{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T08:24:18Z","timestamp":1792139058450,"version":"4.4.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001803","name":"Charles Darwin University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001803","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Acute respiratory exacerbations in bronchiectasis are important as they impair quality of life and are associated with accelerated lung function decline. Yet, no validated methods exist to identify children at increased risk of exacerbations. We therefore determined if peripheral blood gene expression (GE) signatures can identify those at risk of an impending exacerbation. Thirty-one children with bronchiectasis had RNA extracted from peripheral blood collected whilst they were clinically stable, with 22 having an exacerbation during the next 3 months. Microarray assays using the HumanHT-12 v4.0 Expression BeadChip identified differentially expressed genes (\n                      <jats:italic>p<\/jats:italic>\n                      value\u2009\u2264\u20090.05, fold change\u2009&gt;\u20091.5). The top targets were verified using real-time quantitative polymerase chain reaction (rt-qPCR) assays, and receiver operating characteristics and area under the curve (AUC) were assessed. Functional analysis of these genes was performed using Ingenuity Pathway Analysis. Overall, 647 entities were significantly dysregulated (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) in the exacerbation group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200922), and pathway analysis identified neutrophil degranulation as the dominant affected pathway, which was also significantly inhibited (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Forty entities (32 genes) were associated with a future exacerbation (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05, fold change\u2009\u2265\u20091.5) and six genes (\n                      <jats:italic>ANXA3<\/jats:italic>\n                      ,\n                      <jats:italic>ALAS2<\/jats:italic>\n                      ,\n                      <jats:italic>DEFA1<\/jats:italic>\n                      ,\n                      <jats:italic>ALPL<\/jats:italic>\n                      ,\n                      <jats:italic>SNCA<\/jats:italic>\n                      ,\n                      <jats:italic>PROK2<\/jats:italic>\n                      ) were verified using RT-qPCR (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.04) as the most discriminatory.\n                      <jats:italic>DEFA1<\/jats:italic>\n                      and\n                      <jats:italic>ANXA3<\/jats:italic>\n                      had the highest AUC (0.92, 95% confidence interval [CI] 0.82\u20131.00, and 0.87, 95% CI 0.73\u20131.00, respectively). We identified neutrophil-associated genes from peripheral blood that could be potential biomarkers for children with bronchiectasis at increased risk of exacerbations during the next 3 months. These GE signatures warrant further investigation and validation in larger, independent cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key messages<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Exacerbations in paediatric bronchiectasis are important.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Peripheral blood gene expression may help identify children at risk of exacerbations.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Six neutrophil-associated genes were associated with a future exacerbation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Identifying predictive gene expression signatures warrants further investigation.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00109-026-02662-0","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:02:53Z","timestamp":1775001773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neutrophil-related gene expression profile is associated with future paediatric bronchiectasis exacerbations"],"prefix":"10.1007","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4241-8697","authenticated-orcid":false,"given":"Hannah E.","family":"O\u2019Farrell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Goyal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne B.