Impact of Sleep Apnea on Cardioembolic Risk in Patients With Atrial Fibrillation: Data From the ESADA Cohort.

BACKGROUND AND PURPOSE: An accurate determination of the cardioembolic risk in patients with atrial fibrillation (AF) is crucial to prevent consequences like stroke. Obstructive sleep apnea (OSA) is a known risk factor for both AF and stroke. We aim to explore a possible association between OSA and an increased cardioembolic risk in patients with AF. METHODS: We assessed data from the ESADA (European Sleep Apnea Database) cohort where patients with known AF and OSA were included. Parameters of OSA severity and related hypoxia like lowest Spo2 and 4% oxygen desaturation index were analyzed. Patients were stratified according to their cardioembolic risk estimated with the CHA2DS2-VASc score. RESULTS: From the initial cohort of 14 646 patients, a final set of 363 patients were included in the analysis. Indices of hypoxia during sleep were associated with increased CHA2DS2-VASc score (4% oxygen desaturation index 17.9 versus 29.6 versus 30.5 events/hour and the lowest Spo2 81.2 versus 77.8 versus 77.5% for low, moderate, and high cardioembolic risk, respectively, P<0.05). CONCLUSIONS: These results support the potential role of OSA-related hypoxia in the risk for cardioembolic complications such as stroke in patients with AF.

Periodic limb movements during sleep and blood pressure changes in sleep apnoea: Data from the European Sleep Apnoea Database.

BACKGROUND AND OBJECTIVE: OSA and PLMS are known to induce acute BP swings during sleep. Our current study aimed to address the independent effect of PLMS on BP in an unselected OSA patient cohort. METHODS: This cross-sectional analysis included 1487 patients (1110 males, no previous hypertension diagnosis or treatment, mean age: 52.5 years, mean BMI: 30.5 kg/m2 ) with significant OSA (defined as AHI ≥ 10) recruited from the European Sleep Apnoea Cohort. Patients underwent overnight PSG. Patients were stratified into two groups: patients with significant PLMS (PLMSI > 25 events/hour of sleep) and patients without significant PLMS (PLMSI < 25 events/hour of sleep). SBP, DBP and PP were the variables of interest. For each of these, a multivariate regression linear model was fitted to evaluate the relationship between PLMS and outcome adjusting for sociodemographic and clinical covariates (gender, age, BMI, AHI, ESS, diabetes, smoking and sleep efficiency). RESULTS: The univariate analysis of SBP showed an increment of BP equal to 4.70 mm Hg (P < 0.001) in patients with significant PLMS compared to patients without significant PLMS. This increment remained significant after implementing a multivariate regression model (2.64 mm Hg, P = 0.044). No significant increment of BP was observed for DBP and PP. CONCLUSION: PLMS is associated with a rise in SBP regardless of AHI, independent of clinical and sociodemographic confounders. A PLMS phenotype may carry an increased risk for cardiovascular disease in OSA patients.

Association of JAG1 gene polymorphism with systemic blood pressure in patients with obstructive sleep apnea: a prospective cohort study.

AIM: To assess the effects of single nucleotide polymorphisms (SNPs) on blood pressure control in patients with obstructive sleep apnea (OSA). METHODS: This prospective observational cohort study, conducted between 2004 and 2014, examined the associations of SNPs of JAG1, GUCY1A3-GUCY1B3, SH2B3, and NPR3-C5orf23 genes with systolic and diastolic blood pressure (SBP, DBP) in 1179 adults evaluated for OSA with overnight polysomnography. Genotyping was performed by unlabeled probe melting analysis. RESULTS: The patients were predominantly male (69.6%, mean age 52±11 years, apnea-hypopnea index 34±31 episodes/h). Only JAG1 genotype was associated with SBP and DBP: compared with AA homozygotes, G allele carriers (pooled GG and AG genotype) had significantly higher morning SBP (132±19 vs 129±18 mm Hg; P=0.009) and morning and evening DBP (85±11 vs 83±10 mm Hg, P=0.004; 86±10 vs 84±10 mm Hg, P=0.012, respectively); the differences remained significant after the correction for multiple SNPs testing. In multivariate analyses, oxygen desaturation index and JAG1 genotype independently predicted morning SBP (P=0.001, P=0.003, respectively) and DBP (P<0.001, P=0.005, respectively), and evening SBP (P=0.019, P=0.048, respectively) and DBP (P=0.018, P=0.018, respectively). CONCLUSION: This is the first replication study of the SNPs recently linked to arterial hypertension in general population by genome-wide association studies. Our findings suggest that JAG1 genotype is related to blood pressure control in OSA: G allele was associated with higher morning and evening SBP and DBP.

