Halitosis

Jaisri R. Thoppay, Andreas Filippi, Katharine Ciarrocca,John Greenman, and Scott S. De Rossi

ContentsIntroduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2

Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Local Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Systemic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Psychogenic Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

Clinical Pathologic Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Patient Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

J.R. Thoppay (*)Oral Medicine, Orofacial Pain and Geriatric Programs,Orofacial Pain and Geriatric Oral Health Programs,Department of Oral and Maxillofacial Surgery, VCUSchool of Dentistry and VCU Medical Center, VirginiaCommonwealth University, Richmond, VA, USAe-mail: jthoppay@vcu.edu

A. FilippiDepartment for Oral Surgery, Oral Radiology and OralMedicine and Center of Salivary Diagnostics andHyposalivation, University Center for Dental MedicineBasel, University of Basel, Basel, Switzerlande-mail: andreas.filippi@unibas.ch

K. CiarroccaDental College of Georgia, Augusta University, Augusta,GA, USAe-mail: kciarrocca@augusta.edu

J. GreenmanFaculty of Health and Life Sciences, Bristol, UKe-mail: John.Greenman@uwe.ac.uk

S.S. De RossiUNC School of Dentistry, Chapel Hill, NC, USAe-mail: scott_derossi@unc.edu

# Springer International Publishing AG 2018C.S. Farah et al. (eds.), Contemporary Oral Medicine,https://doi.org/10.1007/978-3-319-28100-1_27-1

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History and Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17Clinical Presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18Diagnostic Tools . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Conclusions and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

AbstractHalitosis, commonly known as bad breath, isan unpleasant symptom that can present as asocial problem compromising quality of life.This condition may affect individuals of allages and may be a transient episode or a long-lasting problem depending on the cause. Insome cases, patients may present withpseudo-halitosis, whereby there is a beliefthat they have bad breath despite their malodornot being perceived or detected, either by thosearound them or by objective analysis. Halitosiscan occur due to local factors, or in rare casesbe attributed to systemic etiologies. Forpatients who present with halitosis exclusivelyfrom local oral factors, improving oral healthincluding tongue cleaning, treating dry mouthand alleviating local causes, may be beneficial.For patients with a systemic etiology for theirhalitosis, a multidisciplinary managementapproach may be necessary.

KeywordsBad breath � Oral malodor � Halitosis � Pseudo-halitosis � Breath disorders

Introduction

The potential emanation of malodor from breath iscalled halitosis, which is derived from the Latinword halitus meaning “breath” or halare “tobreath” with a suffix from the Greek based noun-osis (Douglas Harper 2016). Although manydescriptions of this terminology are available,they are inadequate in precisely defining the var-ious presentation of this condition (Porter andFedele 2014; Aydin and Harvey-Woodworth

2014). Patients with halitosis often present toeither a dentist or a primary care medical doctor.

Halitosis is broadly classified into genuinehalitosis, pseudo-halitosis, and halitophobia(Miyazaki et al. 1995) and as either intra-oral orextra-oral (Tangerman and Winkel 2010).Although these classifications are widely used,neither are universally accepted as classificationand criteria for genuine halitosis. Also thisdoes not appropriately differentiate genuinehalitosis from underlying pseudo-halitosis andhalitophobia. Many authors have used pseudo-halitosis, halitophobia, or delusional halitosissynonymously (Murata et al. 2002); however,these are not synonymous. A perceived pseudo-presentation occurs in the absence of any identifi-able cause or presence of objectively significantmalodor and is often referred to as pseudo-halitosis providing that the patient realizes (whenfaced with objective feedback) that they do notactually have bad breath (Brunner et al. 2010).Halitophobia, on the other hand, delineates indi-viduals who stubbornly refuse to accept objectiveevidence which rules out an identifiable cause andcannot be convinced that their breath is anythingbut malodorous (Seemann et al. 2014; Aydin andHarvey-Woodworth 2014). Halitophobia mayoften synonymously be used as delusional halito-sis by clinicians; however, delusional halitosis is amonosymptomatic hypochondriasis, or otherwisean imaginary halitosis, and is a manifestation ofolfactory reference syndrome. Halitophobia refersto patients who often dislike or worry about hav-ing bad breadth (Hayashi et al. 2010; Bollen andBeikler 2012).

Genuine halitosis may be physiological orpathological with both the subjective complaintand objective detection and measurement byorganoleptic evaluations or analytic instruments.

2 J.R. Thoppay et al.

Typically, genuine halitosis is multifactorial asillustrated in Fig. 1. It can potentially presentwith any combination of local and/or systemicconditions reflecting the multifactorial nature ofthe complaint. Accurate understanding of halito-sis is essential for efficient and appropriate clinicalmanagement of the complaint (Tangerman 2002;Bolepalli et al. 2015).

Epidemiology

Halitosis is a common condition that is present in50–65% of the world’s population (Mokeem2014). A Dutch survey agency has reported thathalitosis is one of the top 100 human social vex-ations based on a public investigation in the Neth-erlands in 2005 (Bollen and Beikler 2012).Despite this condition being a significant sourceof exasperation, a precise estimate of prevalenceis not possible as epidemiological studies are lim-ited (Bollen and Beikler 2012). There are severalreasons for the lack of scientific data about hali-tosis. There is the absence of standardizedapproaches in evaluation methods as well as thedifference in cultural and racial appreciation of

odors. Further, the presence of halitosis may beself-reported by the patient or brought to discus-sion by a spouse or acquaintances. Halitosis isoften socially difficult to discuss or accept sinceit is impossible for anyone to smell their ownbreath. Therefore, it often relies on others aroundthe individual to highlight the problem. This isfurther complicated by social stigma and thereluctance of those around the individual withbad breath to inform them of the issue. Indeedany dialogue about oral malodor may not alwaysbe a pleasant point of discussion. Sometimes peo-ple who interact with the individual with badbreath may not openly discuss the issue; ratherthey may display a gesture of repulsion as theyexperience bad breath. This may prompt the indi-vidual’s awareness of halitosis. When halitosis istransient, it is often not reported and hence furthercomplicates epidemiological studies.

Halitosis is a problem of all centuries, occur-ring universally in both genders and affectingpatients of all ages with varying prevalencerates. Oral malodor has been recognized in theliterature from ancient times (Fischman 1997).Descriptive epidemiological studies show thatmoderate chronic halitosis affects approximately

Local factors-Oral cause

Saliva, pH, Plaque calculus, periodontal disease, Dental caries, food impaction etc.,

Systemic factors Extra-oral cause

Underlying systemic disease

Psychogenic factorsExtra-oral cause

Underlying psychiatric disease, stress, anxiety etc.,

Volatile sulfur compounds

Fig. 1 Multifactorialrelationship in etiology ofhalitosis

Halitosis 3

one-third of the population, whereas severe hali-tosis may involve less than 5% of the population(Rosing and Loesche 2011). The correlationbetween age and malodor indicates an increasingintensity of odor in older adults. Though age is notstrictly a risk factor for malodor, comorbiditiessuch as increased incidence of periodontal diseasein association with tongue coating are reportedas key factors that aggravate oral malodor in theelderly population (Miyazaki et al. 1995).

About 80–90% of halitosis cases are thought tobe due to high local concentrations of intra-oralmicrobial populations particularly those of tonguebiofilms (cells within a salivary domain) and alsothe biofilms associated with teeth and periodontaltissues. Main causes include gingival and peri-odontal pathologies, tongue coating, caries, orpoor oral hygiene. In comparison to the tongue,the gingival crevice serves as a host-tissue-serumdomain, especially in cases of gingival patholo-gies, dental caries, and poor oral hygiene. Extra-oral causes of halitosis contribute to about10–20% of all cases and are caused by poor diet,alcohol abuse, tobacco smoking, certain drugs,and diseases of other parts of the digestive tractas well as some systemic conditions (Zalewskaet al. 2012; Tangerman and Winkel 2010). More-over, it is entirely feasible that both intra-oral andextra-oral conditions may both contribute to totalbad breath levels simultaneously.

