Articles

AllergicRhinitis: keys for the clinician

Rinitis Alérgica: claves para el clínico
Campuzano-Revilla, Gabriela P.

Gabriela P. Campuzano-Revilla Abstract: Allergic rhinitis (AR) and asthma are the most
ca267709@uaeh.edu.mx common inflammatory diseases of the airways. According to the
Universidad Autónoma del Estado de Hidalgo, México review of the literature, there is a prevalence of AR of 10-40%
worldwide. AR is defined as a type I allergic disease caused
by immunoglobulin E mediated inflammation. e symptoms
include nasal congestion, watery rhinorrhea and sneezing. In
Mexican Journal of Medical Research ICSA most cases it is accompanied by ocular symptoms like ocular
Universidad Autónoma del Estado de Hidalgo, México
ISSN-e: 2007-5235 redness, tearing and itchy eyes. AR can have an influence on
Periodicity: Semestral the quality of life in patients, for example: sleep disturbances,
vol. 10, no. 19, 34-40, 2022
sitioweb@uaeh.edu.mx fatigue, irritability, depression, also affect the attention, learning
and memory deficits. e classification of AR is seasonal AR,
Received: 30 July 2021 perennial AR, other classification is by duration of symptoms,
Accepted: 05 October 2021
Published: 05 January 2022 like intermittent, persistent, also a severity classification, based
on disturbances in quality life, proposed by the Allergic Rhinitis
URL: http://portal.amelica.org/ameli/journal/587/5872989009/ and Its Impact on Asthma (ARIA). e first steps in the
diagnosis are the clinical history and physical examination of
the patient. Also, the diagnosis can include laboratory tests
like skin prick test and the determination of immunoglobulin
is work is licensed under Creative Commons Attribution- E levels in serum. In the first line of the treatment there is
NonCommercial-NoDerivs 4.0 International. the no pharmacologic changes in the patient’s life, emphasizing
the avoidance of contact between the patient and the allergen,
and the pharmacological treatment are the second-generation
antihistamines, inhaled glucocorticoids and immunotherapy,
also alternative treatments can be used like acupuncture, ginger
extract and probiotic therapy. Allergic rhinitis represents a
limitation in the daily activity of those affected, it affects their
quality of life, interferes with their ability to sleep, as well as their
life at work and school.

Keywords: Allergic rhinitis, allergen, allergy, IgE,

immunoglobin E.

Resumen: La rinitis alérgica (RA) y el asma son las enfermedades

inflamatorias más comunes de las vías respiratorias. De acuerdo
a la revisión de la literatura existe una prevalencia de RA
del 10-40% en todo el mundo. La RA se define como una
enfermedad alérgica de tipo I causada por una inflamación
mediada por la inmunoglobulina E. El conjunto de estos
síntomas de la RA incluye congestión nasal, rinorrea acuosa y
estornudos. En la mayoría de los casos se acompaña de síntomas
oculares como el enrojecimiento ocular, lagrimeo y picor de
los ojos. La RA puede influir en la calidad de vida de los
pacientes, por ejemplo, en las alteraciones del sueño, la fatiga,
la irritabilidad, la depresión, también afecta a la atención, el
aprendizaje y los pacientes pueden sufrir déficit de memoria.
La clasificación de la RA es estacional, perenne, existe una

Non-profit publishing model to preserve the academic and open nature of scientific
communication

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clasificación por la duración de los síntomas como intermitente,

persistente, también existe una clasificación de la gravedad,
basada en las perturbaciones en la calidad de vida, propuestas
por el Allergic Rhinitis and Its Impact on Asthma (ARIA).
El primer paso en el diagnóstico es la historia clínica y la
exploración física del paciente. El diagnóstico también puede
incluir pruebas de laboratorio como la prueba de punción
cutánea y los anticuerpos de inmunoglobulina E en suero. La
primera línea de tratamiento son los cambios no farmacológicos
en la vida del paciente, haciendo hincapié en evitar el contacto
del paciente con el alérgeno, y el tratamiento farmacológico son
los antihistamínicos de segunda generación, los glucocorticoides
inhalados y la inmunoterapia, también se pueden utilizar
tratamientos alternativos, como la acupuntura, el extracto de
jengibre y la terapia probiótica. La rinitis alérgica representa una
limitación en la actividad diaria de los afectados, desde su calidad
de vida, interfiere con la capacidad de dormir, así como en el
trabajo y la escuela.

