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Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers: data from a 1200-patient critical care randomized trial

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@article{57252ecc73954c43b18280665ca41e55,
title = "Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers: data from a 1200-patient critical care randomized trial",
abstract = "BACKGROUND: It is unclear whether biomarkers of alveolar damage (surfactant protein D, SPD) or conductive airway damage (club cell secretory protein 16, CC16) measured early after intensive care admittance are associated with one-month clinical respiratory prognosis. If patients who do not recover respiratory function within one month can be identified early, future experimental lung interventions can be aimed toward this high-risk group. We aimed to determine, in a heterogenous critically ill population, whether baseline profound alveolar damage or conductive airway damage has clinical respiratory impact one month after intensive care admittance.METHODS: Biobank study of biomarkers of alveolar and conductive airway damage in intensive care patients was conducted. This was a sub-study of 758 intubated patients from a 1200-patient randomized trial. We split the cohort into a {"}learning cohort{"} and {"}validating cohort{"} based on geographical criteria: northern sites (learning) and southern sites (validating).RESULTS: Baseline SPD above the 85th percentile in the {"}learning cohort{"} predicted low chance of successful weaning from ventilator within 28 days (adjusted hazard ratio 0.6 [95{\%} CI 0.4-0.9], p = 0.005); this was confirmed in the validating cohort. CC16 did not predict the endpoint. The absolute risk of not being successfully weaned within the first month was 48/106 (45.3{\%}) vs. 175/652 (26.8{\%}), p < 0.0001 (high SPD vs. low SPD). The chance of being {"}alive and without ventilator ≥20 days within the first month{"} was lower among patients with high SPD (adjusted OR 0.2 [95{\%} CI 0.2-0.4], p < 0.0001), confirmed in the validating cohort, and the risk of ARDS was higher among patients with high SPD (adjusted OR 3.4 [95{\%} CI 1.0-11.4], p = 0.04)-also confirmed in the validating cohort.CONCLUSION: Early profound alveolar damage in intubated patients can be identified by SPD blood measurement at intensive care admission, and high SPD level is a strong independent predictor that the patient suffers from ARDS and will not recover independent respiratory function within one month. This knowledge can be used to improve diagnostic and prognostic models and to identify the patients who most likely will benefit from experimental interventions aiming to preserve alveolar tissue and therefore respiratory function. Trial registration This is a sub-study to the Procalcitonin And Survival Study (PASS), Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.",
author = "Jensen, {Jens-Ulrik S} and Itenov, {Theis S} and Thormar, {Katrin M} and Lars Hein and Mohr, {Thomas T} and Andersen, {Mads H} and Jesper L{\o}ken and Hamid Tousi and Bettina Lundgren and Boesen, {Hans Christian} and Johansen, {Maria E} and Ostrowski, {Sisse R} and Johansson, {P{\"a}r I} and Jesper Grarup and J{\o}rgen Vestbo and Lundgren, {Jens D} and {Procalcitonin And Survival Study (PASS) Group (Arash Afshari, Kim Ekelund, members)} and Arash Afshari and Kim Ekelund and Morten Bestle",
year = "2016",
doi = "10.1186/s13613-016-0212-y",
language = "English",
volume = "6",
pages = "114",
journal = "Journal of Intensive Care",
issn = "2110-5820",
publisher = "SpringerOpen",
number = "1",

}

RIS

TY - JOUR

T1 - Prediction of non-recovery from ventilator-demanding acute respiratory failure, ARDS and death using lung damage biomarkers

T2 - data from a 1200-patient critical care randomized trial

AU - Jensen, Jens-Ulrik S

AU - Itenov, Theis S

AU - Thormar, Katrin M

AU - Hein, Lars

AU - Mohr, Thomas T

AU - Andersen, Mads H

AU - Løken, Jesper

AU - Tousi, Hamid

AU - Lundgren, Bettina

AU - Boesen, Hans Christian

AU - Johansen, Maria E

AU - Ostrowski, Sisse R

AU - Johansson, Pär I

AU - Grarup, Jesper

AU - Vestbo, Jørgen

AU - Lundgren, Jens D

AU - Procalcitonin And Survival Study (PASS) Group (Arash Afshari, Kim Ekelund, members)

