Health status deterioration in patients with chronic obstructive pulmonary disease

This study examined health status decline in patients with chronic obstructive pulmonary disease (COPD). Data are from the Inhaled Steroids in Obstructive Lung Disease (ISOLDE) trial. After an 8-wk run-in, 751 patients (566 male), mean age 64 yr, were randomized to receive fluticasone propionate (FP) 500 microg twice daily (376 patients) or placebo (375 patients). Mean baseline postbronchodilator FEV1 was 50 +/- 15% predicted. Patients completed the St George's Respiratory Questionnaire (SGRQ) and the Short-Form 36 (SF-36) at baseline and every 6 mo for 3 yr. FEV1 and smoking status were assessed at baseline and at 3-mo intervals. A total of 387 (212 FP) patients completed the trial. All SGRQ components (p = 0.03 to 0.004) and Physical Function, Mental Health, Energy/ Vitality, and Physical Role Limitation scales of the SF-36 (p = 0.05 to 0.005) deteriorated faster in the placebo group. FEV1 and SGRQ scores correlated at baseline values (r = -0.25, p < 0.0001), as did change in FEV1 and change in SGRQ (Delta r = -0.24, p < 0.0001). At baseline values smokers had worse SGRQ Total, Symptoms, and Impacts scores than ex-smokers. This difference was maintained throughout the study. Smoking status did not influence the rate of decline in health status. The SGRQ Total scores of FP-treated patients took 59% longer than placebo to deteriorate by a clinically significant amount. We conclude that health status decline in moderate to severe COPD can be reduced by high-dose fluticasone.     

Prognostic value of nutritional status in chronic obstructive pulmonary disease

The association between low body mass index (BMI) and poor prognosis in patients with chronic obstructive pulmonary disease (COPD) is a common clinical observation. We prospectively examined whether BMI is an independent predictor of mortality in subjects with COPD from the Copenhagen City Heart Study. In total, 1,218 men and 914 women, aged 21 to 89 yr, with airway obstruction defined as an FEV(1)-to-FVC ratio of less than 0.7, were included in the analyses. Spirometric values, BMI, smoking habits, and respiratory symptoms were assessed at the time of study enrollment, and mortality from COPD and from all causes during 17 yr of follow-up was analyzed with multivariate Cox regression models. After adjustment for age, ventilatory function, and smoking habits, low BMI was predictive of a poor prognosis (i.e., higher mortality), with relative risks (RRs) in underweight subjects as compared with that in subjects of normal weight of 1.64 (95% confidence interval [CI]: 1.20 to 2.23) in men and 1.42 (95% CI: 1.07 to 1.89) in women. However, the association between BMI and survival differed significantly with stage of COPD. In mild and moderate COPD there was a nonsignificant U-shaped relationship, with the lowest risk occurring in normal-weight to overweight subjects, whereas in severe COPD, mortality continued to decrease with increasing BMI (test for trend: p < 0.001). Similar results were found for COPD-related deaths, with the strongest associations found in severe COPD (RR for low versus high BMI: 7.11 [95% CI: 2.97 to 17.05]). We conclude that low BMI is an independent risk factor for mortality in subjects with COPD, and that the association is strongest in subjects with severe COPD.     

Hyperhomocysteinaemia in chronic liver diseases: role of disease stage, vitamin status and methylenetetrahydrofolate reductase genetics.

BACKGROUND/AIMS: The liver plays a key role in sulphur aminoacid metabolism hence, homocysteine metabolism may be impaired in chronic liver diseases. The aim of this study was to investigate, in patients affected by chronic liver diseases, (1) the prevalence of hyperhomocysteinaemia and (2) the role of its determinants such as the stage and the aetiology of disease, vitamin status, genetic documented alterations (methylenetetrahydrofolate reductase deficiency) and presence/absence of documented malignant evolution (hepatocellular carcinoma). MATERIAL AND METHODS: One hundred and thirty patients with chronic liver disease (34 with chronic active hepatitis, 12 with fatty liver and 88 with liver cirrhosis) and 50 healthy age-matched control subjects were included into the study. RESULTS: Hyperhomocysteinaemia was defined as homocysteine plasma levels greater than 12.6 micromol/l. Hyperhomocysteinaemia prevalence in liver cirrhosis group was 40.9%, significantly higher (all P<0.01) with respect to controls (12%), chronic active hepatitis (14.7%) and fatty liver (25%) groups and increased with Child-Pugh stage [Child A: 22.2%, Child B (50%); Child C (58.3%)]. In chronic-active hepatitis and liver cirrhosis, the prevalence of subjects with methylenetetrahydrofolate reductase C677-->T mutation (both as CT and as TT) and hyperhomocysteinaemia results in significantly higher levels with respect to controls. Methylenetetrahydrofolate reductase C677-->T mutation and disease stage showed to be the most important predictive factors of hyperhomocysteinaemia in liver cirrhosis whereas the influence of homocysteine-related vitamin status seems to have a secondary role. CONCLUSIONS: In conclusion hyperhomocysteinaemia is highly prevalent in liver cirrhosis but not in other chronic liver diseases; it may contribute to fibrogenesis and vascular complication of liver cirrhosis.     

The nutritional status of patients with chronic obstructive pulmonary disease

The nutritional status of 38 patients with chronic obstructive pulmonary disease (COPD) was assessed by dietary intake, anthropometric measurements biochemical analysis, and immunologic testing. The mean intakes for 9 nutrients were significantly greater than the 1974 Recommended Dietary Allowances of the National Academy of Sciences. Results of the anthropometric measurements for usual weight for height, fat stores, and muscle mass were significantly less than standard. Of the 32 subjects evaluated for immunocompetence, 9 were anergic (induration, 0) on all 3 skin tests. The results of this study indicated that the marasmic type of protein calorie malnutrition is a common finding among patients with COPD, and that patients with COPD who are immunoincompetent may be more susceptible to mixed protein calorie malnutrition of the kwashiorkor-marasmus type.     

Vitamin and mineral status in elderly patients with chronic obstructive pulmonary disease

Introduction: Eating problems are common in patients with chronic obstructive pulmonary disease (COPD), and intake of micronutrients might be lower than recommended. Objective: To study dietary intake, serum and urinary concentration of trace elements and vitamins in elderly underweight patients with established severe COPD. Methods: Outpatients at a university clinic for lung medicine, with COPD, 70–85 years old, with no other serious disease, and with a body mass index (BMI) of ≤20 kg/m² and an FEV₁of <50 % predicted were recruited. Body composition and bone density were evaluated with dual energy X‐ray absorptiometry. Dietary intake was studied by a trained dietitian using diet‐history interview. Blood and urine samples were analysed for various vitamins and trace elements. Results: Seventeen of 30 recruited patients took part. Osteoporosis or osteopaenia was found in 16 patients. Dietary intake of energy and macronutrients was in line with recommendations for healthy individuals. Intake of protein did not meet recommendations for COPD patients. Intake of polyunsaturated fatty acids was lower than recommended and intake of saturated fatty acids was higher than recommended. Mean intake of vitamin D and folic acid was far below recommendations. Serum concentrations for folic acid and methylmalonate and plasma concentrations for homocysteine were below normal in several patients. Conclusion: Intake of vitamin D and calcium is often low in older COPD patients, which might contribute to osteoporosis. Low intake of folic acid might also be a problem. The results support prophylaxis with calcium, vitamin D and folic acid. Please cite this paper as: Andersson I, Grönberg A, Slinde F, Bosaeus I and Larsson S. Vitamin and mineral status in elderly patients with chronic obstructive pulmonary disease. The Clinical Respiratory Journal 2007;1:23–29.     

慢性阻塞性肺疾病发病机制研究现状与展望

慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）是严重危害人类健康的呼吸系统疾病,患病人数多,美国有2400万人患有不同程度的COPD气流受限（airflow limitation）,这些病例中一半以上没有得到诊断。社会经济负担重,死亡率高,仅美国每年因COPD死亡的人数就超过12万人心。     

慢性阻塞性肺疾病与骨质疏松症相关性研究现状

慢性阻塞性肺疾病（COPD）具有高患病率、高致残率、高病死率的特点,主要累及肺脏,但也可引起全身不良反应,其中骨质疏松症是常见的肺外表现之一。近年来COPD合并骨质疏松症患病率明显增加,并成为COPD患者致残、致死的重要因素之一。为了更好地探讨COPD和骨质疏松症的关系,本文将着重介绍COPD与骨质疏松症相关性方面的新进展,以期对其诱因和预防、治疗有一个全面的认识。     

维生素D与慢性阻塞性肺疾病的研究进展

慢性阻塞性肺疾病(COPD)是呼吸系统常见慢性疾病,目前发病率和病死率逐年上升,给个人和社会带来沉重的负担.近年来,人们在努力研究和开发预防和治疗COPD新药的同时,也逐渐发现维生索D这一常见药物与COPD在起病原因、发病机制、发病过程等诸多方面存在关联.     

