IL-17 Promotes Nitric Oxide Production in Non-Small-Cell Lung Cancer.

INTRODUCTION: Lung cancer is the second most frequent malignancy worldwide, but its aetiology is still unclear. Inflammatory cytokines and Th cells, including Th17, are now emerging as being involved in NSCLC pathways, thus postulating a role of IL-17 in tumour angiogenesis by stimulating the vascular endothelial growth factor and the release of nitric oxide. Despite the fact that many biomarkers are used for chest malignancy diagnosis, data on FeNO levels and inflammatory cytokines in NSCLC are still few. Our study aimed to evaluate the relationship between pulmonary nitric oxide production and VEGF and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. METHODS: FeNO measurement and lung function tests were performed in both patients affected by NCSLC and controls; EBC samples were also taken, and Th1 (IL-1, IL-6, IL-12, IFN-g, TNF-a), Th17 (IL-17, IL-23) and Th2 (IL-4, IL-5, IL-13) related cytokines were measured. RESULTS: Th1 and Th17-related cytokines in EBC, except for IFN-gamma and TNF-alpha, were significantly higher in patients than in healthy controls, whereas no differences were seen for Th2-related cytokines. FeNO at the flow rate of 50 mL/s, JawNO and CalvNO levels were significantly higher in patients affected by NSCLC compared to controls. Significant correlations were found between FeNO 50 mL/s and IL-17, IL-1 and VEGF. JawNO levels positively correlated with IL-6, IL-17 and VEGF. No correlations were found between FeNO and Th2-related cytokines. CONCLUSION: This is the first report assessing a relationship between FeNO levels and Th17-related cytokines in the EBC of patients affected by early-stage NSCLC. IL-17, which could promote angiogenesis through the VEGF pathway, might be indirectly responsible for the increased lung production of NO in patients with NSCLC.

Thymic stromal lymphopoietin in human pancreatic ductal adenocarcinoma: expression and prognostic significance.

Thymic stromal lymphopoietin (TSLP) has emerged as an important, but contradictory, player conditioning tumor growth. In certain contexts, by driving T helper (h) 2 responses via tumor-associated OX40 Ligand (OX40L)+ dendritic cells (DCs), TSLP may play a pro-tumorigenic role. The study elucidates the importance of TSPL in pancreatic ductal adenocarcinoma (PDAC), by analyzing: i) TSLP levels in PDAC cell-line supernatants and plasma from patients with locally-advanced/metastatic PDAC, pre- and post-treatment with different chemotherapeutic protocols, in comparison with healthy donors; ii) TSLP and OX40L expression in PDAC and normal pancreatic tissues, by immunohistochemistry; iii) OX40L expression on ex vivo-generated normal DCs in the presence of tumor-derived TSLP, by flow cytometry; iv) clinical relevance in terms of diagnostic and prognostic value and influence on treatment modality and response. Some PDAC cell lines, such as BxPC-3, expressed both TSLP mRNA and protein. Normal DCs, generated ex vivo in the presence of TSLP-rich-cell supernatants, displayed increased expression of OX40L, reduced by the addition of a neutralizing anti-TSLP polyclonal antibody. OX40L+ cells were detected in pancreatic tumor inflammatory infiltrates. Abnormally elevated TSLP levels were detected in situ in tumor cells and, systemically, in locally-advanced/metastatic PDAC patients. Of the chemotherapeutic protocols applied, gemcitabine plus oxaliplatin (GEMOX) significantly increased circulating TSLP levels. Elevated plasma TSLP concentration was associated with shorter overall survival and increased risk of poor outcome. Plasma TSLP measurement successfully discriminated PDAC patients from healthy controls. These data show that TSLP secreted by pancreatic cancer cells may directly impact PDAC biology and patient outcome.

Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and quality-of-life impacting disorder, with an underlying immunological mechanism similar to other conditions such as eosinophilic asthma or atopic eczema. Areas covered: This review article summarizes the most recent evidence on the main immunological mechanisms involved in the pathogenesis and the perpetuation of CRSwNP, with a particular focus on the key role of epithelium-derived inflammation as a consequence of the interaction with the airborne environment. Expert commentary: The increase in knowledge of the immunology of CRSwNP leads to the development of therapeutical strategies based upon the use of biologic agents that, according to a personalized and precision medicine approach, will provide each single patient with the most suitable immunological treatment.

Basophil Membrane Expression of Epithelial Cytokine Receptors in Patients with Severe Asthma.

BACKGROUND: Severe asthma is a heterogeneous disease, which is characterized by airway damage and remodeling. All triggers of asthma, such as allergens, bacteria, viruses, and pollutants, interact with the airway epithelial cells, which drive the airway inflammatory response through the release of cytokines, particularly IL-25, IL-33, and thymic stromal lymphopoietin (TSLP). OBJECTIVES AND METHODS: To investigate whether the expression of the IL-25, IL-33, and TSLP receptors on the basophil membrane are associated with asthma severity. Twenty-six patients with asthma (11 severe and 15 moderate/mild) and 10 healthy subjects (controls) were enrolled in the study. The results of the basophil activation test and flow cytometry analysis were assessed to investigate basophil membrane expression of IL-25, TSLP, and IL-33 receptors before and after IgE stimulation. RESULTS: IL-25 and IL-33 receptor expression on the basophil membrane at baseline were significantly higher in patients with severe asthma than in those with mild/moderate asthma or healthy subjects, independent of atopy, eosinophilia, asthma control, and exacerbation frequency. Following IgE stimulation, a significantly higher increase in the IL-25 and IL-33 receptors was observed in mild/moderate versus severe asthma. CONCLUSIONS: The high expression of the IL-25 and IL-33 receptors on the basophil membrane of patients with severe asthma indicates an overstimulation of basophils by these cytokines in severe asthma. This finding can possibly be used as a biomarker of asthma severity.

The utility of blood neuroendocrine gene transcript measurement in the diagnosis of bronchopulmonary neuroendocrine tumours and as a tool to evaluate surgical resection and disease progression.

OBJECTIVES: The management of bronchopulmonary neuroendocrine tumours (BPNETs) is difficult, since imaging, histology and biomarkers have a limited value in diagnosis, predicting outcome and defining therapeutic efficacy. We evaluated a NET multigene blood test (NETest) to diagnose BPNETs, assess disease status and evaluate surgical resection. METHODS: (i) Diagnostic cohort: BP carcinoids (n = 118)-typical carcinoid, n = 67 and atypical carcinoid, n = 51; other lung NEN (large-cell neuroendocrine carcinoma and small-cell lung carcinoma, n = 13); adenocarcinoma, (n = 26); squamous cell carcinoma (n = 23); controls (n = 90) and chronic obstructive pulmonary disease (n = 18). (ii) Surgical cohort, n = 28: BP carcinoids (n = 16: typical carcinoid 12; atypical carcinoid 4); large-cell neuroendocrine carcinoma, n = 3; lung adenocarcinoma, n = 8 and squamous cell carcinoma, n = 1. Blood sampling was performed presurgery and 30 days post-surgery. Transcript levels measured by quantitative polymerase chain reaction were calculated as activity scores (0-100% scale: normal < 14%) and compared with chromogranin A (enzyme-linked immunosorbent assay; normal <109 ng/ml). RESULTS: NETest was significantly elevated in carcinoids (48.7 ± 27%) versus controls (6 ± 6%, P < 0.001) with metrics: sensitivity 93%, specificity 89%, positive predictive value 92% and negative predictive value 91%. NETest differentiated progressive disease (73 ± 22%) from stable disease (36 ± 19%, P < 0.001) and R0 resections (10 ± 5%, P < 0.001, area under the curve: 0.98). Levels in chronic obstructive pulmonary disease and lung cancers were 18-24% while elevated in small-cell lung carcinoma/large-cell neuroendocrine carcinoma (59 ± 10%). In BPNETs on postoperative Day 30, NETest decreased by 60% (P < 0.001). Chromogranin A was elevated in only 40% of carcinoids and not altered by surgery. CONCLUSIONS: Blood NET gene levels accurately identified BPNETs (100%) and differentiated these from controls, benign and malignant lung disease. Progressive disease could be identified and surgical resection verified. Chromogranin A had no clinical utility. Monitoring NET transcript levels in blood will facilitate management by detecting residual tumour and identifying progressive disease.

