Komorbiditäten bei COPD

Chronic obstructive pulmonary disease (COPD) is often associated with comorbidities. Cardiovascular diseases, weight loss, loss of fat free mass combined with muscle dysfunction, osteoporosis and depression are the main comorbidities in COPD. Cardiovascular comorbidities, weight loss and loss of fat free mass are predictors of mortality of patients with COPD. Thus, the extrapulmonary manifestations are meaningful parameters of clinical assessment. Systemic inflammation is probably the key to the extrapulmonary signs of COPD.     

Depressive symptoms, inflammatory markers and body composition in elderly with and without chronic obstructive pulmonary disease (COPD)

Our aim was to assess the relationships between cortisol, interleukin-2 (Il-2) and tumor necrosis factor-α (TNF-α) levels in elderly with and without COPD presenting with or without depressive symptoms. Forty COPD patients and 53 elderly individuals with no COPD took part in the study. Depressive symptoms (Geriatric Depression Scale=GDS-15), IL-2 and TNF-α, serum cortisol, number of comorbidities, smoking habits and body composition were evaluated. The prevalence of depressive symptoms was higher in COPD group. The number of comorbidities was higher in patients with depressive symptoms. No differences were found between IL-2, TNF-α and cortisol levels, years of smoking and smoked pack-years in the groups. The COPD group obtained lower body mass index (BMI) and fat content and higher fat free mass index as well as greater nutritional depletion. Conclusions: Depressive symptoms as well as fat and lean body composition, due to preserved BMI in those with nutritional depletion, must be investigated.     

Relation between physical capacity, nutritional status and systemic inflammation in COPD

Background: Decreased physical capacity, weight loss, fat‐free mass depletion and systemic inflammation are frequently observed in patients with chronic obstructive pulmonary disease (COPD). Objective: Our aim was to examine relations between physical capacity, nutritional status, systemic inflammation and disease severity in COPD. Method: Forty nine patients with moderate to severe COPD were included in the study. Spirometry was preformed. Physical capacity was determined by a progressive symptom limited cycle ergo meter test, incremental shuttle walking test, 12‐minute walk distance and hand grip strength test. Nutritional status was investigated by anthropometric measurements, (weight, height, arm and leg circumferences and skinfold thickness) and bioelectrical impedance assessment was performed. Blood samples were analyzed for C‐reactive protein (CRP) and fibrinogen. Result: Working capacity was positively related to forced expiratory volume in 1 s (FEV₁) (p < 0.001), body mass index and fat free mass index (p = 0.01) and negatively related to CRP (p = 0.02) and fibrinogen (p = 0.03). Incremental shuttle walk test was positively related to FEV₁ (p < 0.001) and negatively to CRP (p = 0.048). Hand grip strength was positively related to fat free mass index, and arm and leg circumferences. Fifty to 76% of the variation in physical capacity was accounted for when age, gender, FEV₁, fat free mass index and CRP were combined in a multiple regression model. Conclusion: Physical capacity in chronic obstructive pulmonary disease is related to lung function, body composition and systemic inflammation. A depiction of all three aspects of the disease might be important when targeting interventions in chronic obstructive pulmonary disease. Please cite this paper as: Hallin R, Janson C, Arnardottir RH, Olsson R, Emtner M, Branth S, Boman G and Slinde F. Relation between physical capacity, nutritional status and systemic inflammation in COPD. Clin Respir J 2011; 5: 136–142.     

Associations between the rate,amount, and composition of weight loss as predictors of spontaneous weight regain in adults achieving clinically significant weight loss: A systematic review and meta‐regression

Weight regain following weight loss is common although little is known regarding the associations between amount, rate, and composition of weight loss and weight regain. Forty‐three studies (52 groups; n = 2379) with longitudinal body composition measurements were identified in which weight loss (≥5%) and subsequent weight regain (≥2%) occurred. Data were synthesized for changes in weight and body composition. Meta‐regression models were used to investigate associations between amount, rate, and composition of weight loss and weight regain. Individuals lost 10.9% of their body weight over 13 weeks composed of 19.6% fat‐free mass, followed by a regain of 5.4% body weight over 44 weeks composed of 21.6% fat‐free mass. Associations between the amount (P < 0.001) and rate (P = 0.049) of weight loss and their interaction (P = 0.042) with weight regain were observed. Fat‐free mass (P = 0.017) and fat mass (P < 0.001) loss both predicted weight regain although the effect of fat‐free mass was attenuated following adjustment. The amount (P < 0.001), but not the rate of weight loss (P = 0.150), was associated with fat‐free mass loss. The amount and rate of weight loss were significant and interacting factors associated with weight regain. Loss of fat‐free mass and fat mass explained greater variance in weight regain than weight loss alone.     

