Evaluation of photodynamic therapy in pericoronitis: Protocol of randomized, controlled, double-blind study

Tânia Oppido Schalch, Michelle Palmieri, Priscila Larcher Longo, Paulo Henrique Braz-Silva, Isabel Peixoto Tortamano, Edgard Michel-Crosato, Marcia Pinto Alves Mayer, Waldyr Antonio Jorge, Sandra Kalil Bussadori, Christiane Pavani, Renata Matalon Negreiros, Anna Carolina Ratto Tempestini Horliana, Tânia Oppido Schalch, Michelle Palmieri, Priscila Larcher Longo, Paulo Henrique Braz-Silva, Isabel Peixoto Tortamano, Edgard Michel-Crosato, Marcia Pinto Alves Mayer, Waldyr Antonio Jorge, Sandra Kalil Bussadori, Christiane Pavani, Renata Matalon Negreiros, Anna Carolina Ratto Tempestini Horliana

Abstract

Introduction: Pericoronitis is a common disease in the eruption phase of third molars, sometimes debilitating, with an impact on the quality of life. The most indicated treatment in the initial phase is the irrigation for cleanliness of the region. In order to reduce the chances of systemic dissemination of the infection and antibiotics use, it is mandatory to test effective treatments in the initial phase of pericoronitis avoiding the evolution of the infectious disease. Photodynamic therapy (PDT) is an interesting alternative because it is an effective antimicrobial treatment that is easy to perform and does not select bacterial resistance. The methylene blue (MB) used in PDT has been studied in an oral formulation, which optimizes the formation of monomers increasing its antimicrobial action.

Objective: The aim of this study is to evaluate the effectiveness of PDT with MB in an astringent vehicle in pericoronitis on the initial phase in healthy patients through microbiological, clinical, and immune response. The impact of pericoronitis on oral health-related quality of life (OHRQoL) of these patients will also be evaluated.

Method: In this randomized, controlled, double-blind clinical bioequivalence protocol, 64 healthy patients with pericoronitis will be evaluated. Patients will be randomized into the positive control group (G1) (n = 32): irrigation with sterile saline and PDT (conventional MB at 0.005% concentration and irradiation with low intensity laser λ = 660 nm, 9J per point and radiant exposure of 318 J/cm), and the experimental group (G2) (n = 32): treatment identical to G1, however, MB will be delivered in a new formulation for oral use. Microbiological analysis will be performed by RT-PCR for the bacterium Tannerella forsythia. Gingival crevicular fluid and saliva will be collected to evaluate cytokines by Luminex assay (Luminex Corporation, Austin, TX). The pain (visual analogue scale), swelling and buccal opening (digital caliper), and OHRQoL will also be evaluated through the OHIP-14 questionnaire. The variables will be evaluated in T1 (baseline), T2 (immediately after PDT), and T3 (4th day after PDT). Registration: clinicaltrials.gov NCT03576105. Registered in July 2018.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Irradiation points.
Figure 2
Figure 2
Visual analog scale (VAS).
Figure 3
Figure 3
Three pre-established facial measures. The criteria for the determination of edema—(I) corner of the eye to angle of the jaw, (II) tragus to the labial commissure, and (III) tragus to pogonion.
Figure 4
Figure 4
Flowchart presenting an overview of the study.

References

    1. Batinjan G, Filipović ZI, Rupić I, et al. Assessing health-related quality of life with antimicrobial photodynamic therapy (APDT) and low level laser therapy (LLLT) after third molar removal. J Lasers Med Sci 2013;4:120–6.
    1. Bacellar IO, Tsubone TM, Pavani C, et al. Photodynamic efficiency: from molecular photochemistry to cell death. Int J Mol Sci 2015;16:20523–59.
    1. Birang E, Talebi Ardekani MR, Rajabzadeh M, et al. Evaluation of effectiveness of photodynamic therapy with low-level diode laser in nonsurgical treatment of peri-implantitis. J Lasers Med Sci 2017;8:136–42.
    1. Mota AC, França CM, Prates R, et al. Effect of photodynamic therapy for treatment of halitosis in adolescents: a controlled, microbiological, clinical trial. Effect of photodynamic therapy for the treatment of halitosis in adolescents: a controlled, microbiological, clinical trial. J Biophotonics 2016;9:1337–43.
    1. Eroglu CN, Tunc SK, Erten R, Usumez A Clinical and Histological Evaluation of the Efficacy of Antimicrobial Photodynamic Therapy used in addition to Antibiotic Therapy in Pericoronitis Treatment. Photodiagnosis Photodyn Ther. 2018 Feb 24. pii: S1572-1000(17)30526-4. doi:10.1016/j.pdpdt.2018.02.018. [Epub ahead of print]
    1. Nuñez SC, Yoshimura TM, Ribeiro MS, et al. Urea enhances the photodynamic efficiency of methylene blue. J Photochem Photobiol B 2015;150:31–7.
    1. Mota AC, Gonçalves ML, Bortoletto C, Olivan SR, Salgueiro M, Godoy C, Altavista OM, Pinto MM, Horliana AC, Motta LJ, Bussadori SK. Evaluation of the effectiveness of phodynamic for endodontic treatment of primary teeth: study protocol for a randomized controlled clinical trial. Trial.n.16,551, 2015
    1. Silva LA, Novaes AB, Jr, de Oliveira RR, et al. Antimicrobial photodynamic therapy for treatment of teeth with apical periodontitis: a histopathological evaluation. Joe 2012;38:360–6.
    1. Candeo LC, Rigonato-Oliveira NC, Brito AA, et al. Effects of periodontitis on the development of asthma: the role of photodynamic therapy. PLoS One 2017;12:e0187945.
    1. Azaripour A, Dittrich S, Van Noorden CJF, et al. Efficacy of photodynamic therapy as adjunct treatment of chronic periodontitis: a systematic review and meta-analysis. Lasers Med Sci 2018;33:407–23.
    1. George S, Kishen A. Photophysical, photochemical, and photobiological characterization of methylene blue formulations for light-activated root canal disinfection. J Biomed Opt 2007;12:034029.
    1. Joseph B, Janam P, Narayanan S, et al. Is antimicrobial photodynamic therapy effective as an adjunct to scaling and root planing in patients with chronic periodontitis? A systematic review. Biomolecules 2017;7: pii: E79. doi: 10.3390/biom7040079.
    1. Corrêa MG, Oliveira DH, Saraceni CH, et al. Short-term microbiological effects of photodynamic therapy in non-surgical periodontal treatment of residual pockets: a split-mouth RCT. Lasers Surg Med 2016;48:944–50.
    1. Camacho-Alonso F, Julián-Belmonte E, Chiva-García F, et al. Bactericidal efficacy of photodynamic therapy and chitosan in root canals experimentally infected with Enterococcus faecalis: an in vitro study. Photomed Laser Surg 2017;35:184–9.
    1. Fernandes Kristianne Porta Santos; Ferrari, Raquel Agnelli Mesquita; França, Cristiane Miranda. Biofotonica conceitos e aplicações. Uninove, Sao Paulo: Universidade Nove de Julho, 2017. 249
    1. Fontana CR, Abernethy AD, Som S, et al. The antibacterial effect of photodynamic therapy in dental plaque-derived biofilms. J Periodontal Res 2009;44:751–9.
    1. Kellesarian SV, Malignaggi VR, Majoka HA, et al. Effect of laser-assisted scaling and root planing on the expression of pro-inflammatory cytokines in the gingival crevicular fluid of patients with chronic periodontitis: a systematic review. Photodiagnosis Photodyn Ther 2017;18:63–77.
    1. Röhrig B, Prel JB, Wachtlin D, et al. Sample size calculation in clinical trials part 13 of a series on evaluation of scientific publications. Dtsch Arztebl Int 2010;107:552–6.
