Surgical and Regenerative Treatment Options for Empty Nose Syndrome: A Systematic Review

Article information

Clin Exp Otorhinolaryngol. 2024;17(3):241-252

Publication date (electronic) : 2024 July 4

doi : https://doi.org/10.21053/ceo.2023.00038

Do Hyun Kim ¹

, Mohammed Abdullah Basurrah ²

, Soo Whan Kim ¹

, Sung Won Kim^,¹

¹Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

²Department of Surgery, College of Medicine, Taif University, Taif, Saudi Arabia

Corresponding author: Sung Won Kim Department of Otolaryngology-Head and Neck Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea Tel: +82-2-2258-6216, Fax: +82-2-535-1354 Email: kswent@catholic.ac.kr

Received 2024 January 30; Revised 2024 June 21; Accepted 2024 July 4.

Abstract

Objectives

Patients with empty nose syndrome typically experience paradoxical nasal congestion, nasal dryness, epistaxis, and suffocation. Conservative management is generally preferred for empty nose syndrome. However, some patients continue to experience persistent symptoms. When symptoms do not resolve, surgical options are considered. Therefore, we reviewed the surgical and regenerative treatment options for empty nose syndrome.

Methods

PubMed, Embase, Scopus, Cochrane Register of Controlled Trials, and Google Scholar were searched from the earliest date provided in the database until December 2022. This review included studies that assessed treatment outcomes using patient symptom scores, including the Sino-Nasal Outcome Test (SNOT-20, -22, and -25) and the Empty Nose Syndrome 6-Item Questionnaire, supplemented by various clinical examinations.

Results

Twenty-eight studies were analyzed. Various materials were utilized, including submucosal injectable materials, allografts/xenografts/cadaveric implants, autologous implants, and synthetic implants. The polyethylene implant was the most commonly used (23.3%), followed by autologous, homologous, or cadaveric costal cartilage (20%). The anterior-inferior lateral nasal wall was the most frequent site of administration. Most studies indicated that surgical intervention led to significant improvements in clinical outcomes, as evidenced by endoscopic exams, acoustic rhinometry, and computed tomography scans, along with patient-reported enhancements in nasal symptoms, psychological well-being, and overall health-related quality of life. However, several studies found no improvement in certain psychological-related questionnaires or saccharin transit times. The average follow-up duration was 12.0 months (range, 2.0–27.6 months). Only two studies reported postoperative adverse effects.

Conclusion

Several surgical options and recent tissue regeneration techniques have demonstrated efficacy in treating empty nose syndrome. However, more detailed investigations involving a larger number of participants and a randomized control study are necessary to establish a standardized treatment protocol for patients with empty nose syndrome.

Keywords: Atrophic Rhinitis; Therapeutics; Operative Surgical Procedures; Sino-Nasal Outcome Test; Review

INTRODUCTION

Empty nose syndrome is an iatrogenic disorder that develops after nasal surgery, particularly surgery on the inferior turbinates [1-3]. The term “empty nose syndrome” was coined by Kern and Stenkvist in 1994 to describe the significant loss of intranasal tissue around the inferior and middle turbinates [4]. This condition is characterized by a paradoxical sensation of nasal obstruction despite a widened nasal airway. Symptoms vary and include nasal crusting, dryness, intermittent bleeding, thick nasal discharge, facial pain, feelings of suffocation, difficulty breathing through the nose, excessive airflow, shortness of breath, and inadequate lung inflation [1,5-7]. Therefore, empty nose syndrome is associated with impaired quality of life and psychological distress. Patients may suffer from poor sleep quality, difficulty concentrating, anxiety, panic attacks, and suicidal ideation [8,9]. Many patients with empty nose syndrome are considered to have either neuropathy or rhinitis hystericus. Furthermore, the sensation of an “empty nose” is often viewed as a normal part of recovery following nasal surgery, leading to the neglect and mistreatment of these symptoms in patients with empty nose syndrome [10]. Although empty nose syndrome is traditionally managed with conservative care, recent studies suggest that surgical interventions or mucosal regenerative approaches can provide long-term symptom relief.

This systematic review examined surgical and regenerative treatment options for empty nose syndrome, compared their advantages and disadvantages, and aimed to offer valuable insights into treatment policies for patients with intractable empty nose syndrome.

MATERIALS AND METHODS

Search strategy

The Institutional Review Board of the Catholic University of Korea waived approval for this study because it is a systematic review and meta-analysis based exclusively on published literature. This study followed the population (patients with empty nose syndrome), intervention (surgery of the nasal cavity), comparison (not specified), outcomes (symptoms or endoscopic scores), and study design (not limited) framework. We searched the following electronic databases for studies published from the time the literature search was available until December 2022: PubMed, Embase, Scopus, Cochrane Register of Controlled Trials, and Google Scholar. The search terms included “empty nose syndrome,” “atrophic rhinitis,” and “treatment.” The search strategy was developed in collaboration with a librarian who had over 10 years of experience in conducting information searches. Review articles, non-human studies, and studies with missing information on materials and methods were excluded. In addition, among the literature searched for atrophic rhinitis, etiologies other than empty nose syndrome secondary to iatrogenic causes were excluded. We comprehensively reviewed the references cited in relevant studies to identify additional papers. Supplementary Table 1 presents the details of our search strategy. Fig. 1 provides an overview of the study selection process. Two reviewers (SWK and MAB) independently screened the titles and abstracts; studies that were irrelevant to the subject matter were excluded. Discrepancies between the reviewers were resolved through discussion with a third reviewer (SWK). Full-text versions of potentially eligible studies were reviewed for eligibility. The study protocol was registered on the Open Science Framework (https://osf.io/3uamv/).

Fig. 1.

Study selection process.

Data curation and risk of bias assessment

We systematically collected data from eligible studies that met our selection criteria, including the number of patients, scale and score used for endoscopic findings, and incidence or percentage of postoperative adverse events, such as adhesions, middle turbinate lateralization, polypoid change, and need for postoperative therapeutic intervention. Data were collected in a standardized format using established forms [11-14]. Treatment measurements were evaluated using various methods, such as endoscopic exams, computed tomography, symptom scoring systems (such as the Sino-Nasal Outcome Test, Empty Nose Syndrome 6-Item Questionnaire, visual analog scale, Nasal Obstruction Symptom Evaluation, and Rhinosinusitis Quality of Life), psychological change questionnaires or overall health-related quality of life scoring questionnaires (such as the Beck Depression Inventory, Beck Anxiety Inventory, Generalized Anxiety Disorder 7-item scale, and Patient Health Questionnaire-9), saccharin transit time, acoustic rhinometry, and rhinomanometry. We evaluated the quality of the included studies using the Newcastle-Ottawa Scale. In addition, the Cochrane Risk of Bias tool was used to assess the risk of bias in randomized controlled studies.

RESULTS

Our review included 28 studies [15-42]. Tables 1 and 2 provide details on the characteristics of the included studies, while Supplementary Tables 2 and 3 present a summary of the risk of bias assessment. In both randomized controlled studies, the randomization process was judged to have “some concerns.” All nonrandomized controlled studies assessed using The Newcastle-Ottawa Scale were rated as good quality. The majority of the studies were case series and case-control studies, with only two being randomized controlled trials. Additionally, more than half of the reports (57.1%) utilized the cotton test [5,43] for pretreatment evaluation.

Table 1.

Characteristics of the included studies

Table 2.

Summary of patient-reported outcome measurements

Several materials have been used as intranasal implants, including various autologous transplants such as dermal fat, septal, conchal, and costal cartilage. Other implants include homologous costal cartilage, acellular dermis graft (AlloDerm, LifeCell Corp.), polyethylene implant (Medpor, Porex Surgical Inc.), silastic sheet, β-tricalcium phosphate implant (Sinus-Up Implants, Kasios), and porcine small intestine submucosal xenograft (Biodesign, Cook Biomedical). Additionally, materials such as hydroxyapatite cement, carboxymethylcellulose or glycerin gel, Placentrex, hyaluronic acid, platelet-rich plasma, and autologous lipoaspirate injection formulations have been used to treat empty nose syndrome, with favorable effects reported regardless of the substance administered. Only one study, which analyzed the effects of administering platelet-rich plasma after performing submucosal diathermy, reported no significant difference in saccharin transit time between the two groups [20]. However, the effectiveness of injectable substances such as Placentrex, platelet-rich plasma, and hyaluronic acid gel injection decreases after 3–6 months.

