[Tuberculosis and the modern ideal of living]. / Die Tuberkulose und das moderne Wohnideal.

Sunlight and fresh air belong to the everyday life's myths. It has influenced our times and personal lives as much as industrialization. Today we are hardly aware of the multiple and omnipresent consequences of this myth. The modern movement with all its facets including modern architecture is barely conceivable without it. What is the link between this triad with all its effects and tuberculosis, the oldest and most important infectious disease which still claims more than 3 million deaths per year worldwide? Tuberculosis was treated by sunlight and fresh air at all times. This treatment was at its zenith during the second half of the 19th century after Hermann Brehmer had initiated this treatment within sanatoria in 1862. The sanatorium vogue lasted until the middle of the last century when streptomycin was isolated by Selman Waksman 1943. A new type of hospital was necessary for treating the patients with sunlight and fresh air: the sanatorium with its wide windows, sheltered open balconies, terraces and "Liegehallen". In return, this airy type of building was the forrunner of a new architectural style, called "Neues Bauen". The latter has profoundly influenced our modern ideal of living since Le Corbusiier built the Villa Savoye, one of the architectural highlights of the 20th century.

Effect of physical and chemical methods of homogenization on inflammatory mediators in sputum of asthma patients.

BACKGROUND: Dithiothreitol (DTT), which is used for sputum homogenization, may split S-S bonds of the bronchial mucins as well as other proteins and, thus, may have a detrimental effect on inflammatory mediators that are present in sputum. OBJECTIVE: To evaluate the effects of physical sputum homogenization, using ultrasonic and chemical (ie, DTT) means, on the concentrations of eosinophil cationic protein (ECP), eosinophil protein X (EPX), eosinophil peroxidase (EPO), and myeloperoxidase (MPO) in the sputum of patients with asthma. METHODS: The collection of sputum samples from nine patients with asthma was induced by their inhaling a sterile 3% saline solution for 10 min from an ultrasonic nebulizer. One half of the sputum sample was homogenized by ultrasound, and the other half was liquefied by DTT. The supernatant of the ultrasonically homogenized specimen was divided into the following three portions: (1) immediately frozen; (2) stored for 15 min at 37 degrees C; and (3) additionally treated with DTT. The supernatant of the sputum sample that was liquefied by DTT was divided into the following two portions: (1) immediately frozen; and (2) additionally subjected to ultrasound. The concentrations of ECP, EPO, EPX, and MPO in the sputum samples were measured using immunoassays. RESULTS: Statistically significant differences were found between the ultrasonically homogenized specimens that had been either processed immediately or stored at 37 degrees C and those treated by DTT, but only for concentrations of EPO and MPO (p < 0.005). No effect of temperature on the mediators in the ultrasonically homogenized specimens could be detected. Ultrasonic homogenization had no influence on the mediators in the samples liquefied by DTT. However, the addition of DTT to the cell-free supernatant of the ultrasonically homogenized sputum samples caused a significant fall in measured EPO and MPO concentrations. CONCLUSIONS: The sputum processing by DTT caused a statistically significant fall in EPO and MPO concentrations but did not significantly influence the measured concentrations of ECP and EPX.

The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review.

The role of N-acetylcysteine (NAC) in the treatment of chronic bronchitis is unclear. Since a number of studies have been published on this topic, a systematic review of published studies seems justified. A systematic search (Medline, Embase, Cochrane Library, bibliographies, no language restriction) for published randomized trials comparing oral NAC with placebo in patients with chronic bronchitis was performed. Dichotomous data on prevention of exacerbation, improvement of symptoms and adverse effects were extracted from original reports. The relative benefit and number-needed-to-treat were calculated for both individual trials and combined data. Thirty-nine trials were retrieved; eleven (2,011 analysed patients), published 1976-1994, were regarded as relevant and valid according to preset criteria. In nine studies, 351 of 723 (48.5%) patients receiving NAC had no exacerbation compared with 229 of 733 (31.2%) patients receiving placebo (relative benefit 1.56 (95% confidence interval (CI) 1.37-1.77), number-needed-to-treat 5.8 (95% CI 4.5-8.1). There was no evidence of any effect of study period (12-24 weeks) or cumulative dose of NAC on efficacy. In five trials, 286 of 466 (61.4%) patients receiving NAC reported improvement of their symptoms compared with 160 of 462 (34.6%) patients receiving placebo (relative benefit 1.78 (95% CI 1.54-2.05), number-needed-to-treat 3.7 (95% CI 3.0-4.9)). With NAC, 68 of 666 (10.2%) patients reported gastrointestinal adverse effects compared with 73 of 671 (10.9%) taking placebo. With NAC, 79 of 1,207 (6.5%) patients withdrew from the study due to adverse effects, compared with 87 of 1,234 (7.1%) receiving placebo. In conclusion, with treatment periods of approximately 12-24 weeks, oral N-acetylcysteine reduces the risk of exacerbations and improves symptoms in patients with chronic bronchitis compared with placebo, without increasing the risk of adverse effects. Whether this benefit is sufficient to justify the routine and long-term use of N-acetylcysteine in all patients with chronic bronchitis should be addressed in further studies and cost-effectiveness analyses.

