{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:31:51Z","timestamp":1790937111357,"version":"4.1.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Tuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Concentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>HIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201110-1769oc","type":"journal-article","created":{"date-parts":[[2012,2,17]],"date-time":"2012-02-17T00:51:46Z","timestamp":1329439906000},"page":"989-997","source":"Crossref","is-referenced-by-count":132,"title":["Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases"],"prefix":"10.1093","volume":"185","author":[{"given":"Naomi F.","family":"Walker","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunity"},{"name":"Wellcome Trust Centre for Clinical Tropical Medicine"},{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon O.","family":"Clark","sequence":"additional","affiliation":[{"name":"Health Protection Agency, Porton Down, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tolu","family":"Oni","sequence":"additional","affiliation":[{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Division of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Andreu","sequence":"additional","affiliation":[{"name":"Division of Microbiology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liku","family":"Tezera","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Singh","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u00edsa","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic L.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Health Protection Agency, Porton Down, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A.","family":"Tree","sequence":"additional","affiliation":[{"name":"Health Protection Agency, Porton Down, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanine M.","family":"D'Armiento","sequence":"additional","affiliation":[{"name":"Department of Medicine, Columbia University, New York, New York; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Meintjes","sequence":"additional","affiliation":[{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Division of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco A.","family":"Mauri","sequence":"additional","affiliation":[{"name":"Division of Histopathology, Imperial College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Williams","sequence":"additional","affiliation":[{"name":"Health Protection Agency, Porton Down, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Clinical Tropical Medicine"},{"name":"Clinical Infectious Diseases Research Initiative, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa"},{"name":"Division of Medicine"},{"name":"Medical Research Council National Institute for Medical Research, Mill Hill, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon S.","family":"Friedland","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity"},{"name":"Wellcome Trust Centre for Clinical Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Elkington","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity"},{"name":"Wellcome Trust Centre for Clinical Tropical Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,5,1]]},"reference":[{"key":"2026032101163056700_bib1","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1126\/science.1185449","article-title":"The population dynamics and control of tuberculosis","volume":"328","author":"Dye","year":"2010","journal-title":"Science"},{"key":"2026032101163056700_bib2","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1136\/bmj.325.7375.1282","article-title":"Current medical treatment for tuberculosis","volume":"325","author":"Chan","year":"2002","journal-title":"BMJ"},{"key":"2026032101163056700_bib3","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1016\/S0140-6736(09)60331-7","article-title":"Epidemiology of anti-tuberculosis drug resistance 2002\u201307: an updated analysis of the global project on anti-tuberculosis drug resistance surveillance","volume":"373","author":"Wright","year":"2009","journal-title":"Lancet"},{"key":"2026032101163056700_bib4","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1164\/rccm.200911-1768OC","article-title":"Development of extensively drug-resistant tuberculosis during multidrug-resistant tuberculosis treatment","volume":"182","author":"Shin","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101163056700_bib5","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1164\/rccm.200907-0989OC","article-title":"HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality","volume":"181","author":"Gandhi","year":"2010","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101163056700_bib6","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1164\/rccm.201102-0325UP","article-title":"Update in tuberculosis and nontuberculous mycobacterial disease 2010","volume":"184","author":"Yew","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101163056700_bib7","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1146\/annurev.immunol.021908.132703","article-title":"Cell-mediated immune responses in tuberculosis","volume":"27","author":"Cooper","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"2026032101163056700_bib8","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1164\/rccm.201008-1246CI","article-title":"Novel developments in the epidemic of human immunodeficiency virus and tuberculosis coinfection","volume":"183","author":"Anandaiah","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101163056700_bib9","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/S0140-6736(03)14333-4","article-title":"Tuberculosis","volume":"362","author":"Frieden","year":"2003","journal-title":"Lancet"},{"key":"2026032101163056700_bib10","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1164\/rccm.201006-0963PP","article-title":"Human lung immunity against mycobacterium tuberculosis: insights into pathogenesis and protection","volume":"183","author":"Schwander","year":"2011","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101163056700_bib11","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1128\/CMR.00042-10","article-title":"HIV and tuberculosis: a deadly human