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Article Type: Supplement Article

Treatment of Oral Malodour. Medium-term efficacy of mechanical and/or chemical agents: -a systematic reviewD.E. Slot 1, S. De Geest 2, G.A. van der Weijden 1 & M. Quirynen 2

Authors’ affiliations: 1

Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), The Netherlands 2

Department of Oral Health Sciences, Katholieke Universiteit Leuven, University Hospitals & Dentistry Leuven, Periodontology, Leuven, Belgium

CONFLICT OF INTEREST AND SOURCE OF FUNDING STATEMENT: The authors declare that they have no conflict of interest.

Ethical approval was not required.

This study was self-funded by the authors and their institutions.

This study was initiated

by the European Federation of Periodontology (XI European Workshop) within the theme: Effective Prevention of Periodontal and Peri-implant diseases Organized November 2014 in Segovia, Spain.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/jcpe.12378 This article is protected by copyright. All rights reserved.

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Quirynen, Slot and Van der Weijden have formerly received

either external advisor fees, lecturer fees or research grants from companies that produce oral malodour products. Among these were: Procter & Gamble, Colgate, GABA, Sara Lee, Dentaid, Lactona and Unilever

Running title: Management of oral malodour

Key words: bad breath, oral malodour, dentifrice, halitosis, mouthwash, mouthrinse, intraoral malodour, review, tongue cleaning, toothpaste,

Corresponding author: DE (Dagmar Else) Slot Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, Gustav Mahlerlaan 3004, NL-1081 LA Amsterdam, The Netherlands. Phone: (31)-20-5980-179/307 E-mail: [email protected]

Abstract Focused question: In systemically healthy patients what is the effect of a dentifrice (DF), a mouthwash (MW), tongue cleaning (TC), or any combination of these as adjunct to toothbrushing on intra-oral malodour and tongue coating as compared to toothbrushing alone, when used for a minimum follow-up period of 2 weeks?

Material and Methods: The MEDLINE-PubMed, Cochrane-CENTRAL and EMBASE databases were searched up to August 2014. Measurements of Volatile Sulphur Compounds (VSC) and organoleptic (ORG) scores of oral malodour were selected as outcome variables. Data were extracted and a descriptive analysis was performed.

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Results: Independent screening of 1054 unique papers resulted in 12 eligible clinical trials with a medium-term (≥2 weeks) duration. The majority of studies provided a significant reduction in oral malodour when evaluating products with an active ingredient (incorporated in a DF or a MW) used adjunctively to toothbrushing. The added value of tongue cleaning over a MW was evaluated in 1 study.

Conclusion: Due to very limited evidence, the potential effect of a specifically formulated dentifrice, a mouthwash or a tongue scraper for treating oral malodour is in general unclear. For mouthwashes containing the active ingredients chlorhexidine+cetylpyridinium chloride+zinc(CHX+CPC+Zn) and zinc chloride+cetylpyridinium chloride (ZnCl+CPC) most evidence was available. The strength of a recommendation to use these products was graded to be ‘weak’.

Clinical relevance Scientific rationale for the study: Systematic reviews on the treatment of oral malodour have evaluated experiments irrespective of the follow-up time. In the current systematic review the prolonged effects (≥ 2 weeks) of the adjunctive use of mechanical and/or chemical products are reviewed.

Principal findings: This systematic review demonstrates improvements of the level of volatile sulphur compounds and organoleptic scores favoring the adjunctive use of dentifrices and mouthwashes with specific active ingredients. Also when used in a combination with tongue cleaning, most products provided beneficial effects of varying magnitudes.

Practical implications: Within the limitations of this systematic review various active ingredients appear to have a beneficial effect. For mouthwashes containing chlorhexidine in combination with cetylpyridinium chloride (CPC) and zinc, as well as CPC in combination with zinc chloride, most evidence (≥2 experiments) was retrieved. The recommendation emerging from the collective evidence to use these products was graded to be ‘weak’.

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Introduction Individuals can suffer from persistent oral malodour (halitosis) In many cases, the cause can be found in the oral cavity in which case this is referred to as intra-oral halitosis or oral malodour (Dadamio et al. 2013a/b, Delanghe et al. 1997). Quirynen et al. (2009) assessed the aetiology and characteristics of 2000 patients with oral malodour complaints (often for several years) who visited a multidisciplinary oral malodour clinic in Leuven (Belgium), In 75.8% of the patients, an intra-oral cause for their complaints was found. In 4.2% the cause was identified as originating from the ear, nose, throat or other pathologies (i.e. gastro-intestinal/respiratory tract infections, systemic diseases). In 4.5% a combination of different aetiologies was identified, and in 15.7% of the individuals the complaint was judged as being pseudo-halitosis/halitophobia. Oral malodour is primarily the result of the degradation of organic substrates by anaerobic

bacteria of the oral cavity. In those patients with malodour originating from the oral cavity the distribution of underlying aetiological factors was tongue coating (57.3%), gingivitis/periodontitis (14.7%) or a combination of the two (24.0%), xerostomia (3.3%), candida infection (0.3%), and overhanging restorations/caries (0.4%) (Quirynen et al. 2009). The treatment is mostly done by eliminating the cause (bacteria and/or their substrates) either mechanically, chemically or a combination of both, or by masking/capturing the odorous compounds (Dadamio et al. 2013a/b). The first systematic reviews which addressed the treatment of oral malodour were performed

in collaboration with the Cochrane Oral Health Group. Weak and unreliable evidence was found that tongue scrapers (cleaners) have a benefit over toothbrushes in the reduction of halitosis in adults (Outhouse et al. 2006). Mouthrinses containing antibacterial agents (i.e. chlorhexidine(CHX) and cetylpyridinium chloride (CPC) may play a role in reducing the levels of halitosis-producing bacteria on the tongue. Chlorine dioxide and zinc containing mouthrinses can be effective in neutralisation of odouriferous sulphur compounds (Fedorowicz et al. 2008). More recently another systematic review demonstrated that tongue brushing or tongue scraping of the dorsum of the tongue, successfully reduced breath odour and tongue coating. However, the evidence for the beneficial effect of mechanical tongue cleaning in real oral malodour patients was weak since this could only be confirmed in one included study (Van der Sleen et al. 2010). Recently Kuo and coworkers (2013) concluded that the use of toothbrushing plus tongue cleaning compared with toothbrushing alone significantly reduced the indicators of halitosis. However, there is insufficient evidence to recommend frequency, duration, or delivery method of tongue cleaning. Based on a recent systematic review of Blom and co-workers (2012), nearly all mouthwashes

with active ingredients appear to be beneficial in reducing oral malodour, both in the short- and longer-term. The most compelling evidence was provided for CHX mouthwashes (MW), and for those

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that contained a combination of CHX, CPC and zinc (Zn). The data with respect to the reduction of tongue coating were sparse and none of the included studies showed a significant effect (Blom et al. 2012). A recent review on dentifrices (DF) concluded that antibacterial ingredients such as triclosan, and metal ions like stannous and zinc appear to be effective in controlling oral malodour (Dadamio et al. 2013a). Toothpaste formulations have been modified to carry these antimicrobial agents. Moreover, oxidizing agents were added in an attempt to influence the process of oral malodour formation (Dadamio et al. 2013b). All systematic reviews described above selected for inclusion papers without restrictions to

the follow-up time. The present systematic review focussed on those studies reporting on the medium-term effect of cause related interventions, by analyzing the effect after a minimum follow-up period of two weeks. In addition combinations of mechanical and chemical interventions were also reviewed. A restriction was made to include only those studies that evaluated the treatment of patients with malodour originating from the oral cavity, because other cases of halitosis (extra-oral causes such as systemic diseases/gastro-intestinal/respiratory tract infections) require a different, pathology specific, approach.

