Interventions for managing halitosis
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the effects of different interventions for the management of halitosis.
Background
The term halitosis is a general term used to describe any disagreeable odour of expired air, regardless of its origin. The lay term, bad breath, is the generally accepted term for foul smells emanating from the mouth but the term oral malodour is reserved for halitosis originating from the oral cavity (Tangerman 2002). Mouthwashes and tongue scrapers are popular ways of dealing with oral malodour.
Description of the condition
Prevalence and aetiology
The reliability of relevant epidemiological data has been questioned, but the prevalence of halitosis has been reported to be as high as 50% (Yaegaki 2000). In a study in Japan 24% of patients complained of oral malodour (Miyazaki 1995) while in France it was reported that between 50% and 60% of the population suffer from chronic halitosis (Meningaud 1999). In Belgium (Leuven) a study evaluated the characteristics of 2000 patients who visited a halitosis clinic, and reported that 76% of the patients had a possible oral cause e.g. tongue coating 43%, gingivitis/periodontitis 11% or a combination of the two 18% (Quirynen 2009).The most recent literature review reported a wide variation in the prevalence of halitosis around the world, with a rate ranging from 22% to 50% of the population (Akaji 2014).
It is now fairly widely accepted that halitosis originates from the oral cavity (Ayers 1998; Delanghe 1997; De Geest 2016). Accumulation of bacteria and food residues at the posterior part and in the furrows of the tongue (Seeman 2014; van Steenberghe 1997) is considered to be the major cause (Scully 1997). Interdental plaque and gingivitis may also play a contributory role, and although periodontal pockets may produce putrid odours, their contribution to oral malodour is still unclear (De Geest 2016; Morita 2001).
Halitosis‐causing bacteria are the primary sources of volatile sulphur compounds (VSC); the chief components of which are hydrogen sulphide and methyl mercaptans (Kleinberg 1990; Tonzetich 1977). Volatile sulphur compounds and other additional odours such as indole, skatole, putrescine and cadaverine (Kleinberg 1995) are produced through the bacterial metabolic degradation of food debris, desquamated cells, saliva proteins, dental plaque and microbial putrefaction (Ratcliff 1999). The periodontal pocket also provides an ideal environment for VSC production thus explaining why patients with periodontal disease often complain of oral malodour (Morita 2001). The intensity of clinical bad breath has been shown to be significantly associated with the amount of intraoral VSC level and to be correlated directly with periodontal health status (Bosy 1994; Replogle 1996; Stamou 2005).
Classification of halitosis
Halitosis has been defined as an unpleasant odour exhaled through the mouth and upper airways, caused by biofilm accumulation on the dorsum of the tongue, the interdental spaces or due to periodontal disease, although the condition is multifactorial and may involve both oral and non‐oral conditions (Oliveira‐Neto 2013; van den Broek 2007).
Although this classification has not been universally accepted by all experts in the field there is general agreement that halitosis can be categorised as genuine halitosis, pseudo‐halitosis and halitophobia (Yaegaki 2000). Genuine halitosis has been further subclassified as physiological halitosis in which there is no readily apparent disease or pathological condition, or pathological halitosis which occurs as a result of an infective process of the oral tissues. Pseudo‐halitosis is a condition in which there is absence of halitosis but the patient believes that they have oral malodour. Halitophobia can occur when there is no physical or social evidence to suggest that halitosis is present and which can persist after treatment for either genuine halitosis or as pseudo‐halitosis.
Organoleptic measurement by trained breath judges is considered to be the gold standard and the most reliable way of evaluating malodour (Rosenberg 1995), but this has been contested by studies showing that measurements with the halimeter appear to be more reproducible albeit possibly less reliable than organoleptic methods (Silwood 2001). Methods of assessment of levels of malodour include those which are very simple, highly subjective and others which are complex, time consuming and involve the use of sophisticated equipment:
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organoleptic (Tsunoda 1981);
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portable VSC monitor, the halimeter (Rosenberg 1991);
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gas chromatography coupled with flame‐photometric detection (Solis‐Gaffar 1975);
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culture of plaque and periodontal pocket exudates (Loesche 1995).
