Total desmosines in plasma and urine correlate with lung function.

The aim of the present study was to evaluate the relationship between the matrix degradation biomarkers, desmosine and isodesmosine (desmosines), and lung function. Plasma and creatinine-corrected urinary total desmosines (P- and U-desmosines, respectively), lung function and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were measured in a cohort of subjects from the Swedish Twin Registry. Concentrations of U- and P-desmosines were measured in 349 and 318 subjects, respectively; approximately one-third of subjects had chronic obstructive pulmonary disease (COPD). Age, female sex, body mass index (BMI) and smoking were significantly associated with U-desmosines in a multiple linear regression analysis. In the overall population, after adjustments for age, sex, height, BMI and smoking, concentrations of U-desmosines were significantly correlated with all lung function measures, and P-desmosines with forced expiratory volume in 1 s and D(L,CO) (p<0.05). With the exception of residual volume versus P-desmosines, relationships between concentrations of desmosines and lung function measures were markedly stronger in subjects with COPD compared with those without COPD. These cross-sectional data showing associations between desmosines and several lung function variables suggest that desmosines, particularly U-desmosines, could be a useful biomarker of COPD status.

Health effects of a subway environment in healthy volunteers.

Environmental particle exposure, often estimated as the particulate mass of particles with a diameter <10 microm, <2.5 microm or <1 microm (PM(10), PM(2.5) or PM(1)), is known to have a negative impact on the health of the population. Little is known about how the size and origin of particles influence the effects. We have previously shown that exposure to a road tunnel environment causes a cellular inflammatory response in the airways of healthy individuals. In the present study, our aim was to investigate potential airway health effects from exposure to a subway environment. 20 healthy volunteers were exposed to a subway and a control environment for 2 h, followed by measurements of lung function and the inflammatory response in the lower airways (bronchoscopy) and in the peripheral blood. No cellular response was found in the airways after exposure to the subway environment. In the blood, we found a statistically significant increase in fibrinogen and regulatory T-cells expressing CD4/CD25/FOXP3. Subway and road tunnel environments have similar levels of PM(10) and PM(2.5), whilst the concentrations of ultrafine particles, nitrogen monoxide and dioxide are lower in the subway. Although no cellular response was detected, the findings indicate a biological response to the subway environment. Our studies show that using gravimetric estimates of ambient particulate air pollution alone may have clear limitations in health-risk assessment.

Physical workload, low back pain and neck-shoulder pain: a Swedish twin study.

OBJECTIVES: To investigate if high physical workload is associated with low back pain (LBP) and/or neck-shoulder pain (NSP) when taking into account the influence of genetic and shared environmental factors. Further, the study aims to explore the potential influence of genetic and shared environmental factors in the associations between high physical workload and the three disorder subgroups: solely LBP, solely NSP, and concurrent LBP and NSP. METHODS: Data on 16,107 monozygotic and dizygotic twins, born during 1959-1985, were obtained from a cross-sectional study, performed in 2005-2006 by the Swedish Twin Registry. Odds ratios (ORs) calculated in cohort analyses and co-twin control analyses were used to assess the associations between high physical workload and LBP and NSP when controlling for genetic and shared environmental factors. RESULTS: In the cohort analysis, the association between high physical workload and the group with any one symptom (LBP and/or NSP) was OR 1.47 (95% CI 1.37 to 1.57). The co-twin control analyses indicated that the association was not confounded by genetic and shared environmental factors with OR 1.34 (95% CI 1.02 to 1.75) for dizygotic twins and OR 1.44 (95% CI 1.06 to 1.95) for monozygotic twins. In the cohort analyses the association with high physical workload was higher for concurrent LBP and NSP (OR 1.80 (95% CI 1.62 to 1.99)) than for solely LBP (OR 1.41 (95% CI 1.27 to 1.57)) and solely NSP (OR 1.31 (95% CI 1.20 to 1.43)). Concurrent LBP and NSP was the only group that showed a stepwise decrease of the point estimates between the cohort analysis and the co-twin control analyses, OR 1.71 (95% CI 1.00 to 2.94) for dizygotic twins, and OR 1.29 (95% CI 0.64 to 2.59) for monozygotic twins indicating confounding by genetic and shared environmental factors. CONCLUSIONS: High physical workload was associated with LBP and/or NSP even after adjusting for genetic or shared environmental factors. Only for concurrent LBP and NSP, genetic and shared environmental factors seemed to have an influence on the association with high physical workload.