Hyperhomocysteinaemia and vitamin B12 deficiency: the long-term effects in cardiovascular disease

BACKGROUND: An elevated plasma homocysteine level is an established risk factor for cardiovascular disease. Vitamin B12 plays a key role in homocysteine metabolism and could be the main factor in causing cardiovascular disease as well. OBJECTIVES: The aim of this study was to assess whether vitamin B12 deficiency or hyperhomocysteinaemia is associated with recurrent cardiovascular events. METHODS: Overall, 211 patients discharged alive from our Coronary Care Unit were recruited from February till May 1998. Serum vitamin B12 and plasma homocysteine levels were measured in fasting blood samples. Patient characteristics, medical information and cardiovascular risk factors were assessed from medical files. Patients were followed for 5 years and the prevalence of cardiovascular mortality and morbidity was collected. RESULTS: In the follow-up period of 810 person-years, 48 (21%) of the patients experienced a nonfatal recurrent cardiovascular event and another 14 (7%) died of a cardiovascular cause. Among those with ischaemic heart disease at discharge, no difference in survival was found between the patients with a low (<250 pmol/l) or a high vitamin B12 level (p = 0.21). In patients with hyperhomocysteinaemia (>16 micromol/l), an increased risk of a recurrent cardio vascular event (p = 0.05) in comparison to those with normal plasma homocysteine levels was proven (adjusted hazard ratio of 2.22 (95% CI: 1.40-3.04). CONCLUSIONS: In conclusion, high plasma homocysteine concentration, but not a low serum vitamin B12 concentration, increases the risk of cardiovascular morbidity and mortality in patients with ischaemic heart disease.     

维生素D与基质金属蛋白酶-9在慢性阻塞性肺疾病中的表达及相关性分析

目的检测COPD患者血清中25羟维生素D[-25-hydroxyvitaminD,25-（OH）D]与基质金属蛋白酶-9（matrixmetalloproteinase-9,MMP-9）的表达水平并探讨两者之间的关系。方法收集2012年1月至2012年3月在长沙市第三医院呼吸内科住院的38例COPD急性加重期患者（COPD急性加重组）和同期同院门诊随诊的40例COPD稳定期患者（COPD稳定组）,同时选择30例在同院体检中心健康体检者（对照组）。采用ELISA法测定并比较3组受试者血清25-（OH）D和MMP-9的表达水平,分别探讨c（）PD稳定组和急性加重组中血清25-（OH）D和MMP-9水平之间的关系。结果①3组的血清25～（OH）D水平比较,cOPD急性加重组和COPD稳定组分别低于对照组（F=86．63,P〈0．01）,COPD急性加重组低于COPD稳定组（F=86．63,P〈0．05）;3组的血清MMP-9水平比较,COPD急性加重组和COPD稳定组分别高于对照组（F=436．02,PG0．01）,COPD急性加重组高于以）PD稳定组（F=436．02,PG0．01）。②COPD稳定组25～（OH）D与MMP-9水平呈负相关（r=-0．638,PG0．01）。COPD急性加重组25（OH）D与MMP-9水平呈负相关（r=-0．579,PG0．01）。结论维生素D在C（）PD中呈低表达而MMP-9呈高表达。在COPD患者中,维生素D水平可能会影响MMP-9的表达。     

Cardiac disease in chronic obstructive pulmonary disease

The cardiac manifestations of chronic obstructive pulmonary disease (COPD) are numerous. Impairments of right ventricular dysfunction and pulmonary vascular disease are well known to complicate the clinical course of COPD and correlate inversely with survival. The pathogenesis of pulmonary vascular disease in COPD is likely multifactorial and related to alterations in gas exchange and vascular biology, as well as structural changes of the pulmonary vasculature and mechanical factors. Several modalities currently exist for the assessment of pulmonary vascular disease in COPD, but right heart catheterization remains the gold standard. Although no specific therapy other than oxygen has been generally accepted for the treatment of pulmonary hypertension in this population, there has been renewed interest in specific pulmonary vasodilators. The coexistence of COPD and coronary artery disease occurs frequently. This association is likely related to shared risk factors as well as similar pathogenic mechanisms, such as systemic inflammation. Management strategies for the care of patients with COPD and coronary artery disease are similar to those without COPD, but care must be given to address their respiratory limitations. Arrhythmias occur frequently in patients with COPD, but are rarely fatal and can generally be treated medically. Use of beta-blockers in the management of cardiac disease, while a theoretical concern in patients with increased airway resistance, is generally safe with the use of cardioselective agents.     