The Effect of Pulmonary Rehabilitation in Mountain Environment on Exercise Capacity and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis.

BACKGROUND We aimed to test the effectiveness of the pulmonary rehabilitation in a mountain environment on the pulmonary function, physical performance, dyspnea, affective factors, and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB), as well as to determine predictors of clinical improvement. MATERIAL AND METHODS 128 consecutive patients (90 diagnosed with COPD and 38 diagnosed with CB) underwent comprehensive pulmonary rehabilitation for a duration of 3 weeks in one of 3 mountain health resorts in the High Tatras. The examination included spirometry (FEV1 and FEV1/FVC), 6-minute walk test (6MWT), Borg scale of dyspnea, and assessment of depression (Zung score), anxiety (Beck score), and QoL using the SF-36 scales. RESULTS After the study intervention, all patients in both monitored groups demonstrated significant improvements in objective measurements in which large treatment effect was achieved (for FEV1 η²=0.218, for 6MWT η²=0.771). Similarly, in subjective measurements a large effect was achieved (for the Beck score: η²=0.599, for the Zung score: η²=0.536). QoL improved after the intervention in all the monitored SF-36 scales in both groups (P<0.001 for all). In patients with COPD, the improvement of exercise capacity was positively correlated with baseline 6MWT and FEV1, and negatively with the Beck anxiety score and the Borg dyspnea score, whereas, only improvement in the mental summary component of QoL was negatively correlated with baseline 6MWT and FEV1 (P<0.05 for all). CONCLUSIONS Rehabilitation in a mountain environment has proven to be effective in both the reported diagnoses of COPD and CB. Improvements in both functional and subjective indicators were observed. These findings support the use of this treatment modality.

Non-Invasive Positive Pressure Ventilation Use-Practice Recommendations of the Slovak Society of Pulmonology and Phthisiology.

Non-invasive positive pressure ventilation (NIPPV) is increasingly used as a treatment method for patients with respiratory failure. The first recommendations for the use of NIPPV in Slovakia were developed by the Slovak Society of Pulmonology and Phthisiology in 2007 and were partially revised in 2015. New scientific evidence prompted the present update, which is based on widely accepted international guidelines and was adapted to address local needs. Important features of the present update include a classification of acute indications for NIPPV into three categories based on the level of supporting evidence, namely 1. definite indications for in-hospital use of NIPPV; 2. possible indications for in-hospital use of NIPPV; and 3. disorders and states in which in-hospital use of NIPPV is not recommended. The current update also reflects the importance of comorbid sleep-related breathing disorders and other chronic respiratory conditions, as well as the use and limitations of continuous positive airway pressure therapy. Since oxygen therapy is often administered along with NIPPV, guidance on the safe use of oxygen in NIPPV-treated patients has also been included. Also, the present update extends the range of its users, addressing the needs of specialists in pediatric respiratory medicine as a novelty.

Predictors of Quality-of-Life Improvement at Different Minimum Clinically Important Difference Values in Patients with Chronic Obstructive Pulmonary Disease after Climatic Rehabilitation Treatment.

BACKGROUND: The minimum clinically important difference (MCID) for the St George's Respiratory Questionnaire (SGRQ) is debated in chronic obstructive pulmonary disease (COPD) quality-of-life (QoL) assessments. This study aimed to determine whether there is a difference in predictors of clinically significant improvement between the traditional (value of 4) and newly proposed MCID SGRQ (value of 7) after climatic rehabilitation treatment. Climatic rehabilitation treatment consists of two main parts: climatotherapy, which typically involves the controlled exposure of individuals to natural environmental elements, and climatic rehabilitation, which includes other therapeutic factors such as physical activities as well as educating the patient to change their lifestyle. METHODS: This study included 90 consecutive patients diagnosed with COPD who underwent structured complex pulmonary rehabilitation in High Tatras, part of the Carpathian Mountains. The examination before and after treatment included spirometry, QoL assessment using the SGRQ, 6 min walk test (6-MWT), and the Borg, Beck and Zung scale. RESULTS: Patients showed statistically significant improvement after the intervention in FEV1, FEV1/FVC, 6-MWT, (p < 0.001), anxiety scores, depression, and improvement in dyspnoea both before and after the 6-MWT (p < 0.001). For both MCID for SGRQ levels 4 and 7, we confirmed the same predictors of clinical improvement for bronchial obstruction grade (spirometry) and exercise capacity (6-MWT), for quality of life in activity score and total score. CONCLUSION: The results suggest that both the proposed MCID for SGRQ values could be sufficient to assess the clinical significance of the achieved change in health status when assessing the need for pulmonary rehabilitation comprising climatotherapy in patients with COPD.

