Abstract
Allergic rhinitis (AR) is one of the most common types of allergy worldwide. It has significant negative impact on the quality of life (QOL). One of the available causal treatments of AR is allergen specific immunotherapy which remains effective even after the end of treatment course, unlike symptomatic drugs. AR patients aged above five years, allergic to unavoidable allergen like house dust, mite etc., and refractory to maximal pharmacotherapy were included in present study. Patients allergic to avoidable allergen, taking beta-blocker medication, having other immunological disease, and who were pregnant, breast-feeding or lost to follow up, were excluded from the study. All patients included in the study underwent sublingual immunotherapy (SLIT). The impact of treatment is measured by calculating the difference between SNOT-20 score before and after treatment (which is 6 months interval). Total 30 patients were studied. Paired-t test calculated value of cumulative score and nasal symptom score are 7.853 and 6.85 respectively. Both are greater than table value of 2.46. So paired-t test shows that SLIT is very much effective in treatment of AR. The present study re-establish the fact that SLIT not only reduces AR symptoms, it also improves the QOL. It has very good patient compliance with minimal side effects.
Keywords: Allergic rhinitis, Quality of life, Sublingual immunotherapy, Sino-Nasal Outcome Test
Introduction
Allergic rhinitis (AR) is one of the most common types of allergy worldwide [1]. American Academy of Otolaryngology Head and Neck Surgery foundation described AR as an inflammatory disease of the nasal mucosa induced by an IgE-mediated reaction, following exposure to an allergen to which the affected patient is sensitized. It is characterized by nasal congestion, rhinorrhoea, sneezing, and/or nasal itching [2]. Prevalence of AR has increased during recent times ranging from 1.4 to 45% [1]. It has significant negative impact on the quality of life (QOL) [3]. Diagnosis of AR is based on history, clinical examination and laboratory investigations including positive skin prick test and/or raised serum IgE specific antibody [2]. Treatment of AR can be classified into following categories: (1) allergen avoidance, (2) pharmacotherapy, and (3) immunotherapy [1, 2, 4]. Allergen avoidance is the safest way, but not always feasible [1, 2, 4]. Pharmacotherapy only reduces allergic symptoms rather than reversing basic immunologic mechanism of AR [1, 2, 4]. One of the available causal treatments of AR is allergen specific immunotherapy which remains effective even after the end of treatment course, unlike symptomatic drugs. Allergen specific immunotherapy modifies the basic immunologic mechanism of the disease by inducing desensitization through gradually increasing the dose of specific allergen over an optimum period of time [1, 4, 5]. Subcutaneous immunotherapy (SCIT) has been the traditional form of allergen specific immunotherapy. Recently, the sublingual immunotherapy (SLIT) has gained considerable interest as an alternative [6]. The aim of the present study is to evaluate the clinical efficacy of SLIT in allergic rhinitis using 20 items Sino-Nasal Outcome Test (SNOT-20) score.
Materials and Methods
A Prospective observational study was done in a Healthcare facility in Kolkata from 1st December 2018 to 30th November 2019. Institutional ethical committee clearance and informed consent from the participants were taken. First one month was utilised for preparatory phase, next ten months for data collection phase and last one month for statistical analysis. All patients of AR underwent skin prick test. AR patients aged above five years, allergic to unavoidable allergen like house dust, mite etc., and refractory to maximal pharmacotherapy were included in present study. Maximal pharmacotherapy is defined as extensive treatment using antibiotic, antihistaminic, mucolytic with oral and/or nasal steroid for a period of 6 weeks. Patients allergic to avoidable allergen, taking beta-blocker medication, having other immunological disease, and who were pregnant, breast-feeding or lost to follow up, were excluded from the study. Patients fulfilling these criterias, were selected by simple random sampling method using random number table. All patients included in the study were treated with sublingual immunotherapy (SLIT). In SLIT, vaccines were started at lower dose and gradually increased on a regular basis until a therapeutic dose was reached. Drops were administered by patient at home after receiving first dose at the clinic. SLIT was given biweekly for each allergen separately with gradually increasing dose. Drops were to be taken below the tongue and patients were advised to wait for few minutes and then swallow the drops. Food intake was prohibited one hour before and after taking SLIT. The impact of treatment is measured by calculating the difference between SNOT-20 score before and after treatment (which is 6 months interval). The possible range of SNOT-20 score for each symptom is 0–5, with a higher score indicating a greater allergic rhinitis related health burden. We also categorized SNOT-20 questionnaires into nasal symptom subset comprising of need to blow nose, sneezing, running nose, cough, post nasal discharge and thick nasal discharge to assess the effect of immunotherapy. Statistical analysis was done by paired-t test.
