Open Journal of Pediatrics, 2013, 3, 133-138 OJPed
http://dx.doi.org/10.4236/ojped.2013.32024 Published Online June 2013 (http://www.SciRP.org/journal/ojped/)
Allergic and nonallergic rhinitis in children: The role of
nasal cytology
Maria Cristina Provero1, Al ber to Macchi 2, Sara Antognazza1, Maddalena Marinoni1, Luigi Nespoli1*
1Department of Clinical and Experimental Medicine, University of Insubria, c/o Ospedale Filippo del Ponte, Varese, Italy
2Otorhinolaringology Clinic University of Insubria Varese, AICNA, c/o Ospedale di Circolo, Varese, Italy
Received 31 January 2013; revised 2 March 2013; accepted 11 March 2013
Copyright © 2013 Maria Cristina Provero et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Nasal cytology is a diagnostic tool currently used in
rhinology to study either allergic and vasomotor rhi-
nological disorders or infectious and inflammatory
rhinitis. Over the past few years nasal cytology has
been rarely used in pediatrics, nevertheless its clinical
and scientific applications seem to be very promising.
The advantages of this technique are different: the
ease of performance, the noninvasiveness allowing
repetition and the low cost. We evaluated 100 chil-
dren, from 2 to 15 years old, referred to our outpa-
tient service for allergic children for suspected aller-
gic rhinitis (AR). After skin prick test (SPT) or Radio
Allergo Sorbent Test (RAST), 59/100 subjects were
classified as affected by AR, while 8 children refused
to be tested. According to ARIA guidelines, the 59
children with AR (4 - 15 years old) were divided in 56
with persistent AR and 3 with an intermittent form.
Nine out of 59 children with AR had a significant
number of neutrophils and eosinophils at the nasal
cytology, documenting the presence of “minimal per-
sistent inflammation”. Eleven out of 59 AR patients
showed a positive swab for bacteria. Children with
nonallergic rhinitis (NAR) were 33/100 (2 - 15 years
old). After nasal cytology, 17/33 children were classi-
fied as NARES (nonallergic rhinitis with eosinophils),
including one X-linked agammaglobulinemia (XLA)
child, 1/33 as NARESMA (nonallergic rhinitis with
eosinophils and mast cell) and another 1/33 as
NARMA (nonallergic rhinitis with mast cell). In con-
clusion, nasal cyto logy allowed us to correctly classify
children with NAR and to better assess the condition
of children with AR.
Keywords: Allergic Rhinitis; Children; Nasal Cytology;
Nonallergic Rhinitis; X-Linked Agammaglobulinemia
1. INTRODUCTION
Nasal cytology is a diagnostic tool currently used in rhi-
nology to study either allergic and vasomotor rhinologi-
cal disorders or infectious and inflammatory rhinitis
[1-3].
The rationale of this method is based on the knowl-
edge that the nasal mucosa of healthy individuals is con-
stituted by four cytotypes (ciliata, mucipara, striata and
basalis) and does not show other cells except, rarely,
neutrophils and, very rarely, bacteria. So, the detection of
eosinophils, mast cells, bacteria and fungal hyphae is a
sign of a possible pathology [4].
Since it can detect cellular changes of epithelium ex-
posed to physico-chemical inflammation [5,6], acute or
chronic infections of different etiology (viral, bacterial,
fungal or parasitic) [7], it has been a subject of clinical
and scientific interest for the past decades [4,8]. In par-
ticular it provided an important contribution to the defini-
tion and understanding of the pathophysiologic mecha-
nism of allergic and nonallergic rhinitis and to the identi-
fication of new pathological entities [9], such as the non-
allergic rhinitis (NAR) with eosinophilia (nonallergic
rhinitis with eosinophils, NARES), with mast cells (non-
allergic rhinitis with mast cell, NARMA), neutrophilic
forms (nonallergic rhinitis with neutrophils, NARNE)
and, finally, the eosinophil-mast cells (nonallergic rhini-
tis with eosinophils and mast cell, NARESMA) [10,11].
There are still few reports on nasal cytology in pediat-
ric population [7,12] and most of them are quite histori-
cal [3,4].
Samples can be obtained by biopsy but nasal biopsies
are hardly feasible as a routine method and the caregivers
may not agree [13].
Today the material can be collected without any trau-
matic intervention on the child and this technique (scrap-
ing and swab sampling) has opened a diagnostic path.
Considering an allergic child with seasonal or persis-
*Corresponding author.

