Quadriceps muscle weakness and atrophy are associated with a differential epigenetic profile in advanced COPD

2015 ◽  
Vol 128 (12) ◽  
pp. 905-921 ◽  
Author(s):  
Ester Puig-Vilanova ◽  
Juana Martínez-Llorens ◽  
Pilar Ausin ◽  
Josep Roca ◽  
Joaquim Gea ◽  
...  
Keyword(s):  
Muscle Weakness ◽  
Vastus Lateralis ◽  
Muscle Growth ◽  
Quadriceps Muscle ◽  
Sirtuin 1 ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Epigenetic Events ◽  
Severe Copd

Epigenetic mechanisms regulate muscle mass and function in models of muscle dysfunction and atrophy. We assessed whether quadriceps muscle weakness and atrophy are associated with a differential expression profile of epigenetic events in patients with advanced COPD (chronic obstructive pulmonary disease). In vastus lateralis (VL) of sedentary severe COPD patients (n=41), who were further subdivided into those with (n=25) and without (n=16) muscle weakness and healthy controls (n=19), expression of muscle-enriched miRNAs, histone acetyltransferases (HATs) and deacetylases (HDACs), growth and atrophy signalling markers, total protein and histone acetylation, transcription factors, small ubiquitin-related modifier (SUMO) ligases and muscle structure were explored. All subjects were clinically evaluated. Compared with controls, in VL of all COPD together and in muscle-weakness patients, expression of miR-1, miR-206 and miR-27a, levels of lysine-acetylated proteins and histones and acetylated histone 3 were increased, whereas expression of HDAC3, HDAC4, sirtuin-1 (SIRT-1), IGF-1 (insulin-like growth factor-1) were decreased, Akt (v-akt murine thymoma viral oncogene homologue 1) expression did not differ, follistatin expression was greater, whereas myostatin expression was lower, serum reponse factor (SRF) expression was increased and fibre size of fast-twitch fibres was significantly reduced. In VL of severe COPD patients with muscle weakness and atrophy, epigenetic events regulate muscle differentiation rather than proliferation and muscle growth and atrophy signalling, probably as feedback mechanisms to prevent those muscles from undergoing further atrophy. Lysine-hyperacetylation of histones may drive enhanced protein catabolism in those muscles. These findings may help design novel therapeutic strategies (enhancers of miRNAs promoting myogenesis and acetylation inhibitors) to selectively target muscle weakness and atrophy in severe COPD.

scholarly journals Prevalence of obstructive sleep apnea among patients with chronic obstructive pulmonary disease

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Osama Ibrahim Mohammad ◽  
Ahmed Gouda Elgazzar ◽  
Shymaa Mohammad Mahfouz ◽  
Marwa Elsayed Elnaggar
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obese Patients ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Obstructive Sleep ◽  
Severe Copd

Abstract Background The conjunction of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) is known as overlap syndrome (OS). The coexistence of these diseases has cardiovascular morbidity and mortality. The aim of this study is to assess the prevalence of OSA in COPD patients. One hundred COPD patients (obese and non-obese) performed sleep questionnaires and polysomnograms. Results OSA prevalence in COPD was 50% and it increases with increasing disease severity (P < 0.001). The highest prevalence of OSA was found in obese patients with severe COPD; 90.5% of these patients have OSA. In the OSA group, obese patients were found to have significantly higher STOP-Bang Questionnaire (SBQ), Epworth Sleep Scale (ESS), modified medical research council (mMRC) dyspnea scale, apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and oxygen desaturation index (ODI). Both obese and non-obese COPD patients showed significant positive correlations between AHI and smoking index (SI), SBQ, ESS, mMRC, ODI, and neck circumference (NC). Conclusions From this study, it can be concluded that moderate and severe COPD patients had a higher diagnosis of sleep-disordered breathing. Also, obese-COPD patients are more susceptible to develop OSA. Trial registration Name of the registry: Benha University Protocol Record Benha U123, Obstructive Sleep Apnea Prevalence in Patients With Chronic Obstructive Pulmonary Diseases. Trial registration number: NCT04903639. Date of registry: 5/22/2021 (retrospective study).

scholarly journals Decreased plasma epidermal growth factor (EGF) levels in patients with severe chronic obstructive pulmonary disease

Pneumologia ◽  
2019 ◽  
Vol 68 (1) ◽  
pp. 21-26
Author(s):  
Retno AS Soemarwoto ◽  
Andika Chandra Putra ◽  
Syazili Mustofa ◽  
◽  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Pulmonary Disease ◽  
Plasma Levels ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Epidermal Growth ◽  
Severe Copd