Materials and Methods

The protocol of this systematic review detailing the review method was developed ‘a priori’ following initial discussion between members of the research team. It was conducted in accordance with the Cochrane handbook (Higgings & Green 2011) for systematic reviews of interventions and with the guidelines of Transparent Reporting of Systematic Reviews and Meta-analyses (PRISMA-statement) (Moher et al. 2009).

Focused PICO questions (Copanitsanou & Valkeapaa 2013) Based on randomized controlled clinical trials (RCT) with systemically healthy individuals, what is the effect of a dentifrice (DF), a mouthwash (MW), tongue cleaning (TC), or any combination of these as adjunct to toothbrushing on oral malodour parameters assessed by Volatile Sulphur Compounds(VSC) levels or organoleptic scores (ORG) as compared to toothbrushing alone when used for a follow-up period ≥ 2 weeks?

Search strategy Three internet sources were queried to search for appropriate papers. These sources included the National Library of Medicine, Washington, D. C. (MEDLINE-PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE (Excerpta Medical Database by Elsevier). All three

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databases were searched for eligible studies up to September 2014. For details regarding the search terms used, see Box 1.

Screening and selection Two reviewers (SDG and DES) independently screened all titles and abstracts for eligible papers. If eligibility aspects were present in the title or abstract the paper was selected for further reading. After selection, the full-text papers were read in detail by two reviewers (SDG and DES). Any disagreement between the two reviewers was resolved after additional discussion. If a disagreement persisted, the judgment of a third reviewer (GAW) was decisive. The papers that fulfilled all selection criteria were processed for data extraction. Only handsearching done as part of the Cochrane Worldwide Handsearching Programme and uploaded to CENTRAL was included (see the Cochrane Masterlist for details of journal issues searched to date). All reference lists of the selected studies were hand-searched for additional papers that could possibly meet the eligibility criteria. Unpublished work was not sought.

The eligibility criteria were as follows: •

Randomized Controlled clinical Trials (RCTs).

•

Papers written in English.

•

Studies conducted in humans:

•

o

≥18 years old,

o

in good general health,

Intervention: a dentifrice (DF), a mouthwash (MW), tongue cleaning (TC), or a combination of these to toothbrushing alone.

•

Comparison: toothbrushing alone or toothbrushing combined with the adjunctive use of a placebo MW or a DF without active ingredients.

•

Breath improvement evaluation via one or more of the following clinical parameters: o

Organoleptic scores (ORG),

o

Volatile Sulphur Compound (VSC) levels as assessed using a Halimeter and/or Oral

®

®

Chroma . •

Follow-up period of ≥2 weeks.

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Assessment of heterogeneity The heterogeneity of the outcome variables across studies was explored according to the following factors: •

Study design, study population, evaluation period.

•

Subjects characteristics and smoking habits.

•

Intervention regimens and procedures.

•

Lost to follow-up, side effects and industry (commercial) funding.

Quality assessment Two reviewers (SDG and DES) scored the methodological quality of the included studies according to the method described in detail by Keukenmeester et al. (2012) (for scoring items see Appendix S2 ). In short, when random allocation, defined eligibility criteria, masking of examiners, masking of patients, balanced experimental groups, identical treatment between groups (except for the intervention) and reporting of follow-up were present, the study was classified as having an estimated low risk of bias. When one of these eight criteria was missing, the study was considered to have an estimated moderate risk of bias. When two or more of these criteria were missing, the study was considered to have an estimated high risk of bias, as previously proposed by Van der Weijden et al. (2009).

Statistical analyses Data extraction The data from those papers that met the selection criteria were extracted and processed for further analysis. For studies that presented an intermediate outcome assessment, only the baseline and final outcomes were used. Two reviewers (SDG and DES) evaluated the selected papers for baseline-, end- and incremental mean values, and standard deviation (SD). Disagreements were resolved by discussion, and if the disagreement persisted, the judgment of a third reviewer (GAW) was decisive. For those papers that provided insufficient data to be included in the analysis the first or corresponding authors were contacted to determine if additional data could be provided. To warrant a precise estimate any data approximation in figures was avoided.

Data analysis Data extraction revealed considerable heterogeneity in many aspects of the included studies and, therefore, a meta-analysis could not be carried out. Therefore the data of all studies were summarized and presented in a descriptive manner.

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Grading the ‘body of evidence’ The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system, as proposed by the GRADE working group, was used to grade the evidence emerging from this systematic review (GRADE, Guyatt et al. 2008). Two reviewers (DES & GAW) rated the quality of the evidence as well as the strength of the recommendations according to the following aspects: study design, estimated risk of bias of the individual studies; consistency and precision among the study outcomes; directness of the study results; detection of publication bias and magnitude of the effect. Any disagreement between the two reviewers was resolved following additional discussion. Grading was performed in relation to active ingredients for which a minimum of two experiments had been retrieved.

Results Search & selection results The searches resulted in 1054 unique papers (for details, see Figure 1). The screening of titles and abstracts initially resulted in 46 papers. Based on detailed reading of full texts, another 32 papers were excluded. The reasons for exclusion are explained in the online Appendix S1. The reference lists of the selected papers did not reveal any additional suitable papers. Thus, 14 papers studies were identified as eligible for inclusion in this systematic review, according to defined criteria for study design, participants, intervention and outcome. It is noteworthy that three experiments each were presented in two separate papers: Roldan et al. (2003) and Winkel et al. (2003); Ademovski et al. (2012, 2013) and Hu et al. (2003, 2005). Navada et al. (2008) published two experiments in a single paper, resulting in a final total inclusion of 12 experiments. None of the included studies evaluated the effect on tongue cleaning as a primary intervention. In total five experiments evaluated the effect of a MW on oral malodour. Five clinical experiments evaluated the effect of DF and two experiments evaluated combinations of these interventions.

Assessment of heterogeneity Considerable heterogeneity was observed in the 12 included clinical experiments with respect to study design, evaluation period, study population, number, gender and age of participants. Information regarding the study characteristics is displayed in detail in Table 1.

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Study design, evaluation period, research groups All included studies were double blind RCTs, mostly having a parallel design with the exception of two cross-over experiments (Peruzzo et al. 2007, Ademovski et al. 2012/2013). The evaluation period varied from 2 weeks to 6 months. Allocation concealment procedures were not described in any of the selected studies. Two papers describing the same experiment (Roldan et al. 2003, Winkel et al. 2003) were from collaborating research groups. The research group of Hu and co-workers (2003, 2005, 2013) contributed with 2 included experiments in this systematic review. All other papers were from different research groups.

