Association of Hyper-Low-Density Lipoprotein and Hypo-High-Density Lipoprotein Cholesterolemia with Low Saliva Flow Rates in Japanese Community-Dwelling Elders

Abstract Introduction The associations of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) with reduced saliva flow rates have not been previously reported. Objective The present study aimed to assess the association of cholesterolemia with reduced saliva flow rates in community-dwelling elderly subjects. Methods The present study analyzed 342 participants (170 males and 172 females aged between 78 and 79 years old). Unstimulated salivary flow rate (USFR) was assessed using a cotton roll method. Low-USFR was defined as 0.10 g/30 seconds. Stimulated salivary flow rate (SSFR) was assessed by having the participants chew tasteless gum for 3minutes. Low-SSFR was defined as 1.0 mL/minute. Blood samples were collected for the measurement of LDL-C, HDL-C, rheumatoid factor, hemoglobin A1c, and creatinine. To assess depression, the General Health Questionnaire 30 was used. A standardized questionnaire was completed, covering the current and previous medications of the participants and smoking status. We stratified the serum LDL-C levels of the participants as normal, moderate or severe hyper-LDL cholesterolemia and serum HDL-C levels as normal or hypo-HDL cholesterolemia. Multivariate logistic regression models were established and low-USFR or low-SSFR were set as dependent variables in the aforementioned models. Results After controlling for the effects of the other variables, the odds ratios (ORs) (95% confidence intervals [CIs]) for low-USFR were 2.25 (1.10-4.61) for moderate and 5.69 (1.55-20.8) for severe hyper-LDL cholesterolemia, while that of hypo-HDL cholesterolemia was 3.40 (1.33-8.69). Severe hyper-LDL cholesterolemia was also associated with low-SSFR with an OR of 3.89 (1.39-10.88). Conclusion Elderly patients with cholesterolemia have a risk of reduced salivary flow rate.

Association of Hyper-Low-Density Lipoprotein and Hypo-High-Density Lipoprotein Cholesterolemia with Low Saliva Flow Rates in Japanese Community-Dwelling Elders.

Introduction The associations of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) with reduced saliva flow rates have not been previously reported. Objective The present study aimed to assess the association of cholesterolemia with reduced saliva flow rates in community-dwelling elderly subjects. Methods The present study analyzed 342 participants (170 males and 172 females aged between 78 and 79 years old). Unstimulated salivary flow rate (USFR) was assessed using a cotton roll method. Low-USFR was defined as 0.10 g/30 seconds. Stimulated salivary flow rate (SSFR) was assessed by having the participants chew tasteless gum for 3 minutes. Low-SSFR was defined as 1.0 mL/minute. Blood samples were collected for the measurement of LDL-C, HDL-C, rheumatoid factor, hemoglobin A1c, and creatinine. To assess depression, the General Health Questionnaire 30 was used. A standardized questionnaire was completed, covering the current and previous medications of the participants and smoking status. We stratified the serum LDL-C levels of the participants as normal, moderate or severe hyper-LDL cholesterolemia and serum HDL-C levels as normal or hypo-HDL cholesterolemia. Multivariate logistic regression models were established and low-USFR or low-SSFR were set as dependent variables in the aforementioned models. Results After controlling for the effects of the other variables, the odds ratios (ORs) (95% confidence intervals [CIs]) for low-USFR were 2.25 (1.10-4.61) for moderate and 5.69 (1.55-20.8) for severe hyper-LDL cholesterolemia, while that of hypo-HDL cholesterolemia was 3.40 (1.33-8.69). Severe hyper-LDL cholesterolemia was also associated with low-SSFR with an OR of 3.89 (1.39-10.88). Conclusion Elderly patients with cholesterolemia have a risk of reduced salivary flow rate.

Characteristics of medication-induced xerostomia and effect of treatment.

