Unreported Exacerbations of COPD Could Affect Outcomes of Clinical Trials

April 24, 2019

Unreported exacerbations of chronic obstructive pulmonary disease (COPD) in clinical trials may be more prevalent than researchers realize, and this could cause them to underestimate the frequency of clinically significant exacerbations. This could affect the conclusions studies reach about the effectiveness of treatments.

Patients with chronic obstructive pulmonary disease (COPD) who fail to report exacerbations could create serious implications in clinical trials, according to the study in the International Journal of Chronic Obstructive Pulmonary Disease.

“In our study 23.5% of patients would have been reclassified from infrequent to frequent exacerbators if unreported exacerbations were counted. Therefore underreporting of exacerbations may lead to incorrect classification and treatment in COPD patients,” researchers said.

The phenomenon may also affect how studies report effectiveness of treatments, the researchers found. "Most clinical trials utilise event-based exacerbation definitions and therefore may underestimate the frequency of exacerbations and the effects of treatments," they wrote.

Clinically diagnosed COPD patients were recruited from June 2011 to December 2013. Patients diagnosed with asthma were excluded. A total of 43 participants in stable condition attended an initial visit at baseline for clinical assessment and spirometry measurements, which included forced expiratory volume in 1 second (FEV1), forced vital capacity, and peak expiratory flow. Patients met with the study team once a month for a period of 3 months and were followed up for a minimum of 6 months.

Participants also reported to the study team when they developed symptoms of an upper respiratory tract infection, an increase in sputum volume, or symptoms of dyspnea or cough. Clinical data as well as blood and airway samples were collected both when patients were stable and when they were experiencing exacerbations. Inflammatory markers were measured and virological and bacterial analyses were performed.

Of the 43 patients recruited, 3 did not complete a minimum of 6 months of follow up and were excluded from data analysis. Throughout the study, a total of 27 exacerbations were reported by 17 participants. No differences were found in clinical characteristics between participants who reported an exacerbation and those who didn’t. While 13 exacerbations were reported to the patients’ healthcare providers, 14 went unreported and untreated.

Researchers found no differences in symptoms, lung function, inflammatory markers, and incidence of infection between participants who reported or didn’t reported exacerbations. Participants who reported all exacerbations had higher BODE scores (body mass index, airflow obstruction, dyspnea,exercise capacity), lower FEV1, and a higher frequency of exacerbations than those who didn't. Researchers determined that failure to report an exacerbation was not related to the severity, cause, or inflammatory profile of the exacerbation. It was also found that those with less severe COPD and a lower frequency of exacerbations were less likely to report an exacerbation. The decision to report an exacerbation was not determined to be an objective marker of exacerbation severity.

“Patients with more severe COPD do have higher reporting rates,” researchers noted. “Therefore, exacerbations may be particularly underreported in milder COPD patients and the higher incidence of exacerbations in more severe COPD may partly reflect differences in exacerbation reporting.”

The Global Initiative for Obstructive Lung Disease defines an exacerbation as an acute worsening of respiratory symptoms that results in additional therapy. Acute exacerbations are major causes of morbidity and mortality in patients with COPD and their prevention is a major therapeutic goal of treatment.

The reasons why patients abstain from reporting exacerbations remain unclear. Researchers suggest that a better understanding of the factors that determine a failure to report exacerbations is required to improve future reporting.

“The study findings need to be replicated in larger numbers and particularly in patients with more severe COPD to further examine the effects of baseline disease severity on exacerbation reporting. Non-reporting of exacerbations may lead to adverse outcomes in patients, incorrect classification of disease severity and incorrect treatment decisions. A better understanding of the factors that influence patients’ decisions not to report exacerbations is required to increase reporting and improve outcomes for COPD patients,” researchers concluded.

Reference

Calderazzo MA, Trujillo-Torralbo MB, Finney LJ, et al. Inflammation and infections in unreported chronic obstructive pulmonary disease exacerbations. Int J Chron Obstruct Pulmon Dis. 2019;14:823-833. doi: 10.2147/COPD.S191946