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Environmental variables responsible for the increasing allergic disease burden observed in developed countries over the last century have yet to be adequately characterized. Meta-analyses of epidemiological studies presented in the first half of this paper demonstrate a correlation between farm-associated exposures (i.e., livestock, pets, unpasteurized milk, and endotoxin) and a reduction in allergic risk during childhood. Laboratory investigations discussed in the second half of the paper characterize the intrinsic immunostimulatory activities of living environments. Considered together, experimental findings presented herein suggest a novel paradigm by which early life home exposures to microbial products and other allergen-nonspecific immunostimulants modify allergic risk.

Background: Among inner-city children with asthma, cockroach allergen exposure has been associated with allergic sensitization., Objective: We hypothesized that cockroach allergen levels in homes would be associated with sensitization to cockroach allergens in children., Methods: From a low-income preschool program, 341 four-year-old children selected on the basis of the willingness of their caregivers to participate in the study were enrolled. Dust from their beds and kitchens were analyzed for cockroach (Bla g 2), mouse (mouse urinary proteins), and cat allergens (Fel d 1). Serum samples were analyzed for allergen-specific IgE antibodies by immunoassay., Results: Bla g 2 levels >1 U/g in children's bed and kitchen dust samples were independently associated with cockroach-specific IgE (odds ratio [OR], 2.7; 95% CI, 1.1-6.4; and OR, 3.4; 95% CI, 1.2-9.4, respectively), adjusting for sex, ethnicity, asthma, pet ownership, mother's allergic sensitization, environmental tobacco smoke, and having lived in other homes. Bla g 2 was associated (OR, 3.6; 95% CI, 1.0-13.1) with cockroach-specific IgE among children with asthma. Among children without asthma, the ORs were similar (OR, 3.0; 95% CI, 0.9-10.3), but the association was not statistically significant., Conclusion: Concentrations of the major cockroach allergen, Bla g 2, in settled dust were associated with cockroach-specific IgE independent of other factors in a cohort of 4-year-old inner-city children.

Background: Integrating horse stables with built-up areas may lead to conflicts. Dispersion of horse allergen may become a health risk for allergic people. The aim was to measure the dispersion of horse allergen around a stable, considering wind speed and direction and vegetation. The disturbance of staff at a workplace nearby a stable was investigated., Methods: Air sampling was performed around a stable (32 horses) at distances of 50-500 m in all directions. Sampling was done with a pump and an IOM sampler. Samples were collected at 50 points during all seasons. Horse allergen levels were determined using ELISA. Disturbance by horses was studied with a questionnaire handed to the employees in an office near the stable., Results: The median horse allergen level at the stable entrance was 316 U/m(3), in the horse fields 40 U/m(3) and in the whole source area 16 U/m(3), which declined to <2 U/m(3) at about 50 m from the source area. Downwind of the prevailing winds low levels of horse allergen (2-4 U/m(3)) could sometimes be detected at up to 500 m. The staff, including those allergic to horses, managed to tolerate horses close to the workplace., Conclusions: At low winds horse allergen spread in ambient air about 50 m from the stable and horse fields. At higher winds low allergen levels were sometimes found in open areas up to 500 m from the source area. These levels were similar to those found in the office after moving away from the stable area. The employees did not report more symptoms of allergy or asthma while working close to the stable compared to after the move., (2007 S. Karger AG, Basel)

(1-->3)-beta-D-Glucans, a cell wall component in most microfungi, are suggested to play a role in the development of respiratory and general symptoms in organic dust-related diseases. The mechanisms by which they induce these effects are, however, not clear. In the present study, mediator release and its potentiation by the (1-->3)-beta-D-glucan as well as by the (1-->6)-beta-D-glucan found in yeast and other fungi were therefore examined. Blood leucocytes from healthy volunteers and from patients allergic to house dust mite were incubated with (1-->3)-beta-D-glucans with increasing 1,6-branchings: curdlan [a linear (1-->3)-beta-D-glucan], laminarin and scleroglucan, and furthermore with pustulan, a linear (1-->6)-beta-D-glucan. Histamine release was not observed on exposure to the glucans only, but in the presence of anti-immunoglobulin E (IgE) antibody or specific antigens, all the glucans investigated led to an enhancement of the IgE-mediated histamine release. The glucans induced a significant potentiation of the mediator release when present at concentrations in the range of 2-5 x 10(-5) M. These results suggest that (1-->3)-beta-D-glucan as well as (1-->6)-beta-D-glucan aggravates IgE-mediated histamine release. Knowledge concerning the effects of glucans on immune responses may be of importance for understanding and treating inflammatory and allergic diseases.

Allergens play an essential role in atopic dermatitis, either intrinsic or extrinsic. They provoke cutaneous inflammation via IgE-dependent and cell-mediated immune reactions. Food allergens have a well-known contribution to disease activity of atopic dermatitis, especially in infants and young children. However, the importance of inhaled allergens is still under investigation. For clinical implication, identification of individualized allergens is an ideal strategy for better control of atopic dermatitis and avoidance of atopic march. The aim of this article is to discuss the common allergens in atopic dermatitis (AD), the specificity and sensitivity of laboratory tests for allergens, and the clinical effect of various preventions.

The aim of this study was to determine the level of two major mite allergens Dermatophagoides pteronyssinus (Der p 1) and Dermatophagoides farinae (Der f 1) in 30 urban homes in Zagreb, Croatia, using the enzyme immunoassay with two monoclonal antibodies which has been established as the reference method for indoor allergen analysis. Dust samples were taken by vacuuming a carpeted area and collected on cellulose filters. The ranges of Der p 1 and Der f 1 were (0.1-12.5) microg g-1 (median 0.32 microg g-1) and (0.1-31.2) microg g-1 (median 0.35 microg g-1), respectively. Der p 1 and Der f 1 (>2 microg g-1) associated with increased risk of sensitization to mite allergens were found in approximately 16% homes for each allergen. The sum of allergen (Der p 1 + Der f 1) exceeded the lower threshold in 27% of homes. Analytical evaluation of the ELISA assay showed satisfactory results for precision (intra-assay CV <6.9%, inter-assay CV<13.3%), accuracy (91% to 93%), and sensitivity (2 ng mL-1). The ELISA assay for the measurement of dust mite allergens demonstrated very good analytical characteristics for routine laboratory use, and will provide the essential basis for our future studies of various indoor allergens.

Coronary ischemic events increase significantly following a "bad air" day. Ambient particulate matter (PM10) is the pollutant most strongly associated with these events. PM10 produces inflammatory injury to the lower airways. It is not clear, however, whether pulmonary inflammation translates to a systemic response. Lipopolysaccharide (LPS) is a proinflammatory molecule often associated with the coarse fraction of PM. It was hypothesized that PM>2.5 from coal plus LPS induce pulmonary inflammation leading to a systemic inflammatory response. Mice were intratracheally instilled with saline, PM (200 microg), PM + LPS10 (PM + 10 microg LPS), or PM + LPS100 (PM + 100 microg LPS). Eighteen hours later, histologic analysis was performed on lungs from each group. Pulmonary and systemic inflammation were assessed by measuring the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in the pulmonary supernatant and plasma. In a follow-up study, the effects of LPS alone were assessed. Histologic analysis revealed a dose-dependent elevation in pulmonary inflammation with all treatments. Pulmonary TNF-alpha and IL-6 both increased significantly with PM + LPS100 treatment. Regarding plasma, TNF-alpha significantly increased in both PM + LPS10 and PM + LPS100 treatments. For plasma IL-6, all groups tended to rise with a significant increase in the PM + LPS100 group. The results of the follow-up study indicate that the responses to PM + LPS were not due to LPS alone. These results suggest that coarse coal fly ash PM>2.5 combined with LPS produced pulmonary and systemic inflammatory responses. The resulting low-level systemic inflammation may contribute to the increased severity of ischemic heart disease observed immediately following a bad air day.

The acute effects of pure inhaled glucan on respiratory inflammation remain inconclusive and not sufficiently examined with regards to the simultaneous interaction of glucan, endotoxin (lipopolysaccharide, LPS), and house dust in airway inflammation. This study aims at determining effects of simultaneous exposure to office dust and glucan on nasal and pulmonary inflammation. This is relevant for humans with occupational exposure in waste handling and farming and buildings with mold problems. Office dust collected from Danish offices was spiked with 1% (1-3)-beta-glucan (curdlan). Guinea pig nasal cavity volume was measured by acoustic rhinometry (AR) and animals were exposed by inhalation for 4 h to curdlan-spiked dust, unspiked dust, purified air (negative controls), or LPS (positive controls). After exposure (+5 h) or the following day (+18 h), measurements were repeated by AR and followed by bronchoalveolar lavage (BAL). Total and differential cell counts, interleukin (IL)-8 in BAL fluid, and change in nasal volume were compared between groups. A 5-10% increase in nasal volume was seen for all groups including clean air except for a significant 5% decrease for spiked-dust inhalation (+18 h). No marked differences were observed in BAL cells or IL-8 except in LPS-exposed controls. The delayed decrease of nasal cavity volume after exposure to glucan spiked dust suggests a slow effect on the upper airways for curdlan and office dust together, though no pulmonary response or direct signs of inflammation were observed. Glucan-spiked office dust exposures produced a delayed nasal subacute congestion in guinea pigs compared to office dust alone, but extrapolated to nasal congestion in humans, paralleling the nasal congestion seen in human volunteers exposed to the same dust, this may not have clinical importance.

Background: There is a paucity of longitudinal studies of allergen sensitization in childhood., Objective: To investigate the pattern of sensitization in early childhood., Methods: A nested cohort of children (n = 543) were followed up from birth and given a skin prick test (SPT) at 1, 2, and 3 years of age. A detailed clinical history was obtained., Results: The prevalences of sensitization to aeroallergens were 1.3%, 6.4%, and 10.7% at 1, 2, and 3 years of age. The figures for food allergens were 2.8%, 3.9%, and 3.7%. There was a statistically significant increase in the prevalence of sensitization to >or=1 allergen between years 1 and 2 (P < .001) and years 2 and 3 (P = .032). Among those with a positive SPT at 1 year, 29% tested positive to additional allergens at 2 years (P = .0054). Sensitization to milk or egg at 1 year was a predictor for increased sensitization to peanut at 3 years (odds ratio, 34.8; P < .0001). Sensitization to egg at 1 year was associated with increased sensitization to aeroallergens at 3 years (odds ratios, house dust mite, 27.1, P < .001; cat, 8.9, P < .01; grass, 11.8, P = .005). For peanut and cat allergens, wheal size increases with the age of the child (P = .009 and P = .017, respectively)., Conclusion: Sensitization to allergens as demonstrated by positive SPT tends to increase with age, and this change can be detected in the first 3 years of life., Clinical Implications: The high predictive value for early sensitization and a linear increase in SPT reactivity provide an opportunity for early intervention.

Purpose: The purpose of this study was to analyze the cutaneous sensitivity to a variety of allergens in patients with vernal keratoconjunctivitis (VKC) and to demonstrate the relation between skin response and clinical aspects of the disease., Methods: Twenty patients with vernal keratoconjunctivitis were randomly chosen from the External Disease and Cornea Sector. They were clinically evaluated, and a score ranging from 0 to 20 was applied based on signs and symptoms on ophthalmic examination. All subjects underwent a skin prick test against standardized allergens, such as house dust mites D. pteronyssinus, D. farinae, and Blomia tropicalis, as well as allergens from cat, dog, fungi and feather., Results: Seventy-five per cent of patients were positive for at least one of the allergens tested. House dust mites were responsible for the majority of the cases (75%). There was a poor correlation between the clinical score and sensitivity to allergens (r= - 0.119 for fungi; r= - 0.174 for dog; r= - 0.243 for house dust mites; r= - 0.090 for feather). A significant correlation was found only for cat allergen extract (r = - 0.510; p=0.024)., Conclusions: Our study demonstrated poor correlation between cutaneous hypersensitivity tests and clinical findings in patients with vernal keratoconjuntivitis. We concluded that skin response to inhalant allergens is not a useful test to identify clinical severity and chronicity of inflammatory process in this disease.

Esparto is a gramineous plant that has multiple applications in today's industry. Several cases of hypersensitivity pneumonitis (HP) caused by esparto inhalation have been reported, but only one case of asthma caused by Aspergillus fumigatus contaminating esparto has been communicated. We report a case of asthma induced by esparto inhalation in a 58-year-old man, who is a building industry worker, with subclinical sensitization to grass pollen. The relation between clinical symptoms and work activities was supported by peak expiratory flow (PEF) monitorization; PEF values decreased by 20% the days he handled esparto. Prick test with esparto was positive. Immunoblot analysis revealed several allergens in the esparto extract, some of them present in Lolium and A. fumigatus extracts. IgE immunoblot inhibition revealed a complete inhibition of lolium and A. fumigatus IgE reactive bands by esparto proteins. The patient then avoided the exposure to esparto at work and has remained asymptomatic for the last 2 years. In conclusion, this is a case of occupational asthma caused by esparto dust mediated by IgE antibodies. Proteins of A. fumigatus as well as proteins from this gramineous plant, which cross-reacted with esparto allergens, were responsible for the disease.

Background: House dust mites (HDMs) represent significant indoor allergen sources for patients with atopic dermatitis (AD). Subcutaneous allergen-specific immunotherapy (SCIT) has been shown to be successful in patients with allergic rhinitis and mild asthma and might represent an attractive therapeutic option for the long-term treatment of HDM sensitizations in AD patients. However, only a few studies have been conducted on the effectiveness of HDM SCIT in AD, resulting in controversial clinical results. Data on immunological changes induced by SCIT in AD patients are rare., Objectives: We performed an open pilot study to assess clinical changes and objective laboratory parameters and evaluate the benefit of HDM SCIT in 25 AD patients with IgE-mediated sensitization against HDM., Methods: The severity of AD was evaluated by the severity scoring of atopic dermatitis system (SCORAD). Specific IgE and IgG4 against HDM and serum levels of TARC/CCL17, MDC/CCL22, IL-16, IL-4, IFN-gamma, IL-10 and TGF-beta1 were measured during SCIT., Results: Subjective and objective SCORAD improved significantly within only 4 weeks of treatment. The level of the tolerogenic cytokine IL-10 increased, whereas CCL17 and IL-16 decreased in the sera of the patients during SCIT. Allergen specific IgE decreased, while IgG4 increased during SCIT., Conclusion: In this open-label pilot study, SCIT with an HDM extract in patients with AD led to a significant improvement of AD mirrored by a reduction of SCORAD as well as serological and immunological changes, which might serve as valuable parameters to estimate the therapeutic effect of SCIT.

