Environmental Exposure to Endotoxin and Its Relation to Asthma in School-Age Children
Charlotte Braun-Fahrländer, M.D., Josef Riedler, M.D., Udo Herz, Ph.D., Waltraud Eder, M.D., Marco Waser, M.Sc., Leticia Grize, Ph.D., Soyoun Maisch, M.D., David Carr, B.Sc., Florian Gerlach, Albrecht Bufe, M.D., Ph.D., Roger P. Lauener, M.D., Rudolf Schierl, Ph.D., Harald Renz, M.D., Dennis Nowak, M.D., Erika von Mutius, M.D., for the Allergy and Endotoxin Study Team
Background In early life, the innate immune system can recognizeboth viable and nonviable parts of microorganisms. Immune activationmay direct the immune response, thus conferring tolerance toallergens such as animal dander or tree and grass pollen.
Methods Parents of children who were 6 to 13 years of age andwere living in rural areas of Germany, Austria, or Switzerlandwhere there were both farming and nonfarming households completeda standardized questionnaire on asthma and hay fever. Bloodsamples were obtained from the children and tested for atopicsensitization; peripheral-blood leukocytes were also harvestedfrom the samples for testing. The levels of endotoxin in thebedding used by these children were examined in relation toclinical findings and to the cytokine-production profiles ofperipheral-blood leukocytes that had been stimulated with lipopolysaccharideand staphylococcal enterotoxin B. Complete data were availablefor 812 children.
Results Endotoxin levels in samples of dust from the child'smattress were inversely related to the occurrence of hay fever,atopic asthma, and atopic sensitization. Nonatopic wheeze wasnot significantly associated with the endotoxin level. Cytokineproduction by leukocytes (production of tumor necrosis factor, interferon-, interleukin-10, and interleukin-12) was inverselyrelated to the endotoxin level in the bedding, indicating amarked down-regulation of immune responses in exposed children.
Conclusions A subject's environmental exposure to endotoxinmay have a crucial role in the development of tolerance to ubiquitousallergens found in natural environments.
Asthma is the most common chronic disease in childhood and accountsfor substantial morbidity and health care costs. Although variousenvironmental factors have been thought to play key parts inthe development of asthma and allergies,1,2,3 the causes ofthese diseases remain unclear.
One intriguing hypothesis is that changes in the type and degreeof stimulation from the microbial environment associated withimprovements in public health and hygiene may increase the predispositionto chronic allergic conditions during childhood.4 Exposure tomicrobes can occur in the absence of infection. For example,viable and nonviable parts of microorganisms are found in varyingconcentrations in many indoor and outdoor environments. Thesemicrobial substances are recognized by the innate immune systemin the absence of overt infection, and they induce a potentinflammatory response.5 Therefore, environmental exposure tomicrobial products may have a crucial role during the maturationof a child's immune response, causing the development of toleranceto other components of his or her natural environment, suchas pollen and animal dander.
We investigated the relation between exposure to microbial productsand the occurrence of childhood asthma and allergies in an environmentrich in opportunities for such exposure — that is, a ruralenvironment where some families engage in farming. We measuredendotoxin — a cell-wall component of gram-negative bacteria— in samples of dust from the mattresses of children andthen related the levels of endotoxin to the prevalence of asthmaand allergies and to serum levels of specific IgE. We also assessedthe cytokine-production profile of peripheral-blood leukocytesafter activation of the innate immune system by stimulationwith lipopolysaccharide and staphylococcal enterotoxin B.
Methods
Study Population
This cross-sectional survey was conducted in rural areas ofAustria, Germany, and Switzerland, as previously described.6Participating parents (2618 of 3504 potential participants [74.7percent]) were asked to consent to the measurement of specificIgE in their children's serum, the assessment of the cytokine-productionprofile of the children's peripheral-blood leukocytes afterstimulation with lipopolysaccharide and staphylococcal enterotoxinB, and the collection of dust samples from the children's bedding.The final analysis was restricted to 812 children with completedata and similar ethnic origin (categorized as German, Austrian,or Swiss nationality), in order to avoid potential confoundingby ethnic background.7
Approval to conduct the survey was obtained from the three localethics committees for human studies and from the principalsof the schools attended by the children. Written informed consentwas obtained from the parents of all children.
Dust Sampling
We collected dust by vacuuming each mattress for two minutesper square meter of surface area. The material obtained wasdivided in two for measurement of endotoxin and allergen content.Dust was collected on special filters provided by the AlleregologiskLaboratorium Kopenhagen.8 All field workers were centrally trainedand certified to ensure similarity of sampling.
Measurements of Endotoxin Levels
One dust sample was stored at room temperature and shipped withinone week after collection to the central laboratory (in Munich,Germany). Endotoxin content was measured by a kinetic limulusassay, as described by Hollander et al.9 Endotoxin results wereexpressed as endotoxin units per milligram of dust and as endotoxinunits per square meter of surface area of the sampled mattress.All endotoxin levels were within the limits of detection ofthe assay.
Measurements of Allergen Levels in Dust Samples
The second dust sample was frozen at –20°C for atleast two days and then shipped to one central laboratory (UniversityChildren's Hospital Charité, Berlin, Germany) and storedat 4°C until it was analyzed for Dermatophagoides pteronyssinus(Der p1), D. farinae (Der f1), and Felis domesticus (Fel d1),as previously described.3 The lower limit of detection was 10ng per gram of dust for Der p1 and Der f1 and 16 ng per gramof dust for Fel d1; results are expressed in nanograms of majorallergen per gram of mattress dust. For allergen levels belowthe limit of detection (9.7 percent for Der p1, 5.5 percentfor Der f1, and 0.2 percent for Fel d1), the mean value betweenzero and the limit of detection was used.
Questionnaire and Interview
The prevalence of diseases and symptoms and potential explanatoryand confounding factors were assessed by a questionnaire givento the parents that included the questions of the InternationalStudy of Asthma and Allergies in Childhood,10 as described previously.6Farmers' children were defined as children whose parents answered"yes" to the question "Does your child live on a farm?" In aninterview with the parents as part of the home visit, we obtaineddetails of the timing of the child's exposure to stables andto farm milk. Exposure to farming during the first year of lifewas defined as exposure to stables during the first year oflife, consumption of milk directly from the farm during thefirst year of life, or both.
Testing for Specific IgE in Serum
The level of specific IgE against airborne allergens in allserum samples was measured by fluorescence enzyme immunoassayin a central laboratory (University Children's Hospital Charité,Berlin). Atopy was defined by at least one positive test forspecific IgE indicating a titer of at least 3.5 kU per literfor one or more of the six airborne allergens (house dust mites,storage mites, grass pollen, birch pollen, cat dander, and cowepithelium).
