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Occupational exposure to chemicals is one of the main causes of respiratory allergy and asthma. Identification of chemicals that trigger allergic asthma is difficult as underlying processes and specific markers have not yet been clearly defined. Moreover, adequate classification of the respiratory toxicity of chemicals is hampered due to the lack of validated in vivo and in vitro test methods. The study of differential gene expression profiles in appropriate human in vitro cell systems is a promising approach to identify selective markers for respiratory allergy. As alveolar macrophages display important immunological and inflammatory properties in response to foreign substances in the lung, we aimed at gaining more insight in changes of human macrophages transcriptome and to identify selective genetic markers for respiratory sensitization in response to hexamethylene diisocyanate (HDI). In vitro cultures of human THP-1 cells were differentiated into macrophages and exposed to 55 μg/ml HDI for 6 and 10 h. Using human oligonucleotide microarrays, changes were observed in the expression of genes that are involved in diverse biological and molecular processes, including detoxification, oxidative stress, cytokine signaling, and apoptosis, which can lead to the development of asthma. These genes are possible markers for respiratory sensitization caused by isocyanates.

Background Recent findings indicate that Staphylococcus aureus and its products may be involved in the modification of nasal polyposis. The purpose of this study was to investigate the presence of S. aureus enterotoxin genes and the agr subtype in bacterial DNA of S. aureus strains isolated from the middle meatus of nasal polyp and control patients. Methods S. aureus strains were isolated from nasal polyp patients and controls. The strains were screened using PCR for their agr subtype, classic superantigens (SEA, SEB, SEC, SED or TSST-1), the egc cluster (SEG, SEI, SEM, SEN, and SEO and other enterotoxins (SEE, SEH, SEJ, SEK, and SEL) distinct from the egc locus. Results Seventy-five percent of S. aureus strains had at least one enterotoxin in their DNA. The egc gene cluster was identified in 27 (67.5%) strains. At least one classic enterotoxin gene was present in 42.5% of the strains. Interestingly, there were no differences in enterotoxin genes between S. aureus strains isolated from controls compared with nasal polyposis patients. In controls, an equal distribution among the four agr groups was found, while 73% of the NPs strains belonged to agr groups I and II. Conclusion In this study we found no significant difference between strains from nasal polyp patients and controls in the presence of enterotoxin genes. However, in NPs, a higher number of strains belonged to agr I or II, which are associated with strains causing enterotoxin-mediated disease.

Histamine is the primary mediator involved the pathophysiology of allergic rhinitis and chronic urticaria, and this explains the prominent role that histamine H(1)-receptor antagonists have in the treatment of these disorders. However, histamine is clearly not the only mediator involved in the inflammatory cascade. There is an emerging view that drugs which can inhibit a broader range of inflammatory processes may prove to be more effective in providing symptomatic relief in both allergic rhinitis and chronic urticaria. This is an important consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative which provides a scientific basis for defining what are the desirable properties of an 'ideal' antihistamine. In this review of rupatadine, a newer dual inhibitor of histamine H(1)- and PAF-receptors, we evaluate the evidence for a mechanism of action which includes anti-inflammatory effects in addition to a powerful inhibition of H(1)- and PAF-receptors. We assess this in relation to the clinical efficacy (particularly the speed of onset of action) and safety of rupatadine, and importantly its longer term utility in everyday life. In clinical trials, rupatadine has been shown to be an effective and well-tolerated treatment for allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of action, producing rapid symptomatic relief, and it also has an extended duration of clinical activity which allows once-daily administration. In comparative clinical trials rupatadine was shown to be at least as effective as drugs such as loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms in adult/adolescent patients with seasonal, perennial or persistent allergic rhinitis. Importantly, rupatadine demonstrated no adverse cardiovascular effects in preclinical or extensive clinical testing, nor negative significant effects on cognition or psychomotor performance (including a practical driving study). It improved the overall well-being of patients with allergic rhinitis or CIU based on findings from quality of life questionnaires and patient global rating scores in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of histamine H(1)- and PAF-receptors, which has been shown to be an effective and generally well-tolerated treatment for allergic rhinitis and chronic urticaria. It possesses a broader profile of anti-inflammatory properties inhibiting both inflammatory cells and a range of mediators involved in the early- and late-phase inflammatory response, but the clinical relevance of these effects remain to be clarified.

Allergic rhinitis is a symptomatic disorder of the nose induced after allergen exposure by an IgE-mediated inflammation of the membranes lining the nose. It is a global health problem that causes major illness and disability worldwide. Over 600 million patients from all countries, all ethnic groups and of all ages suffer from allergic rhinitis. It affects social life, sleep, school and work and its economic impact is substantial. Risk factors for allergic rhinitis are well identified. Indoor and outdoor allergens as well as occupational agents cause rhinitis and other allergic diseases. The role of indoor and outdoor pollution is probably very important, but has yet to be fully understood both for the occurrence of the disease and its manifestations. In 1999, during the Allergic Rhinitis and its Impact on Asthma (ARIA) WHO workshop, the expert panel proposed a new classification for allergic rhinitis which was subdivided into 'intermittent' or 'persistent' disease. This classification is now validated. The diagnosis of allergic rhinitis is often quite easy, but in some cases it may cause problems and many patients are still under-diagnosed, often because they do not perceive the symptoms of rhinitis as a disease impairing their social life, school and work. The management of allergic rhinitis is well established and the ARIA expert panel based its recommendations on evidence using an extensive review of the literature available up to December 1999. The statements of evidence for the development of these guidelines followed WHO rules and were based on those of Shekelle et al. A large number of papers have been published since 2000 and are extensively reviewed in the 2008 Update using the same evidence-based system. Recommendations for the management of allergic rhinitis are similar in both the ARIA workshop report and the 2008 Update. In the future, the GRADE approach will be used, but is not yet available. Another important aspect of the ARIA guidelines was to consider co-morbidities. Both allergic rhinitis and asthma are systemic inflammatory conditions and often co-exist in the same patients. In the 2008 Update, these links have been confirmed. The ARIA document is not intended to be a standard-of-care document for individual countries. It is provided as a basis for physicians, health care professionals and organizations involved in the treatment of allergic rhinitis and asthma in various countries to facilitate the development of relevant local standard-of-care documents for patients.

