Pediatr Allergy Immunol 2008

DOI: 10.1111/j.1399-3038.2007.00675.x
2008 The Authors
Journal compilation 2008 Blackwell Munksgaard

PEDIATRIC ALLERGY AND

IMMUNOLOGY

High
rhinitisprevalence and
in children young
with onset of
bronchial allergic
asthma
Masuda
alence S, Fujisawa T, Katsumata H, Atsuta J, Iguchi K. High prev- 1,2
asthma.and young onset of allergic rhinitis in children with bronchial Sawako Masuda , Takao
Pediatr Allergy Immunol 2008. 2,3
Fujisawa , Hajime Katsumata ,
2,3
2008 The Authors 3
Jun Atsuta and Kosei Iguchi
2,3
Journal compilation 2008 Blackwell Munksgaard 1
Department of Otorhinolaryngology, Mie National
Hospital, Tsu, Japan, 2Institute for Clinical Research,
Bronchial
major asthmaforand
risk of
factor theallergic rhinitisofoften
development co-exist,
asthma. and rhinitis
However, is a
the reported Mie National Hospital, Tsu, Japan, 3Department of
incidence
this wasallergic
studyupper to rhinitis
elucidate in incidence
the asthmatic children
of allergicvaries widely.
rhinitis, The aim
theofonset age of
chronic
symptoms and lower airway symptoms, and the correlation these twoof Pediatrics, Mie National Hospital, Tsu, Japan
and 210)in
(ageslower asthmatic
with
airway asthma
symptoms
children.
was was A cohort
evaluated.
lled out
of 130 consecutive
A questionnaire
by the parents.
children
regarding
Objective upper
diagnosis of allergic rhinitis wasand
alsospeci
made con the IgE
basis of rhinoscopy,
nasal
The
cytology,
Persistent nasalof
incidence
nasal challenge,
symptoms
allergic were present
rhinitis was 77.7%in83.8%
serum of the (CAP-RAST).
asthmatic children.
ndings. The mean onset age of asthma was based on the objective
2.8
the rst year of life in 8.9% of the children. In children with as early as
yr, and that of rhinitis was 2.9 yr. Nasal symptoms started
comorbid
preceded inasthma
31.7%,and andallergic
both rhinitis,inrhinitis
started the samepreceded
year in in 33.7%, asthma
rhinitis
lower was
airways asymptomatic.
occurred Concomitant
inrhinitis
34.6% exacerbation
of the total 130in of26.7%.
children. theTheseIn 7.9%,
upper and
results
demonstrate
the that allergic manifested early life in the majority of
subsequent development of asthma and possible early intervention. to
asthmatic children. Persistent nasal symptoms in infancy may point

Key words: bronchial asthma; allergic rhinitis;

comorbidity; age of onset; child

Takao Fujisawa, MD, Institute for Clinical Research,

Mie National Hospital, 357 Osato-Kubota, Tsu, Mie
514-0125, Japan
Tel.: +81 59 232 2531
Fax: +81 59 231 5218
E-mail: fujisawa@mie-m.hosp.go.jp

Accepted 2 October 2007

Prevalence
increasing of 2)allergic
(1, it diseases
andbronchial
is widely inaccepted
children is
that dicult because of the in
highearly
frequency of upper
allergictogether.
rhinitis and asthma commonly respiratory
addition, infections
young childhood. In
occur
allergic
mostly rhinitis
based
However,
inon
thewith
patients
a 6.2%
reported prevalence
asthma,
questionnaire which of
is
to This
the nasal symptoms.
questionnaire Tochildren
overcome
method,
rarely
we performed
complain
the limitation
objec-
of
oftive
the
patients, rangesmay from to 95%
to the (3). diagnosis
endoscopy, of allergic
nasal specirhinitis
cytology, based
nasal on the nasal
wide
there variability be attributed
is noof standardized questionnaire fact that
forwith
the test, and with
children serum
asthma. c IgE in provoca-
cohorttion
a enabled of
diagnosis
rhinitis
respiratory
rhinitis
andsymptoms
asthma often and that
ignore
because of
patients
their
their upper
more to eectively
identify true utilize This
prevalence
approach
a ofquestionnaire
allergic rhinitis
us
andin toa
prominent lower airway symptoms ning ned population
deHere, of childhood asthma.
allergic nasal symptoms in children(3).
is De
even more we found that the majority of children
with asthma at a mean age of 5 yr also had

