The Impact of Surgical Posterior Nasal Nerve Cryoablation on Symptoms and Disease-Specific Quality of Life in Patients With Chronic Rhinitis

Abstract

Objective:

Preliminary data have demonstrated long-term efficacy of posterior nasal nerve (PNN) cryoablation in reducing rhinitis symptoms for patients with allergic rhinitis (AR) and nonallergic rhinitis (NAR). We sought to evaluate the impact of procedural cryoablation of the PNN on quality of life (QOL) in patients with AR and NAR.

Methods:

Adult patients undergoing PNN cryoablation for AR or NAR after appropriate medical therapy were included for analysis. Demographics, medical therapies, baseline rhinitis symptom (total nasal symptom score [TNSS]), and disease-specific QOL (mini-rhinoconjunctivitis quality of life questionnaire [mini-RQLQ]) were recorded. The Wilcoxon signed-rank test was used to test for significant changes in baseline test scores posttreatment. Absolute and relative improvement in outcomes was determined for each participant. Secondary outcomes were assessed with univariate and multivariate analyses.

Results:

Fourteen patients were enrolled with a mean follow-up of 16.5 weeks. The TNSS and mini-RQLQ scores significantly improved after PNN cryoablation (median δs [interquartile range]: −4 [3] and −1.61 [1.08], respectively; both P = .0002). The minimal clinically important difference for the TNSS and mini-RQLQ was obtained in 92.9% of patients in each category. Relative mean percentage (%) improvement after PNN cryoablation in the TNSS and mini-RQLQ was 40.7% and 40.5% (standard deviation = 24.9 and 29.5, respectively), respectively, for all patients. Patients with NAR (n = 10) reported mean improvement of 41.3% (29.1) as measured by the TNSS and 49.6% (25.9) by mini-RQLQ. Patients with AR reported mean percentage improvement in TNSS and mini-RQLQ scores of 39.5% (12.1) and 24.6% (28.5), respectively. Patients who had been prescribed a nasal anticholinergic for management prior to PNN cryoablation had statistically significantly increased improvement in mini-RQLQ scores from pre- to post-procedure (P = .0387).

Conclusion:

Surgical cryoablation of the PNN significantly improves both symptoms and disease-specific QOL in majority of patients with AR and NAR.

Keywords

allergic rhinitis nonallergic rhinitis mixed rhinitis chronic rhinitis posterior nasal nerve cryoablation quality of life

Introduction

Chronic rhinitis affects over 80 million individuals in the United States, and through extrapolation of prevalence studies, approximately 450 million people worldwide.^1
-3 The magnitude of the population affected by this disease process results in a well-documented economic impact. Over 3 billion dollars (USD) of direct medical cost and over 11 billion dollars of treatment cost were attributed to allergic rhinitis (AR) alone in the early 2000s.⁴ This is further compounded by the loss of productivity, with nearly a quarter of all lost productivity in the United States could be attributed to this condition.⁵ For patients who have exhausted medical therapies, there have traditionally been limited surgical options. Therefore, definitive or lasting treatments for chronic rhinitis are a pressing topic of research given both the individual patient and societal implications.

Chronic rhinitis is traditionally divided into 3 categories: AR, nonallergic rhinitis (NAR), and mixed rhinitis. There is significant overlap in the presentations and symptomatology of these disease processes, creating a challenge in distinguishing the contributing etiologies to a patient’s symptoms.² A consensus definition of AR per the 2015 Clinical Practice Guidelines for allergic rhinitis is the following: “an immunoglobulin E (IgE)-mediated inflammatory response of the nasal mucous membranes after exposure to inhaled allergens.”^6(pS2) In contrast, NAR is characterized by symptoms that are not a result of IgE-mediated responses.³ Mixed rhinitis includes those patients with etiologies falling into both categories.

