ESTIMATED MORBIDITY FOR NON

COMMUNICABLE DISEASES IN INDIA

70000000
65 million
60000000

50000000

40000000

Asthma
30000000
25 million 54 m 28 million

COPD
20000000

10000000
1 million
0.6 million
0
Cancer IHD Stroke Diabetes Chronic respiratory
disease

(Nongkynrih B et al, JAPI 2004 Feb; 52: 118-123)

WHO, 2002 data
80-85% of chronic respiratory diseases in our
country are due to
ASTHMA & COPD
 Respiratory Diseases

Asthma COPD Allergic Rhinitis

 No. of patients with Asthma

30 CRORES 1.5 – 2 CRORES

• Estimated prevalence of Asthma is increasing 50% every 10

years
ASTHMA
Asthma is a long term disease that affects the airways.

Tubes that carry air in and out

of your lungs.

Lets understand the respiratory

system…….
Parts of the respiratory system
Parts of the respiratory system (Contd…)
 Parts of the respiratory system (Contd…)

AIRWAYS
Cross Section of Airway Wall
 Classification of the nervous system
Nervous system

Peripheral Central

Somatic Autonomic

Sympathetic Parasympathetic
 ALLERGY

A reaction to a specific substance which is foreign to the body.

Allergen is the substance which induces an allergic response.

Normal individual Allergic individual

• Allergen stimulates production of • Allergen stimulates excess

IgE, in equal no. to allergen. production of IgE.

• Allergen  destroyed • Some Allergens get destroyed.

• Rest cause allergic reaction.

 Triggers
Triggers factors are things that when inhaled can start asthma.
They can vary from person to person.

Pollen
Dust Dust mite Animal From plants
dander
Recognition of asthma triggers and
Exercise
avoiding them Smoke from
is the first step towards controllingfirecrackers
asthma…
Strong smells
Cigarette smoke Smoke
Cold air
On entry of these triggers

The airways get narrower

Less air flows through the lungs

AIRWAY OBSTRUCTION
(Blockage in the airways)

This causes symptoms like...........

 Asthma Symptoms
 Breathlessness or dyspnoea
(especially at night or after some exertion)

 Wheezing
(a whistling sound while breathing out)

 Cough
(especially at night or after some exertion)

 Chest tightness
(feeling of congestion)
 Definition
Asthma
is a
Chronic Inflammatory Disease
characterized by
Airway Hyperresponsiveness
to a variety of stimuli resulting in
Bronchospasm
which reverses, spontaneously
or with treatment.
 ABC of Asthma
A
Airway hyper-responsiveness
(Airways over-react to triggers)

B
Bronchospasm
(Sudden constriction in bronchial tubes)

C
Chronic inflammation
(Long term swelling)
 Exercise Induced Asthma (EIA)
Asthma attacks which occur after strenuous exercise. EIA symptoms
occur after 3-8 min of exertion
 Nocturnal Asthma

• Nighttime symptoms of wheezing, cough, breathlessness is known as

nocturnal asthma.

• 70% of deaths due to asthma occur at night.

Causes of Nocturnal Asthma

- Exposure to dust mite, animal dander

- Gastro-oesophageal reflux

- Post nasal drip

- Increased parasympathetic activity

- Increased sensitivity to histamine

 Diagnosing Asthma

1. History taking

2. Measurements of lung function

3. Bronchodilator reversibility test

 1. History taking
(Ask questions to Diagnose Asthma)
 Does the patient have a troublesome cough, worse particularly at night, or
on awakening?

 Does the patient cough after physical activity (e.g.. Playing)?

 Does the patient have breathing problems during a particular season (or
change of season)?

 Do the patient’s colds ‘go to the chest’ or take more than 10 days to resolve?

 Does the patient use any medication (e.g. bronchodilator) when symptoms
occur? Do you get relief?
 If the patient answers “YES” to any of the
above questions, suspect Asthma.

