Xerostomia and hyposalivation.

World Workshop on Oral Medicine VIII: Development of a core outcome set for dry mouth: a systematic review of outcome domains for salivary hypofunction

The salivary gland is a complex organ exhibiting a branching, 3-dimensional structure made up of acinar (saliva-producing), and ductal (saliva transporting and modifying) epithelial cells. The high surface area of the gland allows it to efficiently provide the mouth with saliva, maintaining oral cleanliness and comfort. Salivary gland hypofunction, a significant clinical problem often caused by the autoimmune disease Sjögren's syndrome or head and neck radiation for cancer patients, affects millions of Americans and is characterized by a loss of function of salivary gland acinar cells. Chronic xerostomia, or dry mouth, arises as a result of salivary gland hypofunction and can lead to tooth decay, tooth loss, gum disease, and oral infections, as well as a decreased ability to chew, swallow, and speak. Treatment options for patients with salivary gland hypofunction include the use of artificial saliva which is temporary and often inadequate, or medications to stimulate residual acinar cells which can introduce unwanted side effects.

Salivary gland (SG) hypofunction and oral dryness can be induced by radiotherapy for head and neck cancers or autoimmune disorders. These are common clinical conditions that involve loss of saliva-secreting epithelial cells. Several oral complications arise with SG hypofunction that interfere with routine daily activities such as chewing, swallowing, and speaking. Hence, there is a need for replacing these saliva-secreting cells. Recently, researchers have proposed to repair SG hypofunction via various cell-based approaches in three-dimensional (3D) scaffold-based systems. However, majority of the scaffolds used cannot be translated clinically due to the presence of non-human-based substrates. Herein, saliva-secreting organoids/mini-glands were developed using a new scaffold/substrate-free culture system named magnetic 3D levitation (M3DL), which assembles and levitates magnetized primary SG-derived cells (SGDCs), allowing them to produce their own extracellular matrices. Primary SGDCs were assembled in M3DL to generate SG-like organoids in well-established SG epithelial differentiation conditions for 7days. After such culture time, these organoids consistently presented uniform spheres with greater cell viability and pro-mitotic cells, when compared with conventional salisphere cultures. Additionally, organoids formed by M3DL expressed SG-specific markers from different cellular compartments: acinar epithelial including adherens junctions (NKCC1, cholinergic muscarinic receptor type 3, E-cadherin, and EpCAM); ductal epithelial and myoepithelial (cytokeratin 14 and α-smooth muscle actin); and neuronal (β3-tubulin and vesicular acetylcholine transferase). Lastly, intracellular calcium and α-amylase activity assays showed functional organoids with SG-specific secretory activity upon cholinergic stimulation. Thus, the functional organoid produced herein indicate that this M3DL system can be a promising tool to generate SG-like mini-glands for SG secretory repair.

The purposes of this study were to examine the effects of oral exercise intended to improve the function of the oral cavity in the elderly and their quality of life to pave the way for the development of oral-health promotion programmes geared towards the elderly. The subjects were 78 female Koreans who resided in Seoul and were aged 65 years and older. During a 3-month period, an oral function promotion programme was conducted twice a week, between 10.00 am and 12.00 pm, applying oral exercise suggested by a Japanese public health centre. A survey was conducted by interviewing the selected women to determine the state of their subjective dry mouth, quality of life related to oral health and jaw functional limitation. Their opening, unstimulated whole saliva and pronunciation speed were measured before and after the oral function exercise programme. The subjects showed a significant improvement in subjective dry mouth symptoms, relevant behaviour, the level of discomfort caused by dry mouth and subjective jaw functional limitation during mastication and swallowing and emotional expression after receiving the oral exercise. After the oral exercise, there was a significant increase in mouth opening, unstimulated whole saliva and speaking speed ('patakala' pronunciation) after oral exercise. There was also significant progress in their quality of life related to oral health. Overall improvement in subjective dry mouth symptoms and relevant behaviour over time after oral exercise had a positive correlation with the level of improvement in discomfort triggered by dry mouth and mastication. The level of improvement in OHIP-14 had a positive correlation with the level of overall improvement in dry mouth symptoms and behaviour, the level of improvement in discomfort by dry mouth and that in mastication and swallowing. This study showed the effects of the oral function promotion programme and correlation of oral condition and oral health-related quality of life. It is suggested that this oral function promotion programme has positive effects on both objective and subjective oral conditions. It is strongly recommended that this programme, along with other oral health promotion programmes, be implemented to improve oral function and oral health-related quality of life for the elderly.

<div>Abstract<p>Head and neck cancer patients treated by radiation commonly suffer from a devastating side effect known as dry-mouth syndrome, which results from the irreversible loss of salivary gland function via mechanisms that are not completely understood. In this study, we used a mouse model of radiation-induced salivary hypofunction to investigate the outcomes of DNA damage in the head and neck region. We demonstrate that the loss of salivary function was closely accompanied by cellular senescence, as evidenced by a persistent DNA damage response (γH2AX and 53BP1) and the expression of senescence-associated markers (SA-βgal, p19ARF, and DcR2) and secretory phenotype (SASP) factors (PAI-1 and IL6). Notably, profound apoptosis or necrosis was not observed in irradiated regions. Signs of cellular senescence were also apparent in irradiated salivary glands surgically resected from human patients who underwent radiotherapy. Importantly, using IL6 knockout mice, we found that sustained expression of IL6 in the salivary gland long after initiation of radiation-induced DNA damage was required for both senescence and hypofunction. Additionally, we demonstrate that IL6 pretreatment prevented both senescence and salivary gland hypofunction via a mechanism involving enhanced DNA damage repair. Collectively, these results indicate that cellular senescence is a fundamental mechanism driving radiation-induced damage in the salivary gland and suggest that IL6 pretreatment may represent a promising therapeutic strategy to preserve salivary gland function in head and neck cancer patients undergoing radiotherapy. <i>Cancer Res; 76(5); 1170–80. ©2016 AACR</i>.</p></div>

Severe salivary gland hypofunction is frequently found in patients with Sjögren's syndrome and those who receiving therapeutic irradiation in their head and neck regions for cancer treatment. Both groups of patients experience symptoms such as xerostomia (dry mouth), dysphagia (impaired chewing and swallowing), severe dental caries, altered taste, oro-pharyngeal infections (candidiasis), mucositis, pain and discomfort. One innovative approach of regenerative medicine for the treatment of salivary gland hypo-function is speculated in RS Redman, E Mezey et al. 2009: stem cells can be directly deposited by cannulation into the gland as a potent method in reviving the functions of the impaired organ. Presumably, the migrated foreign stem cells will differentiate into glandular cells to function as part of the host salivary gland. Also, this cannulation technique is an expedient and effective delivery method for clinical gene transfer application. Here we illustrate the steps involved in performing the cannulation procedure on the mouse submandibular salivary gland via the Wharton's duct (Fig 1). C3H mice (Charles River, Montreal, QC, Canada) are used for this experiment, which have been kept under clean conventional conditions at the McGill University animal resource center. All experiments have been approved by the University Animal Care Committee and were in accordance with the guidelines of the Canadian Council on Animal Care. For this experiment, a trypan blue solution is infused into the gland through the opening of the Wharton's duct using a insulin syringe with a 29-gauge needle encased inside a polyethylene tube. Subsequently, the mouse is dissected to show that the infusions migrated into the gland successfully.

Radiation induced structural damage of salivary gland including reducing acinar cell and fibrosis. These changes result in hypofunction of salivary gland which has a significant impact on the quality of life of head and neck cancer patients who treated with radiotherapy. Nevertheless, no preventive method has been found. Metformin, a diabetes drug, has recently attracted considerable attention because it can cause tissue regeneration by anti‐inflammatory action and influencing stem cells. This study examined the effects of metformin on salivary gland tissue damage caused by radiation therapy. Cultured human parotid epithelial cells are irradiated with 15 Gy of 4MV X‐rays. The analysis including DNA damage, inflammatory markers and proliferation, is conducted to confirm the effect of metformin. Similarly, an in vivo mouse model is established. Histologic and functional analyses, such as salivary flow rate and lag time, are performed. The in vitro experiment revealed irradiation increased DNA damage, NF‐кB, IL‐6, and apoptosis with reduced proliferation. The treatment with metformin decreased the radiation‐induced DNA damage and inflammation, and increased proliferation. The in vivo model also shows the same results. The group taking metformin after irradiation has preserved salivary gland parenchyma compared to irradiation only group, and the functional analysis results are comparable to the normal group. Histologic and functional analysis shows that metformin reduced radiation‐induced hypofunction of salivary gland. Hence, metformin can be used to prevent radiation‐induced salivary gland dysfunction.

BackgroundThis study aimed to investigate the homogeneity of the major salivary glands in multiple sclerosis (MS) patients using ultrasonography (USG), assess DMFT indices, measure resting salivary flow rates, and compare these values with healthy individuals.MethodsIn this study, 20 individuals diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) (mean age 36.15 ± 8.51) and 20 systemically healthy individuals (mean age 35.7 ± 9.22) were included. Oral and radiologic examinations were performed in all individuals. The parotid and submandibular salivary glands were examined using USG, and their homogeneity was assessed based on the scoring system recommended by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) study group. Resting salivary flow rates and DMFT indices were measured, and the obtained data were subjected to statistical analysis.ResultsThe parotid glands exhibited more heterogeneity on USG within the MS patient group than the control group, with a statistically significant difference between the two groups (p = 0.015). A statistically significant correlation was observed in total homogeneity values between the patient and control groups (p = 0.021). Furthermore, the MS patient group exhibited higher DMFT indices and lower salivary flow rates than the control group. The difference between the DMFT indices and salivary flow rate between the patient groups was statistically significant (p = 0.004 and p = 0.002 respectively).ConclusionsThe parenchyma of the major salivary glands in MS patients exhibited decreased homogeneity than the healthy controls. Additionally, the MS group showed a decrease in salivary flow rate and an increase in the DMFT index. Autonomic dysfunction and medications used for MS are thought to cause salivary gland hypofunction and dry mouth. It can be interpreted that hyposalivation and motor skill losses in MS patients lead to an increase in DMFT index.

Role of Antimuscarinics Combined With Alpha-blockers in the Management of Urinary Storage Symptoms in Patients With Benign Prostatic Hyperplasia: An Updated Systematic Review and Meta-analysis.

Objectives Periodontal disease, characterized by subgingival biofilm dysbiosis and Porphyromonas gingivalis (P. gingivalis) colonization, has been increasingly implicated in Alzheimer’s disease (AD) pathogenesis. This review systematically delineates the pathophysiological mechanisms underlying the periodontal–AD nexus, highlighting olfactory dysfunction (OD) and salivary gland hypofunction as putative prodromal biomarkers for periodontal disease-associated AD progression. Methods PubMed/MEDLINE database was systematically searched for English-language articles published between January 1994 and March 2025. Search terms encompassed periodontal disease, Porphyromonas gingivalis, Alzheimer’s disease, neuroinflammation, olfactory dysfunction, salivary gland hypofunction, blood-brain barrier, microglial activation, and cognitive decline. Results Periodontal disease compromises blood-brain barrier integrity via bacterial translocation, systemic pro-inflammatory mediator dissemination, and peripheral immune cell activation, thereby potentiating microglial polarization and neuroinflammatory cascades integral to early AD neuropathology. Both OD and salivary gland hypofunction demonstrate robust associations with periodontal disease severity and constitute sensitive biomarkers for prodromal AD. Conclusions Periodontal disease-mediated neuroinflammation constitutes a pivotal mechanistic pathway linking oral dysbiosis to AD onset. OD and salivary gland hypofunction emerge as promising early diagnostic indicators for periodontal disease-associated AD susceptibility, warranting prospective clinical validation.

