Chronic Obstructive Pulmonary Disease Impairment Research Articles

Cardiopulmonary exercise testing versus pulmonary function test in the assessment of respiratory impairment in chronic obstructive pulmonary disease patients.

Cardiopulmonary exercise testing (CPET) is a non-invasive method for the determination of disability and comprehensive evaluation of exercise responses involving the cardiovascular, pulmonary and musculoskeletal systems. To assess exercise performance measured by CPET in different chronic obstructive pulmonary disease (COPD) stages and to compare between pulmonary function test (PFT) and CPET in assessing the degree of respiratory impairment. Sixty patients diagnosed with COPD were enrolled in the study. Modified Medical Research Council scale (mMRC) and COPD assessment test (CAT) to evaluate dyspnea symptom. PFT and CPET were performed. There was a significant decrease in peak VO2 and anaerobic threshold in patients with stages III, IV (P < 0.001), while COPD stage I, II had significantly higher minute ventilation, tidal volume and oxygen pulse (P < 0.001). 76.67% of patients were similarly classified by CPET and PFT, while 23.33% were found to be less impaired according to CPET when compared to PFT. A significant correlation between both VE/VO2 (r = 0.31, 95% CI 0.19-0.92, P < 0.001) and VE/VCO2 (r = 0.69, 95% CI 0.86-1.08, P < 0.001) with FEV1. Whereas, an inverse correlation were found between both VE/VCO 2 (r = -0.34, 95% CI -0.77 -1.11, P < 0.001) and VE/VO2 (r = -0.55, 95% CI -0.88 to -0.15, P < 0.001), with the degree of air trapping as estimated by RV/TLC ratio. No significant correlation between neither CAT nor MRC and exercise testing parameters. CPET is an extremely valuable method for the determination of functional capacity and exercise intolerance in COPD rather than PFT. CPET is considered a gold-standard tool for better evaluation of respiratory impairment in COPD.

MiR-4456/CCL3/CCR5 Pathway in the Pathogenesis of Tight Junction Impairment in Chronic Obstructive Pulmonary Disease.

Background: Cigarette smoke exposure (CSE) is a major cause of chronic obstructive pulmonary disease (COPD). The smoke disrupts cell-cell adhesion by inducing epithelial barrier damage to the tight junction (TJ) proteins. Even though the inflammatory mechanism of chemokine (C-C motif) ligand 3 (CCL3) in COPD has gained increasing attention in the research community, however, the underlying signaling pathway, remains unknown. Objectives: To identify the relationship of CCL3 in the pathogenesis of tight junction impairment in COPD and the pathway through which CSE causes damage to TJ in COPD via CCL3, both in vivo and in vitro. Methods: We screened the inflammatory factors in the peripheral blood mononuclear cells (PBMCs) from healthy controls and patients at each GOLD 1-4 stage of chronic obstructive pulmonary disease. RT-PCR, western blot, and ELISA were used to detect the levels of CCL3, ZO-1, and occludin after Cigarette smoke exposure. Immunofluorescence was applied to examine the impairment of the TJs in 16-HBE and A549 cells. The reverse assay was used to detect the effect of a CCR5 antagonist (DAPTA) in COPD. In the CSE-induced COPD mouse model, H&E staining and lung function tests were used to evaluate the pathological and physical states in each group. Immunofluorescence was used to assess the impairment of TJs in each group. ELISA and RT-PCR were used to examine the mRNA or protein expression of CCL3 or miR-4456 in each group. Results: The in vivo and in vitro results showed that CCL3 expression was increased in COPD compared with healthy controls. CCL3 caused significant injury to TJs through its C-C chemokine receptor type 5 (CCR5), while miR-4456 could suppress the effect of CCL3 on TJs by binding to the 3′-UTR of CCL3. Conclusion: miR-4456/CCL3/CCR5 pathway may be a potential target pathway for the treatment of COPD.

Balance impairment in individuals with COPD: a systematic review with meta-analysis

BackgroundPeople with chronic obstructive pulmonary disease (COPD) are four times more likely to fall than healthy peers, leading to increased morbidity and mortality. Poor balance is a major risk factor...

