Transcriptomics reveals shared immunosuppressive landscapes in ventilator-associated lower respiratory tract infections (VA-LRTI) patients.

BACKGROUND: Ventilator-associated pneumonia (VAP) represents a transitory status of immunoparalysis, and we hypothesized that ventilator-associated tracheobronchitis (VAT) could share also some degree of immune response to a respiratory infection. RESEARCH DESIGN AND METHODS: A prospective observational study in five medical ICUs to evaluate immunological alterations of patients with VA-LRTI. Immunological gene expression profiles in the blood using whole transcriptome microarrays in the first 24 hours following diagnosis. The area under the receiver operating characteristic curve (AUROC) was used to assess the accuracy of mRNA levels to differentiate VA-LRTI and lack of infection. A principal component analysis (PCA) was employed for analyzing the impact of each genetic expression footprint variable in explaining the variance of the cohort. RESULTS: There was overlapping between the three classes of patients encompassing gene expression levels of 8 genes (i.e. HLA, IL2RA, CD40LG, ICOS, CCR7, CD1C, CD3E). HLA-DRA was equally low among VAT and VAP patients characterizing immune depression, and significantly lower than the control group. CONCLUSIONS: Our findings suggest that VAP and VAT are not so different regarding gene expression levels suggesting a degree of immunosuppression. Our results indicate a state of immunoparalysis in respiratory infections in critically ill patients.

Invasive Pulmonary Aspergillosis: Not Only a Disease Affecting Immunosuppressed Patients.

Fungal infections have become a common threat in Intensive Care Units (ICU). The epidemiology of invasive fungal diseases (IFD) has been extensively studied in patients severely immunosuppressed over the last 20-30 years, however, the type of patients that have been admitted to hospitals in the last decade has made the healthcare system and ICU a different setting with more vulnerable hosts. Patients admitted to an ICU tend to have older age and higher severity of disease. Moreover, the number of patients being treated in ICU are often immunosuppressed as a result of the widespread use of immunomodulatory agents, such as corticosteroids, chemotherapy, and biological agents. The development of Invasive Pulmonary aspergillosis (IPA) reflects a different clinical trajectory to affected patients. The increasing use of corticosteroids would probably explain the higher incidence of IPA especially in critically ill patients. In refractory septic shock, severe community-acquired pneumonia (SCAP), and acute respiratory distress syndrome (ARDS), the use of corticosteroids has re-emerged in order to decrease unacceptably high mortality rates associated with these clinical conditions. It is also pertinent to note that different reports have used different diagnosis criteria, and this might explain the different incidence rates. Another layer of complexity to better understand current IPA data is related to more aggressive acquisition of samples through invasive respiratory examinations.

A single-centre prospective cohort study: prone positioning in awake, non-intubated patients with covid-19 hypoxemic failure.

INTRODUCTION: A surge in critically ill patients with respiratory failure due to Covid-19 has overwhelmed ICU capacity in many healthcare systems across the world. Given a guarded prognosis and significant resource limitations, less invasive, inventive approaches such as prone positioning (PP) of non-intubated patients with hypoxemic respiratory failure were considered. AIMS AND OBJECTIVES: This is a prospective observational study and the aim is to evaluate the impact of awake PP at the ward level on the oxygenation levels of patients with COVID-19. We also are investigating as secondary outcomes, the risk factors for treatment failure among awake non-intubated patients who tolerated PP compared to those who did not. The primary outcome of this trial is the change in SpO2:FiO2 (SF) ratio from admission to discharge in the participants who tolerated PP compared to those that did not. Secondary outcomes included amongst others are ICU admission rate, in-hospital mortality, and length of stay. METHODS: A total of 63 patients admitted to Beaumont Hospital (BH), Dublin between January and February of 2021 with Covid-19 requiring supplemental oxygen were recruited. RESULTS: A total of 47 (74%) participants were reported as tolerating and 16 (26%) as non-tolerating PP. The mean rank in the primary endpoint in the tolerating group was 38 vs. 16 in the non-tolerating. This was statistically significant (P < 0.001). CONCLUSION: PP was associated with improvements in oxygenation parameters without any reported serious adverse events. A well-designed, randomised control trial, testing the efficacy of PP in non-intubated Covid-19 patients is needed, before the widespread adoption of this practice.