Severe Xerostomia Research Articles

Comparative efficacy of non-pharmacological interventions on xerostomia and salivary flow rate among hemodialysis patients: a systematic review and network meta-analysis

Abstract Background Xerostomia is a distressing symptom experienced by patients undergoing dialysis. We sought to compare and rank the efficacy of different non-pharmacological interventions on xerostomia and salivary flow rate among dialysis patients. Methods A systematic search was conducted in six English databases: Pubmed, CINAHL, Scopus, Web of Science, Embase, and Cochrane trials, in April 2023. Screening, quality appraisal, and data extraction were undertaken by two independent reviewers. A network meta-analysis was performed to assess the relative efficacy of different non-pharmacological interventions. Results The analysis included 11 randomized controlled trials involving 739 patients and eight non-pharmacological interventions. The pairwise analysis indicated that in comparison with the control group, sugarless candy, chewing sugarless gum, acupressure auricular, and licorice mouthwash had a significant positive effect on reducing the severity of xerostomia, also transcutaneous electrical nerve stimulation (TENS), licorice mouthwash, sugarless chewing gum, photobiomodulation, and pure water mouthwash, significantly improved saliva flow rate. The network analysis indicated that sugarless chewing gum significantly reduced the symptoms of xerostomia, while TENS and sugarless chewing gum were effective in improving UWS. Chewing sugarless gum and using TENS were the top-ranked interventions for relieving xerostomia and enhancing saliva flow rate among dialysis patients, respectively. Conclusions Several non-pharmacological interventions have demonstrated effectiveness in relieving xerostomia and enhancing saliva flow rates. While further research may be needed to confirm and refine these findings the interventions used in this review offer promising results and should be incorporated into the standard care of dialysis patients experiencing these symptoms to enhance their quality of life and oral health.

Sjogren's syndrome due to immune checkpoint inhibitors (ICIs): Insights from a single-institution series and systematic review of the literature.

Careful adverse event assessment and management are important when prescribing immune checkpoint inhibitors (ICIs) to cancer patients. Iatrogenic Sjogren's syndrome is a relatively rare immune-related adverse event (irAEs) that affects the moisture-producing glands. We describe a series of four patients who developed Sjogren's syndrome while being treated with ICIs at a community cancer center in Southern California, USA (1/1/2017-12/31/2023). Patient, drug and disease-related data were collected by retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases in the literature (1/1/2016-12/31//2023). Of 224 cancer patients at our center treated with ICIs, four (1.8%) developed iatrogenic Sjogren's syndrome. All of our patients were male; three received PD-1 inhibitors (nivolumab, pembrolizumab) and one received the PD-L1 inhibitor atezolizumab. The median time to development of Sjogren's syndrome was 24 weeks (range, 8-36 weeks); dry mouth symptoms were more prominent than dry eye symptoms. None of the patients had elevated SS-A, SS-B or antinuclear antibodies. One patient developed multiple tooth cavities and had several extractions, due to severe xerostomia. Management of all patients was primarily symptomatic. Two cases were irreversible; one was reversible and the 4th case is undermined as he is still on ICI therapy. Our systematic review of the literature identified 80 cases in five articles. Incidence of xerostomia was twice of that of xerophthalmia. The male/female ratio was 1.5:1. SS-A, SS-B, or antinuclear antibodies were found in only 9% of patients. Steroids were reported to have had only a limited role in management. The incidence of Sjogren's syndrome due to ICIs in our center was 1.8%. Details of clinical course and management in these patients are presented. Caring for patients with ICI-related Sjogren's syndrome is facilitated by a multidisciplinary effort including oncologists, otolaryngologists, dentists, ophthalmologists and rheumatologists. Expanding the knowledge base pertaining to iatrogenic Sjogren's syndrome in patients on ICIs will be helpful in promoting early detection and treatment, and improving outcomes.

Xerostomia in patients with heart failure - prevalence, intensity and reported strategies of symptom reduction