Rationale: Although it is widely assumed that the incidence of childhood respiratory allergies to common aeroallergens is directly related to allergen exposure in early life, few longitudinal studies have investigated this issue, and available data are scarce and mainly limited to high-risk groups., Objectives: To assess, in a prospective manner and in a general population, the role of early life exposures to Der p1 and Fel d1 on the inception of sensitization and asthma., Methods: Pregnant women and their children were recruited for the Asthma Multicentre Infant Cohort Study. Overall, 1,611 newborns were initially enrolled in three cohorts in the United Kingdom and Spain. Der p1 and Fel d1 allergens were measured in household dust samples at 3 months of age for 1,474 (91.5%) participants, and skin prick tests were performed at 6 years of age on 1,182 (80.2%) participants. Wheeze and diagnosed asthma were reported in yearly questionnaires., Measurements and Main Results: Exposure to Der p1 early in life was not related to a positive specific prick test or to asthma or persistent wheeze at 6 years of age. Fel d1 showed an association with all these outcomes (third vs. first tertile; odds ratio, 4.43 for positive specific prick test and 2.6 for diagnosed asthma)., Conclusions: Dose-response relationships between allergen exposure and sensitization or asthma may be allergen specific and nonlinear; a minimum threshold level is needed to induce sensitization, but no dose-response relationship exists above this level. The effect of a particular allergen seems to be similar on atopy and asthma inception.

Background: There is evidence that the specificity of the IgE binding in allergy tests can vary for different populations., Objective: We aimed to examine the allergenic specificity of IgE binding in sera from house dust mite (HDM)-atopic subjects in a tropical Australian Aboriginal community., Methods: Sera shown to contain IgE antibodies to an HDM extract of Dermatophagoides pteronyssinus were examined for IgE binding to a panel of nine purified HDM allergens from this mite species by quantitative microtitre assays. IgG antibody binding (IgG1 and IgG4) was also measured., Results: The IgE-binding activity in the sera from the Aboriginal community was not directed to the expected major groups 1 and 2 HDM allergens but instead to the group 4 amylase allergen. There was also little IgE binding to the potentially cross-reactive tropomyosin (Der p 10) or arginine kinase (Der p 20) allergens. The IgG4 antibody was rarely detected and limited to the Der p 4 allergen. IgG1 antibody binding was frequently measured to all the allergens regardless of an individual's atopic status, whereas in urban communities it is restricted to the major allergens and to atopic subjects., Conclusion: The high IgE anti-HDM response of Australian Aboriginals predominantly bound Der p 4 and not the Der p 1 and 2 allergens, showing a distinctive allergy that could affect the disease outcome and diagnosis.

Background: Demand for expensive tests such as allergen-specific IgE is expanding far faster than for cheaper tests: at Burton Hospital the annual growth rate is 24%. Different hospitals have different policies on allergen testing. We report a comparison of the effect of requesting policy on diagnostic yield., Methods: All results from five years of allergen testing were downloaded from the data warehouse at Burton, and a representative sample of recent results was evaluated from Ipswich Hospital. Statistical analysis by chi(2) test and significance tests for differences of proportions were carried out., Results: Ipswich hospital used a standard four-allergen panel for respiratory patients and demonstrated a statistically significantly lower positivity rate for three of those four allergens. No relationship between the number of allergens tested and the probability of a positive result was shown - the probability of a positive result was approximately 0.3. Number of allergen-specific IgE tests requested/patient have remained roughly constant over 5(1/2) years but total demand has increased., Conclusions: Selective requesting for allergen-specific IgE testing may be more effective than use of a standard panel but this cannot be conclusively proven. It is not appropriate to attempt to limit workload by specifying a maximum number of tests that are allowed for any individual patient.

Beta(2)-adrenoceptors are widely distributed and occur on airway epithelial cells. The aim of this study was to find out whether the two long-acting beta(2)-agonists formoterol and salmeterol influence interleukin-6 (IL-6) and -8 (IL-8) release from airway epithelial cells in vitro. A549 cells and primary bronchial epithelial cells (PBEC) were stimulated with organic dust from pig barns. Non-stimulated and dust-stimulated cells were incubated for 24h with formoterol or salmeterol (10(-13)-10(-6)M) and the release of IL-6 and IL-8 into the medium was assessed by ELISA technique. Propranolol (10(-5)M) or sotalol (10(-3)M) were used to block the beta(2)-agonist mediated effects. Formoterol and salmeterol both induced enhancement of IL-6 and IL-8 release and added to the effect of organic dust. This enhanced release was blocked by a beta-blocker in PBEC but not in A549 cells. To our knowledge, this is the first time beta(2)-agonists have been shown to stimulate IL-6 release from airway epithelial cells. The results indicate different mechanisms of beta(2)-agonist action in bronchial and alveolar epithelial cells. Furthermore, our results indicate that A549 cells do not possess functional beta(2)-adrenoceptors.

The STAT3 transcription factor is critical for cytokine signaling and the acute phase response, but its role in allergic asthma is largely undefined. To investigate the role of STAT3 in mediating allergic inflammation, we used chemical and genetic approaches to inactivate STAT3 in the airway epithelium of mice. In a murine model of chronic asthma, we demonstrate that the administration of house dust mite (HDM) leads to robust STAT3 activation in the airway epithelium, smooth muscle, and immune cells in the lungs of C57BL/6 mice. To investigate the role of STAT3 in HDM-induced airway inflammation, a conditional knockout of STAT3 in the airway epithelium was generated, e-STAT3-/-. We determined that e-STAT3-/- mice had a significant decrease in HDM-induced airway eosinophilia, lung Th2 accumulation, and chemokines compared with wild-type animals. Importantly, the e-STAT3-/- mice had a significant decrease in airway hyperresponsiveness to methacholine. The administration of two STAT kinase inhibitors diminished STAT3 activation and markedly abrogated the HDM-induced lung inflammation. These findings suggest that STAT3 acts as a novel epithelial regulator of the allergic response by altering Th2 cell recruitment and effector function, and thus, targeting this molecule may provide the basis for a novel asthma therapy.

Skin prick tests (SPTs) play an important role in the diagnosis of bakers asthma and epidemiological field studies on frequencies of sensitization to wheat or rye flour. In many epidemiological studies the investigators have tried to reveal the determinants of specific sensitization, and atopy appears to be a very strong determinant for sensitization to flour allergens. Age and gender have not reported to be determinants of sensitization. Only one study found that sensitization in wheat flour with skin prick test was significantly associated with cigarette smoking. Few data are available on sensitization to wheat flour in populations without occupational exposure to bakery allergens. The aim of this study was to investigate the sensitization of wheat flour and other baking allergens (oat, barley, and rye flour) in traditional bakers and in cleaners in a big hospital in the same area. In addition the correlation of atopy with specific sensitization and the correlation of specific sensitization with age, sex, working hours, working years, smoking status and pack/years with use of skin prick tests.

