Association Between Acute Kidney Injury During Invasive Mechanical Ventilation and ICU Outcomes and Respiratory System Mechanics.

Unlabelled: Compare ICU outcomes and respiratory system mechanics in patients with and without acute kidney injury during invasive mechanical ventilation.

Designs: Retrospective cohort study.

Settings: ICUs of the University of California, San Diego, from January 1, 2014, to November 30, 2016.

Absolute quantification of plasma mitochondrial DNA by droplet digital PCR marks COVID-19 severity over time during intensive care unit admissions.

Increased plasma mitochondrial DNA concentrations are associated with poor outcomes in multiple critical illnesses, including COVID-19. However, current methods of cell-free mitochondrial DNA quantification in plasma are time-consuming and lack reproducibility. Here, we used next-generation sequencing to characterize the size and genome location of circulating mitochondrial DNA in critically ill subjects with COVID-19 to develop a facile and optimal method of quantification by droplet digital PCR.

Quantifying unintended exposure to high tidal volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria.

Purpose: Breath stacking dyssynchrony generates higher tidal volumes than intended, potentially increasing lung injury risk in acute respiratory distress syndrome (ARDS). Lack of validated criteria to quantify breath stacking dyssynchrony contributes to its under-recognition. This study evaluates performance of novel, objective criteria for quantifying breath stacking dyssynchrony (BREATHE criteria) compared to existing definitions and tests if neuromuscular blockade eliminates high-volume breath stacking dyssynchrony in ARDS.

Estimating dead-space fraction for secondary analyses of acute respiratory distress syndrome clinical trials.

Objectives: Pulmonary dead-space fraction is one of few lung-specific independent predictors of mortality from acute respiratory distress syndrome. However, it is not measured routinely in clinical trials and thus altogether ignored in secondary analyses that shape future research directions and clinical practice. This study sought to validate an estimate of dead-space fraction for use in secondary analyses of clinical trials.

Impaired pulmonary defense against Pseudomonas aeruginosa in VEGF gene inactivated mouse lung.

Repeated bacterial and viral infections are known to contribute to worsening lung function in several respiratory diseases, including asthma, cystic fibrosis, and chronic obstructive pulmonary disease (COPD). Previous studies have reported alveolar wall cell apoptosis and parenchymal damage in adult pulmonary VEGF gene ablated mice. We hypothesized that VEGF expressed by type II cells is also necessary to provide an effective host defense against bacteria in part by maintaining surfactant homeostasis.

Efficacy of methylprednisolone in preventing lung injury following pulmonary thromboendarterectomy.

Background: We sought to determine the efficacy and safety of perioperative treatment with methylprednisolone on the development of lung injury after pulmonary thromboendarterectomy.

Methods: This was a randomized, prospective, double-blind, placebo-controlled study of 98 adult patients with chronic thromboembolic pulmonary hypertension who were undergoing pulmonary thromboendarterectomy at a single institution. The patients received either placebo (n = 47) or methylprednisolone (n = 51) (30 mg/kg in the cardiopulmonary bypass prime, 500 mg IV bolus following the final circulatory arrest, and 250 mg IV bolus 36 h after surgery).

Recombinant surfactant protein C-based surfactant for patients with severe direct lung injury.

Rationale: Patients with acute lung injury have impaired function of the lung surfactant system. Prior clinical trials have shown that treatment with exogenous recombinant surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation and have suggested that treatment of patients with severe direct lung injury may decrease mortality.

Objectives: Determine the clinical benefit of administering an rSP-C-based synthetic surfactant to patients with severe direct lung injury due to pneumonia or aspiration.

An informatics strategy to assure enrollment criteria compliance in studies of the critically ill.

Up to 18% of acutely ill patients randomized into multicenter clinical trials may not satisfy inclusion/exclusion criteria. To improve compliance with such criteria in an ICU-based multicenter international drug trial, we established a novel Internet/telephone-based strategy for providing rapid case approval or disapproval by centralized panels of critical care physicians. We assessed whether these panels could acquire and record accurate patient information, and whether this approach would minimize enrollment of ineligible patients and could be accomplished in a timely fashion.

Beyond mortality: future clinical research in acute lung injury.

Mortality in National Heart, Lung and Blood Institute-sponsored clinical trials of treatments for acute lung injury (ALI) has decreased dramatically during the past two decades. As a consequence, design of such trials based on a mortality outcome requires ever-increasing numbers of patients. Recognizing that advances in clinical trial design might be applicable to these trials and might allow trials with fewer patients, the National Heart, Lung and Blood Institute convened a workshop of extramural experts from several disciplines.

A Search for subgroups of patients with ARDS who may benefit from surfactant replacement therapy: a pooled analysis of five studies with recombinant surfactant protein-C surfactant (Venticute).

Background: Studies to date have shown no survival benefit for the use of exogenous surfactant to treat patients with the ARDS. To identify specific patient subgroups for future study, we performed an exploratory post hoc analysis of clinical trials of recombinant surfactant protein-C (rSP-C) surfactant (Venticute; Nycomed GmbH; Konstanz, Germany).

Methods: We performed a pooled analysis of all five multicenter studies in which patients with ARDS due to various predisposing events were treated with rSP-C surfactant.

Effect of recombinant surfactant protein C-based surfactant on the acute respiratory distress syndrome.

Background: Preclinical studies suggest that exogenous surfactant may be of value in the treatment of the acute respiratory distress syndrome (ARDS), and two phase 2 clinical trials have shown a trend toward benefit. We conducted two phase 3 studies of a protein-containing surfactant in adults with ARDS.

Methods: In two multicenter, randomized, double-blind trials involving 448 patients with ARDS from various causes, we compared standard therapy alone with standard therapy plus up to four intratracheal doses of a recombinant surfactant protein C-based surfactant given within a period of 24 hours.

Surfactant from diving aquatic mammals.

Diving mammals that descend to depths of 50-70 m or greater fully collapse the gas exchanging portions of their lungs and then reexpand these areas with ascent. To investigate whether these animals may have evolved a uniquely developed surfactant system to facilitate repetitive alveolar collapse and expansion, we have analyzed surfactant in bronchoalveolar lavage fluid (BAL) obtained from nine pinnipeds and from pigs and humans. In contrast to BAL from terrestrial mammals, BAL from pinnipeds has a higher concentration of phospholipid and relatively more fluidic phosphatidylcholine molecular species, perhaps to facilitate rapid spreading during alveolar reexpansion.

Acute lung injury in 2003.

During the past several decades, clinical investigators world-wide have continued to study the causes, pathophysiology, and treatment strategies for acute lung injury (ALI). This syndrome, which is characterized by nonhydrostatic pulmonary edema and hypoxemia associated with a variety of etiologies, is slowly becoming better understood as a result of these efforts.

Treatment of acute respiratory distress syndrome with recombinant surfactant protein C surfactant.

We performed a phase I/II trial in North America of a recombinant surfactant protein C-based surfactant (Venticute) as treatment for the acute respiratory distress syndrome. Patients were prospectively randomized to receive either standard therapy or standard therapy plus one of two doses of exogenous surfactant given four times over 24 hours. Surfactant administration was well tolerated.

Effect of CTP:phosphocholine cytidylyltransferase overexpression on the mouse lung surfactant system.

CTP:phosphocholine cytidylyltransferase (CT) is the rate-limiting enzyme in the biosynthesis by type II pneumocytes of phosphatidylcholine (PC), the predominant phospholipid in lung surfactant. Augmentation of endogenous CT activity might therefore result in enhanced surfactant PC production. To test this hypothesis, transgenic mice were created in which rat CT (rCT) was expressed under control of the human surfactant protein C (SP-C) promoter.

The future of surfactant therapy for patients with acute lung injury - new requirements and new surfactants.

New requirements must be considered when designing trials of new lung surfactants for patients with acute lung injury (ALI). Radiographic inclusion criteria must be carefully applied if they are to generate reproducible patient groups. Strategies for ventilation are now known to significantly affect outcome and also must be clearly defined and applied.

Lung surfactant in subacute pulmonary disease.

Pulmonary surfactant is a surface active material composed of both lipids and proteins that is produced by alveolar type II pneumocytes. Abnormalities of surfactant in the immature lung or in the acutely inflamed mature lung are well described. However, in a variety of subacute diseases of the mature lung, abnormalities of lung surfactant may also be of importance.