Altered Lung Mechanics Research Articles

Mechanical and morphological characterization of the emphysematous lung tissue

Irreversible alveolar airspace enlargement is the main characteristic of pulmonary emphysema, which has been extensively studied using animal models. While the alterations in lung mechanics associated with these morphological changes have been documented in the literature, the study of the mechanical behavior of parenchymal tissue from emphysematous lungs has been poorly investigated. In this work, we characterize the mechanical and morphological properties of lung tissue in elastase-induced emphysema rat models under varying severity conditions. We analyze the non-linear tissue behavior using suitable hyperelastic constitutive models that enable to compare different non-linear responses in terms of hyperelastic material parameters. We further analyze the effect of the elastase dose on alveolar morphology and tissue material parameters and study their connection with respiratory-system mechanical parameters. Our results show that while the lung mechanical function is not significantly influenced by the elastase treatment, the tissue mechanical behavior and alveolar morphology are markedly affected by it. We further show a strong association between alveolar enlargement and tissue softening, not evidenced by respiratory-system compliance. Our findings highlight the importance of understanding tissue mechanics in emphysematous lungs, as changes in tissue properties could detect the early stages of emphysema remodeling. Statement of significanceGas exchange is vital for life and strongly relies on the mechanical function of the lungs. Pulmonary emphysema is a prevalent respiratory disease where alveolar walls are damaged, causing alveolar enlargement that induces harmful changes in the mechanical response of the lungs. In this work, we study how the mechanical properties of lung tissue change during emphysema. Our results from animal models show that tissue properties are more sensitive to alveolar enlargement due to emphysema than other mechanical properties that describe the function of the whole respiratory system.

Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO2), we developed a model of repetitive exposure to SO2 in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular (PV) disease. Although abnormalities in small airways were not sufficient to alter lung mechanics, PV remodeling resulted in the development of pulmonary hypertension and reduced exercise tolerance in SO2-exposed mice. SO2 exposure led to increased formation of isolevuglandins (isoLGs) adducts and superoxide dismutase 2 (SOD2) acetylation in endothelial cells, which were attenuated by treatment with the isoLG scavenger 2-hydroxybenzylamine acetate (2-HOBA). In addition, 2-HOBA treatment or Siruin-3 overexpression in a transgenic mouse model prevented vascular remodeling following SO2 exposure. In summary, our results indicate that repetitive SO2 exposure recapitulates many aspects of PDRS and that oxidative stress appears to mediate PV remodeling in this model. Together, these findings provide new insights regarding the critical mechanisms underlying PDRS.NEW & NOTEWORTHY We developed a mice model of "post-deployment respiratory syndrome" (PDRS), a condition in Veterans with unexplained exertional dyspnea. Our model successfully recapitulates many of the pathological and physiological features of the syndrome, revealing involvement of the ROS-isoLGs-Sirt3-SOD2 pathway in pulmonary vasculature pathology. Our study provides additional knowledge about effects and long-term consequences of sulfur dioxide exposure on the respiratory system, serving as a valuable tool for future PDRS research.

Effect of expiratory flow limitation on ventilation/perfusion mismatch and perioperative lung function during pneumoperitoneum and Trendelenburg position.

Laparoscopic surgery and Trendelenburg position may affect the respiratory function and alter the gas exchange. Further the reduction of the lung volumes may contribute to the development of expiratory flow limitation (EFL). The latter is associated with an increased risk of postoperative pulmonary complications. Our aim was to investigate the incidence of EFL and to evaluate its effect on pulmonary function and intraoperative V/Q mismatch. This is a prospective study on patients undergoing elective laparoscopic gynecological surgery. We evaluated respiratory mechanics, V/Q mismatch and presence of EFL after anesthesia induction, during pneumoperitoneum and Trendelenburg position and at the end of surgery. Intraoperative gas exchange and hemodynamic were also recorded. Clinical data were collected until seven days after surgery to evaluate the onset of pulmonary postoperative complications (PPCs). Among the 66 patients enrolled, 25/66 (38%) exhibited EFL during surgery, of whom 10/66 (15%) after anesthesia induction, and the remaining 15 patients after pneumoperitoneum and Trendelenburg position. Median PEEP able to reverse flow limitation was 7 [7-10] cmH2O after anesthesia induction and 9 [8-15] cmH2O after pneumoperitoneum and Trendelenburg position. Patients with EFL had significantly higher shunt (17 [2-25] vs. 9 [1-19]; P=0.05), low V̇/Q̇ (27 [20-70] vs. 15 [10-22]; P=0.05) and high V̇/Q̇ (10 [7-14] vs. 6 [4-7]; P=0.024). At the end of surgery, only high V/Q was significantly higher in EFL patients. Further, they exhibited higher incidence of postoperative pulmonary complication (48% (12/25) vs. 15% (6/41), P=0.005), hypoxemia and hypercapnia (80% [20/25] vs. 32% [13/41]; P<0.001). Expiratory flow limitation is a common phenomenon during gynecological laparoscopic surgery associated with worsen gas exchange, increased V/Q mismatch and altered lung mechanics. Our study showed that patients experiencing EFL during surgery showed a higher risk for PPCs.

Effect of prolonged lipopolysaccharide exposure on lung function and health

RationalePatients with Chronic Obstructive Pulmonary Disease often have persistent inflammation of the airways that lead to symptoms of chronic bronchitis and airway obstruction. While it is known that long term exposure to cigarette smoke can cause persistent airways inflammation, it is not clear if this is a direct result of tobacco exposure or if it is a result of chronic inflammation. We hypothesized that a recurrent and prolonged inflammatory insult would result in alterations in lung mechanics characterized by airway obstruction.Methods. To test the independent effects of recurrent and persistent lung inflammation on lung mechanics, C57Bl/6 8 week old male mice were treated weekly with PBS or lipopolysaccharide (LPS) via direct intratracheal injection. Monthly, we evaluated lung function analysis including: airway resistance and compliance, tissue damping, pressure volume loops, and forced expiratory volume using the flexiVent system.Results. Airway resistance at month 1 was 0.5543±0.017 PBS vs 0.552±0.009 cmH2O.s/mL LPS (p=0.999), month 2 0.5177±0.015 PBS vs 0.576±0.017 LPS (p=0.999), month 3 0.461± 0.03 PBS vs 0.47±0.038 cmH2O.s/mL LPS (p=0.999), month 5 0.43±0.015 PBS vs 0.468±0.026 cmH2O.s/mL LPS (p=0.999), month 6 PBS 0.408± 0.06 vs LPS 0.6465±0.18 cmH2O.s/mL (p=0.999), and month 7 PBS 0.384 ± 0.023 vs LPS 0.3498 ± 0.015 cmH2O.s/mL (p=0.999). Forced expiratory volume 0.1 (FEV 0.1) at month 1 was 0.4±0.08 PBS vs 0.803±0.107 mL LPS (p=0.999), month 2 0.2115±0.01 PBS vs 0.184±0.03 mL LPS (p=0.999), month 3 1.071±0.09 PBS vs 1.098±0.06 mL LPS (p=0.999), month 5 0.853±0.243 vs 0.756±0.21 mL LPS (p=0.999), month 6 2.671±1.06 PBS vs 1.669±0.87 mL LPS (p=0.999), month 7 0.9049±0.27 PBS vs 1.127±0.152 mL LPS (p=0.999).ConclusionIt is well known that chronic smoking can have a significant impact of lung function. Through this project we aimed to discover whether chronic inflammation alone would alter lung function. Interestingly even after weekly direct intratracheal injections of LPS there were no significant changes in lung function compared to PBS treated mice. We have shown here that chronic inflammation alone was not sufficient to alter lung function in mice, and that the decrease in lung function seen in chronic smokers is attributable to numerous factors and not inflammation alone.

English

Obesity is a significant risk factor for cardiovascular disorders, metabolic disorders, osteoarthritis, multiple cancers, serious mental illness, hypertension, dyslipidemia, diabetes mellitus and coronary artery disease. Obesity has been reported to promote oxidative stress, as obesity stimulates the penetration and activation of macrophages and monocytes into adipose tissue which, in turn, releases elevated levels of pro-inflammatory adipokines, such as tumour necrosis factor-alpha ( TNFa) and interleukin-6 (IL-6).Insulin resistance is associated with both type 2 diabetes and obesity. Alteration of lung mechanics in obese patients, including decreased lung capacities, decreased compliance, irregular breathing and perfusion and gas exchange, and respiratory muscle inefficiency, can predispose to increased risk and severity of respiratory infections. Obesity and atherosclerosis pathogenesis have many popular causes. In all cases, lipids, oxidized LDL particles and free fatty acids trigger the inflammatory response and induce the disease. In this review article, we have focused on different morbidities related to obesity. KEYWORDS Obesity, Diabetes Mellitus, Hypertension, Oxidative Stress, Osteoarthritis

Postexposure Liponucleotide Prophylaxis and Treatment Attenuates Acute Respiratory Distress Syndrome in Influenza-infected Mice.

There is an urgent need for new drugs for patients with acute respiratory distress syndrome (ARDS), including those with coronavirus disease (COVID-19). ARDS in influenza-infected mice is associated with reduced concentrations of liponucleotides (essential precursors for de novo phospholipid synthesis) in alveolar type II (ATII) epithelial cells. Because surfactant phospholipid synthesis is a primary function of ATII cells, we hypothesized that disrupting this process could contribute significantly to the pathogenesis of influenza-induced ARDS. The goal of this study was to determine whether parenteral liponucleotide supplementation can attenuate ARDS. C57BL/6 mice inoculated intranasally with 10,000 plaque-forming units/mouse of H1N1 influenza A/WSN/33 virus were treated with CDP (cytidine 5'-diphospho)-choline (100 μg/mouse i.p.) ± CDP -diacylglycerol 16:0/16:0 (10 μg/mouse i.p.) once daily from 1 to 5 days after inoculation (to model postexposure influenza prophylaxis) or as a single dose on Day 5 (to model treatment of patients with ongoing influenza-induced ARDS). Daily postexposure prophylaxis with CDP-choline attenuated influenza-induced hypoxemia, pulmonary edema, alterations in lung mechanics, impairment of alveolar fluid clearance, and pulmonary inflammation without altering viral replication. These effects were not recapitulated by the daily administration of CTP (cytidine triphosphate) and/or choline. Daily coadministration of CDP-diacylglycerol significantly enhanced the beneficial effects of CDP-choline and also modified the ATII cell lipidome, reversing the infection-induced decrease in phosphatidylcholine and increasing concentrations of most other lipid classes in ATII cells. Single-dose treatment with both liponucleotides at 5 days after inoculation also attenuated hypoxemia, altered lung mechanics, and inflammation. Overall, our data show that liponucleotides act rapidly to reduce disease severity in mice with severe influenza-induced ARDS.

Antenatal Endotoxin Impairs Lung Mechanics and Increases Sensitivity to Ventilator-Induced Lung Injury in Newborn Rat Pups.

Perinatal inflammation due to chorioamnionitis and ventilator-induced lung injury (VILI) at birth is independent risk factors for the development of bronchopulmonary dysplasia (BPD). We have previously shown that antenatal endotoxin (ETX) causes abnormal lung structure and function in 2-week-old rats, but whether ETX impairs lung mechanics at birth and increases risk for VILI is unknown. Fetal rats were exposed to 10 μg endotoxin or saline via intra-amniotic injection. At birth (D0) or 7 days (D7), rats received 90 min of lung protective ventilation [PROTECT group; tidal volume (Vt) = 6 ml/kg with positive end expiratory pressure (PEEP) = 2 cmH2O]; P20 ventilation [plateau pressure (Pplat) = 20 cmH2O, PEEP = 0]; or P24 ventilation (Pplat = 24 cmH2O, PEEP = 0, only applied to D7). Prior to prolonged ventilation at D0, endotoxin-exposed rats had decreased compliance and inspiratory capacity (IC) compared to controls. At D7, endotoxin was associated with reduced compliance. High-pressure ventilation (P20 and P24) tended to increase IC and compliance in all saline-treated groups. Ventilation at D0 with P20 increased IC and compliance when applied to saline-treated but not endotoxin-exposed pups. At D7, P24 ventilation of endotoxin-exposed pups increased elastance, bronchoalveolar lavage protein content, and IL-1b and TEN-C mRNA expression in comparison to the saline group. In summary, antenatal endotoxin exposure alters lung mechanics at birth and 1 week of life and increases susceptibility to VILI as observed in lung mechanics, alveolocapillary barrier injury, and inflammatory mRNA expression. We speculate that antenatal inflammation primes the lung for a more marked VILI response, suggesting an adverse synergistic effect of antenatal and postnatal exposures.

Body Habitus and Dynamic Surgical Conditions Independently Impair Pulmonary Mechanics during Robotic-assisted Laparoscopic Surgery.

Body habitus, pneumoperitoneum, and Trendelenburg positioning may each independently impair lung mechanics during robotic laparoscopic surgery. This study hypothesized that increasing body mass index is associated with more mechanical strain and alveolar collapse, and these impairments are exacerbated by pneumoperitoneum and Trendelenburg positioning. This cross-sectional study measured respiratory flow, airway pressures, and esophageal pressures in 91 subjects with body mass index ranging from 18.3 to 60.6 kg/m2. Pulmonary mechanics were quantified at four stages: (1) supine and level after intubation, (2) with pneumoperitoneum, (3) in Trendelenburg docked with the surgical robot, and (4) level without pneumoperitoneum. Subjects were stratified into five body mass index categories (less than 25, 25 to 29.9, 30 to 34.9, 35 to 39.9, and 40 or higher), and respiratory mechanics were compared over surgical stages using generalized estimating equations. The optimal positive end-expiratory pressure settings needed to achieve positive end-expiratory transpulmonary pressures were calculated. At baseline, transpulmonary driving pressures increased in each body mass index category (1.9 ± 0.5 cm H2O; mean difference ± SD; P < 0.006), and subjects with a body mass index of 40 or higher had decreased mean end-expiratory transpulmonary pressures compared with those with body mass index of less than 25 (-7.5 ± 6.3 vs. -1.3 ± 3.4 cm H2O; P < 0.001). Pneumoperitoneum and Trendelenburg each further elevated transpulmonary driving pressures (2.8 ± 0.7 and 4.7 ± 1.0 cm H2O, respectively; P < 0.001) and depressed end-expiratory transpulmonary pressures (-3.4 ± 1.3 and -4.5 ± 1.5 cm H2O, respectively; P < 0.001) compared with baseline. Optimal positive end-expiratory pressure was greater than set positive end-expiratory pressure in 79% of subjects at baseline, 88% with pneumoperitoneum, 95% in Trendelenburg, and ranged from 0 to 36.6 cm H2O depending on body mass index and surgical stage. Increasing body mass index induces significant alterations in lung mechanics during robotic laparoscopic surgery, but there is a wide range in the degree of impairment. Positive end-expiratory pressure settings may need individualization based on body mass index and surgical conditions.

Airway Hyperresponsiveness, Inflammation, and Pulmonary Emphysema in Rodent Models Designed to Mimic Exposure to Fuel Oil-Derived Volatile Organic Compounds Encountered during an Experimental Oil Spill.

