C. M. Van Drunen

Chronic rhinosinusitis in Europe--an underestimated disease. A GA²LEN study.

To cite this article: Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlén SE, Forsberg B, Gunnbjörnsdóttir M, Kasper L, Krämer U, Kowalski ML, Lange B, Lundbäck B, Salagean E, Todo‐Bom A, Tomassen P, Toskala E, van Drunen CM, Bousquet J, Zuberbier T, Jarvis D, Burney P. Chronic rhinosinusitis in Europe – an underestimated disease. A GA2LEN study. Allergy 2011; 66: 1216–1223.

Integrated Cytogenetic Map of Chromosome Arm 4S of A. thaliana: Structural Organization of Heterochromatic Knob and Centromere Region

We have constructed an integrated cytogenetic map of chromosome arm 4S of Arabidopsis thaliana. The map shows the detailed positions of various multicopy and unique sequences relative to euchromatin and heterochromatin segments. A quantitative analysis of the map positions at subsequent meiotic stages revealed a striking pattern of spatial and temporal variation in chromatin condensation for euchromatin and heterochromatin. For example, the centromere region consists of three domains with distinguishable structural, molecular, and functional properties. We also characterized a conspicuous heterochromatic knob of approximately 700 kb that accommodates a tandem repeat and several dispersed pericentromere-specific repeats. Moreover, our data provide evidence for an inversion event that relocated pericentromeric sequences to an interstitial position, resulting in the heterochromatic knob.

Viruses and bacteria in acute asthma exacerbations--a GA² LEN-DARE systematic review

To cite this article: Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet J, Braido F, Brusselle G, Canonica GW, Carlsen KH, Chanez P, Fokkens WJ, Garcia‐Garcia M, Gjomarkaj M, Haahtela T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska‐Polak A, Lødrup‐Carlsen K, Mäkelä M, Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki E, Rukhadze M, Stipic‐Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, Xatzipsalti M, Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations – A GA2LEN‐DARE systematic review. Allergy 2011; 66: 458–468.

Mechanisms of virus‐induced asthma exacerbations: state‐of‐the‐art. A GA2LEN and InterAirways document

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.

Important research questions in allergy and related diseases: 3-chronic rhinosinusitis and nasal polyposis - a GALEN study.

Chronic rhinosinusitis is one of the most common health care challenges, with significant direct medical costs and severe impact on lower airway disease and general health outcomes. The diagnosis of chronic rhinosinusitis (CRS) currently is based on clinical signs, nasal endoscopy and CT scanning, and therapeutic recommendations are focussing on 2 classes of drugs, corticosteroids and antibiotics. A better understanding of the pathogenesis and the factors amplifying mucosal inflammation therefore seems to be crucial for the development of new diagnostic and therapeutic tools. In an effort to extend knowledge in this area, the WP 2.7.2 of the GA2LEN network of excellence currently collects data and samples of 1000 CRS patients and 250 control subjects. The main objective of this project is to characterize patients with upper airway disease on the basis of clinical parameters, infectious agents, inflammatory mechanisms and remodeling processes. This collaborative research will result in better knowledge on patient phenotypes, pathomechanisms, and subtypes in chronic rhinosinusitis. This review summarizes the state of the art on chronic rhinosinusitis and nasal polyposis in different aspects of the disease. It defines potential gaps in the current research, and points to future research perspectives and targets.

How epithelial cells detect danger : aiding the immune response

The epithelial layer occupies a strategic important location between an organisms’ interior and exterior environment. Although as such it forms a physical barrier between both environments, it became clear that the role of the epithelium extends far beyond this rather passive role. Through specialized receptors and other more general mechanisms, the epithelial layer is not only able to sense changes in its environment but also to actively respond to these changes. These responses allow the epithelium to contribute to wound and tissue repair, to the defense against micro‐organisms, and to the control and regulation of the locale immune response. In this review, we focus on signals acting on epithelium from the exterior environment, how these signals are processed and identify research challenges.

