Asthma

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

3
 ‘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

4
 Asthma

• No uniform agreement on the definition of

asthma.

• GINA (Global Initiative for Asthma ) definition is

most widely accepted.........

5
 ASTHMA is chronic inflammatory disorder of
airways associated with
Airway hyper-responsiveness
Widespread variable airflow obstruction in
the lung

Recurrent episodes of
• Wheezing,
• Breathlessness, Airway obstruction is
• Chest tightness and reversible
• Coughing, either spontaneously or
particularly at night or with treatment
early morning

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

 Epidemiology

7
 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

8 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, Sri Lanka, Taiwan, Thailand and Vietnam
9 Total patients = 4805 Lai C et al. Respirology 2011;16: 688–697
 Epidemiology
Prevalence in India
Estimates of prevalence rates of chronic asthma by age
(cases/ 100,000 persons)

Year Locality <15 years 15-59 60 years

years and above

2011 Urban 861 1865 8,628

Rural 1024 2615 11,747

2016 Urban 874 1892 8,752

(projected)

Rural 1039 2653 11,917

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

10
 Epidemiology
Estimates of Economic burden
of asthma in India (Rs. in crores)
Year Chronic Acute Total

1996 960.05 167.07 1127.12

2001 1543.74 267.63 1811.37
2006 2294.73 388.84 2683.57
2011 3197.60 528.84 3726.44
2016 4180.35 672.52 4852.86
(Estimated)

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

11
 Pathophysiology of Asthma

12
 Pathophysiology of Asthma
Airflow limitation caused by a variety of changes in airway

• Bronchoconstriction—bronchial smooth muscle contraction

that quickly narrows airways in response to exposure to a
variety of stimuli, including allergens or irritants.

• Airway hyperresponsiveness—an exaggerated

bronchoconstrictor response to stimuli.

• Airway edema—as 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.

If yes, If no,
• Innate immunity - Hygiene hypothesisTH1 response persistent TH2
• certain infections early in life, and response and
• exposure to other children, lower incidence higher rates
of asthma of asthma
• less frequent use of antibiotics and/or
• and country living

14 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 Ω-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.

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

16
 Diagnosis of Asthma

17
 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
18 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

20
 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 Uncontrolled
any week)

None or (twice or
Daytime symptoms >twice a week
less/week)
Limitations of
None Any
activities
Three or more
Nocturnal symptoms features of partly
None Any
or awakening controlled asthma
present in any week
Need for reliever None or minimal
rescue (twice or less/week) >twice a week

< 80% predicted or

Lung function
Normal personal best on any
(FEV1 or PEF)
day

24 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 β2 agonist
• Systemic glucocorticoids
• Sedation is contracted in treatment of
exacerbation
• Intravenous magnesium, β2 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

27
 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

29
 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 Cushing’s 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
30
 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 co-administered 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), Cushing’s 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

31 IN/SFC/0029/12 Valid upto March 2014