American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Oct 2021
Association Between Initial Treatment Strategy and Long-term Survival in Pulmonary Arterial Hypertension.
Rationale: The relationship between the initial treatment strategy and survival in pulmonary arterial hypertension (PAH) remains uncertain. Objectives: To evaluate the long-term survival of patients with PAH categorized according to the initial treatment strategy. Methods: A retrospective analysis of incident patients with idiopathic, heritable, or anorexigen-induced PAH enrolled in the French Pulmonary Hypertension Registry (January 2006 to December 2018) was conducted. ⋯ In multivariable Cox regression, triple therapy was independently associated with a lower risk of death (hazard ratio, 0.29; 95% confidence interval, 0.11-0.80; P = 0.017). Among the 148 patients initiated on a parenteral prostacyclin, those on triple therapy had a higher survival rate than those on monotherapy or dual therapy. Conclusions: Initial triple-combination therapy that includes parenteral prostacyclin seems to be associated with a higher survival rate in PAH, particularly in the youngest high-risk patients.
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Am. J. Respir. Crit. Care Med. · Oct 2021
Prenatal Ambient Ultrafine Particle Exposure and Childhood Asthma in the Northeastern United States.
Rationale: Ambient ultrafine particles (UFPs; with an aerodynamic diameter < 0.1 μm) may exert greater toxicity than other pollution components because of their enhanced oxidative capacity and ability to translocate systemically. Studies examining associations between prenatal UFP exposure and childhood asthma remain sparse. Objectives: We used daily UFP exposure estimates to identify windows of susceptibility of prenatal UFP exposure related to asthma in children, accounting for sex-specific effects. ⋯ Bayesian distributed lag interaction models indicated sex differences in the windows of susceptibility, with the highest risk of asthma seen in females exposed to higher UFP concentrations during late pregnancy. Conclusions: Prenatal UFP exposure was associated with asthma development in children, independent of correlated ambient NO2 and temperature. Findings will benefit future research and policy-makers who are considering appropriate regulations to reduce the adverse effects of UFPs on child respiratory health.
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Am. J. Respir. Crit. Care Med. · Oct 2021
Innate-like Gene Expression of Lung-resident Memory CD8+ T-cells During Experimental Human Influenza: A Clinical Study.
Rationale: Suboptimal vaccine immunogenicity and antigenic mismatch, compounded by poor uptake, means that influenza remains a major global disease. T cells recognizing peptides derived from conserved viral proteins could enhance vaccine-induced cross-strain protection. Objectives: To investigate the kinetics, phenotypes, and function of influenza virus-specific CD8+ resident memory T (Trm) cells in the lower airway and infer the molecular pathways associated with their response to infection in vivo. ⋯ However, gene set enrichment analysis of BAL-fluid CD8+ T cells showed primarily innate cell-related pathways and, during infection, included upregulation of innate chemokines (Cxcl1, Cxcl10, and Cxcl16) that were also expressed by CD8+ cells in bronchial tissues. Conclusions: CD8+ Trm cells in the human lung display innate-like gene and protein expression that demonstrates blurred divisions between innate and adaptive immunity. Clinical study registered with www.clinicaltrials.gov (NCT02755948).
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Am. J. Respir. Crit. Care Med. · Oct 2021
Research Needs for Inpatient Management of Severe Alcohol Withdrawal Syndrome: An Official American Thoracic Society Research Statement.
Background: Severe alcohol withdrawal syndrome (SAWS) is highly morbid, costly, and common among hospitalized patients, yet minimal evidence exists to guide inpatient management. Research needs in this field are broad, spanning the translational science spectrum. Goals: This research statement aims to describe what is known about SAWS, identify knowledge gaps, and offer recommendations for research in each domain of the Institute of Medicine T0-T4 continuum to advance the care of hospitalized patients who experience SAWS. ⋯ Major themes included 1) the need to investigate non-γ-aminobutyric acid pathways for alcohol withdrawal syndrome treatment; 2) harnessing retrospective and electronic health record data to identify risk factors and create objective severity scoring systems, particularly for acutely ill patients with SAWS; 3) the need for more robust comparative-effectiveness data to identify optimal SAWS treatment strategies; and 4) recommendations to accelerate implementation of effective treatments into practice. Conclusions: The dearth of evidence supporting management decisions for hospitalized patients with SAWS, many of whom require critical care, represents both a call to action and an opportunity for the American Thoracic Society and larger scientific communities to improve care for a vulnerable patient population. This report highlights basic, clinical, and implementation research that diverse experts agree will have the greatest impact on improving care for hospitalized patients with SAWS.