“Dry mouth” and “Flammer” syndromes—neglected risks in adolescents and new concepts by predictive, preventive and personalised approach
“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.
KeywordsPredictive preventive personalised medicine Hyposalivation Xerostomia Sicca syndrome Periodontitis Voice disorder Digestive disorder Flammer syndrome Phenotype Dehydration Patient stratification Impaired wound healing
The authors thank the European Association for Predictive, Preventive and Personalised Medicine, EPMA, Brussels, Belgium, for professional support in organising current multicentre study.
Olga Golubnitschaja is the project coordinator who has created scientific concepts and hypotheses presented in the manuscript; she has drafted the manuscript. Anatoly Kunin has coordinated the research, performed patient recruitment and data analysis in Russia, analysed the corresponding patient database and selected disease free individuals for the reference group and individuals with hyposalivation involved in the study. Natalia Moiseeva has provided the final data from interviewing the groups of comparison. Jiri Polivka Jr. has performed complete statistical analysis. All the authors have read and approved the final manuscript.
The study has been supported by the National Sustainability Program I (NPU I) Nr. LO1503, Ministry of Education, Youth and Sports, Czech Republic, and MH CZ-DRO (Faculty Hospital in Plzen-FNPl, 00669806) and the Charles University Research Fund (Progres Q39).
Compliance with ethical standards
All the patients and individuals involved in the study were informed about the purposes of the study and consequently have signed their “consent of the patient”. All procedures involving human participants were performed with the permission of the Ethical Committee of the Voronezh N.N. Burdenko State Medical University, Voronezh, Russia in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
The authors declare that they have no competing interests.
Healthy individuals were informed about the purposes of the study and have signed their consent for publishing the data. Patients interviewed for creating the case reports were informed about the purposes of the study and have signed their consent for publishing the data.
- 1.Pedersen AML, Sørensen CE, Proctor GB, Carpenter GH. Salivary functions in mastication, taste and textural perception, swallowing and initial digestion. Oral Dis. 2018; https://doi.org/10.1111/odi.12867.
- 3.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. https://doi.org/10.1007/s13167-017-0108-4.
- 7.Shigeyama C, Ansai T, Awano S, Soh I, Yoshida A, Hamasaki T, et al. 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;106:833–9. https://doi.org/10.1016/j.tripleo.2008.07.005.CrossRefPubMedGoogle Scholar
- 9.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; https://doi.org/10.1007/s00784-018-2393-2.
- 12.Gonzales JA, Chou A, Rose-Nussbaumer JR, Bunya VY, Criswell LA, Shiboski CH, et al. How are ocular signs and symptoms of dry eye associated with depression in women with and without Sjögren syndrome? Am J Ophthalmol. 2018;191:42–8. https://doi.org/10.1016/j.ajo.2018.04.004.CrossRefPubMedGoogle Scholar
- 16.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;8:141–57. https://doi.org/10.1007/s13167-017-0092-8.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.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.
- 18.Flammer Syndrome [Internet]. [cited 2018 Jul 12]. Available from: http://www.flammer-syndrome.ch/index.php?id=32.
- 24.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.Google Scholar
- 25.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.
- 29.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; https://doi.org/10.1016/j.jped.2018.02.007.
- 34.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. https://doi.org/10.3389/fonc.2018.00035.CrossRefPubMedPubMedCentralGoogle Scholar