Background:Fuel oil–derived volatile organic compounds (VOCs) inhalation is associated with accidental marine spills. After the Prestige petroleum tanker sank off northern Spain in 2002 and the Deepwater Horizon oil rig catastrophe in 2009, subjects involved in environmental decontamination showed signs of ongoing or residual lung disease up to 5 y after the exposure.Objectives:We aimed at investigating mechanisms driving persistent respiratory disease by developing an animal model of inhalational exposure to fuel oil–derived VOCs.Methods:Female Wistar and Brown Norway (BN) rats and C57BL mice were exposed to VOCs produced from fuel oil mimicking the Prestige spill. Exposed animals inhaled the VOCs 2 h daily, 5 d per week, for 3 wk. Airway responsiveness to methacholine (MCh) was assessed, and bronchoalveolar lavage (BAL) and lung tissues were analyzed after the exposure and following a 2-wk washout.Results:Consistent with data from human studies, both strains of rats that inhaled fuel oil–derived VOCs developed airway hyperresponsiveness that persisted after the washout period, in the absence of detectable inflammation in any lung compartment. Histopathology and quantitative morphology revealed the development of peripherally distributed pulmonary emphysema, which persisted after the washout period, associated with increased alveolar septal cell apoptosis, microvascular endothelial damage of the lung parenchyma, and inhibited expression of vascular endothelial growth factor (VEGF).Discussion:In this rat model, fuel oil VOCs inhalation elicited alveolar septal cell apoptosis, likely due to DNA damage. In turn, the development of a peculiar pulmonary emphysema pattern altered lung mechanics and caused persistent noninflammatory airway hyperresponsiveness. Such findings suggest to us that humans might also respond to VOCs through physiopathological pathways different from those chiefly involved in typical cigarette smoke–driven emphysema in chronic obstructive pulmonary disease (COPD). If so, this study could form the basis for a novel disease mechanism for lasting respiratory disease following inhalational exposure to catastrophic fuel oil spills. https://doi.org/10.1289/EHP4178

Surfactant replacement therapy: from biological basis to current clinical practice.

This review summarizes the current knowledge on the physiological action of endogenous and exogenous pulmonary surfactant, the role of different types of animal-derived and synthetic surfactants for RDS therapy, different modes of administration, potential risks and strategies of ventilation, and highlights the most promising aims for future development. Scientists have clarified the physicochemical properties and functions of the different components of surfactant, and part of this successful research is derived from the characterization of genetic diseases affecting surfactant composition or function. Knowledge from functional tests of surfactant action, its immunochemistry, kinetics and homeostasis are important also for improving therapy with animal-derived surfactant preparations and for the development of modified surfactants. In the past decade newly designed artificial surfactants and additives have gained much attention and have proven different advantages, but their particular role still has to be defined. For clinical practice, alternative administration techniques as well as postsurfactant ventilation modes, taking into account alterations in lung mechanics after surfactant placement, may be important in optimizing the potential of this most important drug in neonatology.

P.715 Caffeine prevents behavioral alterations related to schizoprenia caused by chemical hypoxia in neonatal period

Acute viral respiratory infections (VRI) are the most common diseases in humans and are associated with high morbidity and mortality in infants and the elderly. Children with congenital heart disease (CHD) are more susceptible to get severe forms of VRI due to their altered lung mechanics, leading to several complications, such as increased hospital stay, longer mechanical ventilation, and higher mortality. This study aimed to identify the frequency of VRI in children with CHD undergoing cardiac surgery, and to compare the major outcomes according to the presence or absence of a VRI.This was a longitudinal, observational cohort study. Nasopharyngeal secretion samples were collected pre- and postoperatively for patients undergoing cardiac surgery, from May 2013 to May 2014. Respiratory viruses were detected using CLART Pneumovir®.Forty-eight patients were enrolled. We found a VRI preoperatively in 16 children with CHD before surgery (33.3%), and the frequency of new infections was 8.3% (4 patients). However, in this study, in univariate analyses, the two groups did not differ in any of the studied outcomes. In the multivariate regression models, adjusting for age and STAT category, the presence of a VRI did not show a significant effect on the major outcomes.In conclusion, VRI was frequent in children undergoing open-heart surgery, but the presence of a VRI did not impact on major outcomes in this cohort.

