Pulmonary surfactant in asthma.

Pulmonary surfactant is vital in human respiration. It maintains alveoli and terminal conducting airways open and therefore promotes an efficient gas exchange and low resistance in the airways during breathing dynamics. Lack or dysfunction of the pulmonary surfactant system is associated with severe lung disorders.

Case report: anti-fibrillarin autoantibodies induced by viral molecular mimicry in a paediatric patient.

Background: Anti-fibrillarin autoantibodies (AFA) as serological hallmarks of systemic sclerosis, mainly react with epitopes arranged in the NH2-(aa-1-80) and COOH-terminal-(aa-276-321)-domains of fibrillarin. Interestingly, the fibrillarin NH2-hexapeptide sequence is shared with an Epstein-Barr-virus (EBV)-encoded nuclear antigen.

Case Presentation: We herein report a case of a 14-year-old girl presenting with a history of vomiting, sore throat, arthralgias and fever.

Effect of therapeutic hypothermia on surfactant proteins, anti-inflammatory and pro-fibrotic mediators.

Objectives: To study the effect of hypothermia on surfactant proteins, anti-inflammatory and pro-fibrotic mediators DESIGN: Prospective, pragmatic study enrolling asphyxiated neonates without lung injury. Surfactant proteins (SP), Club cell secretory protein (CC-10), tumor growth factor-β1 (TGF-β1), human fibroblast growth factor-2 (hFGF) and anti-inflammatory interleukins (IL) were measured in broncho-alveolar lavage fluids obtained before, during and after hypothermia.

Results: Twelve neonates were studied.

Surfactant status assessment and personalized therapy for surfactant deficiency or dysfunction.

Surfactant is a pivotal neonatal drug used both for respiratory distress syndrome due to surfactant deficiency and for more complex surfactant dysfunctions (such as in case of neonatal acute respiratory distress syndrome). Despite its importance, indications for surfactant therapy are often based on oversimplified criteria. Lung biology and modern monitoring provide several diagnostic tools to assess the patient surfactant status and they can be used for a personalized surfactant therapy.

The dynamics of circulating tumour DNA (ctDNA) during treatment reflects tumour response in advanced melanoma patients.

Despite the introduction of targeted (BRAFi/MEKi) and immune checkpoint inhibitors (ICIs) has significantly reduced the recurrence rate and improved the overall survival (OS) of patients with Stage III and IV melanoma, only a percentage will benefit of durable disease control. The aim of this study was to examine whether the levels of circulating tumour DNA (ctDNA) in plasma of advanced melanoma patients undergoing BRAFi/MEKi or ICIs vary according to the patients' survival outcomes (i.e.

Early life surfactant protein-D levels in bronchoalveolar lavage fluids of extremely preterm neonates.

Surfactant protein-D (SP-D) is a hydrophilic protein with multiple crucial anti-inflammatory and immunological functions. It might play a role in the development and course of pulmonary infections, acute respiratory distress syndrome, and other respiratory disorders. Only few small neonatal studies have investigated SP-D: we aimed to investigate the links between this protein, measured in the first hours of life in extremely preterm neonates, and clinical outcomes, as well its relationship with pulmonary secretory phospholipase A2 (sPLA2).

Airway allergy causes alveolar macrophage death, profound alveolar disorganization and surfactant dysfunction.

Respiratory disorders caused by allergy have been associated to bronchiolar inflammation leading to life-threatening airway narrowing. However, whether airway allergy causes alveolar dysfunction contributing to the pathology of allergic asthma remains unaddressed. To explore whether airway allergy causes alveolar dysfunction that might contribute to the pathology of allergic asthma, alveolar structural and functional alterations were analyzed during house dust mite (HDM)-induced airway allergy in mice, by flow cytometry, light and electron microscopy, monocyte transfer experiments, assessment of intra-alveolarly-located cells, analysis of alveolar macrophage regeneration in : chimeras, analysis of surfactant-associated proteins, and study of lung surfactant biophysical properties by captive bubble surfactometry.

Bile acid-induced lung injury: update of reverse translational biology.

The presence of bile acids in lung tissue is associated with some clinical features observed in various medical specialties, but it took time to understand that these are due to a "bile acid-induced lung injury" since specific translational studies and cross-disciplinary awareness were lacking. We used a reverse translational approach to update and summarize the current knowledge about the mechanisms of bile acid-induced lung injury. This has been done in a cross-disciplinary fashion since these conditions may occur in patients of various ages and in different medical fields.

