BACKGROUND: "Dry mouth" syndrome (chronic hyposalivation) can be caused by a number of pathophysiological conditions such as acute and chronic stress exposure, abnormal body weight (both too high and too low ones), eating disorders (such as anorexia nervosa), metabolic syndrome(s), Sjögren's and Sicca syndromes, drugs and head/neck radiotherapy application. In turn, the chronic hyposalivation as a suboptimal health condition significantly reduces quality of life, may indicate a systemic dehydration, provokes and contributes to a number of pathologies such as a strongly compromised protection of the oral cavity, chronic infections and inflammatory processes, periodontitis, voice and digestive disorders. Consequently, "dry mouth" syndrome might be extremely useful as an indicator for an in-depth diagnostics of both-co-existing and snowballing health-threating conditions. However, predictive diagnostics, targeted prevention and personalisation of treatments are evidently underdeveloped for individuals at high risk suffering from the "dry mouth" syndrome. WORKING HYPOTHESIS AND METHODOLOGY: In the current study, we have hypothesised that individuals demonstrating "Flammer syndrome" (FS) phenotype may suffer from the "dry mouth" syndrome more frequently, due to disturbed microcirculation, psychological factors (obsessional personality/perfectionism), and diminished feeling of thirst with consequently insufficient daily liquid intake potentially resulting in the systemic dehydration with individually pronounced level of severity. If confirmed, FS phenotyping linked to the chronic hyposalivation might be predictive for individuals at risk identified by innovative screening programmes. To verify the working hypothesis, healthy individuals (negative control group) versus individuals with evident hyposalivation as well as patients diagnosed with periodontitis (positive control group) observed and treated at the dental clinic were investigated. The degree to which an individual is affected by hyposalivation was determined by the Bother xerostomia Index utilising a questionnaire of 10 issue-specific items and monitoring of a typically matt roof of the mouth in dental practice. An extent to which individuals included in the study are the carriers of the FS phenotype was estimated by the specialised 15-item questionnaire. RESULTS AND CONCLUSIONS: For both-the target group (hyposalivation) and positive control group (periodontitis)-FS phenotype was demonstrated to be more specific compared to the disease-free (negative control) group. Moreover, self-reports provided by interviewed adolescents of the target group frequently recorded remarkable discomfort related to "dry mouth" syndrome, acute and chronic otorhinolaryngological infections and even delayed wound healing. Further, interviewed adolescents do worry about the symptoms which might be indicative for potential diseases; they are also amazed that too little attention is currently paid to the issue by caregivers. In conclusion, FS questionnaire linked to the "dry mouth" syndrome is strongly recommended for application in primary healthcare. Consequently, targeted preventive measures can be triggered early in life. For example, traditional, complementary and alternative medicine demonstrates positive therapeutic effects in individuals suffering from xerostomia. For in-depth diagnostics, epi/genetic regulations involved into pathophysiologic mechanisms of hyposalivation in FS-affected individuals should be thoroughly investigated at molecular level. Identified biomarker panels might be of great clinical utility for predictive diagnostics and patient stratification that, further, would sufficiently improve personalised care to the patient.

Breast Cancer Research Centre Rheinische Friedrich Wilhelms University of Bonn Bonn Germany

Centre for Integrated Oncology Cologne Bonn Rheinische Friedrich Wilhelms University of Bonn Bonn Germany

Dentistry Faculty Departments of Maxillofacial Surgery and Hospital Dentistry Voronezh N N Burdenko State Medical University Voronezh Russia

Department of Histology and Embryology and Biomedical Centre Faculty of Medicine in Pilsen Charles University Prague Czech Republic

Department of Neurology University Hospital Pilsen Pilsen Czech Republic

Radiological Clinic Rheinische Friedrich Wilhelms University of Bonn Sigmund Freud Str 25 53105 Bonn Germany

Zobrazit více v PubMed

Pedersen AML, Sørensen CE, Proctor GB, Carpenter GH. Salivary functions in mastication, taste and textural perception, swallowing and initial digestion. Oral Dis. 2018; 10.1111/odi.12867. PubMed

Berk LB, Shivnani AT, Small W. Pathophysiology and management of radiation-induced xerostomia. J Support Oncol. 2005;3:191–200. PubMed

Mileguir D, Golubnitschaja O. Human saliva as a powerful source of information: multi-omics biomarker panels, In: EPMA World Congress: traditional forum in predictive, preventive and personalised medicine for multi-professional consideration and consolidation. EPMA J. 2017;8:1–54. 10.1007/s13167-017-0108-4.