Results
Total 30 patients were studied. SNOT-20 score of all patients before and after SLIT are shown in Tables 1 and 2 respectively. Total scores of all symptoms are hereby directed as cumulative score and total score of nasal symptoms are stated as nasal symptoms score. In case of cumulative score paired-t test calculated value is 7.853 and in case of nasal symptom score paired-t test calculated value is 6.85. In 1% confidence (α = 0.01) level table value is 2.46. p < 0.01 was considered as statistically significant. Here in both the occasions in paired-t test, calculated value is greater than table value. In both the occasion H0 (null hypothesis) is rejected and H1 (alternate hypothesis) is accepted. So paired-t test shows that treatment by SLIT is effective. The efficacy of treatment by means of symptom evaluation was more than expected in the present study. All patients were highly satisfied without any noticeable adverse effect.
Table 1.
SNOT-20 score before sublingual immunotherapy
| Before immunotherapy snot score | Symptom | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient serial number | Need to blow nose | Sneezing | Running nose | Cough | Post nasal discharge | Thick nasal discharge | Ear fullness | Dizziness | Ear pain | Facial pain | Difficulty in falling asleep |
| 1 | 3 | 5 | 4 | 4 | 2 | 2 | 2 | 2 | 0 | 4 | 1 |
| 2 | 5 | 5 | 5 | 4 | 3 | 2 | 2 | 4 | 1 | 1 | 1 |
| 3 | 5 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 |
| 4 | 5 | 5 | 5 | 2 | 3 | 3 | 0 | 4 | 0 | 0 | 3 |
| 5 | 3 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| 6 | 4 | 4 | 4 | 3 | 2 | 2 | 1 | 0 | 0 | 0 | 2 |
| 7 | 5 | 5 | 3 | 1 | 1 | 4 | 5 | 4 | 4 | 5 | 2 |
| 8 | 2 | 3 | 1 | 1 | 0 | 0 | 3 | 0 | 4 | 4 | 1 |
| 9 | 5 | 5 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 10 | 0 | 1 | 0 | 0 | 2 | 3 | 2 | 1 | 0 | 2 | 3 |
| 11 | 2 | 3 | 4 | 4 | 3 | 3 | 0 | 0 | 0 | 2 | 2 |
| 12 | 3 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 0 | 0 | 0 |
| 13 | 5 | 2 | 2 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 14 | 3 | 3 | 4 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 1 |
| 15 | 0 | 5 | 2 | 0 | 0 | 0 | 3 | 2 | 4 | 0 | 0 |
| 16 | 0 | 2 | 3 | 4 | 2 | 2 | 0 | 0 | 0 | 0 | 0 |
| 17 | 3 | 5 | 4 | 5 | 4 | 4 | 4 | 3 | 4 | 0 | 4 |
| 18 | 0 | 5 | 0 | 3 | 1 | 1 | 0 | 2 | 0 | 0 | 0 |
| 19 | 3 | 5 | 3 | 1 | 3 | 3 | 0 | 0 | 0 | 0 | 5 |
| 20 | 5 | 4 | 4 | 1 | 3 | 1 | 3 | 1 | 0 | 0 | 3 |
| 21 | 1 | 5 | 3 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
| 22 | 1 | 2 | 0 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 23 | 2 | 5 | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| 24 | 5 | 5 | 5 | 3 | 4 | 4 | 3 | 0 | 0 | 0 | 4 |
| 25 | 0 | 0 | 5 | 3 | 0 | 0 | 3 | 0 | 3 | 0 | 3 |
| 26 | 4 | 4 | 4 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| 27 | 5 | 4 | 5 | 4 | 3 | 1 | 2 | 0 | 0 | 0 | 2 |
| 28 | 4 | 4 | 3 | 2 | 4 | 2 | 1 | 1 | 0 | 3 | 1 |
| 29 | 4 | 5 | 5 | 5 | 3 | 1 | 0 | 2 | 1 | 0 | 0 |
| 30 | 5 | 3 | 4 | 5 | 4 | 1 | 0 | 3 | 1 | 0 | 1 |
| Before immunotherapy snot score | Symptom | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient serial number | Wake up at night | Lack of good night's sleep | Wake up tired | Fatigue | Reduced productivity | Reduced concentration | Frustrated /Restless/Irritable | Sad | Embarrassed | Cumulative score | Nasal symptom score |
| 1 | 1 | 1 | 4 | 4 | 4 | 4 | 4 | 2 | 2 | 55 | 20 |
| 2 | 1 | 1 | 3 | 3 | 1 | 4 | 4 | 3 | 1 | 54 | 24 |
| 3 | 4 | 5 | 0 | 2 | 0 | 2 | 4 | 4 | 3 | 36 | 8 |
| 4 | 0 | 3 | 0 | 0 | 2 | 2 | 2 | 0 | 0 | 39 | 23 |
| 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 8 |
| 6 | 2 | 1 | 1 | 0 | 1 | 2 | 2 | 0 | 0 | 31 | 19 |
| 7 | 2 | 2 | 3 | 4 | 2 | 4 | 5 | 3 | 2 | 66 | 19 |
| 8 | 1 | 3 | 4 | 2 | 0 | 0 | 3 | 3 | 1 | 36 | 7 |
| 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15 | 15 |
| 10 | 2 | 3 | 0 | 3 | 2 | 3 | 1 | 2 | 3 | 33 | 6 |
| 11 | 0 | 2 | 1 | 1 | 1 | 1 | 4 | 2 | 3 | 38 | 19 |
| 12 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 3 |
| 13 | 4 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 20 | 13 |
| 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 15 | 14 |
| 15 | 0 | 0 | 3 | 0 | 2 | 1 | 3 | 1 | 3 | 29 | 7 |
| 16 | 0 | 0 | 0 | 1 | 1 | 2 | 2 | 0 | 1 | 20 | 13 |
| 17 | 2 | 1 | 4 | 3 | 4 | 4 | 5 | 5 | 4 | 72 | 25 |
| 18 | 0 | 0 | 3 | 2 | 1 | 4 | 4 | 0 | 1 | 27 | 10 |