Etiology

Intra-oral chronic malodor is primarily a conditionof the tongue surface whereby microbial biofilms(which form within tongue crypts, fissures, andpapillae) generate odiferous volatile organic com-pounds (VOCs), some of which (e.g., the volatilesulfur compounds [VSC]) partition into thegas phase headspace above the tongue (i.e., oralcavity). Even in periodontal disease, the tonguesurface is thought to contribute more thanthe periodontal crevice to a malodor, due to itsmuch larger surface area (at the microscale) thanthe teeth and gingiva. Also in periodontal disease, ahigher flow rate of the gingival crevicular fluid(which is rich in VSC substrates like cysteine

and methionine) drips onto the tongue surface andsoaks into the biofilm matrix and is then trans-formed into VOC and VSC by microbial enzymes.For morning breath and hyposalivation, the nutrientsubstrate supply rate to the biofilm microorganisms(i.e., salivary flow) is severely limited. Thisincreases the residence time of the fluid phasewithin the tongue biofilm matrix, since there is noflushing action or dilution from salivary flow.Increasing the residence time provides a longerenzyme-substrate interaction time, and moremicro-bial transformations which proceed to completion,especially hydrolysis of salivary mucin (glycopro-teins) – the main source of organic nutrients, whichproceeds in a two-stage process. Glycohydrolases(enzymes responsible for deglycosylation) firstremove the sugar moieties leaving a peptide back-bone or core, which is then attacked by microbialproteases and finally digested into amino acids orsmall peptides (i.e., cell membrane transportablesmall molecules) allowing the microbes to trans-form these substrates into products (including VOCand VSC). Hence, the first step (deglycosylation ofsalivary glycoproteins) may be an important step inoral malodor production. Salivary mucins are acommon source of proteins causing malodor.Trapped epithelial cell components also consist ofvarious glycoproteins. Glycoprotein degradationcommences with the detachment of the variousglyco-sugars from the protein core, and glycosylhy-drolases are commonly found in Gram-positivebacterial species. The exposed protein core is thenunprotected against the activities of various types ofproteases and peptidases, particularly those pro-duced by anaerobic Gram-negative species, underanaerobic conditions. Figure 2 summarizes the eti-ology of halitosis.

Local Factors

Oral malodor results from conditions suchas periodontal disease, inadequate saliva flow,inadequate or failed dental restorations, tongue-coating accumulation, or unclean dentures. Thedecomposition of organic substrates by oral anaer-obic bacteria produces VOC, and in particularVSCs that lead to halitosis.

4 J.R. Thoppay et al.

PhysiologicalIn general, local causes of halitosis can be physi-ological which can be transient due to the circa-dian rhythm in human salivary flow that naturallydiminishes during sleep, or due to the certaincharacteristic odor of food substances. This typeof malodor is attributable to putrefaction ofretained oral epithelial cells and food debris caus-ing an unpleasant odor, which disappears whennormal salivary flow resumes or food debrisare cleared (Rosing and Loesche 2011). Otherphysiologic causes may be hormonal, such asconditions reported during menstruation, whichmay be due to high VSCs. The pH of salivaand salivary levels of Prevotella intermedia insubjects with preexisting periodontitis were sig-nificantly higher in the ovulation phase than in thefollicular phase. A change in salivary pH andchanges in VSC and P. intermedia during themenstrual cycles of women with periodontitisseems to correlate to the level of oral malodor(Kawamoto et al. 2010). Further, during men-strual phases, it was noted that the salivary anti-oxidant capacity decreased, while bleeding onprobing and P. intermedia counts increased, overthe course of the menstrual cycle in women withperiodontitis. Antioxidant capacity could beinvolved in the pathogenesis of periodontitis(Kawamoto et al. 2012). However, the associa-tions are not well studied or clearly explained andthere is limited evidence in the literature.

PathologicalOral malodor predominantly caused by local path-ologic factors are periodontal disease (Fig. 3),poor or low salivary flow, failed dental restora-tions such as fractured crown and bridges orclass II restorations with loss of contact or failedrestoration margins (Fig. 4), coated tongue and/orglossitis, food impaction between teeth, hairytongue, fissured tongue, fungal infections, oralsquamous cell carcinoma, or unclean dentures.Extensive studies on halitosis have predominantlyfocused on periodontal disease and tongue biofilmcoating (Fig. 5) as primary contributing elementsof halitosis in the oral cavity. This may be dueto the high prevalence of these conditions, andperiodontal disease–associated bacteria (even ifdisplaced onto the tongue as a transient colonizer)are capable of producing significant amountsof VSCs. Decomposition of organic substancesby oral anaerobic bacteria produces VSCs leadingto halitosis (Tonzetich 1978).

Systemic Factors

Extra-oral or non-oral factors can cause halitosis.Extra-oral halitosis has origins outside the mouth.It has been reported to arise from certain systemicdiseases such as acute febrile illness, chronicsinusitis, or post nasal drip. Also metabolic disor-ders such as diabetic ketoacidosis may cause

Etiology of halitosis

Physiological[Generally transient]

Local Systemic

Pathological

Local Systemic Medication

and Substance induced

Psychogenic

Fig. 2 Etiology of halitosis

Halitosis 5

malodor. Consumption of medications and certainfoods may result in characteristic malodor thatmay be specific to the medication or food respec-tively. Extra-oral halitosis can be divided intotwo groups: blood-borne and non-blood-bornehalitosis. The conditions and its specific odorant,for example, dimethyl sulfide producing pungentodor and hydrogen sulfide producing a rotten egg

odor, the details of specific odors and their etiol-ogy are illustrated in Table 1 (Tangerman andWinkel 2010; Tangerman et al. 2012; Tangerman2002; Tangerman and Winkel 2007; Fergusonet al. 2014).

In extra-oral blood-borne halitosis, volatileodorous compounds are produced as a result ofvarious metabolic processes. Odorous volatile

Fig. 4 Fractured dentalrestorations. Class IIrestoration (a), and portionof gold crown (b)

Fig. 3 (a) and (b) Plaque accumulation (white arrows) and gingival bleeding (black arrow)

6 J.R. Thoppay et al.

sulfur compounds also cause most of the reportedcases of blood-borne halitosis. In extra-oralblood-borne halitosis, VOC that are produced inthe body that result from metabolic processes aretaken by the blood stream and are transported tothe lungs and result in exchange of gases resultingin exhalation of VOC in exhaled air. Breath anal-ysis of exhaled air with VOC has shown correla-tion to the underlying metabolic condition. Forexample, a high level of dimethyl sulfide (DMS)content in breath and venous blood was observedin cirrhotic liver disease. However, the nature ofthe compounds differs from that of the volatilesfound in halitosis of oral origin in contrast to theextra-oral etiologic agents causing halitosis(Tangerman and Winkel 2010; Tangerman et al.2012; Tangerman 2002; Tangerman and Winkel2007; Erovic Ademovski et al. 2012; Katsineloset al. 2007).

Non-blood borne halitosis may result frompredominantly upper respiratory tract infectionsincluding the nose and occasionally from thelower respiratory tract as reported in several casestudies. Such patients may have bad breath from

nasal origin than from oral areas (Tangerman andWinkel 2010).

Medication and Substance-InducedHalitosis caused by medications, food, or othersubstances can be due to exogenous or endoge-nous processes. The exogenous process is tran-sient. Oral odor can be affected by intake of foodsuch as garlic, certain spices, and drinks such ascoffee. Such presentations may be transient.

Endogenous processes of halitosis either(a) predispose or promote bacterial activity lead-ing to putrefaction causing malodor or (b) reduceor modify the salivary flow (Madhushankari et al.2015). Certain foods or substances are capableof altering the oral environment such as oral dry-ness or by providing a source of high concentra-tion of protein or sugar. Furthermore, dairyproducts are known to break down in the mouth,leading to the release of amino acids that are richin sulfur. Both onion and garlic also contain highconcentrations of sulfur compounds (e.g., allyl-methyl sulfide), which can pass through the liningof the intestine into the bloodstream and

Fig. 5 (a) Tongue coating in areas of hyperplastic papilla (arrow) in contrast with other areas. (b) Tongue coating withyellow hue due to food colorants

Halitosis 7

subsequently be released into the lungs and thenexhaled.

Halitosis can also be caused by side effectsfrom medications or by odor from substancessuch as alcohol, tobacco, or betel. Smoking orchewing tobacco products and alcohol consump-tion may cause long-standing halitosis by dryingthe oral mucosa (Porter 2011). Nicotine stainsmay be strongly adherent to oral hard and softtissues (Fig. 6), and hence nicotine-induced hali-tosis may be persistent even after cessation ofnicotine use. Cigarette smoking not only raisesthe concentration of volatile compounds in the

mouth and lungs but also further aggravates thesituation because of its drying effect on the oralmucosa (Aydin and Harvey-Woodworth 2014;Zalewska et al. 2012; Porter 2011).

