Assessment of Quantiferon®-CMV and Immuknow® Assays in CMV-seropositive Lung Transplant Recipients to Stratify Risk of CMV Infection

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Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study / Valor predictivo del test de función de la inmunidad celular para infecciones distintas a CMV en receptores de un trasplante pulmonar: un estudio multicéntrico, prospectivo y observacional

Introduction: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. Methods: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. Results: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225–525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). Conclusion: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression. (AU)

Introducción: El test de función de la inmunidad celular (ImmuKnow®) es un método que mide el estado de la inmunidad celular en pacientes inmunosuprimidos. Se estudió su valor pronóstico para predecir infecciones diferentes a citomegalovirus (CMV) en receptores de un trasplante pulmonar. Métodos: Se realizó un estudio observacional prospectivo multicéntrico de 92 pacientes seguidos desde los 6 a los 12 meses postrasplante. El test se realizó a los 6, 8, 10 y 12 meses. Resultados: Veintitrés pacientes (25%) desarrollaron 29 infecciones no debidas a CMV entre los 6 y los 12 meses posteriores al trasplante. A los 6 meses, la respuesta inmune fue moderada (ATP 225-525ng/ml) en 14 (15,2%) pacientes y baja (ATP<225ng/ml) en 78 (84,8%); ningún paciente tuvo una respuesta fuerte (ATP>525ng/ml). Solo uno de 14 (7,1%) pacientes con una respuesta moderada desarrolló una infección diferente a CMV en los 6 meses siguientes a la realización del test en comparación con 22 de 78 (28,2%) con respuesta baja, indicando una sensibilidad del 95,7%, una especificidad del 18,8%, un valor predictivo positivo del 28,2% y un valor predictivo negativo del 92,9% (AUC 0,64; p=0,043). Se registraron tasas de rechazo agudo similares en pacientes con ATP medio >225 frente a <225ng/ml durante el período de estudio (7,1 frente al 9,1%; p=0,81). Conclusión: Aunque el test ImmuKnow® no parece útil para predecir infecciones diferentes al CMV, podría identificar pacientes con riesgo muy bajo y ayudarnos a definir un objetivo de inmunosupresión óptima. (AU)

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

INTRODUCTION: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. METHODS: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. RESULTS: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225-525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). CONCLUSION: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

INTRODUCTION: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. METHODS: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. RESULTS: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225-525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). CONCLUSION: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Early Surgical Management of Bronchial Dehiscence After Single-Lung Transplantation: A Case Report.

Anastomotic airway complications after lung transplantation affect up to 20% of patients. Bronchial stenosis is the most frequent complication, while dehiscence of bronchial anastomosis is a rarely seen complication, with report incidences between 1% and 10%. Despite its low incidence, dehiscence of bronchial anastomoses remains a disastrous complication in the posttransplantation period without a well-established management protocol. We present a challenging case of complete bronchial dehiscence after unilateral lung transplantation in a patient with interstitial lung fibrosis (ILF) that occurred on postoperative day 10. The dehiscence was diagnosed early and the patient's status was stable for repeat thoracotomy, therefore, an early surgical approach was preferable to conservative management or bronchoscopy. Aggressive early surgical management in a stable patient allows for complete debridement with removal of the detritus that impedes correct anastomosis healing and permits the removal of microbial vegetations with successful results.

Efficacy and safety of short-term treatment with isoniazid and rifampicin for latent tuberculosis infection in lung transplant candidates.

BACKGROUND: The current recommendation for the treatment of latent tuberculosis infection (LTBI) in solid organ transplant candidates is isoniazid for 9 months, but this treatment has the main problem of frequently reaching the posttransplant period. METHODS: This is the study of efficacy and safety of a 3-month regimen with isoniazid and rifampicin (3HR) in lung transplant candidates in the Reina Sofía Hospital in Córdoba. RESULTS: Three hundred and ninety-eight lung transplant patients were evaluated. Ninety-two (24.9%) had LTBI and just 22 received the 3HR treatment. One additional patient was treated because he had a history of previous incomplete treatment for active TB. None of the treated patients developed posttransplant tuberculosis compared to three of the 62 patients with LTBI who were not treated (4.8%). Three patients could not conclude the 3HR treatment (13%), but only two had adverse effects (8.7%). CONCLUSIONS: Treatment of LTBI in lung transplant candidates using a short course of 3HR appears to be effective and safe in preventing posttransplant TB in lung transplant recipients.

Lung transplantation for cystic fibrosis: differential characteristics and outcomes between children and adults.

