Serum amyloid A opposes lipoxin A4 to mediate glucocorticoid refractory lung inflammation in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) will soon be the third most common cause of death globally. Despite smoking cessation, neutrophilic mucosal inflammation persistently damages the airways and fails to protect from recurrent infections. This maladaptive and excess inflammation is also refractory to glucocorticosteroids (GC). Here, we identify serum amyloid A (SAA) as a candidate mediator of GC refractory inflammation in COPD. Extrahepatic SAA was detected locally in COPD bronchoalveolar lavage fluid, which correlated with IL-8 and neutrophil elastase, consistent with neutrophil recruitment and activation. Immunohistochemistry detected SAA was in close proximity to airway epithelium, and in vitro SAA triggered release of IL-8 and other proinflammatory mediators by airway epithelial cells in an ALX/FPR2 (formyl peptide receptor 2) receptor-dependent manner. Lipoxin A(4) (LXA(4)) can also interact with ALX/FPR2 receptors and lead to allosteric inhibition of SAA-initiated epithelial responses (pA(2) 13 nM). During acute exacerbation, peripheral blood SAA levels increased dramatically and were disproportionately increased relative to LXA(4). Human lung macrophages (CD68(+)) colocalized with SAA and GCs markedly increased SAA in vitro (THP-1, pEC(50) 43 nM). To determine its direct actions, SAA was administered into murine lung, leading to induction of CXC chemokine ligand 1/2 and a neutrophilic response that was inhibited by 15-epi-LXA(4) but not dexamethasone. Taken together, these findings identify SAA as a therapeutic target for inhibition and implicate SAA as a mediator of GC-resistant lung inflammation that can overwhelm organ protective signaling by lipoxins at ALX/FPR2 receptors.

Respiratory effects of bioaerosols: exposure-response study among salmon-processing workers.

OBJECTIVES: The aim of the study was to determine exposure-response relationships in salmon-processing workers. METHODS: Cross-shift FEV1, acute respiratory symptoms, and exposure to total protein, parvalbumin and endotoxin were main variables measured during one workweek. Exposure-response relationships were analyzed by Generalized Estimation Equations of cross-week data and by multiple regressions of day-to-day data. RESULTS: Exposure levels were higher in those workers who reported use of water hose. GEE showed negative coefficients for interaction between TP exposure and time (days) on cross-week change of FEV1. Multiple regressions showed significant associations between TP levels and cross-shift change of FEV1 and symptoms (cough, chest tightness) only for Monday shifts. CONCLUSIONS: A tolerance effect during the course of a workweek is suggested. Use of water hose is a risk process with regard to the liberation of measured components of bioaerosols.

Comparison of personal exposure to black carbon levels with fixed-site monitoring data and with dispersion modelling and the influence of activity patterns and environment.

BACKGROUND: Short-term studies of health effects from ambient air pollution usually rely on fixed site monitoring data or spatio-temporal models for exposure characterization, but the relation to personal exposure is often not known. OBJECTIVE: We aimed to explore this relation for black carbon (BC) in central Stockholm. METHODS: Families (n = 46) with an infant, one parent working and one parent on parental leave, carried battery-operated BC instruments for 7 days. Routine BC monitoring data were obtained from rural background (RB) and urban background (UB) sites. Outdoor levels of BC at home and work were estimated in 24 h periods by dispersion modelling based on hourly real-time meteorological data, and statistical meteorological data representing annual mean conditions. Global radiation, air pressure, precipitation, temperature, and wind speed data were obtained from the UB station. All families lived in the city centre, within 4 km of the UB station. RESULTS: The average level of 24 h personal BC was 425 (s.d. 181) ng/m3 for parents on leave, and 394 (s.d. 143) ng/m3 for working parents. The corresponding fixed-site monitoring observations were 148 (s.d. 139) at RB and 317 (s.d. 149) ng/m3 at UB. Modelled BC levels at home and at work were 493 (s.d. 228) and 331 (s.d. 173) ng/m3, respectively. UB, RB and air pressure explained only 21% of personal 24 h BC variability for parents on leave and 25% for working parents. Modelled home BC and observed air pressure explained 23% of personal BC, and adding modelled BC at work increased the explanation to 34% for the working parents. IMPACT: Short-term studies of health effects from ambient air pollution usually rely on fixed site monitoring data or spatio-temporal models for exposure characterization, but the relation to actual personal exposure is often not known. In this study we showed that both routine monitoring and modelled data explained less than 35% of variability in personal black carbon exposure. Hence, short-term health effects studies based on fixed site monitoring or spatio-temporal modelling are likely to be underpowered and subject to bias.

Asthma Is Associated With Increased Sickness Absence Among Young Adults.

BACKGROUND: There is limited knowledge about how asthma affects sickness absence in young adulthood. OBJECTIVE: To examine how asthma and different asthma phenotypes affect sickness absence among young adults and potential modifying factors. A secondary aim was to estimate productivity losses related to sickness absence for asthma. METHODS: The study included 2391 participants from the Swedish population-based cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology). Information on asthma, asthma phenotypes, and lifestyle factors was collected from questionnaires and clinical examinations at age approximately 24 years (2016-2019). Information on sickness absence for longer than 14 days was obtained from a national register for the years 2020 and 2021. Associations between asthma, asthma phenotypes, and sickness absence were analyzed with logistic regression models adjusted for sex, birth year, education, and overweight status. RESULTS: At age 24 years, 272 (11.4%) fulfilled the definition of asthma. Sickness absence was more common among those with asthma than among those without (15.1% vs 8.7%; P = .001; adjusted odds ratio 1.73; 95% CI, 1.19-2.51). Analyses of asthma phenotypes showed that the association tended to be stronger for persistent asthma, uncontrolled asthma, and asthma in combination with rhinitis; no consistent differences were observed across phenotypes related to allergic sensitization or inflammation. The association tended to be stronger among those with overweight than among those with normal weight. Asthma, especially uncontrolled asthma, was associated with higher productivity losses from sickness absence. CONCLUSIONS: Asthma may be associated with higher sickness absence and productivity losses. Achieving better asthma control and reducing allergic symptoms may reduce sickness absence among individuals with asthma.

Improved Air Quality and Asthma Incidence from School-Age to Young Adulthood: A Population-based Prospective Cohort Study.

Background The benefits of improved air quality on asthma remain understudied. Therefore, our aim was to investigate associations of changes in ambient air pollution with incident asthma from school-age until young adulthood in an area with mostly low air pollution levels. Methods Participants in the BAMSE birth cohort from Stockholm without asthma before the 8-year follow-up were included (N=2371). We estimated the association of change in individual-level air pollutant exposure (particulate matter with diameter ⩽2.5 µm (PM2.5) and, ⩽10 µm (PM10), black carbon (BC) and nitrogen oxides (NOx)) from the first year of life to the 8-year follow-up with asthma incidence from the 8-year until the 24-year follow-up. Multi-pollutant trajectories were identified using Group-Based Multivariate Trajectory model. We also used parametric g-computation to quantify the asthma incidence under different hypothetical interventions regarding air pollution levels. Results Air pollution levels at residency decreased during the period, with median reductions of 5.6% for PM2.5, 3.1% for PM10, 5.9% for BC, and 26.8% for NOx. A total of 395 incident asthma cases were identified from the 8-year until the 24-year follow-up. The odds ratio for asthma was 0.89 (95%CI: 0.80, 0.99) for each interquartile range reduction in PM2.5 (equal to 8.1% reduction). Associations appeared less clear for PM10, BC and NOx. Five multi-pollutant trajectories were identified, where the largest reduction trajectory displayed the lowest odds of asthma (OR=0.55, 95%CI: 0.31, 0.98) compared with the least reduction trajectory. If the PM2.5 exposure had not declined up to the 8-year follow-up, the hypothetical asthma incidence was estimated to have been 10.9% higher (95%CI: 0.8%, 20.8%). Conclusions Decrease in PM2.5 levels during childhood was associated with lower risk of incident asthma from school-age to young adulthood in an area with relatively low air pollution levels, suggesting broad respiratory health benefits from improved air quality. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Cat and house dust mite allergen content is stable in frozen dust over time.

BACKGROUND: Dust from indoor environments consists of animal allergens, pollen, endotoxins, and other substances which may exacerbate symptoms in sensitive individuals. In prospective cohort studies, dust is often collected from indoor environments in order to assess allergen exposure and possible relationships to health outcomes. Typically, large numbers of samples are collected and kept frozen until further analysis, sometimes several years later. To date, there is insufficient knowledge about what happens to the dust and its contents during storage. OBJECTIVES: In the present study, our aim was to analyze allergen content over a 30 month period frozen dust collected from beds in homes in order to simulate a study design of exposure assessment commonly used in epidemiological studies. METHODS: Thirty-seven dust samples from mattresses in homes were collected using a Duststream dust collector. Each dust sample was subdivided into six aliquots. One tube (baseline) was extracted and analyzed for cat and house dust mite (HDM) allergen content using ELISA, all other tubes were stored at -80 °C until further handling. Approximately every six months (6, 12, 18, and 30 months), dust from one tube was thawed, extracted and analyzed the same way. Data was log-transformed and analyzed using linear regression. RESULTS: No trend for decreasing or increasing cat (p = 0.606) or HDM (p = 0.928) allergen levels could be observed over time. Levels of cat allergen were considerably higher in mattresses from homes with cats compared to homes without cats (p < 0.001). CONCLUSION: It is important to assess the allergen stability in dust before designing costly and labor-intensive studies of allergen exposure and health outcomes, commonly used in environmental epidemiology. Although the present study showed that cat and HDM allergens remained stable in dust stored at -80 °C during a 2.5 year period, analyses of other allergens or substances in frozen dust and evaluating the effect of longer storage times is desirable.

