Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy.

BACKGROUND: Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases. RESULTS: Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children's respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (ß = - 1.75, p = 0.015) after adjustment for child's sex, age, BMI, parents' smoking status, allergic history, and education levels, PM2.5, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65-0.99). CONCLUSIONS: Exposure to BBzP in settled dust might increase children's respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.

Cytokines and growth factors in a biologic product obtained from patients' urine as immune-modulators to treat autoimmune and allergic diseases.

At "Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C." in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an "immune-modulator" has been developed. In this study, we will refer to this treatment substance as the "immune-modulator." In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator. Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay. Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1ß, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65-70% of samples; IL5, IL-1B, and IL-17 in 50-60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20-30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1ß, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment. The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.

Longitudinal effect of phthalates exposure on allergic diseases in children.

BACKGROUND: Environmental chemicals, such as phthalates, phenols, and parabens, may affect children's immune development and contribute to the risk of atopic diseases and asthma. OBJECTIVE: To evaluate the associations between prenatal and childhood phthalate exposure and atopic diseases in children at the age of 9 years. METHODS: This analysis is restricted to 145 mother-child pairs from the prospective Polish Mother and Child Cohort Study. Phthalate metabolite levels were assessed in the urine samples collected from mothers during the third trimester of pregnancy and from children at age of 2 and 9 years. For the appropriate recognition of children's health status, a questionnaire was administered to the mothers and completed with information from the medical record of each child. The clinical examination was performed by a pediatrician/allergist in the presence of the mother or a relative. RESULTS: A higher urine concentration of mono-2-ethyl-5-oxohexyl phthalate increased the risk of food allergy in children at the age of 9 years (odds ratio [OR], 1.75; 95% CI, 1.19-2.57; P = .004) and decreased the risk of atopic dermatitis (OR, 0.49; 95% CI, 0.27-0.87; P = .02). For mono-2-ethyl-5-hydroxyhexyl phthalate, an increased risk of atopic dermatitis was observed (OR, 1.90; 95% CI, 1.18-3.05; P = .008). A higher urine concentration of mono-benzyl phthalate increased the risk of asthma in children (OR, 1.67; 95% CI, 1.08-2.58; P = .02), but the risk of asthma decreased when the concentration of mono-2-ethylhexyl phthalate was higher (OR, 0.64; 95% CI, 10.43-0.97; P = .04). CONCLUSION: Our study has not provided clear evidence of the negative effect of phthalate exposure during pregnancy and within the 9 years after birth on allergic diseases in children.

Associations between urine iodine and allergic diseases in the Korean National Health and Nutrition Examination Survey 2013-2015: A STROBE-compliant article.

BACKGROUND: The associations between excessive iodine intake and allergic diseases have not been evaluated. PURPOSE: We aimed to investigate the associations of allergic diseases with urinary iodine concentration (UIC). STUDY DESIGN: A nation-wide population-based survey conducted by the the Korean Centers for Disease Control and Prevention METHODS: In total, 5598 participants older than 19 years who participated in the Korean National Health and Nutrition Examination Survey 2013-2015 were enrolled for analysis. Multiple logistic regression analysis was used to determine the odds ratios for allergic diseases according to UIC. RESULTS: Allergic diseases were associated with the highest UIC quartile. Compared with subjects in lower UIC quartiles, subjects in the highest UIC quartile were at greater risk for atopic dermatitis (OR = 1.471, 95% CI, 1.028-2.107) and allergic rhinitis (OR = 1.362, 95% CI, 1.129-1.644) after adjustment for age and sex. CONCLUSION: This study revealed that the highest UIC quartile is associated with allergic diseases. Further laboratory and clinical studies are needed to evaluate the associations between excessive iodine intake and allergic diseases.

Associations between allergic symptoms and phosphate flame retardants in dust and their urinary metabolites among school children.