Abstract Background Xerostomia is a common symptom in patients with chronic heart failure (CHF), with a reported prevalence rate of up to 62%. It is defined as the perception of oral dryness, along with swallowing difficulties, oral burning, and altered taste. Despite being a widespread symptom, xerostomia is insufficiently studied CHF patients from german-speaking countries. Purpose The purpose of this study was to assess the prevalence, perceived intensity, and severity of xerostomia in German CHF patients. Additionally, patients´ reported strategies of symptom reduction were investigated. Methods Multi-center, cross-sectional study. Patients with a confirmed diagnosis of heart failure were recruited during visits to heart failure outpatient clinics or while hospitalized for any reason. If they consented to participate, they received a self-administered questionnaire containing questions about xerostomia, perceived distress and severity of xerostomia, and patients' measures to reduce xerostomia. Disease-related data were extracted from the patients' medical records. Perceived intensity of mouth dryness was measured using a visual analog scale (VAS) with 0 for "little dry" and 100 for "maximum imaginable dryness." To assess the severity of xerostomia, the short version of the xerostomia inventory (XI) was used with 5 items inquiring about the frequency of specific xerostomia symptoms. Sumscores of the XI ranged from 5 to 15, with higher scores indicating a higher severity of xerostomia. Measures to reduce dry mouth could be stated in patients' own words. Results Overall, 371 patients with a mean age of 62.4 (± 14.9) took part in this study. Most patients (230; 62%) had CHF with reduced ejection fraction. The main aetiology for heart failure was ischemic heart disease (118; 31.8%), followed by dilated cardiomyopathy (116; 31.3%). Out of 371 patients, 361 answered the question of whether they had suffered from dry mouth in the last three days. The prevalence rate of xerostomia was 65% (n=234) (95% CI: 60%; 70%). Perceived intensity of mouth dryness, using VAS, was 55.5 (± 22.3). The median severity score of the XI was 9 (Interquartile-Range: 8;11). Patients mostly experienced dry mouth in the morning and at night. The most frequently mentioned measures against dry mouth were drinking something (water, juice, coffee, tea, buttermilk), rinsing or moistening the mouth, sucking candies (sugar-free candies, peppermint, lemon, menthol), eating fruits, and using chewing gums. Conclusion Xerostomia is a widespread symptom in German heart failure patients, affecting more than half of the patients included in the study. The intensity and degree of severity appear to be in a medium range. CHF patients used various interventions to relieve the burden of xerostomia. These measures should be further investigated for their effectiveness.

Xerostomia in a Group of Turkish Patients Using an Online Survey During the COVID-19 Pandemic.

Background Xerostomia is defined as the subjective feeling of dry mouth and affects millions of patients worldwide. Most studies are based on samples of the elderly in nursing homes. This study aimed to investigate the presence of xerostomia and the severity of self-reported xerostomia by sociodemographic variables and to evaluate xerostomia symptoms (self-reported halitosis, burning mouth, and mouth sores) in young adults. Methodology A questionnaire regarding sociodemographic data and the 11-item Xerostomia Inventory was delivered to patients aged 20-65 years who applied to the Ankara University Faculty of Dentistry for dental treatment before the COVID-19 pandemic. Statistical analyses were performed to determine the relationships between the presence of xerostomia and other variables such as age, gender, the presence of a systemic disease, medication use, smoking, alcohol consumption, and the use of removable prostheses. Results A total of 300 patients were included in the study. Xerostomia presence of 54.6% (164 patients) was identified. A significant relationship was found between age and xerostomia (p = 0.023; p = 0.001). The presence of xerostomia decreased as age increased. Xerostomia was more common in female patients (p = 0.028; p = 0.004). The presence of xerostomia was found to be high, not only in the elderly but also in younger adults. Conclusions This study sheds light on the current status, symptoms, and etiology of xerostomia presence in the young population in Turkey. Factors associated with xerostomia were age, female gender, and the number of cigarettes smoked per day. In this study, the high presence of xerostomia was due to smoking.

Potential predictive value of IVIM MR for xerostomia in nasopharyngeal carcinoma

Background and PurposeXerostomia, caused by radiation-induced parotid damage, is the most commonly reported radiotherapy (RT) complication for nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the value of intravoxel incoherent motion (IVIM) MR in monitoring radiation-induced parotid gland damage and predicting the risk of xerostomia. MethodsFifty-four NPC patients were enrolled and underwent at least three IVIM MR scans: before (pre-RT), after 5 fractions of (5th-RT), halfway through (mid-RT), and after RT (post-RT). The degree of xerostomia patients was assessed before each MR examination. Furthermore, the time when patients first reported xerostomia symptoms was recorded. The changes in IVIM parameters throughout RT, as well as the relationships between IVIM parameters and xerostomia, were analysed. ResultAll IVIM parameters increased significantly from pre-RT to post-RT (p < 0.001). The rates of D, D* and f increase increased significantly from pre-RT to mid-RT (p < 0.001), indicating that cell necrosis mainly occurs in the first half of RT. In multivariate analysis, N3 (p = 0.014), pre-D (p = 0.007) and pre-D* (p = 0.003) were independent factors influencing xerostomia. D and f were significantly higher at 5th-RT than at pre-RT (both p < 0.05). IVIM detected parotid gland injury at 5th-RT at an average scanning time of 6.18 ± 1.07 days, earlier than the 11.94 ± 2.61 days when the patient first complained of xerostomia according to the RTOG scale (p < 0.001). ConclusionsIVIM MR can dynamically monitor radiation-induced parotid gland damage and assess it earlier and more objectively than RTOG toxicity. Moreover, IVIM can screen people at risk of more severe xerostomia early.