Background: (1-3)-Beta-D-glucan is a fungal cell wall component, suspected to cause respiratory symptoms in adults. However, very little is known on the possible health effects of (1-3)-beta-D-glucan during infancy. We examined the association between (1-3)-beta-D-glucan exposure and the prevalence of allergen sensitization and wheezing during the first year of life in a birth cohort of 574 infants born to atopic parents. Endotoxin exposure was included as a possible confounder., Methods: (1-3)-Beta-D-glucan and endotoxin exposures were measured in settled dust collected from infants' primary activity rooms. The primary outcomes at approximately age one included parental reports of recurrent wheezing and allergen sensitization evaluated by skin prick testing to a panel of 15 aeroallergens as well as milk and egg white., Results: Exposure to high (1-3)-beta-D-glucan concentration (within fourth quartile) was associated with reduced likelihood of both recurrent wheezing [adjusted OR (aOR) = 0.39, 95% CI = 0.16-0.93] and recurrent wheezing combined with allergen sensitization (aOR = 0.13, 95% CI = 0.03-0.61). Similar trends were found between (1-3)-beta-D-glucan concentrations and allergen sensitization (aOR = 0.57, 95% CI = 0.30-1.10). In contrast, recurrent wheezing with or without allergen sensitization was positively associated with low (1-3)-beta-D-glucan exposure within the first quartile (aOR = 3.04, 95% CI = 1.25-7.38; aOR = 4.89, 95% CI = 1.02-23.57). There were no significant associations between endotoxin exposure and the studied health outcomes., Conclusions: This is the first study to report that indoor exposure to high levels of (1-3)-beta-D-glucan (concentration >60 microg/g) is associated with decreased risk for recurrent wheezing among infants born to atopic parents. This effect was more pronounced in the subgroup of allergen-sensitized infants.

It has been hypothesized that specific immunotherapy (SIT) significantly decreases the development of new allergen sensitizations in mono-sensitized patients. In this study, we evaluated the effect of SIT on the development of new allergen sensitizations in 129 asthmatic children mono-sensitized to house dust mite. SIT was accepted by only 70 of them (SIT group). The remaining 59 children were treated only with medication (control group). At the end of the study we found that 33% of all patients developed new sensitizations. Surprisingly, the prevalence of new sensitizations was significantly higher in the SIT group (45.5%) than in the control group (18.1 %). Ash tree (Fraxinus excelsior), Olive and Meadow fescue (Festuca elatior) were the most common allergens responsible for the new sensitizations. We conclude that SIT did not prevent the onset of new sensitizations in asthmatic children mono-sensitized to house dust mite.

Earlier hopes that determination of lymphocyte subpopulations might become a strong diagnostic tool in environmental medicine have not been fulfilled in recent years. Analysis of the scientific literature rather shows that there are only few examples for environmental exposures causing reproducible shifts of lymphocyte subpopulations. Moreover, current knowledge suggests that "environmental diseases" are not associated with characteristic changes of subpopulation patterns. If lymphocyte subpopulations are analyzed, each diagnostic step, including indication, sample handling, analytic procedure and data-interpretation, should adhere to good quality criteria. Taking all together, the determination of lymphocyte subpopulations in the context of environmental medicine comes under category IV of the criteria of the Commission for Methods and Quality Assurance in Environmental Medicine of the German federal health authority (Robert Koch-Institute; RKI): "A procedure cannot be recommended because there is not sufficient information to justify it" (here: no solid trends in epidemiological examinations), "and because theoretical considerations speak against an application" (here: high physiological variability and missing exposure or substance specificity).

Background: Exposure to allergen may induce a modified T(H)2 response characterized by high IgG(4) levels, absence of IgE sensitization, and a decreased risk of allergic respiratory symptoms., Objective: To assess the association of IgG(4) level with allergic respiratory symptoms in a community-based sample of adults., Methods: Information on exposure to cats, respiratory symptoms, and mattress allergen levels was obtained from 2780 adults. Levels of cat and house dust mite (HDM) specific IgE, IgG, and IgG(4) were measured. The association of exposure to allergen with IgG(4) and of IgG(4) with symptoms was assessed., Results: Geometric mean (GM) cat specific IgG and IgG(4) was higher in subjects who had a cat that was allowed in the bedroom than in subjects without a cat (adjusted ratio of GM IgG(4), 1.41; 95% CI, 1.25-1.57). Levels of HDM specific IgG and IgG(4) were similar in subjects with undetectable and high (>20.22 microg/g) mattress Der 1 levels (adjusted ratio of GM IgG(4), 1.02; 95% CI, 0.89-1.17). There was no evidence that high cat or HDM specific IgG(4) levels were associated with less IgE sensitization or with fewer symptoms., Conclusion: In this community-based sample of adults, high IgG(4) levels to cat or HDM were not associated with a lower risk of allergic respiratory symptoms., Clinical Implications: In adults, high cat allergen exposure does not protect against respiratory symptoms.

There is growing evidence linking poor housing conditions and respiratory diseases, including asthma. The association between housing conditions and asthma in the inner city has been attributed in part to cockroach and mouse infestation and the resulting allergen exposures. Multiple social and behavioral factors can influence environmental exposures and health conditions, necessitating a thorough examination of such factors. As part of the Healthy Public Housing Initiative, we evaluated the association between physical and household characteristics and pest-related allergen levels in three public housing developments in Boston, MA. We detected cockroach allergens (Bla g 1 and Bla g 2) in bedroom air, bed, and especially high concentrations in kitchen samples. In multivariate Tobit regressions controlling for development and season, clutter and lack of cleanliness in the apartment were associated with a tenfold increase in Bla g 1 concentration in the air, a sevenfold increase in Bla g 1 and an eightfold increase in Bla g 2 concentrations in the bed, and an 11-fold increase in Bla g 2 in the kitchen (p<0.05 for all). Holes in the wall/ceiling were associated with a six- to 11-fold increase in kitchen cockroach allergen concentrations (p<0.05). Occupancy in an apartment unit of 2 years or more was also associated with increased cockroach allergen concentrations. In contrast, there were low concentrations of mouse urinary protein in this population. In conclusion, these results suggest that interventions in these homes should focus on reducing cockroach allergen concentrations and that building-wide interventions should be supplemented with targeted efforts focused on high-risk units.

Allergen-specific immunotherapy is the only treatment that provides long lasting relief of allergic symptoms. Currently, it is based on repeated administration of allergen extracts. To improve the safety and efficacy of allergen extract-based immunotherapy, application of hypoallergens, i.e. modified allergens with reduced IgE binding capacity but retained T-cell reactivity, has been proposed. It may, however, be difficult to predict how to modify an allergen to create a hypoallergen. Directed molecular evolution by DNA shuffling and screening provides a means by which to evolve proteins having novel or improved functional properties without knowledge of structure-function relationships of the target molecules. With the aim to generate hypoallergens we applied multigene DNA shuffling on three group 2 dust mite allergen genes, two isoforms of Lep d 2 and Gly d 2. DNA shuffling yielded a library of genes from which encoded shuffled allergens were expressed and screened. A positive selection was made for full-length, high-expressing clones, and screening for low binding to IgE from mite allergic patients was performed using an IgE bead-based binding assay. Nine selected shuffled allergens revealed 80-fold reduced to completely abolished IgE binding compared with the parental allergens in IgE binding competition experiments. Two hypoallergen candidates stimulated allergen-specific T-cell proliferation and cytokine production at comparable levels as the wild-type allergens in patient peripheral blood mononuclear cell cultures. The two candidates also induced blocking Lep d 2-specific IgG antibodies in immunized mice. We conclude that directed molecular evolution is a powerful approach to generate hypoallergens for potential use in allergen-specific immunotherapy.

