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Supplemental Digital Content is available in the text., Objectives: We have setup for the first time a long-term (72 hr) respiratory distress syndrome model in spontaneously breathing surfactant-deficient newborn piglets to investigate the continuous positive airway pressure failure rate with nebulized poractant alfa compared with that with the intubation surfactant extubation technique or continuous positive airway pressure only. Design: Prospective randomized animal study. Setting: Biocruces-Bizkaia Health Research Institute Animal Facility. Subjects-Interventions: Eighteen newborn piglets (n = 6/group) with surfactant-deficient respiratory distress syndrome were randomized to three continuous positive airway pressure–ventilated groups: 1) nebulized surfactant (poractant alfa 400 mg/kg) via a customized investigational eFlow-Neos vibrating membrane nebulizer system, 2) bolus administration using the Intubation Surfactant Extubation method (200 mg/kg), or 3) continuous positive airway pressure alone. Measurements and Main Results: Pulmonary and hemodynamic variables were assessed at 6-hour intervals for 72 hours. Lung and brain histological analyses were performed. After bronchoalveolar lavages, piglets developed respiratory distress syndrome. Over the follow-up, both surfactant-treated groups had significantly better pulmonary outcomes than the continuous positive airway pressure alone group. Furthermore, unlike in the continuous positive airway pressure group, there were no cases of respiratory failure in either of the surfactant-treated groups. Conclusions: In newborn piglets with respiratory distress syndrome, the nebulization of 400 mg/kg of poractant alfa using a customized investigational eFlow-Neos nebulizer was found to be safe and effective in reducing the risk of respiratory failure in the 72 hours after treatment.

Supplemental Digital Content is available in the text., Objectives: The current clinical treatment of neonates with respiratory distress syndrome includes endotracheal intubation and intratracheal instillation of exogenous surfactant. Nebulization of surfactant offers an attractive alternative. The aims of this study were to test nebulization as a noninvasive method of administering surfactant and determine the optimal dose for the treatment of respiratory distress syndrome–associated pathophysiology of the neonatal lungs. Design: Prospective, randomized, animal model study. Setting: An experimental laboratory. Subjects: Thirty-six newborn piglets. Interventions: Different doses (100, 200, 400, and 600 mg/kg) of poractant alfa were administered via a vibrating membrane nebulizer (eFlow-Neos; Pari Pharma GmbH, Starnberg, Germany) or a bolus administration using the intubation–surfactant–extubation (Insure) technique (200 mg/kg) to spontaneously breathing newborn piglets (n = 6/group) with bronchoalveolar lavage–induced respiratory distress syndrome during nasal continuous positive airway pressure (180 min). Measurements and Main Results: Pulmonary, hemodynamic, and cerebral effects were assessed. Histologic analysis of lung and brain tissue was also performed. After repeated bronchoalveolar lavage, newborn piglets developed severe respiratory distress syndrome. Rapid improvement in pulmonary status was observed in the Insure group, whereas a dose-response effect was observed in nebulized surfactant groups. Nebulized poractant alfa was more effective at doses higher than 100 mg/kg and was associated with similar pulmonary, hemodynamic, and cerebral behavior to that in the Insure group, but improved lung injury scores. Conclusions: In newborn piglets with severe bronchoalveolar lavage–induced respiratory distress syndrome, our results demonstrate that the administration of nebulized poractant alfa using an investigational customized eFlow-Neos nebulizer is an effective and safe noninvasive surfactant administration technique.

A CUSUM chart method is presented as an alternative tool for continuous monitoring of an electromagnetic field-based (EMF) antifouling (AF) treatment of a heat exchanger cooled by seawater. During an initial experimental phase, biofilm growth was allowed in a heat exchanger formed of four tubes until sufficient growth had been established. In two of the tubes, continuous EMF treatment was then applied. The heat transfer resistance and heat duty (heat transfer per unit time) results showed that biofilm adhesion was reduced by the EMF treatment. EMF treatments resulted in a 35% improvement in the heat transfer resistance values. The proposed CUSUM chart method showed that the EMF treatment increased the useful life of the heat exchanger by ∼20 days. Thus, CUSUM charts proved to be an efficient tool for continuous monitoring of an AF treatment using data collected online and can also be used to reduce operation and maintenance costs.

