever
500 µg R (n=1,105)

Symbicort 160/4.5 µg 1 inhalation bd as maintenance + Symbicort as

reliever (SMART)
(n=1,107)

Visit: 1 2 3 4 5
Week: -2 0 8 16 24

Adapted from Kuna P, et al. Int J Clin Pract 2007; 61(5):725-736

 COMPASS
Time to first severe exacerbation* (primary variable)
15 Seretide (25/125 2 bd) + SABA as reliever
Patients with severe exacerbations (%)

Symbicort (320/9 bd) + SABA as reliever

Symbicort (160/4.5 bd ) + as reliever
NS

10 p=0.0034
p=0.023

5
Symbicort SMART reduced rate
of exacerbations by:
 39% vs. Seretide maintenance + SABA
 28% vs. Symbicort maintenance + SABA

0
0 20 40 60 80 100 120 140 160
Days since randomisation

* Severe exacerbations defined as hospitalisation, ER visit or course of oral corticosteroids ≥ 3 days.

Adapted from Kuna P, et al. Int J Clin Pract 2007; 61(5):725-736
 COMPASS: Corticosteroid use

Symbicort + Symbicort
Level of use Seretide + SABA
(n=1,118) SABA SMART (n=1,103)
(n=1,099)

Mean ICS dose

mg/day (metered dose) 500 (FP) 800 (BUD) 604 (BUD)
BDP mg equivalents* 1,000 800 604
(Potency Adjusted – BTS/SIGN 2014)

Oral corticosteroid use/group

Days with use/6 months 1,132 1,044 619

*Calculations assume an adherence rate of 100%

FD= Fixed dose; FP= fluticasone propionate; BDP = beclometasone dipropionate
BUD= budesonide; SMART = Symbicort Maintenance And Reliever Therapy
Adapted from Kuna P, et al. Int J Clin Pract 2007; 61(5):725-736
 Compared with other regimens, BUD/FORM SMART
reduced severe exacerbations requiring interventions

BUD + SABA BUD/FORM + SABA BUD/FORM + FORM

45
FP/SAL + SABA BUD/FORM SMART
Severe exacerbations requiring intervention

40
35
30
per 100 patients/yr

25
20
15
10
5
0
STEAM 1 STEP 2 AHEAD 3 STAY 4 COMPASS 5 SMILE 6
1. Rabe KF et al. Chest 2006;129:246–56.
2. Scicchitano R et al. Curr Med Res Opin 2004;20:1403–18.
3. Bousquet J et al. Respir Med 2007;101:2437–46.
4. O’Byrne PM et al. Am J Respir Crit Care Med 2005;171:129–36.
BUD/FORM, budesonide/formoterol; FP/SAL, fluticasone propionate/salmeterol; 5. Kuna P et al. Int J Clin Pract 2007;61:725–36.
SABA, short-acting β2-agonist; SMART, budesonide/formoterol maintenance and reliever therapy. 6. Rabe KF et al. Lancet 2006;368:744–53.
 Step 4 – two or more controllers
+ as-needed inhaled reliever
STEP 5

STEP 4

STEP 3 Refer for

PREFERRED STEP 1 STEP 2 add-on
CONTROLLER treatment
CHOICE e.g.
Med/high tiotropium,*
anti-IgE,
ICS/LABA anti-IL5*
Low dose
Low dose ICS ICS/LABA**

Other Consider low Med/high dose ICS Add tiotropium* Add low
Leukotriene receptor antagonists (LTRA)
controller dose OCS
dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS
options (or + theoph*) + LTRA
(or + theoph*)

RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or

low dose ICS/formoterol#

*Not for children <12 years

**For children 6-11 years, the preferred Step 3 treatment is medium dose ICS
#For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy
 Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations
GINA 2017, Box 3-5, Step 4 © Global Initiative for Asthma
 Step 5 – higher level care and/or add-on
treatment
• Preferred option is referral for specialist investigation and consideration of
add-on treatment
– If symptoms uncontrolled or exacerbations persist despite Step 4 treatment,
check inhaler technique and adherence before referring
– Add-on tiotropium for patients ≥12 years with history of exacerbations
– Add-on anti-IgE (omalizumab) for patients with severe allergic asthma
– Add-on anti-IL5 (mepolizumab (SC) or reslizumab (IV)) for severe eosinophilic
asthma (≥12 yrs)
• Other add-on treatment options at Step 5 include:
– Sputum-guided treatment: this is available in specialized centers; reduces
exacerbations and/or corticosteroid dose
– Add-on low dose oral corticosteroids (≤7.5mg/day prednisone equivalent): this
may benefit some patients, but has significant systemic side-effects. Assess and
monitor for osteoporosis
– See ERS/ATS Severe Asthma Guidelines (Chung et al, ERJ 2014) for more detail.
 Reviewing response and adjusting
treatment
• How often should asthma be reviewed?
– 1-3 months after treatment started, then every 3-12 months
– During pregnancy, every 4-6 weeks
– After an exacerbation, within 1 week
• Stepping up asthma treatment
– Sustained step-up, for at least 2-3 months if asthma poorly controlled
• Important: first check for common causes (symptoms not due to asthma, incorrect inhaler technique, poor
adherence)
– Short-term step-up, for 1-2 weeks, e.g. with viral infection or allergen
• May be initiated by patient with written asthma action plan
– Day-to-day adjustment
• For patients prescribed low-dose ICS/formoterol maintenance and reliever regimen*
• Stepping down asthma treatment
– Consider step-down after good control maintained for 3 months
– Find each patient’s minimum effective dose, that controls both symptoms and exacerbations

• Approved only for low dose beclometasone/formoterol and low dose budesonide/formoterol
 Case 4
• A 22 year old lady with persistent asthma
symptoms and exacerbations despite ICS,
consider
• A. step up with ICS/LABA
• B. Medium dose ICS
• C. Tiotropium by mist inhaler
• D. check inhaler technique, adherence
 How to distinguish between uncontrolled
and severe asthma
Watch patient using their Compare inhaler technique with a device-
specific checklist, and correct errors;
inhaler. Discuss adherence recheck frequently. Have an empathic
and barriers to use discussion about barriers to adherence.

If lung function normal during symptoms,

Confirm the diagnosis consider halving ICS dose and repeating
of asthma lung function after 2–3 weeks.

Remove potential Check for risk factors or inducers such as

smoking, beta-blockers, NSAIDs, allergen
risk factors. Assess and exposure. Check for comorbidities such as
manage comorbidities rhinitis, obesity, GERD, depression/anxiety.

Consider step up to next treatment level.

Consider treatment Use shared decision-making, and balance
step-up potential benefits and risks.

If asthma still uncontrolled after 3–6 months

Refer to a specialist or on Step 4 treatment, refer for expert advice.
severe asthma clinic Refer earlier if asthma symptoms severe,
or doubts about diagnosis.

GINA 2017, Box 2-4 (5/5) © Global Initiative for Asthma

 Management of severe asthma
• Optimize dose of ICS/LABA
– Complete resistance to ICS is rare
– Consider therapeutic trial of higher dose
• Consider low dose maintenance oral corticosteroids
– Monitor for and manage side-effects, including osteoporosis
• Add-on treatments without phenotyping
– Tiotropium - reduces exacerbations (history of exacerbations, age ≥12 years)
– Theophylline, LTRA – limited benefit
• Phenotype-guided treatment
– Severe allergic asthma: add-on omalizumab (anti-IgE)
– Severe eosinophilic asthma: add-on mepolizumab or reslizumab (anti-IL5)
– Sputum-guided treatment to reduce exacerbations and/or steroid dose
– Aspirin-exacerbated respiratory disease: consider add-on LTRA
• Non-pharmacological interventions
– Consider bronchial thermoplasty for selected patients
– Comprehensive adherence-promoting program
• For detailed guidelines, see Chung et al, ERJ 2014
Thank you