Mechanical ventilation guided by driving pressure optimizes local pulmonary biomechanics in an ovine model.

Mechanical ventilation exposes the lung to injurious stresses and strains that can negatively affect clinical outcomes in acute respiratory distress syndrome or cause pulmonary complications after general anesthesia. Excess global lung strain, estimated as increased respiratory system driving pressure, is associated with mortality related to mechanical ventilation. The role of small-dimension biomechanical factors underlying this association and their spatial heterogeneity within the lung are currently unknown.

Regional pulmonary perfusion, blood volume, and their relationship change in experimental early ARDS.

Regional pulmonary perfusion (Q) has been investigated using blood volume (F) imaging as an easier-to-measure surrogate. However, it is unclear if changing pulmonary conditions could affect their relationship. We hypothesized that vascular changes in early acute respiratory distress syndrome (ARDS) affect Q and F differently.

Lung functional imaging.

Pulmonary functional imaging modalities such as computed tomography, magnetic resonance imaging and nuclear imaging can quantitatively assess regional lung functional parameters and their distributions. These include ventilation, perfusion, gas exchange at the microvascular level and biomechanical properties, among other variables. This review describes the rationale, strengths and limitations of the various imaging modalities employed for lung functional imaging.

Dynamic lung aeration and strain with positive end-expiratory pressure individualized to maximal compliance versus ARDSNet low-stretch strategy: a study in a surfactant depletion model of lung injury.

Background: Positive end-expiratory pressure (PEEP) individualized to a maximal respiratory system compliance directly implies minimal driving pressures with potential outcome benefits, yet, raises concerns on static and dynamic overinflation, strain and cyclic recruitment. Detailed accurate assessment and understanding of these has been hampered by methodological limitations. We aimed to investigate the effects of a maximal compliance-guided PEEP strategy on dynamic lung aeration, strain and tidal recruitment using current four-dimensional computed tomography (CT) techniques and analytical methods of tissue deformation in a surfactant depletion experimental model of acute respiratory distress syndrome (ARDS).

Worsening of lung perfusion to tissue density distributions during early acute lung injury.

Lung perfusion magnitude and distribution are essential for oxygenation and, potentially, lung inflammation and protection during acute respiratory distress syndrome (ARDS). Yet, perfusion patterns and their relationship to inflammation are unknown pre-ARDS. We aimed to assess perfusion/density ratios and spatial perfusion-density distributions and associate these to lung inflammation, during early lung injury in large animals at different physiological conditions caused by different systemic inflammation and positive end-expiratory pressure (PEEP) levels.

Improving pulmonary perfusion assessment by dynamic contrast-enhanced computed tomography in an experimental lung injury model.

Pulmonary perfusion has been poorly characterized in acute respiratory distress syndrome (ARDS). Optimizing protocols to measure pulmonary blood flow (PBF) via dynamic contrast-enhanced (DCE) computed tomography (CT) could improve understanding of how ARDS alters pulmonary perfusion. In this study, comparative evaluations of injection protocols and tracer-kinetic analysis models were performed based on DCE-CT data measured in ventilated pigs with and without lung injury.

Perfusion imaging heterogeneity during NO inhalation distinguishes pulmonary arterial hypertension (PAH) from healthy subjects and has potential as an imaging biomarker.

Background: Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient's response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects.

Smoking and Human Immunodeficiency Virus 1 Infection Promote Retention of CD8 T Cells in the Airway Mucosa.

Smoking and human immunodeficiency virus 1 (HIV-1) infection are risk factors for chronic obstructive pulmonary disease (COPD), which is among the most common comorbid conditions in people living with HIV-1. HIV-1 infection leads to persistent expansion of CD8 T cells, and CD8 T cell-mediated inflammation has been implicated in COPD pathogenesis. In this study, we investigated the effects of HIV-1 infection and smoking on T-cell dynamics in patients at risk of COPD.

Endogenous Carbon Monoxide Production and Diffusing Capacity of the Lung for Carbon Monoxide in Sepsis-Induced Acute Respiratory Distress Syndrome.

