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Background Intranasal drug delivery offers a non-invasive and convenient dosing option for patients and physicians, especially for conditions requiring chronic/repeated-treatment administration. However, in some cases such delivery may be harmful to nasal and olfactory epithelia. Objective The aim of this study was to assess the potential impact of long-term intermittent treatment with esketamine nasal spray, taken in conjunction with an oral antidepressant (AD), on olfactory function and nasal tolerability in patients with treatment-resistant depression (TRD). Methods A total of 1142 patients with TRD participated from four multicenter, randomized, double-blind, phase III studies: three short-term studies (two in patients aged 18–64 years, one in patients ≥65 years), and one long-term maintenance study of esketamine nasal spray + AD versus placebo nasal spray + AD. Across the four studies, assessments were performed at 208 sites in 21 countries. Olfactory function was measured using the 40-item University of Pennsylvania Smell Identification Test (UPSIT ® ) and the single-staircase Snap & Sniff ® Odor Detection Threshold Test (S&S-T). Nasal tolerability, including nasal examinations and a quantitative, self-administered nasal symptom questionnaire (NSQ), was also assessed. Data were analyzed using analyses of covariance. Results Of 1142 participants, 734 were women (64.3%). The mean age of all participants ranged from 45.7 to 70.0 years across the studies. Overall, 855 patients received esketamine nasal spray + AD and 432 received placebo nasal spray + AD. Objective evaluation of nasal function showed no evidence of an adverse impact following esketamine administration. Based on the UPSIT ® and S&S-T results, intranasal administration of esketamine had no effect on the odor identification or threshold test scores compared with placebo nasal spray + oral AD. Similarly, repeated administration with esketamine nasal spray had no meaningful impact on assessments of nasal function. No dose–response relationship was observed between esketamine doses and the olfactory test scores. Esketamine nasal spray was well tolerated, as indicated by responses on the NSQ and negative nasal examination findings. Conclusion Findings from this analysis indicate that there was no evidence of adverse effect on either olfactory or nasal health measures with repeated intermittent administration of esketamine nasal spray at any dose over the course of short-term (4 weeks) or long-term (16–100 weeks) studies. Clinical trial registration TRANSFORM-1: NCT02417064, date of registration: 15/04/2015; TRANSFORM-2: NCT02418585, date of registration: 16/04/2015; TRANSFORM-3: NCT02422186, date of registration: 21/04/2015; SUSTAIN-1: NCT02493868, date of registration: 10/07/2015.

ObjectivesAs a rose geranium in sesame oil spray product has been anecdotally noted to improve nasal vestibulitis symptoms, this study was designed to assess whether patients with nasal vestibulitis associated with cancer-directed therapy experienced symptomatic improvements from it.MethodsPatients with breast cancer, prescribed rose geranium nasal spray, were identified by looking at pharmacy records and patient diagnosis at Mayo Clinic Rochester. Patient medical information, as well as documentation of symptoms, were gleaned from medical charts. Questionnaires were sent to patients regarding their experiences.ResultsOf the 40 patients with breast cancer who were prescribed rose geranium nasal spray, 100% were receiving cancer-directed therapy: 58 % were receiving taxane chemotherapy; others received a variety of cytotoxic and targeted therapy treatments. Twenty patients who had used the spray product returned surveys. Patient-reported nasal symptoms included bleeding (90%), dryness (86%), pain (81%), scabbing (67%) and sores (52%); patients consistently reported symptoms at a higher proportion than did healthcare providers. All patients who used the rose geranium nasal spray reported symptomatic benefit; one reported a little benefit, 11 (55%) reported moderate benefit and eight (40%) reported dramatic or complete resolution of symptoms. The therapy was well tolerated in most patients.ConclusionsRose geranium in sesame oil nasal spray appears to improve patient-reported nasal symptoms associated with cancer-directed therapy.

Objective and design This double-blind cross-over study compared the potential of bilastine, cetirizine, and fexofenadine to relieve the symptoms of allergic rhinitis. Subjects and methods Seventy-five allergic volunteers were challenged with grass pollen in the Vienna Challenge Chamber (VCC) on two consecutive days of allergen provocation; 6 h on day 1 and 4 h day 2. Bilastine 20 mg, cetirizine 10 mg, fexofenadine 120 mg, or placebo were taken orally 2 h after the start of provocation on day 1 only. Total nasal symptom scores, the global symptom scores, nasal secretions, and eye symptoms were assessed on both day 1 and day 2. Results and conclusions Bilastine had a rapid onset of action, within 1 h, and a long duration of action, greater than 26 h. Cetirizine was similar. Fexofenadine was similar on day 1 but less effective on day 2, indicating a shorter duration of action. Bilastine, like cetirizine and fexofenadine, was safe and well tolerated in this study.

