Annals of the American Thoracic Society
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Randomized Controlled Trial Multicenter Study
"Do not resuscitate" decisions in acute respiratory distress syndrome. A secondary analysis of clinical trial data.
Factors and outcomes associated with end-of-life decision-making among patients during clinical trials in the intensive care unit are unclear. ⋯ The vast majority of deaths among clinical trial patients with ARDS were preceded by a DNR order. Unlike other studies of end-of-life decision-making in the intensive care unit, nearly all patients who became DNR died. The impact of variation of practice in end-of-life decision-making during clinical trials warrants further study.
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The airway epithelium is the primary site of the earliest pathologic changes induced by smoking, contributing to the development of chronic obstructive pulmonary disease (COPD). The normal human airway epithelium is composed of several major cell types, including differentiated ciliated and secretory cells, intermediate undifferentiated cells, and basal cells (BC). BC contain the stem/progenitor cell population responsible for maintenance of the normally differentiated airway epithelium. ⋯ Significant progress has been recently made in understanding the biology of human airway BC, including gene expression features, stem/progenitor, and other functions, including interaction with other airway cell types. Accumulating evidence suggests that human airway BC function as both sensors and cellular sources of various cytokines and growth factors relevant to smoking-associated airway injury, as well as the origin of various molecular and histological phenotypes relevant to the pathogenesis of COPD. In the context of these considerations, we suggest that early BC-specific smoking-induced molecular changes are critical to the pathogenesis of COPD, and these represent a candidate target for novel therapeutic approaches to prevent COPD progression in susceptible individuals.
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Neurocognitive impairments are associated with reduced quality of life and may adversely affect medical compliance, but their prevalence after lung transplantation has not been extensively studied. ⋯ Neurocognitive impairments are prevalent among lung transplant candidates and appear to worsen in some patients after transplant. Delirium during hospitalization is associated with worse neurocognitive function after transplant among patients without cystic fibrosis.
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Asthma and chronic obstructive pulmonary disease (COPD) are highly prevalent chronic inflammatory diseases of the airways, with differences in etiology, pathogenesis, immunologic mechanisms, clinical presentation, comorbidities, prognosis, and response to treatment. In mild to moderate early-onset allergic asthma, the Th2-driven eosinophilic airway inflammation and the ensuing disease can be well controlled with maintenance treatment with inhaled corticosteroids (ICS). In real-life settings, asthma control can be improved by facilitating adherence to ICS treatment and by optimizing inhaler technique. ⋯ In COPD, there is a high unmet need for safe and effective antiinflammatory treatments that not only prevent exacerbations but also have a beneficial impact on the course of the disease and improve survival. Although several new approaches aim to target the chronic neutrophilic pulmonary inflammation per se in patients with COPD, strategies that target the underlying causes of the pulmonary neutrophilia (e.g., smoking, chronic infection, and oxidative stress) might be more successful. In both chronic airway diseases (especially in more difficult, complex cases), the choice of the optimal treatment should be based not only on arbitrary clinical labels but also on the underlying immunopathology.