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Respiratory virus infections linked to complication in lung transplant recipients
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Recent findings published in Clinical Infectious Diseases suggested that symptomatic respiratory virus infection is independently associated with the occurrence of chronic lung allograft dysfunction, a complication in lung transplant recipients that causes long-term allograft failure and death.
“If the association were confirmed in future prospective studies, at a minimum, it could identify specific patients at increased risk for development of [chronic lung allograft dysfunction (CLAD)] who could then be entered into trials of preventative or treatment strategies,” researchers wrote.
Researchers evaluated 250 adults who received a lung transplant at the University of Washington Medical Center between January 2007 and May 2012 to determine whether patients who develop respiratory virus infections were more likely to develop CLAD. They adjusted the results for age, type of transplantation (bilateral vs. single lung), acute rejection and cytomegalovirus (CMV) pneumonia.
Fifty patients were diagnosed with CLAD within a median duration of 95 weeks post-transplantation. Seventy-nine patients experienced 114 respiratory virus infections, with a median time of 19 weeks to first infection. Among patients who developed CLAD, 42% of patients had at least one respiratory virus infection vs. 28% of patients who did not develop CLAD.
Patients with respiratory virus infections were at an increased risk of developing CLAD 3 months (HR = 4.77; 95% CI, 1.91-11.64), 6 months (HR = 3.37; 95% CI, 1.5-7.54) and 12 months (HR = 2.44; 95% CI, 1.2-4.96) after infection.
A similar trend was observed in the composite endpoint of CLAD and death. The risk was greatest at 3 months (HR = 4.85; 95% CI, 2.76-8.43) and gradually declined by 12 months (HR = 2.75; 95% CI, 1.72-4.37).
The researchers concluded that the relationship between respiratory virus infection and CLAD warrants further research in a large, multicenter study.
“Although we found an independent association of symptomatic [respiratory virus infection] with CLAD, it is possible that [respiratory virus infection] could simply be a marker for patients who are otherwise predisposed to CLAD, rather than a cause of CLAD,” they wrote.
In a related editorial, Bradley J. Gardiner, MD, and David R. Snydman, MD, from the division of geographic medicine and infectious diseases at Tufts University School of Medicine, Boston, agreed that respiratory viruses likely lead to CLAD because of their transmissibility, pathogenicity and ubiquity.
“The interaction between these microorganisms and the host immune system becomes increasingly important in lung transplant recipients,” they wrote. “It seems likely that the development of [bronchiolitis obliterans syndrome] is a consequence of the complex interplay among the host immune system, the lung allograft, and the microbiome within it, perhaps as a form of immune ‘collateral damage’.”
Due to the “devastating impact” of CLAD in lung transplant recipients, Gardiner and Snydman noted that new treatment options and targets must be pursued. The development of new antiviral agents such as brincidofovir (Chimerix), pleconaril (Picovir, Schering-Plough), ALN-RSV01 (Alnylam Pharmaceuticals Inc.) and targeted antibodies would be “ideal” for these patients, they wrote, and routine screening as well as vaccination are other key strategies that could improve outcomes. – by Stephanie Viguers
Disclosure: One study author reports receiving funds from Ansun Biopharma and Gilead Sciences, and another author reports serving as a consultant for Gilead and Roche/Genetech. Snydman reports receiving funds from Chimerix, Cubist, Genetech, Merck and Seres Health.
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