Subject characteristics and smoking habits All of the study participants of the selected studies were in good general health. The majority of the studies used absence of periodontal disease as an inclusion criteria. Rassameemasmaung et al. (2007) allowed for mild to moderate chronic gingivitis patients. Quirynen et al. (2005) specifically selected patients diagnosed with moderate periodontitis (at least two multi-rooted and two singlerooted teeth in the first quadrant with probing depths ≥6 mm and radiographic evidence of bone loss ≥1/3 of the root length). Seven studies defined inclusion criteria for the oral malodour status with cutoff points for organoleptic scores ranging from >1 up to ≥ 4, and/or VSC level measurement with a varying minimal threshold of ≥ 80 ppb up to >170 ppb. One experiment used the presence of tongue coating as an additional inclusion criterion (Roldan et al. 2003, Winkel et al. 2003). Hu et al. (2003/2005) mentioned existing oral malodour but it was unclear how this was assessed, either professionally, by an apparatus or self-reported. Five studies enrolled only non-smoking participants (Wigger- Alberti et al 2010, Rassameemasmaung et al.(2007), Borden et al. (2002), Peruzzo et al. (2007), Ademovski et al. (2012/2013)), for two others there was no clear specification about smoking status of the participants (Codipilly et al. (2004), Hu et al. (2013)). The other studies did allow for inclusion of smokers although four papers (Roldan et al. (2003) / Winkel et al. (2003), Navada et al. (2008), Hu et al. (2003/2005), Quirynen et al. (2005)) mentioned that a non-smoking period was taken into account prior to the moment of breath odour assessment. The effect of smoking status on the outcome parameters was not (sub)analyzed in any of the included studies.

Intervention regimens and procedures Different active ingredients were used in the MW or DF. There was a variance with respect to mouthwash volume used, duration of rinsing, and daily frequency. Also for dentifrice a variation was seen in how often and how long participants brushed and for the type of toothbrush provided. In the selected studies, oral hygiene instruction was not provided consistently on a structured basis. Neither was a baseline professional prophylaxis regularly part of the study protocol

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Side effects & industry funding The majority of papers did not report on adverse events during the follow-up period. The reported side effects mainly focused on tooth staining, evaluated by an index/score (Wigger-Alberti et al. 2010, Roldan et al. 2003/Winkel et al. 2003, Quirynen et al. 2005) or on subjective perception (Rassameemasmaung et al. 2007). Results indicate that products can cause staining, but not to a level that will influence the compliance. Study funding either by the use of material or as a grant was mentioned in the majority of the studies. Some studies involved various industry partners.. Four studies were written in collaboration with authors affiliated with a product for the management of oral malodour (Borden et al. 2002, Hu et al. 2013, Navada et al. 2008, Hu et al. 2003,2005).

Quality assessment Quality assessment outcomes, including external, internal, and statistical validity, are presented in online Appendix S2. Based on a summary of these criteria, the estimated potential risk of bias was considered to be ‘low’ for four included studies(Rassameemasmaung et al. 2007, Codipilly et al.

2004, Roldan et al. 2003, Winkel et al. 2003, Borden et al. 2002), ‘moderate’ for six (Hu et al. 2013, Peruzzo et al. 2007, Nevada et al. 2008, Hu et al. 2003/2005, Quirynen et al. 2005), and ‘high’ for one study (Wigger-Alberti et al. 2010).

Study outcomes The online Appendix S3 shows the results from the data extraction. Different indices and their modifications have been used. Information regarding the changes within each intervention group for the various indices is presented. Analyses of within group changes were not commonly reported in the studies included in this review.

Between groups Data did not allow for a metaanalysis due to the observed heterogeneity in study designs, products and ingredients used, outcome measures and/or data presentation. Table 2 provides a descriptive analysis of the individual studies summarizing the significant differences observed between the treatment groups, clustered by intervention MW, DF or combinations (MW+TC). All studies provided significant differences in VSC levels, organoleptic scores or both, favoring all investigated products MW or DF with an active ingredient, used as an adjunct to tooth brushing. The additional effect of tongue cleaning over a MW was evaluated in only 1 study.

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Evidence profile Table 3 shows a summary of the various factors used to rate the quality of evidence and strength of recommendations according to GRADE (Guyatt et al. 2008). Grading was only possible for the combination of ingredients CHX+CPC+Zn and ZnCl+CPC in mouthwashes because for both combinations at least two studies were retrieved. Data were found to be inconsistent and a publication bias was considered to be possible. The estimated potential risk of bias varied from ‘low’ to ‘high’ for CHX+CPC+Zn studies and the magnitude of the effect for ZnCl+CPC varied from ‘moderate’ to ‘small’. Taken all items together the body of evidence and the strength of the recommendation emerging from this review is considered to be ‘weak’ with respect to impact on oral malodour.

Discussion Oral malodour is a common complaint with significant socio-cultural impact such as personal discomfort and social embarrassment. Epidemiological research on oral malodour is limited. The prevalence of oral malodour is unclear because epidemiological data are based mainly on subjective self-estimation, which is limited in accuracy and sensitivity. Studies are also complicated by a difference in cultural and racial appreciation of odours, which implies for patients as well as for investigators. There is also an absence of uniformity in diagnostic methods, both for organoleptic measurements and for the use of devices. Irrespective of the method used to assess oral malodour, and independent of the study population, large scale studies seem to indicate that one in four subjects (25%) really suffers from persistent oral malodour (Miyazaki et al. 1995, Söder et al. 2000, Liu et al. 2006). Van den Broek and co-workers (2007) evaluated in their review the current knowledge concerning the aetiology of oral malodour. Microbial degradation of proteins present in saliva, food debris, gingival crevicular fluid, interdental plaque, shed epithelial cells, postnasal drip, and/or blood are the main causes of oral malodour (Laleman et al. 2014). Due to this process of metabolic degradation, malodourous gases are formed. The most important volatile sulphur compounds (VSCs) involved in halitosis are hydrogen sulphide (H2S), methyl mercaptan (CH3SH)

and dimethyl sulphide (CH3)2S. These VSCs are mainly produced by Gram-negative anaerobic oral

bacteria. In general, intraoral conditions, like insufficient oral hygiene, periodontitis or tongue coating are considered to be the most important causes (80-90%) (Bollen & Beilker 2012). Therefore dental professionals are the first in line to be confronted with this problem. A cause-related therapy can be directed either to (i) the involved bacteria, (ii) the substrate used by these bacteria, and/or (iii) the bad smelling volatile compounds. As such the following treatment strategies can be applied: mechanical reduction of intraoral microorganisms and/or their nutrients (substrates), chemical reduction of the

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oral microbial load, and/or rendering malodourous gases non-volatile. The malodourous gases can be masked (e.g. mint-containing lozenges or aromas). The latter can be considered as a non-cause related (deodorizing) therapy, with improvements of only short duration (hours). Their temporary effect is explained by flushing away oral debris, diminishing the bacterial load, and leaving a pleasant, refreshing taste (via the aromas). Such mouthrinses should be marketed as oral deodorants, this in analogy to deodorant soaps (the latter used to control and/or eliminate body malodours (Loesche 1999).