Measurement of VSC levels can be carried out by a variety of methods: organoleptic which are considered subjective by some investigators but are the ones of most relevance to patients (Tsunoda 1981), and the more complex gas chromatography techniques (Solis‐Gaffar 1975). Portable computerized VSC monitors or halimeters are available, they are compact, easy to use and relatively inexpensive (Pedrazzi 2004) but have their limitations in that they have a high sensitivity for hydrogen sulphide, but low sensitivity for one of the other sources of malodour, methyl mercaptan (Rosenberg 1991). A correlation rate has been reported between the self estimation of bad breath and the presence of oral malodour as determined by organoleptic examination by odour‐judge assessment in patients with slight or moderate oral halitosis (Romano 2010).
Description of the intervention
At present there are no standard and accepted protocols for the treatment of oral malodour (Morita 2001). Patients who are conscious that they have halitosis may attempt to mask it through compulsive brushing or with a range of over the counter methods such as chewing gum, mints, scented liquid drops, and the use of mouthrinses (Borden 2002). Most of these merely provide a competing and temporary smell that is capable of masking the unfavourable malodour. Some mouthrinses contain certain components that can neutralise the malodour or the bacteria which produce it. The most common of these include alcohol, zinc, phenol, chlorhexidine and folic acid. Reduction of the causative bacteria can also be accomplished through improving oral hygiene (Tonzetich 1978) in addition to cleaning of the tongue (Rosenberg 1996). This can be achieved by brushing or scraping the dorsum of the tongue to dislodge trapped food, cells, and bacteria from between the filiform papillae. Methods for treating or masking halitosis include:
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mechanical methods: tongue cleaners which are more commonly made of plastic, resin, rubber. These may contain nylon bristles and grooves or corrugations but they must be smooth. Toothbrushes can be used but these should normally have soft bristles (or extra soft bristles) only (Pedrazzi 2004);
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chemical methods: these include a range of mouthwashes containing antimicrobials such as chlorhexidine (0.2% to 0.12%), cetylpyridinium chloride (0.05% to 0.07%), hydrogen peroxide and essential oils to combat proteolytic odoriferous bacteria, producing VSCs, and those that mask odours, without interfering with microbial viability (zinc chloride or lactate, chlorine dioxide – 0.3%). Combinations of antimicrobial agents in one mouthwash, such as zinc salts and essential oils or zinc salts and chlorhexidine or cetylpyridinium chloride are also available (van den Broek 2008).
Some combinations of mechanical and chemical methods have also been explored, with the combination of brushes and toothpastes containing zinc salts or even toothbrushes and chlorhexidine or other antimicrobial agents (Slot 2015; Slots 2012).
How the intervention might work
A range of mechanical and chemical hygiene (mouthrinses) methods have been advocated (Oliveira‐Neto 2013), however the effectiveness of any intervention may be influenced by the nature of the mouthrinse formulation (Fedorowicz 2008), or by the type of mechanical device (dental floss, toothbrush, toothpaste) used to reduce VSCs (Oliveira‐Neto 2013).
The intervention needs to be able to reduce, eliminate or mask the production of VSCs, i.e. actions aimed at minimising the food available for odoriferous bacteria, reduce the total number exists of these bacteria, or make any environment where VSC‐producing bacteria live, less hospitable. The success of any halitosis intervention appears to hinge on the reduction of VSC levels and other foul volatiles and consequently the majority focus on mechanical and chemical options.
Mechanical interventions (i.e. brushing, flossing and tongue scraping) aim to reduce the numbers of VSC‐producing bacteria, residual food matter and cellular debris from the gingivae and tongue. In an earlier version of a systematic review of the effectiveness of tongue scraping for treating halitosis, the review authors found that mechanical tongue cleaning with tongue scrapers appeared to have very limited and short acting benefits in controlling halitosis (Outhouse 2006).
