Contribution of c-erbB-2 and topoisomerase IIalpha to chemoresistance in ovarian cancer.

Overexpression of the c-erbB-2 (HER-2/neu) oncogene, which encodes a transmembrane receptor tyrosine kinase, has been shown to be associated with poor prognosis in ovarian and breast cancer. Recent studies indicate that c-erbB-2 may also be involved in determining the chemosensitivity of human cancers. In the present study, we examined the role of c-erbB-2 for chemoresistance in ovarian cancer. Overexpression of c-erbB-2 mRNA in tumor tissue was associated with a shorter survival of patients with primary ovarian cancer (P = 0.0001; n = 77) and was an independent prognostic factor in the proportional-hazard model adjusted for International Federation of Gynecologists and Obstetricians stage, residual disease, chemotherapy, and age (P = 0.035). A significant association between expression of c-erbB-2 mRNA and survival was obtained for the subgroup of patients who received a standard chemotherapy with carboplatin or cisplatin and cyclophosphamide (P = 0.0003), whereas only a nonsignificant trend was observed for patients who did not receive a standard chemotherapy (P = 0.124). In addition, the application of a standard chemotherapy improved the survival of patients with relatively low c-erbB-2 expression (P = 0.013) but not of patients with overexpression of c-erbB-2 (P = 0.359). Expression of c-erbB-2 mRNA correlated with expression of topoisomerase IIalpha mRNA determined by a reverse semiquantitative PCR technique (P = 0.009), whereas expression of c-erbB-2 and topoisomerase IIbeta mRNA did not correlate (P = 0.221). To examine the hypothesis that coamplified and/or coregulated topoisomerase IIalpha contributes to the resistance of c-erbB-2-overexpressing carcinomas, we established a chemosensitivity assay using primary cells from an ovarian carcinoma that overexpressed both c-erbB-2 and topoisomerase IIalpha. The combination of carboplatin with nontoxic concentrations of the topoisomerase II inhibitors etoposide or novobiocin enhanced the toxicity of carboplatin. In contrast, the tyrosine kinase inhibitor emodin exhibited no chemosensitizing effect in cells of this individual carcinoma. In conclusion, overexpression of c-erbB-2 was associated with poor prognosis and poor response to chemotherapy. The data suggest that topoisomerase IIlalpha, which correlates with c-erbB-2 expression, contributes to the resistance of c-erbB-2-overexpressing carcinomas.

Aromatic hydroxylation in nasal lavage fluid following ambient ozone exposure.

Ozone at ambient concentrations affects lung function and initiates an inflammatory response of the airways. However, the underlying mechanisms are poorly understood. In vitro studies have shown that ozone reacts with water to give reactive hydroxyl radicals capable of oxidizing a wide range of biomolecules. We conducted a study to determine if in vivo hydroxyl radical attack on human airways occurs under natural exposure to ozone. The relation of orthotyrosine to para-tyrosine as a measure of hydroxyl radical attack was analyzed in nasal lavage samples of 44 primary school children in an epidemiologic study. Repeated nasal lavages were performed between May and October 1991 both following "low" (daily half-hour maximum < 140 micrograms/m3, approximately 70 ppb) and "high" (daily half-hour maximum > 180 micrograms/m3, approximately 90 ppb) ozone exposure. Concomitantly, lung function tests were performed. On average, 11.6 (6-16) nasal lavages were performed for each of 24 study days (10 days following "low" ozone exposure and 14 days following "high" ozone exposure). Average ortho-tyrosine (median; 5-95% percentile) for each child was 0.037 mumol/L (0.016-0.064 mumol/L) and average para-tyrosine was 15.7 mumol/L (9.8-24.1 mumol/L). Ortho-tyrosine (as percentage of tyrosine) was significantly higher following days with "high" ozone exposure (0.18%) vs. days following "low" ozone exposure (0.02%; p = .0001). Ortho-tyrosine showed an inverse relationship with forced vital capacity (p = .01) but was not related to inflammation of the upper airways as assessed by cell counts of polymorphonuclear neutrophils. Hydroxyl radical attack subsequent to ambient ozone occurs in the upper airways of healthy children and is related to lung function decrements.

Risk of childhood leukemia and parental self-reported occupational exposure to chemicals, dusts, and fumes: results from pooled analyses of German population-based case-control studies.

