Nasal Respiratory Insufficiency (NRI) is a common condition, with a 30%−40% prevalence in the general population.1 The main structure that influences nasal airflow resistance is the inferior turbinate. In fact, studies performing selective decongestion of the inferior turbinate mucosa have shown a 2/3 decrease in nasal resistance.2 Nasal turbinates possess a cavernous vascular system surrounded by elastic and muscular tissue that allows them to change size according to congestion or decongestion.3

Certain nasal pathologies cause hypertrophy of this tissue, which leads to NRI and nasal obstruction. Initial treatment of rhinitis consists of medical therapy, mainly with intranasal corticosteroids and antihistamines.4 In unresponsive patients, clinical guidelines describe several surgical options on the inferior turbinates, such as radiofrequency, cryosurgery, external fracture, microdebrider-assisted turbinoplasty, excision and submucosal resection or partial turbinectomy.5

Although inferior turbinate surgery has been extensively studied and its safety has been well established, it has a high incidence of minor complications, with scabs being the most frequent.6 Until now, the most common postoperative treatment is saline lavage. However, in recent years, therapeutic alternatives have emerged with the aim of improving the time and quality of postoperative recovery.

One of the most studied therapeutic alternatives is the nebulized solution of hyaluronic acid. Several authors have demonstrated improvements related to its use during the postoperative period in terms of quality of life, mucociliary clearance, nasal obstruction, rhinorrhea and nasal dryness.7–9 However, most of the scientific evidence comes from studies performed in patients undergoing endoscopic nasal surgery for chronic rhinosinusitis, a surgery with similar intranasal complications, including scabs and nasal secretions, that are usually more severe than turbinate surgery.

Another effective alternative is nasal xylitol, which has a grade A recommendation in the clinical guidelines of the European Rhinological Society (EPOS guidelines).10 Xylitol has shown potential in treating recurrent respiratory infections when used in nasal lavage11 as well as preventing post-surgical crusting and post-surgical nasal mucosal superinfection following septoplasty and endoscopic sinus surgery.12

Aluneb isotónico® is a medical device authorized for postoperative treatment after nasal surgery containing sodium hyaluronate 0.1%, xylitol 5%, potassium phosphate monobasic 0.05%, and potassium phosphate dibasic 0.03%. In Spain and Italy, it is available over the counter and has a very high safety profile according to previous clinical studies with the product.13 It is authorized for use in both children and adults. It is applied with the intranasal mucosal atomization device (MAD™) nasal irrigation system that allows nebulization in particles of 30−100 microns in diameter.

This randomized clinical trial aims to specifically evaluate the effect of Aluneb® hyaluronic acid plus xilitol in the postoperative treatment of inferior turbinate radiofrequency in adults compared to nebulized isotonic saline.

Participants were recruited between October 2020 to June 2023. 3 participants were lost after the randomization; 2 due to COVID infection (1 in the hyaluronic acid plus xilitol group, 1 in the saline group), and 1 did not attend the postoperative revision (hyaluronic acid plus xilitol group). These patients were excluded and replaced with new participants.

This study has identified better outcomes of hyaluronic plus xylitol nasal nebulization compared to nasal nebulization of saline alone in patients undergoing exclusively turbinate radiofrequency ablation.

There are no other studies conducted exclusively in patients undergoing radiofrequency turbinate ablation. There is one previous RCT by Baptista et al.,21 using hyaluronic plus xylitol nasal rinse on septoplasty plus turbinate surgery. There are no other studies exclusively on turbinate surgery patients, so we will compare our results with Baptista et al. RCT as a surrogate.

The primary endpoints were nasal crusts and nasal symptoms. Reduction of crusting is of utmost importance, as we have identified that scabs are closely related to other variables such as epistaxis and self-reported nasal obstruction. In addition, avoiding crusts improves patient satisfaction and quality of life, at the time it reduces postoperative office visits and economic costs. In our study, we found increased crusting during the first 2 weeks as usual, but these scabs were higher in the saline group. Then both groups decreased, but this decrease was greater in the experimental group (P < .05). It is remarkable that both groups had scabs before surgery, as all the included patients had severe rhinitis. However, after two months of follow-up, the experimental group had less scabbing than before surgery.

The mechanism by which Aluneb® hyaluronic acid plus xilitol may have decreased nasal scabs has been widely discussed and reported in literature. Hyaluronic acid improves mucosal healing, moisturizes the area, and increases mucociliary clearance,8 while xylitol acts as a bacteriostatic agent.