The Kinematic Chain of Arm Elevation Is Impaired in Patients with Chronic Obstructive Pulmonary Disease

Patients with chronic obstructive pulmonary disease (COPD) often complain about difficulties in performing activities with their arms above shoulders height. These difficulties have been associated with increased cardiorespiratory demand and altered lung mechanics; however, musculoskeletal-related mechanisms may also contribute to constrain the mechanics of the upper body quadrant, increasing the effort to perform the activities. This exploratory research aimed to assess potential changes in the kinematic chain of arm elevation in patients with COPD. A secondary analysis from a cross-sectional exploratory case-control and prediction study was conducted in 15 patients with COPD (2 females) and 15 controls (8 females) matched for age and body mass index. The sagittal alignment and active range of motion (ROM) of the head, thoracic spine and shoulder complex were measured, using a computer software, in digital lateral photographs obtained in three different testing positions: arms at rest, arms at 90° of shoulder flexion and full arm elevation. From rest to full arm elevation, both groups moved from a more flexed to a less flexed or more upright thoracic spine position (∼7°, p < 0.001, 0.419 < <0.767). However, the COPD group showed significantly less shoulder flexion (∼12°, p = 0.007, d = 1.05) and thoracic spine extension (∼6°, p = 0.015, = 0.139) ROM than the control group in the full arm elevation position. These findings suggest that this population may show changes in the kinematic chain of arm elevation that possibly contribute to arm movement-related complains and limited performance in their daily living.

Maternal protein restriction during perinatal life affects lung mechanics and the surfactant system during early postnatal life in female rats.

Limited information is available on how fetal growth retardation (FGR) affects the lung in the neonatal period in males and females. This led us to test the hypothesis that FGR alters lung mechanics and the surfactant system during the neonatal period. To test this hypothesis a model of FGR was utilized in which pregnant rat dams were fed a low protein diet during both the gestation and lactation period. We subsequently analyzed lung mechanics using a FlexiVent ventilator in male and female pups at postnatal day 7 and 21. Lung lavage material was obtained at postnatal day 1, 7 and 21, and was used for analysis of the surfactant system which included measurement of the pool size of surfactant and its subfraction as well as the surface tension reducing ability of the surfactant. The main result of the study was a significantly lower lung compliance and higher tissue elastance which was observed in FGR female offspring at day 21 compared to control offspring. In addition, female LP offspring exhibited lower surfactant pool sizes at postnatal day 1compared to controls. These changes were not observed in the male offspring. It is concluded that FGR has a different impact on pulmonary function and on surfactant in female, as compared to male, offspring.

INOS Inhibition Reduces Lung Mechanical Alterations and Remodeling Induced by Particulate Matter in Mice.

Background. The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and acute lung damage is well known. However, the mechanism involved in the effects of repeated exposures of PM in the lung injury is poorly documented. This study tested the hypotheses that chronic nasal instillation of residual oil fly ash (ROFA) induced not only distal lung and airway inflammation but also remodeling. In addition, we evaluated the effects of inducible nitric oxide inhibition in these responses. For this purpose, airway and lung parenchyma were evaluated by quantitative analysis of collagen and elastic fibers, immunohistochemistry for macrophages, neutrophils, inducible nitric oxide synthase (iNOS), neuronal nitric oxide synthase (nNOS), and alveolar septa 8-iso prostaglandin F2α (8-iso-PGF-2α) detection. Anesthetized in vivo (airway resistance, elastance, H, G, and Raw) respiratory mechanics were also analyzed. C57BL6 mice received daily 60ul of ROFA (intranasal) for five (ROFA-5d) or fifteen days (ROFA-15d). Controls have received saline (SAL). Part of the animals has received 1400W (SAL+1400W and ROFA-15d+1400W), an iNOS inhibitor, for four days before the end of the protocol. A marked neutrophil and macrophage infiltration and an increase in the iNOS, nNOS, and 8-iso-PGF2 α expression was observed in peribronchiolar and alveolar wall both in ROFA-5d and in ROFA-15d groups. There was an increment of the collagen and elastic fibers in alveolar and airway walls in ROFA-15d group. The iNOS inhibition reduced all alterations induced by ROFA, except for the 8-iso-PGF2 α expression. In conclusion, repeated particulate matter exposures induce extracellular matrix remodeling of airway and alveolar walls, which could contribute to the pulmonary mechanical changes observed. The mechanism involved is, at least, dependent on the inducible nitric oxide activation.

Comparative Study between Different Modes of Ventilation during Cardiopulmonary Bypass and its Effect on Postoperative Pulmonary Dysfunction.