Also a doctor should ask about:

 Does anyone else in your family suffer from Asthma,
Allergies, Frequent Colds ?
2. Measurements of lung function

The Peak Flow Meter

The thermometer for Asthma

 3. Bronchodilator reversibility test
1. Measure peak flow reading

2. Give bronchodilator

3. Wait for 10 to 15 minutes

4. Measure peak flow reading again

5. If: 15 – 20 % increase in this reading from previous

6. Indication of a significant degree of reversible airflow obstruction

ASTHMA
 Peak Flow Master
• Diagnose asthma >15 % improvement in PEFR

( Reversibility )

• Monitoring > 20 % variability in AM-PM PEFR indicates poor

control

• To determine effectiveness of therapy

• Identify factors which worsen asthma

• Warn of an impending attack

• Incentive for the patients

 Inflammatory Cells

RBCs WBCs Platelets

Granulocytes Agranulocytes

Eosinophils Lymphocytes
Basophils Monocytes
(T cells &
Neutrophils B cells) Macrophages
Mast cells
INFLAMMATION
Treatment of Asthma
 Routes of administration of
anti-asthma drugs

Which is the best route for anti-asthmatic drugs???

Oral Inhaled Parenteral

Tablets Injections
Metered dose inhaler (MDI)

Syrup
Dry powder inhaler (DPI)

Nebulizers
 ORAL OR INHALED

Eyes Ears
Eye Drops Ear Drops

Lungs
INHALERS
Skin
Lotions / ointments
NOT ORALS Nasal blockage
Nasal inhaler
 ORAL OR INHALED

For Example…..

• Tab ASTHALIN 4mg = 4000 mcg

• 100mcg/Puff ASTHALIN x 2 puff = 200 mcg

4000/200 = 20

20 times less drug is required for

desired effect from INHALATION route!
 ORAL OR INHALED

Oral Inhaled
• Large dosage used • Small amount of dosage used
• Greater side effects • Lesser side effects
• Slow onset of action • Fast onset of action
(e.g. bronchodilators)
• Not useful in acute
symptoms • Useful in acute symptoms
 Advantages of inhalation therapy
over oral route

 Direct action in lungs

 Small doses required
 Quick onset of Action
 Minimum side effects
 Asthma Disease
Bronchospasm & Inflammation (Swelling)

• Bronchospasm needs a Reliever

Bronchodilator

• Inflammation (Swelling) needs a Controller

Anti-inflammatory
 Drug treatment

Relievers Controllers
Bronchodilators Anti-inflammatory
Quickly relieve symptoms Prevent asthma attacks

Onset of action: faster Onset of action: slower

Duration of action: short Duration of action: long

Rescue medicine Regular medicine

 AVAILABLE DRUGS

RELIEVERS CONTROLLERS
 Short acting  Long acting
bronchodilators bronchodilators
 Inhaled Corticosteroids
 Combination Therapy
 Anti Leukotrienes
 Cipla
AVAILABLE RELIEVERS
Short acting bronchodilators

Salbutamol - ASTHALIN
Levosalbutamol - LEVOLIN

To be taken as and when required

 Cipla
AVAILABLE CONTROLLERS
Inhaled corticosteroids Long acting bronchodilators

Beclomethasone Salmeterol
BECLATE SEROBID
Budesonide
Formoterol
BUDECORT
FORATEC
Fluticasone
FLOHALE Anti-leukotrienes
Montelukast
Ciclesonide MONTAIR
CICLOHALE
To be taken regularly ,
whether patient has symptoms or not
 Cipla
AVAILABLE CONTROLLERS (Contd…)
ICS + bronchodilators

SEROFLO – Salmeterol / Fluticasone

FORACORT – Budesonide / Formoterol
SIMPLYONE – Ciclesonide / Formoterol
FULLFORM – Beclomethasone / Formoterol
BEKFORM - Beclomethasone / Formoterol
AEROCORT - Beclomethasone / Salbutamol
To be taken regularly ,
whether patient has symptoms or not
 THE STORY OF ASTHMA TREATMENT

Traditional treatment
Ideal treatment Occasional Relievers
Regular Controllers
Steroid
Mechanism of Action

