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353 Secretory IgA Is Reduced in Lung Transplant Recipients and Is Associated with Community Acquired Respiratory Viral Infection
S122
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
Perfusion (n⫽6) O2 consumption (mL/100g/min)
0.08⫾0.01
–
–
Lactate production: Initial, final (mmol/ min)
0.031⫾0.004, 0.007⫾0.002
–
0.004 (initial vs final)
Cardiac output (mL/min)
0.004
Measurement During perfusion mean⫾SEM
Final assessment median(IQR)
D.C. Chambers. Queensland Centre for Pulmonary Transplantation & Vascular Disease, The Prince Charles Hospital, Brisbane, QLD, Australia.
Cold Storage (n⫽7)
p value
1285 (1120-1413)
280 (235-455)
LV dP/dt max (mmHg/sec) 2092 (1986-2153)
190 (139-395)
0.003
Efficiency (Joules/mL O2 consumed)
0.24 (0.19-0.34)
0.01 (0.00-0.07)
0.01
0.7 (0.3-1.6)
5.1 (4.4-6.3)
0.01
Lactate rise (mmol/L)
Conclusions: Crystalloid microperfusion: 1. Facilitates aerobic metabolism and resuscitates the DCD heart. 2. Provides functional and metabolic recovery superior to cold storage and comparable to blood perfusion. 3. Shows promise for improved clinical preservation of DCD and marginal donors. 352 Community Acquired Respiratory Viral Infection Is a Risk Factor for Death after Lung Transplantation D.C. Chambers,1 A. Burke,1 T.W.V. Daniels,2 S.T. Yerkovich,1 P.M.A. Hopkins.1 1Qld Centre for Pulmonary Transplantation & Vascular Disease, The Prince Charles Hospital, Brisbane, QLD, Australia; 2Department of Respiratory Medicine, Southampton University Hospital, Southampton, Hampshire, United Kingdom. Purpose: Community acquired respiratory viral (CARV) infections are believed to contribute to morbidity and mortality after lung transplantation, but previous studies have not conclusively established the evidence base in this area. Methods and Materials: A prospective cohort study was performed at a single centre from August 1998 to March 2010 (n⫽180 lung transplant recipients). CARV infection (human metapneumovirus (hMPV), respiratory syncytial virus (RSV), influenza A (Flu A), influenza B (Flu B), adenovirus and parainfluenza virus (PIV)) was confirmed using polymerase chain reaction of upper (nasopharangeal swab) and/or lower (bronchoalveolar lavage) respiratory tract secretions in a patient with compatible clinical findings and a ⬎ 10% fall in FEV1. CARV infection and BOS were included as segmented time-dependent covariates in a Cox proportional hazards model with death as the outcome variable. Results: 87 patients (43% of the total cohort) had a total of 147 separate CARV episodes: 42 PIV, 26 hMPV, 37 RSV, 26 Flu A, 10 Flu B, and 6 adenovirus. Only BOS (HR 3.84 (2.12-6.97), p⬍0.001) and low serum IgA (HR 0.75 (0.58-0.96), p⫽0.02) were risk factors for acquiring CARV infection. Infection with either RSV or hMPV was associated with an increased risk of death (HR 3.54 (1.86-6.98), p ⬍0.001), and the effect persisted after multivariate analysis. Predictors of time to death post-transplant Univariate
HR
95% CI
p value
Presence of BOS RSV infection hMPV infection PIV infection RSV or hMPV infection
86.40 2.69 2.44 1.86 3.54
21.77-342.94 1.30-5.54 1.06-5.6 0.83-4.17 1.83-6.85
⬍0.001 0.007 0.036 0.134 ⬍0.001
Multivariate
HR
95% CI
p value
Presence of BOS RSV or hMPV infection
67.04 2.12
16.77-268.07 1.06-4.25
⬍0.001 0.035
Conclusions: Patients with BOS and low serum IgA are more prone to CARV infection. Infection with hMPV and RSV, but not other CARVs, is independently associated with an increased likelihood of death. 353 Secretory IgA Is Reduced in Lung Transplant Recipients and Is Associated with Community Acquired Respiratory Viral Infection S.T. Yerkovich, M.E. Tan, W.G. Dodt, D.L. Enever, P.M.A. Hopkins,
Purpose: As the only commonly transplanted organ exposed to the atmosphere, the lung allograft is easily accessible to bacterial and viral pathogens, and hence may be particularly vulnerable to local humoral immune deficiencies. The aim of this study was to investigate lung concentrations of IgG and secretory IgA (sIgA) post-transplant. Methods and Materials: Bronchoalveolar (BAL) fluid was obtained from 74 transplant patients who underwent 201 bronchoscopies, and control patients undergoing bronchoscopy for a non-infectious indication or during a non-related surgical procedure (n⫽40). Total IgG and sIgA were measured by ELISA in BAL. Demographic data, bacterial colonisation and confirmed history of community acquired respiratory viral (CARV) infection (human metapneumovirus, respiratory syncytial virus, influenza A, influenza B, adenovirus and parainfluenza virus) were recorded. Data are presented as median (interquartile range, ng/ml). Results: Paired analysis identified that IgG levels fell during the early post-transplant period (⬍4 months, n⫽26, p⬍0.001) and then stabilised thereafter, while sIgA levels were constant over this period. Compared to control patients (IgG 475 (63–1164), sIgA 24624 (14595-59512)), transplant patients (median time post-Tx 28 months) had lower levels of sIgA (11852 (7725-20681), p⬍0.001) but higher IgG levels (1069 (629 –1580), p⫽0.001). Reduced sIgA levels were associated with a history of CARV infection (p⫽0.014), and were inversely proportional to the number of recorded CARV infections (r⫽ ⫺0.299, p⫽0.013). There was no association between CARV and IgG levels. Neither IgG nor sIgA levels differed in patients who were colonised with Ps. aeruginosa. There was no association between immunoglobulin levels and sex, age, transplant type (85% double lung), pre-transplant diagnosis (42% CF, 34% COPD), basiliximab induction or rejection burden. Conclusions: Secretory IgA levels are lower after lung transplantation putting the recipient at risk of CARV infection. 354 Viral Infection in IPF Native Lung Is an Independent Risk Factor for Primary Graft Dysfunction F. Calabrese,1 F. Lunardi,1 E. Balestro,2 E. Rossi,2 D. Brotto,1 M. Loy,2 E. Perissinotto,3 F. Rea.2 1Medical Diagnostic Sciences and Special Therapies, University of Padua Medical School, Padua, Italy; 2Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy; 3Environmental Medicine and Public Health, University of Padua Medical School, Padua, Italy. Purpose: Idiopathic pulmonary fibrosis-IPF- is a chronic progressive form of interstitial lung disease, unresponsive to medical treatment, and lung transplantation-LT- has been demonstrated as a viable therapeutic option.The etiology of the disease is unknown although herpesviruses have often been identified in IPF lungs and thought to be a potential cofactor for the development and/or progression of IPF. Preliminary studies report a poor prognosis of viral IPF patients. No data are available on the post-transplant follow-up in cases associated with viral infections. Methods and Materials: Fifty-five IPF patients (39 males and 16 females, mean age⫾SD:55⫾8yrs) undergoing LT (33 single vs 22 bilateral LT) were studied. Tissue molecular viral investigations (both polymerase chain reaction and in situ hybridization) detected herpesviral infection in 20/55 (36%) of patients.The presence of diffuse alveolar damage/edema/organizing pneumonia in the first biopsy consistent with primary graft dysfunction-PGD- due to ischemia/reperfusion injury was evaluated and confirmed by functional and radiological findings. Moreover, acute rejections (AR index-ARI-: no. of acute rejections/total no. of biopsies %), were recorded in 143 scheduled transbronchial biopsies collected in the first post-transplant year (considering at least two biopsies in each patient).The relationships between major recipient/donor characteristics and graft dysfunction parameters (ARI and PGD) were investigated using univariate and multivariate analyses. Results: A significant higher frequency of PGD was detected in viral IPF patients (50% vs 14%, p⫽0.03), and multivariate analysis identified an increased risk for PGD to be associated with viral infection independently from recipient/donor characteristics.Although not statistically significant, a higher ARI was detected in viral cases (median value 50% vs 25%).
