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COPD: Effectiveness of Therapies (2007-2008)

Citation:

Cerda B, Soto C, Albaladejo MD, Martinez P, Sanchez-Gascon F, Tomas-Barberan F, Espin JC.  Pomegranate juice supplementation in chronic obstructive pulmonary disease: a 5-week randomized, double-blind, placebo-controlled trial. European Journal of Clinical Nutrition 2006, 60:245-253.

PubMed ID: 16278692
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To conduct a randomized, double-blind, placebo-controlled trial to evaluate the effect of daily consumption of polyphenol-rich pomegranate juice (PJ) with high antioxidant activity for 5 weeks on the oxidative stress and clinical features of patients with stable COPD.
Inclusion Criteria:
  • Physician diagnosed COPD
  • No acute axacerbation of COPD during 8 weeks before the study
  • No home oxygen therapy required
Exclusion Criteria:
  • Asthma history
  • Positive prick test
  • Atopy
  • Vegetarian diet
  • Weight reducing dietary regimen
  • Alcoholism
  • Consumption of vitamin supplements or nutraceuticals
  • Diabetes
  • Other respiratory diseases
  • Hyperlipidemia
  • History of gastrointestinal disease
  • Any chronic disease besides COPD
Description of Study Protocol:

Recruitment

Volunteers solicited from patient population of the 'University Vergen de La Arrixaca Hospital'  in Murcia, Spain

Design

Randomized, double blind, placebo-controlled trial

Blinding used (if applicable)

Two randomized groups of 15 provided 400 ml beverages (pomegranate juice or synthetic orange flavored placebo) in equal type, opaque bottles that were indistinguishable to study volunteers and subjects; physicians and researchers blinded to beverages distributed

Intervention (if applicable)

Consumption of either 400 ml pomegranate juice or matched placebo for 5 weeks; Trolox Equivalent Antioxidant Capacity (TEAC) of PJ, 14 hematological and 18 serobiochemical blood parameters, respiratory function variables, bioavailability of  PJ polyphenols (plasma and urine) and urinary isoprostane were evaluated.

Statistical Analysis

Subject number requirement determination (Wonnacott and Wonnacott, 1990) for 95% confidence interval, ANOVA values expressed as mean + SD; (SPSS 11.0.1 Chicago IL, USA).

Data Collection Summary:

Timing of Measurements

 Baseline, and weekly times 5 weeks, AM: 

  • Respiratory function; Forced expiratory volume (FEV), forced vital capacity (FVC) and FEV/FVC
  • Serobiochemical, hematological and urinary 8-iso-PGF2alpha

Dependent Variables

  • respiratory function variables - FEV, FVC and FEV/FVC by vitalograph spirometer
  • serobiochemical; glucose, urea, creatinine, uric acid, total protein, albumin, total bilirubin, cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, alanine aminotransfease (ALT), aspartate aminotransferase (AST), ferritin; byautomated biochemical auto analyser (Roche HITACHI), lipoproteins by electrophoresis (Beckman)
  • hematological; red blood cell, hemoglobin, hematocrit, mean corpuscular volume mean corpuscular heme concentration, platelets, mean platelet volume, leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils by automated hematological analyser
  • urinary 8-iso-PGF2alpha  by immunoassay
  • clinical symptoms; COPD severity, dyspnea score (PaO2 and Pa CO2) by ABL 520 gas analyser, smoking, infections and inhalation therapy

Independent Variables

  • Consumption of either 400 ml pomegranate juice or matched placebo for 5 weeks
  • Controlled diet was followed for 2 weeks prior to trial in which berries, pomegranates, chocolates, nuts and wine were forbidden
  • Polyphenol and Trolox Equivalent Antioxidant Capacity (TEAC) by HPLC analysis

Control Variables

 

Description of Actual Data Sample:

Initial N: 30 men enrolled

Attrition (final N): 30; PJ group n=15, placebo group n=15

Age: PJ group 60.00 + 10.90; placebo group 63.40 + 8.90

Ethnicity: not mentioned

Other relevant demographics

Anthropometrics comparable distribution age, BMI, COPD severity, dyspnea score, smoking status, infections and respiratory therapy

Location: Murcia, Spain

 

Summary of Results:

Other Findings

COPD patients received 4 mmol/l TEAC daily and 140 mmol/l TEAC at the end of the 5 week trial.  Ingested polyphenols were not detected in plasma or urine.  Two EA derived metabolited conjugated with glucoronic acid were identified in plasma and urine.  No relation was found (p >0.05) between the metabolism of PJ polyphenols and age of patents , dyspena score, COPD stage, respiratory function or any other clinical manifestation associated to COPD.

There were no statistically significant differences in any of the serobiochemical or hematological parameters withn each group over the 5 week study.  There were no significant differences between baseline values of the two groups. 

Placebo effect was reported in that patients in both groups declared improvement in ability to carry out daily tasks.

Author Conclusion:
PJ supplementation adds no benefit to standard therapy in patients with stable COPD.  The understanding of the different bioavailability of dietary polyphenols is critical before claiming any antioxidant-related benefit.
Funding Source:
Reviewer Comments:
Small numbers in groups but the authors did determine the minimum number of subjects needed.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? No
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) No
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? No
  4.4. Were reasons for withdrawals similar across groups? ???
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? ???
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes