Hemoglobin May Be Promising Biomarker of Clinical Outcomes

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Hemoglobin, the protein that carries oxygen in blood, may be a promising biomarker to assess the clinical outcomes of patients with chronic obstructive pulmonary disease (COPD), a large U.S.-based study has found.

The findings indicate that unusually high or low levels of hemoglobin were linked to worse clinical outcomes. According to the scientists, “these findings lay the foundation for research regarding potential therapeutic targeting of haemoglobin in management of COPD.”

The study, “Haemoglobin as a biomarker for clinical outcomes in chronic obstructive pulmonary disease,” was published in ERJ Open Research.

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As a disease that is characterized by inflammation, COPD may disturb the process by which the body makes blood cells by favoring the production of certain immune cells at the expense of red blood cells, among others.

Anemia, a condition marked by low numbers of red blood cells or hemoglobin, is thought to affect about one-third of COPD patients. At the other end of the spectrum is polycythemia, a condition marked by abnormally high numbers of red blood cells or hemoglobin that may occur secondary to COPD in some people.

While several past studies have linked anemia to poorer clinical outcomes, not many have looked at polycythemia. To bridge this gap in knowledge, a team of researchers in the U.S. set out to study the relationship between hemoglobin levels — across its entire range — and COPD clinical outcomes.

“Such an understanding could guide future therapeutic targeting of haemoglobin in COPD management,” the researchers wrote.

Data came from COPDGene, a large study originally designed to identify genetic factors associated with chronic inflammatory disease. COPDGene took place between 2007 and 2012 at 21 clinical centers in the U.S., with follow-up visits scheduled every five years.

In the study, disease symptoms were measured using the COPD Assessment Test (CAT) score and the modified Medical Research Council (mMRC) dyspnea score. Dyspnea, or shortness of breath, is one of the most common symptoms of COPD. Quality of life was assessed using the St. George’s Respiratory Questionnaire (SGRQ) score and the 36-item Short Form (SF-36) general health survey.

Physical fitness was evaluated using the six-minute walk test, which measures the distance a person can walk on a flat surface within six minutes. Exacerbations, or episodes of disease worsening, were counted based on the number of self-reported episodes of increased COPD symptoms requiring treatment with antibiotics or steroids.

Of the more than 10,000 people who participated in COPDGene, 2,539 were selected for the new analysis.

All had a COPD stage 1–4, corresponding to mild to very severe disease, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) system, which is based on the values of forced expiratory volume in one second (FEV1) — a lung function parameter that measures how much air a patient can forcefully exhale in a single second.

A test to measure hemoglobin levels revealed that 366 (14%) patients had anemia and 125 (5%) had polycythemia. The remaining 2,048 (81%) had normal hemoglobin levels.

Those with anemia were mostly African American and had other illnesses affecting the heart and kidneys. In turn, those with polycythemia were mostly current smokers, with no specific racial background indicated. Notably, more than 80% of those with polycythemia were male. Regardless of hemoglobin levels, all patients had similar FEV1 predicted values.

Statistical analyses revealed that anemia — but not polycythemia — was linked to worse clinical outcomes, including worse COPD symptoms, poorer quality of life, reduced physical fitness, and more severe exacerbations.

When researchers looked at the hemoglobin levels as a continuum, however, they found that worse disease was observed at both ends of the spectrum.

Patients with polycythaemia “tended towards higher rates of severe exacerbations,” the researchers noted, but no statistical significance was found for either moderate or severe exacerbations.

These findings indicate that “haemoglobin derangements towards either extreme of the observed range are associated with increased morbidity in COPD,” the researchers wrote.

“Further investigation is necessary to determine whether haemoglobin derangement drives morbidity or merely reflects systemic inflammation, and whether correcting haemoglobin towards the normal range improves morbidity,” they wrote.