Introduction: Diffuse alveolar damage (DAD) is the pathological hallmark of acute respiratory distress syndrome (ARDS), however, the presence of DAD in the clinical criteria of ARDS patients by Berlin definition is little known. This study is designed to investigate the role of DAD in ARDS patients who underwent open lung biopsy. Methods: We retrospectively reviewed all ARDS patients who met the Berlin definition and underwent open lung biopsy from January 1999 to January 2014 in a referred medical center. DAD is characterized by hyaline membrane formation, lung edema, inflammation, hemorrhage and alveolar epithelial cell injury. Clinical data including baseline characteristics, severity of ARDS, clinical and pathological diagnoses, and survival outcomes were analyzed. Results: A total of 1838 patients with ARDS were identified and open lung biopsies were performed on 101 patients (5.5 %) during the study period. Of these 101 patients, the severity of ARDS on diagnosis was mild of 16.8 %, moderate of 56.5 % and severe of 26.7 %. The hospital mortality rate was not significant difference between the three groups (64.7 % vs 61.4 % vs 55.6 %, p = 0.81). Of the 101 clinical ARDS patients with open lung biopsies, 56.4 % (57/101) patients had DAD according to biopsy results. The proportion of DAD were 76.5 % (13/17) in mild, 56.1 % (32/57) in moderate and 44.4 % (12/27) in severe ARDS and there is no significant difference between the three groups (p = 0.113). Pathological findings of DAD patients had a higher hospital mortality rate than non-DAD patients (71.9 % vs 45.5 %, p = 0.007). Pathological findings of DAD (odds ratio: 3.554, 95 % CI, 1.385–9.12; p = 0.008) and Sequential Organ Failure Assessment score on the biopsy day (odds ratio: 1.424, 95 % CI, 1.187–1.707; p<0.001) were significantly and independently associated with hospital mortality. The baseline demographics and clinical characteristics were not significantly different between DAD and non-DAD patients. Conclusions: The correlation of pathological findings of DAD and ARDS diagnosed by Berlin definition is modest. A pathological finding of DAD in ARDS patients is associated with hospital mortality and there are no clinical characteristics that could identify DAD patients before open lung biopsy.

The survival predictors and optimal mechanical ventilator settings in patients with severe acute respiratory distress syndrome (ARDS) undergoing extracorporeal membrane oxygenation (ECMO) are uncertain. This study was designed to investigate the influences of clinical variables and mechanical ventilation settings on the outcomes for severe ARDS patients receiving ECMO. We reviewed severe ARDS patients who received ECMO due to refractory hypoxemia from May 2006 to October 2015. Serial mechanical ventilator settings before and after ECMO and factors associated with survival were analyzed. A total of 158 severe ARDS patients received ECMO were finally analyzed. Overall intensive care unit (ICU) mortality was 55.1%. After ECMO initiation, tidal volume, peak inspiratory pressure and dynamic driving pressure were decreased, while positive end-expiratory pressure levels were relative maintained. After ECMO initiation, nonsurvivors had significantly higher dynamic driving pressure until day 7 than survivors. Cox proportional hazards regression model revealed that immunocompromised [hazard ratio 1.957; 95% confidence interval (CI) 1.216–3.147; p = 0.006], Acute Physiology and Chronic Health Evaluation (APACHE) II score (hazard ratio 1.039; 95% CI 1.005–1.073; p = 0.023), ARDS duration before ECMO (hazard ratio 1.002; 95% CI 1.000–1.003; p = 0.029) and mean dynamic driving pressure from day 1 to 3 on ECMO (hazard ratio 1.070; 95% CI 1.026–1.116; p = 0.002) were independently associated with ICU mortality. For severe ARDS patients receiving ECMO, immunocompromised status, APACHE II score and the duration of ARDS before ECMO initiation were significantly associated with ICU survival. Higher dynamic driving pressure during first 3 days of ECMO support was also independently associated with increased ICU mortality.

Pneumonia is the leading risk factor of acute respiratory distress syndrome (ARDS). It is increasing studies in patients with pneumonia to reveal that coinfection with viral and bacterial infection can lead to poorer outcomes than no coinfection. This study evaluated the role of coinfection identified through bronchoalveolar lavage (BAL) examination on the outcomes of pneumonia-related ARDS. We performed a prospective observational study at Chang Gung Memorial Hospital from October 2012 to May 2015. Adult patients were included if they met the Berlin definition of ARDS. The indications for BAL were clinically suspected pneumonia-related ARDS and no definite microbial sample identified from tracheal aspirate or sputum. The presence of microbial pathogens and clinical outcomes were analyzed. Of the 19,936 patients screened, 902 (4.5%) fulfilled the Berlin definition of ARDS. Of these patients, 255 (22.7%) had pneumonia-related ARDS and were included for analysis. A total of 142 (55.7%) patients were identified to have a microbial pathogen through BAL and were classified into three groups: a virus-only group (n = 41 [28.9%]), no virus group (n = 60 [42.2%]), and coinfection group (n = 41 [28.9%]). ARDS severity did not differ significantly between the groups (P = 0.43). The hospital mortality rates were 53.7% in virus-only identified group, 63.3% in no virus identified group, and 80.5% in coinfection identified group. The coinfection group had significantly higher mortality than virus-only group (80.5% vs. 53.7%; P = 0.01). In patients with pneumonia-related ARDS, the BAL pathogen-positive patients had a trend of higher mortality rate than pathogen-negative patients. Coinfection with a virus and another pathogen was associated with increased hospital mortality in pneumonia-related ARDS patients.