Abstract ND09: Actinium-225 -PSMA-Trillium (BAY 3563254): Preclinical evaluation and clinical imaging study of a novel 225Ac-labeled PSMA-targeting small molecule triad for the treatment of mCRPC

Abstract With the approval of a PSMA-targeting small molecule labeled with the beta-emitter lutetium-177, PSMA is considered a clinically validated target for the treatment of mCRPC. Although effective, many patients treated with this therapeutic experience only transient clinical benefit, and G1/2 xerostomia is common due to salivary gland toxicity. Since the linear energy transfer and degree of induced DNA damage of alpha particles far exceeds that of beta particles, several investigational PSMA-targeting small molecules labeled with the alpha-emitter 225Ac have generated encouraging preliminary efficacy signals, but with severe xerostomia as a common dose-limiting toxicity. 225Ac-PSMA-Trillium is a novel PSMA-targeting radioligand consisting of a triad of important features: (1) a high-affinity PSMA inhibitor for specific tumor-targeting; (2) a customized albumin-binding domain designed to prolong plasma residence time and increase the therapeutic index by improving tumor uptake while reducing salivary gland uptake; and (3) a “macropa” chelator for efficient and stable radiolabeling with actinium-225. A series of compounds containing the same high-affinity PSMA-targeting moiety, but different chain lengths and albumin-binding domains, were evaluated to identify the optimal combination of features required to achieve the best therapeutic index. In vitro preclinical characterization was performed to test affinities for PSMA and albumin, compound stability and cell-killing potential in LNCaP and 22Rv1 CDX models as well as KuCaP-1 PDX model. Preclinical in vivo investigation of selected compounds showed increased plasma residence time, reduced uptake in normal organs, strong uptake and retention in PSMA-expressing tumors and robust anti-tumor activity. These analyses led to the selection of compounds for further evaluation in a Phase 0 imaging and PK study in mCRPC patients (NCT05773703). In this Phase 0 study, PSMA-Trillium compounds were labeled with indium-111 via a DOTA chelator and used as surrogates to facilitate longitudinal imaging. In patients, 111In-PSMA-Trillium demonstrated targeting to PSMA-expressing tumors as defined by PET/PSMA scans and a plasma residence time consistent with albumin-binding affinities. Importantly, 111In-PSMA-Trillium showed robust uptake and prolonged retention in tumors, and reduced uptake and relatively fast washout from salivary glands. Based on these preclinical data and clinical imaging results, a therapeutic first-in-human trial to evaluate 225Ac-PSMA-Trillium in patients with prostate cancer is anticipated to begin enrolling patients in the first half of 2024. Citation Format: Sabine Zitzmann-Kolbe, Jacob Hesterman, Patricia E. Cole, Nicolas Salem, Alex Papple, Michael Jeffers, Goekben Koca, Thorsten Poethko, Miroslav Dostalek, Shawn Hillier, John W. Babich. Actinium-225 -PSMA-Trillium (BAY 3563254): Preclinical evaluation and clinical imaging study of a novel 225Ac-labeled PSMA-targeting small molecule triad for the treatment of mCRPC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr ND09.

Subjective Oral Dryness following Hematopoietic Cell Transplantation: A Report from the Orastem Study

Xerostomia, or subjective oral dryness, is a serious complaint after hematopoietic cell transplantation (HCT). Xerostomia is rated as one of the most bothersome symptoms by HCT recipients, negatively affecting quality of life. This substudy of the Orastem study, a prospective longitudinal, international, observational, multicenter study, aimed to describe the prevalence and severity of xerostomia following HCT. Furthermore, the effect of the conditioning regimen, type of transplantation, and oral mucosal changes related to chronic graft-versus-host disease (cGVHD) in the development of xerostomia were studied. All HCT recipients rated xerostomia on a scale of 0 to 10 before the conditioning regimen, several times early post-HCT, and at 3 months post-HCT, and only allogeneic HCT recipients also rated xerostomia at 6 and 12 months post-HCT. In addition, stimulated whole mouth saliva was collected several times. Linear regression models and longitudinal mixed-effects models were created to investigate the influence of risk indicators on xerostomia. A total of 99 autologous and 163 allogeneic HCT recipients were included from 6 study sites in Sweden, Canada, the Netherlands, and the United States. The prevalence of xerostomia was 40% before the conditioning regimen, 87% early post-HCT, and 64% at 3 months post-HCT. Complaints after autologous HCT were transient in nature, while the severity of xerostomia in allogeneic HCT recipients remained elevated at 12 months post-HCT. Compared to autologous HCT recipients, allogeneic HCT recipients experienced 1.0 point more xerostomia (95% confidence interval [CI], .1 to 2.0) early post-HCT and 1.7 points more (95% CI, .4 to 3.0) at 3 months post-HCT. Allogeneic HCT recipients receiving a high-intensity conditioning regimen experienced more xerostomia compared to those receiving a nonmyeloablative or reduced-intensity conditioning regimen. The difference was 2.0 points (95% CI, 1.1 to 2.9) early post-HCT, 1.8 points (95% CI, .3 to 3.3) after 3 months, and 1.7 points (95% CI, .0 to 3.3) after 12 months. Total body irradiation as part of the conditioning regimen and oral mucosal changes related to cGVHD did not significantly influence the severity of xerostomia. Conditioning regimen intensity was a significant risk indicator in the development of xerostomia, whereas total body irradiation was not. Allogeneic HCT recipients experienced more xerostomia than autologous HCT recipients, a difference that cannot be explained by a reduction in stimulated salivary flow rate or the development of oral mucosal changes related to cGVHD.

