Abstract
Allergic rhinitis (AR) is a type I hypersensitivity reaction of the nasal mucosa, primarily mediated by IgE, with a complex etiology, determined by genetic and environmental interactions. Several mechanisms by which AR affect middle ear and cause conductive hearing loss have been well described. There is paucity of data regarding involvement of inner ear in AR patients leading to sensorineural hearing loss. However, endolymphatic sac and outer hair cells have been hypothesized to be the seat of immunoreactivity. To study the audiological profile in AR and effect of AR on inner ear functions. 100 cases of AR patients (55 males, 45 females, mean age group 21–30 years) and 100 controls (65 males, 35 females, mean age group 41–50 years) were enrolled in study. All underwent thorough clinical ear, nose and throat examination, diagnostic nasal endoscopy and otoendoscopy, followed by audiological assessment including pure tone audiometry, tympanometry and oto-acoustic emission test. Hearing results of both the groups were compared and analysed statistically. Thirty two patients among case group had sensorineural hearing loss, pronounced at 4000 and 8000 Hz frequencies. 18 patients showed conductive hearing loss in the form of type B or type C tympanogram. 32 patients of AR patients showed unusual oto-acoustic emission test. We found higher prevalence of high frequency sensorineural hearing loss in pure tone audiometry and abnormal OAEs in patients having upper airway allergy. The likely seat of damage appears to be the inner ear as evidenced by recordings of OAE in allergic patients.
Keywords: Allergic rhinitis, Sensorineural hearing loss, Oto acoustic emission, Outer hair cells, Endolymphatic sac, Duct
Introduction
Allergic Rhinitis is a hypersensitivity reaction (type 1) of the nasal mucosa, primarily mediated by immunoglobulin E (Ig E) that is regarded to have a complex etiology determined by genetic and environmental interactions. Approximate prevalence figures for allergic rhinitis vary widely from 0.8 to 39.7 percent and is on an increasing trend [1].
Aetiopathogenesis of allergic rhinitis is complex, involving cells, mediators, cytokines, chemokines, neuropeptides and adhesion molecules which cooperate in a complex manner to produce the specific symptoms of allergic rhinitis and non specific hyperactivity. This reaction is divided in four phases: sensitization to allergen; subsequent reaction to allergen–early phase; late phase reaction; systemic activation [2]. Genetic factors are certainly involved in the aetiology of allergic rhinitis. Having parents who are atopic may increase the risk of a child having an allergic disease by 3–6 times [3]. The best established risk factor for allergic rhinitis is family history of allergy especially allergic rhinitis [4]. Genes involved in atopy include loci on 5q, 11q, 12q [5]. Atopy is a key condition in the development of allergic diseases, particularly with the IgE-mediated mechanism. It is a disorder with strong familial tendency, usually starting in childhood or adolescence, when patients become sensitized and produce IgE antibodies in response to ordinary allergens [6, 7]. The complex mechanisms of inheritance, from genetic predisposition of atopy to atopic (allergic) diseases, are still incompletely understood (Figs. 1, 2, 3 and 4).
Fig. 1.
Occupation comparison between cases(group A + B) and controls(group C)
Fig. 2.
Personal habits comparison between cases(group A + B) and controls(group C)
Fig. 3.
Comparison of allergic rhinitis type between group A and B
Fig. 4.
Symptom comparison between group A and B
A hypothesized model has been developed to explain the pathogenesis of middle ear diseases like Eustachian tube dysfunction, Otitis media with effusion in patients of allergic rhinitis. Nasal inflammation because of allergens can lead to inflammatory swelling and obstruction of Eustachian tube, which in turn increases the negative pressure in middle ear and causes improper ventilation. Negative middle ear under pressure allows fluid influx from pharynx which results in insufflations or aspiration of nasopharyngeal secretions that contain bacteria, virus, and/or allergens. Sustained obstruction and dysfunction of the Eustachian tube, persistent effusion, and unresolved bacterial infections leads to chronic OME. This model has been extensively tested and proven by pure tone audiometry and tympanometric studies [8]. In addition to hearing loss, chronic OME may be associated with learning difficulties and delay in language development [9].
Allergic rhinitis may involve the inner ear. The scientific basis for this is poorly understood. The seat of immunoactivity in the inner ear seems to reside in the endolymphatic sac and in the endolymphatic duct. However, the inner ear has been found to demonstrate both cellular and humoral immunity. Immunoglobulins G, M and A and secretory components have all been found in the endolymphatic sac while plasma cells and macrophages have been found in the perisaccular connective tissue [10].
