Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities

John S. Kim; Gísli Þór Axelsson; Matthew Moll; Michaela R. Anderson; Elana J. Bernstein; Rachel K. Putman; Tomoyuki Hida; Hiroto Hatabu; Eric A. Hoffman; Ganesh Raghu; Steven M. Kawut; Margaret F. Doyle; Russell Tracy; Lenore J. Launer; Ani Manichaikul; Stephen S. Rich; David J. Lederer; Vilmundur G Guðnason; Brian D. Hobbs; Michael H. Cho; Gary M. Hunninghake; Christine Kim Garcia; Gunnar Guðmundsson; R. Graham Barr; Anna J. Podolanczuk

doi:10.1164/rccm.202108-1967oc

Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities

John S. Kim^*, Gísli Þór Axelsson, Matthew Moll, Michaela R. Anderson, Elana J. Bernstein, Rachel K. Putman, Tomoyuki Hida, Hiroto Hatabu, Eric A. Hoffman, Ganesh Raghu, Steven M. Kawut, Margaret F. Doyle, Russell Tracy, Lenore J. Launer, Ani Manichaikul, Stephen S. Rich, David J. Lederer, Vilmundur G Guðnason, Brian D. Hobbs, Michael H. ChoGary M. Hunninghake, Christine Kim Garcia, Gunnar Guðmundsson, R. Graham Barr, Anna J. Podolanczuk

^*Corresponding author for this work

Landspitali - The National University Hospital of Iceland, Iceland, University of Iceland

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n = 3,547), COPDGene (Genetic Epidemiology of COPD, n = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGESReykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

Original language	English
Pages (from-to)	795-805
Number of pages	11
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	205
Issue number	7
DOIs	https://doi.org/10.1164/rccm.202108-1967oc
Publication status	Published - 1 Apr 2022

Bibliographical note

Funding Information:
The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study was supported by NHLBI (NIH) grants R01-HL077612, R01-HL093081, and RC1-HL100543 and contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169. MESA was also funded by National Center for Advancing Translational Sciences (NIH) grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420. The Age, Gene/Environment Susceptibility-Reykjavik Study was supported by National Institute on Aging (NIH) contracts N01-AG-1-2100 and HHSN27120120022C, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The COPDGene project described was supported by NHLBI award numbers U01 HL089897 and U01 HL089856. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI or the NIH. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion. The ECLIPSE study was funded by GlaxoSmithKline (NCT00292552; GSK code SCO104960). Also supported by the Pulmonary Fibrosis Foundation Scholars Award and NHLBI grant K23-HL-150301 (J.S.K.); NHLBI grants K23-HL-1502080 (M.R.A.), K23-HL-140087 (R.K.P.), and K23-HL-140199 (A.J.P.); National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-075112 (E.J.B.); and NHLBI grants K24-HL-103844 (S.M.K.); R01-HL111024, R01-HL130974, and R01-HL135142 (G.M.H.); and R01-HL103676 (C.K.G.). Further support was by the Icelandic Research Fund, project grant 141513-051 (G.G. and V.G.); the Landspitali Scientific Fund grants A-2019-029, A-2019-030, A-2020-018, A-2020-017, and A2021-018; as well as the University of Iceland Research Fund 2021 (G.G.) and the Eimskip University Fund (G.T.A.); NHLBI grant T32HL007427 (M.M.); and NIH grants K08HL136928 (B.D.H.) and R01HL137927 and R01HL135142 (M.H.C.).

Publisher Copyright:
© 2022 by the American Thoracic Society.

Other keywords

immunity
interstitial lung abnormalities
monocyte
Monocytes
Lung/diagnostic imaging
Humans
Respiratory System Abnormalities
Adult
Tomography, X-Ray Computed
Lung Diseases, Interstitial

Access to Document

10.1164/rccm.202108-1967oc

Lung research suggests new way to detect, monitor lung diseases
Guðnason, V. G.
1/02/22 → 2/02/22
6 items of Media coverage
University of Iceland, Iceland
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Kim, J. S., Axelsson, G. Þ., Moll, M., Anderson, M. R., Bernstein, E. J., Putman, R. K., Hida, T., Hatabu, H., Hoffman, E. A., Raghu, G., Kawut, S. M., Doyle, M. F., Tracy, R., Launer, L. J., Manichaikul, A., Rich, S. S., Lederer, D. J., Guðnason, V. G., Hobbs, B. D., ... Podolanczuk, A. J. (2022). Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities. American Journal of Respiratory and Critical Care Medicine, 205(7), 795-805. https://doi.org/10.1164/rccm.202108-1967oc