A recent large-scale United States study reported an association between parental exposure to hydrocarbons at work and the risk of childhood leukemia. Parental occupational exposure to different chemicals and industrial dusts or fumes also was assessed in three German case-control studies that were conducted from 1992-1997. The design and methods of exposure assessment were similar for these studies; therefore, they were pooled for this analysis. In total, these three studies involved 1138 cases of acute lymphocytic leukemia (ALL) and 2962 controls. We found that maternal exposure to paints or lacquers during the preconception period (odds ratio, 1.6; 95% confidence interval, 1.1-2.4) and during the index pregnancy (odds ratio, 2.0; 95% confidence interval, 1.2-3.3) was related to an increased risk of childhood ALL. Whereas our findings for exposure to paints or lacquers confirmed observations from the United States study, we failed to confirm associations between risk of ALL and maternal exposure to solvents and parental exposure to plastic materials. Our studies provide some evidence that parental occupational exposure to certain substances may be associated with cancer risk in offspring; however, more specific studies are needed to identify such substances and the doses that may be hazardous.

Associations between childhood cancer and ionizing radiation: results of a population-based case-control study in Germany.

In order to investigate the associations between sources of exposure to ionizing radiation and childhood cancer in Germany, a matched case-control study including children under the age of 15 years was conducted. Cases were identified from the German Childhood Cancer Registry; controls came from population registration offices. Exposure was assessed via questionnaires and parental interviews. The study comprises 1184 leukemia cases, 234 non-Hodgkin's lymphomas, 940 solid tumors, and 2588 controls. Preconception parental occupational exposures were positively but not statistically significantly related to all of the cancer types in the study. Maternal occupational exposure during pregnancy was a risk factor for childhood lymphomas [odds ratio (OR) = 3.87, 95% confidence interval (CI): 1.54-9.75] but not for leukemia or solid tumors. ORs for parental occupational exposures were noticeably more pronounced in leukemia cases who were diagnosed in their first 18 months of life. A preconception paternal occupation in the nuclear industry under dosimetric surveillance yielded an OR of 1.80 (95% CI: 0.71-4.58). However, radiation doses of these fathers were often unknown or below the level of detection, and no dose exceeded 30 mSv. Prenatal X-ray examinations of the father (but not of the mother) were significantly related to childhood leukemia (OR = 1.33; 95% CI: 1.10-1.61). No effects were observed for postnatal X-ray examinations of the child. The results suggest that, in Germany at present, exposures to ionizing radiation do not play a noticeable role in the development of childhood cancers. The major strengths of the study are its size and the population basis. The validity of the data from parental questionnaires and the possibility of residual confounding by socioeconomic factors are potential drawbacks.

Childhood leukaemia and exposure to pesticides: results of a case-control study in northern Germany.

The association between childhood leukaemia and exposure to pesticides was examined in a population-based case-control study conducted in Lower Saxony, Northern Germany. Between July 1988 and June 1992, 219 newly diagnosed cases were identified, of whom 173 participated in the study. Two sex- and age-matched control groups were recruited: local controls from the same communities as the newly diagnosed cases of leukaemia and state controls from other randomly selected communities in Lower Saxony. An additional study group consisted of 175 cases of solid tumours. When the leukaemia cases were compared with the local controls, positive associations with parental occupational exposure, particularly agriculture-related exposure, were observed, which were statistically non-significant. A significant association was found for pesticide use in gardens (odds ratio = 2.52, 95% confidence interval: 1.0-6.1). No positive associations were seen when the leukaemia cases were compared to the state controls, but this finding could be explained by a higher proportion of state controls living in rural areas. In communities with a significantly elevated standardised incidence ratio of childhood leukaemia over the last decade (1984-1993), the prevalence of pesticide use in the garden was 21%, compared with the 10% in other communities. None of the examined risk factors were more common among cases of solid tumours. Our findings add some evidence to the hypothesis that pesticides are a risk factor for childhood leukaemia, and there are good reasons to consider abundant pesticide use in rural areas as a possible cause for clustering of childhood leukaemia.

Detection of strands in native aortic valves by transesophageal echocardiography.

Prevalence and echocardiographic characteristics of strands on the leaflets of native aortic valves were examined. According to our data, the strands we found in 39% of patients are most likely Lambl's excrescences.

Assessing the effect of time-varying covariates in cross-sectional studies.

