Waking up in a trap: Cancer patients who have undergone successful treatment can experience relapse of their disease years or even decades later. This is because cancer cells that have disseminated beyond the primary tumor site enter a state of dormancy, where they remain viable but not proliferating. Eventually, by mechanisms that are poorly understood, these clinically undetectable cells “wake up” and form actively growing metastases. Studying mouse models, Albrengues et al. found that sustained lung inflammation and the accompanying formation of neutrophil extracellular traps (NETs) could convert dormant cancer cells to aggressive lung metastases (see the Perspective by Aguirre-Ghiso). Awakening of these cells was associated with NET-mediated remodeling of the extracellular matrix and could be prevented by an antibody against the remodeled version of a matrix protein called laminin-111. Science , this issue p. eaao4227 ; see also p. 1314

Purpose of the review Air pollution continues to be a major public health concern affecting nine out of 10 individuals living in urban areas worldwide. Exposure to air pollution is the ninth leading risk factor for cardiopulmonary mortality. The aim of this review is to examine the current literature for the most recent updates on health effects of specific air pollutants and their impact on asthma, chronic obstructive pulmonary disease, lung cancer, and respiratory infection. Recent findings A total of 52 publications were reviewed to establish new insights as to how air pollution is associated with pulmonary morbidity and mortality. Considerable past evidence suggests that air pollution is an important factor that enhances pulmonary disease, while also causing greater harm in susceptible populations, such as children, the elderly, and those of low socio-economic status worldwide. Asthma, chronic obstructive pulmonary disease, lung cancer, and respiratory infections all seem to be exacerbated because of exposure to a variety of environmental air pollutants with the greatest effects because of particulate matter, ozone, and nitrogen oxides. New publications reviewed reaffirm these findings. Summary Continued vigilance will be essential to lessen the effects of air pollution on human health and pulmonary disease. Cooperation at a multinational level will be required on the part of governments, industry, energy-based enterprises, and the public working together to solve our air quality issues at the local, national, and global level.

Background: Exposure to environmental tobacco smoke (ETS) leads to higher rates of pulmonary diseases and infections in children. To study the biochemical changes that may precede lung diseases, metabolomic effects on fetal and maternal lungs and plasma from rats exposed to ETS were compared to filtered air control animals. Genome- reconstructed metabolic pathways may be used to map and interpret dysregulation in metabolic networks. However, mass spectrometry-based non-targeted metabolomics datasets often comprise many metabolites for which links to enzymatic reactions have not yet been reported. Hence, network visualizations that rely on current biochemical databases are incomplete and also fail to visualize novel, structurally unidentified metabolites.Results: We present a novel approach to integrate biochemical pathway and chemical relationships to map all detected metabolites in network graphs (MetaMapp) using KEGG reactant pair database, Tanimoto chemical and NIST mass spectral similarity scores. In fetal and maternal lungs, and in maternal blood plasma from pregnant rats exposed to environmental tobacco smoke (ETS), 459 unique metabolites comprising 179 structurally identified compounds were detected by gas chromatography time of flight mass spectrometry (GC-TOF MS) and BinBase data processing. MetaMapp graphs in Cytoscape showed much clearer metabolic modularity and complete content visualization compared to conventional biochemical mapping approaches. Cytoscape visualization of differential statistics results using these graphs showed that overall, fetal lung metabolism was more impaired than lungs and blood metabolism in dams. Fetuses from ETS-exposed dams expressed lower lipid and nucleotide levels and higher amounts of energy metabolism intermediates than control animals, indicating lower biosynthetic rates of metabolites for cell division, structural proteins and lipids that are critical for in lung development.Conclusions: MetaMapp graphs efficiently visualizes mass spectrometry based metabolomics datasets as network graphs in Cytoscape, and highlights metabolic alterations that can be associated with higher rate of pulmonary diseases and infections in children prenatally exposed to ETS. The MetaMapp scripts can be accessed athttp://metamapp.fiehnlab.ucdavis.edu.

Although it is well accepted that air pollution exposure exacerbates preexisting airway disease, it has not been firmly established that long-term pollution exposure increases the risk of new-onset asthma or chronic obstruction pulmonary disease (COPD). This Workshop brought together experts on mechanistic, epidemiological, and clinical aspects of airway disease to review current knowledge regarding whether air pollution is a causal factor in the development of asthma and/or COPD. Speakers presented recent evidence in their respective areas of expertise related to air pollution and new airway disease incidence, followed by interactive discussions. A writing committee summarized their collective findings. The Epidemiology Group found that long-term exposure to air pollution, especially metrics of traffic-related air pollution such as nitrogen dioxide and black carbon, is associated with onset of childhood asthma. However, the evidence for a causal role in adult-onset asthma or COPD remains insufficient. The Mechanistic Group concluded that air pollution exposure can cause airway remodeling, which can lead to asthma or COPD, as well as asthma-like phenotypes that worsen with long-term exposure to air pollution, especially fine particulate matter and ozone. The Clinical Group concluded that air pollution is a plausible contributor to the onset of both asthma and COPD. Available evidence indicates that long-term exposure to air pollution is a cause of childhood asthma, but the evidence for a similar determination for adult asthma or COPD remains insufficient. Further research is needed to elucidate the exact biological mechanism underlying incident childhood asthma, and the specific air pollutant that causes it.

There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lung disease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low- to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided.

The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties that induce inflammation and oxidative stress in biological systems. Oxidative stress reflects the imbalance between the generation of reactive oxygen species and the biochemical mechanisms to detoxify and repair the damage resulting from reactive intermediates. This review examines current research on incidental and engineered nanoparticles in terms of their health effects on lungs and the mechanisms by which oxidative stress via physicochemical characteristics influences toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review also briefly discusses some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site-specific fashion.