American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2020
Disease Progression Modeling in Chronic Obstructive Pulmonary Disease.
Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging. Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD. Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. ⋯ Individuals with early changes were 2.5 times more likely to meet COPD diagnostic criteria at follow-up. Conclusions: We demonstrate two distinct patterns of disease progression in COPD using SuStaIn, likely representing different endotypes. One third of healthy smokers have detectable imaging changes, suggesting a new biomarker of "early COPD."
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Am. J. Respir. Crit. Care Med. · Feb 2020
Respiratory Syncytial Virus Disease Severity Is Associated with Distinct CD8+ T-Cell Profiles.
Rationale: Respiratory syncytial virus (RSV) causes significant morbidity and mortality in infants worldwide. Although T-helper type 2 (Th2) cell pathology is implicated in severe disease, the mechanisms underlying the development of immunopathology are incompletely understood. Objectives: We aimed to identify local immune responses associated with severe RSV in infants. ⋯ Patients with greater frequencies of Tc1, CD8+ T cells expressing IL-17 (Tc17), and CD4+ T cells expressing IL-17 (Th17) had shorter durations of hospitalization. Conclusions: Severe RSV disease was associated with distinct T-cell profiles. Tc1, Tc17, and Th17 were associated with shorter hospital stay and may play a protective role, whereas Tc2 cells may play a previously underappreciated role in pathology.
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Am. J. Respir. Crit. Care Med. · Feb 2020
Nasal Pneumococcal Density Is Associated with Microaspiration and Heightened Human Alveolar Macrophage Responsiveness to Bacterial Pathogens.
Rationale: Pneumococcal pneumonia remains a global health problem. Colonization of the nasopharynx with Streptococcus pneumoniae (Spn), although a prerequisite of infection, is the main source of exposure and immunological boosting in children and adults. However, our knowledge of how nasal colonization impacts on the lung cells, especially on the predominant alveolar macrophage (AM) population, is limited. ⋯ Similarly, AM-heightened opsonophagocytic capacity was correlated with nasopharyngeal pneumococcal density (r = 0.61, P = 0.025). Conclusions: Our findings demonstrate that nasal colonization with pneumococcus and microaspiration prime AMs, leading to brisker responsiveness to both pneumococcus and unrelated bacterial pathogens. The relative abundance of AMs in the alveolar spaces, alongside their potential for nonspecific protection, render them an attractive target for novel vaccines.