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Biomedical subjects

André Coste

Publications and source records attributed to André Coste.

7 recordsLinked to original sources

In vitro experiments and numerical simulations of airflow in realistic nasal airway geometry.

Pressure-flow relationships measured in human plastinated specimen of both nasal cavities and maxillary sinuses were compared to those obtained by numerical airflow simulations in a numerical three-dimensional reconstruction issued from CT scans of the plastinated specimen. For experiments, flow rates up to 1,500 ml/s were tested using three different gases: HeO(2), Air, and SF(6). Numerical inspiratory airflow simulations were performed for flow rates up to 353 ml/s in both the nostrils using a finite-volume-based method under steady-state conditions with CFD software using a laminar model. The good agreement between measured and numerically computed total pressure drops observed up to a flow rate of 250 ml/s is an important step to validate the ability of CFD software to describe flow in a physiologically realistic binasal model. The major total pressure drop was localized in the nasal valve region. Airflow was found to be predominant in the inferior median part of nasal cavities. Two main vortices were observed downstream from the nasal valve and toward the olfactory region. In the future, CFD software will be a useful tool for the clinician by providing a better understanding of the complexity of three-dimensional breathing flow in the nasal cavities allowing more appropriate management of the patient's symptoms.

Computer Simulation↗

Impairment of nitric oxide output of conducting airways in primary ciliary dyskinesia.

Nasal nitric oxide (NO) concentration is dramatically reduced in primary ciliary dyskinesia (PCD). The aims of this study were to apply a multiple-flow NO analysis to investigate whether NO output from the bronchial tree was affected in a similar way to nasal NO output, and to search for a relationship between flow-independent exchange parameters and airflow limitation. Multiple flow rate analysis of exhaled NO, allowing the calculation of maximum airway wall flux and alveolar NO concentration, was performed in 17 PCD patients (median age, 25-75th percentiles: 13.5, 12.1-17.6) with documented ultrastructural cilia abnormalities and 28 healthy subjects (16.0, 11.0-21.0). Median maximum airway wall flux and median alveolar NO concentration were significantly reduced in PCD patients compared to healthy subjects: 16.0, 7.5-29.5, vs. 25.0, 15.0-32.5 nl/min (P<0.05) and 2.5, 1.6-3.3, vs. 5.0, 3.6-6.5 ppb (P<0.01), respectively. Significant correlations between maximum airway wall flux and airflow limitation were found, i.e., resistance of respiratory system (rho=0.74, P<0.005), forced expiratory volume in one second (FEV(1))/VC (rho= -0.61, P<0.05), FEV(1) (rho=-0.52, P< 0.05), mid expiratory flow between 25 and 75% of forced vital capacity (MEF(25-75)) (rho=-0.54, P<0.05), and maximal instantaneous expiratory flow at 50% of the vital capacity (MEF(50)) (rho=-0.55, P<0.05). In conclusion, the impairment of NO output is less pronounced in the lower than in the upper (nasal) respiratory tract in PCD. A decrease in maximal NO output from conducting airways is associated with limited airflow impairment.

Adolescent↗

Nasal wall compliance in vasomotor rhinitis.

Nasal compliance is a measure related to the blood volume in the nasal mucosa. The objective of this study was to better understand the vascular response in vasomotor rhinitis by measuring nasal cross-sectional area and nasal compliance before and after mucosal decongestion in 10 patients with vasomotor rhinitis compared with 10 healthy subjects. Nasal compliance was inferred by measuring nasal area by acoustic rhinometry at pressures ranging from atmospheric pressure to a negative pressure of -10 cmH2O. Mucosal decongestion was obtained with one puff per nostril of 0.05% oxymetazoline. At atmospheric pressure, nasal cross-sectional areas were similar in the vasomotor rhinitis group and the healthy subject group. Mucosal decongestion did not induce any decrease of nasal compliance in patients with vasomotor rhinitis in contrast with healthy subjects. Our results support the hypothesis, already proposed, of an autonomic dysfunction based on a paradoxical response of the nasal mucosa in vasomotor rhinitis. Moreover, the clearly different behavior between healthy subjects and vasomotor rhinitis subjects suggests that nasal compliance measurement may therefore represent a potential line of research to develop a diagnostic tool for vasomotor rhinitis, which remains a diagnosis of exclusion.

Adult↗

TGF-beta 1 downregulates CFTR expression and function in nasal polyps of non-CF patients.

Nasal polyposis is a chronic inflammatory disease of the upper airways. It has been suggested that ion transports and CFTR expression could be modified in epithelial cells from nasal polyps of non-cystic fibrosis patients. We compared human nasal epithelial cells from nasal polyps (NP) with control nasal mucosa (CM). The level of CFTR mRNA was studied by Northern blot analysis and protein expression was studied by immunoprecipitation both ex vivo and in vitro in primary cultures of human nasal epithelial cells at the air-liquid interface. Ion transports were evaluated by short-circuit measurements in vitro. CFTR gene and protein expressions were significantly decreased in NP native tissues and in culture on day 4, when a global defect of ion transports was observed in NP cultures, but not in CM. We evaluated the effect of transforming growth factor (TGF)-beta 1 on CFTR expression and function in NP cultures on day 14 and showed, for the first time, that TGF-beta 1 was able to significantly downregulate the level of CFTR mRNA and cAMP-dependent current in NP cultures. Finally, we showed that the effects of TGF-beta 1 on ion transports could be reversed after 48-h removal of TGF-beta1 in NP cultures. In conclusion, our data strongly suggest that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression.

