Abstract
Objective
To demonstrate that among patients with acute respiratory distress syndrome (ARDS), the presence of diffuse alveolar damage (DAD) at histological examination, as compared to its absence, defines a specific subphenotype.
Methods
We studied 149 patients who died in our ICU with the clinical diagnosis of ARDS according to the Berlin Definition (BD) and who had autopsy examination. We compared the change over time of different clinical variables in patients with (n = 49) and without (n = 100) DAD. A predictive model for the presence of DAD was developed and validated in an independent cohort of 57 patients with ARDS and postmortem examination (21 of them with DAD).
Results
Patients with DAD, as compared to patients without DAD, had a lower PaO2/FiO2 ratio and dynamic respiratory system compliance, and a higher SOFA score and INR, and were more likely to die of hypoxemia and less likely to die of shock. In multivariate analysis, variables associated with DAD [odds ratio, 95 % confidence interval (CI)] were PaO2/FiO2 ratio [0.988 (0.981–0.995)], dynamic respiratory system compliance [0.937 (0.892–0.984)] and age [0.972 (0.946–0.999)]. Areas under the ROC curve (95 % CI) for the classification of DAD using the regression model or the BD were, respectively, 0.74 (0.65–0.82) and 0.64 (0.55–0.72) (p = 0.03). In the validation cohort, the areas under the ROC curve for the diagnosis of DAD were 0.73 (0.56–0.90) and 0.67 (0.54–0.81) for the regression model and the BD, respectively.
Conclusions
The presence of DAD appears to define a specific subphenotype in patients with ARDS. Targeting patients with DAD within the population of patients with the clinical diagnosis of ARDS might be appropriate to find effective therapies for this condition.
Similar content being viewed by others
References
Villar J, Blanco J, Manuel Añón J et al (2011) The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med 37:1932–1941
Zambon M, Vincent JL (2008) Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest 133:1120–1127
Thille AW, Esteban A, Fernandez-Segoviano P et al (2013) Comparison of the Berlin definition for acute respiratory distress syndrome with autopsy. Am J Respir Crit Care Med 187:761–767
Mukhopadhyay S, Parambil JG (2012) Acute interstitial pneumonia (AIP): relationship to Hamman-Rich syndrome, diffuse alveolar damage (DAD), and acute respiratory distress syndrome (ARDS). Semin Respir Crit Care Med 233:476–485
American Thoracic S, European Respiratory S. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias (2002) This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 165:277–304
Katzenstein AL, Bloor CM, Leibow AA (1976) Diffuse alveolar damage–the role of oxygen, shock, and related factors. A review. Am J Pathol 85:209–228
Ashbaugh DG, Bigelow DB, Petty TL, Levine BE (1967) Acute respiratory distress in adults. Lancet 2:319–323
Esteban A, Fernandez-Segoviano P, Frutos-Vivar F et al (2004) Comparison of clinical criteria for the acute respiratory distress syndrome with autopsy findings. Ann Intern Med 141:440–445
Patel SR, Karmpaliotis D, Ayas NT et al (2004) The role of open-lung biopsy in ARDS. Chest 125:197–202
Kao KC, Tsai YH, Wu YK et al (2006) Open lung biopsy in early-stage acute respiratory distress syndrome. Crit Care 10:R106
Pinheiro BV, Muraoka FS, Assis RV et al (2007) Accuracy of clinical diagnosis of acute respiratory distress syndrome in comparison with autopsy findings. J Brasil Pneumol 33:423–428
de Hemptinne Q, Remmelink M, Brimioulle S et al (2009) ARDS: a clinicopathological confrontation. Chest 135:944–949
Sarmiento X, Almirall J, Guardiola JJ et al (2011) Study on the clinicopathological correlation in the secondary acute respiratory distress syndrome. Med Intensiva 35:22–27
Sarmiento X, Guardiola JJ, Almirall J et al (2011) Discrepancy between clinical criteria for diagnosing acute respiratory distress syndrome secondary to community acquired pneumonia with autopsy findings of diffuse alveolar damage. Resp Med 105:1170–1175
Thille AW, Esteban A, Fernández-Segoviano P et al (2013) Chronology of histological lesions in acute respiratory distress syndrome with diffuse alveolar damage: a prospective cohort study of clinical autopsies. Lancet Respir Med 1:395–401
Guerin C, Bayle F, Leray V, Debord S, Stoian A, Yonis H, Roudaut JB, Bourdin G, Devouassoux-Shisheboran M, Bucher E, Ayzac L, Lantuejoul S, Philipponnet C, Kemeny JL, Souweine B, Richard JC (2015) Open lung biopsy in nonresolving ARDS frequently identifies diffuse alveolar damage regardless of the severity stage and may have implications for patient management. Intensive Care Med 41:222–230
Kao KC, Hu HC, Chang CH, Hung CY, Chiu LC, Li SH, Lin SW, Chuang LP, Wang CW, Li LF, Chen NH, Yang CT, Huang CC, Tsai YH (2015) Diffuse alveolar damage associated mortality in selected acute respiratory distress syndrome patients with open lung biopsy. Crit Care 19:228
Thompson BT, Matthay MA (2013) The Berlin definition of ARDS versus pathological evidence of diffuse alveolar damage. Am J Respir Crit Care Med 187:675–677
Thille AW, Vuylsteke A, Bersten A (2015) Does the Berlin definition for acute respiratory distress syndrome predict the presence of diffuse alveolar damage? Intensive Care Med 41(2):342–344
Binnie A, Tsang JL, dos Santos CC (2014) Biomarkers in acute respiratory distress syndrome. Curr Opin Crit Care. 20:47–55
Tonelli AR, Zein J, Adams J, Ioannidis JP (2014) Effects of interventions on survival in acute respiratory distress syndrome: an umbrella review of 159 published randomized trials and 29 meta-analyses. Intensive Care Med 40:769–787
Cardinal-Fernández P, Ballén-Barragán, Lorente JA (2014) ARDS: a clinical syndrome or a pathological entity? In: VincentJL (ed) Annual update in intensive care and emergency medicine. Springer, Berlin, pp 219–229
Cardinal-Fernández P, Esteban A, Thompson BT, Lorente JA (2015) ARDS: lessons learned from the heart. Chest 147:7–8
Definition Task Force ARDS, Ranieri VM, Rubenfeld GD, Thompson BT et al (2012) Acute respiratory distress syndrome: the Berlin definition. JAMA 307:2526–2533
Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963
Guerin C, Reignier J, Richard JC et al (2013) Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 368:2159–2168
Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A, Jaber S, Arnal JM, Perez D, Seghboyan JM, Constantin JM, Courant P, Lefrant JY, Guérin C, Prat G, Morange S, Roch A, ACURASYS Study Investigators (2010) Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 363:1107–1116
Network The Acute Respiratory Distress Syndrome (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342:1301–1308
Calfee CS, Delucchi K, Parsons PE, the NHLBI ARDS Network (2014) Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials. Lancet Respir Med 2:611–620
Network The Acute Respiratory Distress Syndrome (2004) Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 351:327–336
Ferguson ND, Frutos-Vivar F, Esteban A et al (2005) Acute respiratory distress syndrome: underrecognition by clinicians and diagnostic accuracy of three clinical definitions. Crit Care Med 33:2228–2234
Rubenfeld GD, Caldwell E, Granton J, Hudson LD, Matthay MA (1999) Interobserver variability in applying a radiographic definition for ARDS. Chest 116:1347–1353
Acknowledgments
Instituto de Salud Carlos III FIS PI 12/02898, and FIS PI 12/02451. European Network (7th FP) ITN 264864.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Additional information
Take-home message: The presence of DAD in ARDS patients defines a specific clinical-pathological entity, which means that the knowledge sourced from ARDS studies which do not take histology into account should be considered very cautiously as they include different entities (only half of ARDS patients present DAD).
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Lorente, J.A., Cardinal-Fernández, P., Muñoz, D. et al. Acute respiratory distress syndrome in patients with and without diffuse alveolar damage: an autopsy study. Intensive Care Med 41, 1921–1930 (2015). https://doi.org/10.1007/s00134-015-4046-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00134-015-4046-0