Clinical evaluation of xerostomia manifestations in young-old and middle-old adults

Relevance. The subjective evaluation and analysis of clinical manifestations and risk factors for the development of xerostomia in young- and middle-old adults living in Novosibirsk and the Novosibirsk region plays a leading role in choosing the treatment strategy for this category of patients.Material and methods. A single-stage open study involved 101 people, of whom 48% (n = 49) were male and 52% (n = 52) were female. The average age of the examined was 66.3 [60.0; 88.0] years; 64 subjects were young-old patients (60.0; 75.0), and 37 subjects were middle-old patients (75.0; 88.0). All examined patients underwent an assessment of their dental status and subjective evaluation of xerostomia severity using the validated Russian version of the "The Summated Xerostomia Inventory" (XI). Xerostomia diagnosis in the study patients included the examination according to "The Challacombe Scale of Clinical Oral Dryness" (CSCOD) and sialometry. Taking records of comorbidities, malnutrition syndrome, systemic medications, and bad habits helped to study the risk factors for xerostomia development.Results. The analysis of the subjective evaluation and signs in older patients most frequently revealed moderate xerostomia. There was a moderate negative correlation between the age of the examined and the salivary secretion rate (ρ = -0.578, p &lt; 0.01). Women more often showed severe xerostomia (p &lt; 0.001). The examination of 87.6% of the subjects revealed xerostomia manifestations, confirmed by clinical signs and laboratory data. In 12.4% of patients with complaints and clinical signs of x erostomia, sialometry did not confirm xerostomia.Conclusion. The study results showed a decrease in the secretion rate in older patients with age. In women, complaints and clinical and laboratory signs of xerostomia were more pronounced. Patients' subjective assessment of dry mouth manifestations did not always correspond to the xerostomia clinical and laboratory diagnostic data. The prevalence of xerogenic risk factors was established in young-old and middle-old patients.

Characterization of dysgeusia and xerostomia in patients with multiple myeloma treated with the T-cell redirecting GPRC5D bispecific antibody talquetamab.

In recent years, various immunotherapies have improved the survival of patients with multiple myeloma (MM). However, there remains an unmet need for novel agents. Talquetamab is the first-in-class GPRC5D-targeting T-cell redirecting bispecific antibody, which has substantial activity in advanced MM. Rapidly after the start of talquetamab treatment, patients reported taste changes (dysgeusia; 60% of patients), and a feeling of dry mouth (xerostomia; 30-57% of patients), which may be related to expression of the target antigen in healthy tissues, such as taste buds. Here, we aimed at better characterizing these oral toxicities. We measured salivary flow and the ability to taste (objectively and patient-reported), assessed the feeling of dry mouth, and evaluated quality of life before and 8 weeks after the start of talquetamab therapy in eight heavily pretreated MM patients. Talquetamab treatment led to the rapid and significant decrease in objectively measured taste scores (total score 8.8 ± 2.0 vs 4.9 ± 2.5). All patients reported moderate to severe taste changes. Moreover, patients experienced severe xerostomia after the initiation of talquetamab treatment, in the absence of changes in unstimulated and stimulated salivary flow. Because of these oral toxicities a significant impairment in global health status/(oral health related) quality of life was reported. Studying taste changes in patients treated with talquetamab following up on the described leads provides a new and unique opportunity to further unravel the pathophysiology of taste changes after cancer treatment.