The limitations of mechanical methods to effectively reach and remove VSC‐producing bacteria from all oral ecological sites are acknowledged. The possibility that mouthrinses may be more effective in reaching the less accessible parts of the oral cavity, their greater social acceptance and ease of use has led to the development of a large number and range of over the counter mouthrinses (Ayers 1998; Richter 1996).
A number of mouthrinses contain antibacterial agents in addition to flavouring agents and these have been generally categorised into those that neutralise and those that mask the odour. Components which neutralise can further be divided into those that affect the bacteria directly or the chemical compounds they produce, and include chlorhexidine, phenol, Triclosan, chlorine dioxide, alcohol and metal ions, the most common of which is zinc (Carvalho 2004; Farrell 2006). Some of the odour‐masking agents, consist of essential oils, which can also provide a competing and purely temporary smell that is capable of disguising the unfavourable malodour.
Tongue cleaning has been claimed to reduce oral malodour by decreasing VSC concentration by 20% to 70% (Tonzetich 1977). A recent study compared both mechanical and mouthrinses for treatment of morning breath and the authors concluded that chlorhexidine and mechanical oral hygiene reduced bad breath for longer periods than tongue cleaning alone (Oliveira‐Neto 2013).
The possibility of any adverse effects associated with continuous usage of mouthrinses or tongue scraping are the focus of continuing research.
Why it is important to do this review
Halitosis can be serious enough to cause personal embarrassment, reduce self esteem and adversely affect personal relationships. It may also be a barrier to certain types of employment. There is existing uncertainty as to which is the most effective method of oral malodour control. The most popular method used involves mouthwash containing chemicals which destroy odour‐forming bacteria and include other odour‐masking constituent which can disguise the smell. The simplicity in use and social acceptance of mouthrinses appear to support their popularity over mechanical means.
This review will include the previous reviews on tongue scraping (Outhouse 2006) and mouthrinses (Fedorowicz 2008) for halitosis.
Objectives
To assess the effects of different interventions for the management of halitosis.
Methods
Criteria for considering studies for this review
Types of studies
We will only include randomised controlled trials.
Types of participants
We will include studies that recruited adolescents and adult participants over the age of 16 who presented with a clinical or self assessed diagnosis of halitosis, with no significant comorbidity or health condition that might lead to increased halitosis (e.g. diabetes). We will exclude studies which had been conducted on participants with refractory and severe chronic periodontal diseases.
Types of interventions
Any intervention for the management of halitosis compared to another or placebo, or no intervention. The active interventions or controls would have been administered over a minimum of one week and with no upper time limit.
Studies which include single use mouthwashes will not be considered for this review.
Types of outcome measures
We will not consider these prespecified outcomes as criteria for including studies in this review, but they are a representative list of the outcomes of interest within whichever studies were included. See section 5.1.2 in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
Primary outcomes
For the primary outcomes in this review we will consider self expressed (perceived) (Greenman 2004) and organoleptic (human nose) assessments of halitosis using any validated malodour intensity scale.
Secondary outcomes
We will consider both the self assessment (including quality of life) and the assessment of halitosis as measured by a halimeter, portable sulphide monitor or gas chromatography coupled with flame‐photometric detection.
Additional outcomes which will be considered include determination of peak and steady‐state volatile sulphur compound levels using a sulphide monitor, prior to and at several time‐points after any intervention.
Adverse events
We will report on any specific adverse effects related to any clinically diagnosed hypersensitivity or other reactions to the interventions.
