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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Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease. COPD exacerbations have a major impact on morbidity and mortality. The etiology of COPD exacerbations is largely due to viral and bacterial infections in combination with underlying inflammation that is typically neutrophilic, although it is eosinophilic in 10 to 25% of cases. ⋯ These biomarkers include C-reactive protein, procalcitonin, and peripheral blood eosinophil count, which are readily available. We are therefore at a point of making personalized antibiotic and corticosteroid therapy in COPD exacerbations a reality. Integration of the wealth of emerging data to further define the complexity of exacerbations also promises to identify new targets and biomarkers to treat COPD exacerbations.
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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.
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Several studies suggest that nasal nitric oxide (nNO) measurement could be a test for primary ciliary dyskinesia (PCD), but the procedure and interpretation have not been standardized. ⋯ Using a standardized protocol in multicenter studies, nNO measurement accurately identifies individuals with PCD, and supports its usefulness as a test to support the clinical diagnosis of PCD.