The most common site for administration was the anterior-inferior lateral nasal wall, followed by the inferior turbinate, nasal floor, and septum. Treatment outcomes were assessed using a variety of methods, including endoscopic exams, computed tomography, symptom scoring systems, saccharin transit time, acoustic rhinometry, and rhinomanometry. Most studies reported improvements in nasal symptom scoring systems, such as the SinoNasal Outcome Test, Empty Nose Syndrome 6-Item Questionnaire, visual analog scale, Nasal Obstruction Symptom Evaluation, and Rhinosinusitis Quality of Life. Additionally, favorable outcomes were generally observed in the results of endoscopic exams, computed tomography, acoustic rhinometry, and rhinomanometry. However, the results were mixed in psychological change questionnaires or overall health-related quality of life scoring questionnaires, including the Beck Depression Inventory, Beck Anxiety Inventory, Generalized Anxiety Disorder 7-item scale, and Patient Health Questionnaire-9. The average follow-up duration was 12.0 months (range, 2.0–27.6 months). Only two studies reported postoperative adverse effects [27,31], including exposed implants and pressure sensation in the upper alveolar dentition.

DISCUSSION

Numerous nasal surgical procedures, such as inferior turbinectomy or turbinoplasty, are routinely performed in otorhinolaryngology departments. Among these procedures, a significant number of patients may develop empty nose syndrome, which shares clinical features with atrophic rhinitis [4]. In most cases, conservative treatment is the initial choice. However, some patients do not respond to treatment, and their numbers are growing annually. A study from a decade ago indicated that only up to 21% of patients showed marginal clinical improvement even after undergoing surgical treatment [44]. Despite this, more refined surgical techniques have been developed recently, and interest in regenerative treatment options has been growing [45]. Therefore, this review aimed to organize and evaluate the literature on surgical and regenerative treatment options for patients with empty nose syndrome. Although the available literature lacks randomized controlled trials, most studies have reported significant symptom improvement regardless of the treatment option used, and implantable materials have demonstrated longer-term effects compared to injectable materials.

The pathophysiology of empty nose syndrome involves decreased air resistance in the nasal cavity due to structural changes. This condition leads to non-physiological air flow (inspiratory turbulent flow) and increased drying from a rise in shearing force on the mucosal surface area [7]. These changes result in fibrosis of the submucosal tissue of the nasal mucosa and a reduction in secretory cells [46]. Surgical interventions aim to reconstruct the deformed nasal structure, maintain humidity, and reduce air flow turbulence. In this context, the cotton test [5] serves as a valuable diagnostic tool for empty nose syndrome, helping to predict surgical outcomes and identify intervention sites. The test, which is utilized in over half of the studies, involves inserting a dry cotton plug into the area of tissue loss in the nasal cavity, particularly in the caudal region of the inferior meatus. This plug helps restore the nasal structure’s size and shape, as well as the original airflow pattern. Therefore, clinicians can assess the potential for alleviating a patient’s pain. Despite enduring severe symptoms of empty nose syndrome for extended periods, some patients report a dramatic improvement in symptoms within minutes of applying the cotton plug [43].

The classical intervention for treating empty nose syndrome is known as Young’s procedure, or the modified Young’s procedure [47,48]. Other interventions aim to reduce the size of nasal passages to dimensions similar to those before surgery or injury. This reduction aids in warming and humidifying inhaled air and helps minimize the formation of turbulent flow in the widened nasal cavity, which results from airflow passing through narrow nostrils [43]. Various materials, including submucosal injectable materials, allografts/xenografts/cadaveric implants, autologous implants, and synthetic implants, are used to achieve these outcomes.

The primary advantage of submucosal injection is its ease of administration under local anesthesia, which makes it an appealing option for patients who have concerns about general anesthesia or surgery, as well as for those whose medical comorbidities complicate the use of general anesthesia. Materials that promote tissue regeneration, such as Placentrex and platelet-rich plasma, are particularly effective when administered early after nasal surgery while tissue healing is ongoing. Additionally, substances that were previously utilized for filler or vocal cord augmentation, including hyaluronic acid gel, carboxymethylcellulose, and glycerin gel, have been employed to alleviate symptoms of empty nose syndrome, with benefits lasting between 2 and 12 months.