An accurate diagnosis portends a favorable regimen for patients with chronic rhinitis by providing a treatment that is targeted at the etiology of the disease. A number of topical therapies are available for use such as decongestants, steroids, anticholinergics, and antihistamines. However, compliance among patients with chronic rhinitis is poor; the literature has demonstrated that almost two-thirds of patients do not take their medications regularly, and up to one-third believe the medications to be ineffective.⁷ Historically, definitive surgical treatment has been vidian neurectomy, with the goal of eliminating the parasympathetic innervation to the nasal mucosa. This is an operative procedure requiring general anesthesia and may result in postoperative sequelae such as xerophthalmia.⁸

More recently, posterior nasal nerve (PNN) cryoablation has emerged as a low morbidity alternative to vidian neurectomy. It involves an in-office procedure that spares patients general anesthesia and the potential sequelae associated with transecting the vidian nerve. Contemporary sponsored studies have demonstrated improvements in the quality of life (QOL) of patients with chronic rhinitis undergoing PNN cryoablation.⁹ Although these data are promising, there remains a relative paucity of surgical outcomes for this novel therapy. Our objective was to evaluate the impact of PNN cryoablation on both the symptomatology and disease-specific QOL of patients with AR and NAR.

Patients and Methods

Institutional Review Board approval (ID# 1563028-2) was obtained for this retrospective study at the University of California Davis Medical Center. Sequential patients undergoing PNN cryoablation for AR, mixed rhinitis, or NAR between October 2018 and January 2020 were retrospectively analyzed in this single institution study. Patients who had persistent AR or NAR were considered candidates for the procedure and included in this study. Allergic rhinitis was determined by blood or skin prick testing with an IgE-mediated response. Patients who did not fill out the total nasal symptom score (TNSS) or the mini-rhinoconjunctivitis quality of life questionnaire (mini-RQLQ) or had follow-up less than 6 weeks were excluded. Patients undergoing simultaneously in-office procedures such as inferior turbinate reduction or balloon sinuplasty were excluded.

All patients underwent an in-office procedure with a single surgeon via cryoprobe application against the lateral nasal wall (Figure 1) with an anesthetic regimen as previously described by Steele et al.¹⁰ The inferior meatus was not treated in any of the analyzed patients. Demographics, comorbidities (chronic rhinosinusitis [CRS], primary headache disorder, temporomandibular joint (TMJ) dysfunction, facial pain syndrome, depression/anxiety, smoker), and prior medical therapies were recorded. Baseline and follow-up measures of disease-specific QOL, collected as part of the standard of care, were used for investigational purposes. Total nasal symptom score is a validated symptom severity scoring system that measures each of the following symptoms: nasal congestion, nasal itching, sneezing, and rhinorrhea. A 4-point scale is used (0-3) for each question, where 0 indicates no symptoms and 3 indicates intolerable symptoms that interfere with daily activity. Total nasal symptom score is calculated by adding the sum of each score for a maximum of 12. The RQLQ is a 14-question validated QOL measure of 5 rhinoconjunctivitis dimensions (activities, practical problems, nose symptoms, eye symptoms, and other symptoms) and uses a scale of 0 to 6 for each question. A score of 0 indicates “not troubled,” whereas a score of 6 indicates “extremely troubled.” The mini-RQLQ is scored by averaging each question for a maximum of 6. Total nasal symptom score and mini-RQLQ were collected on the day of surgery and at subsequent follow-up visits.

Figure 1.

In-office posterior nasal nerve cryoablation. The cryoprobe is held against the lateral nasal wall at the location where the posterior nasal nerve branches exit the pterygopalatine fossa.

The Wilcoxon signed-rank test was used to test for significant improvement from baseline for both tests. Absolute and relative improvement in outcomes was determined for each participant. Potential variation in baseline QOL status was considered further when evaluating postoperative improvements by calculating the mean percentages (%) of absolute relative improvement in QOL outcomes determined for each participant using the algorithm: ([mean preoperative score − mean postoperative score]/mean preoperative score) × 100.

Clinical significance for outcome measures was determined by the minimal clinically important difference (MCID) of 0.55 and 0.4 for the TNSS and mini-RQLQ, respectively.¹¹

Secondary outcome measures evaluated outcome variation based on the type of rhinitis (allergic vs mixed vs nonallergic), comorbidities, length of follow-up, gender, or age to the differences noted in the pre- and postintervention TNSS and mini-RQLQ scores. Atopy was confirmed with blood or skin testing. The Wilcoxon sum rank test or Kruskal-Wallis test was used for categorical variables. Spearman correlation was used for numerical variables. The variables that were significant at 0.1 level were included in a multiple linear regression model for both TNSS and mini-RQLQ outcome measures.

All statistical analyses were conducted using SAS software for Windows version 9.4 (SAS Institute Inc). A P value of less than.05 was considered statistically significant.

