• Increase Font Size
  • Decrease Font Size
  • View as PDF

COPD: Effectiveness of Therapies (2007-2008)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine the prognostic significance of body weight changes in patients with COPD.
Inclusion Criteria:
  • COPD according to American Thoracic Society guidelines
  • FEV1 < 70% predicted with an increase in FEV1 < 15% of the predicted value after administration of a bronchodilating agonist (400 ug salbutamol)

Additional criteria for RCT:

  • BMI > 29
Exclusion Criteria:
  • Unstable disease
  • Malignancies
  • IDDM
  • Thyroid or cardiovascular disease
  • None had received nutritional therapy prior to or during the rehabilitation period
Description of Study Protocol:

Recruitment

RCT:  203 patients studied during January 1, 1988 and January 1, 1992

Retrospective Cohort:  Data collected from COPD patients admitted to a pulmonary rehab center between January 1, 1986 and January 1, 1990.

Design:  Randomized Controlled Trial / Retrospective Cohort

Randomized Controlled Trial:  Post hoc analysis of 203 patients with COPD

Retrospective Cohort:  400 patients with COPD, none had received nutritional therapy

Blinding used (if applicable):  not possible 

Intervention (if applicable)

  • In RCT, the physiologic effects of nutritional therapy alone (n=71) or in combination with anabolic steroid treatment (n=67) after 8 weeks in depleted and nondepleted subjects
  • Nutritional therapy consisted of daily high caloric liquid supplement (420 kcal/200 ml, 51% fat, 35% carbohydrate, 14% protein)
  • Anabolic steroid treatment consisted of 4 intramuscular injections with nandrolone decanoate (men: 50 mg, women: 25 mg)
  • Placebo group received intramuscular injections with arachis oil

Statistical Analysis

Univariate analysis of survival was performed using Kaplan-Meier method.  Log-rank chi-square test for comparing survival between groups was used to analyze the association of clinical characteristics at entry with survival.  Cox proportional hazards model was used to quantify the relationship between baseline variables of age, sex, spirometry, arterial blood gases, BMI, smoking, and subsequent overall mortality.

Data Collection Summary:

Timing of Measurements

At baseline and after 8 weeks of treatment.

Dependent Variables

  • Survival and mortality assessed as overall mortality
  • FEV1 and inspiratory vital capacity measured with wet spirometer
  • Arterial blood gases analyzed on blood gas analyzer
  • Body height, weight, BMI
  • Respiratory muscle strength measured as mouth pressure during maximal static inspiratory maneuvers
  • Exercise performance measured with a 12-minute walk 100 m long

Independent Variables

  • Nutritional therapy alone (n=71) or in combination with anabolic steroid treatment (n=67) after 8 weeks in depleted and nondepleted subjects
  • Weight gain
  • Improvement of maximal inspiratory mouth pressure

Control Variables

  • Age
  • Sex
  • Lung function
  • Recent weight loss
  • Smoking
Description of Actual Data Sample:

Initial N: 203 subjects in RCT, 400 in retrospective cohort (72% male)

Attrition (final N):  203 in RCT, 400 in cohort

Age:  65 +/- 0.6 years in RCT, 65 +/- 0.5 years in cohort

Ethnicity: not mentioned

Other relevant demographics:

Anthropometrics:  No differences in age, IVC, and resting arterial blood gas determinations seen between classes.

Location:  The Netherlands

 

Summary of Results:

Multivariate Analysis of Predictors of Mortality:  Prospective Study

Variables RR

95% Confidence Interval

P Value
Change in Weight 0.996 0.992 - 0.999 0.01

Change in Pimax

0.990

0.976 - 1.004

NS
Treatment, P vs A 0.753 0.447 - 1.267 NS
Treatment, N vs A 0.872 0.530 - 1.432 NS
BMI 0.868 0.803 - 0.939 <0.001
FEV1 0.983 0.962 - 1.003 NS
IVC 0.995 0.982 - 1.008 NS
PaO2 0.877 0.751 - 1.024 NS
PaCO2 0.977 0.707 - 1.352 NS

Age, years

1.056

1.022 - 1.090

<0.001

Other Findings

In the retrospective cohort:

Low BMI (P < 0.001), age (P < 0.0001) and low PaO2 (P < 0.05) were significant independent predictors of increased mortality.

Survival was significantly decreased in both underweight and normal weight patients as compared with overweight and obese patients (P < 0.0001).

After stratification of the group into BMI quintiles a threshold value of 25 kg/m2 was identified below which the mortality risk was clearly increased.

In the RCT:

Nutritional intervention resulted in a significant increase in weight, fat-free mass, and fat mass, whereas no significant changes in any of these parameters was seen in the placebo group.

Weight gain (>2 kg/8 weeks) in depleted and nondepleted patients with COPD, as well as increase in maximal inspiratory mouth pressure during the 8-week treatment, were significant predictors of survival.

On Cox regression analysis, weight change entered as a time-dependent covariate remained an independent predictor of mortality in addition to all variables that were entered in the retrospective study.

On multivariate analysis weight gain in depleted and non-depleted patients with COPD was an independent predictor of survival in addition to BMI and age.

 

Author Conclusion:
In conclusion, the present survival analyses provide further evidence to support the hypothesis that body weight has an independent effect on survival in COPD.  Moreover, the negative effect of low body weight can be reversed by appropriate therapy.
Funding Source:
Reviewer Comments:
Combination of 2 studies.
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? Yes
  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) Yes
  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? Yes
  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? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  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%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  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? No
  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? Yes
  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? Yes
  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? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  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? Yes
  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)? N/A
  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? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
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