[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 34.238.248.103. Please contact the publisher to request reinstatement.
[Skip to Content Landing]
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    Views 1,681
    Citations 0
    Original Investigation
    Pulmonary Medicine
    July 13, 2020

    Association of Neutrophil to Lymphocyte Ratio With Pulmonary Function in a 30-Year Longitudinal Study of US Veterans

    Author Affiliations
    • 1Laboratory of Environmental Precision Biosciences, Mailman School of Public Health, Columbia University, New York, New York
    • 2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
    • 3Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Boston, Massachusetts
    • 4Department of Medicine, Boston University School of Medicine, Boston, Massachusetts
    • 5Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
    • 6Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
    • 7Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, Massachusetts
    • 8Division of Pediatric Pulmonary Medicine, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Rochester, New York
    • 9Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
    JAMA Netw Open. 2020;3(7):e2010350. doi:10.1001/jamanetworkopen.2020.10350
    Key Points español 中文 (chinese)

    Question  Is the neutrophil to lymphocyte ratio (NLR) associated with lung function decline and chronic obstructive pulmonary disease risk at the population level?

    Findings  This cohort study of 1549 US veterans with more than 30 years of follow-up found that higher NLR was associated with lower lung function and higher chronic obstructive pulmonary disease risk. Additionally, NLR was associated with AHRR hypomethylation, the top DNA methylation signature of lung function changes, which may mediate the adverse association of NLR-related inflammation with lung function.

    Meaning  These findings suggest that NLR may be a useful, readily obtainable, and inexpensive tool to identify people with high risks of lung function impairment and chronic obstructive pulmonary disease.

    Abstract

    Importance  Chronic obstructive pulmonary disease (COPD) is a critical public health burden. The neutrophil to lymphocyte ratio (NLR), an inflammation biomarker, has been associated with COPD morbidity and mortality; however, its associations with lung function decline and COPD development are poorly understood.

    Objective  To explore the associations of NLR with lung function decline and COPD risks.

    Design, Setting, and Participants  This longitudinal cohort study included white male veterans in the US with more than 30 years of follow-up to investigate the associations of NLR with lung function, COPD, and hypomethylation of cg05575921, the top DNA methylation marker of lung function changes in response to tobacco smoking. This study included 7466 visits from 1549 participants, each examined up to 13 times between 1982 and 2018. A subgroup of 1411 participants without COPD at baseline were selected to analyze the association of NLR with incident COPD. Data were analyzed from September 2019 to January 2020.

    Exposures  The primary exposure was NLR, which was estimated using automated whole blood cell counts based on a blood sample collected at each visit. The methylation level of cg05575921 was measured in blood DNA from a subgroup of 1228 visits.

    Main Outcomes and Measures  The outcomes of interest were lung function, measured as forced respiratory volume in the first second (FEV1) in liters, forced vital capacity (FVC) in liters, percentage of FVC exhaled in the first second (FEV1/FVC), and maximal midexpiratory flow rate (MMEF) in liters per minute and COPD status, defined as meeting the Global Initiative for Chronic Obstructive Lung Diseases stage II (or higher) criteria. Both outcomes were measured as each visit.

    Results  Among 1549 included men (mean [SD] age, 68.3 [9.3] years) with 7466 visits from 1982 to 2018, a 1-unit increase in NLR was associated with statistically significant mean (SE) decreases of 0.021 (0.004) L in FEV1, 0.016 (0.005) L in FVC, 0.290% (0.005) L in FVC, 0.290% (0.065%) in FEV1/FVC, and 3.65 (0.916) L/min MMEF. Changes in NLR up to approximately 10 years were associated with corresponding longitudinal changes in lung function. Furthermore, this increase in NLR was associated with 9% higher odds of COPD (odds ratio, 1.09 [95% CI, 1.03-1.15]) for all visits and 27% higher risk of incident COPD (odds ratio, 1.07 [95% CI, 1.07-1.51]) for participants without COPD at baseline. Additionally, a 1-unit increase in NLR was associated with a mean (SE) decrease of 0.0048 (0.0021 in cg05575921 hypomethylation, which may mediate the adverse association of NLR-related inflammation on lung function.

    Conclusions and Relevance  These findings suggest that NLR may be a clinically relevant biomarker associated with high risk of lung function impairment and COPD alone or in combination with DNA methylation profiles.

    ×