Original Paper
Int Arch Allergy Immunol 2010;151:137–141
DOI: 10.1159/000236003
Nasal Lavage in Pregnant Women with
Seasonal Allergic Rhinitis:
A Randomized Study
Werner Garavello a, b Edgardo Somigliana c Barbara Acaia c Lorenzo Gaini b
Lorenzo Pignataro b Renato Maria Gaini a
a
Department of Otorhinolaryngology, DNTB, University of Milano-Bicocca, Monza, and b Department of
Otorhinolaryngology, c Fondazione Ospedale Maggiore Policlinico, IRCCS, Mangiagalli e Regina Elena, Milano, Italy
Key Words
Allergic rhinitis ⴢ Nasal rinsing ⴢ Pregnancy
Abstract
Background: Nasal rinsing appears particularly suitable in
the management of pregnant women with seasonal allergic
rhinitis since no deleterious effects on the fetus are to be ex-
pected. However, to date, no studies have specifically inves-
tigated this option. Methods: Pregnant women with season-
al allergic rhinitis were randomized to intranasal lavage with
hypertonic saline solution 3 times daily (n = 22) versus no lo-
cal therapy (n = 23) during a 6-week period corresponding
to the pollen season. Patients were invited to keep a daily
record of rhinitis symptoms (rhinorrea, obstruction, nasal
itching and sneezing), to record consumption of oral antihis-
tamine and to undergo rhinomanometry. Results: The rhini-
tis score was similar at study entry but a statistically signifi-
cant improvement in this score was observed in the study
group during all subsequent weeks (p ! 0.001 for weeks 2–
6). The mean number of daily antihistamines use per patient
per week was significantly reduced at weeks 2, 3 and 6 (p !
0.001, p ! 0.001 and p = 0.001, respectively). Baseline rhino-
manometry performed at week 1 showed similar nasal resis-
tance in the study and control groups. In contrast, a statisti-
cally significant difference emerged in the 2 following
© 2009 S. Karger AG, Basel
1018–2438/10/1512–0137$26.00/0
Fax +41 61 306 12 34
E-Mail karger@karger.ch Accessible online at:
www.karger.com www.karger.com/iaa
Received: February 23, 2009
Accepted after revision: April 24, 2009
Published online: September 15, 2009
evaluations. At week 3, nasal resistance in the study and con-
trol groups was 0.96 8 0.44 and 1.38 8 0.52 Pa/ml/s, respec-
tively (p = 0.006). At week 6, it was 0.94 8 0.38 and 1.35 8
0.60 Pa/ml/s, respectively (p = 0.006). No adverse effect was
reported in the active group. Conclusions: Nasal rinsing is a
safe and effective treatment option in pregnant women
with seasonal allergic rhinitis. Copyright © 2009 S. Karger AG, Basel
Introduction
Allergic rhinitis is common during pregnancy since
nasal obstruction may be aggravated by pregnancy itself
[1]. Pregnancy may initiate or increase nasal allergy and
the course of allergic rhinitis is often altered significant-
ly by pregnancy [2, 3]. Studies evaluating changes in al-
lergic rhinitis symptoms with pregnancy demonstrate
that approximately one third of women worsen during
that time [4, 5]. The use of specific medical treatment is
often required. The use of any medication in any patient
entails acceptance of risks, but the use of pharmacother-
apy during pregnancy involves consideration of addition-
al risks. Since safety studies on medication use during
pregnancy rarely support definitive conclusions, caution
should always be taken when administering a drug to a
Correspondence to: Dr. Werner Garavello
Department of Otorhinolaryngology
Ospedale San Gerardo, University of Milano-Bicocca
Via Pergolesi, 33, IT–20052 Monza (Italy)
Tel. +39 039 233 3623, Fax +39 039 324 017, E-Mail werner.garavello@unimib.it
pregnant woman as most medications cross the placenta
[6–8]. The fear is particularly high during the first tri-
mester when organogenesis occurs [9].
The management of allergic rhinitis includes allergen
avoidance, pharmacological treatment and specific im-
munotherapy [10, 11]. While measures aimed to remove
allergen exposure have first to be considered, this may
not be always effective, particularly for outdoor allergens.
Pharmacological treatment is often necessary. The most
commonly used medications are antihistamines and cor-
ticosteroids [11, 12]. In this context, a less extensively in-
vestigated but simple alternative is the use of nasal rinsing
with isotonic or hypertonic solutions. This approach ap-
pears particularly appealing in the management of preg-
nant women since no deleterious effects on the fetus are
expected. Benefits of nasal irrigation as an adjunctive
treatment modality have been reported in many sinona-
sal diseases, including allergies [13–15]. In 2 previous
studies by our group, we documented remarkable bene-
fits of nasal rinsing with hypertonic solutions in infants
with allergic rhinitis or rhinoconjunctivitis [16, 17]. To
our knowledge, no studies have specifically investigated
the benefits of this treatment in pregnant women.
Material and Methods
Between November 2006 and March 2007, pregnant women
referred to the San Gerardo Hospital (Monza, Italy) who had been
affected by Parietaria pollen allergic rhinitis for at least 5 years
were invited to participate in this randomized study. Specifically,
the following criteria for inclusion were adopted: (1) typical an-
amnesis for seasonal allergic rhinitis; (2) marked positivity of the
prick tests (62 plus) to Parietaria pollen extracts in a hydrogly-
ceric solution titrated at 20,000 biological units/ml (SARM Aller-
geni, Guidonia, Italy), and assessed according to the already
known guidelines [18], and (3) uncomplicated pregnancy whose
expected delivery date was after the pollen season. Patients were
excluded because of: (1) coexistence of nasal polyposis and/or
bronchial asthma; (2) sensitization to other allergens, and (3) pre-
vious specific immunotherapy. All patients were under the care
of one of the authors (W.G.). The study was approved by the local
institutional review board and all patients gave their informed
consent before entering the study. Based on grass pollen count
observed in 2007, a study period lasting for 6 weeks from April 30
to June 11, 2007 was decided. Results from a volumetric pollen
trap (Burkard Manufacturing, Rickmansworth, UK) located in
our area confirmed that this study period was largely coincident
with the pollen season.
Patients were recruited up to March 26, 2007, and were ran-
domly assigned to the active or control group according to ran-
domization tables. Sealed opaque envelopes containing the treat-
ment allocation were opened after randomization just before the
initiation of the study period. The allocation sequence was pre-
138 Int Arch Allergy Immunol 2010;151:137–141
pared by one of the authors (E.S.). Another author (W.G.) enrolled
and assigned patients to the treatment groups. Women and physi-
cians were not blinded to treatment allocation. Patients random-
ized to the active group were instructed to carry out intranasal
lavage 3 times daily using the hypertonic saline solution (NaCl
3%, 925 8 30 mOsm/kg, pH 7.45 8 0.2) administered using a
disposable syringe filled with 20 ml sterile solution (10 ml in each
nostril) at room temperature. They were instructed to energeti-
cally breathe in during administration. No local therapy was pre-
scribed to the control group. Compliance to treatment was not
ensured. During the study period, patients were instructed to
keep a daily record of 4 allergic symptoms. The degree of severity
of the nasal symptoms rhinorrea, obstruction, nasal itching and
sneezing, was recorded on a scale of 0–4 (0 = none; 1 = slight; 2 =
mild; 3 = moderate; 4 = severe). A total score (ranging from 0 to
16) representing the sum of scores of these 4 symptoms was used
to calculate a mean daily rhinitis score per patient for each week
of the pollen season. Patients of both groups were also allowed to
use oral antihistamines when needed and to record the relative
intake. This information was used to calculate the mean number
of daily antihistamines use per patient per week. The choice of the
preparation (cetirizine, levocetirizine, oxatomide, loratadine or
desloratadine) and the dosage was left up to the patients. Finally,
patients were invited to record adverse effects, if present.
Rhinomanometry was performed in all recruited patients at 3
different time points during the study period (the first, third and
sixth weeks). The examination was performed as previously de-
scribed [19]. Briefly, nasal airflow was measured by active ante-
rior rhinomanometry. Patients wore a tight-fitting facemask, and
breathed through one nostril while keeping their mouth closed.
A sensor, placed in the contralateral nostril, recorded data on pre-
and postnasal pressures via airflow and pressure transducers. The
instrument (Rhinomanometer Menfis; Amplifon, Italy) was con-
nected to a personal computer. The signals of transnasal airflow
and pressure were amplified, digitalized and saved for statistical
analysis. Nasal resistance was measured in milliliters per second
as the sum of the recorded airflow through the right and left nos-
trils at a pressure difference of 150 Pa across the nasal passage.
Four or more airflow measurements were performed for each pa-
tient, and the mean value was recorded when reproducible values
were achieved. Normal values are !0.50 Pa/ml/s.
The primary aim was to evaluate the impact of nasal rinsing
on allergic rhinitis symptoms at the time women became symp-
tomatic. Secondary outcomes were the intake of antihistamines
and nasal resistance. Statistical analysis was performed using un-
paired Student’s t test to compare rhinitis score and antihistamine
use. Differences were always confirmed, also using non-paramet-
ric Wilcoxon’s test for unpaired data. Basal characteristics of the
2 groups were compared using Fisher’s exact test or unpaired Stu-
dent’s t test, as appropriate. p ! 0.05 was considered significant in
all comparisons. Calculation of the sample size a priori was not
performed since this type of calculation is strongly determined by
the rate of the event (symptoms of allergic disease and use of oral
antihistamine) in the control group. Unfortunately, the allergen
concentration is influenced by weather and may thus vary widely
from one year to the other. As a consequence, frequency and se-
verity of symptoms of allergic rhinitis also vary widely from one
year to the other.
Garavello /Somigliana /Acaia /Gaini /
Pignataro /Gaini
 16
57 patients
selected 14

5 declined to 12

Clinical rhinitis score

participate
in the study 10

52 patients 8
randomized
6

4
26 assigned to treatment 26 assigned to control
2

0
3 declined to 1 2 3 4 5 6
participate Study period (weeks)
before 3 censored
treatment, during
1 censored treatment
Fig. 2. Mean 8 SD of the rhinitis score during the 6-week period
during
treatment
of the Parietaria season for both patients treated with nasal irriga-
tion (solid line) and controls (dotted line). The total score (ranging
from 0 to 16) was calculated as the sum of scores of 4 different
22 completed the study 23 completed the study
symptoms (rhinorrea, obstruction, nasal itching and sneezing).
This score was similar at study entry (week 1). A statistically sig-
nificant reduction of this score was observed in the study group
during all subsequent weeks (p ! 0.001 for weeks 2–6).
Fig. 1. Trial profile. Fifty-seven women were eligible, 5 of them
declined to participate and 52 were randomized to the treatment
(n = 26) and control (n = 26) groups. Three women in the study
group declined to participate prior to initiation of the study. Four
Results
women were censored during treatment. Three of them (1 in the
study group and 2 in the control group) did not complete the study
period due to low adherence to the study protocol or personal rea- The trial profile is shown in figure 1. Fifty-seven wom-
sons and 1 (control group) developed preeclampsia and was ad- en satisfied our selection criteria, 52 were randomized (26
mitted to hospital. Overall, 45 women (22 in the study group and per arm). Seven patients withdrew after randomization
23 in the control group) were available for data analysis.
so that 45 women completed the study (22 in the study
group and 23 in the control group) and were available for
data analysis. Baseline characteristics of these 2 groups
Table 1. Baseline characteristics of patients completing the were similar (table 1). No adverse effect was reported in
study the active group.
Evidence from patients’ diary cards showed signifi-
Characteristics Nasal lavage Controls cant clinical benefits in women who received a regimen
(n = 22) (n = 23)
of 3-times daily nasal rinsing with hypertonic saline so-
Age, years 23.985.4 24.485.8 lution during the pollen season (fig. 2). Whereas the mean
Duration of disease, years 7.982.9 9.484.7 weekly rhinitis score at week 1 was similar in the study
Parity and control groups (3.7 8 1.6 and 4.1 8 1.9, respectively,
Nulliparae 13 (59%) 12 (52%) p = 0.57), a highly statistically significant benefit was
Pluriparae 9 (41%) 11 (48%)
documented in all subsequent weeks when exposure to
Gestational age
I trimester 8 (36%) 10 (43%) Parietaria allergens occurred (p ! 0.001 for weeks 2–6).
II trimester 6 (28%) 5 (22%) Similar results were observed when focusing on the
III trimester 8 (36%) 8 (35%) use of oral antihistamines. Whereas the intake of these
drugs were similar in the study and control groups at
None of the variables was found to significantly differ between
the 2 study groups.
week 1 (0.9 8 1.0 and 1.0 8 1.1 tablets daily, respective-
ly, p = 0.66), a benefit of nasal rinsing was subsequently

Nasal Lavage in Allergic Rhinitis during Int Arch Allergy Immunol 2010;151:137–141 139
Pregnancy

6
5
Number of antihistamines/week
4
3
2
1
0
1 2 3 4
Study period (weeks)
Fig. 3. Mean 8 SD of the oral antihistamine intake during the 6-
week period of the Parietaria season for both patients treated with
nasal irrigation (solid line) and controls (dotted line). The mean
number of daily antihistamines use per patient per week is shown.
This score was similar at study entry (week 1, p = 0.66) and at week
4 (p = 0.25), significantly different at weeks 2, 3 and 6 (p ! 0.001,
p ! 0.001 and p = 0.001, respectively) and of borderline signifi-
cance at week 5 (p = 0.07).
observed. Specifically, a statistically significant differ-
ence was documented in 3 out of the 5 remaining weeks
of the study period (weeks 2, 3 and 6). A borderline sig-
nificance was observed at week 5 (p = 0.07) whereas no
differences could be observed at week 4. These results are
illustrated in figure 3.
Baseline rhinomanometry performed at week 1 showed
similar nasal resistance in the study and control groups
(0.65 8 0.35 and 0.59 8 0.30 Pa/ml/s respectively, p =
0.55). A statistically significant difference emerged in the
2 following evaluations. At week 3, nasal resistance in the
study and control groups was 0.96 8 0.44 and 1.38 8
0.52 Pa/ml/s, respectively (p = 0.006). At week 6, it was
0.94 8 0.38 and 1.35 8 0.60 Pa/ml/s, respectively (p =
0.006).
Discussion
In this study, we have demonstrated that nasal rinsing
with hypertonic saline is an effective option in the man-
agement of pregnant women with seasonal allergic rhini-
tis. Patients receiving this treatment report a strong ben-
140 Int Arch Allergy Immunol 2010;151:137–141
efit in terms of symptoms. The value of this approach is
further supported by the reduced intake of oral antihis-
tamines and by results from rhinomanometry indicating
that nasal resistance is improved in the active group.
Moreover, it is wise to note that no adverse effect was re-
ported, thus supporting the safety of this approach.
A controversy in our study may be related to the study
design since our trial was not blinded and we did not use
placebo. Although such study design would have been
preferable, the extreme specificity of the way of adminis-
tration hampers its application. In this context, it should
be noted that none of the available studies have conduct-
ed a true double-blinded placebo-controlled trial. From
5 6
an experimental point of view, prescribing nasal rinsing
with alternative solutions to the control group is a poor
option since the benefits of this treatment are partly due
to its mechanical effects and are thus independent from
the product used.
Overall, we do not believe that the placebo effect played
a crucial role in our trial, for at least 3 reasons. First, the
benefits of the treatment are not limited to the improve-
ment in rhinitis score or the use of oral antihistamine.
Results from rhinomanometry also showed that nasal re-
sistance is reduced in women receiving nasal rinsing. A
placebo effect could not explain this result. Second, a
striking difference has emerged between the active and
the control group. It is highly unlikely that the placebo
effect per se could explain such a marked difference.
Third, the control group also received a medical treat-
ment (oral antihistamines, if needed). A more significant
placebo effect would have been expected if no therapy
rather than medical therapy was prescribed. Overall, al-
though a role for the placebo effect cannot be ruled out,
it is unlikely that this effect could explain the results ob-
served in this trial. Of note, in our study, compliance with
the protocol was extremely high, patients were under the
care of only 1 experienced physician and basal character-
istics of the 2 study groups were similar. Therefore, we
estimate that other important sources of bias in our trial
can be excluded.
The exact mechanism by which nasal irrigation has an
effect is not well understood and is likely multifaceted. At
least 3 different effects may improve the ability of nasal
mucosa to reduce the pathologic effects of inflammatory
mediators and other triggers of allergic rhinitis. They in-
clude the following. (1) The direct cleaning effect: as the
saline passes through the nasal cavity, it thins and re-
moves obstructive mucus and crusts; this mechanism is
likely responsible for the immediate sense of improved
breathing that many subjects report [20–22]. (2) Removal
Garavello /Somigliana /Acaia /Gaini /
Pignataro /Gaini
or reduction of inflammatory mediators: nasal mucus
contains inflammatory mediators such as histamine,
prostaglandins, leukotrienes and eosinophil-released
major basic protein [23, 24]. (3) Improved mucociliary
function: an improved mucociliary clearance with in-
creased ciliary beat frequency has been shown in patients
receiving nasal rinsing [25, 26].
In conclusion, nasal rinsing with hypertonic saline is
a safe and effective treatment option in pregnant women
with seasonal allergic rhinitis. Physicians facing this clin-
ical situation should always consider the possibility of
prescribing this simple but valuable treatment. Future
studies are required to better clarify the precise role of
this option in the armamentarium of available treat-
ments.

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Pregnancy
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