Clinical presentation and pulmonary function tests in post-acute COVID-19 patients.

AIMS: The study analysed post-acute COVID-19 symptoms and the pulmonary function test (PFT) results in patients surviving the native strain of the virus. METHODS: The study was prospective; the inclusion criteria were positive PCR test for SARS-CoV-2 and age 18-100. Exclusion criteria were active respiratory infection, known or suspicious pre-existing pulmonary disease, cardiac failure, recent or acute pulmonary embolism, anaemia, and neuromuscular diseases. The recruitment period was 1st March 2020 - 25th December 2020. The initial examination was performed 4-12 weeks after the disease onset. All subjects underwent physical examination, anamnesis, chest x-ray and PFT. RESULTS: The study involved 785 subjects (345 male) mean age 53.8 (SD 14.6). The disease severity groups were: mild (G1), moderate (G2) and severe/critical (G3). Anosmia was present in the acute disease phase in 45.2% of G1 patients, but only in 4.5% of G3 patients. Dyspnoea occurred frequently in more severe groups (40%, 51.8% and 63.7% for G1, G2 and G3 respectively), while cough and fatigue showed no relationship to disease severity. Females were more likely to experience persistent symptoms. PFT results were significantly decreased in more severe groups compared to the mild COVID-19 patients, diffusing capacity was 86.3%, 79% and 68% of predicted values in G1, G2 and G3 respectively. CONCLUSION: Anosmia during the acute phase was associated with mild disease, persisting dyspnoea was more frequent after more severe COVID-19. Females tended to have persisting symptoms in post-acute phase more frequently. PFT results showed decrease with disease severity.

Baseline clusters and the response to positive airway pressure treatment in obstructive sleep apnoea patients: longitudinal data from the European Sleep Apnea Database cohort.

Introduction: The European Sleep Apnea Database was used to identify distinguishable obstructive sleep apnoea (OSA) phenotypes and to investigate the clinical outcome during positive airway pressure (PAP) treatment. Method: Prospective OSA patient data were recruited from 35 sleep clinics in 21 European countries. Unsupervised cluster analysis (anthropometrics, clinical variables) was performed in a random sample (n=5000). Subsequently, all patients were assigned to the clusters using a conditional inference tree classifier. Responses to PAP treatment change in apnoea severity and Epworth sleepiness scale (ESS) were assessed in relation to baseline patient clusters and at short- and long-term follow-up. Results: At baseline, 20 164 patients were assigned (mean age 54.1±12.2 years, 73% male, median apnoea-hypopnoea index (AHI) 27.3 (interquartile range (IQR) 14.1-49.3) events·h-1, and ESS 9.8±5.3) to seven distinct clusters based on anthropometrics, comorbidities and symptoms. At PAP follow-up (median 210 [IQR 134-465] days), the observed AHI reduction (n=1075) was similar, whereas the ESS response (n=3938) varied: largest reduction in cluster 3 (young healthy symptomatic males) and 6 (symptomatic males with psychiatric disorders, -5.0 and -5.1 units, respectively (all p<0.01), limited reduction in clusters 2 (obese males with systemic hypertension) and 5 (elderly multimorbid obese males, -4.2 (p<0.05) and -3.7 (p<0.001), respectively). Residual sleepiness in cluster 5 was particularly evident at long-term follow-up (p<0.05). Conclusion: OSA patients can be classified into clusters based on clinically identifiable features. Importantly, these clusters may be useful for prediction of both short- and long-term responses to PAP intervention.

Management of obstructive sleep apnea in Europe - A 10-year follow-up.