An acellular dermis graft (AlloDerm) and a porcine small intestine submucosal xenograft (Biodesign) have been designed to integrate into the implanted tissue over time. Cadaveric ribs, along with decellularized and irradiated tissues, carry a low risk of inflammatory reactions [38]. Although these materials can reduce the morbidity of harvesting autografts, they are relatively expensive.

Autologous cartilage is highly biocompatible and carries the lowest risk of an inflammatory response following transplantation. Septal, auricular, and costal cartilages are all potential sources for autologous cartilage grafts. However, septal cartilage is less commonly used due to the risk of inducing empty nose syndrome, a condition often associated with septoturbinoplasty. While conchal cartilage is frequently utilized for auricular cartilage grafts, costal cartilage is preferred in the treatment of empty nose syndrome because of its thickness and ease of insertion [22]. Additionally, costal cartilage enables the harvesting of a large quantity, making it ideal for addressing the total defect of the inferior turbinate. Consequently, it is extensively used in research involving autologous cartilage. Nevertheless, the extraction of costal cartilage can lead to donor-site morbidities, such as pneumothorax and chest wall deformities [49]. In such cases, homologous (cadaveric) costal cartilage is an alternative.

In addition to autologous and allolgeneic grafts, synthetic implants are also employed in the treatment of empty nose syndrome. Porous polyethylene, commonly known as Medpor, is the most frequently used implant. Other alternatives include silicone sheets, hydroxyapatite cement, and β-tricalcium phosphate implants (Sinus-Up Implants). Synthetic implants are cost-effective and simple to manipulate. However, they are associated with a relatively high risk of complications, such as foreign body reactions, extrusion, and infection. Implant formulations demonstrated more long-lasting effects than injectable formulations. However, due to the delicate and sensitive nature of the nasal mucosa, implanted materials may become exposed or cause pain following insertion. Conversely, injectable materials carry a risk of causing ophthalmic complications, though such incidents are extremely rare [50,51].

Recent advancements in cell-based organoid technologies and tissue engineering have facilitated the development of mucosal tissue regeneration using stem cells and scaffolds that sustain this effect [45,52]. Additionally, there have been reports of human turbinate-derived stem cells being applied to scaffolds in both three-dimensional printed and spheroid forms, serving as a niche for mucosal regeneration [52-54]. These advancements are expected to integrate the benefits of both injectable and implant formulations, offering a potential solution to the limitations inherent to each method.

This study has several limitations. The majority of the studies reviewed in this manuscript were heterogeneous case series or case-control studies, which did not allow for a direct comparison of interventions. Additionally, some reports lacked detailed descriptions of the main procedures and potential adverse effects. The heterogeneity and insufficient data precluded the possibility of conducting a meta-analysis to ascertain the effects. A significant limitation in assessing the symptoms and severity of empty nose syndrome is the absence of standardized diagnostic criteria specific to the condition. Recently, questionnaires such as the ENSQ-6 have demonstrated potential in more accurately addressing empty nose syndrome, yet they require further validation. The development of standardized assessment tools for empty nose syndrome is crucial for comparing treatment methods and evaluating the efficacy of new interventions.

Various surgical modalities, along with tissue regeneration methodologies, have shown favorable outcomes in managing empty nose syndrome. These methods have improved the structural changes in the nasal cavity and have positively impacted patients’ scores on nasal symptom-, psychological-, or overall health-related quality of life questionnaires. However, there is a need to establish a standardized protocol for assessing patients with empty nose syndrome and conduct well-designed clinical investigations in order to address the unmet gaps in exploring optimal treatment options for these patients.

HIGHLIGHTS

▪ The main goal of surgery for empty nose syndrome is to restore the normal nasal airflow, thereby relieving the severe discomfort in nasal breathing in affected patients.

▪ Selection of the appropriate surgical options and grafting materials should be customized, with careful consideration of the patient’s symptoms and nasal anatomy.

▪ Tissue regeneration techniques could be cautiously considered to aid in the treatment of empty nose syndrome patients; however, future research is needed to elucidate this possibility given the limited number of existing studies.

Notes

Do Hyun Kim is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

AUTHOR CONTRIBUTIONS

Conceptualization: DHK, SWK, SWK. Data curation: DHK, MAB, SWK (Sung Won Kim). Writing–original draft: DHK. Writing–review & final editing: all authors.

