Function In Chronic Obstructive Pulmonary Disease Patients Research Articles

Lobar analysis of collapsibility indices to assess functional lung volumes in COPD patients.

BackgroundWe investigated correlations between lung volume collapsibility indices and pulmonary function test (PFT) results and assessed lobar differences in chronic obstructive pulmonary disease (COPD) patients, using paired inspiratory and expiratory three dimensional (3D) computed tomography (CT) images.MethodsWe retrospectively assessed 28 COPD patients who underwent paired inspiratory and expiratory CT and PFT exams on the same day. A computer-aided diagnostic system calculated total lobar volume and emphysematous lobar volume (ELV). Normal lobar volume (NLV) was determined by subtracting ELV from total lobar volume, both for inspiratory phase (NLVI) and for expiratory phase (NLVE). We also determined lobar collapsibility indices: NLV collapsibility ratio (NLVCR) (%) = (1 − NLVE/NLVI) × 100%. Associations between lobar volumes and PFT results, and collapsibility indices and PFT results were determined by Pearson correlation analysis.ResultsNLVCR values were significantly correlated with PFT results. Forced expiratory volume in 1 second, measured as percent of predicted results (FEV1%P) was significantly correlated with NLVCR values for the lower lobes (P<0.01), whereas this correlation was not significant for the upper lobes (P=0.05). FEV1%P results were also moderately correlated with inspiratory, expiratory ELV (ELVI,E) for the lower lobes (P<0.05). In contrast, the ratio of the diffusion capacity for carbon monoxide to alveolar gas volume, measured as percent of predicted (DLCO/VA%P) results were strongly correlated with ELVI for the upper lobes (P<0.001), whereas this correlation with NLVCR values was weaker for upper lobes (P<0.01) and was not significant for the lower lobes (P=0.26).ConclusionFEV1%P results were correlated with NLV collapsibility indices for lower lobes, whereas DLCO/VA%P results were correlated with NLV collapsibility indices and ELV for upper lobes. Thus, evaluating lobar NLV collapsibility might be useful for estimating pulmonary function in COPD patients.

The correlation between lung sound distribution and pulmonary function in COPD patients.

BackgroundRegional lung sound intensity in chronic obstructive pulmonary disease (COPD) patients is influenced by the severity and distribution of emphysema, obstructed peripheral airways, and altered ribcage and diaphragm configurations and movements due to hyperinflation. Changes in the lung sound distribution accompanied by pulmonary function improvements in COPD patients were observed after bronchodilator inhalation. We investigated the association of lung sound distribution with pulmonary functions, and the effects of emphysematous lesions on this association. These studies were designed to acquire the basic knowledge necessary for the application of lung sound analysis in the physiological evaluation of COPD patients.MethodsPulmonary function tests and the percentage of upper- and lower-lung sound intensity (quantitative lung data [QLD]) were evaluated in 47 stable male COPD patients (54 - 82 years of age). In 39 patients, computed tomography taken within 6 months of the study was available and analyzed.ResultsThe ratio of lower QLD to upper QLD showed significant positive correlations with FEV1 %predicted (%FEV1; ρ = 0.45, p<0.005) and MEF50 %predicted (%MEF50; ρ = 0.46, p<0.005). These correlations were not observed in COPD patients with dominant emphysema (% low attenuation area >40%, n = 20) and were stronger in less emphysematous patients (n = 19, %FEV1; ρ = 0.64, p<0.005, %MEF50; ρ = 0.71, p<0.001).ConclusionsIn COPD patients, the ratio of lower- to upper-lung sound intensities decreased according to the severity of obstructive changes, although emphysematous lesions considerably affected lung sound distribution.

Daily variation in lung function in COPD patients with combined albuterol and ipratropium: Results from a 4-week, randomized, crossover study

