Maternal diet during pregnancy and risk of allergic diseases in children up to 7-9 years old from Polish Mother and Child Cohort study.

BACKGROUND: The impact of maternal diet during pregnancy on the risk of allergic diseases in childhood is an increasing scientific and public health concern. We evaluated the associations of maternal type of diet and essential elements and vitamins intake during pregnancy with offspring allergic and respiratory outcomes. METHODS: The study population included 557 mother-child pairs from Polish Mother and Child Cohort (REPRO_PL). Based on the Food Frequency Questionnaire filled in between the 20th-24th week of pregnancy, overall maternal diet was evaluated as the difference between the Prudent Dietary Pattern (PDP) score and Western Dietary Pattern (WDP) score ((PDP-WDP) score) and maternal achievement of dietary recommendations (estimated average requirement, EAR) for essential elements and vitamins was assessed. Children's health examination at age of 1, 2, and 7-9 years covered the following symptoms: infections, wheezing/asthma, food allergy, allergic rhinitis, and atopic dermatitis. At age of 7-9 years, children underwent spirometry and skin-prick tests. RESULTS: Children of the mothers who were not achieving adequate intake of vitamin C during pregnancy had a higher risk of wheezing and having more than two infections within the first two years of life comparing to those who met EAR (OR = 2.6, p = 0.05, and OR = 2.3, p = 0.04, respectively). Inadequate intake of vitamin E during pregnancy was related to a higher risk of atopic dermatitis (OR = 2.7, p = 0.04), whereas inadequate intake of magnesium during pregnancy was associated with the risk of wheezing in the offspring at age of two years (OR = 3.7, p = 0.03). A lower (PDP-WDP) score during pregnancy (indicating unhealthier diet) was associated with a higher risk of infections (OR = 1.5, p = 0.007) but a lower risk of atopic dermatitis (OR = 0.7, p = 0.02) at age of 7-9 years. CONCLUSIONS: These results may contribute to the body of evidence for the impact of maternal diet during pregnancy for children's optimal health, however further studies are needed before drawing conclusions and recommendations for clinical practice.

[The usefulness of bronchial challenge tests in the diagnosis of occupational asthma]. / Ocena nadreaktywnosci oskrzeli i jej zastosowanie w diagnostyce astmy zwiazanej z praca.

Bronchial hyperresponsiveness (BHR) is the individual ability to respond with bronchoconstriction to a variety of specific and nonspecific stimuli which do not cause these symptoms among healthy subjects. Bronchial hyperresponsiveness is one of the hallmark features of asthma. The degree of bronchial hyperresponsiveness is variable among individuals with asthma and may correlate to its severity (the more severe asthma the higher bronchial hyperreactivity). Bronchial hyperresponsiveness is evaluated by performing bronchial provocation test (BPT). Provocation tests are classified - according to their mechanisms - into direct and indirect tests. Direct challenge tests are highly sensitive and they are used primarily to rule out asthma. In contrast, provocation tests with indirect stimuli are less sensitive but more specific to the direct tests; they are used generally to confirm the diagnosis of asthma and they allow for more accurate conclusions about inflammatory lesions in the case of a patient. Bronchial provocation tests play a significant role in occupational medicine. They are particularly relevant to be performed prior to employment, during periodic examinations, and to diagnose and monitor both occupational asthma and work-related asthma. This article presents selected bronchial provocation tests and their usefulness in the diagnosis of occupational asthma. Med Pr 2018;69(4):457-471.

[Diagnostic accuracy of specific IgE antibodies measurements in occupational airway allergy to high molecular weight agents]. / Trafnosc diagnostyczna oznaczen alergenowo swoistych przeciwcial IgE w zawodowej alergii dróg oddechowych na czynniki o duzej masie czasteczkowej.

