Distinguishing the associations between daily mortality and hospital admissions and nitrogen dioxide from those of particulate matter: a systematic review and meta-analysis.

OBJECTIVES: To quantitatively assess time-series studies of daily nitrogen dioxide (NO2) and mortality and hospital admissions which also controlled for particulate matter (PM) to determine whether or to what extent the NO2 associations are independent of PM. DESIGN: A systematic review and meta-analysis. METHODS: Time-series studies-published in peer-reviewed journals worldwide, up to May 2011-that reported both single-pollutant and two-pollutant model estimates for NO2 and PM were ascertained from bibliographic databases (PubMed, EMBASE and Web of Science) and reviews. Random-effects summary estimates were calculated globally and stratified by different geographical regions, and effect modification was investigated. OUTCOME MEASURES: Mortality and hospital admissions for various cardiovascular or respiratory diseases in different age groups in the general population. RESULTS: 60 eligible studies were identified, and meta-analysis was conducted on 23 outcomes. Two-pollutant model study estimates generally showed that the NO2 associations were independent of PM mass. For all-cause mortality, a 10 µg/m(3) increase in 24-hour NO2 was associated with a 0.78% (95% CI 0.47% to 1.09%) increase in the risk of death, which reduced to 0.60% (0.33% to 0.87%) after control for PM. Heterogeneity between geographical region-specific estimates was removed by control for PM (I(2) from 66.9% to 0%). Estimates of PM and daily mortality assembled from the same studies were greatly attenuated after control for NO2: from 0.51% (0.29% to 0.74%) to 0.18% (-0.11% to 0.47%) per 10 µg/m(3) PM10 and 0.74% (0.34% to 1.14%) to 0.54% (-0.25% to 1.34%) for PM2.5. CONCLUSIONS: The association between short-term exposure to NO2 and adverse health outcomes is largely independent of PM mass. Further studies should attempt to investigate whether this is a generic PM effect or whether it is modified by the source and physicochemical characteristics of PM. This finding strengthens the argument for NO2 having a causal role in health effects.

Traffic pollution and the incidence of cardiorespiratory outcomes in an adult cohort in London.

OBJECTIVES: The epidemiological evidence for adverse health effects of long-term exposure to air and noise pollution from traffic is not coherent. Further, the relative roles of background versus near traffic pollution concentrations in this process are unclear. We investigated relationships between modelled concentrations of air and noise pollution from traffic and incident cardiorespiratory disease in London. METHODS: Among 211 016 adults aged 40-79 years registered in 75 Greater London practices between 2005 and 2011, the first diagnosis for a range of cardiovascular and respiratory outcomes were identified from primary care and hospital records. Annual baseline concentrations for nitrogen oxide (NOx), particulate matter with a median aerodynamic diameter <2.5 µm (PM2.5) attributable to exhaust and non-exhaust sources, traffic intensity and noise were estimated at 20 m2 resolution from dispersion models, linked to clinical data via residential postcode. HRs were adjusted for confounders including smoking and area deprivation. RESULTS: The largest observed associations were between traffic-related air pollution and heart failure (HR=1.10 for 20 µg/m3 change in NOx, 95% CI 1.01 to 1.21). However, no other outcomes were consistently associated with any of the pollution indicators, including noise. The greater variations in modelled air pollution from traffic between practices, versus within, hampered meaningful fine spatial scale analyses. CONCLUSIONS: The associations observed with heart failure may suggest exacerbatory effects rather than underlying chronic disease. However, the overall failure to observe wider associations with traffic pollution may reflect that exposure estimates based on residence inadequately represent the relevant pattern of personal exposure, and future studies must address this issue.

Long-term exposure to ambient ozone and mortality: a quantitative systematic review and meta-analysis of evidence from cohort studies.