BackgroundThe bronchodilator response to short-acting β2-agonist and short-acting muscarinic antagonist monotherapies varies on a day-to-day basis within individual patients. The objective of this study was to compare daily variation in bronchodilator response to the combined use of albuterol and ipratropium with monotherapies in patients with chronic obstructive pulmonary disease (COPD). MethodsThis was a 4-week, randomized, open-label, two-period crossover study in patients with COPD. Patients were randomized 1:1 to receive albuterol via metered dose inhaler followed by ipratropium or vice versa during treatment Period 1 (10–14 days). The order of treatments was then reversed during treatment Period 2 (10–14 days). Pre-defined efficacy endpoints were: forced expiratory volume in 1 s (FEV1), derived FEV1, inspiratory capacity (IC) and daily variability of FEV1 and IC as measured by coefficient of variation (CV). ResultsAlbuterol and ipratropium improved FEV1 when administered as the first bronchodilator, compared with pre-dose values (0.269 and 0.243 L, respectively). Administration of the second bronchodilator provided further improvements in lung function, but to a lesser magnitude than the first bronchodilator (0.094 L for both treatments). A statistically significant reduction in daily variability in FEV1 was observed for dual bronchodilator therapy compared with monotherapy (difference in CV = 0.007; p = 0.019) and pre-dose values (no treatment; difference in CV = 0.022; p < 0.001). ConclusionsThe free combination of albuterol and ipratropium resulted in greater improvements and lower day-to-day variability in FEV1 compared with either monotherapy or no bronchodilator therapy. The reduced daily variability may be an important therapeutic advantage of using different classes of bronchodilators in COPD. Trial registrationNCT01691482.

Resultados funcionales del trasplante pulmonar en la enfermedad pulmonar obstructiva crónica

IntroductionLung transplantation (LT) is a therapeutic option with controversial results in chronic obstructive pulmonary disease (COPD). We aimed to analyze the outcomes of transplantation in terms of lung function and to identify prognostic factors. MethodA retrospective analysis of 107 patients with COPD receiving lung transplants in the La Fe Hospital between 1991 and 2008 was performed. Preoperative variables, pulmonary function tests before and after LT, surgical procedure variables and long-term monitoring, expressed as mean or percentage, as applicable, were analyzed. Spirometric results before and after LT were analyzed. Linear or logistic regression were used for multivariate analysis depending on the variable. ResultsNinety-four men (87.9%) and 13 women (12.1%) were transplanted, with a mean age±standard deviation of 52.58±8.05 years; 71% of LTs were double-lung transplantations. Spirometric values improved after LT: FVC: +1.22L (+34.9%), FEV1: +1.66L (+56.7%) and FEF25-75: +1.85L (+50.8%); P=.001. This functional improvement was maintained after 5 years only in the group with BODE score >7 (P=.001). Recipient height, type of LT, use of extracorporeal circulation during the surgical procedure, presence of bronchiolitis obliterans syndrome and the age and cause of death of the donor significantly influenced lung function over time. ConclusionsLT improves lung function in COPD patients. This improvement was maintained at 5years only in patients with BODE>7. Double lung transplantation provides better functional results than single-lung transplantation.

Impaired laryngopharyngeal sensitivity in patients with COPD: The association with swallow function

Research indicates that patients with Chronic Obstructive Pulmonary Disease (COPD) have increased aspiration risk. Several factors may pre-dispose a patient to aspiration including a reduction in laryngopharyngeal sensitivity (LPS). Reduced LPS has been associated with increased aspiration risk in pathologies including stroke; however, this has not been examined in COPD. This study aims to explore possible associations between LPS and swallowing function in COPD patients, and determine whether a LPS predictive value may be used as a method of evaluating dysphagia risk in this patient population. Twenty participants with COPD underwent LPS discrimination testing, respiratory function testing, self-reporting swallowing questionnaire, clinical swallowing examination, and fibre-optic endoscopic evaluation of swallowing (FEES). Participants with COPD demonstrated impaired LPS defined by elevated laryngeal adductor reflex thresholds and high incidence of pharyngeal residue on FEES. Positive correlations were identified between their clinical swallowing examination and FEES results for the presence of laryngeal penetration/aspiration (p < 0.04), vallecular residue (p < 0.01), and piriform residue (p < 0.01). In conclusion, COPD patients have reduced laryngopharyngeal mechanosensitivity and impaired swallowing function characterized primarily by pharyngeal stasis. The combination of these deficits may place patients with COPD at increased aspiration risk due to lack of detection of pharyngeal residue and subsequent inhalation of pharyngeal contents.

