P A Steerenberg

National Institute for Public Health and the Environment (RIVM), Utrecht, Utrecht, Netherlands

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Publications (221)624.41 Total impact

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    ABSTRACT: The function of ammonia as tobacco additive is subject of scientific debate. It is argued that ammonia, by increasing the proportion of free nicotine, increases the absorption of nicotine in smokers. As a result of the addition of ammonia to cigarettes, smokers get exposed to higher internal nicotine doses and become more addicted to the product. On two occasions, the nicotine absorption in blood was measured after smoking a commercial cigarette of either brand 1 or brand 2, which differed 3.8-fold in ammonium salt content. Using a standardized smoking regime (six puffs, 30 s puff interval, 7 s breath hold before exhalation), 51 regular smokers smoked brand 1 (Caballero Smooth Flavor; 0.89 mg ammonium per gram tobacco) and brand 2 (Gauloise Brunes; 3.43 mg ammonium per gram tobacco). Puff volumes and cardiovascular parameters were monitored during and following smoking, respectively. Measurement of serum nicotine level in the blood samples collected over time following smoking of the two brands, showed that total amount of nicotine absorbed did not differ between the two brands. Present results demonstrate that smoking tobacco containing a higher amount of the tobacco additive ammonium does not increase the absorption of nicotine in the smoker's body.
    No preview · Article · Dec 2011 · Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association
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    ABSTRACT: We conducted a multicenter prospective study to assess the effects of occupational exposure to ethylenebisdithiocarbamate fungicides and/or other pesticides on self-reported asthma and asthmatic symptoms. This multicenter study was conducted among 248 workers exposed to pesticides and 231 non-exposed workers from five field studies. The five field studies were carried out in The Netherlands, Italy, Finland, and two studies in Bulgaria. Subjects constituting this cohort completed a self-administered questionnaire at baseline (before the start of exposure). Ethylenethiourea in urine was determined to assess exposure to ethylenebisdithiocarbamates. In multivariate analyses adjusted for all potential confounders (age, education, residence, smoking, gender, and field study), we found inverse associations, all not statistically significant, between occupational exposure to pesticides and asthma diagnosis (OR 0.41; 95% CI 0.15-1.11), complains of chest tightness (OR 0.60; 95% CI 0.36-1.02), wheeze (OR 0.56; 95% CI 0.32-0.98), asthma attack (OR 0.52; 95% CI 0.12-2.25), and asthma medication (OR 0.79; 95% CI 0.25-2.53). Furthermore, we reported null associations for multivariate analysis using ethylenethiourea as determinant for exposure. Although exposure to pesticides remains a potential health risk, our results do not suggest an association between exposure to ethylenebisdithiocarbamates and/or other pesticides used in our study on asthma and asthmatic symptoms.
    No preview · Article · Oct 2008 · Human & Experimental Toxicology
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    ABSTRACT: In this study, the prolonged low-dose exposure of mixtures of pesticides has been examined on hematological parameters and components of the immune defense in occupationally exposed humans. This investigation was carried out in five field studies in: the Netherlands (flower bulb growers, mainly re-entry workers), Italy (vineyard workers), Finland (potato farmers), and Bulgaria (workers from a zineb factory and greenhouse workers). Immunotoxicity was studied by measuring hematological parameters, complement, immunoglobulins, lymphocyte subpopulations, natural killer cells, autoimmunity, and antibody responses to hepatitis B vaccination. The total study population consisted of 248 pesticide-exposed and 231 non-occupationally exposed workers. As a surrogate measure of pesticide exposure the urinary excretion of ethylenethiourea (ETU), the main metabolite ethylenebisdithiocarbamates was measured. A significantly higher level of ETU in occupationally exposed subjects compared with controls (2.7 +/- 8.1 microg/g vs 0.5 +/- 3.7 microg/g creatinine) was found. Statistically significant differences, albeit very low, were found for complement C3 and C4 and the immunoglobulin classes IgG4 and IgA. For complement and IgG4, the levels were slightly increased and the level of IgA was decreased. In the lymphocyte populations, the CD8 subpopulation was increased. No effects were found on autoimmune antibodies and antibody response to hepatitis vaccination. In conclusion, pesticide exposure under various work place conditions in Europe was associated only with some subtle effects on the immune system, which may suggest that occupational exposure to pesticides does not influence the immunologic system in a clinically significant fashion, and does not pose a significant health risk to the exposed subjects.
    No preview · Article · Oct 2008 · Human & Experimental Toxicology
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    ABSTRACT: The aim of this study was to investigate the health effects induced by exposure to the fungicide mancozeb in Italian vineyard workers. Ninety-three Italian subjects entered the study - 48 vine-growers intermittently exposed to mancozeb and 45 healthy controls. The subjects were investigated three times: before the seasonal application of pesticides (T0), 30 days after the beginning of the application period (T30), and 45 days after T0 (T45). At T0 the comparison between agricultural workers and controls showed a higher prevalence of cold or flu symptoms, a statistically significant lower percentage of monocytes, higher absolute count of T lymphocytes, CD4 and natural killer cells, and lower plasma levels of IgA and IgM in workers. Such differences were not confirmed at T30 and T45. In fact at T30 in exposed workers, besides a significant increase of urinary ethylenethiourea, confirming mancozeb exposure, T lymphocytes, CD4 and natural killer cells, IgA and IgM returned to values comparable to those observed in controls. Moreover, no other differences in clinical signs, haematological, and immune parameters, such as the immune functional capability evaluated as a response to hepatitis B vaccination, was observed. Altogether the differences between exposed and controls were not consistently correlated to any clinical impairment and suggest that the seasonal application of mancozeb does not pose a significant health risk to exposed subjects.
    No preview · Article · Nov 2007 · Biomarkers

  • No preview · Article · Sep 2006 · Toxicology Letters
  • Peter A Steerenberg · Frieda Daamen · Eefke Weesendorp · Henk Van Loveren
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    ABSTRACT: It is well known that ultraviolet (UV) radiation induces erythema, immunosuppression and carcinogenesis. We hypothesized that chronic exposure to solar UV radiation induces adaptation that eventually prevents the suppression of acquired immunity. We studied adaptation for UV-induced immunosuppression after chronic exposure of mice to a suberythemal dose of solar simulated radiation (SSR) with Cleo Natural lamps, and subsequent exposure to an immunosuppressive dose of solar or UVB radiation (TL12). After UV dosing, the mice were sensitized and challenged with either diphenylcyclopropenone (DPCP) or picryl chloride (PCl). To assess the adaptation induced by solar simulated radiation, we measured the proliferative response and cytokine production of skin-draining lymph node cells after immunization to DPCP, the contact hypersensitivity (CHS) response to PCl, and thymine-thymine (T-T) cyclobutane dimers in the skin of mice. After induction of immunosuppression by SSR or by TL12 lamps, the proliferative response of draining lymph node cells after challenge with DPCP, or the CHS after challenge with PCl, showed significant suppression of the immune response. Chronic irradiation from SSR preceding the immunosuppressive dose of UV failed to restore the suppressed immune response. Reduced lipopolysaccharide-triggered cytokine production (of IL-12p40, IFN-gamma, IL-6 and TNF-alpha) by draining lymph node cells of mice sensitized and challenged with DPCP indicated that no adaptation is induced. In addition, the mice were not protected from T-T dimer DNA damage after chronic solar irradiation. Our studies reveal no evidence that chronic exposure to low doses of SSR induces adaptation to UV-induced suppression of acquired immunity.
    No preview · Article · Aug 2006 · Journal of Photochemistry and Photobiology B Biology
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    ABSTRACT: Given that there are widely different prevalence rates of respiratory allergies and asthma between the countries of Europe and that exposure to ambient particulate matter (PM) is substantial in urban environments throughout Europe, an EU project entitled "Respiratory Allergy and Inflammation Due to Ambient Particles" (RAIAP) was set up. The project focused on the role of physical and chemical composition of PM on release of cytokines of cells in vitro, on respiratory inflammation in vivo, and on adjuvant potency in allergy animal models. Coarse (2.5-10 microm) and fine (0.15-2.5 microm) particles were collected during the spring, summer and winter in Rome (I), Oslo (N), Lodz (PL), and Amsterdam (NL). Markers within the same model were often well correlated. Markers of inflammation in the in vitro and in vivo models also showed a high degree of correlation. In contrast, correlation between parameters in the different allergy models and between allergy and inflammation markers was generally poor. This suggests that various bioassays are needed to assess the potential hazard of PM. The present study also showed that by clustering chemical constituents of PM based on the overall response pattern in the bioassays, five distinct groups could be identified. The clusters of traffic, industrial combustion and/or incinerators (TICI), and combustion of black and brown coal/wood smoke (BBCW) were associated primarily with adjuvant activity for respiratory allergy, whereas clusters of crustal of material (CM) and sea spray (SS) are predominantly associated with measures for inflammation and acute toxicity. The cluster of secondary inorganic aerosol and long-range transport aerosol (SIALT) was exclusive associated with systemic allergy. The present study has shown that biological effect of PM can be linked to one or more PM emission sources and that this linkage requires a wide range of bioassays.
    Full-text · Article · Jun 2006 · Inhalation Toxicology
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    ABSTRACT: Exhaled nitric oxide (eNO) has shown good validity for the assessment of airway inflammation in asthmatic children. In large-scale epidemiological studies, this method would be preferred above airway challenge tests, because it is a quick and easy applicable tool. In this study, we aimed to assess the discriminatory capacity of eNO, and prechallenge FEV1 for airway hyper-responsiveness (AHR) in 8-13-year old schoolchildren. Parents completed the ISAAC questionnaire, and children were tested for atopy, AHR to hypertonic (4.5%) saline (HS), and eNO. Diagnostic value was assessed by the area under the receiver operating curves (ROC), and calculation of positive and negative predicted values at different cut-off points for eNO and prechallenge FEV1. Areas under the ROC-curves of AHR were 0.65 for eNO and 0.62 for FEV1. Values increased to 0.71 and respectively 0.75 for a combined occurrence of AHR and current wheeze. Highest sensitivity and specificity were obtained at a cut-off value of 43 ppb for eNO and 103% predicted for FEV1. At these cut-off values, the positive predictive values for the presence of AHR in symptomatic children were respectively 83% (eNO) and 33% (FEV1), and negative predictive values in asymptomatic children were, respectively, 90 (eNO) and 80% (FEV1). Exhaled nitric oxide is a valid screening tool for AHR to HS in children that present with current wheeze, and it outperforms FEV1 as a predictor of AHR.
    Full-text · Article · Jan 2006 · Allergy
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    ABSTRACT: Contradictory results have been published on the immune-stimulating effects of vitamin E. Using a randomized placebo-controlled design, the effect of 15 month's daily supplementation with 200 mg vitamin E on two biomarkers of immunocompetence, i.e. serum DHEA sulfate ester (DHEA-S) and neopterin, was studied. Of the 100 relatively healthy Dutch elderly subjects included in the study, 50 were supplemented with vitamin E and 50 received placebo. As compared to placebo, vitamin E supplementation affected neither serum DHEA-S nor serum neopterin level. This corroborates with the finding that vitamin E supplementation did not affect infection-related severity measures, i.e. total number of days with respiratory infection, and total duration of the infections. It is concluded that vitamin E supplementation does not substantially alter the immunocompetence markers DHEA and neopterin in elderly subjects, and may explain our recently reported failure of vitamin E supplementation to afford protection against acute respiratory infections.
    No preview · Article · Oct 2005 · International Journal for Vitamin and Nutrition Research

  • No preview · Article · Jun 2005
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    ABSTRACT: Various particulate matter (PM) samples were tested for their adjuvant potency in an animal model of allergy (ovalbumin) in the European Union study entitled Respiratory Allergy and Inflammation Due to Ambient Particles. Coarse and fine ambient particles were collected during spring, summer, and winter in Rome, Oslo, Lodz, Amsterdam, and De Zilk. De Zilk, at the Dutch seaside, has mainly westerly winds and served as a negative pollution control. EHC-93 (Ottawa dust) was used as a positive control. We studied the adjuvant potency of the particle antibody responses to ovalbumin and histopathological changes in the lung. After a sensitization phase by coexposure to EHC-93 and ovalbumin, the antibody response to ovalbumin and inflammatory responses in the lung were huge. There was more adjuvant activity in reaction to 9-mg/ml samples than to 3-mg/ml samples. A best-fit analysis of these samples shows that the ambient coarse and fine particles at these sites, in combination with allergens, have severe to mild adjuvant activity in the order Lodz, Rome, Oslo, and Amsterdam. A high dose of the fine fraction was more potent than a high dose of the coarse fraction, except at De Zilk, where the reverse was true. Spring and winter PM was more potent than summer PM. Depending on the site, either a water-soluble or a water-insoluble fraction was responsible for the adjuvant activity. A concentration of 3 mg/ml is effective for screening high-activity samples, as is a concentration of 9 mg/ml for screening low-activity samples in the ovalbumin-mouse model.
    No preview · Article · Apr 2005 · Inhalation Toxicology
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    ABSTRACT: In the framework of an EU project entitled, "Respiratory Allergy and Inflammation due to Ambient Particles (RAIAP)", various ambient particulate matter samples were tested for their adjuvant potency in an animal allergy model to ovalbumin. Coarse (2.5-10 microm) and fine (0.15-2.5 microm) particles were collected during the spring, summer, and winter in Rome, Oslo, Lodz, and Amsterdam. Coarse and fine particles were also collected near a seaside location in the Netherlands, where prevailing winds are westerly. These latter particles served as a control, with a minimum contribution by traffic. Ottawa dust (EHC-93) was used as a standard reference sample. Immunoglobulins (IgE, IgG1, and IgG2a), histopathological changes in the lung, cytokines, and the number of cells and their differentiation in lung lavages were used as effect parameters to study the adjuvant potency of these particles. The particles (3 mg/ml) were mixed with ovalbumin (0.4 mg/ml) and intranasally administered during the sensitization or the challenge phase. Intranasal administration of ovalbumin only induced very little antibody response, but introduced a minor inflammatory response in the lung or BAL during the sensitization and challenge phase. On the contrary, after coexposure to EHC-93 and ovalbumin, a major increase was found in immunoglobulin levels specific for ovalbumin, and a major inflammatory response in lung and BAL was induced. Coexposure to ovalbumin with 4 out of 12 collected PM samples (3 mg/ml) resulted in an increase of mainly IgE and IgG1. The histopathological changes consisted of a small to severe peribronchial and perivascular inflammatory response, a hypertrophy of bronchiolar mucous cells and an increase in eosinophils and neutrophils in the BAL. Statistical evaluation of the above-mentioned parameters showed associations with PMx (coarse and fine), site, season, season x PMx, season x site and (PMx) x site. In addition, adjuvant activity of the PMx can be ranked as Lodz > Rome = Amsterdam > Oslo. When the different seasons were compared for IgE, PM from winter was found more active compared to PM from spring and summer. Only for the histopathological lesions, statistically significant difference in effects was found between coarse and fine (coarse > fine). No associations were found between the endotoxin content and the biological effects parameters, although endotoxin was much more confined to the coarse fraction. In conclusion, PM, both coarse and fine, and from various geographic sites, was found to differ in adjuvant activity; furthermore, winter was found more active than spring and summer.