A differentiated approach to complex treatment of radioiodine-induced salivary gland lesions

The number of patients treated with radioactive iodine for highly differentiated thyroid carcinomas who develop chronic radiation-induced salivary gland lesions is constantly rising, that necessitates the search for new pathogenetically focused approaches and methods of treatment considering the stage of the process and pre-existing risk factors.&#x0D; Aim. The aim of the study was to determine the clinical effectiveness of a new pathogenetic therapy based on a differentiated and personalized approach compared to standard approaches for radioactive iodine-induced salivary glands lesions.&#x0D; Materials and methods. The prospective study included 60 patients (5 men and 55 women, aged 45.0 ± 0.5 years) with chronic radioactive iodine-induced salivary gland lesions following radiation treatment. The patients were divided into 2 groups depending on the type of therapy they received. The clinical effectiveness of the developed methods was evaluated with the use of objective clinical criteria within a year after radioiodine therapy.&#x0D; Results. Our approach demonstrated reliably improved treatment outcomes compared to standard techniques. Thus, the treatment we offered, which included long-acting glucocorticoids, proteolysis inhibitors, and sialendoscopic techniques, completely resolved or minimized the clinical manifestations of the disease in 73.3 % of patients (33.3 % in the control group) one year after the start of treatment. The therapeutic effect was not found only in 6.7 % of patients compared to 20.0 % in the control group.&#x0D; The developed approach effectively eliminated saliva outflow disorders and inflammatory symptoms, with significantly better results of the treatment group compared to the control group (χ2 = 6.20; p &lt; 0.05 and χ2 = 6.67; p &lt; 0.05). The disorders of secretory function were more difficult to correct, especially in the later stages of the disease, associated with severe xerostomia development.&#x0D; Conclusions. The differentiated use of the developed pathogenetically oriented complex treatment enabled us to significantly improve the condition of patients with chronic radiation-induced sialoadenitis during the observation period of up to 1 year. This treatment also outperformed traditional symptomatic correction in solving the problem of saliva retention (χ2 = 6.67; p &lt; 0.05) and inflammation manifestations (χ2 = 6.20; p &lt; 0.05). Clinical symptoms of the disease were fully resolved or reduced in 73.3 % of patients versus 33.3 % in control group and partially improved in 20.0 % versus 46.0 % of control group within 12 months after radiation exposure. Longterm treatment and strict adherence to lifestyle and oral hygiene recommendations were required to achieve the desired clinical result and stable remission of clinical symptoms in patients with chronic radiation sialoadenitis.

Claudin-10 Decrease in the Submandibular Gland Contributes to Xerostomia

Tight junction proteins play a crucial role in paracellular transport in salivary gland epithelia. It is clear that severe xerostomia in patients with HELIX syndrome is caused by mutations in the claudin-10 gene. However, little is known about the expression pattern and role of claudin-10 in saliva secretion in physical and disease conditions. In the present study, we found that only claudin-10b transcript was expressed in human and mouse submandibular gland (SMG) tissues, and claudin-10 protein was dominantly distributed at the apicolateral membranes of acini in human, rat, and mouse SMGs. Overexpression of claudin-10 significantly reduced transepithelial electrical resistance and increased paracellular transport of dextran and Na+ in SMG-C6 cells. In C57BL/6 mice, pilocarpine stimulation promoted secretion and cation concentration in saliva in a dose-dependent increase. Assembly of claudin-10 to the most apicolateral portions in acini of SMGs was observed in the lower pilocarpine (1 mg/kg)–treated group, and this phenomenon was much obvious in the higher pilocarpine (10 mg/kg)–treated group. Furthermore, 7-, 14-, and 21-wk-old nonobese diabetic (NOD) and BALB/c mice were used to mimic the progression of hyposalivation in Sjögren syndrome. Intensity of claudin-10 protein was obviously lower in SMGs of 14- and 21-wk-old NOD mice compared with that of age-matched BALB/c mice. In the cultured mouse SMG tissues, interferon-γ (IFN-γ) downregulated claudin-10 expression. In claudin-10–overexpressed SMG-C6 cells, paracellular permeability was decreased. Furthermore, IFN-γ stimulation increased p-STAT1 level, whereas pretreatment with JAK/STAT1 antagonist significantly alleviated the IFN-γ–induced claudin-10 downregulation. These results indicate that claudin-10 functions as a pore-forming component in acinar epithelia of SMGs, assembly of claudin-10 is required for saliva secretion, and downregulation of claudin-10 induces hyposecretion. These findings may provide new clues to novel therapeutic targets on hyposalivation.

