Time for new reference values for ventilatory lung function.

OBJECTIVE: The anthropometrical data of our aging population has significantly changed within the last five decades. Therefore the question arises whether or not the commonly used reference values of the European Community (ECCS) for lung function, may still be accepted today. Measured values for elderly are classified by extrapolation beyond the range of reference equations. MATERIAL AND METHODS: Lung function was examined by pneumotachography for recording static lung volumes and flow-volume-curves in 257 asymptomatic non smoking males, aged 20-90 years. Results were compared to the reference values of ECCS, SAPALDIA, LuftiBus, and NHANES. RESULTS: For analysis age and height dependence of investigated respiratory parameters (VC, FVC, FEV(1), FEV(1) %FVC, PEF, MEF(75,50,25)) can for simplicity be described by linear functions (y = a . height(H)-b . age (A)+c). The forced expiratory volume in one second, FEV(1), was calculated by FEV(1) = 0.0432 . H-0.0347 . A -2.114; where H - height, A - age; r = 0.78. Mean FEV(1) for younger subjects was found to be 106.1 +/- 11.2% of the ECCS reference values and 97.8 +/- 11.7% in older subjects. For all parameters investigated linear regressions on age were steeper than described by the ECCS reference values. The regression of lung function to height largely follows the ECCS prescriptions. SUMMARY: Bochum lung function values of healthy subjects showed a steeper age descent compared to the reference values of the ECCS. The alternatively discussed reference values of the SAPALDIA-, NHANES- or LuftiBus-Study are higher, but do not cover all necessary parameters and/or the age range. A multi centre study for contemporary reference values is recommended.

Exhaled breath condensate analysis: evaluation of a methodological setting for epidemiological field studies.

The analysis of exhaled breath condensate (EBC) is a noninvasive method to determine airway inflammation. There is accumulating evidence that pH, nitrogen oxides (NOx), and leukotriene B4 (LTB4) are suitable markers of inflammatory airway diseases. It was the aim of the present pilot study to evaluate a protocol of EBC sampling and processing for epidemiologic field studies. EBC samples were repeatedly obtained by 16 healthy adults on each of four days over two consecutive weeks. The effects of sample collection (volume vs. time, with vs. without nose-clip) and sample processing on volume, pH, NOx, and LTB4 as well as within-day, between-day, and between-week reproducibility were assessed. We found that wearing a nose-clip had no significant effects on mediators. Sampling time was the major determinant of the volume. Reproducibility was fairly good. Storage at 4-6 degrees C for 24 h had no significant effects on NOx and LTB4 concentrations, but resulted in an increase of pH. In conclusion, wearing a nose-clip during EBC collection is not recommended in terms of convenience and compliance for repeated investigations. Samples for the analyses of NOx and LTB4 can be transported under usual conditions, but pH should preferably be determined at the workplace.

A 3-year cohort study on short-term effects of air pollution in Germany. 1. Influences of medication and season.

A 3-year cohort study which started in September 1987 investigates the effect of air pollution in adult patients with chronic obstructive airway disease. Of 108 patients recruited during the pilot phase in 1987 only eight patients had left the study prematurely. The most important components of the study are the daily peakflow measurements and a diary on medication and symptoms. In a preliminary analysis the influence of medication and season has been analyzed for the period September 1988 to June 1989 for 53 patients. In general, the reactions to seasonal changes were small. However, a significant decrease in peak-flow values by about 5% was found for the months of May and June compared to December for patients with chronic bronchitis, emphysema and asthma.

Occupational obstructive airway diseases in Germany.

In industrialized countries, occupational asthma caused by allergens and irritants due to workplace exposure is increasing. More than 8,000 such claims were made in Germany (10.5% of all decided occupational disease claims) in 1995; 1,900 were confirmed (6.5% of all confirmed claims). The legal basis and the occupational disease-related regulations of trade-assigned statutory accident insurance institutions ('Berufsgenossenschaften') in Germany are described. Hitherto, three occupational disease categories for obstructive airway disorders existed: due to sensitizing agents, due to chemical-irritative or toxic agents, and due to isocyanates. Approximately 40% of accepted claims for occupational asthma and rhinitis result from exposure to flour. Ongoing changes in the recognition of work-related airway disease symptoms account for differences in the incidence and prevalence as reported over the years. Recently, chronic obstructive bronchitis and/or emphysema of hard coal miners have been included in the German list of occupational diseases.