    No preview · Article · Dec 2004 · Toxicology and Applied Pharmacology
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    ABSTRACT: In previous studies, we have shown strong adjuvant activity for Ottawa dust (EHC-93) after coexposure of the BALB/c mouse to EHC-93 and ovalbumin. Mice were intranasally sensitized at days 0 and 14 with 200 microg ovalbumin and 150 microg EHC-93, and challenged with ovalbumin at days 35, 38, and 41 with 200 microg ovalbumin. Mice were autopsied at day 42. This adjuvant activity was shown for the antibody response to ovalbumin (immunoglobulins E, G1, and G2a), histopathological lesions in the lung, cytokines, and the numbers of eosinophils in lung lavages. To study the mechanisms of this adjuvant activity, mice (BALB/cC.D2-Vil6) with natural-resistance-associated macrophage protein (Nramp1s), BALB/c mice pretreated with the antioxidant N-acetylcysteine (NAC), mice (B6.129P2-Nos2tmLau) deficient in inducible nitric oxide synthase (iNOS), and mice with interleukin-4 (IL-4) deficiency (BALB/cIl4< tm2Nnt) were coexposed to ovalbumin and EHC-93. Our studies have shown that the adjuvant activity induced after such coexposure does not change if the macrophage activation of the mice is disturbed or if the mice have been pretreated with N-acetylcysteine. In addition, the adjuvant activity does not develop through the pathway in which inducible nitric oxide synthase is involved. Because the histopathological lesions are statistically significant less in the IL-4 knockout strain in comparison with the wild type, we conclude that interleukin-4 might play an important role in the adjuvant activity caused by EHC-93.
    No preview · Article · Dec 2004 · Inhalation Toxicology
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    ABSTRACT: of this paper is to compare observed values of immune parameters obtained in the CESAR study (The Central Europe Study of Air Pollution and Respiratory Health, funded by EC PHARE program) with ranges derived from other large population-based studies. Data were collected in healthy school children aged 9-11 years, in 6 countries: Bulgaria, the Czech Republic, Hungary, Poland, Romania and the Slovak Republic with the same standard approach in 1996. Random samples of 85 children per country, from 19 communities were selected from children having completed the health questionnaire, in total 495 children were analyzed. Lymphocyte subsets were determined by two-colour flow cytometric immunophenotyping using the lysed whole blood method (Becton-Dickinson). For determination of immunoglobulin concentration in sera nephelometric method (Behring Nephelometer system) was used. Medians, (5th-95th percentiles) of the lymphocyte subsets absolute count (x 10(9)/l) were as follows: CD19+ B cells 0.36 (0.13-0.66), total CD3+ T cells 1.74 (0.98-2.90), CD3+CD4+ helper-inducer T cells 0.95 (0.47-1.78), CD3+CD8+ suppressor/cytotoxic T cells 0.71 (0.38-1.22), CD3-CD16+56+ NK cells 0.36 (0.14-0.78), and for CD3+CD4+/CD3+CD8+ ratio 1.4 (0.8-2.4). Medians, (5th-95th percentiles) of percentages of lymphocyte subpopulations (%) were as follows: CD19+ B 13 (7-22), CD3+ T 70 (59-80), CD3+CD4+ T 38 (27-48), CD3+CD8+ T 28 (20-39), CD3-CD16+56+ NK cells 14 (6-27). Medians, (2.5th-97.5th percentiles) of the total immunoglobulin [g/l] were 11.7 (7.4-18.2) for IgG, 1.2 (0.5-2.5) for IgM, and 1.5 (0.5-3.4) for IgA. Based on the aspects of the size of the CESAR immune biomarker study and on the use of the standardized protocols we recommend to use the reference ranges on lymphocyte subsets and immunoglobulin in Europe as provided by this study.
