Exacerbations in Mild COPD Leads to Decline in Lung Function

Following acute exacerbations, patients with mild chronic obstructive pulmonary disease (COPD) were found to have the most significant loss in long-term lung function.

The findings were published in the American Journal of Respiratory and Critical Care Medicine.

“Very early on in this disease – at a time when outside a study like ours the majority of people would not have been diagnosed with COPD – patients appear to be losing lung function,” said lead study author Mark T. Dransfield, MD. “The whole medical community is focused on the latter stages of COPD, when, like diabetes and heart disease and other chronic diseases, we should probably be focused on prevent morbidity much earlier.”

Those who participated in the study were part of the multicenter, longitudinal, observational cohort study called COPDGene, which evaluated the underlying genetic factors of the disease. The COPDGene study enrolled more than 1000 African American and white COPD patients, who were current or former smokers.

For the current study, researchers analyzed data from the first 2000 participants who returned for a follow-up visit 5 years after joining the COPDGene study. Participants were grouped by severity of their disease based on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.

Additionally, the study identified participants with Preserved Ratio Impaired Spirometry (PRISm). These are patients who do not meet the GOLD criteria for COPD, but have reduced FEV1 (<80% of expected) but a normal FEV1/FVC ratio (>0.70%).

FEV1 was defined as the amount of air an individual could forcibly exhale in 1 second. FVC was the total amount of air that could be exhaled after the person took the deepest possible breath.

Exacerbations and acute respiratory events were defined as requiring antibiotics or systemic steroids, while severe exacerbations required hospitalization. The results of the analysis showed that across all the groups, which included individuals without COPD and those with PRISm, exacerbations and severe exacerbations were found to be common with 36.7% reporting events during the past 5 years.       

Overall, exacerbations of COPD patients were associated with FEV1 decline in excess of that predicted by aging and other time-dependent factors. For those with mild COPD (GOLD1), patients experienced the greatest FEV1 decline, with each exacerbation associated with an additionally 23 mL/year decline.

Each severe exacerbation was associated with an additional 87 mL/year decline. Moderate (GOLD 2) and severe (GOLD 3) COPD patients saw statistically significant, but smaller, declines in FEV1 with each exacerbation, compared with individuals with mild COPD.

To the researchers’ surprise, when they looked at smokers without an acute respiratory event, it was found that they did not experience FEV1. The same results were seen in those with PRISm who had an exacerbation of any severity.

Similar results were seen among patients with severe COPD (GOLD 4), which authors noted most likely reflected survivor bias. There was a steeper FEV1 decline experienced in current and intermittent smokers (9mL) compared with former smokers (2mL).

The findings revealed that individuals with mild COPD appear to have the greatest loss of lung function following an exacerbation.

“(Preventing exacerbations in this group) could reduce the risk of developing severe COPD,” Dransfield said.

As of now, medications that are used to prevent exacerbations are rarely, if ever, studied in patients with mild COPD. Dransfield believed that a randomized trial of this particular group may be warranted.

The study authors emphasized that although the study highlighted lung function loss associated with exacerbations in mild COPD patients, this does not mean that patients with severe COPD are not important. That is because these losses have important detrimental effects on patient health, despite being smaller, according to the study.

Researchers also highlighted in their current study, the 2 groups of smokers without COPD, and those with PRISm, experienced significant respiratory symptoms and impairment as a result of an acute respiratory event or exacerbation; however, they did not lose lung function.

This suggests the need for further studies in this area, which may shed some light on the heterogeneity of COPD, resulting in better treatments for distinct features in patients.

The authors noted that since this is an observational study, it cannot determine the causality or directionality between lung function loss and exacerbations, but instead shows it is possible that lung function loss leads to exacerbations.

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