Effect of Autoimmune Cell Therapy on Immune Cell Content in Patients with COPD: A Randomized Controlled Trial.

OBJECTIVE: To explore the effect of autoimmune cell therapy on immune cells in patients with chronic obstructive pulmonary disease (COPD) and to provide a reference for clinical treatment of COPD. METHODS: Sixty patients with stable COPD were randomly divided into control group and treatment group (n = 30). The control group was given conventional treatment, and the treatment group was given one autoimmune cell therapy on the basis of conventional treatment. The serum levels of CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the peripheral blood were detected by flow cytometry. Possible adverse reactions were detected at any time during treatment. RESULTS: There were no significant differences in the contents of CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the serum of the control group (P > 0.05). Compared with before treatment, the contents of CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the serum of the treatment group were significantly increased (P < 0.05). The ratio of CD4 + /CD8+ T cells in both control and treatment groups did not change significantly during treatment (P > 0.05). There were no significant differences in serum CD3+ T cells, CD4+ T cells, CD8+ cells, B cells, and NK cells in the treatment group at 30 days and 90 days after treatment (P > 0.05), but they were significantly higher than those in the control group (P < 0.05). CONCLUSION: Autoimmune cell therapy can significantly increase the level of immune cells in the body and can be maintained for a long period of time, which has certain clinical benefits for recurrent respiratory tract infections and acute exacerbation in patients with COPD.

Effect of urban air pollution on CRP and coagulation: a study on inpatients with acute exacerbation of chronic obstructive pulmonary disease.

PURPOSE: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important event in the course of chronic obstructive pulmonary disease that negatively affects patients' quality of life and leads to higher socioeconomic costs. While previous studies have demonstrated a significant association between urban air pollution and hospitalization for AECOPD, there is a lack of research on the impact of particulate matter (PM) on inflammation and coagulation in AECOPD inpatients. Therefore, this study investigated the association of changes in coagulation function and C-reactive protein (CRP) with PM levels in the days preceding hospitalization. PATIENTS AND METHODS: We reviewed the medical records of AECOPD patients admitted to Putuo Hospital, Shanghai University of Traditional Chinese Medicine, between March 2017 and September 2019. We analyzed the association of coagulation function and CRP level in AECOPD patients with PM levels in the days before hospitalization. Multivariate unconditional logistic regression analyses were used to evaluate the adjusted odds ratio (OR) and 95% confidence interval (CI) for the association of CRP data with hospitalization day. Kruskal-Wallis tests were used to evaluate mean aerodynamic diameter of ≥ 2.5 µm (PM2.5) exposure on the day before hospitalization; we assessed its association with changes in prothrombin time (PT) in AECOPD inpatients with different Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes. RESULTS: The peripheral blood PT of AECOPD patients with PM2.5 ≥ 25 mg/L on the day before hospitalization were lower than those of patients with PM2.5 < 25 mg/L (t = 2.052, p = 0.041). Patients with severe GOLD class exposed to greater than 25 mg/L of PM2.5on the day before hospitalization showed significant differences in PT (F = 9.683, p = 0.008). Peripheral blood CRP levels of AECOPD patients exposed to PM2.5 ≥ 25 mg/L and PM10 ≥ 50 mg/L on the day before hospitalization were higher than those of patients exposed to PM2.5 < 25 mg/L and PM10 < 50 mg/L (t = 2.008, p = 0.046; t = 2.637, p = 0.009). Exposure to < 25 mg/L of PM2.5 on the day before hospitalization was significantly associated with CRP levels (adjusted OR 1.91; 95% CI 1.101, 3.315; p = 0.024). CONCLUSION: Exposure of patients with AECOPD to high PM levels on the day before hospitalization was associated with an increased CRP level and shortened PT. Moreover, PM2.5 had a greater effect on CRP level and PT than mean aerodynamic diameter of ≥ 10 µm (PM10). AECOPD patients with severe GOLD class were more sensitive to PM2.5-induced shortening of PT than those with other GOLD classes.

Electroacupuncture inhibits IL-17/IL-17R and post-receptor MAPK signaling pathways in a rat model of chronic obstructive pulmonary disease.