Acknowledgements

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (RS-2023-00209494, 2019M3E5D5064110), and a Korean Fund for Regenerative Medicine (KFRM) grant funded by the Korean government (23C0121L1).

SUPPLEMENTARY MATERIALS

Supplementary materials can be found online at https://doi.org/10.21053/ceo.2023.00038.

Supplementary Table 1.

Search strategy

ceo-2023-00038-Supplementary-Table-1.pdf

Supplementary Table 2.

Quality assessment of randomized controlled studies

ceo-2023-00038-Supplementary-Table-2.pdf

Supplementary Table 3.

Quality assessment of non-randomized controlled studies

ceo-2023-00038-Supplementary-Table-3.pdf

SUPPLEMENTARY REFERENCESceo-2023-00038-Supplementary-References.pdf

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Table 1.

Characteristics of the included studies

Study	Study design	No. of patients	Sex (male: female)	Age (yr)	Cases/controls (n)	Nation	Previous surgical history	Preoperative assessment	Intervention	Anesthesia	Location	Treatment outcomes	Result	Follow-up (mo)
Jang et al. (2011) [18]	Case-control	17	11:6	41.4±15.0 (20–66)	Treatment, 14/normal side, 14	Korea	NA	-	Septal, conchal, autologous, or homologous costal cartilage (Tutoplast-processed costal cartilage, Tutogen Medical)	G/A	Nasal floor	CT, VAS	Significant improvement in nasal mucosa thickness (CT) and VAS	11.8 (6–27)
Jung et al. (2013) [22]	Case-control	31	22:9	43.5 (29–57)	Conchal, n=17/costal, 14 cartilage	Korea	NA	-	Conchal cartilage, costal cartilage (autologous/homologous: Tutoplast-processed costal cartilage; Tutogen Medical)	G/A	Anterior-inferior lateral nasal wall	SNOT-25	Conchal cartilage and costal cartilage were both effective, but costal cartilage was more effective	6.9±2.0
Park et al. (2018) [30]	Case report	1	0:1	63	NA	Korea	NA	-	Autologous costal cartilage	G/A	Anterior-inferior lateral nasal wall	SNOT-25	Significant improvement in SNOT-25	24
Malik et al. (2021) [38]	Case series	6	3:3	51.6±22.8	NA	USA	NA	Cotton test	Cadaveric cost cartilage	NA	Anterior-inferior lateral nasal wall	ENS6Q, computational fluid dynamics	Significant improvement in ENS6Q, restoration of nasal airflow to the inferior meatus (computational fluid dynamics)	7
Dholakia et al. (2021) [35]	Case series	17	8:9	52.1±13.2	NA	USA	NA	Cotton test, menthol test	Packaged, decellularized, and irradiated segments of cadaveric rib cartilage	G/A	Anterior-inferior lateral nasal wall	ENS6Q, SNOT-22, GAD-7, PHQ-9	Significant improvement in ENS6Q and SNOT-22	12
Dholakia et al. (2021) [35]	Case series	17	8:9	52.1±13.2	NA	USA	NA	Cotton test, menthol test		G/A	Anterior-inferior lateral nasal wall	ENS6Q, SNOT-22, GAD-7, PHQ-9	GAD-7 and PHQ-9 were not improved	12
Chang et al. (2021) [34]	Case report	2	2:0	NA	NA	Taiwan	NA	Cotton test	Platelet-rich fibrin scaffolds embedded with a diced cartilage graft	G/A	Anterior-inferior lateral nasal wall	ENS6Q, endoscopic exam	Significant improvement in ENS6Q; the implant was well positioned after 12 months	12