1
Masuda et al.

allergic
rhinitis rhinitis
occurred and that theearly
relatively onsetin of allergic
life, either Although Japanese cedar pollen (JCP)rhinitis
is the
concurrently or prior to asthma, in 60% of the major
in allergen
Japan (7,(9) to
8), cause seasonal allergic
patients. prevalence
JCP, in this study.andit we
does not relate
focused to asthma
on HDM, not
The severity of rhinitis symptoms was deter-
Subjects and methods mined according to the Japanese practice guide-
line for nasal allergy (10). In brief, the severity of
We evaluated
with atopic a cohort ofasthma
bronchial children who <10 yr ofMie
visited age
National
consecutive Hospital s pediatric
12 months. We allergy
included clinic during
only the nasal congestion was classied into four grades,
pre-pubertal
asthma the often children
seen in because natural outgrow of
found
ders. The analysis
diagnosis of adolescent
the
of two
atopic
age may disor-
comorbid asthma
con-
was i.e., no congestion was none, congestion of one
con
wheezermed on the
andsensitivity basis
dyspnea, to of a
reversible history of recurrent
tion, and
allergen as evidenced by at leastbronchoconstric-
a positive one inhalant
CAP-RAST.
side was mild, occasional congestion of both
One-hundred
girls, ages 210;and thirty
mean: 5.3 children
yr) who in (86 boys, 44
consecutively sides was moderate, and complete congestion
visitedcat
Classi ourionclinic
of thewere cases enrolled
according the
to study.
the
international
persistent, 18.6% guideline (4) showed
as moderate 77.9% and
persistent, as mild was severe. The severity of rhinorrhea and
3.5%
consent aswassevere
obtained persistent
from the asthma.
parents Informed sneezing was also classied into four grades on
patients.
sensitized atAllleasttheto children
house dustwere found of
mite (HDM). to the
be
A questionnaire
included questions was lled out
concerning by the parents.
nasal symp-It the basis of the number of nose blows and
toms, onset
asthma, ages ofbetween
correlation rhinitis nasal and bronchial
symptoms sneezes per day, i.e., <1 was none, 15 was
and
allergicasthma symptoms, and family history of
whether
symptoms adiseases.
physician
as being
The
had
due
parents
ever were also
diagnosed the asked
nasal mild, 610 was moderate and >10 was severe.
nasal symptoms
positive answer towas
the de to
nedallergies.
following on question:
the basisPersistent
of
Hasa
your childof
episodes hadsneezing,
a long-lasting
apart runny
from or stuy nose
colds? Those or The severity of rhinitis was assigned to that of the
who answered
when the problem started.yes were asked about the age highest grade in any of the symptoms.
After the
cytology, and questionnaire,
allergen rhinoscopy,
provocation tests nasal
were
performed.
allergic The
rhinitis diagnosis
was based of
on HDM-sensitized
(i) presence of The chi-squared test was used to compare
eosinophils in
provocation test nasal
with asmears;
HDM (ii) positive
allergen disc;nasal
and
(iii)
RAST. positive
The speci c serum
children who IgE had
to HDM at by CAP-
least two proportions of the data in dierent groups.
positive factors
allergic rhinitis. of Because
the criteria HDM were isconthe rmedmostas
prevalent
patients inhalant
with allergen
perennial allergicandrhinitis
the majority
are coversof
sensi- A dierence in percentages was considered
tized to HDM in Japan (5, 6), the
most of perennial allergic rhinitis in the country. criteria signicant when the p-value was <0.05.

