Thorax
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The mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP) channel family are potential candidates. We have used an in vitro model of sensory neurons and human rhinovirus (HRV-16) to study the effect of virus infection on TRP expression. ⋯ We show for the first time that rhinovirus can infect neuronal cells. Furthermore, infection causes upregulation of TRP channels by channel-specific mechanisms. The increase in TRPA1 and TRPV1 levels can be mediated by soluble factors induced by infection whereas TRPM8 requires replicating virus. TRP channels may be novel therapeutic targets for controlling virus-induced cough.
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The lung clearance index (LCI) is a promising endpoint for use in cystic fibrosis (CF) clinical trials, but correlations with validated clinical endpoints have not yet been established. ⋯ Baseline LCI predicts PE in young patients with CF and correlates with CFQ-Rresp, a validated patient-reported outcome, even in the subgroup with normal FEV1. These data further support the use of LCI as a surrogate outcome measure in CF clinical trials.
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Randomized Controlled Trial
Airway gene expression in COPD is dynamic with inhaled corticosteroid treatment and reflects biological pathways associated with disease activity.
A core feature of chronic obstructive pulmonary disease (COPD) is the accelerated decline in forced expiratory volume in one second (FEV1). The recent Groningen and Leiden Universities study of Corticosteroids in Obstructive Lung Disease (GLUCOLD) study suggested that particular phenotypes of COPD benefit from fluticasone±salmeterol by reducing the rate of FEV1 decline, yet the underlying mechanisms are unknown. ⋯ The present study suggests that gene expression in biological pathways of COPD is dynamic with treatment and reflects disease activity. This study opens the gate to targeted and molecular phenotype-driven therapy of COPD.
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Spirometric Z scores by lambda-mu-sigma (LMS) rigorously account for age-related changes in lung function. Recently, the Global Lung Function Initiative (GLI) expanded LMS spirometric Z scores to multiple ethnicities. Hence, in aging populations, the GLI provides an opportunity to rigorously evaluate ethnic differences in respiratory impairment, including airflow limitation and restrictive pattern. ⋯ In an aging population, we found ethnic differences in GLI-defined respiratory impairment. In particular, African Americans had high rates of respiratory impairment that were associated with mortality but not respiratory symptoms.