Real-time indoor PM measurements during dust storms and the association with lung function in COPD patients

Background. Environmental health research focused on outdoors particular matter (PM) exposure, yet studies indicate that most of the PM exposure occurs indoors. While indoor is affected by outdoor PM, it can be influenced by additional indoor factors. Dust storm (DS) originated PM were suggested to be a significant risk factor for pulmonary morbidity. During the DS patients can be exposed to the extremely high PM even indoors. Aims. Analysis of the association between outdoor and indoor PM during DS and none-DS days, and the effect of the desert dust exposure on patients with Chronic Obstructive Pulmonary Disease (COPD). Methods. Population comprised 86 patients with moderate-severe COPD residing in Beer Sheva city (Negev desert, Israel). Concentrations of PM10, PM2.5, and PM1 were measured inside and outside household during none-DS and DS days. A multivariate regression analysis was used to assess factors associated with indoor PM concentration. Pulmonary function tests were done at the baseline and after the DS. Results. First results (74 households) show very high indoors PM concentrations during DS; PM10 levels reached 1000 µg/m3 while the outdoor levels were 2000 µg/m3. A much stronger correlation was found between outdoor and indoor levels during DS compared with none-DS day: PM10 (DS day: r=0.733, P&lt;0.05 vs. none-DS day: r=0.38, P&lt;0.05), PM2.5 (DS day: r=0.741, P&lt;0.05 vs. none-DS day: r=0.273, P&lt;0.05), PM1 (DS day: r=0.678, P&lt;0.05 vs. none-DS day: r=0.551, P&lt;0.05). The multivariate analysis showed that indoor PM is influenced by outdoor PM and pets presence. FEV1 (forced expiratory volume in 1 second) during DS day was lower in average by 10% than at the baseline. Conclusions. Indoor PM concentrations increase significantly during DS events with a strong correlation to the ambient air. During DS days there is a worsening in lung function of COPD patients, despite the fact the patients spend most of their time indoors.

Effect of Thoracic Lymphatic Pump Technique on Pulmonary Function in COPD Patients

Introduction: Chronic Obstructive Pulmonary Disease (COPD) is characterized by chronic airflow limitation, range of pathological changes in the lung, some significant extra-pulmonary effects, and important co-morbidities and risk factors which may contribute to the severity of the disease in individual patients. Once developed, COPD and its co-morbidities cannot be cured, so must be treated continuously. Treatment options include not only pharmacological & surgical therapies but also use of osteopathic manipulative treatment (OMT). If OMT can reduce pain & immobility associated with pulmonary disease, then it should increase thoracic excursion. Aim: To analyze whether the application of the Thoracic Lymphatic Pump without activation on COPD patients influences their lung function parameters. Methodology: An Experimental Cross Sectional Study with 50 COPD diagnosed patients with COPD grade I - III according to GOLD guidelines were divided in two groups, 25 in Experimental Group(A) & 25 in Control Group(B). Pulmonary function test(Measuring VC, FEV1, FVC, FEV1/FVC RATIO, PEF and FEF) was the outcome measure. Group A was given the TLP manipulation and 10 mins nebulization. Group B was given only nebulization. Results: There were significant improvements in the VC, FVC, FEV1, FEV1/FVC values of both the groups. The FEF values showed significant improvements in experimental group as compared to control group. The means of the difference between the pre and post values of both the groups showed no statistical significance.

Pulmonary perfusion with oxygenated blood or custodiol HTK solution during cardiac surgery for postoperative pulmonary function in COPD patients: a trial protocol for the randomized, clinical, parallel group, assessor and data analyst blinded Pulmonary Protection Trial

BackgroundFive to thirty percent of patients undergoing cardiac surgery present with chronic obstructive pulmonary disease (COPD) and have a 2- to 10-fold higher 30-day mortality risk. Cardiopulmonary bypass (CPB) creates a whole body systemic inflammatory response syndrome (SIRS) that could impair pulmonary function. Impaired pulmonary function can, however, be attenuated by pulmonary perfusion with oxygenated blood or custodiol HTK (histidine-tryptophan-ketoglutarate) solution.Methods/DesignThe Pulmonary Protection Trial (PP-Trial) randomizes 90 patients undergoing CPB-dependent cardiac surgery to evaluate whether pulmonary perfusion with oxygenated blood or custodiol HTK solution reduces postoperative pulmonary dysfunction in COPD patients. Further, we aim for a non-randomized evaluation of postoperative pulmonary function after transcatheter aortic-valve implantation (TAVI). The primary outcome measure is the oxygenation index measured from anesthesia induction to the end of surgery and until 24 hours after anesthesia induction for a total of six evaluations.DiscussionPatients with COPD may be impaired by hypoxemia and SIRS. Thus, prolonged recovery and even postoperative complications and death may be reflected by the degree of hypoxemia and SIRS. The limited sample size does not aim for confirmatory conclusions on mortality, cardiovascular complications or risk of pneumonia and sepsis, but the PP-Trial is considered an important feasibility trial paving the road for a multicenter confirmatory trial.Trial registrationClinicalTrials.gov: NCT01614951.

Esophageal motility pattern and gastro-esophageal reflux in chronic obstructive pulmonary disease.

The association of esophageal motility and gastroesophageal reflux symptoms with respiratory symptoms is not well established in patients with chronic obstructive pulmonary disease (COPD). The aim of this work is to study the abnormalities of esophageal function in COPD patients and study its relation to smoking index, body mass index and indices of hyperinflation. This study included 40 male COPD patients and 10 healthy controls. The patients and controls were subjected to spirometry, body plethysmography, esophageal manometry and 24hr pH-metry. Upper gastrointestinal symptoms were found in 55% of patients, hypotensive upper esophageal sphincter pressure in 65% of patients and hypotensive lower esophageal sphincter pressure in 52.5% of patients. Pathological acid reflux was found in 35% of patients. The severity of GERD increased with increased age, smoking index and body mass index, p<0.005. There was negative correlation between LESP and UESP compared with indices of hyperinflation, p<0.001. There was high prevalence of esophageal motility disorders in COPD patients, LESP and UESP were significantly negatively correlated to indices of hyperinflation. There was a high prevalence of GERD in COPD patents especially elderly, severe stage of COPD, high smoking index and high body mass index (BMI).

Sixty-four slice spiral CT low-dose chest two-phase scanning for lung density measurement in assessing the pulmonary function in patients with chronic obstructive pulmonary disease

To explore the value of 64 slice spiral CT (SCT) low-dose chest scanning at full inspiration and full expiration for lung density measurement in assessing the pulmonary function in patients with chronic obstructive pulmonary disease (COPD). Totally 36 COPD patients (the COPD group) underwent pulmonary function tests (PFT) and were essentially verified COPD; 30 healthy people (the control group) were selected whose 64 slice SCT chest scanning was normal. The 2 groups underwent chest 64 slice SCT low-dose scanning at full inspiration and full expiration. After the scanning, the lung was measured by CT Pulmo software. The lung was divided into 3 regions by scanning layers. We measured and calculated the density indexes of each region (including the upper, middle, lower field, and the total lung) of the 2 groups. All density indexes were lung density at full inspiration and full expiration (Din, Dex), density difference (Dex-Din), density ratio (Dex/ Din), density variation percentage (Din-Dex)/Din. All patients underwent PFT and 64 slice SCT within 3 days, whose pulmonary function was tested by Master Lab ( Jaeger, Germany). The indexes were the percentage of actual value and expected value of forced expiratory volume at the first second (FEV1%) and the ratio of first second forced expiratory volume to forced vital capacity (FEV1/FVC). Then we compared with the CT indexes between the COPD group and the control group. The relevant indicators of lung densities were analyzed in comparison with the indicators of FEV1% and FEV1/FVC by Pearson correlation analysis. The density indexes of each region and total lung, and the Din in the control group and the COPD group were compared. The difference between them was statistically significant (P<0.05). The difference among other indexes was also statistically significant (P<0.01). Excellent correlation was found between Dex, Dex-Din, Dex/ Din and (Din-Dex)/ Din indexes with FEV1% and FEV1/FVC (r=0.566, 0.686, 0.568, 0.580, -0.565, -0.598, 0.565 and 0.598; P<0.01) Sixty-four slice SCT low-dose two-phase scanning density indexes are closely related to the indicators (FEV1% and FEV1/FVC) of clinical lung function tests, which can be used to evaluate the lung function in COPD patients conventiently and accurately.

Impairment of left ventricular function in patients with mild-to-moderate chronic obstructive pulmonary disease

Objective To determine whether the extent of airflow obstruction is associated with left ventricular function in mild-to-moderate chronic obstructive pulmonary disease (COPD) patients.Methods Left ventricle end diastolic volume ( LVEDV ),left ventricle end systolic volume ( LVESV ),left ventricle stroke volume( LVSV),left ventricle ejection fraction( LVEF),heart rate ( HR),cardiac output ( CO) and cardiac index (CI) were measured by ultrasonic cardiogram.Thirty-one patients with chronic bronchitis,42 mild-to-moderate COPD patients and 16 controls with normal lung function were recruited.The relations between the extent of airflow obstruction and the impairment of left ventricular function were analyzed.Results There were no significant differences of LVEDV,LVESV,LVSV,HR,CO or CI between the control and chronic bronchitis groups.LVEDV,LVESV,LVSV,CO and CI of chronic bronchitis group were significantly higher than those of mild-to-moderate COPD group while HR was lower.LVEDV,LVESV,LVSV,CO and CI had a positive correlation with forced expiratory volume in 1 second ( FEV1 ),forced vital capacity (FVC) and FEV1/FVC ratio.And HR had a negative correlation with FEV1 and FEV1/FVC.LVEF was positively correlated with FVC,but not with FEV1 and FEV1/FVC.LVEDV,LVESV,LVSV,HR,CO and CI were linearly related with FEV1.Conclusions Left ventricular function is maintained in chronic bronchitis patients. Left ventricular function,especially left ventricular end diastolic filling,deteriorates among the mild-to-moderate COPD patients.The extent of airflow obstruction may reflect the impairment of left ventricular function in COPD patients. Key words: Pulmonary disease, chronic obstructive; Ventricular function, left; Airflow obstruction

&lt;I&gt;HELICOBACTER PYLORI&lt;/I&gt; INFECTION IN NEVER-SMOKING MALE PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE AND ITS RELATION TO LUNG FUNCTION

There is a recent epidemiologic and serologic evidence for relationship between Helicobacter pylori (H. pylori) infection and Chronic Obstructive Pulmonary Disease (COPD). In order to assess the relationship between H. pylori infection and COPD and its impact on lung function we performed a cross-sectional study including 84 never-smoking male patients with COPD and an equal number of never-smoking males without chronic respiratory disease matched to the COPD patients by age. Evaluation of the study subjects included evaluation of H. pylori serological status, baseline and post-bronchodilator spirometry. We found significantly higher H. pylori seropositivity in COPD patients than in controls (76.2 Vs 34.5%, p = 0.041). The prevalence of H. pylori seropositivity did not differ significantly between patients with mild, moderate and severe COPD. Borderline significance was registered for the difference of the forced expiratory volume in one second (FEV1) mean value between seropositive and seronegative COPD patients (56.4 vs. 59.2, p = 0.063). The mean degree of FEV1 reversibility did not differ significantly between seropositive and seronegative COPD patients. Our findings indicate that in cross-sectional analysis there is higher prevalence of H. pylori seropositivity in COPD than in non-COPD patients, as well as that H. pylori infection has not significant impact on lung function in COPD patients.

Impact of non-tuberculous mycobacteria on pulmonary function decline in chronic obstructive pulmonary disease

Although chronic obstructive pulmonary disease (COPD) is a common form of structural lung disease associated with pulmonary non-tuberculous mycobacteria (NTM) infection, no longitudinal studies have investigated the role of NTM in COPD disease progression. From 2000 to 2008, spirometry-confirmed COPD patients with sputum specimens sent for mycobacterial cultures were included. Analysis of clinical, microbiological and pulmonary function data was performed. The 251 patients were divided into three groups according to the number of NTM isolates: multiple (n = 47), single (n = 63), and no (n = 141) isolates. Mycobacterium avium complex was the most common species in multiple isolates (36.2%) and single isolate (28.6%) groups. Overall, 24.7% of COPD patients had been admitted for exacerbations at least once a year, and patients with multiple and single NTM isolates were more than twice as likely as those with no isolate to experience such exacerbations (38.3% vs. 31.7% vs. 17.0%). After controlling for confounders, patients with multiple NTM isolates had a greater decline in forced expiratory volume in one second than those with single or no isolates (-79.4 ± 32.8 ml vs. -61.6 ± 31.9 ml and -56.2 ± 31.5 ml). This study suggests that NTM may play a role in disease progression and deterioration of pulmonary function in COPD patients.

