American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Jul 2023
Oropharyngeal Microbiota Clusters in Children with Asthma/Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways and Exacerbations Risk.
Rationale: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances. Objectives: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles. Methods: Oropharyngeal swabs from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) pediatric asthma or wheezing cohort were characterized using 16S ribosomal RNA gene sequencing, and unsupervised hierarchical clustering was performed on the Bray-Curtis β-diversity. ⋯ The oropharyngeal clusters were different in the enrichment scores of TGF-β (transforming growth factor-β) (highest in the Veillonella cluster) and Wnt/β-catenin signaling (highest in the Haemophilus cluster) transcriptomic pathways in blood (all q values <0.05). Conclusions: Analysis of the oropharyngeal microbiota of children with asthma or wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with risk for exacerbation and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiologic insights and potentially new treatment approaches.
-
Am. J. Respir. Crit. Care Med. · Jul 2023
Validity and Reliability of the Fatigue Severity Scale in a Real-World Interstitial Lung Disease Cohort.
Rationale: Fatigue is a common and debilitating symptom for people living with interstitial lung disease (ILD). Studies on fatigue in ILD are limited, and little headway has been made toward developing interventions targeting the alleviation of fatigue. A barrier to progress is a lack of knowledge around the performance characteristics of a patient-reported outcome measure to assess fatigue in patients with ILD. ⋯ Conclusions: Fatigue is an important patient-centered outcome in ILD that is poorly correlated with physiological measures of disease severity, including lung function and walk distance. These findings further support the need for a reliable and valid measure of patient-reported fatigue in ILD. The FSS possesses acceptable performance characteristics for assessing fatigue and distinguishing different degrees of fatigue among patients with ILD.
-
Am. J. Respir. Crit. Care Med. · Jul 2023
Clusterin Neutralizes the Inflammatory and Cytotoxic Properties of Extracellular Histones.
Rationale: Extracellular histones, released into the surrounding environment during extensive cell death, promote inflammation and cell death, and these deleterious roles have been well documented in sepsis. Clusterin (CLU) is a ubiquitous extracellular protein that chaperones misfolded proteins and promotes their removal. Objectives: We investigated whether CLU could protect against the deleterious properties of histones. ⋯ Accordingly, CLU deficiency was associated with increased mortality in mouse models of sepsis and endotoxemia. Finally, CLU supplementation improved mouse survival in a sepsis model. Conclusions: This study identifies CLU as a central endogenous histone-neutralizing molecule and suggests that, in pathologies with extensive cell death, CLU supplementation may improve disease tolerance and host survival.