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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 4  |  Page : 400-405

Sex difference in response to cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease


Department of Chest Diseases and Tuberculosis, Faculty of Medicine, Assiut University, Assiut, Egypt

Date of Submission03-Feb-2020
Date of Decision11-Feb-2020
Date of Acceptance23-Feb-2020
Date of Web Publication20-Nov-2020

Correspondence Address:
Aliaa S Ahmed
Demonstrator at Department of Chest Disease and Tuberculosis Assiut University, Assiut
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JCMRP.JCMRP_26_20

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  Abstract 


Background
Cardiopulmonary exercise testing is an important clinical tool to evaluate exercise capacity and to predict the outcome in patients with chronic obstructive pulmonary disease (COPD).
Aim
To evaluate exercise tolerance and pulmonary function in COPD patients in relation to sex.
Patients and methods
This prospective cross-sectional analytic study has been conducted in Assiut University Hospital, Chest Department from May, 2017 to January, 2019. Sixty patients with clinical and functional diagnosis of COPD were subjected to: baseline dyspnea assessment assessed by modified Medical Research Council and COPD assessment test, arterial blood gas analysis preexercise and postexercise, pulmonary function test, and cardiopulmonary exercise testing. The patients were divided into two groups: each group included 30 men and 30 women.
Results
There were no significant differences between both sexes in response to exercise with the exception of significantly higher oxygen consumption (VO2% predicted) in men (in men = 49.53 ± 9.08, in women = 44.83 ± 7.60, P = 0.03) and that women had significantly higher lactate threshold than men (lactate threshold = 55.46 ± 5.32 and 50.57 ± 7.74, respectively, P = 0.02). Female patients had significantly lower breathing reserve and significantly lower respiratory frequency (P < 0.001). Male patients had significantly lower heart ratemax, and significantly higher heart rate reserve than women (P < 0.001 and 0.04, respectively).
Conclusions
There were no significant differences between both sexes in response to exercise except that men with COPD had significantly higher oxygen consumption and exercise capacity (peak VO2) than women with COPD.

Keywords: cardiopulmonary exercise testing, chronic obstructive pulmonary disease, sex, peak VO2, pulmonary function test


How to cite this article:
Sayed SS, Mohamed-Hussein AA, Magdy DM, Ahmed AS. Sex difference in response to cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease. J Curr Med Res Pract 2020;5:400-5

How to cite this URL:
Sayed SS, Mohamed-Hussein AA, Magdy DM, Ahmed AS. Sex difference in response to cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease. J Curr Med Res Pract [serial online] 2020 [cited 2020 Dec 1];5:400-5. Available from: http://www.jcmrp.eg.net/text.asp?2020/5/4/400/301050




  Introduction Top


Cardiopulmonary exercise testing (CPET) is a methodology that has changed the approach to patients' functional evaluation, linking performance, and physiological parameters to the underlying metabolic substratum and providing exercise capacity descriptors, for example, peak oxygen uptake (peak VO2). An accurate assessment of the exercise capacity of patients with chronic obstructive pulmonary disease (COPD) is important for exercise prescription and for determining response to therapy. CPET is useful for determining the causes of exercise limitation and for assessing the maximal exercise capacity of patients with COPD[1].

For the most part, women and men who participate in exercise training have similar responses in cardiovascular, respiratory, and metabolic functions (providing that size and activity level are normalized). Relative increases in VO2 max are equivalent for women and men[2].

Several sex differences have been noted in acute response to exercise. At the same absolute rate of exercise, women have a higher heart rate response than men, primarily because of a lower stroke volume. This lower stroke volume is a function of smaller heart size and smaller blood volume[3].

CPET is clinically useful in the objective determination of exercise capacity (VO2 peak) and limitations[4]. Thus, the current study aims to assess sex difference in response to exercise in COPD patients.


  Patients and Methods Top


This prospective cross-sectional analytic study has been conducted in Assiut University Hospital, Chest Department, Cardiopulmonary Exercise Testing Unit and Pulmonary Function Unit from May, 2017 to January, 2019. The study protocol was approved by the Faculty of Ethics Committee, Assiut University and patients signed an informed consent (IRB no: 17100985).