Direct and indirect exposure to horse: risk for sensitization and asthma.

Most studies on the sensitization to horse allergens in populations without professional exposure have been carried out in geographical areas where the rate of horse ownership is high and horse riding is popular. Very few studies have been carried out in populations living in large urban areas. This gap in the literature probably reflects the widespread view that prevalence of horse-related allergy is low in urban populations because the latter are not regularly exposed to horses. On the contrary, we suggest that urban areas constitute a model useful to study potential modalities of exposure and sensitization to horse allergen by other routes of exposure than horse-riding. In this article, we describe the risks related to various modalities of exposure to horse allergen, clinical aspects of airway sensitization to horse allergens in patients living in urban areas, and non-occupational exposure to horse allergen. In addition, we illuminate some aspects related to dispersion of horse allergens from sources such as stables to indoor environments.

Comparison of measured residential black carbon levels outdoors and indoors with fixed-site monitoring data and with dispersion modelling.

Epidemiologic studies on health effects of air pollution usually rely on time-series of ambient monitoring data or on spatially modelled levels. Little is known how well these estimate residential outdoor and indoor levels. We investigated the agreement of measured residential black carbon (BC) levels outdoors and indoors with fixed-site monitoring data and with levels calculated using a Gaussian dispersion model. One-week residential outdoor and indoor BC measurements were conducted for 15 families living in central Stockholm. Time-series from urban background and street-level monitors were compared to these measurements. The observed weekly concentrations were also standardized to reflect annual averages, using urban background levels, and compared spatially to long-term levels as estimated by dispersion modelling. Weekly average outdoor BC level was 472 ng/m3 (range 261-797 ng/m3). The corresponding fixed-site urban background and street levels were 313 and 1039 ng/m3, respectively. Urban background variation explained 50% of the temporal variation in residential outdoor levels averaged over 24 h. Modelled residential long-term outdoor levels were on average comparable with the standardized measured home outdoor levels, and explained 49% of the spatial variability. The median indoor/outdoor ratio across all addresses was 0.79, with no difference between day and night time. Common exposure estimation approaches in the epidemiology of health effects related to BC displayed high validity for residencies in central Stockholm. Urban background monitored levels explained half of the outdoor day-to-day variability at residential addresses. Long-term dispersion modelling explained half of the spatial differences in outdoor levels. Indoor BC concentrations tended to be somewhat lower than outdoor levels.

Personal exposure to black carbon in Stockholm, using different intra-urban transport modes.

The traffic microenvironment has been shown to be a major contributor to the total personal exposure of black carbon (BC), and is key to local actions aiming at reducing health risks associated with such exposure. The main aim of the study was to get a better understanding of the determinants of traffic-related personal exposure to BC in an urban environment. Personal exposure to ambient levels of BC was monitored while walking, cycling and traveling by bus or car along four streets and while cycling alternative routes simultaneously. Monitoring was performed during morning and afternoon peak hours and at midday, with a portable aethalometer recording one-minute mean values. In all, >4000 unique travel passages were performed. Stepwise Linear Regression was used to assess predictors to personal exposure levels of BC. The personal BC concentration ranged 0.03-37 µg/m3. The average concentrations were lowest while walking (1.7 µg/m3) and highest traveling by bus (2.7 µg/m3). However, only 22% of the variability could be explained by travel mode, urban background BC and wind speed. BC concentrations measured inside a car were on average 33% lower than measured simultaneously outside the car. Choosing an alternative bicycle route with less traffic resulted in up to 1.4 µg/m3 lower personal exposure concentrations. In conclusion, traveling by bus rendered the highest personal BC concentrations. But when taking travel time and inhalation rate into account, the travel-related exposure dose was predicted to be highest during walking and cycling. It is however probable that the benefits from physical activity outweigh health risks associated with this higher exposure dose. It is clear that road traffic makes an important contribution to personal exposure to BC regardless of mode of intra-urban transport. Our data suggest that commuting along routes with lower BC levels would substantially decrease commuter's exposure.

Ten Lessons for Good Practice for the INHERIT Triple Win: Health, Equity, and Environmental Sustainability.

