Respiratory mechanics and gas exchanges in the early course of COVID-19 ARDS: a hypothesis-generating study.

RATIONALE: COVID-19 ARDS could differ from typical forms of the syndrome. OBJECTIVE: Pulmonary microvascular injury and thrombosis are increasingly reported as constitutive features of COVID-19 respiratory failure. Our aim was to study pulmonary mechanics and gas exchanges in COVID-2019 ARDS patients studied early after initiating protective invasive mechanical ventilation, seeking after corresponding pathophysiological and biological characteristics. METHODS: Between March 22 and March 30, 2020 respiratory mechanics, gas exchanges, circulating endothelial cells (CEC) as markers of endothelial damage, and D-dimers were studied in 22 moderate-to-severe COVID-19 ARDS patients, 1 [1-4] day after intubation (median [IQR]). MEASUREMENTS AND MAIN RESULTS: Thirteen moderate and 9 severe COVID-19 ARDS patients were studied after initiation of high PEEP protective mechanical ventilation. We observed moderately decreased respiratory system compliance: 39.5 [33.1-44.7] mL/cmH2O and end-expiratory lung volume: 2100 [1721-2434] mL. Gas exchanges were characterized by hypercapnia 55 [44-62] mmHg, high physiological dead-space (VD/VT): 75 [69-85.5] % and ventilatory ratio (VR): 2.9 [2.2-3.4]. VD/VT and VR were significantly correlated: r2 = 0.24, p = 0.014. No pulmonary embolism was suspected at the time of measurements. CECs and D-dimers were elevated as compared to normal values: 24 [12-46] cells per mL and 1483 [999-2217] ng/mL, respectively. CONCLUSIONS: We observed early in the course of COVID-19 ARDS high VD/VT in association with biological markers of endothelial damage and thrombosis. High VD/VT can be explained by high PEEP settings and added instrumental dead space, with a possible associated role of COVID-19-triggered pulmonary microvascular endothelial damage and microthrombotic process.

[Inhalation therapy: inhaled generics, inhaled antidotes, the future of anti-infectives and the indications of inhaled pentamidine. GAT aerosolstorming, Paris 2012]. / Aérosolthérapie : les génériques par voie inhalée, les antidotes en aérosol, le futur des anti-infectieux et les indications de la pentamidine en aérosol. Aérosolstorming du GAT, Paris 2012.

The working group on aerosol therapy (GAT) of the Société de pneumologie de langue française (SPLF) organized its third "Aerosolstorming" in 2012. During the course of one day, different aspects of inhaled therapy were discussed, and these will be treated separately in two articles, this one being the first. Inhaled products represent a large volume of prescriptions both in the community and in hospital settings and they involve various specialties particularly ENT and respiratory care. Technical aspects of the development of these products, their mode of administration and compliance with their indications are key elements for the effective therapeutic use of inhaled treatments. In this first article, we will review issues concerning generic inhaled products, the existence of inhaled antidotes, new anti-infective agents and indications for inhaled pentamidine.

[Inhalation therapy: inhaled corticosteroids in ENT, development and technical challenges of powder inhalers, nebulisers synchronized with breathing and aerosol size distribution. GAT aerosolstorming, Paris 2012]. / Aérosolthérapie : les corticoïdes inhalés en ORL, le développement et les défis techniques des inhalateurs de poudre, les nébuliseurs couplés à la respiration et la granulométrie d'un aérosol. Aerosolstorming du GAT, Paris 2012.

The working group on aerosol therapy (GAT) of the Société de Pneumologie de Langue Française (SPLF) has organized its third Aerosolstorming in 2012. During one single day, different aspects of inhaled therapies have been treated and are detailed in two articles, this one being the second. This text deals with the indications of inhaled corticosteroids in ENT, the development and technical challenges of powder inhalers, the advantages and disadvantages of each type of technologies to measure the particle sizes of inhaled treatments.

Structure and chemical composition of layers adsorbed at interfaces with champagne.

The structure and the chemical composition of the layer adsorbed at interfaces involving champagne have been investigated using native champagne, as well as ultrafiltrate (UFch) and ultraconcentrate (UCch) obtained by ultrafiltration with a 10(4) nominal molar mass cutoff. The layer adsorbed at the air/liquid interface was examined by surface tension and ellipsometry kinetic measurements. Brewster angle microscopy demonstrated that the layer formed on polystyrene by adsorption or drop evaporation was heterogeneous, with a domain structure presenting similarities with the layer adsorbed at the air/liquid interface. The surface chemical composition of polystyrene with the adlayer was determined by X-ray photoelectron spectroscopy (XPS). The contribution of champagne constituents varied according to the liquid (native, UFch, and UCch) and to the procedure of adlayer formation (evaporation, adsorption, and adsorption + rinsing). However, their chemical composition was not significantly influenced either by ultrafiltration or by the procedure of deposition on polystyrene. Modeling this composition in terms of classes of model compounds gave approximately 35% (w/w) of proteins and 65% (w/w) of polysaccharides. In the adlayer, the carboxyl groups or esters represent about 18% of carbon due to nonpolypeptidic compounds, indicating the presence of either uronic acids in the complex structure of pectic polysaccharides or of polyphenolic esters. This structural and chemical information and its relationship with the experimental procedures indicate that proteins alone cannot be used as a realistic model for the macromolecules forming the adsorption layer of champagne. Polysaccharides, the other major macromolecular components of champagne wine, are assembled with proteins at the interfaces, in agreement with the heterogeneous character of the adsorbed layer at interfaces.