Malodor can result as a side effect from med-ications. For example, nitrates prescribed totreat angina or hypertension can cause malodor;however, stopping the medication may not bereasonable (Madhushankari et al. 2015). Drugssuch as lithium salts, griseofulvin, dimethyl sulf-oxide, antihistaminic, phenothiazine derivatives,chloral hydrate, amphetamines, suplatasilate, met-ronidazole, penicillamine, thiocarbamide, ethyl

Table 1 Systemic causes and characteristic odorants

System/condition Condition Malodorant Odor nature

General Acute febrile illnessPyrexia

Dimethylsulfide

Pungent, rottencabbage

ENT Chronic sinusitisUpper respiratory tract infectionPostnasal dripNasal foreign bodiesMalignancy

Hydrogensulfide

Rotten eggs

Methylmercaptan

Pungent, rottencabbage

Musty odor

Esophageal Pharyngo-esophageal diverticulum, gastro-esophagealreflux diseaseZenker’s diverticle

Hydrogensulfide

Rotten eggs

Methylmercaptan

Pungent, rottencabbage

Gastrointestinal Pyloric stenosisduodenal obstructioninflammatory bowel disease

Dimethylsulfide

Unpleasantlysweet

n-Butyric acid Rancid

Constipation, obstruction Skatole Fecal like

Metabolic Metabolic syndrome Dimethylsulfide

Unpleasantlysweet

Diabetic ketoacidosis Acetone Fruity

Fish odor syndrome Trimethylamine Fishy

Renal Renal failureUremia

Ammonia Pleasantly sweet

Dimethylamine

Fishy

Trimethylamine Fishy

Hormonal Menstruation Dimethylsulfide

Unpleasantlysweet

Hepatic Hepatic failure Dimethylsulfide

Unpleasantlysweet

Hematologic Leukemia Dimethylsulfide

Unpleasantlysweet

Hydrogensulfide

Rotten eggs

Methymercaptan

Pungent, rottencabbage

8 J.R. Thoppay et al.

alcohol, diuretics, benzodiazepines, nitrites andnitrates, bisphosphonates, arsenic salts, disulfi-ram, and cytotoxic agents can also cause halitosis(Table 2). These medications have a tendency tocause dry mouth and occasionally salivary glandhypofunction, lowering oral pH which facilitatesproduction of VSCs. Some medications such asoral contraceptives can also aggravate periodontaldisease (Heasman and Hughes 2014), as can anti-hypertensive medications causing gingival hyper-plasia, which increases the prevalence ofperiodontal disease by increasing sulfide andnitrate producing bacteria resulting in oral mal-odor (Porter and Fedele 2014; Bollen and Beikler2012; Aylikci and Colak 2013; Porter and Scully2006).

Psychogenic Factors

Halitosis is a symptom related to both somaticand emotional status. When the subjective andobjective factors of oral malodor that initiate thecomplaints of oral malodor do not have evidentclinical correlation to any organic pathology, thatraises the possibility of psychological aspectsinvolved with a complaint of halitosis (Eli et al.1996). Several psychosocial factors such as

subjective health, economic status, and stresslevels have been associated with halitosis.Stressed or anxious individuals typically moreeasily perceive halitosis compared to stress-freeindividuals (Alzoubi et al. 2015). Psychopatho-logical problems have been proposed to eitherinduce or aggravate halitosis (Nosratzehi et al.2017). The prompt may originate from awarenessto the problem because of personal sensitivity orbrought to notice by surrounding people or both(Eli et al. 1996). Individuals with genuine halito-sis may feel some emotional changes, regardlessof the actual degree of halitosis (Suzuki et al.2008). Not only patients with pseudo-halitosisbut also those with genuine halitosis may havean accompanying psychological condition. Aquestionnaire can be used to evaluate the psycho-logical condition of a patient with reported halito-sis. Psychologists and Psychiatrists frequently useestablished questionnaires to diagnose underlyingpsychiatric problems; however, when halitosis isthe primary complaint with a possible psychiatricfactor, then the psychological questionnaires can-not be recommended for use at the initial visit,because their use may cause a patient to believethat the clinician suspects a psychosomatic condi-tion. As stated previously, the etiology of halitosisis typically multifactorial, and hence an individualmay in fact have genuine halitosis complicated bypsychogenic factors. Contrarily, patients withpseudo-halitosis and halitophobia believe thatthey have oral malodor, even in the absence ofany offensive halitosis (Eli et al. 1996). Further,in almost all cases of delusional halitosis, there isusually an underlying psychosomatic problem,which can range from an overvalued belief to afrank delusional disorder. Sometimes the delu-sion may be so firm that the individual can hardlybe dissuaded from their belief of mouth odor(Hayashi et al. 2010; Akpata et al. 2009).Patients with delusional halitosis perceive otherpeople’s behavior such as covering of the nose oraverting the face as an indication that their breathis offensive. This makes then believe that theyhave offensive odor and seek care (Akpata et al.2009).

Fig. 6 Nicotine staining of dentition (arrows)

Halitosis 9

Clinical Pathologic Features

Pathophysiology

Local FactorsHalitosis originating in the oral cavity is mostfrequently associated with poor oral hygiene, aheavy bacterial load of biofilms on tongue coat-ing, dental plaque (Fig. 3), dental caries, gingivi-tis, oral mucositis (Fig. 7), periodontitis (Fig. 8), afissured tongue (Fig. 9), hairy tongue or oral car-cinoma (Fig. 10). Dental plaque, periodontalpockets or pockets around dental implants, andtongue coating are important sources of malodor.However, the dorsoposterior surface of the tongueis the most significant site that emanates odor.This is best explained by the tongue having thelargest surface area in the mouth with pits, fis-sures, and papillary structures. Subsequently, it

has a high potential to form a bacterial biofilmcoating which constitutes a relatively large bacte-rial population (Fig. 11). The biofilm “matrix” canhouse or trap epithelial cell debris, blood cells,precipitated saliva proteins, and food debris aswell as many species of oral bacteria that metab-olize these substrates to produce VSCs (Amouet al. 2014; Bolepalli et al. 2015; Ren et al. 2016).

Oral flora microorganisms potentially respon-sible for halitosis are Streptococcus salivarius,Lysobacter-type species, Veillonella dispar,Actinomyces odontolyticus, Atopobium parvulumand Veillonella atypica, Bacillus subtilus,Proteus vulgaris, Pseudomonas aeruginosa,coliforms, Bacteroides melanogenicus, Clostrid-ium sporogenes, C. histolyticum, Treponemadenticola, Porphyromonas gingivalis,Porphyromonas endodontalis, Prevotellaintermedia, Bacteroides loescheii, Enterobac-teriaceae, Tannerella forsythensis, Centipeda

Table 2 Medication induced halitosis

Medications that cause malodor

• Chloral hydrate• Nitrites and nitrates• Dimethyl sulphoxide• Disulphiram• Some cytotoxic agents• Phenothiazines• Amphetamines• Triamterene• Lithium salts• Arsenic salts• Paraldehyde• Thicarbamide• Penicillamine• Metranidazole• Bisphoshonates• Ethylalcohol• Griseofulvin

Medications that may cause oral dryness that may secondarily cause halitosis due to salivary changes:

• Antihistamines• Tricyclic antidepressants• Anti epileptic/antiparkinsonism medications• Diuretics• Antihypertensive• Anxiolytics and antipsychotics• Anorexiant• Anticholinergics/antispasmodics• Muscle relaxants• Narcotics• Sedatives

10 J.R. Thoppay et al.

periodontii, Eikenella corrodens, Fusobacteriumnucleatum, and other unidentified oral bacteria(Burton et al. 2006; Kamaraj et al. 2011; Grover

et al. 2015; Awano et al. 2002). They have beenassociated with proteolytic activity in the oralcavity. Deglycosylation of salivary glycoproteinsis an initial step in oral malodor production.Salivary mucins are the most common source ofproteins causing malodor. Epithelial cell compo-nents contain various glycoproteins. Glycoproteinlysis starts with the detachment of the protein

Fig. 7 Oral mucositis with erythema and ulceration (whitearrow) and gingival desquamation (black arrow)

Fig. 8 Periodontitis with gingival recession exposing theroot surface (white arrow) and gingival erythema (blackarrows)

Fig. 9 Fissured dorsal tongue

Fig. 10 Oral squamous cell carcinoma of gingiva andbuccal vestibule

Halitosis 11

from the carbohydrate portion. Gram-positivebacterial activity is necessary for processing ofthe protein core leading to glycoprotein lysis,which is then further degraded by Gram-negativemicroorganisms under anaerobic conditions. Pro-teolysis and amino acid utilization of the proteincore are generally produced by Gram-negativebacteria (Grover et al. 2015; Sterer and Rosenberg2002).

