Epidemiology

The Big Asthma Lie

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2.3.1 Occupational Exposure. Because engineering of NPs is relatively new, and long-term exposure may be needed before any adverse effects can be identified and attributed, there is little epidemiological evidence. On the other hand, there is extensive epidemiology on long-term and short-term exposure to dusts in many industries. The main problem is relevance, i.e. that these results do not necessarily generalise to the new nano-materials that are currently being developed precisely because they have new properties, and so health effects may also be different from those of existing, well-studied materials.

The most relevant occupational epidemiology studies are from the carbon black industry. Sorahan et al.50 followed up an inconclusive early study by Hodgson and Jones51 of mortality in male carbon black workers in five factories in Great Britain. Their main results, based on 1147 male manual workers employed for 12 months or more, showed a statistically significant excess of lung cancer compared to deaths expected based on death rates for England and Wales, with clear differences between factories. However, there was no evidence of a gradient with time since first employment and, after adjustment for factory and other risk factors, no clear evidence of a trend with cumulative exposures, i.e. the study did not show any clear evidence that the excess was work related. However, data limitations imply that the possibility of some effect cannot be ruled out. Mortality overall from non-malignant respiratory disease and circulatory disease was similar to that expected, based on age-specific death rates for men in England and Wales.

A series of papers on the respiratory health of workers in the European carbon black industry, including chest radiographs52,53 and lung function and respiratory symptoms,52,54 show some adverse effects of exposure to carbon black dust on respiratory health. Results from two cross-sectional surveys (1991-92 and 1994-95) of lung function and respiratory symptoms in overlapping though non-identical groups of about 2000 workers at 19 and 16 plants, respectively, showed some consistent evidence of effects on respiratory symptoms and lung function (FEV1 and mid-flow rather than FVC), which appear to be associated principally with recent rather than cumulative expo-sure.54 There was, in addition, clear radiological evidence of dust retention, and relationships of radiological endpoints with cumulative dust exposure, though little evidence of what is usually called radiologically identified disease (i.e. Category 2 or more small opacities). Qualitatively similar results were found in studies cross-sectionally52 and longitudinally.53

The main implications of these results are reassuring with regard to carbon black. Small methodological variations would surely give rise to somewhat different results, but not to markedly different conclusions, i.e. it is highly unlikely that severe work-related risks remain unidentified. Unfortunately, there is limited information about the size of the primary particles in the carbon black studies, and the toxicity of NPs is affected by other factors also. Thus, it is not possible to generalise from these results.

Epidemiology following exposure to other particles does not help greatly. Mortality and morbidity results from studies of workers producing titanium dioxide (TiO2) were reviewed by Hext et al.55 Overall, these results are similar in nature to those for carbon black. However, nanoparticle TiO2 is a very small fraction of the overall market and the results applied particularly to coarser TiO2. Welders are exposed to very fine particles. There is a huge literature on mortality and morbidity of welders. However, the effects depend on exactly what metals are being welded and so it is difficult to extrapolate to the new nanotechnology industries. We note, however, that some of the effects may be immediate (acute). There is an extensive literature confirming excess cancer mortality (lung cancer, mesothelioma) and respiratory morbidity following occupational exposure to asbestos, as well as studies of other fibres. This may be relevant, because of the fibrous shape of some new nanomaterials. Characteristics determining toxicity are length greater than 10-15 mm, diameter less than 3 mm, and solubility in the lung milieu, with a further contribution from surface properties. Nanotubes with these characteristics might be expected to show similar hazards; risks would depend on dose inhaled and retained. Finally, most studies of particles in outdoor air are based on mass concentrations of particulate matter (PM). There are some studies of particle number, almost all from Germany or from Finland. These are more relevant to nano-particles, e.g. from traffic. They show adverse effects associated with the ultrafine fraction of respirable particles on mortality and on individuals with asthma;56 the effect of ultrafine particles seems to be delayed by a few days.

2.3.2 Environmental Exposure. It is well known that daily variations in particles in outdoor air are associated with a very wide range of adverse health effects, including increased cardio-respiratory mortality, increased hospital admissions from respiratory and cardiac causes, increases in visits to primary care physicians (GPs), increases in work and school absenteeism, exacerbations of asthma and changes in detailed measures of respiratory and cardiac health such as lung function and heart rate variability. Furthermore, long-term exposure to outdoor particles has been shown to be associated with earlier mortality (reduced life expectancy) in adults and with increased mortality in infants.

These results are based on studies of mass concentrations of ambient particles, for example measured as PM10 or PM2.5, principally because mass concentrations in PM10, and increasingly in PM2 5 also, are measured routinely in a wide range of locations in North America, in Europe (including the UK) and elsewhere. It has long been conjectured however that small particles from combustion sources have a key role in driving the PM-health relationships. This has led to an interest in epidemiology which can differentiate the effects of ultrafine from larger respirable particles, using, for example, measure of particle size.

There is as yet a limited number of relevant epidemiological studies, almost all from Germany or from Finland. One of the German studies examines mortality.57 The other studies examine panels of people with impaired health, mostly pollution-related changes in the respiratory health of people with asthma, though cardiovascular health endpoints have been studied also.

Papers up to and including those published in 2002 have been reviewed in detail by Morawska et al.56 They conclude the following:

• There are adverse effects associated with the ultrafine fraction of respirable particles.

• Those effects are shown on mortality in the general population, and on panels of individuals with asthma or other impaired health.

• The studies suggest a more-or-less immediate effect of fine particles as conventionally measured (PM2.5), whereas the effect of ultrafine particles seems to be delayed by a few days.

• This suggests that fine particles are insufficient as a surrogate for ultrafine particles.

In addition, there have been more recent publications which add information to the role of nanoparticles using the number metric as a surrogate measure. A study from Rome of out-of-hospital sudden death58 showed that death was related to particle numbers in the nano-size range, particularly on the day of death, but to a greater degree than either particle mass or carbon monoxide concentrations. On the other hand, a study of elderly individuals with coronary artery disease suggested that particle mass (PM2.5) was the more important driver of health effects although particle numbers did relate to activity restriction.59

These studies support the toxicological findings, earlier, that the effects of dust depend not only on its size, but also on what kind of dust it is. In order to draw general conclusions it is important to characterise as well as possible the nature and size distribution of the aerosols to which workers are exposed, and to track in sufficient detail workers' time spent in these conditions. In particular, epidemiology has limited value for assessing the effects of NPs unless it can differentiate (in time and space) between exposure to nanoparticles and exposure to particles from other sources. Finally, as ever, study power is a factor - numbers of subjects, length of follow-up, variation in exposure -implying a need for multi-centre studies with associated issues of design and management.

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Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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