BACKGROUND: Phosphate flame retardants (PFRs) are ubiquitously detected in indoor environments. Despite increasing health concerns pertaining to PFR exposure, few epidemiological studies have examined PFR exposure and its effect on children's allergies. OBJECTIVES: To investigate the association between PFRs in house dust, their metabolites in urine, and symptoms of wheeze and allergies among school-aged children. METHODS: A total of 128 elementary school-aged children were enrolled. House dust samples were collected from upper-surface objects. Urine samples were collected from the first morning void. Levels of 11 PFRs in dust and 14 PFR metabolites in urine were measured. Parent-reported symptoms of wheeze, rhinoconjunctivitis, and eczema were evaluated using the International Study of Asthma and Allergies in Childhood questionnaire. The odds ratios (ORs) of the Ln transformed PFR concentrations and categorical values were calculated using a logistic regression model adjusted for sex, grade, dampness index, annual house income, and creatinine level (for PFR metabolites only). RESULTS: The prevalence rates of wheeze, rhinoconjunctivitis, and eczema were 22.7%, 36.7%, and 28.1%, respectively. A significant association between tris(1,3-dichloroisopropyl) phosphate (TDCIPP) in dust and eczema was observed: OR (95% confidence interval), 1.44 (1.13-1.82) (>limit of detection (LOD) vs LOD vs

Bisphenol A exposure may increase the risk of development of atopic disorders in children.

BACKGROUND: Little is known about the effect of Bisphenol A (BPA) on atopic disorders. OBJECTIVE: To investigated the associations (i) between postnatal BPA exposure and allergic diseases in children; (ii) between BPA and IgE levels for the possible disease pathogenesis; and (iii) gender-based differences. METHODS: A total of 453 children from Childhood Environment and Allergic Diseases Study cohort with urine and blood samples were recruited in Taiwan. Urinary BPA glucoronide (BPAG) levels were measured by UPLC-MS/MS at ages 3 and 6 years. The associations between BPAG levels at different ages and IgE levels and the development of allergic diseases were evaluated by multivariate linear regression and logistic regression. A mediation analysis was also conducted to evaluate how much risk of allergic diseases in relation to BPA exposure is explained by IgE changes. RESULTS: The BPAG levels at age 3 were positively associated with IgE levels at age 3 (ß=64.85kU/l per ln-unit increase BPAG level; 95% CI, 14.59-115.11kU/l). Stratified by gender, BPAG levels at age 3 were positively associated with IgE levels at age 3, particularly in girls (ß=139.23kU/l; 95% CI, 57.38-221.09kU/l). Similar results were also found at age 6. Urinary BPAG levels at age 3 were significantly associated with asthma at ages 3 and 6, with OR (95%CI) of 1.29(1.08-1.55) and 1.27(1.04-1.55). We estimated that 70% of the total effect of BPA exposure on asthma is mediated by IgE levels. CONCLUSIONS: BPA exposures were associated with IgE levels and may increase the risk of development of allergic diseases in children particularly in girls.

The associations of triclosan and paraben exposure with allergen sensitization and wheeze in children.

Triclosan and parabens are chemicals used in personal care and medical products as microbicides and preservatives. Triclosan and paraben exposure may be associated with allergy (atopy), but these associations have not been evaluated with respect to other atopic states such as eczema (atopic dermatitis). This study examines the associations of urinary triclosan and paraben concentrations with allergic sensitization and asthma in children according to eczema history. We performed a cross-sectional analysis of U.S. children aged 6-18 years who participated in the National Health and Nutrition Examination Survey (2005-2006). Triclosan and paraben concentrations were measured in urine. We assessed associations of triclosan and parabens with allergic sensitization and asthma using multivariable logistic regression in 837 children with complete data and stratified our results by eczema status. After covariate adjustment, triclosan and methyl and propyl paraben concentrations were positively associated with the odds of aeroallergen sensitization. Eczema did not significantly modify the association between triclosan or paraben levels and aeroallergen sensitization, asthma, or wheeze. The odds of parent-reported atopic asthma increased 34% (95% CI, 0, 81) across triclosan concentration quartiles. Increasing triclosan concentrations (quartiles) were associated with 2.3 times the odds of food sensitization (95% CI, 1.14, 4.44) among children with eczema, but not among children without eczema (OR, 1.25; 95% CI 0.93, 1.68; effect measure modification, p = 0.04). Triclosan and paraben exposures may increase the risk of atopic asthma and aeroallergen sensitization. Prospective studies are necessary to confirm these findings and determine if these chemicals pose a risk to children's health.

Allergological and toxicological aspects in a multiple chemical sensitivity cohort.

BACKGROUND: Multiple chemical sensitivity (MCS) is a chronic condition characterized by an exaggerated response to toxicants. We ascertained the prevalence of allergy to metals and toxicological aspects in MCS patients. METHODS: We conducted a retrospective review of medical records of 41 patients with MCS. We performed patch testing (n = 21) for dental series and did lymphocyte transformation test (n = 18) for metals. We measured mercury in samples of blood (n = 19), urine (n = 19), saliva (n = 20), and scalp hair (n = 17) to investigate the association between mercury levels and cases of MCS. RESULTS: The prevalence of metal immune hypersensitivity in a subset of 26 patients was 92.3 percent. Elevations of mercury occurred in 81.2 percent (26 of 32). The mean (±SD) in blood concentrations of mercury was 7.6 ± 13.6 µg/L; mean in urine was 1.9 ± 2.5 µg/L; mean in scalp hair was 2.2 ± 2.5 µg/g; mean in saliva was 38.1 ± 52.1 µg/L. Subgroup analyses showed that elevation of mercury levels in biological matrices were associated with mercury amalgams in patients with MCS (22 patients), compared with controls (8 patients) (odds ratio 11 : 95 percent confidence interval 1.5 to 81.6; P = 0.023). CONCLUSIONS: Our data show an increased prevalence of metal allergy and elevation of mercury levels in bioindicators among patients with MCS.

Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children.

BACKGROUND: Bisphenol A (BPA) is used widely to manufacture food container linings. Mouse models suggest exposure to BPA might increase allergic inflammation. OBJECTIVES: We hypothesized that BPA exposure, as assessed based on urinary BPA concentrations, would be associated with increased odds of wheeze and asthma and increased fraction of exhaled nitric oxide (Feno) values in children. METHODS: The Columbia Center for Children's Environmental Health recruited pregnant women for a prospective birth cohort study (n = 568). Mothers during the third trimester and children at ages 3, 5, and 7 years provided spot urine samples. Total urinary BPA concentrations were measured by using online solid-phase extraction, high-performance liquid chromatography, isotope-dilution tandem mass spectrometry. Wheeze in the last 12 months was measured by using questionnaires at ages 5, 6, and 7 years. Asthma was determined by a physician once between ages 5 and 12 years. Feno values were measured at ages 7 to 11 years. RESULTS: Prenatal urinary BPA concentrations were associated inversely with wheeze at age 5 years (odds ratio [OR], 0.7; 95% CI, 0.5-0.9; P = .02). Urinary BPA concentrations at age 3 years were associated positively with wheeze at ages 5 years (OR, 1.4; 95% CI, 1.1-1.8; P = .02) and 6 years (OR, 1.4; 95% CI, 1.0-1.9; P = .03). BPA concentrations at age 7 years were associated with wheeze at age 7 years (OR, 1.4; 95% CI, 1.0-1.9; P = .04) and Feno values (ß = 0.1; 95% CI, 0.02-0.2; P = .02). BPA concentrations at ages 3, 5, and 7 years were associated with asthma (OR, 1.5 [95% CI, 1.1-2.0], P = .005; OR, 1.4 [95% CI, 1.0-1.9], P = .03; and OR, 1.5 [95% CI, 1.0-2.1], P = .04, respectively). CONCLUSIONS: This is the first report of an association between postnatal urinary BPA concentrations and asthma in children.