Assessment of Cytokine Production by Peripheral-Blood Leukocytes
Venous blood was drawn at school from all 812 children. Heparinizedblood was diluted in a ratio of 1:8 in RPMI culture medium supplementedwith 10 percent heat-inactivated fetal-calf serum to a finalvolume of 1 ml. Cells were stimulated either with 10 µgof lipopolysaccharide per milliliter for 24 hours or with staphylococcalenterotoxin B for 72 hours at 37°C, in an environment of5 percent carbon dioxide in humidified air. Cell-free supernatantswere stored at –80°C and shipped to the central laboratoryfor measurement of interferon- (limit of detection, 16 pg permilliliter), tumor necrosis factor (limit of detection, 16pg per milliliter), interleukin-10 (limit of detection, 8 pgper milliliter), and interleukin-12 (limit of detection, 8 pgper milliliter) by commercially available enzyme-linked immunosorbentassays (OptEIA, Pharmingen). Each sample was tested in duplicateby the serial dilution of a standard supplied by the companywith a known cytokine level. Differential blood counts werealso performed, and cytokine production was expressed in picogramsper 1 million peripheral-blood leukocytes. To ensure consistentperformance in sampling and culture procedures, laboratory personnelin the study centers participated in a one-week training andcertification program.
Statistical Analysis
Endotoxin levels were log10-transformed. Multivariate logistic-regressionanalyses, in which the endotoxin level was treated as a continuousvariable, were performed with SAS software,11 with adjustmentfor age, sex, study area, family history of asthma and hay fever,educational level of the parents, and number of older siblings(the basic model). In addition, potential confounding by farmingstatus, exposure to farming during the first year of life, exposureto cats or dogs during the first year of life, and allergenlevels (log-transformed values for Der f1, Der p1, and Fel d1)was evaluated. We included an interaction term to assess whetherthe effect of endotoxin on asthma and wheeze in children withatopic sensitization (a specific IgE level of at least 0.35kU per liter) would be different from the effect in childrenwithout atopic sensitization.
To evaluate potential threshold values or other nonlinearityin the relation between exposure and response, S-Plus softwarewas used to perform local nonparametric smoothing.12 The logitof the rates of symptoms was expressed as a continuous functionof endotoxin level, obtained by local nonparametric smoothingwith control for the covariates mentioned above. The smoothingparameter for each model was determined on the basis of Akaike'sinformation criterion.12 In the same way, the association betweenendotoxin levels and cytokine response was assessed. Cytokinelevels were log-transformed, and the association of these levelswith the level of endotoxin exposure was expressed as the ratioof the covariate-adjusted geometric mean cytokine level in childrenin the highest quartile of endotoxin exposure to the mean levelin children in the lowest quartile. The regression analyseswere repeated with a restricted sample of children from nonfarminghouseholds with adjustment for known allergy-avoidance measures(removal of pets or carpets because of allergies in the family),exposure to cats or dogs during the first year of life, andexposure to farming during the first year of life.
Results
Complete data were available for 812 children, 319 from farmingfamilies and 493 from nonfarming families. The mean (±SD)age was 9.5±1.2 years. The adjusted odds ratios for asthmaand hay-fever symptoms in relation to the farming status didnot differ significantly between the group with complete dataand the group with only the self-administered questionnaire(0.59 vs. 0.48 for asthma and 0.44 vs. 0.32 for hay-fever symptoms).6The relations between farming status and environmental-exposurevariables and health outcomes are shown in Table 1.
Table 1. Environmental Exposure and Prevalence of Health Outcomes, According to Farming Status.
The results of multivariate logistic-regression analyses estimatingthe effect of the mattress endotoxin level and the endotoxinload on the rates of symptoms and disease, with adjustment forknown covariates, are shown in Table 2. The data are presentedas adjusted odds ratios for symptoms or disease with an increasefrom the lowest quartile to the highest quartile of endotoxinexposure. Current endotoxin exposure showed a strong inverseassociation with hay fever, hay-fever symptoms, and atopic sensitization.Smoothed plots of the prevalence of hay fever, hay-fever symptoms,and atopic sensitization in relation to the level of endotoxinexposure, with control for covariates, showed a largely monotonicdecrease in prevalence with an increasing endotoxin load (Figure 1).Similar results were obtained in analyses in which the endotoxinlevel was used as the exposure variable (data not shown).
Table 2. Associations between Current Endotoxin Exposure (Level and Load) and Asthma, Wheeze, Hay Fever, and Atopic Sensitization in the Total Sample and in the Subgroup of Children from Nonfarming Households.
Figure 1. Smoothed Plots of the Prevalence of Hay Fever (Panel A), Hay-Fever Symptoms (Panel B), and Atopic Sensitization (Panel C) in Relation to the Log-Transformed Endotoxin-Load Values.
The analyses controlled for age, sex, study area, family history of asthma and hay fever, educational level of the parents, and number of siblings. For each outcome, there was a monotonic decrease with increasing endotoxin load. A smoothing span of 0.9 was used for all three graphs.
An inverse relation was also found between the level of endotoxinexposure and the capacity of peripheral-blood leukocytes toproduce inflammatory and regulatory cytokines after stimulationwith lipopolysaccharide (Figure 2). The associations betweenendotoxin exposure (in endotoxin units per square meter) andthe production of tumor necrosis factor , interferon-, interleukin-10,and interleukin-12, expressed as ratios of the mean level ofcytokine production for children in the highest quartile ofendotoxin exposure to the mean level for children in the lowestquartile, were 0.81 (95 percent confidence interval, 0.74 to0.89), 0.80 (95 percent confidence interval, 0.70 to 0.92),0.93 (95 percent confidence interval, 0.81 to 1.07), and 0.87(95 percent confidence interval, 0.77 to 0.98), respectively.The corresponding results after stimulation with staphylococcalenterotoxin B were 0.83 (95 percent confidence interval, 0.74to 0.93), 1.05 (95 percent confidence interval, 0.95 to 1.17),0.97 (95 percent confidence interval, 0.84 to 1.11), and 0.96(95 percent confidence interval, 0.86 to 1.06), respectively.
Figure 2. Smoothed Plots of the Log-Transformed Capacity of Peripheral-Blood Leukocytes (PBL) to Produce Tumor Necrosis Factor (TNF-) (Panel A), Interferon- (IFN-) (Panel B), Interleukin-12 (Panel C), and Interleukin-10 (Panel D) after Stimulation with Lipopolysaccharide (LPS) or Staphylococcal Enterotoxin B (SEB) in Relation to the Log-Transformed Endotoxin-Load Values.
Analyses were controlled for age, sex, study area, family history of asthma and hay fever, educational level of the parents, and number of siblings; the analysis shows an inverse relation between the level of endotoxin exposure and cytokine response, except in the case of the production of IFN- after SEB stimulation. A smoothing span of 0.9 was used for all four graphs.
The association between endotoxin exposure and wheeze duringthe past year showed a different expo-sure–response pattern.There was a strong negative association for atopic wheeze andasthma, whereas for nonatopic wheeze and asthma, there was anonsignificant trend toward increasing prevalence with increasesin the current level of endotoxin exposure (Table 2 and Figure 3).However, the term for the interaction between the levelof endotoxin exposure and atopic status did not reach statisticalsignificance. Exposure to farming in the first year of lifeshowed a strong inverse association with all health outcomes,including nonatopic wheeze and asthma, independently of thecurrent level of endotoxin exposure (Table 3). Additional adjustmentfor other potential confounders, including the levels of allergens(Der f1, Der p1, and Fel d1) in mattress dust, farming status,exposure to pets during the first year of life, and exposureto farming during the first year of life, did not change theresults. To evaluate whether the results might be generalizedto a nonfarming population and to adjust for potential uncontrolledconfounding associated with a farming lifestyle, we restrictedthe sample to children from nonfarming households and also adjustedfor exposure to stables and consumption of milk directly fromthe farm during the first year of life. Again, strong negativeassociations — albeit not all statistically significant(probably because of the sample size) — between the levelof endotoxin exposure and atopic outcomes were observed, whereaspositive associations were found for nonatopic wheeze (Table 2).
