CF Patients Infected with CMV May Have Faster Disease Progression, Study Finds

People with cystic fibrosis (CF) who have been infected by cytomegalovirus (CMV) are more likely to experience faster disease progression and reach end-stage lung disease compared to those who have not been infected, a study shows.

Findings of the study, “Cytomegalovirus — an unrecognised potential contributor to cystic fibrosis disease progression?,” were published in the European Respiratory Journal.

CF is a genetic disorder caused by mutations in the CFTR gene, which provides instructions to make the cystic fibrosis transmembrane conductance regulator (CFTR) protein. This protein works as a channel that transports electrically charged molecules and water in and out of cells.

In people with CF, this type of molecule transport is impaired, leading to a buildup of fluid in the lungs that makes breathing more difficult and patients more likely to develop lung infections. Life expectancy for CF patients is relatively short (an average of 37 years), and for that reason, many patients choose to undergo lung transplant, if possible.

CMV is a common type of herpes virus that spreads through close contact with bodily fluids. It is often contracted during late adolescence and early adulthood, and is perceived as harmless, with people who have been infected usually asymptomatic. Still, it can have a severe impact on people’s health. Even in the general population, infection by CMV can lead to cognitive impairment, frailty, heart disease, and all-cause mortality.

For patients with CF, infection by CMV can contribute to poor outcomes, in particular for lung-transplanted patients who may suffer severe chronic transplanted lung dysfunction.

In addition, according to researchers from Canada’s University of Calgary, CMV might be an unknown contributor to disease progression in people with CF.

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“We already know that the cytomegalovirus can harm the health of cystic fibrosis patients who have had a lung transplant, as it can increase the risk of organ rejection, but we know very little about how this virus affects pre-transplant cystic fibrosis patients,” Michael Parkins, MD, associate professor at the University of Calgary and the lead author of the study, said in a press release.

In a retrospective study, Parkins and his team reviewed the medical records of adults with CF who had been referred for lung transplantation at the Calgary Adult Cystic Fibrosis Clinic and  tested for CMV.

From the 71 patients initially referred for lung transplantation since 1991, 59 (83%) received bilateral (double) lung transplant and 12 (16.9%) died before undergoing the procedure. Among the 56 patients who had been included in the final analysis, 30 (54.6%) were infected with CMV.

From all the disease contributing factors considered, including patients’ sex, age, body mass index (BMI), education, genetic background, and presence of viral or bacterial infections, CMV infection was the most important factor found to be linked to CF progression.

Patients who were positive for CMV died or underwent lung transplantation at a much younger age compared to those who had tested negative for CMV, with a mean difference of 9.35 and 7.36 years, respectively.

“Cytomegalovirus is normally dormant in people who have it, but it can become active again and spread more quickly after infection with other bacteria. We know that cystic fibrosis patients are more likely to develop lung infections, so it’s possible that repeated cycles of activation of the virus [exacerbate] the damage to patients’ lungs, contributing to faster disease progression,” Parkins said.

Still, he highlights that this association “does not necessarily mean that cytomegalovirus directly causes more rapid disease progression.” Although these findings provide evidence that CMV infection may have an impact on CF progression, additional studies are warranted to fully understand CMV’s role in this disease.

The authors noted that these findings should be taken with a grain of salt because of the study’s limitations. These include the fact that the study had been carried out in a single location, and included a small sample of patients whose clinical outcomes could not be attributed to a specific cause in some cases.

“This is an exploratory study that raises an interesting hypothesis, however, due to the limitations of the study, it does not confirm a role of the cytomegalovirus in cystic fibrosis. Further observational studies are necessary to be able to confirm the value of these findings,” Tobias Welte, MD, professor at Hannover University in Germany, and president of the European Respiratory Society, said.

Several anti-CMV vaccines are being explored in other medical areas. Supported by these findings, it becomes reasonable that such treatment approaches could be tested among people with CF in order to prevent CMV infection or virus reactivation.

“If this association is confirmed in larger multi-center studies, strategies exploring the use of pre-emptive and prophylactic [preventative] anti-viral treatments, including acyclovir [sold as Zovirax, among other names] or valganciclovir [sold as Valcyte], in specific populations may be in order,” researchers said.

“Individuals with CF who are seronegative for CMV may derive benefit from effective vaccine strategies both acutely and in the long-term setting of their risk for transplant,” they added.