American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Apr 2016
The Early Development of Wheeze: Environmental Determinants and Genetic Susceptibility at 17q21.
Growing up on a farm protects from childhood asthma and early wheeze. Virus-triggered wheeze in infancy predicts asthma in individuals with a genetic asthma risk associated with chromosome 17q21. ⋯ These findings suggest that the chromosome 17q21 locus relates to episodes of acute airway obstruction common to both transient wheeze and asthma. The previously identified asthma risk alleles are the ones susceptible to environmental influences. Thus, this gene-environment interaction reveals two faces of 17q21: The same genotype constitutes genetic risk and allows for environmental protection, thereby providing options for prospective prevention strategies.
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Am. J. Respir. Crit. Care Med. · Apr 2016
Membrane-anchored Serine Protease Matriptase is a Trigger of Pulmonary Fibrogenesis.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease that remains refractory to current therapies. ⋯ These results implicate increased matriptase expression and activity in the pathogenesis of pulmonary fibrosis in human IPF and in an experimental mouse model. Overall, targeting matriptase, or treatment by CM, which is already in clinical use for other diseases, may represent potential therapies for IPF.
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Am. J. Respir. Crit. Care Med. · Apr 2016
Oxidative Modifications of Protein Tyrosyl Residues are Increased in Plasma of Human Subjects with Interstitial Lung Disease.
Interstitial lung diseases (ILDs) are associated with oxidative stress. Plasma biomarkers that are directly linked to oxidative stress responses in this disease have not been identified. Stable oxidation products of tyrosine residues in proteins may reflect the oxidative microenvironment in the lung or a systemic inflammatory state. ⋯ We demonstrate an increase in oxidized tyrosine moieties within proteins in the circulating plasma of patients with ILD. These data support the potential for development of oxidative stress-related biomarkers in early diagnosis, prognostication, and/or in evaluating responsiveness to emerging therapies for ILD.