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    14782 results match your criteria American journal of respiratory and critical care medicine[Journal]

    1 OF 296

    Therapeutic Targeting of Vascular Remodeling and Right Heart Failure in PAH with HIF-2α Inhibitor.
    Am J Respir Crit Care Med 2018 Jun 20. Epub 2018 Jun 20.
    Northwestern University, Pediatrics, Chicago, Illinois, United States.
    Rationale: Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vasoconstriction and obliterative vascular remodeling that leads to right heart failure (RHF) and death. Current therapies do not target vascular remodeling and RHF, and only result in modest improvement of morbidity and mortality.

    Objective: To determine whether targeting HIF-2α with a HIF-2α-selective inhibitor could reverse PAH and RHF in different rodent PAH models. Read More

    Reversing Mechanoinductive Desmoplakin (DSP) Expression by CRISPR/dCas9-Mediated Epigenome Editing.
    Am J Respir Crit Care Med 2018 Jun 20. Epub 2018 Jun 20.
    University of Alabama at Birmingham, Birmingham, Alabama, United States ;
    Rationale: Desmoplakin (DSP), the most abundant component of desmosomes which maintain the mechanical integrity of epithelium, is a GWAS-identified genetic risk locus in human idiopathic pulmonary fibrosis (IPF). IPF subjects express a significantly higher level of DSP than control subjects.

    Objectives: Determine potential mechanisms by which DSP is regulated in lung fibrosis Methods: Matrigel-coated soft and stiff polyacrylamide gels were made to simulate the stiffness of normal and fibrotic lungs. Read More

    Diagnosis of Primary Ciliary Dyskinesia. An Official American Thoracic Society Clinical Practice Guideline.
    Am J Respir Crit Care Med 2018 Jun;197(12):e24-e39
    Background: This document presents the American Thoracic Society clinical practice guidelines for the diagnosis of primary ciliary dyskinesia (PCD).

    Target Audience: Clinicians investigating adult and pediatric patients for possible PCD.

    Methods: Systematic reviews and, when appropriate, meta-analyses were conducted to summarize all available evidence pertinent to our clinical questions. Read More

    Abrupt Deflation after Sustained Inflation Causes Lung Injury.
    Am J Respir Crit Care Med 2018 Jun 14. Epub 2018 Jun 14.
    Hospital Sick Children, Department of Critical Care Medicine, Toronto, Ontario, Canada ;
    Rationale: Ventilator management in ARDS focuses on 'setting' parameters and not on ventilator disconnection.

    Objective: To determine if abrupt deflation after sustained inflation causes lung injury.

    Methods: Male Sprague-Dawley rats were ventilated (6 mL·kg-1) and randomized to Control (n=6, PEEP 3 cmH2O; 100 min) or Intervention (n=6, PEEP 3 to 11 cmH2O over 70 min; abrupt deflation to zero PEEP; ventilation for 30 mins). Read More

    Ambient Pollution Related Reprogramming of the Human Small Airway Epithelial Transcriptome.
    Am J Respir Crit Care Med 2018 Jun 13. Epub 2018 Jun 13.
    Weill Cornell Medical College, New York, New York, United States ;
    Rationale: Epidemiological studies have demonstrated that exposure to particulate matter ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Fine air-borne particles <2.5 μm (PM2. Read More

    Macrophage Rac2 Is Required to Reduce the Severity of Cigarette Smoke-induced Pneumonia.
    Am J Respir Crit Care Med 2018 Jun 13. Epub 2018 Jun 13.
    University of Alabama at Birmingham, Medicine, Birmingham, Alabama, United States ;
    Rationale: Cigarette smoking is prevalent in the U.S. and is the leading cause of preventable diseases. Read More

    Azithromycin for Early Pseudomonas Infection in Cystic Fibrosis: The Optimize Randomized Trial.
    Am J Respir Crit Care Med 2018 Jun 11. Epub 2018 Jun 11.
    University of Washington School of Medicine, Pediatrics, Seattle, Washington, United States.
    Rationale: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach complementing traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation (PEx) and inflammation may ultimately prolong time to Pa recurrence.

    Objectives: To test the hypothesis that the addition of azithromycin to TIS in children with CF and early Pa decreases the risk of PEx and prolongs time to Pa recurrence. Read More

    End of Life Strategies Among Patients with Advanced Chronic Obstructive Pulmonary Disease (COPD).
    Am J Respir Crit Care Med 2018 Jun 11. Epub 2018 Jun 11.
    Ottawa Health Research Institute, Ottawa, Ontario, Canada.
    Rationale: The burden of advanced COPD is high globally; however, little is known about how often end of life strategies are used by this population.

