This report has been prepared by the European Academy of Allergy and Clinical Immunology Task Force on Allergic Rhinitis (AR) comorbidities. The aim of this multidisciplinary European consensus document is to highlight the role of multimorbidities in the definition, classification, mechanisms, recommendations for diagnosis and treatment of AR, and to define the needs in this neglected area by a literature review. AR is a systemic allergic disease and is generally associated with numerous multi-morbid disorders, including asthma, eczema, food allergies, eosinophilic oesophagitis (EoE), conjunctivitis, chronic middle ear effusions, rhinosinusitis, adenoid hypertrophy, olfaction disorders, obstructive sleep apnea, disordered sleep and consequent behavioural and educational effects. This report provides up-to-date usable information to: (1) improve the knowledge and skills of allergists, so as to ultimately improve the overall quality of patient care; (2) to increase interest in this area; and (3) to present a unique contribution to the field of upper inflammatory disease.

This EAACI position paper aims at providing a state-of-the-art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug-induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called "entopy" or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.

SummaryBackgroundMyeloid dendritic cells (mDCs) and costimulatory molecules such as ICOSL/B7H2 play a pivotal role in murine experimental asthma, while little is known in human allergic disease.The aim of this study was to characterize the phenotype and ICOSL expression of mDCs from allergic rhinitis patients (AR) and their functional correlates on mDC regulation of T cell responses.MethodsHuman blood myeloid, CD1c+ DCs were isolated from AR or healthy controls. Expression of costimulatory molecules inducible costimulatory ligand (ICOSL) and programmed death ligand 1 (PD‐L1) was analysed in blood mDCs by flow cytometry and in nasal tissue biopsies by dual immunostaining. Blood mDCs were cocultured with (allogeneic) CD4+ T cells before immunoassays for cytokine responses.ResultsmDCs from AR patients expressed a lower level of ICOSL, in both blood and nasal tissue. mDCs from AR were constitutively primed to induce Th2 cytokines and TNF in allogeneic CD4+ T cells, while no difference was observed for IFN‐γ or IL‐10. Production of IL‐10 and IL‐12 did not differ between AR and control mDCs. Blockade of ICOSL in control DCs up‐regulated IL‐13 but not IFN‐γ in cocultures with T cells, while PD‐L1 blockade up‐regulated both IL‐13 and IFN‐γ.ConclusionsOur data show that mDCs from patients with AR display impaired expression of ICOSL, and this defect licenses mDCs to promote aberrant IL‐13‐ and IL‐5‐producing Th2 cell responses.

BACKGROUND:Chronic rhinosinusitis (CRS) defines a group of disorders characterized by persistent inflammation of the sinonasal tract. Epithelial changes and structural remodelling are present, but whether epithelial differentiation is altered remains uncertain.METHODS:To evaluate the differentiation state of the sinonasal epithelium in CRS, sinonasal biopsies from patients with CRS with nasal polyps (CRSwNP) or CRS without nasal polyps (CRSsNP), or with allergic rhinitis (AR), as compared to controls, were processed by immunohistochemistry and RT-qPCR for terminal differentiation (E-cadherin, high molecular weight cytokeratins (Hmw CK) and CK5, vimentin) and lineage differentiation (ß-tubulin IV+ ciliated cells, MUC5AC+ goblet cells, p63 + basal cells). Findings were correlated with subepithelial fibrosis and clinical CT score.RESULTS:Expression of E-cadherin was decreased at protein and mRNA levels in CRSwNP and CRSsNP, as compared to controls. Staining for Hmw CKs was also reduced in CRSwNP and CRSsNP, and CK5 mRNA was decreased in CRSwNP. These features were not due to changes in lineage specification, but associated with increases in vimentin-expressing epithelial cells. In addition, vimentin expression correlated with the basement membrane thickening and with CT score, as well as with tissue eosinophils.CONCLUSION:Features of epithelial dedifferentiation towards a mesenchymal phenotype are observed in CRSwNP and CRSsNP and correlate with airway fibrosis and inflammation.

BackgroundImmunoglobulin (Ig) A represents a first-line defence mechanism in the airways, but little is known regarding its implication in upper airway disorders. This study aimed to address the hypothesis that polymeric Ig receptor (pIgR)-mediated secretory IgA immunity could be impaired in chronic upper airway diseases.MethodsNasal and ethmoidal biopsies, as well as nasal secretions, were collected from patients with chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP), allergic rhinitis (AR) and controls, and assayed for IgA1/IgA2 synthesis, pIgR expression, production of secretory component (SC), IgA and relevant IgA antibodies, and correlated with local eosinophils and inflammatory features (IL-12, IL-13 and ECP).ResultspIgR expression was decreased in the ethmoidal mucosa in patients with CRSwNP (P=0.003) and in AR (P=0.006). This pIgR defect was associated with reduced levels of SC (P=0.007) and IgA antibodies to Staphylococcus aureus enterotoxin B (SAEB) (P=0.003) in nasal secretions from patients with CRSwNP, and with increased IgA deposition in subepithelial areas. pIgR downregulation was selectively observed in patients with tissue eosinophilia, whilst no clear relation to smoking history was observed.ConclusionEpithelial pIgR expression is decreased in patients with CRSwNP and AR and results in decreased SC and IgA antibodies to certain bacterial antigens (SAEB) in nasal secretions of patients with CRSwNP in parallel to subepithelial accumulation of IgA. This defect in mucosal immunity is associated with eosinophilic, Th2-related inflammation.

