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The upper and lower airways are closely linked from an anatomical, histological and immunological point of view, with inflammation in one part of the airways influencing the other part. Despite the concept of global airway disease, the upper airways tend to be overlooked by respiratory physicians. We provide a clinical overview of the most important and recent insights in rhinitis and rhinosinusitis in relation to lower airway disease. We focus on the various exogenous and endogenous factors that play a role in the development and aggravation of chronic upper airway inflammation. In addition to the classical inhaled allergens or microorganisms with well-defined pathophysiological mechanisms in upper airway disease, environmental substances such as cigarette smoke, diesel exhaust particles and occupational agents affecting lower airway homeostasis have recently gained attention in upper airway research. We are only at the beginning of understanding the complex interplay between exogenous and endogenous factors like genetic, immunological and hormonal influences on chronic upper airway inflammation. From a clinical perspective, the involvement of upper and lower airway disease in one patient can only be fully appreciated by doctors capable of understanding the interplay between upper and lower airway inflammation., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Clinical observations suggest that anaphylaxis is more common in adult women compared with adult men, although the mechanistic basis for this sex bias is not well understood., Objectives: We sought to document sex-dependent differences in a mouse model of anaphylaxis and explore the role of female sex hormones and the mechanisms responsible., Methods: Passive systemic anaphylaxis was induced in female and male mice by using histamine, as well as IgE or IgG receptor aggregation. Anaphylaxis was assessed by monitoring body temperature, release of mast cell mediators and/or hematocrit, and lung weight as a measure of vascular permeability. A combination of ovariectomy, estrogen receptor antagonism, and estrogen administration techniques were used to establish estrogen involvement., Results: Anaphylactic responses were more pronounced in female than male mice. The enhanced severity of anaphylaxis in female mice was eliminated after pretreatment with an estrogen receptor antagonist or ovariectomy but restored after administration of estradiol in ovariectomized mice, demonstrating that the sex-specific differences are due to the female steroid estradiol. Estrogen did not affect mast cell responsiveness or anaphylaxis onset. Instead, it increased tissue expression of endothelial nitric oxide synthase (eNOS). Blockage of NOS activity with the inhibitor L-NG-nitroarginine methyl ester or genetic eNOS deficiency abolished the sex-related differences., Conclusion: Our study defines a contribution of estrogen through its regulation of eNOS expression and nitric oxide production to vascular hyperpermeability and intensified anaphylactic responses in female mice, providing additional mechanistic insights into risk factors and possible implications for clinical management in the further exploration of human anaphylaxis., (Published by Elsevier Inc.)

Background: Daily intensive exercise by elite athletes can result in exercise-induced asthma especially in elite swimmers and this may be linked to epithelial damage., Objective: To study airway epithelial damage and release of damage-associated molecular patterns (DAMPs) after intensive exercise in elite athletes and controls., Methods: We recruited competitive swimmers (n = 26), competitive indoor athletes (n = 13) and controls (n = 15) without any history of asthma. Lung function was measured before, immediately after and 24 h after a 90-min intensive exercise protocol. Sputum induction was performed at baseline and 24 h after exercise. Exercise-induced bronchoconstriction (EIB) was assessed by the eucapnic voluntary hyperventilation test., Results: Baseline sputum uric acid, high mobility group box-1, CXCL8 mRNA, sputum neutrophils and serum Clara cell protein-16 (CC-16) were significantly higher in competitive swimmers compared with controls. Intensive swimming for 90 min resulted in an increase of sputum IL-1β, IL-6 and TNF mRNA in competitive swimmers, and of sputum IL-6 mRNA and sputum neutrophils in controls. Although all participants were asymptomatic, seven competitive