1. CURRICULUM VITAE Nama : dr. Muh.Ilyas, Sp.PD, KP, Sp.P (K), FINASIM
Alamat : Jl. Satando 2 No. 8 Makassar. HP /
Pendidikan :
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 :
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

2. “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

3. © Global Initiative for Asthma
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

4. The prevalence of asthma in Indonesia ranges from 5-7%
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

5. Asthma Inflammation: Cells and Mediators
Eosinophil
Mast cell
Allergen
Th2 cell
Asthma Inflammation: Cells and Mediators
Vasodilatation
New vessels
Plasma leak
Oedema
Neutrophil
Mucus
hypersecretion
hyperplasia
Mucus plug
Macrophage
Bronchoconstriction
Hypertrophy/hyperplasia
Cholinergic
reflex
Epithelial shedding
Subepithelial
fibrosis
Sensory nerve
activation
Nerve activation
Source: Peter J. Barnes, MD

6. The Development of Airway Inflammation and
Hyperresponsiveness
Immunologic
stimuli (antigen)
Nonimmunologic
Stimuli (viral infection,
Physical and chemical
stimuli)
Mast cells
Epithelial cells
Macrophage
Eosinophils
Lymphocytes
Autonomic nervous
System
Axon reflex
Neuropeptides
Granulocytic responses:
Neutrophils
Basophils
Activated mononuclear cells
Macrophages
Airway edema
Cellular infiltration
Subepithelial fibrosis
Mucous secretion
Mucosal and vascular
permeability
Airways hyperresponsiveness
asthma
Cell activation
Inflammatory mediators
Smooth muscle contraction
chemotaxis
This slide depicts the sequence of events in the bronchi as the asthmatic lesion evolves. It is noteworthy that there are many cells involved, with a complex interaction among them.Mast cells and eosinophils plays a central role. This slide emphasizes inflammation as the dominant feature of asthma and its relation to hyperresponsiveness.

7. Pathology PATHOGENESIS OF ASTHMA SYMPTOM Airway inflammation
Airflow limitation (hambatan saluran napas)
Usually reverses spontaneously or with
treatment
Airway hyper-responsiveness. Exaggerated bronchoconstriction to a wide range of non-specific stimuli e.g. exercise, cold air
Pathology
Airway inflammation
associated edema, smooth muscle hypertrophy and hyperplasia, thickening of basement membrane, mucous plugging, epithelial damage

8. Asthma worsenings
Asthma Worsening period  almost 90 % (mean 11.8/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

9. Management of Asthma

10. 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

11. Clinical Practice Guidelines
Some guidelines available:
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
There are many guidelines available for the treatment and management of asthma. All of these guidelines are supported by high quality evidence, especially in therapy.
In the next two slides we will review the GINA and CTS guidelines for asthma management.
Abbreviations: BTS: British Thoracic Society; CTS: Canadian Thoracic Society; GINA: Global Initiative for Asthma; NAEPP: National Asthma Education and Prevention Program

12. GINA Guidelines for Management of Asthma Exacerbations
Adaptation from the GINA guidelines for management of exacerbations 2014.
Abbreviations: bpm = beats per minute; GINA = Global Initiative For Asthma; kg = kilogram; min = minute; mg = milligram; O2 = oxygen; PEF = peak expiratory flow; SABA = short-acting beta agonist
Reference:
Pocket guide for asthma management and prevention (for adults and children older than 5 years), Global Initiative for Asthma® (GINA) Available from:
Adapted from Global Initiative For Asthma (GINA). Global Strategy for Asthma Management and Prevention. Revised 2014

13. 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
Adjust Therapy to Achieve and Maintain Control
Inhaled Corticosteroid (ICS)*
*Second-Line: Leukotriene Receptor Antagonist (LTRA)
Low Dose Medium Dose High Dose
≥12 yrs: ≤250 mcg/day† – 500 mcg/day † >500 mcg/day †
6-11 yrs: ≤200 mcg/day† – 400 mcg/day † >400 mcg/day †
Management of asthma in children six years of age and over, and adults, according to the Canadian Thoracic Society of Asthma.
Abbreviations: ICS = inhaled corticosteroid; IgE = LABA = long-acting bronchodilator; LTRA = leukotriene receptor antagonist; mcg = microgram; PEF = peak expiratory flow
Reference:
Lougheed MD, Lemière C, Dell SD, et al. Canadian Thoracic Society Asthma Management Continuum Consensus Summary for children six years of age, and over, and adults. Can Respir J 2010; 17(1):15–24.
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

14. Corticosteroid Effect
Structural cells
Inflammatory cells
Epithelial cell
Numbers
(apoptosis)
Eosinophil
Cytokines
mediators
T-lymphocyte
Endothelial cell
Cytokines
Leak
Glucocorticoids
Mast cell
Numbers
Airway smooth muscle
Macrophage
β2-receptors
Cytokines
Mucus gland
Dendritic cell
Mucus
secretion
Numbers
Barnes. JACI 1998

15. 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
Systemic corticosteroids have shown to be effective in reducing admissions, with earlier use being more beneficial. Since no clear benefit has been demonstrated with high doses of corticosteroids, the current recommendation is to use moderate doses. The best clinical approach is giving corticosteroids as oral treatment, unless patients are vomiting, obtunded, or intubated, in which case IV corticosteroids should be used.
Abbreviations: COPD = chronic obstructive pulmonary disease; IV = intravenous
Administering corticosteroids as early as possible in order to achieve a higher beneficial effect

16. FINAL China Asthma 2010Asthma China 2010
Systemic Corticosteroids Efficacy Key Therapy for Acute Asthma Exacerbations
4/19/2018 4:55 PM
4/19/2018 4:55 PM
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
SECTION IV: SYSTEMIC CORTICOSTEROIDS EFFICACY
Systemic corticosteroids are a 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
Corticosteroid formulations are used differently
Oral agents are used moderate to severe exacerbations
Intravenous agents are used for patients with respiratory arrest or those in the intensive care unit
Intramuscular injection has no advantage over oral administration for preventing relapse 16

17. 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
The Aggarwal analysis was a randomized prospective study with the objective to compare the efficacy and safety of two treatment regimens:
IV MP followed by oral MP and IV HC followed by oral prednisolone in acute bronchial asthma patients. A total of 94 patients with acute asthma were randomly allocated to either of the two treatment groups. Patients in Group A (n = 49) were administered HC 200 mg IV every 6 hours until discharge, followed by oral prednisolone 0.75 mg/kg daily for 2 weeks. Patients in Group B (n = 45) were administered MP 125 mg IV bolus, followed by 40 mg MP IV every 6 hours until discharge, and then oral MP 0.6 mg/kg daily for 2 weeks. Patients were followed-up after 2 weeks of discharge. Clinical and spirometric evaluation were used to assess the response to treatment.
Abbreviations: D/C = discharge; HC = hydrocortisone; hrs = hours; IV = intravenous; kg = kilogram; mg = milligram; MP = methylprednisolone; SABA = short-acting beta agonists; wks = weeks
Reference:
Aggarwal P, Bhoi S. Comparing the efficacy and safety of two regimens of sequential systemic corticosteroids in the treatment of acute exacerbation of bronchial asthma. J Emerg Trauma Shock 2010; 3(3):
SABA as required
Visit:
Days: D/C 2 weeks
Aggarwal P, Bhoi S. J Emerg Trauma Shock 2010

18. 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 ( vs mg/dL; p <0.001)
More hypertension in the HC group (+2.8 vs mmHg; p =< )
At 2 weeks of follow-up, the MP group showed significant improvement over the HC group in PEF and FEV1. There was a significant increase in the blood sugar value at 2 weeks in both groups. However, the increase was greater in the HC group as compared to MP. More hypertension was found in the HC group.
Abbreviations: D/C = discharge; FEV1 = forced expiratory volume in one second; HC = hydrocortisone; hrs = hours; kg = kilogram; L = liter; min = minute; mg = milligram; MP = methylprednisolone; PEF = peak expiratory flow; wks = weeks
Reference:
Aggarwal P, Bhoi S. Comparing the efficacy and safety of two regimens of sequential systemic corticosteroids in the treatment of acute exacerbation of bronchial asthma. J Emerg Trauma Shock 2010; 3(3):231–237.
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

19. Aggarwal Study: Comparing the Efficacy and Safety of two regimens of sequential systemic corticosteroids
The Aggarwal study demonstrated:
Higher efficacy and safety of IV methylprednisolone followed by oral methylprednisolone when compared to IV hydrocortisone followed by oral prednisone in hospitalized asthma patients
Therefore, IV methylprednisolone followed by oral methylprednisolone may comprise the treatment of choice for acute bronchial asthma
This study demonstrated a higher efficacy and safety of IV MP followed by oral MP when compared to IV HC followed by oral prednisone in hospitalized asthma patients, suggesting that IV MP followed by oral MP, may comprise the treatment of choice for acute bronchial asthma.
Abbreviations: IV = intravenous
Reference:
Aggarwal P, Bhoi S. Comparing the efficacy and safety of two regimens of sequential systemic corticosteroids in the treatment of acute exacerbation of bronchial asthma. J Emerg Trauma Shock 2010; 3(3):231–237.

