Margarita Taracido

Case-Crossover Analysis of Air Pollution Health Effects: A Systematic Review of Methodology and Application

Background Case-crossover is one of the most used designs for analyzing the health-related effects of air pollution. Nevertheless, no one has reviewed its application and methodology in this context. Objective We conducted a systematic review of case-crossover (CCO) designs used to study the relationship between air pollution and morbidity and mortality, from the standpoint of methodology and application. Data sources and extraction A search was made of the MEDLINE and EMBASE databases. Reports were classified as methodologic or applied. From the latter, the following information was extracted: author, study location, year, type of population (general or patients), dependent variable(s), independent variable(s), type of CCO design, and whether effect modification was analyzed for variables at the individual level. Data synthesis The review covered 105 reports that fulfilled the inclusion criteria. Of these, 24 addressed methodological aspects, and the remainder involved the design’s application. In the methodological reports, the designs that yielded the best results in simulation were symmetric bidirectional CCO and time-stratified CCO. Furthermore, we observed an increase across time in the use of certain CCO designs, mainly symmetric bidirectional and time-stratified CCO. The dependent variables most frequently analyzed were those relating to hospital morbidity; the pollutants most often studied were those linked to particulate matter. Among the CCO-application reports, 13.6% studied effect modification for variables at the individual level. Conclusions The use of CCO designs has undergone considerable growth; the most widely used designs were those that yielded better results in simulation studies: symmetric bidirectional and time-stratified CCO. However, the advantages of CCO as a method of analysis of variables at the individual level are put to little use.

Air pollution and cardiovascular admissions association in Spain: results within the EMECAS project

Objective: To evaluate the short term effect of air pollution on cardiovascular admissions in 14 Spanish cities Methods: The period under study was from 1995 to 1999. Daily emergency admissions for all cardiovascular diseases (CVD) and heart diseases (HD) were obtained from hospital records, and the corresponding daily levels of particulates, SO2, NO2, CO, and ozone were recorded. The magnitude of association was estimated using Poisson generalised additive models controlling for confounding and overdispersion. For each cause, lagged effects, up to three days, of each pollutant were examined and combined estimates were obtained. For ozone the analyses were restricted to the warm period. One and two pollutant models were performed. Results: Associations were more consistent in lag 0 (concurrent day) and 1 (lag 0–1), except in the case of ozone where there was a more delayed relation (lag 2–3). For combined estimates an increase of 10 μg/m3 in the PM10 levels in lag 0–1 was associated with an increase of 0.9% (95% CI: 0.4 to 1.5%) in the number of hospital admissions for CVD, and 1.6% (0.8 to 2.3%) for HD. For ozone the corresponding estimates for lag 2–3 were 0.7% (0.3 to 1.0) for CVD, and 0.7% (0.1 to 1.2) for HD. An increase of 1 mg/m3 in CO levels was associated with an increase of 2.1% (0.7 to 3.5%) in CVD admissions, and 4.2% (1.3 to 7.1%) in HD admissions. SO2 and NO2 estimates were more sensitive in two pollutant models Conclusions: A short term association between increases in daily levels of air pollutants and the number of daily admissions for cardiovascular diseases, with specificity for heart diseases, has been described in Spanish cities.

Effect of short-term exposure to air pollution and pollen on medical emergency calls: a case-crossover study in Spain.

Background:  A symmetric case‐crossover design was used to analyse the short‐term relationship between air pollution, pollen and emergency calls to medical services.

Respiratory and mental health effects of wildfires: an ecological study in Galician municipalities (north-west Spain)