Occupational exposure to inhalative irritants and methacholine responsiveness.

OBJECTIVES: Occupational exposures to inhalative irritants have been associated with an increased reporting of respiratory symptoms in previous studies. Methacholine responsiveness represents a continuous measure of airway responsiveness. As such, it may be less subject to recall bias and more sensitive to detecting effects of occupational exposure on airways. Such effects may be stronger among atopic persons. The objective of the study was to examine the relationship between self-reports of occupational exposure to dusts, gases, vapors, aerosols, and fumes and methacholine responsiveness. METHODS: A sample was studied of never smokers (N=3044) chosen randomly from 8 areas in Switzerland. Atopy was defined as any positive skin test to 8 inhalative allergens. Nonspecific bronchial reactivity was tested using methacholine chloride and quantified by calculating the slope of the dose-response. RESULTS: The methacholine slopes were 19% [95% confidence interval (95% CI) 6-32] higher for never smokers with exposure to dusts, fumes, vapors, gases, or aerosols than for the unexposed group. When only atopic never smokers were examined. the increase was larger (37%, 95% CI 7-75), and for persons with >2 positive skin prick tests the effect was still higher (42%, 95% CI -1.5-104). Exposure to vapors and aerosols was strongly associated with increased methacholine slopes among the atopic subjects. CONCLUSIONS: Occupational exposure, particularly to dusts and fumes, was associated with increased bronchial reactivity in never smokers in this study. The magnitude of the effect was larger among atopic subjects.

Effect of one year treatment with inhaled fluticasone propionate or beclomethasone dipropionate on bone density and bone metabolism: a randomised parallel group study in adult asthmatic subjects.

BACKGROUND: There is some concern that prolonged treatment with high doses of inhaled corticosteroids may have a detrimental effect on bone mass. The aim of this one year study was to investigate the effects of low and high doses of fluticasone propionate (FP) (400 microg/day and 750 microg/day) and beclomethasone dipropionate (BDP) (800 microg/day and 1500 microg/day) on bone mass and metabolism. METHODS: This was a multicentre, double blind, parallel group study involving 69 mild to moderate asthmatic subjects who were randomised to treatment as follows: 22 to FP400, 21 to BDP800, 13 to FP750, and 13 to BDP1500. Their mean age was 39 years, 67% were men, and all the women were premenopausal. RESULTS: The results of peripheral quantitative computed tomographic (pQCT) measurements (primary variable) showed that, compared with baseline values, there was no loss of trabecular or integral (cortical and trabecular) bone in the distal radius or tibia in any of the patients over the 12 month study period. No consistent pattern emerged from the analysis of changes from baseline in markers of bone formation and resorption after six and 12 months of treatment. CONCLUSION: The results of this study provide reassuring prospective one year data showing that inhaled corticosteroids, in the range of doses used, had no adverse effects on bone mass and metabolism in this group of asthmatic patients.

Does eosinophil cationic protein in sputum and blood reflect bronchial inflammation and obstruction in allergic asthmatics?