By definition, allergy is a multifactorial disease (1), whichcan no longer be studied by single research groups.Networks are therefore essential to achieve optimalresearch outcome. However, the results of this researchneed to be translated for physicians, patients, the publicand policy makers. The networks should, therefore,include all experts, researchers, physicians of differentspecialties, general practitioners, other health care pro-fessionals and patients to accomplish these tasks. In thesenetworks, dissemination of research is the key to theirsuccess.The European Union, having been at the forefront ofallergy research for more than a decade, has led severalnetworks, concerted actions and integrated projects.Projects commenced before 2002 have been reviewed inprevious papers of the journal (2, 3). The EuropeanCommunity Respiratory Health Survey was one of thefirst and most successful assignments (4). Some projectslike European Network For Understanding MechanismsJ. Bousquet

Objective: The main purpose of this study is to determine the treatment effectiveness of pharyngeal flap surgery by measuring speech outcome 1 year after surgery. The authors hypothesized that flap surgery is an effective technique for velopharyngeal inadequacy resulting in improved intelligibility, decreased hypernasality and nasalance scores and normal voice characteristics. Patients and Methods: Objective (Nasometer, Dysphonia Severity Index) as well as subjective (perceptual evaluations) assessment techniques were performed in 7 subjects. Speech evaluations were performed 1 year after flap surgery and comparison was made between the speech results of the preoperative condition (1 week before surgery) and the first postoperative condition (6 weeks after surgery). Results: After pharyngeal flap surgery there was improved though still slightly impaired intelligibility, with normal nasality, normal nasalance values for standard Flemish speech and normal voice characteristics. The normal nasality and nasalance values were not present in the preoperative condition. Persistence of the incorrect production of the thrill sound /r/ and the fricatives /s/ and /sch/ were observed. Conclusion: It is likely that the slightly impaired speech intelligibility is determined by the presence of persistent articulation disorders.

In allergic rhinitis, cross linking of IgE molecules upon allergen contact induces degranulation of mast cells and basophils within the mucosal tissue, and results in the release of typical mediators, which consecutively induce the well-known symptoms. Omalizumab counteracts these interactions by a reduction in serum levels of free IgE. Therapy targeted against IgE also interferes with its binding to the high- as well as the low-affinity receptors, inhibiting the amplification of the Th2-type response. Treatment of allergic rhinitis with anti-IgE has been shown to be safe and to reduce specific symptoms. Furthermore, the combination ofomalizumab with specific immunotherapy (SIT) may offer not only an increase in efficacy, but also in safety in appropriate patients. The currently available studies with omalizumab in allergic rhinitis, as monotherapy or in combination with immunotherapy, are summarized. In nasal polyp disease, a local polyclonal IgE response has recently been described, initiated by Staphylococcus aureus-derived enterotoxins, which at least modifies the inflammatory reaction within the tissue. Evidence accumulates that these enterotoxins act as superantigens resulting in a polyclonal T- and B cell activation with massive IgE formation within the airways. Because of the polyclonality, a range of allergens could possibly maintain a constant degranulation of mast cells present in polyp tissue, which may contribute to the disease severity. We here discuss a proof-of-concept treatment trial with omalizumab in nasal polyposis, which in case of a positive therapeutic response, also would open the door for anti-IgE treatment approaches for severe nonatopic lower airway disease.

Viral infections of the respiratory tract are the most common precipitants of acute asthma exacerbations. Exacerbations are only poorly responsive to current asthma therapies and new approaches to therapy are needed. Viruses, most frequently human rhinoviruses (RV), infect the airway epithelium, generate local and systemic immune responses, as well as neural responses, inducing inflammation and airway hyperresponsiveness. Using in vitro and in vivo experimental models the role of various proinflammatory or anti-inflammatory mediators, antiviral responses and molecular pathways that lead from infection to symptoms has been partly unravelled. In particular, mechanisms of susceptibility to viral infection have been identified and the bronchial epithelium appeared to be a key player. Nevertheless, additional understanding of the integration between the diverse elements of the antiviral response, especially in the context of allergic airway inflammation, as well as the interactions between viral infections and other stimuli that affect airway inflammation and responsiveness may lead to novel strategies in treating and/or preventing asthma exacerbations. This review presents the current knowledge and highlights areas in need of further research.

Background: Chronic rhinosinusitis (CRS) clinically is a heterogeneous group of sinus diseases, which may cover different disease entities, or may represent a disease continuum. Studying inflammatory cells and mediators in clearly defined disease subgroups may lead to a better differentiation of chronic sinus diseases. Methods: Sinonasal mucosal tissue from 10 nasal polyp (NP) patients, 13 cystic fibrosis patients (CF-NP), eight CRS subjects without polyps, and nine control patients were stained for CD3, CD25, CD68, CD20, myeloperoxidase (MPO), CD138 and tissue homogenates were assayed for eotaxin, interleukin (IL)-1 beta, IL-2sR alpha, IL-5, interferon (IFN)-gamma, IL-8, transforming growth factor (TGF)-beta 1, tumor necrosis factor-alpha, and MPO by enzyme-linked immunosorbent assay or UNICAP system. Results: Nasal polyp and CF-NP showed increased numbers and activation of T cells, while only NP displayed an increase in plasma cells. Nasal polyp had significantly higher levels of eosinophilic markers [eosinophils, eotaxin, and eosinophil cationic protein (ECP)] compared with CRS, controls and CF-NP. Chronic rhinosinusitis was characterized by a Th1 polarization with high levels of IFN-gamma and TGF-beta, while NP showed a Th2 polarization with high IL-5 and immunoglobulin (Ig) E concentrations. Nasal polyp and CF-NP were discriminated by edema from CRS and controls, with CF-NP displaying a very prominent neutrophilic inflammation. Conclusions: Based on cellular and mediator profiles, we suggest that CRS, NP, and CF-NP are distinct disease entities within the group of chronic sinus diseases.

Background: Allergic rhinitis (AR) and noninfectious, nonallergic rhinitis (NINA) are common disorders, which may prompt patients to seek medical help. Methods: We performed a survey in a representative sample of the Belgian population (n = 4959) with an overall prevalence of self-declared recent rhinitis symptoms of 39.3%. Detailed information on patients having experienced nasal symptoms over the past year was then obtained from a random sample of respondents (n = 743). Results: The adjusted prevalence was 29.8% for AR and 9.6% for NINA, respectively. According to the ARIA classification, there was significantly more ‘persistent’ symptomatology in the AR group (40.8%) than in NINA (23.5%) (P

Tissue remodelling reported in upper airways include epithelial hyperplasia, increased matrix deposition in the nasal or paranasal lining, matrix degradation and accumulation of plasma proteins. Genetic influences, foetal exposures and early life events may contribute to structural changes such as subepithelial fibrosis from an early age. Other structural alterations are related to duration of the disease and long-term uncontrolled inflammation. Structural changes may increase alteration of the protective functions of the upper airways namely by affecting mucociliary clearance and conditioning of inspired air. The sequences of tissue changes during wound repair of upper airway mucosa after surgery are illustrative of the complexicity of tissue modelling and remodelling and could be considered as an important source of information for a better understanding of the complex relationship between inflammatory reaction, of the subsequent tissue damages and fibroblast metabolism of upper airways.

Allergic rhinitis, rhinosinusitis, and otitis media are among the most common health problems encountered in general practice. Although frequently trivialized, they affect the quality of life, represent a significant socioeconomic burden, and are associated with some serious complications. In addition, allergic rhinitis, rhinosinusitis, and otitis media are often considered as comorbidities. These disorders involve an inflammatory process of the respiratory mucosa of the nose, paranasal sinuses, or middle ear. Because of their well-known anti-inflammatory effects, the role of glucocorticosteroids in the management of these three disorders has been questioned, evaluated, and, in some cases, established.

Summary Epidemiological studies show that the prevalence of asthma and allergic rhinitis (AR) has increased progressively over the past two to three decades. Similarly, there is increasing evidence that asthma and rhinitis frequently co-exist in the same patients and that rhinitis is a risk factor for asthma. Although several guidelines are currently available for the diagnosis and management of AR, the earlier guidelines and their successors were not evidence based, and were developed primarily on the basis of expert opinion, but of course based on the available literature. More recently, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines were published in co-operation with the World Health Organization. These guidelines are evidence based and directed towards managing co-morbid rhinitis and asthma as different manifestations of a single airway disease, rather than as two separate diseases of the nose and the lung. They recommend treatment of AR in a step-wise manner (using a combination of allergen avoidance, pharmacotherapy and immunotherapy), based on the duration and severity of disease, rather than on the basis of type of exposure (i.e seasonal, perennial, occupational), as recommended by previous guidelines. The ARIA guidelines recognize that both the availability and the cost of a particular intervention are likely to determine patient compliance, and therefore recommends a flexible approach based on availability and cost of specific interventions in different countries. Despite the availability of treatment guidelines, there is evidence that the severity of disease is often diagnosed and treated inappropriately by general practitioners (GPs), who frequently do not use a guided treatment strategy, leading to low patient satisfaction and compliance. This suggests a clear need to implement the guidelines among GPs, especially since the vast majority of patients generally trust their GPs to provide appropriate information and optimal medication for the management of their disease.