Inhalation Therapy in
Asthma
 MOA of Bronchodilators
• Beta2-Agonists
• Short acting beta2-agonists
- Salbutamol
- Levosalbutamol
• Long acting beta2-agonists
- Salmeterol
-Formoterol
Mode of action of ß2 agonists
2- agonist

2 -receptor

M P
c A

P
AT Activates Protein Smooth
kinase muscle cell

Decreases
2+
intracellular Ca

Smooth muscle
cell relaxation
Mode of action of inhaled
corticosteroids
Mode of action of inhaled corticosteroids
S Steroid

Steroid
S receptor
complex
CELL
S

NUCLEUS
DNA

New Protein Synthesis

lipocortin
(inhibits)

phospholipase A
phospholipid arachidonic acid

leukotrienes prostaglandins
 Classification of Severity-
GINA
CLASSIFY SEVERITY
Clinical Features Before Treatment

Symptoms Nocturnal FEV1 or PEF

Symptoms

STEP 4 Continuous 60% predicted

Severe Limited physical Frequent Variability > 30%
Persistent activity

Daily 60 - 80% predicted

STEP 3
Attacks affect activity > 1 time week Variability > 30%
Moderate
Persistent

STEP 2 80% predicted

> 1 time a week > 2 times a month
Mild Variability 20 - 30%
Persistent but < 1 time a day

< 1 time a week

STEP 1 Asymptomatic and 80% predicted
22 times
times aa month
month
Intermittent normal PEF Variability < 20%
between attacks

The presence of one feature of severity is sufficient to place patient in that category.
 Stepwise Approach to Asthma Therapy - Adults

Outcome: Asthma Control Outcome: Best

Possible Results

Controller:
 Daily inhaled
corticosteroid
 Daily long –acting
Controller:  When asthma is
inhaled β2-agonist controlled,
Controller:  Daily inhaled  plus (if needed) reduce therapy
Controller: corticosteroid
Daily inhaled
None
 Daily long-acting
corticosteroid  Monitor
inhaled β2-agonist
-Theophylline-SR
-Anti-Leukotriene
-Long-acting inhaled
β2- agonist
-Oral corticosteroid

Reliever: Rapid-acting inhaled β2-agonist prn

STEP 1: STEP 2: STEP
STEP 3:3: STEP 4: STEP
Moderate
Moderate Severe STEP Down
Down
Intermittent Mild Persistent
Persistent
Persistent Persistent
 New GINA guidelines:
Focus on Asthma Control rather than severity
Characteristic Controlled Partly Controlled Uncontrolled
(All of the (Any measure
following) present in any
week)
Daytime symptoms None (twice or More than
less/week) twice/week
Limitations of None Any
activities
Three or more
Nocturnal None Any features of partly
symptoms/awakenin controlled
g asthma present
Need for None (twice or More than in any week
reliever/rescue less/week) twice/week
treatment
Lung function Normal < 80% predicted or
(PEF or FEV1) personal best (if
known)
Exacerbations None One or more/year One in any week
Global Initiative for Asthma (GINA) 2006
 MANAGEMENT APPROACH BASED ON CONTROL

Level of control Treatment Action

Reduce

Controlled Maintain and find lowest

controlling step

Partly controlled Consider stepping up to

gain control

Uncontrolled Increases Step up until controlled

Exacerbation Treat as exacerbation

Treatment Steps
 The New Dimension
In
ASTHMA
CONTROLLERS

Combination Therapy
 THE CHANGE IN VIEW OVER YEARS
Time Period Goal of Management Preferred Medication

1960’s Relieve Epinephrine,

Bronchospasm Salbutamol,
Levosalbutamol

1990’s Prevent and resolve Inhaled

inflammation glucucorticosteroids
Leukotriene modifiers

2000’s Resolve symptoms Combination of ICS

and disease process and LABAs
• It is now well accepted that asthma is an
inflammatory diseases of the airways
• The bronchoconstriction that gives rise to
dyspnoea is effect of the inflammatory
process.

• It is no longer considered sufficient to treat the

episodes of respiratory distress as and when
they occur except in very mild cases.