    Objectives: To describe trends in the use of end of life care strategies by people with advanced COPD in Ontario, Canada.

    Methods: A population-based repeated cross-sectional study examining end of life care strategies in individuals with advanced COPD was conducted. Read More

    Efficacy of an Inhaled Interleukin-13 Antibody Fragment in a Model of Chronic Asthma.
    Am J Respir Crit Care Med 2018 Jun 8. Epub 2018 Jun 8.
    UCB Pharma, Slough, United Kingdom of Great Britain and Northern Ireland ;
    Rationale: Interleukin-13 is an important cytokine implicated in the pathogenesis of allergic asthma and is an attractive target for an inhaled therapeutic.

    Objective: To investigate the efficacy of CDP7766, a nebulized inhaled anti-interleukin-13 monoclonal antibody Fab fragment, in a model of allergic asthma in cynomolgus macaques naturally sensitized to Ascaris suum.

    Methods: CDP7766 was nebulized using a vibrating-membrane nebulizer based on eFlow® technology. Read More

    Unintended Consequences; Fluid Resuscitation Worsens Shock in an Ovine Model of Endotoxemia.
    Am J Respir Crit Care Med 2018 Jun 8. Epub 2018 Jun 8.
    University of Queensland, Critical Care Research Group, Brisbane, Queensland, Australia.
    Background: Fluid resuscitation is widely considered a life saving intervention in septic shock however recent evidence has questioned both its safety and efficacy in sepsis. This study sought to compare fluid resuscitation with vasopressors with vasopressors alone in a hyperdynamic model of ovine endotoxemia.

    Methods: Endotoxemic shock was induced in sixteen sheep after which they received fluid resuscitation with 40mls/kg of 0. Read More

    Lung Dysbiosis, Inflammation, and Injury in Hematopoietic Cell Transplantation.
    Am J Respir Crit Care Med 2018 Jun 7. Epub 2018 Jun 7.
    University of Michigan Health System, Internal Medicine, Ann Arbor, Michigan, United States.
    Rationale: Hematopoietic cell transplantation (HCT) is a common treatment for hematological neoplasms and autoimmune disorders. Among HCT recipients, pulmonary complications are common, morbid, and/or lethal, and have recently been associated with gut dysbiosis. The role of lung microbiota in post-HCT pulmonary complications is unknown. Read More

    Development of Macrolide Resistance and Reinfection in Refractory Mycobacterium avium Complex Lung Disease.
    Am J Respir Crit Care Med 2018 Jun 7. Epub 2018 Jun 7.
    Samsung Medical Center, Sungkyunkwan University School of Medicine, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Seoul, Korea, Republic of ;
    Rationale: Patients with refractory Mycobacterium avium complex lung disease (MAC-LD) undergo long-term macrolide therapy, but macrolide resistance develops infrequently.

    Objectives: The aim of this study was to determine whether reinfection was a factor in the low incidence of macrolide resistance in patients with refractory MAC-LD.

    Methods: Among 481 patients with treatment-naive MAC-LD who started antibiotic treatment between January 2002 and December 2013, we identified 72 patients with refractory disease, characterized by persistently positive sputum cultures despite ≥12 months of treatment. Read More

    Bronchial Dieulafoy's Disease: Visualization of Embolization Particles in Bronchial Aspirate.
    Am J Respir Crit Care Med 2018 Jun 7. Epub 2018 Jun 7.
    Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Service de Réanimation Médico-Chirurgicale, Groupe Hospitalier des Hôpitaux Universitaires de l'Est Parisien. UPMC Université Paris 6., PARIS, France.

    Drug Penetration Gradients Associated with Acquired Drug Resistance in Tuberculosis Patients.
    Am J Respir Crit Care Med 2018 Jun 7. Epub 2018 Jun 7.
    Baylor Institute for Immunology Research, 53620, Dallas, Texas, United States ;
    Rationale: Acquired resistance is an important driver of multidrug-resistant tuberculosis, even with good treatment adherence. However, exactly what initiates the resistance, and how it arises remains poorly understood.

    Objectives: To identify the relationship between drug concentrations and drug susceptibility readouts (MICs) in the tuberculosis cavity. Read More

    Ontogeny and Biology of Human Small Airway Epithelial Club Cells.
    Am J Respir Crit Care Med 2018 Jun 6. Epub 2018 Jun 6.
    Weill Cornell Medical College, New York, New York, United States ;
    Rationale: Little is known about human club ("Clara") cells, dome shaped cells with dense cytoplasmic granules and microvilli that represent the major secretory cells of the human small air-ways (≥6th generation bronchi).

