American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Nov 2010
Randomized Controlled TrialImatinib in pulmonary arterial hypertension patients with inadequate response to established therapy.
Pulmonary arterial hypertension (PAH) is a progressive condition with a poor prognosis. Platelet-derived growth factor receptor (PDGFR) signaling plays an important role in its pathobiology. ⋯ These data from a Phase II study are consistent with imatinib being well tolerated in patients with PAH, and provide proof of concept for further studies evaluating its safety, tolerability, and efficacy in PAH. Clinical trial registered with www.clinicaltrials.gov (NCT00477269).
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Am. J. Respir. Crit. Care Med. · Nov 2010
Comparative StudyLocation and duration of treatment of cystic fibrosis respiratory exacerbations do not affect outcomes.
Individuals with cystic fibrosis (CF) are subject to recurrent respiratory infections (exacerbations) that often require intravenous antibiotic treatment and may result in permanent loss of lung function. The optimal means of delivering therapy remains unclear. ⋯ Intravenous antibiotic therapy for CF respiratory exacerbations administered in the hospital and in the home was found to be equivalent in terms of long-term FEV₁ change and interval between courses of antibiotics. Optimal duration of therapy (7-10 d) may be shorter than current practice. Large prospective studies are needed to answer these essential questions for CF respiratory management.
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Am. J. Respir. Crit. Care Med. · Nov 2010
Wood smoke exposure and gene promoter methylation are associated with increased risk for COPD in smokers.
Wood smoke-associated chronic obstructive pulmonary disease (COPD) is common in women in developing countries but has not been adequately described in developed countries. ⋯ These studies identify a novel link between wood smoke exposure and gene promoter methylation that synergistically increases the risk for reduced lung function in cigarette smokers.
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Am. J. Respir. Crit. Care Med. · Nov 2010
Somatic chromosome abnormalities in the lungs of patients with pulmonary arterial hypertension.
Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasineoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences. ⋯ Our data indicate a high frequency of genetically abnormal subclones within PAH lung vessels and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH.
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Am. J. Respir. Crit. Care Med. · Nov 2010
Randomized Controlled TrialPulmonary vascular dysfunction is associated with poor outcomes in patients with acute lung injury.
Despite the recognition that acute lung injury (ALI) can elevate pulmonary artery (PA) pressure and right ventricular afterload, the impact of pulmonary vascular dysfunction on outcomes of these patients is not well defined. ⋯ Pulmonary vascular dysfunction is common in ALI, and is independently associated with poor outcomes. Future trials targeting pulmonary vascular dysfunction may be indicated.