Allergic diseases and asthma pose an important and increasing problem for populations and health care systems around the world (1). European research groups have been at the forefront of investigations into the early life influences on the causes of these conditions and management of allergy and asthma (2, 3). Moreover, initiatives from the European Commission have led to a greater collaboration between the European countries and beyond in tackling these problems. It has been shown to be both practical and rewarding to exploit the wide variations in culture, environment and health care systems within Europe to study these issues (4). Collaborative projects such as the European Community Respiratory Health Survey (ECRHS), the International Study of Asthma and Allergy in Childhood (ISAAC), and many other, funded by the European Commission, have clearly demonstrated the ability and advantages of European groups working together (1, 5, 6). Although allergy and asthma represent a burden in all countries and regions in Europe there is still a lack of permanent structures to support this type of work. The collaboration between European groups so far has often had a relatively narrow methodological focus and has therefore produced only short-term collaborations without a formal enduring structure. The basic idea of the European Research Area (ERA) is that the aims and goals of future research cannot be met without much greater integration of Europe’s research efforts and capacities. The sixth framework programme is a key instrument of ERA with a budget of 17 500 million. For this reason the sixth framework programme introduces new instruments like networks of excellence from which joint strategies can be developed. These networks have clearly defined thematic objectives and will be directed towards advancing scientific and technological knowledge, within mediumto long-term time-frames (7, 8). P. Van Cauwenberge, J. B. Watelet, T. Van Zele, J. Bousquet, P. Burney, T. Zuberbier, on behalf of the GALEN partners* Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium; University Hospital and INSERM U454, Montpellier, Institut Pasteur Paris, France; Department of Public Health Sciences, Guy's, King's and St Thomas School of Medicine, King's College, London, UK; Department of Dermatology and Allergy, Charit , Berlin, Germany *GALEN partners are given in Appendix.

Clinical guidelines are 'systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances'. They may offer concise instructions on which diagnostic or screening tests to order, stipulate how medical services should be provided, how long patients should stay in hospital, or many other details relevant to clinical practice. This paper argues that guidelines should be simple, adapted to the clinical setting they inform and to treatment availability in their respective geographic context and that they should not be viewed as a yardstick but as support for physicians. The benefits of evidence-based-medicine (EBM), which defines the value of medical interventions in terms of empiric evidence from clinical trials, are growing in many contexts and are well described. Not sufficiently acknowledged, however, are the limits of EBM. A gap still exists between clinical research and clinical practice which should be better recognized and assessed.

Staphylococcus aureus is a frequent germ in the upper airways, and, under appropriate conditions, may produce enterotoxins with superantigenic activities. The classical enterotoxins SEA-E and TSST-l activate B- and T cells, eosinophils, epithelial and other cells, and are able to induce a polyclonal immune response including IgE synthesis and eosinophilic inflammation. We have shown that nasal polyps frequently are colonized with Staphylococcus aureus, inducing a local immune reaction, which aggravates the eosinophilic inflammatory response. IgE antibodies in nasal polyp tissue may be used as diagnostic means for this immune reaction. We consider it probable that enterotoxines from Staphylococcus aureus are crucially contributing to this often difficult to treat disease of the upper airways. Furthermore, recent studies in severe, steroid-dependent asthmatics have shown that IgE-antibodies to enterotoxins are also found in the sera of these patients and similar pathomechanisms as in polyps may apply for the lower airways. To summarize, enterotoxins from Staphylococcus aureus most probably play an at least modulating role in severe upper and lower airway disease.

Objectives/Hypothesis: After failure of medical treatment, chronic rhinosinusitis and nasal polyposis require surgical management. However, little is known about the predictive factors for objective outcome after sinus surgery. The aims of the study were to correlate preoperative, intraoperative, and postoperative clinical factors to healing outcome and to establish their respective predictive values. Study Design: Prospective study. Methods: Eighteen patients who had surgery for chronic rhinosinusitis and 18 who had surgery for nasal polyposis at the Ghent University Hospital (Ghent, Belgium) were followed for a 6-month period. In all, 76 operated sides were independently considered. The healing quality was evaluated by endoscopy weekly and then monthly for a period of 6 months. A logistic regression analysis with healing quality at month 6 as outcome was performed on preoperative, intraoperative, and postoperative factors. Results: Previous sinus surgery (P = .0006) and initial disease (P = .0430) were found to be highly predictive for the healing outcome at month 6, patients with nasal polyposis or previous surgery showing significantly worse objective outcome (P = .0034 and P < .0001, respectively). The preoperative computed tomography scan had no predictive value with respect to the extent of surgery (P = .0281). Postoperative parameters had less predictive value. Conclusion: Initial disease and its severity as reflected by the extent of surgery and surgical antecedents were the best predictors for the objective outcome at 6 months after sinus surgery. Whereas the first postoperative phase showed similar characteristics for all patients, the healing course differed between patients from month 1 to the end point.

Resume Ce compte-rendu a ete prepare par un groupe de l’Academie Europeenne d’Allergologie et d’Immunologie Clinique (European Academy of Allergology and Clinical Immunology, EAACI) representant les cinq sections de l’EAACI ainsi que le Comite directeur de l’EAACI compose de specialistes refletant l’opinion consensuelle sur l’allergie exprimee par differentes specialites cliniques et fondamentales ayant trait a l’allergie. L’objectif de ce compte rendu est de proposer une revision de la nomenclature des reactions allergiques et apparentees pouvant etre utilisee independamment de l’organe cible ou de la tranche d’âge des patients. La nomenclature est fondee sur les connaissances actuelles des mecanismes responsables de l’initiation et de la mediation des reactions allergiques. Cependant, l’intention n’a pas ete de reviser la nomenclature de l’hypersensibilite non allergique.