OBJECTIVE: In 2010, a questionnaire-based study on obstructive sleep apnea (OSA) management in Europe identified differences regarding reimbursement, sleep specialist qualification, and titration procedures. Now, 10 years later, a follow-up study was conducted as part of the ESADA (European Sleep Apnea Database) network to explore the development of OSA management over time. METHODS: The 2010 questionnaire including questions on sleep diagnostic, reimbursement, treatment, and certification was updated with questions on telemedicine and distributed to European Sleep Centers to reflect European OSA management practice. RESULTS: 26 countries (36 sleep centers) participated, representing 20 ESADA and 6 non-ESADA countries. All 21 countries from the 2010 survey participated. In 2010, OSA diagnostic procedures were performed mainly by specialized physicians (86%), whereas now mainly by certified sleep specialists and specialized physicians (69%). Treatment and titration procedures are currently quite homogenous, with a strong trend towards more Autotitrating Positive Airway Pressure treatment (in hospital 73%, at home 62%). From 2010 to 2020, home sleep apnea testing use increased (76%-89%) and polysomnography as sole diagnostic procedure decreased (24%-12%). Availability of a sleep specialist qualification increased (52%-65%) as well as the number of certified polysomnography scorers (certified physicians: 36%-79%; certified technicians: 20%-62%). Telemedicine, not surveyed in 2010, is now in 2020 used in diagnostics (8%), treatment (50%), and follow-up (73%). CONCLUSION: In the past decade, formal qualification of sleep center personnel increased, OSA diagnostic and treatment procedures shifted towards a more automatic approach, and telemedicine became more prominent.

Increased adipose tissue expression of proinflammatory CD40, MKK4 and JNK in patients with very severe chronic obstructive pulmonary disease.

BACKGROUND: CD40, a transmembrane receptor of the tumor necrosis factor gene superfamily, is activated in response to cellular stress, including hypoxia, and orchestrates the process of inflammation via secondary messengers such as mitogen-activated protein kinase kinase 4 (MKK4) and c-Jun NH(2)-terminal kinases (JNK). OBJECTIVES: We hypothesized that CD40, MKK4 and JNK expression is increased in the adipose tissue of patients with very severe chronic obstructive pulmonary disease (COPD). METHODS: In 20 patients with stable COPD, lung function was assessed using body plethysmography, and samples of subcutaneous adipose tissue were analyzed using real-time PCR. Body composition, including fat mass index (FMI), was assessed by bioelectrical impedance. RESULTS: 12 patients in GOLD stage I-III (age 61.6 ± 8.6 years, 4 females, mean partial pressure of oxygen in arterial blood, PaO(2), 9.38 ± 0.21 kPa) were compared to 8 patients in GOLD stage IV (age 62.6 ± 6.3 years, all male, mean PaO(2) 7.70 ± 0.37 kPa). Compared to patients in GOLD stage I-III, patients in GOLD stage IV had lower FMI (p = 0.004), being associated with significantly higher adipose tissue expression of CD40, MKK4 and JNK [ΔΔCt: 2.55 (1.99, 4.40) vs. 1.87 (1.63, 2.23), p = 0.013; 5.19 (3.13, 5.96) vs. 2.98 (2.82, 3.86), p = 0.002; 9.01 (5.12, 11.41) vs. 4.65 (4.42, 6.26), p = 0.001, respectively]. Log-transformed CD40, MKK4 and JNK expression was significantly inversely related to PaO(2), respectively. CONCLUSIONS: Upregulation of proinflammatory CD40, MKK4 and JNK gene expression in adipose tissue in very severe COPD raises the possibility of a role of chronic systemic hypoxia in the pathogenesis of adipose tissue inflammation in COPD.

Obstructive sleep apnoea in adult patients post-tonsillectomy.

