Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia
Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus to...
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creator | Kaspy, Kimberley R. Dell, Sharon D. Davis, Stephanie D. Ferkol, Thomas W. Rosenfeld, Margaret Sagel, Scott D. Milla, Carlos Olivier, Kenneth N. Barber, Andrew T. Wee, Wallace Lin, Feng-Chang Li, Lang Rampakakis, Emmanouil Zariwala, Maimoona A. Knowles, Michael R. Leigh, Margaret W. Shapiro, Adam J. |
description | Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]).
Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT?
This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression.
In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA.
Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both.
ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www.clinicaltrials.gov. |
doi_str_mv | 10.1016/j.chest.2023.12.005 |
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Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT?
This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression.
In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA.
Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both.
ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www.clinicaltrials.gov.</description><identifier>ISSN: 0012-3692</identifier><identifier>ISSN: 1931-3543</identifier><identifier>EISSN: 1931-3543</identifier><identifier>DOI: 10.1016/j.chest.2023.12.005</identifier><identifier>PMID: 38072392</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>heterotaxy ; Kartagener syndrome ; primary ciliary dyskinesia ; situs ambiguus</subject><ispartof>Chest, 2024-05, Vol.165 (5), p.1070-1081</ispartof><rights>2023 American College of Chest Physicians</rights><rights>Copyright © 2023. Published by Elsevier Inc.</rights><rights>Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c309t-8b712189ba13efe07573fb64d4c45015a5f6c09bfe92eaf9120d6dbd314864be3</cites><orcidid>0000-0003-4291-3513 ; 0000-0001-8200-255X ; 0000-0001-6066-6750 ; 0000-0002-3516-8124 ; 0000-0002-6479-5952 ; 0000-0002-7427-8246</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38072392$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaspy, Kimberley R.</creatorcontrib><creatorcontrib>Dell, Sharon D.</creatorcontrib><creatorcontrib>Davis, Stephanie D.</creatorcontrib><creatorcontrib>Ferkol, Thomas W.</creatorcontrib><creatorcontrib>Rosenfeld, Margaret</creatorcontrib><creatorcontrib>Sagel, Scott D.</creatorcontrib><creatorcontrib>Milla, Carlos</creatorcontrib><creatorcontrib>Olivier, Kenneth N.</creatorcontrib><creatorcontrib>Barber, Andrew T.</creatorcontrib><creatorcontrib>Wee, Wallace</creatorcontrib><creatorcontrib>Lin, Feng-Chang</creatorcontrib><creatorcontrib>Li, Lang</creatorcontrib><creatorcontrib>Rampakakis, Emmanouil</creatorcontrib><creatorcontrib>Zariwala, Maimoona A.</creatorcontrib><creatorcontrib>Knowles, Michael R.</creatorcontrib><creatorcontrib>Leigh, Margaret W.</creatorcontrib><creatorcontrib>Shapiro, Adam J.</creatorcontrib><title>Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia</title><title>Chest</title><addtitle>Chest</addtitle><description>Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]).
Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT?
This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression.
In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA.
Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both.
ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www.clinicaltrials.gov.</description><subject>heterotaxy</subject><subject>Kartagener syndrome</subject><subject>primary ciliary dyskinesia</subject><subject>situs ambiguus</subject><issn>0012-3692</issn><issn>1931-3543</issn><issn>1931-3543</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kEtr3DAQgEVpaLbb_oJC8LEXu3pYXuvQw-K0zcJCAknJUcjSODsbP1LJXth_H22c9JjTzMA3r4-Qb4xmjLLixz6zOwhjxikXGeMZpfIDWTAlWCpkLj6SBaWMp6JQ_Jx8DmFPY81U8Ymci5KuuFB8QR5ucZxCsu5qfJhisol5CINFM4JL7nHcJWt3AB8gqVrs0Zo2uZ5GO3QQEuyTaoet89DP6I3HzvhjUmGLp3h5DI_YQ0DzhZw1pg3w9TUuyd_fv-6qq3R7_WdTrbepFVSNaVmvGGelqg0T0ABdyZVo6iJ3uc0lZdLIprBU1Q0oDqZRjFNXuNoJlpdFXoNYku_z3Cc__JuiHt1hsNC2podhCporypUspeQRFTNq_RCCh0Y_zedrRvXJsN7rF8P6ZFgzrqPh2HXxumCqO3D_e96URuDnDEB884DgdbAIvQWHHuyo3YDvLngGAwOOEg</recordid><startdate>20240501</startdate><enddate>20240501</enddate><creator>Kaspy, Kimberley R.</creator><creator>Dell, Sharon D.</creator><creator>Davis, Stephanie D.