Lung microbiota may predict lung transplant rejection, death

Increased lung bacteria may predict chronic rejection and death in healthy adults who undergo lung transplantation, according to data published in The Lancet Respiratory Medicine.

“Lung transplantation is the only treatment for end-stage lung disease, but the average survival after lung transplant is very poor compared to other organ transplants,” Michael P. Combs, MD, clinical lecturer in the division of pulmonary and critical care medicine at the University of Michigan, Ann Arbor, told Healio. “Identifying factors, especially factors which might be modified, that contribute to the development of chronic rejection can help physicians develop treatments that might decrease the risk of developing chronic rejection and prolong survival after transplant.”

The prospective cohort study included 134 adults (mean age, 50.2 years; 40% women) who underwent lung transplantation at the University of Michigan from October 2005 to August 2017. The researchers evaluated bronchoalveolar lavage fluid collected from asymptomatic patients during pre-protocol bronchoscopy 1 year after transplantation. Researchers assessed patients’ lung function every 3 months by spirometry and monitored development of chronic lung allograft transplantation.

The primary endpoint was the composite of chronic lung allograft dysfunction or death 500 days after the 1-year bronchoscopy.

During the 500 days of follow-up, 18% of patients developed chronic lung allograft dysfunction, 4% died before confirmed development and 78% remained free of chronic lung allograft dysfunction.

The researchers reported that lung bacteria predicted chronic lung allograft dysfunction development or death within the 500-day follow-up after controlling for demographic and clinical factors. This relationship between lung bacteria and the primary outcome continued when the researchers analyzed chronic lung allograft dysfunction as a continuous variable (HR = 2.49; 95% CI, 1.38-4.48; P = .0024) or when comparing tertiles of bacterial burden (middle vs. lowest bacterial burden; HR = 4.94; 95% CI, 1.25-19.42; P = .022; highest vs. lowest bacterial burden; HR = 10.56; 95% CI, 2.53-44.08; P = .0012), according to the results.

“After accounting for previously known factors which are associated with developing chronic rejection, having increased numbers of lung bacteria [was] associated with a higher risk of developing chronic rejection after lung transplantation,” Combs told Healio.

Composition of the lung bacteria community was significantly different in patients who survived and remained free of chronic lung allograft dysfunction compared with those who developed chronic lung allograft dysfunction or died (P = .047).

Researchers observed no definitive association between individual bacterial taxa and death or development of chronic lung allograft dysfunction.

According to Combs, the researchers are unsure whether lung bacteria increase in patients with subclinical disease or if the increased lung bacteria directly cause chronic rejection.

“The lung microbiome, generally, and bacterial burden, in particular, are novel and potentially modifiable risk factors for chronic lung allograft dysfunction,” the researchers wrote. “Interventional studies are needed to determine if lung bacterial burden is modifiable or whether variation in lung microbiota explains variation in patient response to therapy after lung transplantation.”

For more information:

Michael P. Combs, MD, can be reached at micombs@med.umich.edu.