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18th September 2023
Three studies presented at the recent European Respiratory Society (ERS) International Congress in Milan, Italy, highlight the various damaging effects of air pollution in early childhood, including on birthweight and the incidence of respiratory infections.
According to a recent consensus statement from the European Respiratory Society on climate change, there is likely to be a disproportionately greater negative impact from global warming on individuals living with respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
One of the most important and detrimental consequences of climate change is the resulting increased levels of air pollution, which is already known to damage the lungs and have other negative consequences such as mental health issues in dementia.
Now, three related studies presented at the ERS International Congress have shed further light on the deleterious effect of air pollution. The studies reveal how pollution not only reduces the birthweight of newborns, but also increases the incidence of respiratory infections experienced by young children.
In the first study (abstract PA311), researchers sought to investigate the association of maternal exposure to air pollution based on what they described as the level of environmental ‘greenness’ during pregnancy, and whether this affected birthweight.
They devised a measure of greenness termed the ‘normalised difference vegetation index‘ (NDVI), which was based on the density of vegetation seen on satellite images. In addition, the team modelled exposure to five known pollutants: nitrogen dioxide (NO2), ozone, black carbon (BC), and two types of particulate matter (PM2.5 and PM10). The levels of these pollutants were estimated for mothers based on their residential address during pregnancy.
The researchers analysed data on 5,434 children from 2,742 mothers. The median NDVI300m was 0.3 (interquartile range, IQR, 0.2 – 0.4). Increases in the level of greenness were positively associated with birthweight. For example, each IQR increase in NDVI300m was associated with an increase in birthweight of 29g, a 23% lower odds of a low birthweight (Odds ratio, OR = 0.77, 95% CI 0.64 – 0.94), as well as a 14% increased odds of a high birthweight (> 4000g) (OR = 1.14, 95% CI 1.02 – 1.26).
Commenting on the findings, lead author, Robin Mzati Sinsamala, a researcher in the department of global public health and primary care at the University of Bergen (UiB), Norway said: ‘The time when babies are growing in the womb is critical for lung development. We know that babies with lower birthweight are susceptible to chest infections, and this can lead on to problems like asthma and COPD later on.
‘Our results suggest that pregnant women exposed to air pollution, even at relatively low levels, give birth to smaller babies. They also suggest that living in a greener area could help counteract this effect. It could be that green areas tend to have lower traffic or that plants help to clear the air of pollution, or green areas may mean it’s easier for pregnant women to be physically active.’
In the second study (abstract PA311), which was published in the journal Pediatric Pulmonology, a UK team from Sussex Medical School and University Hospitals Sussex NHS Foundation Trust sought to evaluate the effect of environmental factors on respiratory infections and symptoms in early childhood.
Researchers turned to data from the GO-CHILD prospective birth cohort study, which explored the role of environment and gene variation on infection and atopy-related outcomes. As part of the study, pregnant women were recruited and their children followed up for infection and respiratory symptoms and outcomes after 12 and 24 months via postal questionnaires.
Information was available for 1,344 children, and the researchers identified how several environmental factors and settings were significantly associated with respiratory infections. For example, use of daycare facilities was associated with a more than two-fold increased risk of pneumonia (odds ratio, OR = 2.39), wheeze (OR = 2.16) and a dry cough (OR = 2.01). There was also a higher risk of developing bronchiolitis (OR = 1.40).
The presence of visible damp in the home increased the risk of wheeze (OR = 1.85) and led to a two-fold increased risk of being prescribed an inhaled corticosteroid (Relative risk, RR = 2.61).
Air pollution also contributed to the risk of respiratory problems. The presence of dense traffic around the child’s home, increased the risk of bronchiolitis (OR = 1.32). However, it was found that the harmful effects of environmental pollution could be mitigated to some extent by measures such as breastfeeding. In fact, continuing to breastfeed beyond six months was associated with a significantly reduced odds of bronchiolitis (OR = 0.55).