Impact of cognitive functions on the quality of spirometry performance in patients with COPD

OBJECTIVE: We researched the relationship between the cognitive scores and the error codes which determine pulmonary function test (PFT) compliance accompanied by the phenotypic findings of chronic obstructive pulmonary disease (COPD) patients. MATERIALS AND METHODS: Patients in a stable condition with COPD, who were diagnosed with the criteria recommended in the international guidelines, were included in the study. PFTs were requested from all the patients during the regular outpatient admission. The following tests were applied to all the patients in a 30-min test session; COPD assessment test, modified British Medical Research Council and neurophysiological tests (Mini-Mental Test, Trail Making Test Part A and B, Clock Drawing Test, Straight and Backward Digit Span, Brown Peterson Task and Verbal Fluency Test). We analyzed the statistical relationship between data collected after cognitive tests and PFT quality data. RESULTS: The study was concluded with a total of 70 patients. When the PFT evaluations of the patients were examined, the percentage of patients who correctly fulfilled the repeatability criteria was found as 28%, who met the acceptability criteria as 57%, and who correctly fulfilled both criteria as 14%. The relationship between the results of patients, who fulfilled both repeatability and acceptability criteria correctly and incorrectly at the same time, with the backward digit span test results was found to be significant (P DISCUSSION AND CONCLUSION: Error codes that identify the compliance in PFTs could be used as predictors of cognitive impairment in COPD.

Nonadherence to treatment and quality of life among patients with chronic obstructive pulmonary disease.

Objectives:Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases. Assessment of medication nonadherence and quality of life (QOL) is important in such chronic diseases. The aim of the study was to describe treatment nonadherence and QOL of COPD patients and their associated factors.Materials and Methods:A cross-sectional study was performed in Mansoura Chest Hospital on 133 already diagnosed inpatient cases of COPD from March to August 2017. Data were collected using two validated questionnaires, Morisky Medication Adherence Scale to assess medication adherence and St George's Respiratory Questionnaire for COPD patients (SGRQ-c) to assess QOL.Results:About 45% of studied group were nonadherent to prescribed medications. Logistic regression analysis showed that duration of disease is the only independent risk factor for nonadherence. The scores on SGRQ-c indicated sever QOL affection in COPD. SGRQ-c scores show significant impairment with the presence of comorbidities, hospital admission, and frequency of exacerbations.Conclusions:Nonadherence to treatment was affected mainly by the duration of disease. QOL impairment in COPD is influenced by broad range of factors suggesting the importance of QOL assessment in those patients. No association was found between nonadherence to treatment and QOL.

Daily Activity Related Quality of Life in Chronic Obstructive Pulmonary Disease in Adults

Abstract:&#x0D; Background: The significant reason for anguish as well as incapacity is chronic obstructive pulmonary disease (COPD). Activities of daily living might be relentlessly curbed among patients with COPD and appraisal needs evaluation regarding influence of infirmity and detriments on day-to-day living. The primary objective was to know the daily activity associated quality of life in COPD adults. The secondary objective was to analyze demographical profile, such as gender and age of COPD subjects as well as evaluate the physical activity related breathlessness in COPD patients.&#x0D; Methodology: This study was executed at Gulab Devi Chest Hospital. We used cross sectional study design to collect the data. For collecting the statistics of 150 subjects aged 40-60 years of either gender Saint George’s Questionnaire was liable. It included the patient’s biodata, effect of COPD on physical activities and limitations in routine work.&#x0D; Results: The ages of 150 COPD patients selected were between 40 and 60 years. Patients were classified into two categories on the basis of disease severity according to GOLD criteria 71 (47.3%) were with moderate severity and 79 (52.7%) were with severe severity. 113 (75.3%) patients were smokers while 37 (24.7%) patients were non-smokers. 110 (73.3%) COPD patients were active smokers in comparison 40 (26.7%) COPD patients were passive smokers. COPD patients with current smoking status were 79 (52.7%) and with past smoking status were 71 (47.3%). 19 (12.7%) COPD patients felt breathlessness while sitting and lying. 53(35.3%) COPD patients felt breathless while getting washed or dressed. 85(56.7%) COPD patients felt breathless while walking around the home. 114 (96%) COPD patients discerned breathlessness while walking up a flight of stairs. 145 (96.7%) COPD patients had breathlessness while playing sports or games. 146 (97.3%) COPD patients experienced difficulty in breathing during activities like carrying load. 88 (58.7%) COPD patients discerned breathlessness during entertainment or recreation. 88 (58.7%) COPD patients discerned breathlessness during entertainment or recreation. 7 (4.7%) COPD patients felt breathlessness while moving from bed or chair.&#x0D; Conclusion: As with the progression of COPD impairment in activities become worse due to breathlessness causing decline in patient’s ability making them unable to complete their task to fulfill the needs of life and ultimately become bed bound due to shortness of breath.

