dr Salim S thalib

2016

BRONCHIALE

What is known about asthma ?

Asthma is a common and potentially serious chronic disease

that can be controlled but not cured.
Asthma causes symptoms such as wheezing, shortness of
breath, chest tightness and cough that vary over time in
their occurrence, frequency and intensity.
Symptoms are associated with variable expiratory airflow,
i.e. difficulty breathing air out of the lungs due to
Bronchoconstriction (airway narrowing)
Airway wall thickening
Increased mucus

Symptoms may be triggered or worsened by factors such as

viral infections, allergens, tobacco smoke, exercise and
stress.
Global Initiative for Asthma

What is known about asthma ?

Asthma can be effectively treated.

When asthma is well-controlled, patients can

Avoid troublesome symptoms during the day and night.

Need little or no reliever medication.
Have productive, physically active lives.
Have normal or near-normal lung function.
Avoid serious asthma flare-ups.
(also called exacerbations, or severe attacks)

Global Initiative for Asthma

Definition of asthma
Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation.
It is defined by the history of respiratory symptoms
such as wheeze, shortness of breath, chest tightness
and cough that vary over time and in intensity,
together with variable expiratory airflow limitation.

Global Initiative for Asthma

Description of asthma
1

Asthma is characterized by variable symptoms of

wheeze, shortness of breath, chest tightness and /or
cough, and by variable expiratory airflow limitation.

Both symptoms and airway limitation characteristically

vary over time and in intensity.
These variations are often triggered by factors such as
exercise, allergen or irritant exposure, change in weather,
or viral respiratory infection.

Description of asthma
2

symptoms and airway limitation may resolve

spontaneously or in response to medication, and may
sometimes be absent for weeks or months at a time. On
the other hand, patients can experience episodic flareups (exacerbation) of asthma that may be lifethreatening and carry a significant burden to patients
and the community.
Asthma is usually associated with airway hyper
responsiveness to direct or indirect stimuli, and with
chronic airway inflammation. these features usually
persist, even when symptoms are absent or lung
function is normal, but may normalize with treatment.

Phenotypes of asthma

Asthma is heterogeneous disease, with different underlying

processes.
Recognizable cluster of demographic, clinical and/or
pathophysiological characteristics are often called asthma
phenotypes.
Many phenotypes have been identified. Some of the most common
include :
Allergic asthma.
Non-allergic asthma.
Late-onset asthma.
Asthma with fixed airflow limitation.
Asthma with obesity.

 Asthma is a phenotypically heterogeneous disorder that

results from complex interactions between environmental
and genetic factors.
The expression of asthma may vary according to age and
gender, association with atopic or specific provoking factors,
type of airway inflammation, or severity of the disease.

Phenotypes of asthma

allergic asthma
allergic asthma this is most easily recognized
asthma phenotype
wich often commences in childhood and is
associated with past and/or family history of
allergic disease such as eczema, allergic rhinitis,
or food or drug allergy.
Examination of the induced sputum of these patients
before treatment often reveals eosinophilic airway
inflammation.
Patients with this asthma phenotype usually
respond well to inhaled corticosteroid( ICS )
treatment.

allergic asthma clinical features

Allergic asthma : clinical features

non allergic asthma

Some adult have asthma that is not
associated with alergy.
cellular profile of the sputum of these patients
may be neutrophilic, eosinophilic or contain
only a few inflammatory cells
(paucigranulocytic).
Patients with non allergic asthma often
respond less well to ICS.

non allergic asthma clinical features

Burden of asthma

Asthma is one of the most common chronic diseases worldwide with

an estimated 300 million affected individuals.
Prevalence is increasing in many countries, especially in children.
Asthma is a major cause of school and work absence.
Health care expenditure on asthma is very high
Developed economies might expect to spend 1-2 percent of total health
care expenditures on asthma.
Developing economies likely to face increased demand due to
increasing prevalence of asthma.
Poorly controlled asthma is expensive.
However, investment in prevention medication is likely to yield cost
savings in emergency care.

Global Initiative for Asthma

50 tahun terakhir..

Patogenesa asthma

Suatu inflamasi kronis di saluran napas.

Banyak sel dan elemen sel yang berperan.
Inflamasi kronis mengawali peningkatan
Hiperaktivitas saluran :

HIPERRESPONSIF SAL. NAPAS

SALURAN NAPAS

FAKTOR PENCETUS

Patogenesa asthma

INFLAMMATION PROCESSING

SYMPTOMS OF ASTHMA

INFLAMMATION PROCESSING

INFLAMMATION
PROCESSING
Acute inflammation

Chronic inflammation

Structural changes

Inflammation processing in asthma

BARNES PJ

ASTHMA IS VARIABLE DISEASE

Faktor risiko asma bronkiale

Faktor penderita
Predisposisi individual untuk pembentukan
/ perlindungan Penyakit asma.

