Effect of neutrophil elastase and its inhibitor EPI-hNE4 on transepithelial sodium transport across normal and cystic fibrosis human nasal epithelial cells

<p>Abstract</p> <p>Background</p> <p>Hyperactivity of the epithelial sodium (Na⁺) channel (ENaC) and increased Na⁺absorption by airway epithelial cells leading to airway surface liquid dehydration and impaired mucociliary clearance are thought to play an important role in the pathogenesis of cystic fibrosis (CF) pulmonary disease. In airway epithelial cells, ENaC is constitutively activated by endogenous trypsin-like serine proteases such as Channel-Activating Proteases (CAPs). It was recently reported that ENaC activity could also be stimulated by apical treatment with human neutrophil elastase (hNE) in a human airway epithelial cell line, suggesting that hNE inhibition could represent a novel therapeutic approach for CF lung disease. However, whether hNE can also activate Na⁺reabsorption in primary human nasal epithelial cells (HNEC) from control or CF patients is currently unknown.</p> <p>Methods</p> <p>We evaluated by short-circuit current (<it>I</it>_sc) measurements the effects of hNE and EPI-hNE4, a specific hNE inhibitor, on ENaC activity in primary cultures of HNEC obtained from control (9) and CF (4) patients.</p> <p>Results</p> <p>Neither hNE nor EPI-hNE4 treatments did modify <it>I</it>_scin control and CF HNEC. Incubation with aprotinin, a Kunitz-type serine protease inhibitor that blocks the activity of endogenous CAPs, decreased <it>I</it>_scby 27.6% and 54% in control and CF HNEC, respectively. In control and CF HNEC pretreated with aprotinin, hNE did significantly stimulate <it>I</it>_sc, an effect which was blocked by EPI-hNE4.</p> <p>Conclusions</p> <p>These results indicate that hNE does activate ENaC and transepithelial Na⁺transport in both normal and CF HNEC, on condition that the activity of endogenous CAPs is first inhibited. The potent inhibitory effect of EPI-hNE4 on hNE-mediated ENaC activation observed in our experiments highlights that the use of EPI-hNE4 could be of interest to reduce ENaC hyperactivity in CF airways.</p

Image-guided sinus surgery

SummaryImage-guided surgery (IGS) is extremely useful for anatomic location in at-risk sinus surgery: extensive inflammatory disease, sinus cavity revision, and frontal sinus, posterior ethmoid, sphenoid or nasosinal tumor surgery. There are two systems on the market, based on electromagnetic and infrared detection, respectively; optimal functioning depends on calibration. IGS is only a location aid, complementary to and not a substitute for endoscopy. It enables the experienced endonasal surgeon to check the endoscopic location at any time, and provides appreciable “psychological” comfort in what are difficult and sometimes stressful operations, the limits of which are being forever pushed back

Atypical Sinusitis in Adults Must Lead to Looking for Cystic Fibrosis and Primary Ciliary Dyskinesia

International audienceHYPOTHESES/OBJECTIVES:: In adults, purulent pansinusitis or nasal polyposis starting early in life or that is permanently infected or associated either with chronic bronchial infection, infertility, or situs inversus are uncommon. In these atypical cases of chronic sinusitis (ACS), a primary dysfunction of the mucociliary clearance can be suspected. Adult patients with ACS were therefore investigated to detect primary ciliary dyskinesia (PCD) or cystic fibrosis (CF).Study design: Open, prospective study.Patients and methods: Forty-two patients with ACS were investigated with ciliary beat frequency and ultrastructure analysis in nasal cells and cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation analysis in blood leukocytes.Results: The diagnosis of PCD was confirmed in seven (17%) patients. At least one CFTR gene mutation was detected in 16 (38%) patients. The diagnosis of CF was suggested in three (7%) compound heterozygous patients. Another 13 (31%) patients were heterozygous for a CFTR gene mutation or a complex allele. Comparison of clinical features of ACS showed that only a family history of chronic sinusitis (P <.01) or chronic bronchitis (P <.02) and the presence of diffuse bronchiectasis (P <.0001) or serous otitis media (P <.0001) were significantly more frequent in PCD patients than in patients carrying CFTR gene mutations or those without PCD or CFTR gene mutations.Conclusions: ACS should be considered a remarkable entity in which congenital abnormalities of epithelial cells are frequently detected (55% of patients). The higher frequency of mutations in ACS patients compared with the general population suggests that heterozygoty for CFTR gene mutation could be a sinusitis-causing status

