Very short sleep duration reveals a proteomic fingerprint that is selectively associated with incident diabetes mellitus but not with incident coronary heart disease: a cohort study.

BACKGROUND: The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease. METHODS: We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46-68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers. Incident events occurring in the first 3 years of follow-up were excluded from analyses. Tenfold cross-fit partialing-out lasso logistic regression adjusted for age and sex was used to identify proteins that significantly predicted sleep duration quintiles when compared with the referent quintile 3 (Q3). Predictive proteins were weighted and combined into proteomic scores (PS) for sleep duration Q1, Q2, Q4, and Q5. Combinations of PS were included in a linear regression model to identify the best predictors of habitual sleep duration. Cox proportional hazards regression models with sleep duration quintiles and sleep-predictive PS as the main exposures were related to iDM and iCHD after adjustment for known covariates. RESULTS: Sixteen unique proteomic markers, predominantly reflecting inflammation and apoptosis, predicted sleep duration quintiles. The combination of PSQ1 and PSQ5 best predicted sleep duration. Mean follow-up times for iDM (n = 522) and iCHD (n = 411) were 21.8 and 22.4 years, respectively. Compared with sleep duration Q3, all sleep duration quintiles were positively and significantly associated with iDM. Only sleep duration Q1 was positively and significantly associated with iCHD. Inclusion of PSQ1 and PSQ5 abrogated the association between sleep duration Q1 and iDM. Moreover, PSQ1 was significantly associated with iDM (HR = 1.27, 95% CI: 1.06-1.53). PSQ1 and PSQ5 were not associated with iCHD and did not markedly attenuate the association between sleep duration Q1 with iCHD. CONCLUSIONS: We here identify plasma proteomic fingerprints of sleep duration and suggest that PSQ1 could explain the association between very short sleep duration and incident DM.

Plasma Concentration of Caspase-8 Is Associated With Short Sleep Duration and the Risk of Incident Diabetes Mellitus.

Context: The biological mechanism for the association between sleep duration and incident diabetes mellitus (DM) is unclear. Sleep duration and caspase-8, a marker of apoptotic activity, have both been implicated in ß-cell function. Objective: To investigate the associations between sleep duration and plasma caspase-8 and incident DM, respectively. Design: Prospective cohort study. Setting: The Malmö Diet and Cancer (MDC) Study is a population-based, prospective study run in the city of Malmö, Sweden. Participants: A total of 4023 individuals from the MDC Study aged 45 to 68 years at baseline without a history of prevalent DM and with information on habitual sleep duration. Main Outcomes: Incident DM. Results: Mean follow-up time was 17.8 years. Sleep duration was the only behavioral variable significantly associated with plasma caspase-8. Plasma caspase-8 was significantly associated with incident DM per standard deviation of its transformed continuous form [hazard ratio (HR) = 1.24; 95% confidence interval (CI), 1.13 to 1.36] and when dichotomized into high (quartile 4) (HR = 1.44; 95% CI, 1.19 to 1.74) compared with low (quartiles 1 to 3) concentrations. Caspase-8 interacted with sleep duration; compared with individuals who had 7 to 8 hours of sleep and low plasma caspase-8, those with high plasma caspase-8 and sleep duration <6 hours (HR = 3.54; 95% CI, 2.12 to 5.90), 6 to 7 hours (HR = 1.81; 95% CI, 1.24 to 2.65), and 8 to 9 hours (HR = 1.54; 95% CI, 1.09 to 2.18) were at significantly increased risks of incident DM. Conclusions: Sleep duration is associated with plasma caspase-8. Caspase-8 independently predicts DM years before disease onset and modifies the effect of sleep duration on incident DM. Future studies should investigate if change of sleep duration modifies plasma concentrations of caspase-8.

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease.