Assessment of Cognitive Impairment in Patients with Chronic Obstructive Pulmonary Disease Using the Rapid Cognitive Screen.

To determine the prevalence of cognitive impairment in chronic obstructive pulmonary disease (COPD) patients using the Rapid Cognitive Screen (RCS). Cross sectional study. A total of 106 men and women with COPD 50 years of age or older. Pulmonary ambulatory clinic in a tertiary academic center in St. Louis, Missouri, USA. We enrolled patients with COPD who completed the RCS tool. Patients were classified as having normal cognition, mild cognitive impairment (MCI), or dementia if they scored ≥ 8, 6-7, or ≤ 5, respectively. The prevalence of each category was measured, and patients' baseline characteristics were compared. One hundred and six patients completed the RCS. Of those, 36 (33.9%) patients scored ≤ 5 on the RCS, 33 (31.1%) scored 6 or 7, and 37 (34.9%) scored ≥ 8. The prevalence of dementia, MCI, and normal cognition were 33.9%, 31.1%, and 34.9%, respectively. Baseline lung function was not different between patients with normal cognition and those with abnormal cognition (FEV1 1.53 ± 0.39 vs 1.45 ± 0.32 L). In patients with abnormal cognition, there was no difference in patients' characteristics between patients with MCI or dementia. Cognitive impairment is highly prevalent in patients with COPD. RCS successfully identified cognitive impairment in COPD. We recommend performing RCS in patients with COPD routinely.

Cognitive Impairment in Chronic Obstructive Pulmonary Disease (COPD): Possible Utility of Marine Bioactive Compounds.

Chronic obstructive pulmonary disease (COPD) is characterized by long-term airflow limitation. Early-onset COPD in non-smoker subjects is ≥60 years and in the elderly is often associated with different comorbidities. Cognitive impairment is one of the most common feature in patients with COPD, and is associated with COPD severity and comorbidities. Cognitive impairment in COPD enhances the assistance requirement in different aspects of daily living, treatment adherence, and effectual self-management.This review describes various bioactive compounds of natural marine sources that modulate different targets shared by both COPD and cognitive impairment and hypothesizes a possible link between these two syndromes.

Left ventricular volume and wall stress are linked to lung function impairment in COPD

BackgroundCardiovascular comorbidities are common in chronic obstructive pulmonary disease (COPD). We examined the association between airflow limitation, hyperinflation and the left ventricle (LV). MethodsPatients from the COPD cohort COSYCONET underwent evaluations including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), effective airway resistance (Reff), intrathoracic gas volume (ITGV), and echocardiographic LV end-diastolic volume (LVEDV), stroke volume (LVSV), end-systolic volume (LVESV), and end-diastolic and end-systolic LV wall stress. Data from Visit 1 (baseline) and Visit 3 (18 months later) were used. In addition to comparisons of both visits, multivariate regression analysis was conducted, followed by structural equation modelling (SEM) with latent variables “Lung” and “Left heart”. ResultsA total of 641 participants were included in this analysis. From Visit 1 to Visit 3, there were significant declines in FEV1 and FEV1/FVC, and increases in Reff, ITGV and LV end-diastolic wall stress, and a borderline significant decrease in LV mass. There were significant correlations of: FEV1% predicted with LVEDV and LVSV; Reff with LVSV; and ITGV with LV mass and LV end-diastolic wall stress. The SEM fitted the data of both visits well (comparative fit index: 0.978, 0.962), with strong correlation between “Lung” and “Left heart”. ConclusionsWe demonstrated a relationship between lung function impairment and LV wall stress in patients with COPD. This supports the hypothesis that LV impairment in COPD could be initiated or promoted, at least partly, by mechanical factors exerted by the lung disorder.

Resveratrol for patients with chronic obstructive pulmonary disease: hype or hope?

Purpose of reviewChronic obstructive pulmonary disease (COPD) is a progressive lung disease with a high prevalence of extrapulmonary manifestations and, frequently, cardiovascular comorbidity. Resveratrol is a food-derived compound with anti-inflammatory, antioxidant, metabolic and cardioprotective potential. Therefore, resveratrol might improve the pulmonary as well as extrapulmonary pathology in COPD. In this review, we will evaluate knowledge on the effects of resveratrol on lung injury, muscle metabolism and cardiovascular risk profile and discuss if resveratrol is a hype or hope for patients with COPD.Recent findingsExperimental models of COPD consistently show decreased inflammation and oxidative stress in the lungs after resveratrol treatment. These beneficial anti-inflammatory and antioxidant properties of resveratrol can indirectly also improve both skeletal and respiratory muscle impairment in COPD. Recent clinical studies in non-COPD populations show improved mitochondrial oxidative metabolism after resveratrol treatment, which could be beneficial for both lung and muscle impairment in COPD. Moreover, preclinical studies suggest cardioprotective effects of resveratrol but results of clinical studies are inconclusive.SummaryResveratrol might be an interesting therapeutic candidate to counteract lung and muscle impairments characteristic to COPD. However, there is no convincing evidence that resveratrol will significantly decrease the cardiovascular risk in patients with COPD.

Independent determinants of disease-related quality of life in COPD &amp;ndash; scope for nonpharmacologic interventions?

PurposeQuality-of-life (QoL) scores in chronic obstructive pulmonary disease (COPD) have a weak relationship with physiologic impairment. We investigated factors associated with poor QoL, focusing on psychological measures potentially amenable to intervention.Patients and methodsWe utilized a pre-existing Birmingham (UK) COPD cohort to assess factors associated with QoL impairment (COPD Assessment Test [CAT] scores). Univariate and multivariate regression models were constructed from three categories of variables: demographic, lung function/COPD-related symptoms, and psychosocial/behavioral factors.ResultsAnalyses were based on self-report questionnaire data from 735 participants. The multivariate model of variables independently associated with CAT included depression, dysfunctional breathing symptoms (Nijmegen score), and illness perception, in addition to COPD symptoms (wheeze, cough), exercise capacity, breathlessness, exacerbations, and deprivation; this model explained 72% of CAT score variation. In a dominance analysis assessing the relative contribution of variables, similar contributions were made by breathlessness (20.2%), illness perception (19.8%), dysfunctional breathing symptoms (17.5%), and depression (12.5%) with other variables contributing <5%.ConclusionPsychological factors significantly contribute to disease-specific QoL impairment in COPD, and potentially explain the mismatch between objective physiologic impairment and patients’ experience of their disease. Interventions targeting psychological factors, illness perception, and dysfunctional breathing should be assessed.

Impaired calcium signaling in muscle fibers from intercostal and foot skeletal muscle in a cigarette smoke-induced mouse model of COPD.

Respiratory and locomotor skeletal muscle dysfunction are common findings in chronic obstructive pulmonary disease (COPD); however, the mechanisms that cause muscle impairment in COPD are unclear. Because Ca2+ signaling in excitation-contraction (E-C) coupling is important for muscle activity, we hypothesized that Ca2+ dysregulation could contribute to muscle dysfunction in COPD. Intercostal and flexor digitorum brevis muscles from control and cigarette smoke-exposed mice were investigated. We used single cell Ca2+ imaging and Western blot assays to assess Ca2+ signals and E-C coupling proteins. We found impaired Ca2+ signals in muscle fibers from both muscle types, without significant changes in releasable Ca2+ or in the expression levels of E-C coupling proteins. Ca2+ dysregulation may contribute or accompany respiratory and locomotor muscle dysfunction in COPD. These findings are of significance to the understanding of the pathophysiological course of COPD in respiratory and locomotor muscles. Muscle Nerve 56: 282-291, 2017.

Cognitive function and living situation in COPD: is there a relationship with self-management and quality of life?

BackgroundCognitive impairment is increasingly being found to be a common comorbidity in chronic obstructive pulmonary disease (COPD). This study sought to understand the relationship of comprehensively measured cognitive function with COPD severity, quality of life, living situation, health care utilization, and self-management abilities.MethodsSubjects with COPD were recruited from the outpatient pulmonary clinic. Cognitive function was assessed using the Montreal Cognitive Assessment (MOCA). Self-management abilities were measured using the Self Management Ability Score 30. Quality of life was measured using the Chronic Respiratory Disease Questionnaire. Pearson correlation was used to assess the bivariate association of the MOCA with other study measures. Multivariate analysis was completed to understand the interaction of the MOCA and living situation on COPD outcomes of hospitalization, quality of life, and self-management ability.ResultsThis study included 100 participants of mean age 70±9.4 years (63% male, 37% female) with COPD (mean FEV1 [forced expiratory volume in 1 second] percentage predicted 40.4±16.7). Mean MOCA score was 23.8±3.9 with 63% of patients having mild cognitive impairment. The MOCA was negatively correlated with age (r=−0.28, P=0.005) and positively correlated with education (r=+0.24, P=0.012). There was no significant correlation between cognitive function and exacerbations, emergency room (ER) visits, or hospitalizations. There was no association between the MOCA score and self-management abilities or quality of life. We tested the interaction of living situation and the MOCA with self-management abilities and found statistical significance (P=0.017), indicating that individuals living alone with higher cognitive function report lower self-management abilities.ConclusionCognitive impairment in COPD does not appear to be meaningfully associated with COPD severity, health outcomes, or self-management abilities. The routine screening for cognitive impairment due to a diagnosis of COPD may not be indicated. Living alone significantly affects the interaction between self-management abilities and cognitive function.

Diffusion capacity of the lung for carbon monoxide – A potential marker of impaired gas exchange or of systemic deconditioning in chronic obstructive lung disease?

Gas exchange impairment is primarily caused by ventilation-perfusion mismatch in chronic obstructive pulmonary disease (COPD), where diffusing capacity of the lungs for carbon monoxide (DLCO) remains the clinical measure. This study investigates whether DLCO: (1) can predict respiratory impairment in COPD, that is, changes in oxygen and carbon dioxide (CO2); (2) is associated with combined risk assessment score for COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) score); and (3) is associated with blood glucose and body mass index (BMI). Fifty patients were included retrospectively. DLCO; arterial blood gas at inspired oxygen (FiO2) = 0.21; oxygen saturation (SpO2) at FiO2 = 0.21 (SpO2 (21)) and FiO2 = 0.15 (SpO2 (15)) were registered. Difference between arterial and end-tidal CO2 (ΔCO2) was calculated. COPD severity was stratified according to GOLD score. The association between DLCO, SpO2, ΔCO2, GOLD score, blood glucose, and BMI was investigated. Multiple regression showed association between DLCO and GOLD score, BMI, and glucose level (R (2) = 0.6, p < 0.0001). Linear and multiple regression showed an association between DLCO and SpO2 (21) (R (2) = 0.3, p = 0.001 and p = 0.03, respectively) without contribution from SpO2 (15) or ΔCO2. A stronger association between DLCO and GOLD score than between DLCO and SpO2 could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed. A weaker association is seen between DLCO and SpO2 (21) without contribution from SpO2 (15) and ΔCO2. This could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed.

Circulating progenitor cells and vascular dysfunction in chronic obstructive pulmonary disease.

