Functional and structural consequences of epithelial cell invasion by Bordetella pertussis adenylate cyclase toxin.

Bordetella pertussis, the causative agent of whopping cough, produces an adenylate cyclase toxin (CyaA) that plays a key role in the host colonization by targeting innate immune cells which express CD11b/CD18, the cellular receptor of CyaA. CyaA is also able to invade non-phagocytic cells, via a unique entry pathway consisting in a direct translocation of its catalytic domain across the cytoplasmic membrane of the cells. Within the cells, CyaA is activated by calmodulin to produce high levels of cyclic adenosine monophosphate (cAMP) and alter cellular physiology.

Pathogenesis of chronic rhinosinusitis with nasal polyps: role of IL-6 in airway epithelial cell dysfunction.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by an alteration in airway epithelial cell functions including barrier function, wound repair mechanisms, mucociliary clearance. The mechanisms leading to epithelial cell dysfunction in nasal polyps (NPs) remain poorly understood. Our hypothesis was that among the inflammatory cytokines involved in NPs, IL-6 could alter epithelial repair mechanisms and mucociliary clearance.

Surfactant delivery in rat lungs: Comparing 3D geometrical simulation model with experimental instillation.

Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures.

FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?

Monoclonal antibodies (mAbs) are promising therapies to treat airway chronic inflammatory disease (asthma or nasal polyps). To date, no study has specifically assessed, in vitro, the potential function of neonatal Fc receptor (FcRn) in IgG transcytosis through the human nasal airway epithelium. The objective of this study was to report the in vitro expression and function of FcRn in nasal human epithelium.

Inflammatory Cellular Response to Mechanical Ventilation in Elastase-Induced Experimental Emphysema: Role of Preexisting Alveolar Macrophages Infiltration.

An excessive pulmonary inflammatory response could explain the poor prognosis of chronic obstructive pulmonary disease (COPD) patients submitted to invasive mechanical ventilation. The aim of this study was to evaluate the response to normal tidal volume mechanical ventilation in an elastase-induced murine model of pulmonary emphysema. In this model, two time points, associated with different levels of lung inflammation but similar lung destruction, were analyzed.

A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part I, experimental analysis.

Mucociliary clearance is one of the major lines of defense of the respiratory system. The mucus layer coating the pulmonary airways is moved along and out of the lung by the activity of motile cilia, thus expelling the particles trapped in it. Here we compare ex vivo measurements of a Newtonian flow induced by cilia beating (using micro-beads as tracers) and a mathematical model of this fluid flow, presented in greater detail in a second companion article.

A new index for characterizing micro-bead motion in a flow induced by ciliary beating: Part II, modeling.

Mucociliary clearance is one of the major lines of defense of the human respiratory system. The mucus layer coating the airways is constantly moved along and out of the lung by the activity of motile cilia, expelling at the same time particles trapped in it. The efficiency of the cilia motion can experimentally be assessed by measuring the velocity of micro-beads traveling through the fluid surrounding the cilia.

Exposure to Bordetella pertussis adenylate cyclase toxin affects integrin-mediated adhesion and mechanics in alveolar epithelial cells.

Background Information: The adenylate cyclase (CyaA) toxin is a major virulent factor of Bordetella pertussis, the causative agent of whooping cough. CyaA toxin is able to invade eukaryotic cells where it produces high levels of cyclic adenosine monophosphate (cAMP) affecting cellular physiology. Whether CyaA toxin can modulate cell matrix adhesion and mechanics of infected cells remains largely unknown.

Characterisation of cellular adhesion reinforcement by multiple bond force spectroscopy in alveolar epithelial cells.

Background Information: Integrin-mediated adhesion is a key process by which cells physically connect with their environment, and express sensitivity and adaptation through mechanotransduction. A critical step of cell adhesion is the formation of the first bonds which individually generate weak contacts (∼tens pN) but can sustain thousand times higher forces (∼tens nN) when associated.

Results: We propose an experimental validation by multiple bond force spectroscopy (MFS) of a stochastic model predicting adhesion reinforcement permitted by non-cooperative, multiple bonds on which force is homogeneously distributed (called parallel bond configuration).

Investigating hyperventilation syndrome in patients suffering from empty nose syndrome.

Objectives/hypothesis: Patients with empty nose syndrome (ENS) following turbinate surgery often complain about breathing difficulties. We set out to determine if dyspnea in patients with ENS was associated with hyperventilation syndrome (HVS). We hypothesized that lower airway symptoms in ENS could be explained by HVS.

A Macroscopic Model for Simulating the Mucociliary Clearance in a Bronchial Bifurcation: The Role of Surface Tension.

The mucociliary clearance in the bronchial tree is the main mechanism by which the lungs clear themselves of deposited particulate matter. In this work, a macroscopic model of the clearance mechanism is proposed. Lubrication theory is applied for thin films with both surface tension effects and a moving wall boundary.

A functional tool to differentiate nasal valve collapse from other causes of nasal obstruction: the FRIED test.

Nasal valve collapse is a dynamic abnormality that is currently diagnosed purely on the basis of clinical features and thus subject to certain interpretation. The aim of this study was to develop a new and reliable functional test to objectively characterize nasal valve collapse. This was an observational prospective study including consecutive patients referred to our center for exploration of chronic nasal congestion.

