Nutritional Status and Body Composition in Patients Suffering From Chronic Respiratory Diseases and Its Correlation With Pulmonary Rehabilitation

As part of an individualized intervention to improve the physical, emotional, and social functioning of patients with chronic respiratory diseases in general and chronic obstructive pulmonary disease in particular, awareness of the presence and consequences of changes in body composition increased enormously during the last decades, and nutritional intervention is considered as an essential component in the comprehensive approach of these patients. This review describes the prevalence and the clinical impact of body composition changes and also provides an update of current intervention strategies. It is argued that body composition, preferentially a three-component evaluation of fat, lean, and bone mass, must become part of a thorough assessment of every patient, admitted for pulmonary rehabilitation

Whole-Body versus Local DXA-Scan for the Diagnosis of Osteoporosis in COPD Patients

Background. Osteoporosis is an extrapulmonary effect of chronic obstructive pulmonary disease (COPD). Diagnosis of osteoporosis is based on BMD measured by DXA-scan. The best location for BMD measurement in COPD has not been determined. Aim of this study was to assess whole-body BMD and BMD of the hip and lumbar spine (local DXA) in COPD patients and compare the prevalence of osteoporosis at these locations. Methods. Whole body as well as local DXA-scan were made in 168 COPD patients entering pulmonary rehabilitation. Patient-relevant characteristics were assessed. Prevalence of osteoporosis was determined. Characteristics of patients without osteoporosis were compared to patients with osteoporosis on local DXA. Results. A higher prevalence of osteoporosis was found using local DXA compared to whole-body DXA (39% versus 21%). One quarter of patients without osteoporosis on whole body-DXA did have osteoporosis on local DXA. Significant differences in patient characteristics between patients without osteoporosis based on both DXA measurements and patients with osteoporosis based on local DXA only were found. Conclusions. DXA of the hip and lumbar spine should be made to assess bone mineral density in COPD patients. The lowest T-score of these locations should be used to diagnose osteoporosis

Altered Cigarette Smoke-Induced Lung Inflammation Due to Ablation of Grx1

Glutaredoxins (Grx) are redox enzymes that remove glutathione bound to protein thiols, know as S-glutathionylation (PSSG). PSSG is a reservoir of GSH and can affect the function of proteins. It inhibits the NF-κB pathway and LPS aspiration in Grx1 KO mice with decreased inflammatory cytokine levels. In this study we investigated whether absence of Grx1 similarly repressed cigarette smoke-induced inflammation in an exposure model in mice. Cigarette smoke exposure for four weeks decreased lung PSSG levels, but increased PSSG in lavaged cells and lavage fluid (BALF). Grx1 KO mice had increased levels of PSSG in lung tissue, BALF and BAL cells in response to smoke compared to wt mice. Importantly, levels of multiple inflammatory mediators in the BALF were decreased in Grx1 KO animals following cigarette smoke exposure compared to wt mice, as were levels of neutrophils, dendritic cells and lymphocytes. On the other hand, macrophage numbers were higher in Grx1 KO mice in response to smoke. Although cigarette smoke in vivo caused inverse effects in inflammatory and resident cells with respect to PSSG, primary macrophages and epithelial cells cultured from Grx1 KO mice both produced less KC compared to cells isolated from WT mice after smoke extract exposure. In this manuscript, we provide evidence that Grx1 has an important role in regulating cigarette smoke-induced lung inflammation which seems to diverge from its effects on total PSSG. Secondly, these data expose the differential effect of cigarette smoke on PSSG in inflammatory versus resident lung cells

Quantitative CT: Associations between Emphysema, Airway Wall Thickness and Body Composition in COPD

The objective of the present study was to determine the association between CT phenotypes—emphysema by low attenuation area and bronchitis by airway wall thickness—and body composition parameters in a large cohort of subjects with and without COPD. In 452 COPD subjects and 459 subjects without COPD, CT scans were performed to determine emphysema (%LAA), airway wall thickness (AWT-Pi10), and lung mass. Muscle wasting based on FFMI was assessed by bioelectrical impedance. In both the men and women with COPD, FFMI was negatively associated with %LAA. FMI was positively associated with AWT-Pi10 in both subjects with and without COPD. Among the subjects with muscle wasting, the percentage emphysema was high, but the predictive value was moderate. In conclusion, the present study strengthens the hypothesis that the subgroup of COPD cases with muscle wasting have emphysema. Airway wall thickness is positively associated with fat mass index in both subjects with and without COPD