Predicted risk of childhood allergy, asthma, and reported symptoms using measured phthalate exposure in dust and urine.

UNLABELLED: The associated risk of phthalate exposure, both parent compounds in the home and their metabolites in urine, to childhood allergic and respiratory morbidity, after adjusting for exposures of indoor pollutants, especially bioaerosols, was comprehensively assessed. Levels of five phthalates in settled dust from the homes of 101 children (3-9 years old) were measured, along with their corresponding urinary metabolites. Other environmental risk factors, including indoor CO2, PM2.5, formaldehyde, 1,3-ß-D-glucan, endotoxin, allergen and fungal levels, were concomitantly examined. Subject's health status was verified by pediatricians, and parents recorded observed daily symptoms of their children for the week that the home investigation visit took place. Significantly increased level of benzylbutyl phthalate, in settled dust, was associated with test case subjects (allergic or asthmatic children). Higher levels of dibutyl phthalate and its metabolites, mono-n-butyl phthalate, and mono-2-ethylhexyl phthalate were found to be the potential risk factors for the health outcomes of interest. Similarly, indoor fungal exposure remained a significant risk factor, especially for reported respiratory symptoms. The relative contribution from exposure to phthalates and indoor biocontaminants in childhood allergic and respiratory morbidity is, for the first time, quantitatively assessed and characterized. PRACTICAL IMPLICATIONS: For asthmatic and allergic children living in subtropical and highly developed environments like homes in Taiwan, controlling environmental exposure of phthalates may be viewed as equally important as avoiding indoor microbial burdens, for the management of allergy-related diseases. It is also recognized that multidisciplinary efforts will be critical in realizing the true underlying mechanisms associated with these observations.

Determination of enzyme matrix metalloproteinases-9 and immune status as indicators of development of the environmental diseases.

The majority of environmental diseases are multifactorial airway illnesses, including genetic background and exposure to different kind of airborne irritants and allergens. Altered lifestyle and changes in environmental exposures contribute to the occurring of these diseases. The term of environmental illnesses includes the disease primarily caused by pollution of air and water, chemical and physical agents, radiation, contaminated food and direct contact with the toxins we are exposed to natural and/or working environment. The members of the matrix metalloproteinase (MMP) family are involved in the pathogenesis of COPD. MMPs comprise a large family of structurally related zinc metalloendopeptidases with different substrate specificities and possibilities to degrade protein constituents of the extracellular matrix. We investigated immunological status and level of MMP-9 in workers occupationally exposed to volatile aromatic hydrocarbons compared to urban residents and rural areas. The phenotypic profiles of peripheral blood lymphocytes were done by flow cytometry. The method of enzyme immunoassay (ELISA) was used to determine enzyme expression of matrix metalloproteinase-9 (MMP-9). The occupationally exposed group had a significantly elevated level of enzyme MMP-9 in the urine, accompanied with augmentation of cells of innate immunity in peripheral blood, which could contribute to the monitoring, early detection of environmental diseases and consequent earlier and more effective treatment.

Relationship between mercury levels in blood and urine and complaints of chronic mercury toxicity from amalgam restorations.

AIM: To determine whether patients complaining of oral and medical symptoms perceived to be associated with chronic mercury toxicity have elevated mercury levels in their blood and urine. METHODS: The study group in this audit were 56 patients presenting to an oral medicine unit with complaints perceived to be related to chronic mercury toxicity. Their symptoms and co-morbidity were charted and mercury levels in blood and urine were biochemically tested by atomic absorption spectrophotometry. RESULTS: None had elevated mercury levels in blood or urine above the normal threshold level. Subgroup analysis showed subjects with oral lesions, autoimmune disorders and multiple sclerosis had relatively and significantly higher mercury levels within this cohort, but within the threshold values. When tested by multiple logistic regression adjusted for age and gender, mercury levels in blood or urine, numbers of amalgams were not significant for multiple sclerosis or previously diagnosed autoimmune disease. CONCLUSION: Mercury levels in blood and urine of this cohort of patients with perceived chronic mercury toxicity were within the normal range in accordance with a national laboratory threshold value.

Polycyclic aromatic hydrocarbon metabolite levels and pediatric allergy and asthma in an inner-city cohort.

Exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with allergic sensitization and asthma. We hypothesized that increased urinary PAH metabolites are associated with allergy or asthma among children age 5 yrs in an inner-city birth cohort. As part of an ongoing prospective birth cohort under the auspices of the Columbia Center for Children's Environmental Health (CCCEH), urine was collected from 5-yr-old children (n = 222) of Dominican American and African American mothers in Northern Manhattan and South Bronx of New York City. Twenty-four PAH metabolites were measured in these specimens, and their levels (unadjusted and specific gravity corrected) were evaluated with IgE levels and asthma outcomes. Ten metabolites were detected in urine from all children. Concentrations ranged higher than those in representative samples of US children ages 6-11 in the National Health and Nutrition Examination Survey (NHANES). Among CCCEH children, compared with African Americans, the Dominican children had higher 2-hydroxynaphthalene but lower 9-hydroxyfluorene and 4-hydroxyphenanthrene concentrations. Increased 3-hydroxyfluorene and 3-hydroxyphenanthrene levels were associated with higher anti-mouse IgE levels (p < 0.05). These plus 2-hydroxynaphthalene, 2-hydroxyflourene and 1-hydroxyphenanthrene concentrations were associated with higher anti-mouse IgE levels on multivariate analyzes. Increased 2-hydroxyphenanthrene, 3-hydroxyphenanthrene and 4-hydroxyphenanthrene levels were associated with higher anti-cat IgE levels (p < 0.05) in univariate, but not multivariate, analyzes. Levels of PAH metabolites were not associated with respiratory symptoms. Measures of PAH metabolites suggest considerable exposure in an urban pediatric population, and possible associations with allergic sensitization to mouse.

Occupational exposure to ethylenebisdithiocarbamates in agriculture and allergy: results from the EUROPIT field study.

This epidemiological study was carried out to evaluate the possible association between occupational exposure to ethylenebisdithiocarbamates (EDBC) and allergy. The study was conducted in four countries in the European Union: The Netherlands, Finland, Italy and Bulgaria. A total of 248 workers exposed to EDBC and 231 non-occupationally exposed subjects entered the study. Exposure to EDBC was measured as urinary ethylenethiourea (ETU) in urinary samples collected at baseline and after 30 days of exposure. Several effect parameters were evaluated including questionnaire data on allergy, Phadiatop, a general allergy test, and specific IgE parameters. These data were also collected at baseline and after 30 days of exposure. Cross-sectional as well as longitudinal comparisons were made, adjusted for potential confounding factors. No association was found between exposure status, EDBC levels and allergic contact dermatitis, allergic rhinitis, food allergy or atopy as measured by the Phadiatop. The prevalence of skin irritation was elevated in the Dutch field study only and is more likely a result of plant contact rather than EDBC exposure. Occupational exposure to sunlight was noted to have a protective effect on atopy in terms of IgE positivity. We conclude that the EDBC exposure levels experienced in our field study are not associated with increased prevalence of allergic symptoms or allergy.

Urinary eosinophilic protein X, atopy, and symptoms suggestive of allergic disease at 3 years of age.