@article{b2099cdc9351464497303bbf6ba62832,

title = "Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities",

abstract = "Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n = 3,547), COPDGene (Genetic Epidemiology of COPD, n = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGESReykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.",

keywords = "immunity, interstitial lung abnormalities, monocyte, Monocytes, Lung/diagnostic imaging, Humans, Respiratory System Abnormalities, Adult, Tomography, X-Ray Computed, Lung Diseases, Interstitial",

author = "Kim, {John S.} and Axelsson, {G{\'i}sli {\TH}{\'o}r} and Matthew Moll and Anderson, {Michaela R.} and Bernstein, {Elana J.} and Putman, {Rachel K.} and Tomoyuki Hida and Hiroto Hatabu and Hoffman, {Eric A.} and Ganesh Raghu and Kawut, {Steven M.} and Doyle, {Margaret F.} and Russell Tracy and Launer, {Lenore J.} and Ani Manichaikul and Rich, {Stephen S.} and Lederer, {David J.} and Gu{\dh}nason, {Vilmundur G} and Hobbs, {Brian D.} and Cho, {Michael H.} and Hunninghake, {Gary M.} and Garcia, {Christine Kim} and Gunnar Gu{\dh}mundsson and Barr, {R. Graham} and Podolanczuk, {Anna J.}",

note = "Funding Information: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study was supported by NHLBI (NIH) grants R01-HL077612, R01-HL093081, and RC1-HL100543 and contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169. MESA was also funded by National Center for Advancing Translational Sciences (NIH) grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420. The Age, Gene/Environment Susceptibility-Reykjavik Study was supported by National Institute on Aging (NIH) contracts N01-AG-1-2100 and HHSN27120120022C, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The COPDGene project described was supported by NHLBI award numbers U01 HL089897 and U01 HL089856. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI or the NIH. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion. The ECLIPSE study was funded by GlaxoSmithKline (NCT00292552; GSK code SCO104960). Also supported by the Pulmonary Fibrosis Foundation Scholars Award and NHLBI grant K23-HL-150301 (J.S.K.); NHLBI grants K23-HL-1502080 (M.R.A.), K23-HL-140087 (R.K.P.), and K23-HL-140199 (A.J.P.); National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-075112 (E.J.B.); and NHLBI grants K24-HL-103844 (S.M.K.); R01-HL111024, R01-HL130974, and R01-HL135142 (G.M.H.); and R01-HL103676 (C.K.G.). Further support was by the Icelandic Research Fund, project grant 141513-051 (G.G. and V.G.); the Landspitali Scientific Fund grants A-2019-029, A-2019-030, A-2020-018, A-2020-017, and A2021-018; as well as the University of Iceland Research Fund 2021 (G.G.) and the Eimskip University Fund (G.T.A.); NHLBI grant T32HL007427 (M.M.); and NIH grants K08HL136928 (B.D.H.) and R01HL137927 and R01HL135142 (M.H.C.). Publisher Copyright: {\textcopyright} 2022 by the American Thoracic Society.",

year = "2022",

month = apr,

day = "1",

doi = "10.1164/rccm.202108-1967oc",

language = "English",

volume = "205",

pages = "795--805",

journal = "American Journal of Respiratory and Critical Care Medicine",

issn = "1073-449X",

publisher = "American Thoracic Society",

number = "7",

}

Kim, JS, Axelsson, GÞ, Moll, M, Anderson, MR, Bernstein, EJ, Putman, RK, Hida, T, Hatabu, H, Hoffman, EA, Raghu, G, Kawut, SM, Doyle, MF, Tracy, R, Launer, LJ, Manichaikul, A, Rich, SS, Lederer, DJ, Guðnason, VG, Hobbs, BD, Cho, MH, Hunninghake, GM, Garcia, CK, Guðmundsson, G, Barr, RG & Podolanczuk, AJ 2022, 'Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities', American Journal of Respiratory and Critical Care Medicine, vol. 205, no. 7, pp. 795-805. https://doi.org/10.1164/rccm.202108-1967oc

TY - JOUR

T1 - Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities

AU - Kim, John S.

