Infectious Etiology of Bronchiolitis Obliterans: The Respiratory Viruses Connection – Myth or Reality?

A variety of viruses, such as the influenza viruses A and B, the human respiratory syncytial virus, the parainfluenza viruses, and the adenoviruses, cause seasonal respiratory tract infections in young children and adults. Also, studies indicate that these viruses are an important group of pathogens in pediatric and adult lung transplant recipients. More importantly, accumulating data on these infections among lung transplant patients suggest that these illnesses may have immediate and long-term implications for the function of the transplanted lung, including the development of bronchiolitis obliterans. This is important because patient survival and allograft function in lung transplantation remain limited by the development of bronchiolitis obliterans. Models of lung transplantation indicate that respiratory viral infections cause acute and chronic airway damage after transplantation. The mechanism leading to allograft damage by respiratory viruses may be related to the production of alloreactive cytokines such as interleukin (IL)-1, tumor necrosis factor, IL-6 and IL-8 during viral replication. Current clinical data are suggestive of a possible role for respiratory viruses in the development of bronchiolitis obliterans, but further control studies are required to evaluate the significance of respiratory virus infections as a causal factor in the development of bronchiolitis obliterans in lung transplantation.     

Respiratory viruses and chronic rejection in lung transplant recipients.

BACKGROUND; Chronic rejection manifested as obliterative bronchiolitis (OB) and bronchiolitis obliterans syndrome (BOS) continue to be major causes of morbidity and mortality after lung transplantation. Community respiratory virus (CRV) infection, including respiratory syncytial virus, parainfluenza virus, and influenza virus, can infect and also cause morbidity in lung transplant recipients. Because CRV and OB/BOS affect the small airways, we sought to determine whether CRV infections predisposed patients to OB/BOS. METHODS: To determine whether CRV predisposed to OB/BOS, a proportional hazards regression analysis of time to OB/BOS was performed with CRV as a time-dependent covariate. To determine the influence of OB/BOS on the subsequent development of CRV infection, we reversed the outcome and time-dependent covariate. To illustrate the effect of CRV on OB/BOS and the effect of OB/BOS on CRV, landmark plots were generated at specific time points. Time to development of OB/BOS was then compared using the Kaplan-Meier method. RESULTS: In our institution, we documented 40 infections caused by CRV in 33 lung transplant recipients during an 11-year period. Community respiratory virus infections occurred predominantly during seasonal community outbreaks, except for parainfluenza infections, which occurred throughout the year. The diagnosis of OB/BOS occurred throughout the year and was not associated with seasonal outbreaks of CRV. Community respiratory virus infection involving both upper and lower respiratory tracts did not predispose to OB or BOS (relative risk [RR], 1.1; 95% confidence interval [CI], 0.52-2.3; p = 0.81). However, patients with documented CRV infection of the lower respiratory tract were predisposed to high-grade BOS development (RR, 2.3; 95% CI, 1.1-4.9; p = 0.04). In addition, a patient with pre-existing OB or BOS was predisposed to developing both upper and lower respiratory tract infection with CRV (RR, 4.2; 95% CI, 1.9-9.4; p < 0.001). CONCLUSIONS: Patients with CRV infection of the lower respiratory tract were predisposed to high-grade BOS development, and patients with OB and BOS were predisposed to CRV infections.     

Influenza and parainfluenza respiratory viral infection requiring admission in adult lung transplant recipients

BACKGROUND: Although influenza and parainfluenza viruses commonly cause respiratory tract infections in the community, their incidence and clinical implications in adult lung transplant recipients have received little attention. METHODS: We performed a retrospective cohort study of influenza and parainfluenza viral infections in adult lung transplant recipients at the University of Pittsburgh Medical Center. RESULTS: Between January 1989 and March 1999, 39 cases (single-lung 25, double-lung 14) of influenza or parainfluenza respiratory viral infection were identified at a mean of 1.7 years (SD+/-1.4) after transplantation. The mean length of admission was 7 days. The cases included 15 patients with influenza (A, 11; B, 4) and 24 with parainfluenza (para1, 7; para2, 2; para3, 15). The median age at diagnosis was 48 years; there were 19 females and 20 males. Symptoms were reported in 30 patients and lasted for a median of 7 days before admission. These included cough (64%), shortness of breath (56%), and temperature elevation (33%). Chest infiltrates were seen in 14 (36%) patients, and 5 (13%) of them required intubation and mechanical ventilation. Viral pneumonia was diagnosed in 10 (5 influenza and 5 parainfluenza) patients, and concurrent bacterial pneumonia occurred in 4 patients. Transbronchial biopsy was performed in 36 patients, of whom 23 (64%) showed some degree of acute allograft rejection. CONCLUSION: Influenza and parainfluenza respiratory viral infections are associated with significant morbidity in adult lung transplant recipients. Active vaccination programs and the development of new antiviral agents active against these viruses are important for prevention.     

Clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin.

BACKGROUND: Paramyxoviral infections are reported in 6% to 21% of lung transplant recipients. Aerosolized ribavirin is used to treat paramyoxviral infections, but data on outcomes of this treatment in lung transplant patients are limited. METHODS: Lung recipients treated with aerosolized ribavirin from 1992 through 2000 for pulmonary respiratory syncytial virus (RSV) or parainfluenza virus (PIV) infection were assessed for the following variables: age; gender; underlying diagnosis; time from transplantation; duration of illness; clinical symptoms; and change from baseline FEV(1) (forced expiratory volume in 1 second). Outcomes included FEV(1) values at 30 and 90 days, need for intubation, development of acute rejection or obliterative bronchiolitis (OB) in the year after treatment; and 90-day and overall mortality. RESULTS: Fifteen patients received ribavirin for a median of 5 days (range 3 to 7) for 17 episodes of RSV (n = 12) or PIV (n = 5) infection. The clinical presentations of RSV and PIV infection were similar. Infection occurred a median of 520 days (range 7 to 1700) after transplantation. Three episodes required intubation; 2 episodes were fatal accounting for a 90-day mortality per episode of 12%. The FEV(1) at presentation declined by 25% (range 4% to 44%) from baseline. In 3 patients the FEV(1) did not return to baseline by 90 days or thereafter. All 3 patients had underlying pulmonary fibrosis (IPF) vs no IPF in 0 of 9 evaluable patients who recovered (p = 0.009). There was no correlation between response to ribavirin and subsequent development of OB. CONCLUSIONS: About 33% of lung transplant patients with lower respiratory tract paramyxoviral infections who were treated with inhaled ribavirin died or did not return to baseline FEV(1). This effect was acute and not associated with later complications, including OB. Underlying IPF may be a risk factor for failure to return to baseline. Larger, prospective, multicenter studies are required to confirm these findings.     

RNA respiratory viral infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice

These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of RNA respiratory viral infections in the pre‐ and post‐transplant period. Viruses reviewed include influenza, respiratory syncytial virus (RSV), parainfluenza, rhinovirus, human metapneumovirus (hMPV), and coronavirus. Diagnosis is by nucleic acid testing due to improved sensitivity, specificity, broad range of detection of viral pathogens, automatization, and turnaround time. Respiratory viral infections may be associated with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. The cornerstone of influenza prevention is annual vaccination and in some cases antiviral prophylaxis. Treatment with neuraminidase inhibitors and other antivirals is reviewed. Prevention of RSV is limited to prophylaxis with palivizumab in select children. Therapy of RSV upper or lower tract disease is controversial but may include oral or aerosolized ribavirin in some populations. There are no approved vaccines or licensed antivirals for parainfluenza, rhinovirus, hMPV, and coronavirus. Potential management strategies for these viruses are given. Future studies should include prospective trials using contemporary molecular diagnostics to understand the true epidemiology, clinical spectrum, and long‐term consequences of respiratory viruses as well as to define preventative and therapeutic measures.     

Community acquired respiratory viral infections after lung transplantation: clinical features and long-term consequences

Community acquired respiratory viruses (CARVs) are increasingly recognized as serious threats to lung transplant recipients. While CARVs such as respiratory syncytial virus, parainfluenza, influenza, and adenovirus usually cause self-limited illnesses in immunocompetent subjects, infections in the transplant recipient can be dramatic. As transplant recipients live longer and diagnostic methods improve, the burden of CARVs will undoubtedly increase. Because of limited therapeutic options, some patients may succumb to CARV infections, while many survivors develop chronic allograft dysfunction. Recognition of this latter phenomenon has implicated CARVs in the pathogenesis of bronchiolitis obliterans.     

Parainfluenza 3 Infections Early After Kidney or Simultaneous Pancreas–Kidney Transplantation

Parainfluenza virus (PIV) can cause serious infections after hematopoietic stem cell or lung transplantation. Limited data exist about PIV infections after kidney transplantation. We describe an outbreak of PIV‐3 in a transplant unit. During the outbreak, 45 patients were treated on the ward for postoperative care after kidney or simultaneous pancreas–kidney (SPK) transplantation. Overall, 29 patients were tested for respiratory viruses (12 patients with respiratory symptoms, 17 asymptomatic exposed patients) from nasopharyngeal swabs using polymerase chain reaction. PIV‐3 infection was confirmed in 12 patients. One patient remained asymptomatic. In others, symptoms were mostly mild upper respiratory tract symptoms and subsided within a few days with symptomatic treatment. Two patients suffered from lower respiratory tract symptoms (dyspnea, hypoxemia, pulmonary infiltrates in chest computed tomography) and required supplemental oxygen. Four of six SPK patients and eight of 39 of kidney transplant patients were infected with PIV (p = 0.04). In patients with follow‐up tests, PIV‐3 shedding was still detected 11–16 days after diagnosis. Despite rapid isolation of symptomatic patients, PIV‐3 findings were diagnosed within 24 days, and the outbreak ceased only after closing the transplant ward temporarily. In conclusion, PIV‐3 infections early after kidney or SPK transplantation were mostly mild. PIV‐3 easily infected immunosuppressed transplant recipients, with prolonged viral shedding.     

The Impact of Infection on Chronic Allograft Dysfunction and Allograft Survival After Solid Organ Transplantation

Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community‐acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction.     

Respiratory Viruses in Lung Transplant Recipients: A Critical Review and Pooled Analysis of Clinical Studies

Lung transplant recipients present an increased risk for severe complications associated with respiratory infections. We conducted a review of the literature examining the clinical relationship between viral respiratory infection and graft complications. Thirty‐four studies describing the clinical impact of influenza, respiratory syncytial virus, parainfluenza, human metapneumovirus, rhinovirus, enterovirus, coronavirus, bocavirus or adenovirus were identified. The detection rate of respiratory viral infection ranged from 1.4% to 60%. Viruses were detected five times more frequently when respiratory symptoms were present [odds ratio (OR) = 4.97; 95% CI = 2.11–11.68]. Based on available observations, we could not observe an association between respiratory viral infection and acute rejection (OR = 1.35; 95% CI = 0.41–4.43). We found a pooled incidence of 18% (9/50) of bronchiolitis obliterans syndrome (BOS) in virus‐positive cases compared to 11.6% (37/319) in virus‐negative cases; however, limited number of BOS events did not allow to confirm the association. Our review confirms a causal relationship between respiratory viruses and respiratory symptoms, but cannot confirm a link between respiratory viruses and acute lung rejection. This is related in part to the heterogeneity and limitations of available studies. The link with BOS needs also to be reassessed in appropriate prospective studies.     

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management.

BACKGROUND: Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. METHODS: English-language articles identified by a MEDLINE search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. RESULTS: The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older (p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness (p = 0.05), more likely to have developed Aspergillus infections later after transplantation (p = 0.019), and tended to have a higher incidence of invasive aspergillosis (p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients (p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([p = 0.045]) infections had significantly higher mortality. CONCLUSIONS: Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart-lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.     

Clinical Impact of Community-Acquired Respiratory Viruses on Bronchiolitis Obliterans After Lung Transplant

