Showing papers in "Rhinology in 2017"

Position Paper on Olfactory Dysfunction

Abstract: Background: Olfactory dysfunction is an increasingly recognised condition, associated with reduced quality of life and major health outcomes such as neurodegeneration and death. However, translational research in this field is limited by heterogeneity in methodological approach, including definitions of impairment, improvement and appropriate assessment techniques. Accordingly, effective treatments are limited. In an effort to encourage high quality and comparable work in this field, among others, we propose the following ideas and recommendations. Whilst full recommendations are outlined in the main document, key points include: -Patients with suspected olfactory loss should undergo a full examination of the head and neck, including rigid nasal endoscopy. -Subjective olfactory assessment should not be undertaken in isolation, given its poor reliability. -Psychophysical assessment tools used in clinical and research settings should include reliable and validated tests of odour threshold, and/or one of odour identification or discrimination. -Comprehensive chemosensory assessment should include gustatory screening. -Smell training can be helpful in patients with olfactory loss of several aetiologies. Conclusions: We hope the current manuscript will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency and generalisability of work in this field.

Effects of olfactory training: a meta-analysis.

Abstract: The neural plasticity of the olfactory system offers possibilities of treatment in terms of stimulation of the sense of smell, and different studies have suggested effectiveness of smell training, i.e., daily exposition to certain odors. To obtain reliable and precise estimates of overall treatment benefit on the olfactory function, we meta-analyzed the effects of smell training reported in 13 previous studies. We analyzed the smell training effectiveness across three different olfactory abilities, smell identification, discrimination and threshold for odor detection. We found a significant, positive effect of olfactory training for all olfactory abilities, with large effects of training on identification, discrimination and TDI-score and small-to-moderate effect in the case of threshold for odor detection. Interestingly, the pattern of results differed across Sniffin Sticks subtests depending on the origin of participants smell disorder, and the smell training duration influenced its effectiveness in the case of identification and the TDI score. Although the exact mechanism of olfactory recovery following the smell training still requires further investigation, our meta-analysis showed that such training should be considered an addition or alternative to existing smell treatment methods.

EUFOREA Rhinology Research Forum 2016: report of the brainstorming sessions on needs and priorities in rhinitis and rhinosinusitis.

Abstract: The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.

Chronic rhinosinusitis and mood disturbance.

Abstract: Background This study is part of the Chronic Rhinosinusitis Epidemiology Study (CRES). The overarching aim is to determine factors that influence the onset and severity of chronic rhinosinusitis (CRS). The aim of this analysis is to determine whether those with CRS are more likely to report psychiatric morbidity and in particular mood disturbance compared with healthy controls. Methods CRES consists of a study-specific questionnaire regarding demographic and socioeconomic factors and past medical history as well as a nasal symptom score (SNOT-22) and SF-36 (QoL - quality of life tool). Both of these tools contain mental health or emotional well-being domains. Participants were specifically asked whether they had ever consulted with their General Practitioner for anxiety or depression. Questionnaires were distributed to patients with CRS attending ENT outpatient clinics at 30 centres across the United Kingdom from 2007-2013. Controls were also recruited at these sites. Patients were divided into subgroups of CRS according to the absence/presence of polyps (CRSsNPs/CRSwNPs) or allergic fungal rhinosinusitis (AFRS). Results Consultations with a family physician for depression or anxiety were higher amongst those with CRS than controls, but this was only significant for those with CRSsNPs. Odds ratio (OR) for CRSsNPs vs controls: 1.89; OR for CRSwNPs: 1.40. Patients with CRS showed significantly higher mental health morbidity than controls across the mental health and emotional wellbeing domains of the SF-36 and SNOT-22. Mean difference in the mental health domain of SF-36 was 8.3 for CRSsNPs and 5.3 for CRSwNPs. For the emotional domain of SNOT-22, differences were 7.7 and 6.3 respectively. Conclusions Depression and anxiety are significantly more common in patients with CRS compared to healthy controls, especially in those with CRSsNPs. This added mental health morbidity needs consideration when managing these patients in primary and secondary care settings.

Association of gastro-oesophageal reflux and chronic rhinosinusitis: systematic review and meta-analysis.

Abstract: Introduction Gastro-oesophageal reflux disease (GORD) has been implicated in the development of chronic rhinosinusitis (CRS). The association of GORD with CRS is systematically assessed from the medical literature. Methodology Embase and MEDLINE were searched using a comprehensive strategy limited to English language and Human subjects. Any study with original data on the experimental, diagnostic, treatment or prognostic association of CRS with GORD was included. Studies without a control group, case reports and review articles were excluded. Results The search returned 958 records, with an additional 10 found from bibliographic lists; this produced 32 studies. The included studies (n=32) consisted of studies reporting pathogenic factors (n=20), epidemiological association (n=8), prognostic interactions (n=3), and a combination of these outcomes (n=1). Potential pathogenic roles for GORD in CRS were supported; CRS subjects had greater prevalence of intranasal Helicobacter pylori and acid reflux than subjects without CRS. CRS is more prevalent in GORD sufferers than those without GORD. Evidence is conflicting for GORD as a factor in CRS treatment failure. Conclusion The results support a significant association of GORD with CRS. Physicians should be cognizant of the potential for acid and non-acid reflux as a driving factor in CRS.

