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Biomedical subjects

D Nowak

Publications and source records attributed to D Nowak.

At least 127 records · Page 7Linked to original sources
PubMed1998

Age-dependent differences in the prevalence of allergic rhinitis and atopic sensitization between an eastern and a western German city.

Recent studies have found a higher prevalence of allergic rhinitis and atopic sensitization among adults living in eastern than those living in western Germany. We hypothesize that prevalence rates were similar before Germany was divided and diverged after the division. Because there are no historical data comparing atopic status between the two parts of Germany, we tested this hypothesis by comparing the prevalence of atopy among persons who were born during different decades. As part of the EC Respiratory Health Survey, a respiratory health questionnaire was mailed to a population-based sample of 8363 subjects aged 20-44 years from a city in the former West Germany (Hamburg) and a city in the former East Germany (Erfurt). Of the target population, 6428 (77%) subjects responded. Subsamples of 731 subjects from Erfurt and 1159 subjects from Hamburg participated in medical examinations, including skin prick tests and specific IgE measurements. Prevalence rates of allergic sensitization were similar in Hamburg and Erfurt for those born in the periods 1946-51 and 1952-61, respectively, but differed between Hamburg and Erfurt subjects born in the period 1962-71. After adjustment for several potential predictors, the younger subjects from Hamburg had a higher odds ratio (OR) of sensitization than those Hamburg subjects born before 1952 (skin prick test reactivity: OR 2.06, any specific IgE > 0.35 kU/l: OR 1.61). The younger subjects from Erfurt were not more frequently sensitized than the older subjects (skin prick test reactivity: OR 1.05, any specific IgE > 0.35 kU/l: OR 0.79). No single allergen could be identified as responsible for the observed difference. We conclude that factors related to a "Western lifestyle", which were prevalent in the West German city during the 1960s and 1970s, may be responsible for the higher prevalence of allergic sensitization observed in Hamburg.

Adult↗
PubMed1998

References values for forced spirometry. Group of the European Community Respiratory Health Survey.

The European Coal and Steel Community (ECSC) prediction equations exemplify a significant effort carried out approximately 15 yrs ago to provide uniform standards for lung function testing, but this set of equations has not been properly validated as yet. The present study evaluates the ECSC reference values and four other sets of prediction equations, using spirometric data collected in 12,900 nonasthmatic subjects (43% lifetime nonsmokers and 36% active smokers) aged 20-44 yrs from the European Community Respiratory Health Survey (ECRHS). Standardized spirometric measurements were obtained using a common protocol in 34 centres in 14 countries. For each prediction equation, the prediction deviations (i.e. observed minus predicted value) for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) were examined for the whole study population and for each centre. For the age range included, the errors about the ECSC equations showed the most prominent underestimation of both predicted FVC (+355 and +360 mL on average in males and females, respectively) and predicted FEV1 (+211 and +200 mL, respectively) among the five studies examined. As expected, FVC and FEV1 in active smokers from the ECRHS were significantly lower than in lifetime nonsmokers (each p<0.01). We conclude that the present European recommendations on lung function reference values should be reconsidered, but further data for nonsymptomatic subjects above the age of 44 yrs are needed.

Adult↗
PubMed1998

[Almitrine in therapy of chronic obstructive respiratory tract diseases with hypoxemia--a clinical multicenter study comparing 2 dosages].

