Previous studies have established that patients aged 65 and older with COPD are at elevated risk for influenza-associated complications, such as hospitalization, ICU admissions, and death. Guidelines recommend that patients with COPD receive seasonal influenza vaccination, but few studies have examined whether flu vaccines may be beneficial in high-risk patients with COPD. Furthermore, it is difficult to estimate the number of deaths attributable to the flu in this patient population.

“In general, vaccines are challenging to study because many people refuse to take them,” says Yinong Young-Xu, SCD. “Patients who participate in vaccine trials or take vaccines often tend to be more health conscious and follow public health guidelines. These patients are usually healthier than those who don’t get vaccinated, even before they get the vaccine.” He adds that many influenza-associated mortalities occur from secondary complications when influenza viruses are no longer detectable.

Survival Benefits of Flu Vaccine Assessed

For a study published in PLOS ONE, Young-Xu and colleagues investigated whether influenza vaccination among patients with COPD could help reduce mortality among veterans aged 65 and older. “The proportion of smokers among male veterans and COPD is higher than the general population,” explains Young-Xu. “We wanted to see if influenza vaccination could help this vulnerable patient population.”

Participants were diagnosed with COPD and received care at the United States Veterans Health Administration (VHA) during four influenza seasons from 2012–2013 to 2015–2016. VHA EHRs and Medicare administrative files were linked to the CDC’s National Death Index cause of death records and influenza surveillance data. Throughout the four influenza seasons, the study authors reviewed data on 1,856,970 person-seasons in which 65% had a record of influenza vaccination while 35% did not.

Influenza Vaccine Helps Prevent Deaths in COPD

“Our study showed that vaccines help to prevent deaths in patients with COPD,” says Young-Xu. Influenza vaccination was associated with a reduced risk of death during the most severe periods of the flu seasons, even after adjusting for comorbidities, demographics, and socioeconomic characteristics. The influenza vaccination was associated with a 75% reduced risk of all-cause mortality, a 76% decreased risk of death from respiratory causes, and an 82% lower risk of death from pneumonia or influenza causes. These associations were strongest when flu activity was at its highest.

Importantly, a significant part of the observed effects was attributed to “healthy vaccinee” bias. A lower mortality risk was found during periods when there was no influenza activity and before patients received the vaccine. Hazard ratios (HRs) for all-cause mortality declined from 0.59 when influenza circulation was lowest (level 1) to 0.25 at the peak of the season, during which the average positive flu test rate was 30% (level 4). Mortality rates from respiratory causes and from pneumonia or influenza were 32% and 51%, respectively (Figure). However, influenza vaccination had no impact on hospitalizations due to urinary tract infections.

Data Increases Confidence in Vaccine Effectiveness

“Clinicians can use these findings to inform their patients with COPD about how getting vaccinated against influenza can potentially save their life,” says Young-Xu. “We also quantified the effect of ‘healthy vaccinees’ and separated these data from the vaccine’s health effects to demonstrate the effectiveness of the flu vaccines for those who get vaccinated, even before they got the vaccine. During peak flu season—when we expect influenza vaccines to be the most helpful in preventing deaths— patients who were vaccinated had a 30% lower mortality rate than those who were unvaccinated. After factoring in a 20% preexisting benefit, the real effect is a 10% reduction in mortality. These data can ensure that clinicians do not overestimate the benefits of these vaccines and help them encourage patients to be cognizant of healthy behaviors such as vaccination.”

According to Young-Xu, the uptake of vaccines during the COVID-19 pandemic is especially complicated. “People accept or refuse vaccination for many different reasons, including their personal beliefs and behaviors,” he says. “Unfortunately, situations can change quickly, vaccine effectiveness can wane over time, and new variants can appear. We plan to study the combined impact of vaccines and health behaviors in future research.”