Aims: To assess potential alterations of the nasal mucosa by clinical and histopathological evaluation of workers exposed to sulphuric acid mists at anodising plants, correlating the findings with duration of exposure and sulphuric acid concentrations in the air, and comparing them with a control group. Methods: Fifty two workers from five plants underwent a clinical evaluation (standard questionnaire, clinical, and ear, nose, and throat examination including nasal endoscopy). For the histopathological study, 20 of the 52 subjects (study group) were randomly selected, as well as 11 unexposed subjects (control group), matched by sex, age, and smoking habits. Nasal biopsy specimens were obtained from the anterior septum mucosa and the anterior curvature of the middle turbinate in each individual. A total of 56 nasal mucosa specimens (37 in the study group and 19 in the control group) were evaluated with regard to normal respiratory epithelium or metaplastic epithelium, atypia or dysplasia, and alterations of the lamina propria. Results: The histopathological study revealed squamous metaplasia in 29 (79%) and atypia in 13 (35%) of the 37 study group samples. No association was found between exposure duration and the clinical and histopathological variables, but a significant association was found between sulphuric acid concentrations higher than 200 μg/m3 and pale mucosal patches and ulcerations in the exposed subjects. Logistic regression analysis showed that the exposed subjects had a fivefold risk of developing atypia compared with the unexposed subjects. Conclusions: Workers exposed to sulphuric acid mists presented with a high incidence of nasal symptoms, and macroscopic and microscopic changes of the nasal mucosa, including squamous atypia and dysplasia. The risk for these histopthological lesions increased with higher sulphuric acid concentrations in the air, revealing an exposure-response relation.

Background Few studies have been carried out on acute effects of cement dust exposure. This study is conducted to investigate the associations between current \"total\" dust exposure and acute respiratory symptoms and respiratory function among cement factory workers. Methods A combined cross-sectional and cross-shift study was conducted in Dire Dawa cement factory in Ethiopia. 40 exposed production workers from the crusher and packing sections and 20 controls from the guards were included. Personal \"total\" dust was measured in the workers' breathing zone and peak expiratory flow (PEF) was measured for all selected workers before and after the shift. When the day shift ended, the acute respiratory symptoms experienced were scored and recorded on a five-point Likert scale using a modified respiratory symptom score questionnaire. Results The highest geometric mean dust exposure was found in the crusher section (38.6 mg/m 3 ) followed by the packing section (18.5 mg/m 3 ) and the guards (0.4 mg/m 3 ). The highest prevalence of respiratory symptoms for the high exposed workers was stuffy nose (85%) followed by shortness of breath (47%) and \"sneezing\" (45%). PEF decreased significantly across the shift in the high exposed group. Multiple linear regression showed a significant negative association between the percentage cross-shift change in PEF and total dust exposure. The number of years of work in high-exposure sections and current smoking were also associated with cross-shift decrease in PEF. Conclusions Total cement dust exposure was related to acute respiratory symptoms and acute ventilatory effects. Implementing measures to control dust and providing adequate personal respiratory protective equipment for the production workers are highly recommended.

Eosinophilic inflammation is a hallmark of chronic rhinosinusitis with nasal polyps. To model this disease process experimentally, nasal sensitization of mice with ovalbumin or aspergillus has been described. Here, we describe a genetically mutant mouse that develops robust spontaneous nasal eosinophilic inflammation. These mice lack the enzyme SHP-1 that down-regulates the IL-4Rα/stat6 signaling pathway. We compared nasal inflammation and inflammatory mediators in SHP-1 deficient mice (mev) and an ovalbumin-induced nasal allergy model. A novel technique of trans-pharyngeal nasal lavage was developed to obtain samples of inflammatory cells from the nasal passages of allergic and mev mice. Total and differential cell counts were performed on cytospin preparations. Expression of tissue mRNA for IL-4, IL-13, and mouse beta-defensin-1 (MBD-1) was determined by quantitative PCR. Eotaxin in the lavage fluid was assessed by ELISA. Allergic and mev mice had increased total cells and eosinophils compared with controls. Expression of IL-4 was similarly increased in both allergic and mev mice, but expression of IL-13 and eotaxin was significantly greater in the allergic mice than mev mice. Eotaxin was significantly up-regulated in both allergic rhinitis and mev mice. In both models of eosinophilic inflammation, down-regulation of the innate immune marker MBD-1 was observed. The mev mice display spontaneous chronic nasal eosinophilic inflammation with potential utility for chronic rhinosinusitis with nasal polyps research. The eosinophilic infiltrate is more robust in the mev mice than allergic mice, but Th2 cytokine expression is not as pronounced. Decreased MBD-1 expression in both models supports the concept that Th2-cytokines down-regulate sinonasal innate immunity in humans, and suggests a role for mouse models in investigating the interaction between adaptive and innate immunity in the sinonasal mucosa.