This study aimed to assess the audiological status of patients with allergic rhinitis seen in the out-patient section of the otolaryngology department of Rajindra Hospital, Government medical college, Patiala, India, compared with a control group. The study also focused on the effects of duration of allergic symptoms on hearing.
Material and Method
This study was an observational case–control analytical study to evaluate hearing status in patients of allergic rhinitis. The study was carried out in the department of ENT, Govt. medical college and Rajindra hospital, Patiala on 200 subjects attending out-patient clinics divided in three groups:
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I.
Group A—allergic rhinitis patients with disease duration < 2 years(n = 50).
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II.
Group B—allergic rhinitis patients with disease duration > 2 years(n = 50).
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III.
Group C—control subjects(n = 100).
Hundred prediagnosed allergic rhinitis patients were enrolled in study as case subjects. They were further divided into two groups(A and B). Group A had patients with disease duration less than 2 years and group B had patients with disease duration more than 2 years. The control group comprised of 100 subjects (group C), who were age and sex-matched to the study group. Control group subjects were selected from relatives and friends accompanying the study group patients; these control subjects had been exposed to a similar environment but were not suffering from allergic rhinitis.
Inclusion criteria included clinically diagnosed patients of allergic rhinitis of both sex of age group (10–40 years). Exclusion criteria included history of ear diseases, history of acoustic trauma (e.g. ototoxic medication, noise exposure), history of chronic metabolic diseases (e. g diabetes mellitus, hypertension, chronic kidney disease), patients with congenital or acquired immune-deficiency disease.
After selection of cases and controls, all the study participants were properly informed about the tests that he/she would undergo and a written informed consent was taken. These selected 200 subjects underwent a detailed clinical workup, including a complete ENT history and examination. This was followed by audiological testing, which included pure tone audiometry (PTA), Impedance audiometry, Otoacoustic emission (OAE). Audiological assessment was done in a sound proof room in out—patient clinic of ENT Department, Rajindra hospital, Patiala. Hearing thresholds were tested using a commercially available ALPS Advanced digital audiometer AD2100. Bone and air conduction thresholds were tested at frequencies between 250 and 8000 Hz, respectively. Hearing loss was defined as a hearing threshold more than 25 dB. Commercially available tympanometer AT235 INTERACOUSTICS was used for tympanometry. A 226 Hz probe tone was used for tympanometry, with pressure varying from + 200 to − 300daPa. Otoacoustic emissions were carried out using systems developed by MAICO DIAGNOSTICS ERO-SCAN Item No.8106838.
Hearing results of both the groups were compared and analysed statistically using Statistical Package for the Social Sciences version 22.0 software for Windows (SPSS Inc, Chicago, Illinois, USA). Descriptive statistics was done for all data and were reported in terms of mean, S.D and percentages. Statistical Significance was taken as p < 0.05.
The study protocol was approved by the Institutional Review Board for Ethical Clearance of Govt. Medical College and Rajindra Hospital and it was performed in accordance with the Code of Ethics of the World Medical Association according to the Declaration of Helsinki of 1975, as revised in 2000.
Results
Pure tone audiometry for both ears was compared between patients with allergic rhinitis (A + B) and control group (group C). In 500, 1000, 2000 Hz frequencies, the hearing threshold was ≥ 25 dB in 1%, 3% and 6% patients in cases group; while it was more than 25 dB in 2%, 3% and 3% of control population. p value at these three frequencies came out to be non significant (Table 1).
Table 1.
Pure tone audiometry comparison between group (A + B) and C
| Pure tone audiometry | Group (A + B) | Group C | Chi square | P value | Significance | |||
|---|---|---|---|---|---|---|---|---|
| No. | % | No. | % | |||||
| 250 | < 25 | 100 | 100 | 99 | 99.0 | 1.020 | 0.312 | NS |
| ≥ 25 | 0 | 0 | 1 | 1.0 | ||||
| 500 | < 25 | 99 | 99.0 | 98 | 98.0 | 1.586 | 0.512 | NS |
| ≥ 25 | 1 | 1.0 | 2 | 2.0 | ||||
| 1000 | < 25 | 97 | 97.0 | 97 | 97.0 | – | – | NS |
| ≥ 25 | 3 | 3.0 | 3 | 3.0 | ||||
| 2000 | < 25 | 94 | 94.0 | 97 | 97.0 | 3.271 | 0.071 | NS |
| ≥ 25 | 6 | 6.0 | 3 | 3.0 | ||||
| 4000 | < 25 | 88 | 88.0 | 98 | 98.0 | 61.440 | < 0.001 | HS |
| ≥ 25 | 12 | 12.0 | 2 | 2.0 | ||||
| 8000 | < 25 | 90 | 90.0 | 99 | 99.0 | 45.172 | < 0.001 | HS |
| ≥ 25 | 10 | 10.0 | 1 | 1.0 | ||||
But at 4000 and 8000 frequencies, the hearing threshold was ≥ 25 dB in 12% and 10% patients in case group, and only 2% and 1% population in control group respectively. p value for these frequencies were highly significant (Table 1).