Asthmatic Patients with Vitamin D Deficiency have Decreased Exacerbations after Vitamin Replacement.

BACKGROUND: Intervention studies with vitamin D in asthma are inconclusive for several reasons, such as inadequate dosing or duration of supplementation or uncontrolled baseline vitamin D status. Our aim was to evaluate the benefit of long term vitamin D add-on in asthmatic patients with actual vitamin D deficiency, that is a serum 25-hydroxy vitamin D (25-OHD ) below 20 ng/mL. METHODS: Serum 25-OHD, asthma exacerbations, spirometry and inhaled corticosteroids (CS) dose were evaluated in a cohort of 119 asthmatic patients. Patients with deficiency were evaluated again after one year vitamin supplementation. RESULTS: 25-OHD was low in 111 patients and was negatively related to exacerbations (p < 0.001), inhaled CS dose (p = 0.008) and asthma severity (p = 0.001). Deficiency was found in 90 patients, 55 of whom took the supplement regularly for one year, while 24 discontinued the study and 11 were not adherent. Patients with vitamin D deficiency after 12 months supplementation showed significant decrease of exacerbations (from 2.6 ± 1.2 to 1.6 ± 1.1, p < 0.001), circulating eosinophils (from 395 ± 330 to 272 ± 212 106/L, p < 0.001), and need of oral CS courses (from 35 to 20, p = 0.007) and improvement of airway obstruction. CONCLUSIONS: Asthma exacerbations are favored by vitamin D deficiency and decrease after long-term vitamin D replacement. Patients who are vitamin D deficient benefit from vitamin D supplementation.

Epidermal growth factor receptor mutations are linked to skip N2 lymph node metastasis in resected non-small-cell lung cancer adenocarcinomas.

Objectives: The impact of skip N2 metastases (i.e. N2 lymph node metastases without N1) on survival in surgically resected non-small lung cancer remains an intriguing and rarely investigated topic. The goal of our study was to elucidate (i) skip N2 influence on overall survival (OS) and time to recurrence (TTR) in patients with resected lung adenocarcinoma and (ii) its link with epidermal growth factor receptor ( EGFR ) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations. Methods: A retrospective analysis of 279 consecutive patients with lung pN2 adenocarcinoma, operated in two institutions between 2003 and 2013, was conducted. OS and TTR were calculated using the Kaplan-Meier method. Crude and multivariable-adjusted comparisons by skip N2 for OS and TTR were performed using the Cox method with shared frailty (accounting for the within-centre correlation). Associations between skip N2 metastasis, clinicopathological characteristics and EGFR and KRAS mutations were investigated using the Fisher exact test and Cramér's V -test. Results: The mean age at the time of surgery was 63 years (±12), and the median follow-up time was 36 months (min 3; max 101). Skip N2 was observed in 54 patients (19%). EGFR mutations were observed in 38 patients (14%); KRAS mutations were seen in 86 patients (31%). Patients with skip N2 metastasis were predominantly non-smokers ( P = 0.001), underwent segmentectomy or limited resections ( P = 0.004) and were not submitted to adjuvant therapy ( P = 0.022). Moreover, there was a correlation between EGFR mutations and skip N2 (Cramér's V : 0.25, P < 0.001). Indeed, EGFR mutations were significantly more frequent in skip N2 tumours (33%) compared with non-skip tumours (10%), P < 0.001. No correlation between skip N2 and KRAS mutations was observed (Cramér's V : 0.05, P = 0.46). The multivariable-adjusted model showed a significant skip N2 protective effect on OS (hazard ratio, HR 0.503; P = 0.014; 95% confidence interval, CI: 0.291-0.8704) but not on TTR (HR 0.788; P = 0.446; 95% CI: 0.427-1.454). Conclusions: In our series, lung adenocarcinoma skip N2 metastasis demonstrated a favourable prognosis. The presence of EGFR mutations could have significance in the better survival and in the specific anatomic pathway of lymphatic metastases exhibited by skip N2 tumours.

