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Keywords:

  • air pollution;
  • allergic rhinitis;
  • indoor environment;
  • novel allergens;
  • psychologically stressful lifestyle;
  • severe and persistent symptoms

Abstract

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References

Most of today’s patients suffering from allergic rhinitis (AR) are sensitized to more than one trigger and suffer from persistent and moderate/severe symptoms, which severely impair their quality of life (QOL). The objective of this article was to review the data on the effect of increased air pollution, changes in indoor environment/lifestyle/affluence, exposure to new allergens and psychologically stressful lifestyles, as also to explore their potential in the development of this more ‘aggressive’ form of disease.

Increased fossil fuel-generated air pollution may increase the risk of allergic sensitization, airway responsiveness to allergens, and allergenicity and the bioavailability of airborne allergens. Changes in indoor environment/lifestyle/affluence appear to have led to more time being spent indoors and resulted in perennial exposure to indoor allergens, changes in sensitization patterns, and polysensitization to a variety of novel cross-reacting exotic food and pet allergens. Although evidence suggests an association between psychological stress and increased risk for atopy and allergic disease, further studies are required to demonstrate this unequivocally.

The more persistent and moderate/severe nature of the disease suggests a need for modification of current treatment strategies and advocacy of the use from the outset of agents, which are both efficacious and safe in managing severe and persistent AR symptoms and in improving the QOL of affected individuals.

Allergic rhinitis (AR) is a debilitating disease that currently affects about 20–30% of the population worldwide (1–3), with children aged 6–14 years being affected the most (1, 4, 5). Indeed, the recent International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three study indicated that children aged 6–7 years were more inclined to increased symptoms of AR than children aged 13–14 years (4).

Although the aetiology, pathophysiology and clinical manifestations of AR are similar in both adults and children (1, 3) and AR is generally classified as seasonal (SAR) or perennial (PAR) allergic rhinitis, based on the time and the nature of major allergen/s triggering the symptoms (1), several studies have demonstrated that most of AR patients have a mixed aetiology, involving sensitization to more than one trigger and manifestation of intermittent and persistent symptoms (6–9). Moreover, many AR patients suffer from moderate/severe symptoms of the disease (7, 10). Indeed, one recent study of over 3000 AR patients consulting general practitioners demonstrated that overall, 93% of the patients had a diagnosis of moderate-to-severe rhinitis and the remaining 7% a diagnosis of mild rhinitis (11). Furthermore, diagnosis of the disease based on the presence of intermittent or persistent symptoms showed that 41.9% of the patients had moderate/severe intermittent rhinitis and 51.2% of patients moderate/severe persistent rhinitis, compared with only 3.9% and 3.0% of the patients with mild intermittent and mild persistent rhinitis, respectively (11; Fig. 1). A greater severity of disease was also associated with greater impairments in QOL, sleep, daily activities and performance at work, and, thus, prompted the authors to suggest that the term moderate/severe should be replaced by the term severe (11).

image

Figure 1.  The percentage of patients, consulting a primary care doctor, suffering from mild or moderate–severe intermittent and persistent symptoms of allergic rhinitis [adapted from Bousquet et al. (11)].

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Despite the wealth of information available on the epidemiology and aetiology of AR, the precise reasons for the differences in the aetiology and the severity of AR in the modern age are neither well established nor studied. These are likely to be multifactorial, however, with an increasing body of evidence implicating environmental and lifestyle changes, such as air pollution, indoor environment/lifestyle/affluence, exposure to new allergens and a psychologically stressful lifestyle; as important risk factors (12, 13). The objective of this article was therefore, to review the currently available data on the effects of air pollution, indoor environment/lifestyle/affluence, exposure to new allergens and a psychologically stressful lifestyle, which might explain the more aggressive nature of the symptoms of AR in the modern age.