When tympanometric studies were carried out between patients of group A and B, it was found that only 5 patients (10%) in group A had abnormal tympanogram. On the other hand, 13 patients (26%) in group B had abnormal tympanogram. This higher number of patients in group B who had abnormal tympanometric findings as compared to group A was statistically significant (Table 2).
Table 2.
Tympanometry comparison between group A and B
| Tympanogram | Group A | Group B | Chi square | P value | Significance | ||
|---|---|---|---|---|---|---|---|
| Number | percentage | Number | Percentage | ||||
| Normal (A) | 45 | 90.0 | 37 | 74.0 | 4.336 | 0.037 | S |
| Abnormal (B/C) | 5 | 10.0 | 13 | 26.0 | |||
Oto acoustic emission test was carried out between patients with Allergic Rhinitis (group A + B) and control group (group C). Oto acoustic emissions were found to be absent in significantly larger number of allergic rhinitis patients as compared to controls. p value calculated for this parameter was found to be highly significant (Table 3).
Table 3.
OTO-ACOUSTIC emission comparison between group (A + B) and C
| OAE | Group (A + B) | Group C | Chi Square | P value | Significance | |||
|---|---|---|---|---|---|---|---|---|
| Number | percentage | Number | Percentage | |||||
| Right | Present | 65 | 65.0 | 93 | 93.0 | 23.629 | < 0.001 | HS |
| Absent | 35 | 35.0 | 7 | 7.0 | ||||
| Left | Present | 65 | 65.0 | 93 | 93.0 | 23.629 | < 0.001 | HS |
| Absent | 35 | 35.0 | 7 | 7.0 | ||||
Discussion
Allergic rhinitis is one of the most common diagnosis made by otolaryngologists in rhinology clinics. It is the most common form of rhinitis, affecting approximately 20% of the world population. While allergic rhinitis itself is not life-threatening (unless accompanied by severe asthma or anaphylaxis), morbidity from the condition can be significant [11–13]. Allergic rhinitis is known to be associated with otitis media, eustachian tube dysfunction, hearing deficit, tinnitus, meniere’s disease, sinusitis, nasal polyps, allergic conjunctivitis and atopic dermatitis. It may also contribute to learning difficulties, sleep disorders, and fatigue [14–16]. However, less emphasis is given on the otological manifestations of the disease. So this study was conducted to determine the audiological profile of allergic rhinitis patients.
We observed an increase in pure tone hearing thresholds across different frequencies in allergic rhinitis patients as compared to age-matched controls. This increase was statistically insignificant at low frequencies, but at higher frequencies(4000 and 8000 Hz),it was found to be highly significant. This hearing loss was sensorineural in character. Definitive cause for sensorineural hearing loss in allergic rhinitis is not known. However, endolymphatic sac has been hypothesised to be the likely seat of immunoreactivity in inner ear. The endolymphatic sac has been shown to be capable of both processing antigen and producing its own local antibody response [17]. The resulting inflammatory mediators and accumulation of toxic metabolic products may interfere with hair cell function leading to sensorineural hearing loss.
Similar findings were given by Sekhon et al. [18], they observed that in allergic rhinitis patients with increase in serum IgE levels, pure tone thresholds were higher at 4000 and 8000 Hz. Singh et al. [19] also found statistically significant higher air conduction thresholds across all frequencies 0.250–16 kHz. Only one study with contradictory finding was by Karabulut et al. [20], where they concluded that patients with allergic rhinitis had better hearing at 8000 Hz. Due to varied results in different studies, it is difficult to determine the frequencies involved in hearing loss in patients of allergic rhinitis. Further research is required to identify the mechanism responsible for sensorineural hearing loss.