syndemic","volume":"24","author":"Kwan","year":"2011","journal-title":"Clin Microbiol Rev"},{"key":"2026032101163056700_bib12","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.3001847","article-title":"Tuberculosis immunopathology: the neglected role of extracellular matrix destruction","volume":"3","author":"Elkington","year":"2011","journal-title":"Sci Transl Med"},{"key":"2026032101163056700_bib13","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1164\/rccm.200505-753OC","article-title":"Mycobacterium tuberculosis, but not vaccine BCG, specifically upregulates matrix metalloproteinase-1","volume":"172","author":"Elkington","year":"2005","journal-title":"Am J Respir Crit Care Med"},{"key":"2026032101163056700_bib14","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1172\/JCI45666","article-title":"MMP-1 drives immunopathology in human tuberculosis and transgenic mice","volume":"121","author":"Elkington","year":"2011","journal-title":"J Clin Invest"},{"key":"2026032101163056700_bib15","doi-asserted-by":"crossref","first-page":"5865","DOI":"10.4049\/jimmunol.0801935","article-title":"Matrix metalloproteinase-1 is regulated in tuberculosis by a p38 MAPK-dependent, p-aminosalicylic acid-sensitive signaling cascade","volume":"182","author":"Rand","year":"2009","journal-title":"J Immunol"},{"key":"2026032101163056700_bib16","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1126\/science.1179663","article-title":"Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium","volume":"327","author":"Volkman","year":"2010","journal-title":"Science"},{"key":"2026032101163056700_bib17","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1172\/JCI57423","article-title":"MMPs in tuberculosis: granuloma creators and tissue destroyers","volume":"121","author":"Salgame","year":"2011","journal-title":"J Clin Invest"},{"key":"2026032101163056700_bib18","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/nrm763","article-title":"Matrix metalloproteinases: a tail of a frog that became a prince","volume":"3","author":"Brinckerhoff","year":"2002","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026032101163056700_bib19","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1034\/j.1600-051x.2001.028002146.x","article-title":"Adjunctive treatment with sub-antimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis","volume":"28","author":"Golub","year":"2001","journal-title":"J Clin Periodontol"},{"key":"2026032101163056700_bib20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jim.2005.11.010","article-title":"Filter sterilization of highly infectious samples to prevent false negative analysis of matrix metalloproteinase activity","volume":"309","author":"Elkington","year":"2006","journal-title":"J Immunol Methods"},{"key":"2026032101163056700_bib21","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1080\/00365540701509899","article-title":"Clinical presentation of adults with pulmonary tuberculosis with and without HIV infection in Nigeria","volume":"40","author":"Lawson","year":"2008","journal-title":"Scand J Infect Dis"},{"key":"2026032101163056700_bib22","doi-asserted-by":"crossref","first-page":"5333","DOI":"10.4049\/jimmunol.175.8.5333","article-title":"Mycobacterium tuberculosis up-regulates matrix metalloproteinase-1 secretion from human airway epithelial cells via a p38 MAPK switch","volume":"175","author":"Elkington","year":"2005","journal-title":"J Immunol"},{"key":"2026032101163056700_bib23","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0378-1135(00)00378-3","article-title":"A guinea pig model of low-dose Mycobacterium bovis aerogenic infection","volume":"80","author":"Chambers","year":"2001","journal-title":"Vet Microbiol"},{"key":"2026032101163056700_bib24","first-page":"574","article-title":"Chronic cough and its association with TB-HIV co-infection: factors affecting help-seeking behaviour in Harare, Zimbabwe","volume":"15","author":"Mavhu","year":"2010","journal-title":"Trop Med Int Health"},{"key":"2026032101163056700_bib25","doi-asserted-by":"crossref","first-page":"289","DOI":"10.2174\/156802606776287045","article-title":"Matrix metalloproteinase inhibitors as prospective agents for the prevention and treatment of cardiovascular and neoplastic diseases","volume":"6","author":"Sang","year":"2006","journal-title":"Curr Top Med Chem"},{"key":"2026032101163056700_bib26","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1165\/rcmb.2007-0011OC","article-title":"Synergistic up-regulation of epithelial cell matrix metalloproteinase-9 secretion in tuberculosis","volume":"37","author":"Elkington","year":"2007","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026032101163056700_bib27","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/jac\/dkr472","article-title":"Rapid measurement of antituberculosis drug activity in vitro and in macrophages using bioluminescence","volume":"67","author":"Andreu","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"2026032101163056700_bib28","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/nri1418","article-title":"Matrix metalloproteinases as modulators of inflammation and innate immunity","volume":"4","author":"Parks","year":"2004","journal-title":"Nat Rev Immunol"},{"key":"2026032101163056700_bib29","doi-asserted-by":"crossref","first-page":"e8881","DOI":"10.1371\/journal.pone.0008881","article-title":"Joint effect of MCP-1 genotype GG and MMP-1 genotype 2G\/2G increases the likelihood of developing pulmonary tuberculosis in BCG-vaccinated individuals","volume":"5","author":"Ganachari","year":"2010","journal-title":"PLoS ONE"},{"key":"2026032101163056700_bib30","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1600-051X.2008.01351.x","article-title":"Systemic MMP inhibition for periodontal wound repair: results of a multi-centre randomized-controlled clinical trial","volume":"36","author":"Gapski","year":"2009","journal-title":"J Clin Periodontol"},{"key":"2026032101163056700_bib31","doi-asserted-by":"crossref","first-page":"685","DOI":"10.2353\/ajpath.2009.081073","article-title":"Doxycycline treatment decreases morbidity and mortality of murine neurocysticercosis: evidence for reduction of apoptosis and matrix metalloproteinase