Steady drainage in emulsions: corrections for surface Plateau borders and a model for high aqueous volume fraction.

We compare extensive experimental results for the gravity-driven steady drainage of oil-in-water emulsions with two theoretical predictions, both based on the assumption of Poiseuille flow. The first is from standard foam drainage theory, applicable at low aqueous volume fractions, for which a correction is derived to account for the effects of the confinement of the emulsion. The second arises from considering the permeability of a model porous medium consisting of solid sphere packings, applicable at higher aqueous volume fractions. We find quantitative agreement between experiment and the foam drainage theory at low aqueous volume fractions. At higher aqueous volume fractions, the reduced flow rate calculated from the permeability theory approaches the master curve of the experimental data. Our experimental data demonstrates the analogy between the problem of electrical flow and liquid flow through foams and emulsions.

The foam/emulsion analogy in structure and drainage.

The often quoted analogy between foams and emulsions is experimentally tested by studying properties after settling and under forced drainage of oil-in-water emulsions of drop size similar as for bubbles generally used in foam experiments. Observations with regard to structure, water fraction and drainage wave properties confirm the expected similarity in the low flow rate range. However, while for foams a convective circulation on the scale of the container sets in for values of water fraction exceeding about 0.2, no such convection is found in emulsions. Here instabilities are only encountered at water fractions of about 0.4, close to the void fraction of random packings of spheres. These take on the form of descending pulses of increased water fraction and lead to the transition from a frozen to a locally agitated structure.

Phase separation in molecular layers of macromolecules at the champagne-air interface.

Bubble and foam stability, which are essential for the hallmark of champagne, rely on the concentration of amphiphilic macromolecules originating from the grape, which form molecular layers at the interface between champagne and gas. Ellipsometry and Brewster angle microscopy experiments were conducted at the air-champagne interface to analyse the lateral organization of the layers of macromolecules. Several kinds of phase separations - leading in some cases to two-dimensional foams - were identified. At the beginning of layer formation, condensed domains develop at the expense of dilute domains. Thereafter, phase separations occur within the condensed domains. These findings may allow advances in the implementation of methods predicting bubble and foam stability of champagnes.

Characterisation by drop tensiometry and by ellipsometry of the adsorption layer formed at the air/champagne wine interface.

A foam ring composed of small bubbles on the surface of a champagne glass is one of its hallmarks. The equilibrium state of that ring is linked with the rate of formation and of disappearance of bubbles. The stability of bubbles is usually ascribed to the occurrence and to the properties of an adsorption layer formed at the gas/liquid interface. Our goal is to characterise such an adsorption layer at the gas/wine interface in order to understand its role in bubble stability. Alcohol in wine lowers the surface tension to 49 mN/m. The adsorption of other molecules may cause a further decrease of 2 mN/m. Such a situation makes the study of adsorption by surface tension measurement inaccurate. To overcome this problem, we have diluted the wine four times with water before its surface tension measurement by pendant drop shape analysis. In these conditions, ethanol lowers the surface tension to 64 mN/m and the adsorption of other molecules of the wine can be monitored over 6-8 mN/m. The usual behaviour of such a diluted wine is a lowering of the surface tension during at least 20 min after drop formation. Since the role of macromolecules on the foaming properties of wine had been previously observed, we have chosen to evaluate the effect of this fraction of the wine molecules on its surface properties. Thus, wines were ultrafiltrated on a membrane with a 10000 molecular mass cut-off. The ultrafiltrate (UF) does not show any decrease of its surface tension over a 20-min period while the ultraconcentrate (UC) has a kinetics similar to that of unfiltered wine. Mixtures of UF and UC have behaviours intermediate between those of these products. A technological treatment of the wine with bentonite, believed to lower the content of macromolecules, yields a wine similar to UF. The effect of ultrafiltration was also analysed by spectroscopic ellipsometry. UF has a spectrum similar to that of a water/alcohol mixture with the same ethanol content and its ellipticity is stable during at least 20 min. On the contrary, wine or UC show spectra with the features of an adsorption layer and those characteristics increase during more than 20 min. Two varieties of vine were compared: 'Chardonnay' and 'Pinot noir'. The former is known to have better foaming properties than the latter. Its surface properties measured in this study are also more pronounced than those of Pinot noir. However, the representation of the dilational modulus against the surface pressure (which, in some instances, may be a mathematical transformation of the state equation) puts all the samples (wines, UF and UC of each) on the same master curve, a fact in favour of a common nature for all the adsorption layers. It can be concluded that surface properties of champagne wines are mostly determined by ethanol and by macromolecules with a molecular mass larger than 10000. Moreover, the adsorption layers seem to have the same nature, irrespective of the vine variety and of the concentration ratio of the wine.