Aerosol therapy in intensive and intermediate care units: prospective observation of 2808 critically ill patients.

Purpose: Unlike in the outpatient setting, delivery of aerosols to critically ill patients may be considered complex, particularly in ventilated patients, and benefits remain to be proven. Many factors influence aerosol delivery and recommendations exist, but little is known about knowledge translation into clinical practice.

Methods: Two-week cross-sectional study to assess the prevalence of aerosol therapy in 81 intensive and intermediate care units in 22 countries.

Multiscale evaluation of cellular adhesion alteration and cytoskeleton remodeling by magnetic bead twisting.

Cellular adhesion forces depend on local biological conditions meaning that adhesion characterization must be performed while preserving cellular integrity. We presently postulate that magnetic bead twisting provides an appropriate stress, i.e.

Total liquid ventilation offers ultra-fast and whole-body cooling in large animals in physiological conditions and during cardiac arrest.

Introduction: Total liquid ventilation (TLV) can cool down the entire body within 10-15 min in small animals. Our goal was to determine whether it could also induce ultra-fast and whole-body cooling in large animals using a specifically dedicated liquid ventilator. Cooling efficiency was evaluated under physiological conditions (beating-heart) and during cardiac arrest with automated chest compressions (CC, intra-arrest).

Phase-contrast helium-3 MRI of aerosol deposition in human airways.

One of the key challenges in the study of health-related aerosols is predicting and monitoring sites of particle deposition in the respiratory tract. The potential health risks of ambient exposure to environmental or workplace aerosols and the beneficial effects of medical aerosols are strongly influenced by the site of aerosol deposition along the respiratory tract. Nuclear medicine is the only current modality that combines quantification and regional localization of aerosol deposition, and this technique remains limited by its spatial and temporal resolutions and by patient exposure to radiation.

Description and microbiology of endotracheal tube biofilm in mechanically ventilated subjects.

Background: A biofilm is found on the inner side of endotracheal tubes (ETT) in mechanically ventilated patients, but its features and role in pneumonia remain unclear.

Methods: This prospective, observational, monocentric study included critically ill ventilated subjects. Measurement of the ETT inner volume was first performed before extubation using the acoustic reflection method.

Evaluation of lung recovery after static administration of three different perfluorocarbons in pigs.

Background: The respiratory properties of perfluorocarbons (PFC) have been widely studied for liquid ventilation in humans and animals. Several PFC were tested but their tolerance may depend on the species. Here, the effects of a single administration of liquid PFC into pig lungs were assessed and compared.

Ventilator-integrated jet nebulization systems: tidal volume control and efficiency of synchronization.

Background: Jet nebulizers constitute the aerosolization devices most frequently used during mechanical ventilation. Continuous nebulization can influence the delivered tidal volume (V(T)) and lead to significant medication loss during expiration. Ventilators thus provide integrated jet nebulization systems that are synchronized during inspiration and ostensibly keep VT constant.

Frictional resistance sheds light on the multicomponent nature of nasal obstruction: a combined in vivo and computational fluid dynamics study.

Exploring nasal flow contributes to better understanding of pathophysiological functions of nasal cavities. We combined the rhinomanometry measurements of 11 patients and computational fluid dynamics (CFD) simulations in 3 nasal airway models to dissect the complex mechanisms that determine nasal flow obstruction: spatial complexity and pressure-dependent deformability of nasal airways. We quantified spatial complexity by calculating longitudinal variations of hydraulic diameter, perimeter and area of nasal cavities, and their impact on flow characteristics by examining the longitudinal variations of the kinetic energy coefficient and the kinetic to potential energy ratio.

Aerosol therapy during mechanical ventilation: an international survey.

Purpose: To describe the practice, knowledge and beliefs about aerosol therapy during mechanical ventilation in an international sample of physicians working in intensive care units (ICU).

Methods: A self-administered survey was emailed to physicians who worked regularly in ICUs. The physicians were identified from the databases of the European and French societies of intensive care medicine and the REVA network.

Force control of endothelium permeability in mechanically stressed pulmonary micro-vascular endothelial cells.

Mechanical factors play a key role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) as contributing to alveolo-capillary barrier dysfunction. This study aims at elucidating the role of the cytoskeleton (CSK) and cell-matrix adhesion system in the stressed endothelium and more precisely in the loss of integrity of the endothelial barrier. We purposely develop a cellular model made of a monolayer of confluent Human Pulmonary Microvascular Endothelial Cells (HPMVECs) whose cytoskeleton (CSK) is directly exposed to sustained cyclic mechanical stress for 1 and 2 h.

Plastinated nasal model: a new concept of anatomically realistic cast.

Background: For many years, researchers have been interested in investigating airflow and aerosol deposition in the nasal cavities. The nasal airways appear to be a complex geometrical system. Thus, in vitro experimental studies are frequently conducted with a more or less biomimetic nasal replica.

Pressure stability with CPAP devices: A bench evaluation.

Background: Continuous positive airway pressure (CPAP) maintains a constant pressure to reduce the patient's work of breathing (WOB). The aim of this study was to measure the additional WOB imposed by four current CPAP devices during simulation of a difficult but commonly encountered clinical situation.

Method: Flow contour, respiratory system compliance and total lung-airway resistance of a patient under CPAP were simulated.