Chronic rhinosinusitis severity is associated with need for asthma-related systemic corticosteroids.

Abstract: Background Chronic rhinosinusitis (CRS) is highly prevalent in patients with asthma. However, no study has evaluated the effect of CRS severity on asthma-related oral corticosteroid use - a marker of poor asthma control and prognosis. We therefore sought to evaluate the association between CRS severity and asthma-related oral corticosteroid use. Methodology Prospective cross-sectional study of 110 adult asthmatic CRS patients. CRS severity was measured using the 22-item Sinonasal Outcomes Test (SNOT-22) and Lund-Kennedy endoscopy score. Number of asthma-related courses of oral corticosteroids in the past year was queried at enrollment. Association was sought between metrics for CRS severity and asthma-related oral corticosteroids use in the last year. Receiver operating characteristic (ROC) curves defined whether SNOT-22 or endoscopy scores could be used for detecting asthma-related oral corticosteroid use. Results The mean SNOT-22 score was 44.9 (standard deviation [SD] : 23.3) and mean endoscopy score was 4.1 (SD: 3.0). The mean number of asthma-related oral corticosteroid courses taken in the last year was 1.1 (SD: 1.9). SNOT-22, but not endoscopy score, was associated with requiring at least one course of asthma-related oral corticosteroids in the last year (odds ratio = 1.03, 95%CI: 1.02 - 1.06, p=0.003), which translates to an odds ratio of 2.0 for a 21-point increase in SNOT-22. ROC analysis identified equally optimal SNOT-22 scores of greater than 32 (sensitivity: 88.1%, specificity: 41.2%) or greater than 65 (sensitivity: 38.1%, specificity: 91.2%) for detecting the need for at least one course of oral corticosteroids within the past year. Conclusions CRS symptom severity is associated with past asthma-related oral corticosteroid use. SNOT-22 scores may be used as a versatile tool to screen for past asthma-related oral corticosteroid use in asthmatic CRS patients - i.e. those at greatest risk from their asthma - with either high sensitivity or high specificity.

The impact of bitter taste receptor genetics on culturable bacteria in chronic rhinosinusitis.

Abstract: Background Extra-oral bitter taste receptors have been associated with innate bacterial defence mechanisms. Genetic variation in T2R38 functionality has been shown to be associated with susceptibility to upper respiratory tract infections and chronic rhinosinusitis (CRS). We sought to independently assess the influence of bitter taste receptor genotype on the presence of culturable bacteria in the sinuses. Methodology A cross-sectional analysis of patients with CRS undergoing surgery was performed. Middle meatal nasal swabs were sent for microbiological evaluation at the time of the procedure. Mucosal biopsies were taken and sent for bitter taste receptor genotype analysis. Sequencing of 3 polymorphisms in the TAS2R38 gene was performed to identify genotypes as super-tasters (PAV/PAV), non-tasters (AVI/AVI) or heterozygous expression (PAV/AVI). The presence of culturable organisms and common pathogens were compared with bitter taste receptor genotypes. Results 25 patients (age 52.4 +/- 18.28 years, 51% female) were assessed. Super-tasters comprised 16% of the group, 24% were non-tasters and 48% had heterozygous expression. A cultured pathogen was grown in 48% of patients; 32% gram-positive, 20% gram-negative, 28% grew Staphylococcus aureus and 12% Pseudomonas aeruginosa. A non-taster genotype was predictive of colonised pathogens. Tissue eosinophilia (more than 10 HPF) was seen in 48%. Conclusion Even in a small sample of patients with CRS, non-taster T2R38 genotype appears to predict the presence of culturable bacteria colonising the sinus cavity at the time of surgery for their condition. A genetic link to patients more likely to become infected is likely.

The effect of systemic treatments on periostin expression reflects their interference with the eosinophilic inflammation in chronic rhinosinusitis with nasal polyps.

Abstract: Background Periostin is a recently discovered biomarker for eosinophilic inflammation Chronic rhinosinusitis with nasal polyps is a T-helper 2-skewed chronic inflammatory airway disease Medical treatments aim to relieve symptoms and maintain clinical control by interfering with the inflammatory cascade The effect on nasal and serum periostin levels is however yet unknown We aimed to evaluate the effect of omalizumab, mepolizumab, methylprednisolone and doxycycline on nasal and systemic periostin expression Methods This study is based on 3 previously published trials Nasal and systemic periostin were assessed in CRSwNP patients, randomly assigned to receive doxycycline (n=14), methylprednisolone (n=14), mepolizumab (n=20) or omalizumab (n=15) There was a control group for each treatment scheme Doxycycline (200 mg on the first day, followed by 100 mg once daily) and methylprednisolone (32-8 mg once daily) were administered during 20 days; mepolizumab was injected at baseline and at 4 weeks Omalizumab was injected every 2 or 4 weeks, following the official drug leaflet Results Methylprednisolone and omalizumab significantly reduced serum periostin levels at 4 and 8 weeks, respectively, after the start of the treatment The effect of methylprednisolone was transient Nasal periostin levels decreased significantly after 8 weeks of treatment with mepolizumab The periostin expression is in accordance with the previously reported effect on the eosinophilic inflammation and clinical outcome Conclusion All treatment options distinctly influence periostin expression, reflecting the interference with the local or systemic eosinophilic inflammatory cascade

Anterior maxillary wall and lacrimal duct relationship - CT analysis for prelacrimal access to the maxillary sinus.

