Spaced Intranasal Corticosteroid Therapy: A Better Treatment Option in Allergic Rhinitis?

Abstract

Intranasal corticosteroids are first-line therapy in the treatment of allergic rhinitis (AR) and are conventionally prescribed once daily as continuous therapy. The decreased consumption of drugs is proposed to have decreased side effects. The present study aimed at comparing the effect of INCS as a spaced therapy with the conventional continuous therapy. Case records of patients with Allergic Rhinitis, who were started on INCS were studied and improvement in symptom score was compared between continuous and spaced therapy groups. In total 182 patients with AR were studied, with 91 patients in each group. Among the total group, 57% were males, 54% were < 40 years of age, 54% had > 10 years of allergy history and 94% had no family history. There was significant improvement in mean Visual Analogue Score (VAS) for all patients in both groups (p = 0.001). However, the comparison of differences in VAS before and after therapy did not show significant difference for the two groups (p = 0.791). Our study suggests that the efficacy of INCS in controlling AR symptoms is observed to be similar with spaced therapy, as in continuous therapy. Spaced therapy may therefore be recommended for better patient compliance, lesser cost and avoidance of the side effects resulting in overall improvement of quality of life for allergic patients.

Introduction

Allergic Rhinitis (AR) is an IgE-mediated inflammatory disease of the nasal mucosa, triggered by exposure to airborne allergens. The primary symptoms of rhinorrhea, nasal block, sneezing and ocular symptoms cause a significant impact on the quality of life of the individual. Although the standard treatment regime starts with avoidance of allergens, pharmacologic agents are used when symptoms persist. Oral antihistamines, intranasal corticosteroids (INCS), combination intranasal therapy of antihistamines and corticosteroids and allergen specific immunotherapy are effective in controlling the symptoms [1]. INCS are the first-line therapy for the treatment of AR [2]. INCS inhibits the early and late-phase allergies in AR by preventing the recruitment of immune cells, and the release of inflammatory mediators from cells involved in the pathophysiology of AR [1].

INCS are prescribed once daily conventionally. The local action of the corticosteroids at the nasal mucosa and its systemic absorption, as the cause of its side effects, have been reported in literature [2]. The decreased consumption of drugs is thought to have decreased side effects. The efficacy of the “as-needed” use of INCS in improving the symptoms of patients is demonstrated in previous studies [3–5]. Clinicians have different modes of therapy to achieve control of clinical symptoms. The present study proposed aims to compare the effect of INCS as a spaced therapy with the conventional daily continuous therapy.

Materials and Methods

This retrospective study was conducted in the Department of Otorhinolaryngology, Believers Church Medical College Hospital, Tiruvalla, Kerala, India. The ethics committee approval has been obtained from the institutional ethical committee. Data on patients who visited our outpatient department with Allergic Rhinitis and who were started on INCS (Fluticasone propionate each puff delivering 50 mcg) were retrospectively obtained from the medical records department of the institution for the duration of the three years (January 2016–January 2019). Variables selected for the study were demographic (age, gender) as well as clinical data (duration and treatment history of allergy along with family history and mode of therapy). In addition to these variables obtained from the case records, Visual Analog Scores (VAS) at the beginning and after three months of therapy and side effects, if any, were also extracted and entered into the data sheet. Participants with complete information in hospital records as per the data sheet requirements of AR were included in the study and those with therapies other than intranasal corticosteroids were excluded.

Mode of therapy for AR:

Clinicians administered INCS either as conventional dose or spaced therapy.

• 1. In conventional method, once daily dosage was administered.

• 2. In spaced therapy, patients were started on once daily dosage for a month followed by, once in alternate days for another month, then once in 3 days for a month, and once in 4 days thereafter for long time or as decided by the treating doctor with consultation. If the patient developed an upper respiratory infection during the therapy, daily use of sprays was advised till acute symptoms subsided and then gradually continued with spaced therapy as before.

Patients were divided into two viz., spaced and continuous. The sample size of each group was 91 patients, with a total of 182 patients for spaced and continuous modes of therapy together. The psychometric response scale, the visual analogue score(VAS) was used to monitor the response to the therapy [6, 7]. The VAS is a 10-point scale, where patients were asked to give a score from 0 to 10, based on their individual symptoms of nasal block, rhinorrhea, itching, sneezing with scores of 0 indicating absolute absence of symptoms and 10 indicating the worst symptoms and discomfort possible. The average of these scores were then used for the data entry.

