Cloé Hupin

Imprinting of the COPD airway epithelium for dedifferentiation and mesenchymal transition

In chronic obstructive pulmonary disease (COPD), epithelial changes and subepithelial fibrosis are salient features in conducting airways. Epithelial-to-mesenchymal transition (EMT) has been recently suggested in COPD, but the mechanisms and relationship to peribronchial fibrosis remain unclear. We hypothesised that de-differentiation of the COPD respiratory epithelium through EMT could participate in airway fibrosis and thereby, in airway obstruction. Surgical lung tissue and primary broncho-epithelial cultures (in air–liquid interface (ALI)) from 104 patients were assessed for EMT markers. Cell cultures were also assayed for mesenchymal features and for the role of transforming growth factor (TGF)-β1. The bronchial epithelium from COPD patients showed increased vimentin and decreased ZO-1 and E-cadherin expression. Increased vimentin expression correlated with basement membrane thickening and airflow limitation. ALI broncho-epithelial cells from COPD patients also displayed EMT phenotype in up to 2 weeks of culture, were more spindle shaped and released more fibronectin. Targeting TGF-β1 during ALI differentiation prevented vimentin induction and fibronectin release. In COPD, the airway epithelium displays features of de-differentiation towards mesenchymal cells, which correlate with peribronchial fibrosis and airflow limitation, and which are partly due to a TGF-β1-driven epithelial reprogramming. The COPD airway epithelium is programmed for mesenchymal transition via a TGF-β1-dependent process http://ow.ly/LhIQb

Features of mesenchymal transition in the airway epithelium from chronic rhinosinusitis

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.

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.

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

Abstract 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.

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.

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

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.

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

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.

Expression of the epithelial polymeric immunoglobulin receptor is decreased in allergic rhinitis and eosinophilic rhinosinusitis

Background Transcytosis of immunoglobulin A (IgA) through polarized bronchial and sinonasal epithelial cells is mediated by the polymeric immunoglobulin receptor (pIgR), which represents the rate-limiting factor for this frontline protective mechanism in the airways. pIgR expression is decreased in COPD, lung cancer and nasopharyngeal carcinoma, while its role in sinonasal chronic inflammatory diseases has not been explored. The aim of this study was thus to assess pIgR expression in sinonasal mucosa of patient with chronic rhinosinusitis with (CRSwNP) or without polyps (CRSsNP) and in allergic rhinitis (AR), as well as IgA and SC (the released soluble part of the pIgR) in nasal secretions.

WS24.3 Evaluation of the performance of sonic nebuliser to target maxillary sinuses

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.