The Journal of Allergy and Clinical Immunology
Volume 115, Issue 6 , Pages 1197-1202, June 2005

Advances in environmental and occupational diseases 2004

  • Anthony J. Frew, MD, FRCP, FAAAAI

      Affiliations

    • Corresponding Author InformationReprint requests: Anthony J. Frew, MD, FRCP, FAAAAI, AIR (Mailpoint 810), Southampton General Hospital, Southampton SO16 6YD, United Kingdom.

From the Allergy and Inflammation Research Group, Infection, Inflammation and Repair Division, School of Medicine, University of Southampton

Received 3 March 2005; received in revised form 5 March 2005; accepted 7 March 2005.

Southampton, United Kingdom

Article Outline

2004 was another good year for publications on environmental and occupational disorders in our journal. The major focus is clearly on the environment and particularly on environmental risk factors for sensitization and asthma. There is a growing consensus that exposure to pets is good, provided there is enough of it. Low levels enhance sensitization, and higher levels protect against the consequences of that sensitization. Following on from previous work on cockroaches, we now see allergy to feral mice as an emergent problem—at least we now have the tools to study this properly. Emphasis seems to be swinging away from the outdoor environment as a cause of allergic disease and toward the indoor environment, which is, after all, where most of us spend most of our lives. New techniques for studying isocyanate allergy might kindle a revival of interest in the mechanisms of occupational asthma caused by low-molecular-weight compounds. But for all types of occupational allergy, prevention remains key, and it is good to see that comprehensive programs of allergen reduction can pay off in reduced rates of latex allergy in health care workers. Further work in the area of recombinant allergens is welcome but needs soon to be translated into new diagnostic and therapeutic strategies. This sector of allergy research remains vibrant, and the editors will continue to welcome outstanding contributions in this area.

Key words: Environment, allergens, pets, mice, endotoxin, latex, risk factors, air pollution

Abbreviations used: HDI, Hexamethylene diisocyanate, LBP, LPS-binding protein

 

2004 was another good year for published research in the Journal of Allergy and Clinical Immunology on environmental and occupational disorders. When we look back in 10 years' time, I think it is fair to say that we will regard this period as something of a watershed because it has witnessed a fundamental change in our views about allergen exposure. Whereas previously we tended to regard the link between allergen exposure and disease as unidirectional, we are now realizing that appropriate levels of allergen exposure can be protective. Therefore although high levels of allergen exposure will undoubtedly trigger symptoms in the sensitized subject, too little exposure might significantly increase the chances of persons becoming exposed in the first place.

This theme was reflected in our pages in 2004, with several articles addressing the relationship between early childhood exposure to allergens and the associated risk of sensitization. As well as the usual domestic animals (cats and dogs), our articles also covered exposure to cockroaches and mice. Other themes covered within environmental and occupational disorders included the identification of new major allergens in plane trees and Chenopodium species and a novel method for producing isocyanate-albumin conjugates that might be more relevant for clinical investigation of suspected occupational asthma. The only disappointment in this year's articles is a relative paucity of work on occupational allergy and asthma. Perhaps occupational hygiene is improving and occupational allergies are becoming less of a problem than they used to be. If true, this would, of course, be a good thing, but occupational allergies do offer an interesting and important opportunity to study the development of allergy in adults, and it would be a pity if this area is being neglected. The editors hope to see more submissions on occupational and environmental allergy during 2005, but for the time being, we hope that this review of our environmental and occupational disorder articles for 2004 is of interest to you.

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Risk factors for allergic sensitization and disease 

There is now a general consensus that the increasing trends in allergic disease reflect a complex gene-environment interaction. Although there is still a lot of interest in the genetic basis of allergic disease, early opportunities to intervene in the allergy epidemic are likely to come from a better understanding of the environmental factors rather than trying to manipulate the gene pool or develop magic bullets based on genetic analysis. In a general review of the area, von Mutius1 outlined the general principles of studying these complex interactions and gave us a gentle nudge in the direction of the role of innate immunity as a potential explanation of the fascinating findings of decreased risks of allergy in farming communities in central Europe. We know that children with atopic parents are at increased risk for allergies, although of course the family home represents a common environment as well. In a long-term study of 428 children in Michigan, Johnson et al2 found that parental history was an important determinant of the relationship between bedroom dust mite levels and the risk of allergy development.

Over the last few years, there has been considerable interest in the possible role of molds and fungi in the causation of asthma and related diseases. Many lawyers have made a specialized practice out of this, and there is an ongoing controversy about whether this should really be regarded as allergic disease or some form of fungal toxic disease. O'Connor et al3 reported on the prevalence of mold sensitivity in children with asthma in 7 communities in the United States and measured the concentrations of airborne fungi within and outside their homes. In general, the airborne fungi that they found indoors were similar to those found outdoors, and the similarities between the various communities were more striking than the differences between them. Factors that increased the relative concentration of fungi in indoor air versus outdoor air included dampness, cockroach infestation, and keeping a cat. Portnoy et al4 reported on sampling techniques for looking at indoor fungi concentrations. In their review they highlighted the problem of variable techniques for assessing fungal load and the consequences of this variability on the interpretation of epidemiologic studies. Experienced laboratories clearly provide better data than those with more limited experience, and there is an obvious need for adequate quality control before clinical decisions are made on the basis of such measurements. Portnoy et al4 set out a range of parameters that should be used for reporting results of fungal surveys and suggest that harmonization between studies is probably more important than the absolute number of studies performed in this area.

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Pet ownership 

Five studies reported on the relationship of pet ownership to atopy and asthma. Arbes et al5 analyzed data from the National Survey of Lead and Allergens in Housing, which looked at 831 US homes and analyzed the dust samples from the bed, bedroom floor, living room floor, and living room sofa. Both dog and cat allergens were present in significant quantities in all homes studied. Levels associated with an increased risk of allergic sensitization were found even in homes without pets, presumably because pet allergens were transported into the homes on clothing. The implication is that it is impossible to avoid dog and cat allergens, even if living without such pets does lead to a lower local level of exposure. Gern et al6 found that exposure to dogs was associated with a reduced risk of allergic sensitization and atopic dermatitis. This risk was further reduced if children had a particular genotype of the CD14 gene. Because CD14 encodes receptors for endotoxin, it suggests that the beneficial effect of exposure to dogs is mediated through their ability to, for example, increase exposure to LPS. These data support the general proposition that exposure to pets in early infancy might be protective against atopy. Conversely, a study of risk factors associated with asthma and allergic sensitization in Kuwait found very low levels of allergens and a very low frequency of pet ownership in this community. Indeed, only 4% of homes had a cat, and 1.5% of homes had a dog. Within this community, the risk of sensitization to cats was significantly higher among those who owned cats. Moreover, despite this relatively low exposure to the allergens of domestic animals, the pattern of childhood asthma in Kuwait was similar to that described in western communities; that is, there is a strong association between sensitization and asthma.7 In an Australian study cat ownership before the age of 18 years was found to protect against the development of atopy and asthma in adulthood. These health outcomes were assessed at a mean age of 28.5 years.8 Given that exposure to domestic animal allergens seems to decrease the risk of sensitization but is also associated with an increased risk of symptoms in those who are sensitized, there is some interest in mechanisms of reducing allergen exposure in public places, including school classrooms. An intriguing study from Sweden suggests that levels of airborne cat allergen can be reduced through simple allergen avoidance measures at school, either by using school uniforms or bans on pet ownership within selected classes. Both of these methods are equally efficient, but the effect on clinical symptoms and long-term outcomes remains to be clarified.9

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Mouse allergens 

It has been known for some time that laboratory animals can cause sensitization and asthma, but the role of mouse allergens in conventional asthma is less clear. Four articles in last year's journal addressed this issue. Two of these were technical, describing assays for mouse allergens in dust samples.10, 11 Time will tell whether polyclonal ELISAs10 or assays for recombinant major allergens11 are optimal for this type of approach, but it is helpful to know that the technologies are now well developed for us to address whether mouse allergens are clinically important in the community. The other 2 studies addressed the prevalence of mouse allergens in US homes. Cohn et al12 found detectable levels of mouse allergens in 82% of US homes, with particularly high rates in kitchen floor dust. Increased concentrations were also observed in high-rise apartments, mobile homes, older homes, and low-income homes. The levels of allergen in US homes were high enough to be likely to cause clinical symptoms. The other study looked at suburban middle-class asthmatic children and found that these were commonly exposed to mouse allergens.13 Interestingly, positive skin test responses to dog allergens were a risk factor for mouse skin test sensitivity, perhaps suggesting that the presence of a dog made it less likely that there was a cat around to kill the mice. Perhaps Tom and Jerry got it right!

Environmental control remains a viable means of controlling allergic disease, despite a number of studies suggesting that allergy might not be quite as important in maintaining the disease as it is in providing a risk factor for development of the disease. Cabana et al14 found that many families were taking environmental actions that were not consistent with current guidelines. Many of these were unlikely to be beneficial, given the complex nature of allergy and its risk factors. Cabana et al14 recommend that improved awareness of recognized methods might help families to be more effective in their approach to allergen avoidance. A multipronged approach to cockroach control can reduce both cockroach numbers and cockroach allergen levels in inner-city homes.15 This article addressed whether the initial reductions achieved within 6 months can be maintained out to 12 months with simple application of insecticides. In contrast to earlier studies, it transpired that the use of insecticides can produce allergen concentrations, even though previous studies have indicated that insecticides alone are ineffective. Recent controversies regarding the effectiveness of house dust mite avoidance were addressed in a study by van den Bemt et al.16 On the basis of the premise that persons spend about one third of their lives in bed and that bedding conditions are ideal for house dust mite growth, it is attractive to consider that mite allergen–impermeable bed covers might be effective in controlling mite-sensitive asthma. There is no doubt that such covers can reduce house dust mite allergen levels in mattresses or, more accurately, on mattresses. Intervention with such covers has been shown to be effective in terms of peak flow, although this particular study had such low baseline levels of symptoms that no improvement could be observed.16

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Outdoor environment 

There is considerable interest in the role of the outdoor environment in the causation and exacerbation of asthma. Nobody is really sure whether outdoor allergens are important in triggering episodes of asthma or hospitalization. Some people believe that allergens are important as a risk factor for the development of asthma but might not play a particularly important part in episodes of asthma once the disease is established. We already know that viral infections are a key trigger for episodes of asthma,17 but allergens can also play a role.18 Dales et al18 reported a daily time series analysis of the association between changes in aeroallergens and daily rates of hospitalization for asthma over a 7-year period in the principal cities of Canada. After accounting for the independent effects of trees and ozone, there was a positive relationship between concentrations of molds, weeds, and grasses on the rate of hospitalization for asthma in these cities. This suggests that airborne allergens are an important cause of asthma morbidity in Canada and that there might be some synergistic effect of ozone and airborne allergens.18

The effect of air pollution on respiratory health is a concern for patients, doctors, and policy makers. Most people are aware from media reports that air pollution can adversely affect respiratory health, but the evidence for a precise mechanism is rather limited. Bernstein et al19 provided a useful review of the health effects of air pollution covering both gaseous and particulate pollutants and their relationship to airways inflammation. By taking a synoptic view, they have been able to give us a useful summary of the possible mechanisms of pollutant-associated adverse health effects that include the direct effect on airways inflammation, oxidative stress generated by transition metals and organic chemicals, covalent modification of intracellular proteins, and direct effects of other biologic compounds, such as endotoxin and glucans, which might have effects on the innate immune system and thereby influence airways inflammation. Other possible mechanisms include direct effects on the autonomic nervous system, perhaps explaining some of the cardiac toxicity and issues surrounding heart rate variability or alternative effects on coagulation, which might explain the increased risk of acute cardiovascular events. Particles can also serve as vectors for allergenic material or as adjuvants, altering the way that the immune system views allergenic particles. Allergists are particularly likely to be consulted by patients asking for information on this area, and although the causes of pollution are not within our direct sphere of influence, we can continue to give our patients the information they need, and we can also keep air pollution on the policy-makers' agenda through our interactions as patient advocates and members of larger health organizations and political structures.19 At the same time, we need to be careful not to overemphasize air pollution. Rabinovitch et al20 reported a school-based study of children with difficult-to-control asthma in Denver, Colorado. These children were followed over 3 consecutive winters to look at the association between gaseous pollutants and exacerbations. Some links were found between ozone levels and daytime symptoms, but other Environmental Protection Agency criteria air pollutants did not seem to be linked to any particular pattern of asthma worsening.20 These findings are consistent with previous studies in Denver, although other large-scale time-series studies from elsewhere in the United States and Europe have suggested that there are associations, at least at the population level. Achieving policy changes in relation to air pollution will depend on demonstrating that there is a significant benefit to be achieved by tackling air pollution. Whatever we might believe about greenhouse gas emissions, health effects of pollution play much more powerfully at the ballot box and therefore have a greater effect on policy makers. However, if we want to make such claims, we have to provide concrete evidence and an analysis of the studies that are available if we are to avoid accusations of special pleading.

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Occupational allergies 

Relatively few articles addressed occupational allergy last year. We had one article on isocyanates and 4 on various aspects of latex allergy. Wisnewski et al21 developed a new method for creating conjugates of hexamethylene diisocyanate (HDI) with human albumin. The rationale for the work is that previous studies have found it difficult to find appropriate materials to assess sensitization to isocyanates. This means that many patients with suspected isocyanate-induced asthma end up being challenged in a simulated workplace exposure rather than assessed by means of laboratory tests. This is a particular problem with HDI, which is much less volatile than other isocyanates. The novel HDI-albumin conjugates were used in serologic assays that demonstrated a clear link between HDI exposure and the IgG titer for HDI-albumin conjugates. Special IgE was also detectable in 6 of 11 patients with isocyanate-induced asthma compared with only 3 of 203 exposed health workers. This method requires validation in other groups of workers but does suggest that isocyanate-induced asthma might in fact be more IgE dependent than has previously been thought. It also offers a realistic prospect of carrying out surveys of sensitization in workplaces with isocyanates. Similar conjugates for other isocyanates would be a useful way to go in terms of validating this approach.

For many years, we have been concerned about the increasing prevalence of latex allergy, both in health care workers and in the general public. Some encouraging news was provided by Allmers et al,22 who reported a decreasing incidence of occupational contact urticaria associated with natural rubber latex allergy in German health care workers. Powdered latex gloves were banned in Germany in 1998, and since then, there has been an 80% reduction in the incidence of suspected cases of occupational latex allergy. Interestingly, only 68% of these cases were identified as occupationally caused, with the remaining 32% presumably reflecting exposure elsewhere, perhaps as a member of the general public. This study is very welcome evidence that intervention through occupational hygiene can lead to a reduction in an important clinical problem. We now need to see whether we can achieve similar reductions in the incidence of latex allergy in the general population. This is a much more difficult group to study, and most surveys tend to depend on presentation rates to clinics and allergy services. But for the time being, we now have pretty clear evidence that avoiding the use of powdered gloves will have a very beneficial effect on the incidence of latex allergy. Although powdered gloves should probably be relegated to the history books, there is some useful information from Brown et al23 indicating that the allergenic particles on powdered gloves are different when one compares surgical and examination gloves. Surgical gloves had allergenic particles that were largely greater than 10 μm in diameter, whereas powdered examination gloves released much more total latex allergen, and 68% of the particles were in the respirable range (2.5-10 μm). Altogether, particles in this size range carry 56% of the airborne latex allergen. The implication is that powdered surgical gloves are probably less important for inhalant allergies to latex compared with examination gloves. This supports the practice of eliminating powdered examination gloves but not necessarily focusing so much on removing powdered surgical gloves.

A separate study looked at the potential of latex gloves to leach out allergenic proteins. The overall allergenic potential of the gloves was assessed with an IgE-inhibition assay. This demonstrated that the 2 allergens Hev b 5 and Hev b 13 were the best markers of overall allergenicity of the gloves. This approach logically means that you could use measurement of the available allergens to predict the potential of any given batch of gloves to be allergenic. This will be important as we now move forward to try and get on top of the residual problem that remains with nonpowdered gloves.24

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Endotoxin 

In a mouse model of latex allergy, Howell et al25 reported that coexposure of latex with endotoxin (LPS) decreased the specific IgE response to latex but increased airways hyperreactivity in a nonspecific manner. They suggest that because significant levels of endotoxin have been found in latex gloves, there might be an interaction between the endotoxin and the latex allergens that affects both the likelihood of becoming sensitized to latex and perhaps the downstream consequences of the sensitization. This study is of course interesting in relation to the role of endotoxin in triggering allergic disease and underlines the importance of knowing the rest of the environmental context when one is looking at relationships between exposure to individual allergens and the likelihood of becoming sensitized. However, it is not clear how one could take this forward to modify the gloves and reduce the risk of sensitization. I suspect that adding endotoxin to the latex products would not necessarily meet with enthusiasm from the regulators. In another animal model Brass et al26 studied mice deficient in the LPS-binding protein (LBP) and found that there were substantially reduced concentrations of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the LBP–deficient mice compared with concentrations in their wild-type control animals. Submucosal cellular proliferation, airways thickening, and TGF-β secretion were also reduced. On one level it is not surprising that the effect of LPS is reduced in mice that have no protein to bind it. At the same time, it does rather suggest that the LBP molecule is a critical component of the response to LPS and cannot be bypassed by binding to CD14 or other components of the LPS signaling complex. LBP is a glycoprotein that binds the lipid A portion of endotoxin and appears to increase the affinity of LPS to CD14. The downstream cellular consequences are perhaps predictable, but it would be very interesting to take these mice and to look at them in relation to other proallergic stimuli. This might allow us to dissect out whether the endotoxin signal is an important part of generating the asthma-like process seen in a variety of animal models. In an accompanying editorial, Bufe and Holst27 suggest that the LBP might be a target molecule for the treatment of allergy and asthma. Clearly, there are 2 separate questions here. The first is whether the role as a transduction molecule can be interrupted by a suitable antagonist. This would deal with responses to endotoxin but would not necessarily be effective in other forms of asthma, in which endotoxin is not so important. Moving forward to use LBP as a target for general allergy and asthma would require a demonstration that LBP was serving as a gatekeeper for other downstream processes that came into play after other triggers apart from LPS.

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Allergens 

Identification of major allergens remains a popular topic, although there is now a priority to move forward and make use of all the information that we have gained to develop novel diagnostic and therapeutic agents. Ibarrola et al28 identified a major allergen of the plane tree Platanus acerifolia. Planes are common trees throughout western cities, partly because they provide excellent summer shade and are visually pleasing. They also can be pollarded regularly, allowing them to remain functional within the confined street space. Moreover, they are relatively resistant to air pollution and do not attack underground water pipes and sewage systems as much as some other trees. The pollination period for plane trees is similar to that for other trees, and therefore its contribution to seasonal allergic rhinoconjunctivitis is sometimes overlooked. Identification of the major allergen, a polygalacturonase, as a new major allergen will allow persons to move forward and develop specialized diagnostic agents and perhaps therapeutic agents to treat tree pollen allergy. Pla a 2 represented about 52% of the total IgE-binding capacity of the plane tree pollen extracts, indicating that it is indeed a major allergen. Related proteins have been found in a number of fruits and nuts, including peach and kiwi.29

The other article reporting on novel allergens described 2 relevant allergens of Chenopodium album pollens.30 Chenopodium species is a perennial plant that has been reported as being responsible for rhinitis in a variety of arid areas, including the central United States, southern Canada, and central and southern Europe. It has been suggested that allergy to Chenopodium species might have been increased by a variety of industrial activities that might have influenced the prevalence of the weed or perhaps its ability to shed large amounts of pollen. Two allergens were described, one of which is a profilin and the other a polcalcin. The existence of these allergenic proteins has been known for some time, but the article reports on their molecular characterization and nucleotide sequences. When combined together, these 2 allergens inhibited about 50% of the IgE binding to whole chenopod pollen extract. Serologically, there is clearly a large overlap between these 2 proteins and the equivalent proteins from olive. This suggests that Chenopodium species is probably an important contributor to the symptoms experienced by patients with olive pollen allergy, a common and important problem throughout the Mediterranean.

Ultimately, the characterization and sequencing of major allergens should lead to an improvement in the consistency and safety of diagnostic and therapeutic allergen products. However, it has not always been straightforward to get soluble and correctly folded proteins, even if one knows the DNA sequence. Van Oort et al31 describe the cloning and expressing of recombinant variants of Dactylis glomerata pollen. In parallel, they investigated whether an efficient purification protocol for the natural group 1 allergens might be a more practical way of generating purified material for immunotherapy. Purification of the natural allergen Dac g 1 revealed at least 3 variants with molecular weights of 33, 30, and 20 kd. The low- and intermediate-size molecules were not well recognized with sandwich ELISAs or competitive RIAs but had similar biologic activity in other assays. These results suggest that purification of the natural variants might be a more realistic approach than trying to achieve glycosylation of recombinant material when one does not really know precisely which amino acids are N- or O-glycosylated. Whichever method proves most efficient, it is obviously desirable that we have allergenic preparations that have the appropriate IgE-binding properties and T-cell epitopes required for their use in diagnostic and therapeutic studies.

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Conclusions 

2004 was another good year for publications on environmental and occupational disorders in our journal. The major focus is clearly on the environment and particularly on environmental risk factors for sensitization and asthma. There is a growing consensus that exposure to pets is good, provided there is enough of it. Low levels enhance sensitization, and higher levels protect against the consequences of that sensitization. Following on from previous work on cockroaches, we now see allergy to feral mice as an emergent problem—at least we now have the tools to study this properly. Emphasis seems to be swinging away from the outdoor environment as a cause of allergic disease and toward the indoor environment, which is, after all, where most of us spend most of our lives. New techniques for studying isocyanate allergy might kindle a revival of interest in the mechanisms of occupational asthma caused by low-molecular-weight compounds. But for all types of occupational allergy, prevention remains key, and it is good to see that comprehensive programs of allergen reduction can pay off in reduced rates of latex allergy in health care workers. Further work in the area of recombinant allergens is welcome but needs soon to be translated into new diagnostic and therapeutic strategies. This sector of allergy research remains vibrant, and the editors will continue to welcome outstanding contributions in this area.

Key advances in environmental and occupational disorders, 2004

A call should be made for standardization of mold allergen assessments in research studies.

Exposure to pets is protective, provided there is enough of it.
•Low levels enhance sensitization.

•Higher levels protect against the consequences of that sensitization.



Allergy to mice might be more important than previously realized.

Many families take inappropriate action to try to control allergen exposure.

Novel HDI-albumin conjugates for research might rekindle interest in the mechanisms of isocyanate-induced asthma.

Latex allergy prevention is effective in reducing rates of latex allergy in health care workers.

Endotoxin protects against sensitization to latex.

New major allergens have been identified from plane tree and Chenopodium species.

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References 

  1. von Mutius E. Influences in allergy: epidemiology and the environment. J Allergy Clin Immunol. 2004;113:373–379
  2. Cole Johnson C, Ownby DR, Havstad SL, Peterson EL. Family history, dust mite exposure in early childhood, and risk for pediatric atopy and asthma. J Allergy Clin Immunol. 2004;114:105–110
  3. O'Connor GT, Walter M, Mitchell H, Kattan M, Morgan WJ, Gruchalla RS, et al. Airborne fungi in the homes of children with asthma in low-income urban communities: the Inner-City Asthma Study. J Allergy Clin Immunol. 2004;114:599–606
  4. Portnoy JM, Barnes CS, Kennedy K. Sampling for indoor fungi. J Allergy Clin Immunol. 2004;113:189–199
  5. Arbes SJ, Cohn RD, Yin M, Muilenberg ML, Friedman W, Zeldin DC. Dog allergen (Can f 1) and cat allergen (Fel d 1) in US homes: results from the National Survey of Lead and Allergens in Housing. J Allergy Clin Immunol. 2004;114:111–117
  6. Gern JE, Reardon CL, Hoffjan S, Nicolae D, Li Z, Roberg KA, et al. Effects of dog ownership and genotype on immune development and atopy in infancy. J Allergy Clin Immunol. 2004;113:307–314
  7. Al-Mousawi MS, Lovel H, Behbehani N, Arifhodzic N, Woodcock A, Custovic A. Asthma and sensitization in a community with low indoor allergen levels and low pet-keeping frequency. J Allergy Clin Immunol. 2004;114:1389–1394
  8. de Meer G, Toelle BG, Ng K, Tovey E, Marks GB. Presence and timing of cat ownership by age 18 and the effect on atopy and asthma at age 28. J Allergy Clin Immunol. 2004;113:433–438
  9. Karlsson AS, Andersson B, Renstrom A, Svedmyr J, Larsson K, Borres MP. Airborne cat allergen reduction in classrooms that use special school clothing or ban pet ownership. J Allergy Clin Immunol. 2004;113:1172–1177
  10. Korpi A, Mantyjarvi R, Rautiainen J, Kaliste E, Kalliokoski P, Renstrom A, et al. Detection of mouse and rat urinary aeroallergens with an improved ELISA. J Allergy Clin Immunol. 2004;113:677–682
  11. Ferrari E, Tsay A, Eggleston PA, Spisni A, Chapman MD. Environmental detection of mouse allergen by means of immunoassay for recombinant Mus m 1. J Allergy Clin Immunol. 2004;114:341–346
  12. Cohn RD, Arbes SJ, Yin M, Jaramillo R, Zeldin DC. National prevalence and exposure risk for mouse allergen in US households. J Allergy Clin Immunol. 2004;113:1167–1171
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  14. Cabana MD, Slish KK, Lewis TC, Brown RW, Nan B, Lin X, et al. Parental management of asthma triggers within a child's environment. J Allergy Clin Immunol. 2004;114:352–357
  15. Arbes SJ, Sever M, Mehta J, Gore JC, Schal C, Vaughn B, et al. Abatement of cockroach allergens (Bla g 1 and Bla g 2) in low-income, urban housing: month 12 continuation results. J Allergy Clin Immunol. 2004;113:109–114
  16. van den Bemt L, van Knapen L, de Vries MP, Jansen M, Cloosterman S, van Schayck CP. Clinical effectiveness of a mite allergen-impermeable bed-covering system in asthmatic mite-sensitive patients. J Allergy Clin Immunol. 2004;114:858–862
  17. Johnston SL, Pattemore PK, Sanderson G, Smith S, Lampe F, Josephs L, et al. Community study of the role of virus infections in exacerbations of asthma in school children in the community. BMJ. 1995;310:1225–1229
  18. Dales RE, Cakmak S, Judek S, Dann T, Coates F, Brook JR, et al. Influence of outdoor aeroallergens on hospitalization for asthma in Canada. J Allergy Clin Immunol. 2004;113:303–306
  19. Bernstein JA, Alexis N, Barnes C, Bernstein IL, Bernstein JA, Nel A, et al. Health effects of air pollution. J Allergy Clin Immunol. 2004;114:1116–1123
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  21. Wisnewski AV, Stowe MH, Cartier A, Liu Q, Liu J, Chen L, et al. Isocyanate vapor-induced antigenicity of human albumin. J Allergy Clin Immunol. 2004;113:1178–1184
  22. Allmers H, Schmengler J, John SM. Decreasing incidence of occupational contact urticaria caused by natural rubber latex allergy in German health care workers. J Allergy Clin Immunol. 2004;114:347–351
  23. Brown RH, Taenkhum K, Buckley TJ, Hamilton RG. Different latex aeroallergen size distributions between powdered surgical and examination gloves: significance for environmental avoidance. J Allergy Clin Immunol. 2004;114:358–363
  24. Yeang HY, Arif SA, Raulf-Heimsoth M, Loke YH, Sander I, Sulong SH, et al. Hev b 5 and Hev b 13 as allergen markers to estimate the allergenic potency of latex gloves. J Allergy Clin Immunol. 2004;114:593–598
  25. Howell MD, Tomazic VJ, Leakakos T, Truscott W, Meade BJ. Immunomodulatory effect of endotoxin on the development of latex allergy. J Allergy Clin Immunol. 2004;113:916–924
  26. Brass DM, Savov JD, Whitehead GS, Maxwell AB, Schwartz DA. LPS binding protein is important in the airway response to inhaled endotoxin. J Allergy Clin Immunol. 2004;114:586–592
  27. Bufe A, Holst O. LPS-binding protein as a target molecule in allergy and asthma. J Allergy Clin Immunol. 2004;114:583–585
  28. Ibarrola I, Arilla MC, Martinez A, Asturias JA. Identification of a polygalacturonase as a major allergen (Pla a 2) from Platanus acerifolia pollen. J Allergy Clin Immunol. 2004;113:1185–1191
  29. Enrique E, Cisteró-Bahima A, Bartolome B, Alonso R, San Miguel-Moncin MM, Bartra J, et al. Platanus acerifolia pollinosis and food allergy. Allergy. 2002;57:351–356
  30. Barderas R, Villalba M, Pascual CY, Batanero E, Rodriguez R. Profilin (Che a 2) and polcalcin (Che a 3) are relevant allergens of Chenopodium album pollen: isolation, amino acid sequences, and immunologic properties. J Allergy Clin Immunol. 2004;113:1192–1198
  31. van Oort E, de Heer PG, Dieker M, van Leeuwen AW, Aalberse RC, van Ree R. Characterization of natural Dac g 1 variants: an alternative to recombinant group 1 allergens. J Allergy Clin Immunol. 2004;114:1124–1130

PII: S0091-6749(05)00525-7

doi:10.1016/j.jaci.2005.03.006

The Journal of Allergy and Clinical Immunology
Volume 115, Issue 6 , Pages 1197-1202, June 2005

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