Figure 3. Smoothed Plots of the Prevalence of Atopic Wheeze (Panel A) and Nonatopic Wheeze (Panel B) in Relation to the Log-Transformed Endotoxin-Load Values.
The analyses were controlled for age, sex, study area, family history of asthma and hay fever, educational level of the parents, and number of siblings. There was a negative association for atopic wheeze, whereas for nonatopic wheeze, there was a nonsignificant positive trend with increasing levels of current endotoxin exposure. For Panel A, a smoothing span of 0.9 was used; for Panel B, a span of 0.5 was used.
Table 3. Association of the Prevalence of Symptoms and Disease with the Current Endotoxin Load and Exposure to Farming during the First Year of Life.
Discussion
These findings suggest that environmental exposure to microbialproducts, as measured by the endotoxin levels in mattress dust,is associated with a significant decrease in the risk of hayfever, atopic sensitization, atopic asthma, and atopic wheezein childhood. This protective effect was observed in childrenfrom farming and nonfarming households, indicating that eventhe lower levels of exposure that occur in nonfarming environmentsmay favorably influence the risk of atopic diseases in childhood.
The mechanisms by which endotoxin exposure may protect againstthe development of atopic immune responses and diseases arenot fully understood. Our findings suggest that by the timea child reaches school age, high levels of environmental exposureto endotoxin have resulted in a marked suppression of the capacityfor cytokine production in response to activation of the innateimmune system. Whereas lipopolysaccharide stimulation triggersan innate immune response by activating mainly antigen-presentingcells, staphylococcal enterotoxin B also activates T cells,resulting in a somewhat different pattern of cytokine production.Reduced responsiveness to stimulation with lipopolysaccharideafter previous stimulation with lipopolysaccharide is a phenomenonreferred to in the literature as lipopolysaccharide tolerance.13,14Our results suggest that such a down-regulation occurs in vivoas a consequence of long-term exposure to environmental endotoxin.Whether this down-regulation is merely a biologic marker ofthe exposure or is causally related to the decreased rate ofatopy cannot be determined on the basis of our data; it is anarea in which further exploration is needed. It has been suggestedthat the innate immune response has an instructive role in adaptiveimmunity.15 Differential expression of lipopolysaccharide receptorsin children from farming and nonfarming households has recentlybeen reported,16 suggesting that the innate immune system respondsto the high microbial burden of the farming environment.
Although only current endotoxin exposure was measured, the levelsare likely to reflect long-term exposure. Therefore, long-term,high-level environmental exposure may favor a state of tolerance,14which may prevent the development of allergic immune responses.We demonstrated that exposure during the first year of lifeto stables and other aspects of farm life that are likely toreflect exposure to microbial products has a strong protectiveeffect against the occurrence of asthma and atopy at schoolage. However, independent of and in addition to this effect,endotoxin exposure at school age was associated with a markedlydecreased risk of atopic outcomes. This protective effect wasalso seen in children with no exposure to farming whose mattressendotoxin levels were similar to levels found in urban homesin the Nether- lands17 and urban areas in the United States,18,19suggesting that exposure to ubiquitous microbial products stronglyaffects the development of atopy and childhood asthma. The increasein the frequency of asthma in inner-city areas of the UnitedStates, by contrast, may be related to other types of environmentalexposure.
The protective effect of endotoxin exposure at school age wasobserved only for atopic wheeze and asthma, not for nonatopicwheeze. Childhood asthma is a complex syndrome with multipleillnesses involving wheezing that develop during the infant,toddler, school-age, and adolescent years, as has been shownin several long-term, prospective surveys in which childrenwere followed from birth to adolescence and adulthood.20,21,22Although, in many cases, asthma is associated with atopic sensitizationto a variety of allergens, illnesses involving wheezing alsooccur in the absence of increased IgE responses. Variationsin genetic background, environmental factors, and the interplayamong them are likely to account for the varying clinical presentationsof wheeze. In studies of human exposure23 and in studies ofanimals,24 endotoxin has been shown to induce airway hyperresponsivenessin healthy, nonatopic subjects but to decrease airway responsivenessin sensitized animals, supporting the notion that the effectis modified by atopy, as we observed. In our study, exposureto farming in the first year of life had a protective effectagainst nonatopic wheeze, whereas exposure to endotoxin at schoolage was related to an increased risk. Therefore, not only anexposed subject's atopic status but also the timing of the exposuredetermines its beneficial or detrimental effects.
Endotoxin was measured in mattress dust, since children comeinto close contact with the microbial environment of their bedswhile sleeping and since the reproducibility of repeated endotoxinmeasurements is greater for dust from the bed than for dustfrom the floor.25 Endotoxin measurements in dust from the bedhave been reported to show little variation over time, withnonsignificant differences over a six-month period.19 Environmentalendotoxin levels are therefore likely to reflect longer-termexposure to microbial compounds. However, the cross-sectionaldesign of our study limited our ability to determine preciselythe duration of exposure represented by current endotoxin measurements,and prospective studies are clearly needed. We did not assessother bacterial components, such as nonmethylated cytidine phosphateguanosine dinucleotides specific for prokaryotic DNA (CpG motifs)or cell-wall components from atypical mycobacteria or gram-positivebacteria such as lipoteichoic acid, which are known to affectimmune responses in ways similar to that of endotoxin.26,27The observed protective effect associated with endotoxin levelsin mattress dust is therefore likely to reflect the effect ofexposure to a much broader spectrum of microbial compounds thangram-negative bacteria alone.
The results of our study indicate that environmental exposureto microbial products as assessed by the measurement of endotoxinlevels in mattress dust is associated with the development oftolerance toward ubiquitous allergens found in natural environments.Mechanisms relating to the recognition of these microbial compoundsby the innate immune system and the regulation of the resultinginflammatory responses through adaptive immunity are likelyto be of key importance for the development of atopic illnessessuch as hay fever and childhood asthma and wheeze. These insightsmay foster the generation of novel strategies aimed at the preventionof these diseases.
Supported by a grant from the Health Department of the Governmentof Salzburg, Austria; by the Zurich Lung Association; by a grantfrom the United Bank of Switzerland; by a grant from the SwissNational Science Foundation; and by the Bavarian Ministry forthe Environment.
We are indebted to our collaborators on the Allergy and EndotoxinStudy Team — Otto Holst (Borstel, Germany), Mynda Schreuerand Gerd Oberfeld (Salzburg, Austria), and Felix Sennhauser(Zurich, Switzerland); to Dr. Susan Lau and her team, UniversityChildren's Hospital Charité, Berlin, for the determinationof the allergen level in dust samples and the measurement ofspecific IgE levels in serum; and to Angelika Kronseder andStefan Gröbmair, Institute of Occupational and EnvironmentalMedicine, University of Munich, for the endotoxin measurements.
Source Information
From the Institute of Social and Preventive Medicine, Basel, Switzerland (C.B.-F., M.W., L.G.); Children's Hospital Salzburg, Salzburg, Austria (J.R., W.E.); the Department of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps University, Marburg, Germany (U.H., H.R.); the Dr. von Hauner Children's Hospital, Munich, Germany (S.M., D.C., F.G., E.M.); the Department of Experimental Pneumology, Ruhr University, Bochum, Germany (A.B.); University Children's Hospital, Zurich, Switzerland (R.P.L.); and the Institute of Occupational and Environmental Medicine, University of Munich, Munich, Germany (R.S., D.N.).
Address reprint requests to Dr. Braun-Fahrländer at the Institute of Social and Preventive Medicine, University of Basel, Steinengraben 49, CH-4051 Basel, Switzerland, or at c.braun{at}unibas.ch.
References
D'Amato G, Liccardi G, D'Amato M. Environmental risk factors (outdoor air pollution and climatic changes) and increased trend of respiratory allergy. J Investig Allergol Clin Immunol 2000;10:123-128. [Web of Science][Medline]
Gold DR. Environmental tobacco smoke, indoor allergens, and childhood asthma. Environ Health Perspect 2000;108:Suppl 4:643-651.
Wahn U, Lau S, Bergmann R, et al. Indoor allergen exposure is a risk factor for sensitization during the first three years of life. J Allergy Clin Immunol 1997;99:763-769. [CrossRef][Web of Science][Medline]
Strachan DP. Family size, infection and atopy: the first decade of the "hygiene hypothesis." Thorax 2000;55:Suppl 1:S2-S10. [CrossRef][Medline]
Delves PJ, Roitt IM. The immune system. N Engl J Med 2000;343:37-49. [Free Full Text]
Riedler J, Braun-Fahrländer C, Eder W, et al. Exposure to farming in early life and development of asthma and allergy: a cross-sectional survey. Lancet 2001;358:1129-1133. [CrossRef][Web of Science][Medline]
Kabesch M, Schaal W, Nicolai T, von Mutius E. Lower prevalence of asthma and atopy in Turkish children living in Germany. Eur Respir J 1999;13:577-582. [Abstract]
Phase II modules of the International Study of Asthma and Allergies in Childhood (ISAAC). Münster, Germany: ISAAC, 1998.
Hollander A, Heederik D, Versloot P, Douwes J. Inhibition and enhancement in the analysis of airborne endotoxin levels in various occupational environments. Am Ind Hyg Assoc J 1993;54:647-653. [Web of Science][Medline]
Asher MI, Keil U, Anderson HR, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J 1995;8:483-491. [Abstract]
SAS, release 8.02. Cary, N.C.: SAS Institute, 2001.
Schade U, Schlegel J, Hofmann K, Brade H, Flach R. Endotoxin tolerant mice produce an inhibitor of tumor necrosis factor synthesis. J Endotoxin Res 1996;3:455-462. [Free Full Text]
Fearon DT, Locksley RM. The instructive role of innate immunity in the acquired immune response. Science 1996;272:50-53. [Abstract]
Lauener R, Birchler T, Adamski J, et al. Expression of CD14 and toll-like receptor 2 in farmers' and non-farmers' children. Lancet 2002;360:465-466. [CrossRef][Medline]
Douwes J, Zuidhof A, Doekes G, et al. (13)-Beta-D-glucan and endotoxin in house dust and peak flow variability in children. Am J Respir Crit Care Med 2000;162:1348-1354. [Free Full Text]
Park JH, Gold DR, Spiegelman DL, Burge HA, Milton DK. House dust endotoxin and wheeze in the first year of life. Am J Respir Crit Care Med 2001;163:322-328. [Free Full Text]
Gereda JE, Leung DY, Thatayatikom A, et al. Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet 2000;355:1680-1683. [CrossRef][Web of Science][Medline]
Strachan DP, Butland BK, Anderson HR. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort. BMJ 1996;312:1195-1199. [Free Full Text]
Silverman M, Wilson N. Wheezing phenotypes in childhood. Thorax 1997;52:936-937. [Web of Science][Medline]
Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. N Engl J Med 1995;332:133-138. [Free Full Text]
Rylander R, Bake B, Fischer JJ, Helander IM. Pulmonary function and symptoms after inhalation of endotoxin. Am Rev Respir Dis 1989;140:981-986. [Web of Science][Medline]
Tulic MK, Wale JL, Holt PG, Sly PD. Modification of the inflammatory response to allergen challenge after exposure to bacterial lipopolysaccharide. Am J Respir Cell Mol Biol 2000;22:604-612. [Free Full Text]
Park JH, Spiegelman DL, Burge HA, Gold DR, Chew GL, Milton DK. Longitudinal study of dust and airborne endotoxin in the home. Environ Health Perspect 2000;108:1023-1028. [Web of Science][Medline]
Abou-Zeid C, Gares MP, Inwald J, et al. Induction of a type 1 immune response to a recombinant antigen from Mycobacterium tuberculosis in Mycobacterium vaccae. Infect Immun 1997;65:1856-1862. [Abstract]
Cleveland MG, Gorham JD, Murphy TL, Tuomanen E, Murphy KM. Lipoteichoic acid preparations of gram-positive bacteria induce interleukin-12 through a CD14-dependent pathway. Infect Immun 1996;64:1906-1912. [Abstract]
Endotoxin and Asthma
Maziak W., Perzanowski M. S., Platts-Mills T. A.E., Speiser D. E., Zippelius A., Braun-Fahrländer C., Lauener R. P., von Mutius E., Weiss S. T.
Extract |
Full Text |
PDF
N Engl J Med 2003;
348:171-174, Jan 9, 2003.
Correspondence
This article has been cited by other articles:
Ryan, P. H., Bernstein, D. I., Lockey, J., Reponen, T., Levin, L., Grinshpun, S., Villareal, M., Khurana Hershey, G. K., Burkle, J., LeMasters, G.
(2009). Exposure to Traffic-related Particles and Endotoxin during Infancy Is Associated with Wheezing at Age 3 Years. Am. J. Respir. Crit. Care Med.
180: 1068-1075
[Abstract][Full Text]
Kim, Y.-S., Hong, S.-W., Choi, J.-P., Shin, T.-S., Moon, H.-G., Choi, E.-J., Jeon, S. G., Oh, S.-Y., Gho, Y. S., Zhu, Z., Kim, Y.-K.
(2009). Vascular Endothelial Growth Factor Is a Key Mediator in the Development of T Cell Priming and Its Polarization to Type 1 and Type 17 T Helper Cells in the Airways. J. Immunol.
183: 5113-5120
[Abstract][Full Text]
Smit, L. A. M., Heederik, D., Doekes, G., Krop, E. J. M., Rijkers, G. T., Wouters, I. M.
(2009). Ex vivo cytokine release reflects sensitivity to occupational endotoxin exposure. Eur Respir J
34: 795-802
[Abstract][Full Text]
von Hertzen, L., Haahtela, T.
(2009). Con: House Dust Mites in Atopic Diseases: Accused for 45 Years but Not Guilty?. Am. J. Respir. Crit. Care Med.
180: 113-119
[Full Text]
Postma, D. S., Koppelman, G. H.
(2009). Genetics of Asthma: Where Are We and Where Do We Go?. Proc Am Thorac Soc
6: 283-287
[Abstract][Full Text]
Subramanian, S. V., Jun, H.-J., Kawachi, I., Wright, R. J.
(2009). Contribution of Race/Ethnicity and Country of Origin to Variations in Lifetime Reported Asthma: Evidence for a Nativity Advantage. AJPH
99: 690-697
[Abstract][Full Text]
TANIGUCHI, Y., YOSHIOKA, N., NISHIZAWA, T., INAGAWA, H., KOHCHI, C., SOMA, G.-I.
(2009). Utility and Safety of LPS-based Fermented Flour Extract as a Macrophage Activator. Anticancer Res
29: 859-864
[Abstract][Full Text]
Smit, L. A. M., Siroux, V., Bouzigon, E., Oryszczyn, M.-P., Lathrop, M., Demenais, F., Kauffmann, F., on behalf of the Epidemiological Study on the Gene,
(2009). CD14 and Toll-like Receptor Gene Polymorphisms, Country Living, and Asthma in Adults. Am. J. Respir. Crit. Care Med.
179: 363-368
[Abstract][Full Text]
Bruce, S, Nyberg, F, Melen, E, James, A, Pulkkinen, V, Orsmark-Pietras, C, Bergstrom, A, Dahlen, B, Wickman, M, von Mutius, E, Doekes, G, Lauener, R, Riedler, J, Eder, W, van Hage, M, Pershagen, G, Scheynius, A, Kere, J
(2009). The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms. J. Med. Genet.
46: 159-167
[Abstract][Full Text]
Eggleston, P. A.
(2009). Complex Interactions of Pollutant and Allergen Exposures and Their Impact on People With Asthma. Pediatrics
123: S160-S167
[Abstract][Full Text]
Duan, W., So, T., Croft, M.
(2008). Antagonism of Airway Tolerance by Endotoxin/Lipopolysaccharide through Promoting OX40L and Suppressing Antigen-Specific Foxp3+ T Regulatory Cells. J. Immunol.
181: 8650-8659
[Abstract][Full Text]
Holgate, S., Bisgaard, H., Bjermer, L., Haahtela, T., Haughney, J., Horne, R., McIvor, A., Palkonen, S., Price, D. B., Thomas, M., Valovirta, E., Wahn, U.
(2008). The Brussels Declaration: the need for change in asthma management. Eur Respir J
32: 1433-1442
[Abstract][Full Text]
Gorelik, L., Kauth, M., Gehlhar, K., Bufe, A., Holst, O., Peters, M.
(2008). Modulation of dendritic cell function by cowshed dust extract. Innate Immunity
14: 345-355
[Abstract]
Henderson, A.
(2008). What have we learned from prospective cohort studies of asthma in children?. Chronic Respiratory Disease
5: 225-231
[Abstract]
Koppelman, G. H., te Meerman, G. J., Postma, D. S.
(2008). Genetic testing for asthma. Eur Respir J
32: 775-782
[Abstract][Full Text]
Douwes, J., Cheng, S., Travier, N., Cohet, C., Niesink, A., McKenzie, J., Cunningham, C., Le Gros, G., von Mutius, E., Pearce, N.
(2008). Farm exposure in utero may protect against asthma, hay fever and eczema. Eur Respir J
32: 603-611
[Abstract][Full Text]
Wahn, H. U.
(2008). Strategies for Atopy Prevention. J. Nutr.
138: 1770S-1772S
[Abstract][Full Text]
Schaumann, F., Muller, M., Braun, A., Luettig, B., Peden, D. B., Hohlfeld, J. M., Krug, N.
(2008). Endotoxin Augments Myeloid Dendritic Cell Influx into the Airways in Patients with Allergic Asthma. Am. J. Respir. Crit. Care Med.
177: 1307-1313
[Abstract][Full Text]
Smit, L. A. M., Heederik, D., Doekes, G., Blom, C., van Zweden, I., Wouters, I. M.
(2008). Exposure-response analysis of allergy and respiratory symptoms in endotoxin-exposed adults. Eur Respir J
31: 1241-1248
[Abstract][Full Text]
Goldberg, M. R., Nadiv, O., Luknar-Gabor, N., Zadik-Mnuhin, G., Tovbin, J., Katz, Y.
(2008). Correlation of Th1-Type Cytokine Expression and Induced Proliferation to Lipopolysaccharide. Am. J. Respir. Cell Mol. Bio.
38: 733-737
[Abstract][Full Text]
Chen, C-M., Morgenstern, V., Bischof, W., Herbarth, O., Borte, M., Behrendt, H., Kramer, U., von Berg, A., Berdel, D., Bauer, C. P., Koletzko, S., Wichmann, H-E., Heinrich, J., the Influences of Lifestyle Related Factors on the,
(2008). Dog ownership and contact during childhood and later allergy development. Eur Respir J
31: 963-973
[Abstract][Full Text]
Miller, R. L., Ho, S.-m.
(2008). Environmental Epigenetics and Asthma: Current Concepts and Call for Studies. Am. J. Respir. Crit. Care Med.
177: 567-573
[Abstract][Full Text]
Tliba, O., Amrani, Y., Panettieri, R. A. Jr
(2008). Is Airway Smooth Muscle the "Missing Link" Modulating Airway Inflammation in Asthma?. Chest
133: 236-242
[Abstract][Full Text]
Wright, R. J., Subramanian, S.V.
(2007). Advancing a Multilevel Framework for Epidemiologic Research on Asthma Disparities. Chest
132: 757S-769S
[Abstract][Full Text]
Balicer, R. D., Grotto, I., Mimouni, M., Mimouni, D.
(2007). Is Childhood Vaccination Associated With Asthma? A Meta-analysis of Observational Studies. Pediatrics
120: e1269-e1277
[Abstract][Full Text]
Tse, K., Horner, A. A
(2007). Update on toll-like receptor-directed therapies for human disease. Ann Rheum Dis
66: iii77-iii80
[Abstract][Full Text]
Schroder, N. W. J., Arditi, M.
(2007). IEIIS Meeting minireview: The role of innate immunity in the pathogenesis of asthma: evidence for the involvement of Toll-like receptor signaling. Innate Immunity
13: 305-312
[Abstract]
Weinmayr, G., Weiland, S. K., Bjorksten, B., Brunekreef, B., Buchele, G., Cookson, W. O. C., Garcia-Marcos, L., Gotua, M., Gratziou, C., van Hage, M., von Mutius, E., Riikjarv, M.-A., Rzehak, P., Stein, R. T., Strachan, D. P., Tsanakas, J., Wickens, K., Wong, G. W., and the ISAAC Phase Two Study Group,
(2007). Atopic Sensitization and the International Variation of Asthma Symptom Prevalence in Children. Am. J. Respir. Crit. Care Med.
