Adding value to daily chest X-rays in the ICU through education, restricted daily orders and indication-based prompting.

Background: Chest X-rays (CXRs) are traditionally obtained daily in all patients on invasive mechanical ventilation (IMV) in the intensive care unit (ICU). We sought to reduce overutilisation of CXRs obtained in the ICU, using a multifaceted intervention to eliminate automated daily studies.

Methods: We first educated ICU staff about the low diagnostic yield of automated daily CXRs, then removed the 'daily' option from the electronic health records-based ordering system, and added a query (CXR indicated or not indicated) to the ICU daily rounding checklist to prompt a CXR order when clinically warranted.

Predicting ventilator-induced lung injury using a lung injury cost function.

Managing patients with acute respiratory distress syndrome (ARDS) requires mechanical ventilation that balances the competing goals of sustaining life while avoiding ventilator-induced lung injury (VILI). In particular, it is reasonable to suppose that for any given ARDS patient, there must exist an optimum pair of values for tidal volume (VT) and positive end-expiratory pressure (PEEP) that together minimize the risk for VILI. To find these optimum values, and thus develop a personalized approach to mechanical ventilation in ARDS, we need to be able to predict how injurious a given ventilation regimen will be in any given patient so that the minimally injurious regimen for that patient can be determined.

Computational Models of Ventilator Induced Lung Injury and Surfactant Dysfunction.

Managing acute respiratory distress syndrome (ARDS) invariably involves the administration of mechanical ventilation, the challenge being to avoid the iatrogenic sequellum known as ventilator-induced lung injury (VILI). Devising individualized ventilation strategies in ARDS requires that patient-specific lung physiology be taken into account, and this is greatly aided by the use of computational models of lung mechanical function that can be matched to physiological measurements made in a given patient. In this review, we discuss recent models that have the potential to serve as the basis for devising minimally injurious modes of mechanical ventilation in ARDS patients.

Neurofibromatosis 1-associated panhypopituitarism presenting as hypoglycaemic seizures and stroke-like symptoms.

A 37-year-old man with a known history of neurofibromatosis 1 (NF1) presented within 2 days of diarrhoeal illness followed by encephalopathy, facial twitching, hypoglycaemia, hypotension, tachycardia and low-grade fever. Examination showed multiple café-au-lait spots and neurofibromas over the trunk, arms and legs and receptive aphasia with right homonymous hemianopia, which resolved. Workup for cardiac, inflammatory and infectious aetiologies was unrevealing.

Synergy between acid and endotoxin in an experimental model of aspiration-related lung injury progression.

Aspiration is a common cause of lung injury, but it is unclear why some cases are self-limited while others progress to acute respiratory distress syndrome (ARDS). Sporadic exposure to more than one insult could account for this variable progression. We investigated whether synergy between airway acid and endotoxin (LPS) amplifies injury severity in mice and whether LPS levels in human patients could corroborate our experimental findings.

A multitiered strategy of simulation training, kit consolidation, and electronic documentation is associated with a reduction in central line-associated bloodstream infections.

Background: Simulation-based training has been associated with reduced central line-associated bloodstream infection (CLABSI) rates. We measured the combined effect of simulation training, electronic medical records (EMR)-based documentation, and standardized kits on CLABSI rates in our medical (MICU) and surgical (SICU) intensive care units (ICU).

Methods: CLABSI events and catheter-days were collected for 19 months prior to and 37 months following an intervention consisting of simulation training in central line insertion for all ICU residents, incorporation of standardized, all-inclusive catheter kits, and EMR-guided documentation.

Endogenous distal airway progenitor cells, lung mechanics, and disproportionate lobar growth following long-term postpneumonectomy in mice.

