Elif Şen, Öznur Akkoca Yıldız, Sevgi Bartu Saryal Pulmonary Diseases Department

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Is there any effect of long-acting bronchodilators (tiotropium and

formoterol) on thoracic gas compression in COPD patients?

Elif Şen, Öznur Akkoca Yıldız, Sevgi Bartu Saryal

Pulmonary Diseases Department Faculty of Medicine, Ankara University

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Thoracic gas compression

During forced expiration, thoracic volume diminishes due to both exhaled air and compressed air.

During forced expiration, the changes of lung volumes are related with the volume of exhaled air and thoracic gas compression volume.

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Thoracic gas compression volume :

Alveolar pressure Respiratory muscle strength

Expiratory effort Hyperinflation

Airway resistance

The dynamic narrowing of the airways causeair trapping and related thoracic gas compression in patients with airflow obstruction during forced expiration.

Thoracic gas compression

volume

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Thoracic gas compression is measured with body plethysmograph during forced expiration.

FVC measured by plethysmograph (FVCp) measures changes in thoracic gas volume that include both compression and displacement of gas,whereas FVC measured at mouth (FVCm) reflects displacement alone, this is because the thoracic gas compression volume can be obtained.

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LV

MV

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Expiratory flow limitation and hyperinflation are the features of COPD.

Therefore, thoracic gas compression volume is higher in subjects with COPD than in normal subjects.

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Recently, the value of the parameters other than expiratory flow is being investigated in the evaluation of bronchodilator activity in COPD.

It may be beneficial to measure the thoracic gas compression volume changes related with the effects of long-acting bronchodilators both on the expiratory flow limitation and hyperinflation, as they are currently used agents in the treatment of COPD.

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Aim:

The aim of this study was to investigate the effects of long-acting bronchodilators (tiotropium and formoterol) on thoracic gas compression.

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Material - Method:

Stable COPD patients were included in the study.

COPD diagnosis was made according to GOLD criteria.

Stable COPD is defined as no acute exacerbation during the last month.

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In all patients, long-acting bronchodilators were discontinued 72 hours before and short-term bronchodilators 6 hours before the test.

In each subject, the test was performed with tiotropium at first.It was repeated 48 hours after the first test.

Measurements were performed by a pressure / flow plethysmograph (Autobox 6200, Sensormedics).

Maximal expiratory flow – volume curves were obtained by the plethysmograph with the door closed.

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The following parameters were measured during forced vital capacity manoeuvre before the study drug ( 0 min)

and

after the drug administration (30. min, 60. min, 120. min)

FEV1, FVC, FEV1/FVC, FEF 25-75

Thoracic gas compression volume :V comp 25, V comp 50,V comp 75 .

Mouth flow/mouth volume and mouth flow/lung volume values were plotted.

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Statistical analysis

Variance analysis, Friedman test were used in evaluating the effects of the study drugs on consecutive measurements. Bonferroni correction was made for p value (p<0,0125).Spearman test was used for the correlations between the parameters. Student’s t test was used for comparison of paired samples.

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Results28 male COPD patients

Mean age: 63,85 ± 9,23

Classification of severity according to GOLD criteria 2003 (n):

Stage 2: 8Stage 3: 10Stage 4: 9

Basal FEV1 mean: 1,19 ± 0,40 L (0,49 – 2,02)

FEV1 % predicted : 40,1 ± 13,79 (19 - 74)

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After tiotropium and formoterol ;

The consecutive measurements of absolute values of FVC, FEV1, FEF 25-75 in 30., 60., 120. minutes of tiotropium and formoterol were significantly increased from the baseline.

VAS score was decreased consecutively.

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mean FVC (L) mean FEV1 (L) meanFEF 25-75(L/s)

mean VAS score

Tiotropium 0 min 2,32±0,68 1,19 ±0,40 0,59 ±0,23 3,32 ± 1,46

Tiotropium 30 min 2,49 ±0,66 1,26 ±0,43 0,67 ±0,48 2,28 ± 1,32

Tiotropium 60 min 2,62 ±0,76 1,29 ±0,41 0,61 ±0,25 2,17 ± 1,30

Tiotropium 120 min 2,60 ±0,67 1,34 ±0,47 0,67 ±0,32 1,92 ± 1,33

Formoterol 0 min 2,33 ±0,75 1,19 ± 0,50 0,57 ±0,29 3,67 ± 1,58

Formoterol 30 min 2,71 ±0,74 1,39 ±0,54 0,67 ±0,32 2,10 ± 1,10

Formoterol 60 min 2,82 ±0,79 1,44 ±0,51 0,70 ±0,30 1,78 ± 1,13

Formoterol 120 min 2,68 ±0,73 1,41 ± 0,49 0,69 ±0,29 1,75 ± 1,14

Significant improvement in consecutive measurements of absolute values of FVC, FEV1, FEF 25-75, in 30., 60., 120. minutes after tiotropium and formoterol

Decrease in VAS scores

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Thoracic gas compression volume

No significant difference of V comp 25,50,75 in consecutive measurements for each of the two study drugs was shown in variance analysis.

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V comp 25 V comp 50 V comp 75

Tiotropium 0 min 0,59 ± 0,36 0,56 ± 0,36 0,39 ± 0,21

Tiotropium 30 min 0,61 ± 0,38 0,57 ± 0,35 0,36 ± 0,21

Tiotropium 60 min 0,63 ± 0,36 0,56 ± 0,28 0,42 ± 0,18

Tiotropium 120 min 0,59 ± 0,32 0,52 ± 0,27 0,39 ± 0,18

Formoterol 0 min 0,61 ± 0,31 0,56 ± 0,29 0,45 ± 0,19

Formoterol 30 min 0,59 ± 0,42 0,53 ± 0,29 0,40 ± 0,19

Formoterol 60 min 0,61 ± 0,37 0,53 ± 0,29 0,41 ± 0,21

Formoterol 120 min 0,53 ± 0,29 0,47 ± 0,26 0,36 ± 0,21

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MF/MV - MF/LV

There were significant differences between the parameters of MF /MV and MF /LV in basal measurement and at the end of the test (120.min).

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MF/MV MF/LV p

Tiotropium 0. min FEV1

1,19 ± 0,41 1,74 ± 0,57 0,000

Tiotropium 0. min FEF25-75

0,60 ± 0,23 2,05 ± 2,03 0,001

Formoterol 0. min FEV1

1,19 ± 0,50 1,80 ± 0,62 0,000

Formoterol 0.min FEF25-75

0,57 ± 0,29 2,87 ± 5,16 0,03

Tiortopium 120.min FEV1

1,34 ± 0,47 1,87 ± 0,51 0,000

Tiotropium 120.min FEF25-75

0,67 ± 0,32 1,88 ± 2,59 0,02

Formoterol 120.min FEV1

1,42 ± 0,50 2,02 ± 0,98 0,000

Formoterol 120.min FEF25-75

0,70 ± 0,29 1,47 ± 1,13 0,000

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There was no significant linear correlation between VAS scores and compression volumes.

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The comparison of each drug according to basal measurement

(0.min and 120.min ) :

There was a significant decrease in V comp 25 and 50 after formoterol between 0 min and 120. min.No significant change after tiotropium.

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0.minV comp 25

120.minV comp 25

p

Tiotropium 0,59 0,59 NS

Formoterol 0,62 0,53 0,040. min

V comp 50120.min

V comp 50p

Tiotropium 0,56 0,52 NS

Formoterol 0,56 0,47 0,04

0.minV comp 75

120.minV comp 75

p

Tiotropium 0,39 0,39 NS

Formoterol 0,45 0,36 NS

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Tiotropium and formoterol

FEV1, FVC, FEV1/FVC, FEF 25-75 values Thoracic gas compression volumes VAS scores showed no significant difference when we compared two drugs.

But there was a significant decrease in Vcomp 25 and 50 after formoterol between 0 min and 120. min.

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Discussion

The value of the parameters other than expiratory flow is being investigated in the evaluation of bronchodilator activity in COPD.

Dynamic narrowing of airways during a forced expiratory manoeuvre in the subjects with flow limitation may create air trapping and a consequent gas compression.

In conclusion, gas compression volume in these patients is increased.

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Long-acting bronchodilators may cause a decrease in thoracic gas compression because of their effect on expiratory flow limitation and hyperinflation.

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Long-acting bronchodilatorsNo significant decrease was detected in gas compression of COPD patients in this study.

A significant decrease in V comp 25 and 50 after formoterol between 0 min and 120. min

What will be the results of long-term use of tiotropium ?

Study group: 28 patients

Consecutive measurements ( 0.,30.,60.,120.min)

What will be the changes on the statistical significance after an increase in the number of the patients ?and

the effect on the results?

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Expiratory flow measurementAir trapping effectThoracic gas compression volume

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Conclusion

Long-acting bronchodilators effect the expiratory flow rates, but their effect on thoracic gas compression volume can not reach a significance in consecutive measurements. However, at the end of the test there is a significant decrease according to basal measurements for formoterol between two tests.

It is necessary to evaluate in a large number of patients.