Commenting on this study, lead author, Dr Tom Ruffles from the Sussex Medical School, said: ‘This research provides some important evidence about how we can help reduce chest infections in babies and toddlers. The benefits of breastfeeding are well-established, and we should continue to support mothers who want to breastfeed their babies. We should also be making every effort to reduce exposure to infections in daycare, keep homes free of damp and mould, reduce tobacco smoking and cut air pollution.’
Finally, researchers in the third study (abstract PA2721), who were part of the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) based at Gentofte Hospital and the University of Copenhagen in Denmark, looked at the level of respiratory infections seen in children who had been born in either a rural or urban location.
Using the COPSAC2010 mother-child cohort, researchers followed the participants from pregnancy until three years of age and recorded whether the children were growing up in urban or rural areas and how many respiratory infections they developed. The researchers also performed an analysis of the airway immune profile in the children at age four weeks and undertook both maternal and child metabolomic profiling during week 24 of their pregnancy and two to three days after birth.
Among 663 children, the team found there was a mean of 16.3 infections, which were mainly respiratory in nature. Among children living in an urban area, there was a 15% higher risk of infections compared to those living in rural areas (adjusted incidence rate ratio = 1.15, 95% CI 1.05 – 1.26, p = 0.002).
Urbanisation resulted in a different airway immune profile and it was this change that increased the risk of infections, they concluded. Furthermore, urbanisation resulted in different maternal and child metabolomic profiles, which significantly increased the risk of infections.
Lead author for the study and COPSAC researcher and physician, Dr Nicklas Brustad, said: ‘Our findings suggest that urban living is an independent risk factor for developing infections in early life when taking account of several related factors such as exposure to air pollution and starting day care. Interestingly, changes in the blood of pregnant mothers and newborn babies, as well as changes in the newborn immune system, seem to partly explain this relationship.
‘Our results suggest that the environment children live in can have an effect on their developing immune system before they are exposed to coughs and colds. We continue to investigate why some otherwise healthy children are more prone to infections than others and what the implications are for later health.
‘We have several other studies planned that will look for risk factors and try to explain the underlying mechanisms using our large amount of data.’
14th September 2023
Using lung progenitor cell transplantation in patients with chronic obstructive pulmonary disease (COPD) appears to improve symptoms and could lead to a cure, according to a study presented at the recent European Respiratory Society (ERS) International Congress 2023 in Milan, Italy.
It has been previously shown that P63+ progenitor cells, which are used by the body to repair and replace damaged tissue, are able to induce lung epithelium regeneration in animal models.
Consequently, in this first-in-human phase 1 clinical trial (abstract OA4297), researchers set out to investigate the efficacy and safety of taking autologous P63+ progenitor cells transplanted into the lungs of patients with COPD.
They demonstrated that the use of P63+ progenitor cells in those with COPD enabled patients to breathe better, walk further and have improved quality of life. This is the first time researchers have shown it‘s possible to repair damaged lung tissue in patients with COPD using their own lung cells.
The trial included 17 COPD patients with a diffusing capacity of the lungs (DLCO) of less than 80% of the predicted value and three control patients. Individuals were autologously transplanted with the P63+ progenitor cells through bronchoscopy, followed by subsequent assessment for both safety and efficacy within 24 weeks.
The cell treatment was well tolerated by all patients and following transplantation, the median DLCO of treated patients increased from a baseline value of 30.00% to 39.70% after 12 weeks and still further to 40.30% after 24 weeks.
When it came to quality of life, the average St George’s Respiratory Questionnaire score of those receiving cell therapy group decreased from 51.3% at baseline to 44.2% after treatment. The median six-minute-walk distance increased from 410m to 447m at 24 weeks.
In addition, two patients with mild emphysema showed resolution of the lesions at 24 weeks by CT imaging.
Professor Wei Zuo, chief scientist of the study and professor in the school of medicine at Tongji University, Shanghai, China, told the congress: ‘P63+ progenitor cells are known for their ability to regenerate the tissues of the airways, and previously we and other scientists have shown in animal experiments that they can repair the damaged epithelial tissue in the alveoli.‘
He added: ‘We found that P63+ progenitor cell transplantation, not only improved the lung
function of patients with COPD, but also relieved their symptoms, such as shortness of breath, loss
of exercise ability and persistent coughing. This means that the patients could live a better life, and
usually with longer life expectancy.
