Download Global Initiative for Asthma

CURRICULUM VITAE
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Nama : dr. Muh.Ilyas, Sp.PD, KP, Sp.P (K), FINASIM
Alamat : Jl. Satando 2 No. 8 Makassar. HP 081381803153
[email protected] / [email protected]
• Pendidikan :
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Dr. Umum (FK UNHAS)
Spesial Penyakit Dalam Pasca Sarjana FK Universitas Hasanuddin
Spesialis Paru dan Kedokteran Di FK Universitas Indonesia
Konsultan Paru & FINASIM : Kolegium Penyakit Dalam Indonesia
Konsultan Asma dan PPOK : Kolegium Pulmonologi Indonesia
Pekerjaan dan Organisasi :
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Staf Divisi Paru dan Perawatan Keritis Respirasi Dept. Ilmu Penyakit Dalam FK UNHAS
Staf Infection Centre , SMF Penyakit Dalam dan SMF Paru RSUP Dr. Wahidin Sudirohusodo
Ketua Program Studi Pulmonologi & Kedokteran Respirasi FK UNHAS
Anggota Kolegium Pulmonologi dan Kedokteran Respirasi Indonesia
Ketua Umum Perhimpunan Dokter Paru (PDPI) Sulawesi dan KTI
Core Team POKJA Asma-PPOK Pengurus Pusat PDPI
Pimpinan Pusat Perhimpunan Kedokteran Haji Indonesia (PERDOKHI)
Sekretaris PERPARI Cab. Makassar
Wakil Ketua Perhimpunan Alergi Imunologi (PERALMUNI) Makassar
“GINA and GOLD recommendation in
emergency use of systemic
corticosteroid to improve quality of
life Asthma and AECB patient”
MUHAMMAD ILYAS
PULMONOLOGY DIVISION DEPARTEMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE UNIVERSITY OF HASANUDDIN
Dr.WAHIDIN SUDIROHUSODO HOSPITAL
MAKASSAR
Definition of Asthma

A chronic inflammatory disorder of the airways

Many cells and cellular elements play a role

Chronic inflammation is associated with airway
hyperresponsiveness that leads to recurrent
episodes of wheezing, breathlessness, chest
tightness, and coughing

Widespread, variable, and often reversible
airflow limitation
© Global Initiative for Asthma
Burden of Asthma

Asthma is one of the most common chronic diseases
worldwide with an estimated 300 million affected
individuals

Prevalence increasing in many countries, especially in
children

A major cause of school/work absence

Poorly controlled asthma is expensive; investment in
prevention medication likely to yield cost savings in
emergency care
The prevalence of asthma in
Indonesia ranges from 5-7%
© Global Initiative for Asthma
Asthma Inflammation: Cells and Mediators
Allergen
Macrophage
Mast cell
Th2 cell
Neutrophil
Eosinophil
Mucus plug
Nerve activation
Epithelial shedding
Subepithelial
fibrosis
Plasma leak
Oedema
Mucus
hypersecretion
hyperplasia
Vasodilatation
New vessels
Source: Peter J. Barnes, MD
Sensory nerve
activation
Cholinergic
reflex
Bronchoconstriction
Hypertrophy/hyperplasia
The Development of Airway Inflammation and
Hyperresponsiveness
Immunologic
stimuli (antigen)
Cell activation
Nonimmunologic
Stimuli (viral infection,
Physical and chemical
stimuli)
Inflammatory mediators
Smooth muscle contraction
chemotaxis
Mast cells
Epithelial cells
Macrophage
Eosinophils
Lymphocytes
Autonomic
nervous
System
-Axon reflex
-Neuropeptides
Granulocytic responses:
Neutrophils
Eosinophils
Basophils
Activated mononuclear cells
Macrophages
Lymphocytes
Inflammatory mediators
Airway edema
Cellular infiltration
Subepithelial fibrosis
Mucous secretion
Mucosal and vascular
permeability
Airways hyperresponsiveness
asthma
PATHOGENESIS OF ASTHMA SYMPTOM
Airflow limitation (hambatan saluran napas)
Usually reverses spontaneously or with
treatment
Pathology
Airway hyper-responsiveness. Exaggerated
bronchoconstriction to a wide range of nonspecific stimuli e.g. exercise, cold air
Airway inflammation
associated edema, smooth muscle hypertrophy and
hyperplasia, thickening of basement membrane,
mucous plugging, epithelial damage
Asthma worsenings
Asthma Worsening period  almost 90 % (mean 11.8/year)1
Uncontrolled (n= 1732)
Not well controlled (n=714)
Well controled (n=965)
0
5
10
15
20
NO. OF WORSENINGS/PATIENT/YEAR
1. Asthma worsenings: Approaches to prevention and management from the Asthma Worsenings Working Group,
Can Respir J Vol 15 Suppl B November/December 2008
Management of Asthma
What are the current asthma
management goals?
Global Initiative for Asthma (GINA) guidelines state that asthma
management should:

Achieve and maintain control of symptoms

Maintain normal activity levels, including exercise

Maintain pulmonary function as close to normal levels
as possible

Prevent asthma exacerbations

Avoid adverse effects from asthma medications

Prevent asthma mortality
Global Strategy for Asthma Management and Prevention Global Initiative for Asthma (GINA) updated 2012
Available from : http//www,ginaasthma.org. Accessed on Jan 27,2014
Clinical Practice Guidelines
• Some guidelines available:
o
o
o
o
NAEPP: National Asthma Education and Prevention Program (USA)
GINA: Global Initiative for Asthma (International)
CTS: Canadian Thoracic Society (Canada)
BTS: British Thoracic Society (UK)
• All guidelines are supported by high quality evidence, especially
in therapy (randomized control trials and Cochrane reviews)
• Most guidelines are consistent for acute asthma
GINA Guidelines for Management of Asthma Exacerbations
Adapted from Global Initiative For Asthma (GINA). Global Strategy for Asthma Management and Prevention. Revised 2014
Asthma Management Continuum for Children
(6 years and over) and Adults
Prednisone
Regularly Reassess
• Control
• Spirometry or PEF
• Inhaler technique
• Adherence
• Triggers
• Co-morbidities
Anti-IgE‡
≥12 yrs: Add LTRA
6-11 yrs: Add LABA or LTRA
≥12 yrs: Add LABA*
6-11 yrs: Increase ICS
Inhaled
Corticosteroid (ICS)*
*Second-Line: Leukotriene Receptor Antagonist (LTRA)
Low Dose
Medium Dose
≥12 yrs: ≤250 mcg/day†
6-11 yrs: ≤200 mcg/day†
251 – 500 mcg/day †
201 – 400 mcg/day †
Fast-acting Bronchodilator on Demand
Environmental Control, Education and Written Action Plan
Confirm Diagnosis
Controlled
Uncontrolled
* Second-line: LTRA; † HFA Beclomethasone or equivalent; ‡ Approved for 12 years and over
Lougheed D, et al. CRJ. 2010
High Dose
>500 mcg/day †
>400 mcg/day †
Corticosteroid Effect
Structural cells
Inflammatory cells
Numbers
(apoptosis)
Epithelial cell
Eosinophil
Cytokines
mediators
T-lymphocyte
Endothelial cell
Cytokines
Mast cell
Leak
Glucocorticoids
Numbers
Airway smooth muscle
Macrophage
β2-receptors
Cytokines
Mucus gland
Dendritic cell
Mucus
secretion
Numbers
Barnes. JACI 1998
The Role of Corticosteroids and Optimal
Management in an Evolving Asthma Marketplace
• Systemic corticosteroids are effective in reducing admissions
• IV treatment should be restricted to vomiting, obtunded, and
intubated patients. Otherwise, the clinical approach is giving
patients oral treatment
• Earlier use of corticosteroids is better than later
• Treatment of choice for asthma COPD overlap syndrome is
methylprednisolone
Administering corticosteroids as early as possible in
order to achieve a higher beneficial effect
Systemic Corticosteroids Efficacy
Key Therapy for Acute Asthma Exacerbations
Early use of corticosteroids is associated with:
• Reduction in hospitalization rate
• Earlier discharge
• Reduced risk of relapse
The main corticosteroids used for asthma include:
• Prednisone
• Prednisolone
• Methylprednisolone
16
Aggarwal Study: Comparing the Efficacy and Safety of
two regimens of sequential systemic corticosteroids
Emergency Department admission

