Abstract
Background: Allergic rhinitis (AR) is a symptomatic condition of the nose, caused by an IgE-mediated inflammation of the nasal membranes. Allergic rhinitis is further split into two categories, based on the duration of symptoms: intermittent (IAR) or persistent (PER) disease. Oral or topical antihistamines and topical nasal steroids are the most popular and efficient treatments for allergic rhinitis. Methods: The present prospective comparative study was done between December 2021 to November 2022, with 64 subjects of PER divided into groups A and B. Group A patients received Fluticasone propionate (50 mcg) combined with Azelastine (140 mcg) nasal spray, whereas Group B patients received standalone Fluticasone propionate (50 mcg) nasal spray. Results: In both groups, the difference in mean TSS between the beginning and end of the 4-week study period was statistically significant (p for both < 0.05). After 4 weeks of treatment, Group A had a TSS of 2.02 ± 0.83 and Group B was at 3.80 ± 1.49; the difference between them was statistically significant (p < 0.05). Conclusions: According to results obtained from the current study, while both fluticasone propionate with azelastine nasal spray and standalone fluticasone propionate nasal spray are widely used for control of symptoms in PER, the former offers better results with significant reduction of symptoms when compared to the latter.
Keywords: Allergic rhinitis, Fluticasone propionate, Azelastine
Introduction
The prevalence of allergic diseases including asthma, rhinitis, anaphylaxis, food ,drug or insect allergy, shows an increasing trend worldwide [1]. Allergic rhinitis is characterized by inflammatory changes in the nasal mucosa caused by exposure to inhaled allergens. It is a common disease, affecting between 0.8 and 39.7% of the world population [2]. True burden of AR in India is unknown, largely because the disease is trivialised and the symptoms are ignored, unless severe [3]. A study done on the subject reported a prevalence rate of 10.6% in the urban population of the national capital city [4].
Rhinitis is defined clinically as having two or more symptoms of anterior or posterior rhinorrhoea, sneezing, nasal blockage and/or itching of the nose during two or more consecutive days for more than one hour on most days [5]. Non-nasal symptoms include conjunctival symptoms and/or itching/irritation of throat. The symptoms of allergic rhinitis cause sleep disruption, exhaustion, depression, and impaired cognitive function, which degrades quality of life and productivity.
A symptom score is a subjective score providing a quantitative measure of an individual’s well-being, using a questionnaire. The Score for Allergic Rhinitis (SFAR) involves 8 components [6], and includes the following: (1) nasal symptoms in the past year, including sneezing, runny nose, and blocked nose; (2) nasal symptoms accompanied with itchy-watery eyes; (3) months of the year in which the nasal symptoms occur; (4) triggers of nasal symptoms, including pollens and house dust; (5) perceived allergic status; (6) previous medical diagnosis of allergy; (7) previous positive tests of allergy; and (8) familial history of allergy. An SFAR cutoff value of > = 7 was found to optimally discriminate between individuals with allergic rhinitis from those not having the same [6].
Current treatment modalities include avoidance of allergens and irritants, and pharmacological management. Medical management for AR includes antihistaminics, mast cell inhibitors along with oral and topical steroids, aimed at symptomatic relief. Ideal duration of such treatment is for as long as there is allergen exposure [7]. Corticosteroids act by reduction in antigen presenting cells (APCs) and inhibiting the migration of mast cells and bssophils to the nasal epithelium and subsequent release of their mediators. Fluticasone propionate is a topically active corticosteroid with low systemic bioavailability and high first pass metabolism, with established efficacy in seasonal and perennial AR. Azelastine nasal spray is an H1-receptor antagonist with mast-cell stabilizing and anti-inflammatory properties, reducing the concentration of leukotrienes, kinins and platelet activating factor [8].
The objective of this study is to clinically evaluate and compare the effectiveness of topical treatment with standalone fluticasone propionate nasal spray and fluticasone propionate with antihistaminic azelastine in patients with persistent allergic rhinitis (PER), in rural population of North India.