Background In recent years, nasal intermittent positive pressure ventilation (NIPPV) has been growing in popularity as a form of noninvasive ventilation for respiratory support in the initial treatment of neonates with surfactant (SF) deficiency. The combination of this type of ventilation with noninvasive SF administration (by nebulization) is an attractive treatment option for respiratory distress syndrome (RDS)-associated pathophysiology of the neonatal lungs. In this study, we aimed to test the tolerability and efficacy of SF nebulization during NIPPV for the treatment of neonatal RDS. Methods Spontaneously-breathing newborn piglets (n = 6/group) with bronchoalveolar lavage (BAL)-induced RDS were assigned to receive during NIPPV (180 min): poractant alfa (400 mg/kg) via an investigational customized vibrating-membrane nebulizer (eFlow-Neos) or poractant alfa (200 mg/kg) as a bolus using the Insure method or no surfactant (controls). Measurement and results We assessed pulmonary, hemodynamic and cerebral effects and performed histological analysis of lung and brain tissue. After repeated BAL, newborn piglets developed severe RDS (FiO2: 1, pH 70 mmHg, PaO2

Background Nasal continuous‐positive airway pressure (nCPAP) with the INSURE (INtubation‐SURfactant‐Extubation) or LISA (Less‐Invasive Surfactant Administration) procedures are increasingly being chosen as the initial treatment for neonates with surfactant deficiency. Our objective was to compare the effects on cerebral oxygenation of different methods for surfactant administration: INSURE and LISA, using a nasogastric tube (NT) or a LISAcath® catheter, in spontaneously breathing SF‐deficient newborn piglets. Methods Eighteen newborn piglets with SF‐deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to INSURE, LISA‐NT, or LISAcath® groups. We assessed pulmonary (gas exchange, lung mechanics, lung histology) and hemodynamic (mean arterial blood pressure, heart rate) changes, cerebral oxygenation (cTOI) and cerebral fractional tissue extraction (cFTOE), with near‐infrared spectroscopy, carotid blood flow and brain histology. Results SF‐deficient piglets developed respiratory distress (FiO2 = 1, pH 70 mmHg, PaO2

BackgroundNasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV), forms of non-invasive ventilation (NIV) for respiratory support, are increasingly being chosen as the initial treatment for neonates with surfactant (SF) deficiency. Our objective was to compare NCPAP with NIPPV with or without SF administration as a primary mode of ventilation.MethodsTwenty-four newborn piglets with SF-deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to NCPAP or NIPPV, with or without SF administration (InSurE method). We evaluated pulmonary, systemic (hemodynamic and oxygen metabolism), and cerebral effects.ResultsSF-deficient piglets developed respiratory distress (FiO2:1, pH 70 mm Hg, PaO2

Biofouling is an undesirable phenomenon in heat exchangers, which adheres slowly and progressively to the inner surface of the tubes, results in a reduction of the heat transfer, and increases the operating and maintenance costs. Controlling this phenomenon is essential to ensure that the equipment operates under optimal conditions. Different biofouling detection methods are currently available, depending on the properties of the fluid or by means of intrusive elements in the process. In this paper, the validation of the CUSUM control graph as an alternative technique to conventional detection methods is proposed. This type of graph is very efficient in the early detection of slow and progressive changes within a process. In a pilot plant, formed by two tubular heat exchangers, biofouling was allowed to grow until experimental variables indicated that growth had occurred. The biofouling growth was monitored through the evolution of the heat transfer resistance Rf, which is a technique that has been widely validated for this purpose, and through the CUSUM control graphs. The variable Rf, clearly indicates the different phases of growth. However, the evolution of this variable depends on the physical-chemical characteristics and biological activity of water. The CUSUM graphs demonstrated a greater predictive capacity with regard to changes in the biological adherence process. Additionally, their results do not depend on the characteristics of water. This new tool could be simply and economically implemented regardless of the heat exchanger’s location.

