Longitudinal decline in lung function in patients with occupational asthma due to western red cedar

BACKGROUND: There are few reports about longitudinal changes in lung function in asthmatic patients. Patients with asthma had a greater loss of lung function than normal healthy adults. To date, there have been no studies about the longitudinal changes in lung function in patients with occupational asthma. METHODS: 280 male patients with red cedar asthma (RCA) who were followed up for at least one year were the study group. The exposed controls consisted of 399 male sawmill workers. Forced expiratory volume in one second (FEV1) was measured with a Collins water spirometer. Changes in FEV1 over time (FEV1 slope) were calculated by a two point method for each subject. Atopy was considered to be present if the subjects showed at least one positive response to three allergens by skin prick test. RESULTS: Multiple regression analysis was carried out to examine factors that might affect longitudinal decline in FEV1. Patients with RCA who were still exposed had a greater decline in FEV1 slope (-26 ml/y) than sawmill workers. Smokers also showed a greater rate of decline in FEV1 (-43 ml/y) than non-smokers. CONCLUSIONS: Patients with RCA who continued to be exposed had a greater rate of decline in FEV1 than sawmill workers. Early diagnosis of occupational asthma and removal of these patients from a specific sensitiser is important in the prevention of further deterioration of lung function and respiratory symptoms.     

Pulmonary function in perlite workers

Pulmonary function was studied in 117 men employed in three plants engaged in the mining and processing of perlite. Of these, 38 had been employed for ten years or more; 18 for 15 years or more and four men for 20 years or more. Review of chest films confirmed previous studies which showed no changes indicative of pneumoconiosis. Measurement of forced vital capacity (FVC) by Jones Pulmonor and by Collins 9-liter spirometer did not show reductions correlated with length of exposure, after effects of cigarette smoking had been taken into account. There was instead a slight increase in FVC associated with years in the perlite industry. The distribution of individuals with FVC below 80% of predicted also showed no association with duration of perlite exposure. Although there were slight reductions in forced expiratory volume in one second (FEV1) and in FEV1/FVC% which were associated with years in the perlite industry and which could not be explained by cigarette smoking, these reductions were not statistically significant. In summary, the population of men available for study in the major perlite-producing area of the United States, who have worked for periods up to 23 years, showed no evidence of pneumoconiosis by chest radiography or by measurement of forced vital capacity. Nevertheless, continued control of dust to ensure exposures below nuisance dust levels is essential. Medical surveillance should also continue with records being retained for periodic reevaluation.     

The course of bronchial asthma in adults. Factors of importance for the annual decline of lung function

The purpose of this study was to describe the relation of various factors of potential importance to the rate of decline in lung function in adults with intrinsic and extrinsic asthma. Of 180 asthmatic patients, 143 (79%) participated in a 10 year follow up examination; 94 patients had intrinsic asthma and 49 extrinsic asthma. Patients with intrinsic asthma had an annual decline in FEV1 of 50 ml, whereas those with extrinsic asthma had a decline of 23 ml; the rate of decline of lung function increased with increasing age in both groups. There was no relation between rate of decline in lung function and number of cigarettes smoked. An inverse relation between initial FEV1 and decline in FEV1 was found for the patients with extrinsic asthma but not for the patients with intrinsic asthma. A high degree of airway variability--that is, reversibility in FEV1--at the time of enrollment was found to be associated with a steeper decline in lung function in patients with intrinsic asthma, whereas increasing degrees of obstruction (decreasing FEV1/VC ratio at enrollment) and need for treatment with corticosteroids were associated with a more pronounced decline in FEV1 in patients with extrinsic asthma. The rate of decline in lung function is greater in patients with intrinsic asthma than in patients with extrinsic asthma; the prognosis for intrinsic and extrinsic asthma is to some extent influenced by different factors, which suggests that the pathogenetic mechanisms underlying intrinsic and extrinsic asthma may differ.     

Thresholds for ultrasonically induced lung hemorrhage in neonatal swine

The threshold for generation of lung hemorrhage in adult mice by pulsed ultrasound has been shown to be approximately 1 MPa at the surface of the lung (10-microseconds pulse and a carrier frequency of 2 MHz). This investigation used neonatal swine to determine if the findings for mice can be generalized to other species. After exploratory observations, the inverse sampling method was used in a primary study (22 animals, 88 exposure sites) to determine the threshold for lung hemorrhage in neonatal swine. The primary study was followed by a separate confirmation study (13 animals, 48 exposure sites), testing the conclusions of the first study and comparing damage at subthreshold levels with sham-exposed animals. A separate investigation explored the histological nature of tissue damage at suprathreshold levels. A 2.3-MHz focused transducer (10 microseconds at 100-Hz pulse-repetition frequency) was incremented vertically for a distance of 2 cm over the chest of the subject for a total exposure period of 16 min. Animals were euthanized and lungs were scored by visual inspection for numbers and areas of gross hemorrhages. The threshold level for hemorrhage was approximately 1.5 MPa peak positive pressure in water at the surface of the animal or, at the surface of the lung, 1.1 MPa peak positive pressure, 1 MPa fundamental pressure, 0.9 MPa maximum negative pressure, 25 W cm-2 pulse average intensity or a mechanical index of 0.6. These values are essentially the same as those reported for adult mice.     

Cyclosporine-induced hypertension and decline in renal function in healthy volunteers

OBJECTIVE: To investigate the effect of cyclosporine A (CsA; Sandimmun Neoral) on systemic and renal hemodynamics, tubular function, and sodium excretion in healthy volunteers. Furthermore, we studied whether CsA enhances the systemic and renal hemodynamic sensitivity to norepinephrine. METHODS: Eighteen healthy volunteers were administered 10 mg/kg CsA or placebo capsules in a double-blind fashion. The mean arterial blood pressure (MAP), renal vascular resistance (RVR), glomerular filtration rate (GFR), and renal clearances of lithium (CLi) and sodium (CNa) were measured for 8 h after ingestion of the capsules. Norepinephrine (2 microg/kg per h) was infused intravenously for 1.5 h into nine subjects. RESULTS: CsA increased the MAP by 17+/-2 mmHg. The GFR decreased by 18+/-2% (P < 0.001) and the RVR increased by 37+/-4% (P< 0.001) after ingestion of CsA. The CsA-induced increase in MAP preceded the CsA-induced fall in GFR. The rise in MAP was followed by an early 35+/-8/0 increase in CNa (P < 0.001). At the end of the 8 h study period, CNa decreased by 25+/-7% (P < 0.001). Using CLi, it was found that the initial natriuresis had been caused by a relative decrease both in proximal and in distal tubular reabsorption of sodium, whereas the late sodium retention was secondary to the CsA-induced fall in GFR. Infusion of norepinephrine increased the MAP, RVR, and filtration fraction, and decreased the renal plasma flow, without CsA having any additional effect. CONCLUSION: It was demonstrated that a single oral dose of CsA caused a rise in blood pressure and transient natriuresis, followed by a fall in GFR and antinatriuresis. Thus, the present study confirms and extends earlier observations that renal dysfunction and sodium retention are not the initiating events in CsA-induced hypertension. The study also affords evidence suggesting that such rises in blood pressure are not mediated by an increased sensitivity to norepinephrine.     

Reduced-size lung transplantation from adult to neonatal swine

BACKGROUND: Lung donor shortage is a critical factor limiting the expansion of pediatric lung transplantation programs. This report details the surgical technical feasibility of a training model of lobar lung transplantation as well as the perioperative monitoring to evaluate the appropriate pulmonary graft function. METHODS: Ten hybrid Large-White pigs underwent left lower lobe lung allotransplantation; Donors weighed 15 to 20 kg and recipients 5 to 7 kg. The first five animals were used to learn the surgical anatomy and to establish the surgical technique and instrumentation's model (Group A). One hour after transplantation the right lung was excluded. Lung function and hemodynamic data were collected sequentially in the following five animals (Group B). RESULTS: The left inferior pulmonary lobe was found to be the most suitable allograft for transplantation. Usually, bronchial size discrepancy allowed telescoping of the airway anastomosis. Left atrial clamping was well tolerated during the pulmonary vein anastomoses. Preoperative antiaggregation and postoperatively heparinization achieved with ACT values over 200 seconds, prevented left atrial thrombosis. After right lung exclusion, hemodynamic changes consisted of a sustained increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics were also modified, with a gradual rise in airway resistance and a fall in compliance. CONCLUSIONS: The neonatal pig tolerates left lobar pulmonary transplantation satisfactorily. Although it is a useful and promising surgical learning model, questions remain regarding the applicability of this experience to clinical pediatric lung transplantation.     

Mucociliary clearance and respiratory function in foundry workers

The aim of the study was to establish whether changes occur in respiratory function, particularly mucociliary clearance, among second fusion smeltery workers. The research covered 93 male smelters employed in steel forming and casting and 116 male workers of an electric power station, considered as non-exposed. Physiological, pathological and occupational histories of all subjects under study were available. An ECCS respiratory symptoms questionnaire was administered to all subjects ad the two groups also underwent a general medical examination, a spirometry and a chest X-ray. During the medical examination sputum was collected from the subjects to measure mucus transport rate on frog palate, expressed as Normalised Frog Palate Transport Rate (NFPTR). For the environmental research, dust, fumes and gas samplings were taken either at a fixed station or by means of personal dosimeters. Environmental research revealed very low concentrations of respiratory irritants (total dust: 0.2-6.8 mg/m3; respirable dust: 0.1-4.9 mg/m3; total silica: < 2-15.5%; respirable silica: < 0.004-0.3 mg/m3; iron: 0.008-0.085 mg/m3; chromium and manganese: < 0.001 mg/m3; fumes and gases: well below the TLV. The two groups were homogeneous with regard to age and smoking habits. Exposed workers showed rales, dyspnoea and spontaneous phlegm more frequently than non-exposed workers. NFPTR alterations were checked in 49 out of 81 exposed and in 18 out of 81 non-exposed subjects (chi squared = 22.9; p < 0.001). Stratification of the results according to smoking habits further confirmed the strong association between occupational exposure and NFPTR alterations. Smelters showed significantly lower mean NFPTR values compared to non-exposed subjects; also, the mean value of NFPTR in the exposed was below 0.70, which is considered the lowest individual limit in normal subjects. The only variable which explains a large part of the variability of NFPTR is past work in a smeltery rather than in an electric power station. The spirometries showed that only the mean PEF values were significantly lower among the exposed. Stratified analysis of the results according to smoking habits in the two groups revealed a close association between smeltery work and reduction of PEF to under 80% of the ECCS 1983 theoretical values, independently of smoking habits. We also compared the mean PEF values, both as measured values and as percent values of the ECCS 1983 theoretical values, stratified for occupational exposure and smoking; the results again showed that differences between these mean values were mainly due to current or past work in the foundry.(ABSTRACT TRUNCATED AT 400 WORDS)     

COPD: using nutrition to prevent respiratory function decline

Close to three-fourths of patients with chronic obstructive pulmonary disease (COPD) suffer from weight loss. Identifying a single cause for this is difficult, as several factors-including chronic mouth breathing, dyspnea, aerophagia, certain medications, and depression-often act in concert. Malnutrition can exacerbate symptoms of COPD by decreasing ventilatory muscle strength, exercise tolerance, and immunocompetence, and by increasing the risk of depression and anxiety. Goals of nutrition intervention are to prevent or reverse malnutrition without worsening the disease process and to improve respiratory function, thereby reducing morbidity and delaying mortality. Recommendations for intake of fats, carbohydrates, protein, and water must be individualized.     

Health effects of airborne pollutants, particularly in swine confinement stalls, from the viewpoint of occupational medicine]

From the point of view of occupational respiratory medicine, an overview on potential health effects of airborne pollutants particularly in swine confinement houses is presented. Airway diseases are the most frequent occupational disorders among farmers in many countries around the world including Germany. Due to various methodological reasons, epidemiological studies in farming populations are more difficult to perform than among non-farmers. Major constituents of swine confinement dust include bacteria, endotoxin, mites, fungal spores, and animal dander. Gaseous pollutants include ammonia, methane, and hydrogen sulfide. In a variety of cross-sectional studies, high prevalences of respiratory symptoms and non-obstructive (and obstructive) bronchitis and Organic Dust Toxic Syndrome have been reported in pig farmers. Nasal and bronchial provocation challenges with swine confinement dust include influx of neutrophils and other inflammatory cells as well as mediators. In cross-sectional and longitudinal studies, endotoxin turns out as the probably most relevant parameter associated with lung function impairment. Further studies are clearly needed focusing on the prognosis of non-obstructive bronchitis in swine farmers and on health effects of reducing airborne contaminants in swine confinement houses.     

Respiratory function and allergic reactions in paper recycling workers

The GABAA receptor is a ligand-gated chloride channel belonging to the superfamily of ligand-gated ion channels of which the nicotinic acetylcholine (nACh) receptor is prototypic. In the central nervous system the GABAA receptor mediates fast neuronal inhibition. To facilitate the study of this receptor, a GABAA receptor-green fluorescent protein (GABAAR-GFP) chimera was constructed by fusing green fluorescent protein (GFP) to the C-terminus region of the GABAA receptor alpha1 subunit. When expressed in Xenopus oocytes, this chimera responded in a manner indistinguishable from the wild-type GABAA receptor with respect to agonist potency, receptor desensitization, allosteric modulation, rectification, and ion selectivity of the channel. The addition of GFP to the GABAA receptor alpha1 subunit did not appear to alter the assembly or efficiency of expression of the GABAA receptor complex. The GABAAR-GFP chimera generated a strong fluorescent signal that was restricted to the animal pole of the oocyte plasma membrane. This signal was readily detectable using either epifluorescence or laser confocal microscopy. To confirm the extracellular location of the GFP portion of the chimera, non-permeabilized oocytes were immunolabeled with an anti-GFP antibody. Fluorescence microscopy showed that GFP was located extracellularly since it was accessible to the GFP antibody. These results confirm the predicted extracellular location of the C-terminus of the GABAA receptor alpha1 subunit and also demonstrate that GFP retains its fluorescent property when expressed extracellularly. The usefulness of the GABAAR-GFP chimera in receptor trafficking was investigated using non-hydrolyzable GTP analogues since GTP binding proteins participate in protein transport in oocytes. Microinjections of GTP-gamma-S but not GDP-beta-S reduced both GABA-gated chloride currents and cell surface GFP fluorescence in oocytes expressing the GABAAR-GFP chimera indicating that the chimera undergoes internalization upon stimulation of oocyte GTP-binding proteins. The results of the present study show that the GABAAR-GFP chimera is functionally similar to the wild-type GABAA receptor and can be used to study receptor trafficking in living cells. This is the first demonstration of a ligand-gated ion channel-GFP chimera for an ion channel belonging to this superfamily and also is the first example of the fusion of GFP to an extracellular domain of an integral membrane protein.     

Smoking and lung function

In a cross-sectional survey of 3 separate communities, we studied the white residents 7 year of age and older in order to determine the relation between cigarette smoking and lung function. We identified 2,817 nonsmokers, 664 ex-smokers, and 1,209 smokers who were further classified as light smokers (1 to 20 cigarettes per day) and heavy smokers (greater than 20 cigarettes per day). Residual lung function (observed-predicted) was examined in these groups for forced expiratory volume in one second (rFEV1) and for maximal expiratory flow rates at 50% and 25% of the vital capacity (rVmax50% and rVmax 25%). Mean residuals by sex, age, and smoking category were compared and revealed an increasing progression of lung function loss with advancing age in males and females in all smoking categories. These age-related trends were due primarily to the amount smoked by persons in each group. The age of onset of these abnormalities was found to be as early as the age group 15 to 24 yr. Abnormalities were greater in smokers than ex-smokers, even when the amount smoked was taken into account. This is suggested improvement in lung function after cessation of smoking. Men and women were found to experience the same relative degree of gain. Also, the contribution of the various smoking habits to lung function loss was assessed using regression analyses and accounted for no more than 15% of the variation of the residual lung function. Combinations of variables were found to explain only slightly more variation than a single variable. The two most important variables were duration of smoking and pack-years. Inhalation and use of filters were not significant. Although the same amount of variation explained by the smoking variables after accounting for age, height, weight, and sex was small, this variation accounted for almost all of the decrease, over age, in residual lung function for smokers and ex-smokers.     

Small airway obliteration in a new swine heterotopic lung and bronchial allograft model

The subcellular localization of the phosphatidylglycerol/phosphatidylinositol transfer protein (PG/PI-TP) of Aspergillus oryzae was investigated using Western blot analysis of the cell protein extracts, a cellular membrane fractionation technique, and transmission electron microscopy. The PG/PI-TP, as detected by Western blot analysis with a specific immune serum, was found to be mainly cytoplasmic and partly associated with intracellular membranes. A fractionation experiment was conducted after homogenization of the filamentous fungus mycelium. The endoplasmic reticulum, Golgi-like vesicles, and the plasma membrane were separated by isopycnic ultracentrifugation on a sucrose gradient, and our data revealed that the immunodetected PG/PI-TP was only associated with the Golgi-like apparatus. All these results were documented by electron microscopy and indicate here for the first time that there exists a specific phospholipid transfer protein in a filamentous fungus that is localized in the cytoplasm and associated with Golgi-like vesicles.     

Regional lung function in unilateral diaphragmatic paralysis

Radioactive xenon-133 was used to study the regional lung function of five patients with unilateral diaphragmatic paralysis unassociated with intrathoracic disease. All patients showed a reduction in total lung capacity to which the affected side contributed an average of 37%. There was a decrease in the amount of inhaled xenon and a lesser decrease in the amount of injected xenon reaching the lung base on the paralysed side.The distribution in the opposite lung did not differ significantly from that found in normal subjects although the proportion of inhaled xenon reaching the lung base was rather less than in the normal group. The washout of injected xenon was normal except for slight impairment at the lung base on the paralysed side in one patient and at both bases in another.     

Oxidative stress and lung function

It has been suggested that lung function can be altered by both free radical and oxidant exposure, while antioxidant vitamin intake is positively related to lung function. However, the information on the relation of blood levels of oxidants and antioxidants to lung function is sparse. The present cross-sectional study, conducted from September 1995 to May 1996, analyzes the association between lung function measured as forced expiratory volume in 1 second (FEV1) with 1) levels of thiobarbituric acid-reactive substances in plasma (p-TBARS) and in low and very low density lipoprotein cholesterol (LDL cholesterol/VLDL cholesterol-TBARS) as indicators of lipid peroxidation and 2) compounds with antioxidant activity, erythrocytic glutathione, plasma glutathione peroxidase, trolox equivalent antioxidant capacity, and serum bilirubin, which may protect against lipid peroxidation. The analysis was carried out in 132 nonsmoking subjects aged 37-73 years who were randomly selected from the residents of Erie and Niagara counties, New York. FEV1 in percent of the predicted value (FEV1%) was negatively and statistical significantly associated with p-TBARS (r = -0.19). A negative association with borderline statistical significance was observed between FEV1% with low density lipoprotein cholesterol/very low density lipoprotein cholesterol-TBARS (r = -0.16) and glutathione (r = -0.16), while FEV1% was positively related to serum bilirubin (r = 0.15). Participants in the lowest quartile of FEV1% showed significantly higher levels of p-TBARS (p = 0.02) and lower levels of bilirubin (p = 0.04) than did those in the highest quartile. Our results suggest that increased lipid peroxidation is associated with pulmonary airway narrowing in the general population.     

A new aspect of the carotid body function controlling hypoxic ventilatory decline in humans

Ventilatory response to eucapnic sustained mild hypoxia was measured in one patient with unilateral and three patients with bilateral carotid body (CB) resection (defined UR and BR, respectively). The profile of ventilatory response in UR patient was initially augmented then gradually declined (biphasic pattern) as generally seen in normal subjects although the absolute magnitude was substantially low. On the other hand, biphasic pattern was disappeared in all three BRs. Lack of hypoxic ventilatory decline (HVD) in the late period of sustained hypoxia was in marked contrast to that reported in the anaesthetized and CB-denervated animals whose ventilation was severely depressed lower than the pre-hypoxic control level. In view of recent knowledge that the analogous mild hypoxia in normal animals and humans elicits an useful adaptation to economize energy expenditure with maintaining reversible excitability in control of respiration, BR patients were considered to have lost this ability. We conclude that in awake humans the CB not only stimulates ventilation but also controls the degree of subsequent HVD during sustained hypoxia.