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Original Research: Critical Care |

The Presence of Diffuse Alveolar Damage on Open Lung Biopsy Is Associated With Mortality in Patients With Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

Pablo Cardinal-Fernández, MD, PhD; Ednan K. Bajwa, MD; Andrea Dominguez-Calvo, MD; Justo M. Menéndez, MD, PhD; Laurent Papazian, MD; B. Taylor Thompson, MD
Author and Funding Information

Dr Cardinal-Fernández is currently at Department of Genetic Medicine, Weill Cornell Medical College (New York, NY).

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

aEmergency Department, Hospital Universitario HM Sanchinarro, Madrid, Spain

bInternal Medicine Department, Hospital Universitario HM Sanchinarro, Madrid, Spain

cUniversidad CEU San Pablo, Madrid, Spain

dDivision of Pulmonary and Critical Care, Department of Medicine, Massachusetts General Hospital, and Harvard Medical School, Boston, MA

eAssistance Publique, Hôpitaux de Marseille, Hôpital Nord, Réanimation des Détresses Respiratoires et des Infections Sévères, Chemin des Bourrely, and the Faculté de Médecine, Aix-Marseille Université, Marseille, France

CORRESPONDENCE TO: Pablo Cardinal-Fernández, MD, PhD, Hospital Universitario HM Sanchinarro, Emergency Department, Calle Oña, 10, 28050 Madrid, Spain


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(5):1155-1164. doi:10.1016/j.chest.2016.02.635
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Objective  Diffuse alveolar damage (DAD) is considered the histologic hallmark of ARDS although DAD is absent in approximately half of patients with ARDS. The clinical implications of having the syndrome of ARDS with DAD vs other histologic patterns is unknown. To address this question, we conducted a meta-analysis of lung biopsy series for patients with ARDS.

Methods  Studies were identified using MEDLINE, EMBASE, Cochrane Register of Controlled Trials, LILACS, and citation review from January 1, 1967, to September 1, 2015. Studies were included if they included all of the following: open lung biopsies (OLB) performed after ARDS diagnosis; a clear definition of ARDS and DAD; histologic results of the OLB indicated the presence or absence of DAD; and mortality reported for the DAD and non-DAD groups. We excluded studies conducted solely on a specific histology subgroup (eg, DAD) and studies with fewer than 5 patients. Two authors independently selected studies for inclusion, and there were no language restrictions.

Results  Of 8 included studies, 4 were high-quality (n = 227) and 4 were middle-quality trials (n = 123). The meta proportion of DAD between all the groups was 0.48 (95% CI, 0.42-0.53; Q test, 31.6; I2, 77.9%; P ≤ .01). The pooled OR for mortality in ARDS with DAD compared with ARDS without DAD was 1.81 (95% CI, 1.14-2.86; Q test, 8.95; I2, 21.8%; P = .256). Age and days elapsed between ARDS diagnosis and OLB as well as sequential organ failure assessment score and Pao2/Fio2 ratio on the day of OLB did not differ between DAD and non-DAD groups.

Conclusions  This meta-analysis demonstrated that ARDS with DAD is associated with higher mortality than ARDS without DAD.

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