In an 8-month prospective, placebo-controlled multi-centre trial involving 64 hypoxaemic COPD patients (mean +/- SD age, 64 +/- 8 years, paO2, 57 +/- 7 mmHg, paCO2, 41 +/- 6 mmHg), we compared the efficacy and acceptability of two different dosages of almitrine, 75 and 100 mg. 21 patients received continuous treatment with almitrine (75 mg), 23 sequential treatment (100 mg, one month of placebo after three months treatment), and 20 were in the placebo group. As defined by the inclusion criteria, none of the patients had clinical or subclinical signs of peripheral neuropathy. Clinical examinations, blood gas analyses and determinations of plasma almitrine levels were performed monthly. Patients underwent spirometry and detailed neurological examination upon entry and at the end of the trial. The percentage of drop-outs was considerably higher among patients under medication (59%) as compared to placebo (10%, p < 0.001) which was particularly due to impaired compliance in the almitrine groups. Comparing arterial paO2 or paCO2 over time by analysis of variance, there was no significant effect of medication on blood gases. However, in patients receiving 100 mg almitrine daily, paO2 was significantly increased vs. placebo after four and six months of treatment, and in patients receiving 75 mg almitrine, mean paCO2 was significantly lowered vs. placebo after four months of medication (t-test, p < 0.05). Neurological findings did not differ between treatments and over time. In conclusion, only certain individual patients may benefit from a treatment with 100 mg almitrine whereas the effect of the 75 mg dosage on paO2 did not differ from placebo.

Aged↗
PubMed1998

Effect of serine proteinase inhibitors on intracellular free calcium rise in human polymorphonuclear leukocytes after stimulation with receptor agonists.

The respiratory burst of polymorphonuclear leukocytes depends on activation of many enzymes and generation of variety of second messengers. One of important links leading to polymorphonuclear leukocytes (PMNL) activation is a transient rise in intracellular free calcium concentration ([Ca2+]i). Serine proteinase inhibitors such as alpha-1-proteinase inhibitor (alpha1PI), phenylmethylsulphonylfluoride (PMSF) and soybean trypsin inhibitor (SBTI) were reported to inhibit human PMNL respiratory burst. In this study we tested the hypothesis whether these inhibitors can inhibit the rise in [Ca2+]i after stimulation of human PMNL with 10(-7) M n-formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) or platelet activating factor (PAF). [Ca2+]i was measured with use of a fluorescent probe Fura-2AM under conditions of 100 nM and 1 mM extracellular Ca2+ concentration. Preincubation of PML with 600 mg/dl of alpha1PI or SBTI for 30 min at 37 degrees C had no influence on Ca2+ response to all agonists in comparison with cells treated with the same concentration of human serum albumin. However, 0.5 mM PMSF enhanced 1.7-fold (p < 0.002) [Ca2+]i rise after challenge with FMLP while did not affect significantly Ca2+ response to PAF and LTB4. The stimulatory effect of PMSF after addition of FMLP was dependent on increased Ca2+ influx from extracellular space. Our results suggest that suppression of PMNL respiratory burst by serine proteinase inhibitors is not mediated via Ca2+ pathway and that some proteases take part in Ca2+ response to FMLP.

Adult↗
PubMed1998

[Health effects of airborne pollutants, particularly in swine confinement stalls, from the viewpoint of occupational medicine].

From the point of view of occupational respiratory medicine, an overview on potential health effects of airborne pollutants particularly in swine confinement houses is presented. Airway diseases are the most frequent occupational disorders among farmers in many countries around the world including Germany. Due to various methodological reasons, epidemiological studies in farming populations are more difficult to perform than among non-farmers. Major constituents of swine confinement dust include bacteria, endotoxin, mites, fungal spores, and animal dander. Gaseous pollutants include ammonia, methane, and hydrogen sulfide. In a variety of cross-sectional studies, high prevalences of respiratory symptoms and non-obstructive (and obstructive) bronchitis and Organic Dust Toxic Syndrome have been reported in pig farmers. Nasal and bronchial provocation challenges with swine confinement dust include influx of neutrophils and other inflammatory cells as well as mediators. In cross-sectional and longitudinal studies, endotoxin turns out as the probably most relevant parameter associated with lung function impairment. Further studies are clearly needed focusing on the prognosis of non-obstructive bronchitis in swine farmers and on health effects of reducing airborne contaminants in swine confinement houses.

Adolescent↗
PubMed1998

Cigarette smoking does not increase hydrogen peroxide levels in expired breath condensate of patients with stable COPD.

