{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T18:59:21Z","timestamp":1780945161961,"version":"3.54.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic airway inflammation and progressive lung injury. The inflammatory profile and systemic involvement remain poorly defined. We applied integrated multi omics (transcriptomics, proteomics, and metagenomics) to characterize inflammatory signatures and explore saliva as a noninvasive marker of systemic inflammation. These findings may support improved disease characterization and inform therapy and monitoring.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This cross sectional, multicenter study included participants with PCD and healthy controls from Houston, Texas; Puerto Rico; and Mexico. Demographic and clinical data were collected in the absence of acute infection. Oral swabs underwent a bulk inflammatory transcriptomic profiling of 590-genes using NanoString nCounter\u00ae and microbiome evaluation via metagenomic sequencing. High sensitivity NULISA\u2122 proteomic profiling of 250-proteins was performed on both saliva and plasma, with results correlated across omic layers. Pathway and gene set analyses were conducted using nSolver Advanced Analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seventy-six participants were enrolled: 51 with PCD and 25 healthy controls. PCD patients, especially those older than 10\u2009years and those with microtubular defects, showed markedly elevated inflammatory gene and protein expression in saliva and plasma. Five inflammatory endotypes were identified: Neutrophilic protease dominant, Dipeptidyl Peptidase 1(DPP\u20111) profile (78%); neutrophilic recruiting, high\u2011Th17 (71%); eosinophilic dominant, high\u2011Th2 (51%); Th2\/Th17\u2011high (47%), and Th2\/Th17\u2011low (25%). PCD demonstrated increased neutrophil, and CD45\u2011related gene expression and activation of ten inflammatory pathways, including NF\u2011\u03baB, oxidative stress, T\u2011cell-receptor, TREG, Th17, TNF, Th1, Th2, TGF-B signaling, and TLR (P\u2009&amp;lt;\u2009.01). Saliva and plasma showed strong molecular concordance. Microbiome analysis revealed significant shifts in diversity and abundance linked to inflammatory pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings show that PCD is characterized by baseline inflammatory activity with marked endotypic heterogeneity, most frequently involving neutrophilic-immune pathways driven by DPP1-associated protease activity and Th17-mediated neutrophil recruitment, while a distinct subset of patients demonstrates a Th2-predominant inflammatory endotype. Salivary inflammatory profiling, which closely mirrors plasma, may offer a practical, non-invasive approach to capturing this patient-level heterogeneity and monitoring systemic immune activity and treatment response, especially with the new anti-inflammatory medications for bronchiectasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/annalsats\/aaoag152","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T18:24:53Z","timestamp":1780943093000},"source":"Crossref","is-referenced-by-count":0,"title":["Multi-Omics Analysis Defines Endotypes and Systemic Inflammation in Primary Ciliary Dyskinesia: A Comparison with Healthy Controls"],"prefix":"10.1093","author":[{"given":"Ricardo A","family":"Mosquera","sequence":"first","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division of Pediatric Pulmonology, Department of Pediatrics, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan Gustavo","family":"Magana-Ceballos","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division of Pediatric Pulmonology, Department of Pediatrics, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfredo","family":"De Jesus Rojas","sequence":"additional","affiliation":[{"name":"Ponce Health Sciences University, Puerto Rico School of Medicine Department of Basic Sciences, , San Juan, PR,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangsheng","family":"Huang","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Department of Immunology, Cell Biology, Molecular Biology, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haniyeh","family":"Koochak","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division of Pediatric Pulmonology, Department of Pediatrics, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E","family":"Tellez","sequence":"additional","affiliation":[{"name":"McGovern Medical School, UTHealth Houston Department of Pediatrics, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Ariel","family":"Castillo-Moguel","sequence":"additional","affiliation":[{"name":"Merida Clinic Department of Pediatric Pulmonology, , Merida, Yucatan,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faraz","family":"Bishehsari","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Department of Internal Medicine\u2014Gastroenterology, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahboobeh","family":"Mahdavinia","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division Director, Allergy & Immunology, Department of Internal Medicine, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos J","family":"Ramos-Benitez","sequence":"additional","affiliation":[{"name":"Ponce Health Sciences University, Puerto Rico School of Medicine Department of Basic Sciences, , San Juan, PR,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomika","family":"Harris","sequence":"additional","affiliation":[{"name":"McGovern Medical School, UTHealth Houston Department of Pediatrics, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aravind","family":"Yadav","sequence":"additional","affiliation":[{"name":"McGovern Medical School, UTHealth Houston Department of Pediatrics, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kereisha","family":"Owens","sequence":"additional","affiliation":[{"name":"McGovern Medical School, UTHealth Houston Department of Pediatrics, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Lemus-Rangel","sequence":"additional","affiliation":[{"name":"National Medical Center \u201cLa Raza,\u201d IMSS Bronchiectasis Clinic, General Hospital, , Mexico City,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Romero","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division of Neonatal-Perinatal Medicine, Department of Pediatrics, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhei","family":"Zuleta","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division of Pediatric Pulmonology, Department of Pediatrics, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ara","family":"Luz","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division of Pediatric Pulmonology, Department of Pediatrics, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anel","family":"Baltazar-Fernandez","sequence":"additional","affiliation":[{"name":"National Medical Center \u201cLa Raza,\u201d IMSS Bronchiectasis Clinic, General Hospital, , Mexico City,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina E","family":"McBeth","sequence":"additional","affiliation":[{"name":"McGovern Medical School, UTHealth Houston Department of Pediatrics, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed","family":"Hashmi","sequence":"additional","affiliation":[{"name":"McGovern Medical School, UTHealth Houston Department of Pediatrics, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Rosario Ortiz","sequence":"additional","affiliation":[{"name":"Ponce Health Sciences University, Puerto Rico School of Medicine Department of Basic Sciences, , San Juan, PR,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Santoyo-Rios","sequence":"additional","affiliation":[{"name":"McGovern Medical School, UTHealth Houston Department of Pediatrics, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Francisco","family":"Loyo-Rodriguez","sequence":"additional","affiliation":[{"name":"Merida Clinic Department of Pediatric Pulmonology, , Merida, Yucatan,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe N","family":"Colasurdo","sequence":"additional","affiliation":[{"name":"The University of Texas Health Science Center at Houston (UTHealth Houston) Division of Pediatric Pulmonology, Department of Pediatrics, McGovern Medical School, , Houston, TX,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,8]]},"container-title":["Annals of the American Thoracic 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