American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jan 2019
Identification of Functional Variants in the FAM13A COPD GWAS Locus by Massively Parallel Reporter Assays.
The identification of causal variants responsible for disease associations from genome-wide association studies (GWASs) facilitates functional understanding of the biological mechanisms by which those genetic variants influence disease susceptibility. ⋯ The human GWAS association near FAM13A may contain independent association signals. MPRAs identified multiple functional variants in this region, including rs2013701, a putative COPD-causing variant with allele-specific regulatory activity.
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Am. J. Respir. Crit. Care Med. · Jan 2019
Randomized Controlled TrialCapturing Exacerbations of Chronic Obstructive Pulmonary Disease with EXACT: A Sub-Analysis of FLAME.
Chronic obstructive pulmonary disease exacerbations accelerate lung function decline, reduce quality of life, and increase mortality. A subset of patients (n = 457) from the FLAME (Effect of Indacaterol Glycopyrronium vs. Fluticasone Salmeterol on COPD Exacerbations) study used the Exacerbations of COPD Tool (EXACT) to capture symptom-defined exacerbations. ⋯ Regardless of the exacerbation definition used, our findings support the use of long-acting β2 agonists/long-acting muscarinic receptor antagonists as the preferred treatment option for patients at risk of future exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT01782326).
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Am. J. Respir. Crit. Care Med. · Jan 2019
Longitudinal Phenotypes of Respiratory Health in a High-Risk Urban Birth Cohort.
Characterization of patterns of wheezing and allergic sensitization in early life may allow for identification of specific environmental exposures impacting asthma development. ⋯ Patterns of wheezing, allergic sensitization, and lung function identified five respiratory phenotypes among inner-city children. Early-life environmental exposure to stress, depression, tobacco smoke, and indoor allergens and microbes differentially associate with specific phenotypes.
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Am. J. Respir. Crit. Care Med. · Jan 2019
Impact of Preeclampsia on the Relationship of Maternal Asthma with Offspring Asthma: An Observation from the VDAART Clinical Trial.
Maternal asthma and preeclampsia have independently been reported to be associated with increased asthma incidence in children of affected mothers. Maternal asthma is also associated with increased risk of preeclampsia development. However, the joint effect of these maternal conditions on child asthma risk is unknown. ⋯ Preeclampsia is associated with increased risk of early life childhood asthma in children less than 3 years old over and above that associated with maternal asthma alone. The results implicate the interplay between maternal factors as strong predictors of offspring asthma and in utero maternal-fetal immune perturbations and developmental dysregulations associated with preeclampsia.