Multi-morbidities of allergic rhinitis in adults: European Academy of Allergy and Clinical Immunology Task Force Report.

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.

Non-allergic rhinitis: Position paper of the European Academy of Allergy and Clinical Immunology.

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.

Chronic inflammatory airway diseases: the central role of the epithelium revisited.

The respiratory epithelium plays a critical role for the maintenance of airway integrity and defense against inhaled particles. Physical barrier provided by apical junctions and mucociliary clearance clears inhaled pathogens, allergens or toxics, to prevent continuous stimulation of adaptive immune responses. The "chemical barrier", consisting of several anti-microbial factors such as lysozyme and lactoferrin, constitutes another protective mechanism of the mucosae against external aggressions before adaptive immune response starts. The reconstruction of damaged respiratory epithelium is crucial to restore this barrier. This review examines the role of the airway epithelium through recent advances in health and chronic inflammatory diseases in the lower conducting airways (in asthma and chronic obstructive pulmonary disease). Better understanding of normal and altered epithelial functions continuously provides new insights into the physiopathology of chronic airway diseases and should help to identify new epithelial-targeted therapies.

Features of mesenchymal transition in the airway epithelium from chronic rhinosinusitis.

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.

Impaired ICOSL in human myeloid dendritic cells promotes Th2 responses in patients with allergic rhinitis and asthma.

BACKGROUND: Myeloid 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. METHODS: Human 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. RESULTS: mDCs 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. CONCLUSIONS: Our 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.

Downregulation of polymeric immunoglobulin receptor and secretory IgA antibodies in eosinophilic upper airway diseases.

BACKGROUND: Immunoglobulin (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. METHODS: Nasal 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). RESULTS: pIgR 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. CONCLUSION: Epithelial 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.

[Delayed diagnosis of Plasmodium falciparum in a soldier in Uganda: false-positive rapid diagnostic test associated with reduced repeats in pfhrp2]. / Retard de diagnostic d'un accès palustre à Plasmodium falciparum chez un militaire en Ouganda : négativité des tests de diagnostic rapide associée à un polymorphisme de l'antigène HRP2.

Rapid diagnostic tests (RDTs) are the best alternative for malaria diagnosis where a microscopic examination cannot be performed. We report here the first case of P. falciparum (false-negative) misdiagnosis in a soldier stationed in Uganda, associated with a reduced number of repeats in the P. falciparum histidine-rich protein 2 gene (pfhrp2). This gene was subsequently sequenced to determine the reason for the discordance between the RDT results and the later microscopic examination. Ten repeats of the type 2 motif AHHAHHAAD and four repeats of the type 7 motif AHHAAD were found. This isolate belongs to the group of non-sensitive parasites (<43 repeats) that are not detected by HRP2 RDTs. This inappropriate case management could have been fatal for the patient. This case confirms the problem of negative RDT results in isolated situations and of basing a therapeutic strategy on these negative results. Investigations should be conducted in Uganda and other areas of Africa to determine the presence and the geographical spread of parasites with pfhrp2 gene deletion to ensure the best performance of RDTs.

Sonic aerosol therapy to target maxillary sinuses.

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 100Hertz (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 100Hz 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 (81m)Kr gas ventilation and of sonic aerosol ((99m)Tc-DTPA) deposition using the NL11SN was performed in vivo in seven healthy volunteers. In parallel, NL11SN gentamicin nebulization was performed, with or without associated 100Hz 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 100Hz sound to (81m)Kr gas ensured paranasal sinus ventilation in healthy volunteers. (99m)Tc-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.

Physiology of the mouth and pharynx, Waldeyer's ring, taste and smell.

This paper reviews the contribution of the different parts of the oral cavity and the pharynx to the basic physiology of breathing, phonation, speech, swallowing, and of Waldeyer's ring to the functioning of the immune system. We discuss the development of taste and smell, as well as possibilities for chemosensory testing in children.

Consequences of chronic inflammation in children on facial growth, growth, behavioural disorders and smell.

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.

Functional consequences of chronic ENT inflammation on the development of hearing and communicative abilities.

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.

Novel influenza A(H1N1) outbreak among French armed forces in 2009: results of Military Influenza Surveillance System.

OBJECTIVES: An outbreak of novel A(H1N1) virus influenza, detected in Mexico in April 2009, spread worldwide in 9 weeks. The aim of this paper is to present the monitoring results of this influenza outbreak among French armed forces. STUDY DESIGN: The period of monitoring by the Military Influenza Surveillance System (MISS) was 9 months, from May 2009 to April 2010. METHODS: The main monitored events were acute respiratory infection (ARI), defined by oral temperature ≥38.5 °C and cough, and laboratory-confirmed influenza. Weekly incidence rates were calculated by relating cases to the number of servicepersons monitored. RESULTS: In continental France, the incidence of ARI increased from September 2009, with a weekly maxima of 401 cases per 100,000 in early December 2009 according to MISS. Estimations of the incidence of consultations which could be related to novel A(H1N1) influenza ranged from 48 to 57 cases per 100,000. CONCLUSIONS: The trends observed by MISS are compatible with French national estimations. The incidence of consultations which could be related to A(H1N1) influenza at the peak of the epidemic (194 cases per 100,000) was much lower than the national estimate (1321 cases per 100,000). This may be due to servicepersons who consulted in civilian facilities and were not monitored. Other explanations are the healthy worker effect and the younger age of the military population.

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: five clinical cases.

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.

Bioavailability study of gitoxin in a solid dosage form.

Although the cardiotonic activity of gitoxin is known for almost half a century, this digitalis glycoside has never been used in therapy, due to its apparent lack of resorption after administration by oral route. Recent studies have demonstrated that the bioavailability of gitoxin could be upraised to 100% provided it be given as a hydroalcoholic solution. The present paper deals with the development of a solid dosage form (tablets) using a physical association of gitoxin and sodium escinate.