Cigarette smoking is the most common factor responsible for the development of chronic obstructive pulmonary disease (COPD) leading to oxidant overload in the lower airways because of the presence of oxidants in cigarette smoke and recruitment and activation of pulmonary phagocytes. In this study we intended to determine whether: 1) patients with stable COPD have higher H2O2 levels in expired breath condensate than healthy nonsmoking subjects and 2) whether cigarette smoking increases H2O2 exhalation in patients with stable COPD. The H2O2 content of the expired breath condensate of 17 healthy nonsmoking subjects and 38 patients (10 current smokers, 17 exsmokers and 11 who have never smoked) with stable COPD (forced expiratory volume in one second (FEV1) 63.3 +/- 15.5% of predicted value) was measured spectrofluorimetrically (homovanillic acid method). The mean H2O2 concentration in the expired breath condensate of COPD subjects was 10-times higher than that found in healthy controls (0.55 +/- 0.69 microM versus 0.05 +/- 0.07 microM, p < 0.005). There were no significant differences between H2O2 levels found in current smokers with COPD (0.44 +/- 0.56 microM) and COPD subjects who have never smoked (0.49 +/- 0.70 microM). No correlation was found between expired H2O2 and daily cigarette consumption or cumulative cigarette consumption in current smokers or exsmokers with COPD. These findings demonstrate that subjects with stable chronic obstructive pulmonary disease exhibit increased H2O2 generation in the airways and that cigarette smoking does not increase H2O2 production.

Breath Tests↗
PubMed1997

Polymorphonuclear leukocytes from asthmatics release more calcium from intracellular stores and have enhanced calcium increase after stimulation with N-formyl-methionyl-leucyl-phenylalanine.

Polymorphonuclear leukocytes isolated from peripheral blood of asthmatics appear to be primed to release more reactive oxygen species than cells of healthy subjects. The enhanced agonist-induced rise in the intracellular free calcium concentration may be responsible for this increased respiratory burst. To test this hypothesis we studied the N-formyl-methionyl-leucyl-phenylalanine- and cyclopiazonic acid--(an inhibitor of Ca(2+)-ATPase of intracellular calcium stores) induced calcium increase in the polymorphonuclear leukocytes of 28 subjects (16 with moderate asthma, 69.6% +/- 8.3% predicted normal peak expiratory flow and 12 normal controls) using a fluorescent probe Fura-2AM at 100 nM and 1 mM extracellular calcium concentrations. In 1 mN calcium, the N-formyl-methionyl-leucyl-phenylalanine-induced calcium increase was 1.7-fold higher in asthmatics than in healthy subjects. Similarly, the contribution of calcium from intracellular stores to the calcium response to N-formyl-methionyl-leucyl-phenylalanine was higher in asthmatics (55% +/- 14% vs. 39% +/- 14%, P < 0.01). The pool of calcium released from intracellular stores by N-formyl-methinoyl-leucyl-phenylalanine and cyclopiazonic acid was 2.3- and 2.2-fold larger than in control cells. There was a correlation between maximal intracellular calcium concentration related to N-formyl-methionyl-leucyl-phenylalanine-induced calcium release from intracellular stores and forced expiratory volume in 1 s expressed as percentage predicted and reversibility in asthmatics (r = 0.63, r = -0.53, P < 0.05). In conclusion, polymorphonuclear leukocytes of asthmatics exhibit an altered calcium response that is mainly dependent on increased calcium release from intracellular stores.

Adult↗
PubMed1997

Effect of 3 hours' passive smoke exposure in the evening on airway tone and responsiveness until next morning.

