Long-term Effects of Post-transplant Respiratory Viral Infections

Data suggest respiratory infections in transplant patients are associated with increased long-term mortality and morbidity.

Respiratory viral infections (RVI) can have severe long-term and sometimes fatal consequences. However, the clinical impact in the transplant population is not well understood. During the 48th annual meeting of the IDSA in Vancouver, Marian G. Michaels, MD, MPH, Professor of Pediatrics and Surgery, Pediatric Infectious Diseases, Children's Hospital of Pittsburgh of UPMC, reviewed data that suggest that RVI may impact mortality and morbidity over the long-term, and that this phenomenon is worthy of study.

Michaels said that immunosuppression can lead to decreased clearance and protracted infections, and that “there is often evidence of direct damage to the lung, particularly with prior lung impairment such as lung transplant, graft versus host disease, and damage to the diaphragm. This can lead to impaired mucociliary function, impaired cough reflex, and lack of lymphatic drainage.” This is accompanied by indirect morbidity in terms of induced epithelial injury and stimulation of alloimmune cells in graft.

Citing data from numerous studies, Michaels pointed out that there is marked mortality associated with RVI and bronchiolitis obliterans syndrome (BOS) in various transplant populations. Further, confirmed community-acquired infections tended to be associated with BOS and death.

Prospective data from a cohort study in Geneva that followed 77 patients over three seasons from 2003 to 2006 showed the presence of 63 community-acquired RVI in 59 of the patients, including rhinovirus, coronavirus, parainfluenza (PIV), respiratory syncytial virus (RSV), human metapneumovirus, and influenza. The investigators found no significant difference between the rate of acute rejections (AR) and virus-negative/virus-positive patients at 30 and 90 days post transplant. Michaels said that the investigators also looked at AR plus RVI together on forced expiratory volume in one second (FEV1) and found that FEV1 gets worse over time. "The follow-up was short -- only six weeks -- but these are intriguing data,” she said.

Michaels also reviewed data on acute rejection in lung transplant from a prospective study of 48 patients with RVI and 45 without in which 18 patients developed BOS during the study. At three months post transplant, 16 of 48 patients with RVI had acute rejection or a reduction in FEV1 of greater than 20%. Additionally, 10 of 16 patients had BOS one year out, and 7 of 16 patients (44%) died, compared with 9 of 45 patents (20%) who did not have RVI.

A prospective study done in Spain involving 386 hematopoietic stem cell transplant (HSCT) adults showed a significant increase in mortality in patients with lower respiratory tract infections (LRTI) both at100 days and two years out, compared with patients who did not have LRTI.

Finally, Michaels presented a case study from her clinic involving a 10-year-old girl with cystic fibrosis who received a double lung transplant. Four months post transplant, she presented with severe shortness of breath, fever, cough, and worsening pulmonary function. A bronchoscopy and biopsy showed adenovirus pneumonia. "She recovered with aggressive supportive treatment and IV cidofovir," Michaels said.

However, her FEV1 never returned to baseline. Although she did not have a rejection, she went on to develop BOS. "She subsequently underwent multiple hospitalizations, multiple other infections, and ultimately died from BOS. In my mind, this youngster's BOS was due to adenovirus," Michaels said.

Prospective surveillance studies using nucleic acid-based assays that include in-patient and outpatient long-term follow-up are needed to better define the true consequences of RVI in these settings. Although the current studies are weighted toward early infections, Michaels said that they do suggest that acute rejection or BOS appear to impact long-term outcomes in lung transplant patients. In hematopoietic stem cell transplant patients, LRTI, PIV, and RSV also appear to be associated with increased risk for negative outcomes.