</creator><creator>Ferkol, Thomas W.</creator><creator>Rosenfeld, Margaret</creator><creator>Sagel, Scott D.</creator><creator>Milla, Carlos</creator><creator>Olivier, Kenneth N.</creator><creator>Barber, Andrew T.</creator><creator>Wee, Wallace</creator><creator>Lin, Feng-Chang</creator><creator>Li, Lang</creator><creator>Rampakakis, Emmanouil</creator><creator>Zariwala, Maimoona A.</creator><creator>Knowles, Michael R.</creator><creator>Leigh, Margaret W.</creator><creator>Shapiro, Adam J.</creator><general>Elsevier Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4291-3513</orcidid><orcidid>https://orcid.org/0000-0001-8200-255X</orcidid><orcidid>https://orcid.org/0000-0001-6066-6750</orcidid><orcidid>https://orcid.org/0000-0002-3516-8124</orcidid><orcidid>https://orcid.org/0000-0002-6479-5952</orcidid><orcidid>https://orcid.org/0000-0002-7427-8246</orcidid></search><sort><creationdate>20240501</creationdate><title>Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia</title><author>Kaspy, Kimberley R. ; Dell, Sharon D. ; Davis, Stephanie D. ; Ferkol, Thomas W. ; Rosenfeld, Margaret ; Sagel, Scott D. ; Milla, Carlos ; Olivier, Kenneth N. ; Barber, Andrew T. ; Wee, Wallace ; Lin, Feng-Chang ; Li, Lang ; Rampakakis, Emmanouil ; Zariwala, Maimoona A. ; Knowles, Michael R. ; Leigh, Margaret W. ; Shapiro, Adam J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c309t-8b712189ba13efe07573fb64d4c45015a5f6c09bfe92eaf9120d6dbd314864be3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>heterotaxy</topic><topic>Kartagener syndrome</topic><topic>primary ciliary dyskinesia</topic><topic>situs ambiguus</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kaspy, Kimberley R.</creatorcontrib><creatorcontrib>Dell, Sharon D.</creatorcontrib><creatorcontrib>Davis, Stephanie D.</creatorcontrib><creatorcontrib>Ferkol, Thomas W.</creatorcontrib><creatorcontrib>Rosenfeld, Margaret</creatorcontrib><creatorcontrib>Sagel, Scott D.</creatorcontrib><creatorcontrib>Milla, Carlos</creatorcontrib><creatorcontrib>Olivier, Kenneth N.</creatorcontrib><creatorcontrib>Barber, Andrew T.</creatorcontrib><creatorcontrib>Wee, Wallace</creatorcontrib><creatorcontrib>Lin, Feng-Chang</creatorcontrib><creatorcontrib>Li, Lang</creatorcontrib><creatorcontrib>Rampakakis, Emmanouil</creatorcontrib><creatorcontrib>Zariwala, Maimoona A.</creatorcontrib><creatorcontrib>Knowles, Michael R.</creatorcontrib><creatorcontrib>Leigh, Margaret W.</creatorcontrib><creatorcontrib>Shapiro, Adam J.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chest</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kaspy, Kimberley R.</au><au>Dell, Sharon D.</au><au>Davis, Stephanie D.</au><au>Ferkol, Thomas W.</au><au>Rosenfeld, Margaret</au><au>Sagel, Scott D.</au><au>Milla, Carlos</au><au>Olivier, Kenneth N.</au><au>Barber, Andrew T.</au><au>Wee, Wallace</au><au>Lin, Feng-Chang</au><au>Li, Lang</au><au>Rampakakis, Emmanouil</au><au>Zariwala, Maimoona A.</au><au>Knowles, Michael R.</au><au>Leigh, Margaret W.</au><au>Shapiro, Adam J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia</atitle><jtitle>Chest</jtitle><addtitle>Chest</addtitle><date>2024-05-01</date><risdate>2024</risdate><volume>165</volume><issue>5</issue><spage>1070</spage><epage>1081</epage><pages>1070-1081</pages><issn>0012-3692</issn><issn>1931-3543</issn><eissn>1931-3543</eissn><abstract>Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]).
Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT?
This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression.
In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA.
Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both.
ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www.clinicaltrials.gov.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>38072392</pmid><doi>10.1016/j.chest.2023.12.005</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4291-3513</orcidid><orcidid>https://orcid.org/0000-0001-8200-255X</orcidid><orcidid>https://orcid.org/0000-0001-6066-6750</orcidid><orcidid>https://orcid.org/0000-0002-3516-8124</orcidid><orcidid>https://orcid.org/0000-0002-6479-5952</orcidid><orcidid>https://orcid.org/0000-0002-7427-8246</orcidid></addata></record> |
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subjects | heterotaxy Kartagener syndrome primary ciliary dyskinesia situs ambiguus |
title | Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia |
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