HLA Distribution in COPD Patients

Abstract

Background: Auto-immunity may contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD), particularly to the presence of emphysema. Auto-immune diseases are characterized by an abnormal distribution of HLA class II alleles (DR and DQ). The distribution of DRB1 and DQB1 alleles has not been investigated in COPD. Methods: To this end, HLA medium-low resolution typing was performed following standardized protocols in 320 clinically stable COPD patients included in the PAC-COPD study. Results were compared with controls of the same geographical and ethnic origin, and potential relationships with the severity of airflow limitation and lung diffusing capacity impairment were explored in patients with COPD. Results: The distribution of DRB1 and DQB1 alleles in COPD was similar to that of controls except for a significantly higher prevalence of DRB1*14 in patients with severe airflow limitation and low diffusing capacity. Conclusions: By and large, HLA distribution was similar in COPD patients and controls, but the HLA class II allele DRB1*14 may contribute to the pathogenesis of severe COPD with emphysema.     

Fatigue in COPD and the Impact of Respiratory Symptoms and Heart Disease—A Population-based Study

Abstract

Background: Fatigue is reported in COPD and in heart disease; however, there are hardly any population based data on the relationship between these conditions. Aim: To describe fatigue in relation to COPD by disease severity and to evaluate the impact of respiratory symptoms and heart disease. Methods: Data were collected in 2007 from the OLIN COPD study; 564 subjects with COPD (FEV₁/FVC < 0.70) and a distribution of disease severity representative for the general population, and 786 subjects without COPD. The Functional Assessment of Chronic Illness Therapy (FACIT)—Fatigue scale was used to assess fatigue (0–52); lower scores represent worse fatigue. Results: Median FACIT-F score was 44.0 in COPD defined by merely spirometric criteria and 42.0 in COPD also reporting respiratory symptoms, significantly lower compared to 46.0 in non-COPD (p = 0.006 and p < 0.001), and decreased by disease severity. The score was lower in COPD stage ≥ II and in COPD with respiratory symptoms already from stage I when compared to non-COPD. Subjects with heart disease reported lower scores than those without heart disease in COPD by all stages and in non-COPD. COPD with respiratory symptoms stage ≥II remained a significant risk factor for clinically significant fatigue also when adjusted for gender, age, heart disease and smoking habits (stage II OR 1.65, CI 1.17-2.31 and stage III-IV OR 2.66, CI 1.11-6.36). Conclusion: Fatigue is common in COPD, and is affected by respiratory symptoms and concomitant heart disease. In COPD with respiratory symptoms stage ≥ II, there is an increased risk for clinically significant fatigue.     

Significance of Medication History at the Time of Entry into the COPDGene Study: Relationship with Exacerbation and CT Metrics

Background: Despite the importance of respiratory medication use in COPD, relatively little is known about which clinical phenotypes were associated with respiratory medications. Methods: To determine the association between respiratory medication use and exacerbations or quantitative CT metrics, we analyzed medication history from 4,484 COPD subjects enrolled in the COPDGene Study. Results: 2,941 (65.6%) subjects were receiving one or more respiratory medications; this group experienced more frequent exacerbations in the year before study entry and had increased gas trapping, emphysema, and subsegmental airway wall area, compared to the patients who were on no respiratory medication. In subgroup analysis, subjects who were on triple therapy (long-acting beta2-agonist [LABA], long-acting muscarinic antagonist [LAMA], and inhaled corticosteroids [ICS]) had the highest frequencies of exacerbations and severe exacerbations and tended to have increased quantitative measures of emphysema and gas trapping on CT compared to other five groups. After adjustment for confounding variables, the triple therapy group experienced more exacerbations and severe exacerbations compared with other five groups. In addition, the LABA+LAMA+ICS group was more likely to have emphysema and gas trapping on CT than other groups in multivariable logistic analysis. Interestingly, the total number of respiratory medications was significantly associated with not only the frequency of exacerbations but also gas trapping and airway wall thickness as assessed by CT scan in multivariable analysis. Conclusions: These results suggest that the use of respiratory medications, especially the number of medications, may identify a more severe phenotype of COPD that is highly susceptible to COPD exacerbations.     

