Chronic Obstructive Pulmonary Disease Grade Research Articles

Microbial and host immune factors as drivers of COPD.

Compartmentalisation of the respiratory tract microbiota in patients with different chronic obstructive pulmonary disease (COPD) severity degrees needs to be systematically investigated. In addition, it is unknown if the inflammatory and emphysematous milieux in patients with COPD are associated with changes in the respiratory tract microbiota and host macrophage gene expression.We performed a cross-sectional study to compare non-COPD controls (n=10) to COPD patients (n=32) with different disease severity degrees. Samples (n=187) were obtained from different sites of the upper and lower respiratory tract. Microbiota analyses were performed by 16S ribosomal RNA gene sequencing and host gene expression analyses by quantitative real-time PCR of distinct markers of bronchoalveolar lavage cells.Overall, the microbial communities of severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 3/4) patients clustered significantly differently to controls and less severe COPD (GOLD 1/2) patients (permutational multivariate ANOVA (MANOVA), p=0.001). However, we could not detect significant associations between the different sampling sites in the lower airways. In addition, the chosen set of host gene expression markers significantly separated COPD GOLD 3/4 patients, and we found correlations between the composition of the microbiota and the host data.In conclusion, this study demonstrates associations between host gene expression and microbiota profiles that may influence the course of COPD.

The effects of NOX4 and TGF-βinvolved in airway remodeling of Chronic Obstructive Pulmonary Disease

To investigate the role of nicotinamide adenine dinucleotide phosphate 4 (NADPH4,NOX4) and transforming growth factor-beta (TGF-β) involve in pathogenesis of airway remodeling in chronic obstructive pulmonary disease (COPD). Lung tissues from 36 COPD patients and 19 patients with normal lung function were enrolled in this study. The volume of airway smooth muscle (ASM)mass was evaluated. The expressions of NOX4, collagen Ⅳ (Col Ⅳ) and TGF-β were tested by a semi-quantitative morphological and/or immunohistochemistry staining method and Western blot, and their correlations with pulmonary functions were analyzed. ①Index of the percentage of the thickness of ASM/external diameter of small airway (WT%) and the percentage of the area of ASM/transverse area of small airway (WA%) were significantly higher in the COPD group than those in controls(P<0.05).②In COPD patients,epithelial cells metaplasia were found and α-SMA and Col Ⅳwere expressed in a part of epithelial cells. The expressions of α-small muscle actin (α-SMA) and Col Ⅰ were increased in COPD patients in comparison with the patients without obstructive airway disorders(P<0.05).③The expression of NOX4 in ASM and epithelial cells of COPD patients was significantly higher in comparison with the patients without COPD. The expression of NOX4 in ASM of small airway were statistically different among different COPD grade (P<0.05). Correlation analysis demonstrated that the level of NOX4 protein in ASM of small airway was inversely associated with pulmonary functions. ④The expression of TGF-β in COPD was significantly higher than that in patients without COPD. ⑤ Correlation analysis demonstrated that the level of NOX4 protein in ASM of small airway, WT% and WA% were inversely associated with pulmonary functions. ①The airway remodeling of COPD is characterized by increasing hyperplasia of small airway smooth muscle.②Remodeling of airway smooth muscle associats with severity of airflow limitation in COPD patients. ③The expressions of NOX4, TGF-β and α-SMA in COPD epithelial cells and small airway smooth muscle cells are significantly enhanced. The expressions of NOX4, α-SMA and TGF-β are positively correlated with the severity of chronic obstructive pulmonary air flow, suggesting that TGF-β and NOX4 signaling may be involved in the development of chronic obstructive pulmonary disease airway remodeling.

