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Diesel vehicle emissions are the major source of genotoxic compounds in ambient air from urban areas. These pollutants are linked to risks of cardiovascular diseases, lung cancer, respiratory infections and adverse neurological effects. Biological events associated with exposure to some air pollutants are widely unknown but applying omics techniques may help to identify the molecular processes that link exposure to disease risk. Most data on health risks are related to long-term exposure, so the aim of this study is to investigate the impact of short-term exposure (two hours) to air pollutants on the blood transcriptome and microRNA expression levels. We analyzed transcriptomics and microRNA expression using microarray technology on blood samples from volunteers participating in studies in London, the Oxford Street cohort, and, in Barcelona, the TAPAS cohort. Personal exposure levels measurements of particulate matter (PM 10 , PM 2.5 ), ultrafine particles (UFPC), nitrogen oxides (NO 2 , NO and NOx), black carbon (BC) and carbon oxides (CO and CO 2 ) were registered for each volunteer. Associations between air pollutant levels and gene/microRNA expression were evaluated using multivariate normal models (MVN). MVN-models identified compound-specific expression of blood cell genes and microRNAs associated with air pollution despite the low exposure levels, the short exposure periods and the relatively small-sized cohorts. Hsa-miR-197-3p, hsa-miR-29a-3p, hsa-miR-15a-5p, hsa-miR-16-5p and hsa-miR-92a-3p are found significantly expressed in association with exposures. These microRNAs target also relevant transcripts, indicating their potential relevance in the research of omics-biomarkers responding to air pollution. Furthermore, these microRNAs are also known to be associated with diseases previously linked to air pollution exposure including several cancers such lung cancer and Alzheimer's disease. In conclusion, we identified in this study promising compound-specific mRNA and microRNA biomarkers after two hours of exposure to low levels of air pollutants during two hours that suggest increased cancer risks. [ABSTRACT FROM AUTHOR]

Background: In 2003, we recorded a striking difference in the prevalence of atopy between village and small-town populations in southwest Poland. Nine years later, we undertook a second survey of the same area. Objective: We sought to assess whether rapid changes in farming practices, driven by accession to the European Union in 2004, were accompanied by an increase in atopy, asthma, and hay fever in these villages. Methods: In 2012, we surveyed 1730 inhabitants older than 5 years (response rate, 85%); 560 villagers and 348 town inhabitants who had taken part in the earlier survey. Participants completed a questionnaire on farm-related exposures and symptoms of asthma and hay fever. Atopy was assessed by using skin prick tests. Results: In 2012, far fewer villagers had contact with cows (4% vs 24.3% in 2003) or pigs (14% vs 33.5%), milked cows (2.7% vs 12.7%), or drank unpasteurized milk (9% vs 35%). Among the villagers, there was a significant increase at all ages in the prevalence of atopy between 2003 and 2012 both in the total population (7.3% vs 19.6%, P < .0001) and among those who took part in both surveys (7.9% vs 17.8%, P < .0001). Among the townspeople, the prevalence of atopy did not change substantially (20% vs 19.9% and 21.7% vs 18.5%, respectively). Hay fever increased 2-fold in the villages (3.0% vs 7.7%) but not in the town (7.1% vs 7.2%); there was little or no change in asthma prevalence in the villages (5.0% vs 4.3%) or town (4.3% vs 5.0%). Conclusions: We report a substantial increase in atopy at all ages and in a remarkably short period of time in a Polish population whose farm-related exposures were dramatically reduced after their country's accession to the European Union. [Copyright &y& Elsevier]

Summary: Background: Defining childhood asthma varies considerably, and the extent of agreement between various measures is not clearly understood in the absence of a recognized ‘gold standard’. We compared different definitions of childhood asthma, identified characteristics that might have influenced their accuracy and an acquisition of an ‘asthma’ label in wheezy and treated children. Methods: Using a prospective, population-based birth cohort of 623 children followed up to the age of 14 years the concordance between parental opinion, doctor''s diagnosis reported by the parent and asthma''s diagnosis in general practice (GP) was analysed using latent class analysis (LCA). Results: At the age of eight, ‘ever asthma’ prevalences ranged from 15.5% (parental opinion) to 21.5% (GP record). 35% of children by the age of eight years had at least one reported label of asthma, reflecting both cross sectional and longitudinal inconsistencies. By the age of 14 years, 16% of children were inconsistently defined as ‘ever asthmatic’ by their parents. The prevalence of ‘ever asthma’ estimated by LCA was 19.3%, indicating a parental report of a doctor''s diagnosis to be the most sensitive and specific definition. The likelihood of being labelled with asthma was higher in those with a parental or sibling history of asthma, but not determined by socio-demographic characteristics. Conclusions: Although the estimates of prevalence were similar for parental reports and GP records, agreement between the three sources was less than expected. Parental report of a doctor''s diagnosis of asthma is sensitive, specific, longitudinally consistent and not subject to large socio-economic bias. [Copyright &y& Elsevier]

Summary: Background: The proportion of patients with cystic fibrosis (CF) who are middle-aged is increasing – and is likely to continue to do so. We surveyed a population of long-term CF survivors to assess their burden of illness and profile their disease characteristics. Methods: A case series (n =112) of patients from one specialist centre who had reached their 40th birthday without transplantation. Hospital records and annual review data were examined. Results: The median age of the group was 43.1 years (range 40–71.1); 57% were men. 68% were diagnosed before 16 years of age. 30% were ΔF508/ΔF508, 76% having at least one ΔF508 allele. When compared with the total adult CF population, the older patients were significantly less likely to have a ΔF508 mutation or colonisation with Stenotrophomonas maltophilia and MRSA; but more likely to have pancreatic sufficiency, colonisation with Pseudomonas aeruginosa or allergic bronchopulmonary aspergillosis. On average they required less than one hospital admission a year; lung function and body mass index were relatively well preserved. Many were married and working. Conclusions: We describe one of the largest surveys to date of CF patients aged more than 40 years. The full spectrum of disease is represented in this population and, importantly, 30% are ΔF508 homozygous. Provision needs to be made for the healthcare needs of this increasing population of older patients. [Copyright &y& Elsevier]

Summary: Background: The aim of this study was to use a longitudinal computerised health care dataset (The Health Improvement Network) to provide information on the overall incidence of cancer, and on the incidence of organ-specific cancers, in people with idiopathic pulmonary fibrosis (IPF) and sarcoidosis in comparison to the general population. Methods: Incident cases of IPF and sarcoidosis were identified with up to four controls matched by age, gender and general practice. Cancer incidence rates were compared between cohorts using Cox regression and adjusting for age, gender and smoking habit. Results: One thousand and sixty-four incident cases of IPF (mean age at diagnosis 71.5 years; 62.4% male) were identified. Overall, the incidence of cancer was increased in people with IPF compared to the general population (rate ratio 1.51; 95% CI 1.20–1.90), but this was largely due to a marked increase in the incidence of lung cancer (rate ratio 4.96; 95% CI 3.00–8.18). One thousand one hundred and fifty-three incident cases of sarcoidosis (mean age at diagnosis 47.0 years; 47.2% male) were identified. There was an overall increased incidence of cancer in sarcoidosis (rate ratio 1.65; 95% CI 1.22–2.24) and this was largely explained by an increase in the incidence of skin cancers (rate ratio 1.86; 95% CI 1.11–3.11). Conclusions: This study provides further evidence of a marked increase in the incidence of lung cancer in people with IPF, but we found no increase in the risk of other cancers. People with sarcoidosis did have an increase risk of skin cancers, but not cancers at other sites. [Copyright &y& Elsevier]