Guidelines of the French Society of Otorhinolaryngology (SFORL). Epistaxis and high blood pressure

International audienceOBJECTIVES:The authors present the guidelines of the French Oto-Rhino-Laryngology - Head and Neck Surgery Society (Société Française d'Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou: SFORL) on epistaxis in high blood pressure.METHODS:A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence.RESULTS:It is recommended to measure the blood pressure of patients in acute-phase epistaxis (Grade A); to control high blood pressure medically in the acute phase of bleeding, to reduce its duration; to monitor blood pressure at the waning of nosebleed; and to control high blood pressure medically in the waning phase to reduce the risk of recurrence. In case of persistent high blood pressure on waning of severe epistaxis, it is recommended to prescribe cardiovascular evaluation to screen for underlying hypertensive disease (Grade B)

Guidelines of the French Society of Otorhinolaryngology (SFORL). First-line treatment of epistaxis in adults

International audienceOBJECTIVES:The authors present the guidelines of the French Otorhinolaryngology-Head and Neck Surgery Society (SFORL) on first-line treatment of epistaxis in adults.METHODS:A multidisciplinary work-group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work-group. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence.RESULTS:In first-line, clearing out blood-clots and bidigital compression are recommended. In case of persistent bleeding, local anesthesia with a vasoconstrictor is essential before nasal diagnostic and therapeutic procedures. When the origin of bleeding is not anterior, nasal endoscopy is an essential procedure, identifying the bleeding site in most cases. In case of active bleeding, cauterization is recommended but is only feasible if the bleeding site is clearly visible. When the bleeding site is not identifiable or the first measures failed, anterior packing may be performed by a non-specialist physician. Epistaxis requires subsequent nasal endoscopy performed by an ENT specialist. Patients should be informed of the measures to be taken in case of epistaxis at home, and the risks associated with the various treatments

Guidelines of the French Society of Otorhinolaryngology (SFORL). Second-line treatment of epistaxis in adults

International audienceOBJECTIVES:The authors present the guidelines of the French Oto-Rhino-Laryngology - Head and Neck Surgery Society (Société Française d'Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou: SFORL) on second-line treatment of epistaxis in adults, after failure of anterior and/or anterior-posterior nasal packing.METHODS:A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence.RESULTS:Arterial embolization should be performed by an experienced interventional neuroradiologist with adequate technical facilities, to reduce the risk of complications. Cerebral and supra-aortic vessel CT angiography should be performed in case of post-traumatic epistaxis with suspected internal carotid injury. In case of persistent bleeding despite endoscopic hemostasis of the sphenopalatine artery, anterior ethmoidal artery hemostasis should be performed via a medial canthal incision, with endoscopic assistance as needed. In case of persistent epistaxis despite the usual surgical and neuroradiological procedures, surgical exploration of the sinonasal cavities should be performed, with elective coagulation in case of bleeding from secondary branches, and/or ethmoidectomy in case of diffuse bleeding. A decision-tree was drawn up for the management of second-line treatment of epistaxis

Computer-assisted analysis helps to detect inner dynein arm abnormalities

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Guidelines of the French Society of Otorhinolaryngology (SFORL) (short version). Specific treatment of epistaxis in Rendu-Osler-Weber disease

International audienceOBJECTIVES:The authors present the guidelines of the French Oto-Rhino-Laryngology - Head and Neck Surgery Society (Société Française d'Oto-Rhino-Laryngologie et de Chirurgie de la Face et du Cou: SFORL) concerning specific treatment of epistaxis in Rendu-Osler-Weber disease.METHODS:A multidisciplinary work-group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence.RESULTS:Rendu-Osler-Weber disease is diagnosed from the presence of at least three of Curaçao's four criteria. In acute epistaxis, bidigital compression is recommended. Embolization is reserved for resistant epistaxis. Non-resorbable nasal packing and cauterization are contraindicated. Patient education is essential. Telangiectasia of the nasal mucosa can be treated by various local means. In the event of insufficient control, systemic administration of tranexamic acid is recommended

Airway cell involvement in intermittent hypoxia-induced airway inflammation

International audienceRespiratory inflammation has been described in patients with obstructive sleep apnea syndrome, but it is unknown whether the increased neutrophil and interleukin (IL)-8 levels observed in induced sputum reflect systemic or local airway inflammation. We assessed the potential role of resident cells in intermittent hypoxia-induced airway inflammation