M. C. Provero et al. / Open Journal of Pediatrics 3 (2013) 133-138 134
tent allergy we usually test him for the presence of spe-
cific IgE (skin prick test and/or Radio Allergo Sorbent
Test), but this diagnosis of “allergic rhinitis” is an indi-
rect one, inferred by the IgE positivity and by his medi-
cal history.
The microscopy examination of the inferior turbinate
cells can directly document the allergic etiology (pres-
ence of eosinophils) and furthermore can show the pres-
ence of microbes and neutrophils.
These findings, which are not unexpected in allergic
children that are prone to infections, allow us to tailor
our treatment by adding antibiotics to the antiallergic
drugs, usually nasal steroids. Local steroids, controlling
the allergic inflammation, may favour infections due to
their immunosuppressing effect and create a vicious cir-
cle.
The possibility to directly visualize what is going on
can add information about the pathophysiology of the
disturbance and it is therefore very important and helpful
for an effective treatment.
This is particularly significant in preschool children
where specific IgE are difficult to document as well as
upper respiratory tract infections are very common.
2. MATERIALS AND METHODS
Referring to our outpatient service for allergic children
for suspected allergic rhinitis (AR), 100 children (2 to 15
years old) were evaluated: 58 males and 42 females.
Children with associated severe Asthma were excluded
from the study.
We collect the medical history by a questionnaire (Ap-
pendix 1) in order to investigate presence of rhinitis,
quality and recurrence of episodes. The child, with his
parents’ help, had to assign a score ranging from 0 to 10,
depending on the intensity of each subjective symptom
(sneezing, itching, eye symptoms, nasal obstruction, oral
breathing, headache, nocturnal snoring, olfactory deficits
and asthma).
Each child underwent to ear nose throat (ENT) evalua-
tion, nasal cytology, skin prick test (SPT) or Radio Al-
lergo Sorbent Test (RAST). We tested a panel of aller-
gens: as pollens, velvet grass (Holcus lanatus), Bermuda
grass (Cynodon dactylon), short ragweed (Ambrosia sp.),
lichwort (Parietaria officinalis), olive tree (Olea europea),
birch tree (Betula verrucosa), nut tree (Corylus avellana),
depending on the allergen exposure of the area; we con-
sidered dust mites (Dermatophagoides pteronyssinus and
Dermatophagoides farinae); as animals, dog (Canis fa-
miliaris) and cat (Felix domesticus); as mould Alternaria
alternata; as food allergens, we tested α-lactalbumin,
lactocasein, egg white and yolk, and peanuts (Arachis
hypogaea).
According to the positivity or negativity of the SPT
and/or RAST, individuals were divided into AR and
NAR groups, respectively. AR group was further subdi-
vided into “intermittent” and “persistent” disease ac-
cording to ARIA guidelines [14]; we also correlated
symptoms to perennial or seasonal allergens. NAR group
was subdivided, according to the nasal smear cytologic
result, into NARES, NARESMA, NARMA and idio-
pathic rhinitis.
Nasal cytology was performed being free of medica-
tions since at least 1 week, except for 10 children under
sublingual immunotherapy (SLIT). Scrapings were col-
lected from the inferior turbinate under careful vision in
anterior rhinoscopy by means of a nasal speculum and
good illumination. The material was transferred on a
glass slide, air-dried and then stained by the May-
Grunwald-Giemsa method. Observation was performed
by an optical microscope at 1000× magnification. We
divided the slide into 10 fields to detect neutrophils,
eosinophils, mast cells and lymphocytes. The cell count
was expressed, per each type, as percentage of total leu-
cocytes.
3. RESULTS
We evaluated 100 children, referred to our outpatient
service for allergic diseases for suspected AR.
According to the correlation between medical history,
physical examination and SPT and/or RAST positivity,
59/100 subjects were classified as affected by AR, while
33/100 children were SPT and/or RAST negative and
were classified as NAR. We had one child affected by
X-linked agammaglobulinemia (XLA), whose SPT were
negative and who suffered of recurrent rhinitis. We per-
formed nasal cytology to identify the nature of his nasal
symptoms.
Eight out of 100 children could not be better defined,
because their parents refused the SPT and/or RAST, so
they had a clinical diagnosis of rhinitis (Figure 1).
According to ARIA guidelines, the 59 children with
AR (age-range 4 - 15 years old) were divided in 56 with
persistent AR and 3 with an intermittent form: 26/56
children had mostly seasonal symptoms associated to the
prevailing allergy to grass pollens, while 30/56 children
RHINITIS (100 CHILDREN)
ALLERGIC RHINITIS
59
NONALLERGIC RHINITIS
33
CLINICALLY
DIAGNOSED RHINITIS*
8
*Parents refused allergic test in vivo or in vitro for their child.