Baker's asthma: still among the most frequent occupational respiratory disorders.

BACKGROUND: Baker's asthma and rhinitis are among the most frequent occupational respiratory disorders. OBJECTIVE: The aim of the study was to evaluate the frequency of work-related symptoms and the clinical relevance of sensitization to allergens in screened and symptomatic bakers. METHODS: Eighty-nine bakers participating in a screening study and 104 bakers filing a claim for compensation were examined with regard to occupational and clinical case history, lung function parameters, and sensitization to bakery allergens by skin prick tests, specific IgE analyses, and inhalative challenge tests. RESULTS: A high prevalence of respiratory disorders, abnormal lung function parameters, and sensitization to bakery allergens exists. Most frequently, bakers with workplace-related respiratory symptoms showed sensitization to wheat flour (64%), rye flour (52%), soy bean flour (25%), and alpha-amylase (21%). The correlation between these sensitizations and asthma case history and inhalative challenge test responses was significant. However, approximately 29% of the bakers with respiratory symptoms showed no sensitization to these bakery allergens, whereas 32% of the sensitized bakers in the screening group had no workplace-related symptoms. Atopic status defined by skin prick test sensitization to common allergens or elevated total IgE levels was found to be a risk factor for the development of sensitization to bakery allergens and respiratory symptoms. On the other hand, there is evidence for an increased frequency of elevated total IgE as the result of occupational allergen exposure because respective findings were observed in bakers without symptoms. CONCLUSION: Sensitization to bakery allergens seems to be the main cause of baker's asthma and rhinitis but cannot explain the asthma case history in each case. Further methods are required to objectively assume irritative pathomechanisms. Our findings indicate the necessity for an improved primary prevention of exposure to inhalative noxae in bakeries.

Protein and allergen content of various natural latex articles.

Proteins remaining in products made of natural rubber latex are potential sensitizers. In the present work, we quantified the releasable protein and allergen contents in 37 brands of latex gloves and 26 other latex products. Our results demonstrate the presence of widely varied protein and allergen contents in various latex articles and the lack of a correlation between the protein and allergen values. These findings may assist hospital management and medical staff to take effective preventive measures.

Comparison of lung-function reference values.

OBJECTIVE: Lung-function reference values play an important role in medical surveillance examinations of occupational and environmental respiratory diseases, in stipulation of preventive measures, in initiation of therapeutic measures, and in granting of benefits to which individuals with lung injuries or occupational lung diseases are entitled (e.g., bronchial asthma, pneumoconiosis, or farmer's lung disease). Prediction equations most widely used are based on studies performed more than 20 years ago and may not represent the findings obtained in today's population. METHODS: We recorded case histories and lung function values of 139 healthy subjects (spirometric and plethysmographic data, T(LCO)) and computed the differences of measured values minus predicted ones as recommended by different authors. RESULTS: The means of these differences can be seen as shifts in our group versus the theoretical (predicted) values of various authors. These shifts, the standardized mean values of residuals, and their probability as determined under the assumptions of the respective regression model and the number of subjects below the threshold limits are given. FVC, FEV1, and FEV1%FVC show mostly good agreement with the recommendations by Crapo et al., Roca et al., Glindmeyer et al., Brändli et al., and Berger et al. Our IVC and FVC values do not differ significantly from each other. Normative flow-volume curve parameters of various authors deviate widely, however, and are not compatible with the values of our control group. Plethysmographically measured volumes (FRC, TLC, and RV) are only insufficiently reflected by Quanjer's reference equations. Measured T(LCO) and K(CO) show good agreement with the predictions of Cotes et al. [11] for females but display less concurrence with the predictions for males. CONCLUSIONS: Our results indicate that the ERS values of FVC, FEV1, and FEV1%FVC mainly applied in Europe should be verified. The much better-evaluated formulas of Brändli et al. are recommended. Furthermore, the age range between 60 and 70 years should be extrapolated from these formulas until better epidemiological data on lung function are available.