Plasma orexin-A levels and body composition in COPD

STUDY OBJECTIVE: To study the role of orexins in regulating body composition in patients with COPD. DESIGN: Prospective study. Patients and measurements: We measured the plasma concentration of orexin-A in 20 patients with COPD and compared the results to those obtained from 10 age-matched control subjects. Patients with COPD were classified into two groups based on their body mass index (BMI): a normal weight (NW) group (BMI > 20) and an underweight (UW) group (BMI < 20). RESULTS: The plasma orexin-A level was significantly lower in patients with COPD than in control subjects. In patients with COPD, the level was significantly lower in the UW group than in the NW group. Plasma orexin-A levels significantly correlated with BMI and fat mass values, but there was no significant relationship between plasma orexin-A levels and the fat-free mass of patients with COPD. CONCLUSION: These results suggest that orexin-A levels are altered with weight loss and changes in body composition in patients with COPD.     

Intermittent versus daily calorie restriction: which diet regimen is more effective for weight loss?

Dietary restriction is an effective strategy for weight loss in obese individuals. The most common form of dietary restriction implemented is daily calorie restriction (CR), which involves reducing energy by 15–60% of usual caloric intake every day. Another form of dietary restriction employed is intermittent CR, which involves 24 h of ad libitum food consumption alternated with 24 h of complete or partial food restriction. Although both diets are effective for weight loss, it remains unknown whether one of these interventions produces superior changes in body weight and body composition when compared to the other. Accordingly, this review examines the effects of daily CR versus intermittent CR on weight loss, fat mass loss and lean mass retention in overweight and obese adults. Results reveal similar weight loss and fat mass loss with 3 to 12 weeks' intermittent CR (4–8%, 11–16%, respectively) and daily CR (5–8%, 10–20%, respectively). In contrast, less fat free mass was lost in response to intermittent CR versus daily CR. These findings suggest that these diets are equally as effective in decreasing body weight and fat mass, although intermittent CR may be more effective for the retention of lean mass.     

Protein,amino acids and obesity treatment

Reviews in Endocrine and Metabolic Disorders - Dietary proteins have been used for years to treat obesity. Body weight loss is beneficial when it concerns fat mass, but loss of fat free mass...     

Resting energy expenditure and protein turnover are increased in patients with severe chronic obstructive pulmonary disease

The mechanisms leading to weight loss in patients with chronic obstructive pulmonary disease (COPD) are poorly understood. Changes in protein metabolism and systemic inflammation may contribute to increased resting energy expenditure (REE) in COPD, leading to an energy imbalance and loss of fat and fat-free mass. The objective of this study was to determine first whether REE was increased in patients with COPD and, second, whether this was associated with increased protein turnover and/or systemic inflammation. Resting energy expenditure was determined using indirect calorimetry in 14 stable outpatients with severe COPD (7 with low and 7 with preserved body mass indices) and 7 healthy controls. Endogenous leucine flux, leucine oxidation, and nonoxidative disposal, indices of whole-body protein breakdown, catabolism, and synthesis, were measured using intravenous infusions of ¹³C-bicarbonate and 1-¹³C-leucine. Total body water, from which fat-free mass and fat mass were calculated, was determined using an intravenous bolus of deuterated water. Plasma markers of systemic inflammation were also measured. As a group, subjects with COPD had increased REE adjusted for fat-free mass (P < .001) and faster rates of endogenous leucine flux (P = .006) and nonoxidative leucine disposal (P = .002) compared with controls. There was a significant correlation between REE and both endogenous leucine flux (P = .02) and nonoxidative leucine disposal (P = .008). Plasma concentrations of the inflammatory markers C-reactive protein and interleukin-6 were not different between COPD subjects and controls. Increased rates of protein turnover are associated with increased REE and loss of fat-free mass in COPD.     