Nasal and Tracheal Cytological Changes After Total Laryngectomy in Long-Term Survivors.

OBJECTIVE: Complete separation of upper and lower respiratory tract after total laryngectomy results in permanent effects on nasal cavities and tracheo-bronchial airways. Aim of this study is evaluating nasal and tracheal cytological alterations of mucosa in laryngectomy long-term survivors, analyzing the feasibility of scraping for cytological examination of tracheal mucosa. METHODS: Twenty-five laryngectomy patients underwent symptoms' evaluation, endoscopic fiber optic examination, prick tests, and nasal and tracheal scraping for cytological exam. Twenty-five healthy subjects underwent the same assessment, except for tracheal scraping. Eleven laryngectomy patients accepted inferior turbinate biopsy for histological examination. RESULTS: Nasal cytological analysis demonstrated mucous cell metaplasia in 20% of laryngectomized patients, but it was absent in all healthy subjects; no squamous cell metaplasia was found in both groups. In 15 patients (60%), bacteria were present, without inflammatory infiltrate. Tracheal cytological analysis demonstrated a quite high rate of squamous cell metaplasia (24%), neutrophilic infiltrate (32%), and presence of bacteria (40%). Histological examination of inferior turbinate showed submucosal stromal fibrosis in all patients and submucosal inflammatory infiltrate in 1 case (9%). CONCLUSION: Nasal cavities and trachea of laryngectomy patients undergo long-term cytological and histological changes of mucosa and submucosa, probably due to airflow modifications.

Vitamin D deficiency and exercise-induced laryngospasm in young competitive rowers.

Exercise-induced dyspnea is common among adolescents and young adults and often originates from exercise-induced bronchoconstriction (EIB). Sometimes, dyspnea corresponds to exercise-induced laryngospasm (EILO), which is a paradoxical decrease in supraglottic/glottic area. Vitamin D deficiency, which occurs frequently at northern latitudes, might favor laryngospasm by impairing calcium transport and slowing striate muscle relaxation. The aim of this study was to evaluate whether vitamin D status has an influence on bronchial and laryngeal responses to exercise in young, healthy athletes. EIB and EILO were investigated during winter in 37 healthy competitive rowers (24 males; age range 13-25 years), using the eucapnic voluntary hyperventilation test (EVH). EIB was diagnosed when forced expiratory volume in the first second decreased by 10%, EILO when maximum mid-inspiratory flow (MIF50) decreased by 20%. Most athletes (86.5%) had vitamin D deficiency (below 30 ng/mL), 29 mild-moderate (78.4%) and 3 severe (8.1%). EVH showed EIB in 10 subjects (27%), EILO in 16 (43.2%), and combined EIB and EILO in 6 (16.2%). Athletes with EILO had lower vitamin D (19.1 ng/mL vs. 27.0 ng/mL, p < 0.001) and higher parathyroid hormone (30.5 pg/mL vs. 19.2 pg/mL, p = 0.006) levels. The degree of laryngoconstriction (post-EVH MIF50 as a percentage of pre-EVH MIF50) was related directly with vitamin D levels (r = 0.51; p = 0.001) and inversely with parathyroid hormone levels (r = -0.53; p = 0.001). We conclude that vitamin D deficiency is common during winter in young athletes living above the 40th parallel north and favors laryngospasm during exercise, probably by disturbing calcium homeostasis. This effect may negatively influence athletic performance.

The Influence of Tissue Ischemia Time on RNA Integrity and Patient-Derived Xenografts (PDX) Engraftment Rate in a Non-Small Cell Lung Cancer (NSCLC) Biobank.