Secretory phospholipase A2 expression and activity in preterm clinical chorioamnionitis with fetal involvement.

Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.

Techniques to evaluate surfactant activity for a personalized therapy of RDS neonates.

According to both European and American Guidelines, preterm neonates have to be treated by nasal continuous air pressure (CPAP) early in the delivery room. The administration of surfactant should be reserved only for babies with respiratory distress syndrome (RDS) with increased oxygen requirement, according to different thresholds of FiO. However, these oxygenation thresholds do not fully take into consideration the lung physiopathology and mechanics or the lung surfactant biology of RDS neonates.

Systematic Analysis of Composition, Interfacial Performance and Effects of Pulmonary Surfactant Preparations on Cellular Uptake and Cytotoxicity of Aerosolized Nanomaterials.

The interplay of particles with pulmonary surfactant, a lipid-protein material pivotal for lung function, is hypothesized as a key factor that has not been routinely considered in the current in vitro models when determining the fate of inhaled nanomaterials. To explain its influence on cellular uptake and protective effects, nanoparticles are studied on two models of alveolar cells, in the absence or presence of pulmonary surfactant. Composition and interfacial performance of native human and porcine surfactants, a commercially available bovine surfactant (Alveofact), and an artificial lung lining fluid are characterized using shotgun lipidomics and biophysical approaches (i.

Let-7a-5p, miR-100-5p, miR-101-3p, and miR-199a-3p Hyperexpression as Potential Predictive Biomarkers in Early Breast Cancer Patients.

Background: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC).

Patients And Methods: We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system.

Strategies to protect surfactant and enhance its activity.

The knowledge about surfactant biology is now deeper and recent research has allowed to clarify its role in several human lung disorders. The balance between surfactant production and consumption is better known and the same applies to their regulatory mechanisms. This has allowed to hypothesize and investigate several new and original strategies to protect surfactant and enhance its activity.

Increased Alveolar Heparan Sulphate and Reduced Pulmonary Surfactant Amount and Function in the Mucopolysaccharidosis IIIA Mouse.

Mucopolysaccharidosis IIIA (MPS IIIA) is a lysosomal storage disease with significant neurological and skeletal pathologies. Respiratory dysfunction is a secondary pathology contributing to mortality in MPS IIIA patients. Pulmonary surfactant is crucial to optimal lung function and has not been investigated in MPS IIIA.

Personalized Medicine for the Management of RDS in Preterm Neonates.

Continuous positive airway pressure and surfactant represent the first- and second-line treatment for respiratory distress syndrome in preterm neonates, as European and American guidelines, since 2013 and 2014, respectively, started to recommend surfactant replacement only when continuous positive airway pressure fails. These recommendations, however, are not personalized to the individual physiopathology. Simple clinical algorithms may have improved the diffusion of neonatal care, but complex medical issues can hardly be addressed with simple solutions.

Dietary Carbohydrates and Fat Induce Distinct Surfactant Alterations in Mice.

Obesity and type 2 diabetes are nutrition-related conditions associated with lung function impairment and pulmonary diseases; however, the underlying pathomechanisms are incompletely understood. Pulmonary surfactant is essential for lung function, and surfactant synthesis by AT2 (alveolar epithelial type 2) cells relies on nutrient uptake. We hypothesized that dietary amounts of carbohydrates or fat affect surfactant homeostasis and composition.

Pulmonary surfactant and drug delivery: Vehiculization, release and targeting of surfactant/tacrolimus formulations.

This work explores the potential for strategizing pulmonary surfactant (PS) for drug delivery over the respiratory air-liquid interface: the interfacial delivery. The efficacy of PS- and interface-assisted drug vehiculization was determined both in vitro and in vivo using a native purified porcine PS combined with the hydrophobic anti-inflammatory drug Tacrolimus (TAC), a calcineurin inhibitor. In vitro assays were conducted in a novel double surface balance setup designed to emulate compression-expansion dynamics applied to interfacially connected drug donor and recipient compartments.

Molecular and biophysical basis for the disruption of lung surfactant function by chemicals.