Sixty patients (30 men and 30 women) fulfilling the clinical and functional diagnosis of stable COPD (at least 3 months without exacerbations) according to GOLD criteria[5] were enrolled into this study. All patients were subjected to the following: careful history taking, full clinical examination, arterial blood gas analysis preexercise and postexercise, pulmonary function test (PFT), and CPET.

Inclusion criteria

Stable COPD patients aged 40–70 years were included. All patients were with clinical features of COPD and associated spirometry compatible with the GOLD criteria. Patients were selected randomly in crossover 1: 1.

Exclusion criteria

Patients with primary cardiac diseases, orthopedic, or neurological conditions affecting the ability of exercise, patients with previous lung resection or malignancies, acute pulmonary embolism, acute exacerbation of COPD, and severe arterial hypertension were excluded.

Methods

  1. Medical history included:


    1. Name, age, sex, smoking history, and other comorbidities
    2. Assessment of baseline dyspnea based on the modified Medical Research Council (mMRC) dyspnea scale. An mMRC score more than or equal to 2 is included as threshold for separating less breathlessness from more breathlessness[5]
    3. COPD assessment test (CAT): eight self-reported questions to evaluate the health status in COPD patients[5]


  2. Resting pulmonary function:


  3. Spirometry (P/N Co9035–12–99; Cosmed SrL, Quark PFTs Ergo, Italy, Milano). including forced expiratory volume in the 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, maximal expiratory flow at 25–75% of FVC (MEF25–75), and maximal voluntary ventilation testing was performed in the pulmonary function lab. Results were expressed in liter and liter/second and as percent predicted

  4. Arterial blood gases analysis:


  5. Blood samples were taken from the radial artery at room air and were analyzed using a blood gas analyzer (Rapid lab 850; C hiron Diagnostics (Made in USA, Bedford), Critical Care Systems). Measurements including pH, arterial oxygen tension PaO2, arterial carbon dioxide tension PaCO2, and arterial oxygen saturation SaO2 were recorded. Arterial blood gases were done before and directly after CPET

  6. CPET


CPET was performed for all patients using a treadmill (Cosmed SrL, Quark PFTs ergo, P/N Co9035–12–99). We prepared an incremental treadmill exercise protocol in which the work rate increased at 1-min intervals. The unloaded VO2 was estimated from the patient's body weight[6].

The following parameters were recorded:

  1. Metabolic response: oxygen consumption VO2(ml/min), VO2(ml/kg/min), and anerobic threshold
  2. Ventilatory response: minute ventilation (VE), breathing reserve, tidal volume (VT), and respiratory frequency
  3. Cardiovascular response: heart rate (HR), oxygen pulse (VO2/HR), HR reserve, and systolic and diastolic blood pressure
  4. Gas exchange response: oxygen saturation (SpO2), ventilatory equivalent for VO2(VE/VO2), and ventilatory equivalent for VCO2(VE/VCO2).


All patients stopped the test due to dyspnea. No cardiovascular complications or primary cardiac reasons for termination were observed during the exercise test.

Statistical analysis

These nonparametric data were collected and were analyzed using the Statistical Package for the Social Sciences (version 20; IBM, Armonk, New York, USA). Continuous data were expressed in the form of mean ± SD or median (range) while nominal data were expressed in the form of frequency (percentage). c2 test was used to compare the nominal data of different groups in the study while Student's t test was used to compare the mean of two different groups and paired t test was used to compare data of the same group before and after exercise. Different correlations of continuous variables in the study were determined with Pearson's correlation. The level of confidence was kept at 95% and hence, the P value was significant if less than 0.05.


  Results Top


Sixty patients with COPD were recruited in this study, 30 (50%) patients were women and 30 (50%) were men.

Patient characteristics in [Table 1] shows that the male and female patients had insignificant differences as regards age, BMI, number of exacerbation and hospital admission, mMRC scale, and CAT assessment tool.
Table 1: Demographic and clinical data of chronic obstructive pulmonary disease patients in both sexes

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On comparison of gasometric parameters before and after exercise [Table 2] it was seen that there was significant decrease in pH, PaO2, and SaO2 and significant increase in PaCO2 and lactic acid after exercise with no significant difference between both sexes.
Table 2: Gasometric parameters of patients based on sex before and after exercise

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As regards PFT, male patients had significantly higher MEF50 in comparison to female patients with no significant difference in FEV1, FVC, FEV1/FVC, MEF75, and MEF25-75 as shown in [Table 3].
Table 3: Pulmonary function in chronic obstructive pulmonary disease patients in both sexes