In the assessment of asthma severity and monitoring of asthma drug therapy, eosinophils and eosinophil cationic protein (ECP) have been identified in blood but rarely in sputum. The aim of our study was to determine if ECP concentrations in blood and sputum reflect bronchial inflammation and obstruction in allergic asthmatics and if inhaled steroids influence this relationship. We carried out a descriptive, cross-sectional study of 42 allergic asthmatic outpatients from a respiratory medicine department, of whom 22 were on beta 2-adrenergic agonists only and 20 were treated with low doses of inhaled steroids. Spirometry and methacholine challenge were performed and eosinophils and ECP values in induced sputum and blood were determined. The age and FEV1 were similar in both groups. It was found that in patients receiving inhaled steroids, the methacholine PD20 was higher than in patients on beta 2-adrenergic agonists only. However, there were no significant differences in serum and sputum ECP between the groups (median 14.5 micrograms/l vs. 17.2 micrograms/l and 235 micrograms/l vs. 301 micrograms/l, respectively). In patients not receiving steroids, sputum ECP correlated positively with eosinophils in sputum (r = 0.61, p < 0.01) and inversely with FEV1 (r = -0.43, p < 0.05). Serum ECP correlated with blood eosinophils and methacholine PD20. In patients treated with inhaled steroids most correlations were no longer significant. We concluded that ECP in sputum, rather than in blood, seems to reflect both eosinophilic inflammation and bronchial obstruction in asthmatics not receiving inhaled steroids. Asthmatics on low doses of inhaled steroids had increased ECP levels in sputum and serum, indicating persistent eosinophilic inflammation of the airways.

Bronchiolitis obliterans organizing pneumonia associated with polymyalgia rheumatica.

The association of bronchiolitis obliterans organizing pneumonia (BOOP) with polymyalgia rheumatica is rare, and only one case has previously been described. This study reports on the case of an 80 yr-old male who presented with malaise, nonproductive cough and exertional dyspnoea for several weeks, along with a history of bilateral shoulder and pelvic girdle pain of several months' duration. The chest radiograph revealed a pneumonic infiltrate in the right lower lobe, which was unresponsive to antibiotics. Bronchoscopy, bronchoalveolar lavage and a transbronchial lung biopsy established the diagnosis of BOOP. The patient improved consistently on steroids. As in other connective diseases, organizing pneumonia may be one of the early manifestations of polymyalgia rheumatica.

Long-term ambient air pollution and respiratory symptoms in adults (SAPALDIA study). The SAPALDIA Team.

The association between long-term exposure to ambient air pollution and respiratory symptoms was investigated in a cross-sectional study in random population samples of adults (aged 18 to 60 yr, n = 9,651) at eight study sites in Switzerland. Information on respiratory symptoms was obtained with an extended version of the European Community Respiratory Health Survey questionnaire. The impact of annual mean concentrations of air pollutants was analyzed separately for never-, former, and current smokers. After controlling for age, body mass index, gender, parental asthma, parental atopy, low education, and foreign citizenship, we found positive associations between annual mean concentrations of NO2, total suspended particulates, and particulates of less than 10 micrometers in aerodynamic diameter (PM10) and reported prevalences of chronic phlegm production, chronic cough or phlegm production, breathlessness at rest during the day, breathlessness during the day or at night, and dyspnea on exertion. We found no associations with wheezing without cold, current asthma, chest tightness, or chronic cough. Among never-smokers, the odds ratio (95% confidence interval) for a 10 micrograms/ m3 increase in the annual mean concentration of PM10 was 1. 35 (1.11 to 1.65) for chronic phlegm production, 1.27 (1.08 to 1.50) for chronic cough or phlegm production, 1.48 (1.23 to 1.78) for breathlessness during the day, 1.33 (1.14 to 1.55) for breathlessness during the day or at night, and 1.32 (1.18 to 1.46) for dyspnea on exertion. No associations were found with annual mean concentrations of O3. Similar associations were also found for former and current smokers, except for chronic phlegm production. The observed associations remained stable when further control was applied for environmental tobacco smoke exposure, past and current occupational exposures, atopy, and early childhood respiratory infections when restricting the analysis to long-term residents and to non- alpine areas, and when excluding subjects with physician-diagnosed asthma. The high correlation between the pollutants makes it difficult to sort out the effect of one single pollutant. This study provides further evidence that long-term exposure to air pollution of rather low levels is associated with higher prevalences of respiratory symptoms in adults.

[Acupuncture and bronchial asthma]. / Akupunktur und Bronchialasthma.