The putrefactive action of these microorgan-isms on endogenous and exogenous proteina-ceous substrates, including saliva, exfoliatedcells, blood, food debris, and leukocytes are pri-marily responsible for the production of methylmercaptan and hydrogen sulfide which are VSCscausing malodor. Also methylamine, dimethyl-amine, propionic acid, butyric acid, indole, katole,and cadaverine have been reported to contribute tooral malodor (Goldberg et al. 1994). The severityof periodontal disease, an increase in the amountof tongue coating, and proteolytic “Benzoyl-DL-arginine-naphthylamide, [BANA] positive” bac-teria, in addition to a reduction in salivary flow

rate, are the main causes for higher oral malodorproduction (De Boever et al. 1994). A positivecorrelation has been demonstrated betweenseverity of periodontitis and VSC levels in sub-jects with periodontal disease who suffer fromoral malodor. Further, higher oral pH than neu-tral physiologic pH favors the process of putre-faction and volatilization (Grover et al. 2015).There is a clear relationship between strength ofodor and increase of pH in biofilm matrix intothe alkaline phase (pH 6.7–pH 8.2). A maximumrate of generation for hydrogen sulfide (H2S) ispH 6.5–7.5, while for methyl mercaptan it isnearer to pH 8.2. Carcinomas of the buccalmucosa, floor of mouth, gingiva, tongue, andpalate typically ulcerate and necrotize evenwhen these lesions are small; thus, oral malodorassociated with oral cancer is characteristicallystronger because they are usually secondarilyinfected.

Systemic FactorsWhile oral factors are localized phenomena, extra-oral halitosis occurs when volatile substancesare absorbed within the body, such as the stomach,intestines, liver, and transferred into the blood-stream that is later exchanged in pulmonary alve-oli and exhaled with breath causing malodor(Tangerman and Winkel 2010). Nasal infectionsare the most common cause of extra-oral halitosis.Such patients have bad breath from the noseinstead of the mouth. This form is probablymore common in very young children who ofteninsert foreign bodies into their nostrils, whichmight lead to an offensive odor from the nose(Tangerman and Winkel 2007). Children withmouth breathing habits may have changes in oralmicrobial flora and excessive oral dryness causingchanges in quality and quantity of oral and oro-pharyngeal secretions resulting in tonsillar infec-tions and tonsilloliths (Fig. 12) which can alsocontribute to malodor (Motta et al. 2011). Ele-vated H2S levels may be due to erosive changesin infected tissue, and elevated methyl mercaptan(CH3SH) levels may be attributable to changes inoral microbiota activity caused by slight changesin pH values (Porter and Scully 2006; Rio et al.2008).

Fig. 11 Coated bacterial slough on palatal mucosa (blackarrow), while lips and tongue show evidence of dryness(white arrows)

12 J.R. Thoppay et al.

VSCs are absorbed by the blood and trans-ported to the lungs where there is an exchange inexhaled air due to a partitioning of the volatilesbetween blood and air in the alveoli. While oralmalodor is largely caused by hydrogen sulfide[H2S] and methyl mercaptan [CH3SH] and to alesser extent by dimethyl sulfide [(CH3)2S]; how-ever, only the latter compound may be detected inblood-borne halitosis (Murata et al. 2002;Tangerman 2002). Both H2S and CH3SH containa free -SH group, which immediately reacts withblood within seconds, resulting in irreversiblebinding and oxidation. This interaction preventstransportation of methyl mercaptan and hydrogensulfide from the blood into the alveolar air andthus into the breath. Dimethyl sulfide, however, isa neutral molecule which is stable in blood andhence can be transported from the blood into thealveolar air which results in elimination by exha-lation. Because of the neutral nature of such sul-fide compounds, they are very stable in blood, andhence it becomes difficult to separate or removefrom breath (Tangerman and Winkel 2010).

Malodors from the stomach are reported to becaused by H. pylori, which results in high VSCs.The odor is unable to escape from the stomachexcept during burping, belching, or vomiting as itis trapped by the esophageal sphincter. It is pos-tulated that VSCs formed by H. pylori in thestomach are transported through the stomach

wall into the blood and then via the lungs intothe breath as alveolar components (Zaric et al.2015). Interestingly, very little of the VSCs appearto reach the bloodstream or breath from microor-ganisms within the small and large intestines toproduce VSC in humans. One possible explana-tion could be that the presence of VSCs in thestomach may be due to swallowing of VSCs insaliva thereby transferring VSC-producing bacte-ria from the mouth into the stomach. This does notexplain the resolution of halitosis through eradi-cation of H. pylori by antibiotics in some studieswhich infers a causal relationship betweenH. pylori infection and halitosis (Werdmulleret al. 2000; Zaric et al. 2015; Kappler and Schafer2014; Katsinelos et al. 2007). On the contrary, onestudy has debunked the causal relationshipbetween H. pylori and halitosis; rather providingan alternative theory that eradication of H. pyloriin the stomach may perhaps also eradicate part ofthe normal VSC-producing bacteria in the mouth,thereby diminishing halitosis (Tangerman et al.2012).

Dimethyl sulfide has been reported as the mainvolatile substance in hepatic dysfunction. Pre-dominantly in end-stage hepatic failure, it has acharacteristic odor called fetor hepaticus. This issaid to have the smell of fresh-cut hay. On theother hand, renal failure may cause a uremicbreath odor that may lessen with treatment of the

Fig. 12 Tonsilloliths noted clinically in palatine tonsils(a) and overlying the left mandibular ramus on an ortho-pantomogram (b) (Image b courtesy of Professor Camile

Farah, Perth Oral Medicine & Dental Sleep Centre, PerthWA, Australia)

Halitosis 13

underlying renal disease which is due to retentionof nitrates and uremic compounds in the body(Han et al. 2014; Tangerman 2002).

A rare condition called trimethylaminuria, alsoknown as fish odor syndrome, gives rise tolongstanding oral and body malodor due to anexcess amount of trimethylamine in the body(Khan and Shagufta 2014). This disorder reflectsdefective flavin mono-oxygenase (FMO) activitywhich is often genetically determined by the pres-ence of several single nucleotide polymorphismsof the FMO3 gene (D’Angelo et al. 2014). Thepresence of FMO3 results in an enzyme withdecreased or abolished functional activity for tri-methylamine N-oxygenation, thus leading to tri-methylaminuria. Occasionally an overload ofprecursors of FMO, for example, following cho-line therapy for Huntington’s chorea orAlzheimer’s disease may also cause tri-methylaminuria. It should be noted that the orig-inal generation of trimethylamine (which isoxidized by FMO) is from bacteria in the colonwhere they produce trimethylamine that is thenabsorbed into the bloodstream from the intestine.It should also be noted that some trimethylamine(along with other organic amines, includingputrescine and cadaverine) can also be generatedby the microbial tongue flora within the oral cav-ity and detected on breath. However, this is atrelatively low levels compared to levels found intrimethylaminuria. Hypermethioninaemia mayalso give rise to oral malodor which is an excessof methionine protein in the blood. This conditioncan occur when methionine is not metabolized.Individuals with hypermethioninemiamay exhibitintellectual disability and neurological problemswith deficits in motor skills (standing or walking),sluggishness, muscle weakness, and liver disease(Oliveira et al. 2015). Also their breath, sweat, or

urine emanates a distinctive boiled cabbage smell(Khan and Shagufta 2014; Porter 2011).

