Metabolomics in COPD

The clinical presentation of chronic obstructive pulmonary disease (COPD) is highly heterogeneous. Attempts have been made to define subpopulations of patients who share clinical characteristics (phenotypes and treatable traits) and/or biological characteristics (endotypes), in order to offer more personalized care. Assigning a patient to any of these groups requires the identification of both clinical and biological markers. Ideally, biological markers should be easily obtained from blood or urine, but these may lack specificity. Biomarkers can be identified initially using conventional or more sophisticated techniques. However, the more sophisticated techniques should be simplified in the future if they are to have clinical utility. The -omics approach offers a methodology that can assist in the investigation and identification of useful markers in both targeted and blind searches. Specifically, metabolomics is the science that studies biological processes involving metabolites, which can be intermediate or final products. The metabolites associated with COPD and their specific phenotypic and endotypic features have been studied using various techniques. Several compounds of particular interest have emerged, namely, several types of lipids and derivatives (mainly phospholipids, but also ceramides, fatty acids and eicosanoids), amino acids, coagulation factors, and nucleic acid components, likely to be involved in their function, protein catabolism, energy production, oxidative stress, immune-inflammatory response and coagulation disorders. However, clear metabolomic profiles of the disease and its various manifestations that may already be applicable in clinical practice still need to be defined.     

COPD in Japan: the Nippon COPD Epidemiology study

OBJECTIVES: Despite high smoking rates, few prevalence studies of COPD have been performed in Asia. The Nippon COPD Epidemiology (NICE) Study used spirometry to measure prevalence of airflow limitation in Japanese adults. METHODOLOGY: Clinical, spirometric, and risk factor exposure data were collected on 2343 subjects aged > or = 40 years who were demographically similar to the Japanese population. Airflow limitation was defined according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (FEV1/FVC < 70%). RESULTS: Prevalence of airflow limitation was 10.9%. Based upon GOLD severity criteria, 56% of these cases were found to be mild, 38% moderate, 5% severe, and 1% very severe. Airflow limitation was significantly more prevalent in males than females (16.4% vs. 5.0%; P < 0.001), in male ever-smokers than female ever-smokers (17.1% vs. 7.5%; P < 0.001), and in older subjects (3.5% in 40-49 years olds vs. 24.4% in those > 70 years; P < 0.001). Of note, airflow limitation was also found in 5.8% of non-smokers and 4.6% of those younger than age 60 years. Only 9.4% of cases with airflow limitation reported a previous diagnosis of COPD. CONCLUSIONS: Prevalence of airflow limitation in Japan is higher than previously reported, suggesting a high degree of under-recognition of COPD. The high prevalence of smoking coupled with an aging population threatens to further increase the burden of COPD, highlighting the need for enhanced screening efforts and interventions of prevention and treatment.     

Biomarkers in COPD

Although there is increasing interest in using pulmonary biomarkers for a more complete and clinically relevant assessment of COPD and a plethora of biomarkers are becoming available, there is little information regarding their reproducibility and correlation with other outcome measurements in COPD. The lack of well-validated biomarkers that can be used for monitoring disease activity, predicting future clinical outcomes and the effect of therapeutic interventions highlights the factual need to identify new biomarkers in COPD. It is likely that, using what is called ‘integrative functional informatics’, which is a novel direction in the interfacing and integration of different technologies (genomics, proteomics, metabolomics and metabonomics, pharmacogenetics, and integrative approaches) for collection and analysis of data on biomarkers, we will be able to identify robust, reliable, and reproducible biomarkers in COPD.     

Malnutrition in COPD

During the last years our knowledge about the malnutrition of patients with COPD has grown. Weight loss is a problem of some patients with COPD, but, as we know today by techniques of body composition measurement much more patients have reduced muscle mass. The reason for this is complex and involves many body systems. Nutritional intervention alone is not successful in many patients. We have to accept that COPD is a kind of systemic disease which does not only involve the lung. Thus, future therapies have to include not only treatment of the bronchial system.     

Sarcopenia in COPD: relationship with COPD severity and prognosis

Objective:

To evaluate the prevalence of sarcopenia in COPD patients, as well as to determine whether sarcopenia correlates with the severity and prognosis of COPD.

Methods:

A cross-sectional study with COPD patients followed at the pulmonary outpatient clinic of our institution. The patients underwent dual-energy X-ray absorptiometry. The diagnosis of sarcopenia was made on the basis of the skeletal muscle index, defined as appendicular lean mass/height² only for low-weight subjects and adjusted for fat mass in normal/overweight subjects. Disease severity (COPD stage) was evaluated with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. The degree of obstruction and prognosis were determined by the Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity (BODE) index.