| 19 | 5 | 2 | 3 | 2 | 3 | 3 | 3 | 3 | 3 | 50 | 18 |
| 20 | 3 | 3 | 3 | 0 | 0 | 3 | 3 | 0 | 3 | 43 | 18 |
| 21 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 2 | 0 | 19 | 11 |
| 22 | 0 | 0 | 0 | 0 | 0 | 3 | 3 | 0 | 0 | 14 | 8 |
| 23 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 12 |
| 24 | 2 | 4 | 4 | 3 | 4 | 5 | 5 | 3 | 5 | 68 | 26 |
| 25 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 17 | 8 |
| 26 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 16 | 16 |
| 27 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 30 | 22 |
| 28 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 0 | 31 | 19 |
| 29 | 1 | 2 | 0 | 2 | 1 | 1 | 2 | 2 | 1 | 38 | 23 |
| 30 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 33 | 22 |
Table 2.
SNOT-20 score after sublingual immunotherapy
| After immunotherapy snot score | Symptom | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient serial number | Need to blow nose | Sneezing | Running nose | Cough | Post nasal discharge | Thick nasal discharge | Ear fullness | Dizziness | Ear pain | Facial pain | Difficulty in falling asleep |
| 1 | 1 | 3 | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 3 | 1 |
| 2 | 3 | 4 | 3 | 2 | 1 | 1 | 0 | 2 | 0 | 0 | 0 |
| 3 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| 4 | 4 | 4 | 3 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 |
| 5 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 6 | 3 | 3 | 3 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 |
| 7 | 5 | 5 | 5 | 1 | 3 | 2 | 3 | 1 | 2 | 2 | 0 |
| 8 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 4 | 2 | 0 |
| 9 | 3 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 10 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 2 |
| 11 | 1 | 1 | 3 | 2 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| 12 | 4 | 0 | 1 | 0 | 4 | 3 | 3 | 0 | 1 | 0 | 1 |
| 13 | 5 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 14 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
| 15 | 0 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| 16 | 0 | 1 | 2 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| 17 | 5 | 5 | 4 | 4 | 2 | 3 | 0 | 0 | 0 | 0 | 2 |
| 18 | 1 | 3 | 1 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| 19 | 1 | 3 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 3 |
| 20 | 3 | 3 | 3 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 |
| 21 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 22 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 23 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 24 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 2 |
| 25 | 0 | 0 | 2 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| 26 | 2 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| 27 | 2 | 1 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 |
| 28 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| 29 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 30 | 2 | 2 | 2 | 1 | 2 | 0 | 0 | 1 | 1 | 0 | 1 |
| After immunotherapy snot score | Symptom | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient serial number | Wake up at night | Lack of good night's sleep | Wake up tired | Fatigue | Reduced productivity | Reduced concentration | Frustrated/Restless/Irritable | Sad | Embarrassed | Cumulative score | Nasal symptom score |
| 1 | 0 | 0 | 3 | 2 | 2 | 1 | 3 | 0 | 0 | 23 | 7 |
| 2 | 0 | 1 | 1 | 1 | 0 | 2 | 2 | 1 | 0 | 24 | 14 |
| 3 | 3 | 3 | 0 | 1 | 0 | 1 | 2 | 1 | 1 | 19 | 5 |
| 4 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 17 | 12 |
| 5 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
| 6 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 17 | 12 |
| 7 | 0 | 1 | 2 | 2 | 3 | 2 | 4 | 2 | 2 | 47 | 21 |
| 8 | 1 | 1 | 2 | 2 | 0 | 0 | 1 | 1 | 0 | 18 | 3 |
| 9 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 9 |
| 10 | 1 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 10 | 1 |
| 11 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 14 | 10 |
| 12 | 0 | 0 | 0 | 1 | 1 | 2 | 2 | 1 | 0 | 24 | 12 |
| 13 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 7 |
| 14 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| 15 | 0 | 1 | 3 | 0 | 0 | 0 | 3 | 2 | 0 | 16 | 5 |
| 16 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 10 | 7 |
| 17 | 4 | 3 | 4 | 5 | 5 | 5 | 4 | 5 | 4 | 64 | 23 |
| 18 | 0 | 0 | 1 | 0 | 0 | 2 | 4 | 0 | 0 | 16 | 8 |