The 66 randomized patients with mild bronchial asthma who took part in this study were divided into three nearly equal groups. Group one was treated with true acupuncture during the first and the fourth month (up to week 16). Group two was treated similarly but needled at non-acupuncture points. The third group served as a control. All patients were allowed to maintain their normal asthma medication with the recommendation to keep the regimen unchanged until week 20, i. e. 4 weeks after termination of the specific treatment. The changes in peak flow variability up to week 16 served as main outcome criterion. Additional parameters included several spirometric analyses as well as various markers in blood and sputum that are specific for the allergic inflammatory reaction of the upper respiratory tract. The values measured showed considerable individual variability. This impeded the demonstration of efficacy. In conclusion it can be stated that there was a consistent, positive yet unspecified effect of the needling in both treated groups which can be interpreted as a trend in affecting the asthmatic condition. This effect could have been more pronounced or even clinically relevant for certain individuals had one considered a separate analysis of the data of each patient.

Use of transition probabilities to estimate the effect of smoking on the duration of episodes of respiratory symptoms in diary data: the Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA).

Incompletely documented symptom episodes pose methodological problems in the analysis of diary data. The aim of this study was to develop a method of estimating the average durations of symptomatic and nonsymptomatic episodes, respectively, coping with the problem of bias due to undocumented days and censored episodes that is found in most diary studies. The authors derived their outcome variables from a Markov model using transition probabilities. To evaluate this method, the authors assessed the impact of active smoking on the duration of episodes of bronchitis symptoms and the corresponding nonsymptomatic periods, respectively, using diary data (1992-1993) obtained from 801 participants in the Swiss Study on Air Pollution and Lung Diseases in Adults. Covariate-adjusted distribution curves for the mean durations of individual episodes were estimated by Cox regression. Median values for light smokers (<10 cigarettes/day) were 60.0 symptom-free days (95% confidence interval (CI) 42.0-78.5) and 4.0 symptomatic days (95% CI 3.0-6.0), respectively, compared with medians of only 21.0 days (95% CI 16.2-29.8) for periods without bronchitis symptoms and 6.0 days (95% CI 4.9-9.0) for episodes of bronchitis symptoms in heavy smokers (> or =30 cigarettes/day). The authors suggest that the Markov method is a feasible approach to the assessment of long term effects of smoking and environmental risk factors on the average duration of symptomatic and nonsymptomatic respiratory episodes.

Associations between lung function and estimated average exposure to NO2 in eight areas of Switzerland. The SAPALDIA Team. Swiss Study of Air Pollution and Lung Diseases in Adults.

In this paper, we present results from the SAPALDIA study (Swiss Study on Air Pollution and Lung Diseases in Adults) regarding associations between lung function [forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1)], as assessed during the cross-sectional study in 1991, and average levels of NO2 exposure within the eight study communities. We distinguished average home outdoor exposure and average personal exposure to NO2 and obtained exposure estimates by computing regional averages of passive sampler measurements performed by a random subsample of SAPALDIA participants in 1993. Previous analyses had revealed associations between average lung function and average air pollution levels between communities. The present results show that such associations may also be seen within communities: a 10-micrograms per m3 increase in average home outdoor and personal exposure to NO2 between zones of residence of the same community was associated with a change in average FVC by -0.59% [95% confidence limits (CL) = 0.01, -1.19] and -0.74% (95% CL = -0.07, -1.41), respectively. These values, however, are smaller than the ones found for the corresponding associations between study communities: -1.67% (95% CL = -1.01, -2.33) and -2.93% (95% CL = -2.11, -3.75), respectively. The different magnitudes of these two types of associations might be explained by differences in spatial variation between various components of air pollution.

Eosinophil cationic protein in sputum is dependent on temperature and time.

