procalcitonin and mr-proadrenomedullin as diagnostic and prognostic biomarkers in icu lung...
DESCRIPTION
Andrea Senna's predoctoral presentation at 6th VHIR Scientific Session. Watch the video of the presentation after the last slide.TRANSCRIPT
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Compromís, expertesa i integració
Andrea Senna Clinical Research/Innovation in Pneumonia and Sepsis (CRIPS)
Vall d’Hebron Institut de Recerca (VHIR)
Procalcitonin and MR-proAdrenomedullin as
diagnostic and prognostic biomarkers in ICU
lung transplanted patients
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FIS PI11/01122
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)
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FIS PI11/01122
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)
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FIS PI11/01122
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)
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FIS PI11/01122
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)
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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
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FIS PI11/01122
Material & Methods
• Single center prospective observational study in the ICU Hospital Vall
d'Hebron
• 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 the
3 next consecutive days
• PCT y pro-ADM values were measured by BRAHMS Kryptor Technology
• Diagnose of the different complications was supported by clinical findings
according to the latest consensus definitions
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FIS PI11/01122
Results
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Transplant Indications
N=36
Pulm. hypertension
Bronchiecstasis
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Type of Transplant
N=36
Left Unilateral;
13, 36%
Right Unilateral;
5, 14%
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Acute Respiratory Failure (ARF)
N=36
4, 44%
5, 56%
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FIS PI11/01122
Mortality
N=36
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FIS PI11/01122
Flowchart
Lung Transplants
N = 36
NO - ARF
(n=27)
ARF
(n=9)
Infections
(n=5)
Rejection
(n=4)
-PCT
-proADM
-PCT
-proADM
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FIS PI11/01122
PCT and MR-proADM
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FIS PI11/01122
Procalcitonin (PCT) - ARF vs. NO ARF
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FIS PI11/01122
Procalcitonin (PCT) – Infection VS. Rejection
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FIS PI11/01122
Procalcitonin (PCT) – Infection VS. Rejection (IRA)
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FIS PI11/01122
Procalcitonin (PCT) - Mortality
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FIS PI11/01122
MR Pro-Adrenomedullin (pro-ADM) – ARF VS. NO ARF
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FIS PI11/01122
MR Pro-Adrenomedullin (pro-ADM) – Infection VS. Rejection
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FIS PI11/01122
MR Pro-Adrenomedullin (pro-ADM) – Infection VS. Rejection
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FIS PI11/01122
MR Pro-Adrenomedullin (pro-ADM) - Mortality
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FIS PI11/01122
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
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FIS PI11/01122
Ongoing
1) Analyze and correlate changes in Exhaled Breath Condensate (EBC) and
BroncoAlveolar Lavage (BAL) with difference in PCT and MR-proADM
2) Include in the analysis changes of CRP values in plasma
3) Analyze and quantify IL6, IL8, IL10 patterns with ELISA methods for specific
inflammation response
4) Correlate clinical variable and respiratory pattern of the donors with the ARF
after lung transplant
5) To evaluate correletion of microorganism with specific patterns of
biomarkers in infections
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Aknowledgment
Jordi Rello, MD, PhD
Judit Sacanell, MD
Laura Ruano, MSc
Elsa Afonso, MSc
Melissa Fernandez, MSc