Allergic rhinitis is one of the most prevalent diseases worldwide and is a substantial public health problem worldwide [1].

It was documented that the global rise in allergic diseases may be linked to lower serum 25-hydroxyvitamin D (25(OH)D) [2,3]. Some previous studies by Bener et al. [4-7]. revealed that Vitamin D deficiency was a major contributing factor to many diseases like asthma and allergic diseases. Several other studies also found that Vitamin D deficiency may lead to an increase in the frequency of asthma and attacks of wheezing and necessitate more medications [7,8]. C-reactive protein (CRP) is a well- known inflammation marker. Serum concentration of CRP is generally determined to assess a systemic inflammation, e.g., pneumonia, allergic rhinitis etc [9].

Some studies have shown that there is an association between severity of allergic rhinitis and serum level of 25 OH vitamin D and C-Reactive Protein, but no consensus has been yet achieved [9,10]. Therefore, we conducted the present study was to compare the vitamin D3 status and C-reactive protein (CRP) among allergic rhinitis patients who were on treatment with either intranasal Fluticasone or oral Levocetrizine and Montelukast therapy.

Aim and Objectives

The aim of the current study was to compare the vitamin D3 status and C-reactive protein (CRP) among allergic rhinitis patients who were on treatment with either intranasal Fluticasone or oral Levocetrizine and Montelukast therapy.

Study Design

The study was a prospective randomized, single blinded, comparative, parallel group study, with two intervention groups.

Study Site

This study was conducted in a Civil Hospital Jogindernagar of Himachal Pradesh, India. 

Study Period

The study was conducted from February 2020 to October 2020.

Study Population

Patients diagnosed with Allergic Rhinitis randomly allocated to the following intervention groups.

• Montelukast tablets 10mg and Levocetrizine Tablet 10mg in the night time

• Fluticasone propionate aqueous nasal spray, 200μg one spray in each nostril twice daily

Inclusion and Exclusion Criteria

Participants of both genders, aged between 15 –45 years were included in the study. Smokers, pregnant women, people with life threatening/chronic persistent severe asthma, chronic respiratory illnesses like bronchiectasis, pulmonary tuberculosis and other obstructive airway disease were excluded from the study. The other exclusion criteria included, recent nasal surgery or anatomic defects of the nose, recent two courses of parenteral steroids within 3 months of screening and presence of any co-morbid systemic illness which may affect the assessment directly or indirectly.

Sample Size

A total of 50 participants were randomly allocated to both the intervention groups, with 25 subjects in each group.

Random Sequence Generation

The participants were randomly allocated to one of the two intervention groups by pre-determined computer-generated random number sequence

Allocation Concealment

Sequentially Numbered, Opaque Sealed Envelopes (SNOSE) method has been used for allocation concealment in the study. The allocated intervention sequence was kept in individual, serially numbered sealed opaque covers and was kept under the custody of an independent statistician. The card board with the intervention name was covered with a silver foil to prevent the visibility. Each time when the participant was recruited the opaque cover was opened and the intervention was communicated to the investigator.

Blinding

The study participant blinding could not be achieved, as the route of administration of two interventions were different. The investigator assessing the treatment outcome and the person analysing the data were blinded for the intervention.

Ethical Considerations

Informed written consent was sought from all the patients, after thoroughly explaining the study objectives, nature of the intervention, risks and benefits of the intervention to the participants. Complete voluntary nature of participation in the study was explained and no undue pressure or coercion was exerted on the patients. Patients were informed that, they are free to withdraw from the study at any point during the course of the trial. Confidentiality of the study participants was maintained throughout the conduction, analysis and reporting of the study findings.

Study Procedure

After obtaining an informed consent, 50 patients who met the eligibility criteria were randomly assigned in to one of the two intervention groups. 25 patients of Group A received Fluticasone propionate aqueous nasal spray, 200μg 1 spray in each nostril twice daily. 25 patients of Group B received Montelukast tablets 10mg and Levocetrizine Tablet 10mg in the night time. All patients were followed up for 6 weeks. At the end of the 6 weeks the recovery status and mean CRP and Vitamin D3 Levels was assessed and the assessments was subject to statistical analysis.

Statistical Analysis

The data was collected and entered in Microsoft Excel Spreadsheet. Statistical analysis was done using statistical software Epi Info v7.2.2. Mean CRP and Vitamin D3 Levels after 6 weeks was taken as primary outcome variables. The two intervention groups were taken as primary explanatory variable. Descriptive analysis of all the explanatory and outcome parameters was done. All the categorical variables were presented in frequencies and percentages. The numerical variables were presented in Means and Standard deviations. The Socio demographic variables like age and gender, baseline clinical variables like symptoms were compared between the two intervention groups, by appropriate cross tabulations. The association between explanatory and outcome parameters was assessed by calculating mean differences and differences in the proportions. Independent sample t-test and chi-square test (Fisher’s-exact test) were used appropriately to assess the statistical significance of these associations and 95% Confidence intervals were also calculated for all the parameters. There was no loss to follow up in both groups. 

In the present study was conducted in Civil Hospital, Joginder nagar, Himachal Pradesh. Among Group A, maximum patients 11(44%) were in age group of 31-40 years while in Group B maximum patients were in age group of 21-30 years (p value 0.004). Among both groups maximum patients were females i.e. in Group A, 14(56%) patients were in female while in Group B 17(68%) patients were females (p value 0.561) (Table 1).