Statistical Analysis

The data obtained were entered into Microsoft Excel sheets and transferred into statistical software (Statistical Package for Social Sciences, Version- 18, Chicago, IL). Descriptive measures on age, gender, years of allergic history, family history and mode of therapy were calculated. Differences in VAS scores (before and after the therapy) were compared for the two groups (Spaced and Continuous) using independent t-test. Further, paired t-test was used to compare pre- and post-differences for spaced and continuous therapy. A p value of less than 0.05 was considered statistically significant.

Results

Totally information on 182 patients was retrieved from the database. 91 patients were on conventional therapy and remaining were on spaced therapy. Among the whole group of patients 103 (56.6%) were males and 79 (43.4%) were females, with a median age of 37 years (range 7–80 years).

88 patients (48.4%) had a family history of allergic rhinitis. 180 (98.9%) patients had taken other modalities of treatment prior to starting intranasal Fluticasone therapy. It was found that 105 (57.7%) patients had sought multiple treatment methods over the years. The previous treatment methods were the use of different tablets at the onset of symptoms by 73 (40.1%) patients, and 2 (1.1%) patients opted for ayurvedic treatment (Table 1).

Table 1.

VAS scores classified according to demographic and clinical variables

	N	Frequency (%)	Mean VAS score before treatment	Mean VAS score after treatment
Age group in years
< 40	98	53.8	27.05	5.30
40–59	52	28.6	33.58	7.15
>  = 60	32	17.6	30.72	6.31
Gender
Male	103	56.6	29.30	6.13
Female	79	43.4	29.90	5.85
No. of years of allergy
<  = 5 years	32	17.6	27.41	5.38
6–10 years	51	28	28.98	6.16
> 10 years	99	54.4	30.56	6.13
Family history
Yes	88	48.4	30.98	6.81
No	94	51.6	28.23	5.26

There was significant improvement in mean VAS Scores for all patients in both continuous and spaced therapy groups (p = 0.001). When the difference in VAS scores before and after therapy for the two groups (spaced and continuous therapy) was compared, there was no significant difference in the groups (p = 0.791, Table 2).

Table 2.

Comparison of pre- and post VAS Scores and improvement in VAS scores according to mode of therapy

Mode of therapy According to VAS Scores
	Frequency	Mean VAS score before treatment	Mean VAS score after treatment	t-value	p-value
Spaced	91	29.34	5.70	50.80	0.001
Continuous	91	29.78	6.31	56.96	0.001
*Difference in VAS scores
Spaced therapy	91	23.64	4.44	0.265	0.791*
Continuous therapy	91	23.47	3.93

*indicates the statistical difference of VAS scores between the two groups, expressed as ‘p value’

Discussion

The efficacy of intranasal corticosteroids in controlling symptoms of allergic rhinitis is well established [8]. Intranasal steroids work locally in the nose, are more effective than systemic steroids with its systemic absorption, and thus leading to lesser side effects. INCS are usually recommended at once daily dosage. The onset of action for INCS starts at time points ranging from 3 to 5 h to 60 h after the first dosage [8]. The sensory attributes of aftertaste, nose runout, throat rundown, and smell may be important factors in patient preference and adherence to therapy. The most common side effects of INCSs are a result of local irritation and include dryness, burning, stinging, blood-tinged secretions, epistaxis and rarely septal perforations [8]. Studies have evaluated atrophy of mucosa and squamous metaplasia on continuous use but without conclusive evidence. Effects of INCS on the hypothalamic pituitary axis have also been studied in the past. There have been reports studying effects of INCS on ocular pressure, glaucoma, lens opacity and posterior subcapsular cataract [8]. The benefits however outweigh the risk when used to treat AR. The compliance of the patient to treatment depends on the effects they feel, in terms of improvement in symptoms and other physical changes they experience, after the medications. The awareness of taking steroids and the fear of dependence on the medication often scares the patient and they decide to quit the medicine on their own.

Our patients were mostly males with a negative family history, who had more than ten years of allergy and most of them have already tried some other modality of therapy to achieve symptom control. There was clinical improvement with both spaced and continuous therapy with INCS, without a statistically significant difference. This can be attributed to the efficacy of the drug, which is achieved equally in spaced and continuous therapies.

The results of our study clearly demonstrate that VAS score differences (before and after therapy) were not significantly different for the spaced therapy from continuous mode of therapy. From our results it may be concluded that the spaced therapy is as effective as the conventional mode of therapy in the treatment of AR. With the achievement of similar control of clinical symptoms, spaced therapy may therefore be recommended for better patient compliance and avoidance of the side effects.