OBJECTIVE: Side-effects of medications cause xerostomia. There have been cases where a medication has been discontinued owing to its severe side-effects. Therefore, the xerostomia must be treated to ensure that the primary disease is managed effectively. This study analyzed the actual status of patients with medication-induced xerostomia and investigates factors associated with its improvement. METHODS: This study assessed 490 patients diagnosed with medication-induced xerostomia who had an unstimulated salivary flow of ≤0.1 mL/min and received treatment for xerostomia at a xerostomia clinic. Patient age, sex, medical history, medications used, disease duration of xerostomia, and psychological disorders were recorded. The anticholinergic burden was assessed using the Anticholinergic Cognitive Burden scale. The unstimulated salivary flow was measured by the spitting method. According to their symptoms and diagnoses, the patients were introduced to oral lubricants, instructed on how to perform massage, and prescribed Japanese herbal medicines, and sialogogues. Factors associated with the subjective improvement of xerostomia and objective changes in the salivary flow rate were recorded at six months. RESULTS: Xerostomia improved in 338 patients (75.3%). The improvement rate was significantly lower in patients with psychiatric disorders (63.6%) (P = 0.009). The improvement rate decreased as more anticholinergics were used (P = 0.018). However, xerostomia improved in approximately 60% of patients receiving three or more anticholinergics. The unstimulated salivary flow increased significantly more in patients who reported an improvement of xerostomia (0.033±0.053 mL/min) than in those who reported no improvement (0.013±0.02 mL/min) (P = 0.025). CONCLUSION: Xerostomia treatment improved oral dryness in 75.3% of patients receiving xerogenic medications in this study. If xerostomia due to side-effects of medications can be improved by treatment, it will greatly contribute to the quality of life of patients with xerogenic medications and may reduce the number of patients who discontinue medications.

Factors associated with xerostomia in perimenopausal women.

OBJECTIVES: Various oral symptoms, including xerostomia and burning mouth syndrome, may occur in menopausal women. These symptoms reduce quality of life (QOL). However, the actual condition of xerostomia after menopause is not clear. The purpose of this study was to reveal the factors associated with xerostomia in perimenopausal women. METHODS: Participants included 118 outpatients (mean age, 49.9 ± 3.2 years; range, 45-55 years) at a department of gynecology in Japan. Information was collected concerning age, medical history, medications, menstrual status, and history of treatment for climacteric symptoms. Oral symptoms, including xerostomia were evaluated with a 3-point scale. The climacteric symptom checklist for Japanese women and 36-Item Short-Form Health were used to evaluate climacteric symptoms and QOL, respectively. In addition, the volume of unstimulated saliva, oral moisture, salivary α-amylase, chromogranin A, and 17-ß estradiol were measured. RESULTS: Higher age, the total number of medications, psychotropic drug, hormone replacement therapy, treatment for climacteric symptoms, sticky mouth, burning sensation of tongue, dryness of nose and 14 of the 21 climacteric symptoms significantly affected xerostomia. In addition, treatment for climacteric symptoms, fall asleep but often awake at night, headaches and dryness of nose were significantly associated with xerostomia. In conclusion, xerostomia is closely associated to factors such as treatment for climacteric symptoms and certain menopausal symptoms, and it may be related to QOL in perimenopausal women.

Menopausal symptoms are associated with oral sensory complaints in perimenopausal women: an observational study.

BACKGROUND: Perimenopausal women experience a wide variety of systemic symptoms: hot flashes, sweating, mental health concerns and various oral sensory complaints (OSC). OSC in perimenopausal women include xerostomia, taste disturbance and burning mouth. However, the factors associated with these OSC have not been identified. The purpose of this investigation was to elucidate the factors associated with OSC in perimenopausal women. METHODS: The study cohort comprised 43 perimenopausal women aged 45-55 years. Data on medical history, medications, menstrual status, menopausal symptoms, quality of life, xerostomia, taste disturbance and burning mouth were collected. Volumes of unstimulated and stimulated saliva were measured. Tongue coating was evaluated according to a tongue coating index. Univariate analysis was performed to identify factors significantly associated with having xerostomia, taste disturbance, burning mouth and more than two OSC (2OSC). Next, the factors strongly associated with these symptoms were examined by logistic regression analysis. RESULTS: The number of menopausal symptoms was significantly higher, and volume of unstimulated saliva was significantly lower in participants with xerostomia, taste disturbance, burning mouth or 2OSC than in those without these characteristics. Agents targeting the central nervous system were more frequently taken by participants with burning mouth and 2OSC than by those without these characteristics. According to logistic regression analysis, the number of menopausal symptoms was an explanatory variable for xerostomia, taste disturbance, burning mouth and 2OSC. CONCLUSIONS: Our findings suggested that OSC associated with the number of menopausal symptoms. Management of menopausal symptoms may decrease OSC, leading to improved quality of life of perimenopausal women.