    Full-text · Article · Oct 2004 · Central European journal of public health
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    ABSTRACT: Release of cytoplasmic granules from grass pollen upon contact with water is thought to be an important source of airborne allergens. To investigate the humoral and cellular responses to intratracheal instillation of Phleum pratense (timothy grass) pollen cytoplasmic granules (PCG) in the Brown Norway rat. PCG were purified from timothy grass pollen by filtration through 5-microm-mesh filters. Rats were sensitized (day 0) and challenged (day 21) intratracheally with purified PCG suspended in saline (6 x 10(6) PCG/rat). Rats were then challenged 4 weeks later (1.5 x 10(6) PCG/rat). Blood samples, bronchial lymph nodes and lungs were collected from the rats 4 days after the second challenge. PCG-specific IgE and IgG1 levels and specificity were determined by ELISA and Western blotting. Pollen, pollen extract and PCG-induced proliferation of lymph node cells were monitored by [(3)H]-thymidine incorporation in a lymph node assay. Histopathological examination was carried out on the lungs. Specific IgE and IgG1 were present in the sera. Cultured lymph node cells proliferated in the presence of pollen, pollen extract and PCG. Western blots showed that all major pollen allergens are recognized by IgE and IgG1 from PCG-treated rats. Histopathological examination revealed features of a mild allergic reaction. In our rat model of allergy, purified timothy grass PCG instillation induced specific antibodies and lymph node cell responses, comparable to those obtained with intact pollen.
    No preview · Article · Oct 2004 · International Archives of Allergy and Immunology

  • No preview · Article · Jun 2004
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    ABSTRACT: Ambient particulate matter may increase respiratory allergic skewing of the T-cell-mediated immune response toward a T-helper-2 (Th2) response, with the consequence that the Th1 response develops less well. Successful clearing of a respiratory bacterial infection depends on an adequate Th1 immune response; therefore, the subject would not control the infection as well if exposed to particulate matter. To substantiate this hypothesis, we examined the effect of exposure to diesel exhaust particles (DEP) and urban particulate matter (EHC-93, Ottawa dust) on rats with a Listeria monocytogenes respiratory infection. Since this hypothesis has been confirmed for ozone, we used it as a positive control. Wistar rats were exposed to ozone (2 mg/m3 for 24 h/day for 7 days) and to DEP or to EHC-93 (50 microg/rat intranasally daily for 7 consecutive days). Twenty-four hours after the last exposure, the rats were infected intratracheally with 1 x 10(6) L. monocytogenes bacteria. The number of L. monocytogenes was determined after 3, 4 and 5 days. Statistically significant increases of the number of L. monocytogenes in rats exposed to ozone were observed in the lungs and spleen at all three times. However, we found no significant differences in the numbers of bacteria that were found in rats exposed to DEP or EHC-93 compared to the saline-treated group at any of the three times. In conclusion, the results of this study do not support the hypothesis that exposure to DEP or EHC-93 reduces subsequent resistance to a respiratory infection in rats.
    No preview · Article · Jun 2004 · Inhalation Toxicology
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    ABSTRACT: Timothy grass (Phleum pratense) pollen allergens are an important cause of allergic symptoms. However, pollen grains are too large to penetrate the deeper airways. Grass pollen is known to release allergen-bearing starch granules (SG) upon contact with water. These granules can create an inhalable allergenic aerosol capable of triggering an early asthmatic response and are implicated in thunderstorm-associated asthma. We studied the humoral (IgE) and bronchial lymph node cells reactivities to SG from timothy grass pollen in pollen-sensitized rats. Brown-Norway rats were sensitized (day 0) and challenged (day 21) intratracheally with intact pollen and kept immunized by pollen intranasal instillation by 4 weeks intervals during 3 months. Blood and bronchial lymph nodes were collected 7 days after the last intranasal challenge. SG were purified from fresh timothy grass pollen using 5 microm mesh filters. To determine the humoral response (IgE) to SG, we developed an original ELISA inhibition test, based on competition between pollen allergens and purified SG. The cell-mediated response to SG in the bronchial lymph node cells was determined by measuring the uptake of [3H]thymidine in a proliferation assay. An antibody response to SG was induced, and purified SG were able to inhibit the IgE ELISA absorbance by 45%. Pollen extract and intact pollen gave inhibitions of 55% and 52%, respectively. A cell-mediated response was also found, as pollen extract, intact pollen and SG triggered proliferation of bronchial lymph node cells. It was confirmed that timothy grass pollen contains allergen-loaded SG, which are released upon contact with water. These granules were shown to be recognized by pollen-sensitized rats sera and to trigger lymph node cell proliferation in these rats. These data provide new arguments supporting the implication of grass pollen SG in allergic asthma.