Palabras clave: Rinitis alérgica, alergeno, alergia, IgE,

inmunoglobulina E.

INTRODUCTION

Atopic syndrome is an exaggerated immunoglobulin E - immune response in reaction to an unknown

allergen.1 Allergic rhinitis (AR) and asthma are the most common inflammatory diseases of the airways2,
and usually persist along the patient’s life.3 Both diseases are frequently coexisting, this concept is based
on epidemiological studies, physiopathology, symptoms and interactions in the airway are similar4, the
prevalence of the association between asthma and rhinitis are 15% to 38% and the present of AR increases the
risk for asthma and patients with uncontrolled asthma symptoms.3 According to the review of the literature,
there is a prevalence of AR of 10-40% worldwide.5,6 Every day, the prevalence of atopic syndromes increases,
especially in countries with low-income population.6 is literature review is intended to create a guide for
the first contact clinician to update, diagnose and treat patients.

DEFINITION

AR is defined as a type I allergic disease of the nasal mucosa, the characteristic symptoms include nasal
congestion, watery rhinorrhea and sneezing7-9, when patient is exposed to the allergen10, caused by an
immunoglobulin E mediated inflammation.5,10 e terms used for this disease entity include: allergic rhinitis,
nasal allergy, nasal hypersensitivity and pollinosis, this last one is a seasonal type of allergic rhinitis, caused
by pollen.9

CLASSIFICATION

e rhinitis management depends on the type of rhinitis, the classification is suggested by e Allergic
Rhinitis and its Impact on Asthma (ARIA), it is classically divided into seasonal AR (SAR) caused mainly
by outdoor allergens, mainly pollen; and perennial AR (PAR) due to indoor allergens like dust mites, molds
and insects.10 Another classification is about the type of duration and divide the AR in: intermittent AR

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Gabriela P. Campuzano-Revilla. AllergicRhinitis: keys for the clinician

(IAR) characterized by a temporal duration, less than 4 days per week or less than 4 consecutive weeks; and
persistent AR (PAR) which symptoms occur for more than 4 consecutive weeks.11 ARIA guidelines proposed
a classification for severity (mild and moderate-severe) by the disturbances of quality of life.12 A classification
of sensitization is: monosensitization, only one allergen is causing the allergy and polysensitization in this
one, exists 2 or more allergen, this finding can only be made by testing allergy (skin testing or serum
Immunoglobulin E).10 According to a biomarkers classification, AR is divided into four endotypes: 1. Type
1 immune response, the biomarkers are neutrophilia and IFNγ 2. Type 2 immune response, the typical
biomarkers are classical cytokines of the TH2 profile, eosinophils and IgE, 3. Neurogenic rhinitis, biomarkers
are neurokinins and substance P and 4. Epithelial dysfunction, having the biomarkers: thymic stroma
lymphopoietic, IL-33 and IL-25.13