Weight loss composition is one‐fourth fat‐free mass: a critical review and critique of this widely cited rule

Maximizing fat loss while preserving lean tissue mass and function is a central goal of modern obesity treatments. A widely cited rule guiding expected loss of lean tissue as fat‐free mass (FFM) states that approximately one‐fourth of weight loss will be FFM (i.e. ΔFFM/ΔWeight = ～0.25), with the remaining three‐fourths being fat mass. This review examines the dynamic relationships between FFM, fat mass and weight changes that follow induction of negative energy balance with hypocaloric dieting and/or exercise. Historical developments in the field are traced with the ‘Quarter FFM Rule’ used as a framework to examine evolving concepts on obesity tissue, excess weight and what is often cited as ‘Forbes' Rule’. Temporal effects in the fractional contribution of FFM to changes in body weight are examined as are lean tissue moderating effects such as ageing, inactivity and exercise that frequently accompany structured low‐calorie diet weight loss protocols. Losses of lean tissue with dieting typically tend to be small, raising questions about study design, power and applied measurement method reliability. Our review elicits important questions related to the fractional loss of lean tissues with dieting and provides a foundation for future research on this topic.     

COPD继发骨质疏松症机制的研究进展

骨质疏松症是COPD的一个重要合并症.COPD患者中骨质疏松症的发病率、病死率增加,这一相关性可能与体质量指数下降和游离脂肪减少、全身炎症反应、激素使用、维生素D的缺乏及患者病理类型等因素有关.本文将对二者相关性及其可能机制的研究进展进行综述.     

Reversal of COPD-associated weight loss using the anabolic agent oxandrolone

STUDY OBJECTIVE: Weight loss is a common complication of COPD, associated with negative outcomes. Weight restoration has been associated with improved outcomes. The effects of oxandrolone, an adjunct to help restore weight, were evaluated in patients with COPD. DESIGN: Prospective, open-label, 4-month clinical trial. SETTING: Twenty-five community-based pulmonary practices throughout the United States. PATIENTS: A primary pulmonary diagnosis of moderate-to-severe COPD as defined by FEV1 < 50% of predicted and FEV1/FVC ratio < 0.7, along with significant involuntary weight loss (weight < or = 90% ideal body weight). INTERVENTIONS: Oral oxandrolone, 10 mg bid. MEASUREMENTS AND RESULTS: Body weight, body composition (bioelectric impedance analysis), spirometry, and 6-min walking distance were measured. Data for 82 patients at 2 months and 55 patients at 4 months are presented. At month 2, 88% of patients had gained a mean +/- SD of 6.0 +/- 4.36 lb (p < 0.05) and 12% had lost a mean of 1.7 +/- 2.15 lb (not statistically significant [NS]). At month 4, 84% had gained a mean of 6.0 +/- 5.83 lb (p < 0.05) and 16% had lost a mean of 1.8 +/- 1.74 lb (NS). Month 4 bioelectric impedance analysis showed the weight to be primarily lean tissue, with a mean increase in body cell mass of 3 +/- 2.6 lb (p < 0.05), and a mean increase in fat of 1.2 +/- 4.6 lb (NS). CONCLUSIONS: Oxandrolone is an effective adjunct to facilitate weight restoration in patients with COPD-associated weight loss. Weight gain is primarily lean body mass. Oxandrolone was relatively well tolerated and, therefore, should be a consideration in the comprehensive management of patients with COPD and weight loss.     

Changes in 24-h area-under-the-curve ghrelin values following diet-induced weight loss are associated with loss of fat-free mass, but not with changes in fat mass, insulin levels or insulin sensitivity

OBJECTIVE: To determine which parameters of body composition or metabolism best correlate with changes in 24 h ghrelin levels following weight loss. DESIGN: A 3-month low-calorie diet followed by 3 months of weight stabilization. SUBJECTS: Twelve overweight and obese adult men and women. MEASUREMENTS: Body composition by underwater weighing, abdominal fat depots, leptin, ghrelin and parameters of insulin and lipid metabolism. RESULTS: Increased 24 h ghrelin levels after weight loss correlated with decreases in body mass index, subcutaneous fat and fat-free mass (FFM), but not with changes in fat mass, fat cell size, leptin, insulin, insulin sensitivity, lipids or free fatty acid levels. The change in FFM correlated with the rise in ghrelin levels independently of body adiposity. DISCUSSION: Alterations in FFM with diet-induced weight loss may play a role in ghrelin regulation. Changes in ghrelin levels could, then, serve as an integrative signal reflecting changes in FFM to hypothalamic centers controlling energy homeostasis.     