Exposure to Particles and Nitrogen Dioxide Among Workers in the Stockholm Underground Train System.

OBJECTIVES: Exposure to fine particles in urban air has been associated with a number of negative health effects. High levels of fine particles have been detected at underground stations in big cities. We investigated the exposure conditions in four occupational groups in the Stockholm underground train system to identify high-exposed groups and study variations in exposure. METHODS: PM1 and PM2.5 were measured during three full work shifts on 44 underground workers. Fluctuations in exposure were monitored by a real-time particle monitoring instrument, pDR, DataRAM. Qualitative analysis of particle content was performed using inductively coupled plasma mass spectrometry. Nitrogen dioxide was measured using passive monitors. RESULTS: For all underground workers, the geometric mean (GM) of PM1 was 18 µg/m3 and of PM2.5 was 37 µg/m3. The particle exposure was highest for cleaners/platform workers, and the GM of PM1 was 31.6 µg/m3 [geometric standard deviation (GSD), 1.6] and of PM2.5 was 76.5 µg/m3 (GSD, 1.3); the particle exposure was lowest for ticket sellers, and the GM of PM1  was 4.9 µg/m3 (GSD, 2.1) and of PM2.5 was 9.3 µg/m3 (GSD, 1.5). The PM1 and PM2.5 levels were five times higher in the underground system than at the street level, and the particles in the underground had high iron content. The train driver's nitrogen dioxide exposure level was 64.1 µg/m3 (GSD, 1.5). CONCLUSIONS: Cleaners and other platform workers were statistically significantly more exposed to particles than train drivers or ticket sellers. Particle concentrations (PM2.5) in the Stockholm underground system were within the same range as in the New York underground system but were much lower than in several older underground systems around the world.

Blood markers of inflammation and coagulation and exposure to airborne particles in employees in the Stockholm underground.

OBJECTIVES: Although associations have been found between levels of ambient airborne particles and cardiovascular disease (CVD) in the general population, little is known about possible cardiovascular effects from high exposure to particles in underground railway systems. This study investigates risk markers for CVD in employees exposed to particles in the Stockholm underground system. METHODS: 79 workers (54 men and 25 women) in the Stockholm underground were investigated between November 2004 and March 2005. All were non-smokers aged 25-50 years. Three exposure groups were delineated: 29 platform workers with high exposure to particles, 29 train drivers with medium exposure and 21 ticket sellers with low exposure (control group). A baseline blood sample was taken after 2 non-working days, and a second sample after 2 working days, for analysis of levels of plasminogen activator inhibitor-1 (PAI-1), high-sensitivity C-reactive protein (hs-CRP), interleukin-6, fibrinogen, von Willebrand factor and factor VII. The study investigated changes in plasma concentrations between sample 1 and sample 2, and differences in average concentrations between the groups. RESULTS: No changes between sample 1 and 2 were found that could be attributed to particle exposure. However, the highly exposed platform workers were found to have higher plasma concentrations of PAI-1 and hs-CRP than the ticket sellers and train drivers. This suggests that particle exposure could have a long-term inflammatory effect. These differences remained for PAI-1 in the comparison between platform workers and ticket sellers after adjusting for body mass index. CONCLUSIONS: Employees who were highly exposed to airborne particles in the Stockholm underground tended to have elevated levels of risk markers for CVD relative to employees with low exposure. However, the differences observed cannot definitely be linked to particle exposure as such.

Mortality, morbidity and occupational exposure to airway-irritating agents among men with a respiratory diagnosis in adolescence.

