International Journal of Pediatric Otorhinolaryngology 77 (2013) 19801983

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International Journal of Pediatric Otorhinolaryngology

journal homepage: www.elsevier.com/locate/ijporl

A study of the role of different forms of chronic rhinitis in the

development of otitis media with effusion in children affected by
adenoid hypertrophy
Nicola Quaranta *, Claudia Milella, Lucia Iannuzzi, Matteo Gelardi
Section of Otolaryngology, Department of Basic Medical Science, Neuroscience and Sensory Organs, University of Bari, Italy

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 27 May 2013
Received in revised form 11 September 2013
Accepted 15 September 2013
Available online 23 September 2013

Objective: The aim of the present study was to evaluate the role of the different forms of chronic rhinitis
in the pathogenesis of otitis media with effusion in children affected by obstructive adenoid
hypertrophy.
Methods: 81 patients, aged between 4 and 15 years (mean age of 6.9 years), affected by obstructive
adenoid hypertrophy were evaluated. All patients underwent accurate history taking, physical
examination with endoscopy of the nasopharynx, skin prick test, nasal cytology and hearing evaluation.
Results: Nasal citology showed that 21% of patients had a non-allergic rhinitis (NAR) subtype, 17.4% NAR
overlapping with infectious rhinitis (IR), 29.6% IR, 4.9% allergic rhinitis (AR), 2.5% AR overlapping with IR
and the remaining 24.6% a negative cytology. The presence of OME was positively correlated with
neutrophils (p = 0.01) and mast cells (p = 0.022), while it was negatively correlated with the presence of
eosinophils (p = 0.02) and bacteria (p = 0.02).
Conclusions: A chronic rhinitis was present in more than 70% of children with AH and 60% of them
showed OME. Nasal cytology together with SPT showed that AR was rarely present in this group of
children, while the mast-cells and neutrophils positively correlated with OME.
2013 Elsevier Ireland Ltd. All rights reserved.

Keywords:
Otitis media with effusion
Adenoid hypertrophy
Rhinitis
Allergy
Nasal cytology

1. Introduction
Adenoid hyperthrophy (AH) is a frequent cause of upper
airways obstruction in children [1]. AH has a typical onset after the
third year of life with symptoms progressively worsening with a
peak age incidence between 4 and 8 years. This clinical condition
apart from typical nasal symptoms, voice and swallowing
disorders, poor sleep quality, and occasionally facial dysmorphisms and dental malocclusion, frequently lead to otitis media with
effusion (OME) [2,3].
OME is dened as an inammation of the middle ear
accompanied by uid collection in the middle ear cleft without
signs and symptoms of acute infection [4]. The etiology of OME is
debated and a large number of theories have been proposed to
explain a condition that is probably multifactorial. Nasal allergy
and AH have received support from some authors [5,6] although

* Corresponding author at: Otolaryngology, University of Bari, Piazza G. Cesare n8

11, 70124 Bari, Italy. Tel.: +39 080 5478849; fax: +39 080 5478752.
E-mail addresses: nicolaantonioadolfo.quaranta@uniba.it (N. Quaranta),
claudiamilella@hotmail.it (C. Milella), aliceiannuzzi@hotmail.com (L. Iannuzzi),
gelardim@inwind.it (M. Gelardi).
0165-5876/$ see front matter 2013 Elsevier Ireland Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijporl.2013.09.017

this view is not widely upheld [7]. AH may contribute to the

development of OME mainly in two ways: a physical obstruction
due to increased adenoid mass causing Eustachian tube dysfunction or a local inammatory reaction in the Eustachian tube and
middle ear caused by release of inammatory mediators [8].
However, although the nose, nasopharynx, Eustachian tube and
middle ear are in an anatomical and functional continuity, not all
the children affected by AH develop OME.
In the recent years the advent of nasal cytology has allowed a
more complete and precise classication of rhinitis [9]. Nasal
cytology is a diagnostic tool currently used in rhinology, with the
aim of assessing cell changes in the nasal epithelium exposed to
irritant or inammatory agents. Its rationale is based on the
knowledge that nasal mucosa of healthy individuals is constituted
by four cytotypes (ciliary cells, muciparous cells, striate cells, basal
cells) and does not show other cells except, rarely, neutrophils and,
very rarely, bacteria. In this view, the detection of cells type
different from these is a sign of possible pathology [10].
According to the results of citology, skin prick test (SPT) and the
period of nasal sampling it is possible to precisely diagnose
infective rhinitis (IR), allergic rhinitis (AR) or different types of
cellular non-allergic rhinitis (NAR). IR is characterized by abundant
bacteria that may be found in extracellular tissue and also inside

