ma7384@cgmh.org.

tw
2015-11-29

lowest

controlling
step
(GINA guidline)

Corticosteroid

2 agonist

Antimuscarinics Leukotriene
antagonist

Xanthine

Monoclonal
antibody

Pathophysiology of asthma

Am J Respir Crit Care Med 150156, 2013

Airway remodelling in asthma

Asian Pac J Allergy Immunol 2013;31:3-10

GINA guideline
Step 1
Preferred
controller

Other
controller

Consider
low dose
ICS

Step 2

Step 3

Step 4

Step 5

Low dose
ICS

Low dose
ICS/LABA

Medium or
high
ICS/LABA

Refer for
add-on
treatment

Leukotriene
receptor
antagonist
(LTRA)
Low dose

Med/high
dose ICS

Add
tiotropium

Add
tiotropium

High dose
ICS+LTRA
(or +

Add low
dose OCS

Low dose
ICS+LTRA
theophylline (or +

theophylline) theophylline)

reliever

As-needed short acting

beta2 agnoist

Ad-needed SABA or low dose

ICS/formoterol

Controller: inhaled Corticosteroid

1950s
Systemic
glucocorticoid

1970s
beclomethasone
inhaler

2000s

Budesonide/
formoterol
Fluticasone/
salmeterol


Died with asthma in USA
(Crude Rate per 100000)
3.6

3.5

3.4

3.3

3.2

3.1

2.9

2.8

2.7
"1999"

"2000"

"2001"

"2002"

"2003"

"2004"

"2005"

"2006"

"2007"

"2008"

"2009"

"2010"

Pharmaceuticals 2010, 3, 514-540

British Journal of Pharmacology (2011) 163

2943

British Journal of Pharmacology (2011) 163 2943

Adult ICS dose

Inhaled
corticosteroid

Low (mcg)

Medium (mcg)

High (mcg)

Beclomethasone
100-200
dipropionate (HFA)

>200-400

>400

Budesonide (DPI)

200-400

>400-800

>800

Ciclesonide (HFA)

80-160

>160-320

>320

Fluticasone
propionate (HFA)

100-250

>250-500

>500

Mometasone
furoate

110-220

>220-440

>440

Triamcinolone
acetonide

400-1000

>1000-2000

>2000

1-2puff daily

Lung deposition

Pharmaceuticals 2010, 3(3), 514-540

Corticosteroids side effect

Inhaled corticosteroids Oral thrush
Asthma poor control
Oral/injected corticosteroid
Thinning skin
muscle weakness
Cushings syndrome
Osteoporosis ...

Inhaled corticosteroids
1. Most effective therapy for
controlling asthma
2. Titrate to minimum dose

3. Mouth washing to prevent oral

candidiasis
( extrafine Foster)

Beta 2 adrenoceptor agonist

Beta 2 adrenoceptor agonist

Epinephrine

Fenoterol
Salbutamol

Salmeterol (onset)
Formoterol (onset)
Pharmacol Rev64:450 504, 2012

smooth
muscle tone

Pharmaceuticals 2010, 3, 1016-1044

Beta 2 adrenoceptor agonist

adverse effect
Tachycardia
Hypokalemia
Tremor

Interaction between
ICS and LABA

Pharmaceuticals 2010, 3(3), 514-540

ICS +

LABA

ICS+LABA: step 3
Step 1
Preferred
controller

Other
controller

Consider
low dose
ICS

Step 2

Step 3

Step 4

Step 5

Low dose
ICS

Low dose
ICS/LABA

Medium or
high
ICS/LABA

Refer for
add-on
treatment

Add
tiotropium

Add
tiotropium

High dose
ICS+LTRA
(or +

Add low
dose OCS

Leukotriene Med/high
receptor
dose ICS
antagonist
(LTRA)
Low dose
ICS+LTRA
Low dose
(or +

theophylline theophylline) theophylline)

reliever

As-needed short acting

beta2 agnoist

Ad-needed SABA or low dose

ICS/formoterol
GINA guideline

ICS+LABA v.s high dose ICS

Cochrane Database Syst Rev. 2010 Apr 14;(4):CD005533

British guideline ICS+LABA

BMJ. 2013 Aug 6;347:f4662

Single-inhaler combination therapy

LABA (formoterol) and inhaled
corticosteroids: maintenance and reliever

Prescriber 1 APR 2015 | DOI: 10.1002/psb.1335

Single
Device

Mp3

Single-inhaler combination therapy

Advantage

Disadvantage

Fewer puffs and

devices
Rapid onset of
bronchodilatation
Ensure adherence with
anti-inflammatory
treatment
Avoid risk of LABA
monotherapy

Difficultly in backtitrating treatment dose

without provision of a
separate inhaler device
containing inhaled
corticosteroid alone
Expense

BMJ. 2013 Aug 6;347:f4662

Cochrane Database Syst Rev. 2013 Dec
16;12:CD009019.

Single-inhaler combination therapy

Lancet Respir Med 2013; 1: 2331

Single-inhaler combination therapy

reduce exacerbations requiring oral

corticosteroids against current best practice
strategies
Cochrane Database Syst Rev. 2013 Apr 30;4:CD007313

Prescriber 1 APR 2015 | DOI: 10.1002/psb.1335

2 adrenoceptor agonist
1. SABA: used only as needed
2. LABA: used in combination with
controller; not be used alone

3. Single-inhaler combination therapy:

reducing the number of inhalers
required

Xanthine

Pharmacol Rev64:450 504, 2012

Theophylline cellular effect

Pharmaceuticals 2010, 3(3), 725-747

Theophylline therapeutic
range(10-20mg/L)

>10mg/L

Pharmaceuticals 2010, 3(3), 725-747

Theophylline low dose (~5mg/L)

AJRCCM 901906, Oct 15, 2013

Decrease clearance

Theophylline
intoxication

Xanthine
1. add on therapy, use in smoker
with asthma (restore HDAC2)
2. Intravenous aminophylline is not
recommended for acute severe
asthma

3.

Antimuscarinics

Asthma cigarette

Ipratropium
Duration: short

Tiotropium

Pharmacol Rev64:450 504, 2012

Tiotropium in asthma poorly

controlled

N Engl J Med 2012;367:1198-207.

Tiotropium add on increase in

lung function (meta-analysis)

Chest. 2015;147(2):388-396

Tiotropium add on increase in

lung function (meta-analysis)

Chest. 2015;147(2):388-396

Anticholinergics
1. Tiotropium: add on therapy for
step 4 and 5
2. Ipratroium bromide: only for
severe exacerbation

Leukotriene receptor antagonist

1. appropriate for patients who have
concomitant allergic rhinitis
2. aspirin sensitive asthma

Monoclonal antibody
Omalizumab block IgE bindings
Lebrikizumab neutralize IL-13
Dupilumab block IL-4/13 receptor
Mepolizumab neutralize IL-5
Benralizumab block IL-5 receptor


1. Allergic bronchopulmonary
aspergillosis: antifungals
2. Severe asthma (treatmentresistant): 5% to 10%

Asthma adherence and compliance

Compliance

Adherence

the extent to which patients

follow physician instructions,
prescriptions, and
proscriptions.

taking medication, following

a diet, and/or executing
lifestyle changes
corresponds with agreed
recommendations from a
health care provider.

It implies that treatment

decision making was
entirely the physicians
responsibility and the
patient must obey or
acquiesce

The main difference

between adherence and
compliance is that
adherence is consensual
J Allergy Clin Immunol: In Practice 2013;1: 123-8

Asia Pac Allergy. 2012 Jan;2(1):67-75

JAMA. 2012 September 12; 308(10): 987997

mild to moderate asthma

controlled by low-dose ICS

JAMA. 2012 September 12; 308(10): 987997

60
D. pteronyssinus

50

D. farinae

40

30

20

10

0
Specific IgE

Chih-Hao Chang, Horng-Chyuan Lin, et al

2012; 27: 1-12


1. Vaccum
2. Wash your bedding weekly in hot water
and use a hot dryer
3. Encasing of mattresses and pillows
4. Keep humidity low by using a
dehumidifier
5. Wall-to-wall carpeting should be removed
N Engl J Med 2004;351:1068-80

?
1.
2.

3.

4.


Check air quality reports in weather
forecasts or on the Internet.
When the air quality is poor, keep your
child indoors and be sure he takes his
asthma control medications.

http://env.g0v.tw/air/

Vitamin D

Am J Respir Crit Care Med Vol 185, Iss. 2,

pp 124132, Jan 15, 2012

Eur Respir J. 2014 May;43(5):1368-77

Allergy. 2000 Dec;55(12):1127-33

Pediatr Allergy Immunol. 2006 Aug;17(5):316-22

Thanks for your

Thanks
for your attention
attention