Chang et al. (2022) [39]	Case series	NA	NA	NA	NA	USA	NA	Cotton test	Irradiated cadaveric rib (MTF Biologics)	G/A	Anterior-inferior lateral nasal wall	ENS6Q, SNOT-22, GAD-7, PHQ-9	Improvement in ENS6Q, SNOT-22, GAD-7, and PHQ-9	6
Ushio et al. (2022) [42]	Case series	6	5:1	NA	NA	Japan	Partial turbinectomy	Cotton test	Autologous auricular cartilage	G/A	Nasal floor	ENS6Q, SNOT-20, SNOT-25, rhinomanometry	Improvement in ENS6Q, SNOT-20, SNOT-25, and rhinomanometry	14.8±4.8
Hosokawa et al. (2022) [40]	Case series	9	8:1	32.22 (18–72)	NA	Japan	NA	Cotton test	Autologous dermal fat	G/A	Nasal floor	ENS6Q	Improvement in ENS6Q	9.6±5.0
Houser et al. (2007) [16]	Case series	8	7:1	18–45	NA	USA	NA	Cotton test	Acellular dermis graft (AlloDerm, LifeCell)	G/A	IT, nasal septum, floor, vestibule	SNOT-20	Significant improvement in SNOT-20	27.6±15.5
Velasquez et al. (2018) [28]	Case series	NA	NA	NA	NA	USA	NA	Cotton test	Porcine small intestine submucosal xenograft (Biodesign, Cook Biomedical)	G/A	Anterior-inferior lateral nasal wall	SNOT-25	Significant improvement in SNOT-25	4
Thamboo et al. (2020) [32]	Case series	10	11:3	43.5±12.1	NA	USA	Turbinectomy/turbinoplasty	Cotton test	Porcine small intestine submucosal xenograft (Biodesign, Cook Biomedical), acellular dermal graft (AlloDerm, LifeCell)	NA	Anterior-inferior lateral	ENS6Q, SNOT-22, GAD-7, PHQ-9	Significant improvement in ENS6Q, SNOT-22, GAD-7, and PHQ-9	6
Jiang et al. (2013) [21]	Case series	19	15:4	32.2 (18–64)	NA	China	Partial/total turbinectomy		Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	IT	Acoustic rhinometry, saccharin transit time, SNOT-20	Significant improvement in SNOT-20 and acoustic rhinometry	12
Tam et al. (2014) [26]	Case series	16	10:6	49.1±10.7	NA	Taiwan	NA	Cotton test	Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	Nasal septum, floor	SNOT-22	Significant improvement in SNOT-22	12
Jiang et al. (2014) [25]	Case series	24	18:6	32.4 (18–64)	NA	China	Partial/total turbinectomy		Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	Anterior-inferior lateral nasal wall	SNOT-25	Significant improvement in SNOT-25	10.5 (3–24)
Lee et al. (2018) [29]	Case-control	30	19:11	NA	Lateral, 16/inferior, 14 nasal wall	Taiwan	Turbinectomy	Cotton test	Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	Anterior-inferior lateral nasal wall	SNOT-22, BDI-II, BAI	Significant improvement (more improved in lateral implants) in SNOT-22, BDI-II, and BAI	12
Huang et al. (2021) [36]	Case series	54	36:18	50.9±12.2	NA	Taiwan	NA	Cotton test	Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	Anterior-inferior lateral nasal wall	SNOT-25, BDI-II, BAI	Significant improvement in SNOT-25, BDI-II, and BAI	12
Chang (2024) [33]	Case series	40	31:9	49.6 (23–67)	Hyposmia, 10/normosmia, 30	Taiwan	Partial/total turbinectomy	Cotton test, menthol test	Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	Anterior-inferior lateral nasal wall	Sniffin’ Sticks 12-items odor identification test (Burghart Instruments, Wedel)	Significant improvement in olfaction in hyposmia group; no significant difference in normosmia group	6