We found anomalous tympanogram(type B/C) in 5 patients of group A and 13 patients of group B (Table 2), which indicated middle ear dysfunction in these patients. A relationship among upper airway allergy, and poor ET function has long been known. An immune reaction caused by mediators of inflammation and cytokines and colony-stimulating factors released by mucosal mast cells and epithelial cells in the nose and nasopharynx produces an edema of the posterior nasopharynx, occluding the proximal portion of ET, thus debilitating the active muscle-assisted tubal opening. This process can lead to an increase in the middle ear pressure negativity with subsequent retraction or atelectasis of the tympanic membrane associated with its thickening, limited mobility and fluid in the middle ear, all of them ultimately leading to conductive hearing loss.
Adeyemo et al. [21] also found abnormal tympanogram (type B/C) patterns in significant proportions in cases as compared with the control group. Fasulna A J et al. [22] included 86 allergic rhinitis children (cases) and equal number of healthy controls(nonallergic) in their study and concluded that otitis media with effusion(OME) was more common in their cases (45%) than controls(9%). Mane et al. [23] studied total 104 patients i.e. 208 ears. Before starting medical treatment(anti-allergic treatment) tympanograms were obtained which showed impaired eustachian tube function in 144 ears (69.24%). After 4 weeks of medical treatment abnormal tympanogram count reduced to 84 ears (40.39%).
OAE was compared between patients with allergic rhinitis cases (group A + B) and control group (group C), unusual OAE was seen in 35% of patients in case group. Also, when compared between patients of group A (less than 2 years) and group B (more than 2 years), group A had 13 patients(26%) with aberrant OAE in comparison to group B which had 22 patients(44%) with abnormal OAE. These variations in OAE results clearly suggests dysfunctional outer hair cell in patients of allergic rhinitis. It has been proposed that the endolymphatic sac can process antigens and produce its own local antibody response; the resulting inflammatory mediators and toxic products may interfere with hair cell function leading to sensorineural hearing loss. In addition, the sac’s fenestrated blood vessels are vulnerable to the effects of vasoactive mediators such as histamine, when released due to allergic reactions elsewhere in the body. Also, higher prevalence of absent otoacoustic emission in group B patients as compared to group A patients reflects upon the possibility of higher incidence or higher intensity of hearing loss with greater duration of allergic symptoms. Additional research is required in this area to explore exact relation between duration of allergy and hearing deficit.
Singh et al. [19] also found abnormal TEOAE results in all 30 allergic rhinitis patients, and abnormal DPOAE results in 27(90 per cent). Dwarkanath et al. [24] also showed low DP-amplitude with poor signal noise ratio(SNR) in allergic rhinitis cases than controls. Sekhon et al. [18] also showed statistical significant difference in the signal noise ratio (SNR) in most frequencies among patients of allergic rhinitis when compared with controls indicating outer hair cell dysfunction in them. In one study done by Mustafa Atilla Nursoy et al. [25], no statistically significant difference was detected between the study group and control group in terms of their signal noise ratios in all frequencies of DPOAE.
Patients who showed absent otoacoustic emission comprised of not only the patients who had problem of hearing, but also those patients of allergic rhinitis who have not yet started experiencing difficulty in hearing (Table 4). This finding throws light on the potential use of OAE testing in detecting the minor or subclinical hair cell dysfunction even before hearing deficit is experienced by the patient. These cases with abnormal OAE recordings included not only the same patients who had given a positive history of hearing deficit and had shown higher pure tone thresholds on PTA but also 15 allergic patients who did not complain of hearing loss, thus giving us insight into the value of ‘early’ OAE testing in patients of allergic rhinitis even before hearing impairment becomes symptomatic.
Table 4.
Role of OAE in early detection of hearing loss in allergic rhinitis
| Hearing loss comp-laint | Prse-nt OAE | Abse-nt OAE | Chi Square | P value | Significance | |||
|---|---|---|---|---|---|---|---|---|
| Number | percentage | Number | Percentage | |||||
| Group A | Yes | 0 | 0.0 | 4 | 8.0 | 12.375 | < 0.001 | HS |
| No | 37 | 74.0 | 9 | 18.0 | ||||
| Group B | Yes | 0 | 0.0 | 16 | 32.0 | 29.947 | < 0.001 | HS |
| No | 28 | 56.0 | 6 | 12.0 | ||||
Conclusion
We were able to demonstrate higher prevalence of high frequency sensorineural hearing loss and peculiar variations of OAEs in patients having allergic rhinitis. These variations were detected even in patients who had no complaints of hearing loss. The likely seat of damage appears to be the outer hair cells in inner ear as evidenced by atypical findings of OAEs. However, definitive cause of involvement of inner ear in allergic rhinitis patients is still unknown and can be a potential area for research in future.
Funding
None.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interests.
Footnotes
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