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Treatment of respiratory syncytial viral and parainfluenza lower respiratory tract infection in lung transplant patients
170
Abstracts
The Journal of Heart and Lung Transplantation February 2001
Purpose: To prospectively define the epidemiology, clinical manifestations and acute sequelae of community acquired respiratory viruses (CRV) in a lung transplant (LTx) cohort. Procedures: From November 1999 to May 2000 we performed prospective viral surveillance on LTx patients (n⫽93) at our institution. Weekly telephone symptom surveys were performed by two nurses for upper (URI) or lower (LRI) respiratory symptoms. Patients who developed URI signs/symptoms (s/s) (rhinorrhea, sore throat or cough) underwent nasal washes (NW); those with s/s of LRI (wheezing, shortness of breath or hypoxia) underwent bronchoalveolar lavage (BAL). Infection was documented by positive rapid antigen (EIA) or rapid shell vial culture (RSVC). All pts received the influenza vaccine prior to November. A total of 96 NW and 48 BAL were performed in 72 symptomatic pts. All documented infections were LRI, except 1 RSV and 2 influenza A which were URIs. Summary: Isolates RSV Parainfluenza Influenza A Any virus Multiple viruses
# pts 11 7 10 28 4
# episodes 13 9 11
incidence 11.8% 7.5% 10.9% 30.1% 3.7%
Twenty-five episodes of biopsy-proven acute rejection developed within 90d. Fourteen episodes of superinfection occurred within 13d in 9 pts. Pneumococcus, Pseudomonas and aspergillus were the isolated pathogens. Conclusions: There was a significant incidence of CRV in symptomatic LTx. CRV LRI is commonly associated with AR in ⬍ 90d and bacteria and fungi superinfection. Prospective screening and early treatment may impact the acute and chronic sequelae of CRV in lung transplant recipients. 62 DIRECT FLUORESCENT ANTIBODY TESTING IN THE DIAGNOSIS OF INFLUENZAE INFECTION IN LUNG TRANSPLANT RECIPIENTS P.M. Hopkins, St. Vincent’s Hospital, Sydney, Australia Introduction: Rapid and reliable diagnosis of respiratory viral infections (RVI) in lung transplant recipients is essential in order to differentiate these from acute rejection or CMV infection which may have overlapping clinical manifestations. Traditional techniques of serology and viral culture are limited by delay in diagnosis and lack of antibody response. Aim: To examine the clinical utility of direct fluorescent antibody (DFA) testing (cost $25 AUD) in lung transplant patients with suspected RVI who presented from August-September 2000. Methods: Nasopharyngeal and throat (NPT) swabs were undertaken to sample epithelial cells followed by the application of monoclonal antibody to adenovirus, RSV, parainfluenza 1-3 and influenza A,B. The Bartels Respiratory Kit was used with all specimens sent to a reference laboratory for MDCK shell culture. Results: 7 of 17 subjects tested positive for influenza - 6 DFA positive (2 of these culture negative) and 1 DFA negative but culture positive. Of influenza subjects (6 type A, 1 B) the average age was 40.5 years, time post-transplantation 36 months, duration of illness 4 days, percentage decline in lung function 26% or absolute volume 510 ml and 6 of 7 patients were hospitalised. All results were available within 24 hours. Conclusions: 1. DFA of a NPT swab is a rapid cost effective non-invasive test of high sensitivity compared with culture in the
diagnosis of influenza infection 2. Routine viral culture of specimens may not be necessary after an initial positive DFA 3. Influenza A may produce significant clinical manifestations in LT recipients and occur in solated mini-epidemics late in the winter season 4. Negative viral culture may reflect in-vitro viral instability or suboptimal specimen handling. 63 TREATMENT OF RESPIRATORY SYNCYTIAL VIRAL AND PARAINFLUENZA LOWER RESPIRATORY TRACT INFECTION IN LUNG TRANSPLANT PATIENTS T.N. Hodges, F.P. Torres, M.R. Zamora, University of Colorado Health Sciences Center, Denver, CO, USA Lower respiratory infections (LRI) due to paramyxoviruses (PMV), respiratory syncytial virus (RSV) and parainfluenza (PIV), are associated with graft dysfunction and mortality following lung transplantation (LTx). RSV hyperimmune globulin (RSVIG), used for prevention and treatment of severe RSV infections may contain high titers against other PMV. We retrospectively reviewed our experience with PMV LRI and therapy with nebulized ribavirin (RV) and RSVIG to determine if this approach attenuates the effects of PMV LRI. From Feb 1992 to Oct 2000 34 episodes of PMV LRI (17 RSV and 17 PIV) in 28 pts were confirmed by direct fluorescent antibody and/or rapid shell vial culture of bronchoalveolar lavage. Onset was seasonal (Sept to May) occurring 511⫹182d post-LTx (range 16-2056). PMV LRI was not related to indication for LTx, recipient age or augmented immunosuppression. Six pts were treated with bronchodilators and steroids (group 1); 18 pts were treated with RV 2gms tid x 5d and RSVIG .75-1.5 gms/kg Ivx1 (Group 2). Solumedrol 5-10mg/kgx3d was given for biopsy proven acute rejection (AR) or clinical bronchiolitis. Follow-up has been 1295⫹/-506d (range 517-2107d) and 683⫹/-275d (range 547697d) for grps 1 and 2, respectively. No deaths occurred in either group. Ten episodes of AR occurred in grp 1, 10 episodes in grp 2 within 90d post-viral infection. Bronchiolitis obliterans syndrome (BOS) occurred in 6/6 pts in grp 1 (onset 142⫹/-105d) vs 1/18 pts in grp 2 (onset 119d). Four pts with prior BOS were excluded. Viral clearance was documents at end of treatment in group 2 pts. No adverse events were attributable to either drug. Combination therapy with aerosolized RV and RSVIG and appears to prevent the progression to bronchiolitis obliterans syndrome in symptomatic PMV LRI in lung transplant patients. 64 INCIDENCE OF BRONCHIOLITIS OBLITERANS SYNDROME UNAFFECTED BY ABSENCE OF CYTOMEGALOVIRUS H. Luckraz, L.D. Sharples, K. McNeil, J. Wallwork, Papworth Hospital NHS Trust, Cambridge, United Kingdom Background: Previously, we reported that prophylaxis against cytomegalovirus (CMV) infection did not influence the incidence of bronchiolitis obliterans syndrome (BOS) at 2 years. The effect of CMV presence without infection, on BOS is still not well understood. Moreover, the incidence and risk factors for BOS in CMV negative matched lung transplants has not been described. Aim: To determine the incidence of BOS in lung transplant patients with CMV negative (-) donors (D) and recipients (R) and evaluate the risk factors that predispose to BOS in this subgroup.
Abstracts
The Journal of Heart and Lung Transplantation February 2001
Purpose: To prospectively define the epidemiology, clinical manifestations and acute sequelae of community acquired respiratory viruses (CRV) in a lung transplant (LTx) cohort. Procedures: From November 1999 to May 2000 we performed prospective viral surveillance on LTx patients (n⫽93) at our institution. Weekly telephone symptom surveys were performed by two nurses for upper (URI) or lower (LRI) respiratory symptoms. Patients who developed URI signs/symptoms (s/s) (rhinorrhea, sore throat or cough) underwent nasal washes (NW); those with s/s of LRI (wheezing, shortness of breath or hypoxia) underwent bronchoalveolar lavage (BAL). Infection was documented by positive rapid antigen (EIA) or rapid shell vial culture (RSVC). All pts received the influenza vaccine prior to November. A total of 96 NW and 48 BAL were performed in 72 symptomatic pts. All documented infections were LRI, except 1 RSV and 2 influenza A which were URIs. Summary: Isolates RSV Parainfluenza Influenza A Any virus Multiple viruses
# pts 11 7 10 28 4
# episodes 13 9 11
incidence 11.8% 7.5% 10.9% 30.1% 3.7%
Twenty-five episodes of biopsy-proven acute rejection developed within 90d. Fourteen episodes of superinfection occurred within 13d in 9 pts. Pneumococcus, Pseudomonas and aspergillus were the isolated pathogens. Conclusions: There was a significant incidence of CRV in symptomatic LTx. CRV LRI is commonly associated with AR in ⬍ 90d and bacteria and fungi superinfection. Prospective screening and early treatment may impact the acute and chronic sequelae of CRV in lung transplant recipients. 62 DIRECT FLUORESCENT ANTIBODY TESTING IN THE DIAGNOSIS OF INFLUENZAE INFECTION IN LUNG TRANSPLANT RECIPIENTS P.M. Hopkins, St. Vincent’s Hospital, Sydney, Australia Introduction: Rapid and reliable diagnosis of respiratory viral infections (RVI) in lung transplant recipients is essential in order to differentiate these from acute rejection or CMV infection which may have overlapping clinical manifestations. Traditional techniques of serology and viral culture are limited by delay in diagnosis and lack of antibody response. Aim: To examine the clinical utility of direct fluorescent antibody (DFA) testing (cost $25 AUD) in lung transplant patients with suspected RVI who presented from August-September 2000. Methods: Nasopharyngeal and throat (NPT) swabs were undertaken to sample epithelial cells followed by the application of monoclonal antibody to adenovirus, RSV, parainfluenza 1-3 and influenza A,B. The Bartels Respiratory Kit was used with all specimens sent to a reference laboratory for MDCK shell culture. Results: 7 of 17 subjects tested positive for influenza - 6 DFA positive (2 of these culture negative) and 1 DFA negative but culture positive. Of influenza subjects (6 type A, 1 B) the average age was 40.5 years, time post-transplantation 36 months, duration of illness 4 days, percentage decline in lung function 26% or absolute volume 510 ml and 6 of 7 patients were hospitalised. All results were available within 24 hours. Conclusions: 1. DFA of a NPT swab is a rapid cost effective non-invasive test of high sensitivity compared with culture in the
diagnosis of influenza infection 2. Routine viral culture of specimens may not be necessary after an initial positive DFA 3. Influenza A may produce significant clinical manifestations in LT recipients and occur in solated mini-epidemics late in the winter season 4. Negative viral culture may reflect in-vitro viral instability or suboptimal specimen handling. 63 TREATMENT OF RESPIRATORY SYNCYTIAL VIRAL AND PARAINFLUENZA LOWER RESPIRATORY TRACT INFECTION IN LUNG TRANSPLANT PATIENTS T.N. Hodges, F.P. Torres, M.R. Zamora, University of Colorado Health Sciences Center, Denver, CO, USA Lower respiratory infections (LRI) due to paramyxoviruses (PMV), respiratory syncytial virus (RSV) and parainfluenza (PIV), are associated with graft dysfunction and mortality following lung transplantation (LTx). RSV hyperimmune globulin (RSVIG), used for prevention and treatment of severe RSV infections may contain high titers against other PMV. We retrospectively reviewed our experience with PMV LRI and therapy with nebulized ribavirin (RV) and RSVIG to determine if this approach attenuates the effects of PMV LRI. From Feb 1992 to Oct 2000 34 episodes of PMV LRI (17 RSV and 17 PIV) in 28 pts were confirmed by direct fluorescent antibody and/or rapid shell vial culture of bronchoalveolar lavage. Onset was seasonal (Sept to May) occurring 511⫹182d post-LTx (range 16-2056). PMV LRI was not related to indication for LTx, recipient age or augmented immunosuppression. Six pts were treated with bronchodilators and steroids (group 1); 18 pts were treated with RV 2gms tid x 5d and RSVIG .75-1.5 gms/kg Ivx1 (Group 2). Solumedrol 5-10mg/kgx3d was given for biopsy proven acute rejection (AR) or clinical bronchiolitis. Follow-up has been 1295⫹/-506d (range 517-2107d) and 683⫹/-275d (range 547697d) for grps 1 and 2, respectively. No deaths occurred in either group. Ten episodes of AR occurred in grp 1, 10 episodes in grp 2 within 90d post-viral infection. Bronchiolitis obliterans syndrome (BOS) occurred in 6/6 pts in grp 1 (onset 142⫹/-105d) vs 1/18 pts in grp 2 (onset 119d). Four pts with prior BOS were excluded. Viral clearance was documents at end of treatment in group 2 pts. No adverse events were attributable to either drug. Combination therapy with aerosolized RV and RSVIG and appears to prevent the progression to bronchiolitis obliterans syndrome in symptomatic PMV LRI in lung transplant patients. 64 INCIDENCE OF BRONCHIOLITIS OBLITERANS SYNDROME UNAFFECTED BY ABSENCE OF CYTOMEGALOVIRUS H. Luckraz, L.D. Sharples, K. McNeil, J. Wallwork, Papworth Hospital NHS Trust, Cambridge, United Kingdom Background: Previously, we reported that prophylaxis against cytomegalovirus (CMV) infection did not influence the incidence of bronchiolitis obliterans syndrome (BOS) at 2 years. The effect of CMV presence without infection, on BOS is still not well understood. Moreover, the incidence and risk factors for BOS in CMV negative matched lung transplants has not been described. Aim: To determine the incidence of BOS in lung transplant patients with CMV negative (-) donors (D) and recipients (R) and evaluate the risk factors that predispose to BOS in this subgroup.