Community-acquired viral respiratory tract infections (RTI) in lung transplant recipients may have a high rate of progression to pneumonia and can be a trigger for immunologically mediated detrimental effects on lung function. A cohort of 100 patients was enrolled from 2001 to 2003 in which 50 patients had clinically diagnosed viral RTI and 50 were asymptomatic. All patients had nasopharyngeal and throat swabs taken for respiratory virus antigen detection, culture and RT-PCR. All patients had pulmonary function tests at regular intervals for 12 months. Rates of rejection, decline in forced expiratory volume (L) in 1 s (FEV-1) and bacterial and fungal superinfection were compared at the 3-month primary endpoint. In the 50 patients with RTI, a microbial etiology was identified in 33 of 50 (66%) and included rhinovirus (9), coronavirus (8), RSV (6), influenza A (5), parainfluenza (4) and human metapneumovirus (1). During the 3-month primary endpoint, 8 of 50 (16%) RTI patients had acute rejection versus 0 of 50 non-RTI patients (p=0.006). The number of patients experiencing a 20% or more decline in FEV-1 by 3 months was 9 of 50 (18%) RTI versus 0 of 50 non-RTI (0%) (p=0.003). In six of these nine patients, the decline in FEV-1 was sustained over a 1-year period consistent with bronchiolitis obliterans syndrome (BOS). Community-acquired respiratory viruses may be associated with the development of acute rejection and BOS.     

Effect of Hypogammaglobulinemia on the Incidence of Community-Acquired Respiratory Viral Infections After Lung Transplantation

Background

Hypogammaglobulinemia (HGG) has been associated with an increased risk of infectious complications in lung transplant recipients, but its effect specifically on community-acquired respiratory viruses (CARVs) remains unknown. This study aimed to determine if lung transplant recipients with HGG are at an increased risk of developing CARV infection. Secondary endpoints included the effect of HGG on lung function, incidence of rejection, and mortality.

Methods

A retrospective review of all lung transplant recipients from 2008 to 2011 was performed. Patients were stratified as either having HGG after transplantation or having normal IgG titers according to their nadir IgG level. HGG was defined a serum IgG level of <700 mg/dL. CARVs included human metapneumovirus, influenza A/B, respiratory syncytial virus A/B, parainfluenza 1/2/3, rhinovirus, and adenovirus isolated from bronchoalveolar lavage/wash, sputum, or nasal swab.

Results

The cohort consisted of 263 patients with a mean follow-up time of 612 ± 356 days. The incidence of CARV infection was 27% in patients with normal IgG titers and 23.4% in patients with HGG (P = .62). No difference in rejection, mortality, or lung function was found between the groups. As expected, patients who ever had a CARV infection had a significantly lower 1-second forced expiratory volume % reference on their most recent spirometry than those who had not had a CARV infection (81.6% vs 86.9%; P = .027).

Conclusions

Although CARV infection has been shown to affect lung graft function, these data suggests that HGG is not associated with the incidence of CARV infection.     

Indirect fluorescent antibody testing of nasopharyngeal swabs for influenza diagnosis in lung transplant recipients.

BACKGROUND: Rapid and reliable diagnosis of respiratory viral infections (RVI) in lung transplant recipients is essential to direct therapy of acute graft dysfunction and identify epidemic trends. Traditional techniques of serology and viral culture are limited by the lack of antibody response and delay in diagnosis. METHODS: We examined the clinical utility of indirect fluorescent antibody (IFA) testing in adult lung transplant patients with suspected RVI, compared with serology and culture. Nasopharyngeal and throat swabs (NT) were obtained to sample epithelial cells, followed by application of monoclonal antibody to respiratory syncytial virus, adenovirus, parainfluenza 1-3 and influenza A and B. The Bartels Respiratory Viral Detection kit was used with IFA results available within 24 hours. RESULTS: Nine of 18 patients tested positive for RVI with influenza A (n = 8) and influenza B (n = 1) detected. The sensitivity of IFA (67%) was higher than that of cell culture (45%). With intensive supportive therapy, infection was self-limiting in bronchiolitis obliterans syndrome (BOS) Grade 0-2 patients. However, patients with BOS Grade 3 manifested an acute exacerbation of airflow obstruction, which proved to be irreversible. CONCLUSIONS: Lung transplant patients with "flu-like" symptoms should proceed to IFA testing of NT swab specimens for early diagnosis. Samples collected within 7 days of symptom onset have high sensitivity as compared with serology and viral culture techniques.     

