American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2022
Race/Ethnicity, Spirometry Reference Equations and Prediction of Incident Clinical Events: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.
Rationale: Normal values for FEV1 and FVC are currently calculated using cross-sectional reference equations that include terms for race/ethnicity, an approach that may reinforce disparities and is of unclear clinical benefit. Objectives: To determine whether race/ethnicity-based spirometry reference equations improve the prediction of incident chronic lower respiratory disease (CLRD) events and mortality compared with race/ethnicity-neutral equations. Methods: The MESA Lung Study, a population-based, prospective cohort study of White, Black, Hispanic, and Asian adults, performed standardized spirometry from 2004 to 2006. ⋯ Findings were similar for mortality (difference in C statistics for FEV1, -0.002; 95% CI, -0.008 to 0.003; difference in C statistics for FVC, -0.004; 95% CI, -0.009 to 0.001). Conclusions: There was no evidence that race/ethnicity-based spirometry reference equations improved the prediction of clinical events compared with race/ethnicity-neutral equations. The inclusion of race/ethnicity in spirometry reference equations should be reconsidered.
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Am. J. Respir. Crit. Care Med. · Mar 2022
Randomized Controlled TrialLong-Term Safety and Efficacy of Tocilizumab in Early Systemic Sclerosis-Interstitial Lung Disease: Open Label Extension of a Phase 3 Randomized Controlled Trial.
Rationale: Tocilizumab, an anti-IL-6 receptor antibody, had no statistically significant effect on skin sclerosis but preserved lung function over 48 weeks in patients with early systemic sclerosis (SSc)-associated interstitial lung disease (ILD) in a phase 3 randomized controlled trial. Objectives: Assess long-term safety and efficacy of tocilizumab. Methods: Adults with diffuse cutaneous SSc for ⩽60 months and elevated acute-phase reactants, including those with ILD, received weekly placebo or tocilizumab 162 mg subcutaneously in the 48-week, double-blind period and then open-label tocilizumab from Weeks 48 to 96 (placebo-tocilizumab; continuous-tocilizumab). ⋯ Conclusions: Tocilizumab preserved lung function, slowing decline in FVC, in patients with SSc, including those with ILD. Long-term safety was consistent with the known safety profile of tocilizumab. Clinical trial registered with www.clinicaltrials.gov (NCT02453256).
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Am. J. Respir. Crit. Care Med. · Mar 2022
Stakeholder Research Priorities to Promote Implementation of Shared Decision-Making for Lung Cancer Screening: An American Thoracic Society and Veterans Affairs Health Services Research and Development Statement.
Rationale: Shared decision-making (SDM) for lung cancer screening (LCS) is recommended in guidelines and required by Medicare, yet it is seldom achieved in practice. The best approach for implementing SDM for LCS remains unknown, and the 2021 U. S. ⋯ Our committee ranked questions that apply innovative implementation approaches to relieve primary care providers of the sole responsibility of SDM for LCS as highest priority. We rated effectiveness constructs that capture the patient experience of SDM as most important. Conclusions: This statement offers a stakeholder-prioritized research agenda and outcomes to advance implementation of SDM for LCS.
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Am. J. Respir. Crit. Care Med. · Mar 2022
Thrombospondin-1 Plays a Major Pathogenic Role in Experimental and Human Bronchopulmonary Dysplasia.
Rationale: Extremely preterm infants develop bronchopulmonary dysplasia (BPD), a chronic lung injury that lacks effective treatment. TSP-1 (thrombospondin-1) is an antiangiogenic protein that activates TGF-β1 (transforming growth factor-β1), a cytokine strongly linked to both experimental and human BPD. Objectives: 1) To examine effects of inhibiting TSP-1-mediated TGF-β1 activation (LSKL [leucine-serine-lysine-leucine]) in neonatal rats with bleomycin-induced lung injury; 2) to examine effects of a TSP-1 mimic (ABT-510) on lung morphology; and 3) to determine whether TSP-1 and related signaling peptides are increased in lungs of human preterm infants at risk for BPD. ⋯ TGF-β1 content correlated with markers of lung injury. Conclusions: TSP-1 inhibits alveologenesis in neonatal rats, in part via the upregulated activity of TGF-β1. Observations in human lungs suggest a similar pathogenic role for TSP-1 in infants at risk for BPD.