Faktor lingkungan
Berperan dalam :
Pembentukan asma individu yg peka (Pemicu)

Menyebabkan gejala berkelanjutan (Pemacu)

Pencetus serangan asma

Faktor risiko asma bronkiale

Faktor lingkungan

Faktor penderita
Genetika
Atopi
Hiperaktivitas jalan
napas
Jenis kelamin
Ras

alergen di dalam rumah

alergen di luar rumah
pemicu di tempat kerja
asap rokok
polusi udara
infeksi saluran napas
infeksi Parasit
faktor sosial ekonomi
jumlah anak dalam keluarga
Diet dan obat-obatan
kegemukan

INFEKSI ASMA : HYGIENE HYPOTHESIS

Diagnosis of asthma

The diagnosis of asthma should be based on:

A history of characteristic symptom patterns
Evidence of variable airflow limitation, from bronchodilator
reversibility testing or other tests.

Document evidence for the diagnosis in the patients notes,

preferably before starting controller treatment
It is often more difficult to confirm the diagnosis after treatment has
been started

Asthma is usually characterized by airway inflammation

and airway hyper responsiveness, but these are not
necessary or sufficient to make the diagnosis of asthma.

Global Initiative for Asthma

Patient with
respiratory symptoms
Are the symptoms typical of asthma?
NO
YES

Detailed history/examination
for asthma
History/examination supports
asthma diagnosis?

Global Initiative for Asthma

Clinical urgency, and

other diagnoses unlikely

Further history and tests for

alternative diagnoses

NO

Alternative diagnosis confirmed?

YES

Perform spirometry/PEF
with reversibility test
Results support asthma diagnosis?

NO
YES

Repeat on another
occasion or arrange
other tests

NO

Confirms asthma diagnosis?

Empiric treatment with
ICS and prn SABA

YES

Review response

NO

YES

Consider trial of treatment for

most likely diagnosis, or refer
for further investigations

Diagnostic testing
within 1-3 months

Treat for ASTHMA

Treat for alternative diagnosis

Diagnosis of asthma symptoms

Increased probability that symptoms are due to asthma if :

More than one type of symptom (wheeze, shortness of breath, cough, chest
tightness)
Symptoms often worse at night or in the early morning
Symptoms vary over time and in intensity
Symptoms are triggered by viral infections, exercise, allergen exposure,
changes in weather, laughter, irritants such as car exhaust fumes, smoke, or
strong smells

Decreased probability that symptoms are due to asthma if:

Isolated cough with no other respiratory symptoms
Chronic production of sputum
Shortness of breath associated with dizziness, light-headedness or
peripheral tingling
Chest pain
Exercise-induced dyspnea with noisy inspiration (stridor)

 Diagnosis of asthma variable airflow

limitation

Confirm presence of airflow limitation

Document that FEV1/FVC is reduced (at least once, when FEV1 is low)
FEV1/ FVC ratio is normally >0.75 0.80 in healthy adults, and
>0.90 in children

Confirm variation in lung function is greater than in healthy

individuals
The greater the variation, or the more times variation is seen, the
greater probability that the diagnosis is asthma
Excessive bronchodilator reversibility (adults: increase in FEV1 >12%
and >200mL; children: increase >12% predicted)
Excessive diurnal variability from 1-2 weeks twice-daily PEF
monitoring (daily amplitude x 100/daily mean, averaged)
Significant increase in FEV1 or PEF after 4 weeks of controller
treatment
If initial testing is negative:
Repeat when patient is symptomatic, or after withholding bronchodilators
Refer for additional tests (especially children 5 years, or the elderly)
Global Initiative for Asthma

Typical spirometric tracings

Flow

Volume
Normal

FEV1
Asthma
(after BD)
Normal
Asthma
(before BD)

Asthma
(after BD)

Asthma
(before BD)

Volume

Time (seconds)
Note: Each FEV1 represents the highest of
three reproducible measurements

Global Initiative for Asthma

 Assessment of asthma

Asthma control - two domains

Assess symptom control over the last 4 weeks
Assess risk factors for poor outcomes, including low lung function

Treatment issues

Check inhaler technique and adherence

Ask about side-effects
Does the patient have a written asthma action plan?
What are the patients attitudes and goals for their asthma?

