American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jul 2021
Multicenter StudySafety and Efficacy of B-Cell Depletion with Rituximab for the Treatment of Systemic Sclerosis Associated Pulmonary Arterial Hypertension: A Multi-center, Double-blind, Randomized, Placebo-controlled Trial.
Rationale: Systemic sclerosis (SSc)-pulmonary arterial hypertension (PAH) is one of the most prevalent and deadly forms of PAH. B cells may contribute to SSc pathogenesis. Objectives: We investigated the safety and efficacy of B-cell depletion for SSc-PAH. ⋯ Conclusions: B-cell depletion therapy is a potentially effective and safe adjuvant treatment for SSc-PAH. Future studies in these patients can confirm whether the identified biomarkers predict rituximab responsiveness. Clinical trial registered with www.clinicaltrails.gov (NCT01086540).
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Am. J. Respir. Crit. Care Med. · Jul 2021
Comparative StudyBlood Transcriptomic Predicts Progression of Pulmonary Fibrosis and Associates Natural Killer Cells.
Rationale: Disease activity in idiopathic pulmonary fibrosis (IPF) remains highly variable, poorly understood, and difficult to predict. Objectives: To identify a predictor using short-term longitudinal changes in gene expression that forecasts future FVC decline and to characterize involved pathways and cell types. Methods: Seventy-four patients from COMET (Correlating Outcomes with Biochemical Markers to Estimate Time-Progression in IPF) cohort were dichotomized as progressors (≥10% FVC decline) or stable. ⋯ Cellular deconvolution using single-cell RNA-sequencing data identified natural killer cells as significantly correlated with progression. Conclusions: Serial transcriptomic change predicts future FVC decline. An analysis of cell types involved in the progressor signature supports the novel involvement of natural killer cells in IPF progression.
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Am. J. Respir. Crit. Care Med. · Jul 2021
Randomized Controlled TrialThe Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial.
Rationale: Childhood asthma is often preceded by recurrent episodes of asthma-like symptoms, which can be triggered by both viral and bacterial agents. Recent randomized controlled trials have shown that azithromycin treatment reduces episode duration and severity through yet undefined mechanisms. Objectives: To study the influence of the airway microbiota on the effect of azithromycin treatment during acute episodes of asthma-like symptoms. ⋯ Furthermore, effect modification of azithromycin was found for five individual OTUs (three OTUs increased and two OTUs decreased the effect; q < 0.05). Conclusions: The airway microbiota in acute episodes of asthma-like symptoms is associated with episode duration and modifies the effect of azithromycin treatment of the episodes in preschool children with recurrent asthma-like symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT01233297).
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Am. J. Respir. Crit. Care Med. · Jul 2021
Particulate Matter and Cardiovascular Risk in Adults with Chronic Obstructive Pulmonary Disease.
Rationale: People with chronic obstructive pulmonary disease (COPD) have an increased risk of cardiovascular disease and may be more susceptible to air pollution exposure. However, no study has examined the association between long-term fine particulate matter exposure (≤2.5 μm in aerodynamic diameter) and risk of cardiovascular events in this potentially vulnerable population. Objectives: To estimate the association between long-term fine particulate matter and risk of cardiovascular events among adults with COPD. ⋯ Fine particulate matter exposure was not associated with acute myocardial infarction or stroke in overall analyses. Conclusions: Long-term fine particulate matter exposure was associated with an increased risk of cardiovascular mortality among adults with COPD. Current regulations may not sufficiently protect those with COPD.
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Am. J. Respir. Crit. Care Med. · Jul 2021
Historical ArticleLatent Tuberculosis: Two Centuries of Confusion.