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20th October 2023
Air pollution contains particulate matter that can carry antibiotic resistance genes, which have been found to accelerate microbial threats to human health. Here, Rod Tucker considers the extent to which air pollution could serve as a primary vector and driving force behind the increasing levels of global antibiotic resistance.
There‘s no doubt that global antibiotic resistance represents a major health challenge and is responsible for a huge number of deaths. For example, in a systematic review looking at the global burden of bacterial antimicrobial resistance in 2019, the authors estimated there were 4.95 million associated deaths.
In addition, data published in 2018 from the European Centre for Disease Prevention and Control estimated that around 33,000 people die each year in the in the European Union and European Economic Area as a direct consequence of infections with antibiotic-resistant bacteria.
Although antibiotic resistance represents the failure of a particular drug, there are a number of underlying factors responsible. Perhaps the greatest risk comes from interconnected human, animal and environmental habitats that are likely to contribute towards the emergence, evolution and spread of antibiotic resistance. In fact, resistance emerges as a result of the local confluence that occurs when bacteria colonise different human and animal hosts, enabling the spread of antibiotic resistant genes.
In response to the global rise in antibiotic resistance, countries have introduced antimicrobial stewardship programmes. Such initiatives represent a coordinated approach to promote the appropriate use of antimicrobials and reduce both microbial resistance and the spread of infections caused by multidrug-resistant organisms.
Antimicrobial stewardship programmes are predicated on the notion that antibiotic use per se, is associated with the development of resistance. However, simply controlling usage may not be an effective means of reducing the rate at which resistance develops.
This was highlighted in a 2018 analysis of the factors driving global antimicrobial resistance. It found that reducing antibiotic consumption would be unlikely to control antimicrobial resistance because the spread of resistant strains and resistance genes seemed to be the most important contributory factor.
So, if this is case, what are the most likely vectors of resistant genes?
In 2018, Chinese researchers profiled the relative abundances of 30 antibiotic resistance genes (ARGs) in urban air carried in particulate matter. They found that urban air is being polluted by ARGs and different cities are challenged with varying health risks due to airborne ARG exposure.
Moreover, fine particulate matter, with a diameter of 2.5 μm or less (i.e. PM2·5), is easily inhaled and therefore serves to increase the intake of airborne ARGs.
But to what extent is air pollution and the carriage of ARGs actually responsible for the spread of resistance?
A more recent study by Chinese researchers tried to answer this question. Writing in the journal Lancet Planetary Health, the team provided the first global estimates of antibiotic resistance and burden of premature deaths attributable to antibiotic resistance resulting from PM2·5 pollution.
They used data from multiple sources and included a number of potential confounders, such as levels of air pollution, antibiotic use, sanitation services, climate, year, and region, from a total of 116 countries collected between 2000 and 2018.
Using raw antibiotic-resistance data on nine pathogens and 43 types of antibiotic agents, the team identified significant global correlations between PM2·5 and antibiotic resistance (R2= 0.42 – 0.76, p<0.0001). Furthermore, these correlations appeared to strengthen over time.
The researchers also estimated that antibiotic resistance derived from PM2·5 led to an estimated 0.48 million premature deaths and 18.2 million years of life lost in 2018 worldwide. In other words, with a positive and robust association between PM2·5 and antibiotic resistance, the findings implied that globally, air pollution, and in particular PM2·5, was an important driving factor.
While the findings from the Lancet Planetary Health study are intriguing, this was an ecological study, which is more suited to the generation of hypotheses, and the finding of an association between air pollution and antibiotic resistance is not necessarily causal.
The authors of the paper also acknowledge some limitations. For instance, several low- and middle-income countries – the likes of which are most affected by antibiotic resistance – did not provide pathogen and antibiotic data.
In addition, the unrestricted use of antibiotics in animal farming was not examined in the study, which is a potentially important determinant of resistance in countries that also tend to have higher air pollution levels.
Finally, the authors also state that ‘some factors could be almost as important as PM2·5 in contributing to antibiotic resistance’. This is another way of stating the obvious: there are lots of other possible factors that could account for the observed association. As information on such data was unavailable, it could not be included in the statistical models.
While it is possible that air pollution is a factor linked to increased levels of antibiotic resistance, in the absence of experimental evidence to support this premise, it remains yet another factor to be considered and addressed, if possible, in the global fight to reduce the adverse outcomes associated with increased antibiotic resistance.
10th March 2023
Work by researchers from San Diego, La Jolla in the US, has shown that an increased exposure to particulate matter 2.5 μm or less in diameter (PM2.5), increases the risk for all-cause and infection-related visits to an emergency department among infants during their first year of life.
