New insights on COPD imaging via CT and MRI

Multidetector-row computed tomography (MDCT) can be used to quantify morphological features and investigate structure/function relationship in COPD. This approach allows a phenotypical definition of COPD patients, and might improve our understanding of disease pathogenesis and suggest new therapeutical options. In recent years, magnetic resonance imaging (MRI) has also become potentially suitable for the assessment of ventilation, perfusion and respiratory mechanics. This review focuses on the established clinical applications of CT, and novel CT and MRI techniques, which may prove valuable in evaluating the structural and functional damage in COPD.     

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.     

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.     

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.     

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.     

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.     

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.     

Redefining Treatment in COPD

COPD is a growing international health concern and it is estimated that by the year 2020 it will rank fifth as a cause of disability worldwide. In response to this problem, the World Health Organization and the US National Institutes of Health convened a panel of experts to draft a consensus strategy to treat patients with COPD. Called the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, they are designed to define and stage the severity of COPD, make recommendations for treatment, and to expand global awareness of the disease. The GOLD guidelines describe a multimodality approach to provide optimal care for the COPD patient population. This includes respiratory and rehabilitative therapy, nutrition services, psychosocial counseling, and surgical care. Bronchodilators form the cornerstone of pharmacologic treatment for COPD. These medications can significantly lessen dyspnea, enhance quality of life, increase airflow, and improve exercise performance. While bronchodilators decrease airway resistance and lessen hyperinflation in patients with COPD, they have not been shown to influence the decline in FEV1 over time or improve survival in this patient population. Recently, long-acting beta2-adrenoceptor agonists (beta2-agonists) such as formoterol and salmeterol and anticholinergic medications including tiotropium bromide have been developed which may further improve symptom management in COPD patients. This article discusses bronchodilator pharmacologic therapy for patients with COPD focusing on beta2-agonists, anticholinergics, and methylxanthines in the light of the recent GOLD consensus statements.     

Bronchodilator reversibility in COPD

COPD is a preventable and treatable disease characterized by airflow limitation that is not fully reversible. The diagnosis of COPD is based on spirometric evidence of airways obstruction following bronchodilator administration. Although it used to be commonly believed that patients with COPD have largely irreversible airflow obstruction, evidence now suggests that a considerable proportion of patients exhibit clinically significant bronchodilator reversibility. The complexity and inherent variability of a patient's acute response to a bronchodilator and the lack of a standardized procedure for assessing bronchodilator reversibility have led to significant confusion surrounding this concept. Although bronchodilator reversibility commonly is defined based on thresholds for improvement in FEV(1), lung volume-based measures of pulmonary function may be of particular importance in patients with severe COPD. The usefulness of acute reversibility to short-acting bronchodilators in predicting a patient's long-term response to bronchodilator maintenance therapy is also unclear, although most studies suggest that a lack of acute response to short-acting bronchodilators does not preclude a beneficial long-term response to maintenance bronchodilator treatment. This review outlines recent findings about the prevalence and usefulness of bronchodilator reversibility in patients with COPD based on the available literature and proposes areas of future research.     

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.