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Procalcitonin and MR-proAdrenomedullin asdiagnostic and prognostic biomarkers in ICUlung transplanted patientsAndrea SennaClinical Research/Innovation in Pneumonia and Sepsis (CRIPS)Vall d’Hebron Institut de Recerca (VHIR) Compromís, expertesa i integració

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Lung Transplantation• Lung transplantation is the only established therapeutic treatment which can extend life expectancy in patients with advanced end-stage pulmonary disease.• The survival rate of patients after 5 years rapidly decrease to 50%, an extremely low number.• The lung transplant has particular and distinctive characteristics that separate them from other solid organ transplantations. (Ahmad S, Shlobin OA, 2011) FIS PI11/01122

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ARF in Lung Transplant• Several complications have been described to be responsible of low survival rate after lung transplantation: – Acute Rejection – Infections• Both complications occur in the form of Acute Respiratory Failure (ARF), being difficult for clinicians to differentiate the cause at baseline• Both complications greatly differ in treatment options• So far, no reliable methods are available for anticipating the diagnosis of complications (Christie JD, Edwards LE, 2011) FIS PI11/01122

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Procalcitonin (PCT)• Precursor peptide from the hormone calcitonin• Has 2 differents type of metabolism depending on the presence of bacterial infection.• PCT is released in response to bacterial toxins and pro-inflammatory mediators• PCT is known as one of the most effective markers of bacterial sepsis• Only few studies has evaluated the usefulness of PCT in LT patients (Bloos et al, 2011) FIS PI11/01122

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MR pro-Adrenomedullin (proADM)• MR-proADM is a fragment of pro-ADM, the precursor of Adrenomedullin• Directly reflects levels of ADM• MR-proADM is a member of calcitonin peptides family• Widely expressed during severe infections• MR-proADM has several effects including immune modulation and vasodilatation (Huang et al, 2009) FIS PI11/01122

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Hypothesis• We aim to assess Procalcitonin and pro-Adrenomedullin as biomarkers for lung transplant short-term complications during post-surgical ICU stay Objectives • to Test the capacity of PCT and proADM to differentiate between Acute Graft Rejection and Lung Infection • to Value the usefulness of PCT and pro-Adremedullin as a prognostic factor of mortality FIS PI11/01122

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Material & Methods• Single center prospective observational study in the ICU Hospital Vall dHebron• 100 Lung transplanted patients (36 already recluted)• Clinical and demographic characteristics of all patients are registered• Approved from the Ethical Committee• Blood samples is collected at days 1,2,3 and 7 after ICU admission (post-transplant)• Upon Acute Respiratory Failure (ARF) detection, blood was collected for the3 next consecutive days• PCT y pro-ADM values were measured by BRAHMS Kryptor Technology• Diagnose of the different complications was supported by clinical findingsaccording to the latest consensus definitions FIS PI11/01122

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Results FIS PI11/01122

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Transplant Indications N=36 Bronchiecstasis Pulm. hypertension FIS PI11/01122

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Type of Transplant N=36 Left Unilateral; 13, 36% Right Unilateral; 5, 14% FIS PI11/01122

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Acute Respiratory Failure (ARF) N=36 4, 44% 5, 56% FIS PI11/01122

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Mortality N=36 FIS PI11/01122

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Flowchart Lung Transplants N = 36-PCT NO - ARF ARF-proADM (n=27) (n=9) -PCT Infections Rejection -proADM (n=5) (n=4) FIS PI11/01122

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PCT and MR-proADM FIS PI11/01122

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Procalcitonin (PCT) - ARF vs. NO ARF FIS PI11/01122

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Procalcitonin (PCT) – Infection VS. Rejection FIS PI11/01122

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Procalcitonin (PCT) – Infection VS. Rejection (IRA) FIS PI11/01122

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Procalcitonin (PCT) - Mortality FIS PI11/01122

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MR Pro-Adrenomedullin (pro-ADM) – ARF VS. NO ARF FIS PI11/01122

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MR Pro-Adrenomedullin (pro-ADM) – Infection VS. Rejection FIS PI11/01122

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MR Pro-Adrenomedullin (pro-ADM) – Infection VS. Rejection FIS PI11/01122

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MR Pro-Adrenomedullin (pro-ADM) - Mortality FIS PI11/01122

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Conclusions• The number of patients undergoing a complication is far too small for definitive conclusions• Preliminary data are encouraging towards the ability of PCT and proADM to diagnose the patients that suffer lung transplant complications• Data suggest proADM may have a prognostic value over mortality at first day of ICU admission FIS PI11/01122

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Ongoing1) Analyze and correlate changes in Exhaled Breath Condensate (EBC) and BroncoAlveolar Lavage (BAL) with difference in PCT and MR-proADM2) Include in the analysis changes of CRP values in plasma3) Analyze and quantify IL6, IL8, IL10 patterns with ELISA methods for specific inflammation response4) Correlate clinical variable and respiratory pattern of the donors with the ARF after lung transplant5) To evaluate correletion of microorganism with specific patterns of biomarkers in infections FIS PI11/01122

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Aknowledgment Jordi Rello, MD, PhD Judit Sacanell, MD Laura Ruano, MSc Elsa Afonso, MSc Melissa Fernandez, MSc FIS PI11/01122