BACKGROUND: The performance of specific inhalation challenge test (SICT) - reference method in diagnostics of occupational allergy - has some limitations due to health status of a particular patient. Therefore, it is extremely important to identify usefulness of other tests, and the evaluation of diagnostic accuracy of commercially available serum specific immunoglobulin E (sIgE) kits to the most common high molecular weight agents has been launched. MATERIAL AND METHODS: The study group comprised 141 subjects - 110 bakers and 31 farmers - with suspicion of occupational airway allergy. All patients underwent evaluation of serum sIgE to occupational allergens with the use of Phadia and Allergopharma kits: in bakers to flour mix and α-amylase, in farmers to epithelium of cow, pig and feathers. Specific inhalation challenge test with workplace allergens performed in all subjects was a reference method for further analysis. RESULTS: Serum specific IgE to flour mix had the highest sensitivity (Phadia - 95.6%, Allergopharma - 88.3%), while its specificity was relatively low (Phadia - 47.8%, Allergopharma - 25%). There were numerous discrepancies between the results of sIgE estimation for particular single allergens (k87, e4, e83), as well as for their mixtures (fx901, fx20, ex71), performed with the kits of both companies (Phadia vs. Allergopharma). CONCLUSIONS: Evaluation of serum specific IgE is characterized by inadequate sensitivity, specificity and predictive value to take the place of specific inhalation challenge test in diagnostics of occupational respiratory allergy. Med Pr 2017;68(1):31-43.

Sensitization to occupational allergens in hairdressing apprentices diagnosed already before entering vocational training.

BACKGROUND: Hairdressers are occupationally exposed to many allergenic and irritating substances. Additionally, hairdressing apprentices are exposed to the same allergens as professional hairdressers, due to the fact that vocational training starts in the beginning of the education. This study was undertaken to investigate early occurrence of sensitization to occupational allergens in hairdressing apprentices before the onset of the vocational training. MATERIAL AND METHODS: Three hundred and seven hairdressing apprentices were assessed using a questionnaire and skin prick tests (SPTs) to common and occupational allergens. The level of total and serum specific immunoglobulin E (IgE) to occupational allergens was evaluated and spirometry was performed. RESULTS: At least one skin and/or respiratory and/or conjunctival symptom was reported by 29.9% of subjects. Among subjects with at least one symptom, 28.2% of them were atopic whereas among 43.4% of them total IgE level was elevated. Atopy was found in 20% cases. In the case of one apprentice, positive SPT for paraphenylenediamine was found. Nearly 33% of apprentices had elevated total IgE level and 5 of them had specific IgE for occupational allergens. CONCLUSIONS: The study revealed that hairdressing apprentices might be sensitized to occupational allergens even before the beginning of vocational training, due to prior non-professional exposure to hairdressing agents. Furthermore, many of them report skin, respiratory and conjunctival symptoms, often connected with chronic disease diagnosis. Thus, candidates for hairdressers should be examined thoroughly before the start of the education and tests for allergy to hairdressing substances are indicated. Med Pr 2016;67(5):567-575.

[Application of recombinant latex allergens in diagnostics of occupational latex allergy]. / Zastosowanie alergenów rekombinowanych w diagnostyce zawodowej alergii na lateks.

Over many years, allergy to natural rubber latex has been a major problem among health care workers (HCW). The diagnosis of occupational allergy requires methods of high diagnostic accuracy in view of certification implications (e.g., a sick worker quits a job). With the development of molecular methods, the frequency of application of recombinant allergens it the diagnostics of allergic diseases continues to increase. This paper reviews the applicability of laboratory tests which use recombinant allergens in the diagnostics of occupational allergy. The diagnosis of latex allergy is based on the presence of clinical symptoms linked with exposure to latex allergens, positive skin prick tests and detection of specific IgE antibodies to latex in serun. Moreover, in some cases specific challenge tests are conducted. The analysis of literature indicates that applying the panel of recombinant latex allergens in diagnostic tests, cross-reactivity can very likely be excluded and/or sensitization can be confirmed without the need for specific challenge tests, which in case of latex allergens carries a potential risk of aeneralized reactions.

High-mobility group box 1 protein levels in serum of subjects after exposure to fire smoke--short communication.