HC 200 mg q 6 hrs/prednisone 0.75 mg/day X 2 wks
Emergency
Department
Treatment
SABA as required
R
MP 40 mg q 6 hours/MP 0.6 mg/kg X day X 2 wks
SABA as required
Visit:
Days:
1
0
6
Aggarwal P, Bhoi S. J Emerg Trauma Shock 2010
12
D/C
2 weeks
Aggarwal Study: Comparing the Efficacy and Safety of
two regimens of sequential systemic corticosteroids
• Fewer relapses in the MP group (0% vs. 8%; p = 0.24)
• More hyperglycemia in the HC group (+ 36.7 vs. + 8.6 mg/dL; p <0.001)
• More hypertension in the HC group (+2.8 vs. -4.7 mmHg; p =< 0.0087)
Group A = intravenous HC followed by oral prednisolone
Group B = intaravenous MP followed by oral MP
Aggarwal P, Bhoi S. J Emerg Trauma Shock 2010
Aggarwal Study: Comparing the Efficacy and Safety of
two regimens of sequential systemic corticosteroids
The Aggarwal study demonstrated:
o Higher efficacy and safety of IV methylprednisolone followed by
oral methylprednisolone when compared to IV hydrocortisone
followed by oral prednisone in hospitalized asthma patients
o Therefore, IV methylprednisolone followed by oral
methylprednisolone may comprise the treatment of choice for
acute bronchial asthma
Impact of Systemic Corticosteroids at Emergency
Department Discharge
50%
Systemic corticosteroids
Placebo
P=.05
% Experiencing
40%
36,4%
P=.05
30%
21,0%
20%
15,6%
10%
5,9%
0%
Need for Repeat Emergency Care
Fiel SB, et al. Am J Med. 1983;75:259-262.
Symptoms
20
Meta-analysis of Benefit of Early Use of Systemic Steroids
5
2
1
0.1 0.2 0.5
Favors CS Therapy
Favors Placebo Therapy
10
Odds Ratio
(Random) 95% CI
Connett Connett
1994a
1994b
Lin
1997
Lin
1999
Littenberg Rodrigo Scarfone Schneider Stein Storr
1986
1994
1993
1988
1990 1987
Tal
Wolfson
1990
Total
1994
Review: Early emergency department treatment of acute asthma with systemic corticosteroids
Comparison: Any steroid (po, IM, IV, inhaled) vs placebo. Outcome: 01 Admitted to hospital
Total events: 159 (CS), 209 (Placebo)
Test for overall effect z=2.86 P=.004
Rowe BH, et al. Cochrane Database Syst Rev. 2005; CD002178.
21
Systemic Corticosteroid Discharge Regimen After
Acute Asthma
• Adults: GINA guidelines recommend a minimum of
7 days with systemic (usually oral) steroid1
• Children: 3-5 days of oral corticosteroid
• No taper required if patient is using inhaled steroid2
• Single-dose intramuscular methylprednisolone administered to
adult asthmatic patients at emergency department discharge
appears to be a viable therapeutic alternative to a course of oral
methylprednisolone3
- Clinicians may choose to base the route of administration of
corticosteroids on concerns about nonadherence or cost of therapy
1.
2.
3.
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Revised 2006. http://www.ginasthma.org
.O’Driscoll BR, et al. Lancet. 1993;341:324-327.
Lahn M, et al. Chest. 2004;126:362-368.
22
Controller
1.
2.
3.
4.
5.
6.
7.
Inhaled glucocorticosteroids (ICS)
Leukotriene modifiers
Long-acting inhaled β2-agonists (LABA) +
inhaled glucocorticosteroids (ICS) = LABACs
Systemic glucocorticosteroids
Theophylline
Cromones
Anti-IgE
2013 Global Initiative for Asthma http//www.ginaasthma.org
Route of Administration:
Intravenous Corticosteroids
•
Intravenous corticosteroids recommended for:
– Impending or actual respiratory arrest1
– Patient in intensive care unit1
– Alternative to oral steroids on admission1
– When patient cannot take oral medication2,3
• Severe dyspnea
• Vomiting
• Inability to swallow
1. National Asthma Education and Prevention Program Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. 2. Gibbs MA,
et al. Acad Emerg Med. 2000;7:800–815. 3. Roy SR, et al. J Asthma. 2003;20:593–604.
24
Methylprednisolone in Acute Asthma
• Pharmacologic advantages of methylprednisolone over other
corticosteroids:
– Greater anti-inflammatory efficacy compared with
prednisone and prednisolone1 with minimal
mineralocorticoid adverse effects2
– 10-fold greater potency in inhibiting T-cell blastogenesis
compared with prednisolone (P<.01)3
• Cytokines produced by T-lymphocytes are important in asthma
pathogenesis4
1.Schimmer BP, Parker KL. Chapter 59. In: Bruton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 2006:1587-1612.
2. Fiel SB, et al. J Asthma. 2006;43:321-331. 3. Hirano T, et al. Immunopharmacology. 1998;40:57-66. 4. Hirano T. Update 2004 Clinical Perspectives on Acute
Asthma Therapy. 2004: 12-16. 5. Braude AC, et al. Lancet. 1983; 2:995-997.
25
Methylprednisolone in Acute Asthma
• Pharmacologic advantages of methylprednisolone over other
corticosteroids:
• Penetration of lung tissue is greater with methylprednisolone than with prednisone5
– May be good option in steroid-resistant patients
– Methylprednisolone resistance significantly less likely to
develop than prednisolone resistance (P<.05)3
– However until recently, no clinical studies have shown correlation
between pharmacologic properties and clinical differences
1. Schimmer BP, Parker KL. Chapter 59. In: Bruton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 2006:1587-1612.
2. Fiel SB, et al. J Asthma. 2006;43:321-331. 3. Hirano T, et al. Immunopharmacology. 1998;40:57-66. 4. Hirano T. Update 2004 Clinical Perspectives on Acute
Asthma Therapy. 2004: 12-16. 5. Braude AC, et al. Lancet. 1983; 2:995-997.
26
Conclusions
• Asthma exacerbation is common in ER
• Asthma exacerbation is preventable
• Bronchospasm mucosal edema inflammation is the
cause of obstruction
• coticosteroid,b2 agonist, anticholinergic is first line
drugs
• asthma in ER indicate poor asthma control
• Asthma is very responsive to corticosteroids
COPD
Definition of COPD