High-intensity knee extensor training restores skeletal muscle function in COPD patients

Improving reduced skeletal muscle function is important for optimising exercise tolerance and quality of life in chronic obstructive pulmonary disease (COPD) patients. By applying high-intensity training to a small muscle group, we hypothesised a normalisation of muscle function. Seven patients with COPD performed 6 weeks (3 days·week(-1)) of high-intensity interval aerobic knee extensor exercise training. Five age-matched healthy individuals served as a reference group. Muscle oxygen uptake and mitochondrial respiration of the vastus lateralis muscle were measured before and after the 6-week training programme. Initial peak work and maximal mitochondrial respiration were reduced in COPD patients and improved significantly after the training programme. Peak power and maximal mitochondrial respiration in vastus lateralis muscle increased to the level of the control subjects and were mainly mediated via improved complex I respiration. Furthermore, when normalised to citrate synthase activity, no difference in maximal respiration was found either after the intervention or compared to controls, suggesting normal functioning mitochondrial complexes. The present study shows that high-intensity training of a restricted muscle group is highly effective in restoring skeletal muscle function in COPD patients.

Cause-specific mortality adjudication in the UPLIFT® COPD trial: Findings and recommendations

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death. In addition MAC determined cause of death was compared with that reported by site investigators (SIs). MAC-assigned causes of death were: respiratory, 35%; cancer, 25%; cardiovascular, 11%; sudden cardiac death, 4.4%; sudden death, 3.4%; other, 8.8%; unknown, 12.4%. Cancer/cardiac deaths were more common in Global Initiative for Chronic Obstructive Lung Disease stage II, respiratory deaths in stages III and IV. Agreement between MAC and SI regarding cause of death was complete (50.2%), incomplete (18.5%) or none (31.3%). The SI classified deaths as cardiac three-fold more frequently than MAC (incidence rate [IR]/100 patient-years 0.797 vs. 0.257), although IR ratios for cardiac deaths for tiotropium vs. control were similar between SI and MAC. Discrepancies between MAC- and SI-adjudicated causes of death are common, especially increased reporting of cardiac deaths by the SI. Future multicentre COPD trials should plan appropriate infrastructure before study initiation to ensure collection and interpretation of fatal events data.

The Role of MAPK and Nrf2 Pathways in Ketanserin-Elicited Attenuation of Cigarette Smoke–Induced IL-8 Production in Human Bronchial Epithelial Cells

Cigarette smoking is a major risk factor in chronic obstructive pulmonary disease (COPD) with chronic airway inflammation as a key feature. Blockade of serotonin receptor 2A (5-HTR(2A)) with ketanserin has been found to improve lung function in COPD patients. Furthermore, ketanserin has been shown to possess anti-inflammatory properties in vivo. In this study, we investigated the antioxidative and anti-inflammatory properties of ketanserin and its underlying mechanism of action on cigarette smoke-induced interleukin (IL)-8 release in vitro. Primary normal human bronchial epithelial cells and human bronchial epithelial cell line (BEAS-2B) were treated with or without ketanserin prior to exposure to cigarette smoke medium (CSM). Exposure to CSM caused elevation of both mRNA and release of IL-8 with increased phosphorylation of p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Consistently, CSM-induced IL-8 release was blocked by SB203580, U0126, or MEK1 small interfering RNA (siRNA) but not SP600125. On the other hand, CSM caused a dose-dependent decrease in the ratio of reduced glutathione to oxidized glutathione (rGSH/GSSG) together with an increased translocation of Nrf2 to the nucleus demonstrated by Western blot analysis. Knock down of Nrf2 by siRNA completely blocked CSM-induced IL-8 release. Ketanserin suppressed CSM-induced IL-8 release by inhibiting p38, ERK1/2 MAPK, and Nrf2 signaling pathways and partially inhibited CSM-induced reduction of rGSH/GSSG ratio. Our data demonstrated the novel antioxidative and anti-inflammatory role of ketanserin via the Nrf2 signaling pathway in CSM-exposed human bronchial epithelial cells. This may open up new perspectives in the development of novel therapeutic targets in the treatment of cigarette smoke-related COPD.