Eosinophil cationic protein (ECP) in sputum may be used to estimate the severity of bronchial inflammation and obstruction in asthmatics as well as to monitor asthma drug therapy. For this purpose, standardized processing of sputum is important. The aim of our study was to determine whether time and temperature influence the ECP concentration in the sputum of asthmatics. The samples of induced sputum obtained from 12 patients with stable asthma were homogenized using ultrasonification, and centrifuged. Supernatants were evenly divided and stored for 1, 6, 24 or 72 h at either 4 or 25 degrees C, then frozen at -80 degrees C. The ECP concentrations were determined using fluoroimmunoassay and compared with the immediately frozen samples. After storing at 4 degrees C, the ECP levels at the four time points were 101.2, 96.0, 98.2 and 90.6% of the initial concentration, respectively. When sputum specimens were stored at 25 degrees C, ECP levels decreased to 96.1, 94.4, 90.7 and 87.7%, respectively. The influence of time on ECP concentrations in sputa was statistically significant (p=0.02). A significant temperature effect was found when comparing the specimens stored at 4 degrees C with those at 25 degrees C (p=0.03). Looking at individual time points, a significant decrease in ECP concentration was only seen at 25 degrees C after 24 and 72 h. We conclude that eosinophilic cationic protein in the sputum of asthmatics decreases in a time- and temperature-dependent process. If sputa cannot be processed after obtaining the specimens, they should be stored in a refrigerator at 4 degrees C, until eosinophilic cationic protein is measured.

[Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA)]. / Etude suisse sur la pollution de l'air et les maladies respiratoires chez l'adulte (SAPALDIA). Swiss Study on Air Pollution and Lung Diseases in Adults.

Long-term health effects of moderate ambient air pollution are rarely investigated. In Switzerland, no large-scale study has addressed this issue so far. Important results of the Swiss Study on Air Pollution and Lung Disease in Adults (SAPALDIA) are presented. During the period 1991-1993, SAPALDIA investigated a random population sample (18-60 years) in eight Swiss areas with different environmental characteristics (Aarau, Basel, Davos, Geneva, Lugano, Montana, Payerne, Wald). In total, 9651 adults (60%) participated in the cross-sectional investigation (part 1, 1991), consisting of the following standardized procedures: questionnaire (interview), forced expiratory lung function test, bronchial challenge with methacholine, atopy assessment (Phadiatop, unspecific total IgE), allergy skin tests, and endexpiratory CO-measurements. Subjects with a history of respiratory symptoms, increased bronchial reactivity, reduced lung function (FEV1/FVC < 80% predicted) and 150 healthy never-smokers were included in the subsequent diary study (part 2; n = 3281, 1992/93). Peak flow (morning and evening), symptoms, medication, personal activity and visits to the doctor were monitored. Across regions, annual mean values ranged from 9 to 52 mg/m3 (NO2) and 10 to 33 mg/m3 (PM10) respectively. Air pollution had effects on prevalence of dyspnea (+41% per 10 mg/m3 increment of the annual mean PM10, 95% CI 20-65%), on symptoms of chronic bronchitis (+31%, 10-55%), on FVC (-3.1%; -3.7 to -2.6%), and FEV1 (-1.1%; -1.7% to -0.5%), on the incidence of respiratory symptoms and the length of symptomfree intervals (11% change per 10 mg/m3 PM10), but not on the prevalence of asthma. Environmental tobacco smoke (ETS) showed impact on wheezing (OR 1.94; 1.39-2.70), asthma (1.39; 1.04-1.86), bronchitis (1.60; 1.24-2.08) and chronic bronchitis (1.50; 1.11-2.02). Health effects of moderate air pollution were confirmed in Switzerland. Although for the individual the relative risks are small, the public health impact may be considerable. An ongoing follow-up will investigate the mortality profile of the SAPALDIA cohort.

Lung function and long term exposure to air pollutants in Switzerland. Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) Team.

The effect of long-term exposure to air pollutants was studied in a cross-sectional population-based sample of adults (aged 18 to 60 yr; n = 9,651) residing in eight different areas in Switzerland. Standardized medical examination included questionnaire data, lung function tests, skin-prick testing, and end-expiratory CO concentration. The impact of annual means of air pollutants on FVC and FEV1 was tested (controlling for age and age squared, sex, height, weight, educational level, nationality, and workplace exposure). Analyses were done separately for healthy never-smokers, ex-smokers (controlling for pack-yr), for current smokers (controlling for cigarettes per day and pack-yr smoked), and for the whole population. Significant and consistent effects on FVC and FEV1 were found for NO2, SO2, and particulate matter < 10 microm (PM10) in all subgroups and in the total population, with PM10 showing the most consistent effect of a 3.4% change in FVC per 10 microg/m3. Results for ozone were less consistent. Atopy did not influence this relationship. The limited number of study areas and high intercorrelation between the pollutants make it difficult to assess the effect of one single pollutant. Our conclusion is that air pollution from fossil fuel combustion, which is the main source of air pollution with SO2, NO2, and PM10 in Switzerland, is associated with decrements in lung function parameters in this study.