Background: Seasonal allergic rhinitis is common globally, and symptoms have been shown to impair learning ability in children in laboratory conditions. Critical examinations in children are often held in the summer during the peak grass pollen season. Objective: To investigate whether seasonal allergic rhinitis adversely impacts examination performance in United Kingdom teenagers. Methods: Case-control analysis of 1834 students (age 15-17 years; 50% girls) sitting for national examinations. Cases were those who dropped 1 or more grades in any of 3 core subjects (mathematics, English, and science) between practice (winter) and final (summer) examinations; controls were those whose grades were either unchanged or improved. Associations between allergic rhinitis symptoms, clinician-diagnosed allergic rhinitis, and allergic rhinitis–related medication use, recorded on examination days immediately before the examination, were assessed using multilevel regression models. Results: Between 38% and 43% of students reported symptoms of seasonal allergic rhinitis on any 1 of the examination days. There were 662 cases (36% of students) and 1172 controls. After adjustment, cases were significantly more likely than controls to have had allergic rhinitis symptoms during the examination period (odds ratio [OR], 1.4; 95% CI, 1.1-1.8; P = .002), to have taken any allergic rhinitis medication (OR, 1.4; 95% CI, 1.1-1.7; P = .01), or to have taken sedating antihistamines (OR, 1.7; 95% CI, 1.1-2.8; P = .03). Conclusion: Current symptomatic allergic rhinitis and rhinitis medication use are associated with a significantly increased risk of unexpectedly dropping a grade in summer examinations. Clinical implications: This is the first time the relationship between symptomatic allergic rhinitis and poor examination performance has been demonstrated, which has significant implications for clinical practice. [Copyright &y& Elsevier]

Background: Although it is widely assumed that childhood sensitization to common aeroallergens is directly related to allergen exposure in early life, few longitudinal studies have investigated this issue, and available data are scarce and mainly limited to high-risk groups. Objective: We sought to assess the role of early exposure to 2 major household aeroallergens (Der p 1 and Fel d 1) in sensitization at the age of 4 years. Methods: Pregnant women and their children were recruited for the Asthma Multicenter Infant Cohort Study. Three cohorts (Ashford in the United Kingdom and Menorca and Barcelona in Spain) followed the same research protocol. A total of 1611 newborn children were initially included in the cohort, from whose homes we collected dust samples at 3 months of age for 1474; Der p 1 and Fel d 1 levels were measured. Of these children, we obtained blood for specific IgE determination in 1019. Results: The risk of Fel d 1 sensitization increased with exposure in a nonlinear manner. No association was found between specific IgE to Der p 1 and aeroallergen levels of exposure at early life in 2 centers, but a positive association was observed in the third. Conclusions: The dose-response relationships between allergen exposure and sensitization differ between allergens and might vary between different locales. The hypothesis that sensitization to house dust mite is directly related to levels of allergen exposure might not apply to the general population or to different ranges of exposure. Clinical implications: Aeroallergen avoidance might not have any important effect on the incidence of sensitization. [Copyright &y& Elsevier]

Background: Exposure to diisocyanates in the workplace is an important cause of occupational asthma. The majority of patients with diisocyanate-induced asthma have no detectable diisocyanate-specific IgE antibodies in serum. There has been much debate as to whether this is due to diisocyanate-induced asthma being mediated by non-IgE mechanisms or whether it is the result of using inappropriate conjugates. Objective: We sought to determine whether RNA message for Cε, IL-4, and other associated inflammatory markers could be detected locally within the bronchial mucosa after diisocyanate challenge. Methods: Fiberoptic bronchoscopic bronchial biopsy specimens were obtained at 24 hours after both a control and an active challenge in 5 patients with positive and 7 patients with negative inhalation test responses to diisocyanates. Using both immunohistochemistry and in situ hybridization, we determined mRNA for Cε, IL-4, IL-5, and other associated inflammatory markers. Results: There was a striking absence of Cε and IL-4 mRNA-positive cells in bronchial biopsy specimens from patients challenged with diisocyanate (Cε median of 0 and interquartile range of 0-1.85; IL-4 median of 0 and interquartile range of 0-0.85). In contrast, there were increased numbers of IL-5–, CD25-, and CD4-positive cells and a trend toward an increase in eosinophils after active challenge with diisocyanate. Conclusion: We found a striking absence of both bronchial Cε and IL-4 RNA message after inhalation challenge with diisocyanates, irrespective of whether the challenge test response was positive or negative. We propose that diisocyanate-induced asthma is a non–IgE-mediated disease, at least in patients in whom specific IgE antibodies to diisocyanates are undetectable. [Copyright &y& Elsevier]

