Per Malmberg

Reference Values for Lung Function Tests in Men: Regression Equations with Smoking Variables

Prediction formulas for static and dynamic spirometry, gas distribution, static lung mechanics and the transfer test were derived from measurements in healthy men. The measurements included total lung capacity, residual volume, airways resistance, static elastic recoil pressure of the lung, static compliance, closing volume, slope of the alveolar plateau (phase III), flow-volume variables (including mean transit time) during breathing of air or a helium/oxygen mixture, and conventional spirometric indices. The results from 146 smokers and 124 never-smokers were evaluated separately and combined. For all lung function tests a single regression equation was obtained. The prediction formulas included time-related smoking variables and were valid for both smokers and never-smokers. For many lung function tests, a nonlinear age coefficient resulted in a significant reduction in variance compared with simple linear models. Heavy tobacco smoking influenced most lung function tests less than ageing from 20 to 70 years, but for airways resistance, transfer factor and phase III the opposite was found.

Induction of IL-8 production in human alveolar macrophages and human bronchial epithelial cells in vitro by swine dust

BACKGROUND Exposure to swine dust causes an intense airway inflammation with increased levels of interleukin 8 (IL-8) and predominantly neutrophils in the nasal and bronchoalveolar lavage fluids of healthy human subjects. It is not clear which components in the swine house environment are responsible for the airway reaction. The aim of the present study was to evaluate and compare the effect in vitro of swine dust components on human alveolar macrophages and bronchial epithelial cells. METHODS Normal human bronchial epithelial cells (NHBE), human pulmonary epithelial carcinoma cell line (A549), and human alveolar macrophages were stimulated with swine dust, lipopolysaccharides (LPS; present in Gram negative bacteria), grain dust (swine feed components), and glucans (a structural component of fungi) in a dose response manner (1–100 μg/ml). RESULTS Swine dust at a concentration of 100 μg/ml increased IL-8 production 20 fold in NHBE cells, 28 fold in A549 cells, and 15 fold in macrophages. LPS (100 μg/ml) stimulated all three cell types significantly, in macrophages to the same extent as swine dust, but in NHBE and A549 cells swine dust was 5–8 times as potent. Grain dust (100 μg/ml) had no effect in A549 cells but stimulated NHBE cells and macrophages. Glucans (100 μg/ml) stimulated A549 cells and macrophages but not NHBE cells. Both glucans and grain dust were weaker stimuli than swine dust and LPS. The LPS content of swine dust solution was 2.16 (0.2) ng/100 μg and of grain dust was 0.53 (0.04) ng/100 μg. CONCLUSIONS Swine dust is a strong stimulus for IL-8 production in both bronchial epithelial cells and human alveolar macrophages, whereas LPS has different potency in these cells.

Gram positive bacteria induce IL-6 and IL-8 production in human alveolar macrophages and epithelial cells.

Background and Objective: Inhalation of dust from swine confinement buildings results in an acute inflammatory reaction in the respiratory tract. The dust has a high microbial content, dominated by Gram positive bacteria. The aim of the present study was to evaluate the significance of bacteria in the induction of IL-6 and IL-8 release from respiratory epithelial cells and alveolar macrophages. The results would give an indication to what extent the bacteria contribute to the toxic inflammation following exposure to swine dust. Methods: Epithelial cells from a human lung carcinoma cell line (A549) and human alveolar macrophages obtained from healthy subjects by bronchoalveolar lavage, were stimulated with swine dust, LPS, one Gram negative and four Gram positive bacteria strains. The dose-response release of IL-6 and IL-8 were studied. In addition, a bacteria-free supernatant was prepared from each strain and used for stimulation. Results: With a few exceptions, a dose-dependent IL-6 and IL-8 release was demonstrated from both cell types after stimulation with bacteria. In epithelial cells, Escherichia coli was the most potent bacteria at the highest concentration of 400 bacteria/cell regarding secretion of both IL-6 and IL-8 (P < 0.001), followed by Staphylococcus hominis and Staphylococcus lentus. In alveolar macrophages, S. lentus was the most potent strain (P < 0.001) in inducing cytokine release (P < 0.001), followed by S. hominis and E. coli concerning IL-6 secretion or Micrococcus luteus and E. coli with respect to IL-8 secretion (P < 0.001). Differences in potency between the various bacteria could be demonstrated, both within the two cell types as well as between the epithelial cells and macrophages. Bacteria-free supernatants were also able to induce cytokine release in both cell types. In macrophages the supernatants were even more potent stimuli than whole bacteria. Conclusions: The results indicate that bacteria or bacterial products could be an important contributing factor to the inflammatory reaction following exposure to swine dust.