EPIDEMIOLOGY

ere are almost 400 million people worldwide affected by AR.14 e experts estimate a prevalence range
between five to twenty two percent of population affected by this disease.15 e International Study of
Asthma and Allergies in Childhood (ISAAC) is a study about the prevalence and severity in atopy syndrome
(asthma, rhinitis and eczema). Evaluated by validated questionnaires, this study was realized from 1992 to
1998 then from 2002 to 2003. It evaluated patients of two age groups 6 to 7 years old and 13 to 14 years old.
e results present an increase in the prevalence of AR from 1990s to the first years of the first decade of the
21st century in low-income and middle-income countries. It decreased or stabilized in Western Europe.14,16
In the systematic review and meta-analysis of 86 cross-sectional studies conducted mainly in Asia and Europe,
then America, Africa and Oceania, this study was performed in children and adolescents. e diagnosis of
AR was mainly using the ISAAC questionnaire for children and adolescents, then the European Community
Respiratory Health Survey (ECRHS) in adults. e study included 291, 726 males and 301,781 females.
e results were: a prevalence in participants under 11 years old, where the symptoms of rhinitis reported
by the parents themselves was 1.27%. ese results did not report sex differences. In the age group between
11 and 17 years old, the prevalence of rhinitis symptoms was 0.90%, in three studies in Korea, Iran and
Kuwait, it showed a higher prevalence in males, but 15 studies had a strong female predominance in this age
group. In adults, patients above 18 years old, there was a prevalence of 0.96% in this case, none of the studies
reported a male predominance, just two studies conducted in Korea and Nigeria presented a borderline male
predominance. In studies conducted in France and Sweden a female predominance was presented.17
In the study where the first transnational survey on symptoms was conducted, the impact on quality of
life and treatment of nasal allergies in Latin America, a cross-national study performed in Argentina, Brazil,
Chile, Colombia, Ecuador, Mexico, Peru and Venezuela included 1088 adults and 457 children and 457
adults. In this study, it was revealed a 7% prevalence of nasal allergies, but only 6.6% had a physician diagnosis
of AR in the Latin American survey. In Peru and Venezuela it was reported the highest prevalence and in
Argentina it was reported the lowest prevalence. Mexico reported a higher prevalence of seasonal allergies in
parents of children and adolescents with nasal allergy, meanwhile Argentina reported the lowest rate.18
A cross-sectional study was realized in 535 children between 3 and 5 years old in Cuenca, Ecuador. e
collected results were of 48% of patients with AR symptoms, but only a small fraction was attributable to
atopy, the total prevalence attributable to skin prick test was 7.9%.19
Another study was a cross-sectional population-based study from 2009 to 2010 in Bogotá, Colombia. e
study included 5978 patients, where the prevalence of AR symptoms was 32%, but only 14% had a prevalence
in physician diagnosis.20

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e local panorama of AR prevalence in Mexico has fluctuations in the prevalence from 5.5% to 47.7%,
in studies conducted on Mexican population.21

CLINICAL MANIFESTATIONS

Cardinal symptoms include nasal congestion, rhinorrhea, sneezing, nasal itching, cough, although multiple
related symptoms may occur.7,8In most cases it is accompanied by ocular symptoms like ocular redness,
tearing and itchy eyes.22,23 e congestion gets worse in the late summer and early fall.24 e severity of the
symptoms determine a disruption of the quality of life, also sleep disturbances like somnolence, falling asleep,
and staying asleep, the patient may present fatigue, irritability, depression, it may also affect the attention,
learning and the memory.25,26 Patients can have excoriations for the persistent congestion, and an increase in
the blood flow in the periorbital region can produce allergic pimples.23 e symptoms depend on the age and
the sex of patients, the changes in Immunoglobulin E in different ages, and the sex hormone levels determine
a change in the symptoms.25

PHYSIOPATHOLOGY

e nasal cavity is composed by bone and cartilage, divided by septum, and lined with pseudostratified
columnar respiratory epithelium. e main function is the regulation of air temperature, humidification
and cleansing of the inspired air.23,27 Mucus maintains hydration and traps particles, bacteria and virus,
and provides an innate immunity.28 e nasal epithelium is the first to have contact with the air in the
respiratory tract and the first line of defense against infectious agents, like induce a mechanism of protection
and inflammation, like in AR the exposure of allergens relates an interaction with recognition receptors16, it
creates a physical and chemical stimulation. is response of the nervous system includes parasympatic and
sympathetic nerves, this nerves transmit signals to the mucosa and generate an itchy sensation and motor
reflexes like sneezing. e stimulation of the nervous system generates an exaggerated response in the nervous
and immune systems.29 e immune system starts a IgE-mediated reaction against inhaled allergens and it
involves a mucus inflammation driven by type 2 helper T (2) cells.5,7,30 e IgE synthetized in the mucosa,
then enters the blood stream through the lymphatic system31, and cysteinyl leukotrienes of the allergen are
recognized by antigen-specific IgE receptors on mast cell and basophils, and have an influence on the mucosal
inflammation in tissue and nasal symptoms (sneezing and rhinorrhea) and ocular symptoms (itching, redness
and watering) mainly caused by the release of histamine, leukotrienes and prostaglandins.5,23,32,33 During
the next hours, through a complex interaction of mast cells, epithelial cells, dendritic cells, T cells, innate
lymphoid cells, eosinophils, and basophils, this due to the release of neuroactive and vasoactive substances
like histamine, prostaglandin D2, tryptase and eosinophil cationic protein7,32,34 and develop an immediate
hypersensitivity13. Aer some hours that the allergen remains in the local tissue, the mucosa is more reactive
to this allergen, even with other strong irritants, resulting in tissue edema and the perpetuation of nasal
congestion.7,32