N. Quaranta et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 19801983

neutrophils as a result of phagocytosis (Fig. 1). AR is characterized

by positive SPT, nasal symptoms occurring when allergens are
present and a quite heterogeneous rhinocytogram. In fact, during
the pollen season, in nasal cytology neutrophils, lymphocytes,
eosinophils and mast cells mostly degranulating are present; by
contrast, outside the pollen season, nasal cytology is negative. NAR
are characterized by negative SPT and the presence of inammatory cells that acts continuously on the nasal mucosa independently from the seasonality. According to the cell found in the nasal
smear NAR are classied in non-allergic rhinitis with eosinophils
(NARES), non-allergic rhinitis with mast-cells (NARMA) (Fig. 2) and
non-allergic rhinitis with eosinophils and mast-cells (NARESMA)
[9,10].
The aim of the present study was therefore to evaluate the role
of the different forms of chronic rhinitis in the pathogenesis of OME
in children affected by obstructive AH.
2. Materials and methods
This was a cross-sectional study with convenience enrolment.
Throughout a 2-year duration (20092011) 81 patients, aged
between 4 and 15 years (mean age of 6.9 years), affected by
obstructive AH and obstructive sleep apnea were evaluated at the
ENT Department of the University of Bari Aldo Moro. All patients
underwent accurate history taking, physical examination with
endoscopy of the rhinopharynx, SPT, nasal cytology and hearing
evaluation. All patients provided an oral informed consent, and the
observational study was notied to the Ethical Committee.
The family history of patients was carefully assessed to determine
the presence of atopy, asthma and aspirin allergy. The patient history
of asthma, aspirin allergy and atopy was also determined.
All the patients underwent a complete ENT evaluation and
exible nasal endoscopy (ENT 2000 exible 3.4 mm broscope
Vision Sciences1, USA) to assess the degree of adenoid hypertrophy [11]. Only children with grade 3 or grade 4 AH, i.e. coanal
obstruction greater than 75%, were included in the study.
Allergic sensitization was assessed by the presence of a positive
SPT carried out and read in accordance with approved methods
[12]. The panel of allergens used included: house dust mite
(Dermatophagoides farinae and D. pteronyssinus); cat; dog; grass
mix; Compositae mix, Parietaria judaica; birch; hazel tree; olive
tree; Alternaria tenuis; Cladosporium; and Aspergilli mix. The
concentration of allergen extracts was 100 I.R./mL (Stallergenes,
Milan, Italy).
Nasal cytology was performed by anterior rhinoscopy, using a
nasal speculum and good lighting. Scrapings of the nasal mucosa
were collected from the middle portion of the inferior turbinate,
using a Rhino-Probe1. Only in very young and poorly compliant
patients cell harvesting was performed by means of a nasal swab
(the one usually used for pharyngeal swab), which is less annoying
and better tolerated by patients [13]. Samples were placed on a
glass slide, xed by air drying and then stained with the MayGrunwald Giemsa (MGG) method (Carlo Erba, Milan, Italy). MGG
staining is the most widely used method in diagnostic nasal
cytology, since all of the cellular components of the nasal mucosa,
from inammatory cells (neutrophils, eosinophils, mast cells,
lymphocytes) to bacteria, spores, fungal hyphae, biolms and
mucous secretions, are easily stained. The slide was observed
under a Nikon E600 light microscope (Nikon, Canada) equipped
with a digital camera (Nikon Coolpix 3:34) for the acquisition of
microscopic images. For the rhinocytogram analysis, 50 microscopic elds were read at a 1000 magnication to assess the
presence of normal and abnormal cellular elements, along with
any microscopic features (spots, special inclusions, etc.) likely to
inuence diagnosis. Cell counts, bacterial and fungal analysis were
carried out by a semi-quantitative grading, as proposed by Meltzer