Nasal polyposis: a cellular-based approach to answering questions.

Nasal polyposis (NP) is a common chronic inflammatorydisease of the nasal mucosa that has a major impact onpatients lives. NP is characterized by benign polypoustissue swellings in the nose that originate from theparanasal sinuses, most often from the anterior ethmoidcomplex (Figs 1 and 2) (1). From there the polyps candescendbetweenthemiddleturbinateandthelateralnasalwall into the nasal cavity causing symptoms such as nasalcongestion, rhinorrhea, hyposmia and facial pressure (2).Treatment with corticosteroids alleviates symptoms,but no curative treatment exists. Often patients requirerecurrent operations and this, in combination with thesymptoms, has a significant effect on the patients qualityof life (3, 4). When tested by means of a disease-independent questionnaire (SF-36), the quality of life inthese patients is worse than in patients suffering fromhypertension, migraine, angina pectoris and head andneck cancer. NP patients have comparable quality of lifescores as patients with chronic obstructive pulmonarydisease (5). Unfortunately, the aetiology of NP is largelyunknown. Although some hypotheses have focused onthe possible involvement of micro-organisms in theaetiology of NP, this has not yet developed into asuccessful treatment alternative.This review aims at discussing some of the difficultiesand pitfalls in NP research, and to identify the importantcellular players and interactions in the pathophysiologyof NP. We would also like to suggest potential relevantfuture directions for research. Understanding the patho-genesis of NP may lead to new treatment options for thisincapacitating disease.Difficulties in NP researchFundamental research into the pathogenesis of NP ishampered by two problems. First, it is unclear how themany different clinical phenotypes of NP influence thepathogenesis. Secondly, it is not clear whether NP shouldbe considered a local disease or a local manifestation of asystemic disease.Many co-morbidities have been described in NP thataffect the prevalence of NP. In the general population theprevalence is 0.5–4.3%, making it one of the mostcommon chronic diseases of the upper respiratory tract.The prevalence of NP is increased in patients with asthma(7–15%), cystic fibrosis (39–56%) or aspirin intolerance(36–96%). Interestingly, although the prevalence isincreased in asthma, this does not seem to hold true forpatients with allergic rhinitis, where the prevalence of NPis unchanged (0.5–4.5%) (2, 6). Chronic rhinosinusitis(CRS) almost always coexists with NP, but the converseis not true, only about 20% of the patients with CRSdevelop nasal polyps (7). Evidence accumulates that CRSwith NP and CRS without NP actually are two differentdisease entities (8, 9).A. B. Rinia

Staphylococcus aureus enterotoxin-specific IgE is associated with asthma in the general population : a GA(2)LEN study

Specific IgE to Staphylococcus aureus enterotoxins (SE‐IgE) has been associated with asthma. In the general population, we aimed to determine the prevalence of and risk factors for serum SE‐IgE and to examine the association with asthma.

Nasal allergies and beyond: a clinical review of the pharmacology, efficacy, and safety of mometasone furoate

Mometasone furoate nasal spray (MFNS; Nasonex®, Schering‐Plough Corporation, Kenilworth, NJ, USA) is an effective and well‐tolerated intranasal corticosteroid approved for the prophylactic treatment of seasonal allergic rhinitis, and the treatment of perennial allergic rhinitis. MFNS is a potent molecule with a rapid onset of action and excellent safety and efficacy profiles. Having recently received approval for the treatment of nasal polyposis, data indicate that MFNS may also be effective in rhinosinusitis.

Allergen induced gene expression of airway epithelial cells shows a possible role for TNF‐α

Background:  Epithelium is more than a physical barrier for pathogens and allergens, as it is also capable of producing mediators in response to these environmental factors. Some of these mediators have an immuno‐modulatory function, suggesting that epithelium is an active component of the immune response. Here, we fully characterize the expression profile of airway epithelial cells in response to house dust mite (HDM) allergen.