Results

Demographics

Fourteen patients were enrolled with a mean follow-up of 16.5 weeks. Four of the patients had AR or mixed rhinitis. The remaining 10 had NAR. Age and gender were also recorded (Table 1). Three patients were excluded due to lack of follow-up and incomplete patient-reported outcome measure forms.

Table 1.

Patient Demographics.

Patient ID	Length of follow-up (weeks)	Age	Gender	Rhinitis type	Comorbidities
1	12	68	M	NAR	Depression/anxiety
2	13	73	M	NAR	Depression/anxiety
3	14	70	M	NAR	Depression/anxiety
4	16	65	M	NAR	Smoker
5	32	39	F	AR	Depression/anxiety
6	6	69	M	NAR	None
7	36	34	F	AR	Primary headache disorder
8	11	75	M	NAR	Depression/anxiety
9	6	40	F	Mixed	Primary headache disorder, depression/anxiety
10	6	74	M	NAR	Smoker
11	6	61	F	NAR	None
12	20	72	M	NAR	Depression/anxiety
13	17	48	M	NAR	Depression/anxiety
14	36	40	F	AR	Depression/anxiety

Abbreviations: AR, allergic rhinitis; F, female; M, male; NAR, nonallergic rhinitis.

Comorbidities

Comorbidities surveyed for included CRS, primary headache disorder, TMJ dysfunction, facial pain syndrome, depression/anxiety, or smoking history as demonstrated in Table 1.

Medical Management

Majority of patients presenting to our clinic initially underwent attempts with medical management prior to being offered PNN cryoablation. The types of therapies trialed for each patient is outlined in Table 2.

Table 2.

Rhinitis Type and Pharmacologic Treatment Prior to PNN Cryoablation.

Rhinitis type	TNS	TNAH	TNAC	Saline	PPI
AR	Yes	Yes	-	Yes	-
AR	Yes	Yes	-	Yes	-
AR	Yes	Yes	-	Yes	Yes
Mixed	Yes	Yes	Yes	Yes	-
NAR	Yes	Yes	Yes	Yes	Yes
NAR	Yes	-	Yes	Yes	Yes
NAR	Yes	-	-	Yes	Yes
NAR	Yes	-	Yes	-	Yes
NAR	Yes	Yes	-	Yes	Yes
NAR	Yes	-	Yes	-	Yes
NAR	-	-	-	-	-
NAR	Yes	Yes	Yes	Yes	Yes
NAR	-	-	Yes	-	-
NAR	Yes	Yes	-	Yes	-

Abbreviations: AR, allergic rhinitis; NAR, nonallergic rhinitis; TNS, topical nasal steroid; TNAH, topical nasal antihistamine; TNAC, topical nasal anticholinergic; PNN, posterior nasal nerve; PPI, proton pump inhibitor.

Outcome Measures

The TNSS and mini-RQLQ scores significantly improved after PNN cryoablation among all patients (−4 [3], −1.61 [1.08], respectively; both P = .0002; Figure 2). Utilizing the MCID of 0.55 and 0.4 for the TNSS and mini-RQLQ, respectively, 13 of the 14 patients obtained clinically important difference (92.9%; 2 separate patients did not obtain MCID, 1 for the TNSS and 1 for the mini-RQLQ). Relative mean percentage (%) improvement for all patients was 40.7% and 40.5% (standard deviation [SE] = 24.9 and 29.5, respectively) as measured by the TNSS and mini-RQLQ, respectively. Patients with NAR (n = 10) reported mean improvement of 41.3% (29.1) as measured by the TNSS and 49.6% (25.9) by mini-RQLQ. Patients with AR or mixed rhinitis reported mean percentage improvement in TNSS and mini-RQLQ scores of 39.5% (12.1) and 24.6% (28.5), respectively.

Figure 2.

Observed change in TNSS and mini-RQLQ after PNN cryoablation (* = statistical significance). PNN indicates posterior nasal nerve; mini-RQLQ, mini-rhinoconjunctivitis quality of life questionnaire; TNSS, total nasal symptom score.

Univariate and Multivariate Analyses

Univariate analysis did not show a statistically significant effect of the patient demographics (age and gender), length of follow-up, type of rhinitis, nor associated comorbidities on the postprocedural outcome on either the TNSS or the mini-RQLQ. Patients who had been prescribed a topical nasal anticholinergic (TNAC) for medical management prior to proceeding with PNN cryoablation had statistically significantly increased improvement on the change in mini-RQLQ scores from pre- to postprocedure (P = .0387; Tables 3 and 4).