swimmers, one indoor athlete and one control met the criteria for EIB., Conclusion: Our findings show that the intensive training combined with exposure to by-products of chlorination induces airway epithelial damage in competitive swimmers. This is associated with increased damage-associated molecular patterns, innate cytokine release and neutrophilic airway inflammation., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The naso-ocular interaction in allergic rhinoconjunctivitis is well recognized from epidemiological, clinical, and experimental observations. The precise mechanisms remain incompletely understood. A new mouse model of allergic rhinoconjunctivitis was used to investigate the contribution of mast cells and trigeminal ganglia activation to conjunctival (conj.) inflammation after nasal allergen provocation., Methods: Sensitized mice were exposed to ovalbumin (OVA) via the nose and/or conjunctiva, and conj. homogenates were analyzed for histamine and substance P (using ELISA) and by eosinophil peroxidase (EPO) and beta-hexosaminidase assays. The conj. effects of nasal allergen deposition were compared with those induced by the mast cell activator C48/80 and with pretreatment of the mast cell stabilizer ketotifen or the transient receptor potential channel receptor (TRP) agonist capsaicin. Protachykinin 1 (TAC1) expression was quantified in the trigeminal ganglia using real time polymerase chain reaction., Results: At 1 hour after nasal application of OVA, increased conj. levels of beta-hexosaminidase (0.68 ± 0.03 nm versus 0.56 ± 0.02 nm; p = 0.02), histamine (751.1 ± 52.17 ng/mL versus 546.3 ± 76.91 ng/mL; p = 0.05), and EPO (0.66 ± 0.09 nm versus 0.37 ± 0.03 nm; p = 0.02) were detected compared with saline. Higher levels of TAC1 expression were found in the trigeminal ganglia at 24 hours after OVA application (1326 ± 255 versus 687.5 ± 90.77 TAC1/beta-actin; p = 0.04). Nasal challenge with C48/80 increased substance P and beta-hexosaminidase levels in the conjunctiva, as well as TAC1 expression. Pretreatment with ketotifen resulted in lower levels of substance P as well as TAC1 expression. Destruction of sensory nerves in the nose by capsaicin reduced the OVA-induced conj. levels of substance P, histamine, and beta-hexosaminidase., Conclusion: Nasal allergen deposition in sensitized mice induced trigeminal TAC1 expression and conj. mast cell degranulation. These data represent a significant step forward in understanding the close interaction between nasal and conj. inflammation in allergy.

Background: Idiopathic rhinitis (IR) is a prevalent condition for which capsaicin nasal spray is the most effective treatment. However, the mechanisms underlying IR and the therapeutic action of capsaicin remain unknown., Objective: We sought to investigate the molecular and cellular bases of IR and the therapeutic action of capsaicin., Methods: Fourteen patients with IR and 12 healthy control subjects (HCs) were treated with intranasal capsaicin. The therapeutic effect was assessed in patients with IR by using visual analog scale and therapeutic response evaluation scores, and nasal hyperreactivity was evaluated by means of cold dry air provocation. Nasal samples served to measure the levels of neuromediators and expression of chemosensory cation channels, protein gene product 9.5 (PGP 9.5), and the mast cell marker c-kit. The effects of capsaicin were also tested in vitro on human nasal epithelial cells and mast cells., Results: Patients with IR had higher baseline transient receptor potential cation channel subfamily V, receptor 1 (TRPV1) expression in the nasal mucosa and higher concentrations of substance P (SP) in nasal secretions than HCs. Symptomatic relief was observed in 11 of 14 patients with IR after capsaicin treatment. Expression of TRPV1; transient receptor potential cation channel subfamily M, receptor 8 (TRPM8); and PGP 9.5 was only reduced in patients with IR after capsaicin treatment. Capsaicin did not alter c-KIT expression or nasal epithelial morphology in patients with IR and HCs nor did it induce apoptosis or necrosis in cultured human nasal epithelial cells and mast cells., Conclusion: IR features an overexpression of TRPV1 in the nasal mucosa and increased SP levels in nasal secretions. Capsaicin exerts its therapeutic action by ablating the TRPV1-SP nociceptive signaling pathway in the nasal mucosa., (Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Chronic inflammation of the upper airways is common