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Grimwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie T.","family":"Yerkovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Baines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"issue":"10150","key":"2662_CR1","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/S0140-6736(18)31554-X","volume":"392","author":"AB Chang","year":"2018","unstructured":"Chang AB, Bush A, Grimwood K (2018) Bronchiectasis in children: diagnosis and treatment. Lancet 392(10150):866\u2013879","journal-title":"Lancet"},{"issue":"4","key":"2662_CR2","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/resp.14479","volume":"28","author":"AB Chang","year":"2023","unstructured":"Chang AB, Bell SC, Byrnes CA, Dawkins P, Holland AE, Kennedy E et al (2023) Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand. Respirology 28(4):339\u2013349","journal-title":"Respirology"},{"issue":"4","key":"2662_CR3","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1016\/j.chest.2018.02.024","volume":"154","author":"MA Martinez-Garcia","year":"2018","unstructured":"Martinez-Garcia MA, Polverino E, Aksamit T (2018) Bronchiectasis and chronic airway disease: it is not just about asthma and COPD. Chest 154(4):737\u2013739","journal-title":"Chest"},{"issue":"8","key":"2662_CR4","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1111\/resp.13280","volume":"23","author":"SR Blackall","year":"2018","unstructured":"Blackall SR, Hong JB, King P, Wong C, Einsiedel L, R\u00e9mond MGW et al (2018) Bronchiectasis in indigenous and non-indigenous residents of Australia and New Zealand. Respirology 23(8):743\u2013749","journal-title":"Respirology"},{"issue":"6","key":"2662_CR5","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.chest.2023.06.040","volume":"164","author":"JM Roberts","year":"2023","unstructured":"Roberts JM, Goyal V, Kularatna S, Chang AB, Kapur N, Chalmers JD et al (2023) The economic burden of bronchiectasis: a systematic review. Chest 164(6):1396\u20131421","journal-title":"Chest"},{"key":"2662_CR6","doi-asserted-by":"crossref","unstructured":"Roberts JM, Newcombe PA, Goyal V, Kularatna S, McPhail SM, Chang AB, et al. Development and validation of a parent proxy bronchiectasis child quality of life instrument: The BC-QoL. ERJ Open Res. 2026:01443\u20132025.","DOI":"10.1183\/23120541.01443-2025"},{"issue":"1","key":"2662_CR7","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-018-0042-3","volume":"4","author":"JD Chalmers","year":"2018","unstructured":"Chalmers JD, Chang AB, Chotirmall SH, Dhar R, McShane PJ (2018) Bronchiectasis. Nat Rev Dis Primers 4(1):45","journal-title":"Nat Rev Dis Primers"},{"issue":"6","key":"2662_CR8","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.arbres.2024.03.003","volume":"60","author":"AB Chang","year":"2024","unstructured":"Chang AB, Dharmage SC, Marchant JM, McCallum GB, Morris PS, Schultz A et al (2024) Improving the diagnosis and treatment of paediatric bronchiectasis through research and translation. Arch Bronconeumol 60(6):364\u2013373","journal-title":"Arch Bronconeumol"},{"issue":"154","key":"2662_CR9","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0055-2019","volume":"28","author":"F Amati","year":"2019","unstructured":"Amati F, Simonetta E, Gramegna A, Tarsia P, Contarini M, Blasi F et al (2019) The biology of pulmonary exacerbations in bronchiectasis. European respiratory review\u202f: an official journal of the European Respiratory Society 28(154):190055","journal-title":"European respiratory review : an official journal of the European Respiratory Society"},{"issue":"1","key":"2662_CR10","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1378\/chest.09-2932","volume":"138","author":"N Kapur","year":"2010","unstructured":"Kapur N, Masters IB, Chang AB (2010) Longitudinal growth and lung function in pediatric non-cystic fibrosis bronchiectasis: what influences lung function stability? Chest 138(1):158\u2013164","journal-title":"Chest"},{"issue":"12","key":"2662_CR11","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1111\/resp.13828","volume":"25","author":"V Goyal","year":"2020","unstructured":"Goyal V, McPhail SM, Hurley F, Grimwood K, Marchant JM, Masters IB et al (2020) Cost of hospitalization for bronchiectasis exacerbation in children. Respirology 25(12):1250\u20131256","journal-title":"Respirology"},{"issue":"3","key":"2662_CR12","volume":"7","author":"AB Chang","year":"2021","unstructured":"Chang AB, Boyd J, Bell L, Goyal V, Masters IB, Powell Z et al (2021) Clinical and research priorities for children and young people with bronchiectasis: an international roadmap. ERJ Open Res 7(3):00122-2021","journal-title":"ERJ Open Res"},{"issue":"173","key":"2662_CR13","doi-asserted-by":"crossref","DOI":"10.1183\/16000617.0085-2024","volume":"33","author":"A De Angelis","year":"2024","unstructured":"De Angelis A, Johnson ED, Sutharsan S, Aliberti S (2024) Exacerbations of bronchiectasis. Eur Respir