Mechanical The basic management of oral malodour is a mechanical reduction of the amount of micro-organisms and substrates in the oral cavity (Van den Broek et al. 2008). Guidelines for the management of oral malodour typically emphasize the need for tongue cleaning using brushes or tongue scrapers. The dorsum of the tongue, with a surface profile that allows accumulation of VSC producing bacteria, is a significant contributor to oral malodour. Indeed several studies confirmed a positive relationship between tongue coating and oral malodour (Van Tornout et al. 2013). A number of clinical trials confirmed that tongue cleaning reduces both the amount of coating (and thus bacterial nutrients) as well as the number of bacteria, and thereby reduces oral malodour effectively (De Boever & Loesche 1995, Gilmore et al. 1973, Gross et al. 1975, Ralph 1988). However, others indicated that the reduction of the microbial load on the tongue after cleaning is negligible and that the malodour reduction probably results from the reduction of the bacterial nutrients (Menon & Coykendall 1994, Quirynen et al. 2004). A systematic review from Van der Sleen and co-workers (2010) stated that tongue cleaning has the potential to successfully reduce breath odour and tongue coating. However, data concerning the effect on chronic oral malodour were found to be insufficient. Also the current review failed to identify a single randomized controlled clinical trial particularly exploring the effect of tongue cleaning with ≥ 2 weeks follow-up.

Chemical The chemical reduction of VSC producing bacteria forms another therapeutic strategy. A range of over-the-counter mouthrinses for controlling mouth odour has been available for some time. The optimal antiseptic agent against oral malodour would be a product with proven, long-lasting efficacy in reducing organoleptic scores and VSC levels (Blom et al. 2012). Furthermore, such a product should have little or no side effects because it may be necessary to use it over longer periods of time. The effectiveness of the active ingredients in oral healthcare products is dependent on their concentration and above a certain concentration the ingredients can have unwanted side effects (Van den Broek et

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al. 2008). The studies in the present review unfortunately showed a strong heterogeneity, not only in the active ingredients tested but also in their use, as well as in the selection of volunteers and outcome variables. As such it prevented a meaningful meta-analysis. However, descriptive analysis of the data (Table 2) indicated that nearly all products with active ingredients showed beneficial effects in reducing oral malodour. Mouthwashes containing AmF, SnF2, Zn, CHX, or CPC, all reduced organoleptic scores. The present observation is in support of a recent systematic review with broader inclusion criteria allowing for short-term (multiple use) data (Blom et al. 2012). These review authors concluded that the most compelling evidence for a mouthwash in reducing oral malodour was provided for CHX especially when combined with CPC and Zn. A recent review, also including shortterm data (Dadamio et al. 2013b), concluded that antibacterial ingredients in toothpastes such as triclosan and metal ions like stannous and zinc appear to be effective in the control of oral malodour. Based on organoleptic assessments the present review supported the effect of active ingredients such as triclosan and Zn (Table 2). Recently, encouraging short-term (1 week) data were published for rinses with antimicrobial ingredients in combination with zinc (CHX+CPC+Zn and AmF+SnF2+Zn)

(Dadamio et al. 2013a). Zinc is an ion with two positive charges (Zn++), which will bind to the twicenegatively loaded sulphur radicals, and thus can reduce the expression of the VSCs. It basically converts for example H2S and CH3SH into non-volatile sulphides. The same applies for other metal ions such as stannous, mercury and copper. (Young et al. 2001). Another therapeutic approach could be the direct inhibition of bacterial enzymes (involved in the production of malodourous gases). The bacterial enzyme methionine-(gamma)-lyase, for example, is responsible for VSC formation by cleaving methionine into methyl-mercaptan, ammonium and (alpha)-keto butyrate and can be inhibited by oral malodour counter-actives (Givaudan 2007).

Microbiology An evaluation of the impact on the supra- or sub gingival microbial load or composition was not the focus of this systematic review. However, four studies included in addition to the clinical data also a microbiological assessment (Roldan & Winkel 2003, Peruzzo et al. 2007, Quirynen et al. 2005, Ademovski et al. 2012). Experiment by Roldan & Winkel (2003) and Quirynen and co-workers (2005) evaluated a mouthwash containing CHX+CPC+Zn for which they collected tongue samples, unstimulated saliva and subgingival plaque samples. It was concluded that there was no significant microbiological difference between the test and control product. Ademovski and co-workers (2012) assessing mouthwashes with a combination of Zn and CHX, sampled the dorsum of the tongue but failed to demonstrate differences in bacterial counts and changes of bacterial load. Peruzzo and coworkers (2007) assessed toothpaste with and without SLS and also found no antibacterial effect in tongue coating samples.

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Strength of the recommendation Various products were tested in the studies retrieved for this review. Only for CHX+CPC+Zn and ZnCl2+CPC some evidence emerged which allowed for a ‘weak’ strength of a recommendation for its

use. For all other products the evidence is insufficiently reliable to make informed decisions. It is undoubtedly clear that more high quality trials are needed to provide definitive answers to this problem. At present there is no consensus about how to assess oral malodour (Laleman et al. 2014). With this in mind it would be helpful to standardize assessments of oral malodour in order to allow future systematic reviewers to combine trials from different research groups more easily.

Limitations This review identified a number of additional potential limitations, which render a comparison between studies very difficult: •

Organoleptic scores were used as outcome variables for oral malodour. The odour judge (sniffer) is still the “gold standard” since the human nose can smell 10.000 different odours (Hatt 2004). The most important disadvantage of the organoleptic assessment is its subjectivity, which explains its low intra- and inter-examiner reliability (Laleman et al. 2014). Researchers are trying to improve the reliability and reproducibility (Greenman et al. 2005), for example, by involving a panel of odour judges (Yaegaki & Coil 2000) and training and calibrating the panel prior to the start of the study (Nachnani et al. 2005). To date, there are several simple portable devices available to quantify certain VSCs (e.g. Halimeter, Oral Chroma, Breathtron). Unfortunately, these devices have a number of shortcomings (e.g. specificity, confounding factors, stability), which translate into moderate correlations between their readings and the organoleptic outcomes (Laleman et al. 2014). These aspects have to be taken into consideration when reading this review.

•

No inclusion criteria were set regarding the diagnosis of halitosis nor a threshold of its measurements.

•

The included in this systematic review study by Rassameemasmaung et al. (2007) included participants with mild to chronic gingivitis, they were referred to the clinic for ‘gingivitis’. Quirynen et al. (2005) conducted the study in moderate periodontitis patients but these were treated for their periodontal problems as part of the study protocol using a one stage full mouth disinfection approach. The data emerging of this systematic review are therefore applicable for those patients with no untreated periodontitis.

•

A cost effectiveness analysis could not be performed because the aspect of costs in relation to the effectiveness of the anti-malodour products was not reported by any of the included studies.

