American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2017
Randomized Controlled Trial Comparative StudyPulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Improved by Simvastatin.
Dysregulated neutrophil functions with age and sepsis are described. Statins are associated with improved infection survival in some observational studies, but trials in critically ill patients have not shown benefit. Statins also alter neutrophil responses in vitro. ⋯ Infections in older adults are associated with prolonged, impaired neutrophil migration, potentially contributing to poor outcomes. Statins improve neutrophil migration in vivo in health and in vitro in milder infective events, but not in severe sepsis, supporting their potential utility as an early intervention during pulmonary infections. Clinical trial registered with www.clinicaltrialsregister.eu (2011-002082-38).
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Am. J. Respir. Crit. Care Med. · Nov 2017
Serum Matrix Metalloproteinase-7, Respiratory Symptoms, and Mortality in Community-dwelling Adults: The Multi-Ethnic Study of Atherosclerosis.
Matrix metalloproteinase-7 (MMP-7) has been implicated in interstitial lung disease pathobiology and proposed as a diagnostic and prognostic biomarker of idiopathic pulmonary fibrosis. ⋯ Serum MMP-7 levels may be a quantitative biomarker of subclinical extracellular matrix remodeling in the lungs of community-dwelling adults, which may facilitate investigation of subclinical interstitial lung disease.
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Am. J. Respir. Crit. Care Med. · Nov 2017
XEN-D0501, a Novel TRPV1 Antagonist, Does Not Reduce Cough in Refractory Cough Patients.
Heightened cough responses to inhaled capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, are characteristic of patients with chronic cough. However, previously, a TRPV1 antagonist (SB-705498) failed to improve spontaneous cough frequency in these patients, despite small reductions in capsaicin-evoked cough. ⋯ XEN-D0501 demonstrated superior efficacy and potency in preclinical and clinical capsaicin challenge studies; despite this improved pharmacodynamic profile, spontaneous cough frequency did not improve, ruling out TRPV1 as an effective therapeutic target for refractory cough. Clinical trial registered with www.clinicaltrialsregister.eu (2014-000306-36).