In cross-sectional studies exposure and disease status of individuals are assessed at the same point in time, but sometimes information on prior exposure status is also gathered. Under such circumstances one approach to assessing the relationship between disease and exposure is using linear or logistic regression analysis, adjusting for exposure status at different points in time. It is shown that estimates for the effect of exposure at a certain point in time, adjusted for exposure at another point in time, are obtained from comparisons between groups with different patterns of exposure. Careful interpretation of the resulting estimates is necessary, taking into account a detailed consideration of possible exposure patterns. In addition, if changes in exposure are caused by the occurrence of the disease, then adjusting for multiple measurements of exposure can give misleading results. A regression analysis on dummy variables describing possible patterns of changes in exposure is proposed as an alternative approach. This approach facilitates interpretation of the resulting estimates. Furthermore, it can serve as a diagnostic tool to check for disease related changes in exposure. For this case transferring exposure change rates of healthy subjects to diseased subjects is suggested as an ad hoc method for assessing the hypothetical current relationship between exposure and disease.

Risk factors for neuroblastoma at different stages of disease. Results from a population-based case-control study in Germany.

Neuroblastoma is one of the childhood cancers included in two recent population-based case-control studies in West Germany. Altogether, 183 children under the age of 8 with neuroblastoma diagnosed in 1988-1994 and 1785 control children sampled from population registration files participated. Information on potential risk factors was obtained from the children's parents by a self-administered questionnaire and subsequent telephone interview. We observed positive associations with the use of oral contraceptives or other sex hormones during pregnancy (particularly with male offspring), a shorter gestational duration, lower birth weight, and maternal alcohol consumption during pregnancy. While the association with maternal use of oral contraceptives or sex hormones was strong for stages I/II (odds ratio 4.5, 95% confidence interval 1.2-16.5), the associations with shorter gestation duration (odds ratio 3.4, 95% confidence interval 1.7-6.7) as well as maternal alcohol consumption during pregnancy (>7 glasses/week odds ratio 5.2, 95% confidence interval 1.3-20.6) were observed only for the unfavourable advanced stages. It is notable that the associations in our study were either observed only for the advanced stages of disease or only for the less advanced stages, but not for both subgroups. This adds to evidence for the hypothesis that neuroblastoma consists of at least two distinct disease entities, which differ in clinical stage at the time of diagnosis.

Influence of maternal smoking on variability of peak expiratory flow rate in school children.

Diurnal variability of peak expiratory flow rates (PEFRs) was assessed in 1,237 children. The PEFR was measured twice daily over a 1-week period. As an index of variability, the log of a week's mean of daily amplitude was calculated. Linear regression analyses revealed a significant positive association between maternal smoking and the variability of PEFR for nonasthmatic children. For these children, exposure to maternal smoking was associated with a 13.7 percent increase (confidence interval [CI], 3.8 to 24.7 percent) in PEFR variability. For asthmatic children an effect was found for nonatopic (54.7 percent increase; CI, 5.5 to 226.8 percent) but not for atopic children (-8.5 percent change; CI, -41.2 to 42.3 percent). In the latter group, there was evidence that mothers changed their smoking habits subsequent to the development of disease in their children. We conclude that exposure to maternal smoking can increase the variability of PEFR and thus might contribute to the development of asthma.

Association of childhood cancer with factors related to pregnancy and birth.

BACKGROUND: It has been hypothesized that risk factors of childhood cancers may already operate during the prenatal and neonatal period. Results of previous epidemiological studies have been inconsistent. METHODS: During 1992-1997 a large case-control study on childhood cancers and a variety of potential risk factors was conducted in Germany. Cases were ascertained by the German Childhood Cancer Registry. Each case was matched to a population-based control of the same age and gender, sampled from the district where the case lived at the date of diagnosis. For the analyses, 2358 cases and 2588 controls were available. RESULTS: Risk of childhood acute leukaemia increased with maternal age < or =20 years at time of delivery (odds ratio [OR] = 1.9, 95% CI: 1.1-3.2), lower (<2500 g: OR = 1.7, 95% CI: 1.1-2.8) and higher birthweight (>4000 g: OR = 1.4, 95% CI: 1.0-1.8, P < 0.05), and hormonal treatment because of infertility (OR = 1.6, 95% CI: 1.0-2.5, P < 0.05). No associations were seen for parental smoking habits, maternal alcohol consumption during pregnancy and fetal losses. Parity was associated only with subgroups of acute leukaemias. Regarding non-Hodgkin's lymphoma we observed an elevated OR for lower birthweight and heavy maternal smoking during pregnancy (>20 cigarettes/day) and a decreased OR for children with one or two siblings. Only a few significant findings were seen for the different groups of solid tumours. CONCLUSIONS: Overall, only weak associations were identified and the evaluated risk factors operating during the neonatal and prenatal period account at most for only a small proportion of childhood cancers.