To study the effect of environmental tobacco smoke (ETS) exposure in the evening on nocturnal changes in airway tone and responsiveness, 17 subjects with mild asthma (mean +/- SD age, 26 +/- 5 years, FEV1% pred., 89 +/- 14%) were exposed to either ambient air (sham) or ETS (20 ppm CO) for 3 h (7:00 to 10:00 p.m.). Seven subjects had a history of ETS-induced respiratory symptoms. Spirometry was performed 2 h before exposure (5:00 p.m.), every 30 min during exposure, and at 11:00 p.m., 3:00 a.m., and 7:00 a.m. The provocative concentrations of methacholine necessary to decrease FEV1 by 20%, PC20FEV1, were assessed at 5:00 p.m., 11:00 p.m., 3:00 a.m., and 7:00 a.m. Compared with pre-exposure measurements, mean FEV1 values during and after ETS exposure were significantly lower than with sham exposure = 0.013 and 0.026). This effect, however, was due to a significant response in single individuals. The higher bronchial responsiveness after ETS than after sham exceeded one doubling concentration in 4, 5, and 4 patients at 11:00 p.m., 3:00 a.m., and 7:00 a.m., respectively. The opposite effect was observed in 2, 2, and 2 patients, respectively. There was no statistically significant mean effect of ETS on airway responsiveness during night; however, there was significant heterogeneity in individual responses (P = 0.0002). Patients with and without a history of ETS-induced symptoms did not show different responses to experimental ETS exposure. In conclusion, our data suggest that in single adult subjects with mild asthma, acute exposure to ETS in the evening can produce a deterioration of airway tone and responsiveness during the night, with wide interindividual variability in the response.

Adult↗
PubMed1997

Effect of 3 hours of passive smoke exposure in the evening on inflammatory markers in bronchoalveolar and nasal lavage fluid in subjects with mild asthma.

OBJECTIVE: The aim of this study was to investigate the effect of environmental tobacco smoke (ETS) exposure in the evening on inflammatory changes in bronchoalveolar (BAL) and nasal lavage (NAL) fluid. METHODS: Ten subjects with mild asthma [mean (+/- SD) age, 25 +/- 2 years, FEV1% pred., 93 +/- 6%, PC20FEV1 0.44 x 5.11 mg/ml methacholine] were exposed to ETS (22.4 +/- 1.2 ppm CO) or ambient air (sham) for 3 h (7.00 to 10.00 p.m). Bronchoscopy was performed the following morning at 7.00 a.m. A visual endoscopic score was assessed, and BAL fluids were analyzed for cellular composition and concentrations of histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, tryptase, prostanoids and leukotrienes. Nasal lavages were performed 30 min prior to and 30 min after exposures, and NAL fluids were analyzed for histamine, albumin, eosinophilic cationic protein, myeloperoxidase, hyaluronic acid, and tryptase. RESULTS: There was a significant rise in symptoms after ETS exposure compared with sham (P < 0.05). Spirometric lung function did not change during or after exposure compared with pre-session values. Visual bronchoscopic scoring revealed no significant effect of ETS exposure, nor did BAL cells and mediators or NAL mediators as compared with pre-challenge or post-sham values. CONCLUSION: In the subjects tested, a 3-h ETS exposure in the evening appeared not to have an inflammatory effect detectable in BAL or NAL fluid.

Adult↗
PubMed1997

Altered intracellular calcium signalling after PAF stimulations in polymorphonuclear leukocytes from asthmatic patients.

Platelet activating factor (PAF), a potent lipid mediator, has been implicated in the pathogenesis of airways inflammation in bronchial asthma. Binding of PAF to its receptor (Nakamura et al., 1991) leads to changes of intracellular Ca2+ concentration ([Ca2+]i) that is crucial to cell activation. Therefore, the aim of our study was to investigate whether PMNL of asthmatic patients stimulated with PAF (10(-7) M) differ in relation to changes of [Ca2+]i from cells of healthy subjects. PMNL from asthmatic patients revealed attenuated first response to PAF stimulation--increase in [Ca2+]i (delta[Ca2+]i) was 1.3-fold lower in cells of asthmatics (P < 0.05) versus PMNL of healthy subjects. As determined in experiments with low extracellular calcium concentration, Ca2+ release from internal stores tended to be increased in asthmatics and hence the difference in total Ca2+ response was related to decrease in Ca2+ influx. Thus the contribution of Ca2+ from internal stores to the total first Ca2+ response upon PAF stimulation was two-fold higher (58 +/- 18 vs. 29 +/- 8%, P < 0.001) in PMNL of asthmatics compared with healthy subjects. Two subsequent Ca2+ responses evoked by stimulations with the agonist in 1 mM Ca2+ buffer did not differ between study groups. In low Ca2+ buffer PMNL of 50% of asthmatics responded to the second stimulation while cells of healthy subjects remained unresponsive. The altered Ca2+ responses in PMNL of asthmatic subjects may reflect previous contact with mediator(s) that occur in vivo which may be at least partially explained by the phenomenon of down regulation reported for PAF receptor upon cell stimulation.

