Jon Ayres

Short-term effects of particulate air pollution on cardiovascular diseases in eight European cities

Study objective: As part of the APHEA project this study examined the association between airborne particles and hospital admissions for cardiac causes (ICD9 390–429) in eight European cities (Barcelona, Birmingham, London, Milan, the Netherlands, Paris, Rome, and Stockholm). All admissions were studied, as well as admissions stratified by age. The association for ischaemic heart disease (ICD9 410–413) and stroke (ICD9 430–438) was also studied, also stratified by age. Design: Autoregressive Poisson models were used that controlled for long term trend, season, influenza epidemics, and meteorology to assess the short-term effects of particles in each city. The study also examined confounding by other pollutants. City specific results were pooled in a second stage regression to obtain more stable estimates and examine the sources of heterogeneity. Main results: The pooled percentage increases associated with a 10 μg/m3 increase in PM10 and black smoke were respectively 0.5% (95% CI: 0.2 to 0.8) and 1.1% (95% CI: 0.4 to 1.8) for cardiac admissions of all ages, 0.7% (95% CI: 0.4 to 1.0) and 1.3% (95% CI: 0.4 to 2.2) for cardiac admissions over 65 years, and, 0.8% (95% CI: 0.3 to 1.2) and 1.1% (95% CI: 0.7 to 1.5) for ischaemic heart disease over 65 years. The effect of PM10 was little changed by control for ozone or SO2, but was substantially reduced (CO) or eliminated (NO2) by control for other traffic related pollutants. The effect of black smoke remained practically unchanged controlling for CO and only somewhat reduced controlling for NO2. Conclusions: These effects of particulate air pollution on cardiac admissions suggest the primary effect is likely to be mainly attributable to diesel exhaust. Results for ischaemic heart disease below 65 years and for stroke over 65 years were inconclusive.

Evaluating the Toxicity of Airborne Particulate Matter and Nanoparticles by Measuring Oxidative Stress Potential—A Workshop Report and Consensus Statement

Background: There is a strong need for laboratory in vitro test systems for the toxicity of airborne particulate matter and nanoparticles. The measurement of oxidative stress potential offers a promising way forward. Objectives:Aworkshop was convened involving leading workers from the field in order to review the available test methods and to generate a Consensus Statement. Discussions: Workshop participants summarised their own research activities as well as discussion the relative merits of different test methods. Conclusions: In vitro test methods have an important role to play in the screening of toxicity in airborne particulate matter and nanoparticles. In vitro cell challenges were preferable to in vitro acellular systems but both have a potential major role to play and offer large cost advantages relative to human or animal inhalation studies and animal in vivo installation experiments. There remains a need to compare tests one with another on standardised samples and also to establish a correlation with the results of population-based epidemiology.

Effect of domestic concentrations of nitrogen dioxide on airway responses to inhaled allergen in asthmatic patients

Nitrogen dioxide is a common indoor pollutant. In the light of suggestions that outdoor air pollution can harm people with asthma, we investigated the effect of 1 h exposures to domestic concentrations of nitrogen dioxide on the airway response to house-dust mite (HDM) allergen in ten patients with mild asthma. Each subject breathed air, 100 ppb nitrogen dioxide, or 400 ppb nitrogen dioxide for 1 h, in double-blind, random order, then immediately underwent a fixed-dose HDM challenge. Baseline forced expiratory volume in 1 s (FEV1) was not affected by any of the gas mixtures. The mean early asthmatic response (maximum percentage change in FEV1 during first 2 h after challenge) was -14.62% (SD 8.03) after air, -14.41% (7.86) after 100 ppb nitrogen dioxide, and -18.64% (7.28) after 400 ppb nitrogen dioxide. The difference between air and 400 ppb (-4.01%) was significant (95% CI -1.34 to -6.69%, p < 0.009), but those between air and 100 ppb and between 100 and 400 ppb were not (0.21 [-3.10 to 3.53]% and -4.23 [-8.75 to 0.29]%). The mean late asthmatic response (maximum percentage change in FEV1) to challenge after air was -2.85% (3.95), after 100 ppb nitrogen dioxide -7.76% (6.92), and after 400 ppb -8.13% (6.64). The difference in means between the air and 400 ppb exposures was significant (-5.28 [-0.73 to -9.83]%, p < 0.02) but those between air and 100 ppb (-4.90 [-10.60 to 0.78]%) and 100 and 400 ppb (0.37 [3.06 to 3.80]%) were not. These findings suggest that nitrogen dioxide, at concentrations encountered in the home environment, can potentiate the specific airway response of patients with mild asthma to inhaled HDM allergen, although the effect is small.

Short term variations in hospital admissions and mortality and particulate air pollution.

OBJECTIVES: To determine the presence and magnitude of any relation between short term variations in ambient concentrations of particulate matter under 10 microns in diameter (PM10) and hospital admissions and mortality in Birmingham, United Kingdom. To find the relative risk associated with various concentrations of PM10, and to estimate the potential public health benefit of reducing PM10 to below various thresholds. METHODS: Retrospective ecological study. Air pollution data were taken from a national network monitoring station between 1 April 1992 and 31 March 1994, and weather data for the same period from the University of Birmingham Weather Service. Daily total hospital admissions for the same period for asthma, bronchitis, pneumonia, chronic obstructive pulmonary disease (COPD), acute ischaemic heart disease, acute cerebrovascular disease, all respiratory conditions, and all circulatory conditions were obtained from the West Midlands Regional Health Authority, as well as daily total deaths from 1 April 1992 to 31 December 1994 for chronic obstructive pulmonary disease, pneumonia, all respiratory diseases, all circulatory diseases, and all causes. Multiple linear regression models were constructed after adjusting for confounding factors (day of week, month, linear trend, relative humidity, and temperature). Relative risk of admission at various thresholds of PM10 was calculated with the model, by comparing risk of admission over the threshold with mean risk of admission over the whole period. Potential public health benefits at various thresholds were calculated with the model to predict the number of admissions of deaths that could be saved if, on each day that the PM10 had exceeded that threshold, it had instead been kept at the threshold level. RESULTS: Significant associations were found between all respiratory admissions, cerebrovascular admissions, and bronchitis admissions and PM10 on the same day. Pneumonia, all respiratory admissions, and asthma admissions were significantly associated with the mean PM10 values for the past three days. Deaths from COPD, all circulatory deaths, and all causes mortality were significantly associated with PM10 24 hours previously, and COPD deaths also with PM10 on the same day. The effect of a 10 micrograms/m3 rise in PM10 was estimated to represent a 2.4% increase in respiratory admissions, a 2.1% increase in cerebrovascular admissions, and a 1.1% increase in all causes mortality. In a population of 1 million, this would represent 0.5 extra respiratory admissions and 0.3 extra deaths. The increase in relative risk was linear without evidence of a threshold. The impact of reducing PM10 to below 70 micrograms/m3 would be small, representing less than 0.1% of respiratory admissions and 0.2% all causes mortality. The impact would be greater at lower thresholds. CONCLUSION: Ambient outdoor concentrations of PM10 in the United Kingdom are significantly associated with several indicators of acute health effect. These associations are similar to and consistent with other studies. However, the estimated size of the public health effect is small, accounting for only a small proportion of hospital admissions and mortality over a two year period.

Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a common, progressive respiratory disease that causes great morbidity and mortality despite treatment. There is evidence for airway inflammation in COPD. Cilomilast is an orally active, potent, selective phosphodiesterase type 4 inhibitor, which in vitro can affect cells thought to be of clinical importance in COPD. Our aim was to assess the safety, efficacy, and dose response of cilomilast in the treatment of patients with this disease. METHODS We did a 6-week, randomised, dose-ranging study in 424 patients with COPD (forced expiratory volume in 1 s [FEV(1)] 46.8% of predicted, FEV(1)/forced vital capacity [FVC] 54.6%, and postsalbutamol reversibility 5.4%). We randomly assigned individuals at 60 European centres to receive cilomilast 5 (n=109), 10 (n=102), or 15 (n=107) mg twice daily, or placebo (n=106). The main outcome measure was trough FEV(1) before and after use of a bronchodilator. Analyses were by intention to treat. FINDINGS Cilomilast 15 mg twice daily significantly improved FEV(1) compared with placebo (mean 130 mL vs -30 mL [95% CI 90-240] at week 6, p<0.0001). FVC and peak expiratory flow were also improved (p=0.001 and p<0.0001, respectively). Quality of life measures did not differ significantly between the groups. There were no significant differences in serious adverse events between the groups. INTERPRETATION Cilomilast 15 mg twice daily might be an effective maintenance treatment for COPD. Further clinical studies are underway.

