American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2013
Randomized Controlled Trial Multicenter StudyRandomized, Double-blind, Placebo-controlled Study of Brodalumab, a Human Anti-IL-17 Receptor Monoclonal Antibody, in Moderate to Severe Asthma.
IL-17 signaling has been implicated in development and persistence of asthma. Cytokine-targeted strategies blocking IL-17 receptor signaling may be beneficial in asthma treatment. ⋯ Inhibition of IL-17 receptor A did not produce a treatment effect in subjects with asthma. The results of the high-reversibility subgroup analysis are of uncertain significance, requiring further study of brodalumab in this asthma subpopulation. Clinical trial registered with www.clinicaltrials.gov (NCT01199289).
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Am. J. Respir. Crit. Care Med. · Dec 2013
ReviewProne Position in Acute Respiratory Distress Syndrome: Rationale, Indications and Limits.
In the prone position, computed tomography scan densities redistribute from dorsal to ventral as the dorsal region tends to reexpand while the ventral zone tends to collapse. Although gravitational influence is similar in both positions, dorsal recruitment usually prevails over ventral derecruitment, because of the need for the lung and its confining chest wall to conform to the same volume. The final result of proning is that the overall lung inflation is more homogeneous from dorsal to ventral than in the supine position, with more homogeneously distributed stress and strain. ⋯ Single-patient and meta-analyses drawing from the four major trials showed significant survival benefit in patients with PaO2/FiO2 lower than 100. The latest PROSEVA (Proning Severe ARDS Patients) trial confirmed these benefits in a formal randomized study. The bulk of data indicates that in severe acute respiratory distress syndrome, carefully performed prone positioning offers an absolute survival advantage of 10-17%, making this intervention highly recommended in this specific population subset.
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Am. J. Respir. Crit. Care Med. · Dec 2013
HRV-C Infection in Young Children with Acute Wheeze is Associated with Increased Acute Respiratory Hospital Admissions.
Human rhinovirus species C (HRV-C) is the most common cause of acute wheezing exacerbations in young children presenting to hospital, but its impact on subsequent respiratory illnesses has not been defined. ⋯ HRV-C-related wheezing illnesses were associated with an increased risk of prior and subsequent hospital respiratory admissions. These associations are consistent with HRV-C causing recurrent severe wheezing illnesses in children who are more susceptible to ARIs.
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Locomotor muscle atrophy develops in patients with chronic obstructive pulmonary disease (COPD) partly because of increased protein degradation by the ubiquitin-proteasome system. It is not known if autophagy also contributes to protein degradation. ⋯ Autophagy is significantly enhanced in locomotor muscles of stable patients with COPD. The degree of autophagy correlates with severity of muscle atrophy and lung function impairment.
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Am. J. Respir. Crit. Care Med. · Dec 2013
Hypoxia Promotes Danger-Mediated Inflammation via RAGE in Cystic Fibrosis.
Hypoxia regulates the inflammatory-antiinflammatory balance by the receptor for advanced glycation end products (RAGE), a versatile sensor of damage-associated molecular patterns. The multiligand nature of RAGE places this receptor in the midst of chronic inflammatory diseases. ⋯ A causal link between hyperactivation of RAGE and inflammation in CF has been observed, such that targeting pathogenic inflammation alleviated inflammation in CF and measurement of sRAGE levels could be a useful biomarker for RAGE-dependent inflammation in patients with CF.