Results
Previous diagnosis of allergic rhinitis
The
their parents of 75
children hadchildren (57.7%) answered
been diagnosed that
asInhaving
allergic
tion, the rhinitis
parents by 11
of another physician.
childrenrhinitis that addi-
thoughtalthoughtheir
children had had allergic
denitive diagnosis had never been made. a

Prevalence and severity of persistent nasal symptoms based

on the questionnaire
The replies
children to the had
(83.8%) questionnaire
had mild revealed
persistent thatsymp-
nasal 109
toms.
erate The
in Thesymptoms
40.0% andwere
severe in 26.9%, mod-
children. combined ratio in
of 16.9%
severe ofandthe
moderate23.1%
gestion, symptoms was 50.4% and
for rhinorrhea for nasal
10.7% con-
for
sneezing.
the 130 Concerning
children had other symptoms,
recurrent 22.3%
epistaxis, 46.2%of
had frequent sni ng, 30.0% had
had a cough, and 32.3% had eye symptoms.snoring, 40.8%

Prevalence of allergic rhinitis based on objective

findings
Rhinoscopy
all and Eosinophilia
the children. nasal cytologyinwere performed
nasal smears in
was
positive
provocationin tests
97 were(74.6%)
positive of 45
in them.
(84.9%) Nasal
of
53 children who could be carried out the test.
Seventy-seven
formed children
because were unable to be per-
the basisthe
(77.7%) oftest
were the
condiagnostic
rmed
theycriteria,
were
as allergic
too101
young.
rhinitis.
On
children
Allpale
the
children
or diagnosed
red with as allergic
swollenrhinoscopy. rhinitis
mucosa and/or had watery 30

Number of patients
discharge
(26.7% of 101 children) had Twenty-seven
mild, 42 (41.6%)
had moderate, and 20 (19.8%) had severe nasal
symptoms. 25
Table 1 of
prevalence summarizes
persistent the relationship between
the questionnaire
allergic and nasal
rhinitis.wasPositive
symptoms
objective
predictive
found
diagnosis
value
by
of
for the
20
questionnaire
value was 42.9%. 81.7%
Actually, and negative
the predictive
parents of 12 15
(11.9%
noticed of total
anypresence subjects)
nasal symptoms children had not
despite
of the
allergic of typical in
rhinitis.didTwenty-nine
their children
mucosal
(22.3% of ndings
total
subjects)
of allergicchildren
rhinitis, not havethe
although objective
parents ndings
of 20 10
children complained
toms diagnosed
in their children. of persistent nasal symp-
were as having Six of those 20 children
sinusitis. 5

0 1 2 3 4 5 6 7 8 9 10
Age at onset of asthma and rhinitis symptoms
Age (yr)
As presented
onset of inasthma
agesonset Fig. 1,andthe rhinitis
distributions of the
The
was mean
2.8and
1.9 age In
yr. of asthma in allwere
89 allergic
children the similar.
withpatients
both Fig. 1.symptoms.
Distribution of the age at onset of asthmaasthma
and rhi-
asthma
symptoms symptomatic
started at 2.9 1.7 yrrhinitis,
of nasal
age. In nitis
total
nasal children (ninClosed
130, bar:
=children onset
2.8with 1.9 of
yr). bronchial
Open bar:(n =onset
in
89, of
children
started as with
early allergic
as the rhinitis,
rst year ofnasal
life symptoms
in 9.0% of 2.9 symptoms
1.7 yr). allergic rhinitis
them and
who were at 2 yr
previouslyof age in 22.5%. In the
diagnosed as having allergicpatients
rhinitis
diagnosisbywasother
3.5 physicians,
1.7 yr. the mean age at the

The children
rhinitis were with asthma
further subdividedwho into
also four
had allergic
groups
Table 1. Prevalence of allergic rhinitis based on objective findings and according
theto101
rst. Of allergic which of the
children whotwo illnesses
were diagnosed started
as
persistent nasal symptoms found by the questionnaire having
preceded in 32 rhinitis,
(31.7%), the
the onset
onset of rhinitis
of asthma
preceded inat 34
manifested the (33.7%),
same andinboth
time 27 diseases
(26.7%)
patients.
atic EightTable
rhinitis. (7.9%) patients had
2 summarizes the asymptom-
patients
Persistent nasal symptoms found by current agethat
is ofofnote andthetheinitial
age of onset of occurred
symptoms the illnesses. It
atthat
an
age
allergic 2 yr regardless
rhinitis of
started the
at airway
a young site,age,
andeither
the questionnaire concurrently
(60.4%). or prior to asthma, in 61 children
+ )
The correlation between upper respiratory symptoms and
Allergic rhinitis bronchial asthma
+ 89* 12 101 (77.7%)
) 20 9 29 (22.3%) Concomitant
withtotal
the 130 exacerbation
bronchial asthma of the upper
occurred airways
in 34.6% of
the
was experienced children. Concomitant
in 33.7% ofthethecaseexacerbation
children with
Total 109 (83.8%) 21 (16.2%) 130 rhinitis.
without Interestingly,
evidence of even in
rhinitis, 37.9% of children
experienced
nasal symptoms
which may had whenthat
indicate their asthma
viral upperexacerbated,
respiratory
infections
Alternate caused
exacerbations of asthma upperexacerbation.
the only and
Positive predictive value and negative predictive value for the questionnaire airway
(0.9%). symptoms were found in onelower
case
were 81.7% and 42.9%, respectively.
*Twenty-seven had mild, 42 had moderate, and 20 had severe nasal symp-
toms. Family history of allergic diseases
Six of them were diagnosed as having sinusitis.
The data oninthe
are shown family Ahistory
Fig. ofhistory
allergicofdiseases
chial
quentlyasthma was 2.
in before
family
signicantly
seen whose
children more bron-
fre-
started early, the onset of nasal
asthma symptoms
or at
Table 2. Current age and the onset age of bronchial asthma and nasal symptoms

Onset age (mean 1 s.d.)

Group (n) Current age (mean 1 s.d.) Sex (M/F) Bronchial asthma Nasal symptoms

Children without allergic rhinitis (asthma alone) (29) 4.2 1.7 19/10 2.3 1.3
Children with asthma and allergic rhinitis (101)
Asthma preceded (32) 6.0 2.1 24/8 2.1 1.5 3.9 1.5
Nasal symptoms preceded (34) 5.6 2.4 21/13 4.2 2.2 2.3 1.6
Both symptoms occur at the same time (27) 4.8 2.3 15/12 2.3 1.6 2.3 1.6
Asymptomatic rhinitis (8) 5.6 2.5 7/1 2.0 1.3

100
* who had objective ndings of rhinitis, which was
80 *
* 42.9%, of the questionnaire. These ndings
60
children without nasal symptoms may have
%

