COPD Abstracts 1

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Randomised vitamin E supplementation and risk of chronic lung disease in the Women's Health Study.
            (Agler et al., 2011) Download
BACKGROUND:  The oxidant/antioxidant balance in lung tissue is hypothesised to contribute to the risk of chronic obstructive pulmonary disease (COPD). Observational studies consistently report higher antioxidant status associated with lower COPD risk, but few randomised studies have been reported. METHODS:  A post hoc analysis of 38,597 women without chronic lung disease at baseline was conducted in the Women's Health Study (WHS) to test the effect of vitamin E on the risk of incident chronic lung disease. The WHS is a randomised double-blind placebo-controlled factorial trial of vitamin E (600 IU every other day) and aspirin (100 mg every other day) in female health professionals aged≥45 years. Using Cox proportional hazards models, the effect of randomised vitamin E assignment on self-reported physician-diagnosed chronic lung disease was evaluated. RESULTS:  During 10 years of follow-up (376,710 person-years), 760 first occurrences of chronic lung disease were reported in the vitamin E arm compared with 846 in the placebo arm (HR 0.90; 95% CI 0.81 to 0.99; p=0.029). This 10% reduction in the risk of incident chronic lung disease was not modified by cigarette smoking, age, randomised aspirin assignment, multivitamin use or dietary vitamin E intake (minimum p for interaction=0.19). Current cigarette smoking was a strong predictor of chronic lung disease risk (HR 4.17; 95% CI 3.70 to 4.70; vs. never smokers). CONCLUSIONS:  In this large randomised trial, assignment to 600 IU vitamin E led to a 10% reduction in the risk of chronic lung disease in women.

Complementary usage of Rhodiola crenulata (L.) in chronic obstructive pulmonary disease patients: the effects on cytokines and T cells.
            (Chen et al., 2015) Download
Although chronic obstructive pulmonary disease (COPD) is an inflammatory disease predominantly involving T cells, no study of Rhodiola as an immunomodulator in COPD patients has been reported. In this study, COPD patients took Rhodiola crenulata 500 mg (n = 38) or placebo (starch/phosphate buffered saline) (n = 19) daily for 12 weeks and were compared with untreated, age-matched, and sex-matched non-COPD control subjects. Our results showed that serum levels of IL-2, IL-10, and IFN-γ in COPD patients before treatment are significantly higher than levels in non-COPD controls (p < 0.05). A significant decrease in IFN-γ was seen in the Rhodiola treatment group (p < 0.05) but not in the placebo group (p > 0.05). The results suggested that Rhodiola treatment had beneficial antiinflammation effects, lower COPD assessment test score and decreased high-sensitivity C-reactive protein, on COPD patients (p < 0.05). The effects of Rhodiola treatment on COPD patients were shown to decrease the IFN-γ concentration and CD8(+) count but increase the expressions of CD4(+) CD25(+) FOXP3(+) and CD4(+) CD25(+) CD45(+) FOXP3(+) in the blood significantly (p < 0.05). This is the first trial using Rhodiola as a complementary therapy for COPD patients. T cells play an important role in the pathogenesis of COPD through the increased expression of CD8(+) T cells and IFN-γ and may be a viable target for potential therapy.

Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation.
            (Dal Negro et al., 2012) Download
BACKGROUND:  Pulmonary Rehabilitation ("Rehabilitation") can improve both lung function and quality of life in patients suffering from chronic obstructive pulmonary disease (COPD) even if only a very small proportion of patients have access to Rehabilitation. Supplementation of Essential Amino Acids (EAAs) might allow COPD patients to achieve some typical Rehabilitation outcomes such as a better physical performance and an improved health status. METHODS:  88 COPD out-patients (GOLD class 3-4) with a body mass index (BMI) < 23 Kg/m2 were randomised to receive EAAs (n = 44) or placebo (n = 44) for twelve weeks. Primary outcome measures were changes in both physical activities in daily life (measured by Sense Wear Armband in terms of mean steps walked in one week) and in quality of life (measured by the St George's Respiratory Questionnaire, SGRQ). RESULTS:  After 12 weeks, the physical performance was significantly increased vs baseline only in patients who received EAAs (1140.33 +/- 524.69 and 638.68 +/- 662.1 steps/day, respectively; p = 0.02), being also the comparison vs the placebo group highly significant (p = 0.003). Similarly, the SGRQ score improved significantly only in EAA patients (69.35 +/- 9.51 vs baseline 72.04 +/- 8.62; p < 0.01), and changes were significantly different from those measured in the placebo group (p < 0.001). Furthermore, when compared to those who received placebo, EAAs patients significantly increased their fat-free mass (p = 0.04), muscle strength (p < 0.01), saturation of oxygen (p = 0.05), serum albumin (p < 0.001), and also ameliorated their original cognitive dysfunction (p = 0.02). CONCLUSIONS:  Oral supplementation with EAAs contribute to improve the daily-life performance in domiciliary severe COPD patients who can not enter any Rehabilitation programme, together with their quality of life; nutritional and cognitive status, and muscle strength.