1981

et al. [14]. In particular the different cells found were graded as

follows: grade 0 (not visible); grade 1 (occasional groups); grade 2
(moderate number); grade 3 (easily visible); grade 4 (many of
which cover the entire eld of view).
Middle ear function was evaluated by means of pure tone
audiometry and tympanometry. Pure tone audiometry was
performed in a sound-proofed cabin using pure tones (250 ms
duration, 25 ms rise/fall time, 50% duty cycle) at octave frequencies
from 125 Hz to 8000 Hz with a maximum intensity of 120 dB SPL
with an Amplaid 309 (Amplaid, Milan, Italy) clinical audiometer.
Tympanometric measurements were performed using a 220 Hz
probe tone with an Amplaid 770 clinical tympanometer (Amplaid,
Milan, Italy). Air Conduction Pure Tone Average (AC-PTA) was
obtained by the mean of thresholds at 0.5, 1, 2 and 4 kHz.
Tympanograms were classied according to Jerger in Type A, B and
C [15].
Sample size was not calculated since no similar studies were
present in literature. A multivariate regression analysis was carried
out to evaluate the association of OME and type of tympanogram,
air-conduction hearing, nasal cytology and denitive rhinological
diagnosis; age and SPT also have been controlled in the analysis.
We considered subjects with OME as cases and subjects without
OME as controls and used a chi square test to evaluate any
difference in the prevalence of the different form of rhinitis. p was
considered signicant when <0.05. All the variables were
presented into a database built with FileMaker Pro software and
analyzed with statistical software STATAMP11 (Copyright 1985
2009 StataCorp LP, College Station, Texas 77845, USA).

3. Results
81 children were evaluated. 48 patients were male and 33 were
females. A family history of asthma was present in 10 cases (12.3%),
for acetylsalicylic acid intolerance in 1 case (1.2%) and for nasal
polyposis in 2 cases (2.5%). Only 7 of 81 patients (8.5%) reported a
history of allergy to inhalants or drugs. 42 children had AH grade 4
and 39 grade 3. The SPT showed positivity in 18 of the 81 (22.2%)
cases: 11 (61%) were positive for house dust mite, 2 (11)% for cat
hair, 7 (39%) for mixed grass pollen and 2 (11%) for mixed feather.
Nasal cytology together with SPT allowed the diagnosis of the
clinical pictures of rhinitis as reported in Table 1. In summary 21%
of patients had a non-allergic rhinitis (NAR) subtype, 17.4% NAR
overlapping with IR, 29.6% IR, 4.9% AR, 2.5% AR overlapping with IR
and the remaining 24.6% a negative cytology.
Of the 81 children 47 (58%) had bilateral OME, while 5 (6%)
unilateral OME. In particular type B tympanogram was present in
80 ears (49.4%), type C was found in 28 ears (17.3%) and type A in

[(Fig._1)TD$IG]

Fig. 1. Infective rhinits: on nasal citology several neutrophils and bacteria, intra and
extracellular, are evident (May-Grunwald Giemsa staining, magnication 1000).

[(Fig._2)TD$IG]

N. Quaranta et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 19801983

1982

Fig. 2. Non-allergic rhinitic with mastcells (NARMA). Mastcells partly degranulating

(May-Grunwald Giemsa staining, magnication 1000).