With the intention to move away from animal testing for the toxicological evaluation of chemicals comes the need to develop new approach methodologies which are mechanism-anchored and target relevant key events leading to an adverse outcome. To date, no validated alternative methods are available for studying the acute inhalation toxicity potential of airborne chemicals but the constrained drop surfactometer measuring the surface tension of a drop of lung surfactant presents as a promising candidate. Indeed, the correlation of the increase in minimum surface tension of lung surfactant in vitro with changes in the breathing patterns of mice after inhalation of test compounds has been shown in multiple studies.

Aging impairs alveolar epithelial type II cell function in acute lung injury.

Morbidity and mortality rates in acute lung injury (ALI) increase with age. As alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.

Telomerase treatment prevents lung profibrotic pathologies associated with physiological aging.

Short/dysfunctional telomeres are at the origin of idiopathic pulmonary fibrosis (IPF) in patients mutant for telomere maintenance genes. However, it remains unknown whether physiological aging leads to short telomeres in the lung, thus leading to IPF with aging. Here, we find that physiological aging in wild-type mice leads to telomere shortening and a reduced proliferative potential of alveolar type II cells and club cells, increased cellular senescence and DNA damage, increased fibroblast activation and collagen deposits, and impaired lung biophysics, suggestive of a fibrosis-like pathology.

Extrapulmonary Surfactant Therapy: Review of Available Data and Research/Development Issues.

Since the discovery of surfactant, a large amount of knowledge has been accumulated about its biology and pharmacology. Surfactant is the cornerstone of neonatal respiratory critical care, but its proteins and phospholipids are produced in various tissues and organs, with possible roles only partially similar to that played in the alveoli. As surfactant research is focused mainly on its respiratory applications, knowledge about the possible role of surfactant in extrapulmonary disorders has never been summarized.

Surfactant-secreted phospholipase A interplay and respiratory outcome in preterm neonates.

Secreted phospholipase A hydrolyzes surfactant phospholipids and is crucial for the inflammatory cascade; preterm neonates are treated with exogenous surfactant, but the interaction between surfactant and phospholipase is unknown. We hypothesize that this interplay is complex and the enzyme plays a relevant role in neonates needing surfactant replacement. We aimed to: ) identify phospholipases A isoforms expressed in preterm lung; ) study the enzyme role on surfactant retreatment and function and the effect of exogenous surfactant on the enzyme system; and ) verify whether phospholipase A is linked to respiratory outcomes.

Surfactant Injury in the Early Phase of Severe Meconium Aspiration Syndrome.

No data are available regarding the effect of meconium on human surfactant in the early stages of severe meconium aspiration syndrome (MAS). In the present study, we sought to characterize the changes in surfactant composition, function, and structure during the early phase of meconium injury. We designed a translational prospective cohort study of nonbronchoscopic BAL of neonates with severe MAS ( = 14) or no lung disease ( = 18).

In Vitro Functional and Structural Characterization of A Synthetic Clinical Pulmonary Surfactant with Enhanced Resistance to Inhibition.

CHF5633 is a novel synthetic clinical pulmonary surfactant preparation composed by two phospholipid species, dipalmitoyl phosphatidylcholine (DPPC) and palmitoyloleoyl phosphatidylglycerol (POPG), and synthetic analogues of the hydrophobic surfactant proteins SP-B and SP-C. In this study, the interfacial properties of CHF5633 in the absence and in the presence of inhibitory serum proteins have been assessed in comparison with a native surfactant purified from porcine lungs and with poractant alpha, a widely used clinical surfactant preparation. The study of the spreading properties of CHF5633 in a Wilhelmy balance, its ability to adsorb and accumulate at air-liquid interfaces as revealed by a multiwell fluorescence assay, and its dynamic behavior under breathing-like compression-expansion cycling in a Captive Bubble Surfactometer (CBS), all revealed that CHF5633 exhibits a good behavior to reduce and sustain surface tensions to values below 5 mN/m.

Circulating tumor cell-related transcripts in blood as prognostic biomarkers of early recurrence after liver resection for colorectal metastases.

Background: Several prognostic factors were proposed to improve early detection of recurrence after liver resection of metastases of colorectal cancer. Circulating tumor cell-related transcripts were evaluated in colorectal cancer patients with conflicting results. The aim of this study was to investigate usefulness of carcinoembryonic antigen CAM5, epidermal growth factor receptor, and ERCC1 transcripts in the bloodstream as predictive factors of recurrence in patients who underwent liver resection for metastases of colorectal cancer.