Medication and Substance-InducedWhen medications and substances are metabo-lized, VSCs are formed as byproducts whichmay cause malodor. Depending on the type andsite of VSC formation, this may cause oral orextra-oral halitosis. Characteristic presentationsof malodorants are presented in Table 3. Oralhalitosis from food products is mostly caused byfood impaction in the oral cavity or is directlyrelated to the characteristic smell of the particularfood product. Malodor caused by food impactionis predominantly due to putrefaction by bacterialactivity resulting in VSCs causing malodor. Foodproducts such as onion and dairy products havea unique flavor and smell that may cause malodor.Such products may cause transient malodor.These foods contain volatile organic compoundsthat give a characteristic taste and smell. Thesecompounds when putrefied by bacterial activity inthe oral cavity or metabolized systemically resultin volatile dienal or sulfuric compounds and leadto malodor. For example, volatile compoundssuch as -(E,E)-2,4-heptadienal smell like stalepeanuts; (E,Z)-2,6-nonadienal has a cucumber-like odor; (E,E)-2,4-decadienal is fatty or rancid-smelling; 3-(methylthio)propanal has an odor likebaked potatoes or soy sauce; and dimethyl trisul-fide smells distinctly like cooked cabbage. Onionand garlic are common food products that areknown for their characteristic odor. While onionand garlic can leave their sulfuric odor in the oralcavity, they can also be absorbed into the blood-stream, enabling a secondary source of odor that isblood borne and exhaled in the breath. Most peo-ple view the smell of fish as an unpleasant odor. Itis equated with a rotting malodor. Food with high

Table 3 Characteristic presentations of malodorants

Substance/food/medication Malodorant Odor

Garlic Allyl methyl sulfide Garlic-like

Onion Methyl propyl sulfide Onion-like

Disulfuram Carbon disulfide Slightly pungent

Dimethyl sulfoxide Dimethyl sulfide Unpleasantly sweet

Cysteamine Dimethyl sulfide Unpleasantly sweet

14 J.R. Thoppay et al.

protein content, when deposited in the oral cavity,has high affinity to odor causing bacteria whoseinteraction under favorable circumstances causesVSCs resulting in malodor. For example, all typesof milk from whole milk to fat-free milk containthe milk protein casein or its hydrolysis compo-nents (amino acids), which in the process of putre-faction are biotransformed into VOC and VSC.Consumption of fermented milk productscontaining live microorganisms with probioticactivity by Lactobacillus species has beneficialeffects on the body (Baltova and Dimitrov2014). By improving the balance of intestinalmicroflora and action against microbes which areresponsible for the production of VSCs are limited(Iwamoto et al. 2010). Also unfavorable condi-tions such as low oral pH may decrease the ben-eficial effects (Porter 2011; Burton et al. 2006;Aprea et al. 2016; Baltova and Dimitrov 2014;Smith et al. 2016; Venkateshwarlu et al. 2004).

In chronic alcoholics, multiple factors play keyroles in causing oral malodor. Aldehydes that areprimary metabolites of ethanol can cause moreharmful effects than alcohol itself due to itsincreased volatility and greater readiness for inter-action with tissues (Suzuki et al. 2009). Further-more, if alcohol consumption is coupled withsmoking, chewing tobacco, or chewing betel,this induces oxidative stress on the tissues andcauses DNA damage and cytotoxicity. In addition,alcohol can cause oral dryness which can lowerthe pH resulting in VSCs production in addition tothe volatile nature of alcohol itself (Suzuki et al.2009).

Psychogenic FactorsIn case of psychogenic malodor, the psychologi-cal state of the sufferer may increase or decreasethe levels of objective malodor (Akos et al. 2012;Pham 2013). Although this has not been satisfac-torily proven, the possible exception to this is theeffect of stress which may have secondary impli-cations for halitosis due to diminished salivaryflow (Singh et al. 2015). Under stress, individualsmay develop hyposalivation, which leads to alonger retention time of the biofilm matrix. Thisresults in a greater degradation rate of retainedproteins in the mouth and consequently increased

levels of VSCs (Fukui et al. 2010). Of interest,during premenstrual syndrome, stress canincrease VSCs without a decrease in salivaryflow (Kawamoto et al. 2010). It is postulated thathormonal changes affect oral bacterialpopulations via diminished tongue and mucouscell desquamation rates and/or weaken the hostimmune system through changes in salivary IgAconcentration. These changes may contribute toan increase in oral VSCs, even in the presence ofnormal salivary flow (Zalewska et al. 2012). How-ever, another study showed that concentrations ofIgA and chromogranin A in saliva were not sig-nificantly different among the groups studied, butthere were higher salivary cortisol concentrationsin subjects with high stress indicators as per theCornell Medical Index (CMI) Health Question-naire (Fukui et al. 2010).

Anxiety increases VSCs levels in the breath asit is associated with hyposalivation; however thediagnosis of anxiety is challenging as even if anindividual has insight regarding their condition,they are unlikely to report it. This is likely due tothe social stigma with mental health illness whichremains significant in today’s society.

Pseudo-halitosis on the other hand may berelated to a fear of social interaction due to per-ceived malodor, which sufferers perceive as verybad, until there is objective evidence that this isnot the case. Many are then re-assured, but somehold on to their belief despite the completeabsence of any objective halitosis. Such individ-uals fall into the category of halitophobic, andthese individuals express a conviction that othersthink that they smell. Patients with delusionalhalitosis or halitophobia believe that they havebad breath, although many have never asked any-one for an objective opinion. They persist in theirbelief despite reassurance, treatment, and counsel-ing (Alzoubi et al. 2015; Suzuki et al. 2009; Eliet al. 1996). Halitophobia may severely affect thelives of some 0.5–1.0% of the adult population;however, there is no generally agreed treatmentprotocol with some cases being treated with anti-depressants, antipsychotics, or psychotherapies(Eli et al. 1996). The condition may indicateunderlying neurosis or psychosis and may indi-cate depression or obsessive compulsive

Halitosis 15

behavior, necessitating psychiatric care (Arenaset al. 2013).

Patient Management

Clinically, patients complaining of halitosis mayhave actual malodor or may present with pseudo-halitosis. A systematic approach is often neces-sary. Patients with genuine halitosis orhalitophobia, irrespective of the type, suffer sig-nificant impact on overall quality of life (Buunk-Werkhoven et al. 2012). The algorithm shown in(Fig. 13) illustrates a stepwise assessment plan(Kapoor et al. 2016; Dal Rio et al. 2007). Aclinical questionnaire (Yaegaki and Coil 1999)

designed to understand underlying psychosomaticconditions has similar questions scatteredthroughout the questionnaire in order to be dis-guised. Any such screening questionnaire pro-vides an opportunity for verbal inquiry to assistin establishing rapport and facilitate the clinician’sbetter understanding. Individuals with pseudo-halitosis have a greater tendency toward neurosisthan subjects with physiologic halitosis or oralpathologic halitosis. A thorough understandingof this condition and the clinician’s scope ofknowledge as well as defining their role managingthis condition is essential. Patients who may haveunderlying systemic conditions or psychiatric fac-tors may need appropriate referral for manage-ment (Seemann et al. 2014).

Chief Complaint

History of present illness

Assessment Subjective and Objective, Medical History, Medications, Social History, Clinical findings,Dental disease, Periodontal disease, Food impaction, Xerostomia, Salivary gland hypofunction, Oral lesions.

Diagnostic tests, organoleptic tests, characteristic odor for local or systemic conditions.

Genuine Halitosis Pseudohalitosis

POSITIVE CLINICAL FINDINGS NEGATIVE CLINICAL FINDINGS

Physiologic Halitosis Pathologic Halitosis

Oral Halitosis Extraoral Halitosis

Non Blood borne Blood borne

TN1TN1, TN2

TN1, TN3

TN1, TN3

TN1, TN4

Patient reports subjective complaints of halitosis without objective physiologic or pathologic findings

Halitophobia

TN 5

Fig. 13 Halitosis diagnostic algorithm (TN – Treatment needs, explained in Table 5)

16 J.R. Thoppay et al.

History and Evaluation

Subjective and objective assessment: Halitosisis not an all or nothing state. Very few individualshave zero scores on the organoleptic scale whichis an intensity scale to measure malodor thatranges between 0 and 5, 5 being very intensemalodor, where the vast majority of individualshave breath levels between 1 and 5, with slightvariations (�0.5 units) throughout the day. Clini-cally, patients complaining of halitosis may haveactual malodor (low, intermediate, or high) or maynot have malodor to the extent to which theyperceive. The dichotomous approach (malodor/no malodor) allows clinicians to use a cutoffpoint on one or more measurement scales (e.g.,from Halimeter, oral chromatography, signalintensity of precursor ions in flow tube mass spec-trometry [SIFT-MS], or organoleptic judge) tosupport the division of halitosis/non-halitosiscases. The majority of patients complaining ofhalitosis are likely to seek advice from a dentistor their general medical practitioner. Aminority ofpatients seek help from a specialist in gastroenter-ology or otorhinolaryngology, who typically onlyassesses and treats sources of halitosis related totheir specialized area. If there is no obvious sourceof halitosis, the patient will likely be referred to anoral health care provider for further assessment of

possible oral causes for halitosis. Therefore, athorough knowledge and understanding of halito-sis is essential as the etiology is oftenmultifactorial.

Self-assessment: The majority of patients(93.9%) with the primary complaint of halitosishave objective evidence of halitosis as judged byorganoleptic methods; however there is an incon-sistent correlation between self-assessment andclinically detectable causative oral disease.Patients with mild-to-moderate halitosis have thehighest correlations between self-assessment andodor assessment of halitosis (Aimetti et al. 2015).A recent study found a good correlation betweenpatients’ self-estimation and clinical oral malodor(Kapoor et al. 2016). It suggested that self-estimation of oral malodor by using the hand-on-mouth technique was useful in the assessment ofrisk factors and detection of one’s own malodorwhich increased the accuracy of patients’ estima-tion of their oral malodor (Pham 2013).