176: 565-574
[Abstract][Full Text]
Glick, M.
(2007). The Dirt on Being Clean: Or, Why More Children Develop Asthma. Journal of the American Dental Association
138: 1188-1189
[Full Text]
Perez, N, Regairaz, L, Bustamante, J, Osimani, N, Bergna, D, Morales, J, Agosti, M R, Gonzalez-Ayala, S, Peltzer, C, Rodrigo, A
(2007). Severity of meningococcal infections is related to anthropometrical parameters. Arch. Dis. Child.
92: 790-794
[Abstract][Full Text]
Lundell, A.-C., Andersson, K., Josefsson, E., Steinkasserer, A., Rudin, A.
(2007). Soluble CD14 and CD83 from Human Neonatal Antigen-Presenting Cells Are Inducible by Commensal Bacteria and Suppress Allergen-Induced Human Neonatal Th2 Differentiation. Infect. Immun.
75: 4097-4104
[Abstract][Full Text]
Radon, K., Windstetter, D., Poluda, A. L., Mueller, B., Mutius, E. v., Koletzko, S., Chronische Autoimmunerkrankungen und Kontakt zu Ti,
(2007). Contact With Farm Animals in Early Life and Juvenile Inflammatory Bowel Disease: A Case-Control Study. Pediatrics
120: 354-361
[Abstract][Full Text]
von Mutius, E.
(2007). Asthma and Allergies in Rural Areas of Europe. Proc Am Thorac Soc
4: 212-216
[Abstract][Full Text]
Martinez, F. D.
(2007). CD14, Endotoxin, and Asthma Risk: Actions and Interactions. Proc Am Thorac Soc
4: 221-225
[Abstract][Full Text]
Johnston, S. L.
(2007). Innate Immunity in the Pathogenesis of Virus-induced Asthma Exacerbations. Proc Am Thorac Soc
4: 267-270
[Abstract][Full Text]
Yoo, J., Tcheurekdjian, H., Lynch, S. V., Cabana, M., Boushey, H. A.
(2007). Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials. Proc Am Thorac Soc
4: 277-282
[Abstract][Full Text]
Kline, J. N.
(2007). Eat Dirt: CpG DNA and Immunomodulation of Asthma. Proc Am Thorac Soc
4: 283-288
[Abstract][Full Text]
Camateros, P., Tamaoka, M., Hassan, M., Marino, R., Moisan, J., Marion, D., Guiot, M.-C., Martin, J. G., Radzioch, D.
(2007). Chronic Asthma-induced Airway Remodeling Is Prevented by Toll-like Receptor-7/8 Ligand S28463. Am. J. Respir. Crit. Care Med.
175: 1241-1249
[Abstract][Full Text]
Schulze, A., van Strien, R. T., Praml, G., Nowak, D., Radon, K.
(2007). Characterisation of asthma among adults with and without childhood farm contact. Eur Respir J
29: 1169-1173
[Abstract][Full Text]
Gehring, U., Heinrich, J., Hoek, G., Giovannangelo, M., Nordling, E., Bellander, T., Gerritsen, J., de Jongste, J. C., Smit, H. A., Wichmann, H-E., Wickman, M., Brunekreef, B.
(2007). Bacteria and mould components in house dust and children's allergic sensitisation. Eur Respir J
29: 1144-1153
[Abstract][Full Text]
Goldberg, S., Israeli, E., Schwartz, S., Shochat, T., Izbicki, G., Toker-Maimon, O., Klement, E., Picard, E.
(2007). Asthma Prevalence, Family Size, and Birth Order. Chest
131: 1747-1752
[Abstract][Full Text]
Kozyrskyj, A. L., Ernst, P., Becker, A. B.
(2007). Increased Risk of Childhood Asthma From Antibiotic Use in Early Life. Chest
131: 1753-1759
[Abstract][Full Text]
Van Hove, C. L., Maes, T., Joos, G. F., Tournoy, K. G.
(2007). Prolonged Inhaled Allergen Exposure Can Induce Persistent Tolerance. Am. J. Respir. Cell Mol. Bio.
36: 573-584
[Abstract][Full Text]
Kim, Y.-K., Oh, S.-Y., Jeon, S. G., Park, H.-W., Lee, S.-Y., Chun, E.-Y., Bang, B., Lee, H.-S., Oh, M.-H., Kim, Y.-S., Kim, J.-H., Gho, Y. S., Cho, S.-H., Min, K.-U., Kim, Y.-Y., Zhu, Z.
(2007). Airway Exposure Levels of Lipopolysaccharide Determine Type 1 versus Type 2 Experimental Asthma. J. Immunol.
178: 5375-5382
[Abstract][Full Text]
Martinez, F. D.
(2007). Gene-Environment Interactions in Asthma: With Apologies to William of Ockham. Proc Am Thorac Soc
4: 26-31
[Abstract][Full Text]
Morgenstern, V, Zutavern, A, Cyrys, J, Brockow, I, Gehring, U, Koletzko, S, Bauer, C P, Reinhardt, D, Wichmann, H-E, Heinrich, J
(2007). Respiratory health and individual estimated exposure to traffic-related air pollutants in a cohort of young children. Occup. Environ. Med.
64: 8-16
[Abstract][Full Text]
Goldberg, M. R., Luknar-Gabor, N., Zadik-Mnuhin, G., Koch, P., Tovbin, J., Katz, Y.
(2007). Synergy between LPS and immobilized anti-human CD3{epsilon} mAb for activation of cord blood CD3+ T cells. Int Immunol
19: 99-103
[Abstract][Full Text]
Pincus-Knackstedt, M. K., Joachim, R. A., Blois, S. M., Douglas, A. J., Orsal, A. S., Klapp, B. F., Wahn, U., Hamelmann, E., Arck, P. C.
(2006). Prenatal Stress Enhances Susceptibility of Murine Adult Offspring toward Airway Inflammation. J. Immunol.
177: 8484-8492
[Abstract][Full Text]
Castro-Giner, F, Kauffmann, F, de Cid, R, Kogevinas, M
(2006). Gene-environment interactions in asthma.. Occup. Environ. Med.
63: 776- 761
[Full Text]
Morris, G. E., Parker, L. C., Ward, J. R., Jones, E. C., Whyte, M. K. B., Brightling, C. E., Bradding, P., Dower, S. K., Sabroe, I.
(2006). Cooperative molecular and cellular networks regulate Toll-like receptor-dependent inflammatory responses. FASEB J.
20: 2153-2155
[Abstract][Full Text]
El-Ekiaby, A., Brianas, L., Skowronski, M. E., Coreno, A. J., Galan, G., Kaeberlein, F. J., Seitz, R. E., Villaba, K. D., Dickey-White, H., McFadden, E. R. Jr.
(2006). Impact of Race on the Severity of Acute Episodes of Asthma and Adrenergic Responsiveness. Am. J. Respir. Crit. Care Med.
174: 508-513
[Abstract][Full Text]
George, C. L. S., White, M. L., Kulhankova, K., Mahajan, A., Thorne, P. S., Snyder, J. M., Kline, J. N.