The host immune response contributes to Haemophilus influenzae virulence

SummaryBackgroundThere is compelling evidence that infections with non-typeable Haemophilus influenzae (NTHi) are associated with exacerbations in COPD patients. However, NTHi has also been isolated frequently during clinically stable disease. In this study we tested the hypothesis that genetically distinct NTHi isolates obtained from COPD patients differ in virulence which could account for dissimilarities in the final outcome of an infection (stable vs. exacerbation).ResultsNTHi isolates (n = 32) were obtained from stable COPD patients, or during exacerbations. Genetically divergent NTHi isolates were selected and induction of inflammation was assessed as an indicator of virulence using different in vitro models. Despite marked genomic differences among NTHi isolates, in vitro studies could not distinguish between NTHi isolates based on their inflammatory capacities. Alternatively, when using a whole blood assay results demonstrated marked inter-, but not intra-individual differences in cytokine release between healthy volunteers irrespective of the origin of the NTHi isolate used.ConclusionResults suggest that the individual immune reactivity might be an important predictor for the clinical outcome (exacerbation vs. no exacerbation) following NTHi infection

Copper-Heparin Inhalation Therapy To Repair Emphysema:A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration

Withdrawal of inhaled glucocorticoids and exacerbations of COPD.

This is the final version of the article. It first appeared from Massachusetts Medical Society via http://dx.doi.org/10.1056/NEJMoa1407154BACKGROUND: Treatment with inhaled glucocorticoids in combination with long-acting bronchodilators is recommended in patients with frequent exacerbations of severe chronic obstructive pulmonary disease (COPD). However, the benefit of inhaled glucocorticoids in addition to two long-acting bronchodilators has not been fully explored. METHODS: In this 12-month, double-blind, parallel-group study, 2485 patients with a history of exacerbation of COPD received triple therapy consisting of tiotropium (at a dose of 18 μg once daily), salmeterol (50 μg twice daily), and the inhaled glucocorticoid fluticasone propionate (500 μg twice daily) during a 6-week run-in period. Patients were then randomly assigned to continued triple therapy or withdrawal of fluticasone in three steps over a 12-week period. The primary end point was the time to the first moderate or severe COPD exacerbation. Spirometric findings, health status, and dyspnea were also monitored. RESULTS: As compared with continued glucocorticoid use, glucocorticoid withdrawal met the prespecified noninferiority criterion of 1.20 for the upper limit of the 95% confidence interval (CI) with respect to the first moderate or severe COPD exacerbation (hazard ratio, 1.06; 95% CI, 0.94 to 1.19). At week 18, when glucocorticoid withdrawal was complete, the adjusted mean reduction from baseline in the trough forced expiratory volume in 1 second was 38 ml greater in the glucocorticoid-withdrawal group than in the glucocorticoid-continuation group (P<0.001); a similar between-group difference (43 ml) was seen at week 52 (P=0.001). No change in dyspnea and minor changes in health status occurred in the glucocorticoid-withdrawal group. CONCLUSIONS: In patients with severe COPD receiving tiotropium plus salmeterol, the risk of moderate or severe exacerbations was similar among those who discontinued inhaled glucocorticoids and those who continued glucocorticoid therapy. However, there was a greater decrease in lung function during the final step of glucocorticoid withdrawal. (Funded by Boehringer Ingelheim Pharma; WISDOM ClinicalTrials.gov number, NCT00975195.).Supported by Boehringer Ingelheim Pharma

The revised GOLD 2017 COPD categorization in relation to comorbidities

Introduction: The COPD classification proposed by the Global Initiative for Obstructive Lung Disease was recently revised, and the A to D grouping is now based on symptoms and exacerbations only. Potential associations with comorbidities have not been assessed so far. Thus the aim of the present study was to determine the relationship between the revised (2017) GOLD groups A-D and major comorbidities. Methods: We used baseline data from the COPD cohort COSYCONET. Comorbidities were identified from patient self-reports and disease-specific medication: gastrointestinal disorders, asthma, sleep apnea, hyperuricemia, hyperlipidemia, diabetes, osteoporosis, mental disorders, heart failure, hypertension, coronary artery disease. The A-D groups were based on either the COPD Assessment Test or the modified Medical Research Council scale. Exacerbations were also categorized as per GOLD recommendations. Results: Data from 2228 patients were analyzed. Using GOLD group A as a reference, group D was associated with nearly all comorbidities, followed by group B and C. When groups A-D were dichotomized as AC vs. BD (symptoms) and AB vs. CD (exacerbations), all comorbidities correlated with symptoms and/or exacerbations. This was true for both mMRC- and CAT-based categorizations. Conclusions: These findings suggest that the recently modified GOLD categorization is clinically relevant beyond being purely an assessment of symptoms and exacerbations. As the A-D groups correlated with the risk of important comorbidities, with some differences in terms of the correlation with symptoms and exacerbations, the findings underline the importance of identifying comorbidities in COPD, particularly in non-responders to therapy who have high symptoms and/or exacerbation rates