ASTHM

Definition
Asthma is a chronic inflammatory disorder
of the airways in which many cells and
cellular elements play a role
The chronic inflammation is associated with
airway hyperresponsiveness that leads to
reccurent
episodes
of
wheezing,
breathlessness, chest thightness, and
coughing particularly at night or in the early
morning
These episodes are usually associated with
widespread,
but
variable,
airflow
obstruction within the lung that is often
reversible either spontaneously or with

Epidemiology

Worldwide Estimated 300 million

affected individuals
Global prevalence 1-18%
Indonesia 5-7%
Baratawidjaya dkk (ISAAC) - Bandung :
Prevalence 2,1% (1995) 5,2% (2001)
73,6% of all visits to Allregy-Immunology
Clinic RSCM

Epidemiology
WHO : 15 million disability-adjusted
life years (DALYs) are lost annually
due to asthma
Annual
worldwide
deaths
from
asthma estimated at 250,000

Development of Asthma

Occupational
sensitizers 1 in
10 cases of asthma
among adults
working age

Patophysiology

Clinical Diagnosis
Symptoms
Physical

Examinations

Symptoms
Episodic

breathlessness
Wheezing
Cough
Chest tightness
Another allergic disease

Symptoms
Patterns

that strongly suggest

asthma:
Variability
Precipitate by non-specific irritants
Worsening at night
Responding to appropiate asthma
therapy

Physical Examination
be normal variable
Wheezing on auscultation
May be found:
May

Cyanosis
Drowsiness
Difficulty speaking
Tachycardia
Hyperinflated chest
Use of accessory muscles, & intercostal
recession

Lung Function Test

Assessing

airway limitation

Spirometry
FEV1
FVC

PEF measurement

Reversibility

Variability

Spirometry
Reversibility in FEV1 12% (or
200 ml) from the pre-bronchodilator
value
Airway limitation FEV1/FVC < 7580%
Reproducible, effort dependent
Ethnic diffrences normal range of
values is wider
Predicted values less reliable in
young people (< 20 y) and in the
elderly (> 70 y)

Differential Diagnosis

Hyperventilation syndrome & panic attacks

Upper airway obstruction & inhaled foreign
bodies
Vocal cord dysfunction
Other forms of obstructive lung disease
COPD
Non-obstructive forms of lung disease
diffuse parenchymal lung disease
Non-respiratory causes of symptoms left
ventricular failure

Classification
Etiology

Hard to identify environmental factors

Asthma

control
Asthma severity

Asthma control classification

Asthma Control Test

SKOR
ACT
19 atau
20-24

25

Artinya
Tidak Terkontrol

Tindakan yang Dilakukan

oleh Dokter
Rekomendasikan peningkatan
dosis LABA/ICS

Pemeliharaan /peningkatan dosis

Terkontrol dengan
LABA/ICS untuk mencapai
Baik
terkontrol sepenuhnya

Terkontrol
Sepenuhnya

Mempertahankan pengobatan
dg LABA/ICS u/ memaksimalkan
manfaat bagi pasien. Jangan
pertimbangkan penurunan
sebelum 6 bulan

Asthma
Classification

Daytime
symptom
frequency

Nighttime
symptom
frequency

Mildintermittent

2 days/week or
less

2 nights/month
or less

Mild persistent

>2days/week,<
1x/day

>2
nights/month

Moderate
persistent

Daily
>1 night/week
continual

Severe
persistent

frequent

Lung function

PEF or FEV1:
80% of
predicted
function
PEF or FEV1:
80% of
predicted
function
PEF or FEV1:6080% of
predicted
function
PEF or FEV1:
60% of

Asthma medications
Route

of administration

Inhaled
Orally
Parenterally (SC, IM, IV)

The major advantage of inhaled therapy

drugs are delivered directly into the
airways local concentrations , less
risk of systemic side effects

Inhaled Drugs

Controller

Reliever

Inhaled Glucocorticosteroid
Leukotriene modifiers
Long acting inhaled 2
Agonist
Theophylline
sodium cromoglycate &
nedocromil sodium
Long acting oral 2 agonist
Anti-IgE
Systemic glucocorticosteroids
Oral anti-allergic compounds
Others: MTX, Cyclosporine,
Gold
Allergen-specific