OBJECTIVE: Interleukin (IL)-17, as a T-helper 17 cell (Th17) cytokine, plays a key role in chronic obstructive pulmonary disease (COPD) pathophysiology including chronic inflammation and airway obstruction, which lead to decreased pulmonary function. The aim of this study was to investigate the effect of acupuncture on IL-17, its receptor (IL-17R) and the mitogen-activated protein kinase (MAPK) signaling pathway, in a rat model of COPD. METHODS: The COPD model was induced in Sprague Dawley rats by exposure to cigarette smoke for 12 weeks. The model rats were treated with electroacupuncture (EA) at BL13 and ST36. The lung function and histology of the rats were observed. IL-17, tumor necrosis factor (TNF)-α, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and in plasma. The leukocytes and macrophages in the BALF were counted. The expression levels of IL-17R were assayed in lung tissue by real-time polymerase chain reaction (PCR), western blotting, and immunohistochemistry. MAPK signaling pathway molecules including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)1/2 and p38, and their phosphorylated forms, were observed in the lung by western blotting. RESULTS: Compared with the control group rats, lung function decreased and there was a severe inflammatory infiltration of the pulmonary parenchyma in the COPD rats. EA effectively improved lung function and alleviated the inflammatory infiltration in the lungs of COPD rats. EA also reversed the elevated total leukocyte and macrophage counts, the high levels of IL-17 and TNF-α, and the low IL-10 content in COPD rats. Meanwhile, EA downregulated the increased mRNA and protein expression of IL-17R, and significantly inhibited the elevated levels of phosphorylated JNK, ERK1/2, and p38 in the lungs of COPD rats. CONCLUSION: Our results suggest that the protective effects of acupuncture therapy on the lungs of COPD rats are likely related to inhibition of IL-17/IL-17R and the post-receptor MAPK signaling pathways.

Clinical Characteristics and Outcomes of Patients With Heart Failure With Reduced Ejection Fraction and Chronic Obstructive Pulmonary Disease: Insights From PARADIGM-HF.

Background Chronic obstructive pulmonary disease (COPD) is a common comorbidity in heart failure with reduced ejection fraction, associated with undertreatment and worse outcomes. New treatments for heart failure with reduced ejection fraction may be particularly important in patients with concomitant COPD. Methods and Results We examined outcomes in 8399 patients with heart failure with reduced ejection fraction, according to COPD status, in the PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Cox regression models were used to compare COPD versus non-COPD subgroups and the effects of sacubitril/valsartan versus enalapril. Patients with COPD (n=1080, 12.9%) were older than patients without COPD (mean 67 versus 63 years; P<0.001), with similar left ventricular ejection fraction (29.9% versus 29.4%), but higher NT-proBNP (N-terminal pro-B-type natriuretic peptide; median, 1741 pg/mL versus 1591 pg/mL; P=0.01), worse functional class (New York Heart Association III/IV 37% versus 23%; P<0.001) and Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (73 versus 81; P<0.001), and more congestion and comorbidity. Medical therapy was similar in patients with and without COPD except for beta-blockade (87% versus 94%; P<0.001) and diuretics (85% versus 80%; P<0.001). After multivariable adjustment, COPD was associated with higher risks of heart failure hospitalization (hazard ratio [HR], 1.32; 95% CI, 1.13-1.54), and the composite of cardiovascular death or heart failure hospitalization (HR, 1.18; 95% CI, 1.05-1.34), but not cardiovascular death (HR, 1.10; 95% CI, 0.94-1.30), or all-cause mortality (HR, 1.14; 95% CI, 0.99-1.31). COPD was also associated with higher risk of all cardiovascular hospitalization (HR, 1.17; 95% CI, 1.05-1.31) and noncardiovascular hospitalization (HR, 1.45; 95% CI, 1.29-1.64). The benefit of sacubitril/valsartan over enalapril was consistent in patients with and without COPD for all end points. Conclusions In PARADIGM-HF, COPD was associated with lower use of beta-blockers and worse health status and was an independent predictor of cardiovascular and noncardiovascular hospitalization. Sacubitril/valsartan was beneficial in this high-risk subgroup. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01035255.

Effect of Monthly Vitamin D Supplementation on Preventing Exacerbations of Asthma or Chronic Obstructive Pulmonary Disease in Older Adults: Post Hoc Analysis of a Randomized Controlled Trial.