AIMS/HYPOTHESIS: Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that any association with sleep duration would not hold for cases of incident CHD occurring before incident diabetes ('non-diabetes CHD') but would hold true for cases of incident CHD following incident diabetes ('diabetes-CHD'). METHODS: A total of 6966 men and 9378 women aged 45-73 years from the Malmö Diet Cancer Study, a population-based, prospective cohort, who had answered questions on habitual sleep duration and did not have a history of prevalent diabetes or CHD were included in the analyses. Incident cases of diabetes and CHD were identified using national registers. Sex-specific Cox proportional hazards regression models were stratified by BMI and adjusted for known covariates of diabetes and CHD. RESULTS: Mean follow-up times for incident diabetes (n = 1137/1016 [men/women]), incident CHD (n = 1170/578), non-diabetes CHD (n = 1016/501) and diabetes-CHD (n = 154/77) were 14.2-15.2 years for men, and 15.8-16.5 years for women. In men, short sleep duration (< 6 h) was associated with incident diabetes (HR 1.35, 95% CI 1.01, 1.80), CHD (HR 1.41, 95% CI 1.06, 1.89) and diabetes-CHD (HR 2.34, 95% CI 1.20, 4.55). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.35, 95% CI 0.98, 1.87). Long sleep duration (≥ 9 h) was associated with incident diabetes (HR 1.37, 95% CI 1.03, 1.83), CHD (HR 1.33, 95% CI 1.01, 1.75) and diabetes-CHD (HR 2.10, 95% CI 1.11, 4.00). Long sleep duration was not associated with incident non-diabetes CHD (HR 1.33, 95% CI 0.98, 1.80). In women, short sleep duration was associated with incident diabetes (HR 1.53, 95% CI 1.16, 2.01), CHD (HR 1.46, 95% CI 1.03, 2.07) and diabetes-CHD (HR 2.88, 95% CI 1.37, 6.08). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.29, 95% CI 0.86, 1.93). CONCLUSIONS/INTERPRETATION: The associations between sleep duration and incident CHD directly reflect the associations between sleep duration and incident diabetes. Incident diabetes may thus be the explanatory mechanism for the association between short and long sleep duration and incident CHD.

A genetic risk score for CAD, psychological stress, and their interaction as predictors of CAD, fatal MI, non-fatal MI and cardiovascular death.

BACKGROUND: Psychological stress is an independent risk factor for cardiovascular disease (CVD), but the mechanism by which stress is associated with CVD is not entirely understood. Although genetic factors are implied in both stress responsivity and cardiovascular reactivity, no studies to date have investigated their interactions with stress for cardiovascular end points. The objective was to elucidate the association and interactions between a genetic risk score (GRS), individual genetic variants and stress for three cardiovascular end points: coronary artery disease (CAD), fatal myocardial infarction (MI), non-fatal MI, and cardiovascular death. METHODS AND FINDINGS: 18,559 participants from the Malmö Diet Cancer Study, a population-based prospective study, were included in the analyses. Cox proportional hazards regression models were used and adjusted for a large number of known predictors of cardiovascular end points. Mean follow-up time in years was 14.6 (CAD; n = 1938), 14.8 (fatal MI; n = 436), 14.8 (non-fatal MI; n = 1108), and 15.1 (cardiovascular death; n = 1071) respectively. GRS was significantly associated with increased risks of CAD (top quartile hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.51-1.96), fatal MI (top quartile HR, 1.62; 95%CI, 1.23-2.15), non-fatal MI (top quartile HR, 1.55; 95%CI, 1.31-1.84), and cardiovascular death (top quartile HR, 1.29; 95%CI, 1.08-1.53). Stress was not independently associated with any end point and did not interact with GRS. Four individual genetic variants interacted unfavorably with stress for end points with mortality outcomes. CONCLUSION: A GRS composed of 50 SNPs and predictive of CAD was found for the first time to also strongly predict fatal MI, non-fatal MI and cardiovascular death. A stress-sensitive component of the GRS was isolated on the basis of individual genetic variants that interacted unfavorably with stress.

Psychological stress and risk of incident atrial fibrillation in men and women with known atrial fibrillation genetic risk scores.

Psychological stress has been reported as a possible trigger of atrial fibrillation (AF). No studies have investigated whether any association between stress and AF could be modified by genetic susceptibility to AF (AF-genetic risk score (AF-GRS)). 8765 men and 13,543 women from the Malmö Diet Cancer Study, a population-based cohort, were included in the analyses. A variable representing stress was constructed from questions measuring job strain, and from one question assessing non-occupational stress. Cox proportional hazards regression models were adjusted for known covariates of AF. Mean follow-up times and number of recorded incident AF were 14.2 years and 1116 events for men, and 15.1 years and 932 events for women. Among women, high stress was associated with AF in the age adjusted model (hazard ratio [HR], 1.22; 95% confidence interval [CI], 1.01-1.47) but not following multivariable adjustment (HR, 1.15; 95% CI, 0.95-1.39). Stress was not associated with incident AF in men. AF-GRS was significantly associated with incident AF for both genders. Stress did not interact significantly with genetic susceptibility to AF in men or women. Chronic stress is not associated with long-term incident hospital diagnosed AF. This association does not appear to be modified by genetic susceptibility to AF.

Serum biomarkers and clinical outcomes in heart failure patients treated de novo with carvedilol.

BACKGROUND: The role of inflammatory and hemodynamic stress biomarkers in heart failure (HF) patients treated de novo with beta-blockers has been poorly studied. METHODS: A total of 86 patients (age 56 ± 9 years, 81 men) with left ventricular ejection fraction (LVEF) < 40% and previously not treated with beta-blockers were initiated on carvedilol. At baseline and 12 months later we performed echocardiography, cardiopulmonary exercise testing, and determined serum levels of B-type natriuretic peptide (BNP), endothelin-1 (ET-1), C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNF -a). Patients were followed up over a total period of 9 ± 3 years from baseline. RESULTS: Increased baseline CRP and its on-treatment decrease were associated with improvement of LVEF (est. coefficient per one SD: 1.6; 95% CI: -0.05,3.28; p = 0.056, and -1.80; -3.43, -0.18; p = 0.030, respectively) and diminishing of LV end-systolic volume index [mL/m2] (-6.83; -11.32; -2.34; p = 0.003, and 5.85; 1.23; -10.46; p = 0.014, respectively). Higher baseline ET-1 and on-treatment increase in TNF-a predicted frequent admissions (> 1) for cardiac complications (odds ratio per one SD: 1.98; 95% CI: 1.09-3.59; p = 0.025, and 2.07, 1.12-3.84, p = 0.021, respectively) whereas higher baseline BNP was associated with increased mortality (hazard ratio per one SD: 2.09, 95% CI: 1.26-3.45; p = 0.004). CONCLUSIONS: Serum biomarkers may have different roles in prediction of clinical outcomes among HF patients treated de novo with carvedilol.

Quantitative detection of myocardial ischaemia by stress echocardiography; a comparison with SPECT.

AIMS: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique angio-mode (AM), provides images for off-line perfusion quantification using Qontrast software, generating values of peak signal intensity (A), myocardial blood flow velocity (beta) and myocardial blood flow (Axbeta). By comparing rest and stress values, their respective reserve values (A-r, beta-r, Axbeta-r) are generated. We evaluated myocardial ischaemia by RTP-ASE Qontrast quantification, compared to visual perfusion evaluation with 99mTc-tetrofosmin single-photon emission computed tomography (SPECT). METHODS AND RESULTS: Patients admitted to SPECT underwent RTP-ASE (SONOS 5500) using AM during Sonovue infusion, before and throughout adenosine stress, also used for SPECT. Visual myocardial perfusion and wall motion analysis, and Qontrast quantification, were blindly compared to one another and to SPECT, at different time points off-line.We analyzed 201 coronary territories (left anterior descendent [LAD], left circumflex [LCx] and right coronary [RCA] artery territories) in 67 patients. SPECT showed ischaemia in 18 patients and 19 territories. Receiver operator characteristics and kappa values showed significant agreement with SPECT only for beta-r and Axbeta-r in all segments: area under the curve 0.678 and 0.665; P < 0.001 and < 0.01, respectively. The closest agreements were seen in the LAD territory: kappa 0.442 for both beta-r and Axbeta-r; P < 0.01. Visual evaluation of ischaemia showed good agreement with SPECT: accuracy 93%; kappa 0.67; P < 0.001; without non-interpretable territories. CONCLUSION: In this agreement study with SPECT, RTP-ASE Qontrast quantification of myocardial ischaemia was less accurate and less feasible than visual evaluation and needs further development to be clinically useful.