The world's challenges of climate change, damage to ecosystems, and social and health inequalities require changes in human behaviours at every level of organisation, among governments, business, communities, and individuals. An important question is how behaviour change can be enabled and supported at the scale and speed required. The research reported in this paper describes important lessons for good practice in changing contexts to modify behaviours for a triple win for health, equity and environmental sustainability. Authors synthesised learning from qualitative, quantitative and cost benefit evaluations of 15 case studies conducted in 12 countries in Europe. The case studies address ways of living (green spaces and energy efficient housing), moving (active transport) and consuming (healthy and sustainable diets) that support the triple win. Ten lessons for good practice were identified. These include bringing a triple win mindset to policy and practice in planning interventions, with potential to improve environmental sustainability, health and equity at the same time. The lessons for good practice are intended to support governmental and non-governmental actors, practitioners and researchers planning to work across sectors to achieve mutual benefits for health and environmental sustainability and in particular to benefit poorer and more socio-economically disadvantaged groups.

Spatial variation of PM elemental composition between and within 20 European study areas--Results of the ESCAPE project.

An increasing number of epidemiological studies suggest that adverse health effects of air pollution may be related to particulate matter (PM) composition, particularly trace metals. However, we lack comprehensive data on the spatial distribution of these elements. We measured PM2.5 and PM10 in twenty study areas across Europe in three seasonal two-week periods over a year using Harvard impactors and standardized protocols. In each area, we selected street (ST), urban (UB) and regional background (RB) sites (totaling 20) to characterize local spatial variability. Elemental composition was determined by energy-dispersive X-ray fluorescence analysis of all PM2.5 and PM10 filters. We selected a priori eight (Cu, Fe, K, Ni, S, Si, V, Zn) well-detected elements of health interest, which also roughly represented different sources including traffic, industry, ports, and wood burning. PM elemental composition varied greatly across Europe, indicating different regional influences. Average street to urban background ratios ranged from 0.90 (V) to 1.60 (Cu) for PM2.5 and from 0.93 (V) to 2.28 (Cu) for PM10. Our selected PM elements were variably correlated with the main pollutants (PM2.5, PM10, PM2.5 absorbance, NO2 and NOx) across Europe: in general, Cu and Fe in all size fractions were highly correlated (Pearson correlations above 0.75); Si and Zn in the coarse fractions were modestly correlated (between 0.5 and 0.75); and the remaining elements in the various size fractions had lower correlations (around 0.5 or below). This variability in correlation demonstrated the distinctly different spatial distributions of most of the elements. Variability of PM10_Cu and Fe was mostly due to within-study area differences (67% and 64% of overall variance, respectively) versus between-study area and exceeded that of most other traffic-related pollutants, including NO2 and soot, signaling the importance of non-tailpipe (e.g., brake wear) emissions in PM.

Determinants of personal exposure to some carcinogenic substances and nitrogen dioxide among the general population in five Swedish cities.

Environmental levels of airborne carcinogenic and related substances are comparatively better known than individual exposure and its determinants. We report on a personal monitoring program involving five Swedish urban populations. The aim of the program was to investigate personal exposure to benzene, 1,3-butadiene, formaldehyde, and nitrogen dioxide (NO2). The measurements were performed among 40 inhabitants during seven consecutive days, in one urban area each year, during 2000-2008. The estimated population exposure levels were 1.95 µg/m(3) for benzene, 0.56 µg/m(3) for 1,3-butadiene, 19.4 µg/m(3) for formaldehyde, and 14.1 µg/m(3) for NO2. Statistical analysis using a mixed-effects model revealed that time spent in traffic and time outdoors contributed to benzene and 1,3- butadiene exposure. For benzene, refueling a car was an additional determinant influencing the exposure level. Smoking or environmental tobacco smoke were significant determinants of exposure to NO2, benzene, and 1,3-butadiene. Those with a gas stove had higher NO2 exposure. Living in a single-family house increased the exposure to formaldehyde significantly. In a variance component model, the between-subject variance dominated for 1,3-butadiene and formaldehyde, whereas the between-city variance dominated for NO2. For benzene, the between-subject and between-cities variances were similar.

Measurement of Horse Allergen (Equ cx) in Schools.

Background. The presence of horse allergen in public places is not well-known, unlike for instance cat and dog allergens, which have been studied extensively. The aim was to investigate the presence of horse allergen in schools and to what extent the influence of number of children with regular horse contact have on indoor allergen levels. Methods. Petri dishes were used to collect airborne dust samples during one week in classrooms. In some cases, vacuumed dust samples were also collected. All samples were extracted, frozen and analysed for Equ cx content shortly after sampling, and some were re-analysed six years later with a more sensitive ELISA assay. Results. Horse allergen levels were significantly higher in classrooms, in which many children had horse contact, regardless of sampling method. Allergen levels in extracts from Petri dish samples, which had been kept frozen, dropped about 53% over a six-year period. Conclusion. Horse allergen was present in classrooms and levels were higher in classrooms where many children had regular horse contact in their leisure time. This suggests that transfer of allergens takes place via contaminated clothing. Measures should be taken to minimize possible transfer and deposition of allergens in pet-free environments, such as schools.