Automatic CPAP Performance in Patients with Sleep Apnea Plus COPD

Abstract

Background: Automatic CPAP devices have demonstrated good results in obtaining optimal fixed CPAP pressure to eliminate respiratory events in patients with sleep apnea-hypopnea syndrome (SAHS). However, automatic CPAP has not been fully studied in patients with COPD plus SAHS. Objectives: To analyse the performance of an automatic CPAP in severe COPD patients compared with SAHS patients with no associated co-morbidity. Methods: We compared 10 consecutive patients with SAHS and no associated co-morbidity and 10 patients with SAHS plus severe COPD who required CPAP titration. Automatic CPAP performance was studied during full-night PSG. Inadequate pressure increase periods, absence of pressure increases in reaction to respiratory events, air leak periods, and pressure behaviour in the face of erratic breathing periods were analysed. Results: The SAHS patients without co-morbidities vs. SAHS plus COPD patients presented: mean sleep efficiency, 80.2 (11.5)% vs. 76.5 (12.1)%; residual AHI, 6.3 (5.2) vs. 5.1 (7.7); residual CT90, 1 (3)% vs. 14 (1)%. The device´s performance demonstrates a mean of 1.2 (1.5) vs. 1.3 (1.2) periods of inadequate pressure increases; absence of pressure increases in reaction to respiratory events, 4.1 (5.4) vs. 0.6 (0.7) times; periods of air leaks, 1.3 (3.8) vs. 13.9 (11.7); mean optimal pressure, 9.1 (1.4) vs. 9.0 (1.9) cm H₂O. Conclusion: Titration with automatic CPAP could be as effective in patients with SAHS plus severe COPD as in patients with SAHS without COPD. However, the presence of more leakages must be taken into account.     

Respiratory Viral Detection and Small Airway Inflammation in Lung Tissue of Patients with Stable,Mild COPD

Background: Viral respiratory tract infections are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). In lung tissue specimens from patients with stable, mild COPD and from control smokers without airflow obstruction, we determined the prevalence and load of nucleic acid from common respiratory viruses and concomitant inflammation of small airways measuring less than 2-mm in diameter. Methods: Frozen lung tissue obtained from patients with stable, mild COPD (n = 20) and control subjects (n = 20) underwent real-time quantitative PCR (qPCR) for 13 respiratory viruses, and quantitative histology for inflammation of small airways. The two groups were compared for viral prevalence and load, and airway inflammation. The relationship between viral load and airway inflammatory cells was also analyzed. Results: Viral nucleic acid were detected in lung tissue of 18/40 (45.0%) of the individuals studied and included seven co-infections that were characterized by a “dominant virus” contributing to most of the total measured viral load. Lung tissue of COPD patients had a significantly higher prevalence of viral nucleic acid (particularly influenza A virus), and increased inflammation of small airways by macrophages and neutrophils versus controls. In qPCR-positive individuals, linear regression analysis showed a direct correlation between viral load and airway neutrophils, and between influenza A virus load and airway macrophages. Conclusion: The lung tissue of patients with stable, mild COPD has a higher prevalence and load of respiratory viruses versus non-obstructed control subjects, and increased inflammation of small airways. Respiratory viruses may represent potential targets in COPD patient management.     

Expression of Interleukin (IL)-10, IL-17A and IL-22 in Serum and Sputum of Stable Chronic Obstructive Pulmonary Disease Patients

Abstract

Interleukin (IL)-17A, IL-22 and IL-10 have been implicated in the development of chronic obstructive pulmonary disease (COPD), but their expression in COPD is uncertain. Here we investigate the expression of IL-17A, IL-22 and IL-10 in the serum and sputum of COPD patients. Blood samples and induced sputum samples were collected from 94 patients with COPD, 23 healthy smokers, and 22 healthy control non-smokers. IL-17A, IL-22 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). We found that: 1) serum and sputum IL-17A were higher in COPD compared to healthy smokers and non-smokers; 2) serum IL-17A increased with COPD stages, it was inversely correlated with percentage of forced expiratory volume in the first second (FEV₁%) reference and positively correlated with C-reactive protein (CRP), Sputum IL-17A levels in the severe COPD patients were positively correlated with sputum neutrophils, and reversely correlated with sputum macraphages (p < 0.01); 3) serum and sputum IL-22 were significantly higher in COPD and healthy smokers than those in the non-smoker group, sputum IL-22 was similar in severe COPD (stage III and IV), which were higher than those in the other groups (p < 0.05); and, 4) serum and sputum IL-10 were similiar in COPD and healthy smokers, which were decreased compared to non-smokers. These data suggest that the increased level of IL-17A in serum and sputum plays important roles in the pathogenesis of COPD. The increased sputum IL-22 might also play important roles in the pathogenesis of COPD, while IL-10 secretion might be not only affected by COPD but also by cigarette smoke.     

The Endocrinologic Changes in Critically Ill Chronic Obstructive Pulmonary Disease Patients

ABSTRACT

Background: Alterations in the neuroendocrine system occur during critical illness. Chronic obstructive pulmonary disease (COPD) itself causes hormonal changes. The aim of this study was to determine neu roendocrine hormones of COPD patients with acute respiratory failure and to investigate the relationship between hormonal changes, mortality, and morbidity.Methods: We enrolled 21 patients (13 F/8 M) with COPD exacerbation requiring artificial airway support. Blood samples were collected on admission to the ICU, and on the day of hospital discharge. Eighteen healthy people were included as controls. Results: Female patients had lower luteinizing hormone (LH), follicle stimulating hormone (FSH), and free triiodothyronine (fT3), and higher prolactin (PRL) levels than controls on admission to the ICU (FSH: 70.3 vs. 29.3 mlU/mL; LH: 26.6 vs. 6.8 mlU/mL; fT3: 2.9 vs. 2.0 pg/mL; PRL: 12.4 vs. 21.3 ng/mL). Male patients had low testosterone and TSH and high PRL but only changes in TSH and PRL reached statistical significance (testosterone: 3.5 vs. 1.5 ng/mL, TSH: 1.1 vs. 0.5 ulU/mL, PRL: 9.7 vs. 14.2 ng/mL). Female patients had lower fT3 than males (fT3_female: 2.7 vs. fT3_male: 2.0 pg/mL). On follow-up, significantly elevated FSH and fT3 and decreased estradiol concentrations were documented among recovered women (FSH: 28.4 vs. 46.6 mlU/mL, fT3,: 2.0 vs. 2.6 pg/mL, E₂: 27.7 vs. 19.0 pg/mL). Patients had high C-reactive protein levels and acute physiologic and chronic health evaluation II scores. Mortality rate was 9.5% and a negative correlation between E₂ and duration of noninvasive mechanical ventilation and length of hospital stay was found in male patients. Conclusion: Men and women with acute respiratory failure in the presence of COPD develop significant changes in the neuroendocrine axis. Hormonal suppression vanishes with disease improvement.     