Acute respiratory distress syndrome (ARDS) involves dysregulated immune-inflammatory responses, characterized by severe oxidative stress and high mortality. Metabolites modulating the inflammatory and immune responses may play a central role in the pathogenesis of ARDS. Most biogenic amines may induce the production of reactive oxygen species, oxidative stress, mitochondrial dysfunction, and programmed cell death. We conducted a prospective study on metabolic profiling specific to the amino acids and biogenic amines of 69 patients with ARDS. Overall, hospital mortality was 52.2%. Between day 1 and day 7 after ARDS onset, plasma kynurenine levels and the kynurenine/tryptophan ratio were significantly higher among non-survivors than in survivors (all p < 0.05). Urine metabolic profiling revealed a significantly higher prevalence of tryptophan degradation and higher concentrations of metabolites downstream of the kynurenine pathway among non-survivors than among survivors upon ARDS onset. Cox regression models revealed that plasma kynurenine levels and the plasma kynurenine/tryptophan ratio on day 1 were independently associated with hospital mortality. The activation of the kynurenine pathway was associated with mortality in patients with ARDS. Metabolic phenotypes and modulating metabolic perturbations of the kynurenine pathway could perhaps serve as prognostic markers or as a target for therapeutic interventions aimed at reducing oxidative stress and mortality in ARDS.

Patients with influenza complicated with pneumonia are at high risk of rapid progression to acute respiratory distress syndrome (ARDS). Prone positioning with longer duration and lung-protective strategies might reduce the mortality level in ARDS. The aim of this study is to investigate the survival predictors of prone positioning in patients with ARDS caused by influenza pneumonia. This retrospective study was conducted by eight tertiary referral centers in Taiwan. From January 1 to March 31 in 2016, all of the patients in intensive care units with virology-proven influenza pneumonia were collected, while all of those patients with ARDS and receiving prone positioning were enrolled. Demographic data, laboratory examinations, management records, ventilator settings and clinical outcomes were collected for analysis. During the study period, 336 patients with severe influenza pneumonia were screened and 263 patients met the diagnosis of ARDS. Totally, 65 patients receiving prone positioning were included for analysis. The 60-day survivors had lower Acute Physiology and Chronic Health Evaluation (APACHE) II score, pneumonia severity index (PSI), creatinine level and lower rate of receiving renal replacement therapy than non-survivors (22.4 ± 8.5 vs. 29.2 ± 7.4, p = 0.003; 106.6 ± 40.9 vs. 135.3 ± 48.6, p = 0.019; 1.2 ± 0.9 mg/dL vs. 3.1 ± 3.6 mg/dL, p = 0.040; and 4% vs. 42%, p < 0.005). Multivariate Cox regression analysis identified PSI (hazard ratio 1.020, 95% confidence interval 1.009–1.032; p < 0.001), renal replacement therapy (hazard ratio 6.248, 95% confidence interval 2.245–17.389; p < 0.001), and increase in dynamic driving pressure (hazard ratio 1.372, 95% confidence interval 1.095–1.718; p = 0.006) which were independent predictors associated with 60-day mortality. In the present study, in evaluating the effect of prone positioning in patients with influenza pneumonia-related ARDS, pneumonia severity index, renal replacement therapy and increase in dynamic driving pressure were associated with 60-day mortality in patients with influenza pneumonia-related ARDS receiving prone positioning.

The incidence of acute respiratory distress syndrome (ARDS) and the mortality rate of H1N1 influenza pneumonia are unclear. The aim of this study is to investigate the clinical features and outcomes of adult patients admitted to intensive care units (ICUs) with H1N1 pneumonia related ARDS. This retrospective study included patients with confirmed H1N1 influenza pneumonia admitted to the ICUs of a medical center between July 2009 and May 2014. We investigated the patients' characteristics, clinical presentations, illness severities, and outcomes. Sixty-six patients were confirmed to have H1N1 influenza pneumonia requiring mechanical ventilation. Fifty-four of those patients (82%) developed ARDS, while their hospital mortality rate was 33% (22/66). There were no significant differences in the ICU and hospital mortality rates of the ARDS and non-ARDS patients. Among the ARDS patients, there were higher rates of solid malignant disease (22.8% vs. 2.8%, p = 0.038) and sepsis (66.7% vs. 33.3%, p = 0.020) and a higher mean tidal volume (8.9 ± 1.8 vs. 7.8 ± 1.9 ml/kg, p = 0.032) in the non-survivors than the survivors. Logistic regression analysis revealed that a high tidal volume (odds ratio = 1.448, 95 % CI = 1.033-2.030; p = 0.032) and sequential organ failure assessment (SOFA) score (odds ratio = 1.233, 95% CI = 1.029-1.478; p = 0.023) were the risk factors of hospital mortality. For H1N1 influenza pneumonia patients admitted to ICUs with mechanical ventilation, there is a high probability of developing ARDS with a modest mortality rate. For patients with ARDS due to H1N1 influenza pneumonia, the tidal volume and SOFA score are the predictors of hospital mortality.