{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:59:05Z","timestamp":1787061545792,"version":"build-2736575974"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T00:00:00Z","timestamp":1680134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100003442","name":"Stony Wold-Herbert Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute chest syndrome (ACS) is an acute complication in SCD but its effects on lung function are not well understood. Inflammation is a key component of SCD pathophysiology but with an unclear association with lung function. We hypothesized that children with ACS had worse lung function than children without ACS and aimed to investigate the association of lung function deficits with inflammatory cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients enrolled in a previous 2-year randomized clinical trial who had consented to future data use, were enrolled for the present exploratory study. Patients were categorized into ACS and non-ACS groups. Demographic and clinical information were collected. Serum samples were used for quantification of serum cytokines and leukotriene B4 levels and pulmonary function tests (PFTs) were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Children with ACS had lower total lung capacity (TLC) at baseline and at 2 years, with a significant decline in forced expiratory volume in 1 sec (FEV1) and mid-maximal expiratory flow rate (FEF25-75%) in the 2 year period (p = 0.015 and p = 0.039 respectively). For children with ACS, serum cytokines IL-5, and IL-13 were higher at baseline and at 2 years compared to children with no ACS. IP-10 and IL-6 were negatively correlated with PFT markers. In multivariable regression using generalized estimating equation approach for factors predicting lung function, age was significantly associated FEV1 (p = 0.047) and ratio of FEV1 and forced vital capacity (FVC)- FEV1\/FVC ratio (p = 0.006); males had lower FEV1\/FVC (p = 0.035) and higher TLC (p = 0.031). Asthma status was associated with FEV1 (p = 0.017) and FVC (p = 0.022); history of ACS was significantly associated with TLC (p = 0.027).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pulmonary function abnormalities were more common and inflammatory markers were elevated in patients with ACS, compared with those without ACS. These findings suggest airway inflammation is present in children with SCD and ACS, which could be contributing to impaired pulmonary function.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0283349","type":"journal-article","created":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T13:38:03Z","timestamp":1680183483000},"page":"e0283349","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Acute chest syndrome, airway inflammation and lung function in sickle cell disease"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6995-5823","authenticated-orcid":true,"given":"Aliva","family":"De","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanford","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhezhen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Brittenham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meyer","family":"Kattan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Lovinsky-Desir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret T.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,3,30]]},"reference":[{"issue":"16","key":"pone.0283349.ref001","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle Cell Disease","volume":"376","author":"FB Piel","year":"2017","journal-title":"N Engl J Med"},{"issue":"24","key":"pone.0283349.ref002","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1182\/blood-2013-05-498311","article-title":"Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies","volume":"122","author":"D Manwani","year":"2013","journal-title":"Blood"},{"issue":"1\u20132","key":"pone.0283349.ref003","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.tracli.2008.03.011","article-title":"Adhesion of sickle red cells to endothelium: myths and future directions.","volume":"15","author":"RP Hebbel","year":"2008","journal-title":"Transfus Clin Biol J Soc Francaise Transfus Sang"},{"issue":"10","key":"pone.0283349.ref004","doi-asserted-by":"crossref","first-page":"4440","DOI":"10.1182\/blood.V87.10.4440.bloodjournal87104440","article-title":"Sickle erythrocytes adhere to polymorphonuclear neutrophils and activate the neutrophil respiratory burst","volume":"87","author":"TC Hofstra","year":"1996","journal-title":"Blood"},{"key":"pone.0283349.ref005","article-title":"Neutrophils, platelets, and inflammatory pathways, at the nexus of sickle cell disease pathophysiology","author":"D Zhang","year":"2016","journal-title":"Blood"},{"issue":"2","key":"pone.0283349.ref006","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/00062752-200203000-00003","article-title":"Sickle cell vaso-occlusion: multistep and multicellular paradigm.","volume":"9","author":"PS Frenette","year":"2002","journal-title":"Curr Opin Hematol"},{"issue":"11","key":"pone.0283349.ref007","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.1164\/rccm.201111-2082CI","article-title":"Pulmonary complications of sickle cell disease","volume":"185","author":"AC Miller","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"issue":"23","key":"pone.0283349.ref008","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM199406093302303","article-title":"Mortality in sickle cell disease. 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