Social support is a key determinant of mental health across multiple populations and contexts. Little is known about social support among UK (ex-)military personnel, especially those with combat injuries following deployment to Afghanistan. This study aimed to investigate the level of perceived social support and its associations with mental health among injured and uninjured UK (ex-)military personnel. An analysis of baseline data from the Armed Services Trauma Rehabilitation Outcome (ADVANCE) prospective cohort study was performed. A representative sample of male UK combat-injured personnel was compared with a frequency-matched sample of uninjured personnel. Validated questionnaires were completed including the Multidimensional Scale of Perceived Social Support (MSPSS). MSPSS score was transformed using linear splines with a knot at ≥ 55. Multivariable logistic regression analyses examined associations between perceived social support and mental health. In total, 521 combat-injured participants (137 with amputations) and 515 uninjured participants were included. Median MSPSS score was 65 (interquartile range [IQR] 54–74). Injured and uninjured participants reported similar MSPSS scores, as did those injured with amputations, and non-amputation injured participants. For each one unit increase in MSPSS score (for scores ≥55), the odds of post-traumatic stress disorder decreased (adjusted odds ratio [AOR] 0.93, 95% confidence interval [CI] 0.91 to 0.96). No such association was found with MSPSS scores below 55 (AOR 0.99, 95% CI 0.97 to 1.01). Similar results were observed for depression and anxiety. Perceived social support may be a target for intervention within this population, irrespective of injury status. • Injured/uninjured UK military personnel report similar levels of social support. • Amputation/non-amputation injured personnel report similar levels of social support. • Social support has a negative association with mental health. [ABSTRACT FROM AUTHOR]

Chronic pain after injury poses a serious health burden. As a result of advances in medical technology, ever more military personnel survive severe combat injuries, but long-term pain outcomes are unknown. We aimed to assess rates of pain in a representative sample of UK military personnel with and without combat injuries. We used data from the ADVANCE cohort study (ISRCTN57285353). Individuals deployed as UK armed forces to Afghanistan were recruited to include those with physical combat injuries, and a frequency-matched uninjured comparison group. Participants completed self-reported questionnaires, including 'overall' pain intensity and self-assessment of post-traumatic stress disorder, anxiety, and depression. A total of 579 participants with combat injury, including 161 with amputations, and 565 uninjured participants were included in the analysis (median 8 yr since injury/deployment). Frequency of moderate or severe pain was 18% (n =202), and was higher in the injured group (n =140, 24%) compared with the uninjured group (n =62, 11%, relative risk: 1.1, 95% confidence interval [CI]: 1.0–1.2, P <0.001), and lower in the amputation injury subgroup (n =31, 19%) compared with the non-amputation injury subgroup (n =109, 26%, relative risk: 0.9, 95% CI: 0.9–1.0, P =0.034). Presence of at least moderate pain was associated with higher rates of post-traumatic stress (RR: 3.7, 95% CI: 2.7–5.0), anxiety (RR: 3.2, 95% CI: 2.4–4.3), and depression (RR: 3.4, 95% CI: 2.7–4.5) after accounting for injury. Combat injury, but not amputation, was associated with a higher frequency of moderate to severe pain intensity in this cohort, and pain was associated with adverse mental health outcomes. [ABSTRACT FROM AUTHOR]