History of present illness: A detailed historyand evaluation that includes a thorough under-standing of the patient’s complaint and analysisof subjective and objective presentation are man-datory. Genuine halitosis as opposed to pseudo-halitosis must be assessed. In the case of genuinehalitosis, evaluation should include a detailed his-tory of oral malodor, triggers, duration,

Table 5 Halitosis and treatment needs

TNstage Presentation Recommendations

TN-1 Physiologic or pathologic malodor, genuinehalitosis, predominantly local cause, occasionallyPseudo or transient halitosis

• Patient education• Oral health maintenance inclusive of home care,tongue cleaning, brushing, flossing antimicrobialmouth rinses, dentifrices, periodic dental evaluations,and oral hygiene visits

TN-2 Genuine halitosis, predominantly pathologic due tolocal factors, periodontal and dental disease, drymouth

• Periodontal treatment and comprehensive dental careincluding, extraction of non restorable teeth,management of oral lesions if present, management ofdry mouth, endodontic treatment, restoration, dentalprosthesis if necessary

TN-3 Genuine halitosis, predominantly extra-oral causedue to systemic diseases, non- blood borne andblood borne

• Referral to physician or medical specialist asapplicable

TN-4 Predominantly pseudo-halitosis • Patient education and counseling• Oral hygiene measures including tongue cleaning

TN-5 Possible halitophobia and pseudo-halitosis • Patient education and counseling• Referral for psychiatric evaluation and management

Halitosis 17

aggravating, and relieving factors (Akos et al.2012; Al-Zahrani et al. 2011).

Health history: A detailed health history thatincludes medical history, medications, includingover the counter products and nutritional sub-stances, should be noted. Social habits such assmoking, alcohol consumption, and substanceabuse may be underlying causes of halitosis.Review of systems may facilitate ruling out anyunderlying cause that may be missed from themedical history (Akos et al. 2012). It is alsoimportant to relate the symptom of halitosis toclinical presentations of dry mouth, saliva pH,dental caries, periodontal disease, the presenceof oral lesions, and overall oral health. Any asso-ciations with underlying systemic conditionsshould also be accounted for (Murata et al.2002). Patients may have multiple factors contrib-uting to halitosis, and these may be a combinationof medication, food, local, systemic, and psycho-logical causes (Rosing and Loesche 2011;Tangerman 2002; Madhushankari et al. 2015; Eliet al. 1996; Singh et al. 2015). When it is deter-mined to be strictly psychogenic, pseudo-halito-sis, or halitophobia, the patient should be referredfor psychiatric evaluation and management(Akpata et al. 2009).

Clinical Presentation

There are various diagnostic methods that havebeen traditionally used by clinicians to effectivelydiagnose this condition. This includes self-assessment, which sometimes prompts patientsto seek care. However, patients cannot smelltheir own breath and rely upon others for thisinformation. There are primarily three measure-ment methods of genuine halitosis. They areorganoleptic measurement, gas chromatography,and sulfide monitoring. Additional or alternativemeasurement methods are BANA test, chemicalsensors, salivary incubation test, quantifyingβ-galactosidase activity, ammonia monitoring,ninhydrin method, and polymerase chain reaction.There are diagnostic tools available to measure theVOC/VSC in exhaled air, which may be veryuseful to assess the condition (Kapoor et al.

2016). The organoleptic method is the “gold stan-dard” and is the most widely used scoring systemfor ranking halitosis using the organoleptic score(Scully et al. 1997).

Diagnostic Tools

Diagnostic tools for assessment of halitosis mayinclude devices that measure VOC/VSC by gaschromatography. The gas chromatographymethod measures the concentration of volatilesulfur-containing compounds in samples ofsaliva, tongue coating, or expired breath by pro-ducing mass spectra (Schmidt et al. 2015). Clini-cally, these tools such as Oral ChromaTM (FIS ANissha Company, Japan/Abiliti Corporation,Chuo-ku, Osaka, Japan) (Fig. 14) (Sinjari et al.2013) and HalimeterTM (Interscan Corporation,USA) (Fig. 15) have been reliable in measuringoral malodor. HalimeterTM identifies VSCs inbreath produced by anaerobic bacteria, whichcan be read in a graph, the Haligram (Fig. 15);however, this product is currently not readilyavailable in the market. HalisensTM

(AI Analytical Innovations, Moosbach, Germany)(Fig. 16) breathometer device analyses breath andcan be connected to a smart device to track oralmalodor. Oral ChromaTM is connected to a com-puter with a specific software program that allowsgraphic creation, which corresponds to the peaksand concentrations of VSCs ranging 0–2913 partsper billion (ppb) with precision after about a fewtrials. A chromatogram helps to assess the levelsof volatile compounds. The threshold levels forbad breath are 112 ppb for hydrogen sulfide,26 ppb for methyl mercaptan, and 8 ppb fordimethyl sulfide (Sinjari et al. 2013). The resultsof these tests may have different influencing fac-tors and variation in scales used. Moreover, thesemeasurement methods are not very easilyimplemented because they require trained exam-iners, and are time consuming and costly. Hence,for reliability at least two diagnostic methods maybe used to validate results (Laleman et al. 2014;Brunner et al. 2010).

Organoleptic measurements: The humannose remains the “gold standard” in detecting

18 J.R. Thoppay et al.

oral malodor (Seemann et al. 2014). The mostwidely used scoring system for ranking halitosisis the organoleptic measurement, which is a sen-sory test scored by the examiner’s perception of asubject’s oral malodor. The reason for which theorganoleptic score remains the gold standard forbreath measurements is that the human nose iscapable of sniffing and defining odors as pleasantor unpleasant. That is, the human nose is capableto detecting unpleasant odors such as VSC as wellas other organic compounds from exhalation(Rosenberg and McCulloch 1992). The examinerperforms the sniff test and scores by sniffing thepatient’s breath and scoring the level of oral mal-odor. The examiner should have a normal sense ofsmell and is required to refrain from drinking

coffee, tea, or juice and abstain from smokingand using scented cosmetics before the assess-ment process.

For the assessment to be effective, the patient isalso required to adhere to stringent instructionswhich include:

• Abstain from taking antibiotics for 3 weeksbefore the assessment

• Abstain from eating garlic, onion, and spicyfoods for 48 h before the assessment

• Avoid using scented cosmetics for 24 h beforethe assessment

• Abstain from ingesting any food or drink atleast 3–4 h before the test, and to omit theirusual oral hygiene practices

Fig. 15 (a) Halimeter (b) Haligram showing the emitted levels of VSO (Images courtesy of Interscan Corporation, CA,USA)

Fig. 14 (a) OralChroma™ separates VSC in oral breathinto hydrogen sulfide, methyl mercaptan and dimethylsulfide (b) Sample being loaded into OralChroma™

(Images courtesy of FIS A Nissha Company, Japan/AbilitiCorporation, Chuo-ku, Osaka, Japan)

Halitosis 19

• Abstain from using oral rinse and breathfresheners

• Abstain from smoking for at least 12 h beforethe assessment (Kim et al. 2010; Coil et al.2002)

Organoleptic scales: The organoleptic scalefocuses on the objective strength of the smells inquestion (target odors) including on occasion“pleasant” smells (e.g., mint flavored mouth-washes). The hedonic scale on the other hand ismore in tune with the subjective feelings of theperceiver in judging smells as “nice” or “nasty”rather than weak or strong smell of target vola-tiles. It should be noted that the organoleptic scaleis what is described as an exponential scale, anal-ogous to decibel for hearing, or lux for luminosity.

In the organoleptic test measurement, thepatient takes a breath by deeply inspiring the airby nostrils and holding awhile, then expiring bythe mouth directly or via a pipette, while the

examiner sniffs the severity of the odor at a dis-tance of 20 cm. The purpose of using a pipette is tolessen the intensity of expiring air. The tube isinserted through a privacy screen (50–70 cm)that separates the examiner and the patient whichfacilitates the effectiveness of the test. An organ-oleptic score [OS] of 0 on the scale is <5 ppbhydrogen sulfide, while a score of “1” mighttypically be a 5 times higher gas concentrationthan a score of zero (i.e., 25x). That is, a score of2, 3, 4, and 5 would be equivalent to 125, 625,3125, and 15,625x higher concentrations,respectively. In contrast, all breath gas analysisinstruments show linear responses (Murata et al.2002). This is important for correlation betweenthe OS and the instrument in question. Theinstrument readout values must be log-plottedagainst OS in order to achieve a straight-linecorrelation, from which parametric rather thannonparametric statistics can be used for compar-isons (Greenman et al. 2004).

