American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Aug 2023
ReviewProgress in the Treatment of Pulmonary Hypertension Associated with Interstitial Lung Disease.
Pulmonary hypertension, frequently complicating the course of patients with fibrotic interstitial lung disease, is associated with significantly increased morbidity and mortality. The availability of multiple medications to treat pulmonary arterial hypertension has resulted in these agents being used beyond their original indication, including in patients with interstitial lung disease. Whether pulmonary hypertension in the context of interstitial lung disease is an adaptive response not to be treated or a maladaptive phenomenon amenable to therapy has been uncertain. ⋯ This concise clinical review provides an overview of prior studies and the issues that have plagued drug development for a patient population in dire need of treatment options. More recently, there has been a paradigm shift, with the largest study to date demonstrating benefit, resulting in the first approved therapy in the United States for patients with interstitial lung disease complicated by pulmonary hypertension. A pragmatic management algorithm in the context of changing definitions, comorbid contributors, and an available treatment option is provided, as are considerations for future clinical trials.
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Am. J. Respir. Crit. Care Med. · Aug 2023
Observational StudyAssociation of Non-Invasive Respiratory Support with Extubation Outcomes in Brain-Injured Patients Receiving Mechanical Ventilation: A Secondary Analysis of ENIO.
Rationale: Noninvasive respiratory support using a high-flow nasal cannula (HFNC) or noninvasive positive pressure ventilation (NIPPV) can decrease the risk of reintubation in patients being liberated from mechanical ventilation, but effects in patients with acute brain injury (ABI) are unknown. Objectives: To evaluate the association between postextubation noninvasive respiratory support and reintubation in patients with ABI being liberated from mechanical ventilation. Methods: This was a secondary analysis of a prospective, observational study of mechanically ventilated patients with ABI (clinicaltrials.gov identifier NCT03400904). ⋯ Conclusions: In a large cohort of brain-injured patients undergoing liberation from mechanical ventilation, prophylactic use of HFNC and NIPPV were not associated with reintubation. Prospective trials are needed to confirm treatment effects in this population. Primary study registered with www.clinicaltrials.gov (NCT03400904).
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Am. J. Respir. Crit. Care Med. · Aug 2023
A Large-Scale Exome-Wide Association Study Identifies Novel Germline Mutations in Lung Cancer.
Rationale: Genome-wide association studies have identified common variants of lung cancer. However, the contribution of rare exome-wide variants, especially protein-coding variants, to cancers remains largely unexplored. Objectives: To evaluate the role of human exomes in genetic predisposition to lung cancer. ⋯ Functional evidence of expression of quantitative trait loci, splicing quantitative trait loci, and isoform expression was found for the four novel genes. Gene-level association tests identified several novel genes, including POT1 (protection of telomeres 1), RTEL1, BSG, and ZNF232. Conclusions: Our findings provide insights into the genetic architecture of human exomes and their role in lung cancer predisposition.
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Am. J. Respir. Crit. Care Med. · Aug 2023
Elevated Pulmonary Arterial Compliance Is Associated with Survival in Pulmonary Hypertension: Results from a Novel Network Medicine Analysis.
Rationale: Predictors of adverse outcome in pulmonary hypertension (PH) are well established; however, data that inform survival are lacking. Objectives: We aim to identify clinical markers and therapeutic targets that inform the survival in PH. Methods: We included data from patients with elevated mean pulmonary artery pressure (mPAP) diagnosed by right heart catheterization in the U. ⋯ The association was strongest in patients with precapillary PH at the time of catheterization, in whom 41% (95% confidence interval, 0.55-0.62; P < 0.001) and 49% (95% confidence interval, 0.38-0.69; P < 0.001) improvements in survival were observed for PAC ⩾3.0 versus <3.0 ml/mm Hg in the discovery and validation cohorts, respectively. Conclusions: These data identify elevated PAC as an important parameter associated with survival in PH. Prospective studies are warranted that consider PAC ⩾3.0 ml/mm Hg as a therapeutic target to achieve through proven interventions.
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Am. J. Respir. Crit. Care Med. · Aug 2023
Impact of Early Hemodynamic Screening on Extremely Preterm Outcomes in a High-Performance Center.
Rationale: Increasing survival of extremely preterm infants with a stable rate of severe intraventricular hemorrhage represents a growing health risk for neonates. Objectives: To evaluate the role of early hemodynamic screening (HS) on the risk of death or severe intraventricular hemorrhage. Methods: All eligible patients 22-26+6 weeks' gestation born and/or admitted <24 hours postnatal age were included. ⋯ A reduction in the primary outcome and each of severe intraventricular hemorrhage, death, death in the first postnatal week, necrotizing enterocolitis, and severe bronchopulmonary dysplasia was seen in the screening era. After adjustment for perinatal confounders and time, screening was independently associated with survival free of severe intraventricular hemorrhage (OR 2.09, 95% CI [1.19, 3.66]). Conclusions: Early HS and physiology-guided care may be an avenue to further improve neonatal outcomes; further evaluation is warranted.