Raymond Agius

Particulate air pollution and the blood

BACKGROUND Particulate air pollution has been associated with excess deaths from, and increases in hospital admissions for, cardiovascular disease among older people. A study was undertaken to determine whether this may be a consequence of alterations in the blood, secondary to pulmonary inflammation caused by the action of fine particles on alveolar cells, by repeatedly measuring haematological factors in older people and relating them to measurements of exposure to airborne particles. METHODS One hundred and twelve individuals aged 60+ years in two UK cities provided repeated blood samples over 18 months, 108 providing the maximum of 12 samples. Estimates of individual exposure to particles of less than 10 μm diameter (PM10), derived from a mathematical model based on activity diaries and comparative measurements of PM10 at multiple sites and during a variety of activities, were made for each three day period prior to blood sampling. The relationships between blood values and estimates of both personal exposure and city centre measurements of PM10 were investigated by analysis of covariance, adjusting for city, season, temperature, and repeated individual measurements. RESULTS Estimated personal exposure to PM10 over the previous three days showed negative correlations with haemoglobin concentration, packed cell volume (PCV), and red blood cell count (p<0.001), and with platelets and factor VII levels (p<0.05). The changes in red cell indices persisted after adjustment for plasma albumin in a sample of 60 of the subjects. City centre PM10 measurements over three days also showed negative correlations with haemoglobin and red cell count (p<0.001) and with PCV and fibrinogen (p<0.05), the relationship with haemoglobin persisting after adjustment for albumin. C reactive protein levels showed a positive association with city centre measurements of PM10 (p<0.01). Based on a linear relationship, the estimated change in haemoglobin associated with an alteration in particle concentration of 100 μg/m3 is estimated to have been 0.44 g/dl (95% CI 0.62 to 0.26) for personal PM10 and 0.73 g/dl (95% CI 1.11 to 0.36) for city centre PM10 measurements. CONCLUSIONS This investigation is the first to estimate personal exposures to PM10 and to demonstrate associations between haematological indices and air pollution. The changes in haemoglobin adjusted for albumin suggest that inhalation of some component of PM10may cause sequestration of red cells in the circulation. We propose that an action of such particles either on lung endothelial cells or on erythrocytes themselves may be responsible for changing red cell adhesiveness. Peripheral sequestration of red cells offers an explanation for the observed cardiovascular effects of particulate air pollution.

Air Pollution Exposure and Lung Function in Children: The ESCAPE Project.

Background: There is evidence for adverse effects of outdoor air pollution on lung function of children. Quantitative summaries of the effects of air pollution on lung function, however, are lacking due to large differences among studies. Objectives: We aimed to study the association between residential exposure to air pollution and lung function in five European birth cohorts with a standardized exposure assessment following a common protocol. Methods: As part of the European Study of Cohorts for Air Pollution Effects (ESCAPE) we analyzed data from birth cohort studies situated in Germany, Sweden, the Netherlands, and the United Kingdom that measured lung function at 6–8 years of age (n = 5,921). Annual average exposure to air pollution [nitrogen oxides (NO2, NOx), mass concentrations of particulate matter with diameters < 2.5, < 10, and 2.5–10 μm (PM2.5, PM10, and PMcoarse), and PM2.5 absorbance] at the birth address and current address was estimated by land-use regression models. Associations of lung function with estimated air pollution levels and traffic indicators were estimated for each cohort using linear regression analysis, and then combined by random effects meta-analysis. Results: Estimated levels of NO2, NOx, PM2.5 absorbance, and PM2.5 at the current address, but not at the birth address, were associated with small decreases in lung function. For example, changes in forced expiratory volume in 1 sec (FEV1) ranged from –0.86% (95% CI: –1.48, –0.24%) for a 20-μg/m3 increase in NOx to –1.77% (95% CI: –3.34, –0.18%) for a 5-μg/m3 increase in PM2.5. Conclusions: Exposure to air pollution may result in reduced lung function in schoolchildren. Citation: Gehring U, Gruzieva O, Agius RM, Beelen R, Custovic A, Cyrys J, Eeftens M, Flexeder C, Fuertes E, Heinrich J, Hoffmann B, de Jongste JC, Kerkhof M, Klümper C, Korek M, Mölter A, Schultz ES, Simpson A, Sugiri D, Svartengren M, von Berg A, Wijga AH, Pershagen G, Brunekreef B. 2013. Air pollution exposure and lung function in children: the ESCAPE project. Environ Health Perspect 121:1357–1364; http://dx.doi.org/10.1289/ehp.1306770

Relationship between chemical structure and the occupational asthma hazard of low molecular weight organic compounds

Aims: To investigate quantitatively, relationships between chemical structure and reported occupational asthma hazard for low molecular weight (LMW) organic compounds; to develop and validate a model linking asthma hazard with chemical substructure; and to generate mechanistic hypotheses that might explain the relationships. Methods: A learning dataset used 78 LMW chemical asthmagens reported in the literature before 1995, and 301 control compounds with recognised occupational exposures and hazards other than respiratory sensitisation. The chemical structures of the asthmagens and control compounds were characterised by the presence of chemical substructure fragments. Odds ratios were calculated for these fragments to determine which were associated with a likelihood of being reported as an occupational asthmagen. Logistic regression modelling was used to identify the independent contribution of these substructures. A post-1995 set of 21 asthmagens and 77 controls were selected to externally validate the model. Results: Nitrogen or oxygen containing functional groups such as isocyanate, amine, acid anhydride, and carbonyl were associated with an occupational asthma hazard, particularly when the functional group was present twice or more in the same molecule. A logistic regression model using only statistically significant independent variables for occupational asthma hazard correctly assigned 90% of the model development set. The external validation showed a sensitivity of 86% and specificity of 99%. Conclusions: Although a wide variety of chemical structures are associated with occupational asthma, bifunctional reactivity is strongly associated with occupational asthma hazard across a range of chemical substructures. This suggests that chemical cross-linking is an important molecular mechanism leading to the development of occupational asthma. The logistic regression model is freely available on the internet and may offer a useful but inexpensive adjunct to the prediction of occupational asthma hazard.

Urban air pollution and cardiopulmonary ill health : a 14.5 year time series study

OBJECTIVES: To examine possible associations between daily concentrations of urban air pollutants and hospital emergency admissions and mortality due to cardiac and pulmonary disease. METHODS: A time series study was conducted in the City of Edinburgh, which has a population of about 450,000. Poisson log linear regression models were used to investigate the relation of the daily event rate with daily air pollution concentrations of sulphur dioxide (SO2) and black smoke from 1981 to 1995, and of nitrogen dioxide (NO2), ozone (O3), carbon monoxide (CO), and particulate matter (PM10) from 1992 to 1995. Adjustments were made for seasonal and weekday variation, daily temperature, and wind speed. RESULTS: The most significant findings were positive associations over the period 1981-95 between black smoke as a mean of the previous three days and daily all cause mortality in people aged > or = 65, and respiratory mortality also in this age group (3.9% increase in mortality for a 10 micrograms/m3 increment in black smoke). For hospital emergency admissions between 1992 and 1995 the two most significant findings (p < 0.05) were for cardiovascular admissions of people aged > or = 65 which showed a positive association with PM10 as a mean of the 3 previous days, and a negative association with O3 as a mean of the previous three days. Analyses of outcomes based on linkage with previous cardiorespiratory emergency admissions did not show substantially different results. CONCLUSION: These data suggest that in the City of Edinburgh, after correction for confounders, there was a small but significant association between concentrations of black smoke and respiratory mortality in the older age group, probably attributable to higher pollution levels in the early part of the study period. There were also generally weak and variable associations between day to day changes in concentrations of urban air pollutants at a single central point and emergency hospital admission rates from cardiac and respiratory disease.

The lagged effect of cold temperature and wind chill on cardiorespiratory mortality in Scotland