Impact of Chronic Obstructive Pulmonary Disease on Risk of Recurrence in Patients with Resected Non-small Cell Lung Cancer

背景与目的肺癌和慢性阻塞性肺病（chronic obstructive pulmonary disease, COPD）和非小细胞肺癌（non-small cell lung cancer, NSCLC）均是呼吸系统的常见病和多发病，在世界范围内均是高发病率和高死亡率的疾病。本研究旨在探讨COPD的严重程度是否影响NSCLC切除术后的远期生存。方法回顾性分析421例肺叶切除术的NSCLC患者资料，根据慢性阻塞性肺疾病全球倡议（Global Initiative for Chronic Obstructive Lung Disease, GOLD）指南对COPD患者严重程度进行分级，将入组患者分为3组，比较临床病理特征和无复发生存（recurrence-free survival, RFS）的差异。结果合并COPD者共172例，其中轻度124例，中度46例，重度2例。随着COPD严重程度增加，术后复发率增加（P < 0.001）。无COPD组、轻度COPD组（GOLD-1）和中重度COPD组（GOLD-2/3）的5年无复发生存率分别为78.1%，70.4%和46.4%，差异有统计学意义（P < 0.001）。单因素分析结果显示，年龄、性别、吸烟史、COPD严重程度、肿瘤直径、组织学类型和病理分期是影响患者无复发生存的危险因素。Cox多因素回归分析结果显示，年龄、性别、中重度COPD和病理分期是影响患者预后的独立危险因素。结论合并中重度COPD是影响NSCLC患者术后无复发生存的独立危险因素，可结合患者术前肺功能来判断预后，更准确地预测复发风险，为高危患者制定合理的个体化治疗方案。

The effect of progressive muscle relaxation on the management of fatigue and quality of sleep in patients with chronic obstructive pulmonary disease: A randomized controlled clinical trial

ObjectiveTo assess the effect of progressive muscle relaxation (PMR) on fatigue and sleep quality of patients with chronic obstructive pulmonary disease (COPD) stages 3 and 4. Materials and methodsThe pretest posttest clinical trial recruited 91 patients COPD grades 3 and 4. Following random assignment of subjects, the treatment group (n = 45) performed PMR for eight weeks and the control group (n = 46) received routine cares. At baseline and after the intervention, fatigue and sleep quality was assessed. Data obtained were analyzed in SPSS. ResultsIt was determined that PMR decreased patients' fatigue level and improved some sleep quality subscales including subjective sleep quality, sleep latency, sleep duration and habitual sleep efficiency, but no improvement was found in global sleep quality and other sleep subscales. ConclusionAn eight-week home-based PMR program can be effective in reducing fatigue and improving certain subscales of sleep quality in patients with COPD stages 3,4. (IRCT2016080124080N3).

The improvement on Respiratory Muscle, Trunk Stability, and health status after Abdominal Drawing-in Maneuver in COPD Patients

Background: Chronic Obstructive Pulmonary Disease (COPD) patients experienced respiratory muscledysfunction, postural instability, and decreasing in health status. Abdominal drawing-in maneuver (ADIM) hasbeen studied in many cases of low back pain for lumbar stabilization, moreover this maneuver is also designedto activate the transversus abdominalis (TA) muscle that involved in expiration. But this exercise has not beenconsidered as a respiration exercise in COPD patients. The purpose of this study was to determine whether theapplication of ADIM to COPD patients would affect the strength of respiratory muscle, improve core musclestability, and health status of COPD patients.Methods:All clinically stable COPD patients who visited PMR clinic at Persahabatan General Hospital wererecruited in the study. They received exercise interventions 2 times a week for 4 weeks. ADIM as a mainprogram is using pressure transducer (Chattanooga, Australia). Each exercise was held 10 repetitions, 10 setswith 2 minutes rest. Strength of respiratory muscle measured by peak cough flow (PCF) and peak flow rate(PFR). Core muscle stability measured by functional reach test (FRT) and the health status measured with CATscore. The measurements were done before and immediately after intervention.Results: Subjects were 8 patients with mean age 62 years old, consisted of 7 men and 1 woman, with 1 patienteach with COPD grade A, B, and C, and 5 patients with COPD grade D. There were increasing of PCF (268.75± 59.146 L/min to 285.00 ±59.522 L/min; p=0.061), PFR (251.3±96.3 L/min to 286.3±92 L/min; p=0.028),FRT (20.2±3.8 cm to 22±3.9 cm; p=0.011), and decreasing of CAT score (14 ±8.685 to 11.50 ±8.848; p=0.027)after ADIM.Conclusion: There were an improvement in respiratory muscle, trunk stability, and CAT after ADIM, so themaneuver is effective for COPD management.Keywords: Abdominal drawing-in maneuver (ADIM), Chronic Obstructive Pulmonary Disease (COPD),COPD Assessment Test (CAT), Functional reach test (FRT), Peak cough flow (PCF), Peak flow rate (PFR)

Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea and a reduction in lung function, quality of life and life expectancy. Apart from smoking cessation, there are no other treatments that slow lung function decline. Roflumilast and cilomilast are oral phosphodiesterase 4 (PDE4) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This is an update of a Cochrane review first published in 2011 and updated in 2013. To evaluate the efficacy and safety of oral PDE4 inhibitors in the management of stable COPD. We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search October 2016). We found other trials from web-based clinical trials registers. We included RCTs if they compared oral PDE4 inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy. One review author extracted data and a second review author checked the data. We reported pooled data in Review Manager as mean differences (MD), standardised mean differences (SMD) or odds ratios (OR). We converted the odds ratios into absolute treatment effects in a 'Summary of findings' table. Thirty-four separate RCTs studying roflumilast (20 trials with 17,627 participants) or cilomilast (14 trials with 6457 participants) met the inclusion criteria, with a duration of between six weeks and one year. These included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II-IV), with a mean age of 64 years.We considered that the methodological quality of the 34 published and unpublished trials was acceptable overall. Treatment with a PDE4 inhibitor was associated with a significant improvement in forced expiratory volume in one second (FEV1) over the trial period compared with placebo (MD 51.53 mL, 95% confidence interval (CI) 43.17 to 59.90, 27 trials with 20,585 participants, moderate-quality evidence due to moderate levels of heterogeneity and risk of reporting bias). There were small improvements in quality of life (St George's Respiratory Questionnaire (SGRQ), MD -1.06 units, 95% CI -1.68 to -0.43, 11 trials with 7645 participants, moderate-quality evidence due to moderate levels of heterogeneity and risk of reporting bias) and COPD-related symptoms, but no significant change in exercise tolerance. Treatment with a PDE4 inhibitor was associated with a reduced likelihood of COPD exacerbation (OR 0.78, 95% CI 0.73 to 0.83; 23 trials with 19,948 participants, high-quality evidence). For every 100 people treated with PDE4 inhibitors, five more remained exacerbation-free during the study period compared with placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 26). More participants in the treatment groups experienced non-serious adverse events compared with controls, particularly a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting or dyspepsia. For every 100 people treated with PDE4 inhibitors, seven more suffered from diarrhoea during the study period compared with placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). Roflumilast in particular was associated with weight loss during the trial period and an increase in insomnia and depressive mood symptoms. There was no significant effect of treatment on non-fatal serious adverse events (OR 0.99, 95% CI 0.91 to 1.07) or mortality (OR 0.97, 95% CI 0.76 to 1.23), although mortality was a rare event during the trials. Participants treated with PDE4 inhibitors were more likely to withdraw from the trials because of adverse effects; on average 14% in the treatment groups withdrew compared with 8% in the control groups. In people with COPD, PDE4 inhibitors offered benefit over placebo in improving lung function and reducing the likelihood of exacerbations; however, they had little impact on quality of life or symptoms. Gastrointestinal adverse effects and weight loss were common, and safety data submitted to the US Food and Drug Administration (FDA) have raised concerns over psychiatric adverse events with roflumilast. The findings of this review give cautious support to the use of PDE4 inhibitors in COPD. They may be best used as add-on therapy in a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management. This is in accordance with the GOLD 2017 guidelines. Longer-term trials are needed to determine whether or not PDE4 inhibitors modify FEV1 decline, hospitalisation or mortality in COPD.