Abstract Background Chronic mucus hypersecretion is a common feature in chronic obstructive pulmonary disease (COPD) and is associated with epidermal growth factor (EGF) activity. Aberrant EGF and its receptor signalling can cause airway hyperproliferation, increase in mucous cell differentiation and mucus hyperproduction. Furthermore, it can also promote subepithelial fibrosis and excessive collagen deposition in COPD. The objective of this research was to investigate the plasma levels of EGF in smokers with COPD in comparison with clinically healthy smokers. In addition, the relationship between the plasma levels of EGF and clinical features was investigated. Methods A cross-sectional study included 82 clinically stable male patients with mild-to-very severe COPD (mean age: 64.5±8.6 years), and the control group consisted of 86 healthy male smokers (mean age: 61.6±9.5 years). To define COPD, we performed spirometry and classified COPD using Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. We analyzed the levels of EGF by enzyme-linked immunosorbent assay in plasma. Results The mean serum levels of EGF were significantly lower in smokers with COPD than those in controls (69.30 and 83.82 pg/mL, respectively, p = 0.046). The plasma levels of EGF were significantly different (p = 0.004) between mild COPD and moderate-to-very severe COPD. There were no significant differences between the levels of EGF in plasma of spontaneous sputum producers (COPD patients) vs. nonsputum producers (p = 0.101) and between nonexacerbated COPD and exacerbated COPD patients(p = 0.138). Conclusions There is a significant difference in the plasma levels of EGF in male smokers with COPD as compared with male healthy smokers. Our findings suggest that the plasma levels of EGF may contribute to the pathogenesis of COPD.

Randomised controlled trial to investigate the use of high-frequency airway oscillations as training to improve dyspnoea (TIDe) in COPD

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217072
Author(s):  
Enya Daynes ◽  
Neil Greening ◽  
Sally J Singh
Keyword(s):  
Muscle Weakness ◽  
High Frequency ◽  
Controlled Trial ◽  
Forced Expiratory Volume ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Registration Number ◽  
Randomised Controlled ◽  
Double Blinded

BackgroundChronic obstructive pulmonary disease (COPD) is characterised by symptomatic dyspnoea and reduced exercise tolerance, in part as a result muscle weakness, for which inspiratory muscle training (IMT) may be useful. Excess mucus hypersecretion commonly coexists in COPD and may lead to reduce ventilation, further impacting on breathlessness. Devices for sputum clearance may be employed to aid mucus expectoration. This trial aimed to explore the effectiveness of a combined IMT and high-frequency airway oscillating (HFAO) device in the management of dyspnoea.MethodsThis was a double-blinded, randomised sham-controlled trial which recruited symptomatic patients with COPD. Patients were randomised to either a HFAO device (Aerosure) or sham device for 8 weeks, three times a day. The primary outcome was the Chronic Respiratory Questionnaire dyspnoea (CRQ-D) domain. Pre-specified subgroup analyses were performed including those with respiratory muscle weakness, excessive sputum and frequent exacerbators.Results104 participants (68% men, mean (SD) age 69.75 years (7.41), forced expiratory volume in 1 s per cent predicted 48.22% (18.75)) were recruited to this study with 96 participants completing. No difference in CRQ-D was seen between groups (0·28, 95% CI −0.19 to 0.75, p=0.24), though meaningful improvements were seen over time in both groups (mean (SD) HFAO 0.45 (0.78), p<0.01; sham 0.73 (1.09), p<0.01). Maximal inspiratory pressure significantly improved in the HFAO group over sham (5.26, 95% CI 0.34 to 10.19, p=0.05). Similar patterns were seen in the subgroup analysis.ConclusionThere were no statistical differences between the HFAO and the sham group in improving dyspnoea measured by the CRQ-D.Trial registration numberISRCTN45695543.

scholarly journals Relationship of the Content of Systemic and Endobronchial Soluble Molecules of CD25, CD38, CD8, and HLA-I-CD8 and Lung Function Parameters in COPD Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Nailya Kubysheva ◽  
Larisa Postnikova ◽  
Svetlana Soodaeva ◽  
Viкtor Novikov ◽  
Tatyana Eliseeva ◽  
...  
Keyword(s):  
Lung Function ◽  
Blood Serum ◽  
Exhaled Breath Condensate ◽  
Diagnostic Methods ◽  
Stable Phase ◽  
Chronic Obstructive ◽  
Exhaled Breath ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Severe Copd