| 19 | 2 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 17 | 7 |
| 20 | 1 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 19 | 12 |
| 21 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 |
| 22 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 |
| 23 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 3 |
| 24 | 1 | 0 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 13 | 6 |
| 25 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 3 |
| 26 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 5 |
| 27 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 9 | 7 |
| 28 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 7 | 5 |
| 29 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 3 |
| 30 | 1 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 16 | 9 |
Discussion
Nowadays AR is one of the major cause of poor QOL that includes abnormal sleep, impairment of daily activities, sport, leisure, abnormal work and school, and troublesome symptoms [3]. Pharmacotherapy may give good result, but the improvement does not last long enough after the medicine is withdrawn. Nevertheless, a substantial proportion of patients report inadequate relief of symptoms despite treatment with maximal pharmacotherapy [1, 2, 4]. It is reasonable to offer allergen specific immunotherapy to those patients. It involves repeated administration of allergen extracts to induce a state of immunological tolerance with the aim of reducing symptoms on subsequent allergen exposure, thereby improving QOL [1, 4, 5]. Allergen specific immunotherapy has been studied and used since Noon’s first report in 1911 [7]. It shifts the immune response from Th2 to Th1 through stimulation of the T-regulatory cell, which secretes interleukin (IL) and transforming growth factor (TGF)-β [8]. These T-regulatory cells with its mediators help to shift the immune response from the IgE to IgG. The IgG antibody especially IgG4 is considered as a blocking antibody which is known to interrupt the inflammatory cascade and stop the inflammatory mechanism initiated by the IgE release [9]. Traditionally, allergen specific immunotherapy has been administered as subcutaneous injections. But it requires specialized centres and resources for its delivery. In an attempt to eliminate these difficulties, alternative routes for the delivery of allergen specific immunotherapy, ideally with equivalent efficacy and a better safety profile, have been sought. Over the last three decades, much attention has been focused on the sublingual route [6]. The first randomized controlled trial worked on SLIT dates back to 1986 [10]. In addition to induction of immunological changes similar to SCIT, local mechanisms in the oral mucosa and/or regional lymph nodes are also important in SLIT [11]. Since the original systematic review in 2003, SLIT has become established as an effective and low‐risk alternative to SCIT [12]. The first dose of SLIT is recommended to be taken under medical supervision in healthcare facility, whereas maintenance treatment is recommended to be self‐administered in the patient’s home. SLIT offers multiple benefits over SCIT including the comfort of avoiding injections, the convenience of home administration, and a favourable safety profile [13]. In 2008, British Society for Allergy and Clinical Immunology (BSACI) announced SLIT as safe immunotherapy for AR and asthma [3]. In 2010, SLIT was included in the latest update of Allergic Rhinitis and its Impact on Asthma (ARIA) guideline for both adults and children [14]. Many researchers report efficacy of SLIT based on objective parameters. But clinical outcome of SLIT can be better assessed from subjective point of view than objective methods. Zhang et al. showed improvement of SNOT-20 scores by 31% from baseline within 3 months of initiation of therapy, and continued to improve progressively during the maintenance phase up to 69%. Greatest improvement was in ear/facial symptoms (up to 86%) and psychological function (up to 77%) followed by rhinologic and sleep function scores (up to 56% and 61% respectively) [15]. Ashkanani et al. showed statistically significant (p value < 0.05) drop in the total score of symptoms from pre-treatment to post-treatment [16]. In the present study the efficacy of treatment by means of SNOT-20 score evaluation was very high.