INTRODUCTION: Bio-repositories are invaluable resources to implement translational cancer research and clinical programs. They represent one of the most powerful tools for biomolecular studies of clinically annotated cohorts, but high quality samples are required to generate reliable molecular readouts and functional studies. The objective of our study was to define the impact of cancer tissue ischemia time on RNA and DNA quality, and for the generation of Patient-Derived Xenografts (PDXs). METHODS: One-hundred thirty-five lung cancer specimens were selected among our Institutional BioBank samples. Associations between different warm (surgical) and cold (ex-vivo) ischemia time ranges and RNA quality or PDXs engraftment rates were assessed. RNA quality was determined by RNA integrity number (RINs) values. Fresh viable tissue fragments were implanted subcutaneously in NSG mice and serially transplanted. RESULTS: RNAs with a RIN>7 were detected in 51% of the sample (70/135), with values of RIN significantly lower (OR 0.08, P = 0.01) in samples preserved for more than 3 hours before cryopreservation. Higher quality DNA samples had a concomitant high RIN. Sixty-three primary tumors (41 adenocarcinoma) were implanted with an overall engraftment rate of 33%. Both prolonged warm (>2 hours) and ex-vivo ischemia time (>10 hours) were associated to a lower engraftment rate (OR 0.09 P = 0.01 and OR 0.04 P = 0.008, respectively). CONCLUSION: RNA quality and PDXs engraftment rate were adversely affected by prolonged ischemia times. Proper tissue collection and processing reduce failure rate. Overall, NSCLC BioBanking represents an innovative modality, which can be successfully executed in routine clinical settings, when stringent Standard Operating Procedures are adopted.

Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps.

Background. T2 inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) may be influenced by epithelial cytokines release (TSLP, IL-25, and IL-33). We investigated the release of TSLP, IL-25, and IL-33 by epithelial CRSwNP cells compared to epithelial sinus mucosa cells of patients with chronic rhinosinusitis without nasal polyps (CRSsNP). Methods. IL-25, IL-33, and TSLP were measured by ELISA in the supernatant of cell cultures derived by CRSwNP (9 patients, 6 atopic) and CRSsNP (7 patients, 2 atopic) in baseline condition and following stimulation with Dermatophagoides pteronyssinus (DP), Aspergillus fumigatus (AF), and poly(I:C). Results. CRSwNP epithelial cells released increased levels of IL-25 (from 0.12 ± 0.06 pg/ml to 0.27 ± 0.1 pg/ml, p < 0.01) and TSLP (from 0.77 ± 0.5 pg/ml to 2.53 ± 1.17 pg/ml, p < 0.001) following poly(I:C) stimulation, while CRSsNP epithelial cells released increased levels of IL-25 and IL-33 following AF and DP stimulation, respectively (IL-25: from 0.18 ± 0.07 pg/ml to 0.51 ± 0.1 pg/ml, p < 0.001; IL-33: from 2.57 ± 1.3 pg/ml to 5.7 ± 3.1 pg/ml, p < 0.001). Conclusions. CRSwNP epithelial cells release TSLP and IL-25 when stimulated by poly(I:C) but not by DP or AF, suggesting that viral infection may contribute to maintain and amplify the T2 immune response seen in CRSwNP.

Nasal and Tracheal Microbial Colonization in Laryngectomized Patients.

OBJECTIVE: Complete separation of upper and lower respiratory tract after total laryngectomy results in loss of physiological nasal functions and presence of "unconditioned" inspired air in lower airways. Aim of this study is evaluating the presence of a microbial colonization of nasal cavities and trachea in laryngectomized long-term survivors. METHODS: Twenty-five laryngectomized patients underwent symptoms' anamnestic evaluation, endoscopic fiber optic nasal and tracheal examination, specimen collection for microbiological exam, and culture. Enrolled patients had at least a 2-year follow-up period in order to evaluate long-term microflora. RESULTS: Gram positive polimicrobic flora represented the main finding in nasal cavities and trachea (92% and 48% of patients, respectively). Other bacteria were non-fermenters Gram negative bacteria, Enterobacteriaceae and Staphylococcus aureus. The same microflora was demonstrated in nasal cavity and trachea in 5 patients (20%), while sterile nasal cavity and trachea were seen in 3 (12%) and 4 (16%) cases, respectively. No fungi were observed in nasal cavity and trachea. CONCLUSION: Nasal cavities and trachea of laryngectomized patients are colonized by nonpathogenic and/or potentially pathogenic bacteria, in absence of signs and symptoms of infection. Colonizer microflora should be kept in mind when a culture from nasal or tracheal swabs is needed in daily practice.

