A multi-environmental source approach to explore associations between metals exposure and olfactory identification among school-age children residing in northern Italy.

BACKGROUND: Metal exposures can adversely impact olfactory function. Few studies have examined this association in children. Further, metal exposure occurs as a mixture, yet previous studies of metal-associated olfactory dysfunction only examined individual metals. Preventing olfactory dysfunctions can improve quality of life and prevent neurodegenerative diseases with long-term health implications. OBJECTIVE: We aimed to test the association between exposure to a mixture of 12 metals measured in environmental sources and olfactory function among children and adolescents residing in the industrialized province of Brescia, Italy. METHODS: We enrolled 130 children between 6 and 13 years old (51.5% females) and used the "Sniffin' Sticks" test to measure olfactory performance in identifying smells. We used a portable X-ray fluorescence instrument to determine concentrations of metals (arsenic (As), calcium, cadmium (Cd), chromium, copper, iron, manganese, lead (Pb), antimony, titanium, vanadium and zinc) in outdoor and indoor deposited dust and soil samples collected from participants' households. We used an extension of weighted quantile sum (WQS) regression to test the association between exposure to metal mixtures in multiple environmental media and olfactory function adjusting for age, sex, socio-economic status, intelligence quotient and parents' smoking status. RESULTS: A higher multi-source mixture was significantly associated with a reduced Sniffin' Sticks identification score (ß = -0.228; 95% CI -0.433, -0.020). Indoor dust concentrations of Pb, Cd and As provided the strongest contributions to this association (13.8%, 13.3% and 10.1%, respectively). The metal mixture in indoor dust contributed more (for 8 metals out of 12) to the association between metals and olfactory function compared to soil or outdoor dust. IMPACT STATEMENT: Among a mixture of 12 metals measured in three different environmental sources (soil, outdoor and indoor dust), we identified Pb, Cd and As measured in indoor dust as the main contributors to reduced olfactory function in children and adolescents residing in an industrialized area. Exposure to indoor pollution can be effectively reduced through individual and public health interventions allowing to prevent the deterioration of olfactory functions. Moreover, the identification of the factors that can deteriorate olfactory functions can be a helpful instrument to improve quality of life and prevent neurodegenerative diseases as long-term health implications.

Characterization of pathological changes in the olfactory system of mice exposed to methylmercury.

Methylmercury (MeHg) is a well-known environmental neurotoxicant that causes severe brain disorders such as Minamata disease. Although some patients with Minamata disease develop olfactory dysfunction, the underlying pathomechanism is largely unknown. We examined the effects of MeHg on the olfactory system using a model of MeHg poisoning in which mice were administered 30 ppm MeHg in drinking water for 8 weeks. Mice exposed to MeHg displayed significant mercury accumulation in the olfactory pathway, including the nasal mucosa, olfactory bulb, and olfactory cortex. The olfactory epithelium was partially atrophied, and olfactory sensory neurons were diminished. The olfactory bulb exhibited an increase in apoptotic cells, hypertrophic astrocytes, and amoeboid microglia, mainly in the granular cell layer. Neuronal cell death was observed in the olfactory cortex, particularly in the ventral tenia tecta. Neuronal cell death was also remarkable in higher-order areas such as the orbitofrontal cortex. Correlation analysis showed that neuronal loss in the olfactory cortex was strongly correlated with the plasma mercury concentration. Our results indicate that MeHg is an olfactory toxicant that damages the central regions involved in odor perception. The model described herein is useful for analyzing the mechanisms and treatments of olfactory dysfunction in MeHg-intoxicated patients.

[Systematic review and Meta-analysis of efficacy and safety of Bidouyan Oral Liquid in treatment of rhinosinusitis].

This study aimed to systematically review the efficacy and safety of Bidouyan Oral Liquid in the treatment of rhinosinu-sitis(RS). CNKI, Wanfang, SinoMed, VIP, Cochrane Library, PubMed, EMbase, Web of Science, and Ovid were searched for the randomized controlled trial(RCT) of Bidouyan Oral Liquid for the treatment of RS patients. Moreover, the reference lists and the grey literature were searched manually. Two researchers independently screened the literature and extracted data. The Cochrane collaboration's tool for assessing risk of bias(RoB 2.0) in randomized trial was used to assess the methodological quality of the included stu-dies. Meta-analysis was performed in RevMan 5.3 and Stata 12.0, and the grades of recommendation, assessment, development and evaluation(GRADE) was employed to evaluate the quality of evidence. A total of 54 RCTs(35 with drug combinations and 19 with single drugs) comprising 7 511 patients(3 973 in the observation group and 3 538 in the control group) were included. Meta-analysis showed that Bidouyan Oral Liquid + conventional treatment was superior to conventional treatment alone in increasing the total response rate(RR=1.19, 95%CI[1.15, 1.24], P<0.000 01) and decreasing the Lund-Kennedy scores(MD=-1.94, 95%CI[-2.61,-1.26], P<0.000 01), Lund-Mackay scores(MD=-2.14, 95%CI[-2.98,-1.31], P<0.000 01), and visual analogue scale(VAS) scores(MD_(total VAS scores)=-1.28, 95%CI[-1.56,-1.01], P<0.000 01; MD_(nasal congestion VAS scores)=-0.58, 95%CI[-0.89,-0.27], P=0.000 2; MD_(runny nose VAS scores)=-0.61, 95%CI[-0.93,-0.29], P=0.000 2; MD_(olfactory dysfunction VAS scores)=-0.43, 95%CI[-0.52,-0.34], P<0.000 01; MD_(head and facial pain VAS scores)=-0.41, 95%CI[-0.57,-0.26], P<0.000 01). Furthermore, the combined treatment outperformed conventional treatment alone in improving the mucociliary transport rate(MTR)(MD=1.64, 95%CI[1.08, 2.20], P<0.000 01) and lowering the levels of inflammatory cytokines{tumor necrosis factor-α(TNF-α)(SMD=-1.95, 95%CI[-2.57,-1.33], P<0.000 01), interleukin-6(IL-6)(SMD=-2.64, 95%CI[-4.08,-1.21], P=0.000 3)} in RS patients. In addition, the combined treatment did not increase the incidence of adverse reactions(RR=0.83, 95%CI[0.44, 1.57], P=0.57). Bidouyan Oral Liquid was superior to conventional treatment in increasing total response rate(RR=1.25, 95%CI[1.18, 1.32], P<0.000 01), decreasing the Lund-Kennedy(P<0.01) and Lund-Mackay scores(P<0.05), alleviating major symptoms(P_(total VAS scores)<0.01; P_(nasal congestion VAS scores)<0.01; P_(runny nose VAS scores)<0.01; P_(olfactory dysfunction VAS scores)<0.05; P_(head and facial pain VAS scores)<0.01), and decreasing adverse reactions(P=0.03). The results showed that either Bidouyan Oral Liquid or Bidouyan Oral Liquid + conventional treatment can increase the total response rate, decrease the Lund-Kennedy and Lund-Mackay scores, and mitigate major symptoms. In addition, Bidouyan Oral Liquid + conventional treatment improved MTR and reduced the expression of TNF-α and IL-6 without causing serious adverse events. However, due to the limited methodological quality of the included studies, large-sample and high-quality RCTs are needed to provide evidence support.

Phantosmia during proton radiation and differences in frequency of phantosmia rates based on proton craniospinal irradiation technique for pediatric brain tumor patients.

BACKGROUND: Unusual olfactory perception, often referred to as "phantosmia" or "cacosmia" has been reported during brain radiotherapy (RT), but is infrequent and does not typically interfere with the ability to deliver treatment. We seek to determine the rate of phantosmia for patients treated with proton craniospinal irradiation (CSI) and identify any potential clinical or treatment-related associations. METHODS: We performed a retrospective review of 127 pediatric patients treated with CSI, followed by a boost to the brain for primary brain tumors in a single institution between 2016 and 2021. Proton CSI was delivered with passive scattering (PS) proton technique (n = 53) or pencil beam scanning technique (PBS) (n = 74). Within the PBS group, treatment delivery to the CSI utilized a single posterior (PA) field (n = 24) or two posterior oblique fields (n = 50). We collected data on phantom smell, nausea/vomiting, and the use of medical intervention. RESULTS: Our cohort included 80 males and 47 females. The median age of patients was 10 years (range: 3-21). Seventy-one patients (56%) received concurrent chemotherapy. During RT, 104 patients (82%) developed worsening nausea, while 63 patients (50%) reported episodes of emesis. Of those patients who were awake during CSI (n = 59), 17 (29%) reported phantosmia. In the non-sedated group, we found a higher rate of phantosmia in patients treated with PBS (n = 16, 42%) than PS (n = 1, 4.7%) (p = .002). Seventy-eight patients (61%) required medical intervention after developing nausea/vomiting or phantosmia during RT. Two patients required sedation due to the malodorous smell during CSI. We did not find any significant difference in nausea/vomiting based on treatment technique. CONCLUSION: Proton technique significantly influenced olfactory perception with greater rates of phantosmia with PBS compared to PS. Prospective studies should be performed to determine the cause of these findings and determine techniques to minimize phantosmia during radiation therapy.

Olfactory-Related Adverse Events: An Analysis of the Food and Drug Administration Adverse Events Reporting System.

OBJECTIVE: Olfactory dysfunction has gained considerable interest with its association to the coronavirus pandemic. Due to the limited literature on olfactory-related adverse events (ORAE) associated with medications, this study investigated ORAE reported in the Food and Drug Administration Adverse Event Reporting System (FAERS) to identify the most frequent medications associated with these reactions. STUDY DESIGN: Cross-sectional analysis SETTING: FAERS database. METHODS: The FAERS database was accessed to obtain ORAEs from 2012 to 2022. Disproportionality analysis was conducted by calculating the proportional reporting ratios (PRR) and reporting odds ratio (ROR) for anosmia, parosmia, hyposmia, and olfactory dysfunction. A PRR > 2 or ROR > 1 was significant. A multivariate logistical model was used to estimate adjusted ROR for gender and country of origin. RESULTS: Our final study population consisted of 1111 cases with the following symptoms: anosmia (672), parosmia (364), hyposmia (71), and olfactory dysfunction (4). The most significant ROR signal scores were found for secukinumab (3.42; 95% confidence interval, CI [1.9, 4.01]) for anosmia, levofloxacin (8.86; 95% CI [2.83, 9.8]) for hyposmia, and pregabalin (6.88; 95% CI [2.23, 8.01]) for parosmia. No significant PRR signal scores were found for anosmia, but significant signals were found for citalopram hydrobromide (17.25; 95% CI [17.01, 17.49]) in hyposmia, and dimethyl fumarate (3.18; 95% CI [3.09, 3.27]) in parosmia. No valid PRR or ROR values were found for olfactory dysfunction. Multivariate analysis did not reveal statistically significant differences between genders for any symptoms, but individuals from non-US countries did exhibit statistically significant elevated risk of anosmia (1.3 (95% CI [1.01, 1.68]). CONCLUSION: Pharmacovigilance studies provide an opportunity to evaluate the safety profile of medications regarding ORAE, particularly for those commonly prescribed for sinonasal symptoms. Findings from this study may function as a resource for prescribers and patients.