Bronchial Asthma

Prof Dr. Mohammad Asim

Consultant Pulmonologist/ Intensive care
Northwest General Hospital and Research Centre,
Peshawar
MBBS,MRCP,FRCP,CCT(Pulmonology/GIM)
Fellow Higher Education Academy(U.K)
Ex-Consultant Warrington and Halton Hospitals UK
 Lay Out
• Epidemiology
• Pathogenesis of Asthma
• Asthma vs COPD
• Diagnosis
• Treatment of Asthma
• New Advances in Treatment of Asthma
SMART (Single Inhaler as Maintenence and
Reliever Therapy ) for Asthma
Bronchial Thermoplasty
 High prevalence of asthma worldwide

The WHO estimated that asthma caused 239,000

deaths worldwide in 2002

Masoli M, et al. Allergy 2004

 Asthma Insights & Control in Pakistan
• 51% of Adults and 32% of
children had severe episodes of
asthma, over the previous year1
9.8 Million
Individuals1 • 47% individuals had moderate to
severe symptoms, over the previous
4 weeks1

• 69% of children and 72% in

adults suffered from sleep
disturbance more than once a
week1

• 50% of respondents reported at

least one hospital admission in the
1. AIRIP 2006. (Abstract) Asian Pacific Society of Respiratory . previous year1
 Asthma Prevalence in Children

On average, 3 children in a classroom of 30 are likely to have

asthma
Epidemiology and Statistics Unit. Trends in Asthma Morbidity and Mortality. NYC: ALA, July 2006.
Asthma – What is It?
• Asthma is a chronic lung
disease that obstructs
airflow

• The obstruction is
reversible

• It involves difficulty in
breathing due to
– Inflammation (swelling)
– Mucus in the airways
– Tightening of muscles
around the airways
Risk Factors that Lead to Asthma Development

Predisposing Factors Contributing Factors

• Atopy  Respiratory infections
Causal Factors  Small size at birth
• Indoor Allergens  Diet
– Domestic mites  Air pollution
– Animal Allergens ◦ Outdoor pollutants
– Cockroach Allergens
– ◦ Indoor pollutants
Fungi
• Outdoor Allergens
 Smoking
– Pollens ◦ Passive Smoking
– Fungi ◦ Active Smoking
• Occupational Sensitizers
Differentiating asthma and COPD
 Can asthma be cured?
• Asthma can be controlled (but not cured) by:
– Avoiding triggers or reducing exposure to triggers
– Using medication to control symptoms

• Medications - generally two types are used

– Controller or long-term drugs
• Taken to prevent excess production of mucus & to reduce
the inflammation and constriction of airway muscles
– Rescue or quick-relief drugs
• Taken to relax muscles around the airways to improve
breathing
Diagnosis
 Diagnosis
• Peak flow monitoring
• Spirometry
• preferred method of measuring airflow limitation
and its reversibility to establish a diagnosis of
asthma.
• An increase in FEV of >12% and 200 ml after
1

administration of a bronchodilator indicates

reversible airflow limitation consistent with
asthma.
Peak flow diary

13
05/25/2023
 Asthma Diagnosis Flow Chart
Patient with respiratory
symptoms no
Are the symptoms typical of Asthma?

Yes

Detailed history/examination of
Asthma
History/examination supports Asthma
Clinical urgency & diagnosis? no Further history & tests
other diagnosis yes for alternative diagnosis
unlikely

Perform Spirometry/PEF with

reversible test
Results support Asthma diagnosis?

Repeat on another occasion or arrange

Empiric treatment their tests No
No
with ICS & SABA Confirms Asthma Diagnosis?
Yes
Review response No
Yes
Diagnostic Testing Consider Trial of Treatment for most
within 1-3 months likely diagnosis or refer for further
investigations Yes
Treat for Asthma Treat for Alternative
Diagnosis
Management of Asthma
Guidelines for management of asthma
• Global INitiative for
Asthma (updated
2018)
Guidelines for management of asthma
• The British Thoracic
Society/Scottish
Intercollegiate
Guidelines Network
• British Guideline on
the Management of
Asthma (updated
2016)
 Treatment
• A stepwise approach to pharmacologic
treatment to achieve and maintain control of
asthma should take into account the safety of
treatment, potential for adverse effects and
the cost of treatment
• Controller medication must be taken daily and
reliever medication may occasionally be used
to treat acute symptoms
 Assessment of Asthma
Day time symptoms more than Yes No
twice/week
In the past 4
Any Night Waking Due to Asthma? Yes No
weeks, has
the patient Reliever needed more than Yes No
had? twice/week
Any activity limitation due to Yes No
Asthma

None of these: Well Controlled

1-2 of these: Partly Controlled
3-4 of these: Uncontrolled
 Management of Asthma (GINA Guidelines
2018)
• The long-term goals of Asthma management are symptom control & risk
reduction
• The aim is to reduce the burden to the patient & their risk of exacerbations,
airways damage & medication side-effects
Control-based Asthma Management Cycle

How often should Asthma be

reviewed?
• 1-3 months after starting the
treatment, then every 3-12
months after that
• During pregnancy: 4-6 weeks
• After exacerbation: within 1 week
 Stepwise management - pharmacotherapy

Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference
Symptoms
Exacerbations
Side-effects Asthma medications
Patient satisfaction Non-pharmacological strategies
Lung function Treat modifiable risk factors

STEP 5

STEP 4
Refer for
add-on *Not for children <12 years
STEP 3
PREFERRED STEP 1 STEP 2 treatment
e.g. **For children 6-11 years, the
CONTROLLER Med/high preferred Step 3 treatment is
tiotropium,*
CHOICE anti-IgE,
ICS/LABA medium dose ICS
Low dose anti-IL5*
#
For patients prescribed
Low dose ICS ICS/LABA** BDP/formoterol or BUD/
formoterol maintenance and
Other Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS Add tiotropium* Add low reliever therapy
controller dose ICS Low dose theophylline* Low dose ICS + LTRA Med/high dose dose OCS
options (or + theoph*) ICS + LTRA  Tiotropium by mist inhaler is
(or + theoph*) an add-on treatment for
patients ≥12 years with a
As-needed short-acting beta2-agonist (SABA) As-needed SABA or history of exacerbations
RELIEVER low dose ICS/formoterol#

GINA 2018, Box 3-5 (2/8) (upper part) © Global Initiative for Asthma www.ginasthma.org
 Salbo (salbutamol)
Short Acting Beta2-agonist (SABA) indicated for:
• Treatment or prevention of bronchospasm in patients aged 4 years and older with
reversible obstructive airway disease
• Prevention of exercise-induced bronchospasm in patients aged 4 years and older

Recommended by GINA Guidelines 2018 in all steps of

Asthma Management
Salbo (salbutamol)
Stepping up Asthma Treatment
1) Sustained step-up, for at least 2-3 months
Important: If symptoms or exacerbations still persists after 2-3 months of
controller treatment, consider the following common issues
before considering a further step-up:
• Incorrect inhaler technique
• Poor adherence
• Smoking
• Co-morbid conditions like; allergic rhinitis

2) Short-term step-up, for 1-2 weeks, e.g. during viral infection or

allergen exposure

3) Day-to-day adjustment
 For patients prescribed low-dose ICS/formoterol maintenance and
reliever regimen
Stepping down Asthma Treatment
Consider stepping down treatment once good asthma control has been
achieved and maintained for 3 months
1) Choose an appropriate time for step-down (no respiratory infection,
patient not travelling, not pregnant)
2) Document the symptom control & lung function, provide a written
asthma plan & book a follow-up visit
3) Reduce the ICS dose by 25-50% at 2-3 months intervals
4) Completely stopping ICS in adults & adolescents with Asthma is not
recommended
• Combination inhalers containing Budesonide &
Formoterol may be used for both rescue & maintenance
therapy
“The use of Budesonide/Formoterol in a single
inhaler as rescue medication instead of a short-
acting B2-agonist, in addition to its use as
controller therapy has been shown to be an
effective treatment regimen.”
 ADDITION OF FORMOTEROL TO INHALED STEROID
95 852 asthmatic patients
FEV1~75% predicted FACET study
90 on ~800µg ICS daily
Bud 800µg + Form 12µg
OPTIMA STUDY: similar results in mild/moderate asthma
FEV1 (% predicted)

85
Bud 200µg + Form 12µg
Bud 800µg
80
Bud 200µg

75 Adding formoterol better than 4x dose of ICS

No tolerance over 1 yr
70
-1 0 1 2 3 6 9 12
run-in
Time (months)
Pauwels R et al NEJM 1997 FACET Study O’Byrne P et al AJRCCM 2001
 TREATMENT OF ASTHMA: CELLULAR EFFECTS
ACUTE LABA
INFLAMMATION
Virus?
Adenosine
Exercise
Fog Sensory nerve
Mast cell Bronchoconstriction Plasma leak
activation
Antigen
Macrophage Eosinophil

AIRWAY
HYPERRESPONSIVENESS
T-cell
Dendritic cell CHRONIC
INFLAMMATION

ICS
 ADD-ON THERAPIES FOR ASTHMA

Low dose inhaled steroids

(400 µg daily or less)
LABA/CS Combination
If not controlled:
Inhalers
Add LA inhaled ß2-agonist
(most effective)
High dose
inhaled steroids Add low dose theophylline
(cheapest)

Add anti-leukotriene
(less effective and expensive)
 EVOLUTION IN ASTHMA THERAPY
CONVENTIONAL FUTURE
No adjustment in Single inhaler:
controller Maintenance
& relief
Combination inhaler
FACET replaces SABA STAY
OPTIMA STEAM
GOAL STEP
SMART = COSMOS
Medication Use

Single inhaler MaintenanceSMILE

And Reliever Therapy COMPASS
AHEAD

Budesonide/formoterol
Fluticasone/salmeterol

Maintenance Maintenance
+ prn SABA + prn Bud/form
 CELLULAR EFFECTS OF “RESCUE” Budesonide/Formoterol

Budesonide/formoterol

EXPLAINS WHY BUD/FORM

Formoterol Budesonide
IS THE MOST EFFECTIVE RELIEVER

Neutrophils Mast cells Eosinophils Th2 cells

Eotaxins IL-5
Airway smooth muscle
 SMART Reduction in Exacerbations
SMART reduces asthma exacerbation rates more effectively than
Salmeterol/ fluticasone
Exacerbations (events/100 patients/year)
* Extrapolated to one year from six month
result

40 -
39%
38
30
32

20
23
* P<0.001 vs. Salmeterol /
Fluticasone+ SABA
10
** P<0.01 vs. 2x
Formoterol/Budesonide + SABA

0
Series1
Salmeterol/ Formoterol/ SMART + as needed
Fluticasone Budesonide bid +
50/250 µg bid + SABA
SABA

COMPASS: Kuna P et al, Int J Clin Prac. 2007; 61: (*A six month double-blind study including 3,335 patients)
 SMART Therapy Uniqueness

Budesonide + Formoterol
 Anti-  Long-acting
inflammatory bronchodilator
agent
 Onset as rapid
 Fast onset as salbutamol
within 3-5 hours (1-3 minutes)
 Demonstrated
 Demonstrated dose response
dose response 6µg to 48µg/day
 Greater efficacy
in combination
with formoterol
vs. higher doses
of budesonide
alone
 EVOLUTION OF ASTHMA TREATMENT
Fluticasone + salmeterol
Oral
Oral
Budesonide + formoterol steroid
steroid

SMART
LABA
New treatments
Any ICS + formoterol? for severe asthma
(1-5% of patients)
needed
ICS
LABA/ICS
ICS High dose
Low dose
Anti-IgE
Anti-TNF??
Short-acting ß2-agonist as needed New drugs
Step 1 Step 2 Step 3 Step 4 Step 5
Mild Mild Moderate Severe
Episodic Persistent Persistent Persistent
Fortide (Budesonide+Formoterol)
Fortide is a combination Inhaler containing a corticosteroid (Budesonide)
and Long Acting Beta2-agonist (Formoterol)
Indicated for:
• Treatment of asthma in patients aged 6 years of age & older
• Maintenance treatment of airflow obstruction & reducing exacerbations in
patients with Chronic Obstructive Pulmonary Disease (COPD) including Chronic
Bronchitis and emphysema

Recommended by GINA Guidelines 2018 as a SMART

Therapy
 Single Maintenance & Reliever Therapy
(SMART)
Regular Regular
maintenance maintenance
budesonide formoterol

FORTIDE
SMART
THERAPY

As needed As needed
budesonide formoterol
-anti-inflammatory
-rapid symptom relief
effects within hours
-prevents
-prevents
exacerbations
exacerbations
 WHAT DO PATIENTS WANT?
Living and Breathing Study
UK qualitative and quantitative study to evaluate patient
understanding of their asthma and determine patient
preferences regarding the delivery of asthma care and
treatment

Patient preferences: SMART

• Treatment as simple as possible Yes
• Fewer inhalers Yes
• Lowest dose of steroid to control symptoms Yes
• Avoid hospitals when possible Yes
• Minimise symptoms Yes

Haughney J et al: Primary Care Resp J 2004

 SMART Vs Patients Needs

Budesonide/formoterol for maintenance and reliever therapy: new quality in asthma management.
10.2217/14750708.5.4.495 © 2008 Future Medicine Ltd ISSN 1475-0708 Therapy (2008) 5(4), 495–512
 THERE IS A STRONG SCIENTIFIC RATIONALE
FOR BUD/FORM SMART THERAPY IN ASTHMA

Maintenance therapy: Rescue therapy:

Highly effective Highly effective

SINGLE INHALER THERAPY

Barnes PJ. Scientific rationale for using a single inhaler for
asthma control. Eur Resp J 2007;25:587-596
 One or Many?

SMART (Single Maintenance &

Reliever Therapy)

or

Which treatment would you choose?

Bronchial Thermoplasty
• Bronchial thermoplasty non drug procedure
• Moderate to severe asthma not controlled with ICS and LABA
• Delivers thermal energy to bronchial wall in a precisely
controlled manner in order to reduce airway smooth muscle
• Reducing airway smooth muscle helps to reduce airways
ability to constrict thereby reducing frequency of
asthma attacks
• Three outpts visits treating different areas
of lungs 3 wks apart
• Expected to complement asthma medications by
providing long lasting asthma control
• Reduce ER visits
• Reduce severe exacerbations
• Reduce days lost of work
 CONCLUSIONS

• SMART more effective in reducing exacerbations than

alternative approaches (comb inhaler + SABA/high dose ICS)

• SMART controls asthma at lower does of ICS and less oral

steroids (reduces total steroid exposure)

• Budesonide/Formoterol is the most effective reliever for asthma

- Rapid effect of formoterol on acute bronchoconstriction
- Rapid anti-inflammatory effect of budesonide
- Positive interaction between formoterol and budesonide

SMART likely to be the most effective therapy for asthma

for at least 15 years!
 Thank you
Any Questions?
Tomorrow’s life is too late, live today.
-MARTIAL c.40-c104.