Carramolino-Cuéllar E, Lauritano D, Silvestre F-J, Carinci F, Lucchese A, Silvestre-Rangil J. Salivary flow and xerostomia in patients with type 2 diabetes. J Oral Pathol Med. 2018;47:526–530. doi: 10.1111/jop.12712. PubMed DOI

Nederfors T. Xerostomia and hyposalivation. Adv Dent Res. 2000;14:48–56. doi: 10.1177/08959374000140010701. PubMed DOI

Sreebny LM. Saliva in health and disease: an appraisal and update. Int Dent J. 2000;50:140–161. doi: 10.1111/j.1875-595X.2000.tb00554.x. PubMed DOI

Shigeyama C, Ansai T, Awano S, Soh I, Yoshida A, Hamasaki T, Kakinoki Y, Tominaga K, Takahashi T, Takehara T. Salivary levels of cortisol and chromogranin A in patients with dry mouth compared with age-matched controls. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008;106:833–839. doi: 10.1016/j.tripleo.2008.07.005. PubMed DOI

Kisely S. No mental health without oral health. Can J Psychiatr Rev Can Psychiatr. 2016;61:277–282. doi: 10.1177/0706743716632523. PubMed DOI PMC

Bulthuis MS, Jan Jager DH, Brand HS. Relationship among perceived stress, xerostomia, and salivary flow rate in patients visiting a saliva clinic. Clin Oral Investig. 2018; 10.1007/s00784-018-2393-2. PubMed PMC

Both T, Dalm VASH, van Hagen PM, van Daele PLA. Reviewing primary Sjögren’s syndrome: beyond the dryness - from pathophysiology to diagnosis and treatment. Int J Med Sci. 2017;14:191–200. doi: 10.7150/ijms.17718. PubMed DOI PMC

Vaillancourt T, Duku E, Decatanzaro D, Macmillan H, Muir C, Schmidt LA. Variation in hypothalamic-pituitary-adrenal axis activity among bullied and non-bullied children. Aggress Behav. 2008;34:294–305. doi: 10.1002/ab.20240. PubMed DOI

Gonzales JA, Chou A, Rose-Nussbaumer JR, Bunya VY, Criswell LA, Shiboski CH, Lietman TM. How are ocular signs and symptoms of dry eye associated with depression in women with and without Sjögren syndrome? Am J Ophthalmol. 2018;191:42–48. doi: 10.1016/j.ajo.2018.04.004. PubMed DOI PMC

Golubnitschaja O. Feeling cold and other underestimated symptoms in breast cancer: anecdotes or individual profiles for advanced patient stratification? EPMA J. 2017;8:17–22. doi: 10.1007/s13167-017-0086-6. PubMed DOI PMC

Zubor P, Gondova A, Polivka J, Kasajova P, Konieczka K, Danko J, Golubnitschaja O. Breast cancer and Flammer syndrome: any symptoms in common for prediction, prevention and personalised medical approach? EPMA J. 2017;8:129–140. doi: 10.1007/s13167-017-0089-3. PubMed DOI PMC

Konieczka K, Ritch R, Traverso CE, Kim DM, Kook MS, Gallino A, Golubnitschaja O, Erb C, Reitsamer HA, Kida T, Kurysheva N, Yao K. Flammer syndrome. EPMA J. 2014;5:11. doi: 10.1186/1878-5085-5-11. PubMed DOI PMC

Bubnov R, Polivka J, Zubor P, Konieczka K, Golubnitschaja O. “Pre-metastatic niches” in breast cancer: are they created by or prior to the tumour onset? “Flammer Syndrome” relevance to address the question. EPMA J. 2017;8:141–157. doi: 10.1007/s13167-017-0092-8. PubMed DOI PMC

Challacombe SJ, Osailan SM, Proctor GB (2015) Clinical scoring scales for assessment of dry mouth. In: Carpenter G, editor. Dry mouth: a clinical guide on causes, effects and treatments [Internet]. Berlin Heidelberg: Springer-Verlag; 2015 [cited 2018 Jul 12]. Available from: //www.springer.com/us/book/9783642551536.

Flammer Syndrome [Internet]. [cited 2018 Jul 12]. Available from: http://www.flammer-syndrome.ch/index.php?id=32.