The Journal of Heart and Lung Transplantation, Vol 30, No 4S, April 2011
Perfusion (n⫽6) O2 consumption (mL/100g/min)
0.08⫾0.01
–
–
Lactate production: Initial, final (mmol/ min)
0.031⫾0.004, 0.007⫾0.002
–
0.004 (initial vs final)
Cardiac output (mL/min)
0.004
Measurement During perfusion mean⫾SEM
Final assessment median(IQR)
D.C. Chambers. Queensland Centre for Pulmonary Transplantation & Vascular Disease, The Prince Charles Hospital, Brisbane, QLD, Australia.
Cold Storage (n⫽7)
p value
1285 (1120-1413)
280 (235-455)
LV dP/dt max (mmHg/sec) 2092 (1986-2153)
190 (139-395)
0.003
Efficiency (Joules/mL O2 consumed)
0.24 (0.19-0.34)
0.01 (0.00-0.07)
0.01
0.7 (0.3-1.6)
5.1 (4.4-6.3)
0.01
Lactate rise (mmol/L)
Conclusions: Crystalloid microperfusion: 1. Facilitates aerobic metabolism and resuscitates the DCD heart. 2. Provides functional and metabolic recovery superior to cold storage and comparable to blood perfusion. 3. Shows promise for improved clinical preservation of DCD and marginal donors. 352 Community Acquired Respiratory Viral Infection Is a Risk Factor for Death after Lung Transplantation D.C. Chambers,1 A. Burke,1 T.W.V. Daniels,2 S.T. Yerkovich,1 P.M.A. Hopkins.1 1Qld Centre for Pulmonary Transplantation & Vascular Disease, The Prince Charles Hospital, Brisbane, QLD, Australia; 2Department of Respiratory Medicine, Southampton University Hospital, Southampton, Hampshire, United Kingdom. Purpose: Community acquired respiratory viral (CARV) infections are believed to contribute to morbidity and mortality after lung transplantation, but previous studies have not conclusively established the evidence base in this area. Methods and Materials: A prospective cohort study was performed at a single centre from August 1998 to March 2010 (n⫽180 lung transplant recipients). CARV infection (human metapneumovirus (hMPV), respiratory syncytial virus (RSV), influenza A (Flu A), influenza B (Flu B), adenovirus and parainfluenza virus (PIV)) was confirmed using polymerase chain reaction of upper (nasopharangeal swab) and/or lower (bronchoalveolar lavage) respiratory tract secretions in a patient with compatible clinical findings and a ⬎ 10% fall in FEV1. CARV infection and BOS were included as segmented time-dependent covariates in a Cox proportional hazards model with death as the outcome variable. Results: 87 patients (43% of the total cohort) had a total of 147 separate CARV episodes: 42 PIV, 26 hMPV, 37 RSV, 26 Flu A, 10 Flu B, and 6 adenovirus. Only BOS (HR 3.84 (2.12-6.97), p⬍0.001) and low serum IgA (HR 0.75 (0.58-0.96), p⫽0.02) were risk factors for acquiring CARV infection. Infection with either RSV or hMPV was associated with an increased risk of death (HR 3.54 (1.86-6.98), p ⬍0.001), and the effect persisted after multivariate analysis. Predictors of time to death post-transplant Univariate
HR
95% CI
p value
Presence of BOS RSV infection hMPV infection PIV infection RSV or hMPV infection
86.40 2.69 2.44 1.86 3.54
21.77-342.94 1.30-5.54 1.06-5.6 0.83-4.17 1.83-6.85
⬍0.001 0.007 0.036 0.134 ⬍0.001
Multivariate
HR
95% CI
p value
Presence of BOS RSV or hMPV infection
67.04 2.12
16.77-268.07 1.06-4.25
⬍0.001 0.035
Conclusions: Patients with BOS and low serum IgA are more prone to CARV infection. Infection with hMPV and RSV, but not other CARVs, is independently associated with an increased likelihood of death. 353 Secretory IgA Is Reduced in Lung Transplant Recipients and Is Associated with Community Acquired Respiratory Viral Infection S.T. Yerkovich, M.E. Tan, W.G. Dodt, D.L. Enever, P.M.A. Hopkins,