Results:

We recruited 91 patients (50 females), with a mean age of 67.4 ± 8.7 years and a mean BMI of 25.8 ± 6.1 kg/m². Sarcopenia was observed in 36 (39.6%) of the patients, with no differences related to gender, age, or smoking status. Sarcopenia was not associated with the GOLD stage or with FEV₁ (used as an indicator of the degree of obstruction). The BMI, percentage of body fat, and total lean mass were lower in the patients with sarcopenia than in those without (p < 0.001). Sarcopenia was more prevalent among the patients in BODE quartile 3 or 4 than among those in BODE quartile 1 or 2 (p = 0.009). The multivariate analysis showed that the BODE quartile was significantly associated with sarcopenia, regardless of age, gender, smoking status, and GOLD stage.

Conclusions:

In COPD patients, sarcopenia appears to be associated with unfavorable changes in body composition and with a poor prognosis.     

COPD

Chronic obstructive lung disease (COPD) is characterized by airflow limitation that is not fully reversible and usually progressive. The disease is associated with an inflammatory response of the lungs to noxious particles, mainly cigarette smoke. Numerous studies suggest a significant association between impaired lung function and the presence of extrapulmonary comorbidities. Systemic inflammation is believed to be a link between COPD and its extrapulmonary manifestations although the exact mechanisms remain unclear. The development and validation of score systems that classify COPD severity not only by lung function represent a new understanding of the disease. This warrants novel therapeutic approaches.     

Nutritional Status in COPD

Changes in nutritional status, such as weight loss and malnutrition, are a very common complication in patients with chronic obstructive pulmonary disease (COPD). These changes primarily affect the patients' quality of life and functional capacity and they are also independent prognostic indicators of both morbidity and mortality. Malnutrition in these patients is due to multiple factors including increases in resting energy expenditure, decreased food intake, the effects of certain drugs, and, perhaps most importantly, a high systemic inflammatory response. The present review covers the most important facets of the prevalence, etiology, pathogenesis, and consequences of malnutrition in COPD and considers which parameters for nutritional assessment are the most satisfactory for use in routine clinical practice. The strategy used to ensure correct nutritional status in these patients is also discussed.     

Modelling COPD in mice

Chronic obstructive pulmonary disease (COPD) is characterised by persistent airflow limitation, neutrophilic inflammation, macrophage accumulation, and the production of cytokines, chemokines and proteases. Cigarette smoking is the major cause of COPD and there is currently no satisfactory therapy to help treat individuals with this disease. A better understanding of the cellular and molecular responses triggered by cigarette smoke may provide new molecular targets for the development of therapeutic agents. This brief review highlights some of the mouse models used to define the cellular, molecular and pathological consequences of cigarette smoke exposure.     

Sleep in COPD patients

An estimated 14 million Americans are afflicted with COPD and are at risk for significant abnormalities in gas exchange and ventilation that are exacerbated by sleep. In addition 10-15% of COPD patients concomitantly suffer from sleep apnea. The term "Overlap Syndrome" was originally coined by Flenley to describe the relationship between COPD and sleep apnea. Patients with overlap syndrome are characterized by having lower PaO2 during wakefulness, higher PaCO2, elevated pulmonary artery pressure and more significant episodes of nocturnal hypoxemia than sleep apnea patients without COPD. COPD and sleep apnea have long been individually recognized for having significantly detrimental affects on the respiratory physiology of patients. The mechanisms of both diseases compromise the gas exchange, oxygenation, and overall mortality and morbidity in the affected patients. While both of these diseases individually represent significant detriment to affected patients, the combination of these two diseases has been shown to have an even more profound affect on patients' oxygenation, gas exchange, and breathing patterns. As our understanding of the physiological processes of sleep develops, the relationship between obstructive sleep apnea and obstructive lung disease has become progressively more apparent. Identification and appropriate management of these patients is particularly important because the 5 year survival of patients with overlap syndrome is lower than that of patients with sleep apnea alone as shown in prospective trials.     

Antioxidant therapies in COPD

Oxidative stress is an important feature in the pathogenesis of COPD. Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD. Antioxidant agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenols (curcumin, resveratrol, green tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have been reported to control nuclear factor-kappaB (NF-κ B) activation, regulation of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory gene expression. Specific spin traps such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo. Since a variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed.