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The Journal of Laryngology & Otology, 1 of 5.


# 2008 JLO (1984) Limited
doi:10.1017/S0022215108003964

Impact of isotonic and hypertonic saline solutions


on mucociliary activity in various nasal pathologies:
clinical study
A URAL, T KOCAK OKTEMER, Y KIZIL, F ILERI, S USLU

Abstract
Objective: To investigate the impact of nasal irrigation with isotonic or hypertonic sodium chloride
solution on mucociliary clearance time in patients with allergic rhinitis, acute sinusitis and chronic sinusitis.
Patients and methods: Mucociliary clearance time was measured using the saccharine clearance test on
132 adults before and after 10 days application of intranasal isotonic or hypertonic saline. Patient numbers
were as follows: controls, 45; allergic rhinitis, 21; acute sinusitis, 24; and chronic sinusitis, 42. The results
before and after irrigation were compared using the Wilcoxon t-test.
Results: Before application of saline solutions, mucociliary clearance times in the three patient
treatment groups were found to be significantly delayed, compared with the control group. Irrigation
with hypertonic saline restored impaired mucociliary clearance in chronic sinusitis patients ( p , 0.05),
while isotonic saline improved mucociliary clearance times significantly in allergic rhinitis and acute
sinusitis patients ( p , 0.05).
Conclusion: Nasal irrigation with isotonic or hypertonic saline can improve mucociliary clearance time
in various nasal pathologies. However, these solutions should be selectively prescribed rather than used
based on anecdotal evidence. Further studies should be conducted to develop a protocol for
standardised use of saline solution irrigation in various nasal pathologies.
Key words: Rhinitis; Saline; Irrigation; Cilia

Introduction
The respiratory tract is protected from airborne
infection and debris by a mucociliary layer that
lines the sinonasal cavity.1 This layer is made up of
columnar, ciliated epithelial cells and goblet cells
embedded in mucus. Foreign particles trapped in
the sticky mucus layer are propelled towards the
nasopharynx, along with the entire mucus layer.1
Nasal mucociliary clearance is the first stage of the
host defence mechanism, and plays a critical role in
protection against infection and external stimuli.2
Mucociliary clearance is primarily regulated by the
amount and rheological properties of secreted
mucin and by ciliary activity. Dysfunction of mucociliary clearance aggravates or enhances the development of various nasal diseases.2
Nasal diseases such as allergic rhinitis and acute
and chronic rhinosinusitis are frequent sources of
morbidity, leading to increased healthcare costs and
loss of productivity.3 Inflammation of the paranasal
sinuses interferes with the transfer of particles
towards the pharynx and delays mucociliary transport time.3 5

Nasal irrigation is a simple and inexpensive treatment which relieves the symptoms of a variety of
sinus and nasal conditions (including infectious and
allergic entities), reduces the use of medical
resources and helps minimise antibiotic resistance.6
Nasal irrigation has been used for centuries to treat
various sinonasal diseases, including sinusitis and
allergic rhinitis.2 4 Isotonic saline was first introduced for nasal irrigation, while hypertonic saline
has recently been popularised as it has been found
to decrease oedema and improve mucociliary
clearance.7
Hypotheses regarding the benefits of irrigation are:
(1) improvement of mucociliary clearance, (2)
decrease in mucosal oedema, (3) decrease in inflammatory mediators, and (4) mechanical cleaning of
inspissated mucus.3 Mucosal stasis, infection and
thickening of secretions are all reported to hinder
mucociliary activity. Removal of inspissated mucus
and debris may cause mucociliary clearance to normalise.8 Irrigation with isotonic or hypertonic saline
solutions may help clear crusts and debris, as well as
increase clearance of secretions and thin the mucus.

From the Department of Otorhinolaryngology, School of Medicine, Gazi University, Ankara, Turkey.
Accepted for publication: 18 August 2008.
1

Isotonic saline is reported to improve mucociliary


clearance mostly through mechanical cleaning, while
hypertonic saline solutions exert their effect by
decreasing oedema and increasing mucociliary clearance through stimulation of ciliary beat frequency,
thinning of mucus and suppression of inflammation.
Some authors state that rhinitis results in delayed
mucociliary transport time, whereas others report no
such change.4,9,10 However, there is no standard protocol for nasal irrigation, and physicians choice of nasal
irrigation solution for different nasal pathologies
usually depends on anecdotal evidence.3,7
In this study, we aimed to investigate the effects of
irrigation of nasal cavities with isotonic or hypertonic
saline solutions on mucociliary transport time, in
cases of allergic rhinitis, acute sinusitis and chronic
sinusitis.
Patients and method
At a tertiary academic centre, 87 patients and 45
healthy volunteers were enrolled, after approval
from the local ethical committee and obtaining
informed consent from participants. Of the 87
patients, acute and chronic sinusitis was diagnosed
in 24 and 42, respectively, via clinical history, physical
examination and paranasal sinus computerised tomography scans. A diagnosis of perennial allergic rhinitis was confirmed in 21 patients via clinical
history, physical examination and skin prick testing
(Lincoln Diagnostic, Decatur, Illinois, USA). The
45 healthy volunteers had no health complaints and
a normal rhinoscopic examination. We excluded
from the study any patients with a history of sinonasal disease (other than allergic rhinitis or acute or
chronic sinusitis), smoking, allergy or upper airway
infection over the past three weeks, as well as
patients using topical or systemic sympathomimetics,
parasympathetic agents or antihistamines.
Mucociliary clearance time was measured using
the saccharine clearance test method described by
Prior et al.11 This is a cheap, simple and effective
method of assessing mucociliary clearance and its
role is widely accepted. Saccharine clearance may
be slow or absent in patients with normal mucociliary
transport, due to technical errors. One of the most
common mistakes is placing the saccharine onto
squamous epithelium; this can be avoided with training.11 In our study, all mucociliary clearance time
measurements were performed by the same physician (who was experienced in saccharine clearance
testing), in an attempt to overcome this problem.
This physician was blinded to the type of irrigation
solution used.
A quarter of a saccharine tablet was placed on the
medial part of the inferior concha, 1.5 cm behind the
anterior end of the inferior turbinate. The patient
was asked to swallow every 30 seconds, and the
interval between the application of saccharine and
the detection of a sweet taste was recorded. Measurements were performed in the same room at a
constant humidity and a temperature of 20 258C.
Subjects were instructed to breathe silently through
the nose and not to sniff.

A URAL, T KOCAK OKTEMER, Y KIZIL et al.

After the initial assessment, each subject was


asked to use a solution of either isotonic saline or
hypertonic saline (3 per cent, pH 7.6) for 10 days.
This assignment was made randomly, and patients
in different groups were matched by age. At the
end of 10 days, a total of 160 ml of solution had
been applied to each nasal cavity in two separate
daily doses. Nasal irrigation was administered using
a disposable syringe filled with 8 ml of solution
(4 ml for each nostril). At the end of the 10-day irrigation period, the test was repeated by the same
physician in the same room.
Mucociliary clearance times were found to have a
normal distribution, using the Kolmogorov
Smirnov test. Analysis of variance was performed
to assess difference in mucociliary clearance time
between the four groups, and Dunnets test was utilised to compare the means of the three clinical
groups with that of controls. A p value of ,0.05
was considered significant.
Results
No patients were lost to follow up, and no serious
side effects or intolerance necessitating cessation
of irrigation were reported by patients during the
study.
Before irrigation, the mucociliary clearance times
of the acute sinusitis, chronic sinusitis and allergic
rhinitis patients were found to be delayed compared
with controls ( p 0.013, p 0.007 and p 0.019,
respectively) (Table I, Figure 1). After irrigation
with hypertonic saline, mucociliary clearance times
improved in chronic sinusitis patients ( p 0.016),
while isotonic saline improved mucociliary clearance
times in acute sinusitis and allergic rhinitis patients
( p 0.044 and p 0.047, respectively) (Table 1,
Figure 2).
Isotonic saline irrigation did not cause any significant change in mucociliary clearance time in chronic
sinusitis patients ( p 0.233). Similarly, irrigation
with hypertonic saline did not significantly alter
mucociliary clearance time in acute sinusitis or

FIG. 1
Effect of isotonic saline irrigation on mucociliary clearance
time in the four groups. C control; AR allergic rhinitis;
AS acute sinusitis; CS chronic sinusitis

ISOTONIC AND HYPERTONIC SALINE SOLUTIONS AND MUCOCILIARY ACTIVITY

TABLE I
MUCOCILIARY CLEARANCE TIME BEFORE AND AFTER IRRIGATION WITH ISOTONIC OR HYPERTONIC SALINE SOLUTIONS

Group

Isotonic saline
Pts (n)

Control
Allergic rhinitis
Acute sinusitis
Chronic sinusitis


15
10
12
24

Average MCT
(min)
Pre

Post

17.53
38.70
25.00
22.20

15.13
21.10
17.75
26.08

Hypertonic saline
p

0.382
0.019
0.041
0.306

Pts (n)

30
11
12
18

Average MCT
(min)
Pre

Post

17.80
27.81
30.08
35.17

20.67
28.18
27.50
22.83

0.446
0.941
0.556
0.016

Significant as p , 0.05. Pts patients; MCT mucociliary clearance time; pre pre-irrigation; post post-irrigation

allergic rhinitis patients ( p 0.370 and p 0.941,


respectively) (Table I). In the control group,
neither the isotonic nor the hypertonic saline solution resulted in any significant change in mucociliary clearance time ( p 0.328 and p 0.244,
respectively).
Discussion
Mucociliary clearance of airway epithelium can be
affected by ciliary beat frequency and rheological
changes in mucus. Efforts have been made to
improve ciliary activity and restore mucociliary clearance in various diseases of the upper respiratory
tract.
Nasal irrigation is commonly prescribed to
patients with acute or chronic rhinosinusitis and
after endoscopic sinus surgery, in order to improve
mucociliary function, decrease mucosal oedema,
decrease inflammatory mediators and mechanically
clear inspissated mucus.8 The use of irrigating solutions also improves the penetration and bioavailability of topical medications.1
In adults, irrigation with hypertonic saline has
been advocated, since it has been found to improve
mucociliary clearance time in both acute and
chronic sinusitis patients.4 In children with chronic
sinusitis, hypertonic saline provided better symptomatic and radiological outcomes than isotonic

FIG. 2
Effect of hypertonic saline irrigation on mucociliary clearance
time in the four groups. C control; AR allergic rhinitis;
AS acute sinusitis; CS chronic sinusitis

saline.12 In our study, we did not detect any difference between the mucociliary clearance times of
acute sinusitis and perennial allergic rhinitis patients
before and after application of hypertonic saline solutions. Unlike chronic sinusitis, these two entities are
less likely to cause permanent epithelial structural
damage and ciliary loss, and therefore a change in
ciliary beat frequency would not be expected. In
acute sinusitis and allergic rhinitis, the amount and
rheological properties of secretions are more likely to
contribute to impairment of mucociliary clearance.13
In these circumstances, temporary dysfunction in
mucociliary transport may occur, but immune system
responses and other homeostatic mechanisms can
enable recovery.11 In a recent study, isotonic saline
was found to be the most physiological irrigation
solution in terms of nasal epithelial cell mucin
secretion and cellular morphology.2 On the other
hand, chronic low-grade infections may give rise to permanent ciliary dysfunction and structural changes in
the epithelium.11,14 Electron microscopy studies have
demonstrated ciliary disorientation, loss of ciliated epithelial cells and an increase in nonciliated cells in
chronic rhinosinusitis patients.3 The more severe the
chronic sinusitis, the more delayed the nasal mucociliary clearance time.9,10
A randomised study of 143 patients investigated
the symptom scores of common cold and rhinitis
patients before and after using isotonic or hypertonic
saline, and before and after observation only. No
difference was found between the symptom scores
of the various groups.15 The use of nasal irrigation
for acute rhinosinusitis is under debate. Our findings
indicate that irrigation with isotonic saline is more
effective in improving mucociliary clearance time in
this patient group.
Hypertonic saline has been found to improve the
symptoms of allergic rhinitis and chronic rhinosinusitis.3 Our findings regarding the benefit of hypertonic
saline irrigation in chronic rhinosinusitis confirm
these results. We found that irrigation with
isotonic saline (but not hypertonic saline) resulted
in improved mucociliary clearance time in
patients with perennial allergic rhinitis. In chronic
sinusitis, the effect of hypertonic saline on mucociliary clearance time is more obvious, since it stimulates
ciliary beat frequency and thus restores the main
impaired mechanism causing mucociliary clearance
delay.