BACKGROUND: Urinary eosinophilic protein X (U-EPX) measurement is easy to perform in children. However, its use for prediction, diagnosis, and monitoring of asthma and atopy is unclear. OBJECTIVE: We sought to investigate the relationship between U-EPX and clinical phenotypes suggestive of allergic diseases. METHODS: U-EPX measurement (RIA), respiratory questionnaires, and skin testing were completed at age 3 years in 903 children followed prospectively from birth. Specific airway resistance was measured in 503 currently asymptomatic children by using whole-body plethysmography during tidal breathing. RESULTS: Nonatopic children with wheezing or eczema had slightly increased U-EPX levels compared with nonatopic asymptomatic children. U-EPX levels (geometric mean EPX/creatinine ratio) were as follows: nonatopic asymptomatic children (n = 313), 61.3 microg/mmol (95% CI, 56.4-66.6 microg/mmol); nonatopic children with wheezing (n = 148), 71.2 microg/mmol (95% CI, 63.2-80.1 microg/mmol); nonatopic children with eczema (n = 90), 65.7 microg/mmol (95% CI, 56.7-76.2 microg/mmol); and nonatopic children with wheezing and eczema (n= 86), 79.7 microg/mmol (95% CI, 67.4-94.3 microg/mmol). Children who had persistent atopy early in life had significantly higher U-EPX levels at age 3 years (nonatopic at 1 and 3 years [n = 263], 63.4 microg/mmol [95% CI, 58.4-69.0 microg/mmol]; atopic at 1 but not 3 years [n = 24], 65.1 microg/mmol [95% CI, 43.8-96.7 microg/mmol]; nonatopic at 1 year and atopic at 3 years [n = 62], 90.0 microg/mmol [95% CI, 74.6-108.4 microg/mmol]; atopic at 1 and 3 years [n = 35], 111.5 microg/mmol [95% CI, 89.2-139.3 microg/mmol]; P <.002). Atopy alone and with wheezing, eczema, or both was associated with significantly increased U-EPX levels (P <.0001). Wheezing appeared to be associated with higher U-EPX levels compared with eczema in both atopic and nonatopic children. The highest U-EPX level was found in atopic children with a history of wheezing and eczema (P <.0001). There was no relationship between U-EPX level and lung function. CONCLUSION: U-EPX level reflects the presence of atopy and associated symptoms and might be useful for monitoring the progression of allergic disease.

[Clinical evaluation of urinary leukotriene e4 levels in children with respiratory syncytial virus infection].

The levels of leukotriene E4 (LTE4) of the urine were determined in 24 pediatric patients with infectious diseases due to respiratory syncytial virus (RSV), i.e., bronchitis, pneumonia, and bronchiolitis, and compared with those in controls without allergic disease. The level for LTE4 of the acute-phase urine was 620+/-562 pg/mg. cr in the pediatric patients infected with RSV, being significantly higher than 190+/-67 pg/mg. cr in controls (P<0.005). The levels for LTE4 of the urine in the recovery phase showed a tendency toward decrease, as compared to those in the acute phase. However, there was no significant difference in the level for LTE4 of the acute-phase urine between the presence and the absence of each of the following conditions: expiratory wheezing; the association of pneumonia; family history of allergic diseases; the association of atopic dermatitis; and a past history of expiratory wheezing. An allergological study also revealed that there was no significant difference in LTE4 level between the presence and the absence of peripheral eosinophilia or between the presence and the absence of the high total level for IgE of the serum or positivity for the specific IgE level in the serum. These results suggest that LT is involved with the pathological conditions of RSV infection, but there are no direct relation between atopic diathesis or expiratory wheezing and the amounts of LT production.

Urinary leukotriene levels are increased during exacerbation of atopic eczema/dermatitis syndrome. Relation to clinical status.