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•

Publication bias: Papers included in the present review primarily reported on the beneficial effects of the active ingredients. Publication of studies with positive outcomes and statistically significant results may represent publication bias. Although no formal test could be performed the risk of publication bias must be considered as potentially possible.

•

Language bias: The restricted use of studies written in the English language may be another limitation.

Conclusion The collective evidence regarding the adjunctive use of products such as dentifrices, mouthwashes and tongue scrapers for reducing oral malodour is in general unclear. For mouthwashes containing active ingredients such as CHX+CPC+Zn and ZnCl+CPC the strength of the recommendation with respect to the potential efficacy to reduce oral malodour is considered to be ‘weak’. More profound research is needed to assess the effect of oral malodour products particularly in halitosis populations.

Acknowledgements The authors acknowledge the support of Joost Bouwman, head librarian of the Academic Center for Dentistry Amsterdam and Stephen Siegel from the Journal of Clinical Dentistry, who helped in the retrieval of the full-text articles. The authors also like to thank the following authors who responded to Blom et al. (2011) on a request for additional data: W. Wigger-Alberti and D.P. Codipilly.

Recommendations for further research The ADA has established Acceptance Program Guidelines that apply to products that have been designed for the management of oral malodour of a non-systemic origin. These include products that are active chemical agents as well as mechanical products. Newly developed products should be evaluated using study protocols satisfying the criteria as formulated by the ADA.

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Supporting information Additional Supporting information may be found in the online version of this article. Online Supporting information legends

ONLINE Appendix S1: Overview of the studies and reason for rejection after full-text reading

ONLINE Appendix S2. Methodological quality and estimated potential risk of bias scores of the included studies

ONLINE Appendix S3. Mean (SD) scores for the different intervention groups with various indices and their modifications. Within groups analysis are presented. S3a. ORG scores S3b. Total VSC measures.

References Ademovski, S., Lingström, P., Winkel, E., Tangerman, A., Persson, G.R. & Renvert, S. (2012) Comparison of different treatment modalities for oral halitosis. Acta Odontologica Scandinavica 70, 224-233. ♦

Ademovski, S.E., Persson, G.R., Winkel, E., Tangerman, A., Lingström, P. & Renvert S. (2013) The short-term treatment effects on the microbiota at the dorsum of the tongue in intra-oral halitosis patients – a randomized clinical trial. Clinical Oral Investigations 17, 463-473. ♦

Bollen CM & Beikler T. (2012) Halitosis: the multidisciplinary approach. International Journal of Oral Science 4, 55-63.

Borden, L.C., Chaves, E.S., Bowman, J.P., Fath, B.M. & Hollar, G.L. (2002) The effect of four mouthrinses on oral malodour. Compendium of Continuing Eduation in Dentistry 23, 531– 540. ♦

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Accepted Article

Blom, T., Slot, D.E., Quirynen, M. & Van der Weijden, G.A. (2012) The effect of mouthrinses on oral malodour: a systematic review. International Journal of Dental Hygiene 10, 209-222.

Codipilly, D.P., Kaufman, H.W. & Kleinberg, I. (2004) Use of a novel group of oral malodour measurements to evaluate an anti-oral malodour mouthrinse (TriOralTM) in humans. The Journal of Clinical Dentistry 15, 98–104. ♦

Copanitsanou, P. & Valkeapää, K. (2014) Effects of education of paediatric patients undergoing elective surgical procedures on their anxiety – a systematic review. Journal of Clinical Nursing 23, 940-954.

Dadamio, J., Van Tornout, M., Teughels, W., Dekeyser, C., Coucke, W. & Quirynen, M. (2013a) Efficacy of different mouthrinse formulations in reducing oral malodour: a randomized clinical trial. Journal of Clinical Periodontology 40, 505-513.

Dadamio, J, Laleman I, Quirynen M. (2013b) The role of toothpastes in oral malodour management. Monographs in Oral Sciences 23, 45-60.

De Boever, E.H. & Loesche, W.J. (1995) Assessing the contribution of anaerobic microflora of the tongue to oral malodour, Journal of the American Dental Association 126, 1384-1393.

Delanghe, G., Ghyselen, J., Feenstra, L., van Steenberghe, D. (1997) Experiences of a Belgian multidisciplinary breath odour clinic. Acta Otorhinolaryngol Belg.;51: 43-48. Fedorowicz, Z., Aljufairi, H., Nasser, M., Outhouse, T.L. & Pedrazzi, V. (2008) Mouthrinses for the treatment of halitosis. Cochrane Database of Systematic Reviews 8, CD006701.

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Givaudan, S. A. (2007) Compositions and methods to counteract oral malodour. International publication number: WO 2007025401 International application number: PCT/CH2006/000459

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Greenman, J., El Maaytah, M., Duffield, J., Spencer, P., Rosenberg, M., Corry, D., Saad, S., Lenton, P., Majerus, G. & Nachnani, S. (2005) Assessing the relationship between concentrations of malodour compounds and odor scores from judges. Journal of the American Dental Association 136, 749-757.

Gross, A., Barnes, C.P. & Lyon, T.C. (1975) Effects of tongue brushing on tongue coating and dental plaque scores. Journal of Dental Research 54, 1236.

Guyatt, G.H., Oxman, A.D., Kunz, R., Jaeschke, R., Helfand, M., Liberati, A., Vist, G.E. & Schünemann, H.J. (2008) GRADE Working Group. Incorporating considerations of resources use into grading recommendations. British Medical Journal 336, 1170-1173.

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Accepted Article

Hatt, H. (2004) Molecular and cellular basis of human olfaction. Chemistry & Biodiversity 1, 18571869.

Higgins, JPT, Green S. CCHB Cochrane Handbook for Systematic Reviews of Interventions (2009). Available at: http://cochrane-handbook.org/ (accessed 24 March 2012).

Hu, D., Zhang, Y.P., Petrone, M., Volpe, A.R., Devizio, W. & Giniger, M. (2005) Clinical effectiveness of a triclosan/copolymer/sodium fluoride dentifrice in controlling oral malodour: a 3-week clinical trial. Oral Diseases 11, (Suppl. 1) 51-53. ♦

Hu, D., Zhang, Y.P., Petrone, M., Volpe, A.R., DeVizio, W. & Proskin, H.M. (2003) Clinical effectiveness of a triclosan/copolymer/sodium-fluoride dentifrice in controlling oral malodour: a three-week clinical trial. Compendium of Continuing Education in Dentistry 24, (9 Suppl.) 34-41. ♦

Hu, D., Li, X., Yin, W., DeVizio, W., Mateo, L.R., Dibart, S. & Zhang, Y.P. (2013) Clinical investigation of oral malodour during long-term use of arginine-containing dentifrices. American Journal of Dentistry 26, 329-334.♦

Keukenmeester, R.S., Slot, D.E., Putt, M. & Van der Weijden, G.A. (2013) The effect of sugar-free chewing gum on plaque and clinical parameters of gingival inflammation: a systematic review. International Journal of Dental Hygiene 11, 2-14.

Kuo, Y.W., Yen, M., Fetzer, S. & Lee, J.D. (2013) Toothbrushing versus toothbrushing plus tongue cleaning in reducing halitosis and tongue coating: a systematic review and meta-analysis. Nursing Research 62, 422-429.