Figure 1. Diagnosis of rhinitis based on clinic and skin prick
test or RAST.

M. C. Provero et al. / Open Journal of Pediatrics 3 (2013) 133-138 135
were allergic to housedust mites and molds and showed
perennial symptoms. Seventeen out of 59 children were
monosensitized to perennial allergens, 12/59 were sensi-
tized to grass pollens and 2/59 children were allergic to
Betula V. and Corylus A. The remaining 28/59 children
were polyallergic patients. Ten out of 59 children with
AR were under SLIT: 5 for perennial allergens and 5 for
grass pollens.
Children with NAR were 33/100 (from 2 to 15 years
old).
The results of the nasal smear of the 59 allergic chil-
dren are reported in Table 1.
Eosinophils were found in 38/59 patients with AR; 17
patients out of these 38 had also at the rhinoscopy hyper-
trophic and pale inferior turbinates, pathognomonic sign
of AR. Nasal cytology showed neutrophils and eosino-
phils in 11/59 children with AR; 9/11 were allergic to
perennial allergens, although they were asymptomatic at
time of evaluation. This result is coherent to the “mini-
mal persistent inflammation” theory [7]. In 6/38 allergic
children we found also bacteria at the rhinocytogram
exam, so we could add antibiotic treatment. In 21 smears
of AR patients eosinophils were not present: 16 children
had a normal cytology, because we did the exam out of
the allergic season, whereas 4 of them had few neutro-
phils, but still in the normal range. Five subjects had
normal cytology but bacteria were present in the smear
suggesting an associated infection.
The nasal cytogram of the children under SLIT
showed eosinophilia in the 5 housedust mites allergic
patients, while 4 smears of grass pollens allergic children
were normal, although the exam was done during the
spring season (April and June).
The swab results of the 33 non allergic children are
shown in Table 2.
The nasal cytogram of 17/33 children with NAR
showed eosinophilia with a persistent disease, so we
could make diagnosis of NARES. One of these patients
was the XLA child. Six of these 17 children at ENT ex-
amination showed hypertrophic and pale inferior turbi-
nates. NARESMA was diagnosed in 1/33 patients and in
another 1/33 NARMA was documented.
The Table 3 shows the results of the 8 SPT/RAST not
Table 1. Nasal cytology in allergic rhinitis.
No. No. No. CYTOLOGY
21 Only eosinophils
11 Eosinophils + neutrophils
38 Eosinophils
6 Eosinophils + neutrophils + bacteria
16 Normal cytology
59 AR
21 No eosinophils
5 Normal cytology + bacteria
tested patients.
One child had several neutrophils in the smear, indi-
cating an infectious rhinitis. Seven with eosinophils
could not be classified as AR or NARES because they
were not tested for type 1 allergy. Nevertheless one child
had a good response to anthistaminic.
The summary of the final results in our patients after
SPT and/or RAST and nasal cytology is reported in Fig-
ure 2.
4. DISCUSSION
While nasal cytology has proved to be very effective in
adult with rhinosinusitis [5-7], it is rarely used in chil-
dren. It is thus difficult to compare our results with sci-
entific references because of the lack of previous studies.
The sample group analyzed is one of the most numerous
groups among those reported in literature [7,12,15].
We must stress that this technique should not be used
routinely, but it is very helpful and informative when
treating children in which allergic tests and/or history are
not concordant. One of this is the XLA child, who is
prone to bacterial infections in the ENT district as first
reported by Bruton in 1952 [16]. The swab showed an
unexpected prevalence of eosinophils.
XLA is a primary immunodeficiency characterized by
the lack of immunoglobulin, B cells, and plasma cells,
secondary to mutation in Bruton’s tyrosine kinase (Btk)
gene. We expected to find an infectious rhinitis, but the
Table 2. Nasal cytology in nonallergic rhinitis.
No. No. CYTOLOGY DIAGNOSIS
17 Eosinophils NARES
1 Eosinophils + mastcells NARESMA
1 Neutrophils + mastcells NARMA
33 NAR
14 Normal cytology IDIOPATHIC
Table 3. Nasal cytology in not tested rhinitis.