Rapid acting inhaled 2

agonist
Short acting oral 2
agonist
Anticholinergic
Systemic
glucocorticosteroid
Theophylline

Controller

Inhaled glucocorticosteroids

the most effective

anti-inflammatory
medications
Efficacy in:
reducing symptoms
Improving QoL
Improving lung function
Decreasing airway
hyperresponsiveness
Controlling airway
inflammation
Reducing frequency &
severity of
exacerbations
Reducing mortality

Dose: 400 ug of
budesonide/day
Tobacco smoking
reduces the
responsiveness to
inhaled
glucocorticosteroids
Local adverse effects:
oropharyngeal
candidiasis, dysphonia,
coughing from upper
airway irritation
Mouth washing, spacer
device

Leukotriene modifiers

Cysteinylleukotriene 1
(CysLT1) receptor
antagonists (montelukast,
pranlukast, and zafirlukast)
& a 5-lipoxygenase
inhibitor (zileuton).
Effects:
small & variable
bronchodilator
< symptoms
improve lung function
< airway inflammation
& asthma exacerbations
Mild persistent asthma,
aspirin-sensitive asthma

used as add-on
therapy:
moderate-severe: <<
the dose of inhaled
glucocorticosteroids
improve asthma control
low/high doses of
inhaled
glucocorticosteroids

less effective than

LABA as add-on
therapy
Zileuton liver
toxicity monitoring

 Combined with inhaled

Long-acting inhaled
2-agonists
glucocorticosteroids esp.

Agents: formoterol and

salmeterol
Effect:
symptom scores
nocturnal asthma
lung function
the use of rapidacting inhaled 2agonists
<< the number of
exacerbations
achieves clinical control
more rapidly

medium dose of inhaled

glucocorticosteroid alone
fails to achieve control of
asthma.
Fixed combination
compliance
rescue & maintenance
causes fewer systemic
adverse effects
(cardiovascular
stimulation, skeletal
muscle tremor, and
hypokalemia) than oral
therapy

Theophylline

bronchodilator, lower dose

modest antiinflammatory properties
sustained-release
formulations 1-2x/d
add-on therapy

Side effects: higher doses

(10 mg/kg BW/d) -->
significant
Adverse effects: GI
symptoms, loose stools,
cardiac arrhythmias,
seizures, death.
Monitoring:
high dose is started
adverse effect on the
usual dose
expected therapeutic aims
are not achieved
conditions known to alter
theophylline metabolism
exist.

not achieve control on

inhaled
glucocorticosteroids alone
less effective than LABA

toxicity Liver disease,

CHF, cimetidine,
quinolones, macrolides

Sodium cromoglycate & Nedocromil

sodium

Long-term treatment of asthma adults

limited
Efficacy:
mild persistent asthma
exercise-induced bronchospasm

Their anti-inflammatory effect weak

Less effective than a low dose of inhaled
glucocorticosteroid

Anti-IgE

Anti-IgE (omalizumab) serum levels of

IgE.
Indication: severe allergic asthma,
uncontrolled on inhaled
glucocorticosteroids
as add-on therapy

Systemic glucocorticosteroids

Long-term oral glucocorticosteroid severely

uncontrolled asthma
Limited by the risk of significant adverse effects
Oral preparations are preferred
The systemic side effects:

osteoporosis, arterial hypertension, diabetes,

hypothalamicpituitary- adrenal axis suppression, obesity,
cataracts, glaucoma, skin thinning cutaneous striae &
easy bruising, muscle weakness

Withdrawal of oral glucocorticosteroids elicit

adrenal failure / unmask underlying disease, such
as Churg-Strauss Syndrome
Caution TB, parasitic infections, osteoporosis,
glaucoma, diabetes, severe depression, peptic
ulcers

Reliever

Rapid-acting inhaled 2agonists

DOC relief of bronchospasm during acute

exacerbations of asthma and for the pretreatment
of exercise-induced bronchoconstriction
salbutamol, terbutaline, fenoterol, levalbuterol
HFA209, reproterol, and pirbuterol.
used only on an as-needed basis at the lowest
dose and frequency required.