Classification of COPD and normal lung airways using feature extraction of electromyographic signals

Airway obstruction is a common component in Chronic Obstructive Pulmonary Disease (COPD). Detection of obstruction and its grading is very essential. Obstruction in the airways, forces the accessory muscles like sternomastoid muscle (SMM) of respiration to work. Normally, only essential muscles of respiration work. In the said paper electromyographic (EMG) analysis of SMM is done for COPD and Normal subjects. We have developed improved slope based onset detection algorithm to detect the onset and offset timing of EMG. Time domain features are extracted for COPD and normal subject. The onset detection algorithm reduces the number of computations by 32.96% and increases accuracy of feature calculation by 40.19%. Dominant time domain features are selected and applied to Support Vector Machine Classifier. The SVM classification algorithm is compared with Threshold and Naïve Bayes classification algorithm. SVM gives the highest accuracy of 87.80%, sensitivity of 89.65% and specificity of 83.33%. Results are also compared with previously used FEV1/FEV6 and Forced Oscillation Technique. The activity of SMM has a significant role in the classification of Normal and COPD subject. Further analysis of SMM can be done to find different grades of COPD.

From COPD epidemiology to studies of pathophysiological disease mechanisms: challenges with regard to study design and recruitment process

ABSTRACT Background: Chronic obstructive pulmonary disease (COPD) is a largely underdiagnosed disease including several phenotypes. In this report, the design of a study intending to evaluate the pathophysiological mechanism in COPD in relation to the specific phenotypes non-rapid and rapid decline in lung function is described together with the recruitment process of the study population derived from a population based study. Method: The OLIN COPD study includes a population-based COPD cohort and referents without COPD identified in 2002–04 (n = 1986), and thereafter followed annually since 2005. Lung function decline was estimated from baseline in 2002–2004 to 2010 (first recruitment phase) or to 2012/2013 (second recruitment phase). Individuals who met the predefined criteria for the following four groups were identified; group A) COPD grade 2–3 with rapid decline in FEV1 and group B) COPD grade 2–3 without rapid decline in FEV1 (≥60 and ≤30 ml/year, respectively), group C) ever-smokers, and group D) non-smokers with normal lung function. Groups A–C included ever-smokers with >10 pack years. The intention was to recruit 15 subjects in each of the groups A-D. Results: From the database groups A–D were identified; group A n = 37, group B n = 29, group C n = 41, and group D n = 55. Fifteen subjects were recruited from groups C and D, while this goal was not reached in the groups A (n = 12) and B (n = 10). The most common reasons for excluding individuals identified as A or B were comorbidities contraindicating bronchoscopy, or inflammatory diseases/immune suppressive medication expected to affect the outcome. Conclusion: The study is expected to generate important results regarding pathophysiological mechanisms associated with rate of decline in lung function among subjects with COPD and the in-detail described recruitment process, including reasons for non-participation, is a strength when interpreting the results in forthcoming studies.

Segmental bronchi collapsibility: computed tomography-based quantification in patients with chronic obstructive pulmonary disease and correlation with emphysema phenotype, corresponding lung volume changes and clinical parameters.

Global pulmonary function tests lack region specific differentiation that might influence therapy in severe chronic obstructive pulmonary disease (COPD) patients. Therefore, the aim of this work was to assess the degree of expiratory 3rd generation bronchial lumen collapsibility in patients with severe COPD using chest-computed tomography (CT), to evaluate emphysema-phenotype, lobar volumes and correlate results with pulmonary function tests. Thin-slice chest-CTs acquired at end-inspiration & end-expiration in 42 COPD GOLD IV patients (19 females, median-age: 65.9 y) from November 2011 to July 2014 were re-evaluated. The cross-sectional area of all segmental bronchi was measured 5 mm below the bronchial origin in both examinations. Lung lobes were semi-automatically segmented, volumes calculated at end-inspiratory and end-expiratory phase and visually defined emphysema-phenotypes defined. Results of CT densitometry were compared with lung functional tests including forced expiratory volume at 1 s (FEV1), total lung capacity (TLC), vital capacity (VC), residual volume (RV), diffusion capacity parameters and the maximal expiratory flow rates (MEFs). Mean expiratory bronchial collapse was 31%, stronger in lobes with homogenous (38.5%) vs. heterogeneous emphysema-phenotype (27.8%, P=0.014). The mean lobar expiratory volume reduction was comparable in both emphysema-phenotypes (volume reduction 18.6%±8.3% in homogenous vs. 17.6%±16.5% in heterogeneous phenotype). The degree of bronchial lumen collapsibility, did not correlate with expiratory volume reduction. MEF25 correlated weakly with 3rd generation airway collapsibility (r=0.339, P=0.03). All patients showed a concentric expiratory reduction of bronchial cross-sectional area. Changes in collapsibility of 3rd generation bronchi in COPD grade IV patients is significantly lower than that in the trachea and the main bronchi. Collapsibility did not correlate with the reduction in lung volume but was significantly higher in lobes with homogeneous vs. heterogeneous emphysema phenotype. Changes in the 3rd generation bronchial calibres between inspiration and expiration are not predictive for the degree of small airway collapsibility and related airflow limitation.

