Skin permeation studies of chromium species - Evaluation of a reconstructed human epidermis model.

A reconstructed human epidermis (RHE) model, the EpiDerm, was investigated and compared to human skin ex vivo regarding tissue penetration and distribution of two chromium species, relevant in both occupational and general exposure in the population. Imaging mass spectrometry was used in analysis of the sectioned tissue. The RHE model gave similar results compared to human skin ex vivo for skin penetration of CrVI. However, the penetration of CrIII into the tissue of the RHE model compared to human skin ex vivo differed markedly, such that in the RHE model the CrIII species accumulated in the tissue layer corresponding to stratum corneum whereas in human skin ex vivo, the CrIII species penetrated evenly through the skin tissue. Further, skin lipids such as cholesterol were less abundant in the RHE model compared to the human skin tissue. Results presented here indicate that the RHE models do not possess the same fundamental properties as human skin tissue. As the RHE models appear to be able to give false negative results, experiments using RHE models for the study of skin penetration should be evaluated with caution.

Interplay of water and reactive elements in oxidation of alumina-forming alloys.

High-temperature alloys are crucial to many important technologies that underpin our civilization. All these materials rely on forming an external oxide layer (scale) for corrosion protection. Despite decades of research on oxide scale growth, many open questions remain, including the crucial role of the so-called reactive elements and water. Here, we reveal the hitherto unknown interplay between reactive elements and water during alumina scale growth, causing a metastable 'messy' nano-structured alumina layer to form. We propose that reactive-element-decorated, hydroxylated interfaces between alumina nanograins enable water to access an inner cathode in the bottom of the scale, at odds with the established scale growth scenario. As evidence, hydride-nanodomains and reactive element/hydrogen (deuterium) co-variation are observed in the alumina scale. The defect-rich alumina subsequently recrystallizes to form a protective scale. First-principles modelling is also performed to validate the RE effect. Our findings open up promising avenues in oxidation research and suggest ways to improve alloy properties.

Repaired oesophageal atresia: respiratory morbidity and pulmonary function in adults.

Although after oesophageal atresia (OA) repair in infancy, respiratory problems are common, their natural history remains unclear. We assessed morbidity, pulmonary function (PF), and bronchial hyperresponsiveness (BHR) in adults with repaired OA respiratory. 588 patients who underwent surgery for OA during 1947-1985 were identified and those 262 who were alive and had their native oesophagus were included. Respiratory symptoms and respiratory symptom-related quality of life (RSRQoL) were assessed by questionnaire and interview, and the patients underwent spirometry, a histamine challenge test, and an exhaled nitric oxide test. For the questionnaires, we added 287 carefully matched general population-derived controls. Among the 101 (58 male) patients, median age 36 yrs (range 22-56 yrs), respiratory morbidity was significantly increased compared to controls. Patients had more respiratory symptoms and infections, as well as asthma and allergies, and more often impaired RSRQoL (p<0.001 for all). PF tests revealed restrictive ventilatory defect in 21 (21%) patients, obstructive ventilatory defect in 21 (21%) patients, and both in 36 (36%) patients. A total of 41 (41%) had BHR, and in 15 (15%), it was consistent with asthma. The most significant risk factors for restrictive ventilatory defect were thoracotomy-induced rib fusions (OR 3.4, 95% CI 1.3-8.7; p = 0.01) and oesophageal epithelial metaplasia (OR 3.0, 95% CI 1.0-8.9; p = 0.05). After repair of OA, respiratory-related morbidity, restrictive ventilatory defect and BHR extended into adulthood. Nearly half the patients had BHR and over half had a restrictive ventilatory defect. Thoracotomy-induced rib fusions and gastro-oesophageal reflux-associated oesophageal epithelial metaplasia were the strongest risk factors for restrictive ventilatory defect.

Mechanisms of asthma in Olympic athletes--practical implications.

Athletes' symptoms may only occur in extreme conditions, which are far from normal. Exercise may increase ventilation up to 200 l/min for short periods in speed and power athletes, and for longer periods in endurance athletes such as swimmers and cross-country skiers. Increasing proportions of young athletes are atopic, i.e. they show signs of IgE-mediated allergy which is, along with the sport event (endurance sport), a major risk factor for asthma and respiratory symptoms. Mechanisms in the etiology and clinical phenotypes vary between disciplines and individuals, and it may be an oversimplification to discuss athlete's asthma as a distinct and unambiguous disease. Nevertheless, the experience on Finnish Olympic athletes suggests at least two different clinical phenotypes, which may reflect different underlying mechanisms. The pattern of 'classical asthma' is characterized by early onset childhood asthma, methacholine responsiveness, atopy and signs of eosinophilic airway inflammation, reflected by increased exhaled nitric oxide levels. Another distinct phenotype includes late onset symptoms (during sports career), bronchial responsiveness to eucapnic hyperventilation test, but not necessarily to inhaled methacholine, and a variable association with atopic markers and nitric oxide. A mixed type of eosinophilic and neutrophilic airway inflammation seems to affect especially swimmers, ice-hockey players, and cross-country skiers. The inflammation may represent a multifactorial trauma, in which both allergic and irritant mechanisms play a role. There is a significant problem of both under- and overdiagnosing asthma in athletes and the need for objective testing is emphasized. Follow-up studies are needed to assess the temporal relationship between asthma and competitive sporting, taking better into account individual disposition, environmental factors (exposure), intensity of training and potential confounders.

Daily versus as-needed inhaled corticosteroid for mild persistent asthma (The Helsinki early intervention childhood asthma study).

OBJECTIVE: To compare the effect of inhaled budesonide given daily or as-needed on mild persistent childhood asthma. Patients, design and INTERVENTIONS: 176 children aged 5-10 years with newly detected asthma were randomly assigned to three treatment groups: (1) continuous budesonide (400 microg twice daily for 1 month, 200 microg twice daily for months 2-6, 100 microg twice daily for months 7-18); (2) budesonide, identical treatment to group 1 during months 1-6, then budesonide for exacerbations as needed for months 7-18; and (3) disodium cromoglycate (DSCG) 10 mg three times daily for months 1-18. Exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. MAIN OUTCOME MEASURES: Lung function, the number of exacerbations and growth. RESULTS: Compared with DSCG the initial regular budesonide treatment resulted in a significantly improved lung function, fewer exacerbations and a small but significant decline in growth velocity. After 18 months, however, the lung function improvements did not differ between the groups. During months 7-18, patients receiving continuous budesonide treatment had significantly fewer exacerbations (mean 0.97), compared with 1.69 in group 2 and 1.58 in group 3. The number of asthma-free days did not differ between regular and intermittent budesonide treatment. Growth velocity was normalised during continuous low-dose budesonide and budesonide therapy given as needed. The latter was associated with catch-up growth. CONCLUSIONS: Regular use of budesonide afforded better asthma control but had a more systemic effect than did use of budesonide as needed. The dose of ICS could be reduced as soon as asthma is controlled. Some children do not seem to need continuous ICS treatment.

Respiratory symptoms, bronchial hyper-responsiveness, and eosinophilic airway inflammation in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Patients with atopic dermatitis (AD) often have symptoms suggestive of asthma or rhinitis. The prevalence and signs of respiratory disease in AD patients have been studied to a limited extent. OBJECTIVES: To assess the prevalence and clustering of respiratory symptoms, bronchial hyper-responsiveness (BHR), and eosinophilic airway inflammation in patients with moderate-to-severe AD. METHODS: Eighty-six consecutive patients with moderate-to-severe AD and 49 randomly selected control subjects without AD were studied by questionnaire, flow volume spirometry, histamine challenge to detect BHR, induced sputum test to detect eosinophilic airway inflammation, and skin prick tests (SPTs) and total serum immunoglobulin (Ig)E measurements to detect atopy. RESULTS: The patients with AD showed increased risk of physician-diagnosed asthma (36% vs. 2%, odds ratio (OR) 10.1, confidence interval (CI) 1.3-79.7, P=0.03), physician-diagnosed allergic rhinitis (AR) (45% vs. 6%, OR 4.5, CI 1.2-16.7, P=0.02), BHR (51% vs. 10%, OR 5.5, CI 1.5-20.1, P=0.01), and sputum eosinophilia (81% vs. 11%, OR 76.1, CI 9.3-623.5, P<0.0001) compared with the control subjects. In AD patients, elevated s-IgE and positive SPTs were associated with the occurrence of physician-diagnosed asthma and AR, BHR, and the presence of sputum eosinophilia. CONCLUSIONS: BHR and eosinophilic airway inflammation are more common in patients with AD than in control subjects. The highest prevalences were seen in patients with AD who were SPT positive and had high IgE levels. Longitudinal studies are needed to assess the outcome of patients with signs of airway disease, in order to identify those who need early initiation of asthma treatment.

Silver deposition on freeze-dried cells allows subcellular localization of cholesterol with imaging TOF-SIMS.

Imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used for characterization and subcellular localization of organic ions in leucocytes adhering to glass surfaces. The cells were fixed by freeze drying in 0.15 m ammonium formate buffer at pH 7.2-7.4. The freeze-dried cells were sputter-coated with silver, and the silver surface was analysed with imaging TOF-SIMS. TOF-SIMS spectra were recorded by scanning the primary ion beam over the analysis area and acquiring positive mass spectra of the ions leaving the surface. The relative brightness of each pixel within the analysis area reflects the signal intensity of a selected ion in that pixel. Data were collected separately at high mass resolution m/delta m > 7000 and at high lateral resolution (= 0.5 micro m). The images were analysed by principal component analysis (PCA). The glass-adhering cells showed a well defined attachment area with a diameter of up to 20 micro m, and an equally well defined cell body, containing the nucleus, with a diameter of 8-10 micro m. On the raw data images, the obtained cholesterol distributions were consistent with a higher cholesterol content of the cell membrane in the attachment area than in the cell body. Using PCA analysis, silver-cationized molecular cholesterol was found localized mainly in the attachment area of the cells. Cholesterol was also seen at higher concentration in circular spots of

Dampness in buildings as a risk factor for health effects, EUROEXPO: a multidisciplinary review of the literature (1998-2000) on dampness and mite exposure in buildings and health effects.

UNLABELLED: The scientific literature on health effects from dampness in buildings, including mite exposure over the period 1998-2000 has been reviewed by an European group (EUROEXPO) of eight scientists in experience from medicine, epidemiology, toxicology and engineering. Forty studies deemed relevant have been the foundation for the conclusions. Dampness in buildings is a risk factor for health effects among atopics and non-atopics both in domestic and in public environments. However, the literature is not conclusive in respect of causative agents, e.g. mites, microbiological agents and organic chemicals from degraded building materials. There is a strong need for more multidisciplinary studies including expertise from all relevant areas. A general conclusion from the work was that there is a strong need for multidisciplinary reviews in scientific journals of articles dealing with associations between indoor environmental factors and health effects. PRACTICAL IMPLICATIONS: There is good evidence for a true association between dampness in buildings and health. As the causative factors behind this association are not known, the main focus in practical investigations should be on finding out and remediate the reasons for the humidity problem.

Prevalence of symptoms, sensitization to rats, and airborne exposure to major rat allergen (Rat n 1) and to endotoxin in rat-exposed workers: a cross-sectional study.

OBJECTIVE: To analyse the relation between airborne exposure to major rat allergen and to endotoxins in exclusively rat-exposed workers and the prevalence of rat-related symptoms and sensitization. METHODS: A total of 113 workers answered a standardized questionnaire on their atopy status, occupational exposure to rats, and possible work-related symptoms. Specific IgE against rat urinary proteins (RUP) was measured for 73 subjects. Individual airborne exposure to Rat n 1 and endotoxin were determined with static (n = 256) samplings. Rat n 1 was measured with enzyme-linked immunosorbent assay (ELISA) and endotoxin by the Limulus method. RESULTS: Forty-four of 113 subjects (38.9%) reported at least one rat-related symptom: asthma (4.4%), rhinitis (34%) and conjunctivitis (16%). Twelve per cent were sensitized to RUP (specific IgE > 0.35 KU/L). But only 30.8% of all symptomatic subjects were sensitized to rat allergens. Airborne Rat n 1 levels were not related to symptoms in workers. Symptomatic patients not sensitized to rats were exposed to higher endotoxin levels, but airborne exposure to endotoxins did not significantly protect against or increase sensitization to RUP or rat-related symptoms. CONCLUSION: Most symptomatic workers were not sensitized to rat allergen; but no significant relation between rat-related symptoms and endotoxin levels was found. This suggests that more studies are needed to determine causes other than rat allergens or endotoxins that may be responsible for symptoms in rat-exposed workers.

Comparison of airway conductance and FEV(1) as measures of airway responsiveness to methacholine. Discrimination of small differences in bronchial responsiveness with Gaw and FEV(1).

When defining bronchial responsiveness in healthy, non-asthmatic, subjects exposed in different working situations, it is not clear whether different outcome measures yield similar results. Therefore, the concentration and dose of methacholine that caused a 20% decrease in forced expiratory volume in 1 s (FEV(1)) (PC20(FEV(1)) and PD20(FEV(1))), the corresponding change in Gaw and the relationship between the dose-response slope (DRS) for FEV(1) and Gaw was studied in different working populations and healthy control subjects (n=1038). The two outcome measures were compared in groups of subjects in whom differences in bronchial responsiveness could be anticipated [atopics (n=72) and non-atopics (n= 207) and subjects exposed (n=54) and not exposed (n=32) to saw dust]. A bronchial challenge was also made before and after exposure in a swine confinement building, an exposure known to increase bronchial responsiveness (n=37). PD20(FEV(1)) was 1.7 mg in atopics and 4.9 mg in non-atopics, 7.1 mg in saw dust exposed and >20 mg in non-exposed subjects and 5.3 mg before and 0.79 mg after exposure to organic dust. There was a correlation between DRS(FEV(1)) and DRS(Gaw), r=0.87 (P<0.001). In subjects who were highly sensitive to methacholine a 20% change in FEV(1) corresponded to <40% change in Gaw, while a 20% decrease in FEV1 corresponded to none or a minor decrease in Gaw in subjects with less methacholine-sensitive airways. The ability to detect differences in bronchial responsiveness between groups, or to detect changes in bronchial responsiveness following exposure was approximately the same for FEV(1) and Gaw. The reproducibility was similar for both variables and a second measurement was within one doubling of the methacholine concentration of the first provocation in approximately 95% of all measurements (n=41). In conclusion, with our methacholine provocation method, FEV(1) and Gaw had similar sensitivity in detecting small differences in bronchial responsiveness in healthy subjects.

Difference in exposure to airborne major rat allergen (Rat n 1) and to endotoxin in rat quarters according to tasks.

UNLABELLED: Endotoxins found in occupational settings constitute a risk factor in the severity of respiratory allergic symptoms. OBJECTIVES: To assess the airborne concentrations of major rat allergen (Rat n 1) and endotoxin under various circumstances. METHODS: We took 483 airborne samples from 12 sites: 114 individual samples for endotoxin measurements and 113 for Rat n 1, from 38 workers (nine animal technicians, nine laboratory technicians, nine scientists and 11 students); and 256 static samples in rat rooms and experimental rooms, with or without disturbance, for simultaneous endotoxin and Rat n 1 measurements. Rat n 1 was measured with a two-site monoclonal ELISA and endotoxins with the Limulus method. RESULTS: Airborne Rat n 1 and endotoxin were significantly higher in rat rooms than in experimental rooms. Animal technicians had the greatest exposure to both Rat n 1 and endotoxin. Cage cleaning and rat feeding induced the highest exposure to Rat n 1 and endotoxin. Furthermore, we observed no significant difference in endotoxin exposure between researchers with or without rat contact during the sample period. There was no correlation between the number of rats present and airborne endotoxin concentrations. CONCLUSIONS: Exposure to airborne Rat n 1 and endotoxin is higher during cleaning and feeding tasks than during any other task, we feel that a major source of both is contaminated bedding that becomes airborne during disturbance.