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[Table 4] shows that VO2(% predicted) was significantly higher in male patients than female patients and that women had significantly higher lactate threshold (LT) than men. Also, female patients had significantly lower breathing reserve and respiratory frequency in comparison to male patients (P < 0.001). Regarding gas exchange response, there were no significant differences between male and female COPD patients. As regards cardiovascular response there was significant decrease in HRmax, and significant increase in HR reserve in men in comparison to female patients (P < 0.001 and 0.04, respectively).
Table 4: Cardiopulmonary exercise test parameters in chronic obstructive pulmonary disease patients in both sexes

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In male patients, it was seen from [Table 5] that FEV1(% predicted) had positive significant correlation with VO2(% predicted), VT (l), and VO2/HR. In female patients, it was noticed that FEV1 had positive significant correlation with VO2(% predicted), VE (min), VT (l), and VO2/HR and it had negative significant correlation with HR reserve.
Table 5: Correlation between forced expiratory volume in the 1 s (% pred.) and exercise parameters in the studied groups

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[Table 6] shows that CAT had positive significant correlation with petCO2(mmHg), and negative significant correlation with VT (l), VO2/HR, and petO2(mmHg). In male patients, CAT had negative significant correlation with VT (l). In female patients, CAT had negative significant correlation with VE (min), VT (l), and VO2/HR.
Table 6: Correlation between chronic obstructive pulmonary disease assessment test and exercise parameters in both groups

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  Discussion Top


Exercise intolerance is a common symptom in COPD, and reflects both cardiorespiratory status, and global disease severity and prognosis[7]. Evaluating exercise capacity allows monitoring of disease and response to intervention. Hence, the current study aimed to assess the difference in lung function and exercise performance and parameters in COPD patients in both sexes.

The main finding in the study was on comparing arterial blood gas, the values at rest and postexercise, the level of pH, PaO2, and SaO2 had decreased and PaCO2 and lactic acid increased significantly after exercise but with no difference in men and women (pH postexercise was significantly lower in women).

These results come in agreement with those of Dantzker and D'Alonzo[8] who examined the effect of low-level, steady-state exercise on pulmonary gas exchange in seven patients with severe COPD and pulmonary hypertension. They reported that exercise led to a significant fall in arterial PaO2 from 76 ± 10 to 63 ± 8 mmHg, a rise in arterial PaCO2 from 56 ± 6 to 62 ± 8 mmHg, and a fall in mixed venous PO2 from 38 ± 2 to 32 ± 2 mmHg. Thus, exercise on a bicycle ergometer resulted in PaO2 reduction and PaCO2 increment, and the authors concluded that exercise-induced hypoxemia in patients with COPD was the result of a fall in mixed venous PO2 and an insufficient increase in overall ventilation[8].

Wagner[9] suggested that patients with advanced COPD can exhibit almost any pattern of arterial blood gas changes from resting values, suggesting that an additional contributing factor to the hypoxemia of exercise is an inadequate ventilatory response, such that VE does not rise as much as does CO2 production or O2 uptake, causing arterial PCO2 to increase and the alveolar-arterial PO2 difference to fall.

Sex-specific differences in pulmonary function and exercise performance in normal individuals are recognized. We examined exercise performance in women and men, and the present study showed that in COPD patients both sexes had insignificant differences in exercise capacity represented at peak VO2(ml/min) and peak VO2(ml/kg/min). Men had significantly higher peak VO2% predicted than women (P = 0.03). This was aligned with Thirapatarapong et al.[10] who reported that men had significantly higher VO2% predicted than women (peak VO2% predicted for males 52 ± 18, for females 37 ± 13, and P < 0.001).

Pinto-Plata et al.[11] studied 453 consecutive patients with COPD stages 1–4. Incremental CPET and PFTs were performed. They showed that women had significantly higher VO2% predicted than men (mean VO2% predicted for males 65 ± 24 and for females 71 ± 21, P = 0.003). However, in the same study after adjustment for sex, age, height, and COPD severity, there was no difference in exercise capacity and VO2% predicted between women and men. This agrees with our finding. Also, after adjustment for weight, VO2(expressed in ml/kg/min) was significantly higher in men than women in all stages of COPD (P > 0.05 for all stages)[11].