It has been recognised for several years that particulate matter comprising particles with a diameter of less than 2.5 micrometres, can penetrate deeply into the lungs, causing irritation and corrosion of the alveolar wall and therefore impairing lung function. PM2.5 comes from a wide range of sources including natural (i.e., dust, sea salt), anthropogenic emissions, e.g., vehicles, as well as household wood burning and from industry. The composition of PM2.5 is a complex mix of inorganic components such as heavy metals, organics (polycyclic aromatic hydrocarbons) and biologicals e.g., bacteria, viruses and fungi. Prior studies have shown that exposure to PM2.5 during pregnancy can increase adverse outcomes and stillbirth and early childhood exposure to air pollutants may play a role in the development of asthma. However, research to data on the impact of early PM2.5 exposure and the risk of hospitalisation during infancy is conflicting, indicating either an increased risk of bronchiolitis or no noticeable effect compared to older children.
In the current study, researchers examined all live births in California between 2014 and 2018 and estimated weekly exposure to particular matter based on the postal (zip) codes using a machine learning model. They set the outcomes of interest as both the first all-cause emergency department (ED) visit and the first infection-related visit based on birth status (pre or full-term).
Particulate matter and ED visits
A total of 983,700 infants, (49.4% female) were included in the analysis.
During the first year of life, the odds of an ED visit for any cause was higher for both pre-term (odds ratio, OR = 1.05, 95% CI 1.04 – 1.06) and full-term infants (OR = 1.05, 95% CI 1.04 – 1.05) for each 5-μg/m3 increase in exposure to PM2.5.
Similarly, there were elevated odds for a respiratory infection-related ED visit, pre-term (OR = 1.03) and full-term (OR = 1.05). In fact, the highest risks for an ED in both types of infant occurred between 18 to 23 weeks.
The authors concluded these elevated risks associated with exposure to particulate matter, may have implications for minimising exposure to air pollution.
Citation
Teyton A et al. Exposure to Air Pollution and Emergency Department Visits During the First Year of Life Among Preterm and Full-term Infants. JAMA Netw Open 2023
23rd September 2022
The exposure to particulate matter derived from air pollution represents a mechanism through which lung cancer can develop among individuals who have never smoked according to the findings of research presented at the European Society for Medical Oncology (ESMO) Congress 2022 by scientists of the Francis Crick Institute and University College London.
Globally in 2020 there were an estimated 2.21 million cases of lung cancer and 1.80 million deaths. There are two primary forms of lung cancer, small cell lung cancer and non-small cell lung cancer (NSCLC) with this latter form accounting for approximately 84% of all cases.
It has been recognised for several years that particulate matter in outdoor air pollution with a size of at least 2.5 micrometers, leads to an 18% higher risk of lung cancer among those who had never smoked. However, the mechanisms driving this increased risk among those who do not smoke has remained unclear.
In the study presented at the ESMO congress, researchers focused on lung cancers due to a mutation in the epidermal growth factor receptor (EGFR), which is a transmembrane receptor tyrosine kinase protein, expressed in some normal epithelial, mesenchymal, and neurogenic tissue.
Moreover, research suggests that EGFR protein expression is a risk factor in patients with NSCLC. Using normal lung tissue samples from humans and mice, the team investigated the consequences of increasing 2.5um particulate matter (PM2.5) concentrations with cancer risk.
Particulate matter exposure and cancer risk
Samples were analysed from 463,679 individuals and the team found that increasing PM2.5 levels were associated with a greater risk for EGFR mutated NSCLC samples from England, South Korea and Taiwan.
This was also associated with an increased risk of mesothelioma (hazard ratio, HR = 1.19), lung (HR = 1.16), anal (HR = 1.23), small intestine (HR=1.30), glioblastoma (HR=1.19), lip, oral cavity and pharynx (HR = 1.15) and laryngeal carcinomas (HR = 1.26) in UK Biobank samples, for each 1 ug/m3 PM2.5 increment.
A further interesting finding was the presence of EGFR driver mutations in 18% of normal lung samples and a further mutation (KRAS) in 33% of samples. The team also showed that PM promoted a macrophage response and a progenitor-like state in lung epithelium harbouring mutant EGFR.
Consistent with particulate matter promoting NSCLC in at-risk epithelium harbouring driver mutations, PM increased tumour burden in three EGFR or KRAS driven lung cancer models in a dose-dependent manner.
Discussing their findings, Charles Swanton who presented the findings at ESMO, said: ‘We found that driver mutations in EGFR and KRAS genes, commonly found in lung cancers, are actually present in normal lung tissue and are a likely consequence of ageing. In our research, these mutations alone only weakly potentiated cancer in laboratory models.
‘However, when lung cells with these mutations were exposed to air pollutants, we saw more cancers and these occurred more quickly than when lung cells with these mutations were not exposed to pollutants, suggesting that air pollution promotes the initiation of lung cancer in cells harbouring driver gene mutations. The next step is to discover why some lung cells with mutations become cancerous when exposed to pollutants while others don’t.’
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