20. Impact of Systemic Corticosteroids at Emergency Department Discharge
FINAL China Asthma 2010Asthma China 2010
Asthma China 2010
Impact of Systemic Corticosteroids at Emergency Department Discharge
4/19/2018 4:55 PM
4/19/2018 4:55 PM
P=.05
Fiel, p 260, col 2, ¶3, li 2
p 261, col 1, ¶1, li 3
P=.05
% Experiencing
IMPACT OF SYSTEMIC CORTICOSTEROIDS AT EMERGENCY
DEPARTMENT DISCHARGE
Patients (N=97) aged years were randomized to receive placebo (n=42) or methylprednisolone (n=34) on discharge after acute asthma episode. Follow-up took place at 7-10 days after treatment in the emergency department and patients were analyzed for the need for repeat emergency care and occurrence of respiratory symptoms.
The study found a discharge regimen of systemic corticosteroids after standard treatment in the emergency department resulted in reduced need for emergency care (5.9% versus 21%) and fewer respiratory symptoms (15.6% versus 36.4%) compared with placebo.
The authors concluded that a short course of high-dose corticosteroids in outpatients reduces the relapse rate and symptoms following an acute asthma attack.
Fiel, p 259, abs
p 260, col 2, ¶3, li 2
Fiel, p 261, col 1, ¶1, li 3, p 260, col 2, ¶3, li 2, p 261, col 1, ¶1, li 3
Fiel SB, et al. Am J Med. 1983;75:
Fiel, p 262, col 2, ¶2, li 1-5
p 259, abstr, li 4-11
Fiel SB, Swartz MA, Glanz K, Francis ME. Efficacy of short-term corticosteroid therapy in outpatient reatment of acute bronchial asthma. Am J Med. 1983;75: 20

21. Meta-analysis of Benefit of Early Use of Systemic Steroids
Asthma China 2010
FINAL China Asthma 2010Asthma China 2010
Meta-analysis of Benefit of Early Use of Systemic Steroids
4/19/2018 4:55 PM
4/19/2018 4:55 PM
Odds Ratio
(Random) 95% CI
Favors Placebo Therapy
Rowe, 2005 A
p 21, fig 1
Favors CS Therapy
META-ANALYSIS OF BENEFIT OF EARLY USE OF SYSTEMIC
STEROIDS: RESULTS
The studies reviewed in the meta-analysis compared the use of any systemic corticosteroid (intravenous, oral, intramuscular, or inhaled) with placebo. The primary outcome measure was admission to the hospital.
As shown, the beneficial effect of corticosteroid therapy was consistent regardless of the route of administration when therapy was initiated within 1 hour of emergency department admission.
Connett Connett Lin Lin Littenberg Rodrigo Scarfone Schneider Stein Storr Tal Wolfson Total
1994a b
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
Rowe 2005 A, p 21, fig 1
Total events: 159 (CS), 209 (Placebo)
Test for overall effect z=2.86 P=.004
Rowe 2005 A, p 21, fig 1
Rowe BH, et al. Cochrane Database Syst Rev. 2005; CD
Rowe BH, Spooner C, Ducharme FM, Bretzlaff JA, Bota GW. Early emergency department treatment of acute asthma with systemic corticosteroids. Cochrane Database Syst Rev. 2005; CD 21