The potential of non-invasive ventilation procedures and new minimally invasive techniques has resulted in the research of alternative approaches as the aerosolization for the treatment of respiratory distress syndrome (RDS). The aim of this work was to design two nebulizer prototypes and to evaluate them studying the particle size distribution of the inhaled droplets generated with distilled water and two perfluorocarbons (PFCs). Different experiments were performed with driving pressures of 1⁻3 bar for each compound. An Aerodynamic Particle Sizer was used to measure the aerodynamic diameter (Da), the mass median aerodynamic diameter (MMAD) and the geometric standard deviation (GSD). The results showed that both prototypes produced heterodisperse aerosols with Da mean values in all cases below 5 m. The initial experiments with distilled water showed MMAD values lower than 9 m and up to 15 m with prototype 1 and prototype 2, respectively. Regarding the PFCs, relatively uniform MMAD values close to 12 m were achieved. The air delivery with outer lumens of prototype 1 presented more suitable mass distribution for the generation and delivery of a uniform aerosol than the two half-circular ring geometry proposed in the prototype 2. Funding: This work has been supported by Consolidated Groups from the Basque Government and Fundation VITAL Fundazioa.

BACKGROUND Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS. METHODS Twenty-one preterm lambs were randomly assigned to receive CHF5633, Curosurf, or no treatment (control). Pulmonary (gas exchange, lung mechanics) and cerebral (carotid artery blood flow, cerebral oxygen metabolism) effects were measured every 30 min for 6 h. Pulmonary and cerebral histological analysis were also performed. RESULTS After delivery, lambs developed severe RDS (FIO2:1, pH 70 mmHg, PaO2

The aerosolization of perfluorocarbons or surfactant has emerged as a feasible alternative to instillation, for the treatment of experimental respiratory distress syndrome. However, the biophysical properties that make these compounds useful in such therapies, significantly affect the performance of nebulizers. Therefore, in vitro studies are required to assess the suitability of new aerosolization technologies for use with these compounds.The aim of the present in vitro study was to investigate the influence of the biophysical properties of perfluorocarbons (PFD, FC75, and PFOB) and a natural porcine surfactant, Curosurf®; on aerosolization and to assess the suitability of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, IC-1.4) coupled to a jet nebulizer, for aerosol delivery of these compounds.With IC-1.23 significantly higher aerosol production rates were achieved (p 0.0001), ranging between 6.05 ± 0.17 mL/min (FC75) and 1.94 ± 0.09 mL/min (Curosurf®), and lower percentage losses of the compound (5-21%), compared to IC-1.1 and IC-1.4 catheters. The lowest aerosolization rates were produced with IC-1.4 ranging from 0.58 ± 0.02 mL/min (FC75) to 0.14 ± 0.01 mL/min (Curosurf®), and this catheter also resulted in the highest percentage losses (25-60%). The mass median aerodynamic diameter (MMAD) ranged between 0.77 μm (PFD) and 8.29 μm (Curosurf®) with IC-1.1, whereas higher MMAD values, of between 4.84 μm (FC75) and 13.42 μm (PFOB), were observed with IC-1.23. Regardless of the catheter used during aerosolization, the perfluorocarbon with the highest kinematic viscosity showed the lowest aerosolization and emission rates and vice versa, which reveals the substantial contribution of this parameter that should accordingly be considered in the design of perfluorocarbon aerosol drug delivery systems.Jet aerosolization of perfluorocarbons or surfactant with the intratracheal inhalation catheters seems to be a suitable method for treating experimental respiratory distress syndrome, because it delivers relatively high doses of perfluorocarbons and surfactant to the lungs in a respirable size droplets.

Respiratory distress syndrome (RDS) represents one of the major causes of mortality among preterm infants, and the best approach to treat it is an open research issue. The use of perfluorocarbons (PFC) along with non-invasive respiratory support techniques has proven the usefulness of PFC as a complementary substance to achieve a more homogeneous surfactant distribution. The aim of this work was to study the inhaled particles generated by means of an intracorporeal inhalation catheter, evaluating the size and mass distribution of different PFC aerosols. In this article, we discuss different experiments with the PFC perfluorodecalin (PFD) and FC75 with a driving pressure of 4-5 bar, evaluating properties such as the aerodynamic diameter (Da), since its value is directly linked to particle deposition in the lung. Furthermore, we develop a numerical model with computational fluid dynamics (CFD) techniques. The computational results showed an accurate prediction of the airflow axial velocity at different downstream positions when compared with the data gathered from the real experiments. The numerical validation of the cumulative mass distribution for PFD particles also confirmed a closer match with the experimental data measured at the optimal distance of 60 mm from the catheter tip. In the case of FC75, the cumulative mass fraction for particles above 10 mu m was considerable higher with a driving pressure of 5 bar. These numerical models could be a helpful tool to assist parametric studies of new non-invasive devices for the treatment of RDS in preterm infants. Consolidated Groups from the Basque Government supported this work. Technical and human support provided by IZO-SGI, SGIker (UPV/EHU) is gratefully acknowledged.