Use of an Australian Quality of Life Tool in Patients with COPD

Abstract

COPD is a leading chronic disease, increasing globally. Given this condition's irreversible and progressive nature, health-related quality of life (HRQOL) is increasingly a primary end-point in COPD management. We evaluated several HRQOL tools with a primary goals of (1) investigating how the generic Assessment Quality of Life (AQOL) functions compared to the Medical Outcomes Study 36-item Short Form Health Survey (SF36) and the St. Georges Respiratory Questionnaire (SGRQ); and (2) considering the extent to which clinical disease severity, as measured by the BODE index, predicts variation in HRQOL reports. Methods: 134 consecutive patients entering a pulmonary rehabilitation program were recruited. Participants completed two generic measures of HRQOL (SF36 and AQOL) and one disease specific measure (SGRQ). The clinical severity of COPD was assessed using a composite global COPD severity score, BODE. Results: Significant associations were demonstrated between AQOL and both the SF36 (r = .68) and SGRQ (r = –.60). BODE significantly predicted AQOL scores (R = –.31); mMRC (R = –.36) and 6MWD (R = .39) were stronger contributors to these predictions than were FEV₁ or BMI. Conclusions: This study establishes convergent validity between AQOL, and the SF36 and SGRQ in patients with COPD. For future studies wishing to examine HRQOL from a generic perspective, we have shown that during cross-sectional analyses AQOL performs similarly to the SF36. In addition we identified that the clinical severity of COPD, as assessed by BODE, significantly influences reports of quality of life made using AQOL. The components of BODE that most strongly contributed to predicting HRQOL were dsypnea and exercise tolerance.     

Enhanced levels of prostaglandin E2 and matrix metalloproteinase-2 correlate with the severity of airflow limitation in stable COPD

Background and objective: Cyclooxygenase-2 (COX-2) and its product prostaglandin E₂ (PGE₂) have been demonstrated to play critical roles in inflammation in respiratory diseases. However, the role of COX-2 in airway remodelling in COPD remains to be elucidated. Matrix metalloproteinase-2 (MMP-2) is associated with both inflammation and airway remodelling in COPD. The objective of this study was to measure the expression of COX-2 and the concentrations of PGE₂ and MMP-2, and to investigate the role of COX-2 and PGE₂ in airflow limitation mediated by MMP-2, in the pathogenesis of COPD. Methods: Forty-three patients with stable COPD, twelve smoking control subjects and ten non-smoking control subjects were enrolled. Induced sputum was obtained for measurement of the concentrations of PGE₂ and MMP-2 by ELISA. COX-2 protein expression was assessed by western blotting. Results: PGE₂ and MMP-2 concentrations were significantly higher in both smoking control subjects and patients with COPD than in non-smoking control subjects (P < 0.01). Moreover, the levels of PGE₂ and MMP-2 were inversely correlated with FEV₁% predicted in COPD patients (PGE₂: r = −0.748, P < 0.01; MMP-2: r = −0.801, P < 0.01). Levels of PGE₂ were also positively correlated with those of MMP-2 in patients with COPD (r = 0.775, P < 0.01). Expression of COX-2 protein was significantly higher in COPD patients than in non-smoking control subjects. Conclusions: COX-2 and its product PGE₂ are not only involved in airway inflammation, but may also contribute to the severity of airflow limitation mediated by MMP-2 during progression of COPD.     

Is Metrnl an Adipokine İnvolved in the Anti-inflammatory Response to Acute Exacerbations of COPD?

Purpose

Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow limitation and systemic inflammation. Recently, there has been growing interest in adipose tissue-mediated inflammation in the pathogenesis of COPD. The aim of our study was to determine the relationships between a new adipocytokine, meteorin-like protein (Metrnl), and acute exacerbations of COPD, smoking, and comorbidities.

Materials and Methods

The study included 313 patients aged 40–65 years in four groups: Group 1: ex-smokers (≥ 20 pack-years) with COPD hospitalized for COPD exacerbation (n = 133), Group 2: current-smokers (≥ 20 pack-years) without COPD (n = 60), Group 3: ex-smokers (≥ 20 pack-years) without COPD (n = 60), and Group 4: never-smokers without COPD (n = 60). Peripheral venous blood samples (5 cc) were collected from all participants. Plasma Metrnl levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kit.

