Stability of multiple trigger wheeze
and episodic viral wheeze in
preschoolers
Gerben ter Riet, AMC-UvA
Lonneke B. van der Mark, AMC-UvA
Jacob Mohrs, AMC-UvA
Ronald B. Geskus, AMC-UvA
Wim M.C. van Aalderen, AMC-UvA
Patrick J.E. Bindels, EUR
Karina E. van Wonderen, AMC-UvA
2
3
Background
• ERS Task Force 2008: tired of retrospective definitions
“transient wheezer”, “persistent wheezer”
• Multiple trigger wheeze (MTW)
• Episodic viral wheeze (EVW)
• Guide treatment: effect modification?
4
Objectives
We investigated the:
1. Prevalence of stable multiple trigger wheeze (MTW) and
episodic viral wheeze (EVW) in a relevant population?
2. Instability patterns over 3 years
3. Association of stable MTW and EVW with asthma at age 6y
5
Methods
• ARCADE study1: 14 GP centers, 2004 - 2011
• 1-5 year olds
• Previous year (EMD): cough (≥2/y), wheeze (≥1/y),
dyspnea (≥1/y)
• 2-year follow-up + formal asthma diagnosis (methacholine)
• ISAAC (symptoms)2
1. van Wonderen KE et al. Prediction and treatment of asthma in preschool children at risk: study design and baseline data
of a prospective cohort study in general practice (ARCADE). BMC Pulm Med. 2009;9:13
2. Asher MI, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 1995;
8(3):483-91
6
Methods
• Q1: “Child wheezed while having a cold in last year?”
• Q2: “Child wheezed while not having a cold in last year?”
• MTW¶: Yes – Yes; EVW¶: Yes – No; NWAS¶: No – No
• Determine status three times: t0, t12, t24
¶
¶
¶
MTW: multiple trigger wheeze
EVW: episodic viral wheeze
NWAS: non-wheezing airway symptoms
7
Methods
Phenotype
ERS label
Baseline
Stable MTW
MTW
Stable EVW
EVW
¶
¶
¶
12 months
24 months
MTW
MTW
EVW
EVW
NWAS
NWAS
Stable NWAS
NWAS
Stable mixed wheeze
MTW
EVW
MTW
MTW
MTW
EVW
..
..
..
EVW
MTW
EVW
MTW
NWAS
MTW
MTW
NWAS
EVW
..
..
..
NWAS
EVW
NWAS
Non-stable wheeze
¶ MTW: multiple trigger wheeze; EVW: episodic viral wheeze; NWAS: non-wheezing airway symptoms
8
Methods
Outcomes
• Prevalences
• Stability over 3 years (transitions, graphs)
• Association with asthma (logistic regression)
9
Results
Children included in ARCADE cohort
(n=771)
Excluded
4 and 5 years old at baseline (n=157)
No questionnaire at baseline (n=49)
One, 2 and 3- year old children
(n=565)
Children with information on phenotype
at 0, 12 and 24 months (n=281)
Excluded
No questionnaire at 12 or 24 months
(n=261)
Information about ICS use unknown
(n=23)
Excluded
Asthma at age 6 unknown (n=75)
Children with asthma outcome at age 6
(n=206)
10
Results
• Prevalence of stable MTW (MTW-MTW-MTW)
10/281 (3.6%; 95%CI 1.9 – 6.4)
• Prevalence of stable EVW (EVW-EVW-EVW)
24/281 (8.5%; 95%CI 5.8 – 12.4)
11
Trajectories originating from
the three main phenotypes.
Numbers are percentages
(adding up to 100% in each
graph)
18
NWAS
N=49
14 16
EVW
8
MTW
NWAS
8
12
EVW
MTW
NWAS
Baseline
20
2
After 24 months
After 12 months
34
N=126
NWAS
32 2
19 4
3
2 2
EVW
EVW
2
MTW
Baseline
After 12 months
After 24 months
76
NWAS
NWAS
MTW
EVW
MTW
NWAS
6
6
EVW
EVW
All others < 5%
MTW
N=106
Baseline
t0
After 12 months
t12
After 24 months
t24
MTW
12
Results
• Association of stable MTW and EVW with asthma at age 6
years (n=206)
Phenotype
Asthma (n=83)
No asthma (n=123)
OR (95%CI)
Stable MTW
8 (9.6)
1 (0.8)
14.4 (1.7-119.1)
Stable EVW
10 (12.0)
5 (4.1)
3.6 (1.2-11.3)
Stable mixed
12 (14.5)
4 (3.3)
5.4 (1.6-17.8)
Non-stable wheeze
39 (47.0)
70 (56.9)
Reference
Stable non-wheeze
14 (16.7)
43 (35.0)
0.6 (0.3-1.2)
Results are not adjusted for other determinants
13
Conclusion
• Multiple trigger wheeze and episodic viral wheeze unstable
• This hampers use as “phenotype” and treatment selection
variable
• Stable MTW in preschoolers quite rare
• Compared to non-stable wheeze, the 3 stable wheeze types in
1-3y olds are associated with asthma at the age of 6y
g.terriet@amc.nl
14
15
ICS
No I C S
16
Strengths & limitations
• Uniform asthma definition
• Misclassification: random?, single episodes underestimation!
• Loss to follow-up = yes  more siblings at t0
• No differentiation between long-term persistent and short-term
intermittent ICS
17