• Shift in the focus of treatment

Bronchodilator Anti-inflammatory

Indian Pediatr 1998; 35: 871-881

Inhaled steroids and risk of death
(NEJM, 2000)
 Factor for Poor response to
inhaled corticosteroids
• No immediate symptomatic relief
• Resulting in low rates of compliance
• No benefit in increasing the dose of ICS
beyond a particular dose
• Flat dose – response curve
• Local side effects (hoarseness, URTIs)
• Systemic side effects (cataracts / growth
retardation/ osteoporosis)
 Flat Dose Response of ICS

Favorable Benefiit-Risk Ratio

R Wanted E
ffects
e
s
p

cts
o

Effe
n

ed
a nt
s

Unw
e

1600mcg Dose
budesonide
 Combination Therapy

Use of ICS and LABA is accepted

as the most effective treatment
regime to control moderate and
severe asthma
 Rationale for Combination
Therapy
A fixed dose combination of a
long-acting beta2-agonist and
an inhaled corticosteroid
 Complementary Action

• Corticosteroids and LABA act on two different

components of asthma.
• Inflammation can be taken care of by steroids
and
• Abnormalities in the bronchial smooth muscle
by LABA.
 Synergistic Activity

• Beta2-agonists are potent activators of

the GC receptor.
• In addition, regular use of inhaled
corticosteroids helps in increasing the
activity of Beta 2-agonists
1) ICS enters the cell membrane, targets the intracellular
inactive steroid receptor and binds to it
2) This leads to formation of an active receptor complex
…..which then binds to a target gene and the result is
anti-inflammatory activity.
4) Synthesis of beta-2 receptor protein which is then
inserted in the cell membrane.
5) LABA interacts with this membrane
associated beta-2 receptor
 6) The subsequent beta-2 submit then interacts with the
inactive corticosteroid receptor leading to a priming of
the receptor. This primed receptor is more susceptible to
activation with steroids and importantly it requires less
steroid then to convert the primed receptor to the active
receptor
 Co deposition

Co-deposition of LABA and steroid

when administered in a single inhaler.
 Flat Dose Response

• Inhaled steroids have a flat dose

response curve. Thus, addition of LABA
to a low dose of inhaled steroid is an
attractive therapeutic option to increasing
the dose of steroid.
 Guidelines

• Prevents tolerance development

• Use of such a combination is in
accordance with current guidelines for
the management of asthma
 Patient Compliance

• Simplifies therapy
• Improves compliance since only one
inhaler is used
 Reduced Cost

• Reduces cost of therapy due to better

control of asthma and a better quality of
life
Rationale of Combination Therapy-RECAP
• Complementary Action
• Synergistic Action
• Co- Deposition
• Taking care of Flat Dose Response
• Guidelines Recommendation
• Patient Compliance
• Reduced Cost
 Combination therapy

• Formoterol ( fast relief and sustained relief )

• Budesonide ( twice or even once daily use )

Dose: 1- 4 inhalations ( OD/BD )

 Combination therapy
• salmeterol (sustained relief )

• fluticasone ( 3 times more potent than

budesonide )

Dose: 1- 2 inhalations (BD )

 Combination therapy
• Formoterol ( fast relief and sustained relief )

• Ciclesonide ( the ideal ICS )

Dose: 1- 4 inhalations ( OD/BD )

 Airway Remodeling

• Permanent structural changes in the airway wall

which are irreversible.
• Increased mucus production
• Fibrosis
• Neovascularization
 Goals of Asthma Therapy
• Minimal (ideally no) chronic symptoms

• Minimal (ideally no) need for “as needed” use of relievers

• No emergency visits

• (Near) normal PEF

• Minimal (infrequent) exacerbations

• PEF circadian variation of less than 20 percent

• No limitations on activities, including exercise

• Minimal (or no) adverse effects from medicine

 MUST KNOW

• Routes of administration of anti-asthma drugs

• Advantages of inhalation therapy over oral route

• Drug therapy for asthma

• Differences between relievers and controllers

• Cipla’s available relievers & controllers