Aims: To investigate the lagged effects of cold temperature on cardiorespiratory mortality and to determine whether “wind chill” is a better predictor of these effects than “dry bulb” temperature. Methods: Generalised linear Poisson regression models were used to investigate the relation between mortality and “dry bulb” and “wind chill” temperatures in the three largest Scottish cities (Glasgow, Edinburgh, and Aberdeen) between January 1981 and December 2001. Effects of temperature on mortality (lags up to one month) were quantified. Analyses were conducted for the whole year and by season (cool and warm seasons). Main results: Temperature was a significant predictor of mortality with the strongest association observed between temperature and respiratory mortality. There was a non-linear association between mortality and temperature. Mortality increased as temperatures fell throughout the range, but the rate of increase was steeper at temperatures below 11°C. The association between temperature and mortality persisted at lag periods beyond two weeks but the effect size generally decreased with increasing lag. For temperatures below 11°C, a 1°C drop in the daytime mean temperature on any one day was associated with an increase in mortality of 2.9% (95% CI 2.5 to 3.4), 3.4% (95% CI 2.6 to 4.1), 4.8% (95% CI 3.5 to 6.2) and 1.7% (95% CI 1.0 to 2.4) over the following month for all cause, cardiovascular, respiratory, and “other” cause mortality respectively. The effect of temperature on mortality was not observed to be significantly modified by season. There was little indication that “wind chill” temperature was a better predictor of mortality than “dry bulb” temperature. Conclusions: Exposure to cold temperature is an important public health problem in Scotland, particularly for those dying from respiratory disease.

The mast cell as a primary effector cell in the pathogenesis of asthma

Holgate, S T Hardy, C Robinson, C Agius, R M Howarth, P H Review United states The Journal of allergy and clinical immunology J Allergy Clin Immunol. 1986 Feb;77(2):274-82.

Personality and stress in consultant psychiatrists

A randomly selected group of consultant psychiatrists (n = 39) working within the NHS in Scotland was compared with a combined group of physicians and surgeons (n = 149) on several variables related to the stress process, including personality traits, coping strategies, psychological distress, burnout, job stress and work demands. Psychiatrists reported fewer clinical work demands (p < .001), and their mean personality scores were significantly different from physicians and surgeons by being high in neuroticism (p = .009), openness (p = .003) and agreeableness (p = .002), and low in conscientiousness (p = .04). Psychiatrists reported higher work-related emotional exhaustion (p = .03) and severe depression (p = .02). However, psychiatrists did not report more work-related stress than physicians and surgeons. Many stress-related variables were highly correlated within the group of psychiatrists, suggesting that there is a very general disposition to experience negative emotion (including job-related stress) in some individuals. Organisational and personal contributions to stress in the practice of psychiatry are considered. There are personality characteristics that might dispose some people toward psychiatry as a career and toward stress. However, there is no evidence to suggest that screening for admission to psychiatry in terms of per sonality or other psychological factors would be useful or advisable.

Air Pollution and Respiratory Infections during Early Childhood: An Analysis of 10 European Birth Cohorts within the ESCAPE Project

Background: Few studies have investigated traffic-related air pollution as a risk factor for respiratory infections during early childhood. Objectives: We aimed to investigate the association between air pollution and pneumonia, croup, and otitis media in 10 European birth cohorts—BAMSE (Sweden), GASPII (Italy), GINIplus and LISAplus (Germany), MAAS (United Kingdom), PIAMA (the Netherlands), and four INMA cohorts (Spain)—and to derive combined effect estimates using meta-analysis. Methods: Parent report of physician-diagnosed pneumonia, otitis media, and croup during early childhood were assessed in relation to annual average pollutant levels [nitrogen dioxide (NO2), nitrogen oxide (NOx), particulate matter ≤ 2.5 μm (PM2.5), PM2.5 absorbance, PM10, PM2.5–10 (coarse PM)], which were estimated using land use regression models and assigned to children based on their residential address at birth. Identical protocols were used to develop regression models for each study area as part of the ESCAPE project. Logistic regression was used to calculate adjusted effect estimates for each study, and random-effects meta-analysis was used to calculate combined estimates. Results: For pneumonia, combined adjusted odds ratios (ORs) were elevated and statistically significant for all pollutants except PM2.5 (e.g., OR = 1.30; 95% CI: 1.02, 1.65 per 10-μg/m3 increase in NO2 and OR = 1.76; 95% CI: 1.00, 3.09 per 10-μg/m3 PM10). For otitis media and croup, results were generally null across all analyses except for NO2 and otitis media (OR = 1.09; 95% CI: 1.02, 1.16 per 10-μg/m3). Conclusion: Our meta-analysis of 10 European birth cohorts within the ESCAPE project found consistent evidence for an association between air pollution and pneumonia in early childhood, and some evidence for an association with otitis media. Citation: MacIntyre EA, Gehring U, Mölter A, Fuertes E, Klümper C, Krämer U, Quass U, Hoffmann B, Gascon M, Brunekreef B, Koppelman GH, Beelen R, Hoek G, Birk M, de Jongste JC, Smit HA, Cyrys J, Gruzieva O, Korek M, Bergström A, Agius RM, de Vocht F, Simpson A, Porta D, Forastiere F, Badaloni C, Cesaroni G, Esplugues A, Fernández-Somoano A, Lerxundi A, Sunyer J, Cirach M, Nieuwenhuijsen MJ, Pershagen G, Heinrich J. 2014. Air pollution and respiratory infections during early childhood: an analysis of 10 European birth cohorts within the ESCAPE project. Environ Health Perspect 122:107–113; http://dx.doi.org/10.1289/ehp.1306755