A topical antibacterial effect of hypertonic saline


has been documented in some studies.12,16
However, our study found no effect of hypertonic
saline on mucociliary clearance time in acute sinusitis
patients, indicating that an antibacterial effect may
not be the main mechanism by which hypertonic
saline improves mucociliary clearance time. Once
suppurative and chronic inflammation is established,
the beneficial effect of hypertonic saline on mucociliary clearance time becomes more obvious.17 Majima
et al. proposed that the retarded nasal mucociliary
clearance seen in chronic sinusitis may be related to
factors other than the rheological properties of
mucus. Histological examination of chronic maxillary sinusitis has shown disorientation of mucosal
epithelia cilia.18 This raises the possibility that the
main effect of hypertonic saline is achieved through
stimulation of ciliary beat frequency.19 Hyperosmolar fluid in the airway causes release of calcium and
prostaglandin E2 from intracellular stores, increasing
the availability of adenosine triphosphate to the
cilia axoneme, resulting in increased ciliary beat
frequency.12,20
Since hypertonic saline has different effects in
patients with allergic rhinitis compared with acute
sinusitis, we believe that the rheological properties of
mucus play an important role as determinants of
mucociliary clearance time in these two conditions.
Isotonic saline provides simple mechanical cleaning
without any osmotic gradient, and decreases inflammatory mediators in the medium by simply flushing out
irritants and mucus.1,13 Garavello et al. reported that
hypertonic saline was useful in patients with seasonal
allergic rhinitis through its effect of decreasing leukotriene C4 levels.6 In our study, we enrolled patients
with perennial allergic rhinitis, since the symptoms
and mucociliary clearance status of seasonal allergic
rhinitis patients could vary throughout the year.
Overall, we speculate that ciliary beat frequency is
a more important determinant of mucociliary clearance time in chronic sinusitis patients. In contrast,
mucociliary clearance time in allergic rhinitis and
acute sinusitis patients is more likely to be influenced
by the rheological properties of mucus. Hypertonic
saline seems to act by affecting ciliary beat frequency,
whereas isotonic saline is more likely to modify the
rheological properties of mucus.
In allergic rhinitis patients, hypertonic saline irrigation has been reported to decrease leukotriene
C4 levels.3 Garavello et al. have supported the use
of hypertonic saline irrigation in seasonal allergic rhinitis patients.6 Georgitis et al. found that irrigation
with isotonic saline led to a decline in histamine
and leukotriene C4 levels in patients with allergic rhinitis.13 In our study, we did not find any improvement
in the mucociliary clearance time of perennial allergic rhinitis patients after hypertonic saline irrigation.
We believe that, in patients with perennial allergic
rhinitis and acute sinusitis, the rheological properties
of mucus (affected by isotonic saline irrigation) are
more important determinants of mucociliary clearance time.
In a recent study, both hypertonic and isotonic
saline solutions were found to improve mucociliary

A URAL, T KOCAK OKTEMER, Y KIZIL et al.

transport and to provide symptomatic relief.5


However, hypertonic saline was reported to be
more irritating to the nasal mucosa. In our study,
we did not encounter intolerance to the saline solutions sufficient to stop treatment; however, lack of
a discrete symptomatic assessment scale would
appear to be a limitation of the study.

. Nasal irrigation is a simple, cheap and effective


treatment for sinonasal pathologies which
reduces symptoms, reduces the need for other
treatment options and helps decrease
antibiotic resistance
. Isotonic and hypertonic saline solutions are
commonly used for nasal irrigation
. This study investigated changes in mucociliary
clearance in patients with allergic rhinitis,
acute sinusitis and chronic sinusitis after
irrigation with isotonic or hypertonic saline
solutions
. Hypertonic saline appeared to improve
mucociliary clearance in chronic sinusitis
patients, while isotonic saline appeared to be
more useful in allergic rhinitis and acute
sinusitis

We are aware that improvement of mucociliary


clearance is not the only indicator of benefit from
saline solution irrigation in cases of nasal pathology.
Symptomatic relief and clinical recovery do not
always move in parallel with restoration of mucociliary clearance time. Clinical, radiological and pathological evaluation should be discretely documented
in order to enable more accurate interpretations.
Conclusion
Nasal irrigation with isotonic and hypertonic saline
solutions is an effective and safe method of improving mucociliary clearance. The potential of nasal irrigation for improving mucociliary clearance should be
utilised according to agreed criteria. Further studies
should be undertaken in order to develop standard
protocols for selective use of saline solutions in
various nasal pathologies.
Acknowledgement
We would like to thank Dr Oytun Emre Sakici, of the
Department of Forestry Engineering, Black Sea
Technical University, Trabzon, for his contribution
to the statistical analysis of the data.
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ISOTONIC AND HYPERTONIC SALINE SOLUTIONS AND MUCOCILIARY ACTIVITY

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Address for correspondence:


Dr Ahmet Ural,
Mamak Cad 43/1 06340,
Demirlibahce,
Ankara, Turkey.
Fax: 90 312 284 78 07
E-mail: ahmetural2001@yahoo.com
Dr A Ural takes responsibility for the integrity of the
content of the paper.
Competing interests: None declared

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