Hypogonadism and male obesity: Focus on unresolved questions

Obesity, increasing in prevalence globally, is the clinical condition most strongly associated with lowered testosterone concentrations in men and presents as one of the strongest predictors of receiving testosterone treatment. While low circulating total testosterone concentrations in modest obesity primarily reflect reduced concentrations of sex hormone binding globulin, more marked obesity can lead to genuine hypothalamic‐pituitary‐testicular axis (HPT) suppression. HPT axis suppression is likely mediated via pro‐inflammatory cytokine and dysregulated leptin signalling and aggravated by associated comorbidities. Whether oestradiol‐mediated negative hypothalamic‐pituitary feedback plays a pathogenic role requires further study. Although the obesity‐hypogonadism relationship is bidirectional, the effects of obesity on testosterone concentrations are more substantial than the effects of testosterone on adiposity. In markedly obese men submitted to bariatric surgery, substantial weight loss is very effective in reactivating the HPT axis. In contrast, lifestyle measures are less effective in reducing weight and generally only associated with modest increases in circulating testosterone. In randomized controlled clinical trials (RCTs), testosterone treatment does not reduce body weight, but modestly reduces fat mass and increases muscle mass. Short‐term studies have shown that testosterone treatment in carefully selected obese men may have modest benefits on symptoms of androgen deficiency and body composition even additive to diet alone. However, longer term, larger RCTs designed for patient‐important outcomes and potential risks are required. Until such trials are available, testosterone treatment cannot be routinely recommended for men with obesity‐associated nonclassical hypogonadism. Lifestyle measures or where indicated bariatric surgery to achieve weight loss, and optimization of comorbidities remain first line.     

Health consequences of obesity in the elderly: a review of four unresolved questions

Obesity prevalence is growing progressively even among older age groups. Controversy exists about the potential harms of obesity in the elderly. Debate persists about the relation between obesity in old age and total or disease-specific mortality, the definition of obesity in the elderly, its clinical relevance, and about the need for its treatment. Knowledge of age-related body composition and fat distribution changes will help us to better understand the relationships between obesity, morbidity and mortality in the elderly. Review of the literature supports that central fat and relative loss of fat-free mass may become relatively more important than BMI in determining the health risk associated with obesity in older ages. Weight gain or fat redistribution in older age may still confer adverse health risks (for earlier mortality, comorbidities conferring independent adverse health risks, or for functional decline). Evaluation of comorbidity and weight history should be performed in the elderly in order to generate a comprehensive assessment of the potential adverse health effects of overweight or obesity. The risks of obesity in the elderly have been underestimated by a number of confounders such as survival effect, competing mortalities, relatively shortened life expectancy in older persons, smoking, weight change and unintentional weight loss. Identification of elderly subjects with sarcopenic obesity is probably clinically relevant, but the definition of sarcopenic obesity, the benefits of its clinical identification, as well as its relation to clinical consequences require further study. Studies on the effect of voluntary weight loss in the elderly are scarce, but they suggest that even small amounts of weight loss (between 5-10% of initial body weight) may be beneficial. In older as well as in younger adults, voluntary weight loss may help to prevent the adverse health consequences of obesity.     

Current pharmacological approaches to the treatment of obesity

Although comprehensive obesity treatment programmes were shown to induce weight loss and to improve risk factors and comorbidities, the weight reduction is moderate and most patients will rapidly regain weight. For these reasons, drugs have been developed or are in development to support and maintain weight loss. At present, two drugs are available for the adjunct treatment of obesity. Sibutramine is a centrally acting inhibitor of noradrenaline and serotonine reuptake, thereby decreasing caloric intake and increasing energy expenditure. Orlistat is a specific lipase inhibitor that impairs fat absorption, thereby reducing fat uptake. Both drugs have been found to be effective and safe in a number of clinical studies for up to two years. The current experience with these drugs raises questions related to the long-term efficacy with particular reference to cardiovascular end-points. In addition, other current and future pharmacological principles for weight reduction are discussed. There is no doubt that an evidence-based rational pharmacological treatment of obesity is still in an early stage.     