and can arbitrarily be divided into rhinitis and rhinosinusitis. Infection and allergy represent two well-characterized and most frequently diagnosed etiologies of upper airway inflammation. Persistent upper airway inflammation caused by agents inhaled in the work environment represents a diagnostic challenge in clinical practice, and its pathophysiology has been little studied. Occupational rhinitis is a recognized medical condition with diagnostic and therapeutic guidelines. In contrast, only limited evidence is available about the relationship between work exposures and rhinosinusitis. This review aims at providing a comprehensive overview of the available literature on occupational upper airway disease with a focus on pathophysiological mechanisms and with an emphasis on the current unmet needs in work-related upper airway disease., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Edema represents a key feature of nasal polyp (NP) disease. Members of the vascular endothelial growth factor (VEGF) family may be involved, but the precise role of VEGF-A, VEGF-B, placental growth factor (PlGF), and their receptors VEGFR1 and VEGFR2 in NP edema formation remains elusive., Objective: Exploring the expression of VEGF family members and their receptors and their correlation with clinical, radiological, and edema markers in NP., Methods: The expression of VEGF-A, VEGF-B, PlGF, VEGFR1, and VEGFR2 was measured in NP (n = 23) and control tissue (n = 22) at mRNA and protein level. Edema was evaluated by measuring albumin levels and wet/dry ratios. Computed tomography (CT) scans were scored using the Lund-Mackay scoring system. IL-5 mRNA expression was determined by real-time RT-PCR. Cell suspensions from NP (n = 10) and control tissue (n = 12) were stimulated in vitro with IL-1β or TNFα., Results: mRNA expression of VEGFR1 and VEGF-B was significantly higher in NP compared with control tissue. Expression levels of VEGF-B and VEGFR1 significantly correlated with NP albumin content (VEGF-B: P = 0.0208; VEGFR1: P = 0.0293), CT scan scores (VEGF-B: P = 0.0075; VEGFR1: P = 0.0068), and IL-5 mRNA (VEGF-B: P = 0.0027; VEGFR1: P = 0.0001). In vitro stimulation of control and NP tissue cell suspensions with IL-1β or TNFα significantly reduced the expression of VEGFR2 in control tissue, without altering VEGFR1 and VEGF-B expression. hVEGF-B induced nitric oxide production in NP macrophages (P < 0.05)., Conclusion: Expression levels of VEGFR1 and VEGF-B correlate with edema and clinical markers of NP disease and therefore represent potential therapeutic targets., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Sinonasal inflammation and symptoms are often underdiagnosed in chronic obstructive pulmonary disease (COPD) patients. So far, it is not known to what extent anti-inflammatory nasal treatment may reduce sinonasal symptoms in COPD patients. This study was designed to examine the effects of nasal anti-inflammatory treatment on sinonasal symptoms and cough in COPD patients., Methods: Thirty-three COPD patients on stable bronchial therapy (salmeterol/fluticasone propionate 50/500 mg b.i.d. for >6 weeks) were randomized to receive fluticasone furoate (FF) or placebo nasal spray at 110 μg once daily for 12 weeks. Sinonasal symptoms and cough were monitored at baseline, at 6 and12 weeks of treatment, and at 4 weeks after cessation of the treatment using a visual analog scale. Levels of cytokines were measured in nasal secretions., Results: In contrast to the placebo group (n = 13), FF patients (n = 14) reported less nasal blockage (10.62 ± 4.21 mm versus 36.57 ± 8.01 mm; p = 0.0026), postnasal drip (1.46 ± 0.29 score versus 2.83 ± 0.38 score; p = 0.03), and nasal discharge (0.23 ± 0.12 score versus 1.77 ± 0.43 score; p = 0.01) after 6 weeks of treatment compared with baseline, which was still present at 12 weeks. FF patients reported less cough compared with baseline (25.54 ± 4.46 mm versus 36.79 ± 5.75 mm; p = 0.04), which was not the case in the placebo group (49.58 ± 10.44 mm versus 42.00 ± 8.05 mm; p = 0.38). Nine of 14 patients in the FF group (64%) reported slight to total relief of nasal symptoms, and this subgroup had a significant decrease in IL-8 levels in nasal secretions after 6 weeks of treatment (850.7 ± 207.2 pg/mL versus 1608 ± 696.5 pg/mL; p = 0.03) compared with baseline., Conclusion: Nasal FF treatment in COPD patients significantly reduced sinonasal symptoms, in parallel with reduced IL-8 in nasal secretion levels and cough.

