A total of 92 patients with COPD were included in the study, of which 13 (14%) had comorbid heart failure. 47 enrolled in group A (started with furosemide in 1st episode, followed by saline in 2nd episode), and 45 in group B (started with saline in 1st episode followed by furosemide in 2nd episode). Females represented 14% of the study participants, majority of them were COPD and enrolled in group B. The average age was 60.43 ± 8.7 years.
Table 1 divides study samples into groups A and B. Group A: started with adjunctive furosemide as 1st episode then saline in 2nd episode; group B started with saline in 1st episode, then furosemide in 2nd episode. The differences in variables between groups A and B were not statistically significant. Furthermore, the presence of heart failure was not significantly differed between group A and B. However, there was a significant difference between groups in smoking status (p = 0.015). Group A had a lower percentage of non-smokers (10.64%) compared to Group B (28.89%). The percentage of ex-smokers was higher in Group A (44.68%) versus Group B (20%). The proportion of current smokers was similar between groups, with 44.68% in Group A and 51.11% in Group B.
Table 1: Characteristics of patients with COPD (N=92) distributed by the type of adjuvants therapy.
variable
|
Gp A (N=47 )
|
Gp B (N=45)
|
test ( p)
|
Age (Mean±SD)
|
59.83±8.75
|
61.07±8.7
|
0.68 (0.498)a
|
Sex
|
|
|
|
female n(%)
|
3(6.38%)
|
10(22.22%)
|
3.538(0.08)b
|
male n(%)
|
44(93.62%)
|
35(77.78%)
|
|
BMI (Mean±SD)
|
24.12±5.65
|
26.22±7.29
|
1.54 (0.127) b
|
Smoking
|
|
|
|
no smoking n(%)
|
5(10.64%)
|
13(28.89%)
|
8.41(0.015*) b
|
ex-smoker n(%)
|
21(44.68%)
|
9(20%)
|
|
smoker n(%)
|
21(44.68%)
|
23(51.11%)
|
|
baseline mMRC
|
|
|
|
1
|
2(4.26%)
|
0(0%)
|
3.109(0.375) b
|
2
|
13(27.66%)
|
18(40%)
|
|
3
|
18(38.3%)
|
15(33.33%)
|
|
4
|
13(27.66%)
|
12(26.67%)
|
|
Comorbidity
|
|
|
|
No
|
35(65.96%)
|
29(64.44%)
|
0.653(0.419) b
|
DM
|
5(10.64%)
|
4(8.89%)
|
0(1) b
|
HTN
|
9(19.15%)
|
5(11.11%)
|
0.612(0.433) b
|
HF
|
6(12.77%)
|
7(15.56%)
|
0.007(0.933) b
|
Gp A: group A started with adjunctive furosemide as 1st episode then saline in 2nd episode, Gp B: group B started with saline in 1st episode, then furosemide in 2nd episode, a: t-test, b: Chi-square test, *p-value <0.05
Table 2 presents the effects of adjuvant treatment with saline and furosemide on key lung function parameters in COPD patients without heart failure. The authors found that compared to baseline, both saline and furosemide significantly improved FVC%, FEV1%, FEV1/FVC, PEF%, FEV25-75%, CAT score, and Borg score (all p < 0.001). Furthermore, furosemide resulted in significantly greater improvements in FVC%, FEV1%, FEV1/FVC, PEF%, FEV25-75%, CAT score, and Borg score compared to saline (all p < 0.001). No significant differences were observed in oxygen saturation between the three groups.
The pairwise comparisons also clarified furosemide significantly differed from saline in Borg scale.
Oxygen saturation did not change significantly with either treatment.
Table 2
Effects of adjuvant treatment with saline and furosemide on lung function parameters in COPD patients without heart failure (N = 79).
Lung function | baseline | Saline | furosemide | p |
FVC% | 61 ± 24.21* | 71 ± 24.95 | 73 ± 18.36 | <0.001 |
FEV1% | 40.66 ± 19.61*,** | 48.88 ± 24.73 | 50.02 ± 23.44 | < 0.001 |
FEV1/FVC | 52.63 ± 14.53* | 49.54 ± 11.84 | 54.52 ± 11.94 | <0.001 |
PEF% | 35.87 ± 19.92* | 38.03 ± 16.94 | 43.08 ± 17.88 | <0.001 |
FEV25-75% | 24.13 ± 10.27* | 28.21 ± 7.8 | 31.95 ± 12.43 | <0.001 |
CAT | 30.43 ± 6.79*,** | 20.21 ± 7.08 | 17.29 ± 7.69 | <0.001 |
Borg | 6.68 ± 1.76*,** | 5.87 ± 1.95*** | 4.37 ± 1.88 | <0.001 |
O2% | 95.73 ± 2.02 | 96.38 ± 1.94 | 96.84 ± 1.84 | 0.127 |
p: p-value of Repeated measure ANOVA test.
*: ]-wise comparison with significant differences between baseline and furosemide.
**: pair-wise comparison with significant differences between baseline and saline.
***: pair-wise comparison with significant differences between saline and furosemide.
Table 3 presents the effects of adjuvant saline and furosemide on lung function in COPD patients with heart failure. The Friedman test showed significant differences between the three groups for all parameters except Borg scale and oxygen saturation. According to the pairwise comparisons, furosemide significantly improved FEV25-75% and CAT score compared to baseline (both p < 0.001). No other significant pairwise differences were observed.
Table 3
Effects of adjuvant treatment with saline and furosemide on lung function parameters in COPD patients with heart failure (N = 13).
Lung function | baseline | Saline | furosemide | p |
FVC% | 53(30–96) | 65(35–88) | 61(45–85) | < 0.001 |
FEV1% | 27(17–75) | 32(21–79) | 33(17–82) | < 0.001 |
FEV1/FVC | 38.8(30.73–69.9) | 41.71(26–77) | 49.1(29.66–74.5) | < 0.001 |
PEF% | 30(15–71) | 26(19–76) | 33(17–78) | < 0.001 |
FEV25-75% | 15(6–80)* | 16(7–77) | 22(7–86) | < 0.001 |
CAT | 31.77 ± 6.06* | 24.92 ± 5.63 | 20.54 ± 6.94 | < 0.001a |
Borg | 6(3–8) | 5(3–7) | 2(4–6) | 0.109 |
O2% | 94.5(87–97) | 95(93–99) | 98(94–99) | 0.661 |
p: p-value for Friedman test.
*: pair-wise comparison with significant differences between baseline and furosemide.
a: p-value of Repeated measure ANOVA test.
Table 4 demonstrates a comparison between group A and B in the 1st and 2nd episodes (Δ1 and Δ2) across different lung function parameters. This between-drug effect comparison in Table 3 showed no statistically significant differences in either Δ1 or Δ2 for both episodes on the primary lung parameters FEV1% and FEV1/FVC between the two groups.
There was a statistically significant difference in Δ1 between group A and group B on FVC%. Starting with nebulized furosemide increased the baseline FVC% by 11.5 ± 6.2 compared to 5.24 ± 1.92 when starting with nebulized saline.
The short airway lung parameters (PEF% and FEV25-75%) along with CAT and Borg scores showed no statistically significant difference in Δ1 between groups A and B. However, a statistically significant difference appeared in Δ2 between groups, revealing a cumulative, delaying, or sequence effect of nebulization.
Table 4
A comparison between group A and B in 1st and 2nd episodes (Δ1 and Δ2) as regard different lung function parameters.
Lung Function | Effect of: | Gp A (n = 47) Mean ± SD | Gp B (n = 45) Mean ± SD | p |
FVC% | 1st episode (Δ1) | 11.5 ± 6.2 | 5.24 ± 1.92 | 0.012* |
| 2nd episode(Δ2) | 6.4 ± 3.1 | 7.24 ± 3.35 | 0.769 |
FEV1% | 1st episode (Δ1) | 8.83 ± 4.64 | 7.96 ± 3.85 | 0.59 |
| 2nd episode(Δ2) | 8.04 ± 5.34 | 10.71 ± 5.82 | 0.208 |
FEV1/FVC | 1st episode (Δ1) | 2.26 ± 1.8 | 1.86 ± 1.19 | 0.781 |
| 2nd episode(Δ2) | 2.92 ± 1.76 | 4.42 ± 2.01 | 0.364 |
PEF % | 1st episode (Δ1) | 4.86 ± 2.09 | 5.87 ± 3.45 | 0.687 |
| 2nd episode(Δ2) | 1.15 ± 0.91 | 10.91 ± 4.74 | <0.001 |
FEV25-75% | 1st episode (Δ1) | 7.85 ± 3.53 | 3.14 ± 1.02 | 0.161 |
| 2nd episode(Δ2) | 4.66 ± 2.27 | 14.02 ± 6.72 | 0.013* |
CAT | 1st episode (Δ1) | -9.51 ± 6.34 | -7.58 ± 4.61 | 0.097 |
| 2nd episode(Δ2) | -8.02 ± 6.71 | -10.89 ± 4.92 | 0.021* |
Borg | 1st episode (Δ1) | -1.45 ± 0.95 | -1.51 ± 0.79 | 0.869 |
| 2nd episode(Δ2) | -0.94 ± 0.77 | -2.38 ± 1.04 | 0.001* |
Gp A started with furosemide after conventional therapy, followed by saline after conventional therapy, hence Δ1 for group A = furosemide and conventional therapy – baseline., Δ2 for group A = saline and conventional therapy – baseline.