Effect of air pollution

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References

Although the role of air pollution in the development of allergic disease is not clear, several studies have demonstrated an association between increased air pollution and the increased risk of allergic sensitization and prevalence of rhinitis worldwide. Studies investigating the effect of pollution resulting from vehicle and industrial emissions have shown associations between increased pollution and increased risk/prevalence of AR rhinitis (14–16). Similarly, pollution resulting from the burning of refined fossil fuels (kerosene and gas) in the home has been shown to increase the risk/prevalence of allergic sensitization and symptoms of allergic disease (17, 18). Assessment of the individual pollutants responsible for the increased risk/prevalence of allergic sensitization and symptoms of allergic disease indicated that increased levels of nitrogen oxides (NOx), sulphur dioxide (SO2), ozone (O3), and particulates with aerodynamic diameter of 10 μm or less (PM10), may be important (14–18), although contradictory findings have been found for the NO2, O3 and PM10 levels in some large-scale studies in children (14, 15).

Several studies, however, have demonstrated that air pollution can increase the allergenicity and bioavailability of airborne pollen allergens, and thereby may promote sensitization and an exaggerated response to allergens in the nasal airways of AR patients. Early studies by Behrendt and colleagues (19) demonstrated that pollen grains collected from industrial regions polluted with high concentrations of organic substances were agglomerated with large numbers of airborne particles, which could lead to both morphological changes in the pollen surface and allergen, and, under appropriate conditions, result in the release of allergenic aerosols (20). Indeed, studies of birch, grass and mugwort pollen collected near roads with heavy traffic have shown that these pollens release significantly higher levels of eicosanoid-like substances than ‘nonpolluted’ pollen (21), thus suggesting a higher proinflammatory potential for these pollens. Similarly, Zinnia elegans pollen, a common flowering plant, collected from heavily polluted areas of central Tehran has been shown to release compounds that are significantly more potent at eliciting skin wheals reactions and increasing total blood immunoglobulin (Ig) E and peripheral blood eosinophilia in sensitized animals, than compounds released from pollen collected from nonpolluted areas (Table 1; 22). More recently, one study showed that exposure to high concentrations of NO2 (50 p.p.m.) and O3 (0.5 p.p.m.) led to significant damage and spontaneous release of pollen cytoplasmic granules (PCG) from Phleum pratense (Timothy grass) pollen, compared with exposure to control air (23). Contact with water led to further release of PCG, indicating that maximal disruption and release of allergen from pollen is likely to occur in the presence of both air pollution and water.

Table 1.   Effect of extracts control pollen and Zinnia elegans pollen collected from polluted and nonpolluted areas around Tehran on serum IgE, eosinophil counts and neutrophils counts in Z. elegans-sensitized guinea pigs [modified from Chegregani et al. (22)]
 ControlNonpollutedPolluted
  1. *P < 0.05 for polluted vs nonpolluted pollen extracts.

  2. IgE, immunoglobulin E.

Total IgE (ng/ml)9.5 ± 2.6104 ± 12.2168.2 ± 18.2*
Eosinophils (×104 cells/ml blood)5.5 ± 1.321.6 ± 3.958.7 ± 5.6*
Neutrophils (×104 cells/ml blood)3.5 ± 1.99.4 ± 2.89.3 ± 3.7

Recently, the impact of climate change on the growth of common ragweed was investigated in urban and rural areas in the USA (24). Ragweed was found to grow faster, flower earlier and produce significantly greater above-ground biomass and ragweed pollen in urban areas than in rural areas, perhaps as a consequence of greater temperatures and CO2 levels in urban areas than in rural areas.

Effect of indoor environment/lifestyle

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References

Improvements in the socioeconomic status of individuals have led to associated improvements in lifestyles and greatly modernized domestic and professional working conditions, and subsequently in individuals spending more time indoors. The increased amount of time spent indoors, however, is not without its disadvantages, because it appears that the emphasis may be swinging away from the outdoor environment towards indoor environment as a major cause of allergic disease (25).

There is increasing evidence of an association between the time spent indoors and changes in sensitization patterns to allergens. An American Lung Association Workshop Report on air pollution and health effects in urban areas (26) suggested that urban populations may be less frequently sensitized to pollens, but more frequently sensitized to cockroach and other indoor allergens. Moreover, poor indoor environments, such as those with mould, house dust mites (HDM), rodents or cockroaches could add to or exacerbate health inequalities resulting from air pollution (26). Indeed, some support for this hypothesis comes from a recent study, which demonstrated that exposure to a combination of 0.3 p.p.m. O3 and 75 μg/m3 total suspended particulate HDM matter was more significantly effective than either agent alone in decreasing PEF and increasing general irritation/discomfort in atopic subjects (27). Investigations of sensitization to the major indoor allergens have indicated that these are likely to include HDM, mould, pollen and animal dander (28, 29) and may be more prevalent among residents from urban areas compared with residents from rural areas (28). It appears that sensitization and allergy to mould has increased substantially over the years (30–32), likely as a consequence of increased dampness and poor ventilation caused by tight insulation of modern homes (33, 34). Although the medical effects of exposure to mould are varied -- including asthma, AR, allergic bronchopulmonary aspergillosis, sinusitis and hypersensitivity pneumonitis (35) -- evidence suggests that in some individuals, mould allergy is likely to manifest itself predominantly as symptoms of rhinitis and conjunctivitis (31, 34).

It is likely that sensitization and perennial exposure to the indoor allergens, many of which are perennial allergens, lead to persistent and severe symptoms of AR observed commonly in present-day AR patients. A population-based epidemiological study conducted in major European countries recently showed that 29% of all AR subjects were suffering from persistent symptoms and that the symptoms were more severe than in patients with intermittent AR (6). Similarly, a patient-based survey of over 3500 AR patients across Europe recently reported that almost two-thirds of these patients had persistent symptoms, which were present for at least 6 months of the year in about 50% of these patients and all year round in 15% of the patients (10). Moreover, at least one of these symptoms was severe enough to interfere with daytime activities and/or sleep in these patients (10).

Effect of exposure to new allergens

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References

In addition to exposure for greater periods and sensitization to the traditional indoor allergens, present-day patients are exposed, intentionally or unintentionally, to a variety of novel allergens, including pollen, food and exotic pet allergens (36–41). Evidence from Europe shows that ragweed and birch pollen allergen, which are not common or indigenous to specific regions/countries in Europe have become established as ‘invasive’ species in some countries and increased markedly over the last two to three decades (36–38), leading to allergic sensitization and the well-documented health outcomes associated with these allergens. Asero and colleagues (38) investigated the effects of exposure to these ‘new’ airborne allergens by reviewing the medical records of all monosensitized patients diagnosed with respiratory allergy in two allergy units in Italy over a period of 10 years (38). The authors showed that most of the patients allergic to ragweed and birch pollen were >30 years of age and had a history of the onset of respiratory allergy (rhinoconjunctivitis and/or asthma) at about 35 years of age (38). This finding is similar to the findings of the Copenhagen Allergy Study (42), and collectively they suggest that previously nonrhinitic individuals may also develop AR much later in life, perhaps as a consequence of environmental and/or lifestyle changes.

It is likely that exposure to a greater variety of allergens for longer periods results in polysensitization of the patients. Indeed, a survey of AR patients who were members of a patient organization in Europe has demonstrated that only 21% of all patients are sensitized to a single trigger, compared with 39% of patients sensitized to at least five triggers and 10–15% of patients sensitized to two to four triggers (10) (Fig. 2). Furthermore, plant/flowers, dust, animal, tobacco smoke and mould allergens were most common triggers in that order, with 77% and 74% of male and female patients, respectively, being sensitized to plants/flower allergens and 17% and 31%, respectively, being sensitized to mould allergens (10). Similarly, a retrospective analysis of the medical records of skin prick test (SPT) performed in paediatric AR patients aged 2–14 years at a children’s hospital in Singapore showed that 97% of the children were SPT-positive for HDMs, 20% for pets, 19% for moulds, 15% for pollens and 10% for kapok (10%) (43), suggesting that polysensitization can also occur early on in life.

image

Figure 2.  The percentage of allergic rhinitis patients sensitized to one or more triggers [pan-European survey of patients who were members of a patient organization; adapted from Valovirta in press (10)].

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The consequence of polysensitization may, at least in part, be the basis for the persistent and severe nature of AR symptoms being suffered by present-day AR patients. A study of 127 Olea europeae (olive) pollen-sensitive AR patients showed that 85% of the patients were sensitized to O. europeae as well as grass/cereals and weed pollens, but not perennial allergens (e.g. HDM), and had AR symptoms throughout the year (44). Moreover, about 60% of the patients who were monosensitized to only olive pollen had symptoms, to a great extent, outside the pollen season, suggesting that cross-reactivity with other nonpollen allergens may also play an important role in the expression of AR. Many studies have demonstrated cross-reactivity between grass/tree pollen and exotic food allergens, suggesting that such cross-reactivity may lead to the development of food allergy in pollinosis patients (39, 40, 45–47). These studies, however, raise the possibility that cross-reactivity between pollen and food allergens may also conversely lead to increased risk and manifestation of persistent and severe symptoms of rhinitis in food- and pollen-sensitized patients.

Similarly, polysensitization may also partly account for the greater expression of comorbid conditions in AR patients. A population-based study of nearly 500 adults tested by SPT for sensitization to 15 common aeroallergens and interviewed for respiratory symptoms and diseases demonstrated that polysensitization was common in subjects aged 26–39 years, with 42% of them reacting to at least four allergens (48). Moreover, the prevalence of asthma and AR or conjunctivitis increased significantly with an increasing number of positive SPT responses (48). A Swedish birth cohort study recently demonstrated that polysensitization to a number of different pollens and inhalant and food allergens determined the type of comorbid allergic disease, including AR, asthma, eczema and food allergy (49).

Effect of psychologically stressful lifestyle

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References

Some studies have indicated that there may be an association between psychological stress and increased risk or manifestation of allergic disease. One study conducted a postal survey, among 10 667 first-year university students in Finland, of the association between risk for asthma and atopic disease and stressful life events over a period of preceding 10 years or more (50). The authors showed that the risk of asthma and, particularly, allergic rhinoconjunctivitis was significantly increased 1.5- to 1.75-fold by the preceding or concomitant stressful life events, such as the death of mother, father or spouse or parental or personal conflicts (50). In contrast, no associations were found between stressful life events and atopic dermatitis. Similarly, evidence from other studies has suggested that stress-relieving activities may decrease allergic responses in atopic individuals. Kimata has demonstrated that listening to soothing music and selective kissing could decrease allergen-specific IgE and alleviate allergic symptoms (51, 52), whereas stress-inducing activities such as playing video games and constant ringing of the phone had the opposite effect of increasing allergen-specific IgE and allergic symptoms, in atopic dermatitis patients (53).

More recently, a review of the data linking the role/potential mechanisms of psychological stress to atopic disease indicated that the enhancement of neuroimmune responses, oxidative stress pathways, glucocorticoid resistance, intestinal dysbiosis and gene–environmental interactions may be important factors (54). The authors concluded that psychological stress may be conceptualized as a ‘social pollutant that may disrupt biological systems related to inflammation through mechanisms potentially overlapping with those altered by physical pollutants and toxicants’ (54).

Implications for management of today’s AR patients

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References

National and international treatment guidelines currently recommend allergen avoidance, pharmacotherapy and immunotherapy for the management of AR (55–57). This approach has also been proposed by the ARIA guidelines for the management of intermittent and persistent AR (1).

In view of the current findings for persistent and generally more severe symptoms of present-day AR patients, it may be that a different treatment approach needs to be adopted for the management of these individuals. In the first instance, it is likely that the patients would need to be tested for sensitization to a much larger number of allergens, including both traditional and more exotic triggers, in order that treatment can be optimized for individual patients. This will be particularly so for newly diagnosed patients and the traditional stepwise treatment policy may need to be reconsidered, especially for individuals who develop AR much later in life. Treatment with proven more effective newer medications may be essential from the outset. In this regard, some of the newer H1-antihistamines, evaluated in well-controlled long-term clinical trials for the treatment of persistent AR may be particularly useful, not only because of their high efficacy and safety in adults and children, but also because they improve the QOL of these individuals (58, 59). Additionally, it is possible that these agents might obviate the need for treatment with nasal steroids in the management of patients with more severe symptoms (60).

While allergen avoidance and immunotherapy are useful, these are nevertheless likely to be of limited value in view of the sensitization of patients to a large number of allergens, with a potential for cross-reactivity and collective activity. Moreover, patients are less likely to be compliant to these treatments due to the comparatively high costs directly associated with immunotherapy and any extensive changes/refurbishment to patients’ dwellings necessary for effective allergen avoidance.

In the context of the disease suffered by present-day AR patients, a proposed treatment course of action will be to use either the newer antihistamines or intranasal steroids as the preferred first choice drugs from the outset because of their established efficacy and safety. During periods of exacerbation, one may be combined with the other. Immunotherapy could be tried in predominantly monosensitized patients.

Conclusions

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References

It is clear that most of present-day AR patients experience symptoms that are both more severe and persistent in nature and these may have developed much later during adulthood, probably as a consequence of a westernized lifestyle, which, by virtue of increases in air pollution, the time spent indoors/lifestyle changes, exposure to both traditional and a variety of novel allergens and psychological stress associated with the lifestyle changes -- increases the risk of sensitization to a wider variety of allergens that are more allergenic and prevalent over the course of the entire year (Fig. 3). This has therapeutic implications and suggests that the currently recommended treatment policies may need to be modified accordingly. While agents that have proven efficacy and safety in long-term persistent, moderate-to-severe AR, and additionally improve the QOL of the affected individuals are undoubtedly going to be the drugs of choice in the management of AR, it is possible that in order to get maximal benefit these may need to be used right from the outset and maybe continuously. This may, in turn, lead to improved and concurrent management of comorbid allergic conditions and, therefore, also be a cost-effective treatment method.

image

Figure 3.  Schematic diagram of the putative factors influencing the severity and duration of symptoms of allergic rhinitis.

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References

  1. Top of page
  2. Abstract
  3. Effect of air pollution
  4. Effect of indoor environment/lifestyle
  5. Effect of exposure to new allergens
  6. Effect of psychologically stressful lifestyle
  7. Implications for management of today’s AR patients
  8. Conclusions
  9. References
  • 1
    Bousquet J, Van Cauwenberge P, Khaltaev N, ARIA Workshop Group. Allergic Rhinitis and its Impact on Asthma (ARIA). J Allergy Clin Immunol 2001;108(Suppl. 5):S147S333.
  • 2
    Gelfand EW, Plaut M, Washington T. Current trends in allergic reactions: a multidisciplinary approach to patient management. Clinician 2003;21:128.
  • 3
    Settipane RA, Lieberman P. Update on nonallergic rhinitis. Ann Allergy Asthma Immunol 2001;86:494507.
  • 4
    Asher MI, Montefort S, Bjorksten B et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006;368:733743.
  • 5
    Galassi C, De Sario M, Biggeri A et al. Changes in prevalence of asthma and allergies among children and adolescents in Italy: 1994-2002. Pediatrics 2006;117:3442.
  • 6
    Bauchau V, Durham SR. Epidemiological characterisation of the intermittent and persistent types of allergic rhinitis. Allergy 2005;60:350353.
  • 7
    Bousquet J, Annesi-Maesano I, Carat F, Leger D, Rugina M, Pribil C et al. Characteristics of intermittent and persistent allergic rhinitis: DREAMS study group. Clin Exp Allergy 2005;35:728732.
  • 8
    Ciprandi G, Cirillo I, Vizzaccaro A, Tosca M, Passalacqua G, Pallestrini E et al. Seasonal and perennial allergic rhinitis: is this classification adherent to real life? Allergy 2005;60:882887.
  • 9
    Van Hoecke H, Vastesaeger N, Dewulf L, Sys L, Van Cauwenberge P. Classification and management of allergic rhinitis patients in general practice during pollen season. Allergy 2006;61:705711.
  • 10
    Valovirta E. The voice of the patients: allergic rhinitis is not a trivial disease. Curr Opinion Allergy Immunol, in press.
  • 11
    Bousquet J, Neukirch F, Bousquet PJ, Gehano P, Klossek JM, Le Ga M et al. Severity and impairment of allergic rhinitis in patients consulting in primary care. J Allergy Clin Immunol 2006;117:158162.
  • 12
    Kaiser HB. Risk factors in allergy/asthma. Allergy Asthma Proc 2004;25:710.
  • 13
    Marshall GD. Internal and external environmental influences in allergic diseases. JAOA 2004;104(Suppl. 5):S1S6.
  • 14
    Hwang BF, Jaakkola JJ, Lee YL, Lin YC, Guo YL. Relation between air pollution and allergic rhinitis in Taiwanese schoolchildren. Respir Res 2006;7:2329.
  • 15
    Penard-Morand C, Charpin D, Raherison C, Kopferschmitt C, Caillaud D, Lavaud F et al. Long-term exposure to background air pollution related to respiratory and allergic health in schoolchildren. Clin Exp Allergy 2005;35:12791287.
  • 16
    Yu JH, Lue KH, Lu KH, Sun HL, Lin YH, Chou MC. The relationship of air pollution to the prevalence of allergic diseases in Taichung and Chu-Shan in 2002. J Microbiol Immunol Infect 2005;38:123126.
  • 17
    Venn AJ, Yemaneberhan H, Bekele Z, Lewis SA, Parry E, Britton J. Increased risk of allergy associated with the use of kerosene fuel in the home. Am J Respir Crit Care Med 2001;164:16601664.
  • 18
    Wong TW, Yu TS, Liu HJ, Wong AH. Household gas cooking: a risk factor for respiratory illnesses in preschool children. Arch Dis Child 2004;89:631636.
  • 19
    Behrendt H, Becker WM, Friedrichs KH, Darsow U, Tomingas R. Interaction between aeroallergens and airborne particulate matter. Int Arch Allergy Immunol 1992;99:425428.
  • 20
    Behrendt H, Ring J. A research strategy for the investigation of the influence of environmental pollutants on the development of allergic sensitization and disease. In: RingJ, BehrendtH, VielufD, editors. New trends in allergy IV. Berlin, Heidelberg: Springer-Verlag, 1997:5160.
  • 21
    Behrendt H, Kasche A, Ebner von Eschenbach C, Risse U, Huss-Marp J, Ring J. Secretion of proinflammatory eicosanoid-like substances precedes allergen release from pollen grains in the initiation of allergic sensitization. Int Arch Allergy Immunol 2001;124:121125.
  • 22
    Chehregani A, Majde A, Moin M, Gholami M, Ali Shariatzadeh M, Nassiri H. Increasing allergy potency of Zinnia pollen grains in polluted areas. Ecotoxicol Environ Safety 2004;58:267272.
  • 23
    Motta AC, Marliere M, Peltre G, Sterenberg PA, Lacroix G. Traffic-related air pollutants induce the release of allergen-containing cytoplasmic granules from grass pollen. Int Arch Allergy Immunol 2006;139:294298.
  • 24
    Ziska LH, Gebhard DE, Frenz DA, Faulkner S, Singer BD, Straka JG. Cities as harbingers of climate change: common ragweed, urbanization, and public health. J Allergy Clin Immunol 2003;111:290295.
  • 25
    Frew AJ. Advances in environmental and occupational diseases 2004. J Allergy Clin Immunol 2005;115:11971202.
  • 26
    American Lung Association. Urban air pollution and health inequalities: a workshop report. Environ Health Perspect 2001;109(Suppl. 3):357374.
  • 27
    Molhave L, Kjaergaard SK, Sisgaard T, Lebowitz M. Interaction between ozone and air borne particulate matter in office air. Indoor Air 2005;15:383392.
  • 28
    Bibi H, Shoseyov D, Feigenbaum D, Nir P, Shiachi R, Scharff S et al. Comparison of positive allergy skin tests among asthmatic children from rural and urban areas living within small geographic area. Ann Allergy Asthma Immunol 2002;88:416420.
  • 29
    Boulet LP, Turcotte H, Laprise C, Lavertu C, Bedard PM, Lavoie A et al. Comparative degree and type of sensitization to common indoor and outdoor allergens in subjects with allergic rhinitis and/or asthma. Clin Exp Allergy 1997;27:5259.
  • 30
    Bobbitt RC Jr, Crandall MS, Venkataraman A, Bernstein JA. Characterization of a population presenting with suspected mold-related health effects. Ann Allergy Asthma Immunol 2005;94:3944.
  • 31
    Gutarowska B, Wiszniewska M, Walusiak J, Piotrowska M, Palczynski C, Zakowska Z. Exposure to moulds in flats and the prevalence of allergic diseases -- preliminary study. Pol J Microbiol 2005;54(Suppl.):1320.
  • 32
    Simoni M, Lombardi E, Berti G, Rusconi F, La Grutta S, Piffer S et al. Effects of indoor exposures on respiratory and allergic disorders. Epidemiol Prev 2005;2(Suppl.):5761.
  • 33
    Jaakkola JJ, Hwang BF, Jaakkola N. Home dampness and molds, parental atopy, and asthma in childhood: a six-year population-based cohort study. Environ Health Perspect 2005;113:357361.
  • 34
    Jacob B, Ritz B, Gehring U, Koch A, Bischof W, Wichmann HE et al. Indoor exposure to molds and allergic sensitization. Environ Health Perspect 2002;110:647653.
  • 35
    Bush RK, Portnov JM, Saxon A, Terr AI, Wood RA. The medical effects of mold exposure. J Allergy Clin Immunol 2006;117:326333.
  • 36
    Dessaint F, Chauvel B, Bretagnolle F. Ragweed (Ambrosia artemisiifolia L.): expansion history of a biological pollutant in France. Médecine/Sciences 2005;21:207209.
  • 37
    Laaidi M, Laaidi K, Besancenot J-P, Thibaudon M. Ragweed in France: an invasive plant and its allergenic pollen. Ann Allergy Asthma Immunol 2003;91:195201.
  • 38
    Asero R. Birch and ragweed pollinosis north of Milan: a model to investigate the effects of exposure to ‘‘new’’ airborne allergens. Allergy 2002;57:10631066.
  • 39
    Bolhaar ST, Van Ree R, Ma Y, Bruijnzeel-Koomen CA, Vieths S, Hoffmann-Sommergruber K et al. Severe allergy to sharon fruit caused by birch pollen. Int Arch Allergy Immunol 2005;136:4552.
  • 40
    Bolhaar ST, Ree R, Bruijnzeel-Koomen CA, Knulst AC, Zuidmeer L. Allergy to jackfruit: a novel example of Bet v 1-related food allergy. Allergy 2004;59:11871192.
  • 41
    San Miguel-Moncín MM, Pineda F, Río C, Alonso R, Tella R, Cisteró-Bahima A. Exotic pets are new allergenic sources: allergy to iguana. J Investig Allergol Clin Immunol 2006;16:212213.
  • 42
    Linneberg A, Petersen J, Nielsen NH, Madsen F, Frølund L, Dirksen A et al. The relationship of alcohol consumption to total immunoglobulin E and the development of immunoglobulin E sensitization: the Copenhagen Allergy Study. Clin Exp Allergy 2003;33:192198.
  • 43
    Kidon MI, See Y, Goh A, Chay OM, Balakrishnan A. Aeroallergen sensitization in pediatric allergic rhinitis in Singapore: is air-conditioning a factor in the tropics? Pediatr Allergy Immunol 2004;15:340343.
  • 44
    Kirmaz C, Yuksel H, Bayrak P, Yilmaz O. Symptoms of the olive pollen allergy: do they really occur only in the pollination season? J Investig Allergol Clin Immunol 2005;15:140145.
  • 45
    Mittag D, Akkerdaas J, Ballmer-Weber BK, Vogel L, Wensing M, Becker WM et al. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol 2004;114:14101417.
  • 46
    Mittag D, Vieths S, Vogel L, Wagner-Loew D, Starke A, Hunziker P et al. Birch pollen-related food allergy to legumes: identification and characterization of the Bet v 1 homologue in mungbean (Vigna radiata), Vig r 1. Clin Exp Allergy 2005;35:10491055.
  • 47
    Ricci G, Righetti F, Menna G, Bellini F, Miniaci A, Masi M. Relationship between Bet v 1 and Bet v 2 specific IgE and food allergy in children with grass pollen respiratory allergy. Mol Immunol 2005;42:12511257.
  • 48
    Pallasaho P, Ronmark E, Haahtela T, Sovijarvi AR, Lundback B. Degree and clinical relevance of sensitization to common allergens among adults: a population study in Helsinki, Finland. Clin Exp Allergy 2006;36:503509.
  • 49
    Ghunaim N, Wickman M, Almqvist C, Soderstrom L, Ahlstedt S, Van Hage M. Sensitization to different pollens and allergic disease in 4-year-old Swedish children. Clin Exp Allergy 2006;36:722727.
  • 50
    Kilpelainen M, Koskenvuo M, Helenius H, Terho EO. Stressful life events promote the manifestation of asthma and atopic diseases. Clin Exp Allergy 2002;32:256263.
  • 51
    Kimata H. Listening to mozart reduces allergic skin wheal responses and in vitro allergen-specific IgE production in atopic dermatitis patients with latex allergy. Behav Med 2003;29:1519.
  • 52
    Kimata H. Kissing selectively decreases allergen-specific IgE production in atopic patients. J Psychosom Res 2006;60:545547.
  • 53
    Kimata H. Enhancement of allergic skin wheal responses in patients with atopic eczema/dermatitis syndrome by playing video games or by a frequently ringing mobile phone. Eur J Clin Invest 2003;33:513517.
  • 54
    Wright RJ, Cohen RT, Cohen S. The impact of stress on the development and expression of atopy. Curr Opin Allergy Clin immunol 2005;5:2329.
  • 55
    Van Cauwenberge P, Bachert C, Passalacqua G et al. Consensus statement on the treatment of allergic rhinitis. Allergy 2000;55:116134.
  • 56
    Dykewicz MS, Fineman S, Skoner DP et al. Diagnosis and management of rhinitis: complete guidelines of the joint task force on practice parameters in allergy, asthma and immunology. Ann Allergy Asthma Immunol 1998;81:478518.
  • 57
    International Rhinitis Management Working Group. International Consensus Report on the diagnosis and management of rhinitis. Allergy 1994;49(Suppl. 9):534.
  • 58
    Bachert C. Levocetirizine: a modern H1-antihistamine for the treatment of allergic rhinitis. Expert Rev Clin Immunol 2005;1:495510.
  • 59
    Canonica GW, Bousquet J, Van Hammee G, Bachert C, Durham SR, Klimek L et al. Levocetirizine improves health-related quality of life and health status in persistent allergic rhinitis. Respir Med 2006;100:17061715.
  • 60
    Mosges R. On the benefit of breaking the rules. Curr Opin Allergy Clin Immunol 2005;5:211213.