American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Dec 2019
Randomized Controlled TrialNintedanib and Sildenafil in Patients with Idiopathic Pulmonary Fibrosis and Right Heart Dysfunction. A Prespecified Subgroup Analysis of a Double-Blind Randomized Clinical Trial (INSTAGE).
Rationale: In the INSTAGE trial in patients with idiopathic pulmonary fibrosis (IPF) and severely impaired gas exchange, nintedanib plus sildenafil was associated with numerical benefits on St. George's Respiratory Questionnaire (SGRQ) total score, brain natriuretic peptide (BNP), and FVC decline versus nintedanib alone. Exploratory analyses of the STEP-IPF (Sildenafil Trial of Exercise Performance in IPF) trial suggested that sildenafil may have a greater effect on SGRQ score in patients with IPF who have right heart dysfunction (RHD). ⋯ Conclusions: In the INSTAGE trial, there were no significant differences in the effects of nintedanib plus sildenafil versus nintedanib alone on changes in SGRQ and FVC between patients with or without echocardiographic signs of RHD at baseline. The benefit of combination therapy on stabilizing BNP was more pronounced in patients with RHD at baseline. Clinical trial registered with www.clinicaltrials.gov (NCT02802345).
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Am. J. Respir. Crit. Care Med. · Dec 2019
Tuberculosis Diagnosis in Children Using Xpert Ultra on Different Respiratory Specimens.
Rationale: Microbiological confirmation of pulmonary tuberculosis in children is desirable. Objectives: To investigate the diagnostic accuracy and incremental yield of Xpert MTB/RIF Ultra (Ultra; Cepheid), a new rapid test, on repeated induced sputum, nasopharyngeal aspirates, and combinations of specimens. Methods: Consecutive South African children hospitalized with suspected pulmonary tuberculosis were enrolled. ⋯ Sensitivity using Ultra on two NPAs was 54.2%, increasing to 87.5% with an IS Ultra. Conclusions: IS provides a better specimen than repeated NPA for rapid diagnosis using Ultra. However, Ultra testing of combinations of specimens provides a novel strategy that can be adapted to identify most children with confirmed pulmonary tuberculosis.
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Am. J. Respir. Crit. Care Med. · Dec 2019
Multicenter StudyVentricular Dysfunction Is a Critical Determinant of Mortality in Congenital Diaphragmatic Hernia.
Rationale: Congenital diaphragmatic hernia (CDH) is an anomaly with a high morbidity and mortality. Cardiac dysfunction may be an important and underrecognized contributor to CDH pathophysiology and determinant of disease severity. Objectives: Our aim was to investigate the association between early, postnatal ventricular dysfunction and outcome among infants with CDH. ⋯ The adjusted risk of death (hazard ratio) for cases with LVdys was 1.96 (95% confidence interval [CI], 1.29-2.98; P = 0.020) and for cases with RV&LVdys was 2.27 (95% CI, 1.77-2.92; P = 0.011). All cardiac dysfunction categories were associated with use of extracorporeal membrane oxygenation (P < 0.005). Conclusions: Early ventricular dysfunction occurs frequently in CDH and is an independent determinant of severity and clinical outcome.
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Am. J. Respir. Crit. Care Med. · Dec 2019
Pulmonary Aptamer Signatures in Children's Interstitial and Diffuse Lung Disease.
Rationale: Biomarker signatures are needed in children with children's interstitial and diffuse lung disease (chILD) to improve diagnostic approaches, increase our understanding of disease pathogenesis, monitor disease progression, and develop new treatment strategies. Proteomic technology using SOMAmer (Slow Off-rate Modified Aptamer) nucleic acid-based protein-binding reagents allows for biomarker discovery. Objectives: We hypothesized that proteins and protein pathways in BAL fluid (BALF) would distinguish children with neuroendocrine cell hyperplasia of infancy (NEHI), surfactant dysfunction mutations, and other chILD diagnoses and control subjects. ⋯ Proteins associated with pulmonary fibrosis and inflammation were associated with the surfactant dysfunction group but not the NEHI group. Using hierarchical clustering analysis, two distinct NEHI endotypes were identified. Conclusions: Distinct proteins and protein pathways can be determined from BALF of children with chILD, and these hold promise to further our understanding of chILD.