Cardiovascular disease in chronic obstructive pulmonary disease

Smoking is a major cause of chronic obstructive pulmonary disease (COPD) and cardiovascular disorders, including coronary heart disease (CHD) and peripheral arterial disease. Smoking-induced inflammation and other risk factors like dyslipidemia cause vascular endothelial damage via oxidative stress, and a vicious cycle with the characteristics of atherosclerosis ensues. Inflammatory cytokines stimulate hepatic acute-phase protein production, and C-reactive protein is now used widely to assess inflammation in the arterial wall. Smoking is associated with many alterations in lipids and lipoproteins, and is also prothrombotic. Global risk assessment, which determines the absolute risk for developing CHD in 10 years, is used widely to determine who should receive lipid-lowering therapy. Major CHD risk factors include age, sex, smoking, blood pressure, lipoproteins, and cholesterol, but COPD is not among them. Future studies should determine the absolute risk for developing CHD in patients with COPD. The 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors (statins) are used widely to treat and prevent cardiovascular disease. The statins may also produce other beneficial pleiotropic effects, including increased nitric oxide and prostacyclin, antithrombosis, and decreased inflammation, perhaps indicating utility in the therapy for COPD. Efforts are currently underway to determine if such antiinflammatory effects are independent of or in addition to simply lowering low-density lipoprotein cholesterol.     

Prognosis in chronic obstructive pulmonary disease

Although many factors have been shown to relate to survival in patients with COPD, the patient's age and baseline postbronchodilator FEV1 are the best predictors of mortality. The presence of mild obstructive airway disease is not indicative of a progressive downhill course and shortened survival. Mortality in patients with a baseline postbronchodilator FEV1 greater than or equal to 50% of predicted was only slightly greater than that of a group of healthy smokers. Investigators attempting to compare survival in patients with COPD should attempt to exclude patients with asthma or asthmatic bronchitis, because these individuals have a much better prognosis than those with typical COPD (emphysema and chronic bronchitis). Patients should be matched closely for age and severity of impairment, because younger individuals and those with milder impairment are likely to live longer. Other factors besides age and baseline FEV1 have been shown to affect survival. Patients who stop smoking are likely to survive longer than those who continue to smoke. The presence of malnutrition has clearly been shown to worsen survival. Further studies will be necessary to determine if corticosteroid therapy can slow down progression of disease in patients with typical COPD. Oxygen therapy improves survival in COPD patients with significant hypoxemia, many of whom also have CO2 retention, polycythemia, and cor pulmonale. There are now multiple studies in the literature suggesting that the type of comprehensive respiratory care provided by pulmonary rehabilitation programs can not only improve the quality of life but also survival in patients with chronic obstructive pulmonary disease.     

Nutrition in chronic obstructive pulmonary disease

Weight loss is a frequently occurring complication in patients with chronic obstructive pulmonary disease (COPD) and is a determining factor of functional capacity, health status, and mortality. Weight loss in COPD is a consequence of increased energy requirements unbalanced by dietary intake. Both metabolic and mechanical inefficiency contribute to the elevated energy expenditure. A disbalance between protein synthesis and protein breakdown may cause a disproportionate depletion of fat-free mass in some patients. Nutritional support is indicated for depleted patients with COPD because it provides not only supportive care, but direct intervention through improvement in respiratory and peripheral skeletal muscle function and in exercise performance. A combination of oral nutritional supplements and exercise or anabolic stimulus appears to be the best treatment approach to obtaining significant functional improvement. Patients responding to this treatment even demonstrated a decreased mortality. Poor response was related to the effects of systemic inflammation on dietary intake and catabolism. The effectiveness of anticatabolic modulation requires further investigation.     

Prognosis in chronic obstructive pulmonary disease

We recruited 985 patients with COPD but without hypoxemia or other serious disease, treated them in a standard fashion, and followed them closely for nearly 3 yr. At the time of recruitment the patients were carefully characterized as to symptom severity, lung function, exercise tolerance, and quality of life, and studies of lung function were repeated during follow-up. Overall mortality was 23% in 3 yr of follow-up. Patient age and the initial value of the FEV1 were the most accurate predictors of death; when FEV1 before bronchodilator was used, the response to bronchodilators was directly related to survival, but this relationship became nonsignificant when postbronchodilator FEV1 was used as a primary predictor. After adjustment for age and FEV1, mortality was related positively to TLC, resting heart rate, and perceived physical disability, and related negatively to exercise tolerance. These relationships, though significant, were relatively weak. When standardized for age and FEV1, mortality in the present series was less than that of a previous series (4), and the same as that of hypoxemic patients with COPD who received continuous home O2 therapy. Changes in FEV1 with time averaged -44 ml/yr, but the standard deviation was large. Patients with low initial values of FEV1 showed relatively little further decline, probably indicating a survivor effect. In patients with well-preserved initial FEV1, rate of decline correlated negatively with bronchodilator response, symptomatic wheezing, and psychological disturbances.