COPD is a preventable and treatable disease with some
significant extrapulmonary effects that may contribute
to the severity in individual patients.
Its pulmonary component is characterized by airflow
limitation that is not fully reversible.
The airflow limitation is usually progressive and
associated with an abnormal inflammatory response of
the lung to noxious particles or gases.
EPIDEMIOLOGY
2020
Ischaemic
heart
disease
CVD
COPD
Lower
Respiratory
Infections
Trachea,
bronchus
& lung cancer
Road traffic
accidents
Murray CJL et al. Lancet 1997; 349:1498-1504
Cellular Mechanisms of COPD
Asthma
Sensitizing agent
COPD
Noxious agent
Asthmatic airway inflammation
CD4+ T-lymphocytes
Eosinophils
COPD airway inflammation
CD8+ T-lymphocytes
Macrophages
Neutrophils
Small airway disease
Parenchymal destruction
Airway inflammation
Airway remodeling
Loss of alveolar attachments
Decrease of elastic recoil
Completely
reversible
Airflow limitation
Completely
irreversible
AECB
CB
CB
is a disease process identified clinically as the presence
of a productive cough
productive cough on most days of the month for
3 months over 2 consecutive years.
CB
is a slowly progressive disease characterized by
episodes of acute exacerbation
CB
Episodes of AE consist of increased cough,
dyspnea, and changes in sputum volume and
purulence
Am J Manag Care. 2004;10:689-96
CHRONIC BRONCHITIS (COPD)
AECB is a common respiratory condition
associated with substantial patient morbidity.
BURDEN
50% of patients who experience acute
Exacerbations report at least 2 episodes per year
20% of patients with AECB will require
hospitalization due to the development of
pneumonia and/or respiratory insufficiency
Cigarette smoke
Viral infection
Microbial
colonization
Bacterial
products
Bacterial
products
Impaired local
defense
Airway
inflammation
Tissue
damage
Can Respir J Vol 10(5): 2003
Loss of cilia
Damaged
epithelium
Altered mucus
Local IgA
breakdown
AECB Stratification
Increased dyspnea
Increased Sputum
Sputum purulence
Type I:
all three
symptoms
Treat
Type II: two
symptoms
Probably
Treat if
include
Purulence
Type III: one
symptom
No
treat
Anthonisen NR et al. Ann Intern Med. 1987;106:196.
Precipitating factors for AECOPD
AG Ghoshal SUPPLEMENT TO JAPI Vol 60 ; 2012
Four Components of COPD Management
1. Assess and monitor
disease
2. Reduce risk factors
3. Manage stable COPD