BACKGROUND: The impact of removing the upper airway lymphoid tissue and in particular, tonsillectomy, in adults with OSA has not been demonstrated in large populations. AIMS: To compare the severity of OSA and the prevalence of cardiovascular, metabolic and respiratory co-morbidities between patients with OSA who had undergone previous tonsillectomy and those who had not. METHODS: The 19,711 participants in this study came from the European sleep apnea database (ESADA) which comprises data from unselected adult patients aged 18-80 years with a history of symptoms suggestive of OSA referred to sleep centers throughout Europe. RESULTS: There were no differences between the two groups in terms of sex ratio and age (146 patients with previous tonsillectomy vs. 19565 patients without). Patients who had undergone tonsillectomy had a lower body mass index (29.3 ± 5.2 kg/m2 vs 32.2 ± 6.6 kg/m2, p < 0.001), lower subjective sleep latency (17.1 ± 17.8 min vs 25.5 ± 30.4 min, p = 0.001), lower ODI (15.7 ± 18.3 events/hour vs 30.7 ± 26.1 events/hour, p < 0.001), and SpO2<90% time during sleep (21.8 ± 47.5 min vs 52.6 ± 80.8 min, p < 0.001). OSA patients with tonsillectomy had a lower prevalence of Type II diabetes mellitus (p = 0.001), hypertension (p < 0.001) and a higher prevalence of hyperlipidemia (p < 0.001) and were less likely to be commenced on CPAP (p < 0.001). CONCLUSION: In a large population of almost 20,000 OSA patients from across Europe, patients who had undergone tonsillectomy presented with less severe OSA at time of diagnosis, and had a lower prevalence of Type II diabetes mellitus and cardiovascular co-morbidities.

Metabolic phenotype and adipose tissue inflammation in patients with chronic obstructive pulmonary disease.

Potential links between metabolic derangements and adipose tissue (AT) inflammation in patients with chronic obstructive pulmonary disease (COPD) are unexplored. We investigated AT expressions of interleukin (IL)-6, tumor necrosis factor (TNF)-α, CD68 (macrophage cell surface receptor), caspase-3, and Bax, and their relationships to the metabolic phenotype in nine cachectic, 12 normal-weight, 12 overweight, and 11 obese patients with COPD (age 62.3 ± 7.2 years). With increasing body mass index, increases in AT expressions of IL-6, TNF-α, and CD68 were observed (P < .001; P = .005; P < .001, resp.), in association with reduced insulin sensitivity (P < .001). No differences were observed between cachectic and normal-weight patients in AT expressions of inflammatory or proapoptotic markers. Adipose tissue CD68 and TNF-α expressions predicted insulin sensitivity independently of known confounders (P = .005; P = .025; R(2) = 0.840). Our results suggest that AT inflammation in obese COPD patients relates to insulin resistance. Cachectic patients remain insulin sensitive, with no AT upregulation of inflammatory or proapoptotic markers.

Erickson solution-focused coaching for weight management in obese patients with obstructive sleep apnoea: ECOHEALTH pilot study.

Coaching as a lifestyle modification approach to weight management is insufficiently explored in obstructive sleep apnoea. We investigated anthropometry and body composition after 20 weeks of Erickson coaching in 26 obstructive sleep apnoea patients (19 males; 47.6 ± 2.4 years). Body weight, neck circumference, waist-to-hip ratio and %body fat significantly decreased after 20 weeks. The mean weight loss was 5.2 per cent ± 1.0 per cent; 20 (77%) participants achieved target reduction of >3 per cent. Coaching session attendance (p = 0.006) and reaching personal goal related to physical performance (p = 0.044) were independently associated with weight loss (multiple regression model R2 = 0.608, p < 0.001). Erickson solution-focused coaching supports adherence to healthy lifestyle and weight reduction in obstructive sleep apnoea.

Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA).

BACKGROUND AND AIM: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). METHODS: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). RESULTS: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). CONCLUSION: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies.

Effects of sleep apnea and kidney dysfunction on objective sleep quality in nondialyzed patients with chronic kidney disease: an ESADA study.