Table 3.

Univariate Analysis for Change in TNSS and mini-RQLQ.^a

Demographic variable	Change in TNSS ρ	P value	Change in mini-RQLQ ρ	P value
1. Age	−.00112	.9970	−.35204	.2171
2. Length of follow-up	−.33070	.2482	.23361	.4215

^a Spearman ρ correlation coefficients for age and length of follow-up.

Table 4.

Univariate Analysis for Change in TNSS and Mini-RQLQ.^a,b

Demographic variable	Change in TNSS		Change in mini-RQLQ
Demographic variable	Median (IQR)	P value	Median (IQR)	P value
1. Gender		.8941		.5166
Male (n = 9)	−4 (−4 to −2)		−1.65 (−1.72 to −1.1)
Female (n = 5)	−4 (−5 to −3)		−0.89 (−1.86 to −0.43)
2. Rhinitis type		.4025		.2064
Nonallergic rhinitis (10)	−3.5 (−4 to −2)		−1.61 (−1.72 to −0.89)
Allergic rhinitis (3)	−4 (−5 to −3)		−0.43 (−1.86 to 0.29)
Mixed rhinitis (1)	−5 (−5 to −5)		−2.29 (−2.29 to −2.29)
3. Headache		.1381		.9287
Yes (2)	−5.0 (−5 to −5)		−1 (−2.29 to 0.29)
No (12)	−3.5 (−4 to −2)		−1.61 (−1.79 to −0.835)
4. Depression/anxiety		.1011		.1067
Yes (9)	−4 (−5 to −4)		−1.72 (−2 to −1.57)
No (5)	−2 (−3 to −1)		−0.89 (−1.1 to −0.65)
5. Smoking history		.3253		1.000
Yes (2)	−2.5 (−3 to −2)		−1.405 (−1.71 to −1.1)
No (12)	−4 (−5 to −2.5)		−1.61 (−1.93 to −0.715)
6. TNS		1.000		.6556
Yes (12)	−4 (−4.5 to −2.5)		−1.61 (−1.79 to −0.715)
No (2)	−3.5 (−5 to −2)		−1.55 (−2 to −1.1)
7. TNAH		.4084		.1983
Yes (8)	−3.5 (−4.5 to −1.5)		−0.835 (−1.79 to −0.54)
No (6)	−4 (−5 to −3)		−1.68 (−2 to −1.57)
8. TNAC		.2889		.0387
Yes (7)	−4 (−5 to −3)		−1.72 (−2.29 to −1.65)
No (7)	−3 (−4 to −2)		−0.78 (−1.57 to −0.43)
9. Saline		1.000		.1614
Yes (10)	−4 (−5 to −2)		−1.23 (−1.72 to −0.65)
No (4)	−3.5 (−4.5 to −2.5)		−1.855 (−2.46 to −1.405)
10. PPI		.4445		.8494
Yes (8)	−3.5 (−4 to −2)		−1.61 (−1.715 to −0.77)
No (6)	−4.5 (−5 to −2)		−1.48 (−2 to −0.78)

Abbreviations: Change in TNSS, difference between preprocedural TNSS and postprocedure TNSS; Change in mini-RQLQ, difference between preprocedural mini-RQLQ and postprocedure mini-RQLQ; IQR, interquartile range; PPI, proton-pump inhibitor; RQLQ, mini-rhinoconjunctivitis quality of life questionnaire; TNS, topical nasal steroid; TNAH, topical nasal antihistamine; TNAC, topical nasal anticholinergic; TNSS, total nasal symptom score.

^a Wilcoxon sum rank test for gender, headache, depression/anxiety, smoking history.

^b Kruskal-Wallis test for rhinitis type.

“Statistically significant values bolded.”

After controlling for baseline TNSS (P = .0004) in the multivariate analysis, patients without depression/anxiety tended to have higher post-TNSS scores by an average of 1.52 (SE = 0.89) points, although this was not statistically significant (P = .1164). For the mini-RQLQ multiple regression, after controlling for baseline (P = .0002), a prior trial on a TNAC increased improvement by an average of 0.93 (SE = 0.35) points (P = .025; Tables 5 and 6).

Table 5.

Multiple Regression Analysis.^a

	R ²	Model P value	Predictor variable
	R ²	Model P value		Estimate	P value
Multiple regression model	.6942	.0015	BLTNSS	0.822	.0004
Multiple regression model	.6942	.0015	Depression/anxiety	-1.516	.1164

Abbreviations: BLTNSS, baseline TNSS; TNSS, total nasal symptom score.

^a Dependent variable: Postprocedural TNSS.

Table 6.

Multiple Regression Analysis.^a

	R ²	Model P value	Predictor variable
	R ²	Model P value		Estimate	P value
Multiple regression model	.8517	.0002	BLMRQLQ	0.966	.0002
			TNAC	−0.93	.0246
			Depression/anxiety	−0.691	.1317

Abbreviations: BLMRQLQ, baseline mini-RQLQ; mini-RQLQ, mini-rhinoconjunctivitis quality of life questionnaire; TNAC, topical nasal anticholinergic.

^a Dependent variable: Postprocedural mini-RQLQ.

Discussion

Differentiating between the subtypes of chronic rhinitis is critical in establishing a first-line treatment response to give patients the best chance of improving symptoms and overall QOL. Clinical practice guidelines for AR make a strong recommendation for topical intranasal steroid use, with the option supplement with combination therapy for patients who fail monotherapy.⁶ The British Society for Allergy and Clinical Immunology has updated treatment recommendations for NAR, an entity with several etiologies and more complex treatment approach.¹² This includes treatment with topical intranasal steroid, intranasal ipratropium, and topical antihistamines.¹² Despite these therapies, many patients remain symptomatic. In our patient cohort, majority were trialed on at least monotherapy of topical medication, with most of those receiving some type of combination therapy as well (Table 2). Patient reported disease-specific QOL as measured by the TNSS and mini-RQLQ remained poor despite these medical therapies and all patients elected to undergo PNN cryoablation.

Prior to procedural surgical cryoablation, there were limited long-term options available to patients with recalcitrant symptoms of chronic rhinitis short of vidian neurectomy, the sequelae of which are well-documented.^8,13,14 Although there are reports of botulinum toxin injection for the treatment of rhinitis, this intervention is also procedural with limited data and short duration of action.¹⁵ Posterior nasal nerve cryoablation is potentially a superior alternative to these treatment methods for chronic rhinitis, although head-to-head comparisons have not been performed. By targeting the postganglionic parasympathetic fibers of the vidian nerve via the PNN, the complications that are observed with vidian neurectomy are avoided.¹⁶ In addition, improvement has been noted to be significant at as early as 6 weeks of postprocedure, and the effects have been shown to be long lasting with at least 9 months of durable symptom control demonstrated.⁹ In this context, our cohort included patients with at least 6 weeks of postprocedural data. With an average follow-up of 4.5 months, including 3 patients with at least 8 months of follow-up demonstrating continued clinical improvement, our study further substantiates previous findings.

The magnitude of the response demonstrated after PNN cryoablation was calculated via relative mean percentage improvement in the TNSS and mini-RQLQ scores, a measurement not previously studied. The patients treated in this study demonstrated approximately 40% improvement in their symptoms and QOL. These data may help to inform both surgeons and patients during the preprocedural shared decision-making process. The robust response observed in both the NAR and AR/mixed rhinitis groups is notable, with meaningful clinical improvement observed in all but 1 patient in regard to both the symptomatology and QOL as measured by the TNSS and mini-RQLQ, respectively. These findings corroborate the results from industry sponsored studies.⁹ The potential implication of both the NAR and AR/mixed groups benefitting from this procedure is that the downstream effect of the numerous etiologies of chronic rhinitis may be mediated through the PNN. One prior study showed significant reduction in the density of nasal glands and inflammatory cell infiltration after PNN resection, suggesting the physiological mechanism of the response to chronic rhinitis of all types as seen after PNN cryoablation.¹⁷

This study is unique in that the patients included underwent topical therapy not limited to a single pharmacologic class and were deemed to be medically recalcitrant prior to proceeding with PNN cryoablation, a criteria not required for candidacy in prior studies.^9,18

-21 One patient did not receive any topical therapy due to such severe, incapacitating osteoarthritis that limited application of a nasal spray. Even so, based on inclusion criteria in prior research, this patient was able to be included in this study while maintaining the applicability of these results. Overall, a positive response was demonstrated after PNN cryoablation in this series of patients with chronic rhinitis.