22. Systemic Corticosteroid Discharge Regimen After Acute Asthma
Asthma China 2010
FINAL China Asthma 2010Asthma China 2010
Systemic Corticosteroid Discharge Regimen After Acute Asthma
4/19/2018 4:55 PM
4/19/2018 4:55 PM
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
GINA, p 69, col 2, ¶6, 1st bullet
O’Driscoll, p 326, col 2, ¶2–¶3, li 6
Lahn, abs, li 14-18
SYSTEMIC CORTICOSTEROID DISCHARGE REGIMEN AFTER ACUTE
ASTHMA
At discharge, patients should usually receive a short course of a systemic corticosteroid to reduce the risk of relapse. Most patients can be switched successfully from intravenous methylprednisolone to oral methylprednisolone or another systemic corticosteroid.1,2 Corticosteroids should be administered along with a continuation of bronchodilator therapy.3
A 7-day course of oral glucocorticosteroid therapy in adults has been found to be as effective as a 14-day course.3
No taper is required if the patient regularly uses an inhaled steroid to manage their asthma.4
Current data suggest that single-dose intramuscular methylprednisolone may be as effective as a course of the oral formulation of the drug. However, the choice of therapy may be determined by concerns regarding the cost of therapy or concerns about patient compliance.5
Rowe, p 280, col 2, ¶4, li 1-3
NAEPP, p 118, col 1, ¶4, li 2-4
GINA, p 69, col2,
1st bullet
GINA, p 69, col 1,
Li 7-8
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Revised
.O’Driscoll BR, et al. Lancet. 1993;341:
Lahn M, et al. Chest. 2004;126:
O’Driscoll, p 326, col 2, ¶2– ¶3, li 6
Lahn, p 362, abstr, li 14-18
1. Rowe BH, Edmonds ML, Spooner CH, Diner B, Camargo CA Jr. Corticosteroid therapy for acute asthma. Respir Med. 2004;98:
2. National Asthma Education and Prevention Program Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. National Institutes of Health, National Heart, Lung, and Blood Institute; Publication
3. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Revised Global Initiative for Asthma Web site. Available at: Accessed January 25, 2007.
4. O’Driscoll BR, Kalra S, Wilson M, et al. Double-blind trial of steroid tapering in acute asthma. Lancet. 1993;341:
5. Lahn M, Bijur P, Gallagher EJ. Randomized clinical trial of intramuscular vs oral methylprednisolone in the treatment of asthma exacerbations following discharge from an emergency department. Chest. 2004;126: 22

23. Controller 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//

24. Route of Administration: Intravenous Corticosteroids
FINAL China Asthma 2010Asthma China 2010
Asthma China 2010
Route of Administration: Intravenous Corticosteroids
4/19/2018 4:55 PM
4/19/2018 4:55 PM
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
NAEPP, p 112, fig 3-11
Gibbs, p 806, col 2, ¶2, li 6-8
Roy, p 597, col 1, ¶3, li 4–col 2, ¶1, l2
ROUTE OF ADMINISTRATION: INTRAVENOUS CORTICOSTEROIDS
Intravenous corticosteroids are recommended as initial therapy in impending or actual respiratory arrest, on admission to the intensive care unit, and as an alternative to oral steroids on hospital admission.1
The intravenous route may also be preferred in severely dyspneic patients; however, in those who are vomiting, unable to swallow, or otherwise unable to consume oral medication, the intravenous route is clearly the only possible one.2,3
NAEPP, p 112, fig 3-11
Gibbs, p 806, col 2, li 6-8
Roy, p 597, col 1, ¶3, li 4–col 2, ¶1, l2
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– Roy SR, et al. J Asthma. 2003;20:593–604.
1. National Asthma Education and Prevention Program Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. National Institutes of Health, National Heart, Lung, and Blood Institute; Publication
2. Gibbs MA, Camargo CA Jr, Rowe BH, Silverman RA. State of the art: therapeutic controversies in severe acute asthma. Acad Emerg Med. 2000;7:
3. Roy SR, Milgrom H. Management of the acute exacerbation of asthma. J Asthma. 2003;40: 24

