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
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).
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Am. J. Respir. Crit. Care Med. · Nov 2017
Excess Ventilation in COPD-heart Failure Overlap: Implications for Dyspnea and Exercise Intolerance.
An increased ventilatory response to exertional metabolic demand (high [Formula: see text]e/[Formula: see text]co2 relationship) is a common finding in patients with coexistent chronic obstructive pulmonary disease and heart failure. ⋯ Heightened neural drive promoting a ventilatory response beyond that required to overcome an increased "wasted" ventilation led to hypocapnia and poor exercise ventilatory efficiency in chronic obstructive pulmonary disease-heart failure overlap. Excessive ventilation led to better arterial oxygenation but at the expense of earlier critical mechanical constraints and intolerable dyspnea.
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Am. J. Respir. Crit. Care Med. · Nov 2017
Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline.
Recommendations regarding key aspects related to the diagnosis and pharmacological treatment of lymphangioleiomyomatosis (LAM) were recently published. We now provide additional recommendations regarding four specific questions related to the diagnosis of LAM and management of pneumothoraces in patients with LAM. ⋯ Evidence-based recommendations for the diagnosis and treatment of patients with LAM are provided. Frequent reassessment and updating will be needed.