No. No.CYTOLOGY DIAGNOSIS
7Eosinophils AR or NARES
8NOT TESTED
1Neutrophils INFECTIOUS RHINITIS
RHINITIS (100 CHILDREN)
AR
59
IDIOP ATH IC
14
NARES
17
NARESMA
1
NARMA
1
UNCLASSIFIABLE
8
Figure 2. Rhinitis classification after nasal cytology.

M. C. Provero et al. / Open Journal of Pediatrics 3 (2013) 133-138 136
nasal smear showed an eosinophilic infiltration allowing
us the diagnosis of NARES. This indicates that the
treatment with systemic antibiotic was not able to control
the recurrent rhinosinusitis because of these allergic cells
[11] and nasal steroids improved the situation.
This observation is in favor of the specificity of the
NARES diagnosis, which should not be considered as
due to allergy towards an unknown allergen, but a true
novel entity.
The nasal cytogram helped us in the diagnosis of AR.
In 9/59 asymptomatic children with AR to perennial
allergens we expected to see a normal exam, but we
found neutrophils and eosinophils, documenting the
presence of “minimal persistent inflammation” [7].
The nasal cytogram of 38/59 children with AR (symp-
toms and positivity to SPT and/or RAST) showed eosi-
nophilia, confirming the isolated allergic form in these
patients. In 21/59 allergic patients the nasal smear was
normal. This confirmed the effectiveness of the treatment,
in particular in those under SLIT. On the other hand, a
significant proportion of allergic children (11/59) showed
also bacteria. In the absence of this result an ineffective-
ness of the antiallergic therapy would have been sus-
pected and it would not have been added the correct
therapy with antibiotic.
Using nasal cytology we could identify cellular rhinitis
(17 NARES, 1 NARESMA and 1 NARMA) in our group
of patients, who without this exam would have remained
with no specific diagnosis and treatment.
Despite our intent was to design nasal cytology just for
allergic patients, it allowed us a specific diagnosis even
in nonallergic ones.
5. CONCLUSIONS
Nasal cytology is useful both from the pathophysiologi-
cal and clinical point of view to better understand the
disease and to follow especially children in which aller-
gic test and/or history are not concordant.
The advantages of nasal cytology are different: the
ease of performance, the noninvasiveness allowing repe-
tition and the low cost.
It is useful to follow the disease during medical treat-
ment by periodic cytologic controls, showing, for exam-
ple, a significant reduction of inflammatory cells or the
disappearance of bacteria.
When considering an allergic child with SPT positivity,
the etiology of an existent rhinitis could not be assumed
to be certainly allergic: only the nasal cytology can di-
rectly confirm such etiology by showing the presence of
an eosinophilic infiltrate. On the other side, the allergic
child is prone to long lasting bacterial infection and even
in this case the nasal cytology can show the existence of
a secondary bacterial infection (neutrophilic infiltrate ±
bacteria).
The effectiveness of the SLIT could be documented by
this technique allowing us to show the disappearance of
the eosinophilic infiltrate. The compliance to the SLIT
could also be assessed by nasal cytology.
It has provided an important contributution to identi-
fication of new pathological entities, such as the nonal-
lergic eosinophilic rhinitis (NARES) or mast cell medi-
ated nasal inflammation (NARESMA).
Despite the proven usefulness of nasal cytology, we
suggest to use this technique not routinely, but mainly
for selected patients or for scientific survey.
6. ACKNOWLEDGEMENTS
We thank the technicians and colleagues of the ENT and pediatric
allergy clinics for the kind and effective collaboration.
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APPENDIX 1
NASAL CYTOLOGY
PATIENT CARD N:
DATE:
SURNAME:
NAME:
Family and Medical History:
Physiological anamnesis/breastfeeding?
Familiarity:
Previous surgery ENT:
Medical therapy:
Associated diseases:
Current medical history (predominant symptom/onset/ recurrence/circadian pattern/triggers/asthenia? irritability?)
Symptoms:
Rhinorrhea: NO ES serous intermittent
mucous persistent
mucopurulent
intensity: 1→10
Sneezing NO YES (………)
Itching NO YES (………)
Eye symptoms NO YES (………)
Nasal obstruction NO YES (………)
Oral breathing NO YES (………)
Headache NO YES (………)
Nocturnal snoring NO YES (………)
Olfactory deficits NO YES (………)
Asthma NO YES (………)
Clinic Examination:
Oropharynx:
Inferior turbinates: (hypertrophic?/pale?)
Tympanic membranes:
Exams:
Skin prick test:
RAST:
Spirometry:
Nasal Cytology:
Other tests
DIAGNOSIS:
THERAPY: