Preliminary study on Japanese cedar pollinosis in an
artificial exposure chamber (OHIO Chamber)
1
Hashiguchi, K.
2
Tang, H.
2
Fujita, T.
3
4
Tsubaki, S.
5
Fujita, M.
Suematsu, K.
6
and Okubo, K.
1. Kitasato Institute Hospital, 2. Shinryo Corporation, 3. Samoncho Clinic,
4. Medical Corporation Shinanokai, Shinanozaka Clinic, 5. Tokyo Research Center
of Clinical Pharmacology CO., LTD, 6. Nippon Medical School, Tokyo, Japan
Introduction
The number of Japanese cedar pollinosis patients has been increasing every year in Japan and recently it is estimated to be up to 16 % of Japanese population.
The pollen season is usually between February and April, during which pollinosis patients are suffering from seasonal allergic rhinitis.
The incredible amount of anti-allergy agent is used, resulting in the undermined QOL and decline in labor productivity. These facts show that JC pollinosis is a social,
economical and medical problem which can not be ignored.
An artificial exposure chamber (OHIO chamber) was built in central Tokyo in order to study seasonal allergic rhinitis.
Since satisfactory outcomes were obtained from the controlled exposure at the OHIO chamber, we were able to conduct preliminary studies on the mildly
symptomatic patients, in which the amount of intranasal/intraocular pollen grains and the development of symptoms in exposed patients were examined out of the
pollen season.
And we also conducted a randomized, placebo-controlled study with epinastine to investigate the clinical efficacy on the mildly symptomatic patients who were
expose to mild to high concentration of JC pollen using the OHIO chamber in the early pollen season.
Subjects
Adult volunteers
with a history of allergic symptoms due to JC pollen for at least 2 years
with positive RAST scores (≧class 2) for JC pollen and negative RAST scores (≦Class 1) for house dust mite.
Study
I
Preliminary study
II
Preliminary study
Randomized, placebo-controlled study
Ten volunteers were enrolled.
Same 10 volunteers as study I
Background
Male
Female
N
5
5
Age
40.8㫧7.2
(34~48)
36.2㫧6.8
(32~43)
A
(n=10)
B
(n=9)
C
(n=10)
Total
(n=29)
Age
42.0㫧9.8
䋨21-57䋩
37.2㫧8.6
䋨21-54䋩
37.7㫧7.9
䋨24-51䋩
39.0㫧8.8
䋨21-57䋩
Male
3
2
1
6
Female
7
7
9
23
16 :15
4500 grains/m3
Up to one hour exposure㪁
10:15
11:15
IN
2500 grains/m3
IN
Two hours exposure
14:15
III
EXIT OHIO
0
EXIT OHIO
Wash the nasal cavities and eyes with saline
15
30
60
90
120 min
Each subject recorded their symptoms (sneezing, rhinorrhea, nasal obstruction,
itchy nose, itchy eyes, and tears) into computers at certain points. (
)
29Jan
Count the pollen number
15
30
45
60
22.1 㫧0.14䋨 㷄䋩
10
0
15
Time (min)
30
45
60
Time (min)
The number of intraocular/intranasal
pollen grains
2000
0
30
60
90
Time (min)
20 / 522 49 / 281
13 /175
䋵
10 / 328
3 /303
Mean pollen number
6 /160
2 /175
AS
12 / 90
Intraocular䋺 13.6 㫧13.6
Intranasal䋺 249.2 㫧120.9
AS
15 /198
Conclusion &
Discussion
I
In the first part of the study, we found that a large number of
pollen was inhaled and precipitated in the nose.
There is a significant difference between pollen grain numbers
in nose and eyes.
The subjects actively inhale pollen grains through their noses,
allowing more pollen to precipitate in the nose, while their eyes
simply received pollen grains and their shedding tears and
blinking had cleared them.
These could be the possible reasons why the number of the
intranasal pollen grains is much larger than that of
the intraocular pollen.
22.2 㫧 0.35 (㷄)
10
120
0
30
60
90
Time (min)
0
0
15
30
60
Time (min)
90
120
Rhinorrhea
1
30
3
60
3
90
6
120
0
1
1
4
4
Nasal obstruction
1
4
6
6
7
Nasal itching
2
4
4
7
8
Eye itching
2
5
6
7
6
0
4500 Pollens/m3
challenge for 2 hr
6000 Pollens/m3
challenge for 2 hr
䃂
䃂
䃂
䃂
䃂
䃂 䃂㪁 䃂
䃂
䃂
䃂
䃂
䃂 䃂㪁
B:
䃂
䃂
䃂
䃂
䃂
䃂 䃂㪁 䃂
䃂
䃂
䃂
䃂
䃂 䃂㪁
C:
䃂
䃂
䃂
䃂
䃂
䃂 䃂㪁 䃂
䃂
䃂
䃂
䃂
䃂 䃂㪁
2
0.23 㫧 0.39
䃂
:epinastine 20mg ; one tablet taken once
䃂:epinastine
a day
䃂
:Placebo : one tablet taken once a day
䃂:Placebo
㪁 :epinastine or Placebo taken before
exposure
(/m33)
6000
4000
2000
0
3
3
Mean changes in Total symptom scores
in questionnaire from baseline
(min)
8
Sneezing
Watery eyes
Visit3
Ministry of the Environment Government
The number of the subjects who showed nose/eye
symptoms during 2 hour allergen exposure
15
Visit2
A: epinastine group (n=10)
B: placebo + epinastine group (n=9)
C: placebo group (n=10)
120
2
Nasal secretion (g/hr)
One subject exited the chamber 10 min earlier because of symptom development.
The rest subjects were able to stay for an hour without developing symptoms.
20
4
Female
6 /260
30
Mean changes in total symptom scores in questionnaire
TV
Male
Temperature (㷄)
Number of pollen ( /m3)
20
3000
40
No. of cedar pollens in Tokyo
0
30
grains/m3
12Feb
44.8 㫧 0.65 (%)
3
0.73 㫧 0.83
One subject showed no symptoms (either nasal or ocular).
No adverse event was reported in this study.
II
In the second part of the study, subjects were exposed to
4500/m3 of JC pollen, which is equivalent to the amount of
airborne pollen grains in the midterm stages of pollen season.
The number of subjects who developed nasal and eye symptoms
increased as time went by after entering the chamber.
As far as pollinosis is concerned, however, our data cannot be
immediately applied to a real case since the results depend on the
amount of pollen, the pollen season, and the severity of the
patients’ symptoms.
Therefore, further investigations are required to decide an
appropriate amount of pollen, to obtain reproducible results, and
to secure the safety of the subjects.
VIsit3 (2/12)
VIsit2 (2/5)
Mean total symptom scores
from baseline
1000
40
4367 㫧 207
Mean total symptom scores
2000
Temperature (㷄)
Number of pollen ( /m3)
3000
Humidity (%)
2572.8 㫧
264.5grains/m3
50
4000
5Feb
A:
50
5000
Humidity (%)
44.7㫧0.48 (%)
4500 Pollens/m3
challenge for 1 hr
1. none, 2. mild, 3. moderate, 4. severe, and 5. very severe.
Results
4000
Visit1
The symptoms were classified as follows:
㪁 Volunteers were allowed to exit the room in case they should
developed allergic symptoms (either in nose or in eyes).
30Jan
2
A
1.5
B
C
1
0.5
0
㪁㪁:P<0.01 (A VS B)
#:P<0.05 (A VS C)
-0.5
-1
㪁㩷㪁
#
0
15
30
60
90
120
0
15
Minutes
30
60
90
120
Minutes
Total symptom scores in questionnaire
Sneezing, nasal discharge, nasal obstruction, itchy eyes, watery eyes
1:No symptom, 2:Mild, 3:Moderate, 4:Severe, 5:Very severe
A: epinastine group
B: placebo + epinastine group
C: placebo group
III
Total symptom scores (TSS) in epinastine group was
significantly lower than those in other groups in an early stage
of the exposure at the Visit 2.
Although significant differences in TSS were not observed
among three groups at the Visit 3, TSS in epinastine group was
lower than those in other groups during allergen exposure.
This study showed that 20 mg of epinastine once daily reduced
the severity of allergic symptoms compared with that once in a
week or placebo in pollen season.