SAPALDIA: methods and participation in the cross-sectional part of the Swiss Study on Air Pollution and Lung Diseases in Adults.

SAPALDIA--the Swiss Study on Air Pollution and Lung Diseases in Adults--focuses on the long term health effects of low to moderate levels of air pollutants as typically seen in different parts of Switzerland. The aim of the SAPALDIA cross-sectional study carried out in 1991 was to determine the prevalence of bronchial asthma, chronic bronchitis and allergic conditions in the adult population of Switzerland and to identify and to determine the respective importance of potentially influencing factors. These could be both personal (smoking habits, allergy status, family history, occupation) and environmental (outdoor and indoor pollution, aeroallergens, climate). A further aim of the cross-sectional study consisted in the identification of individuals susceptible to present symptoms during a two year observation period and to be included in the SAPALDIA follow-up study. This technical report represents the methodological documentation for the cross-sectional study of SAPALDIA. The instruments and the methods of standardisation are presented and discussed. The medical examination consisted of a computerised interview using a standardised questionnaire, the taking of a blood sample for serological tests, allergy skin testing, the measurement of end expiratory CO and body height, and pulmonary function testing followed by methacholine challenge testing or bronchodilatation testing. The pattern of participation and the 9651 participants of the study, representing 59.3% of the sample, are described. Based on information on non-participants gained by telephone interviews and mailed short questionnaires, possible selection biases are quantified and discussed.

IgE levels, atopy markers and hay fever in relation to age, sex and smoking status in a normal adult Swiss population. SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) Team.

Within the framework of the SAPALDIA survey (Swiss study on Air Pollution and Lung Diseases in Adults), we studied the influence of sex, age and smoking habits on total serum IgE and allergen-specific IgE antibody concentrations (assessed by means of the Phadiatop test) and on the prevalence of hay fever. A total of 8,344 subjects aged 18-60 years, comprising 2,776 current smokers, 1,888 former smokers and 3,680 nonsmokers, were included in the study. Smokers had both a statistically significant (p<0.001) higher mean serum IgE concentration (geometric mean 39.7 kU/l), and a higher percentage (27.5%) of persons with elevated serum IgE (> 100 kU/l) than nonsmokers (27.2 kU/l; respectively 20.5%). The IgE level was significantly lower in women than men (p<0.001) in all smoking categories. The percentage of persons with positive atopic markers (positive Phadiatop test, positive skin prick tests to common inhalant allergens) and self-reported hay fever was significantly higher in nonsmokers than in smokers or former smokers. In Phadiatop positive (atopic) subjects, the IgE levels were highest, with a mean of 104.3 kU/l (99.0-109.8), and lowest in Phadiatop-negative nonsmokers at 27.2 kU/L (25.9-28.6). These findings correlate well with the current interpretation of total serum IgE values in screening for atopic diseases in adults (IgE < 20 kU/l: atopy improbable; IgE > 100 kU/l: atopy probable). In multivariate logistic regression models, the prevalence of positive Phadiatop tests, positive skin tests, and atopy decreased significantly with age. The odds of having a positive Phadiatop and skin test, or being atopic were found to decrease on average by 23.0, 21.1 and 21.0%, respectively, with every 10-year increase in age. With respect to smoking status, the odds ratios for the three atopic markers were significantly lower in current and former smokers than in nonsmokers. The prevalence of (self-reported) hay fever was highest in nonsmokers, intermediate in former smokers (odds ratio = 0.81, p<0.05) and lowest in current smokers (odds ratio = 0.76 in comparison to former smokers, p<0.01). The odds ratio of self-reported current hay fever decreased with age at an estimated average of 23% every 10 years. The decrease in former smokers might be slightly faster than in the other two categories. In conclusion, the present results demonstrated that tobacco smoking is associated with increased IgE levels and negatively related to atopy and hay fever. In addition, it is shown that atopy prevalence decreases with age.