Estimating the attributable fraction of mortality from acute respiratory distress syndrome to inform enrichment in future randomised clinical trials.

BACKGROUND: Efficiency of randomised clinical trials of acute respiratory distress syndrome (ARDS) depends on the fraction of deaths attributable to ARDS (AFARDS) to which interventions are targeted. Estimates of AFARDS in subpopulations of ARDS could improve design of ARDS trials. METHODS: We performed a matched case-control study using the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE cohort. Primary outcome was intensive care unit mortality. We used nearest neighbour propensity score matching without replacement to match ARDS to non-ARDS populations. We derived two separate AFARDS estimates by matching patients with ARDS to patients with non-acute hypoxaemic respiratory failure (non-AHRF) and to patients with AHRF with unilateral infiltrates only (AHRF-UL). We also estimated AFARDS in subgroups based on severity of hypoxaemia, number of lung quadrants involved and hyperinflammatory versus hypoinflammatory phenotypes. Additionally, we derived AFAHRF estimates by matching patients with AHRF to non-AHRF controls, and AFAHRF-UL estimates by matching patients with AHRF-UL to non-AHRF controls. RESULTS: Estimated AFARDS was 20.9% (95% CI 10.5% to 31.4%) when compared with AHRF-UL controls and 38.0% (95% CI 34.4% to 41.6%) compared with non-AHRF controls. Within subgroups, estimates for AFARDS compared with AHRF-UL controls were highest in patients with severe hypoxaemia (41.1% (95% CI 25.2% to 57.1%)), in those with four quadrant involvement on chest radiography (28.9% (95% CI 13.4% to 44.3%)) and in the hyperinflammatory subphenotype (26.8% (95% CI 6.9% to 46.7%)). Estimated AFAHRF was 33.8% (95% CI 30.5% to 37.1%) compared with non-AHRF controls. Estimated AFAHRF-UL was 21.3% (95% CI 312.8% to 29.7%) compared with non-AHRF controls. CONCLUSIONS: Overall AFARDS mean values were between 20.9% and 38.0%, with higher AFARDS seen with severe hypoxaemia, four quadrant involvement on chest radiography and hyperinflammatory ARDS.

Outcomes of Patients Presenting with Mild Acute Respiratory Distress Syndrome: Insights from the LUNG SAFE Study.

BACKGROUND: Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population. METHODS: This study analyzed patients from the international prospective Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) who had initial mild acute respiratory distress syndrome in the first day of inclusion. This study defined three groups based on the evolution of severity in the first week: "worsening" if moderate or severe acute respiratory distress syndrome criteria were met, "persisting" if mild acute respiratory distress syndrome criteria were the most severe category, and "improving" if patients did not fulfill acute respiratory distress syndrome criteria any more from day 2. RESULTS: Among 580 patients with initial mild acute respiratory distress syndrome, 18% (103 of 580) continuously improved, 36% (210 of 580) had persisting mild acute respiratory distress syndrome, and 46% (267 of 580) worsened in the first week after acute respiratory distress syndrome onset. Global in-hospital mortality was 30% (172 of 576; specifically 10% [10 of 101], 30% [63 of 210], and 37% [99 of 265] for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively), and the median (interquartile range) duration of mechanical ventilation was 7 (4, 14) days (specifically 3 [2, 5], 7 [4, 14], and 11 [6, 18] days for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively). Admissions for trauma or pneumonia, higher nonpulmonary sequential organ failure assessment score, lower partial pressure of alveolar oxygen/fraction of inspired oxygen, and higher peak inspiratory pressure were independently associated with worsening. CONCLUSIONS: Most patients with initial mild acute respiratory distress syndrome continue to fulfill acute respiratory distress syndrome criteria in the first week, and nearly half worsen in severity. Their mortality is high, particularly in patients with worsening acute respiratory distress syndrome, emphasizing the need for close attention to this patient population.