Head to head comparisons of two modalities of perfusion adenosine stress echocardiography with simultaneous SPECT.

BACKGROUND: Real-time perfusion (RTP) contrast echocardiography can be used during adenosine stress echocardiography (ASE) to evaluate myocardial ischemia. We compared two different types of RTP power modulation techniques, angiomode (AM) and high-resolution grayscale (HR), with 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) for the detection of myocardial ischemia. METHODS: Patients with known or suspected coronary artery disease (CAD), admitted to SPECT, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using AM and HR during Sonovue(R) infusion, before and throughout the adenosine stress, also used for SPECT. Analysis of myocardial perfusion and wall motion by RTP-ASE were done for AM and HR at different time points, blinded to one another and to SPECT. Each segment was attributed to one of the three main coronary vessel areas of interest. RESULTS: In 50 patients, 150 coronary areas were analyzed by SPECT and RTP-ASE AM and HR. SPECT showed evidence of ischemia in 13 out of 50 patients. There was no significant difference between AM and HR in detecting ischemia (p = 0.08). The agreement for AM and HR, compared to SPECT, was 93% and 96%, with Kappa values of 0.67 and 0.75, respectively (p < 0.001). CONCLUSION: There was no significant difference between AM and HR in correctly detecting myocardial ischemia as judged by SPECT. This suggests that different types of RTP modalities give comparable data during RTP-ASE in patients with known or suspected CAD.

Restrictive left ventricular filling pattern and its effect on the clinical course of systolic heart failure in patients receiving carvedilol.

BACKGROUND: To analyze differences in brain natriuretic peptide (BNP) levels depending on mitral flow pattern (MFP) and to assess the effects of carvedilol on changes in MFP, left ventricular function and exercise capacity. METHODS AND RESULTS: The study population consisted of 73 patients with symptomatic heart failure in NYHA classes II and III and LVEF < 40% without prior beta-blockade. In all patients at baseline, before carvedilol, and then at 3 and 12 months after initiation of treatment, the following parameters were assessed: HR(s), serum BNP, echocardiographic parameters, and exercise capacity with gas monitoring during cardiopulmonary stress test. Before carvedilol there was a positive correlation between BNP and E/A (r = 0.17; p = 0.05). BNP was significantly higher in patients with restrictive MFP (rMFP) as compared with nonrestrictive MFP (nrMFP) (541.5 +/- 206.7 vs. 412.6 +/- 207.2; p = 0.009), and lower VO(2peak) in rMFP as compared with nrMFP (12.5 +/- 3.7 vs. 16.5 +/- 4.7; p = 0.001). After initiation of carvedilol, the patients with rMFP had reduced E/A (2.9 vs. 1.4; p = 0.003), and rMFP was changed to nrMFP in 60.8% of patients. Respective BNP concentrations were 342.16 +/- 284.31 vs. 326.40 +/- 264.6; NS. In patients with rMFP VO(2peak) , %N increased significantly from 42.4 +/- 10.2 to 52.4 +/- 14.4; p = 0.012. CONCLUSIONS: In patients with systolic congestive heart failure, the presence of rMFP is related to higher BNP levels and reduced VO(2peak). Chronic treatment with carvedilol replaces rMFP with nrMFP and improves exercise capacity in some patients.

Concentration of BNP, endothelin 1, pro-inflammatory cytokines (TNF-alpha, IL-6) and exercise capacity in patients with heart failure treated with carvedilol.

BACKGROUND: Recent studies on the pathophysiology of heart failure indicate the role of neurohormones and immune and inflammatory processes as potential mechanisms involved in the pathogenesis and clinical course of chronic heart failure (CHF). AIM: To analyse the relationship between concentrations of brain natriuretic peptide (BNP), endothelin-1 (ET-1), inflammatory cytokines (TNF-alpha, IL-6) and cardiopulmonary stress test parameters, and to evaluate their changes during carvedilol treatment. METHODS: The study included 86 patients (81 men and 5 women) aged from 35 to 70 years (56.8+/-9.19) with symptomatic heart failure and left ventricular ejection fraction <40%, receiving an inhibitor of angiotensin II converting enzyme, diuretic and/or digoxin but not beta-blockers. All patients at baseline, and then at 3 and 12 months after treatment, underwent a panel of studies to assess functional capacity according to NYHA, echocardiographic and cardiopulmonary stress test (CPX) parameters, and serum concentrations of BNP, ET-1, TNF-alpha and IL-6. Before introducing carvedilol we found a weak relationship between concentrations of BNP, ET-1, IL-6 and decreased VO2 peak. RESULTS: At 12 months exercise tolerance was significantly improved (exercise stress testing prolonged by 143.9 s, p=0.001) and an increase in metabolic equivalent (MET) by 1.41 (p=0.001) was observed. The VO2 peak was nonsignificantly increased by a mean of 0.9 ml/kg/min. In patients with baseline VO2 peak <14 ml/kg/min the concentrations of ET-1 and TNF-alpha were significantly higher than in the remaining ones, and after treatment they were significantly reduced. In these patients VO2 peak%N was also significantly increased (39.5+/-7.5 vs. 50.1+/-15,0; p=0.013). The number of patients with VO2 peak <14 ml/kg/min also significantly decreased from 39 to 21 (p=0.013). CONCLUSIONS: In patients with HF decreased value of VO2 peak is associated with LV systolic function disorders and increased levels of BNP, ET-1, TNF-alpha and IL-6. Chronic treatment with carvedilol improves LV systolic function, exercise tolerance and peak oxygen consumption and is associated with significant decrease of BNP, ET-1, TNF-alpha and IL-6 concentrations.

Sudden cardiac death risk factors in patients with heart failure treated with carvedilol.

BACKGROUND: Chronic heart failure (CHF) is associated with a high risk of sudden cardiac death (SCD). Most frequently SCD occurs in patients with NYHA class II and III. AIM: To evaluate the influence of prolonged carvedilol therapy on SCD risk in CHF patients. METHODS: The study included 86 patients (81 men and 5 women) aged 56.8+/-9.19 (35-70) years with CHF in NYHA class II and III receiving an ACE inhibitor and diuretics but not beta-blockers. At baseline and after 12 months of carvedilol therapy the following risk factors for SCD were analysed: in angiography - occluded infarct-related artery; in echocardiography - left ventricular ejection fraction (LVEF) <30%, volume of the left ventricle (LVEDV) >140 ml; in ECG at rest - sinus heart rate (HRs) >75/min, sustained atrial fibrillation, increased QTc; in 24-hour ECG recording - complex arrhythmia, blunted heart rate variability (SDNN <100 ms) and abnormal turbulence parameters (TO and TS or one of them); in signal-averaged ECG - late ventricular potentials and prolonged fQRS >114 ms. The analysis of SCD risk factors in basic examination in patients who suddenly died was also performed. RESULTS: During one-year carvedilol therapy heart transplantation was performed in 2 patients; 5 patients died. At 12 months the following risk factors for SCD were significantly changed: HRs >75/min (50 vs. 16 patients, p=0.006), LVEF <30% (37 vs. 14 patients, p=0.01), SDNN <100 ms (19 vs. 9 patients, p=0.04). At 12 months the number of risk factors for SCD in each patient was significantly reduced (p=0.001). In patients who suddenly died we found a greater amount of SCD risk factors in basic examination (7 vs. 5) as compared to alive patients. CONCLUSIONS: Prolonged beta-adrenergic blockade reduces risk of sudden cardiac death through significant LVEF increase, reduction of HR at rest and improvement of HRV.

The usefulness of artificial neural networks in the evaluation of pulmonary efficiency and antioxidant capacity of welders.

OBJECTIVE: The aim of the study was to determine if artificial neural networks (ANNs) may be useful to analyse a complex and large set of data derived from smoking welders for the purpose of finding relationships between parameters describing respiratory system efficiency and antioxidant defence. METHODS: A group of 94 welders employed in a big metallurgic enterprise in Krakow, Poland (men only, aged 29-57 years, all active smokers) occupationally exposed to O(3) and NO(x), were the subjects of this study. They underwent biochemical measurements including total antioxidant status (TAS) and the anti-oxidative defence enzymes superoxide dismutase (SOD) and catalase (CT); biominerals: Fe, Cu, Zn, Mg in blood serum and in hair; the concentrations of albumin, bilirubin, uric acid in blood. The determination of respiratory efficiency was based on a "flow-volume" curve and spirometry. The dependant variables for ANNs were: TAS, SOD, CT. Thirty-one subjects with normal values of all spirometric parameters were selected for the final analysis. RESULTS: Statistically valid relationship between TAS and albumin, Zn and Cu in blood and the two pulmonary parameters forced expiratory volume after 1s (FEV(1)) and middle expiratory flow of 25-75% of vital capacity (MEF(25/75)) were found. Zn concentration almost linearly influenced TAS. For Cu a sigmoid curve was obtained. For albumin concentration as well as for FEV(1) a two-stage curve was observed. CONCLUSIONS: ANNs are useful for the reduction of dimensionality and are suited to analyse a complex and relatively large set of parameters when it is unknown which of these are related. ANNs were useful for finding the relationship between the antioxidant defence and the respiratory system capacity in welders who smoke.

Is magnesium deficit in lymphocytes a part of the mitral valve prolapse syndrome?

Magnesium deficiency has been proposed to be related to the mitral valve prolapse syndrome. However determinations of magnesium concentration in blood serum and hemolysates of red blood cells in this disease revealed divergent results. We investigated 49 patients with the mitral valve prolapse syndrome and 30 healthy individuals, matched by age and gender. The concentration of magnesium was measured in blood plasma and lysates of lymphocytes isolated from venous blood. The magnesium concentration in plasma was similar in both the patients and the healthy controls. By contrast, the magnesium concentration in lysates of lymphocytes was significantly lower (p < 0.03) in the patients with mitral valve prolapse syndrome than in the controls (range: 1.94-10.6 mmol/g of protein in Lymphocyte lysate; median 5.98 and 6.7-9.61 mmol/g of protein; median 7.22). The results obtained suggest that magnesium deficiency may be part of the mechanisms of the mitral valve prolapse syndrome.

Pattern recognition methods in evaluation of the structure of the laboratory data biominerals, antioxidant enzymes, selected biochemical parameters, and pulmonary function of welders.

A wide set of biochemical and spirometrical parameters was applied to a group of 41 welders. The obtained parameters were analyzed by the pattern recognition method: principal-components analysis (PCA) and mutual contribution analysis (MCA). The aim of the investigation was to find out which of 23 parameters had an influence on the pulmonological indices of COPD. It was found that PCA gave a substantial reduction of dimensionality. The most relevant parameters were Fe, Zn, Cu (all elements in blood, not in hair), FEV1, MEF50, bilirubin, TAS, and SOD. Only the relationships of MEF50, Cu, and TAS were statistically valid.

Antioxidant enzymes and pulmonary function in steel mill welders.

It is known that high levels of nitric oxide and ozone lead to disturbances of the balance between oxidants and antioxidants. The purpose of this study was to investigate ventilatory parameters in relation to the antioxidant status measured as total antioxidant status (TAS), superoxide dismutase (SOD) and catalase (CT). The study group consisted of 94 welders, aged 41.2 +/- 10.0 years, employed in the Steel Mill in Kraków, Poland, and exposed to nitric oxides and ozone in concentrations exceeding the threshold limit values. The control group consisted of 115 unexposed healthy workers aged 40.8 +/- 10.2 years. All the subjects under study were smokers. Determination of ventilatory efficiency was based on a "flow-volume" curve and spirometry. TAS was measured using reagents from the Randox Laboratories Ltd, SOD according to Fridovich and CT with Aebi's method. It was found that in the group of welders, the concentrations of TAS, CT and SOD were lower compared to controls (TAS-1.15/1.33 mmol/ml; CT-18.1/28.4 m/gHb, SOD-767.6/855.6 U/gHb). The incidence of extreme obstructive pulmonary disease and small airway disease in the welder group was more frequent than in controls. Changes in the concentration (or activity) of antioxidant parameters cannot be used as early markers of ventilatory dysfunction, although the values in the lowest class of TAS, SOD and CT showed a significantly larger number of welders than controls.