Regulation of B-cell-activating factor expression on the basophil membrane of allergic patients.

BACKGROUND: To investigate the modulation of B-cell-activating factor (BAFF) expression on the basophil membrane of allergic patients. BAFF is an important regulator of B-cell activation, proliferation and immunoglobulin production, which may play a role in respiratory allergic diseases in promoting the production of IgE by B cells. METHODS: Peripheral blood samples of 10 patients with allergic rhinitis, 3 with severe asthma and fungal sensitization (SAFS), 3 with allergic bronchopulmonary aspergillosis (ABPA) and 11 healthy controls were assessed regarding BAFF (CD257) expression using the basophil activation test before and after stimulation with IgE and allergens, as well IgE-independent stimuli, like fMLP, lipotheichoic acid from Staphylococcus aureus (LTA-SA) and lipopolysaccharide (LPS). RESULTS: BAFF membrane expression did not change after IgE and allergen stimulation both in patients and controls, while it was upregulated by Aspergillus stimulation, both in sensitized patients and controls. In both patients and controls, BAFF expression was significantly upregulated following LTA-SA and ß-1,3-glucan exposure (toll-like receptor-2 ligands), but not following LPS stimulation. CONCLUSIONS: Basophils from allergic and healthy subjects constitutively express membrane BAFF, which is not upregulated by IgE or specific allergens but by TLR-2 ligands (LTA-SA and ß-1,3-glucan). Aspergillus fumigatus stimulation was able to upregulate BAFF expression on the basophils of sensitized asthmatic patients, but not via IgE-dependent mechanisms, since results did not differ between the patient and control groups. These findings suggest that basophils may contribute to the polyclonal production of IgE commonly observed in patients with SAFS and ABPA.

Late sensorial alterations in different radiotherapy techniques for nasopharyngeal cancer.

Intensity-modulated radiation therapy (IMRT) for nasopharyngeal cancer (NPC) allowed a better distribution of the dose to the tumor volume, sparing surrounding structures. Aim of the study is the objective evaluation of olfactory and gustatory impairments in patients who underwent chemo-radiotherapy for NPC. Correlation between smell and taste alterations, xerostomy, and radiation technique was investigated. Thirty healthy subjects and 30 patients treated with chemo-radiation therapy for NPC, with at least a 2-years follow-up period, were evaluated. All subjects underwent symptoms evaluation, endoscopic fiber optic nasal examination, taste strips, Sniffin' sticks tests, Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring system. Patients were divided in 2 groups: 2-dimensional radiotherapy/conformal 3-dimensional radiotherapy and IMRT. A higher percentage of rhinorrhea, nasal obstruction, xerostomy, hyposmia, hypogeusia, mucosal hyperemia, and presence of nasopharyngeal secretions was found in irradiated subjects (P < 0.05). Concerning olfactory and gustatory scores, we demonstrated a statistically significant difference between healthy subjects and irradiated patients (P < 0.05), with lower gustatory total score in IMRT group (P < 0.01). In conclusion, chemo-radiotherapy for NPC induces long-term smell and taste impairments, which can compromise quality of life. Although based on small samples, it is also important to consider that IMRT can induce higher taste dysfunction compared with traditional techniques.

Nasal cytological changes as late effects of radiotherapy for nasopharyngeal cancer.