40 allergic rhinitis. Nasal symptoms of young

infants may be unrecognized by the parents,
20
and careful examination is thus important; sev-
0
eral reports, although they deal with adults,
Bronchial Atopic Allergic rhinitis
support this nding. Gaga et al. (11) reported
asthma dermatitis that eosinophil inltration was present in the
Family history
nasal mucosa of asthmatic patients even in the
absence of rhinitis. Some of the asthmatic
Fig.
The 2. The prevalence
patients were divided of into
family history
rhinitis the
of allergic
following groups disease.
on the patients who
symptoms considered themselves
to havefree of nasal
basisonset:
the
asthma
of comorbidity
closed large
preceded;
of asthma
bar, hatched
and
alone;
bar,
relative precedence
Finepreceded;
rhinitis hatched cross of
bar, nasal airwaywere demonstrated
disease (3). evidence of
stripedasthma
bar, bar, bothandsymptoms occurredrhinitis.
asymptomatic at the same
*p <time;
0.05,open Next, we found
asthmatic occurred that
children asstarted the nasal
early symptoms
in life. Nasalin
**p <
common 0.01. A family
inonset
children history
whose of asthma
nasal was
symptoms signi cantly more symptoms
life in 9.0% of mean early children
asthmatic as in the rst year
with of
allergic
beforeinthe
than those whoofhadasthma
asthmaor alone
at theor same timeofstarted
rhinitis with early,
laterasthma
onset. rhinitis, and the onset age of rhinitis was
2 yr. In addition, nasal symptoms preceded
bronchial asthma in 33.7% of the children, and
the same the two symptoms started at the same time in
those
later who time
onset.had as the alone
asthma asthmaorcompared with of
allergic signi
rhinitis in
cant
di erences
atopic inThere
dermatitis
were no statistically
the prevalence
and of rhinitis
allergic a familyamong
history of
the 26.7%. These results indicate that nasal symp-
groups. toms start in infancy in a considerable number of
asthmatic children. An epidemiological study
Discussion (12) reported that children whose rhinitis began
In this study,
allergic rhinitis,weabout
found a highchildren
incidencewithof in the rst year of life were more likely to have
asthma
incidenceat a mean
in previous of80%,
5 yr in
age reports old. Because
varies widely, the
we respiratory symptoms or asthma at age 6 than
employed
objectively direct
in aallexamination
cohort to
of visited diagnose
130 asthma rhinitis
patients
<10 yr of age, of who our pediatric those without. Leynaert et al. (13) indicated that
allergy clinic consecutively within a certain rhinitis that develops in the rst year of life is an
period. early manifestation of an atopic pre-disposition
It is of note that no nasal symptoms were and a risk factor for asthma. A recent large
recognized by the parents of 11.9% of children survey for allergic rhinitis in pre-school children
using ISAAC [The International Study of Asthma
and Allergies in Childhood (14)] written ques-
tionnaire also revealed that rhinitis has a strong
association with wheezing symptoms, asthma
(15).
The present study also showed that one-third
of asthmatic children experienced concomitant
exacerbation of upper and lower airway symp-
toms, even those without objective ndings
of allergic rhinitis. Exacerbation of nasal
symptoms
tion but alsoincludes
viral not onlyinfections,
or bacterial amma-
allergic insuch as a nasal
ber ofsymptoms
subjects. probably
Particular because of small
attention shouldnum- be
common
that any cold
nasal
exacerbation of
or symptoms
sinusitis.
asthma. cannding
This indicates
pre-dispose to paid
young to coexistent
children with lowersymptoms.
nasal airway symptoms
However, in
the
The mechanisms that connect upper and lower eideal
ective time for early
treatment intervention
strategy and the most
remain unknown.
Possible shortcomings
evaluation of symptoms exist
within questionnaire
this study. First, is
airway allergies are under active investigation. prone
age of tonasal
recollection
symptoms. bias especially
This inherent forproblem
the onsetin
Proposed pathogenetic mechanisms include a questionnaire,
this study however,
because we may
included be less
young problematic
children in
with
mean better
have age ofmemory
5 yr and of the parents
toddler ages of them
than would
those of
nasobronchial reex, mouth breathing caused adolescent
our or older
diagnostic counterparts
criteria for would.
objective Second,
allergic
rhinitis
allergen, were
HDM, based
and on
we sensitization
may have to apatients
missed single
with perennial
sensitized to allergic rhinitisallergen.
who may have been
by nasal congestion, and pulmonary aspiration described
most prevalent in other
Subjectsinhalant
perennial and methods,
allergen for
However,
HDM
both
as
is the
allergic
of nasal contents (16). In school age children, rhinitis
other and asthma in Japan and sensitization to
very rare except for seasonal allergen, JCP (5, is
allergens
30).In conclusion,
without HDM sensitization 6,
viruses were detected in 80% of reported epi- we found that 77.7% of asth-
sodes of asthma exacerbations (17). Upper matic children had allergic rhinitis, and their
airway rhinovirus infection is an important risk nasal symptoms started early in life. We reached
factor for asthma exacerbation through various a diagnosis of allergic rhinitis in young children
pathophysiologies to cause allergic inammation based on the objective ndings. As recognition of
in the lower airway, such as ICAM-1 expression rhinitis symptoms in infancy is dicult even for
(18). It has also been demonstrated that rhino- mothers, our ndings suggest the importance of
virus could directly infect lower airways (19). careful nasal examination in young children with
Spreading of allergic inammation from the asthma. A correct diagnosis of allergic rhinitis
upper airway to the lower airway may be induced may be one of the clues for early intervention in
since local allergic sensitization causes systemic respiratory allergic disease in children.
production of allergen-specic IgE and T cells
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