AU - Axelsson, Gísli Þór

AU - Moll, Matthew

AU - Anderson, Michaela R.

AU - Bernstein, Elana J.

AU - Putman, Rachel K.

AU - Hida, Tomoyuki

AU - Hatabu, Hiroto

AU - Hoffman, Eric A.

AU - Raghu, Ganesh

AU - Kawut, Steven M.

AU - Doyle, Margaret F.

AU - Tracy, Russell

AU - Launer, Lenore J.

AU - Manichaikul, Ani

AU - Rich, Stephen S.

AU - Lederer, David J.

AU - Guðnason, Vilmundur G

AU - Hobbs, Brian D.

AU - Cho, Michael H.

AU - Hunninghake, Gary M.

AU - Garcia, Christine Kim

AU - Guðmundsson, Gunnar

AU - Barr, R. Graham

AU - Podolanczuk, Anna J.

N1 - Funding Information: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study was supported by NHLBI (NIH) grants R01-HL077612, R01-HL093081, and RC1-HL100543 and contracts HHSN268201500003I, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169. MESA was also funded by National Center for Advancing Translational Sciences (NIH) grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420. The Age, Gene/Environment Susceptibility-Reykjavik Study was supported by National Institute on Aging (NIH) contracts N01-AG-1-2100 and HHSN27120120022C, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The COPDGene project described was supported by NHLBI award numbers U01 HL089897 and U01 HL089856. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NHLBI or the NIH. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion. The ECLIPSE study was funded by GlaxoSmithKline (NCT00292552; GSK code SCO104960). Also supported by the Pulmonary Fibrosis Foundation Scholars Award and NHLBI grant K23-HL-150301 (J.S.K.); NHLBI grants K23-HL-1502080 (M.R.A.), K23-HL-140087 (R.K.P.), and K23-HL-140199 (A.J.P.); National Institute of Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-075112 (E.J.B.); and NHLBI grants K24-HL-103844 (S.M.K.); R01-HL111024, R01-HL130974, and R01-HL135142 (G.M.H.); and R01-HL103676 (C.K.G.). Further support was by the Icelandic Research Fund, project grant 141513-051 (G.G. and V.G.); the Landspitali Scientific Fund grants A-2019-029, A-2019-030, A-2020-018, A-2020-017, and A2021-018; as well as the University of Iceland Research Fund 2021 (G.G.) and the Eimskip University Fund (G.T.A.); NHLBI grant T32HL007427 (M.M.); and NIH grants K08HL136928 (B.D.H.) and R01HL137927 and R01HL135142 (M.H.C.). Publisher Copyright: © 2022 by the American Thoracic Society.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n = 3,547), COPDGene (Genetic Epidemiology of COPD, n = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGESReykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

AB - Rationale: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. Objectives: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high-attenuation areas, and FVC in four independent cohorts. Methods: We included participants with measured monocyte counts and computed tomographic (CT) imaging enrolled in MESA (Multi-Ethnic Study of Atherosclerosis, n = 484), AGES-Reykjavik (Age/Gene Environment Susceptibility Study, n = 3,547), COPDGene (Genetic Epidemiology of COPD, n = 2,719), and the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points, n = 646). Measurements and Main Results: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.0-1.8), AGES-Reykjavik (OR, 1.2; 95% CI, 1.1-1.3), COPDGene (OR, 1.3; 95% CI, 1.2-1.4), and ECLIPSE (OR, 1.2; 95% CI, 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGESReykjavik (OR, 1.2; 95% CI, 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater high-attenuation areas in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. Conclusions: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

KW - immunity

KW - interstitial lung abnormalities

KW - monocyte

KW - Monocytes

KW - Lung/diagnostic imaging

KW - Humans

KW - Respiratory System Abnormalities

KW - Adult

KW - Tomography, X-Ray Computed

KW - Lung Diseases, Interstitial

UR - http://www.scopus.com/inward/record.url?scp=85128160631&partnerID=8YFLogxK

U2 - 10.1164/rccm.202108-1967oc

DO - 10.1164/rccm.202108-1967oc

M3 - Article

C2 - 34929108

AN - SCOPUS:85128160631

SN - 1073-449X

VL - 205

SP - 795

EP - 805

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 7

ER -

Associations of Monocyte Count and Other Immune Cell Types with Interstitial Lung Abnormalities

Abstract

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Lung research suggests new way to detect, monitor lung diseases

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