Epidemiology of pneumothorax in England

BACKGROUND Little is known of the epidemiology of pneumothorax. Routinely available data on pneumothorax in England are described. METHODS Patients consulting in primary care with a diagnosis of pneumothorax in each year from 1991 to 1995 inclusive were identified from the General Practice Research Database (GPRD). Emergency hospital admissions for pneumothorax were identified for the years 1991–4 from the Hospital Episode Statistics (HES) data. Mortality data for England & Wales were obtained for 1950–97. Analyses of pneumothorax rates by age and sex were performed for all data sources. Seasonal and geographical analyses were carried out for the HES data. RESULTS The overall person consulting rate for pneumothorax (primary and secondary combined) in the GPRD was 24.0/100 000 each year for men and 9.8/100 000 each year for women. Hospital admissions for pneumothorax as a primary diagnosis occurred at an overall incidence of 16.7/100 000 per year and 5.8/100 000 per year for men and women, respectively. Mortality rates were 1.26/million per year for men and 0.62/million per year for women. The age distribution in both men and women showed a biphasic distribution for both GP consultations and hospital admissions. Deaths showed a single peak with highest rates in the elderly. There was an urban-rural trend observed for hospital admissions in the older age group (55+ years) with admission rates in the conurbations significantly higher than in the rural areas. Analysis for trends in mortality data for 1950–97 showed a striking increase in the death rate for pneumothorax in those aged 55+ years between 1960 and 1990, with a steep decline in the 1990s. Mortality in the younger age group (15–34 years) remained low and constant. CONCLUSION There is evidence of two epidemiologically distinct forms of spontaneous pneumothorax in England. The explanation for the rise and fall in mortality for secondary pneumothorax is obscure.

Leukotriene Antagonists as First-Line or Add-on Asthma-Controller Therapy

BACKGROUND Most randomized trials of treatment for asthma study highly selected patients under idealized conditions. METHODS We conducted two parallel, multicenter, pragmatic trials to evaluate the real-world effectiveness of a leukotriene-receptor antagonist (LTRA) as compared with either an inhaled glucocorticoid for first-line asthma-controller therapy or a long-acting beta(2)-agonist (LABA) as add-on therapy in patients already receiving inhaled glucocorticoid therapy. Eligible primary care patients 12 to 80 years of age had impaired asthma-related quality of life (Mini Asthma Quality of Life Questionnaire [MiniAQLQ] score ≤6) or inadequate asthma control (Asthma Control Questionnaire [ACQ] score ≥1). We randomly assigned patients to 2 years of open-label therapy, under the care of their usual physician, with LTRA (148 patients) or an inhaled glucocorticoid (158 patients) in the first-line controller therapy trial and LTRA (170 patients) or LABA (182 patients) added to an inhaled glucocorticoid in the add-on therapy trial. RESULTS Mean MiniAQLQ scores increased by 0.8 to 1.0 point over a period of 2 years in both trials. At 2 months, differences in the MiniAQLQ scores between the two treatment groups met our definition of equivalence (95% confidence interval [CI] for an adjusted mean difference, -0.3 to 0.3). At 2 years, mean MiniAQLQ scores approached equivalence, with an adjusted mean difference between treatment groups of -0.11 (95% CI, -0.35 to 0.13) in the first-line controller therapy trial and of -0.11 (95% CI, -0.32 to 0.11) in the add-on therapy trial. Exacerbation rates and ACQ scores did not differ significantly between the two groups. CONCLUSIONS Study results at 2 months suggest that LTRA was equivalent to an inhaled glucocorticoid as first-line controller therapy and to LABA as add-on therapy for diverse primary care patients. Equivalence was not proved at 2 years. The interpretation of results of pragmatic research may be limited by the crossover between treatment groups and lack of a placebo group. (Funded by the National Coordinating Centre for Health Technology Assessment U.K. and others; Controlled Clinical Trials number, ISRCTN99132811.).