The definition of new markers of local and systemic inflammation of chronic obstructive pulmonary disease (COPD) is one of the priority directions in the study of pathogenesis and diagnostic methods improvement for this disease. We investigated 91 patients with COPD and 21 healthy nonsmokers. The levels of soluble CD25, CD38, CD8, and HLA-I-CD8 molecules in the blood serum and exhaled breath condensate (EBC) in moderate-to-severe COPD patients during exacerbation and stable phase were studied. An unidirectional change in the content of sCD25, sCD38, and sCD8 molecules with increasing severity of COPD was detected. The correlations between the parameters of lung function and sCD8, sCD25, and sHLA-I-CD8 levels in the blood serum and EBC were discovered in patients with severe COPD. The findings suggest a pathogenetic role of the investigated soluble molecules of the COPD development and allow considering the content of sCD8, sCD25, and sHLA-I-CD8 molecules as additional novel systemic and endobronchial markers of the progression of chronic inflammation of this disease.

scholarly journals Study of Factors Associated with Sarcopenia in COPD Patients

2021 ◽  
Vol 33 (1) ◽  
pp. 50-53
Author(s):  
Saleh Ahmed
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Bioelectrical Impedance ◽  
Chronic Obstructive ◽  
College Hospital ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Factors Associated ◽  
Copd Patients ◽  
Severe Copd

Introduction: Sarcopenia is frequently associated with chronic diseases such as chronic obstructive pulmonary disease (COPD). Sarcopenia can be classified as physical frailty where frailty is associated with adverse health outcomes. Sarcopenia was found to be associated with worsening lung function in male COPD patient. Objective was to find out the factors associated with sarcopenia in COPD patients. Materials & Methods: This was cross-sectional observational study was carried out Different Privet Medical in Chandpur and Chandpur Medical College Hospital, Chandpur. Patients diagnosed with COPD according to Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) guidelines were included in this study. Exclusion criteria were unstable cardiac disease, an exacerbation within the preceding 4 weeks, predominant neurological limitation to walking (eg, significant hemiplegia) or contraindication to bioelectrical impedance analysis (BIA) including an implanted pacemaker or defibrillator. All participants gave written informed consent. EWGSOP criteria were applied to outpatients with stable COPD. Results: In uniavariate analysis, age, moderate COPD, severe COPD, obesity, non-elective admission over the past 12 months, MMRC scale and MAP were significantly associated with sarcopenia. In multivariate analysis, age, moderate COPD, severe COPD, obesity and MMRC scale were significantly associated with sarcopenia. Conclusion: Prevalence of sarcopenia was 26%. Independent factors associated with sarcopenia Age (>70 years) years (adjusted odds ratio (AOR) 4.387. Sarcopenia affects about one-quarter of COPD patients. Age, severity of COPD, MMRC scale, and BMI status were the factors associated with sarcopenia. Medicine Today 2021 Vol.33(1): 50-53

scholarly journals Using step counters to promote physical activity and exercise capacity in patients with chronic obstructive pulmonary disease: a meta-analysis

2018 ◽  
Vol 12 ◽  
pp. 175346661878738 ◽  
Author(s):  
Shanhu Qiu ◽  
Xue Cai ◽  
Xuyi Wang ◽  
Can He ◽  
Martina Zügel ◽  
...  
Keyword(s):  
Physical Activity ◽  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Exercise Capacity ◽  
Meta Analysis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Step Counter ◽  
Copd Patients ◽  
Severe Copd

Background: Although step counters are popularly employed for physical rehabilitation in chronic obstructive pulmonary disease (COPD) patients, their effectiveness is inconsistent and even questioned. This meta-analysis aimed to investigate whether step counter use increases physical activity or improves exercise capacity in COPD patients. Methods: Electronic databases were searched for randomized controlled trials that assessed the efficacy of step counter use in increasing physical activity or in improving exercise capacity. Data were aggregated using a random-effects model to get the overall effect sizes [standard mean difference (SMD) with 95% confidence interval (CI)], and subgroup analyses were performed. Results: A total of 15 trials enrolling 1316 patients with moderate to severe COPD were included. Step counter use increased physical activity compared with controls (SMD = 0.57, 95% CI 0.31–0.84), which is equal to a magnitude of 1026 steps/day in daily steps. It also enhanced exercise capacity with an effect size of 0.30 (95% CI 0.16–0.45), approximating to a magnitude of 11.6 m in the 6-min walking distance. Step counter use could augment physical activity (SMD = 0.64, 95% CI 0.19–1.08) and exercise capacity (SMD = 0.32, 95% CI 0.01–0.62) for patients receiving pulmonary rehabilitation. Yet it cannot enhance physical activity or exercise capacity in patients with severe COPD or among studies with intervention durations ⩾6 months (both p > 0.50). Conclusions: Step counter use increases physical activity and improves exercise capacity in COPD patients, at least in the short term, which supports the notion of recommending step counter use in COPD management.

