Assessing sinus aerosol deposition: benefits of SPECT-CT imaging

International audiencePurpose: Aerosol inhalation therapy is one of the methods to treat rhinosinusitis. However the topical drug delivery to the posterior nose and paranasal sinuses shows only limited efficiency. A precise sinusal targeting remains a main challenge for aerosol treatment of sinus disorders. This paper proposes a comparative study of the nasal deposition patterns of micron and submicron particles using planar gamma-scintigraphy imaging vs. a new 3-dimensional (3D) imaging approach based on SPECT-CT measurements. Methods: Radiolabelled nebulizations have been performed on a plastinated model of human nasal cast coupled with a respiratory pump. First, the benefits provided by SPECT-CT imaging were compared with 2D gamma-scintigraphy and radioactive quantification of maxillary sinus lavage as reference for the sonic 2.8 μm aerosol sinusal deposition. Then, the impact on nasal deposition of various airborne particle sizes was assessed. Results: The 2D methodology overestimates aerosol deposition in the maxillary sinuses by a factor 9 whereas the 3D methodology is in agreement with the maxillary sinus lavage reference methodology. Then with the SPECT-CT approach we highlighted that the higher particle size was mainly deposited in the central nasal cavity contrary to the submicron aerosol particles (33.8 ± 0.6% of total deposition for the 2.8 μm particles vs. 1 ± 0.3% for the 230 nm particles). Conclusion: Benefits of SPECT/CT for the assessment of radiolabelled aerosol deposition in rhinology are clearly demonstrated. This 3D methodology should be preferentially used for scintigraphic imaging of sinusal deposition in Human

Impact of acoustic airflow nebulization on intrasinus drug deposition of a human plastinated nasal cast: New insights into the mechanisms involved

International audienceThe impact of 100 Hz (Hertz) acoustic frequency airflow on sinus drug deposition of aerosols was investigated using a human plastinated nasal cast. The influence of drug concentration and endonasal anatomical features on the sinus deposition enhanced by the 100 Hz acoustic airflow was also examined. Plastinated models were anatomically, geometrically and aerodynamically validated (endoscopy, CT scans, acoustic rhinometry and rhinomanometry). Using the gentamicin as a marker, 286 experiments of aerosol deposition were performed. Changes of airborne particles metrology produced under different nebulization conditions (100 Hz acoustic airflow and gentamicin concentration) were also examined. Aerodynamic and geometric investigations highlighted a global behaviour of plastinated models in perfect accordance with a nasal decongested healthy subject. The results of intrasinus drug deposition clearly demonstrated that the aerosols can penetrate into the maxillary sinuses. The 100 Hz acoustic airflow led to increase the deposition of drug into the maxillary sinuses by a factor 2-3 depending on the nebulization conditions. A differential intrasinus deposition of active substance depending on maxillary ostium anatomical features and drug concentration was emphasized. The existence of a specific transport mechanism of penetration of nebulized particles delivered with acoustic airflow was proposed

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Création d’une Unité dédiée d’Accompagnement à la Scolarisation des Enfants avec Autisme (UDASEA) : l’intérêt d’un partenariat entre chercheurs et professionnels.

International audienc

Niveau de preuve du suivi thérapeutique pharmacologique du posaconazole

Le posaconazole, antifongique systémique, est commercialisé en France depuis 2006. Il est indiqué en deuxième ligne dans le traitement des infections fongiques invasives (IFI) [aspergilloses] et en prophylaxie des IFI chez le patient recevant une chimiothérapie ou une greffe de cellules souches hématopoïétiques. L’analyse de la littérature indique l’existence d’une relation concentration-efficacité mais à ce jour aucune étude n’a pu démontrer de relation concentration-toxicité en raison d’un profil de sécurité favorable et de la difficulté d’obtenir des concentrations élevées. En curatif, le maintien des concentrations plasmatiques résiduelles entre 0,5 et 1,5 mg/L semble être un facteur prédictif d’efficacité. En prophylaxie, le seuil de 0,5 mg/L correspondrait à une exposition minimale acceptable. Toutefois cette cible n’est pas encore définie. La saturation de l’absorption du posaconazole au-dessus de la dose per os de 800 mg est un facteur limitant à l’adaptation. À ce titre, le Suivi Thérapeutique Pharmacologique du posaconazole peut être « recommandé »

Effect of three-drug delivery modalities on Olfactory function in chronic sinusitis

Background: Olfactory dysfunction is deemed to be a significant contributor to poor quality of life in chronic rhinosinu-sitis (CRS). Objective: To assess and to compare the effectiveness of three modalities of corticosteroids administration in patients with CRS. Study Design: A prospective randomized controlled study Methods: Thirty patients with CRS were randomized in three groups depending on the route of corticosteroids administration: 16 days by oral route (Medrol (Pfizer, Belgique), 32 mg/8 days-16 mg/4 days-8 mg/4 days); nasal spray (Rhinocort (AstraZeneca, Belgique), 2 × 2 × 64 μg/nostril); or sonic nebulization (Pulmicort (AstraZeneca, Belgique), 2 × 1 mg/4 mL) (Sonic nebulizer, AOHBOX-NL11SN, DTF, France). Olfactory function was assessed using orthonasal threshold discrimination identification and retronasal psychophysical olfactory tests (RNT) before and after the treatment. Same intranasal modalities were previously tested for in vitro airways scintigraphic deposition. Results: In vitro differences in drug deposition pattern between both intranasal modalities were demonstrated. Threshold discrimination identification and RNT were similar between three groups at baseline. Threshold discrimination identification improved by 5.5, 5.8, and -1.1 for sonic nebulization, oral, and nasal spray groups, respectively (P =0.010). This improvement was clinically relevant for oral and nebulized administration. It was similar between oral and nebulized administration but significantly higher than nasal spray administration. Retronasal psychophysical olfactory tests improved similarly for the three groups (P =0.231) Conclusion: Effectiveness of sonic nebulized and oral administration is demonstrated on orthonasal olfactory. The clinical benefit is better than with nasal spray

Impact of a prevention strategy with regard to ozone pollution on the health of respiratory insufficient patients

International audienc

Impact of a prevention strategy with regard to ozone pollution on the health of respiratory insufficient patients

International audienc

Impact d’une stratégie de prévention basée sur la pollution par l’ozone sur la santé de patients atteints d’insuffisance respiratoire

National audienc