Exhaled Volatile Organic Compounds for Asthma Control Classification in Children with Moderate to Severe Asthma: Results from the SysPharmPediA Study.

RATIONALE: Early identification of children with poorly controlled asthma is imperative for optimizing treatment strategies. The analysis of exhaled volatile organic compounds (VOCs) is an emerging approach to identify prognostic and diagnostic biomarkers in pediatric asthma. OBJECTIVES: To assess the accuracy of gas chromatography-mass spectrometry based exhaled metabolite analysis to differentiate between controlled and uncontrolled pediatric asthma. METHODS: This study encompassed a discovery (SysPharmPediA) and validation phase (U-BIOPRED, PANDA). Firstly, exhaled VOCs that discriminated asthma control levels were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled, based on asthma control test scores and number of severe attacks in the past year. Additionally, potential of VOCs in predicting two or more future severe asthma attacks in SysPharmPediA was evaluated. MEASUREMENTS AND MAIN RESULTS: Complete data were available for 196 children (SysPharmPediA=100, U-BIOPRED=49, PANDA=47). In SysPharmPediA, after randomly splitting the population into training (n=51) and test sets (n=49), three compounds (acetophenone, ethylbenzene, and styrene) distinguished between uncontrolled and controlled asthmatics. The area under the receiver operating characteristic curve (AUROCC) for training and test sets were respectively: 0.83 (95% CI: 0.65-1.00) and 0.77 (95% CI: 0.58-0.96). Combinations of these VOCs resulted in AUROCCs of 0.74 ±0.06 (UBIOPRED) and 0.68 ±0.05 (PANDA). Attacks prediction tests, resulted in AUROCCs of 0.71 (95% CI 0.51-0.91) and 0.71 (95% CI 0.52-0.90) for training and test sets. CONCLUSIONS: Exhaled metabolites analysis might enable asthma control classification in children. This should stimulate further development of exhaled metabolites-based point-of-care tests in asthma.

Adverse Events during Prone Positioning of Patients with COVID-19 during a Surge in Hospitalizations-Results of an Observational Study.

This study aimed to determine the prevalence of adverse events in mechanically ventilated adults with COVID-19 who have undergone prone positioning. A total of 100 patients were included retrospectively; 60% were males, the mean age was 64.8 ± 9.1 years, and hospital mortality was 47%. In all, we recorded 118 removals of catheters and tubes in 66 patients; 29.6% were removals of a nasogastric tube, 18.6% of an arterial line, 14.4% of a urinary catheter, and 12.7% of a central venous catheter. Reintubation or repositioning of a tracheotomy tube was required in 19 patients (16.1%), and cardiopulmonary resuscitation in 2 patients (1.7%). We recorded a total of 184 pressure ulcers in 79 patients (on anterior face in 38.5%, anterior thorax in 23.3% and any extremity anteriorly in 15.2%). We observed that body weight (p = 0.021; ß = 0.09 (CI95: 0.01-0.17)) and the cumulative duration of prone positioning (p = 0.005; ß = 0.06 (CI95: 0.02-0.11)) were independently associated with the occurrence of any adverse event. The use of prone positioning in our setting was associated with a greater number of adverse events than previously reported. Body weight and cumulative duration of prone positioning were associated with the occurrence of adverse events; however, other factors during a COVID-19 surge, such as working conditions, staffing, and staff education, could also have contributed to a high prevalence of adverse events.

Single-Cell Transcriptomic and Targeted Genomic Profiling Adjusted for Inflammation and Therapy Bias Reveal CRTAM and PLCB1 as Novel Hub Genes for Anti-Tumor Necrosis Factor Alpha Therapy Response in Crohn's Disease.

BACKGROUND: The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn's disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The single-cell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation.