Abstract
Reinke’s edema (RE) is a benign pathological non-inflammatory disorder of the vocal folds with a wide range of clinical manifestations. We aim to investigate the relationship between Reinke’s edema and some common inhalant abuse. In this case-control study, subjective consisted of 23 patients with RE (the cases), and 50 patients with sinusitis (control) who underwent surgery in the Department of Otolaryngology, between 2015 and 2020. Demographic characteristics, history of some related disease, methods, and the duration of cigarette, and opium consumption were collected through the patients’ files. The chi-square (χ²) test was run to analyze the differences in the categorical and, and the Independent Sample T-test was used to compare two sample means from unrelated groups. A significant level (p-value) was considered less than 0.05. The mean age was 54 ± 12 years, and 42 ± 11 years, respectively for Reinke’s edema and sinusitis. More women had been recorded in the RE group, compared to men. Allergy, unprincipled use of voice and talkativeness, history of laryngeal surgery, and type of disease were correlated to RE (p < 0.05). Also, cigarette smoking was significantly correlated with Reinke’s edema. The average number of cigarettes per day, the duration of smoking, and opium consumption were more frequent in RE (P < 0.05). 90% of the RE and 4% of sinusitis patients were opium consumers. There was a statistically significant difference in the methods of substance use in the two groups of cases and control (p < 0.0001). Among the different methods, the poker and stone method was the most common (69.6%), and the opium smoking pipe was the second most common method. This study also confirmed the hazardous effects of smoking and inhaling opiates in the formation of lesions of the pharynx and larynx. In particular, longer use of these substances will be associated with more serious side effects. Therefore, it seems that people who are addicted to opiates should undergo periodic visits and counseling to reduce and stop their use.
Keywords: Reinke’s Edema, Risk factors, Cigarette smoking, Opium consumption, Larynx
Introduction
Rinke’s edema, also known as vocal cord polyp, is a swelling that covers the entire superficial layer of the lamina propria. It is particularly common in smokers and some people who are exposed to cigarette smoke. Ranke’s edema is not considered a pre-cancer condition, but it indicates that the vocal cords are exposed to damage from cigarette smoke [1, 2].
This disorder is more noticeable in women, but it can also be seen in men. Sometimes the swelling caused by Reinke’s edema is so great that it can lead to shortness of breath, which at first occurs only when there is a lot of activity. Still, eventually, it can also lead to shortness of breath at rest and then even to breathing disorder during sleep [3–5].
The first step in Reinke’s edema treatment is to stop smoking. In advanced cases, recovery is not achieved even if you quit smoking. Although some weeks have passed after the treatment, continued smoking leads to the possibility of recurrence. This causes many otorhinolaryngology experts to prefer recommending smoking cessation, before Reinke’s edema surgery [6].
If Reinke’s edema does not resolve after smoking cessation, micro laryngoscopy is considered the main treatment. Surgery for Renke’s edema may be accompanied by some complications; scarring and roughness can occur after surgery, which is very difficult to repair. The operation increases the volume and eliminates any breathing problems, but because of the high risk of injury, for surgeons, the priority is to stop smoking before any operation [7].
In a study to determine the prevalence of malignant and premalignant tumors in people with pathologically confirmed Reinke’s edema in the United Kingdom between 2001 and 2010, Lim et al. performed 3,902 laryngeal biopsies over 10 years. Among the participants, 189 people (18 men and 171 women) had Rink’s edema, which was confirmed histologically, of which 170 people had no dysplasia, 16 people had mild dysplasia, 2 people had moderate dysplasia, and one person had severe dysplasia. No malignancies were reported. They found that mainly the cases were women and smokers, and the epithelium seems to differentiate towards benign Reinke’s edema rather than malignant. Finally, they concluded that it can reassure the patients that Reinke’s edema will not be a malignant one [8]. In a retrospective study conducted between 2017 and 2019 in a tertiary teaching hospital in eastern India, Swain et al. suggested that childhood smoking and exposure to smoking are directly related to laryngeal manifestations. The results of this study showed that the majority of children with smoking habits were boys (59.37%). The most common diagnosis among children who smoked was laryngeal reflux 40.62%, followed by chronic laryngitis (25%), vocal fold keratosis (18.75%), Reinke’s edema 12.50% and malignancy (3.12%) [9].
Considering the high frequency of Reinke’s edema in smokers, and the deficiency of relevant studies to investigate the relationship between Reinke’s edema and other inhalant abuse, this project was conducted to investigate the prevalence of Reinke’s edema, and its relationship with inhalant abuse, in the patients who underwent surgery in the Ear, Nose, and Throat department of Kerman Shafa Hospital. By knowing the frequency and possible relationships, more complications of the disease can be prevented.
Materials and Methods
Ethical Approval
This study was approved by the Kerman University of Medical Sciences which follows the Helsinki Declaration of 1975 (IR.KMU.AH.REC.1400.122). Informed consent was obtained from all the subjects, before participating in this study.
Study Design
Participants in this study, which was a case-control study, were patients who underwent surgery in the Department of Otolaryngology of Kerman Shafa Hospital, between 2015, and 2020.
The inclusion criteria for the case group were the cases who underwent Reinke’s edema surgery at the ENT Department, during the mentioned time. Reinke’s edema had been confirmed based on the clinical examination and videosteroscopy. The control group was the sinusitis patients who underwent surgery at the Otolaryngology Department, at the same time. The sampling was done by census method, and for each case, two controls were considered. Depending on the type of disease, 23 patients had Reinke’s edema, and 50 patients suffered from sinusitis, were entered in the study. Demographic characterizations were age, sex, marital status, education, job, and income level.
Demographic characteristics, opium consumption, methods, and the duration of opium consumption were collected through the patients’ files. Also the other collected important variables were as follows; allergy, unprincipled use of voice (singing, praising, etc.), talkativeness, history of laryngeal cancer, history of laryngeal surgery, exposure to other inhaled substances (chemicals at work, etc.), smoking, reflux, hypothyroidism.
After data collection, analysis was done using the Statistical Package for the Social Sciences 20 (SPSS Inc., Chicago, IL, USA). The chi-square (χ²) test was run to analyze the differences in the categorical and nominal variables and the Independent sample T-test was run to compare the means of unrelated groups. A significant level (p-value) was considered less than 0.05.
Results
Seventy-three subjects, consisting of 45 (61%) female, and 28 (38%) male, with a mean age of 46 ± 12 years, participated in this study. The mean age was 54 ± 12 years, and 42 ± 11 years, respectively for Reinke’s edema and sinusitis.
The case and control groups’ demographic characterization are shown in Table 1. The results showed no significant differences in age, sex, marital status, education, occupation, and income.
Table 1.
Demographic characterization of the study participants according to type of disease (n = 73)
| Reinke’s edema | sinusitis | P-Value | |
|---|---|---|---|
| Age (mean ± SD) | 54 ± 12 | 42 ± 11 | 0.360 |
| Sex | |||
| Male | 8(34.8) | 20(40.0) | 0.670 |
| Female | 15 (65.2) | 30(60.0) | |
| Marital status -n (%) | |||
| Single | 1 (4.3) | 2 (4.0) | 0.59 |
| Married | 19 (82.6) | 45 (90.0) | |
| Education-n (%) | |||
| illiterate | 3 (13.0) | 2 (4.0) | 0.64 |
| under diploma | 7 (30.4) | 15 (30.0) | |
| diploma | 6 (26.1) | 12 (24.0) | |
| Associate | 4 (17.4) | 13 (26.0) | |
| Bachelor | 3 (13.0) | 8 (16.0) | |
| occupation | |||
| housewife | 14 (60.9) | 23 (46.0) | 0.76 |
| Retired | 1 (4.3) | 2 (4.0) | |
| Driver | 2 (8.7) | 4 (8.0) | |
| farmer | 1 (4.3) | 1 (2.0) | |
| self-employment | 3 (13.0) | 13 (26.0) | |
| Employee | 2 (8.7) | 7 (14.0) | |
| income | |||
| Below the average | 10 (43.5) | 23 (46.0) | 0.84 |
| Average and higher | 13 (56.5) | 27 (54.0) | |
As can be seen in Table 2, when comparing variables associated with laryngeal disease, significant differences were found related to allergy, unprincipled use of voice and talkativeness, history of laryngeal surgery, and type of disease (RE).
Table 2.
Comparison of variables related to laryngeal diseases in two groups (n = 73)
| Reinke’s edema | sinusitis | P-Value | |
|---|---|---|---|
| History of allergy | |||
| Yes | 2 (8.7) | 45 (90.0) | 0.0001 |
| No | 21 (91.3) | 5 (10.0) | |
| Unprincipled use of voice | |||
| Yes | 7 (30.4) | 0 | 0.0001 |
| No | 16 (69.6) | 50 (100.0) | |
| talkativeness | |||
| Yes | 9 (39.1) | 7 (14.0) | 0.016 |
| No | 14 (60.9) | 43 (86.0) | |
| Hypothyroidism | |||
| Yes | 1 (4.3) | 10 (20.0) | 0.082 |
| No | 22 (95.7) | 40 (80.0) | |
| laryngeal cancer | |||
| Yes | 1 (4.3) | 0 | 0.138 |
| No | 22 (95.7) | 50 (100.0) | |
| History of laryngeal surgery | |||
| Yes | 4 (17.4) | 0 | 0.002 |
| No | 19 (82.6) | 50 (100.0) | |
| reflux | |||
| Yes | 5 (21.7) | 14 (28.0) | 0.57 |
| No | 18 (78.3) | 36 (72.0) | |
Chi-square (χ²) test
Table 3 shows the frequency of substance use in the two groups. The results of the chi-square test showed that cigarette smoking was significantly related to Reinke’s edema, while 30% of these patients, and 10% of sinusitis patients were cigarette smokers. The frequency of hookah use was 4.3% in Reinke’s edema patients and 10% in sinusitis patients. The rate of opium consumption was 95.7% in Reinke’s edema patients and 4% in sinusitis patients.
Table 3.
Frequency of opioid (substance) use in two groups (n (%))
| Reinke’s edema (%) | Sinusitis (%) | P-Value | |
|---|---|---|---|
| Cigarette smoking (yes) | 7(30.4) | 5 (10.0) | 0.029 |
| Hookah use (yes) | 1 (4.3) | 5 (10.0) | 0.414 |
| Opium (yes) | 22 (95.7) | 2 (4.0) | 0.000 |
Chi-square (χ²) test
Reinke’s edema patients smoked an average of 11 cigarettes per day, for an average of 15 years. At the same time, sinusitis patients smoked 6 cigarettes per day for an average of 9 years. The average duration of opium use was approximately 13 years in the patients with Reinke’s edema, and 2 years in sinusitis patients (Table 4).
Table 4.
The average number of cigarettes per day, and the duration of smoking (mean ± SD)
| Reinke’s edema | Sinusitis | P-Value | |
|---|---|---|---|
| Cigarette number | 11.14 ± 4.05 | 6.20 ± 3.49 | 0.005 |
| Duration of smoking (year) | 15 ± 5.35 | 9 ± 5.47 | 0.008 |
| Duration of opium consumption (year) | 13.07 ± 4.64 | 2 ± 1.41 | 0.000 |
Independent sample T-test
In Table 5, the frequency of different methods of substance use is presented. There was a statistically significant difference in the methods of substance use in the two groups of cases and control (p < 0.0001). Among the different methods, poker and stone was the most common (69.6%). Four patients with Reinke’s edema (17.4%), and 2 (4%) of the sinusitis patients used opium via a smoking pipe; the second most common method.
Table 5.
Comparison of different methods of substance use in the two groups of cases and control (n (%))
| Reinke’s edema | sinusitis | |
|---|---|---|
| None use | - | 48 (96) |
| poker and stone | 16 (69.6) | - |
| Opium smoking pipe | 4 (17.4) | 2 (4) |
| Oral & poker and stone | 2 (8.7) | - |
| Oral & Opium smoking pipe | 1 (4.3) | - |
| P-Value | 0.000 | |
Chi-square (χ²) test
Discussion
This study which was done during 2015–2020, provides access to data from 23 patients with Reinke’s tumor diagnosis. These patients comprised 31.5% of patients who were admitted to the Department of Otorhinolaryngology at Kerman Shafa Hospital. The control group consisted of patients with sinusitis diagnosis, who accounted for 68.5% of all patients hospitalized in the same department, and during the same time.
The majority of the patients in the two study groups were female. The male patients accounted for 35% of Reinke’s tumor and 40% in the sinusitis group. It’s in accordance with the community distribution of Reinke’s edema, which is found more frequently in women [10]. As the differences in the distribution of the demographic variables such as age, gender, and marital status were not statistically significant, showed the groups homogeneity, related to the mentioned variables.
In our study, the mean age of patients with Reinke’s edema was 53.74 ± 12.13 years. In one study by Sugito et al. (2022) on 2901 patients, with a mean age of 53.2 ± 20.7 years, they reported that the increase in age was a factor in the development of dysphonia, which continuously increases the chance of vocal cord injury, vocal cord atrophy, and laryngeal cancer [11].
The findings did not show a significant difference between occupation and type of disease (sinusitis or Reinke’s edema), income level, and type of disease. Most of the patients in both groups were women, and they were housewives. Allergy history was the most important risk factor for sinusitis, with a statistically significant difference, while unprincipled use of voice and talkativeness were the most important factors, in Reinke’s edema. Also, allergy had no significant effect on the occurrence of Reinke’s edema. Consistent with our results, the unprincipled use of voice was reported as a significant factor in the occurrence of Reinke’s edema. Kravos et al. showed allergy in 20% of Reinke’s edema patients, and 23% in the control group, with no significant difference between the two groups. Other factors such as laryngeal reflux, unprincipled use of voice, unfavorable ergonomic work conditions, and thyroid diseases in patients with Reinke’s edema had significant differences with the control group [12]. Other studies also showed that factors such as extroverts with talkative personalities and occupations with high vocal demands are the most common risk factors for Minimal Associated Pathological Lesions “MAPLs” such as Reinke’s edema, and the other factors that can potentiate vibratory injury are smoking, acid reflux, uncontrolled allergies, and infections [13]. In the reflux cases, it was hypothesized that smoking and reflux, secondary to the creation of the chronic glottal mucositis environment, contribute to the superior distention of the superficial lamina propria [14].
Also, a significant relationship was found between the history of laryngeal surgery and Reinke’s edema. In this study, none of the patients with sinusitis had a history of laryngeal surgery. The history of hypothyroidism was more frequent in Reinke’s edema, but it had no significant relationship with the incidence of the disease in this study. In the other studies, there was no relationship between hypothyroidism and Reinke’s edema, while smoking, vocal misuse, and recurrent respiratory tract infection were mentioned as the main risk factors [15].
Also, 4% of patients were diagnosed with laryngeal cancer, which had no statistically significant relationship with Reinke’s edema. Of course, this result may be because of the small sample size in this study. Both groups of patients had reflux, which was more frequent in the sinusitis patients, but there was no statistically significant difference between reflux and the type of disease.
The findings of our study reported a higher frequency of cigarette smoking in the patients with Reinke’s edema, and a higher hookah use in sinusitis patients. Smoking in Reinke’s edema had a significant relationship with the occurrence of the disease. Another study also found a significant relationship between tobacco use and Reinke’s edema and reported that both the number of cigarettes per day and the duration of smoking affect the clinical manifestation of this disease [16].
The average number of cigarettes per day, the duration of smoking, and the average use of hookah were higher in Reinke’s edema group. It was reported that Reinke’s edema is strongly associated with smoking, vocal misuse, and laryngopharyngeal reflux [16, 17]. Martins et al. reported Reinke’s edema in 9.2% of women with dysphonia (speech disorder), while two-thirds of them were smokers [18]. Nicotine components probably affect angiogenesis by increasing vascular permeability, which causes subepithelial edema [19]. Sakae et al. in the histopathological studies of Reinke’s edema reported that the toxic chemical mediators in cigarettes change the products of collagen fibers. Collagen fibers which are mainly in the middle layers of myxoid stroma and deep layers of lamina propria are affected by smoking [20].
Marcotullio et al., in the study of the risk factors of Reinke’s edema, introduced smoking and tobacco use as the most important risk factor. In their study, a significant relationship was reported between the number of cigarettes consumed per day and the duration of smoking or exposure to tobacco smoke with the incidence of injuries identified in histological examinations and the clinical manifestations of the disease [16].
Reinke’s edema group were more opium consumers (96%), as well they had a longer history of opium consumption compared to the sinusitis patients (13 years, VS 2 years).
The results showed a statistically significant difference in the incidence of Reinke’s edema in the opium consumer, compared to sinusitis, which shows opium use as an important risk factor for Reinke’s edema.
Considering the importance of substance use, the way of consumption was investigated in this study, and the most frequent ways were poker and stone, opium smoking pipe, oral & poker and stone, and oral & opium smoking pipe, respectively. Nazer et al.‘s study in Rafsanjan reported that the most common way of smoking opium was with a poker and stone, then by opium smoking pipe. The ease of using opium with the poker and stone method and somehow hiding the shame of using it has made poker and stone a popular method [21].
The adverse effects of opiates (opium and opium juice) have been reported on the functioning of the bladder, stomach, esophagus, pharynx, and larynx systems [22]. In their study, Bakhshaee et al. found a significant relationship between the use of inhaled opiates and smoking with the occurrence of laryngeal cancer [23]. In many studies, researchers have found a rigorous relationship between glottic and laryngeal squamous cell carcinoma and opium consumption [23–25], and it was shown that long-term opium consumption increases the mortality rate due to both malignant and non-malignant respiratory diseases [26]. However, there are very few articles that have focused on this type of substance addiction and Reinke’s edema, individually for the first time, in the present study it showed a statistically significant relationship between inhaled opiates and Reinke’s syndrome.
Conclusion
This study also confirmed the hazardous effects of smoking and inhaling opiates in the formation of lesions of the pharynx and larynx. The problems range from verbal communication impairment to the occurrence of lesions that may need surgery for treatment. In particular, longer use of these substances will be associated with more serious side effects, as in the present study, this relationship was shown with the occurrence of Reinke’s edema. Therefore, it seems that people who are addicted to opiates should undergo periodic visits and counseling to reduce and stop their use. Also, increasing public awareness about the serious side effects of smoking on pharynx and larynx diseases will be effective in preventing and improving society’s health index.
Acknowledgements
the authors of this study are grateful for the cooperation of the Department of Otolaryngology of Kerman Shafa Hospital staff, for the implementation of this study.
Declarations
Consent for Publication
Not applicable.
Competing interests
There is no any no conflicts of interest.
Footnotes
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