BackgroundIn chronic obstructive pulmonary disease (COPD), decreased progenitor cells and impairment of systemic vascular function have been suggested to confer higher cardiovascular risk. The origin of these changes and their relationship with alterations in the pulmonary circulation are unknown.ObjectivesTo investigate whether changes in the number of circulating hematopoietic progenitor cells are associated with pulmonary hypertension or changes in endothelial function.Methods62 COPD patients and 35 controls (18 non-smokers and 17 smokers) without cardiovascular risk factors other than cigarette smoking were studied. The number of circulating progenitors was measured as CD45+CD34+CD133+ labeled cells by flow cytometry. Endothelial function was assessed by flow-mediated dilation. Markers of inflammation and angiogenesis were also measured in all subjects.ResultsCompared with controls, the number of circulating progenitor cells was reduced in COPD patients. Progenitor cells did not differ between control smokers and non-smokers. COPD patients with pulmonary hypertension showed greater number of progenitor cells than those without pulmonary hypertension. Systemic endothelial function was worse in both control smokers and COPD patients. Interleukin-6, fibrinogen, high sensitivity C-reactive protein, vascular endothelial growth factor and tumor necrosis factor were increased in COPD. In COPD patients, the number of circulating progenitor cells was inversely related to the flow-mediated dilation of systemic arteries.ConclusionsPulmonary and systemic vascular impairment in COPD is associated with cigarette smoking but not with the reduced number of circulating hematopoietic progenitors. The latter appears to be a consequence of the disease itself not related to smoking habit.

The Muscle Oxidative Regulatory Response to Acute Exercise Is Not Impaired in Less Advanced COPD Despite a Decreased Oxidative Phenotype

Already in an early disease stage, patients with chronic obstructive pulmonary disease (COPD) are confronted with impaired skeletal muscle function and physical performance due to a loss of oxidative type I muscle fibers and oxidative capacity (i.e. oxidative phenotype; Oxphen). Physical activity is a well-known stimulus of muscle Oxphen and crucial for its maintenance. We hypothesized that a blunted response of Oxphen genes to an acute bout of exercise could contribute to decreased Oxphen in COPD. For this, 28 patients with less advanced COPD (age 65±7 yrs, FEV1 59±16% predicted) and 15 age- and gender-matched healthy controls performed an incremental cycle ergometry test. The Oxphen response to exercise was determined by the measurement of gene expression levels of Oxphen markers in pre and 4h-post exercise quadriceps biopsies. Because exercise-induced hypoxia and oxidative stress may interfere with Oxphen response, oxygen saturation and oxidative stress markers were assessed as well. Regardless of oxygen desaturation and absolute exercise intensities, the Oxphen regulatory response to exercise was comparable between COPD patients and controls with no evidence of increased oxidative stress. In conclusion, the muscle Oxphen regulatory response to acute exercise is not blunted in less advanced COPD, regardless of exercise-induced hypoxia. Hence, this study provides further rationale for incorporation of exercise training as integrated part of disease management to prevent or slow down loss of muscle Oxphen and related functional impairment in COPD.

The unique alterations of hippocampus and cognitive impairment in chronic obstructive pulmonary disease

BackgroundCognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood.MethodsThirty-seven mild-to-moderate COPD patients, forty-eight severe COPD patients, and thirty-one control subjects were recruited for cognitive test and neuroimaging studies. Serum levels of S100B,pulmonary function and arterial blood gas levels were also evaluated in each subject.ResultsThe hippocampal volume was significantly smaller in COPD patients compared to the control group. It is positively correlated with a mini mental state examination (MMSE) score, SaO2 in mild-to-moderate COPD patients, the levels of PaO2 in both mild-to-moderate and severe COPD patients. Higher S100B concentrations were observed in mild-to-moderate COPD patients, while the highest S100B level was found in severe COPD patients when compared to the control subjects. S100B levels are negatively associated with MMSE in both mild-to-moderate and severe COPD patients and also negatively associated with the hippocampal volume in the total COPD patients.ConclusionsHippocampal atrophy based on quantitative assessment by magnetic resonance imaging does occur in COPD patients, which may be associated with cognitive dysfunction and the most prevalent mechanism accountable for hippocampal atrophy is chronic hypoxemia in COPD. Higher serum S100B levels may be peripheral biochemical marker for cognitive impairment in COPD.

