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

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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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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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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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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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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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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Mortality

N=36

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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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PCT and MR-proADM

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Procalcitonin (PCT) - ARF vs. NO ARF

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Procalcitonin (PCT) – Infection VS. Rejection

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Procalcitonin (PCT) – Infection VS. Rejection (IRA)

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Procalcitonin (PCT) - Mortality

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MR Pro-Adrenomedullin (pro-ADM) – ARF VS. NO ARF

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MR Pro-Adrenomedullin (pro-ADM) – Infection VS. Rejection

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MR Pro-Adrenomedullin (pro-ADM) – Infection VS. Rejection

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MR Pro-Adrenomedullin (pro-ADM) - Mortality

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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

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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