Pulmonary surfactant: a unique biomaterial with life-saving therapeutic applications.

: Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids (approximately 90% of its entire mass) and surfactant proteins (approximately 10% of the mass). It is crucially involved in maintaining lung homeostasis by reducing the values of alveolar liquid surface tension close to zero at end-expiration, thereby avoiding the alveolar collapse, and assembling a chemical and physical barrier against inhaled pathogens. A deficient amount of surfactant or its functional inactivation is directly linked to a wide range of lung pathologies, including the neonatal respiratory distress syndrome. This paper reviews the main biophysical concepts of surfactant activity and its inactivation mechanisms, and describes the past, present and future roles of surfactant replacement therapy, focusing on the exogenous surfactant preparations marketed worldwide and new formulations under development. The closing section describes the pulmonary surfactant in the context of drug delivery. Thanks to its peculiar composition, biocompatibility, and alveolar spreading capability, the surfactant may work not only as a shuttle to the branched anatomy of the lung for other drugs but also as a modulator for their release, opening to innovative therapeutic avenues for the treatment of several respiratory diseases.

Potential of 1.3-diethylbenzimidazolium triiodide in experimental therapy for lung cancer.

e15094 Background: The practice of thoracic oncology demonstrates that the lungs often become affected by cancer. The antitumor effect of chemoradiation therapy can be poor, and surgical treatment is associated with reduced functionality of the organ and therefore reduced quality of life of patients. Therefore, nonspecific agents are required that combine a pronounced antitumor effect and, at the same time, restore pulmonary tissue. Our purpose was to study the effects of 1,3-diethylbenzimidazolium triiodide in a rat model of lung cancer by morphological analysis of pulmonary tissues. Methods: An experimental model of lung cancer was created in 60 male and female rats by subclavian infusion of sarcoma 45 cell suspension in the saline at a dose of 0.5 ml (2×106). Iodine-containing preparation was administered enterally at 0.4 mg/kg daily for 5 days with a 2-day interval; treatment was started immediately after the intravenous injection of malignant cells, the therapy lasted for 8 weeks. The morphological control of the lungs was performed at decapitation of animals, tissue processing and staining, by light microscopy using the LEICA DM LS2 microscope with magnification of up to x100. Results: Hematogenous introduction of tumor cells into the lung caused hemorrhage, “acute swelling” of the alveoli, microabscesses, distelectasis, colonization of interalveolar septa with tumor cells and the formation of large metastatic foci. Involutive changes in the tumor tissue were noted together with signs of pulmonary regeneration: after 5 weeks of the treatment – pronounced activation of immune cells and occurrence of elastic fibers with reserve tortuosity; after 8 weeks - active proliferation of epithelial elements that form the bronchial-alveolar apparatus, an increase in surfactant activity in hypertrophied alveoli, and a significant strengthening of the elastic and collagen framework of the alveolar walls. Conclusions: Morphological correlates of the experimental effect of 1,3-diethylbenzimidazolium triiodide indicate its strong antitumor properties and potential for improving the recovery capabilities of the structure-forming elements of the lung.

Is remote sensing of the surfactant effect on gas transfer velocity possible?

<p>The air-sea gas flux is proportional to the difference of partial pressure between the sea-water and the overlying atmosphere multiplied by gas transfer velocity <em>k</em>, a measure of the effectiveness of the gas exchange. Because wind is the source of turbulence making the gas exchange more effective, <em>k</em> is usually parameterized by wind speed. Unfortunately, measured values of gas transfer velocity at a given wind speed have a large spread in values. Surfactants have been long suspected as the main reason of this variability but few measurements of gas exchange and surfactants have been performed at open sea simultaneously and therefore their results were inconclusive. Only recently, it has been shown that surfactants may decrease the CO<sub>2</sub> air-sea exchange by up to 50%. However the labour intensive methods used for surfactant study make it impossible to collect enough data to map the surfactant coverage or even create a gas transfer velocity parameterization involving a measure of surfactant activity. This is why we propose to use optical fluorescence as a proxy of surfactant activity.</p><p> </p><p>Previous research done by our group showed that fluorescence parameters allow estimation the surfactant enrichment of the surface microlayer, as well as types and origin of fluorescent organic matter involved. We plan to measure, from a research ship, all the variables needed for calculation of gas transfer velocity <em>k</em> (namely CO<sub>2</sub> partial pressure both in water and in air as well as vertical flux of this trace gas) and to use mathematical optimization methods to look for a parameterization involving wind speed and one of the fluorescence parameters which will minimize the residual <em>k</em> variability. Although our research will still involve water sampling and laboratory fluorescence measurements, the knowledge of which absorption and fluorescence emission bands are the best proxy for surfactant activity may allow to create remote sensing products (fluorescence lidars) allowing continuous measurements of surfactant activity at least from the ship board, if not from aircraft and satellites. The improved parameterization of the CO<sub>2</sub> gas transfer velocity will allow better constraining of basin-wide and global air-sea fluxes, an important component of global carbon budget.</p><p> </p><p>If an improved gas transfer velocity parametrization based on surfactant fluorescence spectrum in concert with a turbulence proxy (wind) were to be found, a tantalizing possibility arises of a remote sensing estimation of <em>k</em>. Namely a UV lidar can both excite and measure the fluorescence band identified as proxy of the surfactant effect on the gas transfer velocity. Depending on the wavelength bands needed to be utilized, the effect could be measured from a moving ship (already an improvements on methods needing sampling), an aircraft or possibly even a satellite. We intend to pursue this idea in cruises to both the Baltic and the North Atlantic, possibly in cooperation with other air-sea interaction groups (this presentation is in part an invitation to cooperation).</p>

Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia

Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purified porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperature-dependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of films made of native surfactant. Lipid/protein mixtures designed as models to mimic different surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant films exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more effective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.

The frequency of select adaptation disorders in preterm newborns

Background: Preterm birth, defined as the birth of an infant before 37 complete weeks of gestation, is the single major cause of death and disability in children up to 5 years of age in the developed world. Aim of the study: The study aimed at analyzing select adaptation disorders in newborns delivered between 34–37 weeks of gestation and in particular, (1) determining the frequency of breathing, thermoregulatory, hypoglycemic and pathological hepatic disorders, and (2) examining underlying factors that determine their incidence. Material and methods: The study was carried out according to the documentoscopy on the basis of medical files collected between 2019–2020 at the Neonatal and Preterm Baby Unit in WS SPZOZ (the regional hospital) in Nowa Sól. The records of 102 preterm newborn patients were examined, which included the birth book, detailed newborn observation charts, fever charts and individual patient observation charts. Results: The most commonly diagnosed disorders included hepatitis (21.6%; 50) and thermoregulation disorders (20.3%; 47). Additionally, hypoglycemia and tachypnea were observed in every third child (31.4% and 29.4%, respectively) and almost every fourth newborn experienced some respiratory disorders (23.5%). Among the findings, maternal and gestational age were not found to be statistically significant with respect to an association with the incidence of the disorders examined in the study. However, hepatitis was more frequently diagnosed among naturally born children (64.5%) compared with those delivered by Cesarean (C) section (42.3%, p=0.039). Respiratory disorders were more often found in children delivered by C-section (21.1%) than in those born naturally (3.2%, p=0.022). Conclusions: Hepatitis and thermoregulatory disorders occurred most frequently in preterm infants of all the adaptation disorders examined. The type of delivery was quite determinant for some of the disorders. Hepatitis was found more often in naturally born babies than in those delivered by C-section, whereas respiratory problems occurred more frequently in children delivered by C-section compared with those delivered naturally. Mothers who wish to deliver their babies by C-section should be informed about potential complications associated with the occurrence of respiratory disorders. They can stem from the absorption of pulmonary liquid and inappropriate surfactant activity, which can lead to some serious abnormalities related to the improper exchange of respiratory gases.

Bioreactivity, Guttation and Agents Influencing Surface Tension of Water Emitted by Actively Growing Indoor Mould Isolates

The secretion of metabolites in guttation droplets by indoor moulds is not well documented. This study demonstrates the guttation of metabolites by actively growing common indoor moulds. Old and fresh biomasses of indoor isolates of Aspergillus versicolor, Chaetomium globosum, Penicillium expansum, Trichoderma atroviride, T. trixiae, Rhizopus sp. and Stachybotrys sp. were compared. Metabolic activity indicated by viability staining and guttation of liquid droplets detected in young (<3 weeks old) biomass were absent in old (>6 months old) cultures consisting of dehydrated hyphae and dormant conidia. Fresh (<3 weeks old) biomasses were toxic more than 10 times towards mammalian cell lines (PK-15 and MNA) compared to the old dormant, dry biomasses, when calculated per biomass wet weight and per conidial particle. Surfactant activity was emitted in exudates from fresh biomass of T. atroviride, Rhizopus sp. and Stachybotrys sp. Surfactant activity was also provoked by fresh conidia from T. atroviride and Stachybotrys sp. strains. Water repealing substances were emitted by cultures of P. expansum, T. atroviride and C. globosum strains. The metabolic state of the indoor fungal growth may influence emission of liquid soluble bioreactive metabolites into the indoor air.