Nasal Cytology In Childhood Allergic Rhinitis Biology Essay

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Allergic rhinitis is a commonly encountered ailment which affects 10% to 40% of children worldwide. It impairs quality of life and contributes towards significant quantum of health-care expenditure. In spite of high prevalence of this entity, it is often wrongly diagnosed as infectious rhinitis [2].Medical literature is replete with mention of multifarious clinical and laboratory criteria for diagnosing allergic rhinitis. However till date we do not have a simple diagnostic algorithm that can be universally practiced by medical officers even in the precincts of an out patient department (OPD) of a peripheral hospital.

Quantitative nasal cytology has been cited as a quick, simple, reliable and inexpensive tool for establishing the diagnosis of allergic rhinitis, especially when the findings are interpreted in conjunction with clinical manifestations [3].

Literature survey reveals limited research on the role of nasal cytology amongst pediatric patients. There is also a strong possibility of application of quantitative nasal cytology for evaluating the degree of responsiveness of allergic rhinitis to therapy (such as topical nasal corticosteroid sprays). Presently we have no evidence based data to support the same. Thus the study of quantitative nasal cytology in pediatric population appears to be a promising ground for clinical research. Hence, the study "Nasal cytology in the diagnosis and management of allergic rhinitis in children" was performed.

MATERIAL AND METHODS

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Place of study: A one hundred and forty nine bedded military hospital.

Study Design: Prospective case control study.Duration of Study: Three years.

Sample Population: Boys and girls aged between four to fifteen years presenting in the pediatric OPD of the above hospital.

Inclusion Criteria for case definition:

(i)Symptoms: Running nose, itchiness of nose, nasal congestion, sneezing.

(ii)Signs :Watery nasal discharge, postnasal drip, characteristic change in turbinate colour , swelling of turbinates , pharyngeal inflammation.

Exclusion Criteria:

(i)Children with anatomical causes of rhinitis, namely,deviated nasal septum,choanal atresia,adenoid hypertrophy,intranasal foreign body,nasal polyp,nasal tumour.

(ii) Symptoms dating more than one week.

(iii)Children receiving intranasal steroid / sodium cromoglycate / decongestants/ ketotifen / antihistaminics upto one month prior to enrolment in study.

(iii)Children with sinusitis (after radiological confirmation).

(iv) Children with comorbidities (like bronchial asthma).

(vi)Children with perennial (persistent) allergic rhinitis with round the year symptoms.

Controls: Normal healthy children who were age and sex matched with the cases were taken as controls.

Informed written consent was obtained from parents.

Nasal mucosal scrapings were obtained from the surfaces of middle-thirds of inferior turbinates of both nostrils of subjects and controls with cotton tipped applicator,smeared on glass slides,fixed with 95% ethyl alcohol and stained with modified Wright-Giemsa stain. Slides were then examined under 1000X magnification of a light microscope by pathologist who was blinded to clinical status of the patients.At least 10 well spread high power fields were examined.Quantitative scoring of nasal eosinophils was done according to Meltzer score (Table1)[4,5].Subsequently,intranasal corticosteroid (Mometasone) was administered by spray in appropriate dosage daily for two weeks.It was predecided that therapy would be terminated for a child in case of development of complications or drug intolerance and he or she would then be managed accordingly. Quantitative nasal cytology was repeated after second and sixth week of initiation of intranasal corticosteroid therapy.

Variables that were recorded were as follows:

(i) Quantitative nasal eosinophilia at start of therapy.

(ii) Quantitative nasal eosinophilia at completion of therapy , that is, at second week from initiation of therapy.

Quantitative nasal eosinophilia at sixth week from initiation of therapy.

Complications (if any).

Definite contributory family history of allergies (if any).

Definite history of inhalant allergen exposure (if any).

Definite history of other allergies (eye/ respiratory/ gastrointestinal tract/ skin) (if any)

At conclusion of the study, both groups were compared using appropriate statistical methods and inferences were drawn.

Number of eosinophils

(per 10 High Power Field)

Quantitative Nasal Cytology Score

0

0

0.1 - 1*

0.5 +

1.1 - 5.0*

1 +

6.0 - 15.0*

2 +

16.0 - 20.0*

3 +

> 20.0*

4 +

Table 1. Meltzer Quantitative Scoring System for nasal eosinophilia [4, 5]

(* Mean of cells per 10 high power fields (x1000))

RESULTS

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Breakup of study population is as under:

(i)Total population: 350

(ii)Children with rhinitis: 300 (85.7% of total)

(iii)Children without rhinitis: 50 (14.3% of total)

Mean age group of cases was 8.16 ± 0.3 years (range 4 to 15years). 117 children were between 4 to 8 years age and 183 children were between 8 to 14 years of age. Mean age of controls was 8.75 ± 0.3 years (range 4 to 14 years).Age difference between cases and controls was statistically insignificant (p= 0.4366).Similarly, sex difference between subjects in both the groups was insignificant (p =0.964).

Comparison of quantitative nasal eosinophilia scores (prior to the initiation of therapy) between controls and subjects is shown in Table 2 and Fig 1.Median scores in the rhinitis group were 1 and 2 whereas the corresponding median for the control group, regardless of age, was 0 (p<0.0001).

Quantitative nasal eosinophilia scores in children with allergic rhinitis (with 0.5 as a lower diagnostic cut-off) were significant compared to scores in normal healthy children without symptoms and signs of allergic rhinitis (p=0.022).

Hence it can be inferred that in addition to history and physical examination there is significant utility of quantitative nasal cytology as an adjunctive diagnostic tool for diagnosing allergic rhinitis in children.

After 2 weeks of initiation of therapy with intranasal corticosteroid (mometasone)

All children with allergic rhinitis showed clinical recovery.

Corresponding to clinical recovery, there was significant (p=0.432) and proportionate reduction in the nasal eosinophilia scores of children with allergic rhinitis (Table 4 and Fig 2).

It can be thus inferred that there is significant utility of quantitative nasal cytology scoring in evaluating therapeutic response of intranasal corticosteroids in children suffering from allergic rhinitis.

Test parameters for quantitative nasal eosinophilia score (Meltzer Scoring System) in the diagnosis of allergic rhinitis in children are as follows:

(i)Specificity of test= 47/50 X 100= 94%

(ii)Predictive value of a positive result= 300/303 X 100= 99%

(iii)Predictive value of a negative result = 47/50 X 100 = 94%

Quantitative Nasal Cytology Score

Cases

Controls

4

15

0

3

36

0

2

90

0

1

120

0

0.5

39

3

0

0

47

Total

300

50

Table 2. Distribution of study population prior to initiation of therapy

on the basis of Quantitative Nasal Cytology Score

Eosinophilia Score

Before treatment (number of children)

After treatment (i.e. 2 weeks of intranasal steroids)

(number of children)

After 6 weeks of initiation of therapy

4

15

0

0

3

36

0

0

2

90

0

0

1

120

6

0

0.5

39

4

0

0

0

289

299

Total

300

299*

299*

Table 3. Nasal Eosinophilia scores at initiation,2 weeks and 6 weeks after start of therapy

(*1 child was lost to follow up)

15

36

90

120

39

0

40

60

80

1200

Number

1

2

3

4

0.5

0

Score

Fig 1. Distribution of Subjects and Controls

on the basis of Meltzer Scores

Subjects

Controls

100

20

47

3

0

20

40

60

80

100

120

No of

Children

1

2

3

4

5

Scores

Fig 2.Change in Eosinophilia Score after

intranasal corticosteroid therapy

Before Treatment

After Treatment

DISCUSSION

Allergic rhinitis is an inflammatory disease of the nose characterized by a symptom complex that consists of any combination of the following: sneezing, nasal congestion, nasal itching, and rhinorrhea [2]. It is characterized by influx of eosinophils and basophils into nasal secretions and nasal mucosa [6].Inflammation of the mucous membranes is characterized by a complex interaction of inflammatory mediators but ultimately is triggered by an immunoglobulin E (IgE)-mediated response to an extrinsic protein [3].During natural exposure to allergen, eosinophils in nasal lavage have been observed to increase twenty fold, followed closely by increasing nasal symptoms. In addition, the number of mast cells in the nasal mucosa also increases after pollen exposure [7]. In experimental antigen challenges, a small but significant increase of eosinophils could be observed in nasal lavage fluid within one hour after the challenge procedure prior to a dramatic increase 7 to 11 hours, thereafter [8]. While the release of mast cell mediators characterizes the early allergic nasal response, eosinophils with accompanying basophils play an important role in the late phase nasal response [6].