OBJECTIVES: The survival benefit of lung transplantation (LTx) for cystic fibrosis (CF) patients is well demonstrated. We aim to compare children and adult CF recipients to assess whether there are differences in survival and clinical outcomes, and to identify risk factors for mortality. METHODS: A retrospective analysis of 442 consecutive LTx performed at our institution in a 20-year period was conducted. CF patients were distributed into two groups: children (age <18 years) and adults (age ≥18 years). Donor and recipient general demographic data, perioperative and postoperative factors including 30-day mortality, survival, primary graft dysfunction (PGD), complications, acute rejection (AR) and chronic lung allograft dysfunction (CLAD) were analysed and compared between groups. Univariable, Kaplan-Meier and Cox regression analyses were performed. RESULTS: The study group included 120 consecutive CF patients: 50 children (13 ± 3 years) and 70 adults (25 ± 6 years) undergoing 111 bilateral, 4 lobar, 4 combined and 1 unilateral LTx. Comparative analysis (children versus adults): survival (overall; 5, 10 and 15 years) 57, 45, 35% vs 67, 55, 43% (P = 0.32); survival (1-year survivors; 5, 10 and 15 years): 75, 64, 46% vs 90, 75, 59% (P = 0.09); 30-day mortality: 14 vs 16% (P = 0.27); urgent LTx: 32 vs 17% (P = 0.04); use of cardiopulmonary bypass (CPB): 56 vs 28% (P = 0.002); intensive care unit stay: 20 ± 19 vs 10 ± 9 days (P = 0.006); AR episodes (n): 1.4 ± 0.7 vs 1.2 ± 0.8 (P = 0.004). Incidence of PGD and freedom from CLAD did not differ between groups. Predictors of mortality were: use of CPB (HR 3.12; 95% CI 1.33-7.35; P < 0.01), post-transplant diabetes mellitus (HR 2.49; 95% CI 1.13-5.43; P = 0.02) and pneumonia episodes within the first month post-transplant (HR 2.82; 95% CI 1.27-6.29; P = 0.01). CONCLUSION: Paediatric CF patients usually present with poorer pre-transplant status, require CPB more frequently and have a higher incidence of post-LTx diabetes and infections. This might explain the trend towards a better long-term survival observed in adult CF patients.

Extended recipients but not extended donors are associated with poor outcomes following lung transplantation.

OBJECTIVES: Extended donors (EDs) are safely used to increase the donor pool in lung transplantation (LT), but their influence in critically ill patients (extended recipients [ERs]) remains controversial. We compared LT outcomes matching optimal donors (ODs) or EDs with optimal recipients (ORs) or ERs. METHODS: Three hundred and sixty-five LTs were reviewed. ED criteria: age >55, PaO2/FiO2 < 350 mmHg, pulmonary infiltrates/purulent secretions and ischaemic times >6 h (single LT [SLT]) and >9 h (double LT [DLT]). ER criteria: pulmonary fibrosis or pulmonary hypertension, pretransplant intubation, age >60 years and bypass >2 h. Four groups were created: Group 1 (OD/OR), Group 2 (OD/ER), Group 3 (ED/OR) and Group 4 (ED/ER). Thirty-day mortality, primary graft dysfunction (PGD), onset of bronchiolitis obliterans syndrome (BOS), long-term survival and other transplant outcomes were compared between OD and ED, OR and ER and among the four groups of study. RESULTS: There were 151 SLTs and 214 DLTs. Donors: OD (n = 229) vs ED (n = 136); PGD 8 vs 10% (P = 0.43); 30-day mortality 19 vs 20% (P = 0.53) and survival (1, 5, 10 and 15 years) 67, 47, 34, 26 vs 69, 53, 46 and 29% (P = 0.33). Recipients: OR (n = 182) vs ER (n = 183); PGD 7 vs 10% (P = 0.10); 30-day mortality 15 vs 23% (P = 0.04) and survival (1, 5, 10 and 15 years): 73, 57, 46, 30 vs 61, 42, 29 and 23% (P = 0.002). Four donor/recipient (D/R) groups: Group 1 (n = 122), Group 2 (n = 106), Group 3 (n = 61), Group 4 (n = 76); PGD 10, 6, 3 and 16% (P = 0.05); 30-day mortality 13, 26, 19 and 20%, respectively (P = 0.13); survival (1, 5, 10 and 15 years) 74, 55, 44 and 35% (Group 1), 55, 39, 22 and 16% (Group 2), 70, 59, 48 and 26% (Group 3) and 68, 47, 37 and 22% (Group 4) (P = 0.004). No differences in the onset of BOS were observed among the four study groups. CONCLUSIONS: LT in critically ill recipients is associated with poor early and long-term outcomes, irrespective of the quality of the donor and length of ischaemic times.