Adult↗
PubMed1997

Staphylococcal serine proteinase increases intracellular free calcium concentration in human polymorphonuclear leukocytes.

Staphylococcal serine proteinase (SSP) can influence various functions of human polymorphonuclear leukocytes (PMNL) including chemotaxis and phagocytosis. Since the rise in intracellular free calcium concentration is an important step in signal transduction leading to phagocyte activation, we tested the ability of SSP to increase the intracellular free calcium concentration in human PMNL using the fluorescent calcium indicator Fura-2AM. PMNL isolated from healthy donors responded to SSP in the concentration range of 10 to 100 micrograms/ml. The highest Ca2+ rise (104 +/- 47 nM) was observed for 10 micrograms/ml SSP. It was mainly dependent (81 +/- 11%) on extracellular calcium influx, however, SSP mobilized 68 +/- 7% of Ca2+ from intracellular calcium stores. Boiling of SSP or preincubation with phenylmethylsulphonylfluoride (an serine proteinase inhibitor) did not change its ability to increase intracellular free calcium concentration in PMNL. It suggests that active center of SSP is not responsible for Ca2+ mobilization. Finally, PMNL responded to each of three consecutive stimulations with SSP independently of the presence of high or low extracellular Ca2+ concentration. This may be an additional mechanism responsible for activation of human PMNL and degradation of alveolar walls during the staphylococcal infection in the lower airways.

Adult↗
PubMed1997

Airway responsiveness to sulfur dioxide in an adult population sample.

We determined the prevalence of airway hyperresponsiveness to sulfur dioxide (SO2) in an adult population sample of 790 subjects 20 to 44 yr of age. Subjects were drawn randomly from the population of Hamburg, Northern Germany, within the framework of the European Community Respiratory Health Survey. In addition, we analyzed the relationship between SO2 responsiveness and a number of risk factors, such as a history of respiratory symptoms, methacholine responsiveness, and atopy derived from skin-prick test results. SO2 inhalation challenges were performed during isocapnic hyperventilation at constant rate (40 L x min(-1), for 3 min) with doubling concentrations of SO2 up to a maximum concentration of 2.0 ppm. If subjects achieved a 20% decrease in FEV1 from baseline during the challenge, they were considered to be hyperresponsive to SO2. The raw prevalence of SO2 hyperresponsiveness within the population sample studied was 3.4% (95% confidence interval [CI]: 2.3 to 5.0%). Adjustment for nonparticipation led to an estimated prevalence of SO2 hyperresponsiveness of 5.4%. Among subjects with hyperresponsiveness to methacholine, 22.4% (95% CI: 20.1 to 25.3) demonstrated hyperresponsiveness to SO2. There was no significant correlation between the degrees of hyperresponsiveness to methacholine and SO2. Predictors of a positive SO2 response were hyperresponsiveness to methacholine (p < 0.0001), a positive history of respiratory symptoms (p < 0.05), and a positive skin-prick test to at least one common allergen (p < 0.05). We conclude from these data that airway hyperresponsiveness to SO2 can be found in about 20 to 25% of subjects within the 20- to 44-yr age range who are hyperresponsive to methacholine.

Adult↗
PubMed1997

Increased hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients.

