Inflammatory Biomarkers Distinguish COPD from Asthma-COPD in Some Cases

The inflammatory biomarkers FeNO and EOS can be used as indicators to distinguish people with chronic obstructive pulmonary disease (COPD) from those with COPD combined with asthma, a study has found. 

These biomarkers’ diagnostic value, however, was limited to patients who had not been treated with inhaled glucocorticosteroids and those who never smoked. 

The study, “The Value of Inflammatory Biomarkers in Differentiating Asthma–COPD Overlap from COPD,” was published in the International Journal of Chronic Obstructive Pulmonary Disease.

COPD and asthma are considered different lung conditions, but they have many overlapping symptoms, including chronic coughing, wheezing, and shortness of breath. 

COPD typically occurs in older people, primarily caused by smoking, which leads to regular sputum production and progressive worsening. In contrast, asthma is more common in younger individuals and is mostly triggered by allergens leading to airway inflammation and less sputum.

However, in some people, both conditions occur together — a condition called asthma-COPD overlap (AC) — with prevalence increasing with age. 

Given the overlap in symptoms, there is a need for biomarkers to distinguish patients with COPD from those with both COPD and asthma. 

Two standard markers of airway inflammation used in diagnosing asthma and monitoring treatment are increased blood levels of immune cells called eosinophils (EOS) and higher fractional exhaled nitric oxide (FeNO), in which nitric oxide is produced by the body to fight inflammation. 

Additionally, other immune cells known as neutrophils, as well as the ratio of neutrophils and immune cells called lymphocytes (NLR), were found to be much higher in patients with COPD or asthma-COPD than those in healthy people. 

To find out if EOS, FeNO, and NLR could be discriminating biomarkers for asthma-COPD overlap, researchers based at the First Affiliated Hospital of Xi’an Jiaotong University in China analyzed the medical records of 182 people, including 134 with COPD alone (average age 67.66 years) and 48 patients with ACO (average age 61.13). 

The proportion of study participants with a history of smoking was lower in the ACO group (41.7%) than in the COPD group (59.0%).

Overall, compared to patients with COPD, people with ACO had significantly higher FeNO (median 37.50 parts-per-billion (ppb) vs. 24.50 ppb) and EOS (median 0.20 billion cells per liter vs. 0.10 billion/L). 

This difference also was seen in patients who never had received inhaled glucocorticosteroids and those with a smoking history. 

Only FeNO levels were significantly different between the two groups among patients who had never used glucocorticosteroids or smoked. The neutrophil to lymphocyte ratio was not different between COPD and ACO. 

The finding that EOS was similar in COPD and ACO in steroid-treated patients “may be attributed to the reduced expression of inflammatory biomarkers when using [glucocorticosteroids],” the researchers wrote. 

Higher FeNO levels were positively correlated with increased EOS numbers in patients with COPD and asthma, especially those who never had used glucocorticosteroids and individuals who smoked. 

Also, in ACO patients, low FeNO was positively correlated with worse lung function, as measured by spirometry. To explain this result, the authors suggested that patients with worse lung function “may use more [glucocorticosteroids] to relieve [shortness of breath] symptoms, which reduced the concentrations of FeNO.”

While there was no relationship between lung function and EOS numbers, a lower neutrophil-to-lymphocyte ratio was found to correlate with better lung function. 

In all patients studied, a statistical analysis identified 39.5 ppb of FeNO as the best cut-off value to distinguish COPD from ACO, with an ability to correctly identify ACO of 50% (sensitivity) and the likelihood of finding those without the condition of 83.6% (specificity). The optimal cut-off also was 39.5 ppb among those without glucocorticosteroid use and 31.5 ppb in patients who smoked. 

Regarding EOS, 0.335 billion/L was the best cut-off value to diagnose ACO in all patients, with a 39.6% sensitivity and 90.3% specificity.

The low sensitivity of using EOS indicated that “only FeNO can be used to distinguish the two diseases after excluding the effect of both [corticosteroid] use and smoking history at the same time,” the researchers wrote. After this adjustment, the best cut-off value for FeNO was 27.5 ppb, with 81.8% sensitivity and 60.7% specificity.

The sensitivity improved by combining both biomarker measures. Together, FeNO levels of 39.5 ppb or higher, plus an EOS of 0.335 billion/L or greater, had a 69.8% sensitivity and 75.5% specificity overall. In patients without a history of steroids and smoking, a 91.7% sensitivity and 43.3% specificity were achieved when the two biomarkers were combined (FeNO levels of 27.5 ppb or higher together with EOS of 0.305 billion/L or greater).

“Our results demonstrate that the inflammatory biomarkers FeNO and EOS can be used to support the diagnosis of ACO, especially in patients without a history of [glucocorticosteroid] use and smoking,” the team concluded. “However, there was no diagnostic value of them in patients with a history of smoking and [glucocorticosteroid] use.” 

According to the team, the results need to be confirmed with data from multiple centers and with a larger sample size.