This article presents the early work on a project in Paraguay for epidemiological surveillance using information technologies. This project is a response of our university to a governmental request to establish links of cooperation and development between academic public sectors of Spain and Paraguay. The overall project objective is the promotion of a healthy citizenry through the application of information and communication technologies to the monitoring of populations vulnerable to febrile syndromes (FS). The goal of this project is to create the infrastructure that will allow the population of the country to easily communicate with health centers and provide information on cases of FS. The telephone network will be the main physical support for this communication. The project was formally initiated in January 2009 with the implementation of the prototype system. During the first half of 2010, the pilot project will be implemented in Asuncion, Paraguay.

Objective: Aerosol delivery holds potential to release surfactant or perfluorocarbon (PFC) to the lungs of neonates with respiratory distress syndrome with minimal airway manipulation. Nevertheless, lung deposition in neonates tends to be very low due to extremely low lung volumes, narrow airways and high respiratory rates. In the present study, the feasibility of enhancing lung deposition by intracorporeal delivery of aerosols was investigated using a physical model of neonatal conducting airways. Methods: The main characteristics of the surfactant and PFC aerosols produced by a nebulization system, including the distal air pressure and air flow rate, liquid flow rate and mass median aerodynamic diameter (MMAD), were measured at different driving pressures (4-7 bar). Then, a three-dimensional model of the upper conducting airways of a neonate was manufactured by rapid prototyping and a deposition study was conducted. Results: The nebulization system produced relatively large amounts of aerosol ranging between 0.3 +/- 0.0 ml/min for surfactant at a driving pressure of 4 bar, and 2.0 +/- 0.1 ml/min for distilled water (H(2)Od) at 6 bar, with MMADs between 2.61 +/- 0.1 mu m for PFD at 7 bar and 10.18 +/- 0.4 mu m for FC-75 at 6 bar. The deposition study showed that for surfactant and H(2)Od aerosols, the highest percentage of the aerosolized mass (similar to 65%) was collected beyond the third generation of branching in the airway model. The use of this delivery system in combination with continuous positive airway pressure set at 5 cmH(2)O only increased total airway pressure by 1.59 cmH(2)O at the highest driving pressure (7 bar). Conclusion: This aerosol generating system has the potential to deliver relatively large amounts of surfactant and PFC beyond the third generation of branching in a neonatal airway model with minimal alteration of pre-set respiratory support. This work has been supported by the SAIOTEK 2011 program of the Basque Government (HODEI01, SA-2011/00227) and by the University of the Basque Country (consolidated groups IT 583-13, IT 520-10 and UFI 11/23). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Aerosol delivery of surfactant and perfluorocarbon (PFC) is a desirable therapeutic approach for the treatment of various lung diseases in patients undergoing mechanical ventilation. However, the behavior of these substances during aerosolization differs significantly from that of aqueous solutions. In particular, the high vapor pressure of many PFCs tends to result in greater evaporation during mechanical ventilation.Three PFCs and surfactant were aerosolized during mechanical ventilation by means of three intratracheal inhalation catheters (IC) with different air flow rates (IC-1.23, IC-1.1, and IC-1.4), with their aerosol generating tip placed at the distal end of the endotracheal tube (i.d. 4 mm). The influence of four different ventilation strategies on aerosol production rate and PFC and surfactant recovery was studied. The changes in intrapulmonary pressure produced by the air jets of each IC were measured.With IC-1.23 and IC-1.1, the highest rates of aerosol production were achieved using FC75 (2.27±0.18 and 0.76±0.01, respectively) followed by PFOB (1.74±0.06 and 0.56±0.04), PFD (0.82±0.01 and 0.21±0.01), and surfactant (0.42±0.05 and 0.092±0.01). With IC-1.4 modest aerosol production was obtained irrespective of the aerosolized compound. Mechanical ventilation influenced aerosol recovery, with the trend being toward recovering higher percentages of the compounds with lower peak inspiratory pressure (PIP) and lower respiratory rate (RR) settings. The highest percentages of the initial volume were recovered with IC-1.23 (between 65.43%±4.2 FC75 and 90.21%±4.71 surfactant) followed by IC-1.1 (between 46.48%±4.46 FC75 and 73.19%±2.82 PFOB) and IC-1.4 (between 4.65%±4.36 FC75 and 63.24%±9.71 surfactant). Each of three of the ICs were found to increase the intrapulmonary pressure by about 2-3 cmH₂O during mechanical ventilation.Despite of mechanical ventilation, IC-1.23 and IC-1.1 were able to deliver significant amounts of surfactant and perfluorocarbon to the lung model. Changes in PIP and RR directly influence the percentage of surfactant and perfluorocarbon recovered.