Education

Pharmacologic

Non-pharmacologic ? ?
4. Manage exacerbations
GOALS OF
COPD TREATMENT
1
SMOKING
CESSATION
2
SHORT TERM
GOALS
GLOBAL GOLD
3
LONG TERM
GOALS
IMMEDIATE BENEFITS
RELIEF OF SYMPTOMS
[ BREATHLESSNESS ]
PREVENT DISEASE PROGRESSIVE
REDUCE EXACERBATIONS
IMPROVE QUALITY OF LIFE
IMPROVE EXERCISE TOLERANCE
REDUCE MORTALITY
Can Respir J Vol 10 suppl B 2003
Can Respir J Vol 10 suppl B 2003
Evidences of Methyl Prednisolone For
COPD exacerbations
• Exacerbation of COPD in patients requiring
hospitalization:
– 125 mg IV MP followed by PO therapy improves FEV1 and
decreases hospital length of stay with 1.2 - 2 days.
Niewoehner et al. 1999. Effect of systemic glucocorticoids on exacerbation of
COPD. New England Journal of Medicine; 340(25):1941-1947.
– In patients discharged from emergency department after
an exacerbation of COPD, equivalent of 32 mg Methyl
Prednisolone (Medrol®) PO during 10 days improves
FEV1, dyspnoea index and reduces the risk of relapse.
Aaron et al. 2003. Out-patients oral Methyl Prednisolone after emergency
treatment of COPD. New England Journal of Medicine; 34(26):2618-2680
Classification of COPD
Exacerbations by Severity
American Family Physician Vol 81 (5) ;2010
Evidences of Methyl Prednisolone For
COPD exacerbations
• Exacerbation of COPD in patients not
requiring hospitalization:
– Equivalent of 42 mg Methyl Prednisolone (Medrol®) PO
(tapering) for 9 days improves FEV1, PEF, dyspnoea score
and reduces treatment failure. (Thompson et al 1995.
Controlled trial of oral Methyl Prednisolone in outpatients with acute COPD.
Am. J Respir Crit Care Med; 1995;154:407-412.
CORTICOSTEROIDS IN COPD
Short courses of systemic corticosteroids :
• increase the time to subsequent exacerbation,
• decrease the rate of treatment failure,
• shorten hospital stays, and
• improve hypoxemia and forced expiratory
volume in one second (FEV1)
Arch Intern Med. 2002;162(22):2527-2536.
Am J Respir Crit Care Med. 2007;176(6):532-555
Respir Med. 2008;102(suppl 1):S3-S15.
Glucocorticoids can be differentiated based on their relative
anti-inflammatory potency and salt-retaining effects
Systemic Corticosteroids in COPD
AG Ghoshal SUPPLEMENT TO JAPI Vol 60 ; 2012
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: COPD Medications
Beta2-agonists
Short-acting beta2-agonists
Long-acting beta2-agonists
Anticholinergics
Short-acting anticholinergics
Long-acting anticholinergics
Combination short-acting beta2-agonists + anticholinergic in one inhaler
Combination long-acting beta2-agonist + anticholinergic in one inhaler
Methylxanthines
Inhaled corticosteroids
Combination long-acting beta2-agonists + corticosteroids in one inhaler
Systemic corticosteroids
Phosphodiesterase-4 inhibitors
© 2015 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD
Therapeutic Options: Systemic Corticosteroids
Chronic treatment with systemic
corticosteroids should be avoided
because of an unfavorable benefit-torisk ratio.
© 2015 Global Initiative for Chronic Obstructive Lung Disease
ASTHMA AND COPD
Similarities
1. Asthma and COPD are diseases of
chronic inflammation of the airways
that causes airflow obstruction.
2. Shortness of breath, wheeze and cough
are symptoms experienced by both
asthma and COPD patients.
3. Viral infections and exposure to tobacco
smoke, indoor air pollution
environmental pollution, and
occupational pollution can all cause an
asthma or COPD exacerbation.
4. Asthma and COPD are both diagnosed
through the use of breathing test called
spirometry.
Difference
1. Asthma is defined as an obstruction that
is reversible, where COPD is an
obstruction that is irreversible.
2. The inflammation occurring in asthma
and COPD are different. Asthma is
primarily caused by allergies, where
COPD is caused by bacteria.
3. Asthma and COPD respond differently to
anti-inflammatory medications due to
the differences in inflammation.
4. The goal of treatment is different;
asthma is treated to suppress chronic
inflammation, where COPD is treated to
reduce symptoms.
Prevention is always better than cure !