Chronic obstructive pulmonary disease (COPD) and erectile dysfunction (ED): Results of the BRED observational study.

Most patients with chronic obstructive pulmonary disease (COPD) share many risk factors and similar aetiological agents with erectile dysfunction (ED). Both conditions also cause serious interference with quality of life and sexual relationships. In general, ageing and chronic illness decrease sexual interest, sexual function, and testosterone levels. This observational study included 66 male patients referred to our centre with different grades of COPD. We studied the different correlations between COPD and ED. The data collected from each patient regarded the following features: demographic and social condition; smoking status; clinical status; spirometric measurements. In this group, COPD was diagnosed in 78.8% and ED was present in 83.3% with increased severity in presence of LUTS and nicotinism.

Relative impact of COPD and comorbidities on generic health-related quality of life: a pooled analysis of the COSYCONET patient cohort and control subjects from the KORA and SHIP studies.

BackgroundHealth-related quality of life (HRQL) is an important patient-reported outcome measure used to describe the burden of chronic obstructive pulmonary disease (COPD) which is often accompanied by comorbid conditions.MethodsData from 2275 participants in the COPD cohort COSYCONET and from 4505 lung-healthy control subjects from the population-based KORA and SHIP studies were pooled. Main outcomes were the five dimensions of the generic EQ-5D-3 L questionnaire and two EQ-5D index scores using a tariff based on valuations from the general population and an experience-based tariff.The association of COPD in GOLD grades 1–4 and of several comorbid conditions with the EQ-5D index scores was quantified by multiple linear regression models while adjusting for age, sex, education, body mass index (BMI), and smoking status.ResultsFor all dimensions of the EQ-5D, the proportion of participants reporting problems was higher in the COPD group than in control subjects. COPD was associated with significant reductions in the EQ-5D index scores (-0.05 points for COPD grades 1/2, -0.09 for COPD grade 3, -0.18 for COPD grade 4 according to the preference-based utility tariff, all p < 0.0001). Adjusted mean index scores were 0.89 in control subjects and 0.85, 0.84, 0.81, and 0.72 in COPD grades 1-4 according to the preference-based utility tariff and 0.76, 0.71, 0.68, 0.64, and 0.58 for control subjects and COPD grades 1-4 for the experience-based tariff respectively. Comorbidities had additive negative effects on the index scores; the effect sizes for comorbidities were comparable to or smaller than the effects of COPD grade 3. No statistically significant interactions between COPD and comorbidities were observed. Score differences between COPD patients and control subjects were most pronounced in younger age groups.ConclusionsCompared with control subjects, the considerable reduction of HRQL in patients with COPD was mainly due to respiratory limitations, but observed comorbidities added linearly to this effect. Younger COPD patients showed a greater loss of HRQL and may therefore be in specific need of comprehensive disease management.Trial registrationNCT01245933

Characteristics of elderly patients with COPD and newly diagnosed lung cancer, and factors associated with treatment decision.