As regards LT% predicted, the current study showed that women had significantly higher LT% predicted than men (LT% predicted for females 55.46 ± 5.32 and for males 50.57 ± 7.74). Similar results were reported by Pinto-Plata et al.[11] who found that LT% predicted was significantly higher in women (LT% predicted for females 55 ± 14, for males 48 ± 13 and P > 0.0001).

CPET is useful to measure the functional capacity in COPD patients by assessing the maximum oxygen uptake. Thus, it could be used as a good monitoring tool. In this study, we observed that FEV1(% predicted) had positive significant correlation with VO2(% predicted). These results are consistent with Hena et al.[12] who investigated 58 patients with stable COPD who performed the treadmill test using the Bruce protocol through CPET and categorized them into four groups based on the spirometric data following the GOLD guidelines. The authors observed a significant correlation (r = 0.47, P = 0.001) between FEV1% predicted and maximum oxygen uptake (VO2 max, ml/kg/min).

Limitations

  1. Limited number of patients due to frequent exacerbations in patients followed up in the department
  2. No follow-up of exercise testing after rehabilitation.



  Conclusion Top


The CPET is the gold-standard tool to evaluate dyspnea and exercise tolerance clinically in COPD. There were no significant differences between both sexes in response to exercise except that men with COPD had significantly higher oxygen consumption and exercise capacity (VO2 peak) than women with COPD; FEV1(% predicted) had positive significant correlation with most of ventilatory and gas exchange and it had negative significant correlation with HR reserve and mMRC scale. There were no significant differences between both sexes regarding PFT variables.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Ong KC, Ong YY. Cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease. Ann Acad Med Singapore 2000; 29:648–652.  Back to cited text no. 1
    
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Holloway JB, Baechle TR. Strength training for female athletes. Sport Med 1999; 9:216–228.  Back to cited text no. 2
    
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Gordon NF, Kohl HW, Pollock ML, Vaandrager H, Gibbons LW, Blair SN. Cardiovascular safety of maximal strength testing in healthy adults. Am J Cardiol 1995; 76:851–853.  Back to cited text no. 3
    
4.
Datta D, Normandin E, ZuWallack R. Cardiopulmonary exercise testing in the assessment of exertional dyspnea. Ann Thorac Med 2015; 10:77.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Singh D, Agusti A, Anzueto A, Barnes PJ, Bourbeau J, Celli BR, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019. Eur Respir J 2019; 53:5.  Back to cited text no. 5
    
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Wasserman K, Hansen JE, Sue DY, Stringer WW, Whipp BJ. Principles of exercise testing and interpretation: including pathophysiology and clinical applications. Med Sci Sports Exerc 2005; 37:1249.  Back to cited text no. 6
    
7.
Gerald LB, Sanderson B, Redden D, Bailey WC. Chronic obstructive pulmonary disease stage and 6-minute walk outcome. J Cardiopulm Rehabil Prev 2001; 21:296–299.  Back to cited text no. 7
    
8.
Dantzker DR, D'Alonzo GE. The effect of exercise on pulmonary gas exchange in patients with severe chronic obstructive pulmonary disease. Am Rev Respir Dis 1986; 134:1135–1139.  Back to cited text no. 8
    
9.
Wagner PD. Ventilation-perfusion matching during exercise. Chest 1992; 101:192S–198S.  Back to cited text no. 9
    
10.
Thirapatarapong W, Armstrong HF, Bartels MN. Comparison of cardiopulmonary exercise testing variables in COPD patients with and without coronary artery disease. Heart Lung 2014; 43:146–151.  Back to cited text no. 10
    
11.
Pinto-Plata VM, Celli-Cruz RA, Vassaux C, Torre-Bouscoulet L, Mendes A, Rassulo J, et al. Differences in cardiopulmonary exercise test results by American Thoracic Society/European Respiratory Society-Global Initiative for Chronic Obstructive Lung Disease stage categories and gender. Chest 2007; 132:1204–1211.  Back to cited text no. 11
    
12.
Hena K, Hasina A, Mohammad M, Mohammad M, Mohammad M, Rashidul H. Cardiopulmonary exercise test in evaluation of functional capacity in patients with chronic obstructive pulmonary disease. Respirology 2018; 13420–13452.  Back to cited text no. 12
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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