OBJECTIVES: While there is good evidence for associations between short-term exposure to ozone and a range of adverse health outcomes, the evidence from narrative reviews for long-term exposure is suggestive of associations with respiratory mortality only. We conducted a systematic, quantitative evaluation of the evidence from cohort studies, reporting associations between long-term exposure to ozone and mortality. METHODS: Cohort studies published in peer-reviewed journals indexed in EMBASE and MEDLINE to September 2015 and PubMed to October 2015 and cited in reviews/key publications were identified via search strings using terms relating to study design, pollutant and health outcome. Study details and estimate information were extracted and used to calculate standardised effect estimates expressed as HRs per 10 ppb increment in long-term ozone concentrations. RESULTS: 14 publications from 8 cohorts presented results for ozone and all-cause and cause-specific mortality. We found no evidence of associations between long-term annual O3 concentrations and the risk of death from all causes, cardiovascular or respiratory diseases, or lung cancer. 4 cohorts assessed ozone concentrations measured during the warm season. Summary HRs for cardiovascular and respiratory causes of death derived from 3 cohorts were 1.01 (95% CI 1.00 to 1.02) and 1.03 (95% CI 1.01 to 1.05) per 10 ppb, respectively. CONCLUSIONS: Our quantitative review revealed a paucity of independent studies regarding the associations between long-term exposure to ozone and mortality. The potential impact of climate change and increasing anthropogenic emissions of ozone precursors on ozone levels worldwide suggests further studies of the long-term effects of exposure to high ozone levels are warranted.

Quantitative systematic review of the associations between short-term exposure to nitrogen dioxide and mortality and hospital admissions.

BACKGROUND: Short-term exposure to NO2 has been associated with adverse health effects and there is increasing concern that NO2 is causally related to health effects, not merely a marker of traffic-generated pollution. No comprehensive meta-analysis of the time-series evidence on NO2 has been published since 2007. OBJECTIVE: To quantitatively assess the evidence from epidemiological time-series studies published worldwide to determine whether and to what extent short-term exposure to NO2 is associated with increased numbers of daily deaths and hospital admissions. DESIGN: We conducted a quantitative systematic review of 204 time-series studies of NO2 and daily mortality and hospital admissions for several diagnoses and ages, which were indexed in three bibliographic databases up to May 2011. We calculated random-effects estimates by different geographic regions and globally, and also tested for heterogeneity and small study bias. RESULTS: Sufficient estimates for meta-analysis were available for 43 cause-specific and age-specific combinations of mortality or hospital admissions (25 for 24 h NO2 and 18 of the same combinations for 1 h measures). For the all-age group, a 10 µg/m(3) increase in 24 h NO2 was associated with increases in all-cause, cardiovascular and respiratory mortality (0.71% (95% CI 0.43% to 1.00%), 0.88% (0.63% to 1.13%) and 1.09% (0.75% to 1.42%), respectively), and with hospital admissions for respiratory (0.57% (0.33% to 0.82%)) and cardiovascular (0.66% (0.32% to 1.01%)) diseases. Evidence of heterogeneity between geographical region-specific estimates was identified in more than half of the combinations analysed. CONCLUSIONS: Our review provides clear evidence of health effects associated with short-term exposure to NO2 although further work is required to understand reasons for the regional heterogeneity observed. The growing literature, incorporating large multicentre studies and new evidence from less well-studied regions of the world, supports further quantitative review to assess the independence of NO2 health effects from other air pollutants.

Long-term exposure to outdoor air pollution and the incidence of chronic obstructive pulmonary disease in a national English cohort.