Quantitative assessment of aortic stenosis by three-dimensional echocardiography.

The purpose of this study was to assess the feasibility of three-dimensional echocardiography in aortic stenosis. Planimetric determination of valve area and dynamic volume-rendered display were performed. Three-dimensional echocardiography permits display of any desired plane of the cardiac structure. Thus in the case of aortic stenosis, the plane used for planimetric evaluation can be positioned exactly through the valve orifice. Dynamic volume-rendered display may provide a spatial demonstration of the stenotic valve. In 48 patients aortic valve area was measured by planimetry. The three-dimensional data set was acquired by a workstation in the course of a multiplane transesophageal examination. Results were compared with those obtained by multiplane transesophageal two-dimensional planimetric technique and invasive measurement. A dynamic three-dimensional reconstruction was displayed. Planimetric determination of valve area was possible in 42 (88%) of 48 cases. Statistical analysis of the data acquired showed a good agreement between three-dimensional echocardiography and transesophageal echocardiography (mean difference +0.018 cm2; SD = 0.086) and between three-dimensional echocardiography and the invasive technique (mean difference +0.012 cm2; SD = 0.12). Dynamic volume-rendered display was possible in 42 of 48 cases. Three-dimensional echocardiography permits accurate and reliable determination of aortic valve area. Preoperative spatial recognition of the stenotic valve is possible by dynamic volume-rendered display.

Relationship between atopy and frequent bronchial response to exercise in school children.

The natural history of a bronchial response to exercise (BRE) was studied in a cohort of primary-school children, who were followed over a 2-year period. In 1,094 children, three free-running tests were performed in 1-year intervals. Children who responded in one of the tests were designated as "infrequent" responders (20.5%), whereas those responding at two or all three occasions were designated as "frequent" responders (7.4%). A frequent positive BRE was closely associated with atopy (defined as skin test positivity to 1 of 7 common aeroallergens) and respiratory symptom status. Compared to atopics without respiratory symptoms, an increased risk for a frequent positive BRE was seen for atopic children who were symptomatic during the whole study period [odds ratio (OR) 25.4; confidence interval (CI) 6.9-94.0], who had gained symptoms (OR, 11.0; CI, 2.8-43.2) or who had symptoms at the beginning of the study but had lost them during follow-up (OR, 4.6; CI, 1.0-20.6). A sensitization to dust mites (OR, 8.0; CI, 4.3-15.0) but not to animal dander (OR, 2.3; CI, 1.0-5.2) or pollen (OR, 0.7; CI, 0.3-1.6) was significantly related to a frequent positive BRE. Our findings support the notion that while "children grow out of asthma," they might maintain their bronchial hyperresponsiveness. Regarding specific sensitization, mite allergy seems to play the predominant role.

Relationship between exposure to dust mite allergen and bronchial response to exercise in schoolchildren sensitized to dust mites.

We assessed the relationship between the exposure to dust mite allergens and a bronchial response to exercise in 8-year-old schoolchildren. Dust was collected from the mattresses of 1,291 children and the concentration of mite allergens was estimated by a commercially available ELISA test using monoclonal antibodies (ALK, Copenhagen) against the major allergens of Dermatophagoides pteronyssinus (Der pt) and Dermatophagoides farinae (Der f). A positive bronchial response to exercise (decrease of peak expiratory flow > or = 15% after exercise) occurred in 21 (22.6%) of 101 children sensitized to mite allergens (wheal size > or = 4 mm) and in 51 (4.8%) of 1,070 nonsensitized children. In the highest exposure groups (> 10 micrograms allergen/g dust), 15% of children sensitized to Der f and 20% of children sensitized to Der pt were responsive to exercise. Corresponding figures for the lowest exposure groups (< 0.4 micrograms allergen/g dust) were 11 and 28%, respectively. This negative finding may indicate that measurement of allergen concentration in mattresses does not reflect true exposure or alternatively that at the age of 8 years high exposure to dust mite allergens does not affect bronchial response to exercise in sensitized children.