Rev 33(173):240085","journal-title":"Eur Respir Rev"},{"issue":"2","key":"2662_CR14","volume":"58","author":"YH Giam","year":"2021","unstructured":"Giam YH, Shoemark A, Chalmers JD (2021) Neutrophil dysfunction in bronchiectasis: an emerging role for immunometabolism. Eur Respir J 58(2):2003157","journal-title":"Eur Respir J"},{"issue":"4","key":"2662_CR15","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1002\/ppul.23952","volume":"53","author":"JJV de Vries","year":"2018","unstructured":"de Vries JJV, Chang AB, Marchant JM (2018) Comparison of bronchoscopy and bronchoalveolar lavage findings in three types of suppurative lung disease. Pediatr Pulmonol 53(4):467\u2013474","journal-title":"Pediatr Pulmonol"},{"issue":"6","key":"2662_CR16","doi-asserted-by":"crossref","first-page":"1900303","DOI":"10.1183\/13993003.00303-2019","volume":"53","author":"A Shoemark","year":"2019","unstructured":"Shoemark A, Cant E, Carreto L, Smith A, Oriano M, Keir HR et al (2019) A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation. Eur Respir J 53(6):1900303","journal-title":"Eur Respir J"},{"key":"2662_CR17","doi-asserted-by":"crossref","first-page":"541","DOI":"10.2147\/COPD.S119443","volume":"12","author":"KJ Baines","year":"2017","unstructured":"Baines KJ, Fu JJ, McDonald VM, Gibson PG (2017) Airway gene expression of IL-1 pathway mediators predicts exacerbation risk in obstructive airway disease. Int J Chron Obstruct Pulmon Dis 12:541\u2013550","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"issue":"1","key":"2662_CR18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jaci.2018.12.1020","volume":"144","author":"M Fricker","year":"2019","unstructured":"Fricker M, Gibson PG, Powell H, Simpson JL, Yang IA, Upham JW et al (2019) A sputum 6-gene signature predicts future exacerbations of poorly controlled asthma. J Allergy Clin Immunol 144(1):51-60.e11","journal-title":"J Allergy Clin Immunol"},{"issue":"9","key":"2662_CR19","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/S2213-2600(19)30254-1","volume":"7","author":"V Goyal","year":"2019","unstructured":"Goyal V, Grimwood K, Ware RS, Byrnes CA, Morris PS, Masters IB et al (2019) Efficacy of oral amoxicillin-clavulanate or azithromycin for non-severe respiratory exacerbations in children with bronchiectasis (BEST-1): a multicentre, three-arm, double-blind, randomised placebo-controlled trial. Lancet Respir Med 7(9):791\u2013801","journal-title":"Lancet Respir Med"},{"issue":"10154","key":"2662_CR20","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/S0140-6736(18)31723-9","volume":"392","author":"V Goyal","year":"2018","unstructured":"Goyal V, Grimwood K, Byrnes CA, Morris PS, Masters IB, Ware RS et al (2018) Amoxicillin-clavulanate versus azithromycin for respiratory exacerbations in children with bronchiectasis (BEST-2): a multicentre, double-blind, non-inferiority, randomised controlled trial. Lancet (London, England) 392(10154):1197\u20131206","journal-title":"Lancet (London, England)"},{"issue":"6","key":"2662_CR21","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","volume":"3","author":"TD Schmittgen","year":"2008","unstructured":"Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3(6):1101\u20131108","journal-title":"Nat Protoc"},{"issue":"1","key":"2662_CR22","volume":"21","author":"JG Roy","year":"2020","unstructured":"Roy JG, McElhaney JE, Verschoor CP (2020) Reliable reference genes for the quantification of mRNA in human T-cells and PBMCs stimulated with live influenza virus. BMC Immunol 21(1):4","journal-title":"BMC Immunol"},{"issue":"1","key":"2662_CR23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/sji.12391","volume":"83","author":"DB Oturai","year":"2016","unstructured":"Oturai DB, Sondergaard HB, Bornsen L, Sellebjerg F, Christensen JR (2016) Identification of suitable reference genes for peripheral blood mononuclear cell subset studies in multiple sclerosis. Scand J Immunol 83(1):72\u201380","journal-title":"Scand J Immunol"},{"issue":"3","key":"2662_CR24","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.3892\/ijmm.2020.4661","volume":"46","author":"Z Shao","year":"2020","unstructured":"Shao Z, Wang K, Zhang S, Yuan J, Liao X, Wu C et al (2020) Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene-edited cardiomyocytes. Int J Mol Med 46(3):1225\u20131238","journal-title":"Int J Mol Med"},{"issue":"4","key":"2662_CR25","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1093\/bioinformatics\/btt703","volume":"30","author":"A Kr\u00e4mer","year":"2013","unstructured":"Kr\u00e4mer A, Green J, Pollard J Jr, Tugendreich S (2013) Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30(4):523\u2013530","journal-title":"Bioinformatics"},{"issue":"4","key":"2662_CR26","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1378\/chest.11-0679","volume":"141","author":"N Kapur","year":"2012","unstructured":"Kapur N, Masters IB, Newcombe P, Chang AB (2012) The burden of disease in pediatric non-cystic fibrosis bronchiectasis. Chest 141(4):1018\u20131024","journal-title":"Chest"},{"issue":"3","key":"2662_CR27","first-page":"00122","volume":"7","author":"AB Chang","year":"2021","unstructured":"Chang AB, Boyd J, Bell L, Goyal V, Masters IB, Powell Z et al (2021) Clinical and research priorities for children and young people with bronchiectasis: an international roadmap. ERJ Open Res 7(3):00122\u201302021","journal-title":"ERJ Open Res"},{"issue":"1","key":"2662_CR28","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1164\/rccm.202402-0411OC","volume":"210","author":"DR Mills","year":"2024","unstructured":"Mills DR, Masters IB, Yerkovich ST, McEniery J, Kapur N, Chang AB et al (2024) Radiographic outcomes in pediatric bronchiectasis and factors associated with reversibility. Am J Respir Crit Care Med 210(1):97\u2013107","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"2662_CR29","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1183\/09031936.00027409","volume":"35","author":"KJ Baines","year":"2010","unstructured":"Baines KJ, Simpson JL, Bowden NA, Scott RJ, Gibson PG (2010) Differential gene expression and cytokine production from neutrophils in asthma phenotypes. Eur Respir J 35(3):522\u2013531","journal-title":"Eur Respir J"},{"issue":"1","key":"2662_CR30","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1164\/rccm.202310-1729OC","volume":"210","author":"Y Gao","year":"2024","unstructured":"Gao Y, Richardson H, Dicker AJ, Barton A, Kuzmanova E, Shteinberg M et al (2024) Endotypes of exacerbation in bronchiectasis: an observational cohort study. Am J Respir Crit Care Med 210(1):77\u201386","journal-title":"Am J Respir Crit Care Med"},{"key":"2662_CR31","volume":"42","author":"JD Chalmers","year":"2013","unstructured":"Chalmers JD, Ma A, Turnbull K, Doherty C, Govan JRW, Hill AT (2013) Impaired neutrophil phagocytosis and receptor expression in non-CF bronchiectasis. Eur Respir J 42:2065","journal-title":"Eur Respir J"},{"issue":"2","key":"2662_CR32","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1164\/rccm.200808-1250OC","volume":"180","author":"S Voglis","year":"2009","unstructured":"Voglis S, Quinn K, Tullis E, Liu M, Henriques M, Zubrinich C et al (2009) Human neutrophil peptides and phagocytic deficiency in bronchiectatic lungs. Am J Respir Crit Care Med 180(2):159\u2013166","journal-title":"Am J Respir Crit Care Med"},{"issue":"7","key":"2662_CR33","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1164\/rccm.201712-2423OC","volume":"198","author":"P Bedi","year":"2018","unstructured":"Bedi P, Davidson DJ, McHugh BJ, Rossi AG, Hill AT (2018) Blood neutrophils are reprogrammed in bronchiectasis. Am J Respir Crit Care Med 198(7):880\u2013890","journal-title":"Am J Respir Crit Care Med"},{"issue":"10150","key":"2662_CR34","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/S0140-6736(18)31767-7","volume":"392","author":"PA Flume","year":"2018","unstructured":"Flume PA, Chalmers JD, Olivier KN (2018) Advances in bronchiectasis: endotyping, genetics, microbiome, and disease heterogeneity. Lancet (London, England) 392(10150):880\u2013890","journal-title":"Lancet (London, England)"},{"key":"2662_CR35","doi-asserted-by":"crossref","unstructured":"Le Cabec V, Maridonneau-Parini I. Annexin 3 is associated with cytoplasmic granules in neutrophils and monocytes and translocates to the plasma membrane in activated cells. Biochem J. 1994;303 ( Pt 2)(Pt 2):481\u20137.","DOI":"10.1042\/bj3030481"},{"issue":"4","key":"2662_CR36","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1111\/imm.13239","volume":"161","author":"M Toufiq","year":"2020","unstructured":"Toufiq M, Roelands J, Alfaki M, Syed Ahamed Kabeer B, Saadaoui M, Lakshmanan AP et al (2020) Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data. Immunology 161(4):291\u2013302","journal-title":"Immunology"},{"issue":"5","key":"2662_CR37","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1172\/JCI0213572","volume":"109","author":"RW Vandivier","year":"2002","unstructured":"Vandivier RW, Fadok VA, Hoffmann PR, Bratton DL, Penvari C, Brown KK et al (2002) Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest 109(5):661\u2013670","journal-title":"J Clin