Virological,epidemiological and pathogenic aspects of human polyomaviruses

VIROLOGICAL ASPECTS: Human polyomaviruses (BK virus and JC virus), together with simian polyomaviruses (SV40 virus) share 75% of genomic homology. Their in vivo and in vitro genomes vary. Molecular analyses have identified several genotypes, some of which appear related to the development of viral diseases. Genomic modifications of the regulation area might provide the BKv with a pathogenic aspect thus enhancing the induction of tubulo-interstitial nephropathies in renal transplant recipients. EPIDEMIOLOGY: Human polyomaviruses are ubiquitous and exhibit a sero-prevalence of 60 to 80% in adults. Following a primary infection via the respiratory tract in childhood, these viruses are diffused in the blood using the B-lymphocytes during their latent stage in the urogenital tract. The reactivation that occurs after several years is asymptomatic and urinary excretion of BKv is observed in 4 to 6% of immunocompetent patients. PATHOGENIC POTENTIAL: Human polyomaviruses have a cytopathogenic effect on the urothelium and epithelium of renal transplant recipients. Infection by BKv may provoke hemorrhagic cystitis or urethral stenosis. The JCv is the cause of progressive multifocal leuko-encephalitis. The BKv (and less frequently the JCv) is responsible for tubulo-interstitial nephritis possible leading to renal transplant loss. They also have an oncogenic effect and their implication in the origin of tumours is the subject of many studies.     

Pulmonary infections increase exhaled nitric oxide in lung transplant recipients: a longitudinal study

The aim of this longitudinal study was to test whether pulmonary infections influence fractional exhaled nitric oxide levels (FENO) in otherwise clinically-stable lung transplant recipients. Levels of FENO were measured at least on 11 occasions in nine lung transplant recipients who attended for routine or urgent clinical review over 27.0 +/- 3.2 months period. Diagnosis of infection was based on clinical symptoms, functional measurements and radiological findings. Concentrations of FENO were also determined in 12 healthy volunteers. During follow-up, six patients had one, two had three, and one had four episodes of pulmonary infections. Overall, six upper and 10 lower respiratory tract infections were noted. Recipients with active infections developed increased FENO levels as compared with their own baseline levels measured in the clinically well period (10.8 +/- 1.3 vs. 7.6 +/- 1.1 ppb, p < 0.05). After antibiotic treatment, elevated FENO concentrations returned to baseline in association with full clinical recovery. Baseline FENO levels in lung transplant recipients and in healthy volunteers (6.0 +/- 0.5 ppb) were similar. The sensitivity and specificity of FENO measurement in detecting pulmonary infections were 57 and 96%, respectively. Our data suggest that pulmonary infections are associated with increased FENO levels in patients with lung allografts. Nevertheless, the measurement of FENO by itself as a screening tool for infections seems to be limited by its low sensitivity.     

Respiratory tract viral infections in bone marrow transplant patients

BACKGROUND: Community respiratory viruses such as respiratory syncytial virus (RSV), adenovirus, influenza A, influenza B, and the parainfluenza group are frequent causes of respiratory disease in bone marrow transplant (BMT) patients. MATERIAL AND METHODS: During the period from March 1993 to August 1999, 810 samples of respiratory secretions, nasopharyngeal aspirate (NPA) or bronchoalveolar lavage (BAL), from 722 patients with upper respiratory infections symptoms at the BMT unit of the Federal University in the state of Paraná, Brazil were evaluated for respiratory virus infection. RESULTS: One hundred thirty-six (17%) samples were reactive in 62 patients. RSV was found in 30 of 62 (48%), influenza A in 14 of 62 (23%), influenza B in 9 of 62 (15%), parainfluenza group in 7 of 62 (11%), and adenovirus in 2 of 62 (3%) infected patients. The most frequent clinical manifestations were cough and fever. Pneumonia occurred in 19 of 62 (31%) cases. The mortality rate was 23 of 62 (37%), being higher among patients infected with adenovirus and influenza A. CONCLUSIONS: Infections in BMT patients occurred during the outbreak period of these viruses in the community, highlighting the need to establish surveillance measures in units with immunocompromised patients in addition to the development of sensitive and rapid diagnostic tests for the detection of these viruses in patients with respiratory symptoms.     

Frequency of Pseudomonas aeruginosa Colonizations/Infections in Lung Transplant Recipients

Background

Lower respiratory tract infections remain a leading cause of morbidity and mortality after solid organ transplantation. The particularly increased susceptibility to infection is an especial problem in the early posttransplant period at the initial stage of immunosuppression, owing to direct contact with the hospital environment by mechanical ventilation, biopsies, injections, bronchoscopy, and bladder and vessel catheterizations exacerbated by the impaired clearance mechanisms after denervation of the transplanted lung. Airway colonization with Pseudomonas aeruginosa is common in lung transplant (LT) recipients. Therefore, we performed a retrospective analysis to address the frequency of P aeruginosa infections in our Center.