Konieczka K, Choi HJ, Koch S, Schoetzau A, Küenzi D, Kim DM. Frequency of symptoms and signs of primary vascular dysregulation in Swiss and Korean populations. Klin Monatsbl Augenheilkd. 2014;231:344–347. doi: 10.1055/s-0034-1368239. PubMed DOI

Smokovski I, Risteski M, Polivka J, Zubor P, Konieczka K, Costigliola V, Golubnitschaja O. Postmenopausal breast cancer: European challenge and innovative concepts. EPMA J. 2017;8:159–169. doi: 10.1007/s13167-017-0094-6. PubMed DOI PMC

Konieczka K, Todorova MG, Chackathayil TN, Henrich PB. Cilioretinal artery occlusion in a young patient with flammer syndrome and increased retinal venous pressure. Klin Monatsbl Augenheilkd. 2015;232:576–578. doi: 10.1055/s-0035-1545774. PubMed DOI

Konieczka K, Flammer J, Sternbuch J, Binggeli T, Fraenkl S. Leber’s hereditary optic neuropathy, normal tension glaucoma, and Flammer syndrome: long term follow-up of a patient. Klin Monatsbl Augenheilkd. 2017;234:584–587. doi: 10.1055/s-0042-119564. PubMed DOI

Baban B, Golubnitschaja O. The potential relationship between Flammer and Sjögren syndromes: the chime of dysfunction. EPMA J. 2017;8:333–338. doi: 10.1007/s13167-017-0107-5. PubMed DOI PMC

Change the World - One article at a time [Internet]. [cited 2018 Jul 12]. Available from: https://www.springernature.com/gp/researchers/campaigns/change-the-world?wt_mc=SocialMedia.Twitter.10.CON417.ctw2018_tw_shared_button&utm_medium=socialmedia&utm_source=twitter&utm_content=ctw2018_tw_shared_button&utm_campaign=10_dann_ctw2018_tw_shared_button.

Change the World - Medicine and Public Health [Internet]. [cited 2018 Jul 12]. Available from: https://www.springernature.com/gp/researchers/campaigns/change-the-world/medicine-public-health.

LeBlanc TW, Abernethy AP. Patient-reported outcomes in cancer care - hearing the patient voice at greater volume. Nat Rev Clin Oncol. 2017;14:763–772. doi: 10.1038/nrclinonc.2017.153. PubMed DOI

Golubnitschaja O, Flammer J. Individualised patient profile: clinical utility of Flammer syndrome phenotype and general lessons for predictive, preventive and personalised medicine. EPMA J. 2018;9:15–20. doi: 10.1007/s13167-018-0127-9. PubMed DOI PMC

Orellana MF, Lagravère MO, Boychuk DGJ, Major PW, Flores-Mir C. Prevalence of xerostomia in population-based samples: a systematic review. J Public Health Dent. 2006;66:152–158. doi: 10.1111/j.1752-7325.2006.tb02572.x. PubMed DOI

da Luz Neto LM, de Vasconcelos FMN, da Silva JE, Pinto TCC, Sougey ÉB, Ximenes RCC. Differences in cortisol concentrations in adolescents with eating disorders: a systematic review. J Pediatr (Rio J). 2018; 10.1016/j.jped.2018.02.007. PubMed

Naik PN, Kiran RA, Yalamanchal S, Kumar VA, Goli S, Vashist N. Acupuncture: an alternative therapy in dentistry and its possible applications. Med Acupunct. 2014;26:308–314. doi: 10.1089/acu.2014.1028. PubMed DOI PMC

Blom M, Lundeberg T, Dawidson I, Angmar-Månsson B. Effects on local blood flux of acupuncture stimulation used to treat xerostomia in patients suffering from Sjögren’s syndrome. J Oral Rehabil. 1993;20:541–548. doi: 10.1111/j.1365-2842.1993.tb01641.x. PubMed DOI

Bayat-Movahed S, Shayesteh Y, Mehrizi H, Rezayi S, Bamdad K, Golestan B, Mohamadi M. Effects of qigong exercises on 3 different parameters of human saliva. Chin J Integr Med. 2008;14:262–266. doi: 10.1007/s11655-008-0262-6. PubMed DOI

Zhang J, Zhong L-J, Wang Y, Liu L-M, Cong X, Xiang R-L, Wu LL, Yu GY, Zhang Y. Proteomic analysis reveals an impaired Ca2+/AQP5 pathway in the submandibular gland in hypertension. Sci Rep. 2017;7:14524. doi: 10.1038/s41598-017-15211-0. PubMed DOI PMC

Gabryś HS, Buettner F, Sterzing F, Hauswald H, Bangert M. Design and selection of machine learning methods using radiomics and dosiomics for normal tissue complication probability modeling of xerostomia. Front Oncol. 2018;8:35. doi: 10.3389/fonc.2018.00035. PubMed DOI PMC

Caution, "normal" BMI: health risks associated with potentially masked individual underweight-EPMA Position Paper 2021

Protective Effects of Flavonoids Against Mitochondriopathies and Associated Pathologies: Focus on the Predictive Approach and Personalized Prevention

Biobanks in the era of big data: objectives, challenges, perspectives, and innovations for predictive, preventive, and personalised medicine

Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine

Risks associated with the stroke predisposition at young age: facts and hypotheses in light of individualized predictive and preventive approach

Vaginal dryness: individualised patient profiles, risks and mitigating measures