Abstract Background The Ultra-Low Emission Zone (ULEZ), introduced in Central London in April 2019, aims to enhance air quality and improve public health. The Children's Health in London and Luton (CHILL) study evaluates the impact of the ULEZ on children's health. This analysis focuses on the one-year impacts on the shift towards active travel to school. Methods CHILL is a prospective parallel cohort study of ethnically diverse children, aged 6–9 years attending 84 primary schools within or with catchment areas encompassing London’s ULEZ (intervention) and Luton (non-intervention area). Baseline (2018/19) and one-year follow-up (2019/20) data were collected at school visits from 1992 (58%) children who reported their mode of travel to school ‘today’ (day of assessment). Multilevel logistic regressions were performed to analyse associations between the introduction of the ULEZ and the likelihood of switching from inactive to active travel modes, and vice-versa. Interactions between intervention group status and pre-specified effect modifiers were also explored. Results Among children who took inactive modes at baseline, 42% of children in London and 20% of children in Luton switched to active modes. For children taking active modes at baseline, 5% of children in London and 21% of children in Luton switched to inactive modes. Relative to the children in Luton, children in London were more likely to have switched from inactive to active modes (OR 3.64, 95% CI 1.21–10.92). Children in the intervention group were also less likely to switch from active to inactive modes (OR 0.11, 0.05–0.24). Moderator analyses showed that children living further from school were more likely to switch from inactive to active modes (OR 6.06,1.87–19.68) compared to those living closer (OR 1.43, 0.27–7.54). Conclusions Implementation of clean air zones can increase uptake of active travel to school and was particularly associated with more sustainable and active travel in children living further from school.

OBJECTIVE:Taking a qualitative approach, we aimed to understand how London's Ultra Low Emission Zone (ULEZ) might work to change behaviour and improve health in the context of the school journey. DESIGN:Primary qualitative study embedded within an existing natural experimental study. SETTING:A population-level health intervention implemented across London. PARTICIPANTS:Purposive sampling was used to recruit children (aged 10-11 years) from ethnically and socioeconomically diverse backgrounds within an existing cohort study, Children's Health in London and Luton. METHODS:In-person and online interviews were conducted with 21 families and seven teachers from the children's schools between November 2022 and March 2023. Verbatim transcripts were analysed drawing on Braun and Clarke's reflexive thematic analysis and guided by realist evaluation principles to identify contexts, mechanisms and outcomes using NVivo. RESULTS:Common context, mechanism, outcome (CMO) configurations were identified reflecting congruent narratives across children, parents and teachers, for example, current active travellers (context) reported reductions in pollution (mechanism) leading to improvements in health, including alleviated symptoms of asthma (outcome). These CMOs were broadly captured by two themes: (i) how you travelled before the ULEZ matters: the impact of travel mode on experiences of the ULEZ and (ii) your context matters: the role of socioeconomic position in experiences of the ULEZ. Participants highlighted the potential for the ULEZ to positively impact their choice of travel mode to school, experiences of the journey and their health. However, the impact of the ULEZ differed inequitably by journey length, travel mode before implementation and access to reliable and affordable public transport. CONCLUSIONS:The capacity for the ULEZ to both narrow and exacerbate inequities across different travel contexts suggests when developing such schemes, more emphasis needs to be placed on providing accessible and affordable alternatives to driving.

Background Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs, mostly affecting young and middle-aged women. Significant questions remain as to its pathogenesis, especially the triggers for the associated interstitial lung disease (SSc-ILD). We examined the extent to which SSc and SSc-ILD were related to oxidative stress and altered metal homeostasis at the air-lung interface. Methods In this case-control study, we recruited 20 SSc patients, of which 11 had SSc-ILD. Eighteen healthy individuals were recruited as age-matched healthy controls, for a total of 38 study participants. Low molecular weight antioxidants (ascorbate, urate and glutathione), metal transport and chelation proteins (transferrin and ferritin) and metals (Fe and Cu) concentrations, including a measure of the catalytically active metal pool, were determined in respiratory tract lining fluid (RTLF) collected by bronchoalveolar lavage from the SSc group and compared with healthy controls. Results In the SSc group, 14 individuals were of female sex (70%) and the median age was 57 years (range 35-75). We observed evidence of oxidative stress in the RTLFs of SSc patients, characterised by increased concentrations of glutathione disulphide (GSSG, P<0.01), dehydroascorbate (DHA, P<0.05) and urate (P<0.01). This was associated with elevated RTLF Fe (P=0.07) and Cu (P<0.001), and evidence of a catalytic metal pool, demonstrated by an enhanced rate of ascorbate oxidation in the recovered lavage fluid (p<0.01). Cu concentrations were significantly associated with the ascorbate depletion rate (r=0.76, P<0.001), and GSSG (r=0.38, P<0.05) and protein carbonyl (r=0.44, P<0.01) concentrations. Whilst these markers were all increased in SSc patients, we found no evidence for an association with SSc-ILD. Conclusions These data confirm the presence of oxidative stress in the airways of SSc patients and, for the first time, suggest that an underlying defect in metal homeostasis at the air-lung interface may play a role in disease progression.

Carrying out health research with schools can be both challenging and highly rewarding. Here we describe lessons learned from a research partnership lasting over 5 years, initially with 84 primary schools in London and Luton, and extended to 35 secondary schools, during our children health cohort study. This period included school closures and societal disruption during the COVID-19 pandemic, creating additional challenges to ongoing school participation. Our study involved annual health assessment visits to schools to test over 3000 participants and parental self-report questionnaires, to assess the potential benefits of air quality improvements arising from London Ultra Low Emission Zone (introduced in April 2019) on children’s lung development and health. Measures included height, weight, pre- and post- bronchodilator spirometry, physical activity monitoring, cognitive assessment, epigenetic markers of disease risk, SARS-CoV-2 IgE and IgM antibody testing, and heavy metals testing. The average annual participant attrition for our study was 11.6%. The acceptable threshold outlined in the initial protocol was 20%. All schools continued to participate in the study for 5 years. Central to the study success have been: shared agreement on the importance of the research topic; early preparatory work with stakeholders, a parallel engaging and innovative air pollution learning and outreach programme, incentivising school/teacher co-operation and parental questionnaire completion to boost response rates and mitigate non-response bias; and continuity of contact with the accessible and flexible research team. These successes form a template for other health research studies planning long-term engagement with schools.

Background Air pollution harms health across the life course. Children are at particular risk of adverse effects during development, which may impact on health in later life. Interventions that improve air quality are urgently needed both to improve public health now, and prevent longer-term increased vulnerability to chronic disease. Low Emission Zones are a public health policy intervention aimed at reducing traffic-derived contributions to urban air pollution, but evidence that they deliver health benefits is lacking. We describe a natural experiment study (CHILL: Children’s Health in London and Luton) to evaluate the impacts of the introduction of London’s Ultra Low Emission Zone (ULEZ) on children’s health. Methods CHILL is a prospective two-arm parallel longitudinal cohort study recruiting children at age 6–9 years from primary schools in Central London (the focus of the first phase of the ULEZ) and Luton (a comparator site), with the primary outcome being the impact of changes in annual air pollutant exposures (nitrogen oxides [NOx], nitrogen dioxide [NO 2 ], particulate matter with a diameter of less than 2.5micrograms [PM 2.5 ], and less than 10 micrograms [PM 10 ]) across the two sites on lung function growth, measured as post-bronchodilator forced expiratory volume in one second (FEV 1 ) over five years. Secondary outcomes include physical activity, cognitive development, mental health, quality of life, health inequalities, and a range of respiratory and health economic data. Discussion CHILL’s prospective parallel cohort design will enable robust conclusions to be drawn on the effectiveness of the ULEZ at improving air quality and delivering improvements in children’s respiratory health. With increasing proportions of the world’s population now living in large urban areas exceeding World Health Organisation air pollution limit guidelines, our study findings will have important implications for the design and implementation of Low Emission and Clean Air Zones in the UK, and worldwide. ClinicalTrials.gov NCT04695093 (05/01/2021).

Background Lockdown measures, including school closures, due to the COVID-19 pandemic have caused widespread disruption to children’s lives. The aim of this study was to explore the impact of a national lockdown on children's physical activity using seasonally-matched accelerometery data. Methods Using a pre/post observational design, 179 children aged 8-11 years provided physical activity data measured using hip worn tri-axial accelerometers worn for 5 consecutive days pre-pandemic and during the Jan-Mar 2021 lockdown. Multilevel regression analyses adjusted for covariates were used to assess the impact of lockdown on time spent in sedentary and moderate-to-vigorous physical activity (MVPA). Results A 10.8-minute reduction in daily time spent in moderate-to-vigorous physical activity (standard error [SE]: 2.3min/day, P<0.001), and a 33.2-minute increase in daily sedentary activity (SE: 5.5min/day, P<0.001) were observed during lockdown. This reflected a reduction in daily MVPA for those unable to attend school (-13.1±2.3 min/day, P<0,001) during lockdown, with no significant change for those who continued to attend school (0.4±4.0min/day, P<0.925). Conclusion These findings suggest that the loss of in-person schooling was the single largest impact on physical activity in this cohort of primary school children in London, Luton and Dunstable UK.

Background: COPD is associated with increased oxidative stress in the lungs. The extent to which this contributes to disease etiology is unclear, partially due to the underlying role of physiologic aging. Aim and objectives: We have demonstrated increased oxidative stress in bronchoalveolar lavage (BAL) samples from COPD patients but reported these changes to be partially explained by subject age. Here we examined if oxidative stress in the lungs could be related to increased metal pools at the air-lung interface. Methods: BAL from young and aged never smokers, non-smoking young mild asthmatics, aged smokers without obstructive lung disease and COPD patients, both current and ex-smokers, were analysed for a range of transition metals (Fe, Cu, Zn, As, Cd) using inductively coupled plasma mass spectroscopy. Results: BAL Cu and Zn concentrations were lower in young adults and asthmatics (p<0.001 for both) relative to the aged groups, irrespective of smoking or disease status – see figure. BAL Cu was significantly associated with a range of markers of oxidative stress: glutathione disulphide (r=0.50, P<0.001), dehydroascorbate (r=0.67, P<0.001) and 4-Hydroxynonenal (r=0.43, P<0.001). Conclusions: These data demonstrate that age-related increases in respiratory tract Cu concentrations contribute to increased levels of oxidative stress at the air-lung interface.

Background Diesel exhaust (DE) induces neutrophilia and lymphocytosis in experimentally exposed humans. These responses occur in parallel to nuclear migration of NF-κB and c-Jun, activation of mitogen activated protein kinases and increased production of inflammatory mediators. There remains uncertainty regarding the impact of DE on endogenous antioxidant and xenobiotic defences, mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) and the aryl hydrocarbon receptor (AhR) respectively, and the extent to which cellular antioxidant adaptations protect against the adverse effects of DE. Methods Using immunohistochemistry we investigated the nuclear localization of Nrf2 and AhR in the epithelium of endobronchial mucosal biopsies from healthy subjects six-hours post exposure to DE (PM 10 , 300 µg/m 3 ) versus post-filtered air in a randomized double blind study, as a marker of activation. Cytoplasmic expression of cytochrome P450s, family 1, subfamily A, polypeptide 1 (CYP1A1) and subfamily B, Polypeptide 1 (CYP1B1) were examined to confirm AhR activation; with the expression of aldo–keto reductases (AKR1A1, AKR1C1 and AKR1C3), epoxide hydrolase and NAD(P)H dehydrogenase quinone 1 (NQO1) also quantified. Inflammatory and oxidative stress markers were examined to contextualize the responses observed. Results DE exposure caused an influx of neutrophils to the bronchial airway surface (p = 0.013), as well as increased bronchial submucosal neutrophil (p < 0.001), lymphocyte (p = 0.007) and mast cell (p = 0.002) numbers. In addition, DE exposure enhanced the nuclear translocation of the AhR and increased the CYP1A1 expression in the bronchial epithelium (p = 0.001 and p = 0.028, respectively). Nuclear translocation of AhR was also increased in the submucosal leukocytes (p < 0.001). Epithelial nuclear AhR expression was negatively associated with bronchial submucosal CD3 numbers post DE (r = −0.706, p = 0.002). In contrast, DE did not increase nuclear translocation of Nrf2 and was associated with decreased NQO1 in bronchial epithelial cells (p = 0.02), without affecting CYP1B1, aldo–keto reductases, or epoxide hydrolase protein expression. Conclusion These in vivo human data confirm earlier cell and animal-based observations of the induction of the AhR and CYP1A1 by diesel exhaust. The induction of phase I xenobiotic response occurred in the absence of the induction of antioxidant or phase II xenobiotic defences at the investigated time point 6 h post-exposures. This suggests DE-associated compounds, such as polycyclic aromatic hydrocarbons (PAHs), may induce acute inflammation and alter detoxification enzymes without concomitant protective cellular adaptations in human airways.

Background Introduced in Central London in 2019, the Ultra-Low Emission Zone (ULEZ) aims to improve air quality and population health. This study reports on the one-year findings of a natural experiment study of the ULEZ's effect on children's health and focuses on changes to children's travel to school. We hypothesised that implementing the ULEZ in London would encourage children to switch to active travel to school. Methods Children's Health in London and Luton (CHILL) is a prospective parallel cohort study of 3414 multi-ethnic children aged 6–9 years attending 85 primary schools in Central London (intervention) and Luton (control with similar baseline air quality). Baseline and one-year follow-up data were collected from 3173 children who reported their mode of travel to school 'today' (day of annual health assessment) and 'usually'. Active modes included walking, cycling, scootering, and taking public transport. Inactive modes included taking a car and taxi. Binomial logistic regressions were performed to analyse the impact of the ULEZ on the likelihood of switching from inactive to active travel modes, or vice-versa. Models were adjusted for by age, ethnicity, sex, parent's employment and occupation, and baseline car ownership. Results At baseline, 88% of children in the intervention group reported having used an active form of travel to school, compared to 59% in the control group. Results revealed that, relative to the control group, the intervention group was more likely to switch from inactive to active modes both 'today' (OR 2.59, 95%CI 1.65–4.06) and 'usually' (1.98, 1.07–3.68). Moreover, the intervention group was less likely to shift from active to inactive modes 'today' (0.28, 0.20–0.39) and 'usually' (0.22, 0.13–0.34) compared to the control group. Conclusion Early results indicate that the ULEZ was associated with a shift in children's travel to school towards more sustainable and active travel modes. Future analyses will include methods to more accurately define exposure groups and travel modes using GPS and accelerometer data.

E-cigarette vapour contains free radicals with the potential to induce oxidative stress. Since oxidative stress in airway cells increases platelet-activating factor receptor (PAFR) expression, and PAFR is co-opted by pneumococci to adhere to host cells, we hypothesised that E-cigarette vapour increases pneumococcal adhesion to airway cells.Nasal epithelial PAFR was assessed in non-vaping controls, and in adults before and after 5 min of vaping. We determined the effect of vapour on oxidative stress-induced, PAFR-dependent pneumococcal adhesion to airway epithelial cells in vitro, and on pneumococcal colonisation in the mouse nasopharynx. Elemental analysis of vapour was done by mass spectrometry, and oxidative potential of vapour assessed by antioxidant depletion in vitroThere was no difference in baseline nasal epithelial PAFR expression between vapers (n=11) and controls (n=6). Vaping increased nasal PAFR expression. Nicotine-containing and nicotine-free E-cigarette vapour increased pneumococcal adhesion to airway cells in vitro Vapour-stimulated adhesion in vitro was attenuated by the PAFR blocker CV3988. Nicotine-containing E-cigarette vapour increased mouse nasal PAFR expression, and nasopharyngeal pneumococcal colonisation. Vapour contained redox-active metals, had considerable oxidative activity, and adhesion was attenuated by the antioxidant N-acetyl cysteine.This study suggests that E-cigarette vapour has the potential to increase susceptibility to pneumococcal infection.

Summary Epidemiological studies have consistently shown associations between elevated concentrations of urban particulate matter ( UPM ) air pollution and exacerbations of asthma and chronic obstructive pulmonary disease, which are both associated with viral respiratory infections. The effects of UPM on dendritic cell ( DC ) ‐stimulated CD 4 T lymphocytes have been investigated previously, but little work has focused on CD 8 T‐lymphocyte responses despite their importance in anti‐viral immunity. To address this, we examined the effects of UPM on DC ‐stimulated naive CD 8 T‐cell responses. Expression of the maturation/activation markers CD 83, CCR 7, CD 40 and MHC class I on human myeloid DC s ( mDC s) was characterized by flow cytometry after stimulation with UPM in vitro in the presence/absence of granulocyte–macrophage colony‐stimulating factor ( GM ‐ CSF ). The capacity of these mDC s to stimulate naive CD 8 T‐lymphocyte responses in allogeneic co‐culture was then assessed by measuring T‐cell cytokine secretion using cytometric bead array, and proliferation and frequency of interferon‐ γ ( IFN ‐ γ )‐producing T lymphocytes by flow cytometry. Treatment of mDC s with UPM increased expression of CD 83 and CCR 7, but not MHC class I. In allogeneic co‐cultures, UPM treatment of mDC s enhanced CD 8 T‐cell proliferation and the frequency of IFN ‐ γ + cells. The secretion of tumour necrosis factor‐ α , interleukin‐13, Granzyme A and Granzyme B were also increased. GM ‐ CSF alone, and in concert with UPM , enhanced many of these T‐cell functions. The PM ‐induced increase in Granzyme A was confirmed in a human experimental diesel exposure study. These data demonstrate that UPM treatment of mDC s enhances priming of naive CD 8 T lymphocytes and increases production of pro‐inflammatory cytokines. Such UPM ‐induced stimulation of CD 8 cells may potentiate T‐lymphocyte cytotoxic responses upon concurrent airway infection, increasing bystander damage to the airways.

Background: Although the mechanism underlying air pollution exposure’s adverse effects on lung function is unclear, oxidative stress is implicated in a range of adverse health effects of air pollution. Urinary 8-Oxo-29-deoxyguanosine (8-oxo-dG) is a marker of DNA oxidation and oxidative stress. We sought to assess associations’ between oxidative stress and exposure to fossil fuel derived air pollution in children living in London (UK). Methods: After informed parental consent, healthy children aged 8-14 were recruited from schools in Greater London. Spot urine samples were analysed for 8-oxo-dG using a commercially available ELISA (Trevigen) and normalised against creatinine concentrations. Lung function (FEV1, FVC) was performed on the same day. Children’s short to long term exposure to particulate matter <10 microns (PM10), PM2.5, nitrogen dioxide (NO2), and nitrogen oxides (NOx) was using the London Air Quality Toolkit (LAQT) expressed as mean concentration over the previous 48h, 3mo and 12mo, based on home address. Preliminary statistical analysis was done by Spearman’s rank correlation. Results: 398 children were recruited. 8-oxo-dG was negatively correlated with both FEV1 (-0.166, p=0.002) and FVC (-0.119, p=0.024). 8-oxo-dG positively correlated with modelled exposure at the participants’ home address for the previous 48 h for; NO2 (0.172, p=0.003), NOX (0.161, p=0.005), PM10 (0.163, p=0.005), and PM2.5 (0.117, p=0.04). Discussion These results suggest that oxidative stress is one mechanism underlying the short-term effects of pollutant exposure on lung function in healthy children. We speculate that 8-oxo-dg is a putative biomarker for assessing exposure reduction interventions in this age group.

Background: Population-based estimates of air pollution exposures are typically based on modelling, over varying geographical scales and exposure intervals. These approaches however represent relatively crude estimates of personal exposures. The identification of exposure biomarkers within easily accessible biofluids is a potential solution to this deficiency. We investigated the utility of urinary metal concentrations as biomarkers of exposure over varying time frames. Methods: Spot urine samples (n=400) from children aged 8-14yrs were analysed for metals/metalloids by ICP-MS following nitric acid digestion; data were normalised against creatinine. PM10, PM2.5, and NO2 exposures at children's homes were estimated using the London Air Quality Toolkit, using both short (24hr, 48hr) and long-term (3 or 12 months) concentration means. Crude associations between the metals and exposure estimates were identified using the Spearman Rank correlation. Results: Short term (48h) PM10 and PM2.5 exposures were significantly correlated with barium (PM10: 0.126, p=0.028; PM2.5: 0.133, p=0.021) and molybdenum (PM10: 0.125, p=0.029; PM2.5: 0.146, p=0.011); whereas longer term (3mo) exposures were correlated with arsenic (PM10: 0.122, p=0.032; PM2.5: 0.128, p=0.025) and chromium (PM10: 0.116, p=0.043; PM2.5: 0.141, p=0.014). Annual PM10 was correlated with manganese (0.138, p=0.016). Significant correlations were also observed between NO2 exposures and both iron and manganese, across all four time frames. Conclusions: This analysis provides support for the use of urinary metals as exposure biomarkers for urban pollution, with the associations with manganese corroborating previously reported data.

BackgroundOxidative injury to the airway has been proposed as an important underlying mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). As the extent of oxidant-mediated damage is dependent on the endogenous antioxidant defences within the airways, we examined whether COPD was associated with deficiencies in the antioxidant network within the respiratory tract lining fluids (RTLFs) and resident airway leukocytes. We hypothesised that COPD would be associated with both basal depression of antioxidant defences and impaired adaptive antioxidant responses to cigarette smoke.MethodsLow molecular weight and enzymatic antioxidants together with metal-handling proteins were quantified in bronchoalveolar lavage fluid and airway leukocytes, derived from current (n=9) and ex-smoking COPD patients (n=15), as well as from smokers with normal lung function (n=16) and healthy never smokers (n=13).ResultsCurrent cigarette smoking was associated with an increase in ascorbate and glutathione within peripheral RTLFs in both smokers with normal lung function compared with healthy never smokers and in COPD smokers compared with COPD ex-smokers. In contrast, intra-cellular antioxidant enzyme activities (glutathione peroxidase, glutathione reductase, and catalase) were only up-regulated in smokers with normal lung function compared with healthy never smokers and not in actively smoking COPD patients relative to COPD ex-smokers.ConclusionsWe found no evidence of impaired basal antioxidant defences, within either the RTLFs or airway leukocytes in stable ex-smoking COPD patients compared with healthy never smoking controls. Current cigarette smoking induced an up-regulation of low molecular weight antioxidants in the RTLFs of both control subjects with normal lung function and patients with COPD. Importantly, the present data demonstrated a cigarette smoke–induced increase in intra-cellular antioxidant enzyme activities only within the smokers with normal lung function, implying that patients with COPD who continue to smoke will experience enhanced oxidative stress, prompting disease progression.

Background/Aims To investigate the difference between human umbilical vein endothelial cells (HUVEC) and human ocular microvascular endothelial cell (MVEC) gene expression, and to determine if these differences could improve the understanding of ocular angiogenic diseases.Methods The gene expression profiles of HUVEC and matched unpassaged human choroidal, retinal and iris endothelial cells were conducted using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Selected differences were confirmed by real time PCR. Functional cell proliferation assays were used to support microarray findings.Results HUVEC showed enrichment for probe sets involved in embryological development while ocular MVEC demonstrated enrichment for probe sets for MHC classes I and II, immune responses and cell signal transduction. Comparison of human retinal and choroidal endothelial cells demonstrated significant differences in the expression of probe sets encoding insulin-like growth factor 1 (IGF-1) signalling. Cell proliferation assays demonstrated the stimulatory role of IGF-1 on retinal endothelial cells compared with choroidal endothelial cells.Conclusions Gene expression profiling has demonstrated that HUVEC are probably not a suitable surrogate for the study of ocular angiogenic disorders. There are also significant differences in the gene expression of human retinal and choroidal endothelial cells, which may be important in the mechanism and treatment of choroidal and retinal neovascularisation.

Short-term exposure to a train-derived metal rich particulate aerosol in a subway microenvironment induces oxidative stress in the distal airways

BACKGROUND:Biomass combustion contributes to the production of ambient particulate matter (PM) in rural environments as well as urban settings, but relatively little is known about the health effects of these emissions. The aim of this study was therefore to characterize airway responses in humans exposed to wood smoke PM under controlled conditions. Nineteen healthy volunteers were exposed to both wood smoke, at a particulate matter (PM2.5) concentration of 224 ± 22 μg/m3, and filtered air for three hours with intermittent exercise. The wood smoke was generated employing an experimental set-up with an adjustable wood pellet boiler system under incomplete combustion. Symptoms, lung function, and exhaled NO were measured over exposures, with bronchoscopy performed 24 h post-exposure for characterisation of airway inflammatory and antioxidant responses in airway lavages.RESULTS:Glutathione (GSH) concentrations were enhanced in bronchoalveolar lavage (BAL) after wood smoke exposure vs. air (p = 0.025), together with an increase in upper airway symptoms. Neither lung function, exhaled NO nor systemic nor airway inflammatory parameters in BAL and bronchial mucosal biopsies were significantly affected.CONCLUSIONS:Exposure of healthy subjects to wood smoke, derived from an experimental wood pellet boiler operating under incomplete combustion conditions with PM emissions dominated by organic matter, caused an increase in mucosal symptoms and GSH in the alveolar respiratory tract lining fluids but no acute airway inflammatory responses. We contend that this response reflects a mobilisation of GSH to the air-lung interface, consistent with a protective adaptation to the investigated wood smoke exposure.