Results

Mean Metrnl levels were 28.45 ± 11.27 ng/ml in Group 1, 24.34 ± 4.38 ng/ml in Group 2, 18.84 ± 3.8 ng/ml in Group 3, and 19.44 ± 3.92 ng/ml in Group 4. Group 1 had significantly higher mean Metrnl level compared to the other groups (p = 0.006, p = 0.001, p = 0.001). Metrnl level was also significantly higher in Group 2 when compared with Groups 3 and 4 (p = 0.001, p = 0.005). Group 1 patients with diabetes mellitus and coronary artery disease showed significantly lower Metrnl levels compared to other patients in the group (p = 0.001, p = 0.001).

Conclusion

The high Metrnl level in COPD exacerbations and active smoking may be important in balancing the inflammatory response. However, plasma Metrnl levels were found to be lower in COPD patients with comorbidities.

     

Colored 3-Dimensional Analyses of Respiratory Resistance and Reactance in COPD and Asthma

Background: The forced oscillation technique (FOT) is a noninvasive method with which to measure respiratory system resistance (Rrs) and reactance (Xrs) at a wide range of frequencies during breathing at rest in a short time. The purpose of this study was to assess the differences in Rrs and Xrs between patients with chronic obstructive pulmonary disease (COPD) and asthma using a new method of FOT with colored 3-dimensional visualization. Methods: Fifty-one patients with stable COPD and 49 patients with controlled or partly controlled asthma were enrolled. Whole-breath or within-breath changes of Rrs and Xrs were measured and compared between the diseases. Results: The colored 3-dimensional images clarified the complex oscillatory properties of the respiratory system. Whole-breath resistance (the difference in Rrs at 5 and 20 Hz) and reactance (Xrs at 5 Hz and resonant frequency), and within-breath changes in reactance (Xrs at 5 Hz and resonant frequency) discriminated between patients with COPD and asthma. In multivariate regression analyses, inspiratory-expiratory differences in Xrs at 5 Hz contributed significantly to the differentiation between COPD and asthma, independent of age, gender, body weight, and pulmonary function. Conclusion: This new method of FOT is useful in the differential diagnosis of COPD and asthma.     

Plasma Lipid Profiling Identifies Phosphatidylcholine 34:3 and Triglyceride 52:3 as Potential Markers Associated with Disease Severity and Oxidative Status in Chronic Obstructive Pulmonary Disease

Purpose

To identify plasma alterations in lipid species in patients with chronic obstructive pulmonary disease (COPD), as well as, relationships with smoking status, oxidative and inflammatory markers.

Methods

Plasma was obtained from 100 patients with COPD and 120 healthy controls. Pulmonary function was assessed by plethysmography. Serum levels of IL-6 and TNF-α were determined by ELISA. Oxidative stress parameters were measured using standard methods. Lipids were extracted then analyzed by Matrix-Assisted Laser Desorption and Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF-TOF-MS).

Results

More than 40 lipid compounds were identified within plasma samples. Among these 19 lipid species including plasmalogens (PC O-), phosphatidylcholines (PC), and triglycerides (TG) were significantly altered in COPD. A decreased expression of PC O- (36:1, 36:2, 36:3, 36:4, 38:4, 38:5) species was found in patients with different severities compared to healthy controls. There was also a decrease in PC (34:3, 36:0, 36:4, 36:5, 40:6, 40:7) species in COPD patients. PC (34:3) levels were positively correlated with disease progression and pulmonary function decline (forced expiratory volume in 1 s (FEV₁)) (r?=?0.84, p?<?0.001) and inversely correlated with thiobarbituric acid-reactive substances (TBARS) (r?=?? 0.77, p?<?0.001). TG (50:0, 50:1, 52:1, 52:2, 52:3, 52:4, 54:4) species were altered in COPD patients and in those with advanced disease stages. Significant correlations between FEV₁, TBARS, peroxynitrite, and TG (52:3) were found among COPD patients (r?=?? 0.69; r?=?0.86; r?=?0.77, p?<?0.001, respectively).

Conclusion

PC (34:3) and TG (52:3) could be potential lipid signatures of COPD that correlate with altered pulmonary function and oxidative status.

     

COPD-related Bronchiectasis; Independent Impact on Disease Course and Outcomes

Background: COPD and radiographic bronchiectasis frequently coexist but the effect of this on the clinical course of COPD is not fully understood. We determined the impact of bronchiectasis on clinical outcomes in COPD patients, independent of coexisting emphysema and bronchial wall thickening (BWT). Methods: COPD patients admitted with first exacerbation 1998–2008 were identified retrospectively using ICD10 codes J44.0,1,8,9. Patients with suitable CT scans were graded for severity of bronchiectasis, emphysema and BWT on a 5 point scale (0-absent, 1-minor, 2-mild, 3-moderate, 4-severe). Results: 406 patients (71 ± 11 years, 56% male, FEV₁ 52 ± 23% predicted) were included; 278 (69%) patients had bronchiectasis: minor, 112 (40%); mild, 81 (29%); moderate, 62 (22%); severe 23 (8%). Bronchiectasis severity correlated with severity of BWT (p < 0.001) but not emphysema (p = 0.090). Bronchiectasis independently determined sputum isolation of Pseudomonas aeruginosa (Odds ratio (OR) 1.39 (95% CI 1.07 to 1.80), p = 0.013) and atypical mycobacteria (OR 2.44 (95% CI 1.04 to 5.69), p = 0.040), annual respiratory admissions (p = 0.044) and inpatient days (p < 0.001), but did not predict survival (p = 0.256). Conclusions: Radiographic bronchiectasis in COPD patients is associated with increased respiratory infection and hospitalisation, independent of coexisting emphysema and BWT. COPD-related bronchiectasis is therefore an important diagnosis with potential implications for treatment.     

Prevalence of Airflow Obstruction in Nonsmoking Older Individuals Using Different Spirometric Criteria: The AGES Reykjavik Study

Abstract

Background: The prevalence and characteristics of airway obstruction in older individuals varies widely with the definition used. We used a random sample of never smoking older population in Iceland to compare the prevalence and clinical profile of subjects diagnosed with Chronic Obstructive Pulmonary Disease (COPD) based on different spirometric criteria. Material and methods: The study uses data from the Age, Gene/Environment Susceptibility–Reykjavik Study, comprising survivors from the Reykjavik Study. Procedures included standardized questionnaires and pre-bronchodilator spirometry for measurement of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Results: Total of 495 individuals (150 men and 345 women) met study criteria. Mean age 77 years (range 66-92 years) using fixed ratio (FEV1/FVC < 70%) up to 29% of the population were diagnosed with COPD Stage I. The prevalence of COPD increased with age. Only 7 among 495 (1.4%) were diagnosed with COPD using FEV1/FVC LLN and FEV1 LLN. Conclusion: Application of the GOLD criteria for diagnosis of COPD in older lifelong never smoking subjects identifies a substantial number of non-symptomatic subjects as having COPD. If airway obstruction is defined by FEV1/FVC and FEV1 being below the LLN using appropriate reference equations, only very few non-smoking older individuals fulfill the criteria for COPD.     

D-dimer Levels in Stable COPD Patients: A Case-control Study

ABSTRACT

Background: High D-dimer levels have been detected in patients with chronic obstructive pulmonary disease (COPD) exacerbation, irrespective of presence of venous thromboembolism. On the other hand, there is a continuing debate about the diagnostic efficiency of D-dimer tests in patients with stable COPD. Objectives: We aimed to investigate if basic laboratory investigations suggest hypercoagulability state in stable COPD patients, and if there is an association with D-dimer levels and pulmonary function tests. Methods: We conducted a case-control study. COPD patients and controls were matched for sex and age in a 2:1 matching ratio. D-dimer levels and pulmonary function tests were performed in COPD patients and controls. Results: A total of 58 COPD patients and 30 controls met the inclusion criteria and were included in the analysis. The median of D-dimers was 0.24 ng/mL (IQR: 0.21-0.36 ng/mL) in COPD group and 0.17 ng/mL (IQR: 0.12-0.24 ng/mL) in control group. This difference was not statistically significant (p = 0.102). Using bivariate correlations, we found significant positive correlations between BMI and D-dimers in COPD patients (r = 0.3, p = 0.024). Conclusions: We found that levels of D-dimers in stable COPD were not different as compared to control subjects. Our results also suggest that BMI could lead to disturbances in coagulation system.     

TLR4 Up-regulation and Reduced Foxp3 Expression in Mechanically Ventilated Smokers with Obstructive Chronic Bronchitis

Abstract

Background: Chronic bronchitis (CB) is a risk factor in chronic obstructive pulmonary disease (COPD) for accelerated lung function decline and increased mortality. The lung and systemic inflammatory and immunological profile of COPD patients with CB which acutely experience respiratory failure upon a disease exacerbation is unknown. Methods: In this study, we explored the expression of Foxp3 by western blot analysis, TLR4 by immunocytochemistry and the concentrations of IP-10 and IL-8 by ELISA in the mini-bronchoalveolar lavages (mini-BAL) and in the peripheral blood of patients with respiratory failure requiring intubation and mechanical ventilation. The recruited subjects were separated into three different groups: smokers with CB and COPD (COPD, n = 18), smokers with CB but without COPD (S, n = 8) and patients without CB and without COPD (C, n = 10). Results: In mini-BAL of COPD group, Foxp3 and IP-10 were significantly reduced while TLR4 was significantly increased in comparison to C. TLR4 was also increased in mini-BAL of S. In COPD peripheral blood, Foxp3 was reduced in comparison to C but no significant differences were observed for TLR4 and for IP-10. No significant differences were observed for IL-8 concentrations in the mini-BAL and in the blood of the recruited patients. The mini-BAL TLR4 expression correlated with the Clinical Infective Pulmonary Score. Conclusions: In exacerbated COPD patients with respiratory failure, lung and systemic reduced immune regulatory events (low Foxp3 expression) and lung increased innate immunity responses (high TLR4 expression) occur. These events may contribute to the increased inflammatory events leading to respiratory failure.     

Association of exposure to environmental tobacco smoke in childhood with chronic obstructive pulmonary disease and respiratory symptoms in adults

Background and objective: Exposure to environmental tobacco smoke (ETS) is associated with impaired lung function in childhood, which in turn, is associated with chronic obstructive pulmonary disease (COPD) in adulthood. However, little is known regarding the direct association between childhood exposure to ETS and the development of COPD. The main objective of the present study was to examine the associations between childhood ETS exposure and adult COPD and respiratory symptoms. Methods: Patients with COPD (n = 433) and control subjects (n = 325) participated in the Bergen COPD Cohort Study during 2006–2009. Participants performed spirometry and answered extensive questionnaires. The risk factors for COPD, morning cough, cough with phlegm, chronic cough and dyspnoea were examined using logistic regression analysis. Analyses were stratified by gender. Results: The prevalence of childhood exposure to ETS was 61%. After adjustment, women who were exposed to ETS during childhood had a higher risk of COPD than those who were not exposed: odds ratio 1.9, 95% confidence interval 1.0, 3.7. Other important predictors for COPD and respiratory symptoms among women were occupational dust exposure (COPD), family history of COPD (COPD, all symptoms), current exposure to ETS in the home (morning cough) and education (COPD, dyspnoea). ETS exposure during childhood was associated with respiratory symptoms among males (odds ratios 1.5–1.7). Risk factors for COPD among men were occupational dust exposure, family history of COPD and level of education. Occupational dust exposure and family history of COPD also predicted dyspnoea among males. Conclusions: Exposure to ETS during childhood was associated with COPD and respiratory symptoms in adulthood. Although active smoking is still the most important risk factor for COPD, reduction of childhood ETS exposure could contribute to the prevention of COPD and respiratory symptoms.     

Abnormal Renal Resistive Index in Patients with Mild-to-moderate Chronic Obstructive Pulmonary Disease

Abstract

Background: Arterial rigidity and endothelial dysfunction are systemic manifestations of chronic obstructive pulmonary disease (COPD). The decrease in renal vascular resistance in order to adapt the increase in glomerular filtration rate after oral protein loading is known as normal renal functional reserve. We tested the hypothesis that COPD patients, even in those with mild-to-moderate airflow obstruction, are affected by systemic inflammation associated with abnormal renal functional reserve. Materials and Methods: The study enrolled 24 current smokers with a cigarette smoking history ^25 pack-years and 8 nonsmokers with normal spirometry as control. Doppler sonography detected the renal resistive index (RRI) before and after oral protein loading to determine the renal functional reserve. Pulmonary function and serum tumor necrosis factor 〈 (TNF-〈) levels were analyzed to compare with the renal functional reserve. Results: The smokers were stratified into 3 groups (Group 1: smokers with normal spirometry, Group 2: mild COPD, Group 3: moderate COPD); nonsmokers as Group 4. The baseline RRI levels were similar in Group 1 and Group 4. After protein loading, the RRI elevated in all smoking groups; moreover, Group 3 had the highest RRI and with longer duration than other groups. The smokers with higher serum TNF-〈 levels had a longer RRI elevation. Multiple linear regression revealed forced expiratory volume in one second (FEV₁), serum TNF-〈 levels and aging were independently predictive factors of impaired renal functional reserve. Conclusions: A greater impairment in renal functional reserve of COPD patients was correlated with more severe airway obstruction and inflammation.     

High Expression of Cathepsin E is Associated with the Severity of Airflow Limitation in Patients with COPD

Background: It was reported that Cathepsin E (Cat E) plays a critical role in antigen processing and in the development of pulmonary emphysema. The aim of this study was to investigate the role of Cat E and airflow limitation in the pathogenesis of COPD. Methods: Sixty-five patients with COPD, 20 smoking control subjects without COPD and 15 non-smoking healthy control subjects were enrolled. Cat E and EIC (Elastase inhibitory capacity) expressions were measured by ELISA in sputum and serum samples and compared according to different subgroups. Results: Cat E concentrations were significantly higher in patients with COPD than smoking control and non-smoking control subjects (P < 0.01). The levels of CatE were inversely correlated with FEV₁% predicted in COPD patients (r = ?0.95, P < 0.01). The levels of EIC were inversely positively correlated with FEV₁% predicted in COPD patients (r = 0.926, P < 0.01). Levels of Cat E were also inversely correlated with the levels of EIC (r = ?0.922, P < 0.01). Conclusions: Cat E contributes to the severity of airflow limitation during progression of COPD.     

Socioeconomic Status and Prognosis of COPD in Denmark

We investigated the association between length of school education and 5-year prognosis of chronic obstructive lung disease (COPD), including exacerbations, hospital admissions and survival. We used sample of general population from two independent population studies: The Copenhagen City Heart Study and Copenhagen General Population Study. A total of 6,590 individuals from general population of Copenhagen with COPD defined by the Global initiative for obstructive lung disease criteria were subdivided into 4 groups based on the length of school education: 1,590 with education < 8 years; 3,131 with education 8–10 years, 1,244 with more than 10 years, but no college/university education and 625 with college/university education. Compared with long education, short education was associated with current smoking (p < 0.001), higher prevalence of respiratory symptoms (p < 0.001) and lower forced expiratory volume in the first second in percent of predicted value (FEV₁%pred) (p < 0.001).

Adjusting for sex, age, FEV₁%pred, dyspnea, frequency of previous exacerbations and smoking we observed that shortest school education (in comparison with university education), was associated with a higher risk of COPD exacerbations (hazards ratio 1.65, 95% CI 1.15–2.37) and higher risk of all-cause mortality (hazards ratio 1.96, 95% CI 1.28–2.99). We conclude that even in an economically well-developed country with a health care system (which is largely free of charge), low socioeconomic status, assessed as the length of school education, is associated with a poorer clinical prognosis of COPD.