Abstract: Background The distance between the anterior wall of the maxillary sinus and the nasolacrimal duct shows a large individual variation. Methodology To evaluate the feasibility of accessing the maxillary sinus through a prelacrimal window access (PLWA), a series of 100 paranasal CT scans from adult patients was analysed retrospectively. The distance between the anterior maxillary wall and the anterior border of the lacrimal duct (= prelacrimal window) were measured in 200 sides. Results A distance of more the 7 mm was found in 12.5% maxillary sinuses and would enable straight forward PLWA. A distance between smaller than 7mm and larger than 3mm was present in 56.5% of sinuses, and would make surgical access more demanding. In 31.5% of maxillary sinuses the distance was smaller than or equal to 3mm and in these patients this approach would be difficult without transecting the nasolacrimal duct. Conclusion Only in 12.5% of sinuses a prelacrimal endoscopic access is readily feasible, while in 56.5% temporary tear sac dislocation is required and in 31.5% lacrimal sac dislocation is always needed along with a significant amount of bone removal to enable PLWA.

Prospective open-label evaluation of long-term low-dose doxycycline for difficult-to-treat chronic rhinosinusitis with nasal polyps.

Abstract: Background This study aimed to assess clinical outcomes of long-term low-dose oral doxycycline therapy in difficult-to-treat chronic rhinosinusitis with polyps (CRSwNP). Methods This was a prospective, open-label study of 60 patients with difficult-to-treat CRSwNP who had undergone endoscopic sinus surgery. Patients were divided into two groups: 28 received nasal steroids, saline irrigation, and doxycycline (200 mg on the first day, followed by 100 mg once daily) for 12 weeks, while 30 received only nasal steroids and saline irrigation. The main outcome measure was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Other outcome measures were the SNOT-20, NOSE, and Lund-Kennedy scores. The following parameters were also analyzed: asthma, rhinitis, non-steroidal-exacerbated respiratory disease (NERD), and baseline serum IgG, IgA, IgE, IgM, ANCA, and eosinophil count. Results There was an adequate effect size of doxycycline treatment on clinically meaningful significant improvement of SNOT-20. Patients who received doxycycline also had significantly better outcomes regarding SNOT-20, NOSE, and Lund-Kennedy scores. There was a negative association among a clinically significant improvement of SNOT-20 and presence of asthma, NERD, and elevated serum IgE levels before treatment. Conclusion These findings suggest that doxycycline may have a beneficial role for CRSwNP patients, especially for patients without asthma, NERD or high levels of serum IgE before treatment.

Periostin as a marker of mucosal remodelling in chronic rhinosinusitis.

Abstract: Background Although extracellular matrix (ECM) proteins are associated with irreversible lower airway changes, the relationship with upper airway remodelling which occurs during chronic rhinosinusitis (CRS) is poorly understood. This study assessed the expression of ECM proteins periostin, fibulin-1, fibronectin and collagenIV in nasal mucosa of patients with and without histologic features of remodelling. Methods A cross-sectional study of sinonasal mucosal biopsies taken from patients, undergoing surgery for CRS was performed, where patients were grouped according to remodelling, defined by basement membrane thickening (BMT over 7.5 micrometer) and subepithelial fibrosis. An overall view and three random fields of immunostained tissue sections that included epithelium, basement membrane and submucosa, were imaged using Zeiss Zen software. The area and intensity of positive staining were scored by two blinded observers, using a 12-point ordinal scale of weak to strong. Results 65 patients (47.6 +/- 13.4years, 44.6% female) were assessed. Patients were grouped as controls 26.2%, BMT/no fibrosis 38.5% or BMT and fibrosis 33.8%. Stronger grade of periostin expression was associated with remodelling changes and tissue eosinophilia over 10/HPF. Fibulin-1, fibronectin and collagenIV did not differ. Conclusion Periostin expression was associated with the presence of BMT, fibrosis and tissue eosinophilia and may identify patients undergoing remodelling changes.

The effect of endoscopic sinus surgery on quality of life and absenteeism in patients with chronic rhinosinuitis - a multi-centre study.

Abstract: Background: Chronic rhinosinusitis with and without nasal polyps (CRSw/sNP) are common conditions decreasing health-related quality of life (HRQOL). Individual symptoms capable of predicting outcome after endoscopic sinus surgery (ESS) are poorly defined, and the indirect costs of CRS is rarely reported in Europe. Methodology: Patients with CRSw/sNP admitted for ESS were prospectively enrolled. Patients completed the 22 Sinonasal Outcome Test (SNOT-22), the short-form 36-item questionnaire (SF-36), a Visual Analogue Scale (VAS) and reported CRS-related absenteeism pre- and post-operatively. Results: 181 patients were included. The SNOT-22 score diminished from 51.8 (48.7–55.0) pre-operatively to 33.0 (29.2–36.8) at 6 months. 64% achieved a clinically important improvement in the SNOT-22. SF-36 scores improved statistically significantly in all domains except “Role Emotional”. The VAS score halved from 68 (65–71) to 34 (29–39) at 6 months post-operatively. A pre-operative SNOT-22 score >20 implied a greater chance of score improvement after 6 months. A multivariate model identified individual items associated with SNOT-22. Further, patients that had <12 months of sinus disease derived greatest benefit. CRS-related absenteeism dropped from 8–14 days to 1–7 days 12 months after ESS. Conclusions: This prospective study showed that ESS significantly improved the HRQOL and decreased absenteeism of patients with CRSw/sNP. Shorter duration of disease and “Need to blow nose” and “Blockage/congestion of nose” of SNOT-22 were identified as predictive factors for good surgical outcome.