Le papillome inversé est une tumeur naso-sinusienne rare touchant préférentiellement l’adulte dans la cinquième décennie. Cette tumeur présente trois caractéristiques principales la différenciant singulièrement des autres lésions des cavités naso-sinusiennes : une relative agressivité locale, un fort potentiel de récidive ainsi qu’un risque d’évolution carcinomateuse. Son étiologie reste à ce jour mal connue, mais il est rapporté une association au papillomavirus humain dans près de 40 % des cas, faisant suspecter le rôle de ce virus dans la pathogenèse du papillome inversé. Le traitement est chirurgical par voie endoscopique endonasale ou par voie externe selon l’extension et les caractéristiques de la tumeur. Le suivi est primordial afin de diagnostiquer l’apparition d’une rechute locale souvent précoce mais aussi tardive. La gravité de cette pathologie est représentée par le risque d’association à un carcinome, découvert lors du diagnostic initial ou lors de l’évolution à l’occasion d’une récidive. Il est important de dépister une rechute pour assurer sa prise en charge précoce d’autant qu’elle pourrait être associée à un carcinome ou une tumeur maligne. Une revue exhaustive de la littérature internationale a été réalisée en utilisant les moteurs de recherche PubMed et Embase. Les mots clés suivants ont été utilisés : sinonasal [All Fields] AND (papilloma, inverted [MeSH Terms] OR (papilloma [All Fields] AND inverted [All Fields]) OR inverted papilloma [All Fields] OR (inverted [All Fields] AND papilloma [All Fields])). Tous les articles publiés jusqu’en janvier 2015 faisant référence au papillome inversé naso-sinusien ont été analysés. Cet article fait état des connaissances actuelles concernant cette pathologie.

Hearing processing and communication abilities development may be influenced by chronic inflammation of the airways in children, especially in case of otitis media and/or adenotonsillar hypertrophy. The present review summarizes the influence of adenotonsillar hypertrophy on speech abilities as well as the consequences of otitis media, with a particular focus on peripheral and central hearing, on the development of language, attention, and memory skills.

Aim: Intranasal aerosol administration of drugs is widely used by ENT specialists. Although clinical evidence is still lacking, intranasal nebulization appears to be an interesting therapeutic option for local drug delivery, targeting anatomic sites beyond the nasal valve. The sonic nebulizer NL11SN associates a 100 Hertz (Hz) sound to the aerosolization to improve deposition in the nasal/paranasal sinuses. The aim of the present study was: to evaluate in vivo the influence of associating a 100 Hz sound on sinus ventilation and nasal and pulmonary aerosol deposition in normal volunteers, and; to quantify in vitro aerosol deposition in the maxillary sinuses in a plastinated head model.Material and methods: Scintigraphic analysis of Kr-81m gas ventilation and of sonic aerosol (Tc-99m-DTPA) deposition using the NL11SN was performed in vivo in seven healthy volunteers. In parallel, NL11SN gentamicin nebulization was performed, with or without associated 100 Hz sound, in a plastinated human head model; the gross amount of gentamicin delivered to the paranasal sinuses was determined by fluorescence polarization immunoassay.Results: Associating the 100 Hz sound to Kr-81m gas ensured paranasal sinus ventilation in healthy volunteers. Tc-99m-DTPA particles nebulized with the NL11SN were deposited predominantly in the nasal cavities (2/3, vs 1/3 in the lungs). In vitro, the use of NL11SN in sonic mode increased gentamicin deposition threefold in the plastinated model sinuses (P < 0.002); the resulting antibiotic deposit would be sufficient to induce a local therapeutic effect.Conclusion: The NL11SN nebulizer ensured preferential nasal cavity aerosol deposition and successfully targeted the maxillary sinuses. (C) 2011 Published by Elsevier Masson SAS.