Randomized controlled trials have suggested that vitamin D supplementation can prevent asthma and chronic obstructive pulmonary disease (COPD) exacerbations. For COPD, the benefit appears to be limited to individuals with baseline 25-hydroxyvitamin D (25OHD) levels <25 nmol/L. We performed a post hoc analysis of data from a randomized, double-blinded, placebo-controlled trial to investigate the effect that monthly, high-dose vitamin D supplementation (versus placebo) had on older adults with asthma and/or COPD. Specifically, we investigated whether vitamin D supplementation prevented exacerbations of these conditions. Participants were randomly assigned either to an initial oral dose of 200,000 IU vitamin D3 followed by 100,000 IU monthly or to placebo, with an average follow-up period of 3.3 years. Among the 5110 participants, 775 had asthma or COPD at the beginning of the study, and were eligible for inclusion in this analysis. Exacerbations were defined by the prescription of a short-burst of oral corticosteroids. The mean age of the participants was 67 years old, and 56% were male. The mean baseline blood 25OHD level was 63 nmol/L; 2.3% were <25 nmol/L. Overall, we found that vitamin D supplementation did not affect the exacerbation risk (hazard ratio 1.08; 95%CI 0.84-1.39). Among those with baseline 25OHD <25 nmol/L, however, the hazard ratio was 0.11 (95%CI 0.02-0.51); p for interaction = 0.001. Although monthly vitamin D supplementation had no overall impact on risk of exacerbations of asthma or COPD, we found evidence of a probable benefit among those with severe vitamin D deficiency.

Efficacy of Yiqigubiao pill on chronic obstructive pulmonary disease in rats with the disease induced by lipopolysaccharide and cigarette-smoke fumigation.

OBJECTIVE: To investigate the efficacy of Yiqigubiao pill (YQGB) on chronic obstructive pulmonary disease (COPD) in rats with the COPD induced by lipopolysaccharide (LPS) and cigarette- smoke fumigation. METHODS: In this study, six groups of rats were set up, including control group, model group, positive control group (aminophylline) and YQGB (high, medium and low doses) groups. Tracheal injection of lipopolysaccharide (LPS) and cigarette-smoke fumigation induced COPD in rats. The general condition, incubation period and coughing times, lung function, level of inflammatory factors, leukocyte condition and pathological changes of bronchus and lung tissue were observed in rats of each group. RESULTS: In the COPD rats, the latent period of coughing was shortened and the cough frequency was increased significantly; the pulmonary function was significantly decreased, which was manifested by the increased lung tissue resistance and respiratory system resistance, and the decreasing percentage of forced expiratory volume and forced expiratory volume in the 0.3 s (FEV0.3/FVC); the contents of tumor necrosis factor-alpha (TNF-α) and interleukin-4 in serum were obviously increased, and the NEUT% in bronchoalveolar lavage fluid was significantly increase. YQGB could obviously prolong the latent period of cough, and reduce the cough frequency and the content of TNF-α in serum. YQGB can also significantly reduce respiratory resistance and increase FEV0.3/FVC value. The results of histopathology showed that YQGB significantly reduced the pathological changes of tracheal mucosa and lung caused by COPD. YQGB obviously increased level of AQP1, which was down-regulated in the COPD rats. CONCLUSION: YQGB could significantly improve the pulmonary function, reduce inflammation and alleviate lung and bronchial diseases in the COPD rats.

What factors modify the effect of monthly bolus dose vitamin D supplementation on 25-hydroxyvitamin D concentrations?

The increasing use of vitamin D supplements has stimulated interest in identifying factors that may modify the effect of supplementation on circulating 25-hydroxyvitamin D (25(OH)D) concentrations. Such information is of potential interest to researchers, clinicians and patients when deciding on bolus dose of vitamin D supplementation. We carried out a large randomized controlled trial of 5110 adults aged 50-84 years, of European/Other (84%), Polynesian (11%) and Asian (5%) ethnicity, to whom we gave a standard dose of vitamin D3 supplements (200,000 IU initially, then 100,000 IU monthly) which was taken with high adherence. All participants provided a baseline blood sample, and follow-up blood samples were collected at 6 months and annually for 3 years in a random sample of 441 participants, and also at 2 years in 413 participants enrolled in a bone density sub-study. Serum 25(OH)D was measured by LC/MSMS. Mixed model analyses were carried out on all 854 participants providing follow-up blood samples in multivariable models that included age, sex, ethnicity, body mass index (kg/m2), tobacco smoking, alcohol intake, physical activity, sun exposure, season, medical prescription of high-dose vitamin D3 (Cal.D.Forte tablets), asthma/COPD and the study treatment (vitamin D or placebo). The adjusted mean difference in 25(OH)D in the follow-up points between vitamin D supplementation and placebo groups was inversely related (all p for interaction <0.05) to baseline 25(OH)D, BMI, and hours of sun exposure, and higher in females, elders, and those with high frequency of alcohol, medical prescription of vitamin D, and asthma/COPD. The mean difference was not significantly related to ethnicity (p = 0.12), tobacco (p = 0.34), and vigorous activity (p = 0.33). In summary, these data show that vitamin D status, BMI, sun exposure hours, sex and asthma/COPD modify the 25(OH)D response to vitamin D supplementation. By contrast, ethnicity, tobacco smoking, and vigorous activity do not.

Vitamin D deficiency is associated with respiratory symptoms and airway wall thickening in smokers with and without COPD: a prospective cohort study.

BACKGROUND: Previous studies have established a higher prevalence of vitamin D deficiency in patients with COPD, but the relationship between vitamin D levels and COPD exacerbations remains controversial. In addition, the effect of vitamin D levels on imaging characteristics remains mostly unexplored. Using cross-sectional and longitudinal follow up data from the COPDGene Study, we assessed the association between vitamin D levels on respiratory symptoms, exacerbations, and imaging characteristics. We hypothesized that vitamin D deficiency will be associated with worse respiratory-related outcomes. METHODS: Current and former smokers between ages 45-80 were enrolled the COPDGene Study. Subjects completed questionnaires, spirometry, six-minute walk test, and chest computed tomography scans. A subset of subjects had measurement of serum concentration of 25-hydroxyvitamin D (25(OH)D). Vitamin D deficiency was defined as serum concentration less than 20 ng/mL. Longitudinal follow up was conducted via a web-based or telephone questionnaire. RESULTS: Vitamin D levels were measured on 1544 current and former smokers, of which 981 subjects had sufficient vitamin D levels and 563 subjects had vitamin D deficiency. Subjects with vitamin D deficiency were younger with increased likelihood of being African American, being current smokers, having a lower percent predicted FEV1, and having COPD. Vitamin D deficiency was associated with worse quality of life, increased dyspnea, decreased exercise tolerance, and increased frequency of severe exacerbations. Vitamin D deficiency was also associated with increased segmental airway wall thickness on chest CT scans. CONCLUSION: Vitamin D deficiency was associated with increased respiratory symptoms, decreased functional status, increased frequency of severe exacerbations, as well as airway wall thickening on chest CT scans. Further research is needed to determine the potential impact of vitamin D supplementation to improve disease outcomes.

Translating vitamin D transcriptomics to clinical evidence: Analysis of data in asthma and chronic obstructive pulmonary disease, followed by clinical data meta-analysis.

Vitamin D (VitD) continues to trigger intense scientific controversy, regarding both its bi ological targets and its supplementation doses and regimens. In an effort to resolve this dispute, we mapped VitD transcriptome-wide events in humans, in order to unveil shared patterns or mechanisms with diverse pathologies/tissue profiles and reveal causal effects between VitD actions and specific human diseases, using a recently developed bioinformatics methodology. Using the similarities in analyzed transcriptome data (c-SKL method), we validated our methodology with osteoporosis as an example and further analyzed two other strong hits, specifically chronic obstructive pulmonary disease (COPD) and asthma. The latter revealed no impact of VitD on known molecular pathways. In accordance to this finding, review and meta-analysis of published data, based on an objective measure (Forced Expiratory Volume at one second, FEV1%) did not further reveal any significant effect of VitD on the objective amelioration of either condition. This study may, therefore, be regarded as the first one to explore, in an objective, unbiased and unsupervised manner, the impact of VitD levels and/or interventions in a number of human pathologies.

Effects of High-Dose Vitamin D Replacement on the Serum Levels of Systemic Inflammatory Biomarkers in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) is associated with increased inflammatory responses to noxious particles, which can be further enhanced during Acute Exacerbation of COPD (AECOPD). Considering the important immunoregulatory function of vitamin D, high prevalence of Vitamin D Deficiency (VDD) in COPD patients and a negative link between vitamin D levels and inflammatory biomarkers, suggests the seemingly interesting mechanism of vitamin D effects on inflammation resolution during the conventional treatment of AECOPD. The admitted AECOPD patients with VDD were recruited and randomly allocated to receive either 300,000 IU of intramuscular vitamin D (n = 35) or placebo (n = 35). Primary outcomes included inflammation resolution dynamics, which were assessed by monitoring the serum levels of IL-6, IL-8, and hs-CRP. Symptom recovery was evaluated based on the modified Medical Research Council (mMRC) dyspnea scale on the 1st and 6th days of admission. Secondary outcomes included the length of hospital stay (LOS) and 30-day mortality rates. Inflammatory biomarkers were highest at Day 1. Baseline vitamin D levels were 11.25 ± 3.09 and 10.59 ± 3.90 ng/ml (P = 0.45), which reached 11.35 ± 3.16 and 18.17 ± 4.24 by Day 6 (P < 0.001) in the placebo and, vitamin-D groups, respectively. IL-6 levels significantly decreased in the vitamin-D vs. placebo group on the 6th day (P = 0.02); however, no significant differences were observed in IL-8 (P = 0.15) and hs-CRP (P = 0.24) levels, mMRC scale (P = 0.45), LOS (P = 0.20), and mortality rates (P = 0.61). Vitamin D replacement as adjunctive therapy may accelerate inflammation resolution in hospitalized AECOPD patients. Further studies were needed to establish vitamin D exact role on inflammation resolution in AECOPD.

Vitamin D reduces the serum levels of inflammatory cytokines in rat models of periodontitis and chronic obstructive pulmonary disease.

The purpose of this study was to investigate the effects of vitamin D in rat models of chronic obstructive pulmonary disease (COPD) and periodontitis. Animals with both periodontitis and COPD, or with periodontitis only, were established. Once the animal model was established, experimental groups received intraperitoneal injections of 25-hydroxyvitamin D3 (25-OHD3) for 8 weeks, while control groups received refined peanut oil. After sacrifice, inflammatory status was examined in terms of the serum levels of receptor activator of the nuclear factor κB ligand (RANKL), tumor necrosis factor alpha (TNF-α) and interleukins (IL-1 and IL-10), as well as alveolar bone loss, forced expiratory volume (0.20) (FEV 0.20), and the ratio of FEV0.2 to forced vital capacity. The results showed that 25-OHD3 treatment significantly alleviated inflammation by decreasing the serum levels of RANKL, TNF-α and IL-1 and increasing that of IL-10, while reducing alveolar bone loss and slightly improving lung function. These findings suggest that vitamin D supplementation could be a new clinical approach for the treatment of COPD and periodontitis.

Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials.

BACKGROUND: Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation. METHODS: PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial. RESULTS: Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75). CONCLUSIONS: Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels. TRIAL REGISTRATION NUMBER: CRD42014013953.

Effect of Daiqin phlegm-expelling pill on development of inflammation in rats with chronic obstructive pulmonary disease induced by lipopolysaccharide and smoke.

OBJECTIVE: To investigate the effect of Daiqin phlegm-expelling pill, prepared with Traditional Chinese Medicine (TCM), on the development of inflammation in Sprague-Dawley (SD) rats with chronic obstructive pulmonary disease (COPD) induced by lipopolysaccharide (LPS) and smoke, and to identity the possible underlying mechanism. METHODS: Sixty male rats were divided into 6 groups (healthy control group, untreated group, Daiqin phlegm-expelling pill low, middle and high dose, and ambroxol hydrochloride tablet group). COPD was established in SD rats by sootiness and tracheal instillation with LPS. The rats were treated with Daiqin phlegm-expelling pill at the indicated doses for 28 d, the inflammatory cells in bronchoalveolar lavage fluid (BALF), the concentration of tumor necrosis factor-α (TNF-α), interleukin (IL)-8 and IL-6 in blood and the inflammation in lung were evaluated. RESULTS: The number of inflammatory cells in the BALF and TNF-α, IL-8 and IL-6 level in plasma were significantly reduced in rats with COPD when treated with Daiqin phlegm-expelling pill or ambroxol hydrochloride tablet, compared with those without any treatment. The Daiqin phlegm-expelling pill treated rats with COPD had a attenuated inflammation in lung tissue, compared with the untreated group. CONCLUSION: Daiqin phlegm-expelling pill can significantly restrain the airway inflammation in rats with LPS-smoke induced COPD.

