Asthma

AKHILESH SINGH
MCE-PRIDE
LUCKNOW
1

For use of a registered medical practitioner only

Overview of Presentation
Introduction
Epidemiology of asthma
Pathophysiology
Diagnosis of asthma
Management of asthma
2

Introduction

Asthma
is a Greek word which means
breathless or
to breathe with open mouth

Murthy K. NCMH-Background papers-Burden of diseases in India, 2005

Asthma
No uniform agreement on the
definition of asthma.

GINA (Global Initiative for Asthma )

definition is most widely
accepted.........

ASTHMA is chronic inflammatory

disorder of airways associated with
Airway hyper-responsiveness
Widespread variable airflow obstruction
in the lung

Recurrent episodes
of
Airway obstruction is
Wheezing,
Breathlessness,
reversible
Chest tightness
either spontaneously
and
or with treatment
6

Coughing,
particularly at night
Busse et al. J Allergy Clin Immunol 2007.120, (5):S94-S138
or early morning

Epidemiology

Epidemiology
Global Burden of Asthma
Estimated 300 million patients worldwide with asthma
Global prevalence ranges from 1-18% of population in
different countries
WHO estimate 15 million Disability adjusted life
years (DALYs) are lost annually
Annual worldwide deaths from asthma estimated at
250,000

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Epidemiology
Asthma morbidity in Asia*
Activity limitations in asthma patients

% of patients
with activity
limitations

* China, Hong Kong, India, Indonesia, Korea, Malaysia, Philippines, Singapore,

Lanka, Taiwan,
Lai C et al.Sri
Respirology
2011;16:
Thailand
and
Vietnam
Total patients = 4805
688697

Epidemiology
Prevalence in India
Estimates of prevalence rates of chronic asthma by age
(cases/ 100,000 persons)

Year

Locality

<15
years

15-59
years

60
years
and
above

2011

Urban

861

1865

8,628

Rural

1024

2615

11,747

Urban

874

1892

8,752

Rural

1039

2653

11,917

2016
(projected)

10

Murthy K. NCMH-Background papers-Burden of diseases in India, 2005

Epidemiology
Estimates of Economic burden
of asthma in India (Rs. in crores)
Year

Chronic

Acute

Total

1996
2001
2006
2011
2016

960.05
1543.74
2294.73
3197.60
4180.35

167.07
267.63
388.84
528.84
672.52

1127.12
1811.37
2683.57
3726.44
4852.86

(Estimated)

11

Murthy K. NCMH-Background papers-Burden of diseases in India, 2005

Pathophysiology of Asthma

12

Pathophysiology of Asthma
Airflow limitation caused by a variety of changes in airway
Bronchoconstrictionbronchial smooth muscle
contraction that quickly narrows airways in response to
exposure to a variety of stimuli, including allergens or
irritants.
Airway hyperresponsivenessan exaggerated
bronchoconstrictor response to stimuli.
Airway edemaas the disease becomes more persistent
and inflammation becomes more progressive, edema,
mucus hypersecretion, and formation of inspissatedmucus
plugs further limit airflow.

13

Busse et al. J Allergy Clin Immunol 2007.120, (5):S94-S138

Pathophysiology of Asthma
Causes
Interplay between host factors (particularly genetics) and
environmental exposures
Genetics - Asthma has an inheritable component, but genetics
involved remain complex.
Innate immunity - Hygiene hypothesis

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certain infections early in life,

exposure to other children,
less frequent use of antibiotics and/or
and country living

If yes,

If no,

TH1 response
and
lower incidence
of asthma

persistent TH2
response and
higher rates
of asthma

Busse et al. J Allergy Clin Immunol 2007.120, (5):S94-S138

Continued
Environmental factors
Airborne allergens
Viral respiratory infections
Tobacco smoke
Air pollution (ozone and particulate matter),
Diet (obesity or low intake of antioxidants and
-3 fatty acids)

15

Busse et al. J Allergy Clin Immunol 2007.120, (5):S94-S138

Link between asthma & allergic rhinitis (AR)

United airways disease
40% patients with AR have comorbid asthma.
80% patients with asthma have nasal symptoms.
AR is a risk factor for asthma exacerbations.
ARIA (Allergic Rhinitis & its Impact on Asthma)
guidelines , 1999-2010 suggest - Treat the AR &
asthma together.

16

Corren J. J Allergy Clin Immunol 1997; 99: S781-6

Diagnosis of Asthma

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Diagnosis of asthma
Detailed medical history
Physical examination
Lung function testing: FEV1, FVC, PEF
Noninvasive markers of airway inflammation: FeNO,
FeCO, etc.
Measures of allergic status: Allergen skin test,
serum-IgE

FEV1 - Forced expiratory volume in 1 second,

FVC Forced vital capacity, FeNO Fractional Exhaled Nitric oxide,
PEF Peak expiratory flow, FeCO Fractional Exhaled Carbon Monooxide
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GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Lung function testing

Airflow obstruction is at least partially reversible,
measured by spirometry.
FEV1
Improvement 12% & 200ml from
prebronchodilator value is suggestive of asthma

Some studies indicate that an increase of 10% of

the predicted FEV1 after inhalation of a SABA may
have higher likelihood of separating patients who
have asthma from those who have COPD.