Using a model of postpneumonectomy (PNY) compensatory lung growth in mice, we previously observed an increase in numbers of a putative endogenous distal airway progenitor cell population (CCSP(pos) /pro-SPC(pos) cells located at bronchoalveolar duct junctions [BADJs]), at 3, 7, and 14 days after pneumonectomy, returning to baseline at 28 days post-PNY. As the origin of these cells is poorly understood, we evaluated whether bone marrow cells contributed to the pool of these or other cells during prolonged post-PNY lung regrowth. Naïve and sex-mismatched chimeric mice underwent left PNY and were evaluated at 1, 2, and 3 months for numbers of BADJ CCSP(pos) /pro-SPC(pos) cells and presence of donor-derived marrow cells engrafted as airway or alveolar epithelium.

Elucidating the fuzziness in physician decision making in ARDS.

The current standard of care for patients suffering from acute respiratory distress syndrome (ARDS) is ventilation with a tidal volume of 6 ml/kg predicted body weight (PBW), but variability remains in the tidal volumes that are actually used. This study aims to identify patient scenarios for which there is discordance between physicians in choice of tidal volume and positive end-expiratory pressure (PEEP) in ARDS patients. We developed an algorithm based on fuzzy logic for encapsulating the expertise of individual physicians regarding their use of tidal volume and PEEP in ARDS patients.

The Temporal Evolution of Airways Hyperresponsiveness and Inflammation.

Airways hyperresponsiveness (AHR) is usually produced within days of first antigen exposure in mouse models of asthma. Furthermore, continual antigen challenge eventually results in the resolution of the AHR phenotype. Human asthma also waxes and wanes with time, suggesting that studying the time course of AHR in the allergic mouse would offer insights into the variation in symptoms seen in asthmatics.

Comparative assessment of detergent-based protocols for mouse lung de-cellularization and re-cellularization.

Several different detergent-based methods are currently being explored for de-cellularizing whole lungs for subsequent use as three-dimensional scaffolds for ex vivo lung tissue generation. However, it is not yet clear which of these methods may provide a scaffold that best supports re-cellularization and generation of functional lung tissue. Notably, the detergents used for de-cellularization activate matrix metalloproteinases that can potentially degrade extracellular matrix (ECM) proteins important for subsequent binding and growth of cells inoculated into the de-cellularized scaffolds.

Initial binding and recellularization of decellularized mouse lung scaffolds with bone marrow-derived mesenchymal stromal cells.

Recellularization of whole decellularized lung scaffolds provides a novel approach for generating functional lung tissue ex vivo for subsequent clinical transplantation. To explore the potential utility of stem and progenitor cells in this model, we investigated recellularization of decellularized whole mouse lungs after intratracheal inoculation of bone marrow-derived mesenchymal stromal cells (MSCs). The decellularized lungs maintained structural features of native lungs, including intact vasculature, ability to undergo ventilation, and an extracellular matrix (ECM) scaffold consisting primarily of collagens I and IV, laminin, and fibronectin.

Hemolytic phospholipase C inhibition protects lung function during Pseudomonas aeruginosa infection.

Rationale: The opportunistic pathogen Pseudomonas aeruginosa causes both acute and chronic lung infections and is particularly problematic in patients with cystic fibrosis and those undergoing mechanical ventilation. Decreased lung function contributes significantly to morbidity and mortality during P. aeruginosa infection, and damage inflicted by P.

Quantifying the roles of tidal volume and PEEP in the pathogenesis of ventilator-induced lung injury.

Management of patients with acute lung injury (ALI) rests on achieving a balance between the gas exchanging benefits of mechanical ventilation and the exacerbation of tissue damage in the form of ventilator-induced lung injury (VILI). Optimizing this balance requires an injury cost function relating injury progression to the measurable pressures, flows, and volumes delivered during mechanical ventilation. With this in mind, we mechanically ventilated naive, anesthetized, paralyzed mice for 4 h using either a low or high tidal volume (Vt) with either moderate or zero positive end-expiratory pressure (PEEP).

Effects of central airway shunting on the mechanical impedance of the mouse lung.

The mechanical properties of the lung are embodied in its mechanical input impedance, which it is interpreted in physiological terms by being fit with a mathematical model. The normal lung is extremely well described by a model consisting of a single uniformly ventilated compartment comprised of tissue having a constant-phase impedance, but to describe the abnormal lung it frequently becomes necessary to invoke additional compartments. To date, all evidence of regional mechanical heterogeneity in the mouse lung has been assumed to be of the parallel variety.

Acid aspiration-induced airways hyperresponsiveness in mice.

The role of gastroesophageal reflux and micro-aspiration as a trigger of airways hyperresponsiveness (AHR) in patients with asthma is controversial. The role of acid reflux and aspiration as a direct cause of AHR in normal subjects is also unclear. We speculated that aspiration of a weak acid with a pH (1.

The role of time and pressure on alveolar recruitment.

Inappropriate mechanical ventilation in patients with acute respiratory distress syndrome can lead to ventilator-induced lung injury (VILI) and increase the morbidity and mortality. Reopening collapsed lung units may significantly reduce VILI, but the mechanisms governing lung recruitment are unclear. We thus investigated the dynamics of lung recruitment at the alveolar level.

Neither fibrin nor plasminogen activator inhibitor-1 deficiency protects lung function in a mouse model of acute lung injury.

Fibrin impairs surfactant function in vitro, and inhibition of fibrinolysis by plasminogen activator inhibitor (PAI-1) is thought to promote fibrin accumulation in acute lung injury (ALI). This has led to speculation that impaired PAI-1 and fibrin accumulation should protect lung function in ALI. We tested this hypothesis by investigating ALI severity in fibrinogen-deficient (Fgn-/-) and PAI-1-deficient (PAI-1-/-) mice.

Modeling the dynamics of recruitment and derecruitment in mice with acute lung injury.

Lung recruitment and derecruitment contribute significantly to variations in the elastance of the respiratory system during mechanical ventilation. However, the decreases in elastance that occur with deep inflation are transient, especially in acute lung injury. Bates and Irvin (8) proposed a model of the lung that recreates time-varying changes in elastance as a result of progressive recruitment and derecruitment of lung units.

Nuclear factor-kappaB activation in airway epithelium induces inflammation and hyperresponsiveness.

Rationale: Nuclear factor (NF)-kappaB is a prominent proinflammatory transcription factor that plays a critical role in allergic airway disease. Previous studies demonstrated that inhibition of NF-kappaB in airway epithelium causes attenuation of allergic inflammation.

Objectives: We sought to determine if selective activation of NF-kappaB within the airway epithelium in the absence of other agonists is sufficient to cause allergic airway disease.

The response to recruitment worsens with progression of lung injury and fibrin accumulation in a mouse model of acid aspiration.

Reopening the injured lung with deep inflation (DI) and positive end-expiratory pressure (PEEP) likely depends on the duration and severity of acute lung injury (ALI), key features of which include increased alveolar permeability and fibrin accumulation. We hypothesized that the response to DI and PEEP would worsen as ALI evolves and that this would correspond with increasing accumulation of alveolar fibrin. C57BL/6 mice were anesthetized and aspirated 75 microl of HCl (pH 1.

Airway hyperresponsiveness in allergically inflamed mice: the role of airway closure.

Rationale: Allergically inflamed mice exhibit airway hyperresponsiveness to inhaled methacholine, which computer simulations of lung impedance suggest is due to enhanced lung derecruitment and which we sought to verify in the present study.

Methods: BALB/c mice were sensitized and challenged with ovalbumin to induce allergic inflammation; the control mice were sensitized but received no challenge. The mice were then challenged with inhaled methacholine and respiratory system impedance tracked for the following 10 minutes.

A woman with cough, fever, and micronodular infiltrates on chest radiograph.

Hot tub lung is a form of hypersensitivity pneumonitis (HP) reported to be associated with exposure to large aerosolized inocula of Mycobacterium avium complex (MAC). Although the pathogenesis of the disease is still poorly understood, the pathology of MAC-related HP can be similar to that of sarcoidosis, with well-formed granulomas. We describe a patient with HP featuring well-formed granulomas on transbronchial biopsy specimens, a finding believed to be unique to MAC-related HP, also referred to as "hot tub lung".