Background: The widespread house ant, Monomorium pharaonis (pharaoh ant, PA), was recently identified as a potential cause of respiratory allergies. However, there are no reports of the distribution of PA allergens in various environments. We developed specific ELISA inhibition assays and measured the distribution and amount of PA antigens in household dust samples., Methods: Floor dust was collected at 3-month intervals from 56 homes in Seoul over a 1-year period. PA antigens in fine dusts were quantified by ELISA inhibition assays using rabbit anti-PA sera, and specific IgE to PA antigens in residents' serum was measured by ELISA., Results: In 18 of the 56 homes (32.1%), PA antigen was detected in at least 1 floor dust sample either from the living room or the kitchen. Levels of PA antigens showed seasonal variations with peaks in autumn and winter. The detection rate of PA antigens was significantly higher in homes with visual evidence of PA infestations (70%) than in homes without such infestations (23.9%; p < 0.05). However, a significant amount of PA antigens was still detected in uninfested homes. Thirteen of 113 (11.5%) residents were positive for PA-specific IgE. PA-specific IgE was detected more frequently in residents living in PA antigen-positive homes (19.6%) than in antigen-negative homes (4.8%; p < 0.05)., Conclusion: A considerable level of PA antigens is distributed in the indoor environment. Therefore, inhalant exposure to PA antigens can occur during domestic activities. These results suggest that PAs might be a significant source of aeroallergens in households., (2007 S. Karger AG, Basel)

Background: The allergenic dust mite species Dermatophagoides pteronyssinus and Dermatophagoides farinae generally inhabit warm moist environments. This study tested the hypothesis that these allergenic species may thrive in air conditioner filters., Methods: A year-long investigation of the dust mite population densities and species identities living in air conditioner filters in Shenzhen City in Southern China was performed. Additional data describing the levels of major dust mite allergen proteins from samples collected in July and August 2004 were analyzed. Genetic polymorphism analysis of Der f 1 and Der f 2 genes in the collected animals was also conducted., Results: Our investigation revealed that larval dust mites started to grow in March, from which time their populations proceeded to steadily increase until reaching their population zenith in July and August. The dust mite populations decreased sharply in October and live dust mites were no longer observed in the winter. Among the mites collected in July and August, 30.1 and 25.8% were of the species D. farinae. The concentration of Der f 1 was 3.04 +/- 1.75 and 3.21 +/- 1.84 microg/g dust in July and August, respectively, and that of Der f 2 was 2.15 +/- 0.82 and 2.04 +/- 1.15 microg/g dust. Four types of Der f 1 and 5 types of Der f 2 cDNA sequences were cloned from collected Der f mites. Their sequences were highly homologous with those previously published in GenBank (No. AB034946.1 and No. AB195580.1)., Conclusions: This research demonstrated that Der f allergens exist in the dust of air conditioner filters in this area.

Laboratory and epidemiological studies have provided indirect but compelling evidence that toll-like receptor (TLR) signaling pathways play an important role in host responsiveness to ambient immunostimulatory factors. Nonetheless, direct evidence is limited. This paper will present our experience investigating the innate immunostimulatory activities of sterile house dust extracts (HDEs). In initial studies, bone marrow derived dendritic cells (BMDDCs) were cultured with HDEs, and cytokine production and co-stimulatory molecule expression were evaluated. In additional experiments, the TLR dependence of these responses was determined. HDEs induced concentration-dependent BMDDC activation. Moreover, the relative bioactivities of HDEs correlated with their endotoxin content. Finally, HDE-mediated responses were found to be partially dependent on TLR2, TLR4, and TLR9 and almost completely dependent on MyD88. These investigations provide the first direct evidence that TLR signaling pathways play a key role in innate responsiveness to non-infectious factors ubiquitous in living environments.

Background and Objective: Indoor air quality has become an important factor for sensitization and development of allergic diseases because of increased time spent in homes. We aimed to analyze the possible home-condition risk factors for allergic rhinoconjunctivitis, atopic eczema, and severe disease in schoolchildren aged 5 through 8 years., Material and Methods: The parents of 3360 school children in Pamplona, Spain in the 5-8-year-old age bracket answered questions about rhinitis and eczema symptoms from the protocol of the International Study of Asthma and Allergies in Childhood (ISAAC). The instrument contained additional questions about current home conditions related to mold and dust exposure and about conditions in the first year of life. Associations between the allergic diseases and early and current exposure were studied with chi(2) tests and bivariate and multivariate logistic regression., Results: Exposure to certain home conditions related to molds and dust in the first year of life increased the risk of allergic disease, but having good isolating windows in the first year of life protected against allergic rhinoconjunctivitis and severe atopic eczema. Some current home conditions were also related to an increased risk of current allergic disease; severe atopic eczema was more common among children with single glazing over the bedroom window., Conclusion: Current and first-year-of-life home conditions related to dust and mold exposure should be controlled because they influence the prevalence of allergic rhinoconjunctivitis and atopic eczema diseases. Moreover, having a double-glazed window currently and in the first year of life seems to protect against these diseases.

On-site home visits, consisting of a home inspection, dust sampling, and questionnaires were conducted in 777 homes belonging to an ongoing birth cohort study in Cincinnati, Ohio. Various home characteristics were investigated, and antigen levels (concentrations [microg/g] and loadings [microg/m(2)]; IU for cockroach allergen) in floor dust samples collected in child's primary activity room were analyzed by ELISA. Monoclonal antibodies were used for the analysis of cat, house dust mite, and cockroach allergens, and polyclonal antibodies for Alternaria and dog antigens. The relationship between the antigen levels and home characteristics was investigated through a generalized multiple regression model. More than half of the homes experienced mold/water damage. Cats and dogs were present in 19.7% and 31.1% of homes, respectively. More than 90% of homes had either carpet or area rug covering their floors. Among 777 homes, 87-92% of homes had measurable amount of Alternaria, cat, and dog allergen/antigen in house dust, whereas only 38% and 14% of homes had measurable levels of house dust mite and cockroach, respectively. Alternaria antigen level in house dust was not associated with visual mold/water damage, which was suspected to be one of the sources for this antigen in homes. Instead, the antigen level was high in samples taken in fall and in homes having dogs implicating that Alternaria antigen appears to be transported from outdoors to indoors. A high level was also measured in homes using a dehumidifier (these homes have experienced excessive humidity) and in-home venting of clothes dryer, which might be associated with microclimate affecting mold growth and spore release. The allergen/antigen level (both concentration and loading) of cat, dog and cockroach was significantly associated with the number of cats and dogs, or the appearance of cockroaches, respectively. High level of house dust mite allergen was measured in bedrooms and in homes using dehumidifier and no central forced air heating system. Having indoor plants was shown to reduce allergen levels. Carpeted floor was found to hold larger amount of antigens than non-carpeted floor. Antigen loading demonstrated more consistent and larger numbers of associations with home characteristics compared to antigen concentration. This study encompassed a wide range of home characteristics and various antigen types. Our findings provide information on home characteristics that can be used for allergen avoidance and in planning future exposure assessment studies.

Background: Geohelminth infection and poor hygiene may be protective against allergic sensitization., Objective: To determine whether current helminth infection is associated with a reduced prevalence of allergen skin test sensitization in a Southeast Asian population of children with a high prevalence of hookworm infection., Methods: A total of 1742 Vietnamese schoolchildren were invited to take part in a cross-sectional survey. Allergen skin sensitization to house dust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae) and American cockroach (Periplaneta americana) were measured and stool samples for qualitative and quantitative geohelminth estimation collected., Results: A total of 1601 children age 6 to 18 participated. Sensitization to dust mites was present in 14.4% and to cockroach in 27.6% of children. In a mutually adjusted model, the risk of sensitization to dust mites was reduced in those with higher hookworm burden (adjusted odds ratio [OR] for 350+ vs no eggs per gram, 0.61; 95% CI, 0.39-0.96) and with Ascaris infection (adjusted OR, 0.28; 0.10-0.78), and increased in those using flush toilets (adjusted OR for flush toilet vs none/bush/pit, 2.51; 1.00-6.28). In contrast, sensitization to cockroach was not independently related to geohelminth infection but was increased in those regularly drinking piped or well water rather than from a stream (adjusted OR, 1.33; 1.02-1.75)., Conclusion: Geohelminth infection, sanitation, and water supply influence the risk of allergic sensitization in Vietnamese children. This is consistent with a protective effect against allergy by geohelminth or other gastrointestinal infection., Clinical Implications: If the inverse relationship between geohelminth infection, poor sanitation, and allergic sensitization proves to be causal, drugs derived from parasite products may help to alleviate clinical allergic disease.

To assess the prevalence and the characteristics of exercise-induced bronchoconstriction (EIB) in subjects occupationally exposed to organic dusts we performed a cross-sectional study including 152 exposed subjects (67 textile workers, 42 agricultural workers, and 43 bakers) and 72 unexposed controls. Evaluation of exposed and unexposed subjects included a questionnaire, skin prick tests to common inhalant allergens, spirometry, and exercise challenge tests (ECT). The EIB prevalence found in textile workers was 8.9 %, in agricultural workers 7.1 %, in bakers 6.9 %, and in office workers 5.5 %. The highest bronchial reaction to exercise was found in ECT-positive agricultural workers (26.1+/-6.9), followed by textile workers (25.2+/-7.4), bakers (23.0+/-5.8), and office workers (21.8+/-4.4). EIB was significantly associated with atopy and positive family history of asthma in all exposed groups. EIB was significantly associated with smoking duration in textile workers (P=0.039) and agricultural workers (P=0.027). Bronchial reaction to exercise was significantly greater in smoking than in non-smoking textile (P=0.045) and agricultural workers (P=0.032). Our data suggest that the combination of daily smoking and workplace exposure to certain types of organic dusts could contribute to EIB development and severity.

Objectives: Organic dust is associated with adverse effects on human airways. This study was done to investigate whether the addition of beta-(1,3)-D glucan or aldehydes to office dust causes enhanced inflammation in human airways., Methods: Thirty-six volunteers were exposed randomly to clean air, office dust, dust spiked with glucan, and dust spiked with aldehydes. The three dust exposures contained between 332 and 379 microg dust/m(3). Spiking with 1 gram of dust was done with 10 milligrams of glucan or 0.1 microliters of aldehydes. Acoustic rhinometry, rhinostereometry, nasal lavage, and lung function tests were applied., Results: After the exposures to dust spiked with the glucan and aldehydes, the nasal volume decreased (-1.33 and -1.39 cm(3) (mean), respectively) when compared with the -0.9 cm(3) after clean air or office dust (P=0.036 for a difference in decrease between exposures). After 2-3 hours the aldehyde-spiked dust caused a 0.6-mm swelling of the inferior turbinate, and glucan-spiked dust produced a 0.7-mm swelling (P=0.039 for a difference in the swelling between the four exposures). The preexposure nasal lavage cleaned off the mucosa, and lower cytokine concentrations were found after all of the exposures. For interleukin-8, this decrease in concentration was smaller after the dust exposures spiked with glucan and aldehydes (-2.9 and -25.8 pg/ml, respectively) than after office dust or clean air (-65.9 and -74.1 pg/ml, respectively) (P=0.042). The nasal eosinophil cell concentration increased after exposure to dust spiked with glucan (P=0.045)., Conclusions: beta-(1,3)-D glucan and aldehydes in office dust enhance the inflammatory effects of dust on the upper airways.

Background: Both endotoxin exposure and a single nucleotide polymorphism in one of its receptors, CD14 C-260T, have been separately associated with total serum IgE levels. Furred pets might also influence IgE levels through their effects on endotoxin levels. However, how these factors interact to influence total IgE levels is not well known, especially in adults., Objective: We sought to investigate the interactive relationship between endotoxin levels, pet exposure, and CD14 C-260T genotype on total serum IgE levels in adults., Methods: Mothers enrolled in an ongoing cohort study were genotyped for the CD14 C-260T polymorphism. Exposure to pets was assessed by using questionnaires and dust allergen levels collected in the home. Endotoxin exposure was estimated by using dust collected from mothers' bedroom floors. The primary outcome measure was total serum IgE level., Results: CD14 C-260T genotype was assessed in 517 (85.2%) of the 607 women enrolled in the study. The CD14 C-260T genotype was significantly associated with total IgE levels; however, this relationship appeared to be modified by the level of endotoxin exposure. Similar interactions between CD14 C-260T and pet exposure were not seen, regardless of the measure of pet exposure used., Conclusions: The CD14 C-260T genotype and endotoxin exposure together appear to influence total serum IgE levels in adults. The absence of a similar gene-environment interaction for pet exposure suggests separate mechanisms of action., Clinical Implications: A common polymorphism in the endotoxin receptor, CD14 C-260T, and dust endotoxin levels in the home might interact to influence total serum IgE levels into adulthood.

An increased risk of asthma symptoms has previously been shown in 772 pine sawmill workers. The aim of the current study was to assess the association between dust exposure, lung function and atopy. Subjects with (n = 59) and without (n = 167) asthma symptoms were randomly selected from the previous survey. Lung function and atopy were determined using spirometry and skin-prick tests, respectively. Inhalable dust levels were measured on the same day. The geometric mean dust concentration was 0.52 mg x m(-3). Exposure to dry but not to green dust was associated with asthma symptoms. Green dust was associated with atopic sensitisation, particularly against outdoor allergens; no association was found for dry dust. Forced vital capacity, forced expiratory volume in one second and peak expiratory flow were significantly lower in workers exposed to high levels of green dust (-350 mL, -260 mL and -860 mL x s(-1), respectively) and dry dust (-230 mL, -190 mL and -850 mL x s(-1), respectively). These associations were observed both in subjects with and without asthma symptoms. No associations with cross-shift changes in lung function were found. Exposure to green pine sawdust may be a risk factor for atopy. Both green and dry dust were associated with obstructive as well as restrictive pulmonary effects.

Background: Exposure to the fungus Alternaria alternata is a risk factor for asthma. Few studies have examined Alternaria exposures in indoor environments., Objective: We examined whether exposure to A alternata in US homes was associated with asthma-related outcomes., Methods: The data for this study were collected as part of the National Survey of Lead and Allergens in Housing. This cross-sectional study surveyed a nationally representative sample of 831 housing units inhabited by 2456 individuals in 75 different locations throughout the United States. An interviewer-administered questionnaire obtained information on demographics, household characteristics, and occupants' health status. Exposure to A alternata was assessed by measuring concentrations of A alternata antigens in vacuumed dust samples using a polyclonal anti-A alternata antibody assay. Dust samples were collected from a bed, a sofa, or a chair, and from bedroom, living room, and kitchen floors., Results: Lifetime prevalence of doctor-diagnosed asthma was 11.2%, and 6.9% of the study subjects reported active asthma symptoms in the past 12 months. The prevalence of current symptomatic asthma increased with increasing Alternaria concentrations in US homes; higher levels of A alternata antigens increased the odds of having asthma symptoms in the past year (relative to the lowest tertile, adjusted odds ratio was 1.52, 95% CI, 0.90-2.55 for the 2nd tertile; and 1.84, 95% CI, 1.18-2.85 for the 3rd tertile)., Conclusion: Exposure to A alternata in US homes is associated with active asthma symptoms., Clinical Implications: Measures that reduce indoor exposure to A alternata may help control asthma exacerbations.

Background: Several studies in European homes have described allergen levels from the house dust mite species Dermatophagoides pteronyssinus and to a lesser extent Dermatophagoides farinae, but geographic comparisons of exposure levels and risk factors have been hampered by a lack of standardized methods., Objective: To study the distribution and determinants of the major house dust mite allergens Der p 1 and Der f 1 in 10 European countries using a common protocol., Methods: During home visits with 3580 participants of the European Community Respiratory Health Survey II from 22 study centers, mattress dust was sampled and analyzed for Der p 1, Der f 1, and Der 2 allergen. Information on housing characteristics was obtained by both observations and interview., Results: Der 1 and Der 2 allergens were detectable (>/=0.1 mug/g) in 68% and 53% of the samples, respectively. Large differences in allergen levels between study centers were observed, and geographic patterns for Der p 1 and Der f 1 were different. Low winter temperatures reduced Der p 1 rather than Der f 1. Important risk factors for high allergen levels included an older mattress, a lower floor level of the bedroom, limited ventilation of the bedroom, and dampness for Der p 1 but not for Der f 1., Conclusion: There are large qualitative and quantitative differences of house dust mite allergen levels in Europe, which can partly be explained by geographic and housing characteristics., Clinical Implications: Mite allergen exposure may be reduced by replacing the mattress regularly and increasing ventilation of the bedroom, particularly in winter.

Background: Although it is widely assumed that childhood sensitization to common aeroallergens is directly related to allergen exposure in early life, few longitudinal studies have investigated this issue, and available data are scarce and mainly limited to high-risk groups., Objective: We sought to assess the role of early exposure to 2 major household aeroallergens (Der p 1 and Fel d 1) in sensitization at the age of 4 years., Methods: Pregnant women and their children were recruited for the Asthma Multicenter Infant Cohort Study. Three cohorts (Ashford in the United Kingdom and Menorca and Barcelona in Spain) followed the same research protocol. A total of 1611 newborn children were initially included in the cohort, from whose homes we collected dust samples at 3 months of age for 1474; Der p 1 and Fel d 1 levels were measured. Of these children, we obtained blood for specific IgE determination in 1019., Results: The risk of Fel d 1 sensitization increased with exposure in a nonlinear manner. No association was found between specific IgE to Der p 1 and aeroallergen levels of exposure at early life in 2 centers, but a positive association was observed in the third., Conclusions: The dose-response relationships between allergen exposure and sensitization differ between allergens and might vary between different locales. The hypothesis that sensitization to house dust mite is directly related to levels of allergen exposure might not apply to the general population or to different ranges of exposure., Clinical Implications: Aeroallergen avoidance might not have any important effect on the incidence of sensitization.

The hygiene hypothesis suggests that early life exposure to a nonhygienic environment that contains endotoxin reduces the risk of developing allergic diseases. The mechanisms underlying the hygiene hypothesis are unclear and may involve subtle immune system interactions that occur during maturation. Experimental objectives of this study were to use a novel animal model to test the hygiene hypothesis and to characterize early life immune system responses to a nonhygienic environment. Mice were reared in corn dust, a grain-processing byproduct with a high-endotoxin content and microbial products or in a low-endotoxin environment. The influence of early or later life exposure to corn dust on a subsequent allergen stimulus (ovalbumin) was assessed by bronchoalveolar lavage (BAL) cell analysis, lung histology, serum IgE, and BAL cytokine measurements. The influence of the corn dust environment on the developing pulmonary immune system was assessed by BAL cell analysis and immunostaining of lung tissue. The corn dust environment contained significantly more endotoxin (P < 0.001), and the dust exposures attenuated the cellular inflammatory response to ovalbumin in the adult mouse (P < 0.01) but did not reduce serum IgE levels or alter baseline BAL fluid proinflammatory cytokine levels. The corn dust environment did not induce significant neutrophilia in lavage fluid but significantly increased the number of antigen-presenting cells in alveolar walls early in life by approximately 37%. In conclusion, exposure to a nonhygienic environment did not induce significant airway neutrophilia, yet altered the population of immunologically active cells in the lung and reduced subsequent allergic inflammation.

Background: Cat allergen level in settled house dust and its determinants in Europe are unknown., Objective: The aim of this study is to quantify the level of cat allergens in mattress dust, to study its determinants, and to analyze the relationship with cat specific IgE on community level across European centers., Methods: Trained field workers collected dust from approximately 3000 mattresses during home visits in 22 European Community Respiratory Health Survey II centers. Sieved dust extracts were assayed for cat allergen using a mAb ELISA assay., Results: The overall geometric mean cat allergen was 0.94 microg/g, ranging from 0.12 microg/g in Huelva, Spain, to 3.76 microg/g in Antwerp, Belgium. Current cat owners' homes showed substantially higher levels than past cat owners' and never cat owners' homes (geometric mean and 95% CI, 61.4 microg/g [48.4-77.9] vs 1.37 microg/g [0.97-1.9] vs 0.29 microg/g [0.27-0.31]). Community prevalence of cat ownership was moderately correlated with cat allergen levels in noncat owners (r(s) = 0.50), but not for past or current cat owners. The multilevel model identified community prevalence of cat keeping as the only statistically significant determinant of mattress cat allergen levels for noncat owners. However, averaged cat allergen levels per center were not related to community prevalence of detectable specific IgE to cat., Conclusion: Not having a cat in the home is associated with substantially lower Fel d 1 concentration, but does not protect against high Fel d 1 exposure in communities where cat ownership is common., Clinical Implications: People (including patients with cat allergy) who do not own cats may be exposed to high levels of cat allergen in their home, particularly if they live in communities with high levels of cat ownership.