ObjectiveTo investigate the clinical features, diagnosis, and treatment status of elderly patients with chronic obstructive pulmonary disease (COPD) complicated with lung cancer.Patients and methodsThis was a retrospective study of 206 patients aged >60 years with COPD and newly diagnosed lung cancer at the Tianjin Chest Hospital Respiratory Centre between September 2008 and September 2013. Lung function, radiology, and clinical data were retrieved.ResultsAmong all patients, 57% (117/206) were hospitalized due to acute COPD aggravation, 47% (96/206) had COPD grade III or IV, 95% (195/206), showed diffusion dysfunction in pulmonary function examination, 90% (185/206) had a history of smoking, and 26% (54/206) were treated with inhaled corticosteroids for COPD treatment. Ninety-eight patients suffered from squamous carcinoma, 73 from adenocarcinoma, and 35 from small-cell carcinoma. Clinical staging was I in 36 patients, II in 47 patients, III in 78 patients, and IV in 45 patients. Initial treatments were surgery in 59 patients, chemotherapy in 30 patients, and no treatment in 117 patients. Multivariate analysis showed that age (P<0.001), COPD grades (P=0.01), clinical staging (P<0.001), and pulmonary diffusion function (P=0.007) were independent factors associated with patients with COPD being given treatments for lung cancer.ConclusionYounger patients with lower COPD grades, earlier lung cancer stage, and better pulmonary diffusion function are more likely to receive treatments.

Only severe COPD is associated with being underweight: results from a population survey.

Low body mass index (BMI) and malnutrition in chronic obstructive pulmonary disease (COPD) are associated with a poor prognosis. The prevalence of underweight, as well as overweight, in severity grades of COPD is sparsely investigated in studies of the general population and the associated patterns of risk factors are not well established. The aim of the present study was to determine the association between severity grades of airflow limitation in COPD, and both underweight and obesity when corrected for possible confounding factors.The study is based on pooled data from the OLIN (Obstructive Lung Disease in Northern Sweden) studies. Complete records with lung function, BMI and structured interview data were available from 3942 subjects (50.7% women and 49.3% men). COPD and severity grading were defined using the Global Initiative for Chronic Obstructive Lung Disease criteria. In sensitivity analyses, the lower limit of normal was used.The prevalence of underweight was 7.3% in severe COPD (grades 3 and 4) versus 2.0% in those with normal spirometry. The prevalence of obesity increased from 9.7% in grade 1, to 16.3% in grade 2 and 20.0% in severe COPD, versus 17.7% in those with normal spirometry.In adjusted analysis, of the COPD severity grades, only severe COPD was associated with underweight (OR 3.24, 95% CI 1.0004–10.5), while the COPD severity grades tended to be inversely associated with overweight.

Conceptions of everyday life among people living alone with chronic obstructive pulmonary disease

Objective: The aim of the study was to describe conceptions of everyday life among people living alone with chronic obstructive pulmonary disease (COPD). Background: COPD is a long-standing, chronic condition. As COPD progresses, it commonly affects all aspects of life. The disease creates a complex life situation for the person living alone, as they experience a wide range of difficulties and must adapt to the demands of their brittle body. They report more psychiatric distress than do those with other chronic diseases and appear to have an increased risk of depression. No previous studies have been conducted focusing on people’s conceptions of everyday life when living alone with chronic obstructive pulmonary disease. Methods: A phenomenographic study was conducted in the south of Sweden with 15 women and 9 men who were living alone and suffering from different grades of COPD, ranging from mild to very severe. Data were collected through semi-structured interviews. Results: An overall descriptive category was found, when life changes direction, with three subcategories: COPD creates obstacles in daily life, when the body refuses and loneliness. The disease changed their lives dramatically and both physical and psychological strains appeared. Conclusions: The present study highlights the particular challenges facing people living alone with COPD. To live alone and manage a chronic disease such as COPD is more problematic, than living with a spouse, as they have the option to ask for help when needed and someone to talk to. New technology can reduce social isolation among older people and may act as a potential solution for people living alone with COPD. Through e-health, these people may have the opportunity to be more involved in their own care. To ensure greater security, information, participation, self-care and independence, person-centred care must be systematically implemented within health and social care systems in Sweden.

