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ASTHMA

MANAGEMENT

LONG-TERM THERAPY
Inhalation therapy is
the mainstay therapy
Gaps between treatment goal and the
reality
THE GOAL THE REALITY
• no chronic symptoms  Frequent chronic symptoms
• no asthma attacks  Some asthma attacks
• no emergency visits  Some emergency visits
• no need for quick relief (as  Excessive use of ß2-agonist
needed) ß2-agonist
as reliever
• normal physical activity
 Impaired physical activity
including exercise
including exercise
• lung function as close to
normal as possible  Some “ups” and “downs” in

• no adverse effects from lung function


medicine  Frequent adverse effects from
medicine
Pathogenesis of asthma
Pathogenesis of
asthma
(NHLBI/WHO 1995) Environmental risk factor

Inflammation
Symptoms

Airway
hyperresponsiveness Airflow limitation

Triggers
Asthma is an inflammatory
disease
Inflammation
(–) (+)
• •
Triggers

• •

• •
• •

Normal Asthma

Bronchial hyperreactivity (-) Bronchial hyperreactivity

Symptoms (-) Symptoms (+)


Ca++ Histamin
Ag
Ig E YY
Phosphatidyl Phosphatidyl
Phospholipid Methyl
transferase ethanolamine choline

Phospho
lipase A2 Ca++ Histamin
Arachidonic acid ECF, NCF
lypoxygenase cyclooxygenase

5-HETE Leucotrienes Thromboxanes Prostaglandins


LTB4
LTC4 TXA2 PGD
LTD4 PGF2α
LTE4
Mediator release in
asthma reactions
Diagnosis

Data

Analisis

Planning
Data:
Diagnosis Batuk
Sesak
Mengi
Keluarga asma
Obat asma

Analisis
Asma
Pem.Fisik
Spirometri
APE
Tes Provokasi
Planning
FVC / KVP
the total volume forcibly exhaled
FEV1/ VEP1
the amount exhaled in the first second
6

4
Volume (liters)

3
FEV1 FVC
2

0 1 2 3 4 5 6
Time (sec)
Fig 2. Normal forced expiration curve
Peak Flow Meter /PEFR/APE
ASTHMA PROFILE
ASTHMA PROFILE IN THE WORLD

Globally, over 150 million people diagnosed with asthma

Globally, over 180,000 people die from asthma each year

Globally, the economic burden of asthma are estimated


to be greater than TB and HIV/AIDS or combined

Major factors contributing to asthma morbidity and mortality


are underdiagnosis and inappropriate treatment
PATIENT’S
PROFILE
( Yayasan Asma Indonesia Wilayah SumateraUtara , 200, 93-95)

•More than one year 93 %


•Used anti inflammation 25 %
•Used objective values 9%
•Inhaller tehnique (poor ) 92 %
•Compliance 19 %
•Dose interval 17 %
PATIENT’S PROFILE
( Yayasan Asma Indonesia Wilayah Sumatera Utara, 300, 96-99)

•More than one year 96 %


•Used anti inflammation 32 %
•Used objective values 7%
•Inhaller tehnique (poor ) 89 %
•Compliance 23 %
•Dose interval 21 %
Reflected in Indonesian Asthma Market
(IPMG Nov 2001)

3% 1%
5% Inhaled b2-agonist
Oral b2-agonist
11% Xanthines
NS Antiinflammatory
Inhaled Steroid
Anticholinergics
Antileukotriene
4% Other
46%

5%

25%
World Asthma Market
(IMS 2000)

1%
b2-agonist
16%
Xanthines
NS Antiinflammatory
30% Inhaled Steroid
Anticholinergics
Antileukotriene
5%
Other

6%

7%
35%
Change paradigm
of asthma
To/ To/
Symptoms Diseases
control control
Anti Inflammations is
the mainstay therapy
Inflammation

Controller
Bronchial hyperreactivity
Reliever
Symptoms
Pathogenesis of asthma
Natural History of Asthma
CURE
•UNCORRECT TREATMENT