DIAGNOSIS

e first steps in the diagnosis are the clinical history and physical examination of the patient, recognize
the type of rhinitis (allergic or non-allergic).3Figure 1. Diagnosis for AR, summarizes the steps to diagnose
AR. e interrogatory includes age of onset, duration, frequency, severity, timing during the year, suspected

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Gabriela P. Campuzano-Revilla. AllergicRhinitis: keys for the clinician

triggers, pattern of presentation, and progression of the symptoms10. Also, the past therapeutic and
effectiveness, the personal and family history of atopy conditions, especially asthma, AR coexists with asthma
in 75 to 100% of the patients8. Also asking about potential triggers at home and work like pollen, animals,
tobacco smoke, humidity.22 e physical examination includes, especially in children, a growth assessment,
since airways problems are associated with growth reduction, the inhaled corticosteroids reduce height at
high doses.16 e presence of conjunctivitis, allergic nasal crease, allergic salute or double creases beneath
the eyes or Dennie-Morgan lines, allergic pimples, allergic salute, rubbing of the nose can guide the physician
about a case of AR.35 Patients with moderate to severe AR and with uncontrolled symptoms needs a nasal
examination, with rhinoscopy where the typical appearance in nasal cavity is swollen pale bluish inferior
turbinate edema with copious clear secretions; it is also performed an ear inspection, the otitis media is a
comorbidity in children with AR.16 When the clinical history and physical examination suggest AR, the
confirmatory diagnosis is by skin prick test or blood tests to identify specific antigens and vitro of specific IgE
antibodies.36 e skin prick test allows to directly observe the reaction of the organism to a specific antigen,
as well as activated mast cells and released histamine26, sensitivity ranged from 68% to 100% and specificity
ranged from 70% to 91%16 and can be done safely in the allergy consultation and provides results within
20 minutes35. e main contraindications are an antecedent of anaphylaxis, unstable cardiovascular disease,
some medication like antihistamines, tricyclic antidepressant, β-blockers, since they can suppress the test
results.26 e component- resolved diagnosis is not recommended as a diagnosis routine, the detection of
serum IgE antibodies using a biomarker can be useful to predict morbidities, and persistence in the future.10
e allergen-specific test also can be useful for immunotherapy and guide the content of the vaccine16, also
advantages of using immunoassays for allergy testing are sensitivity to specific antigens and adverse reactions
get eliminated, including anaphylaxis, and the effects on the patient’s skin and the patient should not suppress
the current medication.26

TREATMENT

Non-Pharmacological treatment

To avoid relevant allergens, like pets, pollen, mounds, and irritants like tobacco smoke.37 Also,
dehumidification lower than 50%, as well as the reduction of the exposure to pollen can be reduced by closing
windows, the use of high-efficiency particulate air (HEPA) and limited outdoor time in pollen season, also
eliminating contact with animals can reduce the symptoms and the incidence of AR.22

Pharmacological treatment

Intranasal glucocorticoids and intranasal oral antihistamine drugs are the first-line therapies.35 e initial
treatment is monotherapy and then a combination pharmacologic therapeutic option for AR8. Table 1
shows the pharmacological treatment for AR, it includes the summarized dose, main contraindication for
the main medical option.

Glucocorticoids

ey are considered the most effective medication class for the treatment of all symptoms related to perennial
allergic rhinitis (including nasal congestion) and they provide a more effective relief to symptoms than

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oral antihistamines.35,38 Glucocorticoids are used for acute and chronic rhinosinusitis with and without
nasal polyps, and adenoid hypertrophy with or without middle ear disease, the evidence on intranasal
corticosteroids producing greater nasal symptom relief suggests than topical antihistamines even if there
are no difference in ocular symptoms, corticosteroid nasal sprays include: beclomethasone dipropionate,
budesonide, ciclesonide, flunisolide, fluticasone furoate, fluticasone propionate, triamcinolone acetonide,
and mometasone furoate35, the minimum recommended duration of nasal corticosteroid therapy is 12
weeks.8
Corticosteroids increase the production of reactive oxygen and reactive nitrogen species; they also reduce
the secretion of mucus and the development of inflammatory edema. e process of blocking mucus
production is linked to corticosteroids inhibiting the expression of MUC-2 and MUC-5AC genes. Nasal
corticosteroids are strong vasoconstrictors,so they reduce edema and effusion; and corticosteroids have
noeffect on the innate immune response mechanisms, this effect is observedfrom minute 2 to 20.39
FIGURE 1.
Diagnosis for Allergic Rhinitis.

10, 16, 22, 26, 35, 36

Antihistamines

e antihistamines are the standard therapy for allergic diseases, first-generation antihistamines are not
recommended to treat allergic rhinitis, especially in older patients, because there is a high risk of adverse
reactions, like anxiety, confusion, dyskinesis, sedation or sleepiness, arrhythmias, urinary disturbances,
constipation, hypotension, memory dysfunction, and problems with kinetic coordination, this caused by
the capacity to cross the blood-brain barrier5,35. e sedative properties of H1 antihistamines are caused by
inhibition of the functions of central histamine neurons, hydroxyzine ( 30 mg tablets) significantly prolonged

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Gabriela P. Campuzano-Revilla. AllergicRhinitis: keys for the clinician

the break reaction time while driving a car compared, for this reason the second generation antihistamines
are prefered.39,40
e second-generation antihistamines have a relatively low rate of passage across the blood–brain barrier,
and are minimally sedating or nonsedating; ey are highly selective for H1 receptors and do not have
anticholinergic effects41,42in this group like fexofenadine (30 mg, 60 mg, 180 mg tablets, oral disintegrating
tablet 30 mg, suspension 6 mg/ml), cetirizine, (5 mg and 10 mg tablets, and chewable 5mg tablets, 10
mg, syrup 1 mg/ml), loratadine (10 mg, 60 mg, 180 mg tablets, oral disintegrating 5 mg tablet, 10 mg),
levocetirizine (30 mg tablets,
0.5 mg/ml syrup), desloratadine (5 mg tablets, oral disintegrating 5 mg tablet, syrup 0.5 mg/ml), bilastine
(20 mg tablets) and ebastine (20 mg tablets), all of this are administrated one a day43,44, the majority of
second-generation antihistamines are metabolized by the cytochrome P450 enzyme and interactions with
macrolides, antifungals, and calcium antagonists.41,42 eir first metabolism is through the liver and thus
they are not recommended for patients with significant liver dysfunction; in patients with renal impairment
it is recommended to prescribe azelastine, ebastine, desloratadine and cetirizine.35

Decongestants

Nasal decongestants such as sympathomimetic amine derivatives (phenylephrine) and imidazole derivatives
(oxymetazoline), are not a first-line therapy nor used as a monotherapy, particularly for a prolonged, the
adverse events, increased arterial hypertension, headache, arousal, prostatism, and aggravation of glaucoma,
and urination.35

Leukotriene receptor agonist

e leukotriene receptor agonists like montelukast (10 mg tablet, 4 mg chewable tablet, 5 mg, oral granules:
4 mg) and zafirlukast (10 mg tablet)43, in the evidence, the combination of this with antihistamines is
effective as intranasal corticosteroids, this is recommended when the antihistamine/corticosteroid are not
tolerated.22 Montelukast undergoes extensive CYP 3A4 and CYP 2C9 metabolism, the main interaction is
with phenobarbital, it can decrease montelukast plasma concentrations by up to 40, also rifampin reduce
montelukast concentrations. It has also been found that montelukast can potently inhibit CYP 2C8, for this
reason the coadministration of montelukast with repaglinide, rosiglitazone or cerivastatin.43,44

Immunotherapy

Allergen immunotherapy is very effective, even for local allergic rhinitis, and the shortcomings of
subcutaneous immunotherapy regarding inconvenience and safety are reduced with the introduction of
sublingual immunotherapy (SLIT) and intranasal immunotherapy.9 is therapy reduces the IgE levels, and
block the union between IgE and FcεRI.38 is treatment is the only etiological treatment and it modifies
the natural course of AR.45