Post-Traumatic Stress Disorder (PTSD) has been identified as an independent risk factor for cardiovascular disease, but the mechanisms of this relationship are not well understood. This study investigates the associations between PTSD symptom clusters (hyperarousal, intrusive thoughts, avoidance behaviours and emotional numbing) and mechanisms of cardiovascular disease including cardiometabolic effects, inflammation, and haemodynamic functioning. In the ADVANCE study cohort of UK male military personnel, 1111 participants were assessed for PTSD via questionnaire and cardiovascular risk via venous blood sampling, pulse wave analysis and dual energy x-ray absorptiometry between 2015 and 2020. Variable selection procedures were conducted to assess which of the symptom clusters if any were associated with cardiovascular risk outcomes. Associations were confirmed via robust regression modelling. Avoidance behaviours were associated with greater systolic Blood Pressure (BP) (Adjusted Coefficient (AC) 0.640 (95% Confidence Interval (CI) 0.065, 1.149). Emotional numbing was associated with greater estimated glucose disposal rate (AC -0.021 (95%CI -0.036, −0.005). Hyperarousal was associated with greater levels of (log)triglycerides (exponentiated-AC 1.009 (95%CI 1.002, 1.017). Intrusive thoughts were associated with greater visceral adipose tissue (AC 0.574 (95%CI 0.020, 1.250). Nonlinear relationships were observed between emotional numbing with heart rate and intrusive thoughts with systolic BP. Limited evidence is present for symptom associations with lipoproteins and pulse wave velocity. No associations were observed between PTSD symptom clusters and high sensitivity c-reactive protein, diastolic BP, total cholesterol, or haemoglobin fasting glucose. In conclusion, symptom clusters of PTSD were associated with increased cardiovascular risk via cardiometabolic and haemodynamic functioning mechanisms, but not inflammation. [ABSTRACT FROM AUTHOR]

Background: Studies on the association of farm environments with asthma and atopy have repeatedly observed a protective effect of farming. However, no single specific farm-related exposure explaining this protective farm effect has consistently been identified. Objective: We sought to determine distinct farm exposures that account for the protective effect of farming on asthma and atopy. Methods: In rural regions of Austria, Germany, and Switzerland, 79,888 school-aged children answered a recruiting questionnaire (phase I). In phase II a stratified random subsample of 8,419 children answered a detailed questionnaire on farming environment. Blood samples and specific IgE levels were available for 7,682 of these children. A broad asthma definition was used, comprising symptoms, diagnosis, or treatment ever. Results: Children living on a farm were at significantly reduced risk of asthma (adjusted odds ratio [aOR], 0.68; 95% CI, 0.59-0.78; P < .001), hay fever (aOR, 0.43; 95% CI, 0.36-0.52; P < .001), atopic dermatitis (aOR, 0.80; 95% CI, 0.69-0.93; P = .004), and atopic sensitization (aOR, 0.54; 95% CI, 0.48-0.61; P < .001) compared with nonfarm children. Whereas this overall farm effect could be explained by specific exposures to cows, straw, and farm milk for asthma and exposure to fodder storage rooms and manure for atopic dermatitis, the farm effect on hay fever and atopic sensitization could not be completely explained by the questionnaire items themselves or their diversity. Conclusion: A specific type of farm typical for traditional farming (ie, with cows and cultivation) was protective against asthma, hay fever, and atopy. However, whereas the farm effect on asthma could be explained by specific farm characteristics, there is a link still missing for hay fever and atopy. [ABSTRACT FROM AUTHOR]

[Display omitted] • Largest occupational cohort study conducted in a subway system. • PM 2.5 mass concentration on the London Underground can be 15 times higher than outdoor air in London. • Subway PM exposure amongst staff is heterogenous and drivers have the highest exposures. • Office staff had lower sickness absence rates from all-causes and infections. • No exposure response relationship between PM 2.5 and sickness absence was seen to support causal associations. The London Underground (LU) employs over 19,000 staff, some of whom are exposed to elevated concentrations of particulate matter (PM) within the network. This study quantified the occupational exposure of LU staff to subway PM and investigated the possible association with sickness absence (SA). A job exposure matrix to quantify subway PM 2.5 staff exposure was developed by undertaking measurement campaigns across the LU network. The association between exposure and SA was evaluated using zero-inflated mixed-effects negative binomial models. Staff PM 2.5 exposure varied by job grade and tasks undertaken. Drivers had the highest exposure over a work shift (mean: 261 µg/m3), but concentrations varied significantly by LU line and time the train spent subway. Office staff work in office buildings separate to the LU network and are unexposed to occupational subway PM 2.5. They were found to have lower rates of all-cause and respiratory infection SA compared to non-office staff, those who work across the LU network and are occupational exposed to subway PM 2.5. Train drivers on five out of eight lines showed higher rates of all-cause SA, but no dose–response relationship was seen. Only drivers from one line showed higher rates of SAs from respiratory infections (incidence rate ratio: 1.24, 95% confidence interval 1.10–1.39). Lower-grade customer service (CS) staff showed higher rates of all-cause and respiratory infection SA compared to higher grade CS staff. Doctor-certified chronic respiratory and cardiovascular SAs were associated with occupational PM 2.5 exposure in CS staff and drivers. While some groups with higher occupational exposure to subway PM reported higher rates of SA, no evidence suggests that subway PM is the main contributing factor to SA. This is the largest subway study on health effects of occupational PM 2.5 exposure and may have wider implications for subway workers, contributing to safer working environments. [ABSTRACT FROM AUTHOR]

Abstract Exposure to traffic-related air pollution (TRAP) has been associated with adverse health outcomes but underlying biological mechanisms remain poorly understood. Two randomized crossover trials were used here, the Oxford Street II (London) and the TAPAS II (Barcelona) studies, where volunteers were allocated to high or low air pollution exposures. The two locations represent different exposure scenarios, with Oxford Street characterized by diesel vehicles and Barcelona by normal mixed urban traffic. Levels of five and four pollutants were measured, respectively, using personal exposure monitoring devices. Serum samples were used for metabolomic profiling. The association between TRAP and levels of each metabolic feature was assessed. All pollutant levels were significantly higher at the high pollution sites. 29 and 77 metabolic features were associated with at least one pollutant in the Oxford Street II and TAPAS II studies, respectively, which related to 17 and 30 metabolic compounds. Little overlap was observed across pollutants for metabolic features, suggesting that different pollutants may affect levels of different metabolic features. After observing the annotated compounds, the main pathway suggested in Oxford Street II in association with NO 2 was the acyl-carnitine pathway, previously found to be associated with cardio-respiratory disease. No overlap was found between the metabolic features identified in the two studies. Highlights • Two randomized crossover trials were used to assess the relationship between TRAP and metabolic features with MS-based metabolomics (MWAS) • The locations represent different exposure scenarios, with London characterized by diesel vehicles and Barcelona by normal mixed urban traffic • Levels of 17 and 30 metabolic compounds associated with different air pollutants in the studies, with little overlap in features across pollutants • No overlap found between metabolomic features identified in the two studies, possibly due to different levels of single pollutants • The acyl-carnitine pathway, involved in cardio-respiratory disease, was suggested as a potential pathway in association with NO 2 in one study [ABSTRACT FROM AUTHOR]

Traffic-related air pollution is a complex mixture of particulate matter (PM) and gaseous pollutants, such as nitrogen dioxide (NO2). PM exposure contributes to the pathogenesis of many diseases including several types of cancer, as well as pulmonary, cardiovascular and neurodegenerative diseases. Also exposure to NO2 has been related to increased cardiovascular mortality. In search of an early diagnostic biomarker for improved air pollution-associated health risk assessment, recent human studies have shown that certain circulating miRNAs are altered upon exposure to traffic-related air pollutants. Here, we present for the first time a global analysis of the circulating miRNA genome in an experimental cross-over study of a human population exposed to traffic-related air pollution. By utilizing next-generation sequencing technology and detailed real-time exposure measurements we identified 54 circulating miRNAs to be dose- and pollutant species-dependently associated with PM10, PM2.5, black carbon, ultrafine particles and NO2 already after 2 h of exposure. Bioinformatics analysis suggests that these circulating miRNAs actually reflect the adverse consequences of traffic pollution-induced toxicity in target tissues including the lung, heart, kidney and brain. This study shows the strong potential of circulating miRNAs as novel biomarkers for environmental health risk assessment. [ABSTRACT FROM AUTHOR]