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Asthma shouldnt be
difficult, because ..
Modern pharmacotherapy
Controls
Airway inflammation
and
Variable airflow obstruction
Asthma shouldnt be
difficult,
P'pines
China
Maintenance
Frequent courses
Oral
glucocorticosteroid
(lowest dose)
*in children <6yrs:
moderate-dose ICS
anti-IgE
antibodies
Difficult Asthma
Vocal Cord Dysfunction
Noninvasive markers to identify
and adjust therapy
Single patient controlled trials of
therapy
Referred to DAC
Confirm Diagnosis
Control
Achieved
and
Discharged
or remain
under DAC
Control
Achieved
and
Discharged
Control
NOT
Achieved
and remain
under the
care of DAC
Assessment
Diagnosis: is it asthma ?
Risk profile: will this person die from
their disease?
Triggers
Complications
Asthma management skills
Is it asthma ? Or
COPD
Bronchiectasis
VCD
Hyperventilation
Obesity
Pulmonary hypertension
Churg Strauss vasculitis
VCD masquerades
as asthma
Frequent OCS
Same meds as
severe asthma
60
50
40
30
20
10
0
VCD
alone
& OCS
VCD +
asthma
VCD: objective
confirmation
VCD: history
Symptoms
Dyspnea: inspiratory
Voice symptoms
Tightness: throat
Pain: throat
Nonresponse
B2agonist
Sensory
hyperresponsiveness
Associated diseases
Gerd
Rhinosinusitis
Asthma (!)
VCD: tests
Spirometry:
restrictive, normal
SaO2: normal
Flow vol: variable
extrathoracic AFO
Laryngoscopy:
paradoxical vocal
cord movement
Provocation:
4.5% saline
FEV1
Inspiratory flow loop
Laryngoscopy
Vocal function
S to Z ratio
Max. phonation time
18
16
14
12
10
8
6
4
2
0
CC + VCD
VCD
CC Alone
Voice
Disorders
Normal
Controls
Improvement in Symptom
Scores
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
Breathing
p<.001
Cough
p=.003
Voice
p = .049
Treatment
Upper
airway
p=.034
Limitation
p=.011
Placebo
1.5
Percent
Seconds
1
0.5
0
Treatment p=.018 *
Placebo p=.283
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Treatment p=.041*
3
2.5
2
1.5
1
0.5
0
-0.5
-1
-1.5
Treatment p=.003 *
Placebo p=.222
Placebo p=.193
Semitones
Decibels
Treatment p=.044 *
Placebo p=.539
VCD
Clinical
features: symptoms
Assessment: FOL; flow/vol
Treatment: speech therapy
Mechanisms: irritable larynx
Understanding
Inhaler technique
Self-monitoring
Action plan
Adherence
40
35
30
(%) percent
1.
25
20
15
10
5
0
Did Not Complete
Difficult asthma:
Complications
Osteoporosis
Steroid myopathy
Depression
Obesity
VCD
Diabetes mellitus
Environmental
control
Complications
Oral
glucocorticosteroid
(lowest dose)
*in children <6yrs:
moderate-dose ICS
anti-IgE
antibodies
Assessment
Diagnosis: is it asthma ?
Risk profile: will this person die from
their disease?
Triggers
Complications
Asthma management skills
Step 3
Poor Control
Continues
Poor Control
Continues
DAC
DAC
and
ongoing
Poor
Control
Continues
Triggers and
aggravating
factors
Removed or
Managed
Optimisation of
Therapy and
Education
Omalizumab
OCS
Step 1
Confirm
diagnosis
Trial of Add
on
Therapies
LTRA
MTX
Very mild
Mild
Moderate
Gold
Severe
Eosinophilic Sputum
Non-eosinophilic Sputum
Inflammatory Phenotypes in
Stable Persistent Asthma, on ICS
31%
41%
Eosinophilic
Neutrophilic
Paucigranulocytic
59% Non
eosinophilic
28%
ICS/LABA :adherence !!
OCS: trial
LTRA: add on montelukast
Maintenance OCS: dose adjustment by
sputum eos, [adherence !!!]