    Objective: To define the ontogeny and biology of the human small airway epithelium club cell.

    Methods: The small airway epithelium was sampled from the normal human lung by bronchoscopy and brushing. Read More

    Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study.
    Am J Respir Crit Care Med 2018 Jun 6. Epub 2018 Jun 6.
    Brigham and Women's Hospital, Channing Division of Network Medicine, Boston, Massachusetts, United States.
    Rationale/Objective Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as "restrictive" or "GOLD-Unclassified" spirometry, has expanded the body of knowledge on cross-sectional risk factors. However, longitudinal studies of PRISm remain limited. Methods/Measurements Current and former smokers, age 45-80, were enrolled in COPDGene (Phase 1, 2008-2011) and returned for a 5-year follow up (Phase 2, 2012-2016). Read More

    A Disintegrin and A Metalloproteinase-9 (ADAM9): A Novel Proteinase Culprit with Multifarious Contributions to COPD.
    Am J Respir Crit Care Med 2018 Jun 4. Epub 2018 Jun 4.
    Brigham and Women's Hospital, Boston, Massachusetts, United States ;
    Introduction: Proteinases with a disintegrin and a metalloproteinase domain (ADAMs) have not been well studied in COPD. We investigated whether ADAM9 is linked to COPD in humans and mice.

    Methods: ADAM9 blood and lung levels were measured in COPD patients versus controls, and air- versus cigarette smoke (CS)-exposed wild-type (WT) mice. Read More

    Airway Microbiota Is Associated with Up-Regulation of the PI3K Pathway in Lung Cancer.
    Am J Respir Crit Care Med 2018 Jun 4. Epub 2018 Jun 4.
    New York University, Pulmonary and Critical Care Medicine, New York, New York, United States ;
    Background: In lung cancer, upregulation of the PI3K pathway is an early event that contributes to cell proliferation, survival, and tissue invasion. Upregulation of this pathway was recently described as associated with enrichment of the lower airways with bacteria identified as oral commensals. We hypothesize that host-microbe interactions in the lower airways of subjects with lung cancer affect known cancer pathways. Read More

    Neonatal Pulmonary MRI of Bronchopulmonary Dysplasia Predicts Short-term Clinical Outcomes.
    Am J Respir Crit Care Med 2018 May 23. Epub 2018 May 23.
    Cincinnati Children's Hospital Medical Center, Center for Pulmonary Imaging Research, Cincinnati, Ohio, United States.
    Rationale: Bronchopulmonary dysplasia (BPD) is a serious neonatal pulmonary condition associated with premature birth, but the underlying parenchymal disease and trajectory are poorly characterized. The current NICHD/NHLBI definition of BPD severity is based on degree of prematurity and extent of oxygen requirement. However, no clear link exists between initial diagnosis and clinical outcomes. Read More

    Deterioration of Regional Lung Strain and Inflammation during Early Lung Injury.
    Am J Respir Crit Care Med 2018 May 22. Epub 2018 May 22.
    Massachusetts General Hospital, Harvard University, Department of Anesthesia, Critical Care and Pain Medicine, Boston, Massachusetts, United States ;
    Rationale: The contribution of aeration heterogeneity to lung injury during early mechanical ventilation of uninjured lungs is unknown.

    Objective: Test the hypotheses that a strategy consistent with clinical practice does not protect from worsening in lung strains during the first 24h of ventilation of initially normal lungs exposed to mild systemic endotoxemia in supine versus prone position, and that local neutrophilic inflammation is associated with local strain and blood volume at global strains below a proposed injurious threshold.

    Methods: Voxel level aeration and tidal strain were assessed by computed tomography in sheep ventilated with low tidal volume and positive end-expiratory pressure while receiving intravenous endotoxin. Read More

    A Multicenter RCT of Zephyr® Endobronchial Valve Treatment in Heterogeneous Emphysema (LIBERATE).
    Am J Respir Crit Care Med 2018 May 22. Epub 2018 May 22.
    University Medical Center Groningen, Pulmonary diseases, Groningen, Netherlands.
    Rationale: This is the first multicenter RCT to evaluate effectiveness and safety of Zephyr® Endobronchial Valve EBV® out to 12-months.

    Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation (CV) in the treated lobe.