CHRONIC ASTHMA
AIRWAY
REMODELLING

PERSISTENCE OF INFLAMMATION
AIRWAY REMODELLING CHRONIC ASTHMA
AIRWAY REMODELLING IN ASTHMA

•Desquamation of epithelium
•Increase in airway smooth muscle
•Vascular proliferation
•Collagen deposition
•Thickening of basement membrane
•Increase in bronchial glands
•Vascular congestion
•Oedema formation
•Cellular infiltration
Epithelial Damage

P Jeffery, in: Asthma, Academic Press 1998


AIRWAY REMODELLING IN ASTHMA

e t ic ?
ma c okin
Pha r Eosinophil

Desquamation of epithelium

MBP, ECP
Epithelium

Thickening of basement membrane

Increase in airway smooth muscle


Basement Membrane
Thickening

P Jeffery, in: Asthma, Academic Press 1998


Smooth Muscle Hyperplasia

P Jeffery, in: Asthma, Academic Press 1998


Fatal Asthma

Jeffery,
1994
FE 1
V Symptom

Exacerbatio
n Symptom

od e llin
Rem
g

Time
Era of Asthma management

1930th : Xanthin
1960th : Beta2-agonist
1970th : Steroid inhallation
2000th : Combination
2003th : Single inhaler combination
Steroid depo ?
Evolving treatment options
ICS treatment Adding
introduced LAßA to ICS therapy
Large use of 1972 Kips et al, AJRCCM 2000
Pauwels et al, NEJM 1997
short-acting
Greening et al, Lancet 1992 Single
ß2-agonists
inhaler therapy
1975
(Symbicort®)

“Fear” of
1980 short-acting
ß2-agonists

1985
2000
1990 1995

Bronchospasm Inflammation Remodelling


Controller:
Anti inflammation

Non steroid Steroid


• budesonide
• sodium chromoglicate
(Pulmicort®)
(Intal®) (Inflamid®)
• ketotifen • beclomethasone
dipropionate
• sodium nedocromil (Becotide®)

• triamcinolone
acetonide
Mild Asthma has Airway
Inflammation
ICS Reverses Inflammation
E
E
BM

BM

Pre and post 3 month treatment with BUD 600 µg


bd
Laitinen, J Allergy Clin Immunol, 1992
Reliever
Bronchodilator
∀β 2 - agonist

• Xanthin
•Anticholinergic
BRONCHODILATOR
Short Acting β 2 AGONIST (SABA): Long Acting β 2 AGONIST:

* salbutamol/albuterol (Ventolin ®) (LABA)

* terbutaline (Bricasma®) •salmoterol


* procaterol •formoterol
* fenoterol
* orciprenaline, etc

ANTICHOLINERGIC: XANTHINE:
* atropine sulfate * theophylline

* ipratropium bromide, etc

OTHER SYMPHATOMIMETIC:
* ephedrine
* adrenaline, etc
GINA guidelines 1998/2002:
Focus on ICS and ß2-agonists

Mild Moderate Severe


Intermittent persisten persisten persisten
t t t

Short-acting ß2 prn

ICS

Long-acting ß2

Symbicort not specifically mentioned


Healthy
Healthy Subjects
Subjects Asthma
Asthma in
in Remission
Remission
Increased Membrane Basic Protein (MBP) positive area ( the red stain
stai
and epithelial shedding in the subject in clinical remission.
Van den Toom. AJRRCM 2001; 164: 2107-13
Guidelines on Asthma:
Past and Current Trends

Mild Moderate Severe


Intermittent persisten persisten persisten
t t t

Short-acting ß-agonists2
prn
GINA 1998 LABA+ICS
(adapted) ICS
Current
evidences LABA+ICS
The rationale behind fixed
combination therapy
 To increase adherence to controller
therapy
 To gain better control with less inhaled
steroid
ADULT PATIENTS & CAREGIVERS OF
CHILDREN WITH ASTHMA WERE ASKED
“WHY THEY DID NOT TAKE THEIR INHALED
CORTICOSTEROID AS PRESCRIBED?”