Increase in DNA single-strand break rejoining by continuous exposure of human mononuclear blood cells to radioiodine ((131)I) in vitro.

Radioiodine ((131)I) induced a dose- and time-dependent increase in DNA single-strand breaks (DNA-ssb) in human (G0) mononuclear blood cells (MNC) in vitro. Incubation of MNC with 22MBq (131)I/ml at 4 degrees C caused a linear, time-dependent induction of DNA-ssb (increase in elution rate: 24.7 x 10(-3) h(-1) per 100 min incubation with (131)I). However, if MNC were incubated at 37 degrees C a decrease in the slope of the time effect curve was observed after about 300 min incubation with 22 or 30 MBq (131)I/ml. The goodness of fit of different regression models was assessed by Akaike's Information Criterion (AIC). The best fit was obtained for a non-linear model (y=a+bx+cx(0.5); AIC=53.5; where x is incubation time and y is elution rate), whereas other models including the linear regression model y=a+bx; AIC=38.6) were worse. As the total induction of DNA-ssb at 4 degrees C was constant with time, the decrease in the slope of the time effect curve (DNA-ssb versus time) at 37 degrees C can be interpreted as an increase in rejoining of DNA-ssb. Inhibition of both RNA and protein synthesis clearly increased the extent of DNA-ssb observable after incubation with (131)I. Thus, during continuous exposure of MNC to (131)I, proteins were synthesized which rejoined DNA-ssb. However, incubation of MNC with (131)I (44 MBq/ml) at 37 degrees C under conditions expected to lead to inhibition of RNA and/or protein synthesis still resulted in a decrease of the slope of the time effect curve, indicating a stimulation of DNA-ssb rejoining. Thus, we favour the hypothesis that the increase in the activity of DNA-ssb rejoining, besides de novo synthesis of repair enzymes, is also caused by a post-translational stimulation of DNA-repair enzymes and that this stimulation possibly is mediated by DNA-fragments.

Meta-analyses of studies on the association between electromagnetic fields and childhood cancer.

During the last 15 years several studies have investigated a possible relationship between exposure to electromagnetic fields (EMF) and childhood cancer. There is considerable variation between these studies with respect to methods of exposure assessment and reported results. Methods of exposure assessment range from simple visual criteria to costly and time consuming measurements or estimations of electric flux density. Additional individual refinements further hinder the comparability of results. We carried out several meta-analyses of data published so far taking into account the heterogeneity between studies as far as possible. Our particular interest was to investigate a potential dose-response-like relationship by comparing analyses for different cut-off points of exposure. Our meta-analyses suggest a marginal association between all cancer diagnoses combined and EMF exposure assessed by the two-level wire code (odds ratio, OR = 1.37, 95% confidence interval, CI: 0.94-2.00). Based on this criterion a significant effect was found for bases of leukemia (OR = 1.66, CI: 1.11-2.49) but not for central nervous system (CNS) tumors (OR = 1.5, CI: 0.69-3.26) or lymphomas (OR = 1.32, CI: 0.52-3.37). A significant increase in overall cancer risk with increasing stages of the four-level wire code (P = 0.003) could not be confirmed when data of the initial study performed by Wertheimer and Leeper were excluded (P = 0.17). When the exposure criterion was based on distance to the transmission line, estimated ORs for all cancers combined and for leukemias increased with distances decreasing from 100 to 25 m. Those analyses incorporating data on measured or calculated EMFs demonstrated also an increase of overall cancer risk with higher cut-off points. However, regarding individual diagnoses, this finding was reflected only in the group of brain tumors. One possible explanation for the high degree of heterogeneity between studies--especially with respect to methods of exposure assessment and choice of the respective cutpoint relevant for an increase in cancer risk--could be that published cut-off points were not always chosen in advance, but were selected because in exploratory analyses the most striking results were obtained with these specific cut-off values. Should this speculation be true at least partially, any meta-analysis will yield a false-positive finding. Further results of comparable studies with strictly a priori planned analyses are necessary to properly investigate a possible link between EMF and childhood cancer.

[Asthma screening with a standardized running test]. / Asthmascreening mittels eines standardisierten Lauftests.

