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

Abstract

Background 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. Methods In 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. Results From 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. Conclusion This 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.

Dead-Space Ventilation Indices and Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis*

“…Some studies had more than one cohort of patients for derivation and subsequent validation. We included 29 studies comprising 33 cohorts in our systematic review (5, 9, 10, 18–43) and 16 studies comprising 21 cohorts in our meta-analysis ( Fig. 1 ).…”

“…Among the four cohorts with published data, we extracted mortality rates in every 0.10 intervals of V D /V T in one cohort (21), quintiles in one cohort (5), and a prespecified cut-off of 0.57 in one cohort (32). We obtained mortality based on the prespecified cut-offs of 2.0 for VR from published data in seven cohorts (9, 10, 34, 36, 41), author contacts in three cohorts (35, 37, 38), and the closest value from published data in one cohort (a median of 1.72) (29). Appendix A4, (http://links.lww.com/CCM/H344) displays the values for cut-offs.…”

Feasibility and Safety of Transbronchial Lung Cryobiopsy for Diagnosis of Acute Respiratory Failure with Mechanical Ventilation in Intensive Care Unit

“…Our study included all patients from current and previous studies, making it one of the largest case series to assess the feasibility and safety of TBLC in ARF and ARDS. In ICUs, acute hypoxemic respiratory failure is common and etiologies are heterogeneous [ 25 ]. Bronchioalveolar lavage is an invasive but useful tool for intensivists to differentiate the cause of hypoxemic respiratory failure [ 26 ].…”

Necroptosis in Pneumonia: Therapeutic Strategies and Future Perspectives

“…Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) represents a common and fatal complication in critical illnesses, characterized by increased pulmonary microvascular endothelial cell permeability, destruction of alveolar epithelial tight junctions, and inflammatory damage [ 115 , 116 ]. ARDS is triggered by various etiologies, with pneumonia being the most common cause, followed by extrapulmonary sepsis, aspiration, non-cardiogenic shock, transfusion, and trauma [ 117 , 118 ]. The pathogenesis of ARDS involves inflammatory cell accumulation, oxidative stress, and cellular death [ 116 ].…”