Introduction
Nasal hyperreactivity (NHR) is defined as an increased sensitivity of the nasal mucosa to commonly encountered environmental stimuli. NHR is an important feature of allergic (AR) and non-allergic (NAR) rhinitis (1). A neurogenic origin is believed to be the culprit behind the development of NHR in AR and NAR patients (2).
Patients with AR usually experience provocation of their symptoms by several non-specific physical stimuli such as sudden change in temperature, smoking, or chemical pollutants (3). Cold dry air (CDA) is a physiologic, safe, and tolerable stimulus for the nasal mucosa that has been proven to be a good diagnostic tool in non-specific hyperreactivity (4). Braat et al. (5) demonstrated that CDA provocations were superior to nasal histamine provocations in distinguishing AR patients from healthy controls.
Resection of the vidian nerve has been used to reduce hypersecretion and hypersensitivity of the nasal mucosa in patients with intractable AR. A major disadvantage of this procedure are the risks of decreased lacrimation and numbness of the palate. Therefore, vidian neurectomy has been largely replaced with the less invasive endoscopic transnasal resection of the posterior nasal nerve (TRPN) which spares nerve supply to the lacrimal glands and palate (6). Mori et al. (7) reported that submucous inferior turbinate surgery improved nasal breathing as well as nasal symptoms induced by the allergic reaction in patients with AR. Ogawa et al. (8) combined submucous turbinectomy with posterior nasal neurectomy in patients with severe AR and achieved good results.
The peripheral branches of the posterior nasal nerves run within the tissues of the inferior turbinate close to the bony concha (Figure 1). Unintended surgical resection of these branches has been suggested as an explanation of improvement of allergic symptoms following inferior turbinate reduction (8). Based on this report, Kobayashi et al. (9) described the resection of posterior nasal nerves within the inferior turbinates and reported that the effects of the procedure were equivalent to those of conventional TRPN. However, surgical identification of these branches is surgically demanding and may be troublesome or incomplete.
In the presented study, we used radiofrequency coagulation for submucosal ablation of the peripheral branches of the posterior nasal nerves within the inferior turbinate without the need to identify them individually as described by Kobayashi (9). We then used the CDA provocation protocol described by van Gerven et al. (3) to evaluate the effect of the radiofrequency procedure on NHR in patients with intractable AR.
Methods
A sample of 24 patients was set based on sample size calculations assuming 80% power and 5% significance in acoustic rhinometry parameters changes before and after CDA provocation and considering a minimum average reduction of 15%. All patients were between 16 and 42 years of age and had at least two nasal complaints (nasal obstruction, rhinorrhea, or sneezing). All patients had positive skin prick tests, were nonsmokers, and suffered from troublesome intractable AR symptoms for more than five years.
All patients signed the informed consent forms after being informed about the procedure and the CDA provocation test. The consents and the research protocol were approved by the Committee of Medical Ethics of Alexandria University (approval no: 1119-2019, date: January 12, 2019) according to the Helsinki Declaration.
Exclusion criteria included sinonasal infections, severe septal deviation, nasal polyps, previous nasal surgeries, being lost to follow-up, as well as being pregnant or lactating. Local and systemic corticosteroids, antihistamines, or decongestants were stopped one week before every evaluation. Patients who could not stop medications before the tests were also excluded from the study.
Assessment of nasal symptoms by visual analog scale (VAS) and CDA provocation and acoustic rhinometry were performed at the time of the initial evaluation and 12 months after the radiofrequency procedure.
VAS Scale
All patients were requested to mark their nasal symptoms (nasal obstruction, rhinorrhea, and sneezing) on a VAS (0–10 cm) before and 15 minutes after CDA nasal provocation. The same examiner performed all the tests.
Acoustic Rhinometry
Nasal volumes (V1 and V2) and minimal cross-sectional areas (MCA1 and MCA2) were measured by acoustic rhinometry (RhinoScan SRE2000, Interacoustics, Assens, Denmark) in both nasal cavities. The method for performing acoustic rhinometry is well described elsewhere (10, 11).
Data for three rhinometric curves were collected for each nostril. Irregular tracings or discrepant measurements were discarded. Values considered for analysis were an average of three measurements taken from three technically acceptable curves. All measurements were performed three times and by the same operator.