Table 1: Socio-demiographic Variables of Study Participants

Among Group A, Recovery at 6 weeks was occurred in 9 (36%) patients while in Group B Recovery at 6 weeks was occurred in 17(68%) patients (p value 0.046). So, there was statistically significant recovery at 6 weeks occurred in group who were given intranasal fluticasone (Table 2).

Table 2: Recovery Status Among Study Participants

Among Group A, mean CRP level among patients was 11.64±2.158 while in Group B mean CRP level among patients was 9.24 ±3.218 (p value 0.003). So, there was statistically significant lower mean CRP level was found in group who were given intranasal fluticasone. Among Group A, mean Vitamin D3 level among patients was 27.80±4.463 while in Group B mean Vitamin D3 level among patients was 26.80 ±4.463 (p value 0.218). Although, lower mean Vitamin D3 level was found in group who were given intranasal fluticasone but this difference was not found to be statistically significant (Table 3).

Table 3: Mean CRP and Vitamin D3 Level Among Study Participants According to Groups

Among Group A, mean CRP level in recovered patients was 10.89 ±3.018 while in non-recovered patients mean CRP level was 12.06 ±1.436 (p value 0.198). Although, lower mean CRP level was found in recovered patients in group who were given oral levocetrizine and Montelukast but this difference was not found to be statistically significant. Similarly in Group A, mean Vitamin D3 level among recovered patients was 29.00±5.809 while in no recovered patients mean Vitamin D3 level was 27.13 ±3.538 (p value 0.324). Although, higher mean Vitamin D3 level was found in recovered patients in group who were given oral levocetrizine and Montelukast but this difference was not found to be statistically significant (Table 4).

Table 4: Mean CRP and Vitamin D3 Level among Recovered and Non-Recovered Patients

Among Group B, mean CRP level in recovered patients was 9.35 ±3.141 while in non-recovered patients mean CRP level was 9.00 ±3.586 (p value 0.804). Although, higher mean CRP level was found in recovered patients in group who were given nasal fluticasone but this difference was not found to be statistically significant. Similarly, Among Group B, mean Vitamin D3 level among recovered patients was 26.76 ±4.176 while in non-recovered patients mean Vitamin D3 level was 25.38 ±3.292 (p value 0.418). Although, higher mean Vitamin D3 level was found in recovered patients in group who were given nasal fluticasone but this difference was not found to be statistically significant (Table 4).

Similarly, when we compared both groups according to recovery status, then in recovered patients there was no statistically significant difference in mean CRP and Vitamin D3 level (P value 0.9536 and 0.2486 respectively) in both groups, although the mean CRP and Vitamin D3 level were higher in Group A as compared to group B. But in non-recovered patients, the mean CRP level was statistically higher in Group A as compared to group B (p-value 0.0029) while there was no statistically significant difference in Vitamin D3 level in both groups (p-value 0.8919) (Table 5).

Table 5: Mean CRP and Vitamin D3 Level According to Recovery Status

In the present study, among Group A, Recovery at 6 weeks was occurred in 9(36%) patients while in Group B Recovery at 6 weeks was occurred in 17(68%) patients (p value 0.046). So, there was statistically significant recovery at 6 weeks occurred in group who were given intranasal fluticasone. In corcordence to our findings, in the study done by Apar Jindal et al [11] and Bruce G Martin et al [12] improvement in rhinitis symptom was higher for patients who received Fluticasone propionate aqueous nasal spray as compared to patients who received oral Montelukast.

In the present study, although, lower mean Vitamin D3 level was found in group who were given intranasal fluticasone but this difference was not found to be statistically significant (p value 0.218). Although, lower mean CRP and higher mean Vitamin D3 level was found in recovered patients in group who were given oral levocetrizine and Montelukast as compared to who were not recovered but this difference was not found to be statistically significant (p-value 0.198 and 0.324 respectively). Similarly, higher mean CRP and Vitamin D3 level was found in recovered patients in group who were given nasal fluticasone as compared to who were not recovered but this difference was not found to be statistically significant (p-value 0.804 and p-value 0.418). Similarly, in recovered patients there was no statistically significant difference in mean CRP and Vitamin D3 level (p-value 0.9536 and 0.2486 respectively) in both groups, although the mean CRP and Vitamin D3 level were higher in Group A as compared to group B. But in non-recovered patients, the mean CRP level was statistically higher in Group A as compared to group B (p-value 0.0029) while there was no statistically significant difference in Vitamin D3 level in both groups (p-value 0.8919). Contrary to our findings, in the study done by Venus Vatankhah et al [10] there is a relationship between serum level of vitamin D and suffering from allergic rhinitis. Another study by Abdulbari Bener et al [13] also revealed a high prevalence of Vitamin D deficiency in children with asthma and allergic diseases. 

Similar to our finding, among Allergic rhinitis, CRS with nasal polyps and CRS without nasal polyp groups compared with the control group were statistically not had significant differences in the hs-CRP levels with peripheral blood in the study done by Yavuz Selim Yıldırım et al [14].

Study concluded that although there was statistically significant recovery at 6 weeks occurred in patients who were given intranasal fluticasone spray as compared to patients who were given oral Montelukast and Levocetrizine tablets but there was no statistically significant difference in mean Vitamin D3 and CRP levels in both groups as well as there was no significant association between Vitamin D3 and CRP levels and recovery status of patients in both groups.

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