Low-dose inhaled carbon monoxide is a novel therapeutic under investigation in acute respiratory distress syndrome. The Coburn-Forster-Kane equation is a well-validated model of carbon monoxide uptake that can accurately predict carboxyhemoglobin levels to ensure safe administration of low-dose inhaled carbon monoxide in patients with acute respiratory distress syndrome. Using data from a Phase I trial of low-dose inhaled carbon monoxide, we performed a post hoc analysis to determine if the Coburn-Forster-Kane equation could be used to assess the diffusing capacity of the lung for carbon monoxide and endogenous carbon monoxide production in patients with sepsis-induced acute respiratory distress syndrome.

Consensus Recommendations on the Use of F-FDG PET/CT in Lung Disease.

PET with F-FDG has been increasingly applied, predominantly in the research setting, to study drug effects and pulmonary biology and to monitor disease progression and treatment outcomes in lung diseases that interfere with gas exchange through alterations of the pulmonary parenchyma, airways, or vasculature. To date, however, there are no widely accepted standard acquisition protocols or imaging data analysis methods for pulmonary F-FDG PET/CT in these diseases, resulting in disparate approaches. Hence, comparison of data across the literature is challenging.

Physiological mechanism and spatial distribution of increased alveolar dead-space in early ARDS: An experimental study.

Background: We aimed to investigate the physiological mechanism and spatial distribution of increased physiological dead-space, an early marker of ARDS mortality, in the initial stages of ARDS. We hypothesized that: increased dead-space results from the spatial redistribution of pulmonary perfusion, not ventilation; such redistribution is not related to thromboembolism (ie, areas with perfusion = 0 and infinite ventilation-perfusion ratio, ), but rather to moderate shifts of perfusion increasing in non-dependent regions.

Methods: Five healthy anesthetized sheep received protective ventilation for 20 hours, while endotoxin was continuously infused.

Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep.

Background: Pulmonary atelectasis is frequent in clinical settings. Yet there is limited mechanistic understanding and substantial clinical and biologic controversy on its consequences. The authors hypothesize that atelectasis produces local transcriptomic changes related to immunity and alveolar-capillary barrier function conducive to lung injury and further exacerbated by systemic inflammation.

PET Imaging Reveals Early Pulmonary Perfusion Abnormalities in HIV Infection Similar to Smoking.

Chronic obstructive pulmonary disease (COPD) is the most common noninfectious pulmonary disease among people living with HIV, independent of smoking. However, the cause for this enhanced susceptibility remains unclear, and the effects of HIV on pulmonary perfusion and ventilation are unknown. We used PET/CT in 46 smokers and nonsmokers, 23 of whom had documented HIV infection.

Inflammatory Activity in Atelectatic and Normally Aerated Regions During Early Acute Lung Injury.

Rationale And Objectives: Pulmonary atelectasis presumably promotes and facilitates lung injury. However, data are limited on its direct and remote relation to inflammation. We aimed to assess regional 2-deoxy-2-[F]-fluoro-D-glucose (F-FDG) kinetics representative of inflammation in atelectatic and normally aerated regions in models of early lung injury.

Airway Transmural Pressures in an Airway Tree During Bronchoconstriction in Asthma.

Airway transmural pressure in healthy homogeneous lungs with dilated airways is approximately equal to the difference between intraluminal and pleural pressure. However, bronchoconstriction causes airway narrowing, parenchymal distortion, dynamic hyperinflation, and the emergence of ventilation defects (VDefs) affecting transmural pressure. This study aimed to investigate the changes in transmural pressure caused by bronchoconstriction in a bronchial tree.

Elevation in lung volume and preventing catastrophic airway closure in asthmatics during bronchoconstriction.

Background: Asthma exacerbations cause lung hyperinflation, elevation in load to inspiratory muscles, and decreased breathing capacity that, in severe cases, may lead to inspiratory muscle fatigue and respiratory failure. Hyperinflation has been attributed to a passive mechanical origin; a respiratory system time-constant too long for full exhalation. However, because the increase in volume is also concurrent with activation of inspiratory muscles during exhalation it is unclear whether hyperinflation in broncho-constriction is a passive phenomenon or is actively controlled to avoid airway closure.

A phase I trial of low-dose inhaled carbon monoxide in sepsis-induced ARDS.

Background: Acute respiratory distress syndrome (ARDS) is a prevalent disease with significant mortality for which no effective pharmacologic therapy exists. Low-dose inhaled carbon monoxide (iCO) confers cytoprotection in preclinical models of sepsis and ARDS.

Methods: We conducted a phase I dose escalation trial to assess feasibility and safety of low-dose iCO administration in patients with sepsis-induced ARDS.