Interpretation
It is well-established that atopy and allergic diseases are more
frequent in prepubertal boys. In adolescence, in contrast to asthma and
eczema prevalence that shifts toward females, AR continues to affect
more males up to the age of 20 years(20). In our study, boys outnumbered
the girls (69% vs 31%). However, male gender was not associated with
asthma presence or AR severity. In agreement with previous childhood
studies, allergic conjunctivitis was the most frequent (76.5%)
co-morbidity amongst our patients with AR. Zicari et al.(3) have
included 1200 Italian children with AR, and conjunctivitis were present
in 51.7% of them, whereas Ibanez et al.(21) have reported a prevalence
of 53.6% in 1275 Spanish children. However, the prevalence of
conjunctivitis in our cohort was significantly higher. We note that the
proportion of patients with moderate-severe persistent AR was
substantially higher in our cohort compared to previous childhood
studies(3, 21), and this may account for a higher proportion of those
with ocular symptoms.
According to the united airway disease concept, AR and asthma are common
diseases that frequently occur together, and patients share common
immunopathological features including increased bronchial
hyperresponsiveness and reactivity to a variety of stimuli(6).
Consistent with previous data, asthma was present in 40% of our
patients(3, 19, 21). Previous epidemiological studies have predominantly
emphasized the worsening effect of AR on symptoms of asthma, and it has
been shown that severe and uncontrolled rhinitis symptoms were
associated with severe and uncontrolled asthma in children and
adolescents(22, 23). However, the impact of asthma on the severity and
persistence pattern of AR symptoms in children and adolescents has
rarely been investigated. In our study, in contrast with the
asthma-oriented studies, the rhinitis symptoms were more severe and
persistent in children without asthma(24).
Results of several studies indicated aeroallergen sensitization,
particularly to HDM and Aspergillus, as one of the independent risk
factors for asthma in children(25, 26). In a recent study, Chiu et al.
have found significant association between HDM sensitization and various
urinary metabolites which were significantly associated with childhood
asthma development(27). In our study, the prevalence of HDM and mold
sensitizations was significantly higher in children with asthma whereas
grass pollen sensitization was lower in this group. In the
cross-sectional study by Bousquet et al.(24) which included 591 adults
with AR, HDM allergy was associated with perennial and milder symptoms
(consistent with our results), and - in contrast to our data -
persistent rhinitis. In the study by Zicari et al. which included
2319 Spanish children with AR, no difference was found in terms of
temporal pattern and severity between HDM and grass pollen allergic
children(3). The results of these studies are based on
investigator-led-assignments whilst our sensitization patterns are
data-driven. Boulet et al. have concluded that patients with HDM
sensitizations are more prone to have asthma as a co-morbidity than
those with outdoor allergy(28). In accordance with their findings, lung
function parameters were significantly reduced in this group, and there
was a significant association with asthma. Bertelsen et al.(4) have
speculated that perennial exposure to allergens can be more related to
asthma, when compared to pollen exposure which occurs only during a
limited time period.
Allergy to pets is regarded as a major risk factor for asthma(29). In
the study of Konradsen et al.(30), children with severe asthma had
higher levels of IgE antibodies towards furry animals including cat, dog
and horse. Nevertheless, the number of the studies which investigated
the features of pet allergy in children with AR is limited. Zicari et
al.(3) reported the prevalence of pet sensitization only in 2.5% of
patients, without any clinical relevance to AR symptoms. However, in the
Environment and Childhood Asthma birth cohort study, pet allergens (dog
and cat) were the second most prevalent sensitizing agent in children
with AR and the investigators documented two major sensitization groups
(grass pollen monosensitization vs. grass pollen/furry pets
polysensitization)(4). When they compared the co-morbidities and
clinical characteristics, in contrast to our findings, asthma prevalence
and the severity of bronchial hyperreactivity were greater in children
with pet sensitization. However, in accordance with our findings, pet
sensitization was associated with milder and perennial AR symptoms.
Adenoid hypertrophy (AH) is one of the most frequent co-morbidities in
children with allergic rhinitis(21, 31). Results of previous studies
have reported mold sensitization as a risk factor for adenoid
hypertrophy in children with AR(32, 33). In agreement with this finding,
sensitization to molds was significantly higher in our cluster consisted
of children who underwent tonsillectomy and adenoidectomy when compared
with patients in the grass-sensitized patients with conjunctivitis.
Dogru et al.(33) have found an association between AH and the severity
of AR in children. However, this relationship was not demonstrated in
our study. The plausible explanation for the lack of this association
may be that the children in this cluster were already operated and the
symptom severity could be relieved due to the surgery.
Several clinical implications can be extracted from our findings. Asthma
symptoms should be queried and lung function tests can be performed
especially in children with house dust mite and mold sensitizations.
Severe and persistent symptoms should be expected in children with grass
pollen monosensitization, therefore, physicians can consider early
initiation of the allergen immunotherapy in such children. Pet
sensitization can accompany grass pollen sensitization especially in
boys. A referral to otorhinolaryngologist in order to exclude adenoid
hypertrophy should be considered particularly in children with severe
and treatment-resistant nasal obstruction and snoring.
In conclusion, we have identified four different subgroups of children
with AR using LCA in this cross-sectional study, which were associated
with different patterns of clinical symptoms and comorbidities.
Acknowledgements: We are extremely grateful to all the families
who took part in this study. We would also like to acknowledge the hard
work and dedication of the study team, which includes computer and
laboratory technicians, and nurses.