American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jun 2023
CEACAM6 as a Novel Therapeutic Target to Boost HO-1-mediated Antioxidant Defense in COPD.
Rationale: Tobacco smoking and air pollution are primary causes of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop COPD. The mechanisms underlying the defense against nitrosative/oxidative stress in nonsusceptible smokers to COPD remain largely unresolved. ⋯ Consistently, inhibition of HO-1 activity in hAEC2s increased the susceptibility toward CSE-induced damage. Epithelium-specific CEACAM6 overexpression increased nitrosative/oxidative stress and cell death in human precision-cut lung slices on CSE treatment. Conclusions: CEACAM6 expression determines the hAEC2 sensitivity to nitrosative/oxidative stress triggering emphysema development/progression in susceptible smokers.
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Am. J. Respir. Crit. Care Med. · Jun 2023
Distinct Epithelial-Innate Immune Cell Transcriptional Circuits Underlie Airway Hyperresponsiveness in Asthma.
Rationale: Indirect airway hyperresponsiveness (AHR) is a highly specific feature of asthma, but the underlying mechanisms responsible for driving indirect AHR remain incompletely understood. Objectives: To identify differences in gene expression in epithelial brushings obtained from individuals with asthma who were characterized for indirect AHR in the form of exercise-induced bronchoconstriction (EIB). Methods: RNA-sequencing analysis was performed on epithelial brushings obtained from individuals with asthma with EIB (n = 11) and without EIB (n = 9). ⋯ Furthermore, EOS increase the expression of IFNG and IL13 in response to both IL-18 and IL-33 as well as exposure to AECs. Conclusions: Circuits involving epithelial interactions with MCs and EOS are closely associated with indirect AHR. Ex vivo modeling indicates that epithelial-dependent regulation of these innate cells may be critical in indirect AHR and modulating T2 and non-T2 inflammation in asthma.
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Am. J. Respir. Crit. Care Med. · Jun 2023
Changes in Practice of Controlled Hypothermia After Cardiac Arrest in the Past 20 Years - A Critical Care Perspective.
For 20 years, induced hypothermia and targeted temperature management have been recommended to mitigate brain injury and increase survival after cardiac arrest. On the basis of animal research and small clinical trials, the International Liaison Committee on Resuscitation strongly advocated hypothermia at 32-34 °C for 12-24 hours for comatose patients with out-of-hospital cardiac arrest with initial rhythm of ventricular fibrillation or nonperfusing ventricular tachycardia. The intervention was implemented worldwide. ⋯ Systematic reviews suggest little or no effect of delivering the intervention on the basis of the summary of evidence, and the International Liaison Committee on Resuscitation today recommends only to treat fever and keep body temperature below 37.5 °C (weak recommendation, low-certainty evidence). Here we describe the evolution of temperature management for patients with cardiac arrest during the past 20 years and how the accrued evidence has influenced not only the recommendations but also the guideline process. We also discuss possible paths forward in this field, bringing up both whether fever management is at all beneficial for patients with cardiac arrest and which knowledge gaps future clinical trials in temperature management should address.