Working with male rodents may increase risk of allergy to laboratory animals.

BACKGROUND: Our aim was to study the risk of laboratory animal allergy (LAA) among research staff working in laboratories separate from the animal confinement area. The roles of atopy and exposure intensity in LAA were studied with special regard to exposure to male rodents, who excrete higher levels of urinary allergens than female rodents. METHODS: Eighty rodent-exposed subjects gave blood samples for the analysis of total IgE, Phadiatop, and specific IgE against rat (RUA) and mouse urinary allergens (MUA), and answered questionnaires. Air samples were collected for RUA and MUA aeroallergen measurement in both laboratories and animal confinement facilities. RESULTS: Twenty percent of the subjects had IgE >0.35 kU/l to RUA and/or MUA, and 32% had experienced animal work-related symptoms, although 90% of aeroallergen samples from the research department laboratories were below the detection limit (<0.26 ng RUA per m(3) and <0.8 ng MUA per m(3)). Atopy (positive Phadiatop), total IgE >100 kU/l, other allergies (especially to other animals), or more than 4 years of exposure significantly increased laboratory animal sensitization and symptoms. Working with mainly male rodents gave odds ratios (95% CI) of 3.8 (0.97-15) for sensitization and 4.4 (1.4-14) for symptoms. Subjects with both exposure to mainly male rodents and atopy or elevated total IgE had a 10-fold higher frequency of sensitization than exposed subjects with neither risk factor. CONCLUSION: A majority of subjects with a combination of exposure to mainly male rodents and atopy or elevated total IgE developed sensitization to and symptoms from laboratory animals. Current low exposure seems to maintain the presence of specific IgE. Further measures must be undertaken to provide a safe workplace for laboratory animal workers.

Dampness in buildings and health. Nordic interdisciplinary review of the scientific evidence on associations between exposure to "dampness" in buildings and health effects (NORDDAMP).

Several epidemiological investigations concerning indoor environments have indicated that "dampness" in buildings is associated to health effects such as respiratory symptoms, asthma and allergy. The aim of the present interdisciplinary review is to evaluate this association as shown in the epidemiological literature. A literature search identified 590 peer-reviewed articles of which 61 have been the foundation for this review. The review shows that "dampness" in buildings appears to increase the risk for health effects in the airways, such as cough, wheeze and asthma. Relative risks are in the range of OR 1.4-2.2. There also seems to be an association between "dampness" and other symptoms such as tiredness, headache and airways infections. It is concluded that the evidence for a causal association between "dampness" and health effects is strong. However, the mechanisms are unknown. Several definitions of dampness have been used in the studies, but all seems to be associated with health problems. Sensitisation to mites may be one but obviously not the only mechanism. Even if the mechanisms are unknown, there is sufficient evidence to take preventive measures against dampness in buildings.

Worsening of asthma in children allergic to cats, after indirect exposure to cat at school.

Exposure to cat allergen at school might exacerbate symptoms in asthmatic children with cat allergy. To study this, we identified 410 children, 6-12 yr of age, who were being treated for asthma (inhaled steroids and beta-agonists), were allergic to cats, and had no cat at home. Peak expiratory flow (PEF), asthma symptoms, medication, fever and/or sore throat, and contact with furred pets were recorded twice daily during the last week of summer holidays and the second and third weeks of school. The number of cat owners in each class was recorded. Ninety-two children with asthma reported no contact with furred pets. Among these, children who attended classes with > 18% (median value) cat owners reported significantly decreased PEF, more days with asthma symptoms, and increased use of medication after school started. Those in classes with < or = 18% cat owners reported no change. Children in classes with many cat owners ran a 9-fold increased risk of exacerbated asthma after school start compared with children in classes with few cat owners, after adjusting for age, sex, and fever and/or sore throat. Thus, asthma symptoms, PEF, and the use of asthma medication in children with cat allergy may be affected by indirect cat exposure at school.

Impact of occupation on respiratory disease.

OBJECTIVES: This study identified occupations with a marked impact on sick leaves due to respiratory disease. METHODS: A national sick-leave register containing information on all sick leaves exceeding 14 days, physicians' diagnoses, and the occupational status of all manual and service employees in the private sector in Sweden was studied. Sick leaves during 1992-1994 (N=210,755) were analyzed with special attention to respiratory disease and occupation. RESULTS: Respiratory disease accounted for 4.4% of the total number of sick leaves. The incidence of long-term (> or = 90 days) sick leaves due to respiratory disease was 3 times higher in occupations with a high incidence than in those with a low incidence. There was a high correlation (r=0.80) between the incidence of long-term sick leave due to respiratory disease and sick leave due to all other conditions; this finding suggests that market and selection factors may play an important role in determining the overall risk for sick leave in various occupations. The proportion of sick leaves due to long-term respiratory disease out of all long-term disease was compared between occupations. Agricultural workers had a 46% higher proportion of long-term respiratory disease than metal workers. Industrial workers, food industry workers, and painters were also occupations with an increased risk. These findings could not be explained by differences in age or smoking habits. CONCLUSIONS: Major differences were found among manual and service occupations regarding long-term sick leave due to respiratory disease. Several occupations, in which exposure to respiratory sensitizers and irritants are known to occur, were among those in which workers had an increased risk for long-term respiratory disease.

Is asthma underestimated as a cause of sick leave?

Public interest needs to be focused on the economic burden of asthma on society because of the increasing prevalence of the condition. Asthma is common in individuals of working age and sick leave is an important health-economic issue. In the present study we looked at the prevalence of asthma in a sick leave register. Individuals on sick leave due to asthma, individuals on sick leave due to any other respiratory disorder or symptom and individuals on sick leave due to non-respiratory conditions were included in a questionnaire based study. Individuals in the register diagnosed with asthma could be classified as current asthmatics or possible asthmatics in respectively 94% and 99% of the cases. They were also ex-smokers to a greater extent than the other groups, which was more pronounced in males. However, individuals on sick leave due to 'any other respiratory disorder' could be classified as current asthmatics or possible asthmatics in respectively 19% and 30% of the cases. The corresponding figures in the group on sick leave due to 'other diagnoses' were 7% and 10%. Hence, there is evidence that asthma is an under-reported diagnosis and this must be taken into consideration when sick leave registers are used in health-economic studies.

Different response to doubling and fourfold dose increases in methacholine provocation tests in healthy subjects.

RATIONALE: In a modified methacholine provocation test that was used to study changes in airway responsiveness to occupational irritants or sensitizers in healthy subjects, two protocols were used: a long protocol (doubling methacholine concentrations between dose steps) or a short protocol (fourfold increases in concentration). This modified methacholine provocation allows measurements of the provocative dose causing 20% decrease in FEV(1) (PD(20)) in a high proportion of a normal population. METHODS: The distribution of PD(20) was investigated in healthy nonatopic men without history of allergy or asthma symptoms using the long protocol (n = 101) or the short protocol (n = 309). In addition, 30 healthy subjects underwent methacholine provocation tests using both protocols. RESULTS: PD(20) was defined in 79% of subjects with the long protocol and in 48% of subjects with the short protocol. The provocative concentration of methacholine causing a 20% decline in FEV(1) (PC(20)) and PD(20) were significantly lower using the long protocol: long-protocol PC(20) (median [25th to 75th percentile]), 19.9 mg/mL (3.9 to > 32 mg/mL) compared with short-protocol PC(20), > 32 mg/mL (8.7 to >32 mg/mL; p < 0.0001); long-protocol PD(20), 4.2 mg (1.6 to 20 mg) compared with short-protocol PD(20), > 13.7 (2.6 to > 13.7 mg; p = 0. 006). The differences in PD(20) using short and long protocols were confirmed in a randomized trial of 30 healthy subjects tested with both protocols. CONCLUSION: Using doubling concentrations, PC(20) and PD(20) could be defined in a higher proportion of healthy subjects than a protocol using fourfold dose increases. Furthermore, the doubling protocol results in a PD(20) estimate that is less than half the value obtained when using a protocol with fourfold concentrations between dose steps. The difference remains, whether the methacholine effect is regarded as cumulative or noncumulative. The explanation for the difference between the protocols is unclear.

The salt output of a nebulizer--a comparison between two nebulizer types.

The output of a nebulizer is generally defined as its weight loss during 1 min of nebulization. This mass output includes the weight loss due to evaporation of the solution required to moisten the dry air that is fed through the nebulizer. In order to compare results obtained from studies using different nebulizers we introduce the salt output as the amount of the solution that actually leaves the liquid phase as droplets and not by evaporation. The performance characteristics of a standard jet nebulizer (MA2) and a Sidestream jet neublizer were compared. Mass output was determined at different methacholine concentrations. Salt output was assessed by analysing the remaining salt in the nebulizers after 1 min of nebulization. Overall system performance in terms of forced expiratory volume in 1 sec (FEV1) reduction after 1 min of exposure to individually selected concentrations of methacholine were studied in 15 healthy, non-smoking subjects. Both nebulizer types showed a moderate linear increase of mass output with methacholine concentration. The efficiency coefficient, the quotient between salt output and mass output, was found to be 0.93 and 0.75 for the MA2 and Sidestream nebulizer respectively. These findings were explained by differences in airflow through, and temperature inside, the nebulizers. The salt output of the nebulizers proved to be better correlated to the FEV1-reduction following methacholine inhalation than did the mass output. The relative amount of the salt output that adhered to the acrylic walls of the Sidestream nebulizer drying tower was found to be 9%. We conclude that it is more appropriate to use salt output than mass output as a nebulizer performance descriptor. The study also shows the importance of determining nebulizer system performance under conditions as similar to true provocations as possible.

Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo.

Physical training increases free radical production and consumes antioxidants. It has previously been shown that acute exercise markedly increases the susceptibility of LDL to oxidation but whether such changes are observed during physical training is unknown. We measured circulating antioxidants, lipids and lipoproteins, and blood flow responses to intrabrachial infusions of endothelium-dependent (acetylcholine, ACh, L-N-monomethyl-arginine, L-NMMA) and -independent (sodium nitroprusside, SNP) vasoactive agents, before and after 3 months of running in 9 fit male subjects. Maximal aerobic power increased from 53 +/- 1 to 58 +/- 2 ml/kg min (P < 0.02). All circulating antioxidants (uric acid, SH-groups, alpha-tocopherol, beta-carotene, retinol) except ascorbate decreased significantly during training. Endothelium-dependent vasodilatation in forearm vessels decreased by 32-35% (P < 0.05), as determined from blood flow responses to both a low (10.8 +/- 2.1 vs. 7.3 +/- 1.5 ml/dl min, 0 vs. 3 months) and a high (14.8 +/- 2.6 vs. 9.6 +/- 1.8) ACh dose. The % endothelium-dependent blood flow (% decrease in basal flow by L-NMMA), decreased through training from 37 +/- 3 to 22 +/- 7% (P < 0.05). Blood flow responses to SNP remained unchanged. The decrease in uric acid was significantly correlated with the change in the % decrease in blood flow by L-NMMA (r = 0.74, P < 0.05). The lag time for the susceptibility of plasma LDL to oxidation in vitro, LDL size and the concentration of LDL cholestetol remained unchanged. We conclude that relatively intense aerobic training decreases circulating antioxidant concentrations and impairs endothelial function in forearm vessels.