Fig. 16 HaliSensTM VSCmonitor with sample loadedfor analysis (Image courtesyof AI AnalyticalInnovations GmbH,Moosbach, Germany)

20 J.R. Thoppay et al.

The organoleptic scale by Rosenberg andMcCulloch (1992) (Greenman et al. 2014) uses a6-point scale for testing chlorhexidine against atwo-phase mouthrinse with scores of 0–6 asfollows:

1. No odor2. Barely noticeable odor3. Slight odor4. Moderate odor5. Strong odor6. Extremely foul odor, later changed to strong

odor

VSC monitoring: Chemical and instrumentalanalyses can detect relatively large concentrationsof VSCs; however at lower concentrations theseare insufficiently sensitive to detect. Gas chroma-tography employing a flame ionization detectionsystem can identify methanol, ethanol, and ace-tone but is less efficient in detecting VSCs. Gaschromatography units equipped with highly selec-tive and sensitive flame photometric detectionsystems specific for sulfur compounds can readilyidentify methyl mercaptan, hydrogen sulfide, anddimethyl sulfide in oral breath. VSCs can be mea-sured quantitatively in breath by a gas chromato-graph equipped with a flame photometric detector.The components can be identified by comparingthe mass spectra with those of a computer-basedreference library (Sinjari et al. 2013). OralChromaTM is an ion trap transportable semicon-ductor gas sensor that permits analysis by gaschromatography and mass spectroscopy (Van derSleen et al. 2010; van den Broek et al. 2007). TheVSC monitors detect from 18% to 67% of odorsthat can be effectively matched by the organolep-tic score. Though most of these compounds can bemeasured, certain compounds such as volatilefatty acids (butyrate, propionate), diamines(cadaverine, putrescine) and other foul smellingproducts can only be measured by laboratory-based assays. Though there is equipment avail-able to undertake this, reliability needs to beassessed in further studies. SIFT-MS is a relativelynew technique that is ideally suited to the accurateand sensitive analysis of breath and can detect thepresence of hundreds of different VOCs

simultaneously in real-time measurements.Whichever gas analytic method is chosen, provid-ing the instrument is quantitative for the targetVSCs, the outputs can be log plotted against theorganoleptic scores obtained whenever the twomethods are applied together on the same “sam-ple”. Such correlations show the organolepticmethod to be a valid quantitative method (Szaboet al. 2015). Nevertheless, the ability of the gasanalytic equipment to monitor specific targetanalytes is a clear advantage over the organolepticmethod alone, so such equipment is a valuable aidfor periodic monitoring and prognosis (Marchettiet al. 2015; Akos et al. 2012; De Baat et al. 2014;Szabo et al. 2015; Sinjari et al. 2013).

Microbiologic tests: VSCs are productsresulting from microbial metabolism within oralbiofilms which partitions between the liquidphases and the intra-oral headspace gas phasegiving the resultant product that is responsiblefor malodor. An alternative strategy to measuringthe gases would be to detect and analyze qualita-tively or quantitatively the microbes causing mal-odor. A clear relationship has been establishedbetween the quantity of tongue biofilm (its densityand thickness as a film) and the degree of malodor(Saad et al. 2016). Microbes associated with peri-odontal disease, mostly Treponema denticola,Porphyromonas gingivalis, and Tannerella for-sythia, produce both VSC and volatile fattyacids, detection of which may provide informa-tion that contributes to halitosis. Benzoyl-DL-arginine-naphthylamide (BANA) (Fig. 17), a syn-thetic trypsin substrate forming a colored com-pound due to degradation by enzymes frombacterial organisms, can provide additional infor-mation on compounds other than VSCs. However,full microbiological analysis by viable count offacultative and strict anaerobes by selective recov-ery medium and viable count is beyond the major-ity of general dental practices or breath researchclinics. However, there are other features of oralbiofilms that correlate with the tendency towardsbad breath including the proportion of species thatproduce black H2S-positive colonies on cysteine-iron agar plates and the proportion of species thatare proteolytic. The BANA test uses benzoyl-DL-arginine-naphthylamide which forms a colored

Halitosis 21

compound due to its degradation by enzymessecreted from protease positive species. This testis a chair-side exercise that can be completed in5–10 min and measures levels of enzymesexpressed in situ, directly from a biofilm sample

or scrape. The BANA test has been found tocorrelate significantly with the organolepticscores obtained from the whole mouth, thetongue, and saliva, but less so with VSC(Kozlovsky et al. 1994; De Boever et al. 1994).

Oral health management: Maintainingproper oral hygiene has been reported to minimizelocal causes of halitosis. Comprehensive dentalcare including extraction of nonrestorable teeth,management of oral lesions if present, manage-ment of dry mouth, endodontic treatment, andfabrication of dental prostheses can provide afoundation for eliminating local causes of mal-odor. Periodontal therapy, where appropriate, canfacilitate reduction of halitosis (Kamaraj et al.2011; Stamou et al. 2005; Kuo et al. 2013).

Mechanical methods: Tongue cleansing isone component of oral health maintenance, how-ever rarely the sole treatment for halitosis(Ademovski et al. 2013; Erovic Ademovski et al.2012). Mechanical interventions such as tonguescrapers and tongue brushes (Fig. 18) physically

Fig. 18 Various tongue scrapers and brushes. (1) Stainlesssteel tongue scraper. (2a) OraBrush1 with soft tongue-friendly bristles modelled on a surgical cleaning brush.(2b) Orabrush1 with ultra-soft, micro-pointed bristles

and built-in scraper. (3) The Tongue CleanerTM. (4) Tonguescraper with Bristles on one side and scraper on the otherside. (5) BreathRxTM tongue scraper made of flexiblematerial

O

O

HN

HN

HN

NH

HCI

NH2

Fig. 17 N-α-Benzoyl-DL-arginine naphthylamide hydro-chloride [BANA]

22 J.R. Thoppay et al.

remove bacterial biofilms from the tongue sur-face; however mechanical interventions only pro-vide transient protection that lasts for as little as30 min (Seemann et al. 2014). A combinedapproach using a newly designed sonic tonguebrush with an antimicrobial spray has beenreported to reduce bad breath over a prolongedperiod of at least 6 h. An example of such productis Sonicare TongueCare+TM (Fig. 19) which isavailable in the US market and reports to kill99% of odor causing bacteria using an alcohol-free tongue spray with antibacterialcetylpyridinium chloride (CPC) and Zytex™ toneutralize VSC gases, in a thick, concentratedformula that lubricates the tongue for a gentleclean (Saad et al. 2016). The sonic action pro-duces about 31,000 vibrations per minute tobreak the tongue coating effectively. A higherreduction in malodor and bacterial density hasbeen achieved by combining a mechanical with

a chemical intervention (Saad et al. 2016; Roldanet al. 2005).

Masking agents: Masking agents are com-monly used as the first-line therapy for individualswho have self-diagnosed oral malodor. Use ofbreath mints and chewing gum are common prac-tices and easily accessible. These approaches mayprovide temporary relief for individuals byincreasing salivary secretion and are especiallybeneficial in managing transient malodor (Shiyaoet al. 2015; De Luca-Monasterios et al. 2014). Inaddition, masking agents can play a major role inalleviating halitosis when direct treatmentapproaches to the underlying cause are limited.Similarly mouth rinses containing chlorine diox-ide and zinc salts (Table 4) significantly reduceoral malodor. Both chlorine dioxide and zinc saltsare biocidal and biostatic compounds that kill orreduce the growth and metabolism of biofilm spe-cies. Both are also strong oxidizing agents able toalter the biofilm redox and reduce the activity ofcysteine desulfhydrase (the enzyme responsiblefor H2S production) (Aydin et al. 2016). Thehigher (more oxidative) redox also inhibitscysteine-dependent protease activity, includingtrypsin-like protease from periodontal pathogens.This is facilitated by zinc as it is a strong inhibitorof proteolysis. In addition, the zinc ions forminsoluble sulfides (ZnS), reduce the concentrationof liquid phase H2S, and thus reduce the volatili-zation of H2S and the consequential unpleasantodor. The reactive thiols found in local oral hali-tosis can be bound to zinc salts and can be neu-tralized and effectively withdrawn from the breath(Tangerman and Winkel 2007, 2010; Kappler andSchafer 2014). Examples of currently availableproducts are listed in Table 4.