Intranasal nebulisation seems to be the best therapeutic option for local antibiotic delivery, targeting infected sites beyond the nasal valve, especially for CF patients whose maxillary sinuses (MS) may be a source for bacterial inducing lung infections. In this study, we have evaluated the NL11SN sonic nebuliser (100 Hz) on MS ventilation and on aerosol deposition, in an in vitro model and in normal volunteers. Scintigraphy of 81mKr gas ventilation and of 99mTc-DTPA sonic aerosol deposition with NL11SN (DTF, France) was performed in 7 subjects. MS deposition was quantified using an image processing method. In vitro nebulisations were performed in a plastinated head model either with 99mTc-DTPA or with gentamicin. 99mTc-DTPA deposited in the MS was quantified by image processing method and gentamicin by a fluorescence polarization immunoassay. Ventilation 81mKr images show that the 100 Hz sound increases MS gas ventilation.99mTc-DTPA nebulised in volunteers was mainly deposited into nasal cavities (2/3 vs.1/3 in lungs) with 4.9±2.5% of total nasal deposition in the MS. In the plastinated head model, sonic mode of NL11SN increased the gentamicin deposition in MS by a factor 3 (P<0.05). The 99mTc-DTPA nebulised in the head model was deposited as 44.2±2.0% in the nasal cavities, with 4.6±2.6% into the MS (in term of total nasal deposition). The NL11SN sonic nebuliser can be used efficiently with antibiotics to target the nasal cavities including maxillary sinuses, a major site of bacterial infections. Compared to pulmonary deposition, the amount of sinus drug deposition per unit of tissue surface seems sufficient to induce a local therapeutic effect.

L’administration nasale de médicaments sous forme d’aérosol est largement utilisée par les otorhinolaryngologistes. Bien qu’elle manque d’évaluations cliniques, la nébulisation ORL se présente comme une option thérapeutique intéressante pour l’administration nasale de médicaments. Les aérosols permettraient de cibler les sites anatomiques d’intérêt situés derrière la valve nasale. Le nébuliseur sonique NL11SN utilise l’addition d’un son de 100 Hertz (Hz) à l’aérosol produit afin d’améliorer le dépôt dans les sinus. L’objectif de notre étude était : (1) d’évaluer in vivo chez le volontaire sain l’influence du son sur la ventilation sinusienne et le dépôt nasal et pulmonaire d’un aérosol sonique, et (2) de quantifier in vitro le dépôt d’aérosols soniques dans les sinus maxillaires d’un modèle plastiné. In vivo, une scintigraphie de ventilation au gaz 81mKr et une scintigraphie de dépôt d’aérosol (99mTc-DTPA) sonique produit par le NL11SN étaient réalisées chez sept volontaires sains. En parallèle, des nébulisations de gentamicine étaient réalisées en présence ou en absence du son de 100 Hz sur un modèle de tête humaine plastinée avec le NL11SN. La quantité de gentamicine déposée dans les sinus était dosée par FPIA. L’addition du son de 100 Hz au gaz 81mKr permettait la ventilation des cavités sinusiennes des volontaires sains. Le 99mTc-DTPA nébulisé avec le NL11SN chez les volontaires se déposait majoritairement dans les cavités nasales (2/3 vs 1/3 dans les poumons). In vitro, le NL11SN utilisé en mode sonique a permis d’augmenter d’un facteur 3 (p < 0,002) le dépôt de gentamicine dans les sinus du modèle plastiné. Les quantités d’antibiotiques déposées dans les sinus du modèle plastiné pouvaient être considérées comme suffisantes pour avoir un effet thérapeutique local. Le nébuliseur NL11SN assure un dépôt préférentiel de l’aérosol dans les cavités nasales et cible efficacement les sinus maxillaires.

Adenotonsillar hypertrophy is a common paediatric/otolaryngological disorder that may be associated with secondary growth or facial growth impairment, sleep disturbances, neurocognitive deficits, or smell loss. Surgical removal of the hypertrophic tissue eliminates the mechanical obstacle of the airways and is therefore curative in most cases. The purpose of the present review is to outline the impact of adenotonsillar hypertrophy and adenotonsillectomy on growth, facial growth, sleep, behaviour and smell.

Lymphoepithelial cyst of the nasogenian sulcus: a case report. A rare case of lymphoepithelial cyst formed in the nasogenian sulcus is reported. Lymphoepithelial cysts are comprised of a stratified squamous epithelial lining above dense lymphoid tissue. They are uncommon in the oral region and, to our knowledge, have never been reported in the nasogenian sulcus. Surgical excision was performed and no recurrence was noted after 6 months. In this report, we describe the etiopathogenesis of lymphoepithelial cysts, as well as the differential diagnosis of nasogenian sulcus swellings.

Congenital dacryocystocele (CDC) is recognised as a cause of nasal airway obstruction or respiratory distress in newborns. CDC is caused by the distal obstruction of the lachrymal duct and presents as a cystic formation in the inferior meatus. We discuss five cases of dacryocystocele, together with surgical management and outcome. Endoscopic endonasal marsupialisation and appropriate postoperative care resulted in definitive recovery for all patients. In newborns or infants with nasal obstruction, CDC should be considered in the differential diagnosis, and prompt endoscopic endonasal marsupialisation is mandatory.