Multiple oral complaints develop following high-dose chemo/radiotherapy and hematopoietic cell transplantation (HCT) which can influence quality of life. The purpose of this investigation was to assess quality of life, oral function, taste and smell in a cohort of patients following HCT. A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC)) Quality of Life (QOL) questionnaire (QLQ-C30), with an added oral symptom and function scale and assessment of taste and smell was administered to a consecutive series of patients at day 90-100 post HCT. General QOL was impacted by fatigue, affecting physical, social emotional and cognitive function. While oral function scales appeared to be little affected at day 90-100 post HCT, abnormalities of taste were reported. Reports of changes in taste and smell appeared to parallel each other and changes remained at the time of the survey post-HCT. Change in taste appeared to be closely associated with dry mouth. Patients appeared to have difficulty in differentiating sour and bitter, which had been more affected than salt and sweet taste. Females appeared to report greater changes in taste than males. Increased smell sensitivity and taste change resulted in changes in food preparation in some cases, as did reported increase in sensitivity to sour and bitter taste. Acute complications are well known to affect QOL during the early period following HCT, but little assessment of long-term changes in oral QOL and taste has been conducted following transplant. The EORTC QLQ C-30 questionnaire with the oral addendum provides a measure of the quality of life and oral function, and may provide useful outcome measures for assessment of oral care prevention and management in HCT patients.

Purpose: The aim of the study was to determine the changes in swallowing function and quality of life in early period a er radiotherapy in head and neck cancer (HNC) patients. Methods: Fourty patients with HNC were included in the study. Swallowing function was evaluated by Modified Barium Swallowing Study. Penetration-Aspiration Scale was used to determine the penetration aspiration severity. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and European Organization for the Research and Treatment of Cancer, Quality of Life Assessments in Head and Neck Cancer (EORTC QLQ-H&N35) which are specific to cancer patients with acceptable validity and reliability were used for quality of life assessment. All evaluations were performed three times including before radiotherapy, 1 and 3 months a er radiotherapy. Results: The aspiration severity were gradually increased a er radiotherapy (p 0.0166). Pain and fee - ling illness decreased (p<0.001), swallowing problems, dry mouth, sticky saliva (p<0.001), teeth, mouth-opening problems (p<0.016) increased a er radiotherapy. There was a moderate, negative correlation between aspiration severity and general health status scale (p<0.001). There was a moderate, positive correlation between aspiration severity and symptom scale, swallowing ability, social eating, dry mouth, sticky saliva and coughing (p<0.05). Discussion: It can be concluded that swallowing function and swallowing related quality of life parameters were a ected negatively in the early period a er radiotherapy despite no change in general quality of life perception. It is important for clinicians to be aware of swallowing disorders and its e ects on quality of life in the early period to prevent patients from potential long-term e ects of swallowing disorders on general quality of life.

Introduction Approximately 60% of older adults complain of dry mouth which may be associated with polypharmacy, common in this population. Existing studies have reported treatment approaches to dry mouth but do not address long-term, preventative measures that would more positively benefit the health and wellbeing of older adults.1 Aim This rapid systematic review aims to identify the implications of dry mouth on the physical and psychological wellbeing of older adults with polypharmacy to establish the importance of preventing dry mouth. Methods Studies reporting health implications of dry mouth, in relation to polypharmacy in older adults (&amp;gt;65 years old), were included in this rapid systematic review. MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched using Keywords such as ‘polypharmacy’, ‘dry mouth’, ‘oral health’ and ‘quality of life’ (PROSPERO: CRD42021288945). Joanna Briggs Institute critical appraisal tools were used to assess study quality. Ethical approval was not required for this project due to the methodology of this rapid systematic review. Results Of the 6,852 citations screened, 9 studies (cross-sectional, n = 8; longitudinal, n = 1) were included which comprised 37,459 participants (mean age range: 68.5-85.0 years). Studies were published between 2005 and 2019. Meta-analysis was not possible due to the heterogenicity of outcomes reported; instead, a narrative synthesis was undertaken. The health implications identified in this review were categorised as ‘physical’, such as tooth loss, or ‘psychological’, such as depression. The main physical health implications reported in the studies related to dental health, such as tooth loss and gingivitis, as well as functional impairments, such as chewing and swallowing difficulties. An increase in the number of medicines taken, from 0 to 5, decreased the number of natural teeth remaining from 16.35 ±8.58 to 11.74 ±7.88, respectively. Additionally, the number of dental complications increased from 1.43 ±2.1 to 2.33 ±2.2 as the number of medicines increased from 1 to &amp;gt;3, respectively. There was a paucity of studies (n = 2) that investigated the psychological health implications of dry mouth upon older adult populations. Depression, was however, identified as a significant consequence of dry mouth in older adults with a prevalence as high as 64%.2 An additional 6 psychological health implications were identified, for example, self-consciousness. Discussion/Conclusion This review examined the health implications of dry mouth in relation to polypharmacy in older adults, including physical health and psychological health implications. There were limitations in this review; for example, the predominant cross-sectional study design restricted findings due to the inability to establish longitudinal associations. High levels of physical health implications of dry mouth were observed in older adults with polypharmacy and, to a lesser extent, psychological health implications. The modifiable nature of polypharmacy could pave the way for prevention strategies of dry mouth. The optimisation of medication regimens, to effectively treat chronic conditions but also limit the likelihood of dry mouth, is a practical approach to achieve this.3

