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PERSISTENT ASTHMA
MAGDALENA SIDHARTANI
Dept. of Child Health
Faculty of Medicine Diponegoro University
Review PNAA 2004 and GINA 2009 Review PNAA 2004 and GINA 2009
PNAA 2004 PNAA 2004
Infrequent episodic asthma
Frequent episodic asthma
Persistent asthma
Terminology Severity of asthma Terminology Severity of asthma
Intermittent
Mild persistent
Moderate persistent
Severe persistent
GINA 2009
Controlled
Partly controlled
Uncontrolled
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Levels of asthma control Levels of asthma control
Characteristic Controlled Partly controlled uncontrolled
Daytime
symptoms
Twice or
less/week
More than
twice/week
Three or more
features of
party
controlled
asthma present
in any week
Limitation of
activities
None Any
Nocturnal
symptoms/
awakening
None Any
Need for reliever/
rescue
treatment
Twice or
less/week
More than
twice/week
Lung function
(PEF or
FEV1)
Normal < 80% predicted
or personal
best (if
known)
Asthma Asthma
Episodic disease Episodic disease
Dynamic chronic illness Dynamic chronic illness
Variability overtime Variability overtime
Imperfect overlap between symptoms frequency and lung Imperfect overlap between symptoms frequency and lung
function function
Adding lung function measurement Adding lung function measurement change severity change severity
classification classification change treatment change treatment
Needs review and regular monitoring
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Peak expiratory flow (PEF) Peak expiratory flow (PEF)
Inexpensive Inexpensive
Patients can use at home Patients can use at home
May be helpful for patients with severe disease to monitor May be helpful for patients with severe disease to monitor
their change from baseline every day their change from baseline every day
Not recommended for all patients with mild or moderate Not recommended for all patients with mild or moderate
disease to use every day at home disease to use every day at home
Effort and technique dependent Effort and technique dependent
Should not be used to make diagnosis of asthma Should not be used to make diagnosis of asthma
Lung Function Measurement Lung Function Measurement
Spirometry
Recommended to do spirometry pre Recommended to do spirometry pre-- and post and post-- use use
of an albuterol MDI to of an albuterol MDI to assess assess reversibility of airflow reversibility of airflow
obstruction obstruction
>> 12% reversibility 12% reversibility // increase FEV1 of 200cc is increase FEV1 of 200cc is
significant significant
Obstructive pattern: reduced FEV1/FVC ratio Obstructive pattern: reduced FEV1/FVC ratio
Restrictive pattern: reduced FVC with a normal Restrictive pattern: reduced FVC with a normal
FEV1/FVC ratio FEV1/FVC ratio
Lung Function Measurement Lung Function Measurement
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Spirometry
TTo identify reversible airway obstruction due to o identify reversible airway obstruction due to
triggers triggers
To To diagnose Exercise diagnose Exercise--induced asthma (EIA) or induced asthma (EIA) or
Exercise Exercise--induced bronchospasm (EIB) by measuring induced bronchospasm (EIB) by measuring
FEV1/FVC before FEV1/FVC before and after and after exercise, then for 5 exercise, then for 5--10 10
minute intervals over 20 minute intervals over 20--30 minutes looking for 30 minutes looking for
post post--exercise bronchoconstriction exercise bronchoconstriction
Lung Function Measurement Lung Function Measurement
Goals in Asthma Control Goals in Asthma Control
Achieve and maintain control of symptoms Achieve and maintain control of symptoms
Prevent asthma episodes or attacks Prevent asthma episodes or attacks
Minimal use of reliever medication Minimal use of reliever medication
No emergency visits to doctors or hospitals No emergency visits to doctors or hospitals
Maintain normal activity levels, including exercise Maintain normal activity levels, including exercise
Maintain pulmonary function as close to normal as Maintain pulmonary function as close to normal as
possible possible
Minimal (or no) adverse effects from medicine Minimal (or no) adverse effects from medicine
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Evolving asthma treatment options Evolving asthma treatment options
1975
1980
1985
1990
1995
2000
Large use of
short-acting

2
-agonists
Fear of
short-acting

2
-agonists
Single
inhaler therapy
ICS treatment
introduced
1972
Adding
LAA to ICS therapy
Kips et al, AJRCCM 2000 Pauwels
et al, NEJM 1997 Greening et al,
Lancet 1992
Bronchospasm Inflammation Remodelling
Asthma medications Asthma medications: :
Controller
to control / prevent symptoms &/ attack
long term use
anti-inflammations
inhaled steroid, ALTR, SRT, LABA, oral steroid
Inhalation, oral
RReliever eliever
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Corticosteroids, inhaled Corticosteroids, inhaled
budesonide budesonide
Fluticasone Fluticasone
The most effective anti The most effective anti--inflammatory medications inflammatory medications
Improve lung function Improve lung function
Decrease airway hyper Decrease airway hyper--responsiveness responsiveness
Reduce symptoms Reduce symptoms
Decrease frequency and severity of exacerbations Decrease frequency and severity of exacerbations
Improve Quality of Life (QoL) Improve Quality of Life (QoL)
Corticosteroids Corticosteroids
Inhaled Corticosteroids Inhaled Corticosteroids
Anti Anti--inflammatory (but precise MOA not known) inflammatory (but precise MOA not known)
Act locally in lungs Act locally in lungs
Some systemic absorption Some systemic absorption
Risks of possible growth retardation outweighed by Risks of possible growth retardation outweighed by
benefits of controlling asthma benefits of controlling asthma
Not intended to be used as rescue medication
Efficacy Efficacy takes takes 11--2 weeks 2 weeks
Preferred treatment in persistent asthma Preferred treatment in persistent asthma
Corticosteroids Corticosteroids
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http://www.breathingwell.com/images/immagini/health/asthma_therapy/glucocorticosteroids.jpg
Corticosteroids Corticosteroids
MDI with spacer
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Risk Risk- -benefit ratio of steroid benefit ratio of steroid
Benefit
Steroid
dose
Side-effects
Long Long- -A Acting cting B Beta2 eta2- -A Agonists (LABA) gonists (LABA)
Beta2 Beta2--receptors are the predominant receptors in receptors are the predominant receptors in
bronchial smooth muscle bronchial smooth muscle
Stimulate ATP Stimulate ATP--cAMP cAMP relaxation of bronchial relaxation of bronchial
smooth muscle and inhibition of release of smooth muscle and inhibition of release of
mediators of immediate hypersensitivity mediators of immediate hypersensitivity
Inhibits release of mast cell mediators such as Inhibits release of mast cell mediators such as
histamine, leukotrienes, and prostaglandin histamine, leukotrienes, and prostaglandin--D2 D2
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Salmeterol (Serevent) Salmeterol (Serevent)
Salmeterol with fluticasone (Advair) Salmeterol with fluticasone (Advair)
Should only be used as an Should only be used as an additional treatment additional treatment
when patients are not adequately controlled with when patients are not adequately controlled with ICS ICS
Should not be used as rescue medication Should not be used as rescue medication
Can be used Can be used >>4 4 yrs yrs with a DPI with a DPI
Deaths associated with inappropriate use as only Deaths associated with inappropriate use as only
medication for asthma medication for asthma
Long Long- -A Acting cting B Beta2 eta2- -A Agonists (LABA) gonists (LABA)
Inhaled Steroid + LABA Inhaled Steroid + LABA
Adding LABA to BUD Adding LABA to BUD::
RReduces rate of educes rate of mild mild exacerbations exacerbations
RReduces rate of severe educes rate of severe exacerbations exacerbations
I Improves FEV1 mproves FEV1
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ICS + LABA ICS + LABA
Which LABA ? Which LABA ?
Formoterol Formoterol: :
Immediate relief (as fast as Immediate relief (as fast as salbutamol) salbutamol)
12 hours effect 12 hours effect
Can be combined with budesonide Can be combined with budesonide
Formoterol 4.5 ug + Budesonide 100 ug Formoterol 4.5 ug + Budesonide 100 ug
Salmeterol: Salmeterol:
Salmeterol 50 ug + Fluticasone propionate 100 ug or
250 ug
Formoterol + Budesonide combination
the flexible preventer
A
s
t
h
m
a

s
i
g
n
s
Time
2x2 2x2 1x1
1x2 1x2
Quickly
gains control
Maintains
control
Asthma
worsening
Maintains
control
Reduce to
lowest
adequate
dose that
maintains
control
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Leukotriene receptor antagonists Leukotriene receptor antagonists
Leukotriene Leukotriene--mediated effects include: mediated effects include:
Airway edema Airway edema
Smooth muscle contraction Smooth muscle contraction
Altered cellular activity associated with the inflammatory Altered cellular activity associated with the inflammatory
process process
Receptors in airway smooth muscle cells and Receptors in airway smooth muscle cells and
macrophages and on other pro macrophages and on other pro--inflammatory cells inflammatory cells
(including eosinophils and myeloid stem cells) and (including eosinophils and myeloid stem cells) and
nasal mucosa nasal mucosa
Leukotriene receptor antagonists Leukotriene receptor antagonists
No good long No good long--term studies in pediatrics term studies in pediatrics
Montelukast as young as 2 Montelukast as young as 2 yr dose 1 x 4 yr dose 1 x 4 5 mg 5 mg; ;
zarfirlukast age 7 zarfirlukast age 7 yr dose 2 x 10 mg yr dose 2 x 10 mg
Alternate, but Alternate, but not preferred medication in persistent preferred medication in persistent
asthma and as addition to ICS asthma and as addition to ICS
Showed a statistically significant, but modest Showed a statistically significant, but modest
improvement when used as primary medication improvement when used as primary medication
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Leukotriene Leukotriene
Theophylline Theophylline
Narrow therapeutic index Narrow therapeutic index, m , maintain 5 aintain 5--20 mcg/mL 20 mcg/mL
Sustained release Theophylline (SRT) 5 Sustained release Theophylline (SRT) 5- - 10 mcg/mL 10 mcg/mL
Variability in clearance leads to reach a therapeutic dose Variability in clearance leads to reach a therapeutic dose
Mechanism of action Mechanism of action
Smooth muscle relaxation (bronchodilation) Smooth muscle relaxation (bronchodilation)
Suppression of the response of the airways to stimuli Suppression of the response of the airways to stimuli
Increase force of contraction of diaphragmatic muscles Increase force of contraction of diaphragmatic muscles
Interacts with many other drugs Interacts with many other drugs
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Mast cell stabilizers Mast cell stabilizers
(cromolyn/nedocromil) (cromolyn/nedocromil)
Inhibits release of mediators from mast cells Inhibits release of mediators from mast cells
(degranulation) after specific antigens exposure (degranulation) after specific antigens exposure
Blocks Ca2+ ions from entering the mast cell Blocks Ca2+ ions from entering the mast cell
Safe for pediatrics (including infants) Safe for pediatrics (including infants)
Should be started 2 Should be started 2--4 weeks before allergy season 4 weeks before allergy season
Can be used before exercise (not as good as ICS) Can be used before exercise (not as good as ICS)
Alternate Alternate th/ th/ for persistent asthma for persistent asthma
CONTROLLERS CONTROLLERS
Corticosteroids
Prednisolone, Betamethasone
Beclomethasone, Budesonide
Fluticasone
Combinations
Salmeterol/Fluticasone
Formoterol/Budesonide