OBJECTIVES: The role of outdoor air pollution in the incidence of chronic obstructive pulmonary disease (COPD) remains unclear. We investigated this question using a large, nationally representative cohort based on primary care records linked to hospital admissions. METHODS: A cohort of 812 063 patients aged 40-89 years registered with 205 English general practices in 2002 without a COPD diagnosis was followed from 2003 to 2007. First COPD diagnoses recorded either by a general practitioner (GP) or on admission to hospital were identified. Annual average concentrations in 2002 for particulate matter with an aerodynamic diameter <10 µm (PM10) and <2.5 µm (PM2.5), nitrogen dioxide (NO2), ozone and sulfur dioxide (SO2) at 1 km(2) resolution were estimated from emission-based dispersion models. Hazard ratios (HRs) per interquartile range change were estimated from Cox models adjusting for age, sex, smoking, body mass index and area-level deprivation. RESULTS: 16 034 participants (1.92%) received a COPD diagnosis from their GP and 2910 participants (0.35%) were admitted to hospital for COPD. After adjustment, HRs for GP recorded COPD and PM10, PM2.5 and NO2 were close to unity, positive for SO2 (HR=1.07 (95% CI 1.03 to 1.11) per 2.2 µg/m(3)) and negative for ozone (HR=0.94 (0.89 to 1.00) per 3 µg/m(3)). For admissions HRs for PM2.5 and NO2 remained positive (HRs=1.05 (0.98 to 1.13) and 1.06 (0.98 to 1.15) per 1.9 µg/m(3) and 10.7 µg/m(3), respectively). CONCLUSIONS: This large population-based cohort study found limited, inconclusive evidence for associations between air pollution and COPD incidence. Further work, utilising improved estimates of air pollution over time and enhanced socioeconomic indicators, is required to clarify the association between air pollution and COPD incidence.

Associations between daily mortality in London and combined oxidant capacity, ozone and nitrogen dioxide.

Both nitrogen dioxide (NO2) and ozone (O3) are powerful oxidants in ambient air that are intimately linked through atmospheric chemistry and which continuously interchange over very short timescales. Based upon atmospheric chemistry alone, there is a strong, a priori, reason for considering O3 and NO2 together in epidemiological studies, rather than either of the two pollutants separately in single-pollutant models. This paper compares two approaches to this, using Ox, defined as O3 + NO2, as a single metric and also using O3 and NO2 together in two-pollutant models. We hypothesised that the magnitude of the association between Ox and daily mortality would be greater than for NO2 and O3 individually. Using collocated hourly measurements for O3 and NO2 in London, from 2000 to 2005, we carried out a time series analysis of daily mortality. We investigated O3, NO2 and Ox individually in single-pollutant Poisson regression models and NO2 and O3 jointly in two-pollutant models in both all-year and season-specific analyses. We observed larger associations for mean 24-h concentrations of Ox (1.30 % increase in mortality per 10 ppb) than for O3 (0.87 %) and NO2 (0 %) individually. However, when analysed jointly in two-pollutant models, associations for O3 (1.54 %) and NO2 (1.07 %) were comparable to the Ox association. Season-specific analyses broadly followed this pattern irrespective of whether the Ox concentrations were driven by O3 production (summer) or depletion (winter). This novel approach in air pollution epidemiology captures the simultaneous impact of both oxidants whilst avoiding many of the statistical issues associated with two-pollutant models and potentially simplifies health impact calculations.

Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: a systematic review and meta-analysis.

BACKGROUND: Short-term exposure to outdoor fine particulate matter (particles with a median aerodynamic diameter <2.5 µm (PM2.5)) air pollution has been associated with adverse health effects. Existing literature reviews have been limited in size and scope. METHODS: We conducted a comprehensive, systematic review and meta-analysis of 110 peer-reviewed time series studies indexed in medical databases to May 2011 to assess the evidence for associations between PM2.5 and daily mortality and hospital admissions for a range of diseases and ages. We stratified our analyses by geographical region to determine the consistency of the evidence worldwide and investigated small study bias. RESULTS: Based upon 23 estimates for all-cause mortality, a 10 µg/m(3) increment in PM2.5 was associated with a 1.04% (95% CI 0.52% to 1.56%) increase in the risk of death. Worldwide, there was substantial regional variation (0.25% to 2.08%). Associations for respiratory causes of death were larger than for cardiovascular causes, 1.51% (1.01% to 2.01%) vs 0.84% (0.41% to 1.28%). Positive associations with mortality for most other causes of death and for cardiovascular and respiratory hospital admissions were also observed. We found evidence for small study bias in single-city mortality studies and in multicity studies of cardiovascular disease. CONCLUSIONS: The consistency of the evidence for adverse health effects of short-term exposure to PM2.5 across a range of important health outcomes and diseases supports policy measures to control PM2.5 concentrations. However, reasons for heterogeneity in effect estimates in different regions of the world require further investigation. Small study bias should also be considered in assessing and quantifying health risks from PM2.5.

