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P.M. Mannucci et al.
tries, involving 20,000 cases and 2.5 million deaths, also including a highly polluted and densely populated country such as China, whereas the WHO-GBD IER was mainly based on the less polluted Western Europe, Canada, and USA. In addition, the IER function had been applied only to five main causes of mortality (coronary artery disease, cerebrovascular disease, chronic obstructive pulmonary disease, lung cancer, and lower respiratory tract illness), whereas the study of Burnett et al.8 developed and applied GEMM to the whole world, using mortality data from non-communicable diseases plus pneumonia. They attrib- uted 8.9 million annual deaths to the exposure to ambient air PM2.5, more than twice those attributed by the WHO and the GBD. Applying the GEMM function to Europe, Lelieveld et al.92 reported that the number of PM2.5 - related deaths was as high as 790,000 per year for the whole con- tinent, so that the excess mortality attributable to PM2.5 was more than double the previous GBD estimate (269,000). When the all-cause annual deaths attributed to PM2.5 were calculated for the five most populated European countries and normalized for the number of inhabitants, the highest prevalence of annual premature deaths per 100,000 were recorded in Germany (154), fol- lowed by Poland (150), Italy (136), France (105), and the UK (98). Lelieveld et al.92 have also evaluated the avoidable deaths attributed to each disease and found once more that the major fraction of mortality was due to CVD, with a much higher burden for coronary artery disease than for cerebrovascular disease, COPD, lung cancer and pneumo- nia. A large additional fraction of excess mortality was due to other non-communicable diseases as yet not accurately specified, but arguably associated to CVD, such as hyper- tension and diabetes. Finally, Lelieveld et al. estimated that, in Europeans, PM2.5 air pollution decreases the mean life expectancy by 2.2 years.92
These new findings are striking, indicating as they do that the burden of mortality and, in particular cardiovas- cular mortality, globally as well as in Europe, is much greater than appreciated so far. They provide real, clear support to the statement made by the European Court of Auditors, an institution that has the task of implementing the recommendations issued by the European Union: “European citizens still breathe harmful air, mainly due to weak legislation and poor policy implementation” (https://www.eca.europa.eu/en/Pages/AuditReportsOpini ons.aspx). The allusion to weak legislation and policy implementation is likely to be an indirect criticism to the European Union, that still provides ambient air quality (AAQ) directives that are much less stringent for health preservation than the air quality guidelines (AQG) of the WHO (Table 2), which are in turn close to those adopted in the USA by the Environment Protection Agency (EPA). All in all, these new findings provide striking and real evi- dence to a public statement made by Janez Potocnik, the European Commissioner for the Environment from 2010- 2014: “If you think the economy is more important than the environment, try holding your breath while counting your money” [http://europa.eu/rapid/press- release_SPEECH-13-822_en.htm].
Open issues and research needs
The dramatic dimension of the dire effects on health of air pollution, and particularly of PM2.5, demands more research efforts in order to better understand the patho- genic mechanisms and thus to develop improved weapons
Table 2. Comparison of the ceilings of mean annual concentrations (in 3
μg/mm ) of the main air pollutants according to the current directives for ambient air quality of the European Union (EU) and to the air qual- ity guidelines of the World Health Organization (WHO).
Pollutant
PM10
PM2.5
Nitrogen dioxide Ozone
EU WHO
40 20
25 10 40 40 120 100
for primary and secondary prevention, not only of CVD, but also of other very frequent non-communicable dis- eases such as cancer and respiratory diseases. Furthermore, more and more evidence is accumulating that air pollution has noxious effects on the central nerv- ous system (CNS) through chronic neuroinflammation, neuronal and myelin damage that lead to degenerative neurological diseases and cognitive deficits. There is also a need for more research and knowledge on the growing data showing air pollution impairs the development of the child's brain, affecting attention functions, memory, func- tional integration, and inhibition control mechanisms. More information is needed on the differential vulnerabil- ity of subgroups such as children and pregnant women, the elderly, financially deprived people, and outdoor workers. Furthermore, experimental and epidemiological studies should address the still open and cogent issue of the role of each component of air pollution, with particu- lar emphasis on the chemical components and physical characteristics of PM. There is preliminary evidence that some chemical constituents may be more dangerous than others, such as organic matter, black carbon and nitrates. Other studies have emphasized the risk associated with metals such as vanadium and nickel.93 Furthermore, it is still poorly understood whether or not the different ori- gins of PM (i.e. primary or secondary; natural or anthro- pogenic; from traffic, heating or industry; agriculture or animal farms) have different potencies in causing the adverse effects of PM on health. Therefore, for air quality mitigation policies it is important to consider the interac- tion between the composition and origin of the local pol- luttome and the epidemiological characteristics of the populations concerned.94
Research should also focus on the more extensive meas- urement and the clinical effects of ultrafine particles, since, owing to the fact that they have a diameter of less than 100 nanometers, these are potentially more damaging than larger particles. However, available experimental and epidemiological evidence is limited.95 Finally, an important area of research would be to clarify the relationship between medication intake and air pollution. Conti et al.96 have shown a positive association between PM10 and the level of prescription of cardiorespiratory drugs. They took this to be an indication of cardiovascular and pulmonary events triggered by peaks in air pollution. In this context, it would also be of interest to evaluate whether or not the long-term intake of widely and chronically prescribed medications such as statins, aspirin and β-blockers is asso- ciated with less cardiovascular events, in comparison with individuals not taking these drugs and equally exposed to high pollution levels.
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haematologica | 2019; 104(12)