Comorbidities
Think of rhinosinusitis, GERD, obesity, obstructive sleep apnea,
depression, anxiety
These may contribute to symptoms and poor quality of life

GINA assessment of symptom control

A. Symptom control

Level of asthma symptom control

In the past 4 weeks, has the patient had:

Daytime asthma symptoms more
than twice a week?

Yes No

Any night waking due to asthma?

Yes No

Reliever needed for symptoms*

more than twice a week?

Yes No

Wellcontrolled

Partly
controlled

Uncontrolled

None of
these

1-2 of
these

3-4 of
these

Any activity limitation due to asthma? Yes No

B. Risk factors for poor asthma outcomes

ASSESS PATIENTS RISKS FOR:
Exacerbations
Fixed airflow limitation
Medication side-effects

Assessment of risk factors for poor

asthma outcomes
Risk factors for exacerbations include:

Ever intubated for asthma

Uncontrolled asthma symptoms
Having 1 exacerbation in last 12 months
Low FEV1 (measure lung function at start of treatment, at 3-6 months
to assess personal best, and periodically thereafter)
Incorrect inhaler technique and/or poor adherence
Smoking
Obesity, pregnancy, blood eosinophilia

Risk factors for fixed airflow limitation include:

No ICS treatment, smoking, occupational exposure, mucus
hypersecretion, blood eosinophilia

Risk factors for medication side-effects include:

Frequent oral steroids, high dose/potent ICS, P450 inhibitors

Assessing asthma severity

How?
Asthma severity is assessed retrospectively from the level of
treatment required to control symptoms and exacerbations

When?
Assess asthma severity after patient has been on controller
treatment for several months
Severity is not static it may change over months or years, or as
different treatments become available

Categories of asthma severity

Mild asthma: well-controlled with Steps 1 or 2 (as-needed SABA or
low dose ICS)
Moderate asthma: well-controlled with Step 3 (low-dose
ICS/LABA)
Severe asthma: requires Step 4/5 (moderate or high dose
ICS/LABA add-on), or remains uncontrolled despite this treatment

GINA 2015

The control-based asthma management cycle

Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference
Symptoms
Exacerbations
Side-effects
Patient satisfaction
Lung function

Asthma medications
Non-pharmacological strategies
Treat modifiable risk factors
GINA 2015, Box 3-2

Stepwise management - pharmacotherapy

Diagnosis
Symptom control & risk factors
(including lung function)
Inhaler technique & adherence
Patient preference
Symptoms
Exacerbations
Side-effects

Asthma medications

Patient satisfaction

Non-pharmacological strategies

Lung function

Treat modifiable risk factors

STEP 5
STEP 4
STEP 3
PREFERRED
CONTROLLER
CHOICE

STEP 1

STEP 2

Low dose ICS

Other
controller
options
RELIEVER

Consider low
dose ICS

Leukotriene receptor antagonists (LTRA)

Low dose theophylline*

As-needed short-acting beta2-agonist (SABA)

GINA 2015, Box 3-5 (2/8) (upper part)

Low dose
ICS/LABA*

Med/high
ICS/LABA

Med/high dose ICS Add tiotropium#

Low dose ICS+LTRA High dose ICS
+ LTRA
(or + theoph*)
(or + theoph*)

Refer for
add-on
treatment
e.g.
anti-IgE

Add
tiotropium#
Add low
dose OCS

As-needed SABA or
low dose ICS/formoterol**

Step 1 as-needed inhaled short-acting

beta2-agonist (SABA)

STEP 5

STEP 4
PREFERRED
CONTROLLER
CHOICE

STEP 1

STEP 2

Low dose ICS

Other
controller
options

RELIEVER

Consider low
dose ICS

Leukotriene receptor antagonists (LTRA)

Low dose theophylline*

As-needed short-acting beta2-agonist (SABA)

GINA 2015, Box 3-5, Step 1 (4/8)

STEP 3

Low dose
ICS/LABA*
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)

Med/high
ICS/LABA

Refer for
add-on
treatment
e.g.
anti-IgE

Add tiotropium#
High dose ICS
+ LTRA
(or + theoph*)

Add
tiotropium#
Add low
dose OCS

As-needed SABA or
low dose ICS/formoterol**

Step 2 low-dose controller + as-needed

inhaled SABA

STEP 5

STEP 4
PREFERRED
CONTROLLER
CHOICE

STEP 1

STEP 2

Low dose ICS

Other
controller
options

RELIEVER

Consider low
dose ICS

Leukotriene receptor antagonists (LTRA)

Low dose theophylline*

As-needed short-acting beta2-agonist (SABA)