Cells, Cultured↗

Inspiratory flow in the nose: a model coupling flow and vasoerectile tissue distensibility.

We have developed a discrete multisegmental model describing the coupling between inspiratory flow and nasal wall distensibility. This model is composed of 14 individualized compliant elements, each with its own relationship between cross-sectional area and transmural pressure. Conceptually, this model is based on flow limitation induced by the narrowing of duct due to collapsing pressure. For a given inspiratory pressure and for a given compliance distribution, this model predicts the area profile and inspiratory flow. Acoustic rhinometry and posterior rhinomanometry were used to determine the initial geometric area and mechanical characteristics of each element. The proposed model, used under steady-state conditions, is able to simulate the pressure-flow relationship observed in vivo under normal conditions (4 subjects) and under pathological conditions (4 vasomotor rhinitis and 3 valve syndrome subjects). Our results suggest that nasal wall compliance is an essential parameter to understand the nasal inspiratory flow limitation phenomenon and the associated increase of resistance that is well known to physiologists. By predicting the functional pressure-flow relationship, this model could be a useful tool for the clinician to evaluate the potential effects of treatments.

Adult↗

Computer-assisted analysis helps detect inner dynein arm abnormalities.

The diagnosis of primary ciliary dyskinesia is based on demonstration of ciliary defects, mainly concerning dynein arms. Whereas the absence of outer dynein arms can be easily distinguished, the absence of inner dynein arms is difficult to confirm because of their low contrast on electron microscopy. Ciliary ultrastructure was studied in 40 patients suffering from respiratory tract infections. Conventional transmission electron microscopy showed normal cilia in 6 patients, confirmed a diagnosis of primary ciliary dyskinesia in 26 patients, and was inconclusive in 8 patients. All doubtful cases were related to inner dynein arm determination. Conventional electron microscopic analysis was able to define the ultrastructural phenotype of inner dynein arms in 40.5% of cases (6 presence of inner dynein arms, 13 absence of inner dynein arms). We developed computer-assisted analysis of electron microscopic micrographs to improve inner dynein arm visualization. Computer-assisted analysis consisted of image transformations designed to enhance the signal/noise ratio, based on the symmetry of ciliary axonemes. The sensitivity and specificity of computer-assisted analysis were 100 and 98%, respectively. The efficiency of computer-assisted analysis to visualize inner dynein arms, evaluated in the patients with undetermined phenotype after electron microscopy, was 86% (three normal cilia, seven primary ciliary dyskinesia with absence of outer dynein arms, three primary ciliary dyskinesia with absence of inner dynein arms, five partial absence of inner dynein arms). Computer-assisted analysis of ciliary micrographs improves the characterization of inherited axonemal defects.

Ciliary Motility Disorders↗

HLA-DR and ICAM-1 expression and modulation in epithelial cells from nasal polyps.

OBJECTIVE/HYPOTHESIS: Through human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1) expression, nasal epithelial cells could actively participate in the chronic inflammation and eosinophil infiltration observed in nasal polyps. The objective of the study was to evaluate HLA-DR and ICAM-1 expression in polyp epithelium and in a culture model of polyp epithelial cells allowing ciliated and secretory differentiation. STUDY DESIGN: Prospective non-randomized controlled in vitro study. METHODS: The in vitro HLA-DR and ICAM-1 expression was studied under basal conditions or after exposure to interferon-gamma, transforming growth factor-beta1, lipopolysaccharide, dexamethasone, or cetirizine. HLA-DR and ICAM-1 expression was investigated in situ by immunohistochemical staining of polyps and in vitro by immunofluorescent staining of cell cultures. HLA-DR and ICAM-1 were localized in cultured cells by confocal microscopy. Cultured cells expressing HLA-DR and ICAM-1 were quantified by flow cytometry. RESULTS: Both HLA-DR and ICAM-1 showed significant immunostaining of nasal polyp epithelium. In nasal polyp epithelial cell cultures, less than 5% of cells were positive for HLA-DR whereas 40% were positive for ICAM-1 at day 3. In vitro, HLA-DR was mainly located in the cytoplasm and ICAM-1 predominated on the apicolateral cytoplasmic membrane. Comparison of in situ and in vitro results showed that well-differentiated and poorly differentiated cells predominantly expressed HLA-DR and ICAM-1, respectively. Interferon-gamma significantly increased HLA-DR and ICAM-1 expression, whereas transforming growth factor-beta1 significantly decreased HLA-DR expression and lipopolysaccharide significantly increased ICAM-1 expression. CONCLUSION: HLA-DR and ICAM-1 epithelial expression in nasal polyps in situ and in vitro and their in vitro modulation reinforce the active role of epithelial cells in chronic inflammatory diseases of the upper airways.

Analysis of Variance↗