Nasal closure for severe hereditary haemorrhagic telangiectasia in 100 patients. The Lund modification of the Young's procedure: a 22-year experience.

Abstract: Introduction Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease characterized by recurrent epistaxis, mucocutaneous telangiectasia and visceral arteriovenous malformations. The nosebleeds can be life-threatening and in these circumstances, radical treatment is required. Methods Since 1994, closure of the nose has been undertaken to prevent severe nasal bleeding in patients meeting specific selection criteria. Outcome data collected on this cohort pre- and post-operatively is available for analysis. Results From a cohort of 515 HHT patients, 100 have undergone nasal closure, bilateral ab initio in 81%. Fifty patients completed pre- and post-operative epistaxis severity questionnaires and provided information on post-operative problems and 28 completed a Glasgow Benefit Inventory (GBI). Overall most patients derived significant benefit from the procedure with complete cessation of nasal bleeding in 94%, a highly significant improvement in the epistaxis score and a mean GBI score of 53.4. Loss of smell and taste was the most frequent post-operative complaint. Conclusion HHT can be associated with life-threatening epistaxis significantly affecting patients quality of life. Permanent prevention of airflow is associated with complete or near-total cessation of epistaxis in the majority of patients.

Allergic rhinitis severity can be assessed using a visual analogue scale in mild, moderate and severe.

Abstract: Background Allergic rhinitis is a global healthcare problem due to its high prevalence, impact on individuals and socioeconomic burden for the nations. Allergic rhinitis severity evaluation is the key to a correct treatment, prevention of comorbidities and improving the quality of life of patients. This evaluation should be made with a simple, easy, fast but accurate and reliable methodology, both in a primary care and specialist setting. The visual analogue scale (VAS) meets all requirements to be the ideal tool to assess allergic rhinitis severity and has already been validated by using a single cut-off point, but this classification in two degrees of severity suffer from not allocating the patients uniformly and from giving a blind interval to classify the patients when the score is between 5 to 6 cm. Methodology The main objective of our study is to describe the optimal cut-off points by using a VAS to discriminate between three degrees of allergic rhinitis severity (mild, moderate, and severe) following the ARIA modified severity criteria that has been previously validated. Sensitivity, specificity, positive and negative predictive values just like receiver operating characteristic curves were used to select the best cut-off values. Results In a cross-sectional multicentre study with 3,572 patients included we have found that VAS has a significant correlation with nasal symptom score and quality of life and that the best cut-off points to differentiate between mild, moderate an severe allergic rhinitis are a VAS score of 4 and 7, respectively. Conclusions Allergic rhinitis severity could be assessed in three degrees by using VAS in a simple, easy, and accurate method.

Allergy rhinitis: similarities and differences between children and adults.

Abstract: Background Allergic rhinitis (AR) is a highly prevalent disease worldwide. Although a number of studies have described AR, no studies compared children and adult AR populations. The objective was to compare the AR characteristics between two AR cohorts of children and adults. Methods Two AR cohorts (children and adults) from Spain were studied through observational cross-sectional multicentre studies. AR was classified based on classical (allergen exposure), original (o-ARIA), and modified (m-ARIA) ARIA criteria. AR was evaluated by Total 4-Symptoms Score (T4SS), and disease severity by Visual Analogue Scale (VAS, 0-100 mm). AR comorbidities were also evaluated. Results A total of 5,405 patients (1,275 children, 4,130 adults) were studied. According to symptoms duration, intermittent AR was more frequent in children than in adults. Using o-ARIA severity, more children than adults had moderate/severe AR while, using m-ARIA, more children than adults had severe AR. T4SS was higher in adults than in children. Moreover, VAS was also higher in adults than in children. In addition, asthma atopic dermatitis and conjunctivitis were more associated to children than adults with AR, the frequency of this comorbidities increasing according to higher severity. Conclusions AR in children was more intermittent, severe, with less symptoms but with more comorbidities than in adults. These results suggest AR has similarities but also significant differences between children and adults.

Sleep quality improves with endoscopic sinus surgery in patients with chronic rhinosinusitis and nasal polyposis.