Laleman, I., Dadamio, J., De Geest, S., Dekeyser, C. & Quirynen, M. (2014) Instrumental assessment of halitosis for the general dental practitioner. Journal of Breath Research 8, 017103.

Liu, X.N., Shinada, K., Chen, X.C., Zhang, B.X., Yaegaki, K. & Kawaguchi, Y. (2006) Oral malodourrelated parameters in the Chinese general population. Journal of Clinical Periodontology 33, 31-36.

Loesche W.J. (1999) The effects of antimicrobial mouthrinses on oral malodor and their status relative to US Food and Drug Administration regulations. Quintessence International 30, 311318.

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Accepted Article

Moher, D., Liberati, A., Tetzlaff, J. & Altman, D.G. PRISMA Group. (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Journal of Clinical Epidemiology 62, 1006-1012.

Nachnani, S., Majerus, G., Lenton, P., Hodges, J. & Magallanes, E. (2005) Effect of training on odor judges scoring intensity. Oral Diseases 11, 40-44.

Navada, R., Kumari, H., Le, S. & Zhang, J. (2008) Oral malodour reduction from a zinc-containing toothpaste. The Journal of Clinical Dentistry 19, 69-73. ♦

Outhouse, T.L., Al-Alawi, R., Fedorowicz, Z. & Keenan, J.V. (2006) Tongue scraping for treating halitosis. Cochrane Database of Systematic Reviews 19, CD005519.

Peruzzo, D.C., Jandiroba, P.F. & Nogueira Filho Gda, R. (2007) Use of 0.1% chlorine dioxide to inhibit the formation of morning volatile sulphur compounds (VSC). Brazilian Oral Research 21, 70–74. ♦

PRISMA statement. Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Available at: http://www.prisma-statement.org/ (accessed 01 September 2014).

Quirynen, M., Avontroodt, P., Soers, C., Zhao, H., Pauwels, M. & van Steenberghe, D. (2004) Impact of tongue cleansers on microbial load and taste. Journal of Clinical Periodontology 31, 506510.

Quirynen, M., Zhao, H., Soers, C., Dekeyser, C., Pauwels, M., Coucke, W. & van Steenberghe, D. (2005) The impact of periodontal therapy and the adjunctive effect of antiseptics on breath odor-related outcome variables: a double-blind randomized study. Journal of Periodontology 76, 705-712. ♦

Quirynen M, Dadamio J, Van den Velde S, De Smit M, Dekeyser C, Van Tornout M, Vandekerckhove B. (2009) Characteristics of 2000 patients who visited a halitosis clinic. Journal of Periodontology ;36, 970-975.

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Roldan, S., Winkel, E.G., Herrera, D., Sanz, M. & Van Winkelhoff, A.J. (2003) The effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc lactate on the microflora of oral halitosis patients: a dual-centre, double-blind placebo-controlled study. Journal of Clinical Periodontology 30, 427–434. ♦

Rassameemasmaung, S., Sirikulsathean, A., Amornchat, C., Hirunrat, K., Rojanapanthu, P. & Gritsanapan, W. (2007) Effects of herbal mouthwash containing the pericarp extract of Garcinia mangostana L on halitosis. Journal of the International Academy of Periodontology 9, 19–25. ♦

Söder, B., Johansson, B. & Söder, P.O. (2000) The relation between foetor ex ore, oral hygiene and periodontal disease. Swedish Dental Journal 24, 73-82.

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Accepted Article

Van den Broek, A.M., Feenstra, L. & de Baat, C. (2008) A review of the current literature on management of halitosis. Oral Diseases 14, 30-39.

Van den Broek, A.M., Feenstra, L. & de Baat, C. (2007) A review of the current literature on aetiology and measurement methods of halitosis. Journal of Dentistry. 35, 627-635.

Van der Sleen, M.I., Slot, D.E., Van Trijffel, E., Winkel, E.G. & Van der Weijden, G.A. (2010) Effectiveness of mechanical tongue cleaning on breath odour and tongue coating: a systematic review. International Journal of Dental Hygiene 8, 258-268.

Van der Weijden, F., Dell'Acqua, F. & Slot, D.E. (2009) Alveolar bone dimensional changes of postextraction sockets in humans: a systematic review. Journal of Clinical Periodontology 36, 1048-1058.

Van Tornout, M., Dadamio, J., Coucke, W. & Quirynen, M. (2013) Tongue coating: related factors. Journal of Clinical Periodontology 40, 180-185.

Winkel, E.G., Roldan, S., Van Winkelhoff, A.J., Herrera, D. & Sanz, M. (2003) Clinical effects of a new mouthrinse containing chlorhexidine, cetylpyridinium chloride and zinc-lactate on oral halitosis. A dual-center, double-blind placebo-controlled study. Journal of Clinical Periodontology 30, 300–306.♦

Wigger-Alberti, W., Gysen, K., Axmann, E.M. & Wilhelm, K.P. (2010) Efficacy of a new mouthrinse formulation on the reduction of oral malodour in vivo. A randomized, double-blind, placebocontrolled, 3 week clinical study. Journal of Breath Research 4, 017102. ♦

Yaegaki, K. & Coil, J. (2000) Examination classification and treatment of halitosis; clinical perspectives, Journal Canadian Dental Association 66, 257-261.

Young, A., Jonski, G., Rolla, G.& Wåler, S.M. (2001) Effects of metal salts on the oral production of volatile sulfur-containing compounds (VSC). Journal of Clinical Periodontology 28, 776-781.

♦ studies selected for this review

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Accepted Article

Treatment of Oral Malodour. Medium-term efficacy of mechanical and/or chemical agents:

-a systematic reviewD.E. Slot, S. De Geest, G.A. van der Weijden & M. Quirynen

Boxes, Figures & Tables

Legends for publication

Box 1. Search terms used for PubMed-MEDLINE, Cochrane-CENTRAL and EMBASE. The search strategy [ AND ] was customized appropriately for each of the additional databases taking into account differences in controlled vocabulary and syntax rules. Figure 1. Search, selection and analysis process.

Table 1. Overview of the studies processed for data extraction Table 2. A descriptive summary of statistical significance between treatment groups.

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Accepted Article

Table 3. GRADE evidence profile for impact of the adjunctive effect on oral malodour mouthwash products in combination with toothbrushing, in general healthy patients, when used ≥ 2 weeks.

Box 1. Search terms used for PubMed-MEDLINE, Cochrane-CENTRAL and EMBASE. The search strategy [ AND ] was customized appropriately for each of the additional databases taking into account differences in controlled vocabulary and syntax rules.

The following terms were used in the search strategy:

[

AND

]

The asterisk (*) was used as a truncation symbol.

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Accepted Article

Figure 1.

Analyzed

Included

Eligibility

Screening

Identification

Search, selection and analysis process. Cochrane-CENTRAL 190

PubMed-MEDLINE 1021

Excluded by title and abstract 1008

Unique title & abstracts

Excluded after full reading 32

Selected for full-text reading

EMBASE 170

1054

46 Included from the reference list 0 Final Selection 14*

Tongue cleaning 0 papers

Dentifrices 5 papers

Mouthwashes 6 papers

Combinations 3 papers

Dentifrices 5 experiments

Mouthwashes 5 experiments

Combinations 2 experiments

This article is protected by copyright. All rights reserved.