OBJECTIVES: To examine the influence of an airway diagnosis in adolescence on future health and occupation in Swedish men. METHODS: Data were collected from the linkage of four Swedish national registers: the Military Service Conscription Register, the Population and Housing Censuses, the Inpatient Care Register and the National Cause of Death Register. A job-exposure matrix for airway-irritating substances was developed for application on the conscription cohort. The cohort included 49 321 Swedish men born 1949-51. Three groups-(1) healthy, (2) asthmatics (mild and severe asthma) and (3) subjects with allergic rhinitis without concurrent asthma-were identified at conscription and analysed for mortality, in-patient care and strategies for choice of occupation with emphasis on airway-irritating job exposure. Analyses were adjusted for smoking and childhood socioeconomic position. RESULTS: The prevalence of total asthma was 1.8%, severe asthma 0.45% and allergic rhinitis 2.7%. Mortality for all causes was significantly higher in total asthma, hazard ratio (HR) 1.49 (95% CI 1.00 to 2.23), and lower in allergic rhinitis, HR 0.52 (95% CI 0.30 to 0.91). Asthma was a risk factor for inpatient care while allergic rhinitis was associated with less in-patient care (odds ratio (OR) for total asthma 1.16 (95% CI 1.00 to 1.34), severe asthma 1.38 (95% CI 1.04 to 1.85), allergic rhinitis 0.92 (95% CI 0.82 to 1.03)). Those with asthma tended to avoid jobs with a high probability for airway-irritating exposure (OR 0.88, 95% CI 0.71 to 1.09), but not to the same extent as subjects with allergic rhinitis (OR 0.58, 95% CI 0.47 to 0.70) (ORs from 1990). CONCLUSION: Subjects with asthma did not change their exposure situation to the same extent as subjects with allergic rhinitis. Further, asthmatics had an increased risk for morbidity and mortality compared to healthy subjects and subjects with allergic rhinitis.

Sleep as a predictive factor for the onset and resolution of multi-site pain: a 5-year prospective study.

BACKGROUND: Disturbed sleep and pain often co-exist and the relationship between the two conditions is complex and likely reciprocal. This 5-year prospective study examines whether disturbed sleep can predict the onset of multi-site pain, and whether non-disturbed sleep can predict the resolution of multi-site pain. METHODS: The cohort (n = 1599) was stratified by the number of self-reported pain sites: no pain, pain from 1-2 sites and multi-site pain (≥3 pain sites). Sleep was categorized by self-reported sleep disturbance: sleep A (best sleep), sleep B and sleep C (worst sleep). In the no-pain and pain-from-1-2 sites strata, the association between sleep (A, B and C) and multi-site pain 5 years later was analysed. Further, the prognostic value of sleep for the resolution of multi-site pain at follow-up was calculated for the stratum with multi-site pain at baseline. In the analyses, gender, age, body mass index, smoking, physical activity and work-related exposures were treated as potential confounders. RESULTS: For individuals with no pain at baseline, a significantly higher odds ratio for multi-site pain 5 years later was seen for the tertile reporting worst sleep [odds ratio (OR) 4.55; 95% confidence interval (CI) 1.28-16.12]. Non-disturbed (or less disturbed) sleep had a significant effect when predicting the resolution of multi-site pain (to no pain) (OR 3.96; 95% CI 1.69-9.31). CONCLUSION: In conclusion, sleep could be relevant for predicting both the onset and the resolution of multi-site pain. It seems to be a significant factor to include in research on multi-site pain and when conducting or evaluating intervention programmes for pain.

Regional deposition of 3.6-micron particles and lung function in asthmatic subjects.

In a group of moderately severe asthmatic subjects, regional deposition of 3.6-microns (aerodynamic diameter) monodispersed Teflon particles labeled with 111In was studied twice. The particles were inhaled with maximally deep inhalation at 0.5 l/s. Lung retention was measured at 0, 6, 24, and 48 h by use of a profile scanner equipped with two 13 x 5-cm NaI crystals. The retentions at 24 (Ret24) and 48 h were highly correlated (r = 0.96 with a slope of the regression line close to 1). There was a poor correlation between retention at 6 h and Ret24 (r = 0.54). The Ret24 values at the two exposures were well correlated (r = 0.86). There were significant correlations between airway resistance as well as single-breath nitrogen test phase III and Ret24 (r = 0.70 and 0.67, respectively). The correlation between single-breath nitrogen test phase III and Ret24 persisted also when only subjects within a narrow interval of airway resistance were included. The study indicates that regional deposition can be studied by measurements of Ret24 in subjects with moderately severe asthma and that it is dependent on changes in both large and small airways.

Inhalation and deposition of nebulized sodium cromoglycate in two different particle size distributions in children with asthma.