Cognitive function in COPD

In order to characterise the overall clinical picture of chronic obstructive pulmonary disease (COPD) a better understanding of all relevant comorbidities is required. It is increasingly recognised that COPD is a multi-component disease, but little attention has been paid to its effects on cognitive function. Cognitive dysfunction is associated with increased mortality and disability; however, it remains poorly understood in COPD. This review examines mechanisms of injury and dysfunction to the brain and considers the methods used to evaluate cognition, and assembles evidence concerning the nature and level of cognitive impairment in COPD. Our main findings are: 1) there may be a pattern of cognitive dysfunction specific to COPD; 2) cognitive function is only mildly impaired in patients without hypoxaemia; 3) the incidence of cognitive dysfunction is higher in hypoxaemia; 4) hypoxaemia, hypercapnia, smoking and comorbidities (such as vascular disease) are unlikely to account for all of the cognitive dysfunction seen in COPD; 5) there is weak or no association between cognitive function and mood, fatigue or health status; 6) cognitive dysfunction may be associated with increased mortality and disability; and 7) there is limited evidence for a significant effect of treatment on cognitive function.

Telomere shortening in chronic obstructive pulmonary disease

Chronic oxidative stress and systemic inflammation contribute to the pathology of several chronic diseases, one among which is chronic obstructive pulmonary disease (COPD). In addition, increased oxidative stress and inflammation have been observed to be negatively associated with telomere length (TL). Our aim was to investigate the TL in COPD patients in relation to pulmonary and extrapulmonary disease severity. Furthermore, based on experimental evidence suggesting the effects of oxidative stress on telomere shortening, we studied the association of TL with the antioxidant enzyme superoxide dismutase (SOD). One hundred and two COPD patients with moderate to severe COPD were studied and compared with 19 healthy age-matched controls. Patients were characterized by elevated levels of inflammatory markers (CRP, sTNF-receptors) and lower SOD-activity than the controls (p<0.001), irrespective of the SOD genotype. TL was negatively associated with age (p<0.01) and was significantly shorter in COPD patients than controls (p<0.05). Within the patient group age-adjusted TL variability could not be explained by lung function and smoking history but a modest association was found with the percentage of fat mass (p<0.05). These data provide evidence for a relationship between a disturbed oxidant/antioxidant balance and telomere shortening and indicate that preservation of fat mass may be protective in delaying telomere shortening in COPD patients.

The Mitochondrial Phenotype of Peripheral Muscle in Chronic Obstructive Pulmonary Disease

Peripheral muscle alterations have been recognized to contribute to disability in chronic obstructive pulmonary disease (COPD). To describe the mitochondrial phenotype in a moderate to severe COPD population and age-matched controls. Three primary aspects of mitochondrial function were assessed in permeabilized locomotor muscle fibers. Respiration rates per milligram of fiber weight were significantly lower in COPD muscle compared with healthy age-matched control muscle under various respiratory states. However, when variations in mitochondrial volume were taken into account by normalizing respiration per unit of citrate synthase activity, differences between the two groups were abolished, suggesting the absence of specific mitochondrial respiratory impairment in COPD. H(2)O(2) production per mitochondrion was higher both under basal and ADP-stimulated states, suggesting that mitochondria from COPD muscle have properties that potentiate H(2)O(2) release. Direct assessment of mitochondrial sensitivity to Ca(2+)-induced opening of the permeability transition pore (PTP) indicated that mitochondria from patients with COPD were more resistant to PTP opening than their counterparts in control subjects. Comparison of these results with those of studies comparing healthy glycolytic with oxidative muscle suggests that these differences may be attributable to greater type II fiber expression in COPD muscle, as mitochondria within this fiber type have respiratory function similar to that of mitochondria from type I fibers, and yet are intrinsically prone to greater release of H(2)O(2) and more resistant to PTP opening. These results thus argue against the presence of pathological mitochondrial alterations in this category of patients with COPD.