scholarly journals The CT pulmonary vascular parameters and disease severity in COPD patients on acute exacerbation: a correlation analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tao Yang ◽  
Chihua Chen ◽  
Zhongyuanlong Chen
Keyword(s):  
Acute Exacerbation ◽  
Disease Severity ◽  
Smoking History ◽  
Chronic Obstructive ◽  
Lung Field ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Pulmonary Vessels ◽  
Copd Patients ◽  
Severe Copd

Abstract Background It is necessary to analyze the CT pulmonary vascular parameters and disease severity in chronic obstructive pulmonary disease (COPD) patients to provide evidence support for the management of COPD. Methods COPD patients on acute exacerbation admitted to our hospital from COPD patients from January 2019 to March 2020 was selected. The characteristics and ratio of the cross-sectional area (CSA) of small pulmonary vessels to the total area of the lung field, and the ratio of pulmonary artery and aorta (PA/A) cross-sectional diameter in patients with COPD were analyzed. Results A total of 128 COPD patients were included. There were significant differences in the duration of COPD, smoking history, the PaO2, PaCO2, pH, and FEV1, FVC and FEV1/FVC among COPD patients with different severity (all p < 0.05). The duration of COPD, smoking, PaO2, PaCO2, CSA and PA/A were correlated with the COPD severity (all p < 0.05). Both CSA, PA/A were correlated with post BD FEV1 (all p < 0.05). The cutoff value of CSA and PA/A for the diagnosis of severe COPD was 0.61 and 0.87 respectively, and the AUC of CSA and PA/A for the diagnosis of severe COPD was 0.724 and 0.782 respectively. Conclusions Patients with CSA ≤ 0.61 and PA/A ≥ 0.87 may have higher risks for severe COPD, and more studies are needed in the future to further elucidate the management of COPD.

scholarly journals Nutritional insufficiency in patients having chronic obstructive pulmonary disease

2008 ◽  
Vol 7 (2) ◽  
pp. 14-19
Author(s):  
E. I. Beloborodova ◽  
L. A. Akimova ◽  
V. A. Burkovskaya ◽  
Ye. V. Semenenko ◽  
A. V. Asanova
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Small Intestine ◽  
Pulmonary Disease ◽  
Body Mass ◽  
Chronic Obstructive ◽  
Radioisotope Method ◽  
Obstructive Pulmonary Disease ◽  
Absorption Function ◽  
Copd Patients ◽  
Severe Copd

Absorption function of small intestine concerning fats, proteins, carbohydrates in 68 patients having chronic obstructive pulmonary disease (COPD) was studied in comparison with trophologic insufficiency. Thirty five patients were controls. Absorption was studied based upon van de Kamer method, by radioisotope method and d-xylose test. Decreased absorption was revealed in patients with mean severe and severe COPD. Direct correlations were established between body mass deficiency in COPD patients and decreased absorption function of the small intestine as concerns proteins (r = 0,71), fats (r = 0,55) and carbohydrates (r = 0,48).

scholarly journals Possible Role of Serum Leptin as Biomarker in COPD

Folia Medica ◽  
2019 ◽  
Vol 61 (4) ◽  
pp. 512-521
Author(s):  
Yanitsa A. Zhelyazkova ◽  
Tanya T. Tacheva ◽  
Dimo M. Dimov ◽  
Denitsa G. Vlaykova ◽  
Aneliya V. Bivolarska ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Respiratory Diseases ◽  
Smoking Habits ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Serum Leptin ◽  
Copd Patients ◽  
Severe Copd