(2006). Early exposure to a nonhygienic environment alters pulmonary immunity and allergic responses. Am. J. Physiol. Lung Cell. Mol. Physiol.
291: L512-L522
[Abstract][Full Text]
Kabesch, M.
(2006). A Glitch in the Switch?: Of Endotoxin, CD14, and Allergy.. Am. J. Respir. Crit. Care Med.
174: 365-366
[Full Text]
Simpson, A., John, S. L., Jury, F., Niven, R., Woodcock, A., Ollier, W. E. R., Custovic, A.
(2006). Endotoxin Exposure, CD14, and Allergic Disease: An Interaction between Genes and the Environment. Am. J. Respir. Crit. Care Med.
174: 386-392
[Abstract][Full Text]
Koch, M., Witzenrath, M., Reuter, C., Herma, M., Schutte, H., Suttorp, N., Collins, H., Kaufmann, S. H. E.
(2006). Role of Local Pulmonary IFN-{gamma} Expression in Murine Allergic Airway Inflammation. Am. J. Respir. Cell Mol. Bio.
35: 211-219
[Abstract][Full Text]
Zekveld, C., Bibakis, I., Bibaki-Liakou, V., Pedioti, A., Dimitroulis, I., Harris, J., Newman Taylor, A. J., Cullinan, P.
(2006). The effects of farming and birth order on asthma and allergies. Eur Respir J
28: 82-88
[Abstract][Full Text]
Mirabelli, M. C., Wing, S., Marshall, S. W., Wilcosky, T. C.
(2006). Asthma Symptoms Among Adolescents Who Attend Public Schools That Are Located Near Confined Swine Feeding Operations. Pediatrics
118: e66-e75
[Abstract][Full Text]
Hollingsworth, J. W., Whitehead, G. S., Lin, K. L., Nakano, H., Gunn, M. D., Schwartz, D. A., Cook, D. N.
(2006). TLR4 Signaling Attenuates Ongoing Allergic Inflammation. J. Immunol.
176: 5856-5862
[Abstract][Full Text]
LIPNER, E. M., GOPI, P. G., SUBRAMANI, R., KOLAPPAN, C., SADACHARAM, K., KUMARAN, P., PREVOTS, D. R., NARAYANAN, P. R., NUTMAN, T. B., KUMARASWAMI, V.
(2006). Coincident filarial, intestinal helminth, and mycobacterial infection: helminths fail to influence tuberculin reactivity, but bcg influences hookworm prevalence.. Am J Trop Med Hyg
74: 841-847
[Abstract][Full Text]
Sundy, J. S., Wood, W. A., Watt, J. L., Kline, J. N., Schwartz, D. A.
(2006). Safety of incremental inhaled lipopolysaccharide challenge in humans. Innate Immunity
12: 113-119
[Abstract]
Chen, E., Martin, A. D., Matthews, K. A.
(2006). Understanding Health Disparities: The Role of Race and Socioeconomic Status in Children's Health. AJPH
96: 702-708
[Abstract][Full Text]
Vojdani, A., Erde, J.
(2006). Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: The Ultimate Antagonist (I).. Evid Based Complement Alternat Med
3: 25-30
[Abstract][Full Text]
Nigo, Y. I., Yamashita, M., Hirahara, K., Shinnakasu, R., Inami, M., Kimura, M., Hasegawa, A., Kohno, Y., Nakayama, T.
(2006). Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proc. Natl. Acad. Sci. USA
103: 2286-2291
[Abstract][Full Text]
Peters, M, Kauth, M, Schwarze, J, Korner-Rettberg, C, Riedler, J, Nowak, D, Braun-Fahrlander, C, von Mutius, E, Bufe, A, Holst, O, the ALEX Study Group,
(2006). Inhalation of stable dust extract prevents allergen induced airway inflammation and hyperresponsiveness. Thorax
61: 134-139
[Abstract][Full Text]
Radon, K
(2006). THE TWO SIDES OF THE "ENDOTOXIN COIN". Occup. Environ. Med.
63: 73-78
[Full Text]
Trevillian, L. F., Ponsonby, A.-L., Dwyer, T., Kemp, A., Cochrane, J., Lim, L. L.-Y., Carmichael, A.
(2005). Infant Sleeping Environment and Asthma at 7 Years: A Prospective Cohort Study. AJPH
95: 2238-2245
[Abstract][Full Text]
Malo, J.-L.
(2005). Future advances in work-related asthma and the impact on occupational health. Occup Med (Lond)
55: 606-611
[Abstract][Full Text]
Thorne, P. S., Kulhankova, K., Yin, M., Cohn, R., Arbes, S. J. Jr., Zeldin, D. C.
(2005). Endotoxin Exposure Is a Risk Factor for Asthma: The National Survey of Endotoxin in United States Housing. Am. J. Respir. Crit. Care Med.
172: 1371-1377
[Abstract][Full Text]
Radon, K., Windstetter, D., Solfrank, S., von Mutius, E., Nowak, D., Schwarz, H.-P., for the Chronic Autoimmune Disease and Contact to,
(2005). Exposure to Farming Environments in Early Life and Type 1 Diabetes: A Case-Control Study. Diabetes
54: 3212-3216
[Abstract][Full Text]
Choudhry, S., Avila, P. C., Nazario, S., Ung, N., Kho, J., Rodriguez-Santana, J. R., Casal, J., Tsai, H.-J., Torres, A., Ziv, E., Toscano, M., Sylvia, J. S., Alioto, M., Salazar, M., Gomez, I., Fagan, J. K., Salas, J., Lilly, C., Matallana, H., Castro, R. A., Selman, M., Weiss, S. T., Ford, J. G., Drazen, J. M., Rodriguez-Cintron, W., Chapela, R., Silverman, E. K., Burchard, E. G., from the Genetics of Asthma in Latino Americans (G,
(2005). CD14 Tobacco Gene-Environment Interaction Modifies Asthma Severity and Immunoglobulin E Levels in Latinos with Asthma. Am. J. Respir. Crit. Care Med.
172: 173-182
[Abstract][Full Text]
THORNE, P. S., METWALI, N., AVOL, E., McCONNELL, R. S.
(2005). Surface Sampling for Endotoxin Assessment using Electrostatic Wiping Cloths. ANN OCCUP HYG
49: 401-406
[Abstract][Full Text]
Polack, F. P., Irusta, P. M., Hoffman, S. J., Schiatti, M. P., Melendi, G. A., Delgado, M. F., Laham, F. R., Thumar, B., Hendry, R. M., Melero, J. A., Karron, R. A., Collins, P. L., Kleeberger, S. R.
(2005). The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin. Proc. Natl. Acad. Sci. USA
102: 8996-9001
[Abstract][Full Text]
Bals, R.
(2005). Lipopolysaccharide and the lung: a story of love and hate. Eur Respir J
25: 776-777
[Full Text]
Hayashi, T., Gong, X., Rossetto, C., Shen, C., Takabayashi, K., Redecke, V., Spiegelberg, H., Broide, D., Raz, E.