Antimicrobials: Treatment approaches thatimpact colonization of VSC-producing bacteriain the oral microbiota have the potential of reduc-ing halitosis. Mouth rinses containing chlorhexi-dine have been found beneficial in reducingmicrobial activity (Roldan et al. 2005). Rinsingwith a zinc acetate and chlorhexidine diacetatecontaining mouth rinse resulted in a clinicallyrelevant reduction of intra-oral halitosis during astudy period of 2 weeks (Erovic Ademovskiet al. 2012). Also mouth rinses containing

Fig. 19 Sonicare TongueCare+TM

Halitosis 23

low concentrations of chlorhexidine (0.05%),cetylpyridinium chloride (0.05%), and zinc lactate(0.14%) are effective in the treatment of oral mal-odor (Kang et al. 2015). Morning breath odor canbe successfully reduced by the sole use of anamine fluoride-stannous fluoride-containingmouth rinse twice daily, which significantlyreduces the bacterial load in saliva and retardsplaque formation (Quirynen et al. 2002); however,an adverse effect of this mouthwash is staining(Fig. 20) of the dorsum of the tongue (Winkelet al. 2003; Zhang et al. 2014).

Photodynamic therapy: Recent preliminarystudies highlight the use of photodynamic therapy(PDT) for oral halitosis (Costa da Mota et al.2016). PDT involves the use of a non-toxic pho-tosensitizer along with visible light that facilitatesa state of excitation after absorbing photons and

reacting with oxygen in a medium to cause reac-tive oxygen species. This reaction results in aphototoxic effect on microbes providing antimi-crobial activity to the tissues exposed to PDT. Thedorsal tongue is targeted and treated, resulting inan antimicrobial effect on odor causing microbes,thus reducing oral malodor (Costa da Mota et al.2016; Lopes et al. 2014, 2016).

Medical approaches: Extra-oral halitosis maybe a manifestation of a serious underlying diseaseand contributes to 5–10% of all cases of halitosis.Treatment for extra-oral halitosis is much morecomplicated than for intra-oral halitosis. Odorcharacterization of various odorants in patientswith halitosis may serve as a possible mode foridentification of underlying medical conditions.For example, renal failure is associated with afishy odor (Table 1). In addition, standard gas

Table 4 Products effective for oral malodor reduction (Ref: http://www.tordent.com/pdfs/all%20handouts1.pdf; Aydinet al. 2016; Shiyao et al. 2015; De Luca-Monasterios et al. 2014)

Products Active ingredients Mechanism of action Examples

Maskingagents

Flavoring agents suchas mint extracts thatmask oral malodor

Temporary relief by masking Breath mints, chewing gums,mouthwashes

Chemicalproducts fororal malodorreduction

Zinc salts (chloride,citrate, acetate)

Biocidal and biostatic compoundsproviding sustained breath odorreduction for 3 h by reducing theactivity of cysteine desulfhydrase,form insoluble sulfides (ZnS)reducing the concentration of liquidphase of H2S

a. Toothpastes – TriOral, ListerineTartar Control, Viadent AdvancedCare, Aim TC, Close-Up, TC, KissMy Face Tartar Control, SmartMouth Toothpasteb. Mouthwashes – Lavoris,Listermint, ListerineTartar control

Chlorine dioxide(sodium chlorite)

Biocidal and biostatic compoundsproviding sustained breath odorreduction for 3 h

a. Toothpastes –Oxyfresh, CloySysII, Therabreath, Profreshb. Mouthwashes – Oxyfresh,CloSys II, Therabreath, Enfresh,Profresh

Essential oils Menthol, thymol,eucalyptol

Sustained breath odor reduction for3 h by masking, neutralizing andbiocidal activities

a. Toothpastes – Listerine EC pasteand gel, Breath-So-FreshToothpasteb. Mouthwashes – Listerine ECmouthwash, many store brands

Antimicrobialagents

Chlorhexidine,cetylpyridiniumchloride, aminefluoride-stannousfluoride

Biocidal, antimicrobial activity onodor causing bacteria

Mouthwashes-Peridex, GumPerioshield

Note: Brand names may vary depending on the country of origin.Commercial products (containing combinations of two of the above effective ingredients).TherabreathTM mouthwash and toothpaste, Smart Mouth chlorine dioxide and zinc chloride, Breath-So-Fresh essentialoils and salts, Oxyfresh Zinc chlorine dioxide and zinc chloride

24 J.R. Thoppay et al.

chromatography facilitates specific sulfur detec-tion, which helps to easily differentiate betweenintra-oral and extra-oral blood-borne halitosis, asthese two forms are nearly always caused by thepresence of VSCs (Tangerman and Winkel 2010).Referral to a physician or medical specialist basedon the characteristic malodor and underlyingmedical condition is essential. A multimodalapproach may be necessary. This may includeproviding antimicrobial mouthwashes andmasking agents, comprehensive oral care, man-agement of oral dryness, and of course medicalmanagement of the underlying condition (Roldanet al. 2005).

Psychosocial approaches: Adverse psycho-logical aspects of these patients may lead to clin-ical misjudgment and mismanagement, in whichcase, it may be challenging for clinicians to dealwith patients with psychological conditions suchas pseudo-halitosis or halitophobia. Using anappropriate questionnaire may facilitate screeningfor psychiatric disorders (Yaegaki and Coil 1999).Patients may have underlying psychiatric condi-tions, or the presence of genuine halitosis may

cause psychiatric issues leading to anxiety due tohalitosis (Coil et al. 2002; Suzuki et al. 2008).Delusional halitosis may have occurred in thesepatients due to possible underlying psychoso-matic tendencies. Generally, patients with delu-sional halitosis fail to recognize theirpsychosomatic condition, but a number of theminterpret other people’s behavior as response totheir own bad breath. The most common associ-ated oral factor is abnormal taste and occasionallyfollowed by extra-oral factors and invasive dentaltreatment (Akpata et al. 2009) aggravated bystress (triggering) to a perception of oral malodor.Careful accounting for such presentations is crit-ical for effective management. Patients with pos-sible effect due to their emotional state causing oraggravating their oral malodor may benefit fromearly referral to a psychiatrist for mental healthassessment and appropriate management whichcan alleviate the perception of oral malodor. Con-sequently, treatment needs [TN] in a stepwisemanner as illustrated in the management algo-rithm (Fig. 13) are determined by the classifica-tion of halitosis based on etiology. These are listedas TN-1 through TN-5 as illustrated in Table 5.Individuals who present with self-diagnosed oralmalodor typically attempt to self-manage usinglocal oral care measures (Table 6). Managementof patients based on treatment needs is essentialdue to the multifactorial etiology of halitosis.Many patients may have overlapping etiologies,which may challenge the clinician. Patients withsystemic sources of halitosis, pseudo-halitosis orhalitophobia require a multidisciplinaryapproach.

Conclusions and Future Directions

Halitosis is a common problem with many etiolo-gies. Although local causes may contribute pre-dominantly; underlying systemic causes mayco-exist in 5–10% of patients with this condition.Individuals may also present with pseudo-halito-sis or halitophobia which are challenging condi-tions to manage, especially when coupled withperiods of genuine halitosis. In these cases,unraveling the psychosocial factors at play is

Fig. 20 Areas of discoloration on dorsal tongue aftermouthwash use

Halitosis 25

prudent. Despite the many etiological factorsassociated with halitosis, its pathophysiology hasbeen postulated but remains an enigma. In addi-tion, a universally accepted diagnostic and classi-fication system is yet to be established. Once theetiology of an individual’s halitosis is established,and a correct diagnosis made, patient educationplays a significant role in the management andprognosis of the condition. Although there aremany studies on this topic and various treatmentmodalities available, this condition still lacks asystematic standard of diagnosis and care.Although many treatment modalities are availableto clinicians to assist with the management of oralmalodor, the sole success of therapy relies onpatient satisfaction or perception of relief fromhalitosis.

Cross-References

▶Clinical Evaluation of Oral Diseases▶Gingival Pathology▶ Interface Between Oral and Systemic Disease▶Neurosensory Disturbances including Smelland Taste

▶Normal Variations in the Anatomy, Biology andHistology of the Maxillofacial Region

▶Odontogenic Bacterial Infections▶Odontogenic Pathology▶Oral and Maxillofacial Fungal Infections▶Oral Lichen Planus▶Oral Manifestations of Systemic Diseases andTheir Treatments

▶Oral Mucosal Malignancies▶ Pharmacotherapeutic Approaches in OralMedicine

▶White and Red Lesions of the Oral Mucosa

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