Comparison of wheat and rye flour skin prick test solutions for diagnosis of baker's asthma.

BACKGROUND: Skin prick tests (SPTs) play an important role in the diagnosis of baker's asthma and in the investigation of sensitization frequencies in field studies. It was the aim of our study to compare different SPT solutions for wheat and rye flour sensitization and to assess the validity of test results. METHODS: Skin prick tests with wheat and rye flour were performed in parallel with extracts from different companies and compared with the results of bronchial challenge tests with both flours (69 rye flour and 51 wheat flour challenge tests). Additionally, specific immunoglobulin E (sIgE) to wheat and rye flour were tested. SPT solutions were analysed for protein content and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: Skin prick test solutions for diagnosis of wheat and rye flour sensitization from three companies differed in protein concentrations and composition with the consequence of widely differing SPT results. Sensitivity of SPTs in comparison with allergen-specific bronchial challenge as a gold standard was between 40 and 67%, specificity was between 86 and 100%, the positive predictive value (PPV) ranged from 81 to 100% and the negative predictive value (NPV) from 44 to 70%. These numbers were only marginally affected by using a combination of challenge test result and sIgE value as a more specific gold standard. CONCLUSION: Improvement and standardization of SPT extracts for wheat and rye flour is highly recommended.

Relation between occupational asthma case history, bronchial methacholine challenge, and specific challenge test in patients with suspected occupational asthma.

Inhalative methacholine challenge (MC) was performed in 229 subjects presumed to suffer from occupational asthma due to exposure to airborne latex allergens (n = 62), flour (n = 28), isocyanates (n = 114), or irritants in hairdressers' salons (n = 25). They were also subjected to specific challenges with the occupational agents they were exposed to, completed a questionnaire using an abbreviated version of the ATS-DLD, and were interviewed by an experienced physician. Bronchial hyperresponsiveness in MC was defined by the results obtained in a previous study with 81 healthy volunteers. The threshold in these controls was set at a cumulative MC dose of 0.3 mg, corresponding to a sensitivity of 95%. The main purpose of the study was to investigate whether the MC and/or the occupational asthma case history are reliable predictors of the specific challenge test outcomes. In 40-72% of examined subjects, workplace-related asthma complaints occurred, with bronchial hyperreactivity in the MC ranging from 48% to 61%. However, only 12-25% demonstrated a significant bronchoconstructive reaction in the specific challenge test. MC results are only moderately associated with workplace-related asthma case histories. Positive outcomes of challenges with occupational agents are well correlated with positive MC results plus occupational asthma case histories. The combination of MC and occupational asthma case history shows a relatively high specificity (62%, 86%, 80%), but the sensitivity was moderately low (83%, 71%, 52%). MC sensitivities were 92%, 71%, and 62% (case histories of hairdressers were not available). We conclude that in most cases, occupational asthma (as defined by a specific challenge test response) is combined with bronchial hyperresponsiveness and workplace-related asthmatic symptoms. However, subjects of each exposure group demonstrated bronchial hyperresponsiveness and complained of workplace-related asthmatic symptoms, but occupational asthma could not be proved in the specific challenge test. In subjects with a positive occupational asthma case history, a negative MC test result can almost rule out a positive specific challenges test result. Hence, the MC test can reduce performance of the laborious specific challenge test.

Lung function testing: the dilemma of predicted values in relation to the individual variability.