STUDY OBJECTIVES: Patients with chronic kidney disease (CKD) often report poor sleep quality, but they commonly exhibit OSA. The aim of this study was to evaluate the influence of OSA severity and of estimated glomerular filtration rate impairment on objective sleep quality in nondialyzed patients with CKD, defined as an estimated glomerular filtration rate <60 mL/min/1.73m². METHODS: Polysomnographic sleep characteristics were compared between patients with (n = 430) and without CKD (n = 6,639) in the European Sleep Apnea Database cohort. Comparisons were repeated in 375 patients with CKD and 375 control patients without CKD matched for sleep center, age, sex, and AHI, and in 310 matched CKD and non-CKD patients without psychiatric disturbances. RESULTS: Among all patients with and without CKD, total sleep time was similar but sleep stage N1 (median 8.7% [IQR 4.8-18.0] vs 6.7% [3.6-12.7], respectively) and sleep stage R (12.6% [6.8-17.7] vs 14.2% [8.8-19.8], respectively) significantly differed (P < .0001). No difference in sleep characteristics was observed between matched patients either with or without psychiatric disturbances. After subdividing the matched patients according to AHI tertile (<25, ≥25 to <49, and ≥49 events/h) and estimated glomerular filtration rate (≥60, 45 to <60, <45 mL/min/1.73m²), we found a significant effect of AHI on sleep stages N2, N3, and R (P < .001), but there was no effect of CKD. CONCLUSIONS: In nondialyzed patients with CKD, objective sleep quality is influenced similarly by AHI as in patients without CKD but is not affected by CKD severity. Previously reported poor sleep quality in CKD may partly result from the high prevalence of OSA in CKD.

Nutritional status in relation to respiratory impairment and systemic inflammation in patients with acute exacerbations of COPD.

BACKGROUND: Knowledge of the effects of undernourishment on the severity of respiratory impairment, systemic inflammation and oxidative stress during acute exacerbations of COPD (AECOPD) is limited. In patients with AECOPD, we assessed the relationships between BMI, lung function, and markers of systemic inflammation and oxidative stress. MATERIAL/METHODS: We measured pulmonary function, serum C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, malondialdehyde (MDA), erythrocytic glutathione-peroxidase (GPx), superoxiddismutase (SOD), and catalase (CAT) in 113 patients admitted to the hospital due to an AECOPD (80 males, age 66.2+/-11.0 years, FEV1 41.5+/-13.7% predicted). RESULTS: From the low (<21 kg/m2) towards the normal (21-24.9 kg/m2), high (25-29.9 kg/m2) and obese (>30 kg/m2) BMI groups, FEV1, FEV1-to-forced vital capacity (FVC) ratio, inspiratory capacity (IC), and the IC-to-total lung capacity (IC/TLC) ratio increased (p<0.01; p<0.001; p=0.039; p=0.002, respectively), while residual volume (RV), TLC and RV/TLC ratio were reduced (p<0.001; p<0.001; p=0.018, respectively). Patients with low BMI had significantly lower FEV1, FEV1/FVC, IC and IC/TLC, and higher RV and TLC values compared to the high and obese BMI groups. From the low towards the normal, high and obese BMI, reductions in serum CRP, and a trend towards increases in erythrocytic GPx were observed (p=0.023; p=0.056, respectively). No differences were seen in circulating TNF-alpha, IL-6 or IL-8, MDA or erythrocytic CAT and SOD between the groups. CONCLUSIONS: In patients with acute exacerbations of COPD, low BMI is associated with higher degree of bronchial obstruction and pulmonary hyperinflation, in association with higher circulating CRP levels.

Beta2-adrenergic receptor haplotype and bronchodilator response to salbutamol in patients with acute exacerbations of COPD.

BACKGROUND: The role of the beta2-adrenergic receptor (ADRB2) genotype in patients with chronic obstructive pulmonary disease (COPD) is unclear. In patients with acute exacerbations of COPD (AECOPD), we assessed the role of ADRB2 haplotypes in morning lung function and in the bronchodilator response to salbutamol. MATERIAL/METHODS: In 107 patients with AECOPD, polymorphisms in the amino acid position 16 (Arg16/Gly16) and 27 (Gln27/Glu27) of the ADRB2 gene were assessed by allele-specific polymerase chain reaction, identifying 31 subjects with the Gly16/Glu27-negative and 76 with the Gly16/Glu27-positive ADRB2 haplotype. Pulmonary function and bronchodilator response to salbutamol were assessed using bodyplethysmography. RESULTS: Forced expiratory volume in 1 second (FEV1) and peak expiratory flow (PEF) were significantly higher in the Gly16/Glu27-negative compared to the Gly16/Glu27-positive haplotype group at baseline (49.7+/-2.9% vs 42.4+/-1.8% predicted, P=0.037; 44.0+/-2.2% vs 36.4+/-1.6% predicted, P=0.008, respectively). FEV1, PEF, and forced vital capacity (FVC) increased from baseline to after salbutamol treatment in both the Gly16/Glu27-negative and the Gly16/Glu27-positive ADRB2 haplotype groups (P<0.001 for all comparisons). Values for FEV1 and PEF after administration of the bronchodilator were significantly higher in the Gly16/Glu27-negative haplotype group compared with the Gly16/Glu27-positive haplotype group (P=0.030 and P=0.034, respectively). No differences were observed in DeltaFEV1, DeltaPEF, or DeltaFVC after bronchodilation between the 2 ADRB2 haplotype groups (12.2+/-1.8% vs 14.5+/-1.5% predicted, P=0.393; 12.2+/-3.3% vs 20.8+/-3.2% predicted, P=0.117; 9.1+/-2.3% vs 10.4+/-1.9% predicted, P=0.707, respectively). CONCLUSIONS: The present findings suggest that the ADBR2 gene haplotypes may affect the severity of obstructive ventilatory impairment but not the immediate response to salbutamol during AECOPD.