A2 - Afshari, Arash

A2 - Ekelund, Kim

A2 - Bestle, Morten

PY - 2016

Y1 - 2016

N2 - BACKGROUND: It is unclear whether biomarkers of alveolar damage (surfactant protein D, SPD) or conductive airway damage (club cell secretory protein 16, CC16) measured early after intensive care admittance are associated with one-month clinical respiratory prognosis. If patients who do not recover respiratory function within one month can be identified early, future experimental lung interventions can be aimed toward this high-risk group. We aimed to determine, in a heterogenous critically ill population, whether baseline profound alveolar damage or conductive airway damage has clinical respiratory impact one month after intensive care admittance.METHODS: Biobank study of biomarkers of alveolar and conductive airway damage in intensive care patients was conducted. This was a sub-study of 758 intubated patients from a 1200-patient randomized trial. We split the cohort into a "learning cohort" and "validating cohort" based on geographical criteria: northern sites (learning) and southern sites (validating).RESULTS: Baseline SPD above the 85th percentile in the "learning cohort" predicted low chance of successful weaning from ventilator within 28 days (adjusted hazard ratio 0.6 [95% CI 0.4-0.9], p = 0.005); this was confirmed in the validating cohort. CC16 did not predict the endpoint. The absolute risk of not being successfully weaned within the first month was 48/106 (45.3%) vs. 175/652 (26.8%), p < 0.0001 (high SPD vs. low SPD). The chance of being "alive and without ventilator ≥20 days within the first month" was lower among patients with high SPD (adjusted OR 0.2 [95% CI 0.2-0.4], p < 0.0001), confirmed in the validating cohort, and the risk of ARDS was higher among patients with high SPD (adjusted OR 3.4 [95% CI 1.0-11.4], p = 0.04)-also confirmed in the validating cohort.CONCLUSION: Early profound alveolar damage in intubated patients can be identified by SPD blood measurement at intensive care admission, and high SPD level is a strong independent predictor that the patient suffers from ARDS and will not recover independent respiratory function within one month. This knowledge can be used to improve diagnostic and prognostic models and to identify the patients who most likely will benefit from experimental interventions aiming to preserve alveolar tissue and therefore respiratory function. Trial registration This is a sub-study to the Procalcitonin And Survival Study (PASS), Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.

AB - BACKGROUND: It is unclear whether biomarkers of alveolar damage (surfactant protein D, SPD) or conductive airway damage (club cell secretory protein 16, CC16) measured early after intensive care admittance are associated with one-month clinical respiratory prognosis. If patients who do not recover respiratory function within one month can be identified early, future experimental lung interventions can be aimed toward this high-risk group. We aimed to determine, in a heterogenous critically ill population, whether baseline profound alveolar damage or conductive airway damage has clinical respiratory impact one month after intensive care admittance.METHODS: Biobank study of biomarkers of alveolar and conductive airway damage in intensive care patients was conducted. This was a sub-study of 758 intubated patients from a 1200-patient randomized trial. We split the cohort into a "learning cohort" and "validating cohort" based on geographical criteria: northern sites (learning) and southern sites (validating).RESULTS: Baseline SPD above the 85th percentile in the "learning cohort" predicted low chance of successful weaning from ventilator within 28 days (adjusted hazard ratio 0.6 [95% CI 0.4-0.9], p = 0.005); this was confirmed in the validating cohort. CC16 did not predict the endpoint. The absolute risk of not being successfully weaned within the first month was 48/106 (45.3%) vs. 175/652 (26.8%), p < 0.0001 (high SPD vs. low SPD). The chance of being "alive and without ventilator ≥20 days within the first month" was lower among patients with high SPD (adjusted OR 0.2 [95% CI 0.2-0.4], p < 0.0001), confirmed in the validating cohort, and the risk of ARDS was higher among patients with high SPD (adjusted OR 3.4 [95% CI 1.0-11.4], p = 0.04)-also confirmed in the validating cohort.CONCLUSION: Early profound alveolar damage in intubated patients can be identified by SPD blood measurement at intensive care admission, and high SPD level is a strong independent predictor that the patient suffers from ARDS and will not recover independent respiratory function within one month. This knowledge can be used to improve diagnostic and prognostic models and to identify the patients who most likely will benefit from experimental interventions aiming to preserve alveolar tissue and therefore respiratory function. Trial registration This is a sub-study to the Procalcitonin And Survival Study (PASS), Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.

U2 - 10.1186/s13613-016-0212-y

DO - 10.1186/s13613-016-0212-y

M3 - Journal article

VL - 6

SP - 114

JO - Journal of Intensive Care

JF - Journal of Intensive Care

SN - 2110-5820

IS - 1

ER -

ID: 49246172