Inhalation bronchial challenges with house dust antigen: technique, reactions, comparison with the results of skin tests.
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In this study the maximal mid-expiratory flow (MMEF) was compared with forced expiratory volume in 1 sec (FEV1) by a spirometric investigation of healthy children and children with slight bronchial obstruction. We found that the reproducibility of MMEF was good in both healthy and asthmatic children and that both methods had the same ability to detect abnormality before inhalation of a beta 2-receptor agonist. After such an inhalation the discriminatory power was greater for FEV1 than for MMEF and we therefore prefer FEV1 in estimating bronchial obstruction in children.
Association and linkage studies of beta2-adrenergic receptor (beta2-ADR) polymorphisms in relation to the expression of asthmatic phenotypes and immune regulatory mechanisms have shown inconsistent results. In order to analyse the relevance of particular combinations of single nucleotide polymorphisms (SNPs) or haplotypes of beta2-ADR gene to bronchial asthma, bronchodilator response and total immunoglobulin E (IgE) we determined by direct DNA sequencing five SNPs (in positions: -47, -20, 46, 79, 252) in a group of 180 Caucasian subjects (110 patients with grass allergy and 70 nonatopic controls). The eight different beta2-ADR haplotypes were identified, with three the most common of them representing 92% of the studied cohort. Significantly higher (pcor = 0.0045) bronchodilator response was observed in patients with homozygotic genotype 46A/A in comparison with respective homo- and hetero-zygotes. There was no significant difference in bronchodilator response when beta2-ADR haplotypes were analysed. Significantly higher (pcor = 0.0005) total IgE levels were found in patients with beta2-ADR haplotype -47T/-20T/46A/79C/252G and homozygotic carriers of 46A (pcor = 0.0015) and 79C (pcor = 0.003) genotypes. No significant associations were found in regards to asthmatic phenotype and atopy. These results indicate that depending on phenotype studied, either an individual beta2-ADR SNP or beta2-ADR haplotype might affect disease manifestation.
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Lung function responses to inhaled cotton dust were evaluated in a group of 58 healthy subjects by spirometry (MEFV curves) and forced random noise impedance parameters. Twenty-one of these subjects were also examined by body plethysmography to assess changes in airway resistance (Raw). For the study group as a whole, alterations in lung mechanical function after exposure to cotton dust were detected by maximal expiratory volumes and flows (p less than 0.001) and impedance parameters (p less than 0.01) but not by Raw. Subjects showing responses in MEFV curves also showed increases in Thevenin or effective resistance at low frequencies (R1, R5-9, R5-9/R20-24), suggesting that the limitation of flow occurred predominantly in the peripheral airways. By contrast, non-responders on MEFV measurements were found to have significant increases in effective resistance both at low and at high frequencies (R1, R5-9, R20-24), suggesting a central airways effect. MEFV curve non-responders also exhibited a significantly lower baseline effective resistance profile than MEFV curve responders. The data indicate that under the conditions of the experiment measures of the Thevenin resistance (real part of impedence) by the forced random noise method are reliable indicators of cotton induced bronchoconstriction. Measurement variability, however, suggests that, at present, these are more appropriate for group studies and should remain adjuncts to standard tests of lung function such as spirometry.
OBJECTIVES: Questionnaires, lung function tests, and peak flow measurements are widely used in occupational health care to screen for subjects with respiratory disease. However, the diagnostic performance of these tests is often poor. Application of these tests in a stepwise manner would presumably result in a better characterisation of subjects with respiratory disease. METHODS: Cross sectional data from workers exposed to acid anhydrides, to laboratory animals, and to flour dusts were used. Sensitivity and specificity were calculated from cross tables of different (combinations of) tests for bronchial hyperresponsiveness and bronchial irritability in the past four weeks (BIS). From sensitivity and specificity likelihood ratios were computed and change in probability of BIS was calculated. RESULTS: The prevalence of BIS was 7%, 7%, and 5%, respectively. In all groups questionnaire data provided excellent sensitivity but poor specificity, which was inherent on the broad definition of symptoms. Adding the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio yields almost perfect specificity, and peak expiratory flow (PEF) variability is intermediate in populations in which smoking induced or non-allergic respiratory diseases predominates. In occupational groups in which asthma is a problem, adding PEF measurements will optimise sensitivity and specificity in detection of BIS. The probability of BIS for subjects with a negative combined test outcome was lower than the probability before testing. Subjects with a positive combined test outcome had a probability of BIS after the tests at least three times the probability before. CONCLUSIONS: Combined testing yields better sensitivity and specificity. An advantage of combined testing is an economy in the effort to screen for subjects with BIS. Combined testing resulted in more detailed estimation of the probability of BIS.
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Effective time of the forced expirogram is a sensitive index for the detection of mild airways obstruction. However, there is evidence that this measurement is not superior to maximum flow rates in the lower half of the forced vital capacity or even FEV1 and FEV1% in some patients suffering from obstructive lung disease. Furthermore we noticed that in some patients with a decrease of the forced vital capacity caused by exacerbation of airways obstruction, the effective time was not appreciably changed. We concluded that this apparent disadvantage of the effective time is the result of the different forced vital capacities. To eliminate this error we transformed the forced expirogram to the equivalent curve that the patient would produce, if his forced vital capacity was equal to the predicted mean value for his age, sex, and height. The derived corrected total effective time seems to have increased sensitivity for detection of small changes in expirograms obtained from the same subject or from different subjects.
The effect of the inspiratory flow rate during deep inspiration on the regulation of bronchomotor tone was studied in nine normal and 22 asthmatic subjects. Changes in bronchial tone were assessed by respiratory resistance measured by an oscillation method. In normal subjects with bronchoconstriction induced by methacholine a rapid deep inspiration reduced respiratory resistance more than a slow deep inspiration. Asthmatic subjects with spontaneous airway narrowing showed an increase in respiratory resistance after deep inspiration that was greater after rapid than after slow deep inspiration. On the other hand, in asthmatics with methacholine induced bronchoconstriction, bronchodilatation occurred after deep inspiration and this was also greater after rapid than after slow deep inspiration. Lignocaine inhalation attenuated both bronchoconstriction and bronchodilatation induced by both slow and rapid deep inspiration. These results suggest that the effects of deep inspiration are mediated at least in part via receptors in the airways. It is suggested that in asthmatic patients with spontaneous bronchoconstriction irritant receptor activity will be increased in proportion to the speed of inspiration. After methacholine induced bronchoconstriction stretch receptor activity is likely to behave in a similar fashion, leading to an opposite effect.