    1. Collina GA, Freire F, Santos TPC, et al. Controlling methylene blue aggregation: a more efficient alternative to treat Candida albicans infections using photodynamic therapy. Photochem Photobiol Sci 2018;17:1355–64.
    1. Sampaio-Filho H, Sotto-Ramos J, Pinto EH, et al. Evaluation of low- level laser at auriculotherapy points to reduce postoperative pain in inferior third molar surgery protocol for a ramdomized controlled trial. Trials 2016;17:432.
    1. UStün Y, Erdogan O, Esen E, et al. Comparison of the effects of 2 doses of methylprednisolone on pain, swelling, and trismus after third molar surgery. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 2003;96:535–9.
    1. Sierra SO, Deana AM, Bussadori SK, et al. Choosing between intraoral or extraoral, red or infrared laser irradiation after impacted third molar extraction. Lasers Surg Med 2016;48:511–8.
    1. Kinney JS, Morelli T, Oh M, et al. Crevicular fluid biomarkers and periodontal disease progression. J Clin Periodontol 2014;41:113–20.
    1. Oliveira BH, Nadanovsky P. Psycometric properties of the Brazilian version of the oral health impact profile-short form. Community Dent Oral Epidemiol 2005;33:307–14.
    1. Negreiros RM, Biazevic MG, Jorge WA, et al. Relationship between oral health-related quality of life and the position of the lower third molar: postoperative follow-up. J Oral Maxillofac Surg 2012;70:779–86.
    1. Pell GJ, Gregory GT. Report on a ten year study of a tooth division technique for removal of impacted teeth. Am J Orthod Oral Surg 1942;28:660–6.
    1. Almendros-Marqués N, Berini-Aytés L, Gay-Escoda C. Evaluation of intraexaminer and interexaminer agreement on classifying lower third molars according to the systems of Pell and Gregory and of Winter. J Oral Maxillofac Surg 2008;66:893–9.
    1. Sencimen M, Saygun I, Gulses A, et al. Evaluation of periodontal pathogenes of mandibular third molar pericoronitis by using real time PCR. Int Dent J 2014;64:200–5.
    1. Mendes L, Azevedo NF, Felino A, et al. Relationship between invasion of the periodontium by periodontal pathogens and periodontal disease: a systematic review. Virulence 2015;6:208–15.
    1. Rajasuo A, Jousimies-Somer H, Savolaimen S, et al. Bacteriologic findings in tonsillitis and pericoronitis. Clin Infect Dis 1996;23:51–60.
    1. Rajasuo A, Sihvonen J, Peltola O, et al. Periodontal pathogens in erupting third molars of periodontal healthy subjects. Int J Oral maxillofac Surg 2007;36:818–21.
    1. Peltroche-Llacsahuanga H, Reichhart E, Schmitt W, et al. Investigation of infectious organisms causing pericoronitis of the mandibular third molar. J Oral Maxxillofac Surg 2000;58:611–6.
    1. Sixou JL, Maugaud C, Jolivet-Gougean A, et al. Evaluation of the mandibular third molar pericronitis flora and its susceptibility to different antobiotics prescribed in France. J Clin Microbiol 2003;41:5794–7.
    1. Mansfield JM, Campbell JH, Bhandari AR, et al. Molecular analysis of 16S rRNA genes identifies potentially periodontal pathogenic bacteria and archaea in the plaque of partially erupted third molars. J Oral Maxillofac Surg 2012;70:1507.e1-6–14.e1-6.
    1. Jakovljevic A, Andric M, Milicic AK, et al. Herpesviral-bacterial co-infection in mandibular third molar pericoronitis. Clin Oral Invest 2017;21:1639–46.
    1. Oruba Z, Łabuz P, Macyk W, et al. Periopathogens differ in terms of the susceptibility to toluidine blue O-mediated photodynamic inactivation. Photodiagnosis Photodyn Ther 2017;20:28–34.
    1. 2017. Fernandes KPS e colab. Biofotonica: conceitos e aplicações. ISBN 978-89852-49-4. Sao Paulo UNINOVE.
    1. de Freitas MTM, Soares TT, Aragão MGB, et al. Effect of Photodynamic antimicrobial chemotherapy on mono- and multi-species cariogenic biofilms: A literature review. Photomed Laser Surg 2017;35:239–45.