 45% said they just forgot

 42% said that they felt


well
Stahl AJRCCM, 2002
Combinations once- or twice-daily dosing
offers convenient than single dosing
35
Change in morning PEF (L/min)

30

25

20

15 p<0.001
both treatments vs. budesonide alone
10

0
-5
-10 0 10 20 30 40 50 60 70 80 90
Treatment days

Symbicort® 160/4.5 µg Symbicort® 160/4.5 µg budesonide 200 µg


2 inhalations od 1 inhalation bid 2 inhalations od
Buhl et al, Am J Respir Crit Care Med 2001
Combination therapy

Symbicort®
Budesonide + Formoterol

Seretide®
Fluticasone + Salmoterol
The Beginning of
Treatment
Exacerbation

The beginning of treatment ?

Stable condition

Peak flow meter

Objective 600-700 ( normal )

value
300

0
PEFR Monitoring:
A Major Tool in Asthma Self-Management
Chronic Diseases Monitor

Hypertension Blood pressure

Diabetes Serum glucose

Asthma PEFR
THE GOALS FOR SUCCESSFUL
MANAGEMENT OF ASTHMA
( NHLBI / WHO, 1995)

• Achieve and maintain control of symptoms

•Prevent asthma exacerbations


• Maintain pulmonary function as close to normal
levels as posible
•Maintain normal activity levels, including exercise
•Avoid adverse effect for asthma medications

•Prevent development of irreversible airflow limitation


•Prevent asthma mortality
MANAGEMENT

•ANTI INFLAMMATION, FIRST LINE, EARLY

•BRONCHODILATOR, OBJECTIVE VALUE

• MEDICINE , SELECTIVE

•TIME, PROPERLY

• TECHNIQUE, PROPERLY
•REHABILITATION, DO

•TRIGGER FACTORS, AVOID


THANK YOU
Airway
Airway Remodelling
Remodelling in
in
30
Asthma
Asthma
Subepithelial layer thickness
25

20
(µm)

15

10

5
rs = 0.581
0 p < 0.001

0 2 4 6 8 10 12

Asthma severity score

Correlation between subepithelial layer thickness and asthma severity score


in 34 asthmatic patients.

Chetta CHEST 1997; 111:362-67


GINA 2002
Systemic Glucocorticosteroid (Parenteral)
Systemic glucocorticosteroid speed resolution of exacerbations
and should be considered integral to the management of all
but the mildest exacerbation, especially if:
• The initial rapid acting inhaled ß2-agonist dose has failed
to achieve lasting improvement
• The exacerbation developed even though the patient was already
taking oral glucocorticosteroid
• Previous exacerbations required oral glucacorticosteroid

Intravenous administration may be considered if IV access is


desirable.
In patients being discharge from the emergency departement,
intramuscular administration may be helpful, specially if there
are concerns about compliance.
STEP 4: SEVERE PERSISTENT
Step
CONTROLLER:
daily multiple RELIEVER down
medications •Inhaled ß2- when
• Inhaled steroid agonist
• Long-acting
p.r.n.
controlled
bronchodilator
Avoid or control triggers
• Oral steroid
STEP 3: MODERATE PERSISTENT
CONTROLLER: Patient education
daily medications RELIEVER
• Inhaled steroid and •Inhaled ß2- essential at every
long-acting
bronchodilator
agonist step
• Consider p.r.n.
anti-or control triggers
Avoid
leukotriene
Reduce therapy
STEP 2: MILD PERSISTENT
CONTROLLER:
if controlled for at
daily medications RELIEVER least 3 months
• Inhaled steroid
• Or possibly cromone, oral •Inhaled ß2-
theophylline or anti-leukotriene agonist Continue
p.r.n.
Avoid or control triggers monitoring
STEP 1: INTERMITTENT

CONTROLLER: RELIEVER Step up


none •Inhaled ß2-
if not controlled
agonist
p.r.n. (after check on
Avoid or control triggers inhaler technique
TREATMENT and compliance)
GINA,
GINA, Guidelines
Guidelines 2002
2002