 

Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study
            (de Matos Cavalcante et al., 2012) Download
Chronic obstructive pulmonary disease (COPD), a major cause of death and disability, is attributed to an abnormal inflammatory response by the lungs to noxious substances, primarily from cigarette smoke. Although oxidative stress is regarded as central to the pathogenesis of COPD, very few studies have examined the effects of antioxidants in this condition. This was a randomized, double-blind, placebo-controlled study on the effects of melatonin in COPD. Thirty-six consecutive patients with clinically stable moderate to very severe COPD (30 men; mean+/-S.D.=66.6+/-7.8yr) were randomized to receive 3mg melatonin (N=18) or placebo for 3 months. Oxidative stress was evaluated by 8-isoprostane levels in exhaled breath condensate at baseline (T0) and after one (T1), two (T2), and three months (T3) of treatment. Additionally, exhaled breath condensate levels of IL-8, dyspnea severity (Medical Research Council scale), lung function (spirometry), and functional exercise capacity (six min walk test) were compared at baseline and after treatment. Patients receiving melatonin showed a decrease in 8-isoprostane (T0: mean+/-S.E.M.=20.41+/-2.92pg/mL; T1: 18.56+/-2.68pg/mL; T2: 12.68+/-2.04pg/mL; T3: 12.70+/-2.18pg/mL; P=0.04; repeated measures ANOVA) with significant differences from baseline after 2 (P=0.03) and 3months (P=0.01). Dyspnea was improved by melatonin (P=0.01), despite no significant changes in lung function or exercise capacity. Placebo-treated patients, but not those who were given melatonin, showed an increase in IL-8 (P=0.03). In summary, melatonin administration reduced oxidative stress and improved dyspnea in COPD. Further studies are necessary to determine the potential role for melatonin in the long-term management of these patients.

High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.
            (Lehouck et al., 2012) Download
BACKGROUND:  Low serum 25-hydroxyvitamin D (25-[OH]D) levels have been associated with lower FEV(1), impaired immunologic control, and increased airway inflammation. Because many patients with chronic obstructive pulmonary disease (COPD) have vitamin D deficiency, effects of vitamin D supplementation may extend beyond preventing osteoporosis. OBJECTIVE:  To explore whether supplementation with high doses of vitamin D could reduce the incidence of COPD exacerbations. DESIGN:  Randomized, single-center, double-blind, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00666367) SETTING:  University Hospitals Leuven, Leuven, Belgium. PATIENTS:  182 patients with moderate to very severe COPD and a history of recent exacerbations. INTERVENTION:  100,000 IU of vitamin D supplementation or placebo every 4 weeks for 1 year. MEASUREMENTS:  The primary outcome was time to first exacerbation. Secondary outcomes were exacerbation rate, time to first hospitalization, time to second exacerbation, FEV(1), quality of life, and death. RESULTS:  Mean serum 25-(OH)D levels increased significantly in the vitamin D group compared with the placebo group (mean between-group difference, 30 ng/mL [95% CI, 27 to 33 ng/mL]; P < 0.001). The median time to first exacerbation did not significantly differ between the groups (hazard ratio, 1.1 [CI, 0.82 to 1.56]; P = 0.41), nor did exacerbation rates, FEV(1), hospitalization, quality of life, and death. However, a post hoc analysis in 30 participants with severe vitamin D deficiency (serum 25-[OH]D levels <10 ng/mL) at baseline showed a significant reduction in exacerbations in the vitamin D group (rate ratio, 0.57 [CI, 0.33 to 0.98]; P = 0.042). LIMITATION:  This was a single-center study with a small sample size. CONCLUSION:  High-dose vitamin D supplementation in a sample of patients with COPD did not reduce the incidence of exacerbations. In participants with severe vitamin D deficiency at baseline, supplementation may reduce exacerbations. PRIMARY FUNDING SOURCE:  Applied Biomedical Research Program, Agency for Innovation by Science and Technology (IWT-TBM).

Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial.
            (Martineau et al., 2015) Download
BACKGROUND:  Patients with chronic obstructive pulmonary disease (COPD) often have vitamin D deficiency, which is associated with increased susceptibility to upper respiratory infection-a major precipitant of exacerbation. Multicentre trials of vitamin D supplementation for prevention of exacerbation and upper respiratory infection in patients with COPD are lacking. We therefore investigated whether vitamin D3 (colecalciferol) supplementation would reduce the incidence of moderate or severe COPD exacerbations and upper respiratory infections. METHODS:  We did a randomised, double-blind, placebo-controlled trial of vitamin D3 supplementation in adults with COPD in 60 general practices and four Acute National Health Service Trust clinics in London, UK. Patients were allocated to receive six 2-monthly oral doses of 3 mg vitamin D3 or placebo over 1 year in a 1:1 ratio using computer-generated permuted block randomisation. Participants and study staff were masked to treatment assignment. Coprimary outcomes were time to first moderate or severe exacerbation and first upper respiratory infection. Analysis was by intention to treat. A prespecified subgroup analysis was done to assess whether effects of the intervention on the coprimary outcomes were modified by baseline vitamin D status. This trial is registered with ClinicalTrials.gov, number NCT00977873. FINDINGS:  240 patients were randomly allocated to the vitamin D3 group (n=122) and placebo group (n=118). Vitamin D3 compared with placebo did not affect time to first moderate or severe exacerbation (adjusted hazard ratio 0·86, 95% CI 0·60-1·24, p=0·42) or time to first upper respiratory infection (0·95, 0·69-1·31, p=0·75). Prespecified subgroup analysis showed that vitamin D3 was protective against moderate or severe exacerbation in participants with baseline serum 25-hydroxyvitamin D concentrations of less than 50 nmol/L (0·57, 0·35-0·92, p=0·021), but not in those with baseline 25-hydroxyvitamin D levels of at least 50 nmol/L (1·45, 0·81-2·62, p=0·21; p=0·021 for interaction between allocation and baseline serum 25-hydroxyvitamin D status). Baseline vitamin D status did not modify the effect of the intervention on risk of upper respiratory infection (pinteraction=0·41). INTERPRETATION:  Vitamin D3 supplementation protected against moderate or severe exacerbation, but not upper respiratory infection, in patients with COPD with baseline 25-hydroxyvitamin D levels of less than 50 nmol/L. Our findings suggest that correction of vitamin D deficiency in patients with COPD reduces the risk of moderate or severe exacerbation. FUNDING:  UK National Institute for Health Research.

Randomised, double-blind, placebo-controlled trial of EPs 7630 in adults with COPD.
            (Matthys et al., 2013) Download
BACKGROUND:  Preventing and managing exacerbations is one major component in COPD treatment. We investigated whether EPs 7630, a herbal drug preparation from the roots of Pelargonium sidoides, could prolong time to acute exacerbation in patients with COPD stage II/III. METHODS:  In this randomised, double-blind, placebo-controlled clinical trial, patients were randomly allocated to oral 24-week add-on therapy with 3 × 30 drops/day EPs 7630 (n = 99) or placebo (n = 101) to a standardised baseline-treatment. Primary endpoint was time to first exacerbation of COPD. Secondary endpoints were number of exacerbations, consumption of antibiotics, quality of life, patient satisfaction, inability to work, and tolerability. RESULTS:  Median time to exacerbation was significantly prolonged with EPs 7630 compared to placebo (57 versus 43 days, Kaplan-Maier-estimate; p = 0.005, one-sided centre-stratified log-rank test). The superiority of EPs 7630 was also confirmed in secondary endpoints, e.g., fewer exacerbations, less patients with antibiotic use, improved quality of life, higher patient satisfaction, and less days of inability to work. The incidence of minor gastrointestinal adverse events was higher in the EPs 7630 group. CONCLUSIONS:  The results demonstrate a statistically significant and clinically relevant superiority of add-on therapy with EPs 7630 over placebo and a good long-term tolerability in the treatment of moderate to severe COPD. EPs 7630 prolonged time to exacerbations and reduced exacerbation frequency and antibiotic use. Trial Registration No.: ISRCTN01681733.
EPs 7630 (Pelargonium sidoides)


