ArticleRespiratory research2026
KL-6 assisted subtyping of ARDS: from subtype-specific metabolomics to LPCAT1 as a pathogenic target.
Article in Respiratory research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
backgroundAcute lung injury (ALI) and the resulting acute respiratory distress syndrome (ARDS) exhibit marked clinical and biological heterogeneity, hindering subtype identification, biomarker discovery, and targeted therapy development. We used untargeted metabolomics to identify serum and bronchoalveolar lavage fluid (BALF) biomarkers across ARDS subtypes and potential therapeutic targets. We introduce a KL-6–assisted refinement of the Berlin Definition to separate patients with similar PaO₂/FiO₂ ratios but differing degrees of alveolar epithelial damage.
methodsWe enrolled 166 participants (137 ARDS, 29 controls). Using the Berlin Definition with KL-6–assisted classification, patients were stratified into common and severe subtypes. Serum metabolomes were compared between ARDS and controls and between subtypes; paired serum–BALF profiles characterized systemic vs. pulmonary features. Overlapping metabolites from four comparisons informed target prediction (SwissTargetPrediction, GeneCards), followed by in vitro and in vivo validation in LPS models.
resultsSerum profiles and pathway enrichment differed between ARDS and controls and between subtypes. The severe subtype was enriched in fatty-acid oxidation, dicarboxylic acids, and phospholipid remodeling. Three serum metabolites discriminated severe from other less severe ARDS subtypes (AUC > 0.8). This 3-metabolite panel achieved AUC 0.917 in 10-fold cross-validation. Paired analyses showed predominant systemic alterations with subtype-specific BALF signatures; five BALF metabolites were specific to the severe subtype and correlated with KL-6, oxygenation, inflammation, and CT scores. Five shared LysoPCs highlighted LPCAT1 as the top target. LPS upregulated LPCAT1, and this effect was partially reversed by TAK-242, a TLR4 inhibitor. Knockdown of LPCAT1 reduced inflammatory cytokine and MUC1 (KL-6) release in cell culture supernatants.
conclusionKL-6–assisted subtyping reveals distinct systemic and pulmonary metabolic signatures. Three serum metabolites provide evidence that justifies KL-6 as a marker of epithelial-injury–informed ARDS classification, and our results suggest that LPCAT1 is a promising therapeutic target for ARDS.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.