Search methods for identification of studies
To identify studies for this review, detailed search strategies for each database to be searched will be developed. These will be based on the search strategy developed for MEDLINE (Appendix 1), but revised appropriately for each database to take account of differences in controlled vocabulary and syntax rules. We will use a combination of controlled vocabulary and free text terms. The MEDLINE search strategy will be combined with the Cochrane Highly Sensitive Search Strategy (CHSSS) for identifying randomised trials (RCTs) in MEDLINE: sensitivity maximising version (2008 revision) as referenced in Chapter 6.4.11.1 and detailed in box 6.4.c of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The EMBASE subject search will be linked to an adapted version of the Cochrane Embase Project filter for identifying RCTs in EMBASE via Ovid (seewww.cochranelibrary.com/help/central‐creation‐details.html for information).
Electronic searches
We will search the following databases:
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the Cochrane Oral Health Group Trials Register (to date);
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the Cochrane Central Register of Controlled Trials (the Cochrane Library, current issue);
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MEDLINE via Ovid (1946 to date);
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EMBASE via Ovid (previous six months).
Due to the Cochrane Embase Project to identify all clinical trials on the database and add them to CENTRAL, only the last six months of the EMBASE database will be searched. Please see the searching page on the Cochrane Oral Health website for more information. No other restrictions will be placed on the language or date of publication when searching the electronic databases.
Searching other resources
Trials registers
We will search the following trials registers to the present:
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the World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch).
References from published studies
Two review authors (Vinícius Pedrazzi (VP) and Zbys Fedorowicz (ZF)) will examine the bibliographies of the included and excluded studies for further references to potentially eligible randomised controlled trials.
Correspondence
Two review authors (VP and ZF) will contact trial investigators and ask them to provide missing data or clarify study details.
Adverse effects
We will not conduct a separate search for adverse effects of interventions for halitosis. However, we will examine data on adverse effects from the included studies that were identified.
Data collection and analysis
Selection of studies
Two review authors (VP and ZF) will independently assess the abstracts of studies resulting from the searches. We will obtain full copies of all relevant and potentially relevant studies, those appearing to have met the inclusion criteria, or for which there was insufficient information in the title and abstract to make a clear decision on eligibility. We will assess the full‐text papers independently and resolve any disagreement on the eligibility of included studies through discussion and consensus. We will exclude those records that do not meet the inclusion criteria, and we will note the reasons for their exclusion in the 'Characteristics of excluded studies' section of the review.
Data extraction and management
Two review authors (VP and ZF) will independently collect study details and outcome data using a predetermined form designed for this purpose. We will enter study details into the 'Characteristics of included studies' table in Review Manager (RevMan) (RevMan 2014). The authors will only include data if there is an independently reached consensus.
If reported, we will extract the following details.
(a) Trial methods ‐ method of sequence generation and concealment of allocation sequence; masking of participants, trialists and outcome assessors; exclusion of participants after randomisation; proportion of and reasons for losses to follow‐up.
(b) Participants ‐ country and study setting; sample size; age; ethnicity; inclusion and exclusion criteria.
(c) Intervention ‐ type; concentration, dose, and frequency; route of administration; duration of intervention and follow‐up.
(d) Control ‐ type; duration of intervention and follow‐up.
(e) Outcomes ‐ primary and secondary outcomes as specified in the 'Types of outcome measures' section of this protocol.
If stated, we will record the sources of funding of the included studies.
Assessment of risk of bias in included studies
Two review authors (VP and ZF) will assess the risk of bias of the selected studies independently using Cochrane's tool for assessing risk of bias as described in Chapter 8, section 8.5, in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will compare the evaluations and discuss and resolve any inconsistencies between the review authors.
We will assess the following domains as 'low risk of bias', 'unclear' (uncertain risk of bias), or 'high risk of bias':
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sequence generation;
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allocation concealment;
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blinding of participants and personnel;
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blinding of outcomes assessment;
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incomplete outcome data;
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selective outcome reporting; and
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other bias.
We will report these assessments for each individual study in the 'Risk of bias' tables.