19

Busse et al. J Allergy Clin Immunol 2007.120, (5):S94-S138

Management of Asthma

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Asthma treatments
Inhaled therapy: Drug delivered directly into
the airway, high local concentration, less
risk of systemic side effects.
Delivery of inhaled drug:

Pressurized Metered Dose Inhalers (pMDIs)

Dry Powder inhalers (DPIs)
Nebulizers
Spacers (used with MDI)

Inhalers differ in their drug delivery to the

lower respiratory tract & ease with which a
patient can use the device.
21

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Asthma pharmacotherapy
Quick relievers: Act quickly to provide symptom relief,
bronchodilation, as needed basis.
Short acting inhaled beta 2-adrenoceptor agonists
(SABA): Salbutamol
Systemic glucocorticosteroids
Anticholinergics
Theophylline
Short acting oral beta 2-adrenoceptor agonists

22

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Continued
Controllers: Long term basis, daily, antiinflammatory
effect.
Inhaled corticosteroids (ICS): Fluticasone, Budesonide,
beclomethasone propionate
Long acting inhaled beta 2-adrenoceptor agonists
(LABA): Salmeterol, Formoterol (never use as
monotherapy)
Theophylline
Leukotriene modifiers
Long acting oral beta 2-adrenoceptor agonists
Cromones
Anti-IgE (omalizumab)
Oral glucocorticosteroids
Allergen specific immunotherapy
23

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

GINA Asthma Guidelines 2011

Levels of asthma control (preferably over 4 weeks)
Partly controlled
Outcome

Controlled

(any measure present in

any week)

Daytime symptoms

None or (twice or
less/week)

>twice a week

Limitations of
activities

None

Any

Nocturnal symptoms
or awakening

None

Any

Need for reliever

rescue

None or minimal
(twice or less/week)

>twice a week

Normal

< 80% predicted or

personal best on any
day

Lung function
(FEV1 or PEF)
24

Uncontrolled

Three or more
features of partly
controlled asthma
present in any week

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Management of Acute exacerbation

Oxygen to achieve 90% saturation ( 95%
in children)
Inhaled rapid acting 2 agonist
Systemic glucocorticoids
Sedation is contracted in treatment of
exacerbation
Intravenous magnesium, 2 agonist,
theophylline
Possible intubation and mechanical
ventilation
25

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Instruments for measuring

Asthma Control
Asthma Control Test (ACT)
Asthma Control Questionnaire (ACQ)
Asthma Therapy Assessment Questionnaire
(ATAQ)
Asthma Control Scoring System (ACSS)

26

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Patient education

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Patient education
Patients should be educated about
Difference between relievers and controllers
Potential side effects of medications
Use of inhaler devices
Prevention of symptoms and attacks
Signs that suggest asthma is worsening and actions to
take
Monitoring control of asthma
How and when to seek medical attention
28

GINA Report, Global Strategy for Asthma Management and Prevention http://www.ginasthma.org/ accessed on 13/01/12

Local Indian Guidelines

(Asthma, COPD, Training Modules)
Developed under WHO Govt. of India
Biennium Programmes (2003, 2005,
2007)
Available at:
www.indiachest.org

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30

For the use of Registered Medical Practitioners only

Abbreviated prescribing information for SERETIDETM ACCUHALERTM
Salmeterol and Fluticasone Propionate Accuhaler
Active Ingredient: Seretide Accuhaler 100, 250 and 500 is available as a moulded plastic device containing a
foil strip with 60 blisters, each contains powder for inhalation providing Salmeterol Xinafoate IP equivalent to 50
mcg Salmeterol and Fluticasone Propionate IP, 100mcg, 250mcg and 500mcg respectively. Indications: Regular
treatment of bronchial asthma, where use of a bronchodilator and an inhaled corticosteroid are appropriate
including patients on effective maintenance doses of long-acting -agonists and inhaled corticosteroids, patients
who are symptomatic on current inhaled corticosteroid therapy and patients on regular bronchodilator therapy
who require inhaled corticosteroids. Regular treatment of Chronic Obstructive Pulmonary Disease (COPD)
including chronic bronchitis. Dosage and Administration: Bronchial asthma: Adults and adolescents 12
years and older: One inhalation of 50/100, 50/250 or 50/500mcg twice daily. Adults 18 years and older:
Doubling the dose of all strengths of Seretide for up to 14 days when additional short term inhaled corticosteroid
therapy is needed. Children 4 years and older: One inhalation of 50/100mcg twice daily. No data available for
use in children under 4 years. COPD: For adult patients, one inhalation 50/250 mcg to 50/500 mcg twice daily.
Special patient groups: No need to adjust the dose in elderly patients or in those with renal or hepatic
impairment. Administration: For inhalation only. Use regularly for optimum benefit, even when asymptomatic.
Doctor should regularly reassess the patient. In bronchial asthma, dose should be titrated to the lowest dose
(could include once daily dosage) at which effective control of symptoms is maintained. Contraindications:
History of hypersensitivity to any of the ingredients. Warnings and Precautions: Not indicated for relief of
acute symptoms. Patients should have their relief medication available at all times and should be reviewed by a
physician if increasing use of short-acting bronchodilators to relieve symptoms, sudden and progressive
deterioration in asthma control, increasing corticosteroid therapy or current dosage of Seretide fails to give
adequate control of reversible obstructive airways disease. Additional corticosteroids and antibiotics for infective
exacerbations of asthma or COPD. Do not stop treatment abruptly in asthma due to risk of exacerbation; titrate
down under physician supervision. In COPD, cessation of therapy may be associated with symptomatic
decompensation, should be supervised by a physician. Possibility of pneumonia in patients with COPD.
Administer with caution in active or quiescent pulmonary tuberculosis, thyrotoxicosis, pre-existing cardiovascular
disease, those predisposed to hypokalemia. High doses prescribed for long periods may result in Cushings
syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in
bone mineral density, cataract and glaucoma. Impaired adrenal response in emergency and elective situations
that are likely to produce stress. Consider appropriate corticosteroid treatment. Monitor adrenocortical function
regularly in patients transferring from systemic corticosteroid therapy to inhaled fluticasone propionate. Monitor
height of children regularly in case of prolonged treatment. Very rare reports of increase in blood glucose levels;
to be considered in diabetes mellitus. Concomitant use of fluticasone propionate and ritonavir should be avoided
unless the potential

benefit to the patient outweighs the risk of systemic corticosteroid side-effects. African-American patients
may be at greater risk of serious respiratory-related events or deaths. Caution should be exercised when coadministered with strong CYP3A4 inhibitors (e.g. ketoconazole). Interactions: Avoid -blockers (unless
compelled to use). Inhibitors of P450 3A4 can produce great increase (ritonavir), minor increase
(ketoconazole), negligible increase (erythromycin) in systemic exposure to fluticasone propionate.
Ketoconazole can significantly increase plasma salmeterol exposure. Effects on Ability to Drive and Use
Machines: None noted. Pregnancy and Lactation: Use if the expected benefit to the mother is greater
than any possible risk to the foetus or child. Adverse Reactions: Paradoxical bronchospasm, tremor, cardiac
arrhythmias (atrial fibrillation, supraventricular tachycardia, extrasystoles), Cushings syndrome, Cushingoid
features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral
density, cataract and glaucoma. Common: muscle cramps, hoarseness/dysphonia, oropharyngeal irritation,
headache (transient, reduce with regular therapy), candidiasis (thrush) of the mouth and throat, palpitations,
pneumonia (in COPD patients).Uncommon: rash, contusions, cutaneous hypersensitivity reactions. Rare:
hypersensitivity reactions (angioedema, mainly facial and oropharyngeal oedema), respiratory symptoms
(dyspnoea and/or bronchospasm). Very rare: arthralgia, hypersensitivity reactions (anaphylactic reactions
such as oedema, angioedema, bronchospasm, anaphylactic shock), hyperglycemia, anxiety, sleep disorders
and behavioural changes, including hyperactivity and irritability (predominantly in children). Overdosage:
Salmeterol: Tremor, headache, tachycardia, increases in systolic blood pressure and hypokalaemia.
Antidote: Cardioselective -blocking agents, use with caution in patients with a history of bronchospasm. If
Seretide needs to be withdrawn, provide appropriate replacement corticosteroid therapy. Fluticasone
propionate: May lead to temporary suppression of the hypothalamic-pituitary-adrenal axis, does not usually
require emergency action as normal adrenal function typically recovers within a few days.
Salmeterol/Fluticasone propionate: If higher than approved doses are continued over prolonged periods,
significant adrenocortical suppression is possible. Very rare reports of acute adrenal crisis (potential triggers:
trauma, surgery, infection or any rapid reduction in the dosage of the inhaled fluticasone propionate
component) mainly in children exposed to higher than approved doses over prolonged periods (several
months or years). Observed features include hypoglycaemia associated with decreased consciousness and/or
convulsions. Patients should not receive higher than approved doses of Seretide. Review therapy regularly
and titrate down to the lowest approved dose at which effective control of disease is maintained.
Refer to full prescribing information before use.
Full
prescribing information available on request from GlaxoSmithKline Pharmaceuticals Ltd., Dr. Annie
Besant Road, Worli, Mumbai- 400030.
Version: SER/API/IN/2009/01 v02 dated 15 June 2011
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IN/SFC/0029/12

Valid upto March 2014