Systemic glucocorticosteroid

severe acute exacerbations:

prevent progression of the asthma exacerbation, reduce

the need for referral to emergency departments and
hospitalization, prevent early relapse after emergency
treatment, and reduce the morbidity of the illness

The main effects only evident after 4 to 6 hours.

Oral therapy is preferred and is as effective as IV
hydrocortisone
Dose: 30-50 mg prednisolone/d for 5 to 10 days
~ severity

Anticholinergics

Ipratropium bromide and oxitropium bromide

a less effective reliever than rapid-acting inhaled
2-agonists
The benefits in the long-term management have
not been established
As an alternative bronchodilator adverse
effects rapid acting 2-agonists
Dryness of the mouth and a bitter taste

Theophylline

For relief of asthma symptoms

no additive bronchodilator effect over adequate
doses of rapid-acting 2-agonists, but it may
benefit respiratory drive

Short-acting oral 2-agonists

unable to use inhaled medication

higher prevalence of adverse effects

The Goals

Achieve and maintain control of symptoms

Maintain normal activity levels, including
exercise
Maintain pulmonary function as close to
normal as possible
Prevent asthma exacerbations
Avoid adverse effects from asthma
medications
Prevent asthma mortality

Asthma Exacerbation

Key Point

Provide guide self-management education

(self monitoring +written action plan +
regular review)
Treat modifiable risk factor and
comorbidity eq smoking, obesity, anxiet
Advise about non-pharmacological
therapies and startegies eq physical
activity, weight loss
Consider stepping up if uncontrolled
symptoms, exacerbation or risk, but check
diagnosis, comorbidity, inhaler technique,
adherence
Considering stepping down; symptoms

Stepping Down Treatment When

Asthma Is Controlled

Inhaled glucocorticosteroids alone in medium to high-doses

50% reduction in dose 3 month intervals (Evidence B)
Low-dose of inhaled glucocorticosteroids alone once-daily
dosing (Evidence A)
Inhaled glucocorticosteroid + long-acting 2-agonist :
reducing the dose of inhaled glucocorticosteroid 50% while
continuing the long-acting 2-agonist (Evidence B).
If control is maintained, further reductions in the
glucocorticosteroid should be attempted until a low-dose is
reached, when the long acting 2-agonist may be stopped
(Evidence D).
An alternative switch the combination treatment to once-daily
dosing. A 2nd alternative discontinue the long-acting 2-agonist
at an earlier stage inhaled glucocorticosteroid monotherapy at
the same dose. For some patients these alternative approaches
lead to loss of asthma control (Evidence B)

Stepping Down Treatment When

Asthma Is Controlled

Inhaled glucocorticosteroids + controllers other

than long-acting 2-agonists inhaled
glucocorticosteroid should be reduced by 50%
until a low-dose of inhaled glucocorticosteroid is
reached, then the combination treatment stopped
as described above (Evidence D).
Controller treatment may be stopped if the
patients asthma remains controlled on the lowest
dose of controller and no recurrence of symptoms
occurs for one year (Evidence D).

Stepping Up Treatment In
Response To Loss Of Control

Rapid-onset, short-acting / long-acting 2-agonist

bronchodilators. Repeated dosing with bronchodilators in
this class provides temporary relief until the cause of the
worsening symptoms passes. The need for repeated doses
over more than one or two days signals the need for review
and possible increase of controller therapy.
Inhaled glucocorticosteroids. Temporarily doubling the dose
of inhaled glucocorticosteroids has not been demonstrated
to be effective, no longer recommended (Evidence A).
A four-fold or greater increase has been demonstrated to be
equivalent to a short course of oral glucocorticosteroids in
adult patients with an acute deterioration (Evidence A). The
higher dose should be maintained for 7-14 days.

Stepping Up Treatment In
Response To Loss Of Control

Combination of a rapid and long-acting 2-agonist (formoterol)

and an inhaled glucocorticosteroid (budesonide) in a single
inhaler both as a controller and reliever is effective in
maintaining a high level of asthma control and reduces
exacerbations requiring systemic glucocorticosteroids and
hospitalization (Evidence A).
The usual treatment for an acute exacerbation is a high-dose
of 2-agonist and a burst of systemic glucocorticosteroids
administered orally/ IV