Assessing Potential Biomarkers in COPD to Reduce Corticosteroid, Antibiotic Intake

In a recently published review, researchers outlined the background research and results of clinical trials assessing 2 biomarkers that have been investigated to assist in reducing corticosteroid and antibiotic use in patients with severe chronic obstructive pulmonary disease (COPD) exacerbations: blood eosinophils and procalcitonin (PCT).

Currently, many clinicians utilize the Anthonisen criteria to identify biomarkers of COPD exacerbations, which include increased dyspnea and sputum volumes, among other factors.

However, “such criteria can lead to the antibiotic and corticosteroid overuse, since they do not necessarily differentiate which patients are in need of such treatments, and in case of doubt, treatment will often be initiated to avoid undertreating,” researchers explained.

Use of inhaled corticosteroids (ICS) in patients with COPD is associated with an increased risk of pneumonia, diabetes, osteoporosis, and cataracts. Meanwhile, the overuse of antibiotics for respiratory infections helps drive multidrug resistance.

Other biomarkers for COPD exacerbations, including white blood cell count and C-reactive protein, are also not very sensitive, as they could be elevated for multiple reasons.

Approximately 20% to 40% of patients with COPD exhibit eosinophilic airway inflammation, while under normal conditions, eosinophils are dormant in the blood. Eosinophilic inflammation can be present in stable COPD and during exacerbations. Furthermore, “in healthy persons, eosinophils usually are not found in the lungs, and their presence in the lungs is indicative of an abnormal inflammatory reaction,” the authors wrote.

Although the association between blood eosinophil counts and relevant clinical COPD outcomes is not fully understood, most previous research found higher counts were linked with greater risks of readmissions for COPD, longer hospital stays, and future exacerbations.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommends eosinophil counts be considered when providers weigh administering ICS, as studies have found higher blood eosinophil levels increase the chances of ICS benefits.

Specifically, “the newest GOLD guidelines recommend ICS usage in patients with blood eosinophils ≥300 cells/mcL, and in patients with blood eosinophils >100 cells/mcL, and persistent exacerbations while on bronchodilators,” the researchers said.

Despite the wide use of orally administered systemic corticosteroids for acute exacerbations of COPD, these treatments do not improve long-term lung function decline and instead work to improve symptom recovery. The broad definition of COPD exacerbations may also lead to corticosteroid overuse.

To reduce corticosteroid intake, several investigators have proposed using blood eosinophil counts to guide use.

“One randomized controlled trial (RCT) used blood eosinophils to categorize patients as having eosinophilic or noneosinophilic exacerbations and found noninferiority when treating noneosinophilic exacerbations with placebo rather than systemic corticosteroids. Notably, there was a reduction of 49% in the total corticosteroid prescription for the eosinophil-guided group (P <.001),” the authors noted.

Overall, analyses show these counts could serve as potential biomarkers to help guide corticosteroid therapy for exacerbations. This may also help avoid unnecessary use of systemic corticosteroids.

As a biomarker of bacterial infection, PCT is released 2 to 6 hours following IL- 1β stimulation, the researchers explained. However, “it can be almost completely blocked by coadministration of [inteferon-beta], this suggesting a potential use in diagnosis and eventual applicability in differentiating between viral and bacterial acute-exacerbated COPD [AECOPD].”

Studies have yielded conflicting results when it comes to PCT between patients with viral and bacterial origin of COPD exacerbations, leading the authors to conclude it is not an accurate way to differentiate the two.

RCTs have also been conducted to determine if PTC measurements can predict which patients need antibiotics during a COPD exacerbation. By analyzing patients with lower respiratory tract infections who underwent daily PCT measurements, researchers discontinued antibiotics when levels were below a certain threshold.

One trial including 120 patients revealed “length of antibiotic administration in COPD patients with hospitalization-requiring exacerbation was reduced from 8.5 days to 3.5 days (P <.001).”

Additional larger trials are needed to better understand PCT guidance of antibiotic use in patients with COPD.

“There is evidence at level 1B (one RCT) to support the use of blood eosinophils in reducing the use of systemic corticosteroids in patients admitted to hospital with severe AECOPD,” the authors concluded.

“During admission of AECOPD, PCT measurements approximately every 48 hours can lead to a reduction in antibiotics of at least 30%, without any obvious disadvantages; in fact, such a strategy reduces mortality and antibiotic-related side effects in patients with lower respiratory tract infections (level 1A evidence), effects that seem likely also to apply to COPD patients,” they said.

Reference:

Sivapalan P, Jensen J. Biomarkers in chronic obstructive pulmonary disease: emerging roles of eosinophils and procalcitonin. J Innate Immun. Published online August 24, 2021. doi:10.1159/000517161