Quantitated lung function parameters are usually interpreted in relation to so-called "normal ranges' obtained from healthy study groups. The aim of this paper is the critical review of formulas and the evaluation of intraindividual variation in modern lung function testing. To which extent is the total variation of lung function parameters in cross-sectional studies (usually serving as basis for the normal range) attributed to the intraindividual variation between repeated measurements? This question raises a further question: are lung function values in the normal range really normal? To assess spirometric and body plethysmographic parameters 26 healthy subjects from three medical centers underwent 30-72 measurements over a period of 2 months for the determination of variations due to (1) intraindividual variation over time and (2) interindividual variation. For each subject, predicted values of different lung function parameters published by Quanjer et al. [Eur Respir J 1993; 6:5-40.1], of intrathoracic gas volume by Ulmer et al. [Die Lungenfunktion; Stuttgart, Thieme, 1991] and of total airway resistance by Ruehle and Matthys [Pneumologie 1976;153:223] were applied. When converted into percent predicted and adjusted for differences in medical centers, the intraindividual standard deviation was estimated to be about half of the interindividual standard deviation. We conclude that the normal range of lung function parameters derived from the standard deviation within populations is too wide for the assessment of individual values. Interpretation of individual lung function measurements should primarily be based on the "individual normal range' derived from former lung function measurements of the individual and only secondly on the "predicted value'.

Systemic sclerosis in German uranium miners under special consideration of autoantibody subsets and HLA class II alleles.

Systemic sclerosis (scleroderma) is a connective tissue disease with a wide range of clinical manifestations, with high or low degrees of skin and internal organ involvement together with different antinuclear antibody (ANA) specificities. Several studies provide evidence that males, who are rarely affected by systemic sclerosis, have an increased risk when working in mines. Therefore we reinvestigated 21 male subjects and 6 cases of deceased male patients who had been engaged in East German uranium mines and had shown evidence of this disease in medical examinations. Dermatological investigations, evaluation of chest X-rays and autoantibody estimation were performed. PCR-sequence-specific oligonucleotide typing was used to study the genetic association of HLA-D alleles with autoantibodies typical for scleroderma in these uranium miners suffering from systemic sclerosis and in patients with idiopathic systemic sclerosis. The determined HLA phenotype frequencies and the following statistical analysis (Fisher's exact test (2-sided)) revealed that in comparison with randomly selected controls, alleles DRB1*0300 (DR3) and DQB1*0201 (DQ2) were distinctly increased in the group of affected uranium miners, especially in those with anti-Scl-70 positivity. In contrast, we did not observe significant differences between affected and unaffected miners. Comparing anti-Scl-70-positive affected uranium miners with anti-Scl-70-positive idiopathic systemic sclerosis cases. DRB1*0300 as well as DQB1*0201 were also significantly enhanced in the former group. ACA-positive systemic sclerosis miners had significantly elevated frequencies in DRB1*0100 (DR1) and DRB1*0800 (DR8) only in comparison with unaffected miners and unexposed controls. Our genetic and immunological data lead to the assumption that a different set of HLA-D alleles in combination with exogenous factors is involved in the induction of anti-Scl-70 antibodies in uranium miners that might influence their susceptibility to the disease, whereas the same occupational exposure seems to have no influence on the induction of ACA antibodies.

[Pilot project for evaluation of lung function reference values]. / Pilotprojekt zur Uberprüfung von Lungenfunktionssollwerten.

Lung function tests were performed in this study on 139 adults (mean age 36 years), as well as on 91 female persons between 16 and 18 years of age (the latter just starting on their professional careers), the lungs being healthy in each case in both groups. The findings were compared with the currently accepted reference value formulae after Quanjer et al., and Zapletal as well as further developed reference value formulae after Brändli et al., Most of the measurement data obtained by spirometry for the BGFA group of probands are between the two recommended reference values for adults with better coincidence with Brändli's predictions (exceptions being MMEF25-75 MEF 50 and MEF 25). In our studies we obtained higher values than the reference median values after Quanjer and Zapletal for IVC, FVC, FEV1 and PEF by 6-8% and 5-15%, respectively, whereas the values for adults differ from the predictions made by Brändli et al. by -4% to +5%. The flow data MMEF 75-25, MEF 50 and especially MEF 25 are set at too low levels (by 5-23%) by Zapletal's and Brändli's values. Comparatively, the values predicted by Quanjer et al. for the above mentioned flow-volume parameters (with the exception of MEF 75) are too high by 4% to 12%. There are also considerable differences in respect of the reference values for IGV to the tune of +15% in the BGFA group compared to Quanjer et al.; in the BAFAM group the values differ from those of Zapletal et al. by +17%. RV yields results in the BGFA group which are higher by 11% than according to Quanjer's formulae, whereas in the BAFAM group they are higher by 15% compared to Zapletal's predictions. In respect of Rt there are differences to the predictions by Rühle and Matthys by +16% (BGFA group) and +13% (BAFAM group), respectively. The BAFAM group differs from Zapletal's predictions by +11%. Looking at the reference limit values the overall impression is confirmed that the predictions after Quanjer et al. and mostly also those by Zapletal are too low in respect of the abovementioned lung function parameters (in the majority of cases not 5% of the examined probands, as expected, are below those levels, but only about 2%). Females, who had been underrepresented in the previous healthy proband groups, show larger deviations than males in respect of most of the parameters.(ABSTRACT TRUNCATED AT 400 WORDS)

Effectiveness of a medical surveillance program for the prevention of occupational asthma caused by platinum salts: a nested case-control study.

BACKGROUND: Exposure reduction has proven to be effective in the prevention of occupational asthma. Few data are available on the effectiveness of secondary prevention programs, including medical examinations and removal of workers from exposure sources after detecting symptoms or signs indicative of a beginning disease. OBJECTIVE: We sought to assess the effectiveness of a medical surveillance program in workers with exposure to platinum salts. METHODS: A nested case-control study was performed in 14 workers of a catalyst production plant whose skin prick test (SPT) responses to platinum salt converted from negative to positive during a 5-year prospective cohort study with yearly medical examinations and 42 matched control subjects from the plant who did not experience SPT response conversion. With the exception of 2 subjects, the workers showing SPT response conversion were removed completely from exposure sources and followed for up to 42 months. RESULTS: Work-related new symptoms were reported by 9 of the 14 subjects, and new symptoms without relation to work were reported by 3 subjects at the time of SPT response conversion. Symptoms were not accompanied by a change in FEV(1) or bronchial responsiveness to histamine. Symptoms resolved after transferral, but occasional shortness of breath or wheeze persisted in 4 subjects. SPT reactions decreased or became negative in all workers after complete removal but remained unchanged in a craftsman with ongoing occasional exposure to contaminated materials. CONCLUSION: Although no randomized intervention was performed, this study proves the effectiveness of a medical surveillance program for the prevention of occupational asthma caused by platinum salts.

A clinical and immunological study on 92 workers occupationally exposed to anhydrides.

This study aimed at investigating sensitizing and hazardous effects of a new acid anhydride, pyromellitic dianhydride (PMDA), in addition to those of phthalic anhydride, maleic anhydride and trimellitic anhydride, in a group of 92 exposed workers in two German chemical plants. Of the 92 workers, 56 reported work-related complaints with a predominance of phlegm and dyspnoea in those exposed to anhydride dust for less than 1 year. Haemorrhagic rhinitis occurred only after a prolonged exposure of more than 15 years. Specific IgE antibodies to anhydride-HSA conjugates could be detected in 15 exposed subjects, 12 of whom had work-related symptoms. The IgE-positive group had significantly more impaired lung function parameters than the IgE-negative group. The proportion of IgE-positive subjects was highest in the groups with dyspnoea (5/18), cough (6/24) and rhinitis (11/44) whereas only 1 of 11 workers with haemorrhagic rhinitis had such antibodies. A follow-up study of 23 affected workers was performed after 10 months to assess clinical symptoms, lung function and IgE antibody levels. This follow-up study showed the absence of obstructive ventilation patterns in three out of six subjects in addition to cessation of symptoms in most initially affected workers who were no longer exposed. On the other hand, 14 workers under continuous exposure had comparable pathological findings on re-examination. Our results confirm that anhydrides including the lesser known PMDA, behave as respiratory irritants and as immediate-type sensitizers. They predominantly induced reversible symptoms in workers whose exposure stopped after a working period of about 0.7 years. Abnormal lung function parameters normalized in nearly 50% of these subjects.