(2005). Induction and Inhibition of the Th2 Phenotype Spread: Implications for Childhood Asthma. J. Immunol.
174: 5864-5873
[Abstract][Full Text]
Velasco, G., Campo, M., Manrique, O. J., Bellou, A., He, H., Arestides, R. S. S., Schaub, B., Perkins, D. L., Finn, P. W.
(2005). Toll-Like Receptor 4 or 2 Agonists Decrease Allergic Inflammation. Am. J. Respir. Cell Mol. Bio.
32: 218-224
[Abstract][Full Text]
Elliott, L., Yeatts, K., Loomis, D.
(2004). Ecological associations between asthma prevalence and potential exposure to farming. Eur Respir J
24: 938-941
[Abstract][Full Text]
Boekhorst, J., Siezen, R. J., Zwahlen, M.-C., Vilanova, D., Pridmore, R. D., Mercenier, A., Kleerebezem, M., de Vos, W. M., Brussow, H., Desiere, F.
(2004). The complete genomes of Lactobacillus plantarum and Lactobacillus johnsonii reveal extensive differences in chromosome organization and gene content. Microbiology
150: 3601-3611
[Abstract][Full Text]
Kuipers, H., Heirman, C., Hijdra, D., Muskens, F., Willart, M., van Meirvenne, S., Thielemans, K., Hoogsteden, H. C., Lambrecht, B. N.
(2004). Dendritic cells retrovirally overexpressing IL-12 induce strong Th1 responses to inhaled antigen in the lung but fail to revert established Th2 sensitization. J. Leukoc. Biol.
76: 1028-1038
[Abstract][Full Text]
Busse, W., Banks-Schlegel, S., Noel, P., Ortega, H., Taggart, V., Elias, J.
(2004). Future Research Directions in Asthma: An NHLBI Working Group Report. Am. J. Respir. Crit. Care Med.
170: 683-690
[Abstract][Full Text]
Long, J. A., Fogel-Petrovic, M., Knight, D. A., Thompson, P. J., Upham, J. W.
(2004). Higher Prostaglandin E2 Production by Dendritic Cells from Subjects with Asthma Compared with Normal Subjects. Am. J. Respir. Crit. Care Med.
170: 485-491
[Abstract][Full Text]
Guill, M. F.
(2004). Asthma Update: Epidemiology and Pathophysiology. Pediatr. Rev.
25: 299-305
[Full Text]
Brummel, T., Ching, A., Seroude, L., Simon, A. F., Benzer, S.
(2004). Drosophila lifespan enhancement by exogenous bacteria. Proc. Natl. Acad. Sci. USA
101: 12974-12979
[Abstract][Full Text]
Woodcock, A., Lowe, L. A., Murray, C. S., Simpson, B. M., Pipis, S. D., Kissen, P., Simpson, A., Custovic, A.
(2004). Early Life Environmental Control: Effect on Symptoms, Sensitization, and Lung Function at Age 3 Years. Am. J. Respir. Crit. Care Med.
170: 433-439
[Abstract][Full Text]
Dagoye, D., Bekele, Z., Woldemichael, K., Nida, H., Yimam, M., Venn, A.J., Hall, A., Britton, J.R., Lewis, S.A., Mckeever, T., Hubbard, R.
(2004). Domestic risk factors for wheeze in urban and rural Ethiopian children. QJM
97: 489-498
[Abstract][Full Text]
Gelfand, E. W., Joetham, A., Cui, Z.-H., Balhorn, A., Takeda, K., Taube, C., Dakhama, A.
(2004). Induction and Maintenance of Airway Responsiveness to Allergen Challenge Are Determined at the Age of Initial Sensitization. J. Immunol.
173: 1298-1306
[Abstract][Full Text]
Phipatanakul, W., Celedon, J. C., Raby, B. A., Litonjua, A. A., Milton, D. K., Sredl, D., Weiss, S. T., Gold, D. R.
(2004). Endotoxin Exposure and Eczema in the First Year of Life. Pediatrics
114: 13-18
[Abstract][Full Text]
Bashir, M. E. H., Louie, S., Shi, H. N., Nagler-Anderson, C.
(2004). Toll-Like Receptor 4 Signaling by Intestinal Microbes Influences Susceptibility to Food Allergy. J. Immunol.
172: 6978-6987
[Abstract][Full Text]
Pekkanen, J.
(2004). Commentary: Use of antibiotics and risk of asthma. Int J Epidemiol
33: 564-565
[Full Text]
Gohlke, H., Illig, T., Bahnweg, M., Klopp, N., Andre, E., Altmuller, J., Herbon, N., Werner, M., Knapp, M., Pescollderungg, L., Boner, A., Malerba, G., Pignatti, P. F., Wjst, M.
(2004). Association of the Interleukin-1 Receptor Antagonist Gene with Asthma. Am. J. Respir. Crit. Care Med.
169: 1217-1223
[Abstract][Full Text]
Holgate, S.T.
(2004). Lessons learnt from the epidemic of asthma. QJM
97: 247-257
[Full Text]
Eduard, W, Douwes, J, Omenaas, E, Heederik, D
(2004). Do farming exposures cause or prevent asthma? Results from a study of adult Norwegian farmers. Thorax
59: 381-386
[Abstract][Full Text]
McGeady, S. J.
(2004). Immunocompetence and Allergy. Pediatrics
113: 1107-1113
[Abstract][Full Text]
Rawls, J. F., Samuel, B. S., Gordon, J. I.
(2004). From The Cover: Gnotobiotic zebrafish reveal evolutionarily conserved responses to the gut microbiota. Proc. Natl. Acad. Sci. USA
101: 4596-4601
[Abstract][Full Text]
Nowak, D., Suppli Ulrik, C., von Mutius, E.
(2004). Asthma and atopy: has peak prevalence been reached?. Eur Respir J
23: 359-360
[Full Text]
Holgate, S. T
(2004). The epidemic of asthma and allergy. JRSM
97: 103-110
[Full Text]
Kabesch, M., Lauener, R. P.
(2004). Why Old McDonald had a farm but no allergies: genes, environments, and the hygiene hypothesis. J. Leukoc. Biol.
75: 383-387
[Full Text]
Park, J.-H., Szponar, B., Larsson, L., Gold, D. R., Milton, D. K.
(2004). Characterization of Lipopolysaccharides Present in Settled House Dust. Appl. Environ. Microbiol.
70: 262-267
[Abstract][Full Text]
Lutton, J. D., Winston, R., Rodman, T. C.
(2004). Multiple Sclerosis: Etiological Mechanisms and Future Directions. Exp. Biol. Med.
229: 12-20
[Abstract][Full Text]
Guerra, S., Lohman, I. C., Halonen, M., Martinez, F. D., Wright, A. L.
(2004). Reduced Interferon {gamma} Production and Soluble CD14 Levels in Early Life Predict Recurrent Wheezing by 1 Year of Age. Am. J. Respir. Crit. Care Med.
169: 70-76
[Abstract][Full Text]
, interferon-
, interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children. 
3)-Beta-D-glucan and endotoxin in house dust and peak flow variability in children. Am J Respir Crit Care Med 2000;162:1348-1354. 
Previous