BACKGROUND: Leukotrienes are potent mediators of allergic inflammation and their role in the pathogenesis of allergic disorders, particularly asthma, is well established. Their importance in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS) is still unclear. We aimed to compare urinary cysteinyl leukotriene (Cys-LT) levels during exacerbation and remission of AEDS in relation to clinical status, IgE levels, and eosinophil counts. METHODS: Urinary Cys-LTs were measured by direct enzyme immunoassay in 17 adult patients with AEDS and in 17 healthy controls in whom atopy had been excluded. Cys-LTs were compared during exacerbation and remission of AEDS in relation to the clinical status measured by SCORAD. Total IgE levels were measured by enzyme-linked immunoassay (ELISA). RESULTS: Mean clinical score during the exacerbation was 64.3 +/- 3.1 and during remission 22.4 +/- 4 (P < 0.01). Cys-LTs levels were significantly higher during the exacerbation of AEDS than in the control group (230.9 +/- 20.8 vs 123.2 +/- 9.9 pg/mg creatinine; P < 0.005). During the remission, the difference between AEDS patients and the control group was not significant (96.3 +/- 8.7 vs 123.2 +/- 9.9 pg/mg creatinine; P = 0.8). During AEDS exacerbation Cys-LTs levels were significantly correlated with the clinical status (rS = 0.73, P < 0.01) and with eosinophil counts (r = 0.86; P < 0.01) but not with the duration of the disease, age of patients, or IgE levels. CONCLUSIONS: Our results point to enhanced biosynthesis of Cys-LTs during the AEDS exacerbations. Inflammatory cells, e.g. eosinophils are the most probable source of Cys-LTs. A strong correlation between Cys-LT levels and clinical status may in part explain preliminary clinical observations of efficacy of leukotriene antagonists in alleviating symptoms of AEDS.

Clinical utility of a rapid test for uristatin.

OBJECTIVES: Uristatin is a trypsin inhibitor present in urine that is increased in most patients with bacterial or viral infections and in many with inflammatory disorders. We included the assay of uristatin as part of a screening program carried out by pediatricians on 4207 Japanese schoolchildren to judge the ability of uristatin to identify those with an infection and (or) inflammation of any cause. We used urine dipsticks for the assay of uristatin, creatinine, albumin, blood, leukocyte esterase, and protein. We also performed quantitative assays for uristatin and creatinine. Another aim was to estimate the reference range for uristatin in schoolchildren, ages 5 to 14 yr. METHODS: We prepared dipstick pads that were impregnated with a chromogenic substrate for trypsin and measured the uristatin-caused inhibition of trypsin in urine. We measured creatinine so that the ratio of uristatin to creatinine could be calculated to correct for urine concentration. RESULTS: We obtained quantitative uristatin and creatinine results for 4207 children. Of these, 177 had an abnormal urine dipstick for albumin or blood or protein or leukocyte esterase or a combination of these. We used data from 3622 children to establish the reference range for the uristatin dipsticks. The 3622 were diagnosed by their pediatricians as free from an infection or inflammation of any cause and with normal urine dipstick tests. We recommend an upper reference limit for uristatin by dipstick of < or = 7.5 mg uristatin/g creatinine. The leftover 408 children ( [4207-3622-177] = 408) fell into two groups: 205 with diagnoses of no infection, possible infection, or possible inflammatory disorders. The remaining 203 children were renal disease follow-up cases. The diagnoses were based on a physical examination, microscopic urinalysis plus urine dipstick tests for albumin, blood, creatinine, protein, leukocyte esterase and a complete blood count. In the 205 children, 46 had an abnormal uristatin dipstick test, 39 had an abnormal uristatin by immunoassay, 41 had an abnormal erythrocyte sedimentation rate (ESR), 27 had an abnormal serum C-reactive protein (CRP), and one had an abnormal urine microscopic exam. For the first 938 children in the study, the agreement was 93% of negative dipstick uristatin results and immunoassays. The agreement of positive uristatin dipsticks with immunoassays was 85%. We assumed that the immunoassay results were correct. In the evaluation of 189 children with fever, 62 also had an abnormal uristatin by dipstick. DISCUSSION: A rapid dipstick test for uristatin read on a reflectance photometer gave values that compared well with a quantitative immunoassay method. The uristatin test is sensitive but not specific for any cause of infection or inflammation. Uristatin is easy to determine and appears to be a better indicator than fever, ESR, or CRP for the diagnosis of an infection or inflammation.