the remaining 54 ears (33.3%). In patients with type A tympanogram mean AC-PTA was 15.77 dB HL on the right ear and 15 dB HL
on the left ear, in patients with type B tympanograms mean AC-PTA
was 31.61 dB HL on the right ear and 35.49 dB HL on the left ear
and in patients with type C tympanograms mean AC-PTA was
26.96 dB HL on the right ear and 23.03 dB HL on the left ear.
Statistical analysis performed with a multivariate regression
among all variables showed only the following correlations. Age
and allergy were signicantly correlated (OR = 1.19; 95% CI = 1
1.41; z = 1.95; p = 0.05), while age was negatively correlated to the
presence of neutrophils (OR = 0.7; 95% CI = 0.570.87; z = 3.28;
p = 0.001). An inverse correlation almost reached statistical
signicance between age and nasal bacteria (OR = 0.83; 95%
CI = 0.691; z = 1.94; p = 0.052). The presence of OME was
positively associated with neutrophils (OR = 2.12; 95% CI = 1.2
3.7; z = 2.58; p = 0.01) and mast cells (OR = 4.4; 95% CI = 1.215.5;
z = 2.29; p = 0.022), while it was negatively correlated with the
presence of eosinophils (OR = 0.47; 95% CI = 0.240.92; z = 2.18;
p = 0.02) and bacteria (OR = 0.5; 95% CI = 0.290.89; z = 2.33;
p = 0.02). No other signicant correlations were found among
the analyzed variables. Chi-square test did not show any difference
in patients with and without OME.

4. Discussion
The results of the present study show that 75.4% of children
affected by obstructive AH (grades 34) presented also a chronic
rhinitis. The pathogenesis of AH is multifactorial and among others
factors familiarity and chronic rhinitis have been associated with
this disease [16,17]. Both allergic and non-allergic rhinitis are
chronic rhinitis characterized by the presence of inammatory
cells that acts on the nasal mucosa [10]. While AR has been
correlated to AH [18,19], this is the rst report on the association
between NAR and AH. Cellular NAR such as NARES, NARMA and
Table 1
The number and percentage of patients with different form of chronic rhinitis are
reported. For abbreviations see text.
Diagnosis

Patients (%)

OME (%)

No OME (%)

IR
AR
NARES
NARESMA
NARMA
AR + IR
NARES + IR
NARMA + IR
Negative

24
4
5
3
9
2
12
2
20

14
1
3
1
7
2
7
1
9

10
3
2
2
2
0
5
1
11

ns
ns
ns
ns
ns
ns
ns
ns
ns

(29.6)
(4.9)
(6.2)
(3.7)
(11.1)
(2.5)
(14.9)
(2.5)
(24.6)

(17.3)
(0.8)
(3.7)
(0.8)
(8.6)
(2.5)
(8.6)
(0.8)
(11.1)

(12.3)
(3.7)
(2.5)
(2.5)
(2.5)
(0)
(6.2)
(0.8)
(13.6)

NARESMA are characterized by the presence of high quantity of

inammatory cells that acts continuously on the nasal mucosa
independently form the seasonality [20], differently from AR. In
perennial AR there is a minimal persistent inammation characterized by many neutrophils, few eosinophils and rare signs of
degranulation [21]; while high percentage of degranulating
eosinophils and mastcells occur only in the period of pollinization.
The correlation between AR and AH has been reported only in
patients affected by perennial allergy (house dust mites and
molds) where there is a chronic action of inammatory cells [18].
Cellular NAR have instead an inltrate represented by numerous
eosinophils and mastcells, accompanied by massive signs of
degranulation. All that involves a greater damage to epithelium
that is not limited exclusively to the release of histamine. Mast
cells are a virtual pharmacopeia of biologically active compounds,
and their activation will result in release of histamine and a variety
of other mediators (such as leukotrienes, prostaglandins, eosinophilic chemotactic factor of anaphylaxis, platelet-activating factor,
ecc) that partake in the inammatory reaction. The result is the
damage of the rst function of the mucosa: the protective
epithelial reef [22].
The prevalence of positive SPT in our group of children was
22.2%, a number that is not different from what would be expected
in the normal population [23,24]. In the present study the
prevalence of AR in patients affected by obstructive AH was
7.4%. While some authors reported a higher prevalence of allergy
[25], others found similar results [7,26].
Carr et al. [27] in a prospective study on a group of children
undergoing adenotonsillectomy for obstructive sleep apnea could
not demonstrate that allergy had a role in these patients. Despite
the results of their paper, the authors felt strongly that allergy in
the upper aereodigestive tract was an important factor in the
development of adenotonsillar hypertrophy and therefore hypothesized that an allergic reaction on the mucosal surface of the
adenoids and tonsils predisposes children to a viral insult and
secondary bacterial colonization. The high prevalence of NAR in
our group of patients suggest that the predisposition supposed by
Carr et al. is not only IgE mediated, but also mediated by the
inammatory cells and their by-product found in cellular NAR.
IR may be both the cause and the effect of AH. In fact, while
persistent bacterial infection, intracellular and within bacterial
biolms, has been proposed as an etiological factor in adenotonsillar disease [28], chronic rhinopharyngeal obstruction may also
lead to the stagnation of mucus in the nasal cavity that cause a
chronic nasal infection.
Statistical analysis demonstrated a negative correlation between age and both bacteria and neutrophils suggesting that
independently from the adenoid size older children have a more
mature immune system [29] and/or are able to keep their nose
clean. The overlap between NAR or AR and IR is an interesting
nding. In these cases chronic inammation could be a predisposing factor and could lead to mucus stagnation and infection.
Traditionally the development of OME has been attributed to
hypertrophy of adenoid tissue which causes a mechanical
obstruction of both choanae and the Eustachian tube particularly
when the adenoid are laterally hypertrophic [30,31]; however, not
all children affected by AH develop OME and other factors have
been proposed in the pathogenesis of OME. Local inammatory
reaction in the Eustachian tubes and middle ear caused by release
of inammatory mediators such as histamin has been proposed
almost 20 years ago [8], while recently, the presence of bacterial
biolm on the adenoids has been correlated with otitis media [32].
The results of our study showed that, although OME was not
associated with a specic type of chronic rhinitis, it was positively
correlated with the presence on the nasal smear of mast-cells and
neutrophils, while was negatively correlated with eosinophils and

N. Quaranta et al. / International Journal of Pediatric Otorhinolaryngology 77 (2013) 19801983

bacteria. The role of mast-cells and histamine in the development

of OME has been proposed by several authors [8,3335]. Collins
et al. [8] showed that children with uid present in both ears had
increased amounts of histamine in their adenoid tissue compared
with children with no signs or symptoms of OME. The authors
postulated that the release of this powerful mediator of
inammatory reaction in the Eustachian tube that may eventually
lead to development of a middle ear effusion. Other authors [34,35]
have shown that in children affected by OME there was a higher
number of adenoid subepithelial mastcells compared to children
without OME. The results of the present study conrm the role of
mast-cells in the development of OME in children with obstructive
AH; the presence of mast-cells in the nasal smear, as it happen in
NARMA and NARESMA, was associated with a high risk of
developing a chronic OME.
The presence of neutrophils in nasal cytology in our study was
signicantly correlated with the presence of OME. Similar results
were reported in non-allergic children affected by OME [14].
Neutrophils are present in the nasal smear in all NAR, although in
different percentage, in case of perennial AR together with
eosinophils and in case of IR together with bacteria [10]. In the
present study the presence of neutrophils was the sign of a chronic
inammation of the nasal cavity associated with AH and OME. The
role of chronic infection of the nose and nasopharynx and OME has
been recently proposed [36] and in particular adenoid bacterial
biolms seem to play a fundamental role.
Although nasal cytology has been proved to detect biolms
[37], in the present series we have not found any correlation with
the presence of biolm, since nasal cytology evaluates mucus
taken from the middle portion of the inferior turbinate and
biolms correlated with OME have been detected on adenoid
specimens. The presence of neutrophils therefore represents a
specic sign of chronic inammationinfection since is present in
all forms of acute and chronic rhinitis [10].
It is interesting to note that we have found a signicant inverse
correlation between nasal eosinophils and OME in children
affected by AH. Caffarelli et al. [38] evaluated nasal cytology
and SPT in 40 children with OME and 40 controls. Nasal eosinophils
were signicantly more frequent in OME compared to controls,
however adenoid size was not evaluated and therefore a different
etiology for OME could be hypothesized in this group of patients.
The role of nasal eosinophils in OME has to be better claried.
In conclusion a chronic rhinitis was present in more than 70% of
children with AH and 60% of them showed OME. While a specic
form of chronic rhinitis was not associated with the presence of
OME, nasal cytology together with SPT showed that AR was rarely
present in this group of children, while the mast-cells and
neutrophils positively correlated with OME.
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