American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Sep 2019
A Genetic Risk Score Associated with COPD Susceptibility and Lung Structure on Computed Tomography.
Rationale: Chronic obstructive pulmonary disease (COPD) has been associated with numerous genetic variants, yet the extent to which its genetic risk is mediated by variation in lung structure remains unknown. Objectives: To characterize associations between a genetic risk score (GRS) associated with COPD susceptibility and lung structure on computed tomography (CT). Methods: We analyzed data from MESA Lung (Multi-Ethnic Study of Atherosclerosis Lung Study), a U. ⋯ Lung structure (P < 0.0001), but not the GRS (P > 0.10), improved discrimination of moderate-to-severe COPD cases relative to clinical factors alone. Conclusions: A GRS associated with COPD susceptibility was associated with CT lung structure. Lung structure may be an important mediator of heritability and determinant of personalized COPD risk.
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Am. J. Respir. Crit. Care Med. · Sep 2019
Loss of Microbial Topography between Oral and Nasopharyngeal Microbiota and Development of Respiratory Infections Early in Life.
Rationale: The respiratory microbiota is increasingly being appreciated as an important mediator in the susceptibility to childhood respiratory tract infections (RTIs). Pathogens are presumed to originate from the nasopharyngeal ecosystem. Objectives: To investigate the association between early life respiratory microbiota and development of childhood RTIs. ⋯ This loss of ecological topography was further augmented by start of daycare, and linked to consecutive development of symptomatic infections. Conclusions: Together, our results link the loss of topography to subsequent development of RTI episodes. This may lead to new insights for prevention of RTIs and antibiotic use in childhood.
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Am. J. Respir. Crit. Care Med. · Sep 2019
Knowledge Gaps and Research Priorities in Immune Checkpoint Inhibitor-related Pneumonitis. An Official American Thoracic Society Research Statement.
Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care but are associated with unique adverse events, including potentially life-threatening pneumonitis. The diagnosis of ICI-pneumonitis is increasing; however, the biological mechanisms, clinical and radiologic features, and the diagnosis and management have not been well defined. ⋯ Results: This statement identifies gaps in knowledge and develops potential research questions to further expand knowledge regarding risk, biologic mechanisms, clinical and radiologic presentation, and management of ICI-pneumonitis. Conclusions: Gaps in knowledge of the basic biological mechanisms of ICI-pneumonitis, coupled with a precipitous increase in the use of ICIs alone or combined with other therapies, highlight the importance in triaging research priorities for ICI-pneumonitis.