Dynamics of early phase congestion after nasal allergen provocation.

Abstract

It is generally accepted that congestion during the nasal provocation is most pronounced at about 15 minutes after allergen application. However, it may reach its peak at a different time. This can cause inaccurate assessment of the nasal challenge. The aim of this study was to evaluate the dynamics of early phase congestion during nasal allergen provocation (NPT) and its reproducibility.
Two nasal allergen challenges were performed in 26 allergic rhinitis volunteers. Acoustic Rhinometry measurements were recorded beJbre, and then every 5 minutes/for 30 minutes after the allergen application. The sum of cross-sectional areas at the level of the head of inferior nasal turbinate (CSA-2) of both nasal passages was analyzed.
The mean time to the occurrence of maximum congestion was 20 minutes. The maximum congestion differed significantly from that recorded at 10, 15 and 20 minutes. The observed patterns of congestive response were not consistent, with inter- and intra-individual differences regarding the time to maximum congestion. Percentage change in airway dimension recorded at the maximum congestion was found the least variable.
Evaluation of the maximum congestion pattern during the NPT gives more accurate data compared to a single measurement of nasal patency.

Full text

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Rhinology, 46, 52-55 2008
*Received for publication: January 18, 2007; accepted: October 29, 2007
INTRODUCTION
Nasal allergen provocation is a valuable tool used for diagnos-
ing and monitoring treatment of allergic rhinitis. Objective
assessment of the nasal airways is recommended for evaluation
of nasal allergen provocation
during the nasal allergen provocation (NPT), congestion of
nasal mucosa is most pronounced at about 15 minutes after
allergen application. However, congestion may reach its peak
at a different time. Variability in the time to occurrence of
maximum congestion can lead to an underestimation of the
response to allergen and result in inaccurate assessment of the
challenge. Assessment of nasal patency at maximum conges-
tion has been used to investigate the effect of unilateral nasal
provocation
trol for the effect of the nasal cycle and is therefore preferred
to unilateral
Acoustic rhinometry (AR) is a quick, noninvasive, repro-
ducible method of assessment of nasal cavity geometry consid-
ered suitable for monitoring nasal provocation testing
method enables us to perform repeated measurements as fre-
(1). It is generally accepted that
(2,3). Bilateral nasal provocation enables us to con-
(1,4).
(1,5,6). The
quently as every 5 minutes.
The aim of this study was to evaluate the dynamics of early
phase congestion after nasal allergen provocation and its repro-
ducibility.
MATERIAL AND METHODS
Patients
Twenty-six patients allergic to grass or birch pollen, including
11 women and 15 men, mean age 24 years (range 16 to 34
years), with a history of symptoms during environmental expo-
sure and positive skin prick tests (Allergopharma, Reinbek,
Germany) were included in our study. The exclusion criteria
were: perennial symptoms, significant nasal deformity, nasal
polyposis, immunotherapy (recently or in the past), respiratory
tract infection or treatment with antihistamine drugs during
the previous two weeks (4 weeks for astemizole), treatment
with steroids over the last month or any other drugs the three
days prior to NPT. The protocol was approved by the local
Ethics Committee. The patients gave informed consent before
entering the study.
Background: It is generally accepted that congestion during the nasal provocation is most pro-
nounced at about 15 minutes after allergen application. However, it may reach its peak at a
different time. This can cause inaccurate assessment of the nasal challenge. The aim of this
study was to evaluate the dynamics of early phase congestion during nasal allergen provocation
(NPT) and its reproducibility.
Methods: Two nasal allergen challenges were performed in 26 allergic rhinitis volunteers.
Acoustic Rhinometry measurements were recorded before, and then every 5 minutes for 30 min-
utes after the allergen application. The sum of cross-sectional areas at the level of the head of
inferior nasal turbinate (CSA-2) of both nasal passages was analyzed.
Results: The mean time to the occurrence of maximum congestion was 20 minutes. The maxi-
mum congestion differed significantly from that recorded at 10, 15 and 20 minutes. The
observed patterns of congestive response were not consistent, with inter- and intra-individual
differences regarding the time to maximum congestion. Percentage change in airway dimension
recorded at the maximum congestion was found the least variable.
Conclusions: Evaluation of the maximum congestion pattern during the NPT gives more accu-
rate data compared to a single measurement of nasal patency.
Key words: acoustic rhinometry, allergic rhinitis, nasal provocation, allergen provocation, con-
gestion
SUMMARY
Dynamics of early phase congestion after nasal
allergen provocation*
Tomasz Gotlib
1, Boleslaw Samolinski
2, Antoni Grzanka
2, Jaroslaw Balcerzak
1
1
Department of Otolaryngology, Medical University of Warsaw, Warsaw, Poland
Laboratory of the Prevention of Environmental Hazards, Medical University of Warsaw, Warsaw, Poland
2
‘

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Gotlib et al.
53
Study design
Two provocations were performed at least four weeks apart, in
the autumn and winter. The placebo (allergen solvent) chal-
lenge was assessed during another session.
Allergens
Standardized grass or birch pollen extracts (Allergopharma,
Reinbek, Germany) 5000 BU/ml was used. Two puffs (0.05 ml
each) of the solution at room temperature were applied to both
nostrils of the subject with the use of a metered pump spray
(total applied dose was 1000 BU).
Acoustic rhinometry
AR was carried out with the use of the SRE 2000 rhinometer
(Rhinometrics, Lynge, Denmark) according to the guidelines
of the Standardization Committee on Acoustic Rhinometry
Transparent anatomical nose adaptors and sealing gel were
used. After 20 minutes of acclimatization the baseline mea-
surements were performed every 15 minutes. After the chal-
lenge, measurements were taken every 5 minutes for 30 min-
utes. The sum of cross-sectional areas at the second notch
(CSA-2) for both sides was analyzed. Symptom scores were
recorded on a VAS scale (100 mm length) for seven symp-
toms: itching, sneezing, rhinorrhoea, nasal blockage, dyspnoea,
ocular symptoms and one additional symptom.
(7).
Data analysis
Special software identifying location of the CSA-2 was used.
For each patient, the total CSA-2 decrease at 10, 15, 20 min-
utes and at the maximum congestion observed during a 30-
minute period after the challenge were calculated. Decrease in
the sum of CSA-2 for both sides of the nose after the provoca-
tion was calculated as a change ratio from the initial value.
This parameter, defined as “percentage change in airway” (Δ),
was calculated according to the formula:
Δ = (CSA-2 after decrease - CSA-2 before decrease) / CSA-2
before decrease x 100%
The variability (V) of assessments was calculated according to
the formula:
V = Δ1 – Δ2 / Δ1 + Δ2
Δ1 = percentage change in airway at the first provocation,
Δ2 = percentage change in airway at the second provocation
Statistical evaluation
Student t-test was used.
RESULTS
Compared to the response to the control solution all the chal-
lenges were positive as demonstrated by the symptoms (VAS):
10 mm vs. 206 mm after provocation 1 and 213 mm after
provocation 2 (p < 0.001). Mean total cross-sectional area
remained almost completely unchanged following the applica-
tion of the control solution.
Percentage change in airway (Δ) at 10, 15, 20 minutes and at
maximum congestion after allergen provocation are presented
in Table 2. The maximum congestion measured as percentage
change in airway (Δ) was 38% and 42% during consecutive chal-
lenges. The mean Δ at 10, 15 and 20 minutes were 29%, 30%,
Figure 1. Percentage change in airway (Δ) at 10, 15, 20 minutes and at
the maximum congestion after the provocation. Statistical significance:
* (p < 0,05) - compared to near presented values.
1
2
3
4
5
6
7
8
9
1 0
1 1
1 2
1 3
1 4
1 5
1 6
1 7
1 8
1 9
2 0
2 1
2 2
2 3
2 4
2 5
2 6
5 10 1520253035
subjects
p r o vo catio n 1
p r o vo catio n 2
time [min.]
Figure 2. Time of occurrence of maximum congestion after provoca-
tion 1 – diamonds, and provocation 2 - circles (longitudinal axis) in
individual patients (vertical axis).
Percentage change in airway

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54
Dynamics of congestion…
31%, during the first provocation and 28%, 34%, 38% during the
second provocation respectively (Figure 1). The difference
between Δ at the maximum congestion and each at 10, 15 and
20 minutes was statistically significant for both provocations.
The mean time of maximum congestion occurrence was 20
minutes after allergen application for both challenges (range 5-
30). Maximum congestion reached peak at 15 minutes in 7
(27%) patients during provocation 1 and in 9 (34%) after provo-
cation 2. The difference in time of occurrence of maximum
congestion between the consecutive provocations was 10 min-
utes or more in 10 cases (38%). The same time of occurrence
of maximum congestion was observed in 7 patients
(27%)(Figure2).
The lower variability of Δ was observed for the assessment at
maximum congestion (Figure 3)
DISCUSSION
Several factors have been proven to influence the congestive
response during NPT including a priming effect, sex hor-
mones, environmental factors (temperature, humidity)
difference between mean percentage change in airway (Δ) dur-
ing the first and second provocation in our study was on the
borderline of statistical significance (p = 0.05). Higher mean Δ
after the second provocation is most probably caused by the
priming effect in spite of over four weeks interval between the
challenges. The influence of hormones can not be ruled out
since we did not evaluate hormonal status of female patients
during the challenges.
(8,9). The
CSA 2 is not always the only affected area during the allergen
challenge. In the present study we analyzed exclusively CSA-2
changes in order to avoid comparing congestive responses that
could occur at different depths of the nasal cavity. This could
affect further analysis of the results.
To our knowledge there are only few studies evaluating
dynamics of early phase congestion response with frequent
consecutive measurements after bilateral nasal provocation
(10,11). In these studies the mean-time to maximum congestion
was similar to that found in our study group (i.e. 18-20 min-
utes). In our study group the time to occurrence of maximum
congestion did not depend on the value of percentage change
in airway (Δ). Higher Δ observed after the second provocation
did not influence the mean time to occurrence of maximum
congestion. So far there have been no data proving that time to
maximum congestion could be dependent on allergen dose.
The time to occurrence of maximum congestion is most prob-
ably not an constant subject-dependent feature, since it dif-
fered in consecutive provocations in the same patient in our
study group.
Larivée et al. evaluated the reproducibility of bilateral NPT
with histamine and saline phosphate using AR measurements
every 5 minutes before and after the provocation. The compar-
ison of the congestive response of the rhinitic subjects revealed
that their responses were more dynamic and not steady, com-
pared with those of the normal subjects. In our study group
similar inconsistent patterns of congestive response were
observed
design, Jin et al. observed marked, statistically significant
shortening in period of the nasal cycle after the provocation
(10). In an allergen provocation study with similar
(11).
All these data suggest the activation of a reflex mechanism and
a modification of the nasal cycle besides non-vascular swelling
of the tissue during the NPT. There is evidence that unilateral
provocation induces contralateral increase of the mediators’
concentration, influences the nasal patency, blood flow and
secretion
maximum congestion is variable.
(12-14). This may explain why time of occurrence of
Inter- and intra-individual differences in congestive response
dynamics is the most likely reason for the unsatisfactory sensi-
tivity and specificity of the NPT assessed with a single measure-
ment of the nasal patency and discrepancies between subjective
and objective patient evaluation.
It seems that the optimum period of observation to record maxi-
mum congestion is 30 minutes after allergen application. Results
of previous studies suggest that congestion during the early
phase reaction subsides in most subjects 35 to 60 minutes fol-
lowing allergen application
tion is less pronounced, and observed in only some of patients
(15). In our study group the delayed maximum congestion at 30
minutes was observed in 4 out of 52 provocations only.
Maximum congestion assessment would most probably enable
reduction of the allergen dose in NPT protocols with increas-
ing concentrations of allergen.
(10,11,15). During the late phase conges-
CONCLUSION
Consecutive recordings of nasal patency over 30 minutes after
allergen application allow evaluation of the maximum conges-
tion, which gives more precise data on congestive response to
nasal challenge compared to a single measurement.
Figure 3. Variability (vertical axis) of assessments at the maximum
congestion and at 10, 15 and 20 minutes.

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Gotlib et al.
55
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Tomasz Gotlib MD PhD
Department of Otolaryngology
Medical University of Warsaw
02-097 Warszawa
Poland
Tel. +48-(22)-599 2509
Fax. +48-(22)-599 2041
E-mail: gotlib@amwaw.edu.pl.
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