Rhinoviruses Fatal to Lung Transplant Recipients

GENEVA, Switzerland, Dec. 15 -- A common cold virus can be deadly for lung-transplant recipients, reported researchers here.

Two of 11 recipients infected with human rhinoviruses developed progressive respiratory and graft dysfunction leading to their deaths, reported Laurent Kaiser, M.D., of the University Hospital of Geneva, and colleagues.

The findings flout conventional wisdom holding that human rhinoviruses only infect the upper respiratory tract, the investigators wrote in the second December issue of the American Journal of Respiratory and Critical Care Medicine.

"The report by Dr. Kaiser and colleagues ends once and for all the argument that rhinovirus cannot infect the lower airways," wrote Marc B. Hershenson, M.D., of the University of Michigan in Ann Arbor, and Sebastian L. Johnston, M.D., Ph.D., of the National Heart and Lung Institute at Imperial College in London, in an accompanying editorial.

Dr. Kaiser and colleagues looked at the occurrence of chronic rhinovirus infection in 69 lung transplant recipients at two centers.

Their index case was a patient in whom rhinovirus was isolated repeatedly over a period of several weeks. The investigators and determined that the patient had a chronic infection with a single rhinovirus isolate.

They then looked at an additional 68 patients for the incidence and effects of chronic rhinoviral infections in an ongoing prospective study.

All lung transplant recipients who underwent bronchoalveolar lavage for various diagnostic and therapeutic reasons were screened for the presence of 13 different respiratory viruses with reverse transcription-polymerase chain reaction, and for three atypical bacteria (Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila).

The viruses included rhinovirus, influenza A and B, parainfluenza 1-3, respiratory syncytial virus A and B, enterovirus, human metapneumovirus, and coronaviruses OC43, 229E, and NL63.

The investigators followed patients over 19 months, using molecular analysis to screen for the 13 different respiratory viruses.

They found that three of the patients with lung graft dysfunction had rhinovirus identified by RT-PCR in both the upper and lower airways over 12 months. In two of the cases, rhinoviruses were repeatedly isolated in culture, and genetic sequence analysis confirmed that the infections were caused by persistent strains. In the index patient, the presence of rhinovirus was detected in the lower respiratory parenchyma by transbronchial biopsy.

Among all of the 69 lung transplant recipients, rhinoviral infections were documented in bronchoalveolar lavage specimens from 11 patients (including the index patient). Three presented with a persistent infection, and two of these patients died with graft dysfunction. The remaining eight patients had transient infections.

The authors concluded that lung transplant recipients should be monitored from signs of chronic rhinoviral infections.

"In lung transplant recipients with severe immunosuppression, clinical rhinovirus infection needs to be considered," said Dr. Kaiser. "This point might have substantial implications in terms of diagnostic procedures, clinical management, and anti-viral use, if available."

In their editorial, Dr. Hershenson and Dr. Johnston pointed to recent evidence suggesting that rhinoviruses may evoke inflammatory responses in lung cells independent of viral replication, although replication would be most likely need to induce a large response.

"However, until the present report, which includes positive bronchoalveolar cultures and lung immunochemistry, incontrovertible evidence of rhinoviral replication in the lung in the setting of spontaneous infection has been lacking," they wrote. "This report informs our understanding of the mechanisms underlying rhinovirus-induced exacerbations of asthma and COPD."

"These exciting new data raise the possibility that patients with asthma and other patients with chronic airway disease are unusually susceptible to rhinovirus infection leading to increased rates of exacerbation," they continued. "These results may also help explained the increased susceptibility of children to rhinovirus infections. Further studies on susceptibility to rhinovirus infection in the population are now required."

Neither editorialist reported a financial relationship with a commercial entity that has an interest in the subject of the editorial.