We noted that medical management trial with TNAC led to better response based on postprocedural mini-RQLQ scores, but this did not hold true for the postprocedural TNSS. This finding is supported by literature demonstrating preprocedure patient response to TNACs as predictive of response to PNN cyroablation.²¹ In our patient cohort, the postprocedural relative mean percentage improvement in TNSS and mini-RQLQ scores was especially prominent in patients with NAR, suggesting a potential physiologic benefit in the mediation of their rhinitis symptoms. This may further correlate to the benefit seen in patients trialed on TNACs.

Anxiety and depression are common comorbid conditions in patients with sinonasal inflammatory disorders. Although the incidence of anxiety/depression in this particular cohort is greater than what may be expected (20%-25% of patients with CRS), this could be attributed to sampling error.²² Future study with larger sample sizes is needed to further elucidate this correlation. Patients with depression/anxiety report greater improvement based on the postprocedural TNSS and mini-RQLQ questionnaires after PNN cryoablation while controlling for their baseline responses. This is contradictory to data from studies evaluating patients with CRS and comorbid depression in which the depression exerts a negative impact on symptom burden.²² It is possible that patients with comorbid depression may perceive symptoms worse than patients without comorbid depression and once disease-specific symptoms improve, the patient-reported outcome measures may drop more significantly than those without comorbid psychiatric illness. This multiple regression analysis is insufficient to draw firm conclusions in this aspect but suggests avenues for further research in gauging the candidacy of patients with depression/anxiety for PNN cryoablation.

Our study was limited by a few factors including the lack of a control group. However, the patient population we studied served as their own control group prior to the intervention. In addition, there are potential confounders, especially when considering topical therapy use. Although we tracked preprocedural therapies, the instructed use of either topical or oral medications was not recorded after the procedure. Further, the small sample size of our cohort and the robust response likely contributed to identification of fewer predictive factors with statistical significance. Even so, over 65% of patients (155 of 236) studied who underwent PNN cryoablation for rhinitis were included in industry-sponsored studies, and the 14 patients in this series are a meaningful addition to the nonsponsored study data pool.^{9,10,18,19,21} Future directions for evaluating the use and benefit of PNN cryoablation will include a focus on increasing time of follow-up, distinguishing the benefit of the procedural cryoablation from the ongoing use of intranasal therapeutics, and further categorizing rhinitis subtypes and the patients’ response to PNN cryoablation. Posterior nasal nerve cryoablation reduces TNSS and demonstrates improvement in mini-RQLQ in patients with both AR and NAR by approximately 40% in this cohort. Posterior nasal nerve is an option in the treatment algorithm when escalating therapy from conservative/therapeutic management to surgical management.

Conclusion

This study demonstrates that PNN cryoablation significantly improves symptoms and disease-specific QOL in patients with AR and NAR as measured by TNSS and mini-RQLQ.

Footnotes

Declaration of Conflicting Interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Steele: Intersect—Honorarium; Stryker consultant. Dr Wilson: NIH NCAT.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project described was supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through grant number UL1 TR001860. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

ORCID iD

Farrukh R. Virani

References

Öçal

Bayar Muluk

Mullol

. Epidemiology of allergic rhinitis. In: Cingi

Bayar Muluk

, eds. All Around the Nose: Basic Science, Diseases and Surgical Management. Springer International Publishing; 2020:297–301.

Settipane

Charnock

. Epidemiology of rhinitis: allergic and nonallergic. Clin Allergy Immunol. 2007;19:23–34.

Settipane

. Epidemiology of vasomotor rhinitis. World Allergy Organ J. 2009;2(6):115–118. doi:10.1097/wox.0b013e3181ac91ae. Accessed June 2020. http://europepmc.org/abstract/MED/24229078https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24229078/?tool=EBIhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24229078/pdf/?tool=EBIhttps://doi.org/10.1097/WOX.0b013e3181ac91aehttps://europepmc.org/articles/PMC3650980https://europepmc.org/articles/PMC3650980?pdf=render

Meltzer

Bukstein

. The economic impact of allergic rhinitis and current guidelines for treatment. Ann Allergy, Asthma Immunol. 2011;106(2 Suppl):S12–S16. doi:10.1016/j.anai.2010.10.014

Lamb

Ratner

Johnson

, et al. Economic impact of workplace productivity losses due to allergic rhinitis compared with select medical conditions in the United States from an employer perspective. Curr Med Res Opin. 2006;22(6):1203–1210. doi:10.1185/030079906X112552