Conclusion
AR reduces QOL significantly. Allergen specific immunotherapy is the only available treatment modality which reverses the pathology of AR. SLIT not only reduces AR symptoms, it also improves the QOL. The results of the present study re-establish the fact. It has very good patient compliance with minimal side effects.
Footnotes
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References
- 1.Corren J, Baroody F, Pawankar R, et al. Allergic and non allergic rhinitis. In: Adkinson NF Jr, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF Jr, et al., editors. Middleton's allergy: principles and practice. 8. USA: Elsevier Health Sciences; 2014. pp. 664–685. [Google Scholar]
- 2.Ciprandi G, De Amici M, Negrini S, Marseglia G, Tosca MA. TGF-β and IL-17 serum levels and specific immunotherapy. IntImmunopharmacol. 2009;9(10):1247–1249. doi: 10.1016/j.intimp.2009.07.004. [DOI] [PubMed] [Google Scholar]
- 3.Scadding GK, Durham SR, Mirakian R, et al. BSACI guidelines for the management of allergic and non-allergic rhinitis. ClinExpAllerg. 2008;38:19–42. doi: 10.1111/j.1365-2222.2007.02888.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of immunotherapy. J AllergClinImmunol. 2004;113(6):1025–1034. doi: 10.1016/j.jaci.2004.03.024. [DOI] [PubMed] [Google Scholar]
- 5.Ziegler SF, Buckner JH. FOXP3 and the regulation of Treg/Th17 differentiation. Microbes Infect. 2009;11(5):594–598. doi: 10.1016/j.micinf.2009.04.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Radulovic S, Calderon MA, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2010;12:CD02893. doi: 10.1002/14651858.CD002893.pub2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;1:1572–1573. doi: 10.1016/S0140-6736(00)78276-6. [DOI] [Google Scholar]
- 8.Kawauchi H, Goda K, Tongu M, Yamada T, Aoi N, Morikura I, et al. Short review on sublingual immunotherapy for patients with allergic rhinitis: from bench to bedside. AdvOtorhinolaryngol. 2011;72:103–106. doi: 10.1159/000324631. [DOI] [PubMed] [Google Scholar]
- 9.Bahceciler NN, Arikan C, Taylor A, Akdis M, Blaser K, Barlan IB, et al. Impact of sublingual immunotherapy on specific antibody levels in asthmatic children allergic to house dust mites. Int Arch AllergImmunol. 2005;136(3):287–294. doi: 10.1159/000083956. [DOI] [PubMed] [Google Scholar]
- 10.Scadding GK, Brostoff J. Low dose sublingual therapy in patients with allergic rhinitis due to house dust mite. ClinAllerg. 1986;16(5):483–491. doi: 10.1111/j.1365-2222.1986.tb01983.x. [DOI] [PubMed] [Google Scholar]
- 11.Canonica GW, Cox L, Pawankar R, et al. Sublingual immunotherapy: world allergy organization position paper 2013 update. World Allerg Organ J. 2014;7:1–52. doi: 10.1186/1939-4551-7-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Wilson DR, Torres LI, Durham SR. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev. 2003 doi: 10.1002/14651858. [DOI] [PubMed] [Google Scholar]
- 13.Incorvaia C, Di Rienzo A, Celani C, Makri E, Frati F. Treating allergic rhinitis by sublingual immunotherapy: a review. Ann Ist Super Sanita. 2012;48(2):172–176. doi: 10.4415/ANN_12_02_10. [DOI] [PubMed] [Google Scholar]
- 14.Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, et al. Allergic rhinitis and its impact on Asthma (ARIA) guidelines: 2010 revision. J AllergClinImmunol. 2010;126(3):466–476. doi: 10.1016/j.jaci.2010.06.047. [DOI] [PubMed] [Google Scholar]
- 15.Zhang EZ, Fook-Chong SMC, Leong J-L. Sublingual Immunotherapy for Allergic Rhinitis. Otolaryngol Head Neck Surg. 2012;147(2 Suppl):P256–P256. doi: 10.1177/0194599812451426a417. [DOI] [Google Scholar]
- 16.Ashkanani F, Duhirat EENA, Tamimi ZARA, Hamdadui A, Haidar H. Quality of life improvement after sublingual immunotherapy for allergic rhinitis. J Otolaryngol ENT Res. 2017;9(2):00281. doi: 10.15406/joentr.2017.09.00281. [DOI] [Google Scholar]