Abstract: BACKGROUND: Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) is a chronic disease that has a major impact on generic and disease-specific quality of life. Little is known about the influence of CRSwNP on sleep and what effect surgery for CRSwNP has on sleep quality. The aim of the study was to investigate sleep quality in patients with CRSwNP before and after endoscopic surgery.METHODOLOGY: Forty-two patients filled out four validated sleep questionnaires and one sino/nasal, disease specific quality of life questionnaire before surgery and three months later. A healthy control group filled out the same questionnaires at baseline and after three months.RESULTS: An impact on sleep patterns was found in all sleep questionnaires and surgery clearly improved the quality of sleep. The Sino-nasal outcome test sum score decreased from median 51,5 to 26,5. Epworth sleepiness scale showed a decline in score from score 7.5 to 6.0. Surgery also reduced the risk for obstructive sleep apnoea in 13 patients evaluated by the Berlin Questionnaire and Multivariable Apnea Prediction Index.CONCLUSIONS: Patients with CRSwNP had impaired sleep quality, daytime sleepiness, nasal patency, and risk for sleep apnea, all of which improved after corrective surgery. (Less)

Assessment of efficacy and safety of the herbal medicinal product BNO 1016 in chronic rhinosinusitis

Abstract: Background The objective of this clinical trial (CRS-02) was to assess the efficacy, safety and tolerability of two dosages of the herbal medicinal product BNO 1016 (Sinupret extract) in patients with chronic rhinosinusitis (CRS). Methodology 929 patients suffering from CRS were enrolled in this randomised placebo-controlled trial with a treatment period of 12 weeks. The primary endpoint was the mean Major Symptom Score (MSS) in week 8 and week 12 compared to placebo. Secondary endpoints included further MSS related parameters and responder rates over time. Pharmacoeconomic endpoints were also analysed. Finally, safety and tolerability were evaluated. Results Sinupret extract was not superior over placebo regarding the primary endpoint. However, the results of the secondary endpoints showed a clear trend towards superior efficacy. Therefore, additional post-hoc sensitivity analyses were performed in patients with a baseline MSS over 9 and persistence of disease more than 1 year diagnosed by specialists in otorhinolaryngology. Those patients significantly benefited from Sinupret extract. Therapy was superior for the primary endpoint analysis. Patients were less impaired with respect to work and daily activities. A good safety and tolerability of Sinupret extract was assured in all patients. Conclusions Sinupret extract can safely be administered in patients with CRS. Although the primary endpoint of the study was not significant, a post-hoc subgroup analysis in patients whose disease was diagnosed by a specialist revealed a pronounced treatment effect. Effects in that subgroup were even stronger with longer disease persistence and stronger severity.

The risk of osteoporosis in oral steroid treatment for nasal polyposis: a systematic review.

Abstract: Background Systemic glucocorticoids are often used in the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), and osteoporosis is a well-known complication to steroid treatment, associated with significant morbidity Nevertheless, the burden of steroid induced osteoporosis is unknown in patients with CRSwNP We aimed to assess the risk of acquiring osteoporosis caused by oral steroids in patients with CRSwNP, and provide recommendations on future research and guidelines Methodology Cochrane Review Database, EMBASE, Ovid Medline, and PubMed were searched for studies including adult patients with CRSwNP treated with oral steroids Outcomes were Bone Mineral Density (BMD) and prevalence of fractures in relation to dose and duration of oral steroids In addition, we reviewed general guidelines for treatment with oral steroids Results We identified two studies (n=243) that met the inclusion criteria Doses and durations of oral steroids were over 5 mg/day for more than 3 months and 1 mg/kg body weight/day for 6 to 10 days for 4 or more courses/year The prevalence of low bone mass was 39% and 61%, respectively It was not possible to quantify the overall risk of osteoporosis induced by oral steroids from the studies No studies evaluated prevalence of fracture Conclusions Registry studies and randomized controlled trials would be needed to assess the risk of osteoporosis in CRSwNP patients and future guidelines should include recommendations regarding preventive treatment and recommendations on doses and durations of oral steroids

Sublingual immunotherapy for allergic rhinitis: subjective versus objective tools to evaluate its success.

Abstract: Background Biomarkers that enable objective evaluation of the clinical effects of immunotherapy for allergic rhinitis have yet to be identified. Methods This study included 40 patients who were enrolled in a large randomized, double-blind, placebo-controlled, multicenter study examining the efficacy of sublingual immunotherapy (SLIT) using Japanese cedar (JC) pollen extract during two consecutive pollen seasons from 2010 to 2012. Based on changes in total nasal symptom medication score, patients in the SLIT and placebo groups were subdivided into two subgroups: good responders and poor responders. The levels of JC pollen-specific IL-10+Foxp3+ cells and specific Th2 cytokine-producing cells were measured and the association with the efficacy of SLIT was analysed. Results The total nasal symptom medication score was significantly lower in the SLIT group compared with the placebo group. The number of JC pollen-specific Th2 cytokine-producing cells increased during the pollen season in the placebo group and in poor responders in the SLIT group; however, the increases were inhibited in the good responders in the SLIT group. The number of JC pollen-specific IL-10+Foxp3+ cells increased only in these good responders. Conclusions Changes in levels of allergen-specific Th2 cytokine-producing cells and IL-10+Foxp3+ cells could be objective biomarkers for SLIT.

Postoperative long-term morbidity of extended endoscopic maxillectomy for inverted papilloma.

Abstract: BACKGROUND Extended endoscopic maxillectomy (Sturmann-Canfield procedure) allows full visualization of the maxillary sinus by sectioning the lacrimal duct and removing the medial part of the anterior maxillary wall. The aim of this study is to evaluate the morbidity of Sturmann-Canfield procedure in patients treated for inverted papilloma. METHODOLOGY The clinical records of all patients treated with a Sturmann-Canfield procedure for inverted papilloma from October 2000 to September 2015 at two teaching hospitals were reviewed. All patients were evaluated by nasal endoscopy and lacrimal system patency was assessed. Pre-maxillary cutaneous sensitivity was tested with a Semmes-Weinstein aesthesiometer and thermic stimulation. The SNOT-22 questionnaire was administered. Patients were also asked to report any other post-surgical complaints. RESULTS Fifty-nine patients were identified. Mean follow-up after surgery was 66.3 months. Mean SNOT-22 score was 5.94 (range 0-20); the majority of patients (86%) had a SNOT-22 symptom score of 3 or lower. Mucocoele occurred in 3 (5%) cases. Lacrimal pathway obstruction was observed in 7 (12%) patients. Fourteen (24%) patients complained of paraesthesia in the malar area; hypoesthesia was present in only 5 (8%) cases. Hypoesthesia in the region innervated by the anterior superior alveolar nerve was detected in 17 (29%) patients. One patient reported a slight depression of paralateronasal soft tissues. CONCLUSIONS Although nasal function outcomes and the results from SNOT-22 questionnaires were favourable, a high rate of neurologic and lacrimal complications was observed. Potential morbidity of the intervention, including the possibility of negative aesthetic sequelae, should be discussed during preoperative counselling.

Toll-like receptor activation by sino-nasal mucus in chronic rhinosinusitis.

Abstract: BACKGROUND The sino-nasal disease chronic rhinosinusitis (CRS) is primarily an inflammatory condition that manifests in several ways. However, the aetiology of this complex disease is poorly understood. The aim of this study was to explore the association between toll-like receptor (TLR) activation, host immune response and sino-nasal mucus in healthy and diseased patients. METHODS The activation of TLR2/1 and TLR4 by sino-nasal mucus from 26 CRS patients and 10 healthy controls was measured. In addition, 7 inflammatory cytokines, bacterial community composition and bacterial abundance within the sino-nasal mucus were measured using molecular and diagnostic tools. RESULTS TLR activity was observed in 9/36 samples, including 2 healthy controls. There was a strong, positive correlation between members of the Gammaproteobacteria (Haemophilus, Enterobacter, Pseudomonas) and TLR2/1 and TLR4 activity. Bacterial abundance and cytokine (tumour necrosis factor) abundance were also positively correlated with TLR activity. CONCLUSIONS These findings suggest that a small proportion (20-30%) of individuals in each sub-group are more predisposed to TLR activity, which may be related to bacterial composition, diversity and abundance in the sinuses.

Predictors of unanticipated admission within 30 days of outpatient sinonasal surgery.

Abstract: OBJECTIVES To identify predictive factors of readmission after day-case rhinologic surgery. METHODS A 2-year retrospective chart review of patients scheduled for ambulatory sinonasal surgery in a tertiary medical center was conducted. The operating room and the anesthetic files were screened to identify demographic data, types of procedure, comorbidities and post-operative complications. RESULTS From January 2014 to January 2016, 924 outpatient sinonasal procedures were identified. The overall readmission rate within the 30-postoperative days was 5.1% (2.9% for overnight hospital stay, 2.2% for unplanned post procedure visit to the hospital via the emergency room, or directly to the surgical unit within 30 days of discharge). Age at least 50 years, surgical duration at least 80 min, endoscopic sinus surgery procedures and postoperative nasal packing were identified as negative predictive factors of readmission. CONCLUSION Careful scheduling of those higher-risk patients undergoing sinonasal surgery and appropriate postoperative observation should be implemented to improve healthcare quality in an outpatient setting.

Gastro-oesophageal reflux in patients with chronic rhino-sinusitis investigated with multichannel impedance - pH monitoring.

Abstract: Introduction The pathophysiology of chronic rhinosinusitis (CRS) is unclear. It has been discussed for decades whether gastro-oesophageal reflux (GOR) may be a contributing factor for some patients. The aim of the present study was to evaluate the level of GOR in an unselected group of patients with CRS using multichannel impedance-pH monitoring. Methods Consecutive patients with CRS diagnosed using the EPOS2012 criteria, completed questionnaires on GOR symptoms and were offered 24-h multichannel intraluminal impedance (MII)-pH monitoring. The results were compared with a group of healthy controls. Results Forty-six patients completed MII-pH-monitoring and were compared with 45 control subjects, with comparable age and gender distributions. The median number of reflux episodes in the patients was 56.5 compared with 33 in controls, while, the numbers of proximal reflux episodes was 27.5 versus 3, respectively. Thirty nine patients had abnormal pH-impedance recordings compared with five controls. Conclusion The CRS patients had significantly higher incidences of gastro-oesophageal reflux compared with asymptomatic controls. The results of this study suggest that GOR may be a causative or contributing factor of CRS.

Quality of life after primary septorhinoplasty in deviated- and non-deviated nose measured with ROE, FROI-17 and SF-36.

Abstract: Background Quality of life measurements are gaining in importance. The present study was conducted with the aim to compare patient satisfaction after septorhinoplasty according to their preoperative nasal deformity. Methods The patients completed two disease-specific questionnaires before their surgery: the Functional Rhinoplasty Outcome Inventory (FROI-17), the Rhinoplasty Outcome Evaluation (ROE) and as a general instrument, the Short Form 36 Health Survey (SF-36). The second measurement was taken during an outpatient examination 12 months after their primary septorhinoplasty. Patients were grouped in nasal axis deviation (NAD), nasal hump deformity (NHD) and NAD plus NHD. Additionally the patients with preoperative NAD and NAD+NHD were combined as deviated nose and compared to the non-deviation group. Results One hundred and two patients (51 male and 51 female) underwent primary septorhinoplasty. The ROE- and the FROI-17 overall score including all three subgroups showed significant postoperative improvements. Regarding the SF-36, the postoperative score improved significantly only in two scales (role-functioning physical and mental health). Looking at the the different QoL questionnaires, there were significant postoperative differences in regards to deviated versus non-deviated nose in the FROI-17 overall- and FROI-17 subscores (nasal and general symptoms) and in three scales of the SF-36 (vitality, social functioning, role-functioning emotional), showing a greater postoperative satisfaction in the deviated-nose patient. Conclusion Patients with and without nasal deviation showed improved QoL after their surgery, as measured with the ROE, the FROI-17 and the SF-36. The patients with a nasal deviation showed a significantly better outcome, as measured with the FROI-17, in comparison with the non-deviated group.

Comparison of different endoscopic scoring systems in patients with chronic rhinosinusitis: reliability, validity, responsiveness and correlation.

Abstract: Objectives Previous studies have proposed various endoscopic scoring systems to assess disease severity of patients with chronic rhinosinusitis (CRS). However, those assessments have not been validated. This study was designed to assess the Modified Lund - Kennedy (MLK) and the discharge, inflammation, and polyps/oedema (DIP) endoscopic scoring systems in patients with CRS. Methods A prospective study including 144 patients who underwent functional endoscopic sinus surgery (FESS). All participants were asked to finish SNOT-22, Lund-Mackay CT score and endoscopic examination evaluations before surgery and at 6 months after surgery. Endoscopic examination videos were evaluated using 3 scoring systems by two blinded rhinologists. The scores were compared in terms of responsiveness, validity, reliability and correlation with other scores. Results The MLK and DIP endoscopic scoring systems showed high test-retest reliability and inter-rater reliability. All endoscopic scoring systems showed significant differences between the scores recorded at each time point (all P lower than 0.90 when compared with the Lund - Kennedy (LK) endoscopic scoring system and showed a statistically significant difference in discriminant validity between symptomless and symptomatic cases. The MLK and DIP systems showed high correlations with other subject assessments and no correlation with SNOT-22. Conclusion MLK and DIP exhibit substantial responsiveness, validity and reliability. MLK and DIP may be well suited for clinical and research use.

Altered expression and signalling of EP2 receptor in nasal polyps of AERD patients: role in inflammation and remodelling.

Abstract: Background Down-regulation of the E-prostanoid (EP)2 receptor has been reported in aspirin exacerbated respiratory disease (AERD). We aimed to evaluate the expression and activation of EP receptors in AERD and their role in prostaglandin (PG) E2 signalling. Methods Samples were obtained from nasal mucosa of control subjects (NM-C, n=7) and from nasal polyps of AERD patients (NP-AERD, n=7). Expression of EP1-4 was assessed at baseline. Fibroblasts were stimulated with receptor agonists to measure cAMP levels, cell proliferation and granulocyte-macrophage colony-stimulating factor (GM-CSF) release. Results NM-C and NP-AERD samples and fibroblasts expressed EP2, EP3 and EP4 at baseline. Lower expression of EP2 and higher expression of EP4 was observed in NP-AERD compared with NM-C. Stimulation with PGE2 and butaprost caused a higher increase in cAMP in NM-C than in NP-AERD. On the contrary, CAY10598 produced a higher production of cAMP in NP-AERD compared with NM-C. The anti-proliferative effect of PGE2 and butaprost was lower in NP-AERD than in NM-C fibroblasts. Similarly, the capacity of PGE2 and butaprost to inhibit GM-CSF release was lower in NP-AERD than in NM-C. Conclusions The altered expression of EP2 in AERD may contribute to reduce the capacity of PGE2 to mediate anti-proliferative and anti-inflammatory effects.

The role of endothelin-1 and endothelin receptor antagonists in allergic rhinitis inflammation: ovalbumin-induced rat model.