    Methods: Subjects were enrolled with a 2:1 randomization (EBV: Standard-of-Care (SoC)) at 24 sites. Read More

    Associations between Parasympathetic Activity in the Month after Birth and Wheeze at Age 2-3 Years.
    Am J Respir Crit Care Med 2018 May 22. Epub 2018 May 22.
    Columbia University, 5798, Division of Developmental Neuroscience, Department of Psychiatry, , New York, New York, United States.

    Early Intravascular Events Are Associated with Development of Acute Respiratory Distress Syndrome. A Substudy of the LIPS-A Clinical Trial.
    Am J Respir Crit Care Med 2018 Jun;197(12):1575-1585
    1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
    Rationale: Acute respiratory distress syndrome (ARDS) is a devastating illness with limited therapeutic options. A better understanding of early biochemical and immunological events in ARDS could inform the development of new preventive and treatment strategies.

    Objectives: To determine select peripheral blood lipid mediator and leukocyte responses in patients at risk for ARDS. Read More

    Long-term Triple Therapy De-escalation to Indacaterol/Glycopyrronium in COPD Patients (SUNSET): a Randomized, Double-Blind, Triple-Dummy Clinical Trial.
    Am J Respir Crit Care Med 2018 May 20. Epub 2018 May 20.
    Imperial College London, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland ;
    Rationale: There are no studies on ICS withdrawal in patients on long-term triple therapy in the absence of frequent exacerbations.

    Objective: To evaluate the efficacy and safety of the direct de-escalation from long-term triple therapy to indacaterol/glycopyrronium in non-frequently exacerbating COPD patients.

    Methods: This 26-week, randomized, double-blind, triple-dummy study assessed the direct change from long-term triple therapy to indacaterol/glycopyrronium (110/50μg once daily) or continuation of triple therapy (tiotropium 18μg once daily plus combination of salmeterol/fluticasone propionate [50/500μg] twice daily) in non-frequently exacerbating patients with moderate-to-severe COPD. Read More

    Does Armodafinil Improve Driving Task Performance and Weight Loss in Sleep Apnea? A Randomized Trial.
    Am J Respir Crit Care Med 2018 May 18. Epub 2018 May 18.
    Woolcock Institute for Medical Research, University of Sydney, NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Sydney, New South Wales, Australia.
    RATIONALE Obstructive sleep apnea (OSA) patients unable to tolerate standard treatments have few alternatives. They may benefit from weight loss, but the major symptom of daytime performance impairment may remain during weight loss programs. OBJECTIVES We hypothesized that wakefulness-promoter armodafinil would improve driving task performance over placebo in patients undergoing weight loss. Read More

    Staphylococcus aureus Induces Mucosal Type 2 Immune Response via Epithelial Cell Derived Cytokines.
    Am J Respir Crit Care Med 2018 May 16. Epub 2018 May 16.
    Ghent University, Upper Airways Research Laboratory, ENT Department,, Ghent, Belgium.
    Rationale: Chronic rhinosinusitis with nasal polyps is characterized by a T helper cell 2-skewed upper airway inflammation. Mucosal Staphylococcus aureus colonization is found in the majority of nasal polyps patients. Staphylococcus aureus is known to induce type 2 cytokine release via enterotoxins. Read More

    The Post-injury Inflammatory State and the Bone Marrow Response to Anemia.
    Am J Respir Crit Care Med 2018 May 16. Epub 2018 May 16.
    University of Florida, Surgery, Gainesville, Florida, United States ;
    Rationale: The pathophysiology of persistent injury-associated anemia is incompletely understood, and human data are sparse.

    Objective: To translate pre-clinical findings by characterizing injury-associated anemia among critically ill trauma patients. This study compared elective hip repair patients with an acute stress response to severely injured trauma patients with a prolonged stress response and evaluated the bone marrow response to anemia. Read More

    A Cross Sectional Assessment of Rhinitis Symptoms and Nasal Patency in Relation to Welding Exposure.
    Am J Respir Crit Care Med 2018 May 15. Epub 2018 May 15.
    Centre integre universitaire de sante et de services sociaux du Nord-de-l'Ile-de-Montreal, 439501, Hôpital du Sacré-Cœur de Montréal , Montreal, Quebec, Canada.

    Determinants of Response to Roflumilast in Severe COPD: Pooled Analysis of Two Randomized Trials.
    Am J Respir Crit Care Med 2018 May 15. Epub 2018 May 15.
    University of Nebraska Medical Center, Pulmonary and Critical Care Medicine, Omaha, Nebraska, United States.
    Rationale: Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations. Further characterization of patients most likely to benefit is warranted.

    Objectives: Define characteristics that most robustly identify patients who derive greatest exacerbation risk reduction with roflumilast. Read More

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