Methods
Patient Selection and Study Method
Study Design
This was a prospective study done over 12 months period, starting from 1st December, 2021 and 30th November, 2022. Patients presenting to the out patient department of the ENT and HNS at HIMS, Sitapur were chosen for the study.
All patients enrolled in the study were asked for a complete medical history and their clinical examination done. Patients were enrolled and randomised in either of the two groups, based on the day of presentation as- Group A (receiving Fluticasone propionate 50 mcg + Azelastine 140 mcg nasal spray) on Monday, Wednesday and Friday, whereas Group B (receiving standalone Fluticasone propionate 50 mcg nasal spray) on Tuesday, Thursday and Saturday. Pre and 4 week post treatment assessment were done on the basis of Symptoms evaluation scale, US health and human services FDA for AR, ranging from 0 to 3, given as below:
0 = absent symptoms (no sign/symptom evident).
1 = mild symptoms (sign/symptom present, but minimal awareness; easily tolerated).
2 = moderate symptoms (definite awareness of sign/symptom that is bothersome but tolerable).
3 = severe symptoms (sign/symptom that is hard to tolerate; causes interference with activities of daily living and/or sleeping).
The symptoms assessed were sneezing, nasal block, nasal discharge and nasal itching.
Inclusion Criteria
Patients > 18 years of age, having a persistent AR with a SFAR > = 7, were chosen for the study, with an informed consent.
Exclusion Criteria
Key exclusion criteria included a known allergy to the drug products or any of the inactive ingredients and any significant medical conditions that might interfere with the trial like asthma(using > 3doses of SABA per week),lower respiratory tract disease, emphysema, or chronic bronchitis.
Patients having AR symptoms on account of anatomical abnormalities like deviated nasal septum, nasal tumours or previously operated cases of Nose and PNS.
Statistical Analysis
All the data were calculated using XLSTAT 2018.
Chi Square Test.
Paired t Test.
Unpaired t Test.
Results
64 patients with persistent AR were enrolled in the study and were randomly and equally enrolled in the two groups A and B, which received fluticasone propionate (50 mcg) and azelastine (140 mcg) and standalone fluticasone propionate (50 mcg), respectively.
Of the 64 participants seen during the 1-year study, 42 (65.62%) were males and 22 (34.38%) were females. The mean SD age in group A was 31.16 years and group B was 31.67 years (range 14–75 years). There was no difference among the two group in age distribution. 31 (48.43%) patients were diagnosed with allergic rhinitis using a nasal smear eosinophil count. The most common symptom was excessive sneezing, involving 93% of patients with allergic rhinitis, followed by nasal obstruction (78%), nasal discharge (88%) and nasal itching (82%). The prevalence of allergic rhinitis using SFAR was 31.6%. The SFAR cut-off was set at 0.8 (P < 0.05).
The mean individual symptom score and mean total symptom score across the two groups were equivalent, indicating that all cases had symptoms of a similar severity. The differences in mean TSS before and after 4 weeks study period was statistically significant in both groups (p < 0.05 in both), indicating the effectiveness of both the nasal sprays in the treatment for AR.
The mean total symptom score and mean individual symptom score between two groups prior to study were comparable suggesting that all individuals had symptoms that were similar in severity when the trial began. The differences in mean TSS before and after 4 weeks study period was statistically significant in both groups (p < 0.01 in both). Hence, both fluticasone propionate with azelastine and standalone fluticasone propionate are individually effective in treatment of allergic rhinitis. Additionally, both medications were successful at lowering each person’s symptom score in both groups.
Group A had TSS of 2.02 ± 0.83 and group 2 had TSS of 3.80 ± 1.49 after 4 weeks of treatment and the difference between them was statistically significant (p < 0.05). The difference in reduction of nasal obstruction, nasal discharge and nasal itching was significant between 2 groups after treatment but the difference was insignificant with reduction of sneezing. Therefore, despite the fact that both medications are efficient at treating allergic rhinitis symptoms, group A’s treatment with fluticasone propionate and azelastine showed a significant improvement in symptoms.