BACKGROUND: Radiation therapy is a cornerstone in nasopharyngeal cancer treatment. However, it can induce acute and long-term adverse effects, such as acute mucositis and late submucosal fibrosis. Late toxicities could not only affect submucosa but also mucosal cells, determining long-term cytological changes. OBJECTIVE: Evaluation of delayed nasal cytological alterations in patients who underwent radiation therapy for nasopharyngeal carcinoma (NPC). METHODS: In this case-control study, we analyzed 30 healthy subjects and 30 patients treated with chemotherapy and radiotherapy for NPC between 2003 and 2011, with a median follow-up of 59 months. All subjects underwent symptoms anamnestic evaluation (rhinorrea, nasal obstruction), endoscopic fiber optic nasal examination, skin-prick tests, and nasal scraping for cytological exam. RESULTS: A higher percentage of rhinorrhea, nasal obstruction, mucosal hyperemia, and presence of nasopharyngeal secretions at fiber optic endoscopic exam was found in radiated subjects (p < 0.05). Nasal cytology analysis demonstrated a higher percentage of neutrophilic inflammation and squamous cell metaplasia and mucous cell metaplasia in treated patients (p < 0.05). No cytological atypia was seen. No statistically significant correlation between nasal cytological changes and objective findings, patients' age, tobacco smoking, and gastroesophageal reflux has been found in the radiotherapy group (p > 0.05). CONCLUSION: Radiation therapy induces late nasal mucosal changes, which may be related to clinical consequences, such as abundant mucus production and its consequent endonasal stagnation. In the future, detailed knowledge of cytological changes in patients' nasal mucosa could represent a key prerequisite for the choice of effective interventions for late radiation-induced rhinitis.

Nasal nitric oxide in patients with inherited retinal dystrophies.

BACKGROUND: Ciliopathies refer to a wide variety of diseases in which mutations in the genes encoding proteins involved in ciliogenesis or protein transport to the primary cilia play pathogenetic roles, and in such diseases, retinal involvement may be present. Nitric oxide (NO) plays an important role in airway physiology, including regulation of ciliary motility and host defense. In primary ciliary dyskinesia, a syndromic ciliopathy, nasal NO (nNO) levels were reported to be extremely low compared with controls, possibly reflecting molecular defects leading to structural and functional ciliary abnormalities. We investigated whether decreased nitric levels were also present in patients with retinal inherited dystrophies. METHODS: Nasal NO was measured in a group of patients with syndromic and nonsyndromic inherited retinal dystrophies. RESULTS: Patients with inherited retinal dystrophies, both syndromic and nonsyndromic, had mean nNO levels that were lower than healthy controls. Seven patients had particularly low levels of nNO: 3 patients with retinitis pigmentosa and 4 individual patients with Mainzer-Saldino syndrome, Bardet-Biedl syndrome, Usher syndrome, and cone-rod disease. CONCLUSIONS: These findings provide evidence that there is an underlying abnormal ciliary function involving the nasal epithelium in some patients with inherited retinal dystrophies.

Eosinophilic inflammation of chronic rhinosinusitis with nasal polyps is related to OX40 ligand expression.

The aims of this study were to investigate OX40 ligand expression in sinus tissue from patients with nasal polyposis compared with patients with chronic rhinosinusitis without nasal polyps (NPs), and to determine if OX40 ligand expression is related to eosinophilic sinus infiltration. Twenty patients with chronic rhinosinusitis (11 with and nine without NPs) and seven controls were enrolled in the study. The mRNA expression of OX40 ligand and thymic stromal lymphopoietin and its receptor were analyzed. The immunoreactivity score for OX40 ligand and the eosinophil count were obtained. The mRNA expression and immunoreactivity score of OX40 ligand were higher in patients with nasal polyposis than in patients without NPs, as well as healthy controls. The mRNA expression of thymic stromal lymphopoietin and its receptor was significantly higher in nasal polyposis than in the control, but not significantly higher than in chronic rhinosinusitis without NPs. A correlation between the number of OX40 ligand-positive cells and the number of eosinophils in sinus biopsies was found only in patients with nasal polyposis. In conclusion, the thymic stromal lymphopoietin/OX40 ligand axis is up-regulated in nasal polyposis and is related to the intensity of eosinophilic inflammation.