‘If emphysema progresses, it increases the risk of death. In this trial, we found that P63+ progenitor cell transplantation could repair mild emphysema, making the lung damage disappear. However, we
cannot repair severe emphysema yet.‘
Commenting on the ‘encouraging‘ results, Professor Omar Usmani, head of the European Respiratory Society group on airway disease and professor of respiratory medicine at Imperial College London, UK, added: ‘COPD is in desperate need of new and more effective treatments, so if these results can be confirmed in subsequent clinical trials it will be very exciting. It is also very encouraging that two patients with emphysema responded so well.
‘A limitation of this study is that the uptake of the progenitor cells when they were transplanted back into the patients is uncontrolled. So we do not know whether the lungs of some patients responded better to the transplantation than other. We hope this information may become apparent in future studies.‘
The researchers are planning a phase II trial of the treatment, which will evaluate its efficacy in a
larger group of patients.
11th September 2023
Guidance on how global warming can be addressed in clinical practice has been outlined by the European Respiratory Society (ERS) in its latest consensus statement on climate change and respiratory health.
Published in the European Respiratory Journal, the statement describes climate change as ‘an unfolding major planetary and health crisis’, and a major threat to those with common lung conditions.
This, it says, is linked to the frequent and extreme weather events, prolonged aeroallergen seasons and poorer air quality associated with climate change, which can lead directly to a worsening of health and an increased risk of death.
Traditionally, clinicians have been involved in climate change adaptation strategies such as identifying vulnerable groups and providing advice on how they can protect themselves during heatwaves, for example.
However, the ERS says this clinical role has now expanded to focus on both human and planetary health, which includes contributing to the reduction in greenhouse gas emissions.
According to the ERS, subsequent changes to clinical practice could therefore include promoting green prescriptions such as inhalers; focusing efforts on smoking eradication; and encouraging patients, where appropriate, to engage with nature, take active modes of transport and make more sustainable food choices.
Professor Zorana Jovanovic Andersen, chair of the ERS Environment and Health Committee and professor of environmental epidemiology at the University of Copenhagen, who was one of the authors, said: ‘As respiratory doctors and nurses, we need to be aware of these new risks and do all we can to help alleviate patients’ suffering. We also need to explain the risks to our patients so they can protect themselves from adverse effects of climate change.‘
The consensus statement also highlights that climate change will have a disproportionately greater adverse effect on individuals living with respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD).
It outlines some of the health risks of climate change such as a decline in lung function, increases in allergic responses and/or new cases of chronic (asthma, COPD, lung cancer) or infectious (pneumonia, influenza, tuberculosis, Covid-19) respiratory diseases.
It also identifies a higher risk of exacerbations for existing respiratory diseases, increased use of medication, emergency department visits, hospitalisations and death.
The fact that children are more susceptible to the impact of climate change on lung health is also highlighted, including the fact that the prevention of chronic respiratory disease should start as early as possible as many chronic lung diseases in adults have childhood origins.
Several previous reviews have provided extensive summaries of the different mechanisms by which climate change affects respiratory health, as well as outlining adaptation strategies. The latest statement provides an overview of all major pathways linking climate change with lung health.
While it summarises all of the available evidence, the authors also recognise some gaps in current knowledge. For instance, there is the need for further research to fully map the burden of climate change on respiratory diseases under different global warming scenarios and to understand underlying biological mechanisms, as well as identifying pathways of adaptation that can be translated into public health policies.
Professor Jovanovic Andersen, added: ‘Climate change affects everyone’s health, but arguably, respiratory patients are among the most vulnerable. These are people who already experience breathing difficulties and they are far more sensitive to our changing climate. Their symptoms will become worse, and for some this will be fatal.
‘Air pollution is already damaging our lungs. Now the effects of climate change are becoming a major threat to respiratory patients.’
Indeed, the deleterious respiratory effects of the particulate matter contained within air pollution, are already known to provide a mechanism through which lung cancer can develop among individuals who have never smoked.
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