Salbutamol/Beclomethasone
Mast Cell Stabilisers
Sodium Cromoglycate
Anti-leukotrienes
Montelukast, Zafirlukast
Xanthines
SR Theophylline
Long acting 2 agonists
Salmeterol
Formoterol
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Low dose steroid
Medium dose
steroid
Low dose
steroid + LABA
Low dose
steroid + ALTR
Low dose
steroid +TSR
High dose
steroid
Medium dose
steroid + LABA
Medium dose
steroid + ALTR
Medium dose
steroid + TSR
ORAL STEROID
Longterm asthma management
UKK RESPIROLOGI
GINA updated 2009
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Step down Step down
Wheeze free and well for three Wheeze free and well for three
months: months:
Oral steroid Oral steroid
1 mg/kgBW/month, then 1 mg/kgBW/month, then
SRT SRT
Inhaled steroid: 50 Inhaled steroid: 50-- 100ug/2 100ug/2--4 4
weeks weeks
lung function
monitoring
Interrelated Asthma Management Interrelated Asthma Management
1. Guided self 1. Guided self--management education & management education &
communication communication
Written Written
Problem review Problem review
Coordination & support Coordination & support
2. Asses & monitor asthma (PEFR) 2. Asses & monitor asthma (PEFR)
3. Environmental control measures 3. Environmental control measures
4. Medication plan (accommodate variability 4. Medication plan (accommodate variability
among & within patients) among & within patients)
5. Plan for acute management 5. Plan for acute management
6. Regular follow 6. Regular follow--up care up care
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5 Rs EDUCATION 5 Rs EDUCATION
1. Reach agreement of goals
2. Rehearse skills
3. Repeat messages
4. Reinforce
5. Review
( Taggart, 2001)
THANK THANK
YOU.... YOU....
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CURRICULUM VITAE
Nama : Prof. dr. Magdalena Sidhartani Zain, MSc, Sp.AK
Tempat/tgl lhr: Yogyakarta, 1 Agustus 1946
Alamat : Jl. Pierre Tendean 17 Semarang
Riwayat Pendidikan
SD Keluarga, Kudus, lulus 1958
SMP Keluarga, Kudus, lulus 1961
SMA Sedes Sapientiae, Semarang, lulus1964
Dokter Umum, FK. UNDIP, lulus 1973
Dokter Spesialis Anak, FK. UNDIP, lulus 1983
Dokter Spesialis Anak Konsultan Paru, FKUI-MPPDS IDAI 1992
M.Sc Clinical Epidemiology, Bangkok 1994
PELATIHAN
Internasional
1. Clinical Training for Consultant on Acute Respiratory Infections.
Bangkok, 1991.
2. Pediatric Pulmonology, Vrije Universiteit Amsterdam. Amsterdam,
1995
3. Workshop on Technology Assesment and Management Tools.
Thailand, 1998
4. Strategic Planning for Clinical Epidemiology Unit. Manila. 1999
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Nasional
1. Workshop of Building Linkages Socialization of ICDC project in the West Region.
Palembang,2000
2. Workshop on Curriculum Development and Revision. FK Undip Semarang, 2001
3. Workshop on Evidence Based Medicine. FKUI-FK Undip Semarang, 2001
4. Advanced Pediatric Resuscitation Course. PP IDAI. Semarang, 2002
5. TOT Pembuatan OSCA untuk Uji Kompetensi Tenaga Kesehatan. Semarang, 2003
6. Diagnostic Test for Respiratory Syncytial Virus. WHO-Unpad. Bandung, J2003
7. Pentaloka Penulisan Artikel Ilmiah Kesehatan. Depkes RI. Semarang, 2003
8. National workshop on Integrated Pharmacotherapy Teaching for Medical Undergraduate. 2004
9. Quality Assurance for Medical Education. FK Undip Semarang, 2004
10. Pelatihan Vaksinologi PP IDAI-IDAI Jateng. Semarang, 2006
11. Komite Nasional Etik Penelitian Kesehatan (KNEPK) dengan Komisi-Komisi Etik Penelitian
Kesehatan (KEPK). Semarang, 2006
12. Lokakarya Penyusunan KurikulumBerbasis Kompetensi. FK Undip. Semarang, 2006
13. Pelatihan tutor BBDM. FK UNDIP. Semarang, 2006
14. Lokakarya Nasional Kejadian Ikutan Pasca Imunisasi (KIPI). Jakarta, 2007
15. Lokakarya Contributing Editor Paediatrica Indonesiana., Jakarta 2007