American journal of respiratory and critical care medicine最新文献

Rationale: The precise nature of small airway obstructions in chronic obstructive pulmonary disease (COPD) remains poorly understood, especially at early disease stages. Objectives: This study aimed to characterize small airway obstructions and numbers up to the terminal bronchioles (TBs) in smokers with limited emphysema and end-stage COPD. We hypothesized that obstruction subtypes would differ in morphology, nature, and number from early to end-stage COPD. Methods: Whole lungs were inflated and processed from seven control donors (control: declined for extrapulmonary reasons); from eight donors with a history of smoking, of whom three had <5% emphysema (smokers with no emphysema) and five had >5% emphysema (smokers with emphysema); and from eight patients with end-stage COPD. Micro-computed tomography of tissue was used to assess number of TBs, aerated TBs, and number and type of obstructions and was cross-correlated with histopathology. Measurements and Main Results: Obstructions were mainly present in smokers with emphysema and patients with COPD, resulting in less aerated TBs. On the basis of emphysema extent, more nonaerated TBs were present in regions with no emphysema than in regions with mild emphysema; however, destruction was more prominent in mild emphysema. Multiple types of obstructions were identified, comprising occlusions, webs, and collapses. In smokers with emphysema, obstructions primarily comprised webs and occlusions, whereas all obstruction types were present in COPD. On histopathology, obstructions were identified as mucus plugs. Conclusions: Multiple types of obstruction characterized as mucus plugs were identified in smokers with emphysema and patients with end-stage COPD. Their morphology, nature, and number evolved from smokers with emphysema to end-stage COPD. A shift from obstruction-dominant dysfunction to destruction-dominant pathology was found in smokers on the basis of emphysema presence.

Rationale: One in 10 children experiences sleep-disordered breathing (SDB). Untreated SDB is associated with poor cognition, but the underlying mechanisms are less understood. Objectives: We assessed the relationship between magnetic resonance imaging-derived upper airway volume and children's cognition and regional cortical gray matter volumes. Methods: We used 5-year data from the Adolescent Brain Cognitive Development study (N = 11,875 children; 9-10 yr old at baseline). Upper airway volumes were derived using a deep learning model applied to 5,552,640 brain magnetic resonance imaging slices. The primary outcome was the Total Cognition Composite score from the NIH Toolbox (NIH-TB). Secondary outcomes included other NIH-TB measures and cortical gray matter volumes. Measurements and Main Results: The habitual snoring group had significantly smaller airway volumes than nonsnorers (mean difference, 1.2 cm³; 95% confidence interval [CI], 1.0-1.4 cm³; P < 0.001). Deep learning-derived airway volume predicted the Total Cognition Composite score (estimated mean difference, 3.68 points; 95% CI, 2.41-4.96 points; P < 0.001) per one-unit increase in the natural log of airway volume (∼2.7-fold raw volume increase). This airway volume increase was also associated with an average 0.02-cm³ increase in right temporal pole volume (95% CI, 0.01-0.02 cm³; P < 0.001). Similar airway volume predicted most NIH-TB domain scores and multiple frontal and temporal gray matter volumes. These brain volumes mediated the relationship between airway volume and cognition. Conclusions: We demonstrate a novel application of deep learning-based airway segmentation in a large pediatric cohort. Upper airway volume is a potential biomarker for cognitive outcomes in pediatric SDB, offers insights into neurobiological mechanisms, and informs future studies on risk stratification.

Rationale: Wood smoke exposure is increasing worldwide because of the increase in wildfire events. Various studies have associated exposure to wildfire-derived smoke with adverse respiratory conditions. However, the mechanism by which this occurs is unknown. Previous studies using wood smoke as a model of wildfire smoke have focused on the respiratory immune response and have reported increased neutrophil percentage and cytokine production in airway samples. The effect of wood smoke on the respiratory microbiome, however, has not been examined. Objectives: The objective of this study was to evaluate whether inhaled wood smoke exposure can alter the respiratory microbiome in humans. Methods: Healthy volunteers (N = 54) were subjected to controlled wood smoke exposure (500 μg/m³) for 2 hours, and induced sputum samples were collected and processed for microbiome analysis, immune mediators, and cell differentials at baseline and at 6 hours and 24 hours after exposure. A negative binomial mixed model analysis examined associations between microbiome components and inflammatory cells in sputum. Measurements and Main Results: After wood smoke exposure, although sputum microbiome diversity remained unchanged, the microbiome composition was altered, particularly the abundance of several low-abundance bacteria, including Fretibacterium and Selenomonas, indicating that this inhalational exposure can alter the composition of the sputum microbiome. In addition, a significant decrease in macrophage cells was observed at 24 hours without a significant change in neutrophils. We further found small but significant associations between different taxa and macrophages (per milligram of sputum), including a negative association with Fretibacterium. Conclusions: Together, these findings demonstrate that inhalational wood smoke exposure can modify several low-abundance bacteria within the respiratory microbiome and that these changes are associated with sputum inflammatory cell alterations, providing insights for future studies to focus on respiratory innate immune host-microbiome crosstalk in the context of environmental exposures.