Preliminary study: comparative effects of lung volume therapy between slow and fast deep-breathing techniques on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, 6-minute walking distance, and quality of life in persons with COPD.

BACKGROUND: Lung volume therapy with the Voldyne® device can improve lung volume and has a nonsignificant benefit on respiratory muscle strength via the slow deep-breathing technique (SDBT); whereas respiratory muscle training with a respiratory muscle trainer via the fast deep-breathing technique (FDBT) has produced a significant improvement in people with COPD. Thus, the aim of this study was to compare the efficiency of lung volume therapy with the Voldyne® device with the SDBT and FDBT on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, walking capacity, and quality of life (QoL) in people with COPD. METHODS: A total of 30 COPD patient volunteers with mild (stage I) to moderate (stage II) severity were randomized into two groups: SDBT (n=15) and FDBT (n=15). Pulmonary function (FVC, FEV1, and FEV1/FVC), maximal inspiratory mouth pressure (PImax), oxidative stress status (total antioxidant capacity [TAC], glutathione [GSH], malondialdehyde [MDA], and nitric oxide [NO]), inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and IL-6), 6-minute walking distance (6MWD), and total clinical COPD questionnaire (CCQ) score were evaluated before and after 4 weeks of training. RESULTS: All the parameters had no statistical difference between the groups before training. The PImax, TAC, IL-6, total QoL score, and 6MWD changed significantly in the SDBT group after the 4-week experiment as compared to those in the pre-experimental period, whereas FVC, FEV1, FEV1%, FEV1/FVC%, PImax, TAC, MDA, NO, TNF-α, IL-6, 6MWD, and total CCQ score changed significantly in the FDBT group as compared to those in the pre-experimental period. The FEV1%, PImax, TNF-α, IL-6, and total CCQ score differed significantly in the FDBT group in the post-experimental period as compared to those in the SDBT group. CONCLUSION: This preliminary study concluded that the application of incentive spirometry with the Voldyne® device via fast deep breathing possibly improved respiratory muscle strength and QoL and reduced inflammatory cytokines, MDA, and NO better than that via slow deep breathing among people with COPD.

Effects of acupuncture on nutritional state of patients with stable chronic obstructive pulmonary disease (COPD): re-analysis of COPD acupuncture trial, a randomized controlled trial.

BACKGROUND: There are an increasing number of evidences that chronic obstructive pulmonary disease (COPD) is a systemic illness and that bodyweight loss is its prominent manifestation. We focused on the nutritional outcomes to find out the effectiveness of acupuncture on nutritional state of COPD patients and on their prognosis in our previous interventional study. METHODS: The present study is re-analysis of our previous interventional study, COPD Acupuncture Trial (CAT) published in 2012. Data from CAT was re-analyzed in terms of nutritional status, inflammatory biomarkers, and prognostic index. Nutritional states were evaluated by the measurements of body weight, body composition, and muscle strength, and the nutritional hematological examination results (retinol-binding protein (RBP), prealbumin (PA), transferrin (Tf), and hemoglobin (Hb) in serum), and inflammation biomarkers such as carboxyhemoglobin (COHb), High sensitivity C-reactive protein (Hs-CRP), Tumor Necrosis Factor-alpha (TNF-α), Interleukin 6 (IL-6), and Serum Amyloid A (SAA) were measured. The BODE index was measured in terms of prognosis. These measurements were compared between the real acupuncture group (RAG) and the placebo acupuncture group (PAG). All data are presented as mean (SD) or mean (95% CI). The difference between baseline and final volumes was compared using analysis of covariance (ANCOVA). Moreover, correlations between nutritional hematological examination scores and inflammation biomarker parameters were assessed using Spearman's rank correlation coefficient. RESULTS: After 12 weeks, the change in body weight was significantly greater in the RAG compared with the PAG (mean [SD] difference from baseline: 2.5 [0.4] in RAG vs - 0.5 [1.4] in PAG; mean difference between the groups: 3.00, 95% CI, 2.00 to 4.00 with ANCOVA). Patients in RAG also had improvements in the results of nutritional hematological examination (RBP, PA, Tf, Hb), Inflammation biomarkers (TNF-α, IL-6, SAA, Hs-CRP, COHb) and the BODE index. CONCLUSION: This study demonstrated some clear evidences that acupuncture can be a useful adjunctive therapy to improve nutritional state of COPD patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry ( UMIN000001277 ). Retrospectively registered.