Objective To evaluate the safety and efficacy of a sedation protocol based on intranasal lidocaine spray and midazolam (INM) in children who are anxious and uncooperative when undergoing minor painful or diagnostic procedures, such as peripheral line insertion, venipuncture, intramuscular injection, echocardiogram, CT scan, audiometry testing and dental examination and extractions. Patients and design 46 children, aged 5–50 months, received INM (0.5 mg/kg) via a mucosal atomiser device. To avoid any nasal discomfort a puff of lidocaine spray (10 mg/puff) was administered before INM. The child's degree of sedation was scored using a modified Ramsay sedation scale. A questionnaire was designed to evaluate the parents' and doctors' opinions on the efficacy of the sedation. Statistical analysis was used to compare sedation times with children's age and weight. Results The degree of sedation achieved by INM enabled all procedures to be completed without additional drugs. Premedication with lidocaine spray prevented any nasal discomfort related to the INM. The mean duration of sedation was 23.1 min. The depth of sedation was 1 on the modified Ramsay scale. The questionnaire revealed high levels of satisfaction by both doctors and parents. Sedation start and end times were significantly correlated with age only. No side effects were recorded in the cohort of children studied. Conclusions This study has shown that the combined use of lidocaine spray and atomised INM appears to be a safe and effective method to achieve short-term sedation in children to facilitate medical care and procedures.

Purpose Despite the decreased use of solvent-based paint (SBP) and increased use of water-based paints (WBP) with possible risk for microbial growth, few health studies are available. The aim was to study the symptoms and ocular and nasal biomarkers in house painters in relation to paint use and personal exposure to volatile organic compounds (VOC) and microbial VOC (MVOC) during indoor painting with WBP. Methods All house painters from three major companies and unexposed controls (janitors from one company) were invited, 94% ( N  = 31) and 95% ( N  = 20) of non-asthmatics participated, respectively. Tear film break-up time (BUT), nasal patency by acoustic rhinometry, and biomarkers in nasal lavage (NAL) were measured at work, and a doctor’s administered questionnaire was answered. Personal sampling (8 h) of formaldehyde, VOC, and MVOC was performed in 17 house painters using WBP. Results House painters had increase in ocular symptoms, decreased BUT, and increased NAL-lysozyme, when compared to controls. Painters reporting mucosal irritation from WBP had less nasal patency and higher NAL-myeloperoxidase (NAL-MPO). A large proportion of the VOC consisted of propylenglycol, diglycol ethers, and Texanol. There was an association between 8-h exposure to propylene glycol and NAL-eosinophilic cationic protein (NAL-ECP), 2-phenoxyethanol levels and reduced BUT, sum of aliphatic glycol ethers and increased NAL-MPO. Increased levels of 1-octen-3-ol, one MVOC, were related to reduced nasal patency and increase in NAL-MPO. Conclusions House painters may have a risk for adverse physiological reactions in the ocular and nasal mucosa. A minority of painters susceptible to WBP can react with neutrophilic nasal inflammation. Different chemicals in the paint could cause either neutrophilic or eosinophilic inflammation, or reduced tear film stability. In addition, house painters are exposed to MVOC which may affect the nasal mucosa.

Objective: To investigate the possible impact of long-term occupational exposure to hydrocarbons on respiratory health. Methods: Respiratory health was assessed by questionnaires, spirometry, and exhaled nitric oxide in 250 male workers from a company handling and distributing refined petroleum products (exposed) and 250 electricians (controls). Exposure to hydrocarbons was assessed by personal air monitoring. Results: Aerial exposure to hydrocarbons was low. Respiratory and nasal symptoms were significantly more frequent among exposed subjects than among controls. Although forced vital capacity and forced expiratory volume in 1 second did not differ, ratio of forced expiratory volume in 1 second to forced vital capacity and maximal expiratory flows were significantly lower in exposed than in control subjects, adjusting for smoking. Exhaled nitric oxide was significantly higher among exposed subjects (30.1 ppb) than among controls (21.6 ppb), adjusting for age and smoking. Conclusions: Even low exposure to petroleum-derived hydrocarbons is associated with more respiratory and nasal symptoms, lower pulmonary function, and airway inflammation.