Rationale: Airway hyperreactivity (AHR) is a key feature of bronchial asthma, and inhalation of irritants may facilitate development of nonallergic AHR. Swimmers exposed to hypochlorite (ClO(-))-containing water show a higher risk of developing AHR. We developed a mouse model in which instillation of ClO(-) before ovalbumin (OVA) induces AHR without bronchial inflammatory cells., Objectives: To investigate the mechanisms of ClO(-)-OVA-induced nonallergic AHR., Methods: The involvement of the transient receptor potential ankyrin (TRPA)1 channel was checked in vivo by the use of TRPA1(-/-) mice and in vitro by Ca(2+) imaging experiments. The role of substance P (SP) was investigated by pretreating animals with the receptor antagonist RP67580, by replacing ClO(-) with SP in vivo, and by immunofluorescent staining of large airways of exposed mice. The role of mast cells was evaluated by exposing mast cell-deficient Kit(Wh)/Kit(Wsh) mice to ClO(-)-OVA with or without mast cell reconstitution., Measurements and Main Results: ClO(-)-OVA did not induce AHR in TRPA1(-/-) mice, and ClO(-) generates a Ca(2+) influx in TRPA1-transfected cells. Pretreatment with RP67580 reduces ClO(-)-OVA-induced AHR, although no increased SP expression was shown in the airways. SP-OVA exposure resulted in the same AHR as induced by ClO(-)-OVA. Kit(Wsh)/Kit(Wsh) mice did not develop AHR in response to ClO(-)-OVA unless they were reconstituted with bone marrow-derived mast cells., Conclusions: Induction of AHR by exposure to ClO(-)-OVA depends on a neuroimmune interaction that involves TRPA1-dependent stimulation of sensory neurons and mast cell activation.

State-of-the-art documents like ARIA and EPOS provide clinicians with evidence-based treatment algorithms for allergic rhinitis (AR) and chronic rhinosinusitis (CRS), respectively. The currently available medications can alleviate symptoms associated with AR and RS. In real life, a significant percentage of patients with AR and CRS continue to experience bothersome symptoms despite adequate treatment. This group with so-called severe chronic upper airway disease (SCUAD) represents a therapeutic challenge. The concept of control of disease has only recently been introduced in the field of AR and CRS. In case of poor control of symptoms despite guideline-directed pharmacotherapy, one needs to consider the presence of SCUAD but also treatment-related, diagnosis-related and/or patient-related factors. Treatment-related issues of uncontrolled upper airway disease are linked with the correct choice of treatment and route of administration, symptom-oriented treatment and the evaluation of the need for immunotherapy in allergic patients. The diagnosis of AR and CRS should be reconsidered in case of uncontrolled disease, excluding concomitant anatomic nasal deformities, global airway dysfunction and systemic diseases. Patient-related issues responsible for the lack of control in chronic upper airway inflammation are often but not always linked with adherence to the prescribed medication and education. This review is an initiative taken by the ENT section of the EAACI in conjunction with ARIA and EPOS experts who felt the need to provide a comprehensive overview of the current state of the art of control in upper airway inflammation and stressing the unmet needs in this domain., (© 2012 John Wiley & Sons A/S.)

In less than half a century, allergy, originally perceived as a rare disease, has become a major public health threat, today affecting the lives of more than 60 million people in Europe, and probably close to one billion worldwide, thereby heavily impacting the budgets of public health systems. More disturbingly, its prevalence and impact are on the rise, a development that has been associated with environmental and lifestyle changes accompanying the continuous process of urbanization and globalization. Therefore, there is an urgent need to prioritize and concert research efforts in the field of allergy, in order to achieve sustainable results on prevention, diagnosis and treatment of this most prevalent chronic disease of the 21st century.The European Academy of Allergy and Clinical Immunology (EAACI) is the leading professional organization in the field of allergy, promoting excellence in clinical care, education, training and basic and translational research, all with the ultimate goal of improving the health of allergic patients. The European Federation of Allergy and Airways Diseases Patients' Associations (EFA) is a non-profit network of allergy, asthma and Chronic Obstructive Pulmonary Disorder (COPD) patients' organizations. In support of their missions, the present EAACI Position Paper, in collaboration with EFA, highlights the most important research needs in the field of allergy to serve as key recommendations for future research funding at the national and European levels.Although allergies may involve almost every organ of the body and an array of diverse external factors act as triggers, there are several common themes that need to be prioritized in research efforts. As in many other chronic diseases, effective prevention, curative treatment and accurate, rapid diagnosis represent major unmet needs. Detailed phenotyping/endotyping stands out as widely required in order to arrange or re-categorize clinical syndromes into more coherent, uniform and treatment-responsive groups. Research efforts to unveil the basic pathophysiologic pathways and mechanisms, thus leading to the comprehension and resolution of the pathophysiologic complexity of allergies will allow for the design of novel patient-oriented diagnostic and treatment protocols. Several allergic diseases require well-controlled epidemiological description and surveillance, using disease registries, pharmacoeconomic evaluation, as well as large biobanks. Additionally, there is a need for extensive studies to bring promising new biotechnological innovations, such as biological agents, vaccines of modified allergen molecules and engineered components for allergy diagnosis, closer to clinical practice. Finally, particular attention should be paid to the difficult-to-manage, precarious and costly severe disease forms and/or exacerbations. Nonetheless, currently arising treatments, mainly in the fields of immunotherapy and biologicals, hold great promise for targeted and causal management of allergic conditions. Active involvement of all stakeholders, including Patient Organizations and policy makers are necessary to achieve the aims emphasized herein.

Background: The mechanisms underlying conjunctival symptom reduction by nasal corticosteroids in allergic rhinoconjunctivitis are unknown. A naso-ocular reflex may be present., Objective: To study the effects of nasal fluticasone furoate (FF) on conjunctival symptoms and substance P and histamine levels in tear fluid after nasal grass pollen provocation (GPP)., Methods: A double-blind placebo-controlled study was performed in 26 grass pollen-allergic patients. A selective GPP was performed during the grass pollen season after 2 weeks of FF or placebo treatment. Nasal and conjunctival symptoms were scored using a visual analog scale (VAS), and tear fluid was collected for measuring substance P and histamine using an enzyme-linked immunosorbent assay., Results: Compared with placebo, FF reduced conjunctival symptom scores during the pollen season (-1.75 [-2.75, 0.20] vs 0.0 [0.0, 0.0]; P = .01) and after GPP at 15 minutes (0.05 [-0.42, 1.52] vs 2.05 [0.62, 3.62]; P < .001) and 1 hour (-0.45 [-1.75, 0.1] vs 0.05 [-0.97, 1.85]; P < .01). Treatment with FF decreased substance P levels in tear fluid (44.11 [32.81, 61.02] vs 65.26 [48.62, 79.73] pg/mg protein; P = .0098). Histamine levels in tear fluid showed a GPP-induced increase in the placebo group (7.26 [3.12, 9.69] vs 5.71 [2.05, 7.00] ng/mg protein; P = .02), but not in the FF group (6.77 [3.43, 13.00] vs 5.24 [3.18, 7.06] ng/mg protein; P = .08)., Conclusion: FF nasal spray reduced conjunctival symptoms in grass pollen-allergic patients in parallel with lower substance P levels in tear fluid. These data help in understanding the reduction of conjunctival symptoms by intranasal anti-inflammatory therapy., (Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Placental growth factor (PlGF) and its receptor vascular endothelial growth factor receptor 1 (VEGFR1) play an important role in pathological conditions related to angiogenesis, vascular leakage, and inflammation. This study investigated their contributions to inflammation and the formation of edema in allergic asthma. The expression of PlGF and VEGFR1 was measured in induced sputum of patients with asthma (n = 11) and healthy subjects (n = 11), and in bronchial biopsies of house dust mite (HDM)-allergic patients stimulated with HDM allergens. The effects of the endonasal administration of human PlGF-2 and PlGF deficiency on inflammation and edema were evaluated in a murine model of allergic asthma. The migration of human neutrophils in response to hPlGF-2 was tested in vitro. The expression of PlGF and VEGFR1 was significantly higher in the sputum of patients with asthma, and in Der p 1-induced PlGF in biopsies from HDM-allergic patients. PlGF was increased in the bronchi of ovalbumin (OVA)-challenged mice compared with control mice (65 ± 17 pg/mg versus 18 ± 1 pg/mg, respectively; P < 0.01), and VEGFR1 was expressed in bronchial epithelium, endothelium (control mice), and inflammatory cells (OVA-challenged mice). The endonasal instillation of hPlGF-2 in wild-type, OVA-challenged mice led to an increase in bronchial neutrophils, lung tissue wet/dry ratio, and IL-17. PlGF-deficient mice showed lower numbers of BAL-infiltrating neutrophils, a reduced lung wet/dry ratio, and lower production of IL-17, macrophage inflammatory protein-2, and granulocyte chemotactic protein-2/LPS-induced chemokine compared with wild-type, OVA-challenged mice. hPlGF-2 induced the migration of human neutrophils in vitro in a VEGFR1-dependent way. PlGF and its receptor VEGFR1 are up-regulated in allergic asthma and play a proinflammatory role by inducing tissue edema, and increasing tissue neutrophilia and the production of IL-17.

Background: Chronic rhinosinusitis (CRS) is a frequent condition that is treated by functional endoscopic sinus surgery (FESS) when medical treatment fails. Endogenous as well as exogenous factors may be responsible for persisting symptoms after FESS. The role of occupational exposures on success of FESS has never been investigated., Methods: In this case-control study, we tested the hypothesis that the outcome of FESS procedures is related to exposures at work. Questionnaires were sent to 890 patients who had undergone one or more FESS procedures and to 182 controls. Three independent experts assessed blindly the reported work exposures to inhaled agents. The relationship between exposure and the number of FESS procedures was analyzed., Results: Relevant occupational exposure was reported by 25% of all responding patients undergoing FESS (n = 467) and 12% of controls (n = 69). The prevalence of occupational exposures increased linearly with the number of FESS procedures from 21% in those who had one FESS to 44% in those who had four or more FESS (χ(2)  = 12.74, P < 0.001). Logistic regression analysis with adjustments for potential confounders, including smoking, atopy, and asthma, confirmed that the odds ratio (OR) for reporting occupational exposures was significantly higher in those needing more than one FESS (OR = 1.64) or more than two FESS (OR = 1.97). These results were mainly driven by exposure to low molecular weight agents., Conclusion: Exposure at work appears to be a risk factor for the occurrence of CRS and for its recurrence or persistence, as evidenced by the need for revision surgery., (© 2012 John Wiley & Sons A/S.)

Introduction and Aim: Tonsillectomy is one of the most commonly performed surgical procedures in children; its main indications are recurrent episodes of acute tonsillitis and adenotonsillar hypertrophy. The effectiveness of tonsillectomy for severe recurrent tonsillitis is generally accepted; however its socio-economic cost is less well investigated. This study aims to determine and compare the societal cost of a tonsillectomy and a severe throat infection., Materials and Methods: The costs for both tonsillectomy and severe throat infection were evaluated. Costs of the surgical procedure and hospital stay were calculated based on resource use and personnel input at the participating hospital. The cost of work-related disability for both treatments was measured based on a questionnaire filled in by 275 parents of children undergoing a tonsillectomy. Data from two Belgian institutions (NIS and FOD) were used to calculate the cost of parents' absenteeism., Results: An episode of acute tonsillitis in the child results in a longer period of parents' work absenteeism (mean of 3.1 +/- 0.3 days) compared to tonsillectomy (2.2 +/- 0.2 days). The cost of economic productivity loss amounts to 613 Euros (NIS) or 759 Euros (FOD) for acute tonsillitis and 435 Euros (NIS) or 539 Euros (FOD) for a tonsillectomy. The medical costs linked to the surgical procedure at the local department correspond to 535 Euros and for an acute tonsillitis to 46 Euros., Conclusions: From societal perspective, a tonsillectomy costs the equivalent of 1.4 times the cost of a severe throat infection. This indicates that in children suffering from recurrent acute tonsillitis, watchful waiting results in a higher cost compared to tonsillectomy, given the cumulative costs of parents' absenteeism.

Background: Some epidemiologic studies have indicated that attendance to chlorinated swimming pools is associated with airway hyperreactivity (AHR), allergies and asthma., Aim: To investigate the effects of sodium hypochlorite (NaClO), the main pool disinfectant, on allergic sensitization and airway inflammation in mice., Methods: In a first series of experiments, mice were sensitized to ovalbumin (OVA), followed by OVA aerosols with or without prior nasal instillation of NaClO (3ppm active chlorine). In a second series, naïve mice received 1-7 nasal instillations of OVA, 10min after instillations of NaClO or water. After 1, 3, 5 and 7 exposures airway reactivity to methacholine, cellular inflammation in bronchoalveolar lavage (BAL), serum OVA-specific IgEs and lung Th2 cytokines were measured., Results: In the first mouse model, airway allergy parameters were not significantly altered upon NaClO administration. However in the second model, NaClO exposure prior to OVA did induce AHR, already after 1 combined application. Combined NaClO+OVA exposure did not lead to an influx of inflammatory cells in BAL fluid or production of anti-OVA IgEs. No AHR developed when OVA was heat-denatured, pre-chlorinated, or replaced by bovine serum albumin or lipopolysaccharide., Conclusion: Nasal instillation of NaClO prior to OVA induces AHR without allergic sensitization. This response is OVA-specific., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: Chronic rhinosinusitis with nasal polyposis (NP) represents an invalidating disorder that causes mainly nasal blockage and loss of smell. The aim of this study is to investigate correlations between individual subjective and objective parameters of stable NP disease., Methods: 65 NP patients scored their sinonasal symptoms on a visual analogue scale (VAS) and questionnaires (SNOT-22 and SF-36). Peak nasal inspiratory flow (PNIF) measurement, Sniffinatm Sticks (SS) smell test, blood analysis for eosinophilia, total IgE and culture for Staphylococcus aureus (SA) were performed., Results: VAS scores for nasal blockage correlated with the SNOT-22 and SF-36 scores, which was not observed for VAS of other symptoms. VAS scores for nasal blockage correlated well with PNIF values as well as VAS scores for smell dysfunction and SS results (both p<0.001). NP size correlated with VAS scores for nasal blockage (p<0.01) but not with VAS for other symptoms. NP size showed an inverse correlation with PNIF and SS scores (both p<0.05). Blood eosinophilia correlated with subjective smell reduction (p<0.05). The presence of SA or total IgE levels were not associated with symptoms of NP disease., Conclusion: PNIF and SS are good tools to evaluate symptoms of nasal obstruction and smell reduction in NP disease. Nasal blockage is the only symptom that correlates well with NP size and SNOT-22 scores, whereas smell reduction correlates with blood eosinophilia.