    No preview · Article · Mar 2004 · Clinical & Experimental Allergy
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    ABSTRACT: Differences in the prevalence of allergic sensitisation have been reported in immigrant children living in the same urban environment. The purpose of this study is to investigate the prevalence of allergic sensitisation in school children of Dutch, Turkish and Moroccan origin. The prevalence of sensitisation to aero-allergens was assessed using the skin prick test in a non-selected sample of 512 children (response rate 54%) living in the same inner city district of Utrecht. In addition, exhaled nitric oxide (FeNO) was determined. The prevalence of allergic sensitisation was dependent on the ethnic origin. As compared with Dutch children (19.1%), a higher prevalence of allergic sensitisation was observed in immigrant children for whom both parents were born in Turkey (23.6%, not significant) or Morocco (30.6%, p<0.05). The prevalence of allergic sensitisation in Dutch children was nearly 2 times lower than the reported prevalence in German children. In all sensitised children, the mean FeNO value was significantly (p<0.05) higher than in non-sensitised children, and the mean FeNO level was highest in Moroccan children sensitised to indoor allergens. In The Netherlands, immigrant children show a higher prevalence of allergic sensitisation as compared to Dutch children.
    No preview · Article · Mar 2004 · International Archives of Allergy and Immunology
  • Peter A Steerenberg · Jan G C van Amsterdam
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    ABSTRACT: Assessment of the value of exhaled NO (eNO) is an attractive tool for studying pulmonary disease, considering its wide advantages (i.e., fast analysis, noninvasive sampling, ability to measure large numbers of subjects [including children], and inexpensive in use). Increased concentrations of eNO have been observed in asthmatic patients' airway infections, allergic rhinitis, and bronchiectasis. During inflammation, specific and nonspecific stimuli elicit expression and de novo synthesis of inducible nitric oxide (iNOS). Once generated in the bronchiolar cells, NO is released from the tissue and diffuses to the lumen of the bronchiolis. Of the two sampling ways (on-line and off-line), the off-line method is suitable for monitoring environmental health effects of air pollution and for obtaining an impression of the prevalence of atopy in epidemiological surveys. For this off-line measurement, a balloon method is developed (sampling exhaled air at location) that includes a sample device assuring inflation of balloons at a controlled flow rate and back-pressure. Cigarette smoking and alcohol consumption significantly reduces NO levels in exhaled air because of downregulation of iNOS. Although eNO can be reliably measured and analyzed, the prospective value to detect asthma or allergy is rather low (low sensitivity and low specificity), which makes the diagnostic value of eNO for predicting either allergy or asthma doubtful. Promising results have, however, been observed in corticoid-sparing therapies under guidance of eNO. In addition, measurement of eNO helps to understand the mechanisms of pulmonary disease and may be useful in detecting adverse effects of air pollution.
    No preview · Article · Feb 2004 · Methods in Molecular Biology

Publication Stats

4k Citations
624.41 Total Impact Points


  • 1987-2011
    • National Institute for Public Health and the Environment (RIVM)
      • Laboratory for Health Protection Research
      Utrecht, Utrecht, Netherlands
  • 2003
    • Maastricht University
      Maestricht, Limburg, Netherlands
  • 1987-2003
    • Utrecht University
      • • Institute for Risk Assessment Sciences (IRAS)
      • • Division of Pathology
      • • Division of Pharmacology
      Utrecht, Utrecht, Netherlands
  • 2002
    • Pace University
      New York City, New York, United States
  • 2001
    • Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
  • 1999
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 1998
    • Leiden University Medical Centre
      • Department of Pulmonology
      Leyden, South Holland, Netherlands
  • 1992
    • University of Amsterdam
      • Department of Urology
      Amsterdam, North Holland, Netherlands
  • 1991
    • Radboud University Nijmegen
      Nymegen, Gelderland, Netherlands
  • 1984
    • Laboratories of Pathology Eastern-Netherlands
      Enschede, Overijssel, Netherlands
  • 1981
    • National Cancer Institute (USA)
      베서스다, Maryland, United States