COPD as a multicomponent disease: inventory of dyspnoea, underweight, obesity and fat free mass depletion in primary care.

AIMS: To describe the distribution of COPD disease severity in primary care based on airway obstruction, and to assess the extent to which dyspnoea scores, body mass index (BMI) and fat free mass (FFM) index contribute to the distribution of COPD severity in primary care. DESIGN: Cross sectional population-based study. METHODS: 317 patients with COPD were recruited from an outpatient disease management programme. Prevalence of moderate to severe dyspnoea, underweight, obesity and FFM depletion by GOLD stage were measured. RESULTS: According to GOLD guidelines, 29% of patients had mild COPD, 48% moderate, 17% severe and 5% very severe. A substantial number of patients classified as GOLD stage 2 reported severe dyspnoea (28.1%) and/or suffered from FFM depletion (16.3%). Prevalence of low body weight strongly increased in GOLD stage 4. Prevalence of obesity is highest in GOLD stages 1 and 2. CONCLUSION: The use of a multidimensional grading system, taking into account dyspnoea as well as the nutritional status of COPD patients, is likely to influence the distribution of disease severity in a primary care population. This might have implications for prevention, non-medical treatment, and estimates of health care utilisation in primary care.     

COPD and its comorbidities: Impact,measurement and mechanisms

Chronic obstructive pulmonary disease (COPD) frequently coexists with other conditions often known as comorbidities. The prevalence of most of the common comorbid conditions that accompany COPD has been widely reported. It is also recognized that comorbidities have significant health and economic consequences. Nevertheless, there is scant research examining how comorbidities should be assessed and managed in the context of COPD. Also, the underlying mechanisms linking COPD with its comorbidities are still not fully understood. Owing to these knowledge gaps, current disease‐specific approaches provide clinicians with little guidance in terms of managing comorbid conditions in the clinical care of multi‐diseased COPD patients. This review discusses the concepts of comorbidity and multi‐morbidity in COPD in relation to the overall clinical outcome of COPD management. It also summarizes some of the currently available clinical scores used to measure comorbid conditions and their prognostic abilities. Furthermore, recent developments in the proposed mechanisms linking COPD with its comorbidities are discussed.     

Morphological overview of cardiovascular comorbidities in chronic obstructive pulmonary disease: Frank's sign

ObjectiveCardiovascular diseases are the most common and important comorbidities in patients with chronic obstructive pulmonary disease (COPD). Literature indicates that there may be a relationship between diagonal earlobe crease (DELC) and coronary artery disease (CAD). Accordingly, the present study aimed to assess the relationship with DELC and cardiac comorbidities in patients with COPD during routine physical examination.Materials and MethodsIn this prospective cohort study, we evaluated the demographic data, pulmonary function test (PFT) results, lipid profile, oxygen saturation, and the presence of DELC in patients with COPD and control subjects.ResultsDELC was diagnosed in 155 (62%) of COPD patients and these patients had a higher prevalence of CAD (p = 0.044). Moreover, DELC was diagnosed in 135 men (68.5%) and 20 (37.7%) women in the COPD group (p<0.001) and in 39 (48.8%) men and 14 (56.0%) women in the control group (p = 0.527). On the other hand, CAD was diagnosed in 18% of patients with early-stage COPD (n = 104) and in 30.8% of patients with late-stage COPD (n = 146) (p = 0.041). The sensitivity and specificity of DELC positivity in predicting CAD were 80.65% and 44.15% in COPD patients, respectively.ConclusionThe presence of cardiac comorbidities in COPD patients may play a vital role in the severity of the disease, exacerbations, and may also reduce the treatment response. Accordingly, an earlobe examination of patients with COPD may be useful in predicting the presence of cardiac comorbidities with high sensitivity.