Vitamin D status is associated with muscle strength and quality of life in patients with COPD: a seasonal prospective observation study.

Background: Owing to hospitalization, reduced functional capacity and consequently, less sunlight exposure, suboptimal vitamin D status (25-hydroxyvitamin D [25(OH)D]⩽50 nmol/L) is prevalent among COPD patients. Objective: This study aimed to investigate seasonal changes in vitamin D status and any associated changes in fat-free mass (FFM), muscle strength and quality of life (QoL) in COPD patients. Patients and methods: COPD patients living in Northern Ireland (n=51) completed study visits at the end of winter (March/April) and at the end of summer (September/October), corresponding to the nadir and peak of vitamin D status, respectively. At both time points, serum concentration of 25(OH)D was quantified by liquid chromatography-tandem mass spectrometry, FFM (kg) was measured using bioelectrical impedance and muscle strength (kg) was measured using handgrip dynamometry. QoL was assessed using the validated St George's Respiratory Questionnaire. Results: Mean±SD 25(OH)D concentration was significantly higher at the end of summer compared to the end of winter (52.5±30.5 nmol/L vs 33.7±28.4 nmol/L, P<0.001); and house- bound patients had significantly lower 25(OH)D concentration compared to nonhousebound patients at the end of summer (42.9±4.2 vs 57.2±9.9 nmol/L; P⩽0.001). Muscle strength (at both time points) and QoL (end of summer only) were positively predicted by 25(OH)D concentration, independent of age, sex and smoking status. Conclusion: This study highlights the need for health policies to include a recommendation for year-round vitamin D supplementation in housebound COPD patients, and wintertime supplementation in nonhousebound patients, to maintain optimal 25(OH)D concentrations to protect musculoskeletal health. Furthermore, an optimal vitamin D status may have potential benefits for QoL in these patients.

A pilot data analysis of a metabolomic HPLC-MS/MS study of patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with multiple clinical faces. Metabolomic profiling studies small molecules present in biological samples by combined use of chromatography with mass spectrometry. OBJECTIVES: The goal of our work was to perform a high performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) metabolomic study to compare the concentrations of metabolites in COPD patients and in controls. MATERIAL AND METHODS: Participants were recruited at the University Hospital, Hradec Králové, Czech Republic, with the approval of the ethics committee. The analysis of blood samples was performed at Health Sciences Center (HSC) in Kuwait. The blood samples were analyzed for concentrations of acylcarnitines and amino acids by high performance liquid chromatography (Waters 2690 HPLC; Waters, Milford, USA) and a triple-quadruple tandem mass spectrometer (Quattro LC, Micromass, Manchester, United Kingdom). RESULTS: Groups of 10 subjects with COPD and 10 healthy controls were analyzed. Carnitine analysis showed that the free carnitine to acylcarnitine ratio (C0/AC ratio) was significantly lower in COPD (0.58 µM/L) compared to the controls (0.73 µM/L; p = 0.002). The mean C8/C2 ratio in the COPD group was significantly higher (0.03 µM/L) - in the control group it was 0 µM/L (p = 0.03). Amino acid analysis showed lower levels of phenylalanine in the COPD group (22.05 µM/L) compared to the controls (30.05 µM/L; p = 0.008). The alanine concentrations were significantly lower in the COPD group (173 µM/L) than in the control group (253 µM/L; p = 0.001). The pyroglutamate levels were higher in COPD (1.58 µM/L) than in the controls (1 µM/L; p = 0.040). CONCLUSIONS: The carnitine and acylcarnitine levels in COPD subjects in this study possibly indicate a predisposition to atherosclerosis as a result of inadequate ß-oxidation of fatty acids and show the presence of oxidative stress. Furthermore, the high sensitivity to changes in circulating amino acid levels may allow us to detect subclinical malnutrition and take early preventative interventions such as nutritional supplementation and patient education.

Effect of Oligomeric Proanthocyanidin on the Antioxidant Status and Lung Function of Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND/AIM: Evidence exists that oxidative stress and oxidative damage play a pivotal role in chronic obstructive pulmonary disease (COPD). Oligomeric proanthocyanidins (OPCs) extracted from grape seeds have been shown to exhibit antioxidant capabilities greater than those of vitamin C and E. The objective of this study was to evaluate the effects of OPCs on antioxidant status and lung function in patients with COPD. PATIENTS AND METHODS: Patients were supplemented with 150 mg/day OPC (n=13) orally or with a placebo (n=14) for 8 weeks in a randomized double-blind clinical design. Changes in anthropometric values, lung function, oxidative state, and lipid profiles were assessed after OPC or placebo treatment for 8 weeks. RESULTS: The results showed that OPC supplementation significantly reduced the concentration of malondialdehyde, superoxide dismutase, and total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio. The concentration of HDL-C significantly increased in the OPC-treated group. The plasma triglyceride, TC and low-density lipoprotein cholesterol values and the activities of catalase and glutathione peroxidase also decreased, but did not significantly differ between the OPC- and placebo-treated groups. Lung function was not significantly different between the two groups after 8 weeks. CONCLUSION: OPC supplementation was effective in increasing the antioxidant capacity, in addition to improving the lipid profiles in patients with COPD.

The relationship between Vitamin D status and exacerbation in COPD patients- a literature review.

OBJECTIVE: To investigate the relationship between Vitamin D and exacerbation in COPD patients. METHODS: The PubMed database was searched for articles published from 2012 onwards using search terms related to Vitamin D and exacerbation in COPD patients. Meta-analysis, clinical trials, observational studies, and human studies were included. Non-English articles or articles with full text unavailable were excluded; a total of 15 articles were selected. RESULTS: The association between exacerbation frequency and Vitamin D levels in observational studies remains controversial, however, meta-analysis revealed a negative association between serum Vitamin D and exacerbation. Also, two clinical trials showed that Vitamin D3 supplementation in COPD patients reduced the risk of moderate and severe exacerbation. Vitamin D binding protein (VDBP) polymorphisms seem to affect patient exacerbation susceptibility. CONCLUSIONS: Few studies in literature have data related to diet, 25-hydroxyVitamin D [25(OH)D] and polymorphism in COPD exacerbation. One clinical trial indicates Vitamin D supplementation plays a role in COPD patients with hypovitaminosis D in preventing exacerbations. Further studies are needed to elucidate the role of Vitamin D in this population and to establish the best marker for Vitamin D, which patient subgroups will benefit, and the best supplement dosage without leading to toxicity.

The effect of conjugated linoleic acid on oxidative stress and matrix metalloproteinases 2 and 9 in patients with COPD.

Background: Natural antioxidants in foods may be used in prevention and treatment of oxidative stress and inflammation in COPD. Therefore, this study aimed to evaluate the effect of conjugated linoleic acid (CLA) supplement as natural antioxidants on oxidative stress levels, and MMP2 and MMP9 serum levels in COPD patients. Materials and methods: This clinical trial study was conducted on 90 (supplement group=45 and control group=45) COPD patients in Ardabil city, Iran, in 2015. After obtaining written consent, general information was collected from each patient using a validated and reliable questionnaire. Supplement group received 3.2 g of CLA and those in the control group were given 3.2 g of placebo for 6 weeks on a daily basis. Fasting blood samples were taken from all of the patients for testing of malondialdehyde (MDA), MMP2, and MMP9 levels at the beginning and end of the study. Data were analyzed using Kolmogorov-Smirnov test, independent samples t-test, paired sample t-test, chi-square test, and ANOVA. Results: There were no significant differences between the two groups with regard to mean age, smoking status, and serum level of MDA at the beginning of the study. In the supplement group, the serum level of MDA decreased significantly at the end of the 6th week compared to that in the beginning of the study (p=0.0004), while in the placebo group, the difference was found to be insignificant. The serum level of MMP9 decreased significantly in the supplement group, while in the placebo group its level increased significantly as compared to that at the beginning of the study (p<0.05). The serum levels of MMP2 indicated no significant differences between the two groups neither at the beginning nor at the end of the study. Conclusion: These findings indicated that CLA supplementation may be helpful for COPD patients through inhibiting the production of oxidative stress and controlling MMP9 serum levels.