Gp B started with saline after conventional therapy, followed by furosemide after conventional therapy, hence Δ1 for group B = saline and conventional therapy – baseline., Δ2 for group B = furosemide and conventional therapy – baseline.
p: p-value for independent t test.
*p < 0.05.
GEE model for the effect of pack year index, nebulizer types, and cardiovascular disease on main lung parameters.
The study encompassed a total of 92 patients and employed a robust statistical approach, the Generalized Estimating Equations (GEE) model, to discern the influence of variables such as pack-year index, types of nebulizers used, and the presence of heart failute disease on key pulmonary parameters. We now present a detailed interpretation of the GEE model outcomes appeared in Table 4.
For FVC% GEE model:
As the GEE Table 4 and Fig. 2 show there is a significant enhancement of FVC% response when adding furosemide to Combivent by 9.42% (3.26,15.59) in comparison to 5.83% (0.06,11.61) enhancement if we add nebulized saline to ipratropium-salbutamol. FVC% will decrease significantly by 10% (-15.69, -5.44) for HF patients. As the pack year smoking index increases, FVC% will decrease to 0.16% (-0.19,-0.1). weighted R square for the model = 0.871.
For FEV1% GEE model:
Nebulized Furosemide increases FEV1 by 9.75% whereas saline increases it by 8%. The CI is (4.09,15.41) and (2.26,13.74), respectively.
HF patients' FEV1% will decrease by 12.41%, the 95% CI is (-18.98, -5.84). Figure 3 summarizes the FEV1%model.
As the pack year index increases FEV1 decreases by 0.16% with 95% CI (-0.21,-0.12).
The weighted R2 square = 0.841, according to Table 3.
The ratio of FEV1/FVC significantly increases if we use nebulized furosemide by and by 3.32 with 95% CI (0.06,6.58), but it’s not statistically significant if we use nebulized saline.
It has been found that BMI increases the ratio of FEV1/FVC by 0.67 with 95% CI (0.46,0.89).
Cardiovascular disease patients have lower FEV1/FVC by 8.49 with 95% CI (-12.87, -4.1).
Increases in smoking pack year index decrease FEV1/FVC ratio by 0.10 with 95% CI (-0.13, -0.07). Figure 4 shows the effect of pack year index and HF on FEV1/FVC separated by the nebulizer types.
The model weighted R square = 0.856, according to Table 4.
Table 4
Predictors for different respiratory function tests presented for 92 patients with COPD using GEE model.
Lung function | predictors | Estimates | SE | CI | p | WR2 |
FVC% | | | | | | 0.871 |
| (Intercept) | 71.81 | 2.88 | (66.16,77.46) | < 0.001* | |
| Adjuvant therapyR1: | | | | | |
| Saline | 5.83 | 2.94 | (0.06,11.61) | 0.048* | |
| Furosemide | 9.42 | 3.15 | (3.26,15.59) | 0.003* | |
| Pack index | -0.14 | 0.02 | (-0.19,-0.1) | < 0.001* | |
| Heart FailureR2: (yes) | -10.56 | 2.61 | (-15.69,-5.44) | < 0.001* | |
FEV1% | | | | | | 0.841 |
| (Intercept) | 52.14 | 2.36 | (47.52,56.76) | < 0.001* | |
| Adjuvant therapyR1: | | | | | |
| Saline | 8.00 | 2.93 | (2.26,13.74) | 0.006* | |
| Furosemide | 9.75 | 2.89 | (4.09,15.41) | < 0.001* | |
| Pack index | -0.16 | 0.02 | (-0.21,-0.12) | < 0.001* | |
| Heart FailureR2: (yes) | -12.41 | 3.35 | (-18.98,-5.84) | < 0.001* | |
FEV1/FVC | | | | | | |
| (Intercept) | 39.98 | 3.15 | (33.81,46.15) | < 0.001* | 0.751 |
| Adjuvant therapyR1: | | | | | |
| Saline | 2.40 | 1.70 | (-0.94,5.74) | 0.16 | |
| Furosemide | 3.32 | 1.66 | (0.06,6.58) | 0.045* | |
| Pack index | -0.10 | 0.02 | (-0.13,-0.07) | < 0.001* | |
| Heart FailureR2: (yes) | -8.49 | 2.24 | (-12.87,-4.1) | < 0.001* | |
| BMI | 0.67 | 0.11 | (0.46,0.89) | < 0.001* | |
WR2: Weighted R square.
R1: Reference is baseline (no therapy), R2: Reference is no Heart failure, *p-value < 0.05.