Regarding the secondary endpoint, SNOT-22 experienced an overall decrease in the SNOT-22 in both groups, being lower (4–7 points) at all the postoperative visits in the experimental group, although this difference was not statistically significant. It is also noteworthy that, despite the improvement, neither group reached the normal SNOT-22 value (12 points). Of note is the high baseline SNOT-22 over 40 points in both groups, which is defined as a high value by the EPOS guidelines. This initial value is notably higher than Baptista et al.21 cohorts (29 and 25), but does not differ from other allergic rhinitis cohorts reported in other studies.22

Regarding nasal symptoms assessed through visual analogue scales, there were statistically significant better results for crusts, epistaxis, nasal obstruction and rhinorrhea. Also better results were observed for cacosmia and pain but not being statistically significant. The effect on epistaxis was the most remarkable. The experimental group decreased the epistaxis VAS from the first week after the intervention. Interestingly, there was a significant correlation between crusts and epistaxis, independently of the treatment group since, as mentioned, less scabs, could probably have decreased epistaxis.

However, epistaxis can also be attributed to infection. Both xylitol and hyaluronic acid can exert bactericidal and anti-adhesive effects. Hyaluronic acid can exert in vitro anti-infective and anti-biofilm effects by preventing bacterial adhesion.23 On the other hand, Xylitol is a natural five-carbon sugar alcohol that is commonly used as a sweetener agent and has recently shown potential in treatment of recurrent respiratory infections when used in nasal washes thanks to its innate bactericidal and anti-adhesive effects. Lysozyme, lactoferrin, and β-defensins on the surface of the respiratory tract constitute a part of the local defense system. These have stronger antibacterial activity at low salt concentrations and xylitol is an osmolyte that has a low transepithelial permeability which can reduce the salt concentration to enhance the ability of the airway surface of the nasal mucosa to clear respiratory pathogens.11

Finally, the last secondary endpoint was nasal resistance assessed by rhinomanometry. Nasal resistance was lower in the hyaluronic acid plus xilitol group, but these differences were not statistically significant and probably a larger sample size would have been necessary to detect differences, as this study was underpowered for this variable.

The strengths of this study are, first, the triple blind design. Second, the scab examinations were blinded to the symptoms referred by patients. And third, we could identify differences despite the small sample size.

However, this study may have some limitations and confounding factors that are important to emphasize.

First, surgery was performed by different surgeons. Despite the device being the same, different surgeons may deliver different amounts of energy to the inferior turbinate, which may affect the amount of scar tissue.

Second, sample was expected to be recruited in 6 months. However, we experienced difficulties in including participants, as most people, although willing to collaborate, could not attend all follow-up visits or were afraid to cooperate given the COVID-19 pandemic. Therefore, the recruiting process was extended to 32 months.

The third concern is the atomizer device, which may exert itself a positive effect on recovery. Moffa et al.24 compared different nasal administration devices using a color-based method to determine which device was most effective in topical medication delivery. MAD atomizer provided a more effective way to deliver local drugs deeper and higher in the nasal cavity. In our case, both groups used the MAD atomizer, so the difference cannot be attributed to the method of drug delivery.

Fourth, treatment of the saline group, that was the comparator in our study, may be of concern. Saline nasal rinses are recommended in the EPOS guidelines,10 yet, the quantity is not defined in this guideline. EPOS gudelines state that, up to date, there is not enough evidence to affirm that large-volume rinses are better than low-volume. Being strict, the saline group should not be considered as placebo, since they were receiving the standard of care. In fact, Baptista et al. reported an improvement also in the saline group using MAD nebulizer, which supports that it should indeed not be considered placebo.

Fifth, allergic rhinitis may act as a confounding factor since allergic rhinitis itself improves after hyaluronic acid nebulization.25 In our cohort, allergies were not systematically assessed. It is possible that the prevalence of allergies differed between the experimental and control groups. In such a scenario, given that hyaluronic acid plus xilitol nasal washes also improves allergic rhinitis, participants may have experienced relief from their nasal symptoms not only due to improved surgical healing but also due to the alleviation of allergic rhinitis.

hyaluronic acid plus xilitol demonstrated a significant reduction in nasal crusts, linked to other variables like epistaxis and self-reported nasal obstruction. The VAS scores for epistaxis, nasal obstruction, and rhinorrhea were also significantly improved in the hyaluronic acid plus xilitol group. Nasal resistance was lower in the hyaluronic acid plus xilitol group, although statistical significance was not reached, likely due to the study's limited power for this variable. Hyaluronic acid plus xilitol demonstrated promise in improving postoperative outcomes, future studies with larger sample sizes and different surgical techniques are encouraged.

CCH (design, sample assessment, writing); AGLL (design, writing); BMA (design, sample assessment, writing); MRI (design, sample assessment, writing); DLD (design, sample assessment, writing); JMS (design, writing); SSG (design, sample assessment, critical review of the manuscript); IA (design, sample assessment, critical review of the manuscript).

The study was approved by the ethics committee of Santiago de Compostela (code 2020/389) and was performed in accordance with the ethical standards of the Declaration of Helsinki. All patients signed their informed consent before participating in the study.

Laboratorios Cinfa provided the blinded ampules of the treatment and control group. None of the authors received payment for conducting the study. This study did not receive any grants or external funding.