PurposeThis study evaluated the changes in nutritional status based on quality of life (QoL) item-level analysis to determine whether individual QoL responses might facilitate personal clinical impact.Materials and MethodsThis study retrospectively evaluated QoL data obtained by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) and Quality of Life Questionnaire-Stomach (QLQ-STO22) as well as metabolic-nutritional data obtained by bioelectrical impedance analysis and blood tests. Patients were assessed preoperatively and at the 5-year follow-up. QoL was analyzed at the level of the constituent items. The patients were categorized into vulnerable and non-vulnerable QoL groups for each scale based on their responses to the QoL items and changes in the metabolic-nutritional indices were compared.ResultsMultiple shortcomings in the metabolic-nutritional indices were observed in the vulnerable groups for nausea/vomiting (waist-hip ratio, degree of obesity), dyspnea (hemoglobin, iron), constipation (body fat mass, percent body fat), dysphagia (body fat mass, percent body fat), reflux (body weight, hemoglobin), dry mouth (percent body fat, waist-hip ratio), and taste (body weight, total body water, soft lean mass, body fat mass). The shortcomings in a single index were observed in the vulnerable groups for emotional functioning and pain (EORTC QLQ-C30) and for eating restrictions (EORTC QLQ-STO22).ConclusionsLong-term postoperative QoL deterioration in emotional functioning, nausea/vomiting, pain, dyspnea, constipation, dysphagia, reflux, eating restrictions, dry mouth, and taste were associated with nutritional shortcomings. QoL item-level analysis, instead of scale-level analysis, may help to facilitate personalized treatment for individual QoL respondents.

Head and neck cancer (HNC) treatment results in morbidity impacting quality of life (QOL) in survivorship. This analysis evaluated changes in oral health-related QOL (OH-QOL) up to 2years after curative intent radiation therapy (RT) for HNC patients and factors associated with these changes. 572 HNC patients participated in a multicenter, prospective observational study (OraRad). Data collected included sociodemographic, tumor, and treatment variables. Ten single-item questions and 2 composite scales of swallowing problems and senses problems (taste and smell) from a standard QOL instrument were assessed before RT and at 6-month intervals after RT. The most persistently impacted OH-QOL variables at 24months included: dry mouth; sticky saliva, and senses problems. These measures were most elevated at the 6-month visit. Aspects of swallowing were most impacted by oropharyngeal tumor site, chemotherapy, and non-Hispanic ethnicity. Problems with senses and dry mouth were worse with older age. Dry mouth and sticky saliva increased more among men and those with oropharyngeal cancer, nodal involvement, and use of chemotherapy. Problems with mouth opening were increased by chemotherapy and were more common among non-White and Hispanic individuals. A 1000cGy increase in RT dose was associated with a clinically meaningful change in difficulty swallowing solid food, dry mouth, sticky saliva, sense of taste, and senses problems. Demographic, tumor, and treatment variables impacted OH-QOL for HNC patients up to 2years after RT. Dry mouth is the most intense and sustained toxicity of RT that negatively impacts OH-QOL of HNC survivors. NCT02057510; first posted February 7, 2014.