25. Methylprednisolone in Acute Asthma
FINAL China Asthma 2010Asthma China 2010
Asthma China 2010
Methylprednisolone in Acute Asthma
4/19/2018 4:55 PM
4/19/2018 4:55 PM
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
Schimmer, p 1594, table 59-2
Fiel, p 328, col 2, ¶3, li 2-3
Hirano, 1998, abs, li 10-11
Hirano, 2004, p 12, col 1, li 5-9
Braude, abs, last line
Hirano, 1998, p 61, col 2, ¶2. li 16-21
MEDROL® (METHYLPREDNISOLONE) IN ACUTE ASTHMA
As studied to date, methylprednisolone has 3 pharmacologic advantages versus other steroids: good anti-inflammatory activity1 with little-to-no mineralocorticoid adverse effects,2 enhanced inhibition of T-cell blastogenesis3 (a cell type important for asthma pathogenesis4), and penetration of lung tissue.5
In addition, some data suggest methylprednisolone may be a good option in patients with steroid resistance.3
However, no clinical studies have yet been conducted to determine whether the pharmacologic advantages translate to clinical differences.
Schimmer, p 1594, table 59-2
Fiel, p 328, col 2, ¶3, li 2-3
Braude, abs, last line
Hirano, 2004, p 12, col 1, li 5-9
Hirano, 1998, abs, li 10-11
1.Schimmer BP, Parker KL. Chapter 59. In: Bruton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 2006: Fiel SB, et al. J Asthma. 2006;43: Hirano T, et al. Immunopharmacology. 1998;40: Hirano T. Update 2004 Clinical Perspectives on Acute Asthma Therapy. 2004: Braude AC, et al. Lancet. 1983; 2:
Schimmer BP and Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Bruton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Medical Publishing Division; 2006:
Fiel SB, Vincken W. Systemic corticosteroid therapy for acute asthma exacerbations. J Asthma. 2006;43:
Hirano T, Homma M, Oka K, et al. Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma: comparison of potencies for five glucocorticoids. Immunopharmacology. 1998;40:57-66.
Hirano T. Differential respiratory effects of glucocorticoids. Update 2004 Clinical Perspectives on Acute Asthma Therapy. 2004:
Braude AC, Rebuck AS. Prednisone and methylprednisolone disposition in the lung. Lancet. 1983;2: 25

26. Methylprednisolone in Acute Asthma
FINAL China Asthma 2010Asthma China 2010
Asthma China 2010
Methylprednisolone in Acute Asthma
4/19/2018 4:55 PM
4/19/2018 4:55 PM
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
Schimmer, p 1594, table 59-2
Fiel, p 328, col 2, ¶3, li 2-3
Hirano, 1998, abs, li 10-11
Hirano, 2004, p 12, col 1, li 5-9
Braude, abs, last line
Hirano, 1998, p 61, col 2, ¶2. li 16-21
MEDROL® (METHYLPREDNISOLONE) IN ACUTE ASTHMA
As studied to date, methylprednisolone has 3 pharmacologic advantages versus other steroids: good anti-inflammatory activity1 with little-to-no mineralocorticoid adverse effects,2 enhanced inhibition of T-cell blastogenesis3 (a cell type important for asthma pathogenesis4), and penetration of lung tissue.5
In addition, some data suggest methylprednisolone may be a good option in patients with steroid resistance.3
However, no clinical studies have yet been conducted to determine whether the pharmacologic advantages translate to clinical differences.
Schimmer, p 1594, table 59-2
Fiel, p 328, col 2, ¶3, li 2-3
Braude, abs, last line
Hirano, 2004, p 12, col 1, li 5-9
Hirano, 1998, abs, li 10-11
1. Schimmer BP, Parker KL. Chapter 59. In: Bruton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 2006: Fiel SB, et al. J Asthma. 2006;43: Hirano T, et al. Immunopharmacology. 1998;40: Hirano T. Update 2004 Clinical Perspectives on Acute Asthma Therapy. 2004: Braude AC, et al. Lancet. 1983; 2:
Schimmer BP and Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Bruton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill Medical Publishing Division; 2006:
Fiel SB, Vincken W. Systemic corticosteroid therapy for acute asthma exacerbations. J Asthma. 2006;43:
Hirano T, Homma M, Oka K, et al. Individual variations in lymphocyte-responses to glucocorticoids in patients with bronchial asthma: comparison of potencies for five glucocorticoids. Immunopharmacology. 1998;40:57-66.
Hirano T. Differential respiratory effects of glucocorticoids. Update 2004 Clinical Perspectives on Acute Asthma Therapy. 2004:
Braude AC, Rebuck AS. Prednisone and methylprednisolone disposition in the lung. Lancet. 1983;2: 26

27. 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

28. COPD

29. 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.

30. EPIDEMIOLOGY 2020 CVD COPD Ischaemic heart disease Lower Respiratory
Infections
Trachea,
bronchus
& lung cancer
CVD
COPD
Road traffic accidents
Murray CJL et al. Lancet 1997; 349:

31. Cellular Mechanisms of COPD

32. Asthmatic airway inflammation COPD airway inflammation
Sensitizing agent
COPD
Noxious agent
Asthmatic airway inflammation
CD4+ T-lymphocytes
Eosinophils
COPD airway inflammation
CD8+ T-lymphocytes
Macrophages
Neutrophils
Small airway disease
Airway inflammation
Airway remodeling
Parenchymal destruction
Loss of alveolar attachments
Decrease of elastic recoil
Airflow limitation
Completely
reversible
Completely
irreversible