    1. Usacheva MN, Teichert MC, Biel MA. The role of the methylene blue and toluidine blue monomers and dimers in the photoinactivation of bacteria. J Photochem Photobiol B 2003;71:87–98.
    1. Sharma SK, Chiang LY, Hamblin MR. Photodynamic therapy with fullreness in vivo reality or a dream. Nanomedicine 2011;6:1813–25.
    1. Zucoloto ML, Maroco J, Campos JA. Psychometric properties of the oral health impact profile and new methodological approach. J Dent Res 2014;93:645–50.
    1. Magraw C, Golden B, Phillips C, et al. Pain with pericoronitis affects quality of life. J Oral Maxillofac Surg 2015;73:7–12.
    1. Tang D, Phillips C, Proffit W, et al. Effect of quality of life measures on the decision to remove third molars in subjects with mild pericoronoritis symptoms. J oral Maxillofac Sug 2014;72:1235–43.
    1. Avellaneda-Gimeno V, Figueiredo R, Valmaseda-Castellón E. Quality of life after upper third molar removal: a prospective longitudinal study. Med Oral Patol Oral Cir Bucal 2017;22:e759–66.
    1. Slade GD, Foy SP, Shugars DA, et al. The impact of third molar symptoms, pain, and swelling on oral health-related quality of life. J Oral Maxillofac Surg 2004;62:1118–24.
    1. Alves-Pereira D, Pereira-Silva D, Figueiredo R, et al. Clinician-related factors behind the decision to extract an asymptomatic lower third molar a cross-sectional study based on Spanish and Portuguese dentists. Med Oral Patol Oral Cir Bucal 2017;22:e609–15.
    1. Hendek MK, Şenses F, Kisa Ü, et al. Is the level of nitric oxide in the dental follicular tissues of impacted third molars with a history of recurrent pericoronitis a true marker of oxidative stress? J Oral Maxillofac Surg 2017;75:2058–62.
    1. Ibikunle AA, Adeyemo WL. Oral health-related quality of life following third molar surgery in an African population. Contemp Clin Dent 2017;8:545–51.
    1. McNutt M, Patrick M, Shugars DA, et al. Impact of symptomatic pericoronitis on health related quality of life. J Oral Maxillofac Surg 2008;66:2482–7.
    1. Azevedo SV, Brasil SC, Antunes H, et al. Distribution of macrophages and plasma cells in apical periodontitis and their relationship with clinical and image data. J Clin Exp Dent 2017;9:e1060–5.
    1. Beklen A, Laine M, Ventä I, et al. Role of TNF-alpha and its receptors in pericoronitis. J Dent Res 2005;84:1178–82.
    1. Jose JA, Somaiah S, Muddaiah S, et al. A comparative evaluation of interleukin 1 beta and prostaglandin e2 with and without low-level laser therapy during En masse retraction. Contemp Clin Dent 2018;9:267–75.
    1. Li X, Wang X, Wu D, et al. Interleukin-1β and C-reactive protein level in plasma and gingival crevicular fluid in adolescents with diabetes mellitus. Beijing Da Xue Xue Bao Yi Xue Ban 2018;50:538–42.
    1. Gupta S, Chhina S, Arora SA. A systematic review of biomarkers of gingival crevicular fluid: their predictive role in diagnosis of periodontal disease status. J Oral Biol Craniofac Res 2018;8:98–104.
    1. Bergmann K, Konski CT. A spectroscopic study of methylene blue monomer dimer and complexes with montmorillonite. J Phys Chem 1963;67:2169–77.
    1. Junqueira HC, Severino D, Dias LG, et al. Modulation of methylene blue photochemical properties based on adsorption at aqueous micelle interfaces. Phys Chem Phys 2002;4:2320–8.
    1. Da Collina GA, Tempestini-Horliana AC, da Silva DF, et al. Oral hygiene in intensive care unit patients with photodynamic therapy: study protocol for randomised controlled trial. Trials 2017;18:385.
    1. Avci P, Gupta A, Sadasivam M, et al. Low-level laser (light) therapy (LLLT) in skin: stimulating, healing, restoring. Semin Cutan Med Surg 2013;32:41–52.
    1. Litscher G, Opitz G. Technical parameters for laser acupuncture to elicit peripheral and central effects: state-of-the-art and short guidelines based on results from the Medical University of Graz, the German Academy of Acupuncture, and the Scientific Literature. Evid Based Complement Alternat Med 2012;2012:697096.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa