EUGLOREH project
THE STATUS OF HEALTH IN THE EUROPEAN UNION:
TOWARDS A HEALTHIER EUROPE

FULL REPORT

PART II - HEALTH CONDITIONS

5. HEALTH IMPACTS OF NON COMMUNICABLE DISEASES AND RELATED TIME-TRENDS

5.9. Asthma and allergic rhinitis

5.9.4. Risk factors

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5.9.4. Risk factors

 

Data show a significant increase in cases of allergic respiratory disease. In particular, rhinitis augment seems to be more relevant and is continuously increasing, whilst asthma, after an increment trend, seems currently passing through a stabilization phase. The genesis of this phenomenon is probably related to multiple genetic and environmental factors. Different hypothesis have been formulated, among which the reduction in the prevalence of infections in European countries that seems to be associated to an hyperactivation of the immune system against environmental allergens.

 

The evidence of a possible evolution from one pathology to another is the reason why, in accordance with ARIA guidelines, every patient with allergic rhinitis should undergo asthma assessment and vice versa. A particular attention must be paid to the diagnosis of allergic rhinitis, which is often underestimated by patients and under-diagnosed in all age rangesparticular care should be given to the paediatric population.

 

Numerous surveys on school-age children have shown increasing asthma prevalence with a less publicized but noticeable change in the male to female ratio. In order to confirm this change in the sex ratio, a Scottish study questionnaire survey was performed in 1989 (n=3,390), 1994 (n=4,047), 1999 (n=3,540) and 2004 (n=1,920) in school-children aged 9-11. Over these 15 years the male to female ratio (M:F) significantly narrowed for wheeze (1.34 to 0.98:1 P < 0.0002), asthma (1.74 to 1.02:1 P < 0.0001), eczema (1.42:1 to 0.81:1 P < 0.0001) and hay fever (1.46 to 0.93:1 P < 0.0001). The diagnosis of asthma in children with wheeze was more commonly made in boys in 1989: relative risk (RR) 1.32 (1.12, 1.56), even in those with accompanying eczema and/or hay fever RR 1.20 (0.99, 1.45). By 2004 this sex bias in diagnosis was no longer present, RR 1.01 (0.91, 1.12) for wheeze and 1.02 (0.85, 1.21) for those with wheeze and eczema and/or hay fever. From 1989 to 2004 no significant difference in sex distribution changes between older and younger children occurred, making secular trends in the onset of puberty in females an unlikely contributory factor. The disappearance of the bias to diagnose asthma in symptomatic males but not in females may be in part responsible for the narrowing of the sex ratio, but other factors such as those enhancing the expression of asthma and atopy in females may also be implicated (Osman et al, 2007).

 These findings have been confirmed by other studies. The European Respiratory Health Survey (ECRHS) in Sweden, Norway, Denmark, Iceland and Estonia found an incidence higher among females (2.9 cases.1000 person-yrs(-1)) than among males (1.5 cases.1000 person-yrs(-1)). (Torén et al, 2004).

 

 

Some environmental and occupational factors may determine and aggravate allergy and asthma-related symptoms. Studies such as the ISAAC keep bringing new information about the places where these conditions are progressively rising as lifestyle and environmental factors. The main determinants considered in primary prevention policies at the moment are:

 

1.      exposure to allergens and sensitization;

2.      cigarette smoking and tobacco environmental exposure;

3.      indoor and outdoor pollution;

4.      changes in dietary habits.

 

Asthmatic symptoms are more frequent in particular groups of workers: over 300 substances have been correlated to occupational asthma, whose symptoms are determined by the exposure to chemical or biologic agents at workplace (isocyanates, platinum or nickel salts, complex plants, animal derivatives). Occupational asthma is predominant in adulthood and professional sensitizers are estimated to determine about 1 in 10 cases of asthma in the working age. Occupations at high risk include: farming and agricultural work, painting, cleaning work and plastic manufacturing. The ECRHS-II study (The European Community Respiratory Health Survey-II 2002) investigated the role of exposure to substances in the workplace in new-onset asthma. 6837 participants from 13 countries who previously took part in the ECRHS (1990-95)( European Community Respiratory Health Survey 1994) and did not report asthma-related symptoms at that time were enrolled. A significant excess asthma risk was seen after exposure to substances known to cause occupational asthma (relative risk=1.6, 95% CI 1.1-2.3, P=0.017). Risks were higher for asthma defined by bronchial hyper-reactivity in addition to symptoms (2.4, 1.3-4.6, P=0.008). Among common occupations, a significant excess risk of asthma was seen for nursing (2.2, 1.3-4.0, P=0.007). Asthma risk was also increased in participants who reported an acute symptomatic inhalation event such as fire, mixing cleaning products, or chemical spills (RR=3.3, 95% CI 1.0-11.1, P=0.051). The population-attributable risk for adult asthma due to occupational exposures ranged from 10% to 25%, equivalent to an incidence of new-onset occupational asthma of 250-300 cases per million people per year.

 

The SCARPOL Study (Swiss Study on Childhood Allergy and Respiratory Symptoms with respect to Air Pollution and Climate) (Wüthrich, 2001) is based on a sample of 4470 children from 10 different areas; the prevalence of asthma (ever) for the whole sample was 9%, without differences between age groups. Farm children living in a rural area suffer less frequently from pollinosis (2.4%) and bronchial asthma (1.6%) than children (n = 966) with no direct contact to agriculture, but living in the same area (prevalence of hay-fever 18.3%, of asthma 9.1%).

 

These findings are confirmed by the results of another survey, the PARSIFAL study (Alfvén T et al, 2006). Growing up on a farm was found to have a protective effect: the adjusted odds ratio (OR) for current rhino-conjunctivitis symptoms was 0.50 (95% confidence interval (CI) 0.38-0.65) and 0.53 for allergic sensitization (95% CI 0.42-0.67) for farm children compared to their references.

 

Allergen exposure has been linked to the development of allergic sensitization to the specific allergen in children as well as in adults with occupational exposures. The relationship between allergen exposure and allergic sensitization is a debated issue and seems to be related to different factors, such as type of allergen, allergen doses, duration of exposure and maybe also an individual, genetic susceptibility. Some data have shown a positive correlation between the prevalence of sensitization and exposure to high levels of the epitope Dep p 1 of house dust mites (MAS study, Multicentric Allergy Study). For cat epithelium, this relationship is still unclear (Custovic, 2003; Simpson , 2005; Erwin2005). Exposure to house dust mite or cat allergen is, however, unlikely to contribute to the development of childhood asthma. In turn, pet keeping in the first year of life, particularly, dog keeping, has been inversely related to the development of wheeze and atopic illnesses. Several prospective birth cohort studies found a decreased prevalence of allergic diseases in children having daily contact with pets, in particular with cats and dogs, during early infancy. The protective effect might be attributable to allergen or other exposures associated to pet ownership (Fasce L, 2005), but may also be in part caused by the removal of pets in families with sensitized or symptomatic children or in families with a positive history for atopy at the time the child was born..  The European Community Respiratory Health Survey I showed that seven selected allergens (Dermatophagoides pteronissinus, cat grass, birch,olive pollen, Alternaria and Cladosporium) allow the indentification of almost all sensitized subjects in European Countries (Belgium, France, Iceland, Ireland, Italy, Norway, Spain, Swedem Netherlands, United Kingdom);  The addition of one local allergen  to the battery of tests increased the overall estimated prevalence by only 1% ( Bousquet, 2007)  The same study showed a substantial geographical variation in the prevalence of sensitization to each tested allergen and in the prevalence of sensitization to any allergen. Sensitization to D. Pteronyssinus, grass pollen and cat were usually the most prevalent (Bousquet, 2007)

 

Prevalence of both atopic sensitization and allergic symptoms depend also on geo-climatic conditions and on the distribution of the different aeroallergens. Many studies have reported the prevalence of sensitization using skin prick tests. However, comparisons between studies and between regions are difficult because the number and the type of allergens tested vary widely. The geographical variation of sensitization to environmental allergen as measured by skin tests was established using the European Community Health Respiratory Survey I data, (Bousquet, 2003). Adults aged 2044, living in 35 centres in 15 developed countries, underwent skin tests for allergy to nine common aeroallergens (i) Dermatophagoides pteronyssinus; (ii) timothy grass; (iii) cat; (iv) Cladosporium herbarium; (v) Alternaria alternata; (vi) birch; (vii) Olea europea; (viii) common ragweed; (ix) Parietaria judaica. The agesex standardized prevalence of sensitization was determined and centres with high and low prevalence of sensitization to each allergen and to any of the nine allergens were identified (Tables 5.9.4 to 5.9.6). The lowest sensitization prevalence was 17.1%, the median 36.8% and the highest 54.8%. Sensitization to D. pteronyssinus, grass pollen and cat were usually the most prevalent (median between centre 21.7%, 16.9% and 8.8%, respectively). Timothy grass sensitization was higher than that for any other pollen species. Moreover, this report shows that sensitization to Olea europea and P. judaica is higher in Southern Europe than in Northern Europe and sensitization to the silver birch is higher in Northern Europe than in Southern Europe. These patterns could be predicted by the preferred habitat of each species. Wide variations in the prevalence of sensitization to some allergens were also observed within some countries (e.g. olive in Spain). While this may be due to variations in exposure in some large countries (e.g. Spain), it is also likely that other factors may be important determinants of sensitization. The prevalence of ragweed pollen was low (except in the USA), but this was expected as none of the centres (except Portland) was located in an area with elevated ragweed pollen counts.

 

Table 5.9.4. Highest, median and lowest agesex standardized prevalence for sensitization to each allergen as assessed by skin tests.

 

Table 5.9.5. High or low prevalence of sensitization to each allergen by centre as assessed by skin tests

 

 

 

Centre

d1

e1

g6

m2

m6

t3

t9

w1

w21

Sensitized

Australia

  Melbourne

High

High

High

High

High

Belgium

  South Antwerp

Low

Low

Low

Low

  Antwerp City

High

High

Low

Low

Low

France

  Bordeaux

High

Low

High

Low

  Grenoble

High

Low

High

  Montpellier

Low

High

High

Low

High

High

  Paris

Low

Germany

  Erfurt

Low

Low

ND

High

ND

ND

ND

ND

  Hamburg

High

ND

High

High

ND

ND

ND

ND

Iceland

  Reykjavik

Low

Low

Low

Low

Low

Low

Low

Italy

  Pavia

Low

Low

Low

Low

Low

High

Low

  Turin

Low

High

  Verona

Low

Low

High

High

Ireland

  Dublin

High

Low

Low

New Zealand

  Christchurch

High

High

High

High

  Hawkes Bay

High

High

Low

High

  Wellington

High

High

High

High

Low

High

Norway

  Bergen

Low

Low

Low

High

Low

Low

Low

Low

Spain

  Albacete

Low

Low

Low

Low

Low

Low

High

Low

Low

  Barcelona

Low

Low

High

High

  Galdakao

Low

Low

Low

Low

Low

Low

Low

Low

Low

Low

  Huelva

Low

Low

Low

Low

Low

  Oviedo

Low

Low

Low

Low

Low

Low

Low

Low

Sweden

  Goteborg

Low

High

Low

High

Low

High

  Umea

Low

High

High

High

  Uppsala

Low

High

High

Low

High

Low

Switzerland

  Basel

Low

High

High

High

ND

ND

The Netherlands

  Bergen op Zoom

Low

Low

High

Low

Low

  Geleen

High

High

High

High

High

High

High

High

High

High

  Groningen

Low

Low

Low

Low

UK

  Caerphilly

High

Low

High

  Cambridge

High

High

  Ipswich

High

High

High

High

High

  Norwich

High

High

High

High

High

High

High

High

USA

  Portland

High

High

High

High

High

High

High

High

High

ND, not done (all nine allergens were not tested); d1, Dermatophagoides pteronyssinus; g6, grass; e1, cat; t3, birch; m6, Alternaria; t9, olive pollen; m2, Cladosporium; w21, Parietaria; w1, ragweed.

 

 

Table 5.9.6. Standardized (age, gender) prevalence of sensitization to nine allergens skin tested and standardized (age, gender) prevalence of sensitization each allergens skin tested

 

National data, considered separately, show different findings among European countries. The Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) (Wüthrich et al, 2001), for example, was carried out during 1991-1993 in eight Swiss areas with different environmental characteristics. The cross-sectional examination included 9651 adults, aged 18-60, who all participated in a detailed interview. In addition, in 8357 subjects, complete allergy skin and in-vitro tests were available. 11.1% suffered from current hay fever, 6.8% from asthma, 4.5% from atopic asthma. The prevalence of atopic sensitization (positive skin prick test to any of the tested inhalant allergens and/or positive Phadiatop as an in-vitro screening test for atopy) was 32.3%, with a higher prevalence in males (35.7%) than in females (28.8%). Skin sensitization was predominantly caused by grass pollen (12.7%), followed by house dust mite (8.9%), silver birch pollen (7.9%) and cat epithelia (3.8%).

A very recent study investigated the prevalence of atopy, asthma and their association with familiar and environmental factors among 1450 children aged 13- to 14- and living in Brescia, an industrialized town in the North of Italy (Duse et al, 2007). A modified version of the questionnaire adopted in the Italian Study of Respiratory Disorders in Childhood and Environment, which is an extended version of the ISAAC questionnaire, was used; ninety-nine children (10.2%) had a physician's diagnosis of asthma - 12.4% of the males and 8.0% of the females (P=0.03). Analysis by multiple logistic regression showed an inverse association between physician-diagnosed asthma and female sex (odds ratio, OR = 0.5); presence of relatives in the bedroom in initial years of life (OR = 0.6); attending day care (OR = 0.4) and infant school (OR = 0.4); a positive association with parental history of wheezing (OR = 2.5) and asthma (OR = 3.8); and the child's history of asthmatic bronchitis (OR = 31.9) and atopic eczema (OR = 3.8) in the first 2 years of life. The strength of the associations did not change when restricting the analysis to atopic asthma. In conclusion, atopy and clinical asthma among 13- to 14-yr-old adolescents seem to be significantly associated to some familial and environmental factors, providing further support for the hygiene hypothesis. Prevalence of atopy, but not of asthma, is high in this industrialized area. The strong association found between atopy and clinical asthma suggests that atopy may play a role in causing asthma in genetically predisposed children only.

 

In several studies it has been recently observed that children with a background of migration were less often affected by an atopic disease, than children from local families of low social status. In the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (Schlaud et al, 2007), for instance, information was collected on allergic diseases (asthma, atopic dermatitis, hay fever, allergic contact eczema) from 2003 to 2006 in a population-based sample of 17,641 0-to 17-year-olds, and blood samples were studied for specific IgE antibodies to 20 common allergens. An Italian study emphasized that Albanian migrants to Southern Italy (that responded to a questionnaire based on the ECRHS, underwent skin prick tests and serological assays) presented a low frequency of both sensitization and asthma (1.3%) and rhinitis (15.8%) symptoms, but that these increased with the time spent in Apulia (P=0.04 for hay-fever) (Ventura et al, 2004). A large cross-sectional study (SIDRIA II study, (Migliore et al, 2007) performed in 12 I Italian centres, showed that lifetime asthma and current wheeze were significantly less common among children born abroad than among children born in Italy (lifetime asthma: 5.4% and 9.7% respectively, P < 0.001; current wheeze: 5.2% and 6.9%, respectively, P = 0.04). Lower risks for lifetime asthma (prevalence odds ratio, POR = 0.39; 95% CI: 0.23-0.66) and current wheeze (POR = 0.72; 95% CI: 0.47-1.10) were found in children who had lived in Italy <5 years, while migrant children who had lived in Italy for 5 years or more had risks very similar to Italian children. Moreover, the prevalence of asthma symptoms increased with the numbers of years of living in Italy. These data suggest the importance of environmental factors and lifestyle in the development of both allergic sensitization and symptoms.

 

There is increasing awareness of the harmful effects of smoking in the EU. Tobacco exposure, in fact, is associated to a decline of lung function and, in particular, with a major severity and most frequent exacerbations of symptoms in asthmatic patients. However, the risk of developing allergic disease is still unclear (Landau Paediatr Respir Rev, 2008).

 

Outdoor air pollution aggravates respiratory allergies and is suspected of causing allergies. They are, indeed, more prevalent in large cities than in rural areas, and workers experiencing chronic exposure to gases, fumes, and biological and mineral dusts are particularly susceptible; but yet the prevalence of asthma and allergy does not correlate precisely with air pollution levels in different cities. The RAIAP project 1 (ec.europa.eu/research/quality-of-life/ka4/pdf/brochureka4_en.pdf) has investigated the role of qualitative differences in particulate air pollution at different locations in the different prevalence data of respiratory allergies in Europe. The partners collected  particulate samples from Lodz, Oslo, Rome, Amsterdam and a Dutch coastal location.The project focused on the role of physical and chemical composition of PM on release of cytokines of cells in vitro, on respiratory inflammation in vivo, and on adjuvant potency in allergy animal models. Coarse (2.5-10 microm) and fine (0.15-2.5 microm) particles were collected during the spring, summer and winter in Rome (I), Oslo (N), Lodz (PL), and Amsterdam (NL). Markers within the same model were often well correlated. Markers of inflammation in the in vitro and in vivo models also showed a high degree of correlation. In contrast, correlation between parameters in the different allergy models and between allergy and inflammation markers was generally poor. This suggests that various bioassays are needed to assess the potential hazard of PM. The present study also showed that by clustering chemical constituents of PM based on the overall response pattern in the bioassays, five distinct groups could be identified. The clusters of traffic, industrial combustion and/or incinerators (TICI), and combustion of black and brown coal/wood smoke (BBCW) were associated primarily with adjuvant activity for respiratory allergy, whereas clusters of crustal of material (CM) and sea spray (SS) are predominantly associated with measures for inflammation and acute toxicity. The cluster of secondary inorganic aerosol and long-range transport aerosol (SIALT) was exclusive associated to systemic allergy. The present study showed that biological effect of PM can be linked to one or more PM emission sources and that this linkage requires a wide range of bioassays.(Steerenberg PA 2006)

Fine ambient PM exerted significantly greater IgE adjuvant activity per unit mass than coarse PM. No significant differences were observed between locations or seasons. Substantial higher levels of specific elements of PM such as vanadium (V), nickel (Ni), zinc (Zn), ammonium (NH(4)), and sulfate (SO(4)) were present in the fine compared to coarse PM fractions. However, differences in the content of these elements among fine PM fractions did not reflect the variation in the levels of IgE anti-Ova. Still, when comparing all seasons overall, positive correlations were observed between V, Ni, and SO(4) and the allergen specific IgE levels. The PLN responses (weight and cell number) to Ova and ambient PM in combination were significantly higher than to Ova or PM alone. Still, the PLN assay appears not to be useful as a quantitative assay for the screening of allergy adjuvant activity since no correlation was observed between PLN responses and allergen specific IgE levels. In conclusion, fine ambient PM fractions were consistently found to increase the allergen-specific IgE responses more than the coarse ones. The finding is in agreement with the notion that traffic-related air pollution contributes to the disease burden in asthma and allergy, and points to fine and ultrafine ambient PM as the most important fractions in relation to allergic diseases (Alberg T 2009)

 

Also the indoor environment seems to play an important role. Warm homes with soft furnishings and carpeting tend to have high levels of allergy triggers, such as dust mites, pet fur, moulds, damp tobacco smoke and gas heater fumes. Contributors to indoor air pollution include ambient air pollution, dust, the inefficient burning of fuels for cooking and heating, household chemicals, furnishings wall and floor coverings. Furthermore, there are also suggestions that infants grown in a very hygienic environment are more allergy-prone in later life than those brought up in contact with dirt, animals and other children; early exposure to certain bacteria actually seems to have a protecting role against allergies, according to the so calledHygiene Hypothesis” (Wang, 2006; von Mutius, 2006; Heinrich et al, 2001).

 

Some health effects of air pollution have been linked to the presence of DNA-bound polycyclic aromatic hydrocarbons (PAH-DNA adducts) in exposed individuals. The EXPAH project (http://ec.europa.eu/research/environment/pdf/env_health_projects/air_pollution/ap-hepmeap.pdf) is testing the hypothesis that PAHs carried by airborne particles are the major source of genotoxicity in organic mixtures associated with air pollution. The project is focusing on populations in three European cities. It aims to measure exposures, collect information on lifestyle factors such as diet, and look for DNA adducts, biomarkers of DNA damage, susceptibility factors, and DNA modifications due to oxidative stress. Partners are developing an in vitro human cell model in which to study the genotoxicity of complex mixtures adsorbed onto airborne particles. The results will be used to assess the risk associated with air-pollution-linked exposure to PAHs.

 

Another project (Health effects of particles from motor engine exhaust and ambient air pollution – a European collaborative project) (ec.europa.eu/research/environment/pdf/env_health_projects/air_pollution/ap-hepmeap.pdf) is focusing on motor engine exhaust, in particular on the particulate matter (PM) it contains. In collaboration with an established European epidemiological study, partners are sampling and analysing ambient PM and freshly generated diesel and gasoline engine PM. They are screening the samples for bioactivity in various in vitro systems and on selected target cells. Provocation tests will then be carried out on healthy and more sensitive subjects, such as asthmatic and allergic individuals. Finally, epidemiologists and statisticians will relate the physico-chemical characteristics of the PM to the results of the various tests and to the epidemiological findings.