American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2015
Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart Study.
Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults. ⋯ Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline.
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Am. J. Respir. Crit. Care Med. · Mar 2015
Comparative StudyAmpakines Enhance Weak Endogenous Respiratory Drive and Alleviate Apnea in Perinatal Rats.
Apnea of prematurity, which is prevalent among infants born at less than 34 weeks gestation, is treated with caffeine, theophylline, or aminophylline. However, not all newborns respond adequately to, or tolerate, methylxanthine administration, and thus alternative pharmacological therapies are required. ⋯ The net effect of ampakine enhancement of respiratory drive in perinatal rodents is a marked increase in ventilation and the regularity of respiratory patterns in perinatal rat preparations. Importantly, from the perspective of clinical applications, CX1739 readily crosses the blood-brain barrier, is metabolically stable, and has passed through phase I and II clinical trials in adults.
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Am. J. Respir. Crit. Care Med. · Mar 2015
Impaired BMPRII Signalling in a TGFβ Dependent Mouse Model of Pulmonary Hypertension and in Systemic Sclerosis.
Up to 10% of patients with systemic sclerosis (SSc) develop pulmonary arterial hypertension (PAH). This risk persists throughout the disease and is time dependent, suggesting that SSc is a susceptibility factor. Outcome for SSc-PAH is poor compared with heritable or idiopathic forms, despite clinical and pathological similarities. Although susceptibility in heritable PAH and idiopathic PAH is strongly associated with gene mutations leading to reduced expression of bone morphogenetic protein receptor (BMPR) II, these mutations have not been observed in SSc-PAH. ⋯ We found reduced BMPRII protein in patients with SSc-PAH and a relevant mouse model associated with increased proteasomal degradation of BMPRII. Collectively, these results suggest that impaired BMP signaling, resulting from TGF-β-dependent increased receptor degradation, may promote PAH susceptibility in SSc and provide a unifying mechanism across different forms of PAH.