NTCP modelling of xerostomia after radiotherapy for oropharyngeal cancer using the PRO-CTCAE and CTCAE scoring systems at different time-points post-RT

PurposeThis study aims at determining the parameter values of three normal tissue complication probability (NTCP) models for the contralateral parotid gland, contralateral submandibular gland (SMG) and contralateral salivary glands regarding the endpoint of xerostomia 6–24 months after radiotherapy for oropharynx cancer. MethodsThe treatment and outcome data of 231 patients with favorable risk, HPV-associated oropharyngeal squamous cell carcinoma are analyzed. 60 Gy intensity modulated radiotherapy was delivered to all the patients. The presence and severity of xerostomia was recorded (pre- and post- radiotherapy) by the PRO-CTCAE and the CTCAE scoring systems. In both scoring systems, patients with a change in symptom severity (from baseline) of ≥ 2 were considered responders. ResultsXerostomia was observed in 61.3 %, 39.2 %, 28.6 % and 27.0 % of the patients based on the PRO-CTCAE scoring system at 6-, 12-, 18- and 24-months post-RT, respectively. The AUCs of the contralateral salivary glands ranged between 0.58–0.64 in the LKB model with the gEUD ranging between 20.3 Gy and 24.7 Gy. ConclusionsBased on the PRO-CTCAE scores, mean dose < 22 Gy, V50 < 10 % for the contralateral salivary glands and mean dose < 18 Gy, V45 < 10 % for the contralateral parotid were found to significantly reduce by a factor of 2–3 the risk for radiation induced xerostomia that is observed at 6–24 months post-RT, respectively. Also, gEUD < 22 Gy to the contralateral salivary glands and < 18 Gy to the contralateral parotid was found to significantly reduce the risk for radiation induced xerostomia that is observed at 6–24 months post-RT by 2.0–2.3 times.

Mitochondrial malfunction mediates impaired cholinergic Ca2+ signalling and submandibular salivary gland dysfunction in diabetes

Xerostomia (dry-mouth syndrome) is a painful and debilitating condition that frequently occurs in individuals with diabetes and is associated with impaired saliva production and salivary gland hypofunction. Saliva fluid production relies on Ca2+-coupled secretion driven by neurotransmitter stimulation of submandibular acinar cells. Although impairments in intracellular Ca2+ signalling have been reported in various xerostomia models, the specific Ca2+-dependent mechanisms underlying saliva fluid hypofunction in diabetes remain unclear. In this study, we show that diabetic animals exhibit severe xerostomia, evident by reduced saliva flow rate, diminished total protein content, and decreased amylase activity in the saliva secreted by submandibular glands. These impairments remained resistant to exogenous cholinergic stimulation. In submandibular acinar cells, the intracellular Ca2+ signals evoked by cholinergic stimulation were reduced and delayed in diabetes, caused by malfunctioning mitochondria. Upon initiation of cholinergic-evoked Ca2+ signals, mitochondria accumulate higher Ca2+ and fail to redistribute Ca2+ influx and facilitate the store-operated Ca2+ entry effectively. Structural damage to mitochondria was evident in the acinar cells in diabetes. These findings provide insights into the potential targeting of malfunctioning mitochondria for the treatment of diabetic xerostomia as an alternative strategy to the existing pharmacotherapeutic approaches.This article is part of the Special Issue on "Ukrainian Neuroscience"

Factors influencing xerostomia and oral health-related quality of life in polymedicated patients.

To evaluate whether the severity of xerostomia in older polymedicated patients impacts oral health-related quality of life (OHRQoL). Medication-associated xerostomia is common in older people. Xerostomia may impair OHRQoL. This cross-sectional study included older hypertensive patients from two health centres. We assessed the severity of xerostomia and OHRQoL using the Xerostomia Inventory (XI) tool, and the Oral Health Impact Profile-14 (OHIP-14) instrument, respectively. We measured unstimulated (UWS) and stimulated (SWS) salivary flows. Univariate and multiple linear regression analyses evaluated the associations of XI and OHIP-14 and different explanatory variables. Of the 218 patients enrolled, 51.8% had xerostomia, and 38.1% and 27.5% suffered from UWS and SWS hyposalivation, respectively. Patients with xerostomia, UWS, and SWS hyposalivation scored significantly higher on the XI. However, only those with xerostomia or UWS hyposalivation had significantly higher OHIP-14 scores. A moderate correlation was observed between XI and OHIP-14 scores. The multiple regression model showed that factors with the greatest impact on XI were the patient's complaint of xerostomia, UWS flow rate, age and sex. However, only the XI score was significantly associated with the OHIP-14 score. Xerostomia has a negative impact on OHRQoL in older polymedicated patients, but this impact is less than in other types of xerostomia. Longitudinal studies are needed to determine whether changes in the detected explanatory variables influence XI and OHIP scores in these patients.

