American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · May 2021
NREM Apnea and Hypopnea Duration Varies Across Population Groups and Physiologic Traits.
Rationale: Symptoms and morbidities associated with obstructive sleep apnea (OSA) vary across individuals and are not predicted by the apnea-hypopnea index (AHI). Respiratory event duration is a heritable trait associated with mortality that may further characterize OSA. Objectives: We evaluated how hypopnea and apnea durations in non-REM (NREM) sleep vary across demographic groups and quantified their associations with physiological traits (loop gain, arousal threshold, circulatory delay, and pharyngeal collapsibility). ⋯ Shorter event durations were associated with lower circulatory delay (2.53 ± 0.13 s, P < 0.01), lower arousal threshold (1.39 ± 0.15 s, P < 0.01), reduced collapsibility (-0.71 ± 0.16 s, P < 0.01), and higher loop gain (-0.27 ± 0.11 s, P < 0.05) per SD change. Adjustment for physiological traits attenuated age, sex, and obesity associations and eliminated racial differences in event duration. Conclusions: Average event duration varies across population groups and provides information on ventilatory features and airway collapsibility not captured by the AHI.
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Am. J. Respir. Crit. Care Med. · May 2021
The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality.
Rationale: The association between aging and idiopathic pulmonary fibrosis has been established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated. Objectives: To evaluate the associations among aging biomarkers, ILA, and all-cause mortality. ⋯ Causal inference analysis showed that the association of age with ILA was mediated by IL-6 (P < 0.0001) and TNFR (P = 0.002) and was likely mediated by GDF15 (P = 0.008) in the FHS and was mediated by GDF15 (P = 0.001) in the COPDGene Study. Conclusions: Some aging-related biomarkers are associated with ILA. GDF15, in particular, may explain some of the associations among age, ILA, and mortality.
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Am. J. Respir. Crit. Care Med. · May 2021
Episodic Aspiration with Oral Commensals Induces a MyD88-dependent, Pulmonary Th17 Response that Mitigates Susceptibility to Streptococcus pneumoniae.
Rationale: Cross-sectional human data suggest that enrichment of oral anaerobic bacteria in the lung is associated with an increased T-helper cell type 17 (Th17) inflammatory phenotype. Objectives: In this study, we evaluated the microbial and host immune-response dynamics after aspiration with oral commensals using a preclinical mouse model. Methods: Aspiration with a mixture of human oral commensals (MOC; Prevotella melaninogenica, Veillonella parvula, and Streptococcus mitis) was modeled in mice followed by variable time of killing. ⋯ MOC aspiration before a respiratory challenge with S. pneumoniae led to a decrease in hosts' susceptibility to this pathogen. Conclusions: Thus, in otherwise healthy mice, a single aspiration event with oral commensals is rapidly cleared from the lower airways but induces a prolonged Th17 response that secondarily decreases susceptibility to S. pneumoniae. Translationally, these data implicate an immunoprotective role of episodic microaspiration of oral microbes in the regulation of the lung immune phenotype and mitigation of host susceptibility to infection with lower-airway pathogens.