Chest
-
Pathophysiologic gaps in the actions of currently available treatments for asthma and COPD include neutrophilic inflammation, airway remodeling, and alveolar destruction. All of these processes can be modulated by cyclic adenosine monophosphate-elevating prostaglandins E2 and I2 (also known as prostacyclin). These prostanoids have long been known to elicit bronchodilation and to protect against bronchoconstriction provoked by a variety of stimuli. ⋯ By contrast, excessive prostanoid production and signaling might contribute to both the increased susceptibility to infections that drive COPD exacerbations and the inadequate alveolar repair that characterizes emphysema. Inhibition of endogenous prostanoid synthesis or signaling, thus, has therapeutic potential for these types of patients. By virtue of their pleiotropic capacity to modulate numerous pathophysiologic processes relevant to the expression and natural history of airway diseases, prostanoids emerge as attractive targets for therapeutic manipulation.
-
Multicenter Study
Profusion of opacities in simple coal workers' pneumoconiosis is associated with reduced lung function.
A large body of evidence demonstrates dose-response relationships of cumulative coal mine dust exposure with lung function impairment and with small-opacity profusion. However, medical literature generally holds that simple coal worker's pneumoconiosis (CWP) is not associated with lung function impairment. This study examines the relationship between small-opacity profusion and lung function in US underground coal miners with simple CWP. ⋯ We observed progressively lower lung function across the range of small-opacity profusion. These findings address a long-standing question in occupational medicine and point to the importance of medical surveillance and respiratory disease prevention in this workforce.
-
In recent years, the potentially adverse role of sleep-disordered breathing in cancer incidence and outcomes has emerged. In parallel, animal models of intermittent hypoxia (IH) and sleep fragmentation (SF) emulating the two major components of OSA have lent support to the notion that OSA may enhance the proliferative and invasive properties of solid tumors. Based on several lines of evidence, we propose that OSA-induced increases in sympathetic outflow and alterations in immune function are critically involved in modifying oncologic processes including angiogenesis. In this context, we suggest that OSA, via IH (and potentially SF), promotes changes in several signaling pathways and transcription factors that coordinate malignant transformation and expansion, disrupts host immunologic surveillance, and consequently leads to increased probability of oncogenesis, accelerated tumor proliferation, and invasion, ultimately resulting in adverse outcomes.
-
Smoking-induced lung diseases were extremely rare prior to the 20th century. With commercialization and introduction of machine-made cigarettes, worldwide use skyrocketed and several new pulmonary diseases have been recognized. The majority of pulmonary diseases caused by cigarette smoke (CS) are inflammatory in origin. ⋯ We review here the known cellular and molecular mechanisms of CS-induced diseases, including COPD, respiratory bronchiolitis-interstitial lung disease, desquamative interstitial pneumonia, acute eosinophilic pneumonia, chronic rhinosinusitis, pulmonary Langerhans cell histiocytosis, and chronic bacterial infections. We also discuss inflammation induced by secondhand and thirdhand smoke exposure and the pulmonary diseases that result. New targeted antiinflammatory therapeutic options are currently under investigation and hopefully will yield promising results for the treatment of these highly prevalent smoking-induced diseases.
-
Institutional review boards (IRBs) or research ethics committees provide a core protection for human research participants through advance and periodic independent review of the ethical acceptability of proposals for human research. IRBs were codified in US regulation just over three decades ago and are widely required by law or regulation in jurisdictions globally. Since the inception of IRBs, the research landscape has grown and evolved, as has the system of IRB review and oversight. ⋯ Current focus on centralizing and sharing reviews requires more attention and evidence. Proposed changes to the US federal regulations may bring more changes. Data and resourcefulness are needed to further develop and test review and oversight models that provide adequate and respectful protections of participant rights and welfare and that are appropriate, efficient, and adaptable for current and future research.