It is imperative to mention that a significant number of patients (56%) in Group A complained of an aversion to the taste of the medication that posed problems in patient compliance to the treatment. The same was not reported amongst subjects of Group B, and hence the effect can be attributed to the addition of azelastine in the nasal sprays.
Patient distribution according to gender
| Gender | Group A | Group B | ||
|---|---|---|---|---|
| No. of patients | Percentage | No. of patients | Percentage | |
| Male | 26 | 72.23% | 11 | 30.56% |
| Female | 10 | 27.77% | 25 | 69.44% |
| Total | 36 | 100% | 36 | 100% |
Open in a new tab
The chi-square statistic is 12.5097. The p-value is 0.000405. Significant at p < 0.05
TSS (Total Symptom Score) for the 2 groups
| Group | Before Treatment (Out of 12) | 4 weeks Post Treatment (Out of 12) | P value (Paired t test) |
|---|---|---|---|
| Group A | 9.39 ± 1.21 | 2.02 ± 0.83 | 0.0328 |
| Group B | 9.17 ± 1.27 | 3.80 ± 1.49 | 0.0261 |
| P value (Unpaired t test) | 0.6682 | 0.0015 |
Open in a new tab
Individual symptoms scores for group A before and after treatment
| Symptoms | Before Treatment (Out of 3) | 4 weeks Post Treatment (Out of 3) | P value (Unpaired t test) |
|---|---|---|---|
| Sneezing | 2.78 ± 0.22 | 0.42 ± 0.20 | 0.0002 |
| Nasal Obstruction | 2.62 ± 0.65 | 0.46 ± 0.35 | 0.0071 |
| Nasal Discharge | 2.34 ± 0.30 | 0.30 ± 0.23 | 0.0007 |
| Nasal Itching | 2.03 ± 0.25 | 0.10 ± 0.08 | 0.0002 |
Open in a new tab
Individual symptoms scores for group B before and after treatment
| Symptoms | Before Treatment (Out of 3) | 4 weeks Post Treatment (Out of 3) | P value (Unpaired t test) |
|---|---|---|---|
| Sneezing | 2.73 ± 0.26 | 0.63 ± 0.46 | 0.0023 |
| Nasal Obstruction | 2.65 ± 0.54 | 0.82 ± 0.64 | 0.0193 |
| Nasal Discharge | 2.42 ± 0.38 | 1.07 ± 0.30 | 0.0085 |
| Nasal Itching | 2.11 ± 0.20 | 0.64 ± 0.25 | 0.0014 |
Open in a new tab
Comparison between After treatment for Group A and Group B
| Symptoms | Group A | Group B | P Value (Unpaired t test) |
|---|---|---|---|
| Sneezing | 0.42 ± 0.20 | 0.63 ± 0.46 | 0.5085 |
| Nasal Obstruction | 0.46 ± 0.35 | 0.82 ± 0.64 | 0.4408 |
| Nasal Discharge | 0.30 ± 0.23 | 1.07 ± 0.30 | 0.0243 |
| Nasal Itching | 0.10 ± 0.08 | 0.64 ± 0.25 | 0.0235 |
Open in a new tab
Discussion
Allergic rhinitis is a common and chronic IgE mediated respiratory illness that can affect quality of life and productivity, as well as exacerbate other conditions such as asthma. Treatment is usually directed according to the patient’s age and individual severity if symptoms. Patient education and knowledge of a possible allergen is of primal importance. The most common allergen faced in our OPDs was Parthenium spp.
The demographic differences in age and sex between the two groups wasn’t statistically significant and randomisation was achieved on the basis of the day of presentation of the patient.