Background: Human nasal epithelial cells (hNECs) are the first line of immune defense and are able to produce mediators that recruit, activate and prolong survival of immune cells, among which IL-8 takes an important place. Studies on IL-8 and effects of dexamethasone on hNECs have been hampered by methodological shortcomings. The purpose of the study is to investigate the contribution of freshly isolated hNECs to IL-8 production in chronic rhinosinusitis with nasal polyps (CRSwithNP). Secondly, the effects of dexamethasone treatment on hNEC apoptosis and IL-8 production are investigated., Methodology: hNECs were freshly isolated from nasal polyp tissue and healthy inferior turbinate of NP patients (n=12) and from inferior turbinates of healthy donors (n=19) by protease treatment and two negative selection procedures. hNECs were incubated with IL-1β (10ng/ml), TNFα (10ng/ml) or dexamethasone (10, 100 and 1000 Amicrog/ml). After 24h, IL-8 levels were determined in the supernatants by ELISA. Finally, hNECs were incubated with increasing doses of dexamethasone and stained with trypan-blue and annexin-FITC/PI to study apoptosis., Results: hNECs isolated from nasal turbinates of healthy and NP patients and polyp tissue from NP patients produced similar levels of IL-8. IL-1β induced higher levels of IL-8 production in all types of hNECs without differences between control and NP tissue. Dexamethasone induced apoptosis of hNECs concomitant with abrogation of IL-8 production by hNECs., Conclusions: IL-8 production by human nasal epithelial cells does not differ between NP and healthy tissue under baseline nor stimulatory conditions. Dexamethasone induces apoptosis of hNECs and abrogates IL-8 production.

Background: Several clinical and experimental observations suggest that allergen deposition in the nose may partially be responsible for the induction of conjunctival symptoms in allergic rhinitis. The aims of this study were to evaluate the induction of conjunctival symptoms by selective nasal allergen provocation and to assess the feasibility of the different tools for evaluation of conjunctival allergic inflammation., Methods: Grass pollen allergic subjects with rhinoconjunctivitis symptoms during the pollen season (n = 12) underwent a nasal sham and grass pollen provocation extra-seasonally. Nasal and conjunctival symptoms were scored using the Visual Analogue Scale (VAS) system at baseline, 15 min, 1 h and 24 h after provocation. In addition to Peak Nasal Inspiratory flow (PNIF) measurements, conjunctival inflammation and vascular congestion were evaluated and histamine and substance P levels in tear fluid were measured., Results: Selective nasal grass pollen provocation induced ocular pruritus, lacrimation and conjunctival vascular congestion. PNIF values correlated inversely with lacrimation (r = -0.71, P < 0.001) and ocular pruritus (r = -0.41, P < 0.05). Four out of 11 patients showed a conjunctival eosinophilic inflammation and levels of histamine (r = 0.73, P < 0.05) and substance P (r = 0.67, P = 0.05) in tear fluid correlated with conjunctival symptoms., Conclusion: Selective nasal grass pollen provocation induced conjunctival inflammation, ocular pruritus and lacrimation, which correlated with histamine and substance P levels in tear fluid and inversely with the PNIF values. These data show a naso-ocular interaction in allergic rhinitis and offer objective tools for evaluation of conjunctival inflammation in allergic rhinoconjunctivitis.

Background: Mammary myofibroblastoma is a benign mesenchymal tumor of the breast. Extramammary location is very rare and usually occurs along the embryonic milk-line., Methods and Results: In this article, we present a case of a woman with an infra-auricular swelling. A diagnosis could not be made on CT scans, so the mass was surgically removed. Histological examination showed spindle cells in clusters, with CD34, desmin, and actin expression. The diagnosis of extramammary myofibroblastoma was made., Conclusion: We describe this case because of the unusual location of this rare tumor. Furthermore, we want to highlight the possible relationship between (extra)mammary myofibroblastoma and spindle cell lipoma (SCL). SCL has a predilection site in the posterior neck. Both tumors show the same clinical behavior, a close histological resemblance, and their cells are both immunoreactive for CD34 and CD10. The loss of RB/13q14 and FKHR/13q14 loci, which is typically found in SCL cells, was also shown in this case.