[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-458319-105":59,"doc-detail-458319-en":131},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","integrative-blood-profiling-uncovers-inflammatory-network-signatures-in-high-altitude-pulmonary-edema","Integrative blood profiling uncovers inflammatory network signatures in high-altitude pulmonary edema","","Despite the established role of hypoxia-driven inflammatory mediators in hypoxic pulmonary hypertension, their contribution to high-altitude illnesses—especially high-altitude pulmonary edema (HAPE)—remains unclear. An integrated clinical and multiomics analysis of 83 participants (including HAPE severity strata, HAPE-free sojourners, and long-term high-altitude residents) defines molecular and immunological changes linked to HAPE. The study finds dysregulated oxygenation, 515 differential genes enriched for inflammatory and hypoxia pathways, hub genes with diagnostic value, increased neutrophil proportions, and cytokine and lncRNA-mRNA interactions shaping inflammation.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/integrative-blood-profiling-uncovers-inflammatory-network-signatures-in-high-altitude-pulmonary-edema/458319/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/integrative-blood-profiling-uncovers-inflammatory-network-signatures-in-high-altitude-pulmonary-edema/458319.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-09","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What question does the study address about high-altitude pulmonary edema?","Question",{"text":113,"@type":114},"It investigates whether hypoxia-driven inflammatory mediators contribute to HAPE and its severity, which has remained unclear despite their role in other conditions.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What data types are integrated in the analysis?",{"text":118,"@type":114},"The study integrates clinical assessment with transcriptomic, proteomic, and long noncoding RNA (lncRNA) profiling.",{"name":120,"@type":111,"acceptedAnswer":121},"What immune and molecular signals are highlighted in HAPE?",{"text":122,"@type":114},"HAPE is associated with reduced oxygen saturation, enriched inflammatory and hypoxia pathways, increased neutrophil proportions, and a role for the hypoxia-regulated cytokine OSM, alongside lncRNA-mRNA interactions.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},458319,1791133608,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":46,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":31,"preview_page_count":4},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Bioscience Reports (2025) 45 1–20  \n[https://doi.org/10.1042/BSR20253746](https://doi.org/10.1042/BSR20253746)  \nResearch Article  \nIntegrative blood profiling uncovers inflammatory network signatures in highaltitude pulmonary edema  \nKanika Singh1,2*, Krishna Kumar G1,2*, Manzoor Ali1,2, Raushni Choudhary1,2, Mohit Khadia1, Stanzen Rabyang3, Tashi Thinlas3, Rahul Kumar4,5 and Aastha Mishra1,2  \n1Genomics and Genome Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Delhi, 110025, India; 2Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India; 3Department of Medicine, Sonam Norboo Memorial Hospital, Leh, 194101, India; 4Department of Medicine, University of California San Francisco, San Francisco, California, 94143, U.S.A.; 5Lung Biology Center, Zuckerberg San Francisco General Hospital, San Francisco, California, 94143, U.S.A.  \nCorrespondence: Aastha Mishra ([aastha.mishra@igib.in](aastha.mishra@igib.in))  \n*These authors contributed equally to this work.  \nReceived: 28 June 2025  \nRevised: 1 October 2025  \nAccepted: 16 October 2025  \nVersion of Record  \nPublished: 12 December 2025  \nDespite the well-known role of hypoxia-driven inflammatory mediators in the pathogenesis of hypoxic pulmonary hypertension, their involvement in high-altitude (HA) illnesses, particularly high-altitude pulmonary edema (HAPE), remains unclear. The present study uses an integrated clinical, transcriptomic, proteomic, and long noncoding RNA (lncRNA) profiling of 83 individuals, including HAPE patients segre‐ gated into mild, moderate, and severe categories, HAPE-free sojourners, and long-term HA residents, to highlight the molecular and immunological changes associated with HAPE and its severity. Clinical assess‐ ments revealed significantly reduced peripheral oxygen saturation and elevated respiratory parameters in HAPE patients. Differential gene expression and functional enrichment analyses identified 515 significantly differentially expressed genes, with marked enrichment of inflammatory and hypoxia-associated pathways. Protein–protein interaction network analysis revealed eighteen hub genes, including toll-like receptor (TLR)  \n2 and Forkhead box O3 (FOXO3), with strong diagnostic potential. Immune cell deconvolution analysis and hematological profiling indicated a prominent increase in neutrophil proportion. Interestingly, oncos‐ tatin M (OSM), a hypoxia-regulated predominant cytokine produced by neutrophils, was revealed in the cytokine and transcriptomic profiling, highlighting its role in inflammation and extracellular matrix degrada‐ tion. Co-expression network analysis notably revealed significant alterations that formed a gene module exhibiting a strong correlation with immune response, leukocyte adhesion, and ncRNA processing pathways. Interestingly, these co-expressed partners, LINC01093 and immune-regulatory genes like interleukin-18 receptor 1 and TLR5, appear to regulate the NF-κB signaling pathway, one of the positively enriched pathways in our analysis. Overall, this multiomics approach highlighted a strong inflammatory signature and lncRNA-mRNA interactions associated with HAPE.  \nIntroduction  \nHigh altitude (HA) presents a physiologically challenging environment due to reduced oxygen availability, triggering various cellular and metabolic adaptations to maintain homeostasis [ 1] . Globally, approximately 81.6 million individuals reside at elevations above 2,500 m [2], while over 100 million lowlanders visit HA annually for recreational or occupational purposes, including tourists, trekkers, miners, construction workers, and military personnel [2,3] . However, a subset of individuals develops altitude-associated illnesses, influenced by genetic and epigenetic susceptibility or pre-existing health conditions. A critical yet understudied factor in HA illnesses is the interplay between hypoxia and inflammation [4–6] . While hypoxia-driven inflammatory mediators play a well-documented role in","cbCaihiJCPcrrQuf","https://ap.wps.com/l/cbCaihiJCPcrrQuf","pdf",4754093,"English","# Introduction\n## Study rationale: hypoxia–inflammation in HAPE\n## Clinical features and pathophysiology of HAPE\n# Clinical and multiomics profiling findings\n## Differential gene expression and pathway enrichment\n## Protein interaction networks and hub genes\n## Immune cell deconvolution and neutrophil signals\n## Cytokine discovery and co-expression modules","[{\"question\":\"What question does the study address about high-altitude pulmonary edema?\",\"answer\":\"It investigates whether hypoxia-driven inflammatory mediators contribute to HAPE and its severity, which has remained unclear despite their role in other conditions.\"},{\"question\":\"What data types are integrated in the analysis?\",\"answer\":\"The study integrates clinical assessment with transcriptomic, proteomic, and long noncoding RNA (lncRNA) profiling.\"},{\"question\":\"What immune and molecular signals are highlighted in HAPE?\",\"answer\":\"HAPE is associated with reduced oxygen saturation, enriched inflammatory and hypoxia pathways, increased neutrophil proportions, and a role for the hypoxia-regulated cytokine OSM, alongside lncRNA-mRNA interactions.\"}]","Integrative blood profiling uncovers inflammatory network signatures in high-altitude pulmonary edema | PDF",1790752571]