Background:Postoperative pulmonary dysfunction is a prevalent complication after cardiac surgery; it has many contributing considerations due to either the surgery itself, anomalies to gas exchange or maybe as a result of alterations in lung mechanics. The aim of this study was to compare pressure-controlled ventilation versus volume-controlled ventilation in the presence of no ventilation group as a control group during cardiopulmonary bypass and its effect on postoperative pulmonary dysfunction.Patients and Methods:Sixty-six patients going through open-heart surgeries were included in the study. They divided into three groups (Group P: Pressure-controlled ventilation, Group V: Volume-controlled ventilation, and Group C: Control group with no ventilation) in accordance with the mode of ventilation. Patients studied for chest X-ray, lung ultrasound, arterial oxygen partial pressure to fractional inspired oxygen ratio, alveolar–arterial oxygen gradient, static lung compliance, and dynamic lung compliance, taken after induction of anesthesia, 1-h post-CPB, and 1 h after arrival to cardiac surgical unit.Results:There was no significant difference regarding the chest X-ray and lung ultrasonography results among the three groups of the study. Regarding arterial oxygen partial pressure to fractional inspired oxygen ratio, alveolar–arterial oxygen gradient, static lung compliance, and dynamic lung compliance, the results showed lower values in the postbypass period, and the postoperative period compared to the postinduction period among the three groups of the study with no significant difference.Conclusions:The evidence of clear benefits of maintaining ventilation alone during cardiopulmonary bypass is inconsistent. More studies are required to determine the precise role of different lung protective strategies during cardiopulmonary bypass.

Low‐dose administration of bleomycin leads to early alterations in lung mechanics

What is the central question of this study? When do alterations in pulmonary mechanics occur following chronic low-dose administration of bleomycin? What is the main finding and its importance? Remarkably, we report changes in lung mechanics as early as day7 that corresponded to parameters determined from single-frequency forced oscillation manoeuvres and pressure-volume loops. These changes preceded substantial histological changes or changes in gene expression levels. These findings are significant to refine drug discovery in idiopathic pulmonary fibrosis, where preclinical studies using lung function parameters would enhance the translational potential of drug candidates where lung function readouts are routinely performed in the clinic. Idiopathic pulmonary fibrosis (IPF) is the most widespread form of interstitial lung disease and, currently, there are only limited treatment options available. In preclinical animal models of lung fibrosis, the effectiveness of experimental therapeutics is often deemed successful via reductions in collagen deposition and expression of profibrotic genes in the lung. However, in clinical studies, improvements in lung function are primarily used to gauge the success of therapeutics directed towards IPF. Therefore, we examined whether changes in respiratory system mechanics in the early stages of an experimental model of lung fibrosis can be used to refine drug discovery approaches for IPF. C57BL/6J mice were administered bleomycin (BLM) or a vehicle control i.p. twice a week for 4weeks. At 7, 14, 21, 28 and 33days into the BLM treatment regimen, indices of respiratory system mechanics and pressure-volume relationships were measured. Concomitant with these measurements, histological and gene analyses relevant to lung fibrosis were performed. Alterations in respiratory system mechanics and pressure-volume relationships were observed as early as 7days after the start of BLM administration. Changes in respiratory system mechanics preceded the appearance of histological and molecular indices of lung fibrosis. Administration of BLM leads to early changes in respiratory system mechanics that coincide with the appearance of representative histological and molecular indices of lung fibrosis. Consequently, these data suggest that dampening the early changes in respiratory system mechanics might be used to assess the effectiveness of experimental therapeutics in preclinical animal models of lung fibrosis.

