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Mucus obstruction is a key feature of many inflammatory airway diseases. Neutrophil extracellular traps (NETs) are released upon neutrophil stimulation and consist of extracellular chromatin networks studded with cytotoxic proteins. When released in the airways, these NETs can become part of the airway mucus. We hypothesized that the extracellular DNA and/or oxidative stress (e.g., by the release of reactive oxygen species and myeloperoxidase during NETs formation in the airways) would increase mucus viscoelasticity. We collected human airway mucus from endotracheal tubes of healthy patients admitted for elective surgery and coincubated these samples with NETs from phorbol 12-myristate 13-acetate-stimulated neutrophils. Unstimulated neutrophils served as controls, and blocking experiments were performed with dornase alfa for extracellular DNA and the free radical scavenger dimethylthiourea for oxidation. Compared with controls, the coincubation of mucus with NETs resulted in 1 ) significantly increased mucus viscoelasticity (macrorheology) and 2 ) significantly decreased mesh pore size of the mucus and decreased movement of muco-inert nanoparticles through the mucus (microrheology), but 3 ) NETs did not cause visible changes in the microstructure of the mucus by scanning EM. Incubation with either dornase alfa or dimethylthiourea attenuated the observed changes in macrorheology and microrheology. This suggests that the release of NETs may contribute to airway mucus obstruction by increasing mucus viscoelasticity and that this effect is not solely due to the release of DNA but may in part be due to oxidative stress.

In order to investigate the relationship between air pollution and the respiratory tract microbiota, 114 healthy volunteers aged 18-21 years were selected during the winter heating period in Northeast China; 35 from a lightly polluted region (group A), 40 from a moderately polluted region (group B) and 39 from a heavily polluted region (group C). Microbial genome DNA was extracted from throat swab samples to study the oral flora composition of the volunteers by amplifying and sequencing the V3 regions of prokaryotic 16S rRNA. Lung function tests were also performed. The relative abundance of Bacteroidetes and Fusobacteria were significantly lower and Firmicutes Proteonacteria and Actinobacteria higher in participants from polluted regions. Within bacteria classes, Bacterioida abundance was lower and Clostridia abundance higher in polluted areas, which was also reflected in the order of abundance. In samples from region C, the abundance of Prevotellaceae, Veillonellaceae, Porphyromonadaceae, Fusobacteriaceae Paraprevollaceae and Flavobacteriaceae were lowest among the 3 regions studied, whereas the abundance of Lachnospiraceae and Ruminococcaceae were the highest. From group A to group C, the relative class abundances of Prevotella, Veillonella, Fusobacterium, Camphylobacter and Capnocytophaga Porphyromonas, Peptostreptococcus and Moraxella became lower in polluted areas. Pulmonary function correlated with air pollution and the oropharyngeal microbiota differed within regions of high, medium and low air pollution. Thus, during the winter heating period in Northeast China, the imbalance of the oropharyngeal microbiota might be caused by air pollution and is likely associated with impairment of lung function in young people., (Copyright © 2019 Elsevier Ltd. All rights reserved.)