Radiological imaging features of the salivary glands in xerostomia induced by an immune checkpoint inhibitor.

The clinical features of xerostomia induced by immune checkpoint inhibitors (ICI) are similar to those of Sjögren's syndrome (SS), whereas the immunohistological and serological features are known to differ from those of SS. However, the radiologic imaging features of salivary glands are not yet well known. We report a case of a 56-year-old male patient diagnosed with ICI-induced xerostomia. The patient underwent various imaging examinations to investigate the condition of the salivary glands, which indicated the following: (1) less specific findings on contrast-enhanced computed tomography, (2) mixed with intermediate and low signal intensity on both T1-weighted and fat-suppressed T2-weighted magnetic resonance imaging and poor "salt and pepper" appearance on magnetic resonance sialography, and (3) multiple ovoid hypoechoic areas with hyperechoic bands without acute sialadenitis on ultrasound. These radiologic imaging findings suggested remarkable lymphocyte infiltration, which could be a characteristic of ICI-induced xerostomia.

Gastroesophageal reflux-like symptoms are associated with hyposalivation and oropharyngeal problems in patients with asthma.

BACKGROUND: Previous studies have suggested a significant relationship between hyposalivation and inhalation therapy-induced oropharyngeal problems. However, salivary secretion tests are not widely performed in daily clinical practice. In fact, xerostomia, the complaint of dry mouth, may not indicate hyposalivation. Therefore, we determined the clinical factors associated with hyposalivation in patients with asthma. METHODS: This study is a post-hoc analysis of our previous studies. Adult patients with asthma on maintenance inhalation therapy were enrolled. The participants completed questionnaires on oropharyngeal symptoms and underwent a salivary secretion test. Symptom severity was evaluated using a numerical rating scale (NRS), and salivary secretion was measured using the modified cotton roll method. Using logistic regression analysis, we identified the clinical factors associated with hyposalivation. RESULTS: In total, 531 patients completed the questionnaire (43.8 ± 16.9 years and male/female = 171/360), and 234 patients successfully performed a salivary secretion test, of which 126 (53.8%) were diagnosed with hyposalivation (<0.25 g/min). The patients with hyposalivation were significantly older (p < 0.0001) and had severe xerostomia and/or gastroesophageal reflux-like symptoms (GERLS) (p < 0.0001). Many of these patients had also used inhaled long-acting beta agonists (p = 0.012) and high-dose inhaled corticosteroids (p = 0.024). Multivariate analysis revealed that advanced age (odds ratio [OR] 1.05, p < 0.0001), severe xerostomia (OR 1.02, p = 0.0006) and severe GERLS (OR 1.02, p = 0.001) were independently and significantly associated with hyposalivation. CONCLUSIONS: Age, xerostomia, and GERLS were significantly related to hyposalivation in patients with asthma. To identify oropharyngeal problems in these patients, a careful assessment of the suspected symptoms of gastroesophageal reflux may be useful.

Assessment of inhalation flow patterns of soft mist inhaler co-prescribed with dry powder inhaler using inspiratory flow meter for multi inhalation devices.