Epidemiology of viral respiratory infections in children undergoing heart surgery

BackgroundAcute viral respiratory infections (VRI) are the most common diseases in humans and are associated with high morbidity and mortality in infants and the elderly. Children with congenital heart disease (CHD) are more susceptible to get severe forms of VRI due to their altered lung mechanics, leading to several complications, such as increased hospital stay, longer mechanical ventilation, and higher mortality. This study aimed to identify the frequency of VRI in children with CHD undergoing cardiac surgery, and to compare the major outcomes according to the presence or absence of a VRI. MethodsThis was a longitudinal, observational cohort study. Nasopharyngeal secretion samples were collected pre- and postoperatively for patients undergoing cardiac surgery, from May 2013 to May 2014. Respiratory viruses were detected using CLART Pneumovir®. ResultsForty-eight patients were enrolled. We found a VRI preoperatively in 16 children with CHD before surgery (33.3%), and the frequency of new infections was 8.3% (4 patients). However, in this study, in univariate analyses, the two groups did not differ in any of the studied outcomes. In the multivariate regression models, adjusting for age and STAT category, the presence of a VRI did not show a significant effect on the major outcomes. ConclusionsIn conclusion, VRI was frequent in children undergoing open-heart surgery, but the presence of a VRI did not impact on major outcomes in this cohort.

Pulmonary Effects of Adjusting Tidal Volume to Actual or Ideal Body Weight in Ventilated Obese Mice

Obese patients could be more susceptible to mechanical ventilation (MV)-induced lung injury than non-obese patients due to weight-dependent changes in lung properties. The aim of this study was therefore to evaluate the pulmonary effects of 2 hours low VT MV in a diet-induced obese mice model, with VT calculated on either the actual body weight (VTaw) or the ideal body weight (VTiw) . First, we hypothesized that a MV with VTaw would be associated with altered lung mechanics and an increased lung inflammation. Second, we hypothesised that a MV with a VTiw would preserve lung mechanics and limit lung inflammation. We analyzed lung mechanics and inflammation using bronchoalveolar lavage (BAL) cell counts, flow cytometry tissue analysis and histology. Lung mechanics and inflammation were comparable in control and obese mice receiving VTiw. By contrast, obese mice receiving VTaw had significantly more alterations in lung mechanics, BAL cellularity and lung influx of monocytes as compared to control mice. Their monocyte expression of Gr1 and CD62L was also increased. Alveolar neutrophil infiltration was significantly increased in all obese mice as compared to controls. In conclusion, our findings suggest that protective MV with a VTaw is deleterious, with a marked alteration in lung mechanics and associated lung inflammation as compared to lean mice. With VTiw, lung mechanics and inflammation were close to that of control mice, except for an increased alveolar infiltrate of polymorphonuclear neutrophils. This inflammation might be attenuated by a blunted recruitment of inflammatory cells associated with obesity.

Differential Expression of Aquaporins in Experimental Models of Acute Lung Injury.

The mammalian lung expresses at least three aquaporin (AQP) water channels whose precise role in lung injury or inflammation is still controversial. Three murine models of lung inflammation and corresponding controls were used to evaluate the expression of Aqp1, Aqp4, Aqp5 and Aqp9: lipopolysaccharide (LPS)-induced lung injury; HCl-induced lung injury; and ventilation-induced lung injury (VILI). All models yielded increased lung vascular permeability, and inflammatory cell infiltration in the broncho-alveolar lavage fluid; VILI additionally produced altered lung mechanics. Lung expression of Aqp4 decreased in the models that targeted primarily the alveolar epithelium, i.e. acid aspiration and mechanical ventilation, while Aqp5 expression decreased in the model that appeared to target both the capillary endothelium and alveolar epithelium, i.e. LPS. Participation of aquaporins in the acute inflammatory process depends on localization and the type of lung injury.

Physiology of the lung in idiopathic pulmonary fibrosis.

The clinical expression of idiopathic pulmonary fibrosis (IPF) is directly related to multiple alterations in lung function. These alterations derive from a complex disease process affecting all compartments of the lower respiratory system, from the conducting airways to the lung vasculature. In this article we review the profound alterations in lung mechanics (reduced lung compliance and lung volumes), pulmonary gas exchange (reduced diffusing capacity, increased dead space ventilation, chronic arterial hypoxaemia) and airway physiology (increased cough reflex and increased airway volume), as well as pulmonary haemodynamics related to IPF. The relative contribution of these alterations to exertional limitation and dyspnoea in IPF is discussed.