Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study

Sheng-Yuan Ruan,Lu-Cheng Kuo,Ying-Chun Chien,Chun-Kai Huang,Jung-Yien Chien,Chun-Ta Huang,Ping-Hung Kuo,Huey-Dong Wu,Shih-Chi Ku

doi:10.1186/s12890-021-01557-9

Abstract

BackgroundHeterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described.MethodsIn this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal–Wallis rank tests and Chi-squared tests were used to compare between-etiology differences.ResultsFrom 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia.ConclusionThis study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

Highlights

Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials
We evaluated the differences between bacterial and non-bacterial pneumonia associated ARDS because pneumonia accounts for half of all ARDS cases [4]
Study design and data source This retrospective cohort study was conducted at the National Taiwan University Hospital in Taiwan, and aimed to explore the potential heterogeneity associated with ARDS etiologies by comparing and evaluating gas exchange abnormality, hemodynamic instability, non-pulmonary organ dysfunction, inflammation and coagulation biomarkers, and mortality

Summary

Introduction

Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. Acute respiratory distress syndrome (ARDS) is a clinical syndrome of inflammatory lung injury characterized by non-cardiogenic lung edema, severe hypoxemia and impaired lung mechanics [1, 2]. Pneumonia is the most common etiology of ARDS and accounts for roughly half of all ARDS cases [4, 5]. Other common etiologies include extrapulmonary sepsis, aspiration, noncardiogenic shock, transfusion and trauma [4, 5]. Different etiologies of ARDS can result in different histological and biological changes in the lungs [6, 7]

Objectives

Methods

Results

Discussion

Conclusion