Chest
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For 2 decades, long-acting β-agonists (LABAs) have been associated with increased asthma-related death risks in several randomized trials, even when added to inhaled corticosteroids (ICSs). In reaction, the US Food and Drug Administration (FDA) recently mandated that the manufacturers of LABAs conduct five large, noninferiority, randomized trials of the LABA+ICS combination in 53,000 patients with asthma. Three methodologic issues in these trials could lead to masking of or falsely detecting elevated risks. ⋯ Second, the composite asthma outcome will be dominated by asthma hospitalization, possibly dwarfing an increased risk of asthma-related death, with differences as wide as seven deaths under the LABA+ICS combination vs one death under ICS alone remaining statistically uncertain. Finally, because of the multiple identical trials being requested from the different manufacturers of LABAs, even if each trial is powered at 90%, there is a 41% likelihood that at least one of the trials will not rule out a risk increase when, in truth, there is no risk increase. In view of these impediments, the FDA should preempt such complexities by establishing decision rules regarding the interpretation of the results from these momentous safety trials before their completion, expected in 2017.
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In 2013, the outpatient hospital payment from Medicare for a transbronchial needle aspiration more than doubled. At the same time, the recently updated American College of Chest Physicians guidelines for the diagnosis and management of lung cancer now recommend needle techniques, such as transbronchial needle aspiration, over surgical staging. The convergence of these two events will accelerate the existing forces of technology and economics that have been influencing both the practices of outpatient bronchoscopy and mediastinoscopy and the management of patients with lung cancer over the past 20 years.
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This article provides evidence-based background and recommendations for the development of American College of Chest Physicians guidelines for the diagnosis and management of lung cancer. Specific population, intervention, comparison, and outcome questions were addressed to arrive at consensus recommendations. ⋯ Pathologic assessment of lung cancers is a crucial component for the diagnosis, management, and prognosis of lung cancer, making the pathologist a critical member of the clinical and management team. Selective diagnostic techniques, including limited designed immunohistochemical panels, and decision analysis will increase diagnostic accuracy.
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Chronic pulmonary thromboembolism (CPE) is a challenging diagnosis for clinicians. It is an often-forgotten diagnosis and can be difficult to detect and easily misdiagnosed. The radiologic features on CT pulmonary angiography are subtle and can be further compounded by pathologic mimics and unusual findings observed with disease progression. ⋯ As CPE can be diagnosed at different stages of its disease pathway, such findings may not necessarily arouse suspicion toward a causative diagnosis of chronic embolism. To aid diagnosis for clinicians, this article describes the characteristic vascular and parenchymal CT scan features of chronic emboli, as well as important ancillary findings. We also provide an illustrative case series focusing on CT pulmonary angiography specifically as an imaging modality to highlight the progressive nature of CPE and its sequelae, as well as important radiologic mimics to consider in the differential diagnosis.
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Mechanical ventilation used in patients with acute lung injury can damage pulmonary epithelial cells through production of inflammatory cytokines and excess deposition of the extracellular matrix protein lumican. Lumican participates in macrophage inflammatory protein (MIP)-2 and transforming growth factor-β₁ (TGF-β₁) signaling during the fibroproliferative phase of acute lung injury, which involves a process of epithelial-mesenchymal transition (EMT). The mechanisms regulating interactions between mechanical ventilation and lung injury are unclear. We hypothesized that lung damage and EMT by high tidal volume (Vt) mechanical stretch causes upregulation of lumican that modulates MIP-2 and TGF-β₁ through the extracellular signal-regulated kinase (ERK) 1/2 pathway. ⋯ The data suggest that lumican promotes high Vt mechanical ventilation-induced lung injury and EMT through the activation of the ERK1/2 pathway.