Symptoms of bronchial asthma are a manifestation of airway inflammation. Circulatory leucocytes (predominantly eosinophils, mast cells and neutrophils), release inflammatory mediators, including reactive oxygen species, i.e. superoxide anion which is dismutated to hydrogen peroxide (H2O2). Neutrophils from asthmatics generate greater amounts of these species than those of healthy subjects. Some of the H2O2 and thiobarbituric acid-reactive products (TBARs) can evaporate from alveolar lining fluid, and could be expired from the airways of asthmatics. In this study, therefore, we determined whether asthmatic patients exhale more H2O2 and TBARs than healthy subjects. We examined 10 healthy subjects as a control group and 21 asthmatic subjects. In asthmatic subjects, forced expiratory volume in one second (FEV1), was 68+/-9% of predicted value, peak expiratory flow rate (PEFR) was 65+/-8% pred, and bronchial reversibility was 34+/-5% of prebronchodilated FEV1. The mean H2O2 level measured spectrofluorimetrically in the expired breath condensate of asthmatic subjects was 26 fold higher than that in healthy controls (0.26+/-0.29 vs 0.01+/-0.03 nM; p<0.05). The concentration of TBARs in breath condensate was also higher in asthmatic patients compared with nonasthmatics (0.073+/-0.071 vs 0.004+/-0.009 nM; p<0.05). There was a significant correlation between H2O2 level and concentration of TBARs in asthmatic patients (r=0.74; p<0.01). There was also a strong inverse correlation between H2O2 content of all asthmatics and FEV1% pred (r=-0.63; p<0.005) and PEFR% pred (r=-0.52; p<0.05). We conclude that there are elevated levels of hydrogen peroxide and thiobarbituric acid-reactive products in expired breath condensate of asthmatic patients, and that measurement of these substances in the expired breath condensate could be a simple, noninvasive method that could be used as a biochemical marker of airway inflammation.

Adult↗
PubMed1997

A short protocol for methacholine provocation testing adapted to the Rosenthal-Chai dosimeter technique.

BACKGROUND: The purpose of this study was to develop a rapid and safe methacholine provocation protocol equivalent to the standard dosimeter technique. METHODS: The rapid protocol comprised a short and a long subprotocol. The challenge was started with one of these subprotocols according to the subject's answers to a questionnaire and baseline lung function. If FEV1 dropped by 10% during the short subprotocol, the test was continued with the long subprotocol. The concentrations of methacholine and numbers of inhalations were chosen to match the concentrations of the standard method as closely as possible. To verify the protocol, we compared both methods in 38 subjects with asthma and 10 control subjects. RESULTS: The provocative concentrations of methacholine (PC20FEV1) obtained with the standard method and the rapid method were within one doubling concentration in 38 of 40 subjects. None of the subjects who were normoreactive according to the standard method (PC20FEV1 > 8 mg/mL) responded in the rapid protocol. The standard method required, on average (+/-SD), 34+/-11 min; the rapid method required 15+/-3 min. CONCLUSIONS: The rapid provocation protocol is equivalent to the standard method, without loss in precision and safety, but with considerable saving in time. Therefore, it appears to be particularly suited for studies that require comparability with provocative concentrations obtained with the Rosenthal-Chai dosimeter method.

Adult↗
PubMed1997

Effect of bacterial extract, IRS-19, on the concentration of hydrogen peroxide and myeloperoxidase activity in nasal washings of patients with chronic bronchitis.

Twenty eight adult patients of both sexes with chronic bronchitis participated in an open study to determine the effect of intranasal treatment with IRS-19, an immunomodulating agent, on the number of polymorphonuclear leukocytes (PMNL), H2O2 concentration and myeloperoxidase (MPO) activity in nasal washings. The number of PMNL recovered from nasal spaces increased from 4460 +/- 3960 to 10,490 +/- 10,950 cells/ml (p < 0.02) after two month administration of IRS-19. It was accompanied by 2.6- and 1.4-fold increase (p < 0.001) in MPO activity and H2O2 concentration, respectively. However, no correlation was found between increments in these three variables. Since PMNL and MPO-H2O2-Cl- system are involved in the first line of defense against invading pathogens it is suggested that above mentioned changes may represent one among mechanisms leading to enhancement of antibacterial defence in the airways in response to treatment with IRS-19.

Adjuvants, Immunologic↗