Huang et al. (2022) [41]	Case series	74	54:20	50.0±12.3	NA	Taiwan	NA	Cotton test	Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	Anterior-inferior lateral nasal wall	ENS6Q, SNOT-25, BDI-II, BAI	Significant improvement in ENS6Q and SNOT-25	6
Huang et al. (2022) [41]	Case series	74	54:20	50.0±12.3	NA	Taiwan	NA	Cotton test	Polyethylene implant (Medpor, Porex Surgical Inc.)	L/A	Anterior-inferior lateral nasal wall	ENS6Q, SNOT-25, BDI-II, BAI	BDI-II and BAI were not improved.	6
Bastier et al. (2016) [27]	Case series	14	9:5	45.6±8.5	NA	France	Turbinectomy/turbinoplasty	-	β-Tricalcium phosphate implant (Sinus-Up Implants; Kasios)	G/A	Lateral nasal floor	NOSE, RhinoQOL	Significant improvement in NOSE, RhinoQOL	19.4±13.4
Saafan et al. (2013) [23]	Case-control	24	11:13	27±10	Silastic sheet, 12/acellular dermal graft, 12	Egypt	NA	Cotton test	Silastic sheet, acellular dermal graft (AlloDerm, LifeCell)	G/A	Anterior-inferior lateral nasal wall, nasal septum, floor	SNOT-25	Significant improvement in SNOT-25 in both groups	18 (9–24)
Rice (2000) [15]	Case report	1	0:1	42	NA	USA	Complete turbinectomy	-	Hydroxyapatite cement	NA	Anterior-inferior lateral nasal wall	Endoscopic exam	Holds up well after 1 year	12
Modrzynski (2011) [19]	Case series	3	1:2	56.3±8.0	NA	USA	NA	-	Hyaluronic acid gel (Juvéderm, Allergan Inc.)	L/A	IT, nasal septum	Endoscopic exam	Hyaluronic acid was maintained for up to 6 months, but all except one case (33.3%) showed absorption at 12 months.	12
Borchard et al. (2019) [31]	Case series	14	10:4	44.6±13.8	NA	USA	NA	Cotton test	Carboxymethylcellulose/glycerin gel (Prolaryn, Merz)	L/A	Anterior-inferior lateral nasal wall	ENS6Q, SNOT-22, GAD-7, PHQ-9	Maximum effect after 1 week of administration; decreased effect after 1 or 3 months (ENS6Q, SNOT-22, PHQ-9); maintained up to 3 months after maximal effect after 1 month of administration (GAD-7)	3
Jaswal et al. (2008) [17]	Randomized controlled trial	30	NA	28.3 (18–51)	Placentrex injection, 10/oral rifampicin, 10/control, 10	India	NA	-	Placentrex injection	NA	NA	Endoscopic exam, patient symptom score	In the Placentrex injection group, symptoms recurred at an average of 2.7 months.	4
Salaheldin et al. (2012) [20]	Randomized controlled trial	60	36:24	31.5 (18–50)	Submucosal diathermy with, 15 or without, 15 platelet-rich plasma	Egypt	Turbinoplasty (submucosal diathermy)	-	Platelet-rich plasma injection	G/A	IT	Saccharin transit time	No differences between the two groups	2
Friji et al. (2014) [24]	Case series	5	2:3	NA	NA	India	NA	-	Autologous lipoaspirate with platelet-rich plasma injection	NA	IT	SNOT-20, saccharin transit time	Significant improvement in SNOT-20 and saccharin transit time	6
Kim et al. (2021) [37]	Case-control	22	19:3	53.3±12.1	Platelet-rich plasma/saline spray	Korea	NA	-	Platelet-rich plasma injection	L/A	IT	NOSE, SNOT-22, saccharin transit time	Significant improvement in NOSE and SNOT-22. The saccharin transit time slowed down again after maximal effect at 2 months of administration.	6

