American journal of respiratory and critical care medicine
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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.
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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.
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Am. J. Respir. Crit. Care Med. · Jul 2023
Longitudinal Asthma Phenotypes from Childhood to Middle-Age: A Population-based Cohort Study.
Rationale: Asthma is a heterogeneous condition, and longitudinal phenotyping may provide new insights into the origins and outcomes of the disease. Objectives: We aimed to characterize the longitudinal phenotypes of asthma between the first and sixth decades of life in a population-based cohort study. Methods: Respiratory questionnaires were collected at seven time points in the TAHS (Tasmanian Longitudinal Health Study) when participants were aged 7, 13, 18, 32, 43, 50, and 53 years. ⋯ Late-onset persistent asthma was associated with the greatest comorbidity at age 53 years, with increased risk of mental health disorders and cardiovascular risk factors. Conclusions: Five longitudinal asthma phenotypes were identified between the first and sixth decades of life, including two novel remitting phenotypes. We found differential effects of these phenotypes on risk of chronic obstructive pulmonary disease and nonrespiratory comorbidities in middle age.