American journal of respiratory and critical care medicine
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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.
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Am. J. Respir. Crit. Care Med. · May 2021
Air Pollution as a Risk Factor for Incident COPD and Asthma: 15-Year Population-Based Cohort Study.
Rationale: Current evidence on the relationship between long-term exposure to air pollution and new onset of chronic lung disease is inconclusive. Objectives: To examine associations of incident chronic obstructive pulmonary disease (COPD) and adult-onset asthma with past exposure to fine particulate matter ≤ 2.5 μm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and the redox-weighted average of NO2 and O3 (Ox) and characterize the concentration-response relationship. Methods: We conducted a population-based cohort study of all Ontarians, aged 35-85 years, from 2001 to 2015. ⋯ In addition, we quantified that each IQR increase in pollution exposure yielded 3.0 (2.4-3.6), 3.2 (2.0-4.3), 1.9 (1.3-2.5), and 2.3 (1.7-2.9) excess cases of COPD per 100,000 adults for PM2.5, NO2, O3, and Ox, respectively. Furthermore, most pollutant-COPD relationships exhibited supralinear shapes. Conclusions: Air pollution was associated with a higher incidence of COPD but was not associated with a higher incidence of adult-onset asthma.