Diclofenac Mouthwash as a potential therapy for reducing pain and discomfort in chemo-radiotherapy-induced oral mucositis

AIMS: Oral and/or oropharyngeal acute mucositis during and after chemo-radiotherapy (chemo-RT) for head and neck squamous cell carcinoma (HNSCC) can be extremely painful, sometimes requiring nasogastric feeding to enable adequate nutrition. The MASCC/ISOO evidence- based guidelines recommend benzydamine mouthwash for mucositis prevention in RT (recently updated to include chemo-RT), and a Cochrane systematic review found other agents to be effective in prophylaxis. Diclofenac mouthwash is licenced for painful oral mucosal inflammatory conditions but to our knowledge has not been assessed in chemo-RT associated oral mucositis. METHOD: A clinical observation and service evaluation study in 10 patients undergoing chemo-RT for HNSCC to assess the potential value of diclofenac mouthwash (0.74mg/ml) in reducing symptoms. Patients used 20ml of mouthwash up to 4 times a day starting in week 3 (of a 6 week course of treatment), recording pain and discomfort scores using a visual analogue scale on days 0, 1,7 and 14 (until the end of week 4). As per our current clinical practice, oral mucositis was not clinically scored as an outcome. Statistical analysis was performed using a one-way ANOVA. RESULTS: Using diclofenac mouthwash, 9/10 patients experienced pain score reduction from day 0 (mean score 6.75 +/- SD 1.83) to day 2 (5.05 +/- SD 1.62) and day 14 (4.09 +/- SD 1.96). CONCLUSIONS: Diclofenac mouthwash may be beneficial for managing chemo-RT-induced oral mucositis. While a prospective randomised clinical trial is needed, it can be prescribed for this condition within its current licence

Long-term exposure to PM₁₀ and respiratory health among Parisian subway workers.

Exposure to ambient PM10 may increase the risk of chronic obstructive pulmonary disease (COPD) and lung function decline. We evaluated the long-term exposure to PM10 and its relationship with COPD prevalence and lung function in Parisian subway workers. Participants were randomly selected from a 15,000-subway worker cohort. Individual annual external exposure to PM10 (ePM10) was estimated using a company-specific job-exposure-matrix based on PM10 measurements conducted between 2004 and 2019 in the Parisian subway network. Mean annual inhaled PM10 exposure (iPM10) was modeled as function of ePM10 exposure, inhalation rate, and filtration efficiency of the respiratory protection used. COPD diagnosis was performed in March-May 2021 based on post-bronchodilator spirometry. The relationship between iPM10 and outcomes was assessed using logistic and linear regression models, adjusted for exposure duration and potential confounders. Amongst 254 participants with complete data, 17 were diagnosed as COPD. The mean employment duration was 23.2 ± 7.3years, with annual mean ePM10 of 71.8 ± 33.7 μg/m <sup>3</sup> and iPM10 of 0.59 ± 0.27 μg/shift, respectively. A positive but statistically non-significant association was found for COPD prevalence with iPM10 (OR = 1.034, 95%-CI = 0.781; 1.369, per 100 ng/shift) and ePM10 (OR = 1.029, 95%-CI = 0.879; 1.207, per 10 μg/m <sup>3</sup> ). No decline in lung function was associated with PM10 exposure. However, forced expiratory volume during the first second and forced vital capacity lower than normal were positively associated with exposure duration (OR = 1.125, 95%-CI = 1.004; 1.260 and OR = 1.171, 95%-CI = 0.989; 1.386 per year, respectively). Current smoking was strongly associated with COPD prevalence (OR = 6.85, 95%-CI = 1.87; 25.10) and most lung function parameters. This is the first study assessing the relationship between long-term exposure to subway PM10 and respiratory health in subway workers. The risk estimates related with subway PM10 exposure are compatible with those related to outdoor PM10 exposure in the large recent studies. Large cohorts of subway workers are necessary to confirm these findings