Inflammatory Markers in Blood May Help ID COPD Outcomes Risk

Use of such markers may aid in management of acute exacerbations

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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A dropper squirts blood alongside a number of vials of blood.

Measuring inflammatory markers during routine blood tests in people with chronic obstructive pulmonary disease (COPD) could acute exacerbations at risk of experiencing worse outcomes, according to a small literature review study.

Specifically, the researchers suggest measuring the neutrophil-to-lymphocyte ratio (NLR) — an indicator of systemic or body-wide inflammation.

The prognostic potential of a second parameter, called platelet-to-lymphocyte ratio (PLR), requires further studies, the team noted.

“Pending the results of well-designed prospective studies, the routine use of these inflammatory markers may potentially influence the management” of acute exacerbations in COPD patients upon hospital admission, the researchers wrote.

The study, “Clinical significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in acute exacerbations of COPD: present and future,” was published in the journal European Respiratory Review.

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Acute exacerbations — sudden worsening of respiratory function — is the main cause of hospitalization and death among COPD patients.

Between 9–16% of people with COPD experience more than one acute exacerbation per year, which poses a significant financial burden on both patients and healthcare systems.

The most common standard treatments for exacerbations include a mix of beta 2 agonists or bronchodilators, anti-inflammatory glucocorticoids, and antibiotics. In addition, certain patients may require invasive ventilation.

As of now, there are no biomarkers that have been found to accurately assess the risk for acute exacerbations and for classifying patients upon hospital admission. Such biomarkers would help in patient stratification in COPD — dividing those with the disease into subgroups based on the presence or absence of different characteristics.

It is well known that COPD patients have elevated levels of blood inflammatory markers, with about 70% of them having high levels of at least one such biomarker.

A state of chronic inflammation, a COPD hallmark, alters the levels of platelets — tiny blood cell fragments involved in blood clotting — and neutrophils, white blood cells that are considered the “first responders” of the immune system.

The predictive potential of measuring a combination of circulating biomarkers of inflammation remains a matter of debate, with some studies supporting this concept, while others don’t.

Now, researchers at the University of Sassari, in Italy, and colleagues, sought to clarify whether inflammation markers could play an important role in discriminating between stable COPD and acute exacerbations. To that end, the team reviewed published studies reporting the use of routine blood counts measured in COPD patients at hospital admission.

They specifically focused on two parameters: the NLR and the PLR.

The NLR is the ratio of neutrophils to other immune cells called lymphocytes. It is a biomarker of systemic inflammation, used to predict patient prognosis for certain cancers, autoimmune diseases, kidney disease, and coronary artery disease, among other conditions.

The PLR — the ratio of platelets and lymphocytes — is a maker of acute inflammation and a prothrombotic or high coagulation state.

In their analysis, researchers included studies that assessed NLR and/or PLR measured within 24 to 48 hours of hospital admission in adults with COPD. The findings were then linked to patients’ pre-defined clinical outcomes.

In total, the analysis included 18 studies on NLR and 10 on PLR, found in the PubMed database up to May 2022.

NLR studies analyzed how the ratio correlated with mortality, ICU transfer, invasive ventilation, failure of noninvasive ventilation, and pulmonary hypertension. They also examined the ratio’s correlation with length of hospitalization.

In 15 studies, a statistical analysis was performed to assess the relationship between NLR and patient outcomes.

Overall, 10 of those 15 studies reported a significant positive association — meaning the greater one, the greater the other — between NLR levels and adverse outcomes.

Specifically, patients with higher NLR levels had a higher risk — which was nearly 42 times higher in one case — of experiencing poor outcomes, particularly mortality.

While a link also was reported in certain studies between high NLR values and other adverse parameters, including the need for assisted invasive ventilation or transfer to ICU, “the number of studies investigating outcomes other than mortality was limited,” the researchers wrote.

An even lower number of studies assessed the link between PLR and adverse outcomes in COPD patients with acute exacerbations. Two studies reported a positive and independent association between PLR and mortality, meaning that patients who died had higher PLR levels compared with those who survived.

The low number of studies indicates how “more research is warranted to investigate the predictive capacity of the PLR,” in COPD patients with acute exacerbations, the researchers wrote.

Overall, this literature review suggests that “NLR, a simple and inexpensive inflammatory index that has been increasingly investigated in a wide range of disease states, including COPD, appears to be a promising predictor of mortality in [COPD patients with acute exacerbations],” the researchers wrote.

Conversely, “the current evidence regarding the prognostic value of the PLR is less clear and requires further studies,” they wrote.