Allergic diseases and asthma represent one of the mostcommon chronic pathological conditions throughoutthe world (1, 2). They usually start early in infancy orchildhood and often persist throughout life (3). Theyare extremely common in developed countries. It isestimated that 2–15% of the European populationsuffers from asthma, and that, in some countries,allergy may affect over 50% of children. Moreover,the prevalence of allergic diseases and asthma hasactuallyincreasedduringthepastthreetofourdecades.More recently a similar increase has been noted indeveloping countries, and these diseases now representanimportantproblem(4).IntheEuropeanUnion(EU)theprevalenceandseverityofallergicdiseasesincludingasthma present a serious challenge both to health caresystems and to society as a whole. Specific problemsinclude the continuing increase in the prevalence offood allergy, which is a particular concern because itmay be life-threatening, and it has a major impact onpatient’s lives (7). This problem affects mainly children(5, 6) but also an increasing number of adult pollenallergic patients. Occupational allergy is anotherimportant medical and economic problem which isunder recognized and needs a more careful evaluation(1, 8). The interaction between the indoor and outdoorenvironment is critical for the development of thesediseases (9).Allergic diseases and asthma also seriously affect thesocial life of the patients. Asthma is still a leadingconditionofschoolabsenteeismaswellasamajorcauseof work absenteeism (10) but even more importantlygood investigations regarding the impact of allergies oncognitive functions and the reduced performance ineducation and work are hardly available. Finally, directand indirect costs for allergic diseases and asthma havesharplyrisenwithinthepast10years(11–13).Although the use of asthma guidelines has reducedmorbidity and mortality, the burden of asthma is stillhigh and both the knowledge of better treatmentoptions and their implementation need to be improved(1)asdoesthedevelopmentofmoreeffectivepreventivestrategies. Knowledge of the causes of the atopicresponse and of asthma have greatly increased overthe last decade with major advances in our knowledgeof the effects of infection, diet and the environment.There remains, however, a major gap between thisknowledge and the ability to mount effective preventivecampaigns.J.Bousquet

Background: Nasal polyps (NP) are characterized by pseudocyst formation, whereas the mucosa in chronic sinusitis (CS) only shows a limited oedema. Matrix metalloproteinases (MMPs) are a family of endopeptidases able to degrade the extracellular matrix. Differences in histological features between CS and NP might be related to the respective expression of MMPs and their tissue inhibitors (TIMPs). Objective: The aim of this study was to investigate MMP-7, MMP-9 and TIMP-1 proteins in NP and CS in comparison with normal mucosa. Methods: Nasal samples, obtained from controls (n = 10), from NP (n = 8) and from CS (n = 10), were analysed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Results: In NP, compared with controls, staining for MMP-9 and MMP-7 appeared in blood vessels. Matrix metalloproteinase-9-positive inflammatory cells could be detected in increased numbers in pseudocyst formations. Concentrations of MMP-9 protein was found significantly increased in both CS and NP compared with controls, while MMP-7 was significantly increased in NP compared with controls and CS. Tissue inhibitors of metalloproteinase-1 protein was significantly increased in CS and NP when compared with controls. Conclusions: Chronic sinusitis and NP show different pattern of MMP-7/-9 and TIMP-1 expression. We suggest that this difference in regulation of enzymes is related to the respective tissue remodelling observed in both diseases.

Background: Allergic rhinitis is a common disease altering quality of life. Its treatment is well established and guidelines have been proposed. However, their efficacy has never been tested. The aim of the study was to validate the guidelines of the International Consensus on Rhinitis in the treatment of seasonal allergic rhinitis. Methods: A multicenter, multinational, open label, parallel, randomized study compared two therapeutic strategies in seasonal allergic rhinitis during a 3-week treatment. General practitioners were randomized into two groups. In the first group of 224 patients, doctors followed guidelines from the International Consensus on Rhinitis. Depending on the severity of nasal and ocular symptoms defined using visual analogue scales, patients received ebastine (an oral antihistamine), triamcinolone acetonide (a topical corticosteroid) and/or ophthalmic nedocromil sodium (a topical ocular cromone). In the second group of 241 patients, general practitioners had a free choice of treatment. The primary efficacy end points were quality of life measured using the standardized rhinoconjunctivitis quality of life questionnaire (RQLQ) and the symptom-medication scores assessed daily with an electronic dairy system. Results: Adjusted mean total symptom scores over 21 days were 4.93 in the guidelines strategy group compared with 7.48 in the free-choice treatment group (P = 0.0001). Mean total scores in the RQLQ decreased by 2.19 in the guidelines group compared with a decrease of 1.79 in the free-choice treatment group (P = 0.0001). At 21 days, the least square mean difference in improvement in overall scores for RQLQ in the guidelines group compared with the free-choice treatment group was 0.53, which was greater than the minimal important difference. Conclusions: Patients with seasonal allergic rhinitis often present severe symptoms which are not well recognized or controlled by physicians using their own criteria of severity and treatment. Using a simple method for the evaluation of the severity and a simple therapeutic scheme based on International Guidelines, patients with seasonal allergic rhinitis presented a significant improvement by comparison with those receiving a non-standardized treatment.

Background: Alternative splicing of the interleukin-5 receptor alpha (IL-5Rα)-subunit leads to the generation of a signalling, membrane-anchored (TM) isoform, or a secreted [soluble (SOL)], antagonistic variant. Given the key role of IL-5 in eosinophil function, we investigated SOL IL-5Rα expression pattern in an eosinophil-associated disease such as nasal polyposis (NP). Methods: An SOL IL-5Rα enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction (PCR) were established and applied in serum, nasal secretion and nasal tissue of controls (n = 12), and NP patients (n = 42) with or without asthma. Results: Analysis of serum, nasal secretion, and nasal tissue samples revealed that SOL IL-5Rα protein concentrations were significantly increased in NP vs control tissue. Within the NP group, there was a significant up-regulation of SOL IL-5Rα in patients with systemic airway disease. These findings were confirmed at the mRNA level, using an optimized real-time reverse-transcriptase PCR procedure. Conclusions: This report demonstrates SOL IL-5Rα transcript and protein up-regulation in NP. Soluble IL-5Rα differentiates nasal polyps with or without concomitant asthma. As SOL IL-5Rα is strongly up-regulated for disease and has antagonistic properties in vitro, our studies shed new light on the mechanisms of specific immunomodulatory therapies, such as anti-IL-5.

Summary Allergic rhinitis is a common disease, affecting 25–35% of the population. Allergic rhinitis is still increasing in prevalence. It is characterized by rhinorrhoea, itching, sneezing and nasal obstruction. Allergic rhinitis is classically classified into three groups: seasonal (intermittent), perennial (persistent) and occupational allergic rhinitis. In the ARIA document allergic rhinitis is classified into intermittent and persistent. There is a known relationship between allergic rhinitis and asthma, sinusitis, otitis media with effusion, nasal polyposis and upper respiratory tract infections. Allergic rhinitis results from IgE-mediated allergy, associated with cellular inflammation of the nasal mucosa. The diagnosis of allergic rhinitis is confirmed by a clinical history of typical allergic symptoms and in vivo or in vitro tests for detection of free or cell-bound IgE. Treatment of allergic rhinitis comprises avoidance of the allergens, oral/nasal antihistamines, decongestants, chromones, ipratropium bromide and intranasal/oral corticosteroids. It is advised to follow the international guidelines, ‘a stepwise approach’. Allergic conjunctivitis is the most common ocular allergic disorder, affecting 5–22% of the population. Ocular allergy involves typical symptoms (itching, watery, stringy or ropey discharge and redness), recurrent/intermittent/persistent episodes, a strong personal and/or family history of atopy and an early age of onset. Treatment of allergic conjunctivitis includes oral/intraocular antihistamines, cromones or topical corticosteroids.

Our understanding of the pathophysiology of allergy has moved to the molecular level, while study of epidemiology and genetics has revealed risks of developing allergies based on environmental and genetic profiles, and pharmacoeconomic data have enabled accurate measurement of the immense burden of allergic disease. These advances in allergy research have affected its management, particularly the search for new antiallergy therapies. New therapies should intervene in the systemic allergy inflammatory cascade and provide clinical efficacy that extends to multiple allergic disease states. In addition, these new therapies should present no additional safety issues, offer improvements over existing therapies, and have an impact on disease-impaired quality of life. In vitro studies show that desloratadine, a new, once-daily, nonsedating, selective histamine H1-receptor antagonist, blocks the systemic allergy cascade at multiple points. Desloratadine 5 mg once daily relieves the symptoms of chronic idiopathic urticaria and of both seasonal (SAR) and perennial allergic rhinitis. In patients with concomitant asthma and SAR, asthma symptoms are relieved and beta2-agonist medication use is decreased by desloratadine. Unlike many other second-generation histamine H1-receptor antagonists, desloratadine provides the added benefit of efficacy against nasal obstruction in SAR. Desloratadine improves quality of life by decreasing the impact of allergic symptoms on sleep and on daily activities.

Background: This paper reports a study on the concentrations of the pro-inflammatory cytokines IL-18 and IL-1β in nasal secretions of allergic rhinitis patients in relation to ECP and nasal symptoms. Methods: We measured IL-18 and IL-1β concentrations using ELISA, and eosinophilic cationic protein (ECP) using the CAP system, in nasal secretions of 15 seasonal allergic rhinitis (SAR) patients at six visits throughout the pollen season. Pollen exposure, nasal and ocular symptoms were monitored daily. Furthermore, we measured IL-18, IL-1β and ECP concentrations in nasal secretions of 19 controls and 20 symptomatic persistent allergic rhinitis (PAR) patients with house dust mite allergy. Results: In SAR, the increase of IL-18, IL-1β and ECP paralleled the pollen flight with a time delay. IL-18 and IL-1β significantly increased during the pollen season compared to baseline, and differently from ECP, remained elevated until 4 weeks after the season. In PAR, the concentrations of IL-18 and ECP, but not IL-1β, were significantly higher compared to controls, with IL-18 concentrations also being significantly higher than in SAR. Conclusion: This is the first study to demonstrate the up-regulation of IL-18 in nasal secretions in allergic rhinitis. The persistence of elevated IL-18 concentrations until after the season and the high concentrations in PAR compared to SAR suggests its role in persistent allergic inflammation.