The relative deposition of two inhaled droplet size distributions of sodium cromoglycate produced by a Hudson Updraft II nebulizer was evaluated, using a setup modified from the proposed Comité Européen Normalisé (CEN) standard prEN 13544-1. The modified setup comprised an Andersen 296 impactor and a Spira Electro 2 dosimeter. The setup was characterized prior to use in children with sodium cromoglycate (SCG) and sodium fluoride as tracer aerosol. The main in vivo study was designed to allow nine children with a mean age of 10 years to inhale SCG aerosol at two different relative humidities (RH), a high RH (> 90%) and a low RH (13%), which in turn resulted in two different droplet size distributions. The nebulizer/dosimeter was set to provide 1-sec nebulization during 50 inhalations. Throughout the exposures, the children were instructed to inhale in a consistent manner with target tidal volumes (0.5 L) and inhalation flows (0.4 L/sec). Blood samples were taken at predefined time intervals, and the area under the curve (AUC) was calculated. A lung deposition program, TGLD2, was used to calculate the expected deposition, using the droplet sizes and inhalation parameters obtained during in vivo exposures. The in vivo monitoring of droplet size distribution during the exposure showed that the low, intermediate (room air), and high RHs gave a mean droplet size distribution with a mass median aerosol diameter (MMAD) of 1.2, 1.7, and 2.0 microm, respectively. The average tidal volume over all exposures was 0.51 +/- 0.12 L. The total deposition fraction was 33.4% of the estimated nebulizer output. A correlation was found between tidal volume and the calculated deposited fraction. The results indicate that there is a difference in total deposition, depending on the size of the droplet size distribution, with the larger droplet size distribution (MMAD, 2.0 microm) having a higher total deposition than the smaller droplet size distribution (MMAD, 1.2 microm). The deposition results were in good agreement with the deposition fractions estimated using the TGLD2 software for the inhalation parameters found in the study. The obtained study results can arise from differences in regional deposition, but may also be explained by differences in extrathoracic deposition.

Ambient level of NO2 augments the inflammatory response to inhaled allergen in asthmatics.

Air pollution constitutes an important factor for asthma aggravation, and there is increased concern about respiratory health effects of common air pollutants. The purpose of this study was to examine how exposure to a high ambient concentration nitrogen dioxide (NO2) prior to a bronchial allergen challenge modulated the inflammatory response in the bronchi. Thirteen subjects with mild asthma and allergy were exposed at rest to either purified air or 500 microg x m 3 NO2 for 30 min, followed 4 h later by an allergen inhalation challenge. The exposures (NO2 or air) were performed in random order and at least 4 weeks apart. Lung function during NO2/air exposure and allergen challenge was measured by plethysmography, and then hourly by portable spirometry after exposures. Subjective symptoms were recorded during and after exposure. Bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 19 h after allergen challenge. NO2+allergen enhanced the percentage of neutrophils in both BW and BAL compared to air+allergen (BW 19 vs. 11, P=0.05; BAL 3 vs. 1, P=0.02 median values). The levels of eosinophil cationic protein (ECP) in BW was higher after NO2+allergen compared to air+allergen (90 vs. 3.6 microg/l; P=0.02, median values). There was no NO2-associated effect on symptoms or pulmonary function. These data suggest that ambient NO2 can enhance allergic inflammatory reaction in the airways without causing symptoms or pulmonary dysfunction.

Methylations in hemoglobin from monozygotic twins discordant for cigarette smoking: hereditary and tobacco-related factors.

Dose monitoring of exogenous methylators by measurement of N-methylvaline in hemoglobin (Hb) is rendered difficult due to a relatively high, variable background in unexposed persons. A kinetic study indicates intracellular S-adenosylmethionine to be a main source of these background methylations. A comparison of twin pairs indicates that the variation in methylvaline levels is partly hereditary (P less than 0.001). Therefore, in a study of monozygotic twin pairs discordant for tobacco smoking the resolving power of the monitoring was increased and in vivo doses of methylators from the smoke could be more easily monitored through their adducts to Hb. Probably, twin studies offer a useful tool for the identification and quantification of electrophiles of endogenous and exogenous origin.

Decreased blood lead levels in residents of Stockholm for the period 1980-1984.

A number of measures have been taken to decrease the spread of lead to ambient air and food. In a study of the effect of these and other preventive measures, blood samples from approximately 100 persons living in the inner city area of Stockholm were collected and analyzed for lead content on three different occasions, in 1980, 1983, and 1984. The same subjects were examined on at least two occasions and the analytical method, atomic absorption spectrophotometry, was carefully controlled by means of reference samples on each occasion. The blood lead levels decreased during the observation period. The average blood lead concentrations for all the examined persons were 0.37, 0.26, and 0.25 mumol/l for 1980, 1983, and 1984, respectively. The mean of the differences in individual blood lead levels for 1980 and 1984 was 0.12 mumol/l. This figure corresponds to an average decrease in blood lead of 34% for all the subjects examined in 1980. The decrease occurred mainly during the period 1980-1983 (mean 0.11 mumol/l) and, thereafter, was only slight for the period 1983-1984 (mean 0.01 mumol/l). Factors such as age, sex, and change of residence during the observation period did not influence the final results.

Longitudinal and genetic effects in the relationship between pulmonary function and cognitive performance.

Previous studies have found cognitive deficits in patients with impaired pulmonary function, and recent data from healthy older adults suggest an association of pulmonary function with cognitive function. This 6-year longitudinal study evaluated genetic and environmental sources of covariation in the association of pulmonary function and cognitive performance. The sample included 222 Swedish twin pairs (60% women) with a mean age of 62.3 (+/- 7.7) years (age range: 40-84). Hierarchical multiple regression analyses, controlling for the effects of age, gender, and height, were employed to predict performance on cognitive tests of fluid intelligence (Digit Symbol, Block Design, Digit Span-Backward) and crystallized intelligence (Information) from forced expiratory volume in one second (FEV1). Bivariate cross-twin correlations were used to evaluate the contribution of genetic and environmental factors in the association of pulmonary function and cognitive performance. Results indicated that FEV1 predicted performance on tests of fluid intelligence but not crystallized intelligence at the initial assessment and at the 6-year follow-up. Cross-twin correlational analyses indicated that genetic effects accounted for a greater share of the association of pulmonary function and cognitive performance than environmental effects, but environment also accounted for a substantial share of the covariance.

Individual differences in activity of glutathione peroxidase and catalase studied in monozygotic twins discordant for smoking.

1. Cigarette smoke contains free radicals. The enzymes glutathione peroxidase (GSH-px) and catalase are important parts of the anti-oxidative protecting system. 2. Ten pairs of monozygotic twins, who were discordant for smoking, were analysed in order to determine their erythrocyte glutathione peroxidase and catalase activities and their plasma concentrations of selenium. 3. Analysis of variance (ANOVA) revealed that the difference in activities of catalase and glutathione peroxidase was much less within pairs than between pairs, indicating a large individual variation due to genetic expression or shared environment and no major effect from smoking. 4. The plasma selenium levels of the investigated twins revealed sufficient intake of selenium to maintain maximal activity of GSH-px in erythrocytes. The mean +/- s.d. selenium concentration in plasma for smokers was 98 +/- 16 micrograms l-1 and for non-smokers 111 +/- 16 micrograms l-1. There was no correlation between plasma selenium and glutathione peroxidase in erythrocytes.

Residential radon and lung cancer in Sweden: risk analysis accounting for random error in the exposure assessment.

A large epidemiologic study on residential radon exposure and lung cancer has been conducted in Sweden. An attempt is now made to quantify the impact of random error in the exposure assessment on the risk estimate for lung cancer in this study. The study included 1,360 lung cancer cases, diagnosed from 1980 to 1984, and 2,847 population controls. Radon measurements were performed in 8,992 dwellings occupied by the study subjects some time since 1947. Questionnaires provided information on smoking and other risk factors. Imprecision in the retrospective exposure assessment for radon was estimated from a Monte Carlo technique modeling Swedish conditions. Adjusted risk estimates were obtained from regression analyses based on expected values for true time-weighted average residential radon concentration (TWA), conditional on observed TWA. Without adjustment for random error in the TWA estimates, the linear excess relative risk coefficient was 0.10 per 100 Bq m(-3), but an excess relative risk of about 0.15 to 0.20 per 100 Bq m(-3) was suggested following adjustment. The potentially significant consequences of errors in the retrospective radon exposure assessment should be taken into consideration in the risk estimation as well as in comparisons of results of different studies and in future pooled analyses.

Radionuclide biokinetics database (RBDATA-EULEP): an update.

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.