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Nonallergic rhinitis with eosinophilia syndrome (NARES) is a similar clinical entity which is defined by a syndrome of nasal hyper-reactivity over more than three months, the absence of any atopic factor, and an eosinophilia of nasal secretions 20% greater than the leukocytes [9]. Anosmia is a prominent feature not shared with allergic rhinitis [10]. Patients with NARES do not have elevated IgE antibodies [11].

There are reports of nasal cytology studies performed on patients with allergic rhinitis using different specimen sources and different staining techniques. Lee et al reported an eosinophil: neutrophil ratio in nasal secretions by Wright-Giemsa stain) of > 0.1 to be a critical value for the differentiation between allergic and non-allergic nasal conditions in adults [12]. Miller et al determined the diagnostic value of eosinophils in nasal secretion by Hansel's stain and found sensitivity and specificity for this method to be 70% and 94%, respectively [13]. The results of the above study are in concordance with the findings of our current study, the only exception being that Miller et al had performed the study on adult subjects.

Studies involving allergic rhinitis in children are limited. Zeiger et al studied high risk, atopy-prone children and demonstrated that prevalence and number of nasal basophilic metachromatic cells increased from 4 months to 2 years of age and remained at a plateau thereafter. Nasal eosinophils, in contrast, increased from 4 months to 4 years without reaching a plateau or a peak [14].

Comparing nasal biopsy specimens from patients with symptomatic seasonal allergic rhinitis to a control group, Igarashi et al demonstrated that nasal eosinophilia was significantly higher in the allergic group than in the control group [15].

Our study has shown good correlation between nasal eosinophil scores with history and clinical signs. This substantiates findings of Terada et al who had also demonstrated significant correlation between the increase in nasal airway resistance and the number of activated nasal eosinophils[16].

Till date there is no published report of any study performed to evaluate the role of quantitative nasal cytology (based on quantitative scoring of nasal eosinophilia) in determining therapeutic efficacy of topical corticosteroid therapy in allergic rhinitis. Thus, our study is a pioneering work in this domain.

Recommendations of our study:

(i) Quantitative eosinophil scoring of nasal mucosal scraping can be uniformly and universally recommended as an adjunctive tool for diagnosing allergic rhinitis in children.

(ii) Quantitative eosinophil scoring of nasal mucosal scraping can be universally recommended for evaluating the response to therapy for allergic rhinitis in children.

(iii) Nasal scraping can be recommended in the first episode of allergic rhinitis in children under following conditions:

(a) If the diagnosis of allergic rhinitis cannot be established with certainty with clinical criteria alone.

(b) Before initiation of intranasal corticosteroid therapy.

(iv) Quantitative nasal cytology can be a part of undergraduate medical curriculum so that medical students can be sensitized about this simple technique thus removing the ambiguities associated with the diagnosis and treatment of allergic rhinitis.

(v) There is a case in point in recommending a large, multi-centric, multi-regional, randomized, prospective, triple-blinded study to investigate the role of quantitative nasal cytology in diagnosis and management of allergic rhinitis in all age groups. Cost benefit analysis can be incorporated before recommending this tool for the armed forces medical services.

Fallacies of our study:

(i) Correlation with serum IgE levels has not been studied. Measurement of IgE levels would have helped in ruling out NARES definitively and would also have further augmented the validity of the test.

(ii) Children have been studied in a single location. They might have been possibly exposed to a common set of allergens. There is room for speculation that varying allergens from varying environmental locales can have varying degree of effect on the nasal mucosa and thus on nasal eosinophilia.