Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study
BackgroundNeutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.MethodsWe prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pul...
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2021-07-01
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Anna Cristina C. Carvalho Anna Cristina C. Carvalho Gustavo Amorim Mayla G. M. Melo Mayla G. M. Melo Ana Karla A. Silveira Ana Karla A. Silveira Pedro H. L. Vargas Pedro H. L. Vargas Adriana S. R. Moreira Michael S. Rocha Michael S. Rocha Alexandra B. Souza María B. Arriaga María B. Arriaga María B. Arriaga Mariana Araújo-Pereira Mariana Araújo-Pereira Mariana Araújo-Pereira Marina C. Figueiredo Betina Durovni José R. Lapa-e-Silva Solange Cavalcante Valeria C. Rolla Timothy R. Sterling Marcelo Cordeiro-Santos Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Elisangela C. Silva Elisangela C. Silva Elisangela C. Silva Afrânio L. Kritski Afrânio L. Kritski the RePORT Brazil consortium |
spellingShingle |
Anna Cristina C. Carvalho Anna Cristina C. Carvalho Gustavo Amorim Mayla G. M. Melo Mayla G. M. Melo Ana Karla A. Silveira Ana Karla A. Silveira Pedro H. L. Vargas Pedro H. L. Vargas Adriana S. R. Moreira Michael S. Rocha Michael S. Rocha Alexandra B. Souza María B. Arriaga María B. Arriaga María B. Arriaga Mariana Araújo-Pereira Mariana Araújo-Pereira Mariana Araújo-Pereira Marina C. Figueiredo Betina Durovni José R. Lapa-e-Silva Solange Cavalcante Valeria C. Rolla Timothy R. Sterling Marcelo Cordeiro-Santos Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Elisangela C. Silva Elisangela C. Silva Elisangela C. Silva Afrânio L. Kritski Afrânio L. Kritski the RePORT Brazil consortium Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study Frontiers in Immunology tuberculosis neutrophils treatment outcome biomarker neutrophil count |
author_facet |
Anna Cristina C. Carvalho Anna Cristina C. Carvalho Gustavo Amorim Mayla G. M. Melo Mayla G. M. Melo Ana Karla A. Silveira Ana Karla A. Silveira Pedro H. L. Vargas Pedro H. L. Vargas Adriana S. R. Moreira Michael S. Rocha Michael S. Rocha Alexandra B. Souza María B. Arriaga María B. Arriaga María B. Arriaga Mariana Araújo-Pereira Mariana Araújo-Pereira Mariana Araújo-Pereira Marina C. Figueiredo Betina Durovni José R. Lapa-e-Silva Solange Cavalcante Valeria C. Rolla Timothy R. Sterling Marcelo Cordeiro-Santos Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Bruno B. Andrade Elisangela C. Silva Elisangela C. Silva Elisangela C. Silva Afrânio L. Kritski Afrânio L. Kritski the RePORT Brazil consortium |
author_sort |
Anna Cristina C. Carvalho |
title |
Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study |
title_short |
Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study |
title_full |
Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study |
title_fullStr |
Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study |
title_full_unstemmed |
Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort Study |
title_sort |
pre-treatment neutrophil count as a predictor of antituberculosis therapy outcomes: a multicenter prospective cohort study |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-07-01 |
description |
BackgroundNeutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.MethodsWe prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes.ResultsAmong 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]).ConclusionIncreased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted. |
topic |
tuberculosis neutrophils treatment outcome biomarker neutrophil count |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.661934/full |
work_keys_str_mv |
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doaj-ef7f043ef7914bd2a0ad88d2327810712021-07-02T15:34:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.661934661934Pre-Treatment Neutrophil Count as a Predictor of Antituberculosis Therapy Outcomes: A Multicenter Prospective Cohort StudyAnna Cristina C. Carvalho0Anna Cristina C. Carvalho1Gustavo Amorim2Mayla G. M. Melo3Mayla G. M. Melo4Ana Karla A. Silveira5Ana Karla A. Silveira6Pedro H. L. Vargas7Pedro H. L. Vargas8Adriana S. R. Moreira9Michael S. Rocha10Michael S. Rocha11Alexandra B. Souza12María B. Arriaga13María B. Arriaga14María B. Arriaga15Mariana Araújo-Pereira16Mariana Araújo-Pereira17Mariana Araújo-Pereira18Marina C. Figueiredo19Betina Durovni20José R. Lapa-e-Silva21Solange Cavalcante22Valeria C. Rolla23Timothy R. Sterling24Marcelo Cordeiro-Santos25Bruno B. Andrade26Bruno B. Andrade27Bruno B. Andrade28Bruno B. Andrade29Bruno B. Andrade30Bruno B. Andrade31Elisangela C. Silva32Elisangela C. Silva33Elisangela C. Silva34Afrânio L. Kritski35Afrânio L. Kritski36the RePORT Brazil consortiumLaboratório de Inovações em Terapias, Ensino e Bioprodutos (LITEB), Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, United StatesPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilLaboratório de Micobacteriologia Molecular, Faculdade de Medicina e Complexo Hospitalar Hospital Universitário Clementino Fraga Filho—Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilLaboratório de Micobacteriologia Molecular, Faculdade de Medicina e Complexo Hospitalar Hospital Universitário Clementino Fraga Filho—Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilLaboratório de Micobacteriologia Molecular, Faculdade de Medicina e Complexo Hospitalar Hospital Universitário Clementino Fraga Filho—Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilInstituto Brasileiro para Investigação da Tuberculose, Fundação José Silveira, Salvador, BrazilGerência de Micobacteriologia, Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilLaboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia, Salvador, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilLaboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil0Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States1Secretaria Municipal de Saúde do Rio de Janeiro, Rio de Janeiro, BrazilPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil1Secretaria Municipal de Saúde do Rio de Janeiro, Rio de Janeiro, Brazil2Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil0Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United StatesGerência de Micobacteriologia, Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, BrazilMultinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, BrazilLaboratório de Inflamação e Biomarcadores, Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BrazilFaculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil0Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, United States3Curso de Medicina, Escola Bahiana de Medicina e Saúde Pública, Salvador, Brazil4Curso de Medicina, Universidade Salvador (UNIFACS), Salvador, BrazilPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilLaboratório de Micobacteriologia Molecular, Faculdade de Medicina e Complexo Hospitalar Hospital Universitário Clementino Fraga Filho—Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil5Laboratório Reconhecer Biologia, Centro de Biociência e Biotecniologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Rio de Janeiro, BrazilPrograma Acadêmico de Tuberculose da Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilLaboratório de Micobacteriologia Molecular, Faculdade de Medicina e Complexo Hospitalar Hospital Universitário Clementino Fraga Filho—Instituto de Doenças do Tórax da Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilBackgroundNeutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown.MethodsWe prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes.ResultsAmong 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]).ConclusionIncreased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted.https://www.frontiersin.org/articles/10.3389/fimmu.2021.661934/fulltuberculosisneutrophilstreatment outcomebiomarkerneutrophil count |