Ambient temperature and activation of implantable cardioverter defibrillators.

The degree to which weather influences the occurrence of serious cardiac arrhythmias is not fully understood. To investigate, we studied the timing of activation of implanted cardiac defibrillators (ICDs) in relation to daily outdoor temperatures using a fixed stratum case-crossover approach. All patients attending ICD clinics in London between 1995 and 2003 were recruited onto the study. Temperature exposure for each ICD patient was determined by linking each patient's postcode of residence to their nearest temperature monitoring station in London and the South of England. There were 5,038 activations during the study period. Graphical inspection of ICD activation against temperature suggested increased risk at lower but not higher temperatures. For every 1 °C decrease in ambient temperature, risk of ventricular arrhythmias up to 7 days later increased by 1.2 % (95 % CI -0.6 %, 2.9 %). In threshold models, risk of ventricular arrhythmias increased by 11.2 % (0.5 %, 23.1 %) for every 1° decrease in temperature below 2 °C. Patients over the age of 65 exhibited the highest risk. This large study suggests an inverse relationship between ambient outdoor temperature and risk of ventricular arrhythmias. The highest risk was found for patients over the age of 65. This provides evidence about a mechanism for some cases of low-temperature cardiac death, and suggests a possible strategy for reducing risk among selected cardiac patients by encouraging behaviour modification to minimise cold exposure.

Changes over time in the relationship between symptoms of asthma, rhinoconjunctivitis and eczema: a global perspective from the International Study of Asthma and Allergies in Childhood (ISAAC).

BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC) identified trends in the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema over a seven-year period. We hypothesised that environmental influences on the three diseases are different and therefore investigated the correlation over time between trends in the prevalence of these diseases and their combinations at centre and individual level. METHODS: Centre level analyses were correlations between time trends in the prevalence of symptoms. At an individual level, odds ratios were calculated for associations between symptoms between Phases One and Three. We also investigated potential effect modification in the younger versus older age group; male versus female; and by average Gross National Income per capita (GNI). RESULTS: Both phases were completed in 66 centres in 37 countries for the 6-7 year age group and in 106 centres in 56 countries for the 13-14 year age group. We found that the correlations in time trends were stronger for the older age group than the younger one. Between symptoms of diseases, correlations of time trends were the strongest for rhinoconjunctivitis with eczema and weakest for eczema with asthma. The relationship between the three diseases was generally consistent over the seven-year period, and there was little association found with average GNI. CONCLUSIONS: Despite some increase in the proportion of children with symptoms of asthma, rhinoconjunctivitis and eczema, the pattern between the three diseases has not changed much, suggesting that similar factors may be affecting them at a global level.

Impact of heat on mortality in 15 European cities: attributable deaths under different weather scenarios.

BACKGROUND: High ambient summer temperatures have been shown to influence daily mortality in cities across Europe. Quantification of the population mortality burden attributable to heat is crucial to the development of adaptive approaches. The impact of summer heat on mortality for 15 European cities during the 1990s was evaluated, under hypothetical temperature scenarios warmer and cooler than the mean and under future scenarios derived from the Intergovernmental Panel on Climate Change Special Report on Emission Scenarios (SRES). METHODS: A Monte Carlo approach was used to estimate the number of deaths attributable to heat for each city. These estimates rely on the results of a Bayesian random-effects meta-analysis that combines city-specific heat-mortality functions. RESULTS: The number of heat-attributable deaths per summer ranged from 0 in Dublin to 423 in Paris. The mean attributable fraction of deaths was around 2%. The highest impact was in three Mediterranean cities (Barcelona, Rome and Valencia) and in two continental cities (Paris and Budapest). The largest impact was on persons over 75 years; however, in some cities, important proportions of heat-attributable deaths were also found for younger adults. Heat-attributable deaths markedly increased under warming scenarios. The impact under SRES scenarios was slightly lower or comparable to the impact during the observed hottest year. CONCLUSIONS: Current high summer ambient temperatures have an important impact on European population health. This impact is expected to increase in the future, according to the projected increase of mean ambient temperatures and frequency, intensity and duration of heat waves.