Relationship between Mediator Release from Human Lung Mast Cells in vitro and in vivo

There is now compelling evidence to incriminate bronchial mast cells in the pathogenesis of bronchoconstriction of allergic asthma. Human mast cells isolated from lung tissue or bronchoalveolar lavage release histamine and generate eicosanoids upon IgE-dependent activation. In this paper we present data that raise doubts about the significance of phospholipid methylation in IgE-dependent activation-secretion coupling and provide evidence that drugs such as 3-deazaadenosine inhibit mediator secretion by inhibiting phosphodiesterase, in addition to inhibiting putative methylation pathways. Activation of human mast cells and basophils also stimulates adenylate cyclase to increase levels of cyclic AMP, which, on the basis of pharmacological manipulation with purine nucleosides, we believe is involved in the progression of the secretory response. Human lung cells also generate both cyclo- and lipoxygenase products of arachidonate upon Ca++-dependent stimulation with complex interactions occurring between these pathways in the presence of the leukotriene inhibitor, Piriprost. The role of mast cells in the immediate airway response to inhaled allergens in asthma was demonstrated by showing an interaction between nonspecific bronchial reactivity and mast cell reactivity in predicting the airway response upon antigen inhalation. Further confirmation of this concept was obtained by showing an inverse relationship between the release of histamine and neutrophil chemotactic factor (NCF) into the circulation induced by antigen challenge, and nonspecific airway reactivity. The identification of significant increases in circulating mediators following antigen provocation of patients with seasonal asthma enabled the effects of drugs used in the treatment of asthma to be compared on airway calibre and mast cell mediator release. Sodium cromoglycate partially inhibited the airway and plasma histamine responses with antigen, but totally inhibited the increases in NCF. Salbutamol completely inhibited all responses, while ipratropium bromide, which produced the same bronchoconstriction as achieved with salbutamol, had no effect. The potent H1-antagonist astemizole partially inhibited bronchoconstriction without affecting histamine release. Antigen provocation produced a significant increase in circulating levels of the 13,14-dihydro-15-keto metabolite of PGF2 alpha which could originate from mast cell-derived PGD2. In both retrospective and prospective studies, a close relationship was shown between nonspecific bronchial reactivity and resting airway calibre in asthma.(ABSTRACT TRUNCATED AT 400 WORDS)

Work-related asthma in France: recent trends for the period 2001–2009

Objective Knowledge on the time-course (trends) of work-related asthma (WRA) remains sparse. The aim of this study was to describe WRA trends in terms of industrial activities and the main causal agents in France over the period 2001–2009. Method Data were collected from the French national network of occupational health surveillance and prevention (Réseau National de Vigilance et de Prévention des Pathologies Professionnelles (RNV3P)). Several statistical models (non-parametric test, zero-inflated negative binomial, logistic regression and time-series models) were used and compared with assess trends. Results Over the study period, 2914 WRA cases were included in the network. A significant decrease was observed overall and for some agents such as isocyanates (p=0.007), aldehydes (p=0.01) and latex (p=0.01). Conversely, a significant increase was observed for cases related to exposure to quaternary ammonium compounds (p=0.003). The health and social sector demonstrated both a growing number of cases related to the use of quaternary ammonium compounds and a decrease of cases related to aldehyde and latex exposure. Conclusions WRA declined in France over the study period. The only significant increase concerned WRA related to exposure to quaternary ammonium compounds. Zero-inflated negative binomial and logistic regression models appear to describe adequately these data.