Type 2 Innate Lymphoid Cells in Allergic Disease.

Type II innate lymphoid cells (ILC2) are a novel population of lineage-negative cells that produce high levels of Th2 cytokines IL-5 and IL-13. ILC2 are found in human respiratory and gastrointestinal tissue as well as in skin. Studies from mouse models of asthma and atopic dermatitis suggest a role for ILC2 in promoting allergic inflammation. The epithelial cytokines IL-25, IL-33, and TSLP, as well as the lipid mediator leukotriene D4, have been shown to potently activate ILC2 under specific conditions and supporting the notion that many separate pathways in allergic disease may result in stimulation of ILC2. Ongoing investigations are required to better characterize the relative contribution of ILC2 in allergic inflammation as well as mechanisms by which other cell types including conventional T cells regulate ILC2 survival, proliferation, and cytokine production. Importantly, therapeutic strategies to target ILC2 may reduce allergic inflammation in afflicted individuals. This review summarizes the development, surface marker profile, cytokine production, and upstream regulation of ILC2, and focuses on the role of ILC2 in common allergic diseases

Prostaglandin E2 receptors in asthma and in chronic rhinosinusitis/nasal polyps with and without aspirin hypersensitivity

Chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma frequently coexist and are always present in patients with aspirin exacerbated respiratory disease (AERD). Although the pathogenic mechanisms of this condition are still unknown, AERD may be due, at least in part, to an imbalance in eicosanoid metabolism (increased production of cysteinyl leukotrienes (CysLTs) and reduced biosynthesis of prostaglandin (PG) E2), possibly increasing and perpetuating the process of inflammation. PGE2 results from the metabolism of arachidonic acid (AA) by cyclooxygenase (COX) enzymes, and seems to play a central role in homeostasis maintenance and inflammatory response modulation in airways. Therefore, the abnormal regulation of PGE2 could contribute to the exacerbated processes observed in AERD. PGE2 exerts its actions through four G-protein-coupled receptors designated E-prostanoid (EP) receptors EP1, EP2, EP3, and EP4. Altered PGE2 production as well as differential EP receptor expression has been reported in both upper and lower airways of patients with AERD. Since the heterogeneity of these receptors is the key for the multiple biological effects of PGE2 this review focuses on the studies available to elucidate the importance of these receptors in inflammatory airway diseases

Staphylococcus aureus controls interleukin-5 release in upper airway inflammation

Staphylococcus aureus is a frequent colonizer of the upper airways in chronic rhinosinusitis with nasal polyps, but also resides intramucosally, it has been shown that secreted staphylococcal proteins such as enterotoxins and serine proteases induce the release of cytokines such as IL-5. We have analyzed nasal polyp tissue freshly obtained during routine surgery, which did or did not contain cultivatable S. aureus, to study spontaneous IL-5 production by nasal polyp tissue over 24 and 72 h in tissue culture In S. aureus-positive samples we interfered by killing the bacteria using antibiotics or S. aureus specific intravenous staphylococcal phages (ISP), active or heat-inactivated. Phage-neutralizing antibodies were used to demonstrate the specificity of the phage-mediated effects We monitored S. aureus colony forming units, and identified S. aureus proteins by mass spectrometry We demonstrate that cultivatable S. aureus may be found in type-2 inflamed nasal polyps, the pathogen is replicating within 24 h and secretes proteins, including enterotoxins and serine proteases The presence of S. aureus was associated with a significantly higher release of IL-5 Killing of S. aureus by antibiotics or specific ISP significantly reduced the IL-5 release. The suppressive activity of the bacteriophage on IL-5 be abolished by heat inactivation or anti-phage antibodies. Biological significance In this study, we used high resolution mass spectrometry to identify S. aureus proteins directly in infected nasal polyp tissue and nasal polyp tissue incubated over 24 and 72 h in culture We discovered bacterial proteins including enterotoxins and serine proteases like proteins These experiments indicate a direct role of S. aureus in the regulation of IL-5 production in nasal polyps and may suggest the involvement of bacterial proteins detected in the tissues

Rhinosinusitis and asthma: a very long engagement

Upper and lower airways may be considered as a unique entity, interested by coexisting inflammatory processes that share common etiopathogenic mechanisms. Previous studies have strongly demonstrated a relationship between rhinosinusitis and asthma. This has led to the introduction of the concept of United Airways , which has also been included in the WHO document Allergic Rhinitis and its Impact on Asthma (ARIA); this concept has important consequences also on the treatment of these disorders. To better summarize the evident connection between upper and lower airway disease we decided to describe it as a multilayered construction, each level pointing out more deeply the relationship between these entities

Neglected treatable traits in adult asthma

Het proefschrift beschrijft als eerste een gestructureerde 1-daagse beoordeling van patiënten met ongecontroleerd astma door verschillende medische disciplines in een gespecialiseerd ernstig astmacentrum. De studie toonde aan dat patiënten met ongecontroleerd astma baat hebben bij deze eenmalige uitgebreide beoordeling. Er was sprake van een relevante verbetering van de astmacontrole, kwaliteit van leven en zorggebruik na 1 jaar. Ook bevat het proefschrift een overzicht over neuspoliepen en astma. In dit overzichtsartikel wordt de relatie tussen astma en neuspoliepen beschreven vanuit het oogpunt van de longarts. In de volgende twee hoofdstukken van het proefschrift gaat het over dynamische hyperinflatie bij patiënten met matig tot ernstig astma. De studie laten zien dat bij 81% van de patiënten er sprake was van dynamische hyperinflatie. De ernst van dynamische hyperinflatie ging samen met meer astmasymptomen en beperking bij inspanning. De vervolg studie laat zien dat een behandeling met ontstekingsremmers (eenmalige injectie met een hoge dosis triamcinolon) dynamische hyperinflatie laat afnemen bij patiënten met matig tot ernstig astma. In de laatste studie van het proefschrift werd de uitgifte van orale corticosteroïden (OCS) aan astma patiënten geanalyseerd in Nederland. Uit de studie bleek dat 7,2% van de patiënten met astma werden blootgesteld aan OCS. 2,6% van de patiënten kreeg twee of meer OCS stootkuren en 4,6% kreeg een OCS onderhoudsbehandeling, waarvan slechts ongeveer de helft een goede dosis inhalatiemedicatie gebruikte. De meerderheid van de patiënten die vaak OCS gebruikten kreeg dit voorgeschreven door de huisarts. Ongeveer de helft van de patiënten die vaak een OCS stootkuur kregen en een derde van de patiënten met OCS onderhoudsbehandeling hadden tot drie jaar van te voren geen astmamedicatie voorgeschreven gekregen door een specialist. Dit suggereert dat deze patiënten in de eerstelijnszorg worden behandeld, zonder een beoordeling door een specialist