Leptin is one of the adipokines shown to exert a significant effect in respiratory diseases, including chronic obstructive pulmonary disease (COPD).The aim of the present study was to evaluate the possible role of serum leptin as biomarker in COPD.The serum leptin levels were assessed in 58 patents with stable COPD and 21 controls applying ELISA method.The leptin levels were higher, although not significantly, in COPD patients than in controls (221.52&plusmn;24.28(SE) vs. 165.04&plusmn;26.01 pg/ml, p=0.197). This tendency turned out significant when only females were compared (414.60&plusmn;60.63 vs. 219.40&plusmn;44.15 pg/ml, p=0.038). The levels of leptin were highly dependent on the BMI both in COPD patients (p<0.001) and in controls (p=0.024): they were the highest in obese individuals and decreased with reducing the BMI.In the COPD group, women had significantly higher leptin levels than men (p<0.0001) independent of the BMI. The non-smoking patients had significantly higher leptin levels than ex-smokers (p=0.007) and current smokers (p=0.007). In patients with BMI above 25, several associations were observed: patients with mild COPD had higher serum leptin level than those with severe or very severe COPD (p=0.038); the leptin levels correlated positively with FEV1% (r= 0.304, p=0.045) and FEV1/FVC ratio (I= 0.348, p=0.021), and tended to correlate negatively with ABCD GOLD groups (Rho=-0.300, p=0.043) and with the CAT points (Rho=-0.258, p=0.091); the leptin levels below 300 ng/ml determined 4.08-fold higher risk for more severe COPD.The results of our study confirm that the serum leptin levels depend significantly on the BMI and are interfered by gender and smoking habits. However, this adipokine cannot be used as a serum biomarker for distinguishing COPD patients, but its decrease might be associated with aggravation of the disease.

scholarly journals The phosphodiesterase-4 inhibitor roflumilast reverts proteolysis in skeletal muscle cells of patients with COPD cachexia

2018 ◽  
Vol 125 (2) ◽  
pp. 287-303 ◽  
Author(s):  
Esther Barreiro ◽  
Ester Puig-Vilanova ◽  
Anna Salazar-Degracia ◽  
Sergi Pascual-Guardia ◽  
Carme Casadevall ◽  
...  
Keyword(s):  
Antioxidant Defense ◽  
Ubiquitin Proteasome System ◽  
Sirtuin 1 ◽  
Camp Signaling ◽  
Chronic Obstructive ◽  
Myosin Isoforms ◽  
Beneficial Effects ◽  
Copd Patients ◽  
Ubiquitin Proteasome ◽  
Severe Copd

Peripheral muscle weakness and mass loss are characteristic features in severe chronic obstructive pulmonary disease (COPD). We hypothesized that the phosphodiesterase (PDE)-4 inhibitor roflumilast-induced cAMP may ameliorate proteolysis and metabolism in skeletal muscles of COPD patients with severe muscle wasting. In myogenic precursor cells (isolated from muscle biopsies and cultured up to obtain differentiated myotubes) from 10 severe COPD patients and 10 healthy controls, which were treated with 1 μM roflumilast N-oxide (RNO) for three time cohorts (1, 6, and 24 h), genes of antioxidant defense and oxidative stress marker, myogenesis and muscle metabolism, proteolysis (tyrosine release assay) and ubiquitin-proteasome system markers, autophagy, and myosin isoforms were analyzed using RT-PCR and immunoblotting. In COPD patients at 6 h RNO treatment, myotube tyrosine release, total protein ubiquitination, and tripartite motif-containing protein 32 levels were significantly lower than healthy controls, whereas at 24 h RNO treatment, myotube myosin heavy chain ( MyHC) -I and MyHC-IIx expression levels were upregulated in both patients and controls. In the 6-h RNO cohort, in patients and controls, myotube expression of nuclear factor (erythroid-derived 2)-like 2 ( NRF2) and its downstream antioxidants sirtuin-1, FGF-inducible 14, and insulin-like growth factor-1 was upregulated, whereas that of myocyte-specific enhancer factor 2C, myogenic differentiation, myogenin, myostatin, atrogin-1, and muscle RING-finger protein-1 was downregulated. In myotubes of severe COPD patients with cachexia, roflumilast-induced cAMP signaling exerts beneficial effects by targeting muscle protein breakdown (tyrosine release), along with reduced expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In both patients and controls, roflumilast also favored antioxidant defense through upregulation of the NRF2 pathway and that of the histone deacetylase sirtuin-1, whereas it improved the expression of slow- and fast-twitch myosin isoforms. These findings show that muscle dysfunction and wasting may be targeted by roflumilast-induced cAMP signaling in COPD. These results have potential therapeutic implications, as this PDE-4 inhibitor is currently available for the treatment of systemic inflammation and exacerbations in patients with severe COPD. NEW & NOTEWORTHY In myotubes of cachectic chronic obstructive pulmonary disease (COPD) patients, cAMP signaling exerted beneficial effects by targeting muscle proteolysis and reducing gene expression of proteolytic markers of the ubiquitin-proteasome system and that of myostatin. In myotubes of patients and controls, roflumilast also favored antioxidant defense through upregulation of the nuclear factor (erythroid-derived 2)-like 2 pathway, of sirtuin-1, and of gene expression of slow- and fast-twitch isoforms. These findings have potential clinical implications for the treatment of muscle wasting in patients with COPD and cachexia.

Sign in / Sign up

Export Citation Format

Share Document