Materials and Methods

From January 2004 to December 2008, we performed 33 LT, including 4 heart-lung, 6 double, and 23 single lung transplantations. Respiratory samples were the main diagnostic material undergoing routine microbiological methods.

Results

P aeruginosa was isolated from 13 patients (39.4% of all 33 LT). In 10 cases (30.3%), we observed airway colonization together with lower respiratory tract infections. From 2005 to 2008, P aeruginosa was diagnosed in about 50% of LT patients each year: in 2005, 33.3%; 2006, 57.1%; 2007, 42.9%; and 2008, 40%.

Conclusion

LT recipients in our center are at high risk for pseudomonal airway colonisation and lower respiratory tract infection that may have a significant impact on posttransplant follow-up.     

Respiratory viruses in adult liver transplant recipients.

BACKGROUND: The contribution of respiratory viruses to respiratory disease in adult liver transplant (LT) recipients has not been studied. We performed a prospective audit to document the incidence of respiratory syncytial viruses ([RSVs], parainfluenza virus, influenza virus, and adenovirus) after LT, and to determine their contribution to respiratory disease in this setting. METHODS: Consecutive adult recipients were followed for 8 months after LT. Throat swabs were collected weekly for up to 12 weeks after LT, and virological surveillance was performed using conventional techniques (direct immunofluorescence and cell culture). A polymerase chain reaction assay for RSV was subsequently performed on selected specimens. Clinical data, including episodes of respiratory disease, were also recorded. RESULTS: During the study period, 51 patients received 53 LT. Five patients died, but no viruses were isolated from these patients at any stage. A total of 323 swabs were examined by conventional techniques and yielded 35 viral isolates (10.8%). Herpes simplex virus (type 1) accounted for 33 isolates, none of which were associated with respiratory disease. Two of 323 swabs (0.62%), in 2 patients, yielded respiratory viruses (both RSV); both patients had self-limiting, mild, upper respiratory tract symptoms. In these 2 patients, the polymerase chain reaction assay was more sensitive than conventional techniques and was able to detect extended RSV excretion. Of 51 recipients, 31 (61%) were always negative for viruses. Of 51 recipients, 10 developed respiratory failure, but no respiratory viruses were isolated from any of these patients. CONCLUSIONS: Respiratory viruses are rarely isolated from adult recipients after LT and are not associated with serious morbidity or with mortality. Routine surveillance for respiratory viruses in this patient population is not justified on the basis of this study.     

Clinical implications of respiratory virus infections in solid organ transplant recipients: a prospective study

BACKGROUND: There is limited information about clinical consequences of respiratory virus infections (RVI) in solid organ transplant recipients. No prospective epidemiological study has been published previously. METHODS: We selected a cohort of 152 transplant recipients (cardiac, hepatic and renal transplant recipients). Median time from transplantation was 17 months (range 1-50). They were prospectively followed-up for RVI during 7 months (October to April). Clinical and microbiological evaluation (cell culture, shell vial and polymerase chain reaction technique) of each RVI episode was made. RESULTS: We detected 81 RVI (0.91 episodes/patient/year). Complications were detected in 15/81 episodes (18.5%): acute bronchitis (10 cases), pneumonia (three cases; 3.7% of RVI episodes) and bacterial sinusitis (2 cases). In 4 of 81 episodes (5%), patients needed hospitalization. A respiratory virus was isolated in 17 of 68 nasopharyngeal samples (six respiratory syncytial virus, six influenza, four picornavirus, one adenovirus). Fever presented an 83% positive predictive value for the diagnosis of influenza virus infection among those with a positive microbiological isolation. There were no episodes of acute rejection coincidentally with RVI. Only 54% of the subjects had been previously vaccinated against influenza. CONCLUSIONS: Incidence of RVI among solid organ transplant recipients is similar to general population but complications are higher. A relationship between RVI and rejection was not detected. The rate of influenza vaccination was lower than expected. The presence of fever in a transplant recipient with RVI strongly suggests influenza infection.