Glutathione S-transferase and microsomal epoxide hydrolase gene polymorphisms and risk of chronic obstructive pulmonary disease in Slovak population.

AIM: To determine the risk of chronic obstructive pulmonary disease (COPD) associated with polymorphisms in the glutathione S-transferase (GST) M1, GST T1, and microsomal epoxide hydrolase (EPHX1) genes in a cohort of Slovak population. METHODS: Two hundred and seventeen patients with the diagnosis of COPD and 160 control subjects were enrolled in the study. Blood samples were collected from all subjects and the DNA from peripheral blood lymphocytes was used for subsequent genotyping assays, using polymerase chain reaction and restriction fragment-length polymorphism methods. RESULTS: In an unadjusted model, an increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.20-4.69; P=0.008), compared with the carriers of the Tyr113 allele. However, after the adjustments for age, sex, and smoking status, the risk was not significant (adjusted OR, 1.79; 95% CI, 0.91-3.53; P=0.093). In a combined analysis of gene polymorphisms, the genotype combination EPHX1 His113-His113/GSTM1 null significantly increased the risk of COPD in both, unadjusted (OR, 5.08; 95% CI, 1.70-20.43; P=0.001) and adjusted model (OR, 4.87; 95% CI, 1.57-15.13; P=0.006). CONCLUSION: Although none of the tested gene polymorphisms was significantly related to an increased risk of COPD alone, our results suggest that the homozygous exon 3 mutant variant of EPHX1 gene in the combination with GSTM1 null genotype is a significant predictor of increased susceptibility to COPD in the Slovak population. The findings of the present study emphasize the importance of detoxifying and antioxidant pathways in the pathogenesis of COPD.

Systemic inflammation and systemic oxidative stress in patients with acute exacerbations of COPD.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the inflammatory processes and oxidative stress are closely linked in the lung compartment. However, the relationships between systemic inflammation and parameters of oxidative stress in the systemic circulation during acute exacerbations of COPD remain to be explored. OBJECTIVE: To analyze relationships between erythrocytic glutathione peroxidase (GPx), a marker of systemic oxidative stress, and parameters reflecting systemic inflammation, such as circulating neutrophils, C-reactive protein (CRP), and interleukin (IL)-6, in patients with acute exacerbations of COPD. PATIENTS AND METHODS: We measured erythrocytic GPx activity, circulating neutrophil count, and serum high-sensitivity (hs) CRP and IL-6 in 177 patients admitted to the hospital due to an acute exacerbation of COPD (91 males, mean age 66.8+/-0.9 years, mean FEV1 45.3+/-1.3% predicted). RESULTS: From GOLD Stage II to Stage III and IV, erythrocytic GPx activity significantly decreased [mean+/-SEM: from 44.3+/-1.7 U/g Hb to 40.8+/-1.1 U/g Hb and to 38.4+/-1.5 U/g Hb, p = 0.037], while serum hsCRP increased [median (25th, 75th percentile): from 9.6 (3.0, 23.0) mg/l to 23.3 (6.4, 46.8) mg/l, and to 26.7 (6.5, 117.2) mg/l, p = 0.004]. Erythrocytic GPx activity was significantly inversely related to both, log neutrophil count (r = -0.219, p = 0.003) and log hsCRP (r = -0.199, p = 0.008). CONCLUSIONS: Our study suggests an association between systemic inflammation and systemic oxidative stress reflected by erythrocytic GPx in patients with acute exacerbations of COPD.