Accepted Article

*Three times two papers on the same experiment were included and one paper published two experiments.

Table 1. Overview of the studies processed for data extraction

#

Authors (year)

Study design, duratio n

# Participants baseline (end), Gender, age (mean/range) , characteristi cs

Groups

Regimen: Use & instruction Oral prophylaxis (OP)

Conclusions of the authors of the orginal papers

RCT

? - (174)

a: 250 ppm AmF/SnF + 0.2% Znla MW

15 mL

Parallel

♀: 144, ♂: 32

All 3 CHX rinses were able to significantly reduce oral malodour in patients with increased OLS or VSC values.

MOUTHWA SHES

Wigger-Alberti et al. (2010)

Rassameemasma ung et

Doubleblind 3 weeks

Mean age: 43.1 Range: ? No perio OLS: >2 Systemically healthy

60 sec b: 0.05% CHX + 0.05% CPC + 0.14% Zn-la MW (Halita®, Dentaid, S.A., Barcelona, Spain) c: 0.12% CHX MW (Perio-Aid® Maintenance, Dentaid, Barcelona, Spain) d: Placebo MW

Smokers: no RCT

60 - (60)

Parallel

♀: 48, ♂: 12

Doubleblind

Mean age: 26.15 Range: 17-37

2 weeks

Mild to moderate chronic gingivitis

al.(2007)

2x daily No gargling

OP: No OH instructions: ? Standardized OH products: TB + DF Other devices: ?

a: Herbal MW (Prepared by the Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.)

15 mL

b: Placebo MW

2x daily

Oral malodour: ≥ 80 ppb VSC in morning breath

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60 sec

OP: No (a) & Yes (b) (2 experiments) OH instructions: No Standardized OH products: ? Other devices: ?

Herbal mouthwash that contained the pericarp extract of Garcinia mangostana may be used as an adjunct in treating oral malodour.

Accepted Article Codipilly et al. (2004)

Systemically healthy Smoking: no

RCT

50 - (48) subjects

Parallel

♀: 28, ◊ ♂: 20 ◊

Doubleblind

Mean age: 40.2 ◊ Range: 21- 69 ◊

4 weeks

No perio

20 mL

b: ZnC MW (BreathRx® Discus Dental, Inc., Los Angeles, CA, USA)

2x daily

c: Placebo MW

Oral malodour: ≥ 80 ppb VSC in morning breath

30 sec

Zinc chloride plus sodium chlorite mouthrinse (TriOral) is more effective in reducing oral malodour than a zinc chloride alone mouthrinse.

OP: No OH instructions: ? Standardized OH products: TB + DF Other devices: ?

Systemically healthy Smokers: ?

Roldan et al. (2003) &

RCT

40 - (40)

Winkel et al. (2003)

Parallel

♀: 19, ♂: 21

Doubleblind

Mean age: 43.8 Range: 21-84

2 weeks

No perio

Borden et al. (2002)

a: ZnC + NaClO2 MW (TriOral® triumph pharmaceuticals Inc., St. Louis, MO, USA)

a: 0.05% CHX + 0.05% CPC + 0.14% Zn-la MW (Halita®, Dentaid, S.L., Barcelona, Spain) b: Placebo MW

15 mL 60 sec gargling

The tested mouthrinse was effective for the treatment of oral malodour.

2x daily

OP: No OH instructions: No Standardized OH products: DF Other devices: No other DF or MW, avoid TC

Oral malodour: oral origin, OLS > 1, VSC > 170 ppb, TCI > 4. Systemically healthy Smokers: included (not 12 hrs before examination)

RCT

95 - (84)

Parallel

♀: 66, ♂: 29

Doubleblind 4 weeks

Mean age: ? Range: 19-65 No perio

a: 0.064% Thm, 0.09% Euc + 0.042% Men MW (Listerine® Antiseptic, Pfizer, Inc., Morris Plains, NJ, USA)

? mL

b: 0.075% CPC MW (BreathRx® Dicus Dental, Inc., Culver City, CA, USA)

2x daily

OLS ≥ 4.

c: ClO2 + Zn-ac MW (Oxygene®, Oxyfresh Worldwide, Inc., Spokane, WA, USA)

Systemically healthy

d: Placebo MW

This article is protected by copyright. All rights reserved.

? Sec

OP: ? OH instructions: ? Standardized OH products: TB + DF Other devices: Not allowed

The four mouthrinses reduced oral malodour within 4 hours of single usage. CPC was the most effective, and the placebo was the least effective. CPC was the only mouthrinse that reduced oral malodour from baseline values after 2 and 4 weeks of daily use.

Accepted Article

Smokers: no

DENTIFRIC ES Hu et al. (2013)

Peruzzo et al. (2007)

Navada et al. (2008)

RCT

? – (119)

Parallel

♀: 64, ♂: 55

Doubleblind

Range: 21-70 Mean age: 50,62 ◊

6 months

No perio

a: 1,5% arginine, 1450ppm fluor (NaMPF) dical base

1 min 2x daily

b: 8% arginine, 1450ppm fluor (NaMPF) Ca.carbonate base

TB: ?

c: 1450ppm fluor (NaMPF) dical base

OP: No OH instructions: No Other devices: ?

? min

TB: provided

Oral malodour: ?

No statistical significant difference in oral malodour among subjects using the 3 different DF after 6 months of use.

Systemically healthy Smokers: ?

RCT

25 (25)

Cross-over

♀: 12, ♂: 13

a: SLS DF (SLS-Close Up® Red – Unilever, Sao Paulo, Brazil)

Double blind

Range: 25-35 Mean age: 27

b: SLS free DF (Unilever, Sao Paolo)

30 days

Oral malodour: ?

3x daily

SLS containing DF reduces the VSC formation in morning bad breath in healthy subjects.

OP: Yes (7 days prior baseline) OH instructions: Yes Other devices: Dental floss allowed, no TC or MW.

No perio Systemically healthy Smokers: no

RCT

190 - (188)

Parallel

Range: 18-45

Doubleblind

♀: ? , ♂:?

a: Silica gel DF containing 1000ppm Fluoride with 0,2% Zinc

2 min

b: Placebo DF (1000ppm Fluoride)

TB: ?

2x daily

No perio 4 weeks Oral malodour: VSC 120-250ppb General health: ? Smokers: included (not on morning of examination)

This article is protected by copyright. All rights reserved.

OP: No OH instructions: No Other devices: No instruction

DF with 0,2 % Zinc sulphate is effective in reducing oral malodour, compared to a toothpaste without zinc.