Effect of heme oxygenase-1 polymorphisms on lung function and gene expression

BackgroundOxidative stress induced by smoking is considered to be important in the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Heme oxygenase-1 (HMOX1) is an essential enzyme in heme catabolism that is induced by oxidative stress and may play a protective role as an antioxidant in the lung. We determined whether HMOX1 polymorphisms were associated with lung function in COPD patients and whether the variants had functional effects.MethodsWe genotyped five single nucleotide polymorphisms (SNPs) in the HMOX1 gene in Caucasians who had the fastest (n = 278) and the slowest (n = 304) decline of FEV1 % predicted, selected from smokers in the NHLBI Lung Health Study. These SNPs were also studied in Caucasians with the lowest (n = 535) or the highest (n = 533) baseline lung function. Reporter genes were constructed containing three HMOX1 promoter polymorphisms and the effect of these polymorphisms on H2O2 and hemin-stimulated gene expression was determined. The effect of the HMOX1 rs2071749 SNP on gene expression in alveolar macrophages was investigated.ResultsWe found a nominal association (p = 0.015) between one intronic HMOX1 SNP (rs2071749) and lung function decline but this did not survive correction for multiple comparisons. This SNP was in perfect linkage disequilibrium with rs3761439, located in the promoter of HMOX1. We tested rs3761439 and two other putatively functional polymorphisms (rs2071746 and the (GT)n polymorphism) in reporter gene assays but no significant effects on gene expression were found. There was also no effect of rs2071749 on HMOX1 gene expression in alveolar macrophages.ConclusionsWe found no association of the five HMOX1 tag SNPs with lung function decline and no evidence that the three promoter polymorphisms affected the regulation of the HMOX1 gene.

CA-125 Level Is Associated with Right Ventricular Echocardiographic Parameters in Patients with COPD

A few studies have shown that elevated CA-125 levels are associated with chronic obstructive pulmonary disease (COPD). However, there are no data concerning the associaton between serum CA-125 levels and right ventricular (RV) function in COPD patients. This study aimed to evaluate the relationship between CA-125 level and RV echocardiographic parameters in COPD patients. Fifty-two patients with COPD (39 male/13 female, mean age 68.9 ± 5.7 years) were studied. The control group consisted of 30 age-sex matched healthy volunteers (23 male/7 female, mean age 64.2 ± 6.3 years). Patients were divided into two subgroups: patients without pulmonary hypertension (group I, n = 25) and with pulmonary hypertension (group II, n = 27). Conventional echocardiographic parameters, tissue Doppler imaging (TDI) and CA-125 level measurements were performed in all subjects. Patients in group II had significantly higher CA-125 levels than those in group I and controls (P < 0.01). CA-125 levels in group I were also higher than control group (P < 0.05). CA-125 levels were correlated with left ventricle E/A ratio, systolic pulmonary artery pressure (sPAP), RV myocardial performance index, and RV fractional area change (r = 0.37, 0.56, 0.34, and -0.42, respectively, all with P < 0.05). There was an independent correlation between CA-125 levels and sPAP values (β = 0.76, P < 0.001). Our results show an independent correlation between CA-125 levels and systolic pulmonary artery pressure in COPD patients. The clinical utility of these results at this point in time is unknown and deserves future research.

02 Characterising cardiovascular safety profile of muscarinic antagonist, ipratropium

Chronic Obstructive Pulmonary Disease (COPD) is a disease characterised by inflammation of the airways which accounts for the fourth highest cause of global death. The functional role of Muscarinic receptor...

Treatment of acute chronic obstructive pulmonary disease exacerbation improves right ventricle function

It was shown that cardiac function is impaired in chronic obstructive pulmonary disease (COPD) patients who have severe pulmonary hypertension (PHT). However, no previous reports have evaluated cardiac function in COPD patients before and after medical therapy for acute COPD exacerbation. In this study, we evaluated the cardiac function of COPD patients during acute COPD exacerbation. Thirty-two patients (27 men and 5 women; mean age 59 +/- 8.7 years) with acute COPD exacerbation without PHT were included in the study. Thirty-two age- and sex-matched control subjects (22 men and 10 women; mean age 57 +/- 10 years) were also examined. Right ventricular (RV) and left ventricular (LV) functions were assessed using both conventional and tissue Doppler imaging methods before and after therapy, which were performed according to accepted guidelines. Medical therapy included inhaled beta(2)-agonists, inhaled anticholinergic agents(,) oxygen, systemic corticosteroids, and antibiotics. The systolic tissue Doppler velocity (TSm) in the RV was increased after therapy (13.7 +/- 2.4 vs. 14.4 +/- 2.4 cm/s, P = 0.027). The function of the RV and LV during diastole was also improved, and pulmonary artery pressures decreased after therapy (34 +/- 5.2 vs. 28.2 +/- 4.7 mmHg, P < 0.0001). However, there was no change in LV function during systole. We have demonstrated that treatment of patients with acute COPD exacerbation according to guidelines improves not only pulmonary function, but also RV and LV function and PHT.