BackgroundDuring the summer of 2006, a wave of wildfires struck Galicia (north-west Spain), giving rise to a disaster situation in which a great deal of the territory was destroyed. Unlike other occasions, the wildfires in this case also threatened farms, houses and even human lives, with the result that the perception of disaster and helplessness was the most acute experienced in recent years. This study sought to analyse the respiratory and mental health effects of the August-2006 fires, using consumption of anxiolytics-hypnotics and drugs for obstructive airway diseases as indicators.MethodsWe conducted an analytical, ecological geographical- and temporal-cluster study, using municipality-month as the study unit. The independent variable was exposure to wildfires in August 2006, with municipalities thus being classified into the following three categories: no exposure; medium exposure; and high exposure. Dependent variables were: (1) anxiolytics-hypnotics; and (2) drugs for obstructive airway diseases consumption. These variables were calculated for the two 12-month periods before and after August 2006. Additive models for time series were used for statistical analysis purposes.ResultsThe results revealed a higher consumption of drugs for obstructive airway diseases among pensioners during the months following the wildfires, in municipalities affected versus those unaffected by fire. In terms of consumption of anxiolytics-hypnotics, the results showed a significant increase among men among men overall -pensioners and non-pensioners- in fire-affected municipalities.ConclusionsOur study indicates that wildfires have a significant effect on population health. The coherence of these results suggests that drug utilisation research is a useful tool for studying morbidity associated with environmental incidents.

Original article: Effect of short-term exposure to air pollution and pollen on medical emergency calls: a case-crossover study in Spain

Background:  A symmetric case‐crossover design was used to analyse the short‐term relationship between air pollution, pollen and emergency calls to medical services.

Analysis of case-crossover designs using longitudinal approaches: a simulation study.

Background: Application of case-crossover designs provides an alternative to time-series analysis for analyzing the health-related effects of air pollution. Although some case-crossover studies can control for trend and seasonality by design, to date they have been analyzed as matched case-control studies. Such analyses may exhibit biases and a lower statistical efficiency than traditional time series analyzed with Poisson. Methods: In this article, case-crossover studies are treated as cohort studies in which each subject is observed for a short period of time before and/or after the event, thus making possible analyzing with Andersen-Gill and generalized linear mixed models. We conducted a simulation study to compare the behavior of these models applied to case-crossover designs with time series analyzed with Poisson and with case-crossover analyzed by conditional logistic regression. To this end, we created a random variable that follows a Poisson distribution of low (2/day) and high mean events (22/day). This variable is a function of an unobserved confounding variable (that introduces trend and seasonality) and data on small particulate matter (PM10) from Barcelona. In addition, scenarios were created to assess the effect on exposure exerted by autocorrelation and the magnitude of the pollutant coefficient. Results: The full semisymmetric design analyzed with generalized linear mixed models yields good coverage and a high statistical power for air-pollution effect magnitudes close to the real values but shows bias for high effect magnitudes. This bias seems to be attributable to autocorrelation in the exposure variable. Conclusions: Longitudinal approaches applied to case-crossover designs may prove useful for analyzing the acute effects of environmental exposures.

Relación a corto plazo de la contaminación atmosférica y la mortalidad en 13 ciudades españolas

in the levels of the average of the concurrent and one day lag for black smoke was associated with a 0.8% (CI: 0.4-1.1) increase in mortality. The same in- crease in the concentration of SO2 was associated with a 0.5% (CI: 0.1-1.0) increase in daily deaths, and a 0.6% (CI: 0.3-0.8) increase in the case of NO2. An increase of 1 mg/m3 in the le- vels of CO was associated with an increase of 1.5% (CI: 0.5-2.6) in daily deaths. CONCLUSIONS: There is a short-term association between increases of daily levels of air pollutants and the number of daily deaths in Spanish cities.

El proyecto Emecas: protocolo del estudio multicéntrico en España de los efectos a corto plazo de la contaminación atmosférica sobre la salud