Staphylococcus aureus (S. aureus), one of three pathogenic species of the Gram-positive cocci, is often found as part of the normal microflora of the human skin, the upper respiratory tract, especially the vestibulum nasi, and the intestinal tract. Transmission of the organism is frequently achieved by direct contact with an infected individual, although it may also be airborne or infect via fomites. It is thought that about 25% of the population are permanent carriers of S. aureus and whilst approximately 20% of all human staphylococcal infections are autogenous, several factors have been identified that predispose the host to increased susceptibility to infection by S. aureus (1). These include injury to skin or mucous membrane, abnormal leukocyte function, viral infections (e.g., influenza), metabolic abnormalities (e.g., diabetes mellitus and uraemia) and miscellaneous conditions (e.g., malnutrition, old age, malignancies, etc.). Under appropriate conditions, the organism leads to a variety of clinical conditions, affecting the skin, lungs, heart, central nervous system (CNS), bones and joints, gastrointestinal tract and the blood system (1). Skin infections, lung abscesses, pneumonia, osteomyelitis, food poisoning, fever, scalded skin syndrome and toxic shock syndrome are among the most common conditions. Although the pathogenicity of S. aureus is closely correlated with the production of coagulase enzymes, and many conditions result as a consequence of invasion by the bacterium, these organisms also contain a number of cellular antigens and produce a variety of toxins with superantigenic properties (2, 3). Recent studies of these staphylococcal superantigens have demonstrated that they can influence the activity of both immunomodulatory and pro-inflammatory effector cell types, and therefore may have a potentially important role in the pathogenesis of chronic inflammatory disease.

Resume Les glucocorticosteroides sont de loin les anti-inflammatoires les plus puissants de la pharmacopee en allergologie, et, depuis le debut des annees 1970, leurs preparations locales sont devenues un element therapeutique essentiel dans le traitement de la rhinite allergique. Grâce a une augmentation de leurs proprietes actives, grâce a leur moindre biodisponibilite et a leur meilleure tolerance, les molecules glucocorticosteroides modernes sont, non seulement de plus en plus utilisees en premier choix chez l’adulte mais elles trouvent aussi leur place dans la prise en charge de la rhinite allergique chez l’enfant. Neanmoins, compte tenu de certains rapports scientifiques recents, quelques precisions doivent etre apportees quant a leur utilisation en clinique quotidienne. Enfin, une proposition de lignes directrices pour un traitement raisonne a ete recemment publiee afin de standardiser la prise en charge de la rhinite allergique et de specifier la place de chaque possibilite therapeutique.

The purpose of this study was to document the articulation patterns in children with velo-cardio-facial syndrome. The subjects were 2 children with this syndrome, aged 6 years 6 months and 3 years 11 months. Phonetically transcribed speech samples collected by means of a picture naming test formed the basis for this study. The speech samples were subjected to two types of analyses: independent analyses describing the children’s sound productions regardless of their relation to the adult targets and relational analyses comparing the children’s productions with the adult standard form. It was found that the articulatory problems in velo-cardio-facial syndrome are not simply due to a delay in speech sound acquisition. Articulation errors found in this syndrome are uncharacteristic of normal speech development. Whether errors are syndrome-specific awaits further investigation.

Imaging of the semicircular canals specifically is part of the imaging process of the temporal bone in general. The semicircular canals are easily seen on CT images and 3DFT-CISS-weighted MR images, both performed with 1.0-mm-thick slices, or even thinner slices. In selected cases, the T1-weighted images give unique information on the semicircular canals. This article briefly reviews the variety of semicircular canal anomalies that are most frequently present and can be routinely seen on CT and MR examinations of the temporal bone. It also provides a list that can be used by the radiologist in clinical practice to decide which technique, CT or MR, should be used to detect specific anomalies at the level of the semicircular canals.

Objective To evaluate the use of maxillary sinus puncture as a routine diagnostic procedure to exclude or confirm purulent sinusitis in intensive care unit (ICU) patients presenting with fever or a septic state of unknown origin. Study Design Retrospective. Methods All patients admitted to the ICU at the University Hospital Ghent who required ENT examination to exclude acute sinusitis as possible cause of their otherwise inexplicable fever or septic state underwent maxillary sinus puncture via the inferior meatus. The results of clinical examination and the relation between the presence of foreign bodies (e.g., nasogastric tubes) and culture results from the middle meatus and sinuses were analyzed. Results One hundred five punctures were performed in 53 patients. Macroscopic purulent effusions were obtained from 25 and nonpurulent effusions from 19 sinuses. The presence of a nasogastric tube did not influence puncture results but significantly increased colonization of the middle meatus. Staphylococcus aureus and Gram-negative agents were frequently cultured from sinus aspirates. Although purulent secretions often reveal no growth, most patients present with a multibacterial (40%) or monobacterial (28%) infection. Simple anterior rhinoscopy reduces the need for antral puncture. Only 8% of punctures in patients with a normal clinical examination were positive. Conclusions Antral puncture proves to be a simple, fast, safe, inexpensive, and effective procedure for immediate diagnosis of acute nosocomial sinusitis in ICU patients and is therefore recommended as first procedure in these patients, even when only minor clinical abnormalities are present.

BACKGROUND: As there have been no previously published studies, this multinational, double-blind, randomized, placebo-controlled, parallel group study compared the efficacy, safety and impact on quality of life (QoL) in seasonal allergic rhinitis patients (SAR) of fexofenadine and loratadine (with placebo), when administered once daily. METHODS: Six hundred and eighty-eight SAR patients were randomized to receive fexofenadine HCl 120 mg, loratadine 10 mg or placebo, once daily for 2 weeks. The key parameters were the change from baseline in: mean 24-h reflective total symptom scores (TSS); sum of four individual symptom scores, excluding nasal congestion; instantaneous TSS; individual symptom scores including nasal congestion; and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). Adverse events were recorded. RESULTS: Mean 24-h reflective and instantaneous TSS were significantly reduced by both fexofenadine HCl (both P

Résumé Beaucoup de controverses existent toujours quant au rôle tenu par les virus, bactéries et champignons dans les affections rhino-sinusiennes. Une rhinite virale ne semble pas pouvoir à elle seule induire une sinusite aiguë clinique. Les bactéries déterminent l'image clinique et le devenir de la sinusite. Il n'y a pas trop de controverses quant au rôle des bactéries dans la sinusite aiguë, S. pneumoniae, H. influenzae and M. catarrhalis étant les bactéries les plus souvent retrouvées. Beaucoup plus de rapports contradictoires sont publiés concernant la flore normale des cavités sinusiennes, le rôle des anaérobies et la microbiologie de la sinusite chronique. Les liens entre pathologies infectieuses et allergiques sont plus compliqués à démontrer. Il semble que les virus, en particulier, peuvent influencer la libération de médiateurs inflammatoires et modifier l'évolution de la réaction inflammatoire. De même, leur rôle dans la destruction épithéliale, la mise à nu des terminaisons nerveuses, la sensibilisation de certaines cellules inflammatoires et par-delà, dans l'hyperréactivité des voies respiratoires en général, a été évoqué. Enfin dans le cadre des sinusites, diverses hypothèses ont été émises afin d'expliquer les liens possibles avec l'hyperréactivité bronchique.

A multicenter, double-blind, placebo-controlled study was conducted to investigate the efficacy of an immunostimulant, Ribomunyl, in the prevention of recurrences of infectious rhinitis in adults. This trial involved 327 patients (168 Ribomunyl treated and 159 placebo cases) with an average of 4.3 +/- 1.8 rhinitis episodes per patient recorded during the year preceding the study. The main criterion of efficacy was the cumulative number of recurrences of infectious rhinitis during a 6-month follow-up period, as analyzed by standard tests. An additional analysis of relative risk of recurrences used multivariate failure for time data. Ribomunyl was effective throughout the study period, starting from the first month of treatment: a mean of 1.0 +/- 1.1 recurrences was recorded in the Ribomunyl group as compared to 1.5 +/- 1.4 recurrences in the placebo group; this indicated one-third fewer infections (P = 0.001). The protective effect of Ribomunyl on the relative risk for recurrences was estimated to be 0.58 by multivariate analysis (95% CI: 0.43-0.78, P = 0.0001). Analysis of secondary criteria also favored Ribomunyl: 38.5% less antibiotic courses per patient (0.8 +/- 1.3 vs 1.3 +/- 1.6; P = 0.002) and the number of days with antibiotics (5.6 +/- 9.3 vs 9.1 +/- 12.1; P = 0.002).

The presence of eosinophils was compared in nasal biopsy and smear. Thirty-two nonallergic rhinitis patients, of whom six had nasal polyps, were included in the study. The specimens were studied light-microscopically after staining with hematoxylin-eosin. The association between the presence of polyps and the finding of eosinophils in the biopsy specimens proved to be significant. Ten normal subjects served as controls. It was far more simple to detect eosinophils in the biopsy samples than in the nasal smears. When we considered biopsies with at least four eosinophils in four fields as hypereosinophilic, our group of patients contained 25% nonallergic rhinitis with eosinophilia syndrome (NARES) patients.

Van Cauwenberge PB, De Moor SEG. Physiopathology of H3--receptors and pharmacology of betahistine. Acta Otolaryngol (Stockh) 1997: Suppl 526: 43–46.This article reviews published research on the physiology of histamine H,-receptors. The function of this inhibitory autoreceptor. its localisation and influence on histaminergic neurones as well as histamine-controlled processes are presented together with the role of H3--receptors in the vestibular system. In addition to a summary of the properties of the main H3--agonists and -antagonists, the pharmacology of betahistine and its place in the treatment of vertigo are discussed.

The geographic concentration of retail firms is a remarkable phenomenon. Existing literature suggests that retail firms benefit from spatial concentration in terms of heightened demand. However, the proximity to other firms also intensifies competition and results in higher costs for land and employees. To examine the net impact of these two opposing agglomeration effects, this paper analyzes the impact of localization, urbanization and diversity on firm profitability. The sample consists of Belgian single-establishment retail firms, during the period 2005-2010. The results show that urbanization has a negative and diversity a positive influence on profitability. Furthermore, weak evidence of localization effects is found, depending on the characteristics of the co-located firms. It seems that establishments of multi-establishment firms contribute positively to the profitability of single-establishment firms, while the presence of other single-establishment firms has a negative influence.

Since decades, scholars and policy makers have been interested in how fiscal policy influences entrepreneurship. Until now, research has focused on fiscal policy at the federal or regional level and used macro-economic outcome measures. Considerably less attention was given to how municipal governments can influence economic outcomes at the micro level. The present study examines the effect of municipal taxes, spending and tax compliance costs on firm profitability within the Flemish hospitality industry. This is a unique research setting, since Flemish municipalities have far-ranging fiscal autonomy which has resulted in a proliferation of local taxes, many of which are specific to the hospitality industry. The findings reveal that local taxes have a negative impact on firm profitability, while aggregate public spending has a positive influence. While both influences are economically significant, the tax effect exceeds the public spending impact. Finally, we find no impact of compliance costs from local taxes.