Secondhand smoke levels in Scottish pubs: the effect of smoke-free legislation

Objective: To compare levels of particulate matter, as a marker of secondhand smoke (SHS) levels, in pubs before and 2 months after the implementation of Scottish legislation to prohibit smoking in substantially enclosed public places. Design: Comparison of SHS levels before and after the legislation in a random selection of 41 pubs in 2 Scottish cities. Methods: Fine particulate matter <2.5 μm in diameter (PM2.5) was measured discreetly for 30 min in each bar on 1 or 2 visits in the 8 weeks preceding the starting date of the Smoking, Health and Social Care (Scotland) Act 2005 and then again 2 months after the ban. Repeat visits were undertaken on the same day of the week and at approximately the same time of the day. Results: PM2.5 levels before the introduction of the legislation averaged 246 μg/m3 (range 8–902 μg/m3). The average level reduced to 20 μg/m3 (range 6–104 μg/m3) in the period after the ban. Levels of SHS were reduced in all 53 post-ban visits, with the average reduction being 86% (range 12–99%). PM2.5 concentrations in most pubs post-ban were comparable to the outside ambient air PM2.5 level. Conclusions: This study has produced the largest dataset of pre- and post-ban SHS levels in pubs of all worldwide smoke-free legislations introduced to date. Our results show that compliance with the Smoking, Health and Social Care (Scotland) Act 2005 has been high and this has led to a marked reduction in SHS concentrations in Scottish pubs, thereby reducing both the occupational exposure of workers in the hospitality sector and that of non-smoking patrons.

The association of daily sulfur dioxide air pollution levels with hospital admissions for cardiovascular diseases in Europe (The Aphea-II study)

The objective of this study is to assess the short-term effect of sulfur dioxide (SO(2)) air pollution levels on hospital admissions for cardiovascular diseases. Daily mean hospital admissions for cardiovascular diseases, ischemic heart diseases (IHDs), and stroke in seven European areas (the cities of Birmingham, London, Milan, Paris, Rome, and Stockholm, and in The Netherlands) participating in the multicenter European study of air pollution (Aphea-II), were measured. Time series analysis of daily hospital admission counts was performed using poison autoregressive models. A summary regression coefficient for all cities was provided. Daily numbers of all cardiovascular admissions except stroke, and particularly IHDs, rose significantly with an increase of daily SO(2)levels of the same day and day before. After adjusting for PM(10)(i.e. particles with size <10 microm), the association of SO(2)with IHD admissions remained significant (i.e. an increase of 0.7%; 95% confidence interval=0.1-1.3, per each 10 microg/m(3)increase of SO(2)) among subjects younger than 65 years, but not among subjects older than 65. In the older group the increase was only significant for particles (1.3%; CI 0.7-1.8, per each increase in 10 microg/m(3)of PM(10)). This study provides new evidence for the effects of urban air pollution on cardiac diseases in Europe, and suggests that SO(2)pollution may play an independent role in triggering ischemic cardiac events. From a Public Health perspective these results suggest that reduction in SO(2)levels in European cities could imply a reduction of admissions for IHDs.

Particulate air pollution and panel studies in children: a systematic review

Background: Panel studies have been used to investigate the short term effects of outdoor particulate air pollution across a wide range of environmental settings. Aims: To systematically review the results of such studies in children, estimate summary measures of effect, and investigate potential sources of heterogeneity. Methods: Studies were identified by searching electronic databases to June 2002, including those where outcomes and particulate level measurements were made at least daily for ⩾8 weeks, and analysed using an appropriate regression model. Study results were compared using forest plots, and fixed and random effects summary effect estimates obtained. Publication bias was considered using a funnel plot. Results: Twenty two studies were identified, all except two reporting PM10 (24 hour mean) >50 μg.m−3. Reported effects of PM10 on PEF were widely spread and smaller than those for PM2.5 (fixed effects summary: −0.012 v −0.063 l.min−1 per μg.m−3 rise). A similar pattern was evident for symptoms. Random effects models produced larger estimates. Overall, in between-study comparisons, panels of children with diagnosed asthma or pre-existing respiratory symptoms appeared less affected by PM10 levels than those without, and effect estimates were larger where studies were conducted in higher ozone conditions. Larger PM10 effect estimates were obtained from studies using generalised estimating equations to model autocorrelation and where results were derived by pooling subject specific regression coefficients. A funnel plot of PM10 results for PEF was markedly asymmetrical. Conclusions: The majority of identified studies indicate an adverse effect of particulate air pollution that is greater for PM2.5 than PM10. However, results show considerable heterogeneity and there is evidence consistent with publication bias, so limited confidence may be placed on summary estimates of effect. The possibility of interaction between particle and ozone effects merits further investigation, as does variability due to analytical differences that alter the interpretation of final estimates.