Seidman

Gurgel

Lin

, et al. Clinical practice guideline: allergic rhinitis. Otolaryngol–Head and Neck Surg. 2015;152(1_suppl):S1–S43. doi:10.1177/0194599814561600

Marple

Fornadley

Patel

, et al. Keys to successful management of patients with allergic rhinitis: focus on patient confidence, compliance, and satisfaction. Otolaryngol - Head and Neck Surg. 2007;136(6 Suppl):S107–S124. doi:10.1016/j.otohns.2007.02.031

Sacks

Sivasubramaniam

Chapter 23 - endoscopic vidian neurectomy. In: Chiu

Palmer

Adappa

, eds. Atlas of Endoscopic Sinus and Skull Base Surgery (Second Edition). Content Repository Only!; 2019:191–194. e1.

Chang

Song

Hwang

. Cryosurgical ablation for treatment of rhinitis: a prospective multicenter study. Laryngoscope. 2020;130(8):1877–1884. doi:10.1002/lary.28301

10.

Steele

Hoshal

Kim

, et al. A preliminary report on the effect of gabapentin pretreatment on periprocedural pain during in-office posterior nasal nerve cryoablation. Int Forum Allergy Rhinol. 2020;10(2):159–164. doi:10.1002/alr.22456

11.

Barnes

Vaidyanathan

Williamson

Lipworth

. The minimal clinically important difference in allergic rhinitis. Clin Experi Allergy. 2010;40(2):242–250. doi:10.1111/j.1365-2222.2009.03381.x

12.

Scadding

Kariyawasam

Scadding

, et al. BSACI guideline for the diagnosis and management of allergic and non-allergic rhinitis (Revised Edition 2017; First edition 2007). Clin Exper Allergy. 2017;47(7):856–889. doi:10.1111/cea.12953

13.

Robinson

Wormald

. Endoscopic vidian neurectomy. Am J Rhinol. 2006;20(2):197–202.

14.

Girdhar-Gopal

Okurowski

Strome

. An assessment of postganglionic cryoneurolysis for managing vasomotor rhinitis. Am J Rhinol. 1994;8(4):157–164. doi:10.2500/105065894781874313

15.

Braun

Gürkov

Kramer

Krause

. Septal injection of botulinum neurotoxin A for idiopathic rhinitis: a pilot study. Am J Otolaryngol. 2012;33(1):64–67. doi:10.1016/j.amjoto.2011.01.004

16.

Kikawada

. Endoscopic posterior nasal neurectomy: an alternative to vidian neurectomy. Operat Tech Otolaryngol-Head and Neck Surg. 2007;18(4):297–301. doi:10.1016/j.otot.2007.05.010

17.

Ikeda

Yokoi

Saito

Kawano

Yao

Furukawa

. Effect of resection of the posterior nasal nerve on functional and morphological changes in the inferior turbinate mucosa. Acta Oto-Laryngologica. 2008;128(12):1337–1341. doi:10.1080/00016480801935525

18.

Hwang

Lin

Weiss

Atkins

Johnson

. Cryosurgical posterior nasal tissue ablation for the treatment of rhinitis. Int Forum Allergy Rhinol. 2017;7(10):952–956. doi:10.1002/alr.21991

19.

M. Yen

B. Conley

O’Malley

Byerly

Johnson

. Multiple site cryoablation treatment of the posterior nasal nerve for treatment of chronic rhinitis: an observational feasibility study. Allergy Rhinol. 2020;11:2152656720946996. doi:10.1177/2152656720946996

20.

Kompelli

Janz

Rowan

Nguyen

Soler

. Cryotherapy for the treatment of chronic rhinitis: a qualitative systematic review. Am J Rhinol Allergy. 2018;32(6):491–501. doi:10.1177/1945892418800879

21.

Yoo

Kuan

Batra

Chan

Tajudeen

Craig

. Predictors of rhinorrhea response after posterior nasal nerve cryoablation for chronic rhinitis. Int Forum Allergy Rhinol. 2020;10(7):913–919. doi:10.1002/alr.22574

22.

Litvack

Mace

Smith

. Role of depression in outcomes of endoscopic sinus surgery. Otolaryngol Head Neck Surg. 2011;144(3):446–451. doi:10.1177/0194599810391625