Anticholinergic burden of medications is associated with dry mouth and reflected in minor labial gland secretion

ObjectiveMedications with anticholinergic potential inhibit saliva secretion. Polypharmacy potentiates anticholinergic burden, causing dry mouth symptoms and chronic deterioration of oral health. Patients of any age can be affected by anticholinergic medication-triggered hyposalivation (the objective measure of dry mouth); therefore, seeking predictions of hyposalivation to screen dry mouth is needed. DesignIn our prospective, cross-sectional clinical study, 55 middle-aged adult patients participated. We examined whether the anticholinergic burden calculated from anticholinergic medications (anticholinergic drug score; ADS) and blood serum anticholinergic activity (SAA; the gold standard measure of anticholinergic burden) is associated with hyposalivation. As no prior studies measured minor salivary glands regarding the quantifiable anticholinergic burden, we assessed hyposalivation by the minor saliva flow (MSF) and unstimulated whole saliva (UWS) secretion. ResultsOur data showed a negative linear relationship between SAA and UWS (p < 0.05); when SAA increases by one pmol/ml unit, the saliva flow decreases by 0.058 ml/min. MSF showed a linear correlation (p < 0.005) with UWS. In a multivariate logistic regression model (including age, gender, race, smoking status, xerostomia severity, ADS, and BMI), we identified SAA and age as predictors of hyposalivation (p < 0.05). ConclusionsWe provide evidence for the significant relationship between measurable anticholinergic burden and saliva flow. The correlation between UWS and MSF suggests that both saliva flow rate measurement methods could reflect anticholinergics-induced changes in salivary health.

Perceived Stress, Severity of Xerostomia, and Periodontal Status in Undergraduate Dental Students

Dentistry is a highly stressful program; stress is associated with xerostomia and periodontal disease. Objective: This study aims to investigate the association of perceived stress, severity of xerostomia, and periodontal status in dental students. Methods: This was a two-phase cross-sectional study of 245 Universiti Sains Malaysia (USM) undergraduate dental students. Phase 1 involved administration of the Perceived Stress Scale (PSS-10) and Summated Xerostomia Inventory (SXI). In phase 2, the Community Periodontal Index (CPI) was performed on 150 students to determine their periodontal status. Results: Mean PSS-10 and SXI scores were 19.6 (SD 5.47) and 7.9 (SD 2.04), respectively. Only 7.3% students had healthy periodontium while 17.3% had gingival bleeding, 65.3% had calculus, 6.7% had shallow pockets, and 3.3% had deep pockets. The association of perceived stress, severity of xerostomia, and periodontal status was not significant. Nevertheless, a significant positive correlation was found between PSS-10 and SXI scores (r = 0.318, p &lt; 0.01). Conclusion: Most USM dental students were affected by some degree of periodontal disease, but it was not associated with perceived stress or severity of xerostomia. Students with higher perceived stress had more severe xerostomia. Information from this study could be utilised by the dental school in planning towards providing a stress-free training environment.

Impairment of oral health and its impact on the quality of life of patients with Sjögren's syndrome

AbstractObjectivesThis study aimed to describe the clinical profile and the oral health status and their impact on the quality of life of patients with Sjögren's syndrome (SS).MethodsThrough a cross‐sectional study, patients with SS were compared with those with dry symptoms with no conclusive diagnosis of SS (non‐SS) and patients without complaints of dryness, matched for sex and age (control group). Data related to classification of SS, focus score, unstimulated whole salivary flow (UWSF), dental plaque index, periodontal screening and recording (PSR), decayed, missing and filled teeth (DMFT), and clinical signs of candidiasis were assessed. Colony‐forming units (CFU) of Candida spp were assessed and saliva biochemical analysis was also performed. The Xerostomia Inventory (XI) and Oral Health Impact Profile 14 (OHIP‐14) questionnaire were applied to assess the severity of xerostomia and quality of life.ResultsThirty‐three patients with primary SS, 22 with secondary SS, nine non‐SS, and 23 from control group were included. Patients with primary SS, secondary SS and non‐SS had lower UWSF and higher rates of plaque, PSR and DMFT than the control group. Candida spp. count was also higher in SS groups. Osmolality, buffering capacity and protein concentration in saliva were similar between groups. The scores of XI and OHIP‐14 were higher in the SS and non‐SS groups and showed positive correlation with PSR and DMFT and negative correlation with UWSF.ConclusionSS is associated with poor oral health, mainly related to dental and periodontal problems, which exert a negative impact on quality of life.

Oral health-related quality of life and xerostomia in type 2 diabetic patients.

Diabetes mellitus (DM) is a known risk factor for xerostomia. Oral health-related quality of life (OHRQoL) is a multi-dimensional issue reflecting several effects of the oral condition on the quality of life. The present study aimed to assess OHRQoL and its relationship with xerostomia severity in type 2 diabetic patients. A total of 200 patients participated in this cross-sectional study. The Xerostomia Inventory (XI) assessed xerostomia severity and the Oral Health Impact Profile-14 (OHIP-14) questionnaire evaluated OHRQoL. In addition, the fasting blood sugar (FBS) and glycated hemoglobin (HbA1c) tests were conducted, and the results were recorded, as well as the disease duration and denture wearing. Data analysis employed the t test and Pearson's correlation coefficient. The mean XI score was 22.27 ±6.92 and the mean OHIP-14 score was 13.76 ±8.41. The mean FBS, HbA1c and disease duration values were 161.23 ±49.14 mg/dL, 7.90 ±1.12% and 11.02 ±7.78 years, respectively. The OHIP-14 score correlated significantly with the XI score, age, FBS, HbA1c, the disease duration, and denture wearing (p < 0.05). There was a significant correlation between OHRQoL and xerostomia severity in patients with type 2 DM. Age, denture wearing, the disease duration, and the medical management of DM also correlated significantly with OHRQoL. Treating both the underlying disease and oral health comorbidities, such as xerostomia, seems to be essential for achieving a better OHRQoL in type 2 diabetic patients.