Invest"},{"issue":"5","key":"2662_CR38","doi-asserted-by":"crossref","first-page":"L947","DOI":"10.1152\/ajplung.2001.280.5.L947","volume":"280","author":"H Zhang","year":"2001","unstructured":"Zhang H, Porro G, Orzech N, Mullen B, Liu M, Slutsky AS (2001) Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose-related fashion. Am J Physiol-Lung Cell Mol Physiol 280(5):L947\u2013L954","journal-title":"Am J Physiol-Lung Cell Mol Physiol"},{"issue":"4","key":"2662_CR39","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1378\/chest.14-0131","volume":"146","author":"KJ Baines","year":"2014","unstructured":"Baines KJ, Upham JW, Yerkovich ST, Chang AB, Marchant JM, Carroll M et al (2014) Mediators of neutrophil function in children with protracted bacterial bronchitis. Chest 146(4):1013\u20131020","journal-title":"Chest"},{"key":"2662_CR40","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.lfs.2016.06.005","volume":"157","author":"H Li","year":"2016","unstructured":"Li H, Zhao Y, Li W, Yang J, Wu H (2016) Critical role of neutrophil alkaline phosphatase in the antimicrobial function of neutrophils. Life Sci 157:152\u2013157","journal-title":"Life Sci"},{"issue":"7","key":"2662_CR41","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.bbamcr.2006.05.005","volume":"1763","author":"RS Ajioka","year":"2006","unstructured":"Ajioka RS, Phillips JD, Kushner JP (2006) Biosynthesis of heme in mammals. Biochim Biophys Acta 1763(7):723\u2013736","journal-title":"Biochim Biophys Acta"},{"issue":"1","key":"2662_CR42","doi-asserted-by":"crossref","DOI":"10.3390\/ph12010005","volume":"12","author":"J Neves","year":"2019","unstructured":"Neves J, Haider T, Gassmann M, Muckenthaler MU (2019) Iron homeostasis in the lungs-a balance between health and disease. Pharmaceuticals (Basel) 12(1):5","journal-title":"Pharmaceuticals (Basel)"},{"key":"2662_CR43","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.3389\/fimmu.2017.01620","volume":"8","author":"G Quintela-Carvalho","year":"2017","unstructured":"Quintela-Carvalho G, Luz NF, Celes FS, Zanette DL, Andrade D, Menezes D et al (2017) Heme drives oxidative stress-associated cell death in human neutrophils infected with Leishmania infantum. Front Immunol 8:1620","journal-title":"Front Immunol"},{"issue":"1","key":"2662_CR44","volume":"22","author":"X Zhang","year":"2022","unstructured":"Zhang X, Wu Z, Ma K (2022) SNCA correlates with immune infiltration and serves as a prognostic biomarker in lung adenocarcinoma. BMC Cancer 22(1):406","journal-title":"BMC Cancer"},{"issue":"2","key":"2662_CR45","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1152\/physrev.00012.2017","volume":"98","author":"L Negri","year":"2018","unstructured":"Negri L, Ferrara N (2018) The prokineticins: neuromodulators and mediators of inflammation and myeloid cell-dependent angiogenesis. Physiol Rev 98(2):1055\u20131082","journal-title":"Physiol Rev"},{"issue":"1","key":"2662_CR46","volume":"13","author":"K Wang","year":"2022","unstructured":"Wang K, Wang M, Liao X, Gao S, Hua J, Wu X et al (2022) Locally organised and activated Fth1(hi) neutrophils aggravate inflammation of acute lung injury in an IL-10-dependent manner. Nat Commun 13(1):7703","journal-title":"Nat Commun"},{"issue":"4","key":"2662_CR47","volume":"2","author":"C Margaroli","year":"2021","unstructured":"Margaroli C, Moncada-Giraldo D, Gulick DA, Dobosh B, Giacalone VD, Forrest OA et al (2021) Transcriptional firing represses bactericidal activity in cystic fibrosis airway neutrophils. Cell Rep Med 2(4):100239","journal-title":"Cell Rep Med"},{"issue":"1","key":"2662_CR48","volume":"9","author":"S Zhao","year":"2014","unstructured":"Zhao S, Fung-Leung WP, Bittner A, Ngo K, Liu X (2014) Comparison of RNA-seq and microarray in transcriptome profiling of activated T cells. PLoS One 9(1):e78644","journal-title":"PLoS One"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-026-02662-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-026-02662-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-026-02662-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T01:29:40Z","timestamp":1775006980000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-026-02662-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["2662"],"URL":"https:\/\/doi.org\/10.1007\/s00109-026-02662-0","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"assertion":[{"value":"2 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All parents\/guardians provided written informed consent to participate in the BEST studies and consented to the storage of samples for future research use.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical trial number"}}],"article-number":"59"}}