Purpose: As the only commonly transplanted organ exposed to the atmosphere, the lung allograft is easily accessible to bacterial and viral pathogens, and hence may be particularly vulnerable to local humoral immune deficiencies. The aim of this study was to investigate lung concentrations of IgG and secretory IgA (sIgA) post-transplant. Methods and Materials: Bronchoalveolar (BAL) fluid was obtained from 74 transplant patients who underwent 201 bronchoscopies, and control patients undergoing bronchoscopy for a non-infectious indication or during a non-related surgical procedure (n⫽40). Total IgG and sIgA were measured by ELISA in BAL. Demographic data, bacterial colonisation and confirmed history of community acquired respiratory viral (CARV) infection (human metapneumovirus, respiratory syncytial virus, influenza A, influenza B, adenovirus and parainfluenza virus) were recorded. Data are presented as median (interquartile range, ng/ml). Results: Paired analysis identified that IgG levels fell during the early post-transplant period (⬍4 months, n⫽26, p⬍0.001) and then stabilised thereafter, while sIgA levels were constant over this period. Compared to control patients (IgG 475 (63–1164), sIgA 24624 (14595-59512)), transplant patients (median time post-Tx 28 months) had lower levels of sIgA (11852 (7725-20681), p⬍0.001) but higher IgG levels (1069 (629 –1580), p⫽0.001). Reduced sIgA levels were associated with a history of CARV infection (p⫽0.014), and were inversely proportional to the number of recorded CARV infections (r⫽ ⫺0.299, p⫽0.013). There was no association between CARV and IgG levels. Neither IgG nor sIgA levels differed in patients who were colonised with Ps. aeruginosa. There was no association between immunoglobulin levels and sex, age, transplant type (85% double lung), pre-transplant diagnosis (42% CF, 34% COPD), basiliximab induction or rejection burden. Conclusions: Secretory IgA levels are lower after lung transplantation putting the recipient at risk of CARV infection. 354 Viral Infection in IPF Native Lung Is an Independent Risk Factor for Primary Graft Dysfunction F. Calabrese,1 F. Lunardi,1 E. Balestro,2 E. Rossi,2 D. Brotto,1 M. Loy,2 E. Perissinotto,3 F. Rea.2 1Medical Diagnostic Sciences and Special Therapies, University of Padua Medical School, Padua, Italy; 2Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy; 3Environmental Medicine and Public Health, University of Padua Medical School, Padua, Italy. Purpose: Idiopathic pulmonary fibrosis-IPF- is a chronic progressive form of interstitial lung disease, unresponsive to medical treatment, and lung transplantation-LT- has been demonstrated as a viable therapeutic option.The etiology of the disease is unknown although herpesviruses have often been identified in IPF lungs and thought to be a potential cofactor for the development and/or progression of IPF. Preliminary studies report a poor prognosis of viral IPF patients. No data are available on the post-transplant follow-up in cases associated with viral infections. Methods and Materials: Fifty-five IPF patients (39 males and 16 females, mean age⫾SD:55⫾8yrs) undergoing LT (33 single vs 22 bilateral LT) were studied. Tissue molecular viral investigations (both polymerase chain reaction and in situ hybridization) detected herpesviral infection in 20/55 (36%) of patients.The presence of diffuse alveolar damage/edema/organizing pneumonia in the first biopsy consistent with primary graft dysfunction-PGD- due to ischemia/reperfusion injury was evaluated and confirmed by functional and radiological findings. Moreover, acute rejections (AR index-ARI-: no. of acute rejections/total no. of biopsies %), were recorded in 143 scheduled transbronchial biopsies collected in the first post-transplant year (considering at least two biopsies in each patient).The relationships between major recipient/donor characteristics and graft dysfunction parameters (ARI and PGD) were investigated using univariate and multivariate analyses. Results: A significant higher frequency of PGD was detected in viral IPF patients (50% vs 14%, p⫽0.03), and multivariate analysis identified an increased risk for PGD to be associated with viral infection independently from recipient/donor characteristics.Although not statistically significant, a higher ARI was detected in viral cases (median value 50% vs 25%).