The presence of air pollution particulate matter in cryopreserved placental tissue cells.

Carbonaceous particles seen in frozen human macrophage-enriched placental cells can be used as a biomarker of personal exposure to combustion-derived particulate matter. The feasibility of using frozen tissues will allow for global comparative studies. https://bit.ly/3yANbRi.

Prostaglandin E2 and phagocytosis of inhaled particulate matter by airway macrophages in cystic fibrosis.

BACKGROUND: Exposure to particulate matter (PM) air pollution is associated with adverse health outcomes in children with cystic fibrosis (CF). Airway macrophages (AM) phagocytose and retain inhaled PM in vivo, and the area of carbon in AM reflects both inhaled PM dose and phagocytic function. Since airway prostaglandin-E2 (PGE2) is increased in CF, and PGE2 suppresses AM phagocytosis, we sought evidence for PGE2-mediated suppression of AM phagocytosis of inhaled carbonaceous PM in CF. METHODS: After informed consent, urine was obtained from 20 controls and 24 CF children. In the subgroup of older children, at least one induced sputum was done in 20 controls and 19 CF children. Urinary tetranor PGEM, the major metabolite of PGE2, and sputum PGE2 were measured by mass spectrometry. The area of carbon in AM was determined by image analysis. Exposure to PM was assessed by modelling and personal monitoring. The effect of either PGE2 or CF sputum supernatant on phagocytosis of diesel exhaust particle (DEP) by AM was assessed in vitro. Data were analysed by t-test. RESULTS: Both urinary tetranor PGEM (P<0.05), and sputum PGE2 (P<0.05) were increased in CF . Despite no difference in PM exposure between groups, the area of phagocytosed carbon by AM was decreased in children with CF (P<0.01). PGE2 suppressed phagocytosis of DEP by AM from both controls and CF (P<0.0001). CF sputum supernatant suppressed phagocytosis of DEP by AM (P<0.0001) in a PGE2-dependent manner. CONCLUSION: Increased PGE2 in the CF airway suppresses phagocytosis of inhaled PM by AM.

Evidence for the presence of air pollution nanoparticles in placental tissue cells.

Inhaled particulate matter (PM) from combustion- and friction-sourced air pollution adversely affects organs distant from the lung. A putative mechanism for the remote effect of inhaled PM is that ultrafine, nano-sized fraction (<100 nm) translocates across the air-tissue barrier, directly interacting with phagocytic tissue cells. Although PM is reported in other tissues, whether it is phagocytosed by non-respiratory tissue resident cells is unclear. Using the placenta as an accessible organ for phagocytic cells, we sought to seek evidence for air pollution-derived PM in tissue resident phagocytes. Macrophage-enriched placental cells (MEPCs) were isolated, and examined by light and electron microscopy. MEPC carbon was assessed by image analysis (mean µm2/1000 cells); particle composition and numbers were investigated using magnetic analyses and energy dispersive X-ray spectroscopy. MEPCs phagocytic capacity was assessed by culture with diesel exhaust PM in vitro. Fifteen placentas were analysed. Black inclusions morphologically compatible with inhaled PM were identified within MEPCs from all samples (mean ± SEM carbon loading, 1000 MEPCs/participant of 0.004 ± 0.001 µm2). High resolution scanning/transmission electron microscopy revealed abundant nano-sized particle aggregates within MEPCs. MEPC PM was predominantly carbonaceous but also co-associated with a range of trace metals, indicative of high temperature (i.e. exogenous) generation. MEPCs contained readily-measurable amounts of iron-rich, ferrimagnetic particles, in concentrations/particle number concentrations ranging, respectively, from 8 to 50 ng/g and 10 to 60.107 magnetic particles/g (wet wt) MEPCs. Extracted MEPCs (n = 20/ placenta) were phagocytic for PM since all cells showed increased carbon area after culture with diesel PM in vitro (mean ± SEM increase 7.55 ± 1.26 µm2 carbon PM). These findings demonstrate that inhaled, metal-bearing, air pollution-derived PM can not only translocate to distant organs, but is taken up by tissue resident phagocytes in vivo. The human placenta, and hence probably the fetus, thus appears to be a target for such particles.

First analysis of the Severe Paediatric Asthma Collaborative in Europe registry.

New biologics are being continually developed for paediatric asthma, but it is unclear whether there are sufficient numbers of children in Europe with severe asthma and poor control to recruit to trials needed for registration. To address these questions, the European Respiratory Society funded the Severe Paediatric Asthma Collaborative in Europe (SPACE), a severe asthma registry. We report the first analysis of the SPACE registry, which includes data from 10 paediatric respiratory centres across Europe. Data from 80 children with a clinical diagnosis of severe asthma who were receiving both high-dose inhaled corticosteroid and long-acting ß2-agonist were entered into the registry between January 2019 and January 2020. Suboptimal control was defined by either asthma control test, or Global Initiative for Asthma criteria, or ≥2 severe exacerbations in the previous 12 months, or a combination. Overall, 62 out of 80 (77%) children had suboptimal asthma control, of whom 29 were not prescribed a biologic. However, in 24 there was an option for starting a licensed biologic. 33 children with suboptimal control were prescribed a biologic (omalizumab (n=24), or mepolizumab (n=7), or dupilumab (n=2)), and for 29 there was an option to switch to a different biologic. We conclude that the SPACE registry provides data that will support the planning of studies of asthma biologics. Not all children on biologics achieve good asthma control, and there is need for new trial designs addressing biologic switching.

Key paediatric messages from the 2018 European Respiratory Society International Congress.

In this article, the Group Chairs and early career members of the European Respiratory Society (ERS) Paediatric Assembly highlight some of the most interesting findings in the field of paediatrics which were presented at the 2018 international ERS Congress.

Severe Paediatric Asthma Collaborative in Europe (SPACE): protocol for a European registry.

The development of new asthma biologics and receptor blockers for the treatment of paediatric severe asthma raises challenges. It is unclear whether there are sufficient children in Europe to recruit into randomised placebo-controlled trials to establish efficacy and safety in this age group. In February 2016, the European Respiratory Society funded a clinical research collaboration entitled "Severe Paediatric Asthma Collaborative in Europe" (SPACE). We now report the SPACE protocol for a prospective pan-European observational study of paediatric severe asthma. Inclusion criteria are: 1) age 6-17 years, 2) severe asthma managed at a specialised centre for ≥6 months, 3)clinical and spirometry evidence of asthma, and 4) reaching a pre-defined treatment threshold. The exclusion criterion is the presence of conditions which mimic asthma symptoms. Eligible children will be prospectively recruited into a registry, recording demographics, comorbidities, quality of life, family history, neonatal history, smoking history, asthma background, investigations, and treatment. Follow-up will provide longitudinal data on asthma control and treatment changes. The SPACE registry, by identifying well-phenotyped children eligible for clinical trials, and the amount of overlap in eligibility criteria, will inform the design of European trials in paediatric severe asthma, and facilitate observational research where data from single centres are limited.

Diesel, children and respiratory disease.

Air pollution generated in urban areas is a global public health burden since half of the world's population live in either cities, megacities or periurban areas. Its direct effects include initiating and exacerbating disease, with indirect effects on health mediated via climate change putting the basic needs of water, air and food at risk.

Use of cleaner-burning biomass stoves and airway macrophage black carbon in Malawian women.

Exposure to particulate matter (PM) from burning of biomass for cooking is associated with adverse health effects. It is unknown whether or not cleaner burning biomass-fuelled cookstoves reduce the amount of PM inhaled by women compared with traditional open fires. We sought to assess whether airway macrophage black carbon (AMBC) - a marker of inhaled dose of carbonaceous PM from biomass and fossil fuel combustion - is lower in Malawian women using a cleaner burning biomass-fuelled cookstove compared with those using open fires for cooking. AMBC was assessed in induced sputum samples using image analysis and personal exposure to carbon monoxide (CO) and PM were measured using Aprovecho Indoor Air Pollution meters. A fossil-fuel exposed group of UK women was also studied. Induced sputum samples were obtained from 57 women from which AMBC was determined in 31. Median AMBC was 6.87µm2 (IQR 4.47-18.5) and 4.37µm2 (IQR 2.57-7.38) in the open fire (n=11) and cleaner burning cookstove groups (n=20), respectively (p=0.028). There was no difference in personal exposure to CO and PM between the two groups. UK women (n=5) had lower AMBC (median 0.89µm2, IQR 0.56-1.13) compared with both Malawi women using traditional cookstoves (p<0.001) and those using cleaner cookstoves (p=0.022). We conclude that use of a cleaner burning biomass-fuelled cookstove reduces inhaled PM dose in a way that is not necessarily reflected by personal exposure monitoring.