We will categorise and report the overall risk of bias of each of the included studies according to the following:
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low risk of bias (plausible bias unlikely to seriously alter the results) if all criteria were met;
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unclear risk of bias (plausible bias that raises some doubt about the results) if one or more criteria were assessed as unclear; or
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high risk of bias (plausible bias that seriously weakens confidence in the results) if one or more criteria were not met.
Measures of treatment effect
We will present continuous outcomes on the original scale as reported in each individual study. If similar outcomes are reported using different scales, we will convert these to standardised mean differences (SMD). We will present either mean differences (MD) or SMD with their 95% confidence intervals (CIs).
Dichotomous outcomes will be presented as risk ratios (RR) and 95% CIs, if found significant, we will convert them to either: the number of patients needed to treat to find one additional beneficial outcome (NNTB); or the number needed to treat to find one additional harmful outcome (NNTH).
Unit of analysis issues
Cross‐over trials
Unit of analysis issues can arise in studies where participants have been randomised to multiple treatments in multiple periods or where there has been an inadequate wash‐out period. We will analyse these data based on the advice provided in section 16.4.4 in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will assess the carry‐over and period effects descriptively, and if there is evidence of minimal impact and there are adequate data, we will carry out a paired analysis.
Studies with multiple treatment groups
Studies that are reported with multiple treatment groups have the potential for participant data to contribute to multiple comparisons. We will assess the treatments and determine which are relevant to our review then allocate the non‐intervention participants as the 'shared' group. We will split the 'shared' group equally into the number of comparisons made, as discussed in section 16.5.4 in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).
Dealing with missing data
If we encounter data missing from trials that are less than 10 years old, we will try wherever possible to contact the investigators or sponsors of these studies. We will re‐analyse data according to the intention‐to‐treat (ITT) principle whenever possible.
Assessment of heterogeneity
We will assess clinical heterogeneity by examining the characteristics of the studies and the similarity between the types of participants and the interventions. We will assess the degree of heterogeneity between the studies using the I2 statistic. We will report heterogeneity as important and at least moderate to substantial if the I2 statistic >60% (Higgins 2011). If this can be explained by clinical reasoning and a coherent argument could be made for combining the studies, we will enter these into a meta‐analysis. In cases where the heterogeneity cannot be adequately explained, we will pool the data but will account for any heterogeneity and downgrade the quality of the body of evidence according to GRADE methods.
Assessment of reporting biases
Our assessments of reporting bias will follow the recommendations on testing for funnel plot asymmetry (Egger 1997), as described in section 10.4.3.1 in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will perform these for primary and secondary outcomes for meta‐analysis if we include a minimum number of studies, to allow a reasonable estimate of the effect of intervention (nominally nine studies). We will only present funnel plots if there was some evidence of asymmetry in the plots. We may also explore possible sources of asymmetry with an additional sensitivity analysis.
Data synthesis
Two review authors (VP and ZF) will analyse the data in RevMan (RevMan 2014) and report them in accordance with the advice in Chapter 9 in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will carry out a random‐effects meta‐analysis if we are able to identify an adequate number of studies (n ≥ 3) that investigated similar interventions and reported data that exhibited not more than moderate heterogeneity (Treadwell 2006).
Subgroup analysis and investigation of heterogeneity
We will consider conducting the following subgroup analyses subject to availability of a reasonable number of studies (n ≥ 3) reporting data:
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organoleptic level of halitosis ≥ 3 at baseline;
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evaluation method: organoleptic or halimeter;
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duration of treatment and the time of assessments.
Sensitivity analysis
We will carry out sensitivity analyses to assess the robustness of the results of this review. This will include repeating the analyses with the following adjustment: exclusion of studies at high risk of bias and reporting of any comparative difference between the results of these analyses.
Presentation of main results
We will produce 'Summary of findings' tables for the most important comparisons (GRADEpro 2014) of the following outcomes listed according to priority:
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self expressed change from baseline in halitosis;
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investigator assessed organoleptic change from baseline in halitosis;
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investigator halimeter assessed change from baseline in halitosis;
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adverse events.