Exercise induced asthma is a common feature of asthma in childhood. We performed a standardized free running test in 1461 primary schoolchildren in first grade (mean age: 7.3 years). A decrease of peak expiratory flow of at least 15% after a 6 minutes exercise period was considered a positive response. For a lifetime prevalence of a physician's diagnosis of asthma the sensitivity of the test was 35.4% and the specificity 94.3%. A positive response was associated with atopy (defined as a positive skin prick test) and with the clinical severity of asthma.

Influence of skin prick test criteria on estimation of prevalence and incidence of allergic sensitization in children.

In a prospective cohort study on atopy in childhood, three skin prick tests (SPT) were performed in 1135 primary schoolchildren over a 2-year period. We studied the development of average sizes of allergen wheals in reactive children and of average sizes of histamine wheals in all children, and we investigated the influence of choice of SPT criterion on the prevalence and incidence of sensitization. A year-to-year increase of average allergen wheal sizes as well as of average histamine wheal sizes was observed. These increases seemed to be related to the natural growth of the children. Furthermore, an observer bias effect of the person who did the pricking on average wheal sizes was found. There were considerable differences in estimations of prevalences and incidences depending on the definition of SPT criterion. Estimations using a criterion based solely on the allergen wheal size were affected by variation of allergen wheal sizes caused by growth and observer effects. The ratio criterion was not influenced by observer effects, nor did it seem to be affected by aging effects. In conclusion, our data suggest that the ratio criterion, which relates the size of the allergen wheal to the size of the histamine wheal, is the most appropriate SPT criterion because it is not affected by growth of allergen wheals in childhood and it appears to compensate for possible observer bias.

Variability of peak expiratory flow rate in children: short and long term reproducibility.

BACKGROUND: Variability of peak expiratory flow (PEF) has been proposed as a surrogate for bronchial hyperresponsiveness. The normal range of variability of PEF for children has been reported and the test has been used to screen for asthma in population based studies. However, there is little information on the reproducibility of the method in epidemiological settings. METHODS: In a cohort study of primary school children the variability in PEF was recorded in two consecutive years for one week (first survey) and two weeks (second survey) using mini Wright peak flow meters. PEF was recorded twice daily (morning and evening) and average amplitude as a percentage of mean was calculated as a standard measure of PEF variability for each single week of PEF measurement. Children with PEF variability exceeding the 90% percentile of the distribution for the specific time period were regarded as having increased variability of PEF. RESULTS: Of 66 children with increased PEF variability in the first year, 13 (19.7%) had an abnormal test in the first week of the second year. Of 543 children with normal PEF variability in the first year, 44 (8.1%) had an abnormal test in the second study year (odds ratio 2.8, confidence interval (CI) 1.4 to 5.4). Of 646 children in the second survey 61 (9.4%) were abnormal during the first week and 68 (10.5%) had an increased PEF variability during the second week, but only 24 (3.7%) children had an increased PEF variability in both weeks. The sensitivity (specificity) for doctor-diagnosed asthma (12 month period prevalence) was 36.4% (91.0%) in the first week of the second survey. When measurements of both weeks of the second survey were used to calculate PEF variability there was little improvement in the sensitivity (38.1%) and specificity (91.5%), mainly because of decreased compliance in the second measurement week. CONCLUSIONS: In young children assessment of PEF variability in order to screen for asthma is of limited value because of the low reproducibility of the method.

[Variability of peak expiratory flow in an unselected sample of school children]. / Variabilität des peak expiratory flow bei einer unselektierten Stichprobe von Schulkindern.

In the framework of an epidemiological study, the information by peak flow variability (PEFV) was compared to the history of asthma in a non-selected population of primary-school children (n = 1812). PEFV as assessed by twice daily recordings of PEF for a one week period (n = 1237) was calculated as average of daily amplitudes (AVAM: average amplitude mean) in the case of at least complete data for five days (n = 991). Elevated PEFV defined as AVAM > 12%, was cross-tabulated with the asthma history (self-administered questionnaire). The median (90%-confidence-interval) of AVAM is 6.3% (2.2-15.9%). In 11.2% (n = 111) of the population, AVAM > 12% occurred). The sensitivity of AVAM > 12% with regard to "doctor's diagnosed asthma" (n = 35) is 37%. Under exclusion of children with recurrent wheezy bronchitis a specificity for AVAM > 12% of 90% is found. Our data on primary-school children suggests that PEFV is a specific but only slightly sensitive measurement with regard to previously diagnosed bronchial asthma.