Itraconazole for ABPA
Oral gold/ methotrexate
Parenteral steroid
Itraconazole
Placebo
4
Visits
smoking
infection
Macrolide
? Theophylline
?TNFa
Allergens
Acquired
Immunity
IgE
Activated TH2 Cells
TLR
Macrophages and Epithelial Cells
ICS X
Eosinophilic
Asthma
Innate
Immunity
X LABA
Neutrophilic
Asthma
1200
1000
800
0 wks
4 wks
600
400
75
200
70
0
IL-8
PMN
65
60
55
IL-8
smokers
80
80
70
70
60
60
50
50
40
40
30
30
20
20
10
10
0
EA
NEA
EA
NEA
Symptomatic Asthma
AHR to hypertonic
saline
Severe Persistent
asthma according to the
2002 GINA guidelines
No sensitivity to
macrolide antibiotics
Clarithromycin
Simpson J etal Respirology
Study Design
V1
V2
V3
V4
V5
CAM 1000mg
Screening
Follow Up
Placebo
t=-4
t=0
t=8
t=12
12
12
10
10
8
6
4
ACTIVE
8
6
4
0
Before
After
Before
After
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
-0.1
Macrolide Treatment
Placebo
* p=0.016 versus placebo
Step 3
Poor Control
Continues
Poor Control
Continues
DAC
DAC
and
ongoing
Poor
Control
Continues
Triggers and
aggravating
factors
Removed or
Managed
Optimisation of
Therapy and
Education
Omalizumab
OCS
Step 1
Confirm
diagnosis
Trial of Add
on
Therapies
LTRA
MTX
Very mild
Mild
Moderate
Gold
Severe
Montelukast
Omalizumab
IVIG
Toxic drugs
Oral gold
Methotrexate
Design
ICS Sub group
Vi si t 1 Vi si t 2 Vi si t 3 Vi si t 4 Vi si t 5 Vi si t 6
Vi si t 7
week-2
week0
week2
week4
Run-in
week8
week12
Xolair
Vi si t 8 Vi si t 9 Vi si t 10
Monit oring
week-2 week0
Run-in
Xolair
Xolair
and
wean
OCS
week40
Monitoring
week44
Difficult Asthma
Diagnosis: is it
asthma
Risk profile: will this
person die from
their disease?
Triggers
Complications
Asthma
management skills
Treatment
ICS/LABA
Eos
Neut
N=1 trials
Thankyou !
Case 2 Mr RG
34 yo male
Severe asthma since childhood
OCS dependant: since early childhood
Hospitalisations - 245 since birth
Hospitalisations in the last 12/12
No ICU admissions
1 HDU admission 2002
Respiratory Specialists
Paediatricians: n=1
Adult: n=1
SAC Assessment
Oesteoporosis
Depression
Steroid Myopathy
Cataracts
Treatment
Baseline Characteristics
Weight 64kg
IgE -31
FEV1
2.5
1.5
1
0.5
0
Baseline
60
mg of Prednisolone
Litres
Omalizumab
Omalizumab
and OCS
Weaning
Off
Omalizumab
OCS Dose
50
40
30
20
10
0
Baseline
7
6
5
4
3
2
1
Good
Control
Good QOL
Baseline
Omalizumab
Omalizumab and
OCS Weaning
Off Omalizumab
Asthma QOL
7
6
5
4
3
2
1
Poor QOL 0
Baseline
Omalizumab
Admissions
4
Number of Admissions
3.5
3
2.5
2
1.5
1
0.5
0
52/52 pre Rx On Rx (12/52) On Rx OCS Off RX (25/52) On Rx (16/52) off Rx (60/52) on Rx 34/52)
wean (12/52)
1.42L
FENO
QOL
ACQ
IgE
OCS
50mg
Dose 1
21/3/0
6
0.94L
5.5
2.67
6.14
35
100mg
Dose 2
18/4/0
6
1.18L
8.2
4.13
4.28
49
50mg
Dose 3
23/5/06
2.12L
9.1
4.61
3.71
60
50mg
alternat
e days
Now
Nov 06
1.85L
50mg
Diagnosis: is it
asthma
Risk profile: will this
person die from
disease?
Triggers
Complications
Asthma
management skills
Treatment
ICS/LABA
Eos:
Neut
N=1 trials
Other issues
B2 agonist toxicity
Genotype
Long acting Ach: tiotropium
education
GINA 2006: Asthma
Asthma
treatment steps
Environmental control
Oral
glucocorticosteroid
(lowest dose)
*in children <6yrs:
moderate-dose ICS
anti-IgE
antibodies