Annals of the American Thoracic Society
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During and immediately after birth, neonates are exposed to an environment laden with bacteria, a stark contrast to the sterile environment of the womb. Over the ensuing weeks and months, environmental microbial communities colonize their new host, and subsequent host-microbial cross-talk provides key developmental signals for the host's immune system. Emerging data from epidemiological and cellular research studies suggest that the nature of this cross-talk might be an underlying factor for the development, maintenance, and exacerbation of chronic lung diseases, such as asthma and chronic obstructive pulmonary disease. This review describes recent findings concerning the bacterial microbiota in the airways and places these data within the context of epidemiological and experimental studies that allude to the functional significance of host-microbial cross-talk in pulmonary inflammation.
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Review
How variability in clinical phenotypes should guide research into disease mechanisms in asthma.
Asthma is increasingly being considered as a collection of different phenotypes that present with intermittent wheezing. Unbiased approaches to classifying asthma have led to the identification of distinct phenotypes based on age of onset of disease, atopic state, disease severity or activity, degree of chronic airflow obstruction, and sputum eosinophilia. Linking phenotypes to known disease mechanism is likely to be more fruitful in determining the potential targets necessary for successful therapies of specific endotypes. ⋯ Further progress into asthma mechanisms will be driven by unbiased data integration of multiscale data sets from omics technologies with those phenotypic characteristics and by using mathematical modeling. This will lead to the discovery of new pathways and their integration into endotypes and also set up further hypothesis-driven research. Continued iteration through experimentation or modeling will be needed to refine the phenotypes that relate to outcomes and also delineate specific treatments for specific phenotypes.
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Acute lung injury (ALI) is characterized by inflammation, leukocyte activation, neutrophil recruitment, endothelial dysfunction, and epithelial injury, which are all affected by fever. Fever is common in the intensive care unit, but the relationship between fever and outcomes in ALI has not yet been studied. We evaluated the association of temperature dysregulation with time to ventilator liberation, ventilator-free days, and in-hospital mortality. ⋯ Fever and hypothermia are associated with worse clinical outcomes in ALI, with fever being independently associated with delayed ventilator liberation.
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Airway oxidative stress is broadly defined as an imbalance between prooxidative and antioxidative processes in the airway. Given its direct exposure to the environment, the lung has several mechanisms to prevent an excessive degree of oxidative stress. Both enzymatic and nonenzymatic systems can buffer a wide range of reactive oxidative species and other compounds with oxidative potential. ⋯ Therefore, more than being an imbalance with a predictable threshold after which disease or injury ensues, oxidative stress is a dynamic and continuous process. This might explain why supplementing antioxidants has largely failed to improve diseases such as asthma and chronic obstructive pulmonary disease. However, the therapeutic potential of antioxidants could be greatly improved by taking an approach that considers individual and environmental risk factors, instead of treating oxidative airway stress broadly.
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Our understanding of the clinical implications of eosinophilic airway inflammation has increased significantly over the last 20 years, aided by the development of noninvasive means to assess it. This pattern of airway inflammation can occur in a diverse range of airway diseases. ⋯ Our new understanding of the role of eosinophilic airway inflammation has paved the way for the clinical development of a number of more specific inhibitors that may become new treatment options. Different definitions, ideas of disease, and adoption of biomarkers that are not well known are necessary to fully realize the potential of these treatments.