The patients' inhalation flow pattern is one of the significant determinants for clinical performance of inhalation therapy. However, the development of inhalation flow meters for various inhalation devices has been unable to keep up with the increasing number of newly launched inhalation devices. In the present study, we developed simple attachment orifices for the inhalation flow pattern monitoring system, which are suitable for all commercial inhalers, and investigated the efficacy of the system on the clinical inhalation instruction for patients co-prescribed dry powder inhaler (DPI) and soft mist inhaler (SMI). First, we constructed simple attachment orifices that were adjusted for 13 commercial inhalers, and examined the correlation between orifice and inhalation device. Second, the inhalation flow patterns (peak inspiratory flow rate, PIFR; inhalation duration time, DT) of patients prescribed a combination of DPI and SMI were monitored before and after inhalation instruction. The inhalation resistance of commercial inhalers are listed in the following order; Twincaps® > Handihaler® > Swinghaler® = Clickhaler® > Twisthaler® > Turbuhaler® > Jenuair® > Diskus® = Ellipta® > Diskhaler® > Breezhaler® > Respimat® = pMDI. The pressure drop via orifice was significantly correlated with that via the commercial inhaler. For the confirmation, all participants achieved the DPI criterion of PIFR. On the other hand, 4 participants (6 clinical visits) of 10 experimented participants could not achieve the essential criterion of DT (> 1.5 sec) for SMI, but all participants improved their duration time after inhalation instruction by pharmacists (P<0.05). In the present study, we successfully developed simple attachment orifice suitable for 13 commercial inhalation devices. These data suggested that our simple attachment orifices for the inhalation flow pattern monitoring system can detect patients with inadequate inhalation patterns via SMI.

Factors associated with mucosal dryness in multiple regions and skin: A web-based study in women.

AIM: We hypothesized that feeling mucosal dryness in one body region and the skin may be associated with dryness in other regions and that there are common background factors for dryness. In an earlier web-based survey, we reported prevalence figures of dry eyes, nose, mouth, skin, and vagina. In the present study, additional analyses were made to investigate the factors associated with dryness in each region, and simultaneous dryness in multiple regions. METHODS: A web-based questionnaire was completed by 310 Japanese women. The questions included dryness of the eyes, nose, mouth, vagina, and skin. Menopausal and other symptoms were also addressed. Multiple logistic regression modeling was performed to identify factors associated with dryness in each region and in multiple dry regions. RESULTS: Dry eyes were associated with dryness in the nose and with headache; dry nose was associated with dryness in the vagina and eyes; dry mouth was associated with sticky mouth symptom and dryness of the nose; dry skin was associated with use of xerogenic medications and vaginal discharge; and dryness of the vagina was associated with vaginal itchiness and dry nose. Vaginal discharge (odds ratio, 9.64; 95% confidence interval, 3.15-29.51) and sticky mouth (odds ratio, 6.35; 95% confidence interval, 1.29-31.29) were further associated with dryness in multiple regions. CONCLUSION: The present results confirmed our study hypothesis by showing that dryness in one region was clearly associated with that in another or in multiple regions. The result implies the need for holistic diagnosis and counseling for patients with dryness complaints.

Relationships between the amount of saliva and medications in elderly individuals.

OBJECTIVE: To investigate medications that are related to volume of saliva in the elderly. BACKGROUND DATA: In the elderly, many cases of mouth dryness may represent side effects of medication. MATERIALS AND METHODS: The volume of unstimulated saliva was measured for 30 s (cotton roll test), and with stimulation for 3 min (gum test) in 368 subjects 79-80 years old (177 men, 191 women). Medications were investigated using subject's medication notebooks. RESULTS: Mean volumes of unstimulated and stimulated saliva were 0.14±0.13 and 4.30±2.54 ml respectively. Significant differences were seen between gender and mean volume of saliva. The volume of unstimulated saliva was 0.16±0.15 ml for men and 0.11±0.10 ml for women. The volume of stimulated saliva was 4.99±2.67 ml for men and 3.67±2.25 ml for women. The percentage of subjects taking medication was 64.7% (238/368). Mean number of medications was 2.08±2.26, with no significant difference with gender (2.01±2.37 for men, 2.16±2.16 for women). In a stepwise multiple regression analysis with volume of saliva as the objective variable and number of drugs by category as explanatory variables, significant explanatory variables in addition to gender and number of medications were blood-coagulating agents, Ca antagonists and peptic ulcer drugs for volume of unstimulated saliva, and diabetes medications and peptic ulcer drugs for volume of stimulated saliva. CONCLUSION: These findings suggest that differences exist between gender in volume of saliva for elderly individuals, and that the volume of saliva is affected by the number and type of medications.