Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study

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Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. / Warny, Marie; Helby, Jens; Nordestgaard, Børge Grønne; Birgens, Henrik; Bojesen, Stig Egil.

In: PLoS Medicine, Vol. 15, No. 11, e1002685, 2018.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Warny, M, Helby, J, Nordestgaard, BG, Birgens, H & Bojesen, SE 2018, 'Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study' PLoS Medicine, vol. 15, no. 11, e1002685. https://doi.org/10.1371/journal.pmed.1002685

APA

Warny, M., Helby, J., Nordestgaard, B. G., Birgens, H., & Bojesen, S. E. (2018). Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. PLoS Medicine, 15(11), [e1002685]. https://doi.org/10.1371/journal.pmed.1002685

Vancouver

Warny M, Helby J, Nordestgaard BG, Birgens H, Bojesen SE. Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. PLoS Medicine. 2018;15(11). e1002685. https://doi.org/10.1371/journal.pmed.1002685

Author

Warny, Marie ; Helby, Jens ; Nordestgaard, Børge Grønne ; Birgens, Henrik ; Bojesen, Stig Egil. / Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study. In: PLoS Medicine. 2018 ; Vol. 15, No. 11.

Bibtex

@article{70b409ba9ff346f282a906755ff3f560,
title = "Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study",
abstract = "BACKGROUND: Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection and infection-related death in the general population.METHODS AND FINDINGS: Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401 infections and experienced 1,045 infection-related deaths. Due to the completeness of the Danish civil and health registries, none of the 98,344 individuals were lost to follow-up, and those emigrating (n = 385) or dying (n = 5,636) had their follow-up truncated at the day of emigration or death. At date of examination, mean age was 58 years, and 44,181 (44.9{\%}) were men. Individuals with lymphopenia (lymphocyte count < 1.1 × 109/l, n = 2,352) compared to those with lymphocytes in the reference range (1.1-3.7 × 109/l, n = 93,538) had multivariable-adjusted hazard ratios of 1.41 (95{\%} CI 1.28-1.56) for any infection, 1.31 (1.14-1.52) for pneumonia, 1.44 (1.15-1.79) for skin infection, 1.26 (1.02-1.56) for urinary tract infection, 1.51 (1.21-1.89) for sepsis, 1.38 (1.01-1.88) for diarrheal disease, 2.15 (1.16-3.98) for endocarditis, and 2.26 (1.21-4.24) for other infections. The corresponding hazard ratio for infection-related death was 1.70 (95{\%} CI 1.37-2.10). Analyses were adjusted for age, sex, smoking status, cumulative smoking, alcohol intake, body mass index, plasma C-reactive protein, blood neutrophil count, recent infection, Charlson comorbidity index, autoimmune diseases, medication use, and immunodeficiency/hematologic disease. The findings were robust in all stratified analyses and also when including only events later than 2 years after first examination. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and reverse causation. In principle, fluctuating lymphocyte counts over time might also have influenced analyses, but lymphocyte counts in 5,181 individuals measured 10 years after first examination showed a regression dilution ratio of 0.68.CONCLUSIONS: Lymphopenia was associated with increased risk of hospitalization with infection and increased risk of infection-related death in the general population. Notably, causality cannot be deduced from our data.",
author = "Marie Warny and Jens Helby and Nordestgaard, {B{\o}rge Gr{\o}nne} and Henrik Birgens and Bojesen, {Stig Egil}",
year = "2018",
doi = "10.1371/journal.pmed.1002685",
language = "English",
volume = "15",
journal = "P L o S Medicine (Online)",
issn = "1549-1277",
publisher = "Public Library of Science",
number = "11",