 

Intravenous magnesium sulphate as an adjuvant therapy in acute exacerbations of chronic obstructive pulmonary disease: a single centre, randomised, double-blinded, parallel group, placebo-controlled trial: a pilot study.
            (Mukerji et al., 2015) Download
AIM:  To investigate the effects on lung function of IV magnesium in acute exacerbations of COPD (AECOPD), when given in conjunction with standard bronchodilator therapy. METHODS:  This was a pilot study to a randomised, double-blinded, placebo-controlled trial. 30 patients presenting to ED with AECOPD were included. In addition to standard bronchodilator therapy, 17 patients were given saline, and 13 received 2 g of magnesium sulphate intravenously. Spirometry was carried out at presentation (TA), after initial standard bronchodilator therapy (TB) and immediately (T0), at 60 minutes (T60) and 120 minutes (T120) after trial drug infusion. Primary outcomes were percentage change in FEV1 and FVC at T0, T60 and T120. Secondary outcomes were admission rates, length of stay and requirement for NIV or mechanical ventilation. Trial registration (ANZCTR), ACTRN12613000837729. RESULTS:  Greater improvements were seen in FEV1 at T0, T60 and T120 compared to TB in magnesium group (at T120, mean percentage change in FEV1 was 27.07% with magnesium versus 11.39% in the placebo group, 95%CI 3.7 to 27.7, p=0.01). Similar significantly greater improvements were noted with FVC in the magnesium group, compared to TB. CONCLUSIONS:  IV magnesium sulphate used as an adjunct therapy to standard bronchodilators in AECOPD presenting to ED may improve lung function in the short term.

 


References

Agler, AH, et al. (2011), ‘Randomised vitamin E supplementation and risk of chronic lung disease in the Women’s Health Study.’, Thorax, 66 (4), 320-25. PubMed: 21257986
Chen, SP, et al. (2015), ‘Complementary usage of Rhodiola crenulata (L.) in chronic obstructive pulmonary disease patients: the effects on cytokines and T cells.’, Phytother Res, 29 (4), 518-25. PubMed: 25403334
Dal Negro, RW, et al. (2012), ‘Essential amino acid supplementation in patients with severe COPD: a step towards home rehabilitation.’, Monaldi Arch Chest Dis, 77 (2), 67-75. PubMed: 23193843
de Matos Cavalcante, A. G., et al. (2012), ‘Melatonin reduces lung oxidative stress in patients with chronic obstructive pulmonary disease: a randomized, double-blind, placebo-controlled study’, J Pineal Res, 53 (3), 238-44. PubMed: 22507631
Lehouck, A, et al. (2012), ‘High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial.’, Ann Intern Med, 156 (2), 105-14. PubMed: 22250141
Martineau, AR, et al. (2015), ‘Vitamin D3 supplementation in patients with chronic obstructive pulmonary disease (ViDiCO): a multicentre, double-blind, randomised controlled trial.’, Lancet Respir Med, 3 (2), 120-30. PubMed: 25476069
Matthys, H, et al. (2013), ‘Randomised, double-blind, placebo-controlled trial of EPs 7630 in adults with COPD.’, Respir Med, 107 (5), 691-701. PubMed: 23478193
Mukerji, S, et al. (2015), ‘Intravenous magnesium sulphate as an adjuvant therapy in acute exacerbations of chronic obstructive pulmonary disease: a single centre, randomised, double-blinded, parallel group, placebo-controlled trial: a pilot study.’, N Z Med J, 128 (1425), 34-42. PubMed: 26905985