The effect of gum chewing on xerostomia and salivary flow rate in elderly and medically compromised subjects: a systematic review and meta-analysis

BackgroundXerostomia negatively affects quality of life. Symptoms include oral dryness; thirst; difficulty speaking, chewing, and swallowing food; oral discomfort; mouth soft tissue soreness and infections; and rampant tooth decay. The objective of this systematic review and meta-analysis was to investigate if gum chewing is an intervention that results in objective improvements in salivary flow rates and subjective relief from xerostomia.MethodWe searched electronic databases including Medline, Scopus, Web of Science, Embase, Cochrane Library (CDSR and Central), Google Scholar and the citations of review papers (last searched 31/03/23). The study populations included: 1) elderly people with xerostomia (> 60 years old, any gender, and severity of xerostomia), and 2) medically compromised people with xerostomia. The intervention of interest was gum chewing. Comparisons included gum chewing vs. no gum chewing. The outcomes included salivary flow rate, self-reported xerostomia, and thirst. All settings and study designs were included. We conducted a meta-analysis on studies where measurements of unstimulated whole salivary flow rate for both a gum chewing, and no gum chewing intervention (daily chewing of gum for two weeks or longer) were reported. We assessed risk of bias using Cochrane’s RoB 2 and ROBINS-I tools.ResultsNine thousand six hundred and two studies were screened and 0.26% (n = 25) met the inclusion criteria for the systematic review. Two of the 25 papers had a high overall risk of bias. Of the 25 papers selected for the systematic review, six met the criteria to be included in the meta-analysis which confirmed a significant overall effect of gum on saliva flow outcomes compared to control (SMD = 0.44, 95% CI: 0.22—0.66; p = 0.00008; I2 = 46.53%).ConclusionsChewing gum can increase unstimulated salivary flow rate in elderly and medically compromised people with xerostomia. Increasing the number of days over which gum is chewed increases the improvement in the rate of salivation. Gum chewing is linked with improvements in self-reported levels of xerostomia (although it is noted that no significant effects were detected in five of the studies reviewed). Future studies should eliminate sources of bias, standardise methods to measure salivary flow rate, and use a common instrument to measure subjective relief from xerostomia.Study registrationPROSPERO CRD42021254485.

Smell Dysfunction in Patients with Primary Sjögren's Syndrome: Impact on Quality of Life.

Patients with primary Sjögren's syndrome (pSS) often report smell and taste disturbances. However, the correlation between smell impairment and mucosal dryness is not well understood. The objectives of this study were to investigate the following: (1) the prevalence of smell hypofunction in patients with SS; (2) the impact of smell hypofunction on their quality of life (QoL); (3) whether the patients' smell is correlated with xerostomia; and (4) whether the patients' smell is affected by taste hypofunction, disease duration, age, smoking or self-reported neuropathy. An ethically approved cross-sectional study was conducted on 65 female patients with SS and 62 sex-matched healthy controls. Their smell was assessed using the University of Pennsylvania Smell Identification Test. Their taste acuity was assessed using the Taste Strips Test. A visual analogue scale was used for the self-assessment of smell and taste functions. Xerostomia was assessed by the salivary flow rate, clinical oral dryness score and the Xerostomia Inventory. The patients' QoL and mental health well-being were assessed using validated questionnaires. In the SS group, the patients' smell function was impaired in 27/65 patients compared with the controls (15/62, p < 0.05), and it did not correlate with the severity of xerostomia, taste acuity (r = 0.05, p = 0.6) or self-reported nasal dryness (r = -0.02, p = 0.7). In the patients' group, smell hypofunction was not correlated with disease duration (β = 0.1, 95% CI = -0.07-0.1) or smoking (β = -0.02, 95% CI = -8-7). Age was not correlated with the smell function in the patients' group (β = -0.1, p = 0.5) but was correlated significantly with smell in the healthy participants' group (β = -0.3, p = 0.02). Neuropathy affected 81.2% of the patients' group. Their QoL and mental health well-being were not affected by smell hypofunction. Smell hypofunction appears to be a clinical manifestation in patients with SS, but it does not seem to be associated with the severity of mucosal dryness or with taste disturbance.