Abstract: Objective Desloratadine is a biologically active metabolite of loratadine which is indicated for the treatment of allergic rhinitis. Bosentan is a dual endothelin receptor antagonist used to treatment of pulmonary artery hypertension (PAH). In this study, we aimed to determine the role of endothelins in allergic rhinitis (AR) and the effects of endothelin receptor antagonists in AR rat models through comparison with desloratadine. Methods In total, 20 adult Sprague-Dawley rats were used in this study. An ovalbumin-induced allergic rhinitis model was formed in three study groups except for the control group. Bosentan (100 mg/kg/day) was given to the bosentan-treated group for 7 days and desloratadine (10 mg/kg/day) was administered to the antihistaminic-treated group for 7 days. Nasal symptom scorings and histopathological examinations of the nasal tissues were carried out. Serum IgE levels and ET-1 and TNF-alpha mRNA expression levels were analysed. Between group comparisons for nasal symptoms, histopathological analysis, and molecular analyses were performed with a one-way ANOVA and Duncans multiple comparison tests. Significance was accepted at p smaller than 0.05. Results Bosentan inhibited nasal symptom more significantly than desloratadine. The IgE level, ET-1 and TNF-alpha mRNA expression levels statistically increased in the allergic rhinitis group when compared to other groups. Conversely, the bosentan-treatment group showed a significant recovery from the same parameters. The deterioration in histopathological parameters reached the highest levels in the allergic rhinitis group. The histopathological findings were close to those of the control group in the bosentan and antihistaminic-treated group. Conclusions ET-1 is one of the mediators that impact AR development and ET-1 antagonists can be useful for symptom control and for decreasing allergic inflammation in AR patients.

The persistence of intracellular Staphylococcus aureus in the sinuses: a longitudinal study.

Abstract: Background Staphylococcus aureus (S. aureus) can reside within the sinonasal mucosa in chronic rhinosinusitis patients and causes recurrent infections. Within the host cell, S. aureus can evade host immune detection enabling its own survival. We hypothesise that S. aureus can persist within the sinonasal epithelium for a prolonged period without immune activation. Methodology Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) undergoing two sinus surgeries were included. Immunohistochemistry and Haematoxylin and Eosin stains were used to determine intracellular S. aureus (ICSA) status and inflammatory cell count, respectively. One-way ANOVA and paired t-tests were performed for comparison between ICSA subgroups and within each subgroup, respectively. Results Histopathological specimens from 34 patients (68 procedures) were included. ICSA positivity (ICSA+) was seen in 43 specimens (63.2%) from 26 (76%) patients. 18 (52.9%) of those were ICSA+ in both operations while 8 (23.5%) patients were ICSA+ in only one of the operations. 8 (23.5%) patients were ICSA negative in both operations. There was no difference in the number of eosinophils, lymphocyte and neutrophils between ICSA subgroups. Conclusions This study demonstrated that S. aureus is found intracellularly within CRSwNP tissue at multiple time points without an increase in the number of eosinophils, lymphocytes and neutrophils. This finding supports our hypothesis that ICSA is able to escape from host detection and resides within the sinonasal mucosa despite intense treatment.

Clinimetric properties of the Glasgow Health Status Inventory, Glasgow Benefit Inventory, Peak Nasal Inspiratory Flow, and 4-Phase Rhinomanometry in adults with nasal obstruction

Abstract: BACKGROUND: The validity of many measurement instruments frequently used in rhinology is unknown. This study describes clinimetric properties of well-known subjective and objective outcomes, i.e., the Glasgow Health Status Inventory, Glasgow Benefit Inventory, Peak Nasal Inspiratory Flow, and 4-Phase Rhinomanometry, in adults with nasal obstruction. METHODOLOGY: Construct validity and responsiveness were determined in 111 patients. Inter-rater and intra-rater reliability were analysed in 30 patients. We assessed content validity by interviewing patients and ENT-surgeons; construct validity by comparing hypothesised associations to calculated correlations between the outcomes; inter-rater reliability by having two researchers perform objective measurements in the same patients; intra-rater reliability by having one rater administer all instruments twice within a two-week interval; and responsiveness by comparing patients scores at baseline and three months after septoplasty or non-surgical management. RESULTS: All instruments demonstrated adequate content validity, inter-, and intra-rater reliability. Analyses of construct validity yielded low Pearsons correlations between the subjective and objective outcomes. Comparing septoplasty to non-surgical management, only the Glasgow Health Status Inventory scores were different between the two groups (mean difference 10.4, 95% CI 6.9 - 13.9). CONCLUSION: All measurement instruments scored appropriately on content validity and reliability, but only the subjective GHSI scored well on responsiveness.

Risk factors for epistaxis in patients followed in general practices in Germany.

Abstract: Background The goal of the present study was to analyze the risk factors for epistaxis in patients followed in general practices in Germany. Methods The current study sample included patients aged 18 years or older who received a first epistaxis diagnosis between January 2012 and December 2016 (index date). Epistaxis patients and controls without epistaxis were matched (1:1) on the basis of age, gender, insurance status and physician. Results A total of 16,801 patients with epistaxis and 16,801 control subjects were included in this study. Of the subjects, 53.2% were men, and the mean age was 59.6 years (SD=21.2 years). Epistaxis was found to be positively associated with hypertension, obesity, chronic sinusitis, other disorders of the nose and nasal sinuses, anxiety disorder, and adjustment disorder (ORs ranging from 1.13 to 1.44). Epistaxis was also associated with the prescription of vitamin K antagonists, preparations from the heparin group, platelet aggregation inhibitors excluding heparin, direct thrombin inhibitors, direct factor Xa inhibitors, other antithrombotic agents, selective serotonin reuptake inhibitors and nasal steroids (ORs ranging from 1.15 to 3.55). Conclusions Overall, epistaxis risk is increased by multiple medical and psychiatric disorders. Several antithrombotic and nasal steroid therapies are also associated with this risk.