Comparison of Levels of Heavy Metals in Nasal Concha Tissues in Rural and Urban Regions

Comparison of Levels of Heavy Metals in Nasal Concha Tissues in Rural and Urban Regions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of Levels of Heavy Metals in Nasal Concha Tissues in Rural and Urban Regions Fatih Öner, Nezahat Kurt, Harun Üçüncü This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3982677/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Heavy metal exposure has recently become a problem due to the increasing environmental pollution as urbanization expands. Objective: This prospective case control study was conducted to compare levels of heavy metals in the nasal concha of the patients living in urban and rural who underwent partial inferior concha resection. Methods: Sixty-seven patients were divided into two groups: 38 rural patients and 29 urban patients. Lead (Pb), cadmium (Cd), mercury (Hg), copper (Cu), and manganese (Mn) levels were measured in inferior nasal concha by Inductively Coupled Plasma- Optical Emission Spectrometry. Results: Significance was considered at p < 0.05. The levels of Cu (0.24± 0.048 vs. 0.06± 0.019 µg/g) and Zn (3.29± 0.69 vs. 0.44± 0.14µg/g) of the rural patients were significantly higher compared to urban patients ( p<0.001 ). There was no significant difference in the Cd level between groups. Pb (0.024± 0.009 vs. 0.008± 0.0002 µg/g) and Mn (0.273± 0.01 vs. 0.174± 0.05 µg/g) levels of urban patients were significantly higher than rural patients ( p<0.001 ). Conclusions: Heavy metals accumulate in the nasal concha at different rates in rural and urban areas. Indicating the presence of heavy metals in turbinates and measuring their amount may be helpful for diagnostic purposes in diseases whose etiology is attributed to air pollution; however, the pathophysiology still needs to be clarified. Air Pollution Heavy metals Nasal Mucosa Spectrophotometry Turbinates Figures Figure 1 Figure 2 INTRODUCTION Environmental pollution is a severe problem in industrialized and metropolitan cities, threatening public health 1 , 2 . Each year, 4.2 million people die earlier from heart and respiratory diseases triggered by air pollutants (World Health Organization- 2008) 3 . Pollutants that cause the problem and disturb the natural balance include organic substances, industrial wastes, petroleum derivatives, synthetic agricultural fertilizers, detergents, radiation, pesticides, inorganic salts, synthetic organic chemicals, and waste heat. All of these, directly and indirectly, cause air pollution. Heavy metals are found in almost all of them, mostly in industrial wastes and pesticides. Elements are present in the human body in pure form or compounded form. Although some elements are essential for human physiology, some of them are toxic, such as lead (Pb), mercury (Hg), and cadmium (Cd). Generally, intoxication occurs through accumulation as a result of prolonged exposure. Heavy metals cause the dysfunction of enzyme systems by binding oxygen, nitrogen, and sulfhydryl groups to proteins, revealing their toxic effects 4 . For instance, metalloproteins in the organism contain large amounts of thiol ligands. These ligands have a high affinity for binding elements such as Cd, copper (Cu), and zinc (Zn). Factors such as heavy metal particle size, duration of heavy metal exposure, and age of individuals determine the degree of heavy metal intoxication 5 , 6 . The nose is the main entrance gate of polluted air to the body 7 . Many heavy metals can enter the body through inhaled air. Detection of heavy metal presence in nasal concha tissues may mean that heavy metals in ambient air cause accumulation in nasal mucosal and submucosal tissues by inhalation. Due to the mucociliary activity of the nasal mucous membranes, inhalation and absorption of pollutants can weaken local immune responses in the airways. This study was conducted to compare levels of heavy metals in nasal conchal tissues of patients from urban and rural areas. MATERIALS and METHODS Patients and Study Design Sixty-seven patients (24 females, 43 males) were administered to the Otorhinolaryngology outpatient clinic with nasal obstruction. Most of the selected patients had compensatory nasal concha hypertrophy accompanying nasal septum deviation, and partial resection of the inferior concha was scheduled. The patients were divided into rural (n = 29) and urban (n = 38) groups according to their living areas of at least 15 years after verbal and written informed consent. Patients with diseases that could affect the presence of heavy metals in the nasal concha were excluded. The exclusion criteria were as follow: - Smokers/ex-smokers, - Patients under the age of 18 and over 55, - Patients with nasal polyps or polyposis, - Patients with allergic rhinitis, - Patients with nasal involvement of systemic diseases, - Patients using medication continuously, - Patients who had undergone any previous surgical intervention (septoplasty, concha radiofrequency ablation, partial resection) in the nasal cavity, - Patients working in the industry sector. Partial resection of the inferior concha with septoplasty was performed in 58 patients, and only partial resection of the inferior concha was performed in nine patients. Bilateral inferior concha partial resection was performed in 60 patients, while unilateral resection was performed in seven patients. All patients were operated on under general anesthesia by the same surgeon, and a standard procedure was performed. No local anesthetic was applied to the concha tissue before resection. The inferior turbinates were first medialized with the Cottle elevator, and then the lower-medial parts were cut using concha scissors. We washed the resected turbinate pieces with distilled water, removed the mucus, and attached particles mechanically. The tissues taken were transferred to the sterile tubes without contact anywhere and stored at -80 ͦ C ( Fig. 1 ). Measurements of Metal Concentrations Nasal concha tissues were let to thaw at room temperature. First, conchal bones, if any, were dissected and removed. From the deboned mucosa and submucosal parenchyma tissue, fragments weighing 0.5 g were transferred into a tube and added with 3 ml of acid mixture (HClO4 + HNO3, 5: 1). The samples were incubated at 95 o C for one hour 8 . Solid conchal tissues were hydrolyzed with acid and became liquid at the end of three hours. Solutions were diluted with distilled water to measure heavy metals (Cu, Zn, Cd, Pb, and Mn) spectrophotometrically using the Inductively Coupled Plasma- Optical Emission Spectrometry (Perkin-Elmer, Optima 4300 DV, ICP / OES, Waltham, MA). Statistical analysis After confirmation of the normal distribution of the data in the Kolmogorov Smirnow Test, Student T-Test was used in the comparisons of patient age and Cd, Pb, Cu, Mn, and Zn levels by the patient group (SPSS, version 22, Chicago, IL). Data are presented as a number, percentage, median, mean, and standard deviation. Mann-Whitney U Test was used to analyze age by gender, Cd, Pb, Cu, Mn, and Zn in both groups. Significance was considered at p < 0.05. Ethics The study was approved by the XXXX University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee (Decision no: XXXXX). RESULTS There was no difference in the mean age (p = 0.991; Table 1 ) and gender distribution between the groups (p = 0.991; Table 1 ). The age distribution of the rural group was 18–52 (29.3 ± 9.4), and the urban group was 18–55 (29.1 ± 9.8). There were 17 males (58.6%) and 12 females (41.4%) in the urban group, 26 males (68.4%) and 12 females (31.2%) in the rural group. Cu (0.24 ± 0.048 µg/g) and Zn (3.29 ± 0.69 µg/g) levels of rural patients were significantly higher than Cu (0.06 ± 0.019 µg/g) and Zn (0.44 ± 0.14 µg/g) levels of urban patients ( p < 0.001, p < 0.001 , Table 2 ). The Cd (0.034 ± 0.014 µg/g) level of the rural patients was similar to the Cd level (0.032 ± 0.013 µg/g) of the urban patients (p = 0.505, Table 2 ). Pb (0.024 ± 0.009 µg/g) and Mn (0.273 ± 0.01 µg/g) levels of the urban group were significantly higher than Pb (0.008 ± 0.0002 µg/g) and Mn (0.174 ± 0.05 µg/g) levels of the rural group ( p < 0.001, p < 0.001 , Table 2 , Fig. 2 ). Heavy metal levels in rural and urban patients were independent of age and gender. When the two groups were compared, we detected that the difference between the heavy metal levels occurred due to the residence difference (Table 3 ). DISCUSSION Air pollution is considered a general health hazard. Technologies that facilitate our current world release various pollutants into the atmosphere. Technological products increase the concentration of air pollutants in the atmosphere, containing heavy metals harmful to plants, animals, and humans. When specific risk factors such as genetics, diet, and lifestyle come together with environmental factors, the negative impact of air pollution on human health is likely to increase 9 . For the individual risk assessment of environmental hazards, showing the physical presence of the substances in the body or the negative functional results is essential. The nasal cavity is a usual gateway to the human body for air pollutants and is a well-known target site for toxicity caused by air pollutants 7 . This study reported compassion of levels of heavy metals in nasal conchal tissues in patients living in rural and urban areas. Few studies examine the relationship between nasal mucous membranes, air pollution, and heavy metals. Şenvar 10 compared serum Cu and Zn levels in the patients with atrophic rhinitis and healthy people and reported higher serum Cu levels and lower serum Zn levels in the patient group. A study compared 11 trace elements on the nasal lower concha and nasal septum. There was an age-related increase in Pb levels in both tissues and decreased Zn levels. In another study 12 , exposure to urban pollution in adults in Mexico has been shown to increase the proliferation rate in nasal cells, a risk factor for developing neoplasia. Calderon- Garciduenas et al. 13 found significant differences in biopsies from nasal mucosa of children exposed to outdoor pollutants compared with a healthy control group. Children exposed to polluted air had more complaints about upper airways, such as epistaxis, nasal congestion, dryness, and crusting. As expected in ENT examinations, abnormal nasal mucosal findings such as increased hyperemia and bleeding points in the nasal mucosa, purulent mucus, and sinusitis were observed. The authors reported basal cell hyperplasia, a decrease in ciliary epithelial cell and goblet cell count, submucosal neutrophil infiltration, squamous metaplasia, and dysplasia histopathological analysis of nasal mucosa biopsies of children exposed to air pollutants. In general, very few air pollutants are found in rural regions. If the agricultural industry is developed, particulate matter in airborne pesticides and fertilizers can be considered air pollutants in the rural area 14 . Unlike rural areas, metropolitans are focal points of air pollution due to motor vehicles, industrial facilities, and factories. In urban regions where the population is much more crowded, the primary source of air pollutant particles is traffic density and exhaust gases from diesel and gasoline engines 15 , 16 . Main outdoor air pollutants include carbon monoxide, sulfur dioxide, ozone, nitrogen dioxide, and lead 14 . The polluted air in the city also contains ultrafine particles in high concentrations, and their effect on human health is not fully known 16 , 17 . Glück et al. 18 examined the cytopathological of the nasal mucosa of individuals chronically exposed to diesel engine emissions. They detected goblet cell hyperplasia in the nasal mucosa and inflammatory response caused by increased leukocytes and defined this condition as chemical-induced rhinitis. The major heavy metal in polluted air is Pb 19 . In air pollution caused by exhaust gas, heavy metals enter the body mainly by inhalation 20 . Yılmaz et al. 21 investigated heavy metal levels in the leaves of trees in the city center and countryside. The amount of Pb in the samples of the city center was significantly higher than in rural areas, and they associated these higher Pb levels with exhaust gas and air pollution. In another study 22 , Suchodoller found that the amount of Pb accumulated in the barley and corn planted next to the road was high. They reported that the amount of Pb in the plants decreased as they moved away from the road, and the effect of traffic was not noticed 30–40 m away from the road. Similarly, in our study, Pb levels in the tissues of rural patients were significantly higher than in rural patients (p < 0.001). Youssaf et al. 23 measured tree barks as a bioindicator to assess air pollution in downtown Toronto and reported high levels of Pb and Mn in trees on the roadside with heavy traffic. Our study also found that the urban group's Mn and Pb levels were significantly higher. People are not only exposed to polluted air outdoors. The best-known effect is cigarette smoke, the air pollutant inside. In an experimental study 24 , significant changes were observed in the nasal mucosa of animals exposed to tobacco smoke. Disruptions in intercellular tight junction complexes, significant structural changes in cell membranes, and increased infiltration of neutrophils on the nasal mucosa surface had been demonstrated in exposed animals. Cigarette smoke or occupationally exposed smoke is inhaled directly into the body along with the heavy metals it contains and causes the levels of heavy metals in the blood to rise 25 . In the present study, patients who were smokers and ex-smokers were excluded. Heavy metals inhaled with polluted air cause accumulation in the human body. Heavy metals trigger oxidative stress in the organism, increase reactive oxygen species, lipid peroxidation, and inflammatory cytokines, and exhibit harmful effects 4 , 26 , 27 . Oxidative stress plays a role in the etiopathogenesis of many diseases. It is a challenge to show the harmful effects of exposure to air pollution on human health with evidence. It is necessary to present the pollutant at the same time above the acceptable concentration in ambient air and human tissue, which is a challenging application in the normal population. One limitation of our study is that we only measured five heavy metals. Due to technical limitations, the restricted size of this number can serve as a valuable reference for future investigations into the wide variety of heavy metal alterations. Furthermore, the absence of simultaneous measurements of heavy metal levels in the blood samples of the patients, as well as the absence of indicators indicating the presence of heavy metal air pollution in the urban and rural areas where the patients reside, can be considered. Another aspect of the study that requires improvement is the inability to consider passive smoking status despite the exclusion of active smokers and ex-smokers. When we attribute the cause of a condition to air pollution but the underlying mechanisms are not yet completely understood, showing the presence of heavy metals in the nasal mucosa can be beneficial. In clinical scenarios where there is evidence of heavy metal accumulation and a clear link to diseases, we can mitigate the occurrence of the diseases by implementing preventive measures in urban areas. Declarations Ethics Committee Approval: This study was found to proper with ethical rules by the Atatürk University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee (Decision No: B.30.2.ATA.0.01.00 / 56). Informed Consent: The consent of all patients was obtained for the original data collection. Data Sharing Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Authorship Contributions: Fatih Öner,Md ; Conceptualization (Equal), Data curation (Lead), Formal analysis (Equal), Funding acquisition (Equal), Investigation (Lead), Methodology (Lead), Project administration (Equal), Resources (Lead), Software (Lead), Supervision (Supporting), Validation (Lead), Writing – original draft (Lead), Writing – review & editing (Lead). Nezahat Kurt, PhD ; Conceptualization (Equal), Data curation (Supporting), Formal analysis (Equal), Funding acquisition (Supporting), Investigation (Supporting), Methodology (Supporting), Project administration (Equal), Resources (Supporting), Software (Supporting), Supervision (Supporting), Validation (Supporting), Visualization (Supporting), Writing – original draft (Supporting), Writing – review & editing (Supporting) Harun Üçüncü, Md ; Conceptualization (Equal), Data curation (Supporting), Formal analysis (Supporting), Funding acquisition (Supporting), Investigation (Supporting), Methodology (Equal), Project administration (Supporting), Resources (Supporting), Software (Equal), Supervision (Lead), Validation (Supporting), Visualization (Supporting), Writing – original draft (Supporting), Writing – review & editing (Supporting). This study was conducted in the otolaryngology and medical biochemistry departments at Erzurum Atatürk University Faculty of Medicine (Turkey). Conflict of Interest: No conflict of interest was declared by the authors. Funding: The authors did not receive support from any organization for the submitted work. References Kampa M, Castanas E. Human health effects of air pollution. Environ. Pollut . 2008; 151: 362-367. Hankey S, Marshall JD. Urban form, air pollution, and health. Curr Environ Health Rep. 2017;4: 491-503. GBD 2013 Risk Factors Collaborators, Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet . 2015; 386; 2287-2323. Öner Ü, Özdemir Ş, Öner F , Akdeniz N. Do heavy metals accumulated in saliva involve in the etiopathogenesis of recurrent aphthous stomatitis? Biol Trace Elem Res. 2020; 198: 46-50. Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ. Heavy metal toxicity and the environment. Exp Suppl. 2012: 101; 133-164. Bowler RM, Roels HA, Nakagawa S, et al. Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders. Occup Environ Med. 2007;64: 167-177. Calderón-Garcidueñas L, Rodriguez-Alcaraz A, Garcia R, Barragan G, Villarreal-Calderón A, Madden MC. Cell proliferation in nasal respiratory epithelium of people exposed to urban pollution, Carcinogenesis . 1999;20: 383-389. Gasparik J, Dobias M, Capcarov M, et al. Concentration of cadmium, mercury, zinc, copper and cobalt in the tissues of wild boar (Sus scrofa) hunted in the western Slovakia. J Environ Sci Health A Tox Hazard Subst Environ Eng . 2012; 47: 1212-1216. Glück U, Gebbers JO. The comet assay of nasal epithelia: measurement of DNA damage for the assessment of genotoxic air pollution. Laryngoscope. 2000; 110: 123-125. Şenvar A. Investigation of zinc and copper levels in patients with atrophic rhinitis. J Exp Clin Med. 1982; 2: 107-115. Krmpotíc-Nemaníc J, Valkovíc V, Jaksíc M, Tomíc S, Nemaníc G. Konzentration der Spurenelemente in der unteren Nasenmuschel und im Septum des Menschen [Concentration of trace elements in the inferior turbinates and in the nasal septum of the human]. Laryngol Rhinol Otol (Stuttg). 1987; 66: 622-624. Calderon-Garcidueñas L, Rodriguez-Alcaraz A, Garcia R, et al. Human nasal mucosal changes after exposure to urban pollution. Environ Health Perspect. 1994; 102: 1074-1080. Calderón-Garcidueñas L, Rodriguez-Alcaraz A, Valencia-Salazar G, et al. Nasal biopsies of children exposed to air pollutants. Toxicol Pathol. 2001; 29: 558-564. Holt GR. Effects of air pollution on the upper aerodigestive tract. Otolaryngol Head Neck Surg . 1996; 114: 201-204. Tobías A, Rivas I, Reche C, et al. Short-term effects of ultrafine particles on daily mortality by primary vehicle exhaust versus secondary origin in three Spanish cities. Environ Int. 2018; 111: 144-151. Pey J, Querol X, Alastuey A, Rodríguez S, Putaud JP, Dingenen RV. Source apportionment of urban fine and ultra-fine particle number concentration in a Western Mediterranean city. Atmos Environ . 2009; 43: 4407-4415. Kanninen KM, Lampinen R, Rantanen LM, et al. Olfactory cell cultures to investigate health effects of air pollution exposure: Implications for neurodegeneration. Neurochem Int. 2020; 136: 104729. Glück U, Schütz R, Gebbers JO. Cytopathology of the nasal mucosa in chronic exposure to diesel engine emission: a five-year survey of Swiss customs officers. Environ Health Perspect . 2003; 111: 925-929. Cao Y, Skaug MA, Andersen O, Aaseth J. Chelation therapy in intoxications with mercury, lead and copper. J Trace Elem Med Biol . 2015; 31: 188-192. Karataglis S. Estimation of the toxicity of different metals, using as criterion the degree of root elongation in Triticum aestivum seedlings. Phyton. 1987; 26: 209-217. Yilmaz S, Zengin M. Monitoring environmental pollution in Erzurum by chemical analysis of Scots pine (Pinus sylvestris L.) needles. Environ Int. 2004; 29: 1041-1047. Suchodoller A. Untersuchungen uber den bleigehatt von pflanzen in der nane von strassen und uber die aufnahme and translokation von blei durch pflazen. Berichteder Schweizerischen Botanischen Gesellschaft. 1967; 77: 266-308. Yousaf M, Mandiwana KL, Baig KS, Lu J. Evaluation of acer rubrum tree bark as a bioindicator of atmospheric heavy metal pollution in Toronto, Canada. Water Air Soil Pollut . 2020; 231: 1-9. Carson JL, Brighton LE, Collier AM, Bromberg PA. Correlative ultrastructural investigations of airway epithelium following experimental exposure to defined air pollutants and lifestyle exposure to tobacco smoke. Inhal Toxicol . 2013; 25: 134-140. Afridi HI, Kazi TG, Kazi AG, et al. Levels of arsenic, cadmium, lead, manganese and zinc in biological samples of paralysed steel mill workers with related to controls. Biol Trace Elem Res . 2011; 144: 164-182. Breeher L, Gerr F, Fuortes L. A case report of adult lead toxicity following use of Ayurvedic herbal medication. J Occup Med Toxicol 2013; 8: 26. Atila NE, Atila A, Kaya Z, et al. The Role of manganese, cadmium, chromium and selenium on subjective tinnitus. Biol Trace Elem Res . 2021; 199: 2844-2850. Tables Table 1. Comparison of all patient groups by gender Patients Male Female Total p* Urban 26 (68.4%) 12 (31.6%) 38 0.991 Rural 17 (58.6%) 12 (41.4%) 29 0.991 Student’s t-test Table 2. Heavy metal levels of concha tissues Metals Rural* Urban* t p** Cd 0.034±0.014 0.032±0.013 0.67 0.505 Pb 0.008±0.0002 0.024±0.009 -8.55 <0.001 Cu 0.24±0.048 0.06±0.019 19.25 <0.001 Mn 0.174±0.05 0.273±0.01 17.45 <0,001 Zn 3.29±0.69 0.44±0.14 24.19 <0.001 *Mean ± standard deviation, ** Student’s t-test Table 3. The relationship between age and heavy metals levels Age Cd Pb Cu Mn Zn r -0,14 -0,05 -0,02 0,01 0,01 p* 0,26 0,67 0,87 0,99 0,97 *Pearson Correlation Test Additional Declarations No competing interests reported. Supplementary Files reportgrammarediting.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3982677","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":275177798,"identity":"26d32702-c63c-40b8-ae5a-eb3f6b29bd71","order_by":0,"name":"Fatih Öner","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYBAC9gYGhsMIbgUQMzM34NXCc4AZScuBMyAtjIS1MMN5B9tAJCEt7OcPHi6ouCNn3sB87PHHebXR/O1ALT8qtuHWwpPMcHjGmWfGMgfY0g0ObjueO+MwYwNjz5nbOLXYMwC18LYdTpzBwGMmcXDbsdwGoBZmxjbcWnj4H4O11M9g4P8mcXDOsdz5BLVIQGxJkGDgYZM42FCTu4GwlscGh3nOHDacwcxmJnHm2IHcjUAtB/H5hYc/8fFnnorD8hLszc8kKmrqcuedP3zwwY8K3FoQABI7kGg9QIR6OKgjRfEoGAWjYBSMEAAALztaQPJIJrMAAAAASUVORK5CYII=","orcid":"","institution":"Kastamonu University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Fatih","middleName":"","lastName":"Öner","suffix":""},{"id":275177799,"identity":"228edb39-de37-4d6d-8ddd-6c0faef5378b","order_by":1,"name":"Nezahat Kurt","email":"","orcid":"","institution":"Erzincan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nezahat","middleName":"","lastName":"Kurt","suffix":""},{"id":275177800,"identity":"e30f8106-5146-4fa6-9a85-7f563dad09b7","order_by":2,"name":"Harun Üçüncü","email":"","orcid":"","institution":"Muğla University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Harun","middleName":"","lastName":"Üçüncü","suffix":""}],"badges":[],"createdAt":"2024-02-23 17:39:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3982677/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3982677/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51821042,"identity":"7c877862-1539-45cf-b75e-dc9416aa4daf","added_by":"auto","created_at":"2024-02-29 16:08:09","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":120252,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical Abstract of the Study\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3982677/v1/c4626f9e61529a73c1de9aca.jpg"},{"id":51821041,"identity":"df704dd2-849d-46c2-8530-a6e726fe9a60","added_by":"auto","created_at":"2024-02-29 16:08:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":57915,"visible":true,"origin":"","legend":"\u003cp\u003eLevels of Heavy Metals in Nasal Concha\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-3982677/v1/e17d1a6d55c2417b8318e5ca.jpg"},{"id":52089909,"identity":"2e0fc850-e7fa-42fc-aa87-435b1a3c65ea","added_by":"auto","created_at":"2024-03-06 13:46:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":388197,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3982677/v1/e3fc3d82-910e-4184-8bff-d00735a233f2.pdf"},{"id":51821045,"identity":"e425b3f2-3321-44c5-a975-479c991417ef","added_by":"auto","created_at":"2024-02-29 16:08:09","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":179150,"visible":true,"origin":"","legend":"","description":"","filename":"reportgrammarediting.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3982677/v1/0912b1f861105d039a60aac6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Levels of Heavy Metals in Nasal Concha Tissues in Rural and Urban Regions","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eEnvironmental pollution is a severe problem in industrialized and metropolitan cities, threatening public health \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Each year, 4.2\u0026nbsp;million people die earlier from heart and respiratory diseases triggered by air pollutants (World Health Organization- 2008) \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Pollutants that cause the problem and disturb the natural balance include organic substances, industrial wastes, petroleum derivatives, synthetic agricultural fertilizers, detergents, radiation, pesticides, inorganic salts, synthetic organic chemicals, and waste heat. All of these, directly and indirectly, cause air pollution. Heavy metals are found in almost all of them, mostly in industrial wastes and pesticides.\u003c/p\u003e \u003cp\u003eElements are present in the human body in pure form or compounded form. Although some elements are essential for human physiology, some of them are toxic, such as lead (Pb), mercury (Hg), and cadmium (Cd). Generally, intoxication occurs through accumulation as a result of prolonged exposure. Heavy metals cause the dysfunction of enzyme systems by binding oxygen, nitrogen, and sulfhydryl groups to proteins, revealing their toxic effects\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. For instance, metalloproteins in the organism contain large amounts of thiol ligands. These ligands have a high affinity for binding elements such as Cd, copper (Cu), and zinc (Zn). Factors such as heavy metal particle size, duration of heavy metal exposure, and age of individuals determine the degree of heavy metal intoxication \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe nose is the main entrance gate of polluted air to the body\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Many heavy metals can enter the body through inhaled air. Detection of heavy metal presence in nasal concha tissues may mean that heavy metals in ambient air cause accumulation in nasal mucosal and submucosal tissues by inhalation. Due to the mucociliary activity of the nasal mucous membranes, inhalation and absorption of pollutants can weaken local immune responses in the airways. This study was conducted to compare levels of heavy metals in nasal conchal tissues of patients from urban and rural areas.\u003c/p\u003e"},{"header":"MATERIALS and METHODS","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003ePatients and Study Design\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSixty-seven patients (24 females, 43 males) were administered to the Otorhinolaryngology outpatient clinic with nasal obstruction. Most of the selected patients had compensatory nasal concha hypertrophy accompanying nasal septum deviation, and partial resection of the inferior concha was scheduled. The patients were divided into rural (n = 29) and urban (n = 38) groups according to their living areas of at least 15 years after verbal and written informed consent.\u003c/p\u003e\n\u003cp\u003ePatients with diseases that could affect the presence of heavy metals in the nasal concha were excluded. The exclusion criteria were as follow:\u003c/p\u003e\n\u003cp\u003e- Smokers/ex-smokers,\u003c/p\u003e\n\u003cp\u003e- Patients under the age of 18 and over 55,\u003c/p\u003e\n\u003cp\u003e- Patients with nasal polyps or polyposis,\u003c/p\u003e\n\u003cp\u003e- Patients with allergic rhinitis,\u003c/p\u003e\n\u003cp\u003e- Patients with nasal involvement of systemic diseases,\u003c/p\u003e\n\u003cp\u003e- Patients using medication continuously,\u003c/p\u003e\n\u003cp\u003e- Patients who had undergone any previous surgical intervention (septoplasty, concha radiofrequency ablation, partial resection) in the nasal cavity,\u003c/p\u003e\n\u003cp\u003e- Patients working in the industry sector.\u003c/p\u003e\n\u003cp\u003ePartial resection of the inferior concha with septoplasty was performed in 58 patients, and only partial resection of the inferior concha was performed in nine patients. Bilateral inferior concha partial resection was performed in 60 patients, while unilateral resection was performed in seven patients.\u003c/p\u003e\n\u003cp\u003eAll patients were operated on under general anesthesia by the same surgeon, and a standard procedure was performed. No local anesthetic was applied to the concha tissue before resection. The inferior turbinates were first medialized with the Cottle elevator, and then the lower-medial parts were cut using concha scissors. We washed the resected turbinate pieces with distilled water, removed the mucus, and attached particles mechanically. The tissues taken were transferred to the sterile tubes without contact anywhere and stored at -80 ͦ\u003csup\u003e\u0026nbsp;\u003c/sup\u003eC (\u003cstrong\u003eFig. 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eMeasurements of Metal Concentrations\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNasal concha tissues were let to thaw at room temperature. First, conchal bones, if any, were dissected and removed. From the deboned mucosa and submucosal parenchyma tissue, fragments weighing 0.5 g were transferred into a tube and added with 3 ml of acid mixture (HClO4 + HNO3, 5: 1). The samples were incubated at 95\u003csup\u003eo\u003c/sup\u003eC for one hour \u003csup\u003e8\u003c/sup\u003e. Solid conchal tissues were hydrolyzed with acid and became liquid at the end of three hours. Solutions were diluted with distilled water to measure heavy metals (Cu, Zn, Cd, Pb, and Mn) spectrophotometrically using the Inductively Coupled Plasma- Optical Emission Spectrometry (Perkin-Elmer, Optima 4300 DV, ICP / OES, Waltham, MA).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAfter confirmation of the normal distribution of the data in the Kolmogorov Smirnow Test, Student T-Test was used in the comparisons of patient age and Cd, Pb, Cu, Mn, and Zn levels by the patient group (SPSS, version 22, Chicago, IL). Data are presented as a number, percentage, median, mean, and standard deviation. Mann-Whitney U Test was used to analyze age by gender, Cd, Pb, Cu, Mn, and Zn in both groups. Significance was considered at p \u0026lt; 0.05.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthics\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the XXXX University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee (Decision no: XXXXX).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThere was no difference in the mean age (p\u0026thinsp;=\u0026thinsp;0.991; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and gender distribution between the groups (p\u0026thinsp;=\u0026thinsp;0.991; Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The age distribution of the rural group was 18\u0026ndash;52 (29.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4), and the urban group was 18\u0026ndash;55 (29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8). There were 17 males (58.6%) and 12 females (41.4%) in the urban group, 26 males (68.4%) and 12 females (31.2%) in the rural group.\u003c/p\u003e \u003cp\u003eCu (0.24\u0026thinsp;\u0026plusmn;\u0026thinsp;0.048 \u0026micro;g/g) and Zn (3.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69 \u0026micro;g/g) levels of rural patients were significantly higher than Cu (0.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.019 \u0026micro;g/g) and Zn (0.44\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14 \u0026micro;g/g) levels of urban patients (\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The Cd (0.034\u0026thinsp;\u0026plusmn;\u0026thinsp;0.014 \u0026micro;g/g) level of the rural patients was similar to the Cd level (0.032\u0026thinsp;\u0026plusmn;\u0026thinsp;0.013 \u0026micro;g/g) of the urban patients (p\u0026thinsp;=\u0026thinsp;0.505, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Pb (0.024\u0026thinsp;\u0026plusmn;\u0026thinsp;0.009 \u0026micro;g/g) and Mn (0.273\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01 \u0026micro;g/g) levels of the urban group were significantly higher than Pb (0.008\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0002 \u0026micro;g/g) and Mn (0.174\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05 \u0026micro;g/g) levels of the rural group (\u003cb\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001\u003c/b\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHeavy metal levels in rural and urban patients were independent of age and gender. When the two groups were compared, we detected that the difference between the heavy metal levels occurred due to the residence difference (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAir pollution is considered a general health hazard. Technologies that facilitate our current world release various pollutants into the atmosphere. Technological products increase the concentration of air pollutants in the atmosphere, containing heavy metals harmful to plants, animals, and humans. When specific risk factors such as genetics, diet, and lifestyle come together with environmental factors, the negative impact of air pollution on human health is likely to increase \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. For the individual risk assessment of environmental hazards, showing the physical presence of the substances in the body or the negative functional results is essential. The nasal cavity is a usual gateway to the human body for air pollutants and is a well-known target site for toxicity caused by air pollutants \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. This study reported compassion of levels of heavy metals in nasal conchal tissues in patients living in rural and urban areas.\u003c/p\u003e \u003cp\u003eFew studies examine the relationship between nasal mucous membranes, air pollution, and heavy metals. Şenvar \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e compared serum Cu and Zn levels in the patients with atrophic rhinitis and healthy people and reported higher serum Cu levels and lower serum Zn levels in the patient group. A study compared\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e trace elements on the nasal lower concha and nasal septum. There was an age-related increase in Pb levels in both tissues and decreased Zn levels. In another study\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e, exposure to urban pollution in adults in Mexico has been shown to increase the proliferation rate in nasal cells, a risk factor for developing neoplasia.\u003c/p\u003e \u003cp\u003eCalderon- Garciduenas et al.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e found significant differences in biopsies from nasal mucosa of children exposed to outdoor pollutants compared with a healthy control group. Children exposed to polluted air had more complaints about upper airways, such as epistaxis, nasal congestion, dryness, and crusting. As expected in ENT examinations, abnormal nasal mucosal findings such as increased hyperemia and bleeding points in the nasal mucosa, purulent mucus, and sinusitis were observed. The authors reported basal cell hyperplasia, a decrease in ciliary epithelial cell and goblet cell count, submucosal neutrophil infiltration, squamous metaplasia, and dysplasia histopathological analysis of nasal mucosa biopsies of children exposed to air pollutants.\u003c/p\u003e \u003cp\u003eIn general, very few air pollutants are found in rural regions. If the agricultural industry is developed, particulate matter in airborne pesticides and fertilizers can be considered air pollutants in the rural area\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. Unlike rural areas, metropolitans are focal points of air pollution due to motor vehicles, industrial facilities, and factories. In urban regions where the population is much more crowded, the primary source of air pollutant particles is traffic density and exhaust gases from diesel and gasoline engines\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. Main outdoor air pollutants include carbon monoxide, sulfur dioxide, ozone, nitrogen dioxide, and lead \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e. The polluted air in the city also contains ultrafine particles in high concentrations, and their effect on human health is not fully known \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGl\u0026uuml;ck et al. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e examined the cytopathological of the nasal mucosa of individuals chronically exposed to diesel engine emissions. They detected goblet cell hyperplasia in the nasal mucosa and inflammatory response caused by increased leukocytes and defined this condition as chemical-induced rhinitis.\u003c/p\u003e \u003cp\u003eThe major heavy metal in polluted air is Pb \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. In air pollution caused by exhaust gas, heavy metals enter the body mainly by inhalation \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. Yılmaz et al. \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e investigated heavy metal levels in the leaves of trees in the city center and countryside. The amount of Pb in the samples of the city center was significantly higher than in rural areas, and they associated these higher Pb levels with exhaust gas and air pollution. In another study \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e, Suchodoller found that the amount of Pb accumulated in the barley and corn planted next to the road was high. They reported that the amount of Pb in the plants decreased as they moved away from the road, and the effect of traffic was not noticed 30\u0026ndash;40 m away from the road. Similarly, in our study, Pb levels in the tissues of rural patients were significantly higher than in rural patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eYoussaf et al. \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e measured tree barks as a bioindicator to assess air pollution in downtown Toronto and reported high levels of Pb and Mn in trees on the roadside with heavy traffic. Our study also found that the urban group's Mn and Pb levels were significantly higher.\u003c/p\u003e \u003cp\u003ePeople are not only exposed to polluted air outdoors. The best-known effect is cigarette smoke, the air pollutant inside. In an experimental study \u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e, significant changes were observed in the nasal mucosa of animals exposed to tobacco smoke. Disruptions in intercellular tight junction complexes, significant structural changes in cell membranes, and increased infiltration of neutrophils on the nasal mucosa surface had been demonstrated in exposed animals. Cigarette smoke or occupationally exposed smoke is inhaled directly into the body along with the heavy metals it contains and causes the levels of heavy metals in the blood to rise \u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. In the present study, patients who were smokers and ex-smokers were excluded.\u003c/p\u003e \u003cp\u003eHeavy metals inhaled with polluted air cause accumulation in the human body. Heavy metals trigger oxidative stress in the organism, increase reactive oxygen species, lipid peroxidation, and inflammatory cytokines, and exhibit harmful effects \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Oxidative stress plays a role in the etiopathogenesis of many diseases. It is a challenge to show the harmful effects of exposure to air pollution on human health with evidence. It is necessary to present the pollutant at the same time above the acceptable concentration in ambient air and human tissue, which is a challenging application in the normal population.\u003c/p\u003e \u003cp\u003eOne limitation of our study is that we only measured five heavy metals. Due to technical limitations, the restricted size of this number can serve as a valuable reference for future investigations into the wide variety of heavy metal alterations. Furthermore, the absence of simultaneous measurements of heavy metal levels in the blood samples of the patients, as well as the absence of indicators indicating the presence of heavy metal air pollution in the urban and rural areas where the patients reside, can be considered. Another aspect of the study that requires improvement is the inability to consider passive smoking status despite the exclusion of active smokers and ex-smokers.\u003c/p\u003e \u003cp\u003eWhen we attribute the cause of a condition to air pollution but the underlying mechanisms are not yet completely understood, showing the presence of heavy metals in the nasal mucosa can be beneficial. In clinical scenarios where there is evidence of heavy metal accumulation and a clear link to diseases, we can mitigate the occurrence of the diseases by implementing preventive measures in urban areas.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Committee Approval:\u003c/strong\u003e This study was found to proper with ethical rules by the Atat\u0026uuml;rk University Faculty of Medicine Non-Interventional Clinical Research Ethics Committee (Decision No: B.30.2.ATA.0.01.00 / 56).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent:\u003c/strong\u003e The consent of all patients was obtained for the original data collection.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Sharing Statement:\u003c/strong\u003e The data that support the findings of this study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthorship Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFatih \u0026Ouml;ner,Md\u003c/strong\u003e; Conceptualization (Equal), Data curation (Lead), Formal analysis (Equal), Funding acquisition (Equal), Investigation (Lead), Methodology (Lead), Project administration (Equal), Resources (Lead), Software (Lead), Supervision (Supporting), Validation (Lead), Writing \u0026ndash; original draft (Lead), Writing \u0026ndash; review \u0026amp; editing (Lead).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNezahat Kurt, PhD\u003c/strong\u003e; Conceptualization (Equal), Data curation (Supporting), Formal analysis (Equal), Funding acquisition (Supporting), Investigation (Supporting), Methodology (Supporting), Project administration (Equal), Resources (Supporting), Software (Supporting), Supervision (Supporting), Validation (Supporting), Visualization (Supporting), Writing \u0026ndash; original draft (Supporting), Writing \u0026ndash; review \u0026amp; editing (Supporting)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHarun \u0026Uuml;\u0026ccedil;\u0026uuml;nc\u0026uuml;, Md\u003c/strong\u003e; Conceptualization (Equal), Data curation (Supporting), Formal analysis (Supporting), Funding acquisition (Supporting), Investigation (Supporting), Methodology (Equal), Project administration (Supporting), Resources (Supporting), Software (Equal), Supervision (Lead), Validation (Supporting), Visualization (Supporting), Writing \u0026ndash; original draft (Supporting), Writing \u0026ndash; review \u0026amp; editing (Supporting).\u003c/p\u003e\n\u003cp\u003eThis study was conducted in the otolaryngology and medical biochemistry departments at Erzurum Atat\u0026uuml;rk University Faculty of Medicine (Turkey).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e No conflict of interest was declared by the authors.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors did not receive support from any organization for the submitted work.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKampa M, Castanas E. 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J Exp Clin Med. 1982; 2: 107-115. \u003c/li\u003e\n\u003cli\u003eKrmpot\u0026iacute;c-Neman\u0026iacute;c J, Valkov\u0026iacute;c V, Jaks\u0026iacute;c M, Tom\u0026iacute;c S, Neman\u0026iacute;c G. Konzentration der Spurenelemente in der unteren Nasenmuschel und im Septum des Menschen [Concentration of trace elements in the inferior turbinates and in the nasal septum of the human]. \u003cem\u003eLaryngol Rhinol Otol (Stuttg).\u003c/em\u003e 1987; 66: 622-624. \u003c/li\u003e\n\u003cli\u003eCalderon-Garcidue\u0026ntilde;as L, Rodriguez-Alcaraz A, Garcia R, et al. Human nasal mucosal changes after exposure to urban pollution. \u003cem\u003eEnviron Health Perspect.\u003c/em\u003e 1994; 102: 1074-1080.\u003c/li\u003e\n\u003cli\u003eCalder\u0026oacute;n-Garcidue\u0026ntilde;as L, Rodriguez-Alcaraz A, Valencia-Salazar G, et al. Nasal biopsies of children exposed to air pollutants. \u003cem\u003eToxicol Pathol.\u003c/em\u003e 2001; 29: 558-564. \u003c/li\u003e\n\u003cli\u003eHolt GR. Effects of air pollution on the upper aerodigestive tract. \u003cem\u003eOtolaryngol Head Neck Surg\u003c/em\u003e. 1996; 114: 201-204. \u003c/li\u003e\n\u003cli\u003eTob\u0026iacute;as A, Rivas I, Reche C, et al. Short-term effects of ultrafine particles on daily mortality by primary vehicle exhaust versus secondary origin in three Spanish cities. \u003cem\u003eEnviron Int.\u003c/em\u003e 2018; 111: 144-151. \u003c/li\u003e\n\u003cli\u003ePey J, Querol X, Alastuey A, Rodr\u0026iacute;guez S, Putaud JP, Dingenen RV. Source apportionment of urban fine and ultra-fine particle number concentration in a Western Mediterranean city. \u003cem\u003eAtmos Environ\u003c/em\u003e. 2009; 43: 4407-4415. \u003c/li\u003e\n\u003cli\u003eKanninen KM, Lampinen R, Rantanen LM, et al. Olfactory cell cultures to investigate health effects of air pollution exposure: Implications for neurodegeneration. \u003cem\u003eNeurochem Int.\u003c/em\u003e 2020; 136: 104729.\u003c/li\u003e\n\u003cli\u003eGl\u0026uuml;ck U, Sch\u0026uuml;tz R, Gebbers JO. Cytopathology of the nasal mucosa in chronic exposure to diesel engine emission: a five-year survey of Swiss customs officers. \u003cem\u003eEnviron Health Perspect\u003c/em\u003e. 2003; 111: 925-929. \u003c/li\u003e\n\u003cli\u003eCao Y, Skaug MA, Andersen O, Aaseth J. Chelation therapy in intoxications with mercury, lead and copper. \u003cem\u003eJ Trace Elem Med Biol\u003c/em\u003e. 2015; 31: 188-192. \u003c/li\u003e\n\u003cli\u003eKarataglis S. Estimation of the toxicity of different metals, using as criterion the degree of root elongation in Triticum aestivum seedlings. \u003cem\u003ePhyton.\u003c/em\u003e 1987; 26: 209-217.\u003c/li\u003e\n\u003cli\u003eYilmaz S, Zengin M. Monitoring environmental pollution in Erzurum by chemical analysis of Scots pine (Pinus sylvestris L.) needles. \u003cem\u003eEnviron Int.\u003c/em\u003e 2004; 29: 1041-1047.\u003c/li\u003e\n\u003cli\u003eSuchodoller A. Untersuchungen uber den bleigehatt von pflanzen in der nane von strassen und uber die aufnahme and translokation von blei durch pflazen. \u003cem\u003eBerichteder Schweizerischen Botanischen Gesellschaft.\u003c/em\u003e 1967; 77: 266-308. \u003c/li\u003e\n\u003cli\u003eYousaf M, Mandiwana KL, Baig KS, Lu J. Evaluation of acer rubrum tree bark as a bioindicator of atmospheric heavy metal pollution in Toronto, Canada. \u003cem\u003eWater Air Soil Pollut\u003c/em\u003e. 2020; 231: 1-9. \u003c/li\u003e\n\u003cli\u003eCarson JL, Brighton LE, Collier AM, Bromberg PA. Correlative ultrastructural investigations of airway epithelium following experimental exposure to defined air pollutants and lifestyle exposure to tobacco smoke. \u003cem\u003eInhal Toxicol\u003c/em\u003e. 2013; 25: 134-140. \u003c/li\u003e\n\u003cli\u003eAfridi HI, Kazi TG, Kazi AG, et al. Levels of arsenic, cadmium, lead, manganese and zinc in biological samples of paralysed steel mill workers with related to controls. \u003cem\u003eBiol Trace Elem Res\u003c/em\u003e. 2011; 144: 164-182. \u003c/li\u003e\n\u003cli\u003eBreeher L, Gerr F, Fuortes L. A case report of adult lead toxicity following use of Ayurvedic herbal medication. \u003cem\u003eJ Occup Med Toxicol\u003c/em\u003e 2013; 8: 26. \u003c/li\u003e\n\u003cli\u003eAtila NE, Atila A, Kaya Z, et al. The Role of manganese, cadmium, chromium and selenium on subjective tinnitus. \u003cem\u003eBiol Trace Elem Res\u003c/em\u003e. 2021; 199: 2844-2850.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eComparison of all patient groups by gender\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatients\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMale\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ep*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003eUrban\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e26 (68.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e12 (31.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.991\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003eRural\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e17 (58.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e12 (41.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e0.991\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eStudent\u0026rsquo;s t-test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eHeavy metal levels of concha tissues\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.254859611231101%\" valign=\"top\"\u003e\n \u003cp\u003eMetals\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.4622030237581%\" valign=\"top\"\u003e\n \u003cp\u003eRural*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.509719222462202%\" valign=\"top\"\u003e\n \u003cp\u003eUrban*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.3585313174946%\" valign=\"top\"\u003e\n \u003cp\u003et\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.414686825053995%\" valign=\"top\"\u003e\n \u003cp\u003ep**\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.254859611231101%\" valign=\"top\"\u003e\n \u003cp\u003eCd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.4622030237581%\" valign=\"top\"\u003e\n \u003cp\u003e0.034\u0026plusmn;0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.509719222462202%\" valign=\"top\"\u003e\n \u003cp\u003e0.032\u0026plusmn;0.013\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.3585313174946%\" valign=\"top\"\u003e\n \u003cp\u003e0.67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.414686825053995%\" valign=\"top\"\u003e\n \u003cp\u003e0.505\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.254859611231101%\" valign=\"top\"\u003e\n \u003cp\u003ePb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.4622030237581%\" valign=\"top\"\u003e\n \u003cp\u003e0.008\u0026plusmn;0.0002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.509719222462202%\" valign=\"top\"\u003e\n \u003cp\u003e0.024\u0026plusmn;0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.3585313174946%\" valign=\"top\"\u003e\n \u003cp\u003e-8.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.414686825053995%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.254859611231101%\" valign=\"top\"\u003e\n \u003cp\u003eCu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.4622030237581%\" valign=\"top\"\u003e\n \u003cp\u003e0.24\u0026plusmn;0.048\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.509719222462202%\" valign=\"top\"\u003e\n \u003cp\u003e0.06\u0026plusmn;0.019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.3585313174946%\" valign=\"top\"\u003e\n \u003cp\u003e19.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.414686825053995%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.254859611231101%\" valign=\"top\"\u003e\n \u003cp\u003eMn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.4622030237581%\" valign=\"top\"\u003e\n \u003cp\u003e0.174\u0026plusmn;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.509719222462202%\" valign=\"top\"\u003e\n \u003cp\u003e0.273\u0026plusmn;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.3585313174946%\" valign=\"top\"\u003e\n \u003cp\u003e17.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.414686825053995%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.254859611231101%\" valign=\"top\"\u003e\n \u003cp\u003eZn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.4622030237581%\" valign=\"top\"\u003e\n \u003cp\u003e3.29\u0026plusmn;0.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"28.509719222462202%\" valign=\"top\"\u003e\n \u003cp\u003e0.44\u0026plusmn;0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.3585313174946%\" valign=\"top\"\u003e\n \u003cp\u003e24.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.414686825053995%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Mean \u0026plusmn; standard deviation, ** Student\u0026rsquo;s t-test\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eThe relationship between age and heavy metals levels\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"445\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.078651685393258%\" valign=\"bottom\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.078651685393258%\" valign=\"bottom\"\u003e\n \u003cp\u003eCd\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\" valign=\"bottom\"\u003e\n \u003cp\u003ePb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\" valign=\"bottom\"\u003e\n \u003cp\u003eCu\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\" valign=\"bottom\"\u003e\n \u003cp\u003eMn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.348314606741575%\" valign=\"bottom\"\u003e\n \u003cp\u003eZn\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.078651685393258%\"\u003e\n \u003cp\u003er\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.078651685393258%\"\u003e\n \u003cp\u003e-0,14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\"\u003e\n \u003cp\u003e-0,05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\"\u003e\n \u003cp\u003e-0,02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\"\u003e\n \u003cp\u003e0,01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.348314606741575%\"\u003e\n \u003cp\u003e0,01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"17.078651685393258%\"\u003e\n \u003cp\u003ep*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.078651685393258%\"\u003e\n \u003cp\u003e0,26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\"\u003e\n \u003cp\u003e0,67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\"\u003e\n \u003cp\u003e0,87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.831460674157304%\"\u003e\n \u003cp\u003e0,99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.348314606741575%\"\u003e\n \u003cp\u003e0,97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e*Pearson Correlation Test\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Air Pollution, Heavy metals, Nasal Mucosa, Spectrophotometry, Turbinates","lastPublishedDoi":"10.21203/rs.3.rs-3982677/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3982677/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eHeavy metal exposure has recently become a problem due to the increasing environmental pollution as urbanization expands.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThis prospective case control study was conducted to compare levels of heavy metals in the nasal concha of the patients living in urban and rural who underwent partial inferior concha resection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eSixty-seven patients were divided into two groups: 38 rural patients and 29 urban patients. Lead (Pb), cadmium (Cd), mercury (Hg), copper (Cu), and manganese (Mn) levels were measured in inferior nasal concha by Inductively Coupled Plasma- Optical Emission Spectrometry.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eSignificance was considered at p \u0026lt; 0.05. The levels of Cu (0.24± 0.048 vs. 0.06± 0.019 µg/g) and Zn (3.29± 0.69 vs. 0.44± 0.14µg/g) of the rural patients were significantly higher compared to urban patients (\u003cem\u003e\u003cstrong\u003ep\u0026lt;0.001\u003c/strong\u003e\u003c/em\u003e). There was no significant difference in the Cd level between groups. Pb (0.024± 0.009 vs. 0.008± 0.0002 µg/g) and Mn (0.273± 0.01 vs. 0.174± 0.05 µg/g) levels of urban patients were significantly higher than rural patients (\u003cem\u003e\u003cstrong\u003ep\u0026lt;0.001\u003c/strong\u003e\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eHeavy metals accumulate in the nasal concha at different rates in rural and urban areas. Indicating the presence of heavy metals in turbinates and measuring their amount may be helpful for diagnostic purposes in diseases whose etiology is attributed to air pollution; however, the pathophysiology still needs to be clarified.\u003c/p\u003e","manuscriptTitle":"Comparison of Levels of Heavy Metals in Nasal Concha Tissues in Rural and Urban Regions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-29 16:08:04","doi":"10.21203/rs.3.rs-3982677/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c506f19c-08b4-412d-8a3f-5976ec03d57a","owner":[],"postedDate":"February 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-06T13:38:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-29 16:08:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3982677","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3982677","identity":"rs-3982677","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}