Risk Factors Identified for Exacerbations in Patients Without Flare-ups

Note: This story was updated May 21, 2021, as an earlier version of this article misidentified Renu Jain, PhD, scientific director of medical affairs at GlaxoSmithKline. 

People with chronic obstructive pulmonary disease (COPD) who do not experience exacerbations, or flare-ups, within the previous 12 months are still at risk of experiencing these sudden episodes of disease worsening at any time, new data suggests.

“Findings demonstrated patients who did not experience an exacerbation in the past year may still be at risk for one in the near future,” Renu Jain, PhD, scientific director of medical affairs at GlaxoSmithKline (GSK), one of the authors of the new study, said in an emailed statement to COPD News today.

The investigators also identified three risk factors — history of gastroesophageal reflux, chronic bronchitis, and mild to severe shortness of breath — that were significantly associated with the risk of COPD exacerbations in the future. According to researchers, these findings may aid clinicians in better assessing a patient’s risk for future exacerbations.

“These results may enable providers to easily and proactively identify which patients could be at risk for a detrimental COPD event and potentially lead to overall better management as it pertains to the condition,” Jain said.

Data from this first-of-its-kind analysis of future COPD exacerbations in flare-up-free patients was presented at the American Thoracic Society 2021 International Conference, held online May 14–19. The presentation was titled “Routinely Collected Clinical Features Are Associated with COPD Exacerbations in Individuals Without an Exacerbation History: A COPDGene Analysis.”

Acute exacerbations in COPD are marked by a sudden worsening of symptoms, such as extreme shortness of breath and persistent cough, along with severe fatigue and confusion. Patients who experience exacerbations often require hospitalization and prolonged care, which creates a significant healthcare burden.

Most importantly, exacerbations also are associated with poor outcomes, including higher mortality and greater morbidity. Mortality refers to a higher likelihood of death, while morbidity describes the frequency of the condition.

Currently, the only known risk factor for future COPD exacerbations is a past clinical history of these worsening episodes. However, for the remaining patients who do not have a history of such flare-ups, factors that may help identify those at risk remain unknown. 

To learn more, the team of researchers — from GSK, the University of Michigan, and National Jewish Health, in Colorado — analyzed data from 1,528 participants enrolled in the COPD Genetic Epidemiology study, known as COPDGene.

A majority (58.1%) of the participants were men, and the patients had a mean age of 69. Participants had no exacerbations in the year prior to their five-year study visit and all were followed for at least three years. More than half (66.3%) were former smokers.

Exacerbations of moderate to severe intensity were assessed every six months, either by phone or in virtual follow-up sessions. Overall, the participants had moderate COPD, as shown by a mean FEV1 % predicted of 65.5%. Of note, FEV1, or forced expiratory volume in one second, is a lung function parameter that measures the total amount of air a person is able to forcefully exhale in one second.

During follow-up, 508 patients (33.2%) had at least one moderate or severe exacerbation.

A history of gastroesophageal reflux or GERD, chronic bronchitis, and a score of two or higher on the modified Medical Research Council Dyspnea Score (mMRC) — which evaluates the level of shortness of breath, or dyspnea, in COPD and other respiratory diseases — all were associated with a significantly higher risk of exacerbations over the next three years. For context, a score of two on the mMRC means that a person experiences shortness of breath when hurrying or going up a slight hill.

Specifically, patients with an mMRC score of two or higher were 1.99 times more likely to have exacerbations in the following three years.

All three factors remained significantly associated with an increased risk of future COPD exacerbations even after researchers adjusted data to take into account parameters such as age, sex, smoking history, and FEV₁ % predicted.

Overall, “among COPD patients without history of exacerbation in the previous year, three readily available features — GERD, chronic bronchitis, and mMRC [greater than 2] — are associated with a significantly increased rate of exacerbations over 3 years,” the investigators wrote.

“Through this first-of-its kind analysis, the team has identified routine clinical risk factors associated with the risk of a COPD exacerbation in patients with COPD who do not have a history of exacerbations,” Jain said.

“Our collaboration with COPDGene is an example of how we are constantly striving to expand our knowledge and understanding of COPD and help revolutionize the way that medicines are developed,” she added.