INTRODUCTION: Fire smoke inhalation a recognized etiologic factor of airway injuries. The objective of this study was evaluation of serum high-mobility group box 1 (HMGB1) protein concentration in subjects exposed to fire smoke (SEFS). MATERIAL AND METHODS: The study group consisted of 40 consecutive patients admitted to the Toxicology Unit, Lodz, Poland after exposure to fire smoke. Serum HMGB1 concentrations were measured upon admission to hospital and rechecked on the 2nd and on the day of discharge. Patients also underwent routine toxicological diagnostic procedures applied in case of those exposures, such as carboxyhaemoglobin (COHb) levels and urinary thiocyanate concentrations. The same diagnostic tests were performed in 10 healthy volunteers not exposed to smoke of the control group. RESULTS: The average serum SEFS concentration of HMGB1 protein was not significantly higher on admission in comparison with the respective values recorded on the 2nd day and on the day of discharge. The mean serum level of HMGB1 protein of exposed group was higher than that one in the control group, however the difference was not statistically significant. The highest concentration of HMGB1 protein was noted in serum of 28 subjects exposed to fire smoke reporting at least one symptom and the difference was statistically significant in a comparison with the control group. CONCLUSION: As indicated, an acute exposure to smoke may lead to transient increase of HMGB1 in serum in exposed subjects. Further studies are necessary in order to confirm the importance of this protein in pathogenesis of acute airway injury due to exposure to fire smoke.

Clara Cell protein and myeloperoxidase levels in serum of subjects after exposure to fire smoke.

INTRODUCTION: Fire smoke inhalation is a well-recognized aetiological factor of airway injuries. The objective of this study was evaluation of Clara cell protein (CC16) and myeloperoxidase (MPO) concentrations in serum of patients after exposure to uncontrolled fire smoke. METHODS: The study group consisted of 40 consecutive patients admitted to the Toxicology Unit after exposure to fire smoke. CC16 and MPO concentrations in their serum samples was measured on the day of admission to hospital and rechecked at the 2nd day and on the day of discharge. Patients also underwent routine toxicological diagnostic procedures applied in case of exposures, such as carboxyhaemoglobin (COHb) levels and blood lactate and urinary thiocyanate concentrations. The same diagnostic tests were performed in the control group consisting of 10 healthy subjects not exposed to fire smoke. RESULTS: The average concentration of CC16 in the serum of subjects exposed to toxic factors was significantly higher at the day of admission in comparison with the respective values recorded on the 2nd day and on the day of discharge. The mean level of CC16 in the serum of the exposed group was also significantly higher than that in the control group. Tests for MPO concentrations in the serum did not reveal any significant changes in patients exposed to fire smoke. CONCLUSIONS: As indicated, acute exposure to smoke induces injury at the alveolar level, which results in a transient increase of CC16 in serum of exposed subjects.

Diagnosing of bakers' respiratory allergy: is specific inhalation challenge test essential?

The diagnosis of occupational asthma (OA) and/or rhinitis needs to be confirmed by means of objective methods, because it is followed by important social and financial consequences. The aim of the study was to evaluate sensitivity and specificity of diagnostic methods as skin-prick tests (SPTs) to occupational allergens, evaluation of allergen-specific serum IgE, and nonspecific bronchial hyperreactivity with reference to a specific inhalation challenge test in diagnosing bakers' respiratory allergy due to wheat flour. The study group included 358 bakers suspected of having OA due to wheat flour. They underwent physical examination, SPTs to common and occupational allergens, allergen-specific IgE determination, spirometry, nonspecific bronchial challenge, and specific inhalation test. The sensitivity of SPTs to occupational allergens in recognition of baker's rhinitis was low (47.9%) unlike the estimation of allergen-specific IgE (76.4%), with relatively high specificity (77.4 and 68.3%, respectively). Bronchial hyperreactivity (PC(20) < 8 mg/mL) was the most sensitive method, whereas high degree of bronchial hyperreactivity (PC(20) < 1 mg/m(3)) alone or bronchial hyperreactivity (PC(20) < 8 mg/m(3)) combined with the skin reactivity to wheat flour was the most specific method of recognizing OA. Neither SPTs to occupational allergens nor evaluation of serum allergen-specific IgE alone or combined with nonspecific bronchial hyperreactivity are characterized by sufficient diagnostic accuracy to replace the specific inhalation challenge test. For the establishment of a definite diagnosis of baker's asthma, specific challenge testing with occupational allergens should be performed.

[Cross-reactive carbohydrate determinants in diagnostics of occupational allergy]. / Krzyzowo reagujace determinanty weglowodanowe w diagnostyce alergii zawodowej.

In most cases diagnosis of immediate-type occupational allergy is very complex. Mainly it is caused by diversity of occupational allergens and lack of standardized diagnostic methods. The content of allergic proteins in commercially available skin prick test reagents differs between companies and in some the most important allergens are not named. Also the evaluation of serum specific IgE (asIgE) is characterized by different diagnostic accuracy. In some cases, false-positive results of asIgE detection are the consequence of cross-reaction to common environmental allergens. In those cases it is helpful to determine asIgE for cross-reacting carbohydrate determinants (CCDs) to exclude cross-hypersensitivity. The presented paper reviews the structure of carbohydrate determinants, their prevalence and possible impact on laboratory in vitro tests used in allergy diagnostics, as well as the methods of their identification. Possible applications of CCDs in occupational allergy diagnostics are also discussed.

[Allergy to isothiazolinones in recent years]. / Alergia na izotiazolinony w ostatnich latach.

BACKGROUND: Isothiazolinones are preservatives which are present in cosmetics, household chemicals and many other industrial products. Initially, a mixture of methylchloroisothiazolinone and methylisothiazolinone (MCI/MI - Kathon CG) was used, and then, from the beginning of the 21st century, only methylisothiazolinone. Due to a significant increase in the number of contact dermatitis caused by allergy to this compound, it was withdrawn from leave-on cosmetics, and its concentration in rinse-off cosmetics was reduced. The aim of the study was to analyze the incidence of contact allergy to isothiazolinones among patients in the Nofer Institute of Occupational Medicine, Lódz, the intensification of patch test results and hypersensitivity depending on the occupation, and to assess the contribution of immediate allergy to the occurrence of that hypersensitivity. MATERIAL AND METHODS: In a group of 1137 patients (832 females and 305 males) with suspected contact dermatitis, diagnosed in 2014-2018, patch tests series including methylchloroisothiazolinone/methylisothiazolinone (0.01%) and methylisothiazolinone (0.2%), produced by Chemotechnique Diagnostics, Sweden, were performed. In a group of 29 individuals with contact allergy to isothiazolinones, prick tests with methylisothiazolinone (0.001%, 0.01%, 0.1%, 1%) (Sigma-Aldrich, Germany) were conducted. RESULTS: Of the 1137 subjects, 95 (8.3%) were allergic to isothiazolinones, slightly more often females - 71 (8.5%) than males - 24 (7.9%). In total, 150 positive patch tests with isothiazolinones (13.2%) were obtained. The number of positive results with methylisothiazolinone alone (7.8%) was higher than the number with methylisothiazolinone from Kathon CG (5.4%). Among the subjects sensitized to methylisothiazolinone alone strongly positive patch tests (+++) concerned 60.7%. In the female group, office workers (42.3%) and medical staff (18.3%) predominated, and in the male group - locksmiths, turners, mechanics and similar ones (45.8%), and construction workers (25.0%). Prick tests with methylisothiazolinone were negative, and they became positive after 3-5 h. CONCLUSIONS: Isothiazolinones, particularly methylisothiazolinone, are significant causal factors of contact allergy, including that of occupational origin. They have strongly allergenic properties, and in patch tests they often give very severe inflammatory reactions. The issue of the role of immediate allergy in the pathogenesis of isothiazolinones sensitization requires further research. Med Pr. 2020;71(5):603-11.

[Erratum to the article "Allergy to isothiazolinones in recent years" (Med Pr. 2020;71(5):603-11)]. / Errata do artykulu "Alergia na izotiazolinony w ostatnich latach" (Med. Pr. 2020;71(5):603­611).

The original version of the article can be found at: https://doi.org/10.13075/mp.5893.01037.

Mannitol vs. methacholine in the evaluation of airway responsiveness in bakers' asthma.

OBJECTIVES: Various indirect or direct airway challenge tests are used to measure nonspecific bronchial hyper-responsiveness (NSBHR). The evaluation of NSBHR in diagnosing occupational asthma (OA) is performed, e.g., to monitor the specific inhalation challenge test (SICT). The aim of this study was to preliminarily compare the results of methacholine and mannitol inhalation challenge tests in SICT monitoring in bakers with work-related airway symptoms. MATERIAL AND METHODS: Four bakery workers with a suspicion of OA underwent single-blind placebo-controlled SICTs involving workplace allergens, accompanied by the evaluation of NSBHR with mannitol and methacholine, both before and after SICTs. Clinical examinations, spirometry tests, skin prick tests (SPTs) to common aeroallergens and occupational allergens, as well as tests to determine serum specific IgE antibodies to occupational aeroallergens were also performed. RESULTS: Positive SPTs results to occupational aeroallergens were found in all bakery workers, and specific IgE antibodies to flour were detected in 2 subjects. Three patients displayed positive SICT reactions. In all of these 3 patients, airway responsiveness to methacholine increased significantly. In 2 patients, airway reaction to mannitol was significant, whereas in 1 subject there was no increase in NSBHR after mannitol inhalation. The patient with a negative SICT result did not reveal any changes in NSBHR before and after the test, either to methacholine or mannitol. CONCLUSIONS: The data obtained by the authors show that there is no clear correlation between the methacholine and mannitol inhalation challenge tests in SICT monitoring. Preliminary results indicate the need for further investigations to evaluate the usefulness of the mannitol challenge test in the diagnostics of OA. Int J Occup Med Environ Health. 2020;33(2):235-9.

Bronchial Response to High and Low Molecular Weight Occupational Inhalant Allergens.

PURPOSE: Occupational asthma may be induced by high- or low-molecular weight allergens (HMWA or LMWA, respectively). The study was conducted to compare the pattern of bronchial response in 200 HMWA-induced asthmatics (n = 130) and LMWA-induced asthmatics (n = 70). METHODS: The study participants underwent a single-blind, placebo-controlled specific inhalation challenge (SIC) with workplace allergens, accompanied by evaluation of non-specific bronchial hyperresponsiveness (NSBHR) with methacholine before and after the SIC. RESULTS: A single early bronchial response more frequently occurred in HMWA-induced asthmatics than in LMWA-induced asthmatics (86.2% vs. 20%). An isolated late bronchial response or atypical patterns were more frequently observed in LMWA-induced asthmatics than in LMWA-induced asthmatics (45.7% vs. 3.8% or 34.3% vs. 10%, respectively). Baseline NSBHR before SIC was more often detected in LMWA-induced asthmatics than in HMWA-induced asthmatics (81.4% vs. 54.6%), and the median value of the provocation concentration of methacholine was relevantly lower in these patients before and after SIC. A significant 3-fold increase in NSBHR after SIC was observed more often in LMWA-induced asthmatics than in HMWA-induced asthmatics (82.8% vs. 66.1%). In addition, compared to LMWA-induced asthmatics, HMWA-induced asthmatics were older, were more frequently active smokers, showed lower level of NSBHR, and more frequently continued their work in harmful occupational exposure. CONCLUSIONS: The results of this study suggest that HMWA-induced asthmatics may have milder clinical courses and that there is a possibility of job continuation despite asthma exacerbation requiring medical surveillance.

Allergen-specific IgE to recombinant latex allergens in occupational allergy diagnostics.

OBJECTIVES: Specific challenge tests (SICs) are considered reference tests for allergic occupational diseases diagnosis. However, in numerous cases, SICs cannot be carried out in the diagnosis of allergy to latex due to the risk of generalized reactions. The aim of the study was to evaluate the usefulness of sIgE determination to recombinant latex allergens in diagnostics of occupational respiratory allergy. MATERIALS AND METHODS: The study group comprised 44 healthcare workers (HCW) suspected of suffering from occupational respiratory allergy to latex (they underwent a physical examination, skin-prick tests (SPTs) to common and latex allergens, spirometry and SIC) and 17 controls not occupationally exposed to latex, with a positive sIgE against latex. Each serum was tested for allergen-specific IgE to aeroallergens, latex, eight recombinant latex allergens and CCD-markers. RESULTS: Specific IgE against Hev b5, 6.01, and 6.02 were significantly more frequently detected in HCWs and their mean serum levels were higher compared with the control group. In 26 HCWs with occupational asthma (OA), sensitization to Hev b5, Hev b6.01, Hev b6.02 was significantly more frequent than in 18 HCWs with work-exacerbated asthma (WEA); they had positive results SPT to latex significantly more frequently in comparison with subjects with WEA. CONCLUSIONS: Test for recombinant latex allergens is much more accurate in recognition of latex allergy than test for latex extract, which seems to produce false-positive results in patients with pollen allergy. The measurements of sIgE against recombinant latex allergens Hev b 6.01, 6.02, 5, and 8 are useful in differentiating OA from WEA.

Comparison of biomarkers in serum and induced sputum of patients with occupational asthma and chronic obstructive pulmonary disease.

OBJECTIVES: Occupational asthma and chronic obstructive pulmonary disease (COPD) are associated with the airway inflammatory process. The aim of this study was to compare the sputum and serum markers of inflammation in patients with occupational asthma and COPD. METHODS: The study group included 20 patients with stable COPD, 24 patients with asthma, and 22 healthy subjects. Interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-9 levels in serum and induced sputum as well as fibrinogen and CRP in serum were determined in all the subjects. RESULTS: Higher concentrations of IL-1ß, IL-6, TNF-α, and MMP-9 in induced sputum and an increased concentration of acute-phase proteins in serum were observed in COPD patients compared with healthy subjects. Higher concentrations of IL-1ß and MMP-9 in induced sputum and a higher concentration of C-reactive protein (CRP) were detected in COPD patients than in asthmatic subjects. Never smokers with COPD had significantly higher levels of IL-1ß and MMP-9 in induced sputum than never smoker controls. There was no significant difference between the serum and sputum levels of cytokines and MMP-9 of never smokers and smokers with COPD. CONCLUSIONS: Higher concentrations of IL-1ß and MMP-9 in induced sputum and a higher concentration of CRP in serum allow distinguishing between biomarker profiles of COPD patients and asthmatic patients. Occupational exposure induces a systemic proinflammatory state with increased levels of acute-phase proteins in stable COPD patients. MMP-9 and IL-1ß concentrations are increased in induced sputum of never smokers with COPD, which is associated with occupational exposure.

Identification of cross-reactive carbohydrate determinants in subjects reporting work-related respiratory symptoms.

INTRODUCTION: The role of cross-reactive carbohydrate determinants (CCDs) in diagnostics of occupational allergy remains unclarified and its clinical relevance is still questioned. The aim of the study was to assess the frequency of positive response to CCDs in the subjects with suspected occupational allergy and the relationship between other diagnostic test results and final diagnosis. MATERIAL AND METHODS: The study group included 201 patients. They underwent clinical examination, skin prick test (SPT) to common and occupational allergens, specific serum immunoglobulin (sIgE) determinations, spirometry and specific inhalation challenge test. Moreover, sIgE to CCDs from bromelain was assessed in all subjects. RESULTS: Occupational respiratory allergy was recognized in 64.3% of CCD-positive and 52.4% of CCD-negative patients. Positive SPT results to common and occupational allergens were found in 64.3% and 35.7% of CCD-positive subjects, respectively. In all subjects with CCDs, the sIgE to grass pollens as well as to occupational allergens were detected. The total IgE level > 100 kU/l was significantly associated with the presence of sIgE to CCDs. CONCLUSIONS: sIgE to CCDs were found in 7% of subjects suspected to suffer from occupational respiratory allergy. The presence of CCDs is not significantly associated with occupational respiratory allergy. It is also not more frequent in subjects reporting work-related respiratory symptoms in whom occupational allergy was not confirmed. The elevated total IgE level was related with CCD positivity. In patients with suspected occupational allergy, the presence of sIgE to CCDs in serum did not indicate the irrelevance of positive sIgE to occupational allergens.

Occupational exposure to diisocyanates in polyurethane foam factory workers.

OBJECTIVES: The aim of the study was to evaluate health effects of occupational exposure to diisocyanates (DIC) among polyurethane foam products factory workers. MATERIAL AND METHODS: Thirty workers had a physical examination, skin prick tests with common allergens, allergen-specific immunoglobulin E (IgE) antibodies to diisocyanates and pulmonary function tests. Concentrations of selected isocyanates in the workplace air samples as well as concentration of their metabolites in the urine samples collected from the workers of the plant were determined. RESULTS: The most frequent work-related symptoms reported by the examined subjects were rhinitis and skin symptoms. Sensitization to at least 1 common allergen was noted in 26.7% of the subjects. Spirometry changes of bronchial obstruction of a mild degree was observed in 5 workers. The specific IgE antibodies to toluene diisocyanate (TDI) and 4,4'-methylenebis(phenyl isocyanate) (MDI) were not detected in any of the patients' serum. Cellular profiles of the collected induced sputum (ISP) did not reveal any abnormalities. Air concentrations of TDI isomers ranged 0.2-58.9 µg/m3 and in 7 cases they exceeded the Combined Exposure Index (CEI) value for those compounds. Concentrations of TDI metabolites in post-shift urine samples were significantly higher than in the case of pre-shift urine samples and in 6 cases they exceeded the British Biological Monitoring Guidance Value (BMGV - 1 µmol amine/mol creatinine). We didn't find a correlation between urinary concentrations of TDI, concentrations in the air and concentrations of toluenediamine (TDA) in the post shift urine samples. Lack of such a correlation may be an effect of the respiratory protective equipment use. CONCLUSIONS: Determination of specific IgE in serum is not sensitive enough to serve as a biomarker. Estimation of concentrations of diisocyanate metabolites in urine samples and the presence of work-related allergic symptoms seem to be an adequate method for occupational exposure monitoring of DIC, which may help to determine workers at risk as well as to recognize hazardous workplaces.

Gene p53 mutations, protein p53, and anti-p53 antibodies as biomarkers of cancer process.

The finding that gene mutations and changes in their expression form the basis of cancer processes, has prompted molecular epidemiologists to use biomarkers for detecting damaged genes or proteins synthesized under their control in easily available cellular material or systemic liquids. Mutations in the suppressor gen p53 are thought to be essential for cancer development. This gen is one of the most important regulators of transcription, cellular cycle, DNA repair and apoptosis detected till now. Inactivation of gene p53 leads to uncontrolled cell divisions, and further to transformation of normal cells into the carcinous ones. Observations that mutations in gene p53 appear under conditions of occupational and environmental exposures to chemical and physical carcinogens, such as vinyl chloride, radon, or aflatoxin B1, have proved to be of enormous importance for the occupational and environmental health. Changes in expression of gene p53, and also its mutations, cause variations of cellular protein p53 concentration. Higher cellular protein p53 levels are associated with increased protein transfer to the extracellular liquid and to blood. It has been observed that increased blood serum protein p53 concentrations may have a prognostic value in early diagnosis of lung cancer. The results of a number of studies confirm that accumulation of a mutated form of protein p53, and presumably also large quantities of wild forms of that protein in the cells, may be a factor that triggers the production of anti-p53 antibodies. Statistical analysis showed that anti-p53 antibodies can be regarded as a specific biomarker of cancer process. The prevalence of anti-p53 antibodies correlated with the degree of cancer malignancy. The increased incidence of anti-p53 antibodies was also associated with higher frequency of mutations in gene p53. There are some reports confirming that anti-p53 antibodies emerging in blood serum in the subclinical phase of cancer development may be associated with the occupational exposure to the carcinogenic agents.