American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2019
Complete Tracheal Ring Deformity: A Translational Genomics Approach to Pathogenesis.
Rationale: Complete tracheal ring deformity (CTRD) is a rare congenital abnormality of unknown etiology characterized by circumferentially continuous or nearly continuous cartilaginous tracheal rings, variable degrees of tracheal stenosis and/or shortening, and/or pulmonary arterial sling anomaly. Objectives: To test the hypothesis that CTRD is caused by inherited or de novo mutations in genes required for normal tracheal development. Methods: CTRD and normal tracheal tissues were examined microscopically to define the tracheal abnormalities present in CTRD. ⋯ De novo variants were identified in SHH (Sonic Hedgehog), and inherited variants were identified in HSPG2 (perlecan), ROR2 (receptor tyrosine kinase-like orphan receptor 2), and WLS (Wntless), genes involved in morphogenetic pathways known to mediate tracheoesophageal development in mice. Conclusions: The results of the present study demonstrate that absence of the trachealis muscle is associated with CTRD. Variants predicted to cause disease were identified in genes encoding Hedgehog and Wnt signaling pathway molecules, which are critical to cartilage formation and normal upper airway development in mice.
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Am. J. Respir. Crit. Care Med. · Nov 2019
Impaired Right Ventricular Performance is Associated with Adverse Outcome Following Hypoxic Ischemic Encephalopathy.
Rationale: Asphyxiated neonates with hypoxic ischemic encephalopathy (HIE) are at risk of myocardial dysfunction; however, echocardiography studies are limited and little is known about the relationship between hemodynamics and brain injury. Objectives: To analyze the association between severity of myocardial dysfunction and adverse outcome as defined by the composite of death and/or abnormal magnetic resonance imaging. Methods: Neonates with HIE undergoing therapeutic hypothermia were enrolled. ⋯ High brain regional oxygen saturation (P = 0.007) and low middle cerebral artery resistive index (P = 0.04) were associated with RV dysfunction on post hoc analysis. Conclusions: RV dysfunction is associated with the risk of adverse outcome in asphyxiated patients with HIE undergoing hypothermia. Echocardiography may be a valuable diagnostic and prognostic tool in this vulnerable population.
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Am. J. Respir. Crit. Care Med. · Nov 2019
Tracking Impact of Interstitial Lung Disease in Systemic Sclerosis in a Complete Nationwide Cohort.
Rationale: Interstitial lung disease (ILD) represents a major challenge in systemic sclerosis (SSc), but there are no precise, population-based data on its overall impact, limiting opportunities for screening and management strategies. Objectives: Evaluate impact of ILD in a unique, nationwide, population-based SSc cohort. Methods: ILD was assessed prospectively in the Norwegian SSc (Nor-SSc) cohort, including all 815 patients with SSc resident in the country from 2000 to 2012. ⋯ SMR was inversely related to baseline FVC% and increased at all FVC levels below 100%. In patients with normal-range baseline FVC (80-100%), the 5- and 10-year survival rates correlated with presence or absence of lung fibrosis, being 83% and 80%, respectively, with no fibrosis and 69% and 56%, respectively, with lung fibrosis (P = 0.03). Conclusions: The mere presence of ILD at baseline appears to affect outcome in SSc, suggesting that all patients with SSc should undergo a baseline pulmonary function test and lung HRCT screening to diagnose ILD early and tailor further management.