ArticleAnesthesiology2020
Lung Atelectasis Promotes Immune and Barrier Dysfunction as Revealed by Transcriptome Sequencing in Female Sheep.
Article in Anesthesiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Optimized ventilation strategy for surgery on patients with obesity from the perspective of lung protection: A network meta-analysis.Frontiers in immunology · 2022Pooled it
- Alveolar Collapse as a Threat to Mechanically Ventilated Lungs.American journal of respiratory and critical care medicine · 2024Article
- Pathophysiological profile of non-ventilated lung injury in healthy female pigs undergoing mechanical ventilation.Communications medicine · 2024Article
- Effects of PEEP on regional ventilation-perfusion mismatch in the acute respiratory distress syndrome.Critical care (London, England) · 2022Article
- Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions.Scientific reports · 2022Article
- Perioperative Pulmonary Atelectasis: Part I. Biology and Mechanisms.Anesthesiology · 2022Review
- Isomer-Specific Effects ofAnimals : an open access journal from MDPI · 2021Article
Corrections and comments
- Commented on byRNA Sequencing.2020
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundPulmonary 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.
methodsFemale sheep underwent unilateral lung atelectasis using a left bronchial blocker and thoracotomy while the right lung was ventilated, with (n = 6) or without (n = 6) systemic lipopolysaccharide infusion. Computed tomography guided samples were harvested for NextGen RNA sequencing from atelectatic and aerated lung regions. The Wald test was used to detect differential gene expression as an absolute fold change greater than 1.5 and adjusted P value (Benjamini-Hochberg) less than 0.05. Functional analysis was performed by gene set enrichment analysis.
resultsLipopolysaccharide-unexposed atelectatic versus aerated regions presented 2,363 differentially expressed genes. Lipopolysaccharide exposure induced 3,767 differentially expressed genes in atelectatic lungs but only 1,197 genes in aerated lungs relative to the corresponding lipopolysaccharide-unexposed tissues. Gene set enrichment for immune response in atelectasis versus aerated tissues yielded negative normalized enrichment scores without lipopolysaccharide (less than -1.23, adjusted P value less than 0.05) but positive scores with lipopolysaccharide (greater than 1.33, adjusted P value less than 0.05). Leukocyte-related processes (e.g., leukocyte migration, activation, and mediated immunity) were enhanced in lipopolysaccharide-exposed atelectasis partly through interferon-stimulated genes. Furthermore, atelectasis was associated with negatively enriched gene sets involving alveolar-capillary barrier function irrespective of lipopolysaccharide (normalized enrichment scores less than -1.35, adjusted P value less than 0.05). Yes-associated protein signaling was dysregulated with lower nuclear distribution in atelectatic versus aerated lung (lipopolysaccharide-unexposed: 10.0 ± 4.2 versus 13.4 ± 4.2 arbitrary units, lipopolysaccharide-exposed: 8.1 ± 2.0 versus 11.3 ± 2.4 arbitrary units, effect of lung aeration, P = 0.003).
conclusionsAtelectasis dysregulates the local pulmonary transcriptome with negatively enriched immune response and alveolar-capillary barrier function. Systemic lipopolysaccharide converts the transcriptomic immune response into positive enrichment but does not affect local barrier function transcriptomics. Interferon-stimulated genes and Yes-associated protein might be novel candidate targets for atelectasis-associated injury. EDITOR’S PERSPECTIVE:
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