• The following parameters were recorded:
• The volume of the segment located from 10 to 32 mm from the nostril corresponding to the nasal valve region (V1), and the volume of the segment located between 33 and 64 mm from the nostril, corresponding to the turbinate region (V2).
Minimal cross-sectional area between 0 and 2.3 cm (MCA1) and between 2.3 and 6.4 cm (MCA2).
CDA Provocation
Patients were acclimatized to room temperature (20 °C) for 15 minutes and were exposed to CDA for 15 minutes. The CDA protocol used is described in the study by van Gerven et al. (12). To avoid diurnal variation and intertest error, all provocations were performed in the morning by a single experienced examiner.
Surgical Procedure
All procedures were performed under general anesthesia using an Ellman radiofrequency generator (Surgitron EMC, frequency =3.8 MHz and power =140 watts) and a bipolar straight turbinate handpiece with two parallel 5 cm long needles. We used the COAG setting (partially rectified waves) which diffuses the heat more effectively to the sides. Power setting was 20 watts.
The needles were inserted submucosally in the posterior half of the inferior turbinate and deeply pushed along and close to the medial surface of the turbinate bone toward its posterior end or tail (Figure 2). The average application duration of the radio waves was 5 seconds. The application was stopped once visual blanching of the mucous membrane occurred to limit damage to the overlying mucosa. Typically, three parallel applications were done from superior to inferior. No packing was needed, and all patients were discharged on the same day. The safety profile of the device/procedure was excellent, and there were no safety concerns.
Statistical Analysis
Statistical analysis was performed using the GraphPad Prism software (GraphPad Software, Inc., San Diego, CA. USA). Volume is expressed in cubic centimeters and the results for each group are presented as an average ± standard deviation. The measurements before and after CDA nasal provocation were compared using a paired Student’s t-test and a chi-square test. Values of p<0.05 were considered significant.
Results
The study included 24 patients (11 male and 13 female) with a mean age of 33.5 years. The baseline demographics and characteristics of the patients are shown in Table 1. The procedure was performed smoothly in all patients and their 6-month postoperative follow-up periods were uneventful. None of the patients reported headache or other significant adverse events in the immediate postoperative period.
The patients had significant reductions in mean VAS scores for all nasal symptoms and for total score (Table 2). The mean total VAS score was reduced by 44.2% (percentage difference) and the drop was statistically significant (p=0.0082). CDA provocation increased the mean total VAS scores by 19.9% before surgery and only 10.5% after surgery (Table 3).
The results of acoustic rhinometry evaluation are presented in Tables 4 and 5. Acoustic rhinometric measurements showed an increase in all studied acoustic rhinometry parameters after the radiofrequency procedure, indicating a wider nasal airway. All acoustic rhinometry parameters decreased after CDA provocation. This drop (% difference) was significantly less after surgery. The preoperative total percentage difference after CDA provocation for MCA1, MCA2, and V1, V2 were 37.0%, 40.0%, and 24.7%, 28.0%, respectively. On the other hand, the postoperative total percentage difference after CDA provocation for the same parameters were 16.2%, 13.1%, and 12.7%, 11.7%, respectively (Figure 3). The differences between preoperative and postoperative values were statistically significant (X2=5.9, p=0.0292).
Discussion
Resection of posterior nasal nerves has been reported as an effective procedure to treat AR unresponsive to medical therapy. Since the procedure interrupts both of parasympathetic and afferent sensory nerve fibers, it is expected to decrease rhinorrhea, sneezing, as well as nasal reactivity to noxious stimuli.
Ikeda et al. (13) combined inferior turbinoplasty with TRPN and reported satisfactory results in patients with resistant AR and NAR with eosinophilia (NARES). They named the procedure functional inferior turbinosurgery. Likewise, Ogawa et al. (8) used a similar combination of inferior turbinoplasty and TRPN and reported satisfactory results in patients with perennial AR. Mori et al. (7) mentioned that surgically induced damage to peripheral posterior nasal nerve fiber during turbinoplasty might be a major factor in improving allergic symptoms after submucous turbinectomy. Kobayashi et al. (9) compared submucosal resection of peripheral branches of the posterior nasal nerve within the inferior turbinate with classical TRPN and did not find significant difference in the improvement in symptom scores between the two groups, although transection of the posterior nasal nerve near the sphenopalatine foramen denervates a wider area of the nasal mucosa also including part of the middle turbinate. This is most likely due to the dominant role of the inferior turbinate in normal nasal breathing and reactivity (14, 15).