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TABLE 1
Pharmacological treatment for Allergic Rhinitis

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Gabriela P. Campuzano-Revilla. AllergicRhinitis: keys for the clinician

40, 41, 44

Alternative treatment

In a randomized, double-blind, controlled trial for 3 and 6 weeks, patients with AR were treated with 500
mg of ginger extract compared to those treated with 10 mg loratadine. e efficacy was evaluated from
clinical examinations in a total nasal symptom scores (TNSS), cross-sectional area of the nasal cavity with
acoustic rhinometry and with the quality of life questionnaire of rhino conjunctivitis. e safety of treatment
was measured by blood pressure, blood analysis and history- taking for side effects. e results showed that
the groups treated with both ginger extract and loratadine significantly decreased TNSS scores but there
was no significant differences between the two groups. is study demonstrated that ginger extract is as
good as loratadine in improving nasal symptoms and quality of life of AR patients, but ginger extract is
associated with more adverse effects.46 A meta-analysis about the efficacy of acupuncture in allergic rhinitis
and the evidence of acupuncture treatment for allergic rhinitis in several aspects, including symptom score,
drug score, quality of life score, asthma control score, side effects and laboratory examinationsuch as nasal
function test, serum total immunoglobulin (IgE),nasal secretion smear, and so on.47,48 Different studies
havetested the efficiency of probiotic administration, activating orinhibiting type 1 T-helper cells from the
intestinal microbiota,although the results have not been conclusive, the studies,especially those performed
in animals, as well as those usingprobiotic administration versus placebos, seem to be useful inatopic
diseases, including allergic rhinitis. Different studieshave tested the efficiency of probiotic administration,
activatingor inhibiting type 1 T-helper cells from the intestinalmicrobiota, although the results have not been
conclusive, thestudies, especially those performed in animals, as well as thoseusing probiotic administration
versus placebos, seem to beuseful in atopic diseases, including allergic rhinitis.49

PREVENTION

e attempts to prevent an allergic disease are unccessful16, the polarization in adaptive immune system
and stimulated the innate immune, immunological prevention in infants, are focused on producing TH2.39
e diet in the infant can influence the risk of allergies in children, the deficiency of vitamin D, have a
direct association with the development of AR.42 Studies indicated that prenatal and postnatal probiotics
or prebiotics can reduce the AR.16

FORECAST

AR is a chronic condition that is caused by specific allergens, it is important for patients to try to identify
allergens and/or environmental agents that may precipitate their disease, and this reduce the symptoms, and
have a beneficial prognosis for the pathology.16 e symptoms can interfere in the patient’s life quality with
the ability to sleep, anxiety, depression, fatigue, social interaction, and cognitive dysfuntion.42

CONCLUSION

AR is the most common atopic disease according to current epidemiology, so the clinician in contact with
patients should consider the most important points of this pathology. Also, it really affects the life quality
of patients. e diagnosis ranges from clinical to cabinet tests that can be used by the physician to find the
severity of the pathology, as well as the individualization of the treatment. Priority should be given to changes

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in the patient's lifestyle, as well as the desired line of treatment, to improve the prognosis and avoid possible
complications (mainly asthma) that can have an impact on the patient's quality of life.

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Glossary

AR: Allergic Rhinitis

ARIA: Allergic Rhinitis and its Impact on Asthma ECRHS European Community Respiratory Health
Survey FcεRI High-affinity IgE receptor
H1: Histamine receptor 1.
IAR : Intermittent Allergic Rhinitis
IFNγ 2: Gamma interferon IgE Immunoglobulin E IL-25 Interleukin-25
IL-33: Interleukin-33
ISAAC : International Study of Asthma and Allergies in Childhood
MUC-2: Mucin 2
MUC-5AC: Mucin 5AC
PAR : Perennial Allergic Rhinitis
PAR : Persistent Allergic Rhinitis
SAR: Seasonal Allergic Rhinitis
SLIT : Sublingual immunotherapy
TH2: Lymphocytes helper 2.
TNSS: Total nasal symptom scores

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