title: Case-crossover analysis of air pollution health effects: a systematic review of methodology and application.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Carracedo-Martínez
authors.forename: Margarita
authors.initials: M
authors.lastname: Taracido
authors.forename: Aurelio
authors.initials: A
authors.lastname: Tobias
authors.forename: Marc
authors.initials: M
authors.lastname: Saez
authors.forename: Adolfo
authors.initials: A
authors.lastname: Figueiras
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D004781:Environmental Exposure; D015340:Epidemiologic Research Design; D006801:Humans; D009017:Morbidity; D009026:Mortality
chemical_list: D000393:Air Pollutants