Objectives: Previous studies have demonstrated that persons working with poultry have an increased incidence of chest symptoms and decreased lung function. A study was undertaken to evaluate the usefulness of airway responsiveness measurements to diagnose the presence of airways inflammation and relate this to the workplace exposure., Methods: The group studied comprised of 42 non-smoking poultry workers and 40 controls not exposed to organic dusts. The presence of symptoms was evaluated using a standardized questionnaire for organic dust exposures. Airway responsiveness was measured using the methacholine challenge test. The concentrations of airborne endotoxin and (1-->3)-beta-D-glucan were measured., Results and Conclusions: Exposure levels were in excess of those expected to cause effects in the airways. There was significantly higher airway responsiveness among the workers compared to controls (decrease 9.5 SD 7.5 vs 3.4, SD 3.3). Poultry workers had a higher prevalence of toxic pneumonitis, airways inflammation and chronic bronchitis compared to controls. Endotoxin levels in the poultry buildings exceeded those earlier suggested as the threshold value for airways inflammation.

Inhalation exposure to particulate matter containing endotoxin (or lipopolysaccharide (LPS)) occurs in a variety of occupations. Nasal lavage and induced sputum have been used to evaluate lung inflammation resulting from such exposures. Whole blood assay (WBA) measures cytokine production of leukocytes after ex vivo stimulation with LPS. The present study examined the effectiveness of WBA for evaluating inflammatory responses and susceptibility. C3HeB/FEJ mice were tolerised by LPS injection or sham tolerised with saline. Animals then inhaled either swine barn dust extract containing endotoxin or saline. Bronchoalveolar lavage (BAL) fluid was assayed for leukocyte counts and pro-inflammatory cytokines (interleukin-6, tumour necrosis factor-alpha). Whole blood was stimulated with 10 or 100 ng.mL(-1) of LPS, incubated for 5 or 18 h and assayed for cytokines. Barn dust-exposed groups revealed significantly higher total cells, neutrophils and cytokines in BAL compared with saline-exposed groups. Animals tolerised to LPS and exposed to barn dust demonstrated lower cellular and cytokine BAL responses. Similarly, WBA yielded significantly elevated cytokines with barn dust exposure and reduced responses with tolerisation. This study demonstrates the efficacy of whole blood assay as a biomarker of inhalation exposure to inflammatory agents and its use for assessing susceptibility to organic dust-induced lung inflammation.

Background: Although mechanisms remain a subject of controversy, there is general agreement that living environments influence allergic risk during the first years of life. We reasoned that sterile house dust extracts (HDEs) would have immunologic activities reflective of their environments of origin and therefore would be useful surrogates for investigations of how ambient exposures influence immune homeostasis., Objective: These experiments determined how airway HDE exposures influence adaptive responses to a coadministered antigen and subsequent airway hypersensitivity responses to antigen challenge., Methods: Mice received intranasal ovalbumin (OVA) vaccinations on a weekly basis. Select groups of mice also received intranasal HDE weekly with OVA; daily at one seventh the weekly dose, beginning 7 days before the first OVA sensitization; or both., Results: Weekly intranasal vaccinations with OVA and HDE primed mice for the development of T(H)2-biased immune and airway hypersensitivity responses. In contrast, daily low-dose intranasal HDE exposures protected against the immunologic and pathologic outcomes associated with weekly intranasal OVA/HDE vaccinations. The T(H)2 adjuvant activities of HDEs were found to be dependant on MyD88, a molecule critical for signaling through a majority of Toll-like receptors. Moreover, the tolerogenic activity associated with daily intranasal HDE exposures could be replicated with LPS., Conclusion: These investigations demonstrate that in addition to allergens, living environments contain immunomodulatory materials with both T(H)2 adjuvant and tolerogenic activities., Clinical Implications: As the contents of HDEs are ubiquitous, these experiments might recapitulate and help explain clinically relevant immunologic events involved in the maintenance of aeroallergen tolerance and the dysregulated responses that lead to allergic respiratory diseases.

Cigarette smoking is a known risk factor for many chronic illnesses such as coronary heart and chronic obstructive pulmonary diseases. Smoking is often described as a risk factor for occupational asthma even though its effect on the development of asthma is still under debate and the links between smoking and occupational asthma, occupational rhinitis or occupational sensitization are elusive, controversial and contradictory. This review describes these relationships in a wide range of occupations, from laboratory, farm, brewery and hospital workers, to bakers, printers, cleaners, fish processors and others as observed in cross-sectional, cohort, and case-control studies published over the past thirty-five years i.e. from 1970 to 2005. Surprisingly, the data show there is little to support the view that the risk of occupational asthma is increased in workers who are smokers. However, evidence emerges of an increased risk of occupational sensitization in smoking workers exposed to several high and low molecular weight agents. This in-depth review confirms the relationship between smoking and occupational asthma is complex and contradictory. It deserves more attention and further studies, which need to be conducted without being influenced by selection bias or by the justifiable prejudice against smoking.

Mouse allergen has emerged as an under recognized indoor allergen associated with sensitization and contributing to asthma severity. As part of a study of farm residence, exposures, and risk of allergic diseases in children in New Zealand, 216 living room floor dust samples were analysed for the mouse allergen, Mus m 1. Associations between Mus m 1 and allergic diseases, farm residence, and presence of cats were analysed. Significantly higher levels of Mus m 1 were found in farm dwellings, while the presence of cats was associated with significantly lower Mus m 1 levels. Levels of Mus m 1 in New Zealand were considerably lower than those reported overseas. No significant associations were found between Mus m 1 levels and atopic status or allergic diseases. Mouse allergen is unlikely to be an important indoor allergen for rural New Zealand children.

Smoking is alleged to cause pulmonary fibrosis, but the role of inorganic dust particulates has not been adequately examined. The authors hypothesize that inorganic dust exposure is an independent risk factor for the development of fibrosis in smokers. They studied a prospective series of 34 subjects with open lung biopsies, 18 of whom had adequate lung parenchyma for evaluation. They also examined the relationships between smoking (pack-years), respiratory bronchiolitis (RB), inorganic dusts, and interstitial fibrosis. They graded RB, fibrosis, and particulate dust by means of light microscopy. They performed a semiquantitative analysis of dust burden by using scanning electron microscopy with energy-dispersive X-ray spectroscopy. A logistic regression analysis demonstrated a significant association between smoking and RB (p = .03), but not between smoking and fibrosis or between RB and fibrosis. Fibrosis was significantly associated with silica (p = .004) and titanium (p = .0006) concentrations. The results support the authors' hypothesis.

Matrix metalloproteinases (MMPs) are involved in tissue destruction in allergic airway diseases. We studied the ability of various allergenic substances to directly activate recombinant 92kDa proMMP-9. The substances included hay dust suspension (HDS) and its components (supernatant, particulate matter and wash fluid of particulate matter), storage mite extract and two Aspergillus fumigatus extracts. The allergen suspensions were incubated in vitro with proMMP-9. After incubation the conversion of proMMP-9 to 10kDa lower active forms were studied using gelatin zymography and Western immunoblot quantified by computerized densitometry. All studied allergens except HDS significantly and efficiently activated proMMP-9 as compared to a negative control. At the concentrations employed, the most potent activators were A. fumigatus extracts and mite suspension. The greater potency of mite and fungi as proMMP-9 activators suggests that these allergens may be more damaging to airways even at low concentrations.