Direct and indirect costs of COPD and its comorbidities: Results from the German COSYCONET study

BackgroundReliable up-to-date estimates regarding the economic impact of chronic obstructive pulmonary disease (COPD) are lacking. This study investigates COPD excess healthcare utilization, work absenteeism, and resulting costs within the German COPD cohort COSYCONET. MethodsData from 2139 COPD patients in GOLD grade 1–4 from COSYCONET were compared with 1537 lung-healthy control subjects from the population-based KORA platform. Multiple generalized linear models analyzed the association of COPD grades with healthcare utilization, work absence, and costs from a societal perspective while adjusting for sex, age, education, smoking status, body mass index (BMI), and several comorbidities. ResultsCOPD was significantly associated with excess healthcare utilization, work absence, and premature retirement. Adjusted annual excess cost of COPD in 2012 for GOLD grade 1–4 amounted to €2595 [1770–3678], €3475 [2966–4102], €5955 [5191–6843], and €8924 [7190–10,853] for direct costs, and €8621 [4104–13,857], €9871 [7692–12,777], €16,550 [13,743–20,457], and €27,658 [22,275–35,777] for indirect costs respectively. Comorbidities contributed to the primary effect of COPD on direct costs only. An additional history of cancer or stroke had the largest effect on direct costs, but the effects were smaller than those of COPD grade 3/4. ConclusionsCOPD is associated with substantially higher costs than previously reported.

Impact of chronic obstructive pulmonary disease on postoperative recurrence in patients with resected non-small-cell lung cancer

PurposeThis study aimed to determine whether the severity of chronic obstructive pulmonary disease (COPD) affects recurrence-free survival in non-small-cell lung cancer (NSCLC) patients after surgical resection.Patients and methodsA retrospective study was performed on 421 consecutive patients who had undergone lobectomy for NSCLC from January 2008 to June 2011. Classification of COPD severity was based on guidelines of the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Characteristics among the three subgroups were compared and recurrence-free survivals were analyzed.ResultsA total of 172 patients were diagnosed with COPD (124 as GOLD-1, 46 as GOLD-2, and two as GOLD-3). The frequencies of recurrence were significantly higher in patients with higher COPD grades (P<0.001). Recurrence-free survival at 5 years was 78.1%, 70.4%, and 46.4% in non-COPD, mild COPD, and moderate/severe COPD groups, respectively (P<0.001). By univariate analysis, the age, sex, smoking history, COPD severity, tumor size, histology, and pathological stage were associated with recurrence-free survival. Multivariate analysis showed that older age, male, moderate/severe COPD, and advanced stage were independent risk factors associated with recurrence-free survival.ConclusionNSCLC patients with COPD are at high risk for postoperative recurrence, and moderate/severe COPD is an independent unfavorable prognostic factor.

Sex-specific features of emphysema among current and former smokers with COPD.

Recent studies suggest that males with chronic obstructive pulmonary disease (COPD) have more emphysema than females. It is not known if these differences persist across degrees of COPD severity. Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity.We included non-Hispanic white and African-American subjects from the COPDGene study with at least 10 pack-years of smoking and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (log per cent low-attenuation area (%LAA)) by GOLD spirometry grade among subjects with early-onset COPD (<55 years old) and advanced emphysema (>25% emphysema).Compared with females, males had higher log %LAA: overall (1.97±1.4 versus 1.69±1.6, β=0.32 (0.04), p=1.34×10(-14)), and among non-Hispanic white (p=8.37×10(-14)) and African-American subjects (p=0.002). Females with early-onset COPD, severe emphysema and GOLD grade IV COPD had similar emphysema as males, but markedly fewer pack-years smoking (early-onset, p=0.01; severe emphysema and GOLD grade IV, p<0.001).This study identifies subsets of female smokers with COPD who are particularly susceptible to parenchymal destruction.