activity","volume":"175","author":"Alvarez","year":"2009","journal-title":"Am J Pathol"},{"key":"2026032101163056700_bib32","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1128\/IAI.01949-05","article-title":"Doxycycline reduces mortality and injury to the brain and cochlea in experimental pneumococcal meningitis","volume":"74","author":"Meli","year":"2006","journal-title":"Infect Immun"},{"key":"2026032101163056700_bib33","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1128\/AAC.47.11.3630-3633.2003","article-title":"Doxycycline is anti-inflammatory and inhibits staphylococcal exotoxin-induced cytokines and chemokines","volume":"47","author":"Krakauer","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"2026032101163056700_bib34","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1161\/CIRCULATIONAHA.108.806505","article-title":"Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm: doxycycline selectively depletes aortic wall neutrophils and cytotoxic T cells","volume":"119","author":"Lindeman","year":"2009","journal-title":"Circulation"},{"key":"2026032101163056700_bib35","doi-asserted-by":"crossref","first-page":"6492","DOI":"10.4049\/jimmunol.0903811","article-title":"Mycobacterium tuberculosis upregulates microglial matrix metalloproteinase-1 and -3 expression and secretion via NF-kB and activator protein-1-dependent monocyte networks","volume":"184","author":"Green","year":"2010","journal-title":"J Immunol"},{"key":"2026032101163056700_bib36","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1086\/444545","article-title":"Lung remodeling in pulmonary tuberculosis","volume":"192","author":"Dheda","year":"2005","journal-title":"J Infect Dis"},{"key":"2026032101163056700_bib37","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.tube.2004.07.001","article-title":"A matrix metalloproteinase inhibitor promotes granuloma formation during the early phase of Mycobacterium tuberculosis pulmonary infection","volume":"84","author":"Izzo","year":"2004","journal-title":"Tuberculosis (Edinb)"},{"key":"2026032101163056700_bib38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1046\/j.1365-2613.2000.00152.x","article-title":"Treatment with BB-94, a broad spectrum inhibitor of zinc-dependent metalloproteinases, causes deviation of the cytokine profile towards type-2 in experimental pulmonary tuberculosis in Balb\/c mice","volume":"81","author":"Hernandez-Pando","year":"2000","journal-title":"Int J Exp Pathol"},{"key":"2026032101163056700_bib39","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1146\/annurev.immunol.22.012703.104635","article-title":"Immunity to tuberculosis","volume":"22","author":"North","year":"2004","journal-title":"Annu Rev Immunol"},{"key":"2026032101163056700_bib40","doi-asserted-by":"crossref","first-page":"10253","DOI":"10.1074\/jbc.M007674200","article-title":"Identification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation","volume":"276","author":"Balbin","year":"2001","journal-title":"J Biol Chem"},{"key":"2026032101163056700_bib41","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.tube.2005.09.001","article-title":"Animal models of cavitation in pulmonary tuberculosis","volume":"86","author":"Helke","year":"2006","journal-title":"Tuberculosis (Edinb)"},{"key":"2026032101163056700_bib42","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/emmm.201000079","article-title":"Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism","volume":"2","author":"Kim","year":"2010","journal-title":"EMBO Mol Med"},{"key":"2026032101163056700_bib43","doi-asserted-by":"crossref","first-page":"e12266","DOI":"10.1371\/journal.pone.0012266","article-title":"Transcriptional reprogramming in nonhuman primate (rhesus macaque) tuberculosis granulomas","volume":"5","author":"Mehra","year":"2010","journal-title":"PLoS ONE"},{"key":"2026032101163056700_bib44","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1128\/IAI.01132-08","article-title":"Extrapulmonary dissemination of Mycobacterium bovis but not Mycobacterium tuberculosis in a bronchoscopic rabbit model of cavitary tuberculosis","volume":"77","author":"Nedeltchev","year":"2009","journal-title":"Infect Immun"},{"key":"2026032101163056700_bib45","first-page":"84","article-title":"Antimycobacterial drugs","volume":"9","author":"Heifets","year":"1994","journal-title":"Semin Respir Infect"},{"key":"2026032101163056700_bib46","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1128\/AAC.41.5.1004","article-title":"Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium","volume":"41","author":"Collins","year":"1997","journal-title":"Antimicrob Agents Chemother"},{"key":"2026032101163056700_bib47","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tube.2009.07.002","article-title":"New anti-tuberculosis agents amongst known drugs","volume":"89","author":"Lougheed","year":"2009","journal-title":"Tuberculosis (Edinb)"},{"key":"2026032101163056700_bib48","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/s10096-004-1268-4","article-title":"Multidrug-resistant tuberculosis in Russia: clinical characteristics, analysis of second-line drug resistance and development of standardized therapy","volume":"24","author":"Balabanova","year":"2005","journal-title":"Eur J Clin Microbiol Infect Dis"},{"key":"2026032101163056700_bib49","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/jac\/4.6.509","article-title":"The absorption and sputum penetration of doxycycline","volume":"4","author":"MacArthur","year":"1978","journal-title":"J Antimicrob Chemother"}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/185\/9\/989\/67293189\/ajrccm_185_9_989.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/185\/9\/989\/67293189\/ajrccm_185_9_989.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:16:44Z","timestamp":1774070204000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/185\/9\/989\/8508264"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,1]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2012,5,1]]},"published-print":{"date-parts":[[2012,5,1]]}},"URL":"https:\/\/doi.org\/10.1164\/rccm.201110-1769oc","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2012,5]]},"published":{"date-parts":[[2012,5,1]]}}}