Both the groups in this study reported significant reduction in individual symptom scores post treatment with their respective nasal sprays (p < 0.05). Dykewicz et al. in their study noted an improvement in AR symptoms on treatment with fluticasone nasal sprays [9]. Furthermore, the difference between the 4 week post treatment TSS between groups A and B, was also statistically significant, indicating that the addition of Azelastine in group A incurred additional benefits to the recipients. This is in accordance with the results obtained by Dhanush et al., which notes that Fluticasone with Azelastine sprays offer significant reduction of symptoms when compared with fluticasone propionate alone [10].
At the same time, 56% patients in the group A reported of a bad taste associated with the use of Azelastine sprays, which lead to decreased patient satisfaction and reduced compliance in subjects which were later excluded from the study. This is in accordance to effects reported by Horak et al. in their study [8]. The same maybe overcome upto a certain extent by patient education on the correct dosing technique [8].
Bhadouriya et al. concluded that topical azelastine affords rapid reduction in AR symptoms [11].
Conclusion
According to results obtained from the current study, while both fluticasone propionate with azelastine nasal spray and standalone fluticasone propionate nasal spray are widely used for control of symptoms in PER, the former offers better results with significant reduction of symptoms when compared to the latter. Although, standalone fluticasone spray showed better patient compliance than the fluticasone and azelastine sprays, partly owing to the bitter taste associated with the use of Azelastine in the latter.
Funding
None.
Declarations
Conflicts of Interest
None.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Pawankar R, Canonica GW, Holgate ST, Lockey RF. Allergic diseases as global public health issue.WAO white book on allergy 2011–2012: executive summary.
- 2.Strachan D, Sibbald B, Weiland S et al. Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC). Pediatr Allergy Immunol 1997; 8: 161–76. [DOI] [PubMed]
- 3.Chandrika D. Allergic rhinitis in India: an overview. Int J Otorhinolaryngol Head Neck Surg. 2017;3:1–6. doi: 10.18203/issn.2454-5929.ijohns20164801. [DOI] [Google Scholar]
- 4.Gaur SN, Gupta K, Rajpal S, Singh AB, Rohtagi A. Prevalence of bronchial asthma and allergic rhinitis among urban and rural adult population of Delhi. Indian J Allergy Asthma Immunol. 2006;20:90–97. [Google Scholar]
- 5.International rhinitis management working group. International Consensus Report on diagnosis and Management of Rhinitis. Allergy 1994; 49: S1–34. [PubMed]
- 6.Annesi-Maesano I, Didier A, Klossek M, Chanal I, Moreau D, Bousquet J. The score for allergic rhinitis (SFAR): a simple and valid assessment method in population studies. Allergy. 2002;57:107–114. [DOI] [PubMed]
- 7.Bousquet J, Khaltaev N, Cruz AA, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen) Allergy. 2008;63(Suppl 86):8–160. [DOI] [PubMed]
- 8.Horak F. Effectiveness of twice daily azelastine nasal spray in patients with seasonal allergic rhinitis. Ther Clin Risk Manag. 2008 Oct;4(5):1009-22. doi: 10.2147/tcrm.s3229. PMID: 19209282; PMCID: PMC2621402. [DOI] [PMC free article] [PubMed]
- 9.Dykewicz MS, Kaiser HB, Nathan RA, Goode- Sellers S, Cook CK, Witham LA et al. Fluticasone propionate aqueous nasal spray improves nasal symptoms of seasonal allergic rhinitis when used as needed (prn). Ann Allergy, Asthma Immunol. 2003;91(1):44 – 8. [DOI] [PubMed]
- 10.Dhanush HC, Malashetti S, Chandrashekharayya SH, Khavasi P. Comparative study of fluticasone propionate combined with azelastine versus fluticasone propionate alone as nasal spray in allergic rhinitis. Int J Otorhinolaryngol Head Neck Surg 2021;7:487 – 92.
- 11.Bhadouriya SKS, Srivastava M, Saxena R, Srivastava A. Comparative clinical evaluation of effect of topical verses systemic anti -allergic drug in allergic rhinitis: a prospective study. Int J Otorhinolaryngol Head Neck Surg. 2018;4:141-7.
