The pathophysiology of acute lung injury (ALI) is well characterized, but its real-time assessment at bedside remains a challenge. When patients do not improve after 1 wk despite supportive therapies, physicians have to consider open lung biopsy (OLB) to identify the process(es) at play. Sustained inflammation and inadequate repair are often observed in this context. OLB is neither easy to perform in a critical setting nor exempt from complications. Herein, we explore intravital endoscopic confocal fluorescence microscopy (ECFM) of the lung in vivo combined with the use of fluorescent smart probe(s) activated by myeloperoxidase (MPO). MPO is a granular enzyme expressed by polymorphonuclear neutrophils (PMNs) and alveolar macrophages (AMs), catalyzing the synthesis of hypoclorous acid, a by-product of hydrogen peroxide. Activation of these probes was first validated in vitro in relevant cells (i.e., AMs and PMNs) and on MPO-non-expressing cells (as negative controls) and then tested in vivo using three rat models of ALI and real-time intravital imaging with ECFM. Semiquantitative image analyses revealed that in vivo probe-related cellular/background fluorescence was associated with corresponding enhanced lung enzymatic activity and was partly prevented by specific MPO inhibition. Additional ex vivo phenotyping was performed, confirming that fluorescent cells were neutrophil elastase(+) (PMNs) or CD68(+) (AMs). This work is a first step toward "virtual biopsy" of ALI without OLB.
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http://dx.doi.org/10.1152/ajplung.00289.2014 | DOI Listing |
BMC Infect Dis
January 2025
Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
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January 2025
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA, USA.
Amidst the rising prevalence of respiratory diseases, the importance of effective lung treatment modalities is more critical than ever. However, current drug delivery systems face significant limitations that impede their efficacy and therapeutic outcome. Biohybrid microrobots have shown considerable promise for active in vivo drug delivery, especially for pulmonary applications via intratracheal routes.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Pathology, Dokkyo Medical University School of Medicine and Graduate School of Medicine, 880 Kitakobayashi, Mibu, Shimotsugagun, Tochigi, 321-0293, Japan.
Although alveolar hyperoxia exacerbates lung injury, clinical studies have failed to demonstrate the beneficial effects of lowering the fraction of inspired oxygen (FO) in patients with acute respiratory distress syndrome (ARDS). Atelectasis, which is commonly observed in ARDS, not only leads to hypoxemia but also contributes to lung injury through hypoxia-induced alveolar tissue inflammation. Therefore, it is possible that excessively low FO may enhance hypoxia-induced inflammation in atelectasis, and raising FO to an appropriate level may be a reasonable strategy for its mitigation.
View Article and Find Full Text PDFCurr Opin Crit Care
January 2025
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, University of Milan, Milan, Italy.
Purpose Of Review: The increasing use of prone position, in intubated patients with acute respiratory distress syndrome as well as in patients with acute hypoxemic respiratory failure receiving noninvasive respiratory support, mandates a better definition and monitoring of the response to the manoeuvre. This review will first discuss the definition of the response to prone positioning, which is still largely based on its effect on oxygenation. We will then address monitoring respiratory and hemodynamic responses to prone positioning in intubated patients.
View Article and Find Full Text PDFImmun Inflamm Dis
January 2025
Department of Respiratory and Critical Care Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Background: Acute lung injury (ALI), one of the most severe respiratory system diseases, is prevalent worldwide. Annexin A1 (AnxA1) is an important member of the annexin superfamily, known for its wide range of physiological functions. However, its potential protective effect against lipopolysaccharide (LPS)-induced ALI remains unclear.
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