Nevertheless, submucosal selective identification of all peripheral posterior nasal nerves branches within the inferior turbinate can be surgically demanding, and some branches may be frequently missed. In the presented study, we used the radiofrequency probe to coagulate the inferior turbinate tissue where the peripheral posterior nasal nerves branches normally pass submucosally close to the bony concha obviating the need for individual identification of the branches. Although TRPN denervates a wider area of the nasal mucosa, it is a more surgically demanding procedure that typically requires general anesthesia, and often the exposure and the coagulation of the sphenopalatine artery. Also, some of the branches arising through separate foramina may be missed. On the other hand, the radiofrequency ablation of the peripheral branches of the posterior nasal nerves within the inferior turbinates (RAPN) procedure is a short procedure that is technically easy, minimally invasive, and can be performed under local or general anesthesia. Furthermore, there is practically no risk of postoperative hemorrhage as may occur from the sphenopalatine artery during TRPN. RAPN delivers results comparable to TRPN and can also be combined with complete radiofrequency turbinoplasty if needed.
The results of our study demonstrated a significant and clinically noticeable reduction in symptom severity from the minimally invasive radiofrequency procedure. Patients’ VAS scores were significantly decreased at 12 months postoperatively. A more important observation is the reduction of the nasal mucosal response. Radiofrequency submucous coagulation of the inferior turbinate tissues has been frequently used to reduce the size of the turbinates in patients with AR and NAR. The procedure reduces the size of the turbinate, by scar formation, resulting in improvement of nasal breathing while preserving the mucociliary mechanism of the turbinate. It also decreases the number of nasal glands and vessels, and therefore has also been thought reduce rhinorrhea and congestion (9, 16, 17, 18, 19, 20). Ablation of the peripheral branches of posterior nasal nerves within the inferior turbinate, as described above, further reduces nasal reactivity and sneezing in these patients.
The limitations of this study include the lack of a control arm, and the 12-month follow-up period. While the study showed that RAPN effectively reduced nasal reactivity and improved nasal symptoms in patients with AR, further research is needed to establish its durability and long-term outcomes.
Conclusion
In this study, ablation of the peripheral branches of the posterior nasal nerve has proved to be a safe and efficient technique for reducing nasal reactivity and improving the symptoms of patients with AR unresponsive to medical therapy. The procedure is minimally invasive, easy to perform, and well tolerated by patients. Although this is a preliminary short-term study, the results of the study suggest that RAPN can be one of the treatment options for intractable AR. Further research is required to test the durability of the results.
Main Points
• Interruption of the autonomic supply to the nasal mucosa has been used to improve the symptoms in patients with allergic rhinitis.
• The peripheral branches of the posterior nasal nerve run within the inferior turbinate close to the bony concha.
• Ablation of these branches with radiofrequency energy effectively reduced nasal reactivity and improved the symptoms in the patients.
• The procedure is short, safe, minimally invasive, and much easier to perform than transection of the posterior nasal nerve at the sphenopalatine foramen (TRPN), with comparable results. RAPN can also be performed as an office procedure under local anesthesia.
Ethics Committee Approval: The consents and the research protocol were approved by the Committee of Medical Ethics of Alexandria University (approval no: 1119-2019, date: January 12, 2019) according to the Helsinki Declaration.
Informed Consent: All patients signed the informed consent forms after being informed about the procedure and the CDA provocation test.
Peer-review: Externally peer-reviewed.
Authorship Contributions
Surgical and Medical Practices: S.E., Concept: S.E., Design: S.E., Data Collection and/or Processing: Z.M., A.A.I., R.B., Analysis and/or Interpretation: S.E., A.A.I., Literature Search: Z.M., Writing: S.E., R.B.
Conflict of Interest: The authors have no conflicts of interest to declare.
Financial Disclosure: The authors declared that this study has received no financial support.