Accepted Article

RCT

190 – (187)

Parallel

Range: 18-45

Doubleblind

♀: ? , ♂:? No perio

4 weeks OLS ≥3 General health: ? Smokers: included (not on morning of examination)

Hu et al. (2005)

RCT

? – (81)

+

Parallel

Range: 22-70 Mean age: 44,73 ◊

Hu et al. (2003)

Doubleblind 3 weeks

No perio Systemically healthy Oral Malodour:?

a: 0,3% triclosan, 2% copolymer, 0,243% sodium fluoride in a silica base ( Colgate Total Advanced Frech®, Colgate-Palmolive Company New York USA)

1 min

b: 0,243% sodium fluoride in a silica base (Colgate Cavity Protection Winterfresh Gel®, Colgate-Palmolive Company New York USA)

OP: ? OH instructions: No Other devices: ?

2x daily

A DF containing triclosan/ copolymer/NaF provides effective control of oral malodour up to 12h.

TB: provided

Smokers: included (not on morning of examination)

COMBINATI ON Quirynen et al. (2005)

RCT

45 - ?

a: CHX 0,2% MW + TS

Parallel

Mean age: 47,5

b: CHX 0,05% + CPC 0,05% MW + TS

Doubleblind

♀ 27, ♂18 c: Placebo MW + TS Moderate perio

6 months Oral Malodour:? Systemically healthy Smokers: included

This article is protected by copyright. All rights reserved.

MW: 1 min, 2x daily

OP: Yes (OSFMD + CHXgel) OH instructions: Yes Standardizes OH products: ? Other devices: Interdental brushes

Mechanical debridement in combination with improved oral hygiene (including tongue scraping) reduces the VSC levels in the oral cavity. A CHX 0,2% solution or a CHX 0,05% + CPC 0,05% solution offers a beneficial adjunctive effect.

Accepted Article Ademovski et al. (2012) +

Ademovski et al. (2013)

RCT

21 - 21

a: Zn acetate (0,3%), CHX diacetate (0,025%), Sodium fluoride (0,05%) MW (SB12® Antula Health Care AB, Stockholm, Sweden) + TS (Dentaid, Barcelona, Spain)

Rinse: 10mL, 1min, 2x daily

Cross-over

♀ 10, ♂11

Doubleblind

Mean 45,7y Range 21-66y

2 weeks

No perio Oral malodour: oral origin, OLS ≥2, VSC ≥160ppb

b: Zn acetate (0,3%), CHX diacetate (0,025%), Sodium fluoride (0,05%) MW (SB12® Antula Health Care AB, Stockholm, Sweden)

OP: ? OH instructions: Yes (TS + MW) Standardizes OH products: ? Other devices: ?

Systemically healthy

c: Placebo MW + TS (Dentaid, Barcelona, Spain)

Smokers: no

d: Placebo MW

TS: 5 strokes, as far as possible 2x/day, before rinsing

Rinsing with the active rinse resulted in clinically relevant reductions. The use of a tongue scraper did not provide additional benefits to the active rinse.

TB: Toothbrush TS: Tongue scraper MW: Mouthwash DF: Dentifrice TC: Tongue coating TCI: Tongue coating Index OLS: Organoleptic Score VSC: Volatile Sulphur Compounds OH: Oral Hygiene OP: At initial appointment all teeth were thoroughly scaled and polished. ◊: calculated by the authors of this review based on the presented data in the selected paper ?= unknown/not given ‡: Agents known to interfere with the antibacterial activity of CHX (sulphates, phosphates) were excluded from the dentifrices .

This article is protected by copyright. All rights reserved.

Accepted Article

Table 2. A descriptive summary of statistical significance between treatment groups.

Study #

Wigger-Alberti et al. (2010)

Codipilly et al. (2004)

Roldan et al. (2003) & Winkel et al. (2003)

ORG

VSC

+

+

+

+

c: 0.12% CHX MW

+

+

a: Herbal MW

□

+

Placebo MW

b: Herbal MW + OP

□

+

Placebo MW + OP

a: ZnC + NaClO2 MW

□

+

b: ZnC MW

□

+

+

+

0

?

b: 0.075% CPC MW

+

?

c: ClO2 + Zn-ac MW

0

?

a: 250 ppm AmF/SnF + 0.2% Zn-la MW b: 0.05% CHX + 0.05% CPC + 0.14% Zn-la MW

a: 0.05% CHX + 0.05% CPC + 0.14% Zn-la MW a: 0.064% Thm, 0.09% Euc + 0.042% Men MW

Borden et al. (2002)

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Comparison

Evaluating

Placebo (tap water)

Placebo MW

Placebo MW

Placebo MW

MOUTHWASH

Rassameemasmaung et al. (2007)

Intervention

Accepted Article

a: 1,5% arginine, 1450ppm fluor (NaMPF) dical base

0

□

0

□

+

+

□

+

+

□

+

□

1450ppm fluor (NaMPF)

Hu et al. (2013) b: 8% arginine, 1450ppm fluor (NaMPF) Ca.carbonate base

Peruzzo et al.

Navada et al. (2008)

a: Silica gel DF containing 1000ppm Fluoride with 0,2% Zinc b: Silica gel DF containing 1000ppm Fluoride with 0,2% Zinc

SLS free DF

DENTIFRICE

a: SLS DF

(2007)

dical base

Placebo DF (1000ppm Fluoride) Placebo DF (1000ppm Fluoride)

Hu et al. (2005) & c: 0,3% triclosan, 2% copolymer, 0,243%

Hu et al. (2003) sodium fluoride in a silica base

Quirynen et al.

a: CHX 0,2% MW + TS

□

?

(2005)

b: CHX 0,05% + CPC 0,05% MW + TS

□

?

0,243% sodium fluoride in a silica base

Placebo MW + TS

(0,025%), Sodium fluoride (0,05%) -

+

+

+

Placebo MW - TS

?

+

+

Placebo MW + TS

TS b: Zn acetate (0,3%), CHX diacetate

Ademovski et al.

(0,025%), Sodium fluoride (0,05%) +

(2012) &

TS

Ademovski et al.

Zn acetate (0,3%), CHX c: Zn acetate (0,3%), CHX diacetate

?

0

0

diacetate (0,025%), Sodium fluoride (0,05%)

TS - TS d: Placebo MW + TS

+

0

0

Placebo MW - TS

+ = significant difference in favour of test group, - = significant difference in favour of control group, 0 = no significant difference, □ = no data available, ? = inconclusive data which does not allow to draw conclusions concerning statistical significance, NaF = sodium fluoride

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TONGUE

(0,025%), Sodium fluoride (0,05%) +

SCRAPER

(2013)

MOUTHWASH

a: Zn acetate (0,3%), CHX diacetate

Accepted Article

Table 3. GRADE evidence profile for impact of the adjunctive effect on oral malodour mouthwash products in combination, with toothbrushing in general healthy patients when used ≥ 2 weeks.

GRADE items Study design

Product CHX+CPC+Zn Randomized Controlled Clinical Trial N=2

ZnCl+CPC Randomized Controlled Clinical Trial N=2

Potential risk of bias

Low to high

Low

Consistency

Inconsistent

Inconsistent

Directness

Direct

Direct

Precision

High

High

Possible

Possible

Moderate

Small to moderate

Weak

Weak

Publication bias Magnitude of the effect Body of evidence and strength of the recommendation

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