Proceedings of the American Thoracic Society
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Proliferation, migration, and differentiation of smooth muscle (SM)-like lymphangioleiomyomatosis (LAM) cells in the lungs are pathologic manifestations of pulmonary LAM, a rare lung disease predominantly afflicting women and exacerbated by pregnancy. LAM cells form nodules throughout the lung without any predominant localization, but can also form small cell clusters dispersed within lung parenchyma. LAM cells have the appearance of "immature" SM-like cells, irregularly distributed within the nodule in contrast to organized SM cell layers in airways and vasculature. ⋯ The observation that the TSC1/TSC2 functions as a negative regulator of the mammalian target of rapamycin (mTOR)/p70 S6 kinase (S6K1) signaling pathway yielded the first rapamycin clinical trial for LAM. Although LAM is a rare lung disease, the elucidation of disease-relevant mechanisms of LAM will provide a better understanding of not only SM-like cell growth, migration, and differentiation in LAM but may also offer insights into other metabolic diseases such as cardiovascular diseases, diabetes, and cancer. In this article, we will summarize the progress made in our understanding of LAM, and we will focus on how dysregulation of TSC1/TSC2 signaling results in abnormal proliferation and migration of SM-like LAM cells.
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Emerging evidence suggests that sex and gender differences exist in the prevalence, susceptibility to, severity of, and response to treatment and management of, chronic obstructive pulmonary disease (COPD). However, the identification of knowledge gaps regarding sex, gender, and COPD involves not only pinpointing what areas of etiology, epidemiology, and management need to be examined from a sex and gender perspective (as discussed in other articles of this issue), but also must include discussion of how such new and emerging findings are translated to health care professionals, policy makers, and the general population. ⋯ A preliminary examination of such documents from around the world suggests that many materials continue to present COPD as a disease that primarily afflicts men. This gap in the translation of research knowledge may be specifically problematic for women-for example, because they may not be adequately informed of the symptoms of COPD, be appropriately screened for the disease, or receive appropriate interventions and treatment.
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This article reflects on a multidisciplinary workshop addressing the evidence pertaining to tobacco use, sex, gender, and chronic obstructive pulmonary disease (COPD). In preparation, a literature review was conducted that examined the academic and gray literature on tobacco, COPD, and gender and women, with a view to assessing if and how these literatures spoke to each other. ⋯ The goal of this workshop was to foster the advancement of a research agenda that more tightly links tobacco, COPD, and lung health and that reflects and investigates sex and gender issues, especially in reference to the growing rates of COPD among women. A research agenda for consideration by researchers in the fields of women's health, medicine, tobacco use, COPD, and related fields is offered.
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Review
Exacerbations in chronic obstructive pulmonary disease: do they contribute to disease progression?
The impact of chronic obstructive pulmonary disease (COPD) exacerbations on decline in FEV(1) has been a controversial topic for decades. We will review some of the key studies in this area and discuss potential contributors to inconsistent results of these studies. Dissecting the heterogeneous COPD syndrome into meaningful subtypes and assessing the genetic and environmental influences on COPD-related phenotypes such as exacerbation frequency could clarify the impact of exacerbations on the natural history of COPD.
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The systemic manifestations of chronic obstructive pulmonary disease (COPD) exacerbations are recognized, but our understanding of their etiology and importance is lacking largely due to the small number of systematic and longitudinal studies. Most of the systemic manifestations are likely the result of inflammatory processes. ⋯ Our understanding of the systemic manifestations can be greatly enhanced if we integrate what is known about the basic science of systemic mediators with the translational science of their role in COPD exacerbations. Many overlapping connections and promising avenues of future research come to light with such a viewpoint.