American journal of respiratory and critical care medicine
-
Am. J. Respir. Crit. Care Med. · Jan 2016
Randomized Controlled Trial Multicenter StudyEfficacy of Nintedanib in Idiopathic Pulmonary Fibrosis Across Pre-specified Subgroups in INPULSIS®.
In the two replicate, placebo-controlled, 52-week, phase III INPULSIS trials, nintedanib 150 mg twice daily significantly reduced the annual rate of decline in FVC, the primary endpoint, in subjects with idiopathic pulmonary fibrosis (IPF). It is unknown if this effect was uniform across all subjects treated with nintedanib. ⋯ Pooled data from the INPULSIS trials support a consistent effect of nintedanib across a range of IPF phenotypes by slowing disease progression across a number of prespecified subgroups.
-
Lung cancer is the leading cause of cancer mortality worldwide, and at only 18%, it has one of the lowest 5-year survival rates of all malignancies. With its highly complex mutational landscape, treatment strategies against lung cancer have proved largely ineffective. However with the recent success of immunotherapy trials in lung cancer, there is renewed enthusiasm in targeting the immune component of tumors. ⋯ Although the mechanisms through which inflammation promotes cancer are not fully understood, two connected hypotheses have emerged: an intrinsic pathway, driven by genetic alterations that lead to neoplasia and inflammation, and an extrinsic pathway, driven by inflammatory conditions that increase cancer risk. Here, we discuss the contribution of macrophages to these pathways and subsequently their roles in established tumors. We highlight studies investigating the association of macrophages with lung cancer prognosis and discuss emerging therapeutic strategies for targeting macrophages in the tumor microenvironment.
-
Am. J. Respir. Crit. Care Med. · Jan 2016
The Chitinase Proteins YKL-40 and Chitotriosidase are Increased in Both Asthma and COPD.
Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels. ⋯ YKL-40 and chitotriosidase are increased in asthma and more so in COPD. The data in the present study support these substances as being relatively steroid-insensitive, non-T-helper cell type 2-type biomarkers distinctly related to chronic inflammatory disease processes.
-
Am. J. Respir. Crit. Care Med. · Jan 2016
Inhibition of mTOR Restores Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease.
Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Several molecular mechanisms have been proposed, such as activations of the phosphoinositide-3-kinase/Akt pathway and p38 mitogen-activated protein kinase. However, the mechanism for corticosteroid resistance is still not fully elucidated. ⋯ mTOR inhibition by rapamycin restores corticosteroid sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential novel therapeutic target for COPD.
-
Am. J. Respir. Crit. Care Med. · Jan 2016
Comparative StudyRising Billing for Intermediate Intensive Care Among Hospitalized Medicare Beneficiaries Between 1996 and 2010.
Intermediate care (i.e., step-down or progressive care) is an alternative to the intensive care unit (ICU) for patients with moderate severity of illness. The adoption and current use of intermediate care is unknown. ⋯ Intermediate care billing increased markedly between 1996 and 2010. These findings highlight the need to better define the value, specific practices, and effective use of intermediate care for patients and hospitals.