In every allergic reaction, there is an early response with the allergen exposure, within minutes where there is mast cell degranulation and histamine release causing sneezing, rhinorrhea and congestion [9] (Fig. 1). There is also a late response, hours later where there is a cellular influx mainly eosinophils and an increase in nasal reactivity to further antigen exposure, called priming, clinically causing congestion and is less dramatic. Intranasal corticosteroids are reported to have profound inhibitory effects to this late response [9]. Kazuba et al.studied the ‘as needed’ use of intranasal fluticasone, based on the belief that the allergic individuals who use medications as needed would treat themselves after sensing an early reaction [10]. An intranasal corticosteroid, taken after sensing the symptoms of an immediate response, is thought to block eosinophil infiltration and priming, as reported by Anderson and colleagues in their study [11]. They hypothesized that the ‘as needed’ use of intranasal corticosteroids would reduce allergic inflammation and provide symptom relief. Juniper et al.compared regular and ‘as -needed’ usage of aqueous Beclomethasone and found regular usage to be superior. In another study where the quality of life was assessed, the same authors did not find clinically significant degree of improvement for regular use compared to ‘as -needed’ use [3, 4]. Jen et al.studied the efficacy of ‘as-needed’ intranasal corticosteroid usage, and compared with ‘as-needed’ placebo. They studied the symptom diary, eosinophil count and eosinophilic cationic protein level in nasal lavage with both groups and found the quality of life and other parameters were significantly better in the ‘as needed’ use of INCS [5]. In our study, we postulate the symptom control with spaced usage of steroid. The cellular infiltration of the nasal mucosa and the reactivity of nasal tissue on repeated allergen exposure are thought to be better under check with the spaced usage of corticosteroids.

Fig. 1.

Endoscopic image of Allergic turbinate hypertrophy

Continuous use of intranasal corticosteroids is reported to offer many benefits, such as blockage of the early response and reductions of mast cell migration to the epithelium, IgE synthesis, and the number of dendritic cells in the nasal mucosa. Also, the regular use of corticosteroids could be responsible for increased efficacy by providing a quantitatively superior inhibition of eosinophil influx and the priming response related to the higher cumulative dose [10]. By offering spaced therapy as in our study group, we believe the same effects of INCS on the cellular level would be achieved while the unpleasant side effects of the drug could be avoided, thus improving the patient compliance to the medications.

There is an increasing prevalence of allergic diseases in Indian subcontinent and there is interplay of genetic and environmental factors, resulting in this condition. The air pollution, variations with respect to weather, pollens and fungal spores, insects such as cockroaches, parasitic infestations and other living conditions, across India and sparse meteorological data about environmental allergens makes characterisation of the disease difficult. Lack of standardised allergen tests and unreliable epidemiological data limits our understanding of the disease. Clinical management of the patients can be further compromised by knowledge gaps among practitioners, religious beliefs and myths among patients or parents, social stigma of a chronic ailment, and fear of inhalers being addicted to medications [12]. Published evidence from western literature is not directly applicable to Indian population. The improvement in quality of life by intranasal steroids, is established in Indian populations [13]. The spaced steroid therapy helps to give good symptom control with better patient compliance, lower cost and lesser apprehension about side effects of the drug, and thereby preventing the physiologic changes from the continuous therapy.

Our study has several limitations. This is single center study and the sample size is rather small and not randomized and study design is that of a retrospective design. The actual changes at cellular level on usage of INCS were not studied in the laboratory set up. The interplay of multiple factors in our geographical location limits our understanding of time of the allergic trigger. However our experience with the spaced mode of INCS was acceptable to patients and demonstrated similar efficacy to the conventional therapy. A larger group of patients with multiple clinicians in a multicenter set up could validate these results in future.

Conclusion

The efficacy of intranasal fluticasone therapy in controlling symptoms of allergic rhinitis is observed to be similar in spaced therapy, as in continuous therapy. With the achievement of similar control of clinical symptoms, spaced therapy may therefore be recommended for better patient compliance and avoidance of the side effects. It also helps in achieving lesser cost as well as overall improvement in quality of life of allergic patients.

Author contributions

All authors contributed to the study conception and design. Conceptualization: IT, TT; Methodology: IT, MA, KG; Formal analysis and investigation: GM, TT, MA, KVG;Writing—original draft preparation: TT; Writing—review and editing: IT, TT; Resources—IT, TT, MA, KVG; Supervision-IT.

Funding

None.

Declarations

Conflict of interest

The authors declare that they have no conflict of interest.