33. AECB
is a disease process identified clinically as the presence of a productive cough CB
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
dapat dicegah dan diobati, ditandai dengan hambatan jalan napas yang biasanya progresif dan berhubungan dengan respon inflamasi kronik di saluran napas dan paru terhadap partikel atau gas toksik. Eksaserbasi dan komorbid berkontribusi terhadap derajat beratnya penyakit
Episodes of AE consist of increased cough, dyspnea, and changes in sputum volume and purulence CB
Am J Manag Care. 2004;10:689-96

34. CHRONIC BRONCHITIS (COPD)
AECB is a common respiratory condition
associated with substantial patient morbidity.
50% of patients who experience acute
Exacerbations report at least 2 episodes per year
BURDEN
20% of patients with AECB will require hospitalization due to the development of pneumonia and/or respiratory insufficiency

35. Microbial colonization
Cigarette smoke
Viral infection
Microbial colonization
Bacterial products
Bacterial products
Airway inflammation
Impaired local defense
Loss of cilia
Damaged epithelium
Altered mucus
Local IgA breakdown
Tissue damage
Can Respir J Vol 10(5): 2003

36. AECB Stratification
Increased dyspnea Increased Sputum Sputum purulence
Type I: all three symptoms
Type II: two symptoms
Type III: one symptom
Probably Treat if include Purulence
No treat
Treat
Anthonisen NR et al. Ann Intern Med. 1987;106:196.

37. Precipitating factors for AECOPD
AG Ghoshal SUPPLEMENT TO JAPI Vol 60 ; 2012

38. Four Components of COPD Management
Assess and monitor disease
Reduce risk factors
Manage stable COPD
Education
Pharmacologic
Non-pharmacologic ? ?
Manage exacerbations

39. GOALS OF COPD TREATMENT2
SHORT TERM GOALS
GLOBAL GOLD 1
SMOKING
CESSATION
IMMEDIATE BENEFITS
RELIEF OF SYMPTOMS
[ BREATHLESSNESS ] 3
Bronchodilators
Either
Act as agonists at beta receptors or
Act as antagonists at muscarinic receptors
LONG TERM
GOALS
PREVENT DISEASE PROGRESSIVE
REDUCE EXACERBATIONS
IMPROVE QUALITY OF LIFE
IMPROVE EXERCISE TOLERANCE
REDUCE MORTALITY

40. Can Respir J Vol 10 suppl B 2003

41. Can Respir J Vol 10 suppl B 2003

42. 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 days.
Niewoehner et al Effect of systemic glucocorticoids on exacerbation of COPD. New England Journal of Medicine; 340(25):
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 Out-patients oral Methyl Prednisolone after emergency treatment of COPD. New England Journal of Medicine; 34(26):

43. Classification of COPD Exacerbations by Severity
American Family Physician Vol 81 (5) ;2010

44. 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 Controlled trial of oral Methyl Prednisolone in out-patients with acute COPD.
Am. J Respir Crit Care Med; 1995;154:

45. 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):
Am J Respir Crit Care Med. 2007;176(6):
Respir Med. 2008;102(suppl 1):S3-S15.

46. Glucocorticoids can be differentiated based on their relative anti-inflammatory potency and salt-retaining effects

47. Systemic Corticosteroids in COPD
AG Ghoshal SUPPLEMENT TO JAPI Vol 60 ; 2012

48. © 2015 Global Initiative for Chronic Obstructive Lung Disease
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

49. © 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-to-risk ratio.
© 2015 Global Initiative for Chronic Obstructive Lung Disease

50. ASTHMA AND COPD Similarities Difference
Asthma and COPD are diseases of chronic inflammation of the airways that causes airflow obstruction.
Shortness of breath, wheeze and cough are symptoms experienced by both asthma and COPD patients.
Viral infections and exposure to tobacco smoke, indoor air pollution environmental pollution, and occupational pollution can all cause an asthma or COPD exacerbation.
Asthma and COPD are both diagnosed through the use of breathing test called spirometry.
Asthma is defined as an obstruction that is reversible, where COPD is an obstruction that is irreversible.
The inflammation occurring in asthma and COPD are different. Asthma is primarily caused by allergies, where COPD is caused by bacteria.
Asthma and COPD respond differently to anti-inflammatory medications due to the differences in inflammation.
The goal of treatment is different; asthma is treated to suppress chronic inflammation, where COPD is treated to reduce symptoms.

51. Prevention is always better than cure !
Thank you!