GINA 2015, Box 3-5, Step 2 (5/8)

STEP 3

Low dose
ICS/LABA*

Med/high
ICS/LABA

Med/high dose ICS Add tiotropium#

Low dose ICS+LTRA High dose ICS
+ LTRA
(or + theoph*)
(or + theoph*)

Refer for
add-on
treatment
e.g.
anti-IgE

Add
tiotropium#
Add low
dose OCS

As-needed SABA or
low dose ICS/formoterol**

Step 3 one or two controllers + asneeded inhaled reliever

STEP 5

STEP 4
PREFERRED
CONTROLLER
CHOICE

STEP 1

STEP 2

Low dose ICS

Other
controller
options

RELIEVER

Consider low
dose ICS

Leukotriene receptor antagonists (LTRA)

Low dose theophylline*

As-needed short-acting beta2-agonist (SABA)

GINA 2015, Box 3-5, Step 3 (6/8)

STEP 3

Low dose
ICS/LABA*
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)

Refer for
add-on
treatment
Med/high
e.g.
ICS/LABA anti-IgE

Add tiotropium#
High dose ICS
+ LTRA
(or + theoph*)

Add
tiotropium#
Add low
dose OCS

As-needed SABA or
low dose ICS/formoterol**

Step 4 two or more controllers + asneeded inhaled reliever

STEP 5

STEP 4
PREFERRED
CONTROLLER
CHOICE

STEP 1

STEP 2

Low dose ICS

Other
controller
options

RELIEVER

Consider low
dose ICS

Leukotriene receptor antagonists (LTRA)

Low dose theophylline*

As-needed short-acting beta2-agonist (SABA)

GINA 2015 Box 3-5, Step 4 (7/8)

STEP 3

Low dose
ICS/LABA*

Med/high
ICS/LABA

Med/high dose ICS Add tiotropium#

Low dose ICS+LTRA High dose ICS
+ LTRA
(or + theoph*)
(or + theoph*)

Refer for
add-on
treatment
e.g.
anti-IgE

Add
tiotropium#
Add low
dose OCS

As-needed SABA or
low dose ICS/formoterol**

Global Initiative for Asthma

Step 5 higher level care and/or add-on

treatment

STEP 5

STEP 4
PREFERRED
CONTROLLER
CHOICE

STEP 1

STEP 2

Low dose ICS

Other
controller
options

RELIEVER

Consider low
dose ICS

Leukotriene receptor antagonists (LTRA)

Low dose theophylline*

As-needed short-acting beta2-agonist (SABA)

STEP 3

Low dose
ICS/LABA*

Refer for
add-on
treatment
Med/high
e.g.
ICS/LABA anti-IgE

Med/high dose ICS Add tiotropium#

Low dose ICS+LTRA High dose ICS
+ LTRA
(or + theoph*)
(or + theoph*)

Add
tiotropium#
Add low
dose OCS

As-needed SABA or
low dose ICS/formoterol**

Reviewing response and adjusting

treatment

How often should asthma be reviewed?

1-3 months after treatment started, then every 3-12 months
During pregnancy, every 4-6 weeks
After an exacerbation, within 1 week

Stepping up asthma treatment

Sustained step-up, for at least 2-3 months if asthma poorly controlled
Important: first check for common causes (symptoms not due to asthma,
incorrect inhaler technique, poor adherence)

Short-term step-up, for 1-2 weeks, e.g. with viral infection or allergen
May be initiated by patient with written asthma action plan

Day-to-day adjustment
For patients prescribed low-dose ICS/formoterol maintenance and reliever
regimen*

Stepping down asthma treatment

Consider step-down after good control maintained for 3 months
Find each patients minimum effective dose, that controls both
symptoms and exacerbations

GINA 2015

General principles for stepping down

controller treatment

Aim
To find the lowest dose that controls symptoms and exacerbations, and
minimizes the risk of side-effects

When to consider stepping down

When symptoms have been well controlled and lung function stable for
3 months
No respiratory infection, patient not travelling, not pregnant

Prepare for step-down

Record the level of symptom control and consider risk factors
Make sure the patient has a written asthma action plan
Book a follow-up visit in 1-3 months

Step down through available formulations

Stepping down ICS doses by 2550% at 3 month intervals is feasible and safe
for most patients
See GINA 2015 report Box 3-7 for specific step-down options

Stopping ICS is not recommended in adults with asthma

 Diagnosis of asthma physical examination

Physical examination in people with asthma

Often normal
The most frequent finding is wheezing on auscultation, especially
on forced expiration

Wheezing is also found in other conditions, for example:

Respiratory infections
COPD
Upper airway dysfunction
Endobronchial obstruction
Inhaled foreign body

FLARE UP OF ASTHMA

Wheezing may be absent during severe asthma exacerbations

(silent chest)

Global Initiative for Asthma

Flare up of asthma
A flare-up or exacerbation is an acute or sub-acute
worsening of symptoms and lung function
compared with the patients usual status.
Terminology
Flare-up is the preferred term for discussion with
patients
Exacerbation is a difficult term for patients
Attack has highly variable meanings for patients
and clinicians
Episode does not convey clinical urgency

Common precipitating factors in flare up of asthma

Common precipitating factors in flare up of asthma

Common precipitating factors in flare up of asthma

FLARE UP OF ASTHMA
ACUTE EXACERBATION OF ASTHMA

FLARE UP OF ASTHMA

Identify patients at risk of asthma-related death

Patients at increased risk of asthma-related death should be
identified
Any history of near-fatal asthma requiring intubation
and ventilation
Hospitalization/emergency care for asthma in last 12
months
Not currently using ICS, or poor adherence with ICS
Currently using or recently stopped using OCS
Over-use of SABAs, more than 1 canister/month
History of psychiatric disease or psychosocial problems
Confirmed food allergy in a patient with asthma

Managing exacerbations in primary care

PRIMARY CARE

Patient presents with acute or sub-acute asthma exacerbation

Is it asthma?

ASSESS the PATIENT

Risk factors for asthma-related death?

Severity of exacerbation?

MILD or MODERATE

SEVERE

Talks in phrases, prefers

sitting to lying, not agitated
Respiratory rate increased
Accessory muscles not used
Pulse rate 100120 bpm
O2 saturation (on air) 9095%
PEF >50% predicted or best

Talks in words, sits hunched

forwards, agitated
Respiratory rate >30/min
Accessory muscles in use
Pulse rate >120 bpm
O2 saturation (on air) <90%
PEF 50% predicted or best

LIFE-THREATENING
Drowsy, confused
or silent chest

URGENT

START TREATMENT
SABA 410 puffs by pMDI + spacer,
repeat every 20 minutes for 1 hour
Prednisolone: adults 1 mg/kg, max.
50 mg, children 12 mg/kg, max. 40 mg

WORSENING

TRANSFER TO ACUTE
CARE FACILITY
While waiting: give inhaled
SABA and ipratropium bromide,
O2, systemic corticosteroid

Controlled oxygen (if available): target

saturation 9395% (children: 94-98%)

CONTINUE TREATMENT with SABA as needed

ASSESS RESPONSE AT 1 HOUR (or earlier)

WORSENING

IMPROVING

ASSESS FOR DISCHARGE

ARRANGE at DISCHARGE

Symptoms improved, not needing SABA

Reliever: continue as needed

PEF improving, and >60-80% of personal

best or predicted

Controller: start, or step up. Check inhaler

technique, adherence

Oxygen saturation >94% room air

Prednisolone: continue, usually for 57 days

(3-5 days for children)

Resources at home adequate

Follow up: within 27 days

FOLLOW UP
Reliever: reduce to as-needed
Controller: continue higher dose for short term (12 weeks) or long term (3 months), depending
on background to exacerbation
Risk factors: check and correct modifiable risk factors that may have contributed to exacerbation,
including inhaler technique and adherence
Action plan: Is it understood? Was it used appropriately? Does it need modification?

INHALED
ANTICHOLINERGICS

IPRATROPIUM BROMIDE
OXITROPIUM BROMIDE
TIOTROPIUM BROMIDE

BRONCHODILATORS
FOR ASTHMA
4
COMBINATION
THERAPY

BETA 2
AGONIST

SHORT /LONG ACTING

INHALED
BETA 2 AGONIST

THEOPHYLLINE

IPRATOPRIUM BROMIDE
&
SHORT ACTING INHALED
BETA 2 AGONIST

2
DECREASED
PLASMA
EXUDATION

1
RELAX
AIRWAY SMOOTH
MUSCLE

3
DECREASED
INFLAMMATORY
MEDIATOR
RELEASE

BRONCHODILATORS
IN ASTHMA
5
IMPROVE
RESPIRATORY
MUSCLE
FATIGUE

4
DECREASED
NEUROTRANSMITTER
RELEASE

CONTROL OF THE AIRWAYS

ADRENERGIC & CHOLINERGIC ( MUSCARINIC ) RECEPTORS

ADRENERGIC
RECEPTORS

CHOLINERGIC
RECEPTORS

TERIMA