}

RIS

TY - JOUR

T1 - Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study

AU - Warny, Marie

AU - Helby, Jens

AU - Nordestgaard, Børge Grønne

AU - Birgens, Henrik

AU - Bojesen, Stig Egil

PY - 2018

Y1 - 2018

N2 - BACKGROUND: Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection and infection-related death in the general population.METHODS AND FINDINGS: Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401 infections and experienced 1,045 infection-related deaths. Due to the completeness of the Danish civil and health registries, none of the 98,344 individuals were lost to follow-up, and those emigrating (n = 385) or dying (n = 5,636) had their follow-up truncated at the day of emigration or death. At date of examination, mean age was 58 years, and 44,181 (44.9%) were men. Individuals with lymphopenia (lymphocyte count < 1.1 × 109/l, n = 2,352) compared to those with lymphocytes in the reference range (1.1-3.7 × 109/l, n = 93,538) had multivariable-adjusted hazard ratios of 1.41 (95% CI 1.28-1.56) for any infection, 1.31 (1.14-1.52) for pneumonia, 1.44 (1.15-1.79) for skin infection, 1.26 (1.02-1.56) for urinary tract infection, 1.51 (1.21-1.89) for sepsis, 1.38 (1.01-1.88) for diarrheal disease, 2.15 (1.16-3.98) for endocarditis, and 2.26 (1.21-4.24) for other infections. The corresponding hazard ratio for infection-related death was 1.70 (95% CI 1.37-2.10). Analyses were adjusted for age, sex, smoking status, cumulative smoking, alcohol intake, body mass index, plasma C-reactive protein, blood neutrophil count, recent infection, Charlson comorbidity index, autoimmune diseases, medication use, and immunodeficiency/hematologic disease. The findings were robust in all stratified analyses and also when including only events later than 2 years after first examination. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and reverse causation. In principle, fluctuating lymphocyte counts over time might also have influenced analyses, but lymphocyte counts in 5,181 individuals measured 10 years after first examination showed a regression dilution ratio of 0.68.CONCLUSIONS: Lymphopenia was associated with increased risk of hospitalization with infection and increased risk of infection-related death in the general population. Notably, causality cannot be deduced from our data.

AB - BACKGROUND: Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection and infection-related death in the general population.METHODS AND FINDINGS: Of the invited 220,424 individuals, 99,191 attended examination. We analyzed 98,344 individuals from the Copenhagen General Population Study (Denmark), examined from November 25, 2003, to July 9, 2013, and with available blood lymphocyte count at date of examination. During a median of 6 years of follow-up, they developed 8,401 infections and experienced 1,045 infection-related deaths. Due to the completeness of the Danish civil and health registries, none of the 98,344 individuals were lost to follow-up, and those emigrating (n = 385) or dying (n = 5,636) had their follow-up truncated at the day of emigration or death. At date of examination, mean age was 58 years, and 44,181 (44.9%) were men. Individuals with lymphopenia (lymphocyte count < 1.1 × 109/l, n = 2,352) compared to those with lymphocytes in the reference range (1.1-3.7 × 109/l, n = 93,538) had multivariable-adjusted hazard ratios of 1.41 (95% CI 1.28-1.56) for any infection, 1.31 (1.14-1.52) for pneumonia, 1.44 (1.15-1.79) for skin infection, 1.26 (1.02-1.56) for urinary tract infection, 1.51 (1.21-1.89) for sepsis, 1.38 (1.01-1.88) for diarrheal disease, 2.15 (1.16-3.98) for endocarditis, and 2.26 (1.21-4.24) for other infections. The corresponding hazard ratio for infection-related death was 1.70 (95% CI 1.37-2.10). Analyses were adjusted for age, sex, smoking status, cumulative smoking, alcohol intake, body mass index, plasma C-reactive protein, blood neutrophil count, recent infection, Charlson comorbidity index, autoimmune diseases, medication use, and immunodeficiency/hematologic disease. The findings were robust in all stratified analyses and also when including only events later than 2 years after first examination. However, due to the observational design, the study cannot address questions of causality, and our analyses might theoretically have been affected by residual confounding and reverse causation. In principle, fluctuating lymphocyte counts over time might also have influenced analyses, but lymphocyte counts in 5,181 individuals measured 10 years after first examination showed a regression dilution ratio of 0.68.CONCLUSIONS: Lymphopenia was associated with increased risk of hospitalization with infection and increased risk of infection-related death in the general population. Notably, causality cannot be deduced from our data.

U2 - 10.1371/journal.pmed.1002685

DO - 10.1371/journal.pmed.1002685

M3 - Journal article

VL - 15

JO - P L o S Medicine (Online)

JF - P L o S Medicine (Online)

SN - 1549-1277

IS - 11

M1 - e1002685

ER -

ID: 216567346