Our aim was to develop a computerized system for real-time monitoring of lung mechanics measurements during both gas and liquid ventilation. System accuracy was demonstrated by calculating regression and percent error of the following parameters compared to standard device: airway pressure difference (Delta P(aw)), respiratory frequency (f(R) ), tidal volume (V(T)), minute ventilation (V'(E)), inspiratory and expiratory maximum flows (V'(ins,max), V'(exp,max)), dynamic lung compliance (C(L,dyn) ), resistance of the respiratory system calculated by method of Mead-Whittenberger (R(rs,MW)) and by equivalence to electrical circuits (R(rs,ele)), work of breathing (W(OB)), and overdistension. Outcome measures were evaluated as function of gas exchange, cardiovascular parameters, and lung mechanics including mean airway pressure (mP(aw)). Delata P(aw), V(T), V'(ins,max), V'(exp,max), and V'(E) measurements had correlation coefficients r = 1.00, and %error0.5%. f(R), C(L,dyn), R(rs,MW), R(rs,ele), and W(OB) showed ror = 0.98 and %error5%. Overdistension had r = 0.87 and %error15%. Also, resistance was accurately calculated by a new algorithm. The system was tested in rats in which lung lavage was used to induce acute respiratory failure. After lavage, both gas- and liquid-ventilated groups had increased mP(aw) and W(OB), with decreased V(T), V'(E), C(L,dyn), R(rs,MW), and R(rs,ele) compared to controls. After 1-h ventilation, both injured group had decreased V(T), V'(E) , and C(L,dyn), with increased mP(aw), R(rs,MW), R(rs,ele), and W(OB) . In lung-injured animals, liquid ventilation restored gas exchange, and cardiovascular and lung functions. Our lung mechanics system was able to closely monitor pulmonary function, including during transitions between gas and liquid phases.

Background: The aerosolization of PFC has emerged as a feasible alternative to the instillation for the experimental treatment of Respiratory Distress Syndrome. Aim: To determine the effects of aerosolized perfluorocarbon (PFC) on pulmonary gas exchange and lung function in preterm lambs. Methods: 12 preterm lambs (80-90%GE) were used. Lambs were randomly assigned to receive aerosolized PFC (10 ml/kg/h for 2h), delivered via an inhalation catheter, coupled to a jet nebuliser, and placed at the distal end of the endotracheal tube connected to a ventilator (PFC-aerosol) or not (CONTROL), both groups were maintained during 6h on IMV. Cardiovascular parameters, arterial partial pressure of CO2 (PaCO2), pH, oxygenation index (IO), arterial-alveolar oxygen ratio (a/APO2), alveolar-arterial oxygen gradient (A-a)DO2 and pulmonary function (compliance Cdyn and tidal volumen VT) were measured each 30 min during the experiment. Mean±SD, ANOVA, p< 0.05. Results: After 90min of treatment, animals in PFC-aerosol group, significantly improved gas exchange in comparison to Control group, being the improvement persistent until the end of the experiment: PaCO2 (37±6 vs. 93±12 mmHg), pH (7.41±0.11 vs. 7.15±0.09), IO (9±3 VS. 77±44), a/APO2 (0.29±0.11 vs. 0.04±0.02), (A-a)DO2 (294±133 vs. 572±20). Moreover, the pulmonary function significantly improved after 60 min of treatment in PFC-aerosol group compared to Control group, the improvement was sustained during the experimental period: Cdyn (0.53±0.05 vs. 0.27±0.04 ml/cmH2O/kg), VT (12.5±2.4 vs. 5.2±1.8 ml/kg). During all the experimental period there were not changes on cardiovascular parameters. Conclusion: Our results show that administration of aerosolized PFC improves pulmonary function and gas exchange. FIS07/0733-GV2007111046