Identification of MMP-9 as a biomarker for detecting progression of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a complex immunological disease with multiple pathological features that is primarily induced by smoking together with additional genetic risk factors. COPD is frequently underdiagnosed; forced expiratory volume in the first second (FEV1) is considered to be the main diagnostic measure for COPD, yet it is insufficiently sensitive to monitor disease progression. Biomarkers capable of monitoring COPD progression and severity are needed. In this report, we evaluated matrix metalloproteinase-9 (MMP-9) as an early marker for the detection and staging of COPD, by assessing the mRNA levels of MMP-9 in peripheral blood samples collected from 22 COPD patients, 6 asymptomatic smokers, and 5 healthy controls. Our results demonstrate that the mRNA levels of MMP-9 increased more than two-fold in severe COPD relative to non-COPD smokers or moderate COPD groups. Moreover, in the very severe COPD group, MMP-9 mRNA levels showed a 4-fold increase relative to the non-COPD smokers or the moderate COPD groups, while there was a mild increase (∼40%) when compared to the severe COPD group. Taken together, our results suggest that MMP-9 serves as a biomarker for the grade and severity of COPD.

Health-related quality of life and chronic obstructive pulmonary disease in early stages - longitudinal results from the population-based KORA cohort in a working age population.

BackgroundIt is widely recognized that health-related quality of life (HRQL) is impaired in patients with Chronic Obstructive Pulmonary Disease (COPD), but there is a lack of research on longitudinal associations of COPD and HRQL. This study examined the effects of COPD in early stages of disease on HRQL over ten years in a working-age general population setting in Southern Germany while considering the influence of common comorbidities.MethodsIn the population-based KORA F4 study (2006–08) 1,321 participants aged 41–61 years performed spirometry and reported information on HRQL (measured by the generic SF-12) and comorbidities. For the same participants, HRQL information was available seven years before and three years after the lung function test from the previous S4 (1999–2001) and the F4L follow-up study (2010). Using linear mixed models, the physical and mental component summary scores (PCS-12 / MCS-12) of the SF-12 were compared over time between COPD groups.Results7.8% of participants were classified as having COPD (according to the LLN definition and the Global Lungs Initiative), 59.4% of them in grade 1. Regression models showed a negative cross-sectional association of COPD grade 2+ with PCS-12 which persisted when comorbidities were considered. Adjusted mean PCS-12 scores for the COPD grade 2+ group were reduced (−3.5 (p = 0.008) in F4, −3.3 (p = 0.014) in S4 and −4.7 (p = 0.003) in F4L) compared to the group without airflow limitation. The size of the COPD effect in grade 2+ was similar to the effect of myocardial infarction and cancer. Over ten years, a small decline in PCS-12 was observed in all groups. This decline was larger in participants with COPD grade 2+, but insignificant. Regarding MCS-12, no significant cross-sectional or longitudinal associations with COPD were found.ConclusionDespite small HRQL differences between COPD patients in early disease stages and controls and small changes over ten years, our results indicate that it is important to prevent subjects with airflow limitation from progression to higher grades. Awareness of HRQL impairments in early stages is important for offering early interventions in order to maintain high HRQL in COPD patients.

Functional Balance in Older Adults with Chronic Obstructive Pulmonary Disease

This study assessed functional balance among older adults at all grades of chronic obstructive pulmonary disease (COPD) and explored balance impairment predictors. A cross-sectional study with outpatients with COPD (N = 160; M = 72.2 years, SD = 7.9; mean forced expiratory volume in 1 s = 63.8% predicted, SD = 23.7) was conducted. The Timed Up and Go (TUG) test was used to assess functional balance. Functional balance impairment was defined as a TUG score exceeding the upper limit of the confidence intervals of normative values for healthy older adults. Participants performed the TUG test in 11.0 s (SD = 4.8 s). Functional balance impairment was present in 44.4% of the participants and was significantly more frequent in severe to very severe COPD (62.5%). Body mass index (odds ratio [OR] = 1.12), number of medications (OR = 1.20), restriction in recreational activities (OR = 1.66), and depression score (OR = 1.14) were multivariate predictors of functional balance impairment. Functional balance impairment is present in early COPD, although more evident at advanced grades. These findings highlight the importance of balance assessment in older patients at all COPD grades.