El proyecto EMECAM constato el efecto a corto plazo de la contaminacion atmosferica sobre la mortalidad en 14 ciudades espanolas entre 1990 y 1995. El Estudio Multicentrico Espanol de Contaminacion Atmosferica y Salud (EMECAS) amplia estos objetivos incorporando al analisis datos de morbilidad hospitalaria, utiliza informacion mas reciente y suma un total de 16 ciudades. Se trata de un estudio ecologico de series temporales, siendo las variables respuesta las defunciones diarias y los ingresos hospitalarios urgentes por enfermedades del aparato circulatorio y enfermedades respiratorias en los residentes de cada ciudad. Contaminantes analizados: particulas en suspension, SO2, NO2, CO y O3. Variables de control: meteorologicas, de calendario, estacionalidad y tendencia e incidencia de gripe. Analisis estadistico: estimacion de la asociacion en cada ciudad mediante la construccion de modelos de regresion de Poisson aditivos generalizados, y meta-analisis para la obtencion de estimadores conjuntos. Los niveles medios de contaminantes se situaron por debajo de los establecidos por la normativa actual para el dioxido de azufre, el monoxido de carbono y el ozono. Los valores de NO2 y PM10 se situaron alrededor de los establecidos en la normativa (40 µg/m³). Se trata del primer estudio de la relacion entre contaminacion atmosferica y morbilidad en un conjunto de ciudades espanolas. Los niveles de contaminantes estudiados son moderados para algunos contaminantes, aunque en otros, especialmente NO2 y particulas, podrian representar un problema para el cumplimiento de la normativa vigente.

Do socioeconomic inequalities in mortality vary between different Spanish cities? a pooled cross-sectional analysis.

BackgroundThe relationship between deprivation and mortality in urban settings is well established. This relationship has been found for several causes of death in Spanish cities in independent analyses (the MEDEA project). However, no joint analysis which pools the strength of this relationship across several cities has ever been undertaken. Such an analysis would determine, if appropriate, a joint relationship by linking the associations found.MethodsA pooled cross-sectional analysis of the data from the MEDEA project has been carried out for each of the causes of death studied. Specifically, a meta-analysis has been carried out to pool the relative risks in eleven Spanish cities. Different deprivation-mortality relationships across the cities are considered in the analysis (fixed and random effects models). The size of the cities is also considered as a possible factor explaining differences between cities.ResultsTwenty studies have been carried out for different combinations of sex and causes of death. For nine of them (men: prostate cancer, diabetes, mental illnesses, Alzheimer’s disease, cerebrovascular disease; women: diabetes, mental illnesses, respiratory diseases, cirrhosis) no differences were found between cities in the effect of deprivation on mortality; in four cases (men: respiratory diseases, all causes of mortality; women: breast cancer, Alzheimer’s disease) differences not associated with the size of the city have been determined; in two cases (men: cirrhosis; women: lung cancer) differences strictly linked to the size of the city have been determined, and in five cases (men: lung cancer, ischaemic heart disease; women: ischaemic heart disease, cerebrovascular diseases, all causes of mortality) both kinds of differences have been found. Except for lung cancer in women, every significant relationship between deprivation and mortality goes in the same direction: deprivation increases mortality. Variability in the relative risks across cities was found for general mortality for both sexes.ConclusionsThis study provides a general overview of the relationship between deprivation and mortality for a sample of large Spanish cities combined. This joint study allows the exploration of and, if appropriate, the quantification of the variability in that relationship for the set of cities considered.

Case-crossover design: Basic essentials and applications

Abstract Case-crossover analysis is an observational epidemiological design that was proposed by Maclure in 1991 to assess whether a given intermittent or unusual exposure may have triggered an immediate short-term, acute event. The present article outlines the basics of case-crossover designs, as well as their applications and limitations. The case-crossover design is based on exclusively selecting case subjects. To calculate relative risk, exposure during the period of time prior to the event (case period) is compared against the same subjects exposure during one or more control periods. This method is only appropriate when the exposures are transient in time and have acute short-term effects. For exposures in which there is no trend, a unidirectional approach is the most frequent and consists of selecting one or more control periods prior to the case period. When the exposure displays a time trend (e.g., air pollution), a unidirectional approach will yield biased estimates, and therefore bidirectional case-crossover designs are used, which select control time intervals preceding and subsequent to that of the event. The case-crossover design is being increasingly used across a wide range of fields, including factors triggering traffic, occupational and domestic accidents and acute myocardial infarction, and those involved in air pollution and health and pharmacoepidemiology, among others. Insofar as data-analysis is concerned, case-crossover designs can generally be regarded as matched case-control studies and consequently conditional logistic regression can be applied. Lastly, this study analyzes practical examples of distinct applications of the case-crossover design.