Point-by-point response to Reviewer’s comments
Reviewer 1
We thank the reviewer for his criticisms and suggestions.
1. The authors should elaborate on the novelty of their work…
R: As we stated in the discussion section, our results confirm and extend those of
previous reports (Ora J et al Am J Respir Crit Care Med. 2009;180:964; Ora J et al. J
Appl Physiol 2011; 111:10). In our study, we also provided the first evidence that
obese COPD patients, compared to normal weight COPD patients had a greater
amount of lean body mass, which together with lung hyperinflation was a
determinant factor of maximal exercise capacity in all patients. Therefore, both
pulmonary and non-pulmonary factors may explain the preservation of exercise
tolerance in patients with combined COPD and obesity (page 15, lines 10-16).
2. Have the authors considered stratifying groups according to FFM?
R: When all patients were categorized into two groups according to the median
value of FFM (42 kg in females and 54 kg in males), patients with a FFM value higher
than that of the median showed higher values in peak workload (99 watt ± 36 vs 74
watt ± 25, p < 0.05), peak VO2 (1438 ml/min ± 483 vs 1141 ml/min ±342; p < 0.05)
and in IC/TLC at rest (0.28 ± 0.09 vs 0.39 ± 0.07; p < 0.01) (page 13, lines 4-8).
3. … exercise test between 8-12 minutes but this can make it difficult to compare
groups if the work rate increments are different between groups
R: In our study, NW and OB patients did not differ in work rate increments during
CPET, being 8.5 watts ± 2.5 vs 8.9 ± 2.9 (page 11, lines 20-22).
4. Comparisons at submaximal work rates are often much more informative…
R: We agree with the Reviewer that physiological and sensory comparisons at
submaximal work rates may be more informative than at peak of exercise.
Unfortunately, we did not measure any exercise variable at submaximal work,
except for the oxygen uptake at the anaerobic threshold.
5. Why did the authors choose IC/TLC rather than FRC or RV…
R: In the revised version of the manuscript we reported the FRC and RV values of
NW and OB patients (page 11 lines 14-17, figure 1 and table 1). As expected, FRC
values were significantly higher in NW than OB patients.
6. … hydratation status. How was this controlled? … discussing the limitations of
bioelectrical impedance…
R: We are aware of the limitations of the bioelectrical impedance in the
measurement of FFM. Notably, it is well known its sensitivity to the hydration status.
In our study, all patients underwent routine blood and urine analysis as an initial
screening prior to the rehabilitation program (page 5, lines 5-6). Thus, we could
assess their hydration status by means of the urinalysis, including the urine specific
gravity. All patients showed the urinalysis in the normal range. We discussed this
limitation in the revised version of the manuscript (page 16, line 23, and page 17,
lines 1-3).
7. …data on body fat distribution
R: Unfortunately, our analyzer did not allow us to assess the body fat distribution.
However, in both men and women with obesity the decrease in end-expiratory lung
volume appears to be related to the cumulative effect of increased chest wall fat
rather than to any specific regional chest wall fat distribution (Babb et al Chest
2008, ref # 13). We discussed this limitation in the revised version of the manuscript
(page 17, lines 1-6).
8. Where all tests performed prior to rehabilitation?
R: All exercise tests were performed prior to the rehabilitation program (page 7, line
5)
9. …careful review of the manuscript from a native English speaking colleague.
R: The manuscript was carefully reviewed by a native English speaker
Reviewer 2
We thank the reviewer for his criticisms and suggestions.
1. The main potential original point is the association with greater exercise capacity
and FFM… Please clarify if these correlations hold significant if peak VO2%
predicted is used…it is rather difficult to tease out the contributors of exercise
tolerance in obese subjects by correlation analysis in cross-sectional studies.
R: We absolutely agree with the Reviewer on the value of the correlations between
FFM and peak VO2% predicted. However, the problem is the right choice of the
predicted values, mainly for obese women. Lorenzo and Babb (Chest 2012;
141:1031) specifically addressed their retrospective study to assess and quantify the
cardiorespiratory fitness in normal weight and obese individuals by means of three
currently suggested equations (Wasserman et al, Glaser et al and Riddle et al) for
predicting VO2 peak. Based on their results, they concluded that there was a great
variability between the prediction equations in the women and that a better
prediction equation for obese and non obese women is required. In line with the
Lorenzo & Babb’ results, in our obese and normal weight women with COPD we
found a significant difference, when we compared the peak VO2 values, expressed
as percent of predicted according to Wasserman et al (67% ± 22), Riddle et al (82%
± 26) and Jones equations (92% ± 28) (p<0.05 by ANOVA), respectively. Therefore,
all that remains is to use the absolute value. This is probably the reason why other
studies on exercise capacity and obesity in COPD patients (Ora J et al Am J Respir
Crit Care Med. 2009;180:964; Ora J et al. J Appl Physiol 2011; 111:10) have previously
used only the absolute value to express the peak VO2.
In any case, in the revised version of the manuscript we acknowledge that our study
is a cross-sectional study, and therefore, on the basis of our results we can only infer
and not establish the contributors of exercise tolerance in obese patients with
COPD. Accordingly, we reckon that a further longitudinal study on exercise
tolerance in obese patients, who change their weight and body composition over
time, is needed (page 17, lines 5-9).
2. Does the number of patients with leg fatigue as the contributing/limiting changes
according to the patients’ group?
R: When patients were asked to name the predominant symptom limiting exercise
test, 13 OB and 10 NW named exertion dyspnea, 6 OB and 8 NW named leg fatigue,
whereas 3 OB and 4 NW named both symptoms (page 11, lines 18-21). No
difference was found between the two groups.
3. Some of the data could be better explored in figures…
R: We added a figure showing the differences in lung volumes (Figure 1 of the
revised manuscript).