Exposure of healthy volunteers to swine house dust increases formation of leukotrienes, prostaglandin D2, and bronchial responsiveness to methacholine

BACKGROUND Acute exposure of healthy subjects to swine house dust causes increased bronchial responsiveness to methacholine but no acute bronchoconstriction. The role of cysteinyl leukotrienes and mast cells in increased bronchial responsiveness is unclear. METHODS Ten non-asthmatic subjects were exposed to swine dust for three hours while weighing pigs in a piggery. Urine was collected prior to and for up to 12 hours after entering the piggery and at the same times five days before and the day after exposure. As indices of whole body leukotriene production and mast cell activation, urinary levels of leukotriene E4(LTE4) and 9α,11β-PGF2, the earliest appearing urinary metabolite of prostaglandin D2(PGD2), were measured. Bronchial responsiveness to methacholine was determined five days before and the day after the exposure. RESULTS Methacholine PD20FEV1 decreased from 1.32 mg (95% CI 0.22 to 10.25) before exposure to 0.38 mg (95% CI 0.11 to 1.3) after exposure (p<0.01). Associated with the increase in bronchial responsiveness there was a significant mean difference between post- and pre-challenge levels of LTE4 (difference 38.5 ng/mmol creatinine (95% CI 17.2 to 59.8); p<0.01) and 9α,11β-PGF2 (difference 69 ng/mmol creatinine (95% CI 3.7 to 134.3); p<0.05) on the day of exposure to swine dust. Swine dust exposure induced a 24-fold increase in the total cell number and a 12-fold increase in IL-8 levels in the nasal lavage fluid. The levels of LTB4 and LTE4 in nasal lavage fluid following exposure also increased 5.5-fold and 2-fold, respectively. CONCLUSIONS The findings of this study indicate that cysteinyl leukotrienes and other mast cell mediators contribute to the development of increased bronchial responsiveness following inhalation of organic swine dust.

Learning effects, variation during office hours and reproducibility of static and dynamic spirometry.

Static and dynamic spirometric tests were performed in 21 healthy subjects (21-61 years old, 8 smokers and 9 ex-smokers) on 3 different days within 2 weeks. The design of the study allowed separation of the influence of learning and diurnal changes between 09.00 and 17.00 h. In addition, the reproducibility of the tests and the effect of inhalation of 2.5 mg of terbutaline sulphate were studied. No learning effect was observed. There were slight, but statistically significant differences between morning, noon and afternoon measurements. Thus, the residual volume and flow in the early phase of forced expiration were highest in the afternoon, while maximal voluntary ventilation was lower at noon than in the afternoon or morning. The intraindividual variabilities (defined as standard deviation of difference between first and second measurement) of total lung capacity, vital capacity and forced expiratory volume in 1 s (FEV1) were about 3% of the predicted values. The ratio of intra- to interindividual variability was 0.2-0.3. The remaining tests showed higher variability and a higher intra- to interindividual variability ratio. Terbutaline inhalation caused a significant increase in most forced expiratory flow variables. A 10% increase in FEV1 corresponded to a 50-60% increase in endexpiratory flow. In spite of this, the endexpiratory flow and mean transit time were better discriminators of the effects of bronchodilation in normal subjects.

Association between Exposure to Asbestos and Pleural Effusion. Results from a Questionnaire Study of 31000 Persons

All visitors to a general health survey in 1979, 17,140 men and 14,371 women, completed a questionnaire on smoking habits, exposure to asbestos, silica and welding fumes, and diseases such as pleural effusion, pneumonia, cough, asthma and diabetes. Seven per cent of the men reported exposure to asbestos, 10% to welding fumes, and 6% to silica. Among those who reported work related dust exposure there was a higher proportion of smokers, and smokers exposed to dust smoked more tobacco per day than non exposed smokers. In the group of men 30–59 years of age, who did not indicate exposure to occupational pollutants 2.7% reported previous pleural effusions. However, among asbestos exposed men of the same ages, the prevalence was more than doubled (5.7%, p<0.01). This finding was highly significant in a logistic regression model where age and smoking habits were included. The data indicate that 10% or more of diagnosed cases of pleurisy could be associated with previous asbestos exposure.