Values are presented as mean±SD (range), median (range), or mean±SD.

NA, not available; G/A, general anesthesia; CT, computed tomography; VAS, visual analog scale; SNOT, Sino-Nasal Outcome Test; ENS6Q, Empty Nose Syndrome 6-Item Questionnaire; GAD-7, Generalized Anxiety Disorder 7-item scale; PHQ-9, Patient Health Questionnaire-9; IT, inferior turbinate; L/A, local anesthesia; BDI, Beck Depression Inventory; BAI, Beck Anxiety Inventory; NOSE, Nasal Obstruction Symptom Evaluation; RhinoQOL, Rhinosinusitis Quality of Life; SD, standard deviation.

Table 2.

Summary of patient-reported outcome measurements

Study	Assessment tool (min–max)	Pre–post mean differences (SD)
Jang et al. (2011) [18]	VAS (0–10)	Excessive airflow: 6.2 (3.6)
		Nasal obstruction: 5.0 (3.3)
		Nasal or facial pain: 6.0 (3.7)
		Rhinorrhea or postnasal drip: 2.3 (4.7)
		Headache: 8.5 (2.1)
Jung et al. (2013) [22]	SNOT-25 (0–125)	Conchal cartilage: 18.1
Jung et al. (2013) [22]	SNOT-25 (0–125)	Costal cartilage: 21.9
Park et al. (2018) [30]	SNOT-25 (0–125)	102
Malik et al. (2021) [38]	ENS6Q (0–30)	9.2 (4.9)
Dholakia et al. (2021) [35]	ENS6Q (0–30)	ENS6Q: 10.3
	SNOT-22 (0–110)	SNOT-22: 17.4
	GAD-7 (0–21)	GAD-7: 2.3
	PHQ-9 (0–27)	PHQ-9: 2.8
Chang et al. (2021) [34]	ENS6Q (0–30)	15
Ushio et al. (2022) [42]	ENS6Q (0–30)	ENS6Q: 18.6
	SNOT-20 (0–100)	SNOT-20: 24.9
	SNOT-25 (0–125)	SNOT-25: 8.3
Hosokawa et al. (2022) [40]	ENS6Q (0–30)	15.7 (8.2)
Houser et al. (2007) [16]	SNOT-20 (0–100)	20.4 (24.1)
Velasquez et al. (2018) [28]	SNOT-25 (0–125)	22.6 (15.8)
Thamboo et al. (2020) [32]	ENS6Q (0–30)	ENS6Q: 13.3
	SNOT-22 (0–110)	SNOT-22: 31.2
	GAD-7 (0–21)	GAD-7: 9.5
	PHQ-9 (0–27)	PHQ-9: 8.3
Jiang et al. (2013) [21]	SNOT-20 (0–100)	12.4 (20.2)
Tam et al. (2014) [26]	SNOT-22 (0–110)	23.1 (0.8)
Jiang et al. (2014) [25]	SNOT-25 (0–125)	40.6 (28.1)
Lee et al. (2018) [29]	SNOT-22 (0–110)	Inferior nasal wall: 19.6 (33.1)
Lee et al. (2018) [29]	SNOT-22 (0–110)	Lateral nasal wall: 37.5 (29.0)
Huang et al. (2021) [36]	SNOT-25 (0–125)	SNOT-25: 34.7 (34.3)
	BDI-II (0–63)	BDI-II: 12.9 (18.7)
	BAI (0–63)	BAI: 6.5 (13.3)
Chang (2024) [33]	Sniffin’ Sticks 12-item odor identification test (Burghart Instruments) (0–12)	Hyposmia: –1.1 (1.1)
Chang (2024) [33]		Normosmia: –0.1 (0.1)
Huang et al. (2022) [41]	ENS6Q (0–30)	ENS6Q: 8.4 (7.4)
	SNOT-25 (0–125)	SNOT-25: 33.1 (32.0)
	BDI-II (0–63)	BDI-II: 12.0 (17.2)
	BAI (0–63)	BAI: 9.5 (16.3)
Bastier et al. (2016) [27]	NOSE (0–100)	NOSE: 39.3 (36.0)
Bastier et al. (2016) [27]	RhinoQoL (0–100)	RhinoQoL: 32.7 (33.0)
Saafan et al. (2013) [23]	SNOT-25	Silastic implant group: 38.8 (11.5)
Saafan et al. (2013) [23]	SNOT-25	AlloDerm implant group: 33.8 (17.0)
Borchard et al. (2019) [31]	ENS6Q (0–30)	ENS6Q: 5.3 (14.0)
	SNOT-22 (0–110)	SNOT-22: 11.0 (40.5)
	GAD-7 (0–21)	GAD-7: 3.6 (15.6)
	PHQ-9 (0–27)	PHQ-9: 3.7 (16.1)
Friji et al. (2014) [24]	SNOT-20 (0–100)	28.0 (7.2)
Kim et al. (2021) [37]	NOSE (0–100)	NOSE: 12.3 (53.7)
Kim et al. (2021) [37]	SNOT-22 (0–110)	SNOT-22: 9.4 (62.8)

Post-treatment values were calculated based on the final time point. Measurable study data are listed.

SD, standard deviation; VAS, visual analog scale; SNOT, Sino-Nasal Outcome Test; ENS6Q, Empty Nose Syndrome 6-Item Questionnaire; GAD-7, Generalized Anxiety Disorder 7-item scale; PHQ-9, Patient Health Questionnaire-9; BDI, Beck Depression Inventory; BAI, Beck Anxiety Inventory; NOSE, Nasal Obstruction Symptom Evaluation; RhinoQoL, Rhinosinusitis Quality of Life.