Photodynamic Therapy on Halitosis: History
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Halitosis is a term that consists of any unpleasant odor emanating from the oral cavity, the source of which may be local or systemic. This alteration in mouth odor is the third major cause of the search for oral treatment. Anaerobic bacteria are identified as the main cause of halitosis.

  • photodynamic therapy
  • halitosis
  • laser

1. Comparison 1. Antimicrobial Photodynamic Therapy (aPDT) versus Tongue Scraper

Hydrogen Sulfide (H2S) Gas Measurement

Five RCTs assessed the reduction in halitosis, which was determined by the measurement of H2S using the OralChromaTM device [24,36,41,43,44]. Considering the clinical differences and the lack of some numerical data it was not possible to group the results in meta-analysis. Thus, the estimated effects were reported individually on Table 2.
Table 2. Main results of the included studies on the reduction in Hydrogen Sulfide (H2S) gas concentration measured in ppb (parts per billion).
Study/Year aPDT Tongue Scraper Results/Estimated Effects
da Mota 2021 [44]
  • After 7, 14 and 30 days
no numerical data provided no numerical data provided The authors reported no difference between groups (p > 0.05, n = 30)
do Vale 2020 [43]
  • Immediately, mean
18.5 185.3 The authors reported a reduced H2S concentration in favour of aPDT (p = 0.003, n = 40)
  • After 7 days, mean
218.2 39.0 The authors reported a reduced H2S concentration in favour of aPDT (p = 0.000, n = 40)
Romero 2021 [24]
  • Immediately, mean (SD)
68.3
(±68.0)
100.9 (±103.0) Seems to have no difference between groups, but this results are imprecise (wide CI)
MD −32.6 [95% CI −86.6 to 21.4]; n = 40; p = 0.24, very low-certainty evidence
  • After 7 days, mean (SD)
126.8 (±126.0) 123.1 (±126.0) Seems to have no difference between groups, but this results are imprecise (wide CI)
MD 3.7 [95% CI −67.6 to 75.0]; n = 40; p = 0.92, very low-certainty evidence
  • After 90 days, mean (SD)
152.5 (±176.8) 126.5 (±167.0) Seems to have no difference between groups, but this results are imprecise (wide CI)
MD 26.0 [95% CI −80.5 to 132.5]; n = 40; p = 0.63
Alshahrani 2020 [41]
  • After 14 days, median (IQT)
42 (38) 65 (11.9) The authors reported a reduced H2S concentration in favour of aPDT (p < 0.0001, n = 30)
Lopes 2015 [36]
  • Immediately, median (IQT)
20 (20.2) 53 (7.0) The authors reported a reduced H2S concentration in favour of aPDT (p = 0.008, n = 31)

ppb = parts per billion, H2S: hydrogen sulfide, aPDT = antimicrobial photodynamic therapy; SD: standard deviation; MD: mean difference; 95% CI: 95% confidence interval; IQT: interquartile.

Adverse Events

Only one RCT [43] (40 participants) assessed the presence of adverse events during the study and showed that most of the participants in the tongue scraper group reported discomfort or a gagging sensation during the procedure. No adverse events were observed in the aPDT group (very low-certainty evidence).

Microbiological Analysis

Three RCTs conducted microbiological analysis but it was not possible to conduct a meta-analysis due to the lack of numerical data; thus, the findings of each study were described individually. One RCT [44] reported no statistical difference between aPDT and tongue scrape for the following bacteria investigated: Porphyromonas gingivalis and Tannerella forsythia (p > 0.05, 30 participants). However, the analysis of Treponema denticola identified a statistical difference in favour of aPDT after 7 days (p = 0.004) and 14 days (p = 0.006) post-treatment. Another RCT [36] reported no statistical difference between groups (p = 0.05, 30 participants) regarding microbiological examination. Lastly, one RCT reported no difference between groups [41].

2. Comparison 2. Antimicrobial Photodynamic Therapy (aPDT) plus Tongue Scraper versus Tongue Scraper

Hydrogen Sulfide (H2S) Gas Measurement

Three studies evaluated this outcome but the lack of numerical data precluded performing a meta-analysis and data were described individually:
Labban et al. (2020) [42]: the authors reported significant improvement in H2S concentration in the aPDT plus tongue scraper group when compared with the tongue scraper group (median 148 versus 0 ppb; p = 0.001, 40 participants).
Alshahrani et al. (2020) [41]: the authors reported a reduced H2S concentration in favour of aPDT plus tongue scraper (median [IQT] 0 [0] versus 65 ppb, p = 0.0001, 29 participants).
Lopes et al. (2015) [36]: the authors reported a reduced H2S concentration in favour of aPDT plus tongue scraper (median [IQT] 0 [0] versus 53 [7] ppb, p = 0.0003, 29 participants).

Quality of Life

Estimated effect from one RCT showed an imprecise result on the improvement in the quality of life measured by the OHIP-14 summary scores. There was a wide confidence interval compatible with both a decrease and an increase in the score, and a small sample size (MD 20.05, 95% CI−53.22 to 93.23, 40 participants) [43].

Microbiological Analysis

One RCT reported a statistically significant reduction in Porphyromonas gingivalis with aPDT only after 5 days of treatment (p < 0.05, 40 participants) (no numerical data was provided) [42]. Another RCT reported a statistical bacterial reduction in the aPDT plus tongue scrape group when compared to tongue scrape (p = 0.0003, 29 participants) [36]. Lastly, one RCT reported no difference between groups [41].

Certainty of the Evidence

The certainty of the body of evidence was evaluated with the GRADE approach for primary outcomes assessed in the main comparison: antimicrobial photodynamic therapy (aPDT) versus tongue scraper. The evidence was rated as very low due to methodological limitations and imprecision (wide confidence interval, small sample size and few events). This indicates very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. The summary of findings in Table 3 presented the assessment and judgements.
Table 3. Summary of findings—GRADE approach.
Antimicrobial Photodynamic Therapy (aPDT) versus Tongue Scraper
Population: patients diagnosed with halitosis
Context: outpatient
Intervention: aPDT
Comparison: tongue scraper
Outcomes Anticipated Absolute Effects *
(95% CI)
Relative Effect
(95% CI)
№ of Participants
(Studies)
Certainty of the Evidence
(GRADE)
Comments
Risk with Tongue Scraper Risk with aPDT
Hydrogen Sulfide (H2S) (in ppb)
Assessed immediately
The mean H2S reduction was 100.9 ppb MD 20.05 points higher
(53.22 lower to 93.22 higher)
- 40
(1 RCT)
⨁◯◯◯
VERY LOW a,b
The evidence is very uncertain about the effect of aPDT on H2S reduction immediately and after 7 and 90 days of treatment.
Additionally, 4 other studies seem to present a reduced H2S concentration in favour of aPDT. However, it was not possible to estimate the effect due to the lack of numerical data.
Hydrogen Sulfide (H2S) (in ppb)
Assessed after 7 days
The mean H2S reduction was 123.1 ppb MD 3.7 points higher
(67.6 lower to 75 higher)
- 40
(1 RCT)
⨁◯◯◯
VERY LOW a,b
Hydrogen Sulfide (H2S) (in ppb)
Assessed after 90 days
The mean H2S reduction was 126.5 ppb MD 26 points higher
(80.5 lower
to 132.5 higher)
- 40
(1 RCT)
⨁◯◯◯
VERY LOW a,b
Adverse events during the study see comments see comments Not estimable 40
(1 RCT)
⨁◯◯◯
VERY LOW c,d
No adverse events were reported in the aPDT group, and some participants reported discomfort and gagging sensation in the control group (no numerical data provided)

* The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio. GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. Explanations.a. Downgraded one level due to methodological limitation (incomplete outcome data). b. Downgraded two levels for imprecision: only one study, very small number of participants, wide confidence interval. c. Downgraded two levels due to methodological limitations (lack of information on allocation concealment and blinding of participants). d. Downgraded one level for imprecision: only one study, very small number of participants and no events.

3. Discussion

Halitosis is the third major cause of the search for oral treatment. Thus, it is relevant to address this problem, which can exert a considerable impact on quality of life [2]. The main cause of halitosis is gas (volatile sulfur compounds) produced by bacteria found in coated tongue. Therefore, treatment consists of the control of these bacteria through mechanical removal, chemical removal, or cell death due to phototoxicity [44]. Tongue scraping could be easily carried out by patients themselves and is widely recommended, but it is little practiced due to discomfort, as it can cause nausea, or lack of awareness regarding its use. In addition, studies have shown that self-cleaning of the tongue alone is not completely efficient for reducing halitosis and it should be associated with in-office treatments, such as periodontal ones. Consequently, alternative forms of treatment, such as aPDT, which can be performed in an office, and is less aggressive to the papillae (that can be hurt during the scraping process), are being researched.
The objective of the present study was to evaluate the efficacy of aPDT at reducing halitosis in comparison to other therapies. The authors of this review believe that alternative therapies, such as the one studied herein, have an advantage over tongue scrapers, as the mechanical removal of coated tongue can cause damage to the lingual papillae. In all articles analyzed, aPDT seems to be effective at achieving an immediate reduction in halitosis. Do Vale et al. [43] and Romero et al. [24] found that aPDT was more effective for the treatment of halitosis when compared to the use of a tongue scraper, whereas Mota et al. [44], Lopes et al. [36] and Alshahrani [41] found that this therapy was more effective when combined with the mechanical removal of coated tongue.
The majority of studies used a red laser (λ = 660 nm) as the energy source and the photosensitizer was methylene blue at a concentration of 0.005%. The predominant pre-irradiation time was five minutes, but Romero et al. [24] used a pre-irradiation time of one minute and found that the treatment was effective with this shorter time. The most used energy was 9 J with a power of 100 mW at six points distributed on the dorsum of the tongue. Treatment was performed in a single session in all articles. The researchers who performed follow-up after seven days reported the return to initial H2S concentrations [24,43] whose halitosis remained low until the seventh day. These two authors evaluated edentulous patients, and prosthesis were also cleaned. Interestingly, patients were undergoing fixed orthodontic treatment. Alshahrani 2020 [41] also maintains low concentrations of H2S.
The primary outcome in the majority of articles included in the present review was a reduction in halitosis, which was determined based on the measurement of H2S using the OralChroma device. The studies that employed this device reported a reduction in the concentration of H2S immediately after the application of aPDT. This device employs gas chromatography for the determination of concentrations of volatile sulfur compounds produced by anaerobic bacteria, which is the main cause of halitosis [36]. The authors used a H2S concentration ≥112 ppb for the determination of halitosis. OralChroma is currently considered the gold standard. The diagnosis was previously performed using the organoleptic method, which has fallen into disuse because of the subjectivity of the evaluation.
All researchers who used the OralChroma device followed the manufacturer’s instructions and obeyed the following sequence: the participants were instructed to avoid spicy foods, alcohol, coffee, chewing gum, and mouthwash. On the day of the reading, the participants needed to fast for at least two hours and rinsed their mouths with cysteine (10 mM).
It was not possible to perform a meta-analysis (or sensitivity analysis) for the outcome of the research question of this systematic review. Despite being well designed, the studies showed clinical heterogeneity, especially in relation to the characteristics of the population such as different age range. Literature shows the occurrence of halitosis at all ages, but the causes and habits can change the characteristics in different age groups. In view of the heterogeneity of the studies, it was decided to carry out only the qualitative analysis of the studies. The results of the present systematic review show uncertain evidence about the effects of antimicrobial photodynamic therapy compared to the tongue scraper. The results seem to present better effects with the combination of both methods (aPDT and tongue scraper) when compared to the tongue scraper. However, since the available evidence was classified as very low certainty by the GRADE approach, further studies should be conducted to support these findings and to establish the number and periodicity of sessions needed to achieve the complete resolution of this problem.
The predominant use of methylene blue is related to the wavelengths employed by these researchers, which ranged from 655 to 660 nm (red laser). Mota et al. [44], Lopes et al. [36], and Vale et al. [43] applied the photosensitizer and waited for five minutes of pre-irradiation time, and Romero et al. [24] waited only one minute.
The parameters used for aPDT were quite similar among the studies, as the majority were performed by the same research group. All studies used red laser. Mota et al. [44], Lopes et al. [36], and Vale et al. [43] and Romero et al. [24] and used an energy of 9 J and power of 100 mW at six points on the dorsum of the tongue for 90 s per point. All papers in the present review performed a single session of aPDT.
Mota et al. [44], Lopes et al. [36] and Alshahrani 2020 [41] conducted similar studies, in which three groups were compared: (1) treatment with aPDT; (2) treatment with a tongue scraper; and (3) combination of aPDT and tongue scraper. In the study by Lopes et al. [36], the reduction in the concentration of H2S was 97% in Group 1, 88.6% in Group 2, and 100% in Group 3. Additionally, in the Alshahrani 2020 [41] study, Group 1 (aPDT) decreased 95%, Group 2 (TS) 89,4% and Group 3 (aPDT + TS) 100% in 15 days. Mota et al. [44] did not provide numerical data.
Do Vale et al. [43] and Romero et al. [24] allocated the participants into two groups: experimental (treatment with aPDT) and control (treatment with tongue scraper). In the study by do Vale et al. [43], the authors found a reduction in halitosis after both treatments. However, significant differences between groups were found immediately after treatment and at the seven-day follow-up, with greater reductions in hydrogen sulfide concentrations in the group treated with aPDT.

Lopes et al. [36] found that aPDT was effective at achieving an immediate reduction in halitosis and therefore constitutes a treatment option for this condition that does not harm the papillae, as occurs in conventional treatment with a tongue scraper. However, the authors found that the application of 90 s per point at six points on the dorsum of the tongue caused certain discomfort among the patients and suggested further studies to test different energies. Do Vale et al. [43] conducted a study with patients who wore complete dentures. The authors concluded that aPDT seems to be effective at reducing H2S immediately after treatment and that this effect was maintained at the seventh day follow-up. Laban et al. [42] concluded that antimicrobial PDT seems to help in reducing H2S concentration and improving quality of life in elderly patients wearing dentures. There also a reduction in P. gingivalis that occurred only in the short-term follow-up. Da Mota et al. [44] concluded that aPDT using a red LED and 0.005% methylene blue caused an immediate reduction in halitosis, but the effect was not maintained after 7, 14, or 30 days. Additionally, they found no reduction in the number of bacteria investigated or the quantification of universal 16S rRNA. Romero et al. [24] reinforces the oral hygiene behavior associated with aPDT or tongue scraper was not able to reduce halitosis after 90-day follow-up. Despite halitosis remaining higher than 112 ppb in all follow-up periods, the mean values remain two- or three-fold smaller than baseline values. Future studies should include other oral hygiene behavior to achieve better results in the treatment of halitosis. Alshahrani [41] concludes that PDT along with tongue scraping showed immediate reduction in H2S and reduction in oral pathogens in adolescent patients undergoing fixed orthodontic treatment for 15 days.

This entry is adapted from the peer-reviewed paper 10.3390/s22020469

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