Biomedical Research

Abstract

Smoking is a major risk factor in COPD [Chronic Obstructive Pulmonary Disease]. It contributes to inflammation and oxidative stress which are implicated in hyperlipidemia and lung function decline. Exercise may result in anti-inflammatory effects which limit smoking induced changes in COPD. The aim of the present study was to evaluate the oxidant antioxidant imbalance and lipid profile in exercising and non-exercising COPD groups and included 50 patients in each group. The results indicated that the lung functions were significantly reduced in those not doing exercise. The serum levels of antioxidant enzymes (SOD, Catalase and GPX) were significantly lower in non exercising group as compared to exercising group(p<0.001) while the levels of MDA (Malondialdehyde) were significantly higher in the same group(p<0.001).The levels of HDL(p<0.001) were significantly higher and VLDL(p=0.03) were significantly lower in exercising group as compared to non exercising group. The present study indicates that exercise has beneficial role in COPD and reduces Oxidant Anti Oxidant imbalance and improves lipid profile and it may be due to antiinflammatory effects of exercise.

Keywords

COPD, exercising, non-exercising, smokers, Oxidant Anti-Oxidant, lung functions, lipid profile, inflammation

Introduction

WHO recognizes that chronic obstructive pulmonary disease (COPD), carries much importance in matters of public health [1]. Smoking is a major risk factor and smoking is known to have hyperlipidemic effects [2,3]. Oxidative stress is implicated in COPD which initiate inflammatory responses in the lungs [4]. COPD results in reduction in physical activity and poor quality of life. Exercise training increases aerobic power, increase lactate threshold, improves acid buffering and improves quality of life and provides a feeling of self belief and wellbeing in COPD patients. Exercise is included in pulmonary rehabilitation in COPD [5,6]. Various researches worldwide have suggested that symptom limited interval training and strength training increases exercise capacity for COPD patients, moreover exercise in moderation is shown to improve lipid profile and antioxidant defenses in smokers [7] thus present study was undertaken to evaluate Oxidant Anti- Oxidant imbalance and lipid profile in those COPD patients following self-exercise regime.

Materials and Methods

The present study was undertaken in the Departments of Physiology, Biochemistry and TB and Respiratory Diseases and included 100 newly diagnosed patients of COPD selected from OPD of TB and Respiratory Diseases, JNMC, AMU , Aligarh. The study period was between January to April 2010. Institutional Ethical Committee clearance was obtained. Subjects were then divided into two groups of fifty each (those doing exercise and those who don’t do any type of exercise) on the basis of history of atleast thirty minutes exercise per day regularly for atleast past three months. Subjects doing any type of exercise prescribed or recommended by a Physician were excluded i.e. exercising group included strictly those who were following their self regime of exercise like walking or jogging etc.

Inclusion and Exclusion Criteria: Only newly diagnosed cases of COPD (selected from among those attending TB and Respiratory Diseases OPD) having history of smoking and willingness to participate were included in the present study. Subjects suffering from Hypertension, Bronchial Asthma, Diabetes or any illness other than COPD in which Oxidant Anti Oxidant imbalance is implicated in the cause were excluded. Those taking Anti - Oxidants and Anti-Hyperlipidemic medications were excluded from the study.

The lung functions were done using Mir Spirolab II spirometer and the patients with COPD were selected according to the guidelines of GOLD [8]. With prior consent and aseptic precautions 8 ml of venous blood was drawn from peripheral vein of the subjects after overnight fasting. Estimation of antioxidant enzymes namely Catalase (units/mgm of serum proteins) was done by the method of Aebi [9], Glutathione Peroxidase(nmol NADPH oxidized/min/mgm of serum proteins) by the method of Paglia and Valentine [10],Superoxide Dismutase( units/mgm of Serum Proteins) by method of McCord and Fridovich [11] respectively. MDA(nmol/ml) an indirect measure of free radical activity was estimated according to the method of Philpot [12]. Protein was estimated using Lowry method [13]. Lipid profile namely Total cholesterol( TC), Triglycerides (TG) and HDL(high density lipoprotein) were estimated using commercially available kits ; LDL(low density lipoprotein) was estimated applying Friedwald formula [14]. VLDL (very low density lipoprotein) cholestrol was estimated by formula Triglycerides/5.

Statistical analysis: The data obtained was statistically analyzed using SPSS 17.0(Statistical Package for Social Sciences). The comparison of lung functions, oxidant anti- oxidants and lipid profile parameters between exercising and non exercising COPD group was done using student’s t test. P value of less than 0.05 was taken to be statistically significant.

Results and Observations: 100 male Subjects having COPD with history of smoking were selected and grouped into exercising and non-exercising groups. The mean age of former group was 39.78±7.65 while that of latter group was 40.19±9.50 years (Table 1). The spirometric values namely FVC,FEV1,FEV1/FVC % and FEV1 % Predicted were significantly lower in non exercising group in comparison with those doing exercise (P<0.001 for all) (Table 2). The estimated values of GPX(glutathione peroxidase), SOD(superoxide dismutase) and Catalase were significantly lower (p<0.001 for all) in non exercising group but the levels of MDA were higher(p<0.001) in the same as compared to exercising group (Table 3). The levels of HDL(<0.001) were significantly higher and VLDL(p=0.03) were significantly lower in exercising group as compared to non exercising group (Table 4).

Table 1: Anthropometry (*p<0.05 is significant).

Table 2: Pulmonary Functions in COPD Patients (*p<0.05 is significant).

Table 3: Oxidant Anti-Oxidant Status in COPD Patients(*p<0.05 is significant).

Table 4: Lipid Profile in COPD Patients(*p<0.05 is significant).

Discussion

In the present study the levels of HDL and VLDL were improved in smoker COPD group doing exercise which can be attributed to beneficial effects of exercise on lipid status [7]. Improvement in lipid profile has been shown in unsupervised jogging and prolonged aerobic exercises [15,16]. In our study smokers not doing any sort of exercise had deranged lipid profile which can be explained on the basis of effects of smoking on lipid profile [3].

In present study the levels of anti oxidant enzymes were reduced and MDA which is an indirect measure of free radical activity was increased in non exercising COPD group in comparison to exercising COPD group. Oxidative stress is implicated in pathogenesis of COPD and contribute to inflammatory processes and proteolytic activity [17] which is thus expected to be present in both study groups though inflammatory markers have not been evaluated in the present study. In recent years the role of inflammatory cytokines has been demonstrated in oxidative stress [18]. The possible explanation for lower oxidant anti-oxidant imbalance in exercising COPD group in our study can be due to recent findings which suggest that exercise have potent anti inflammatory effect and enhance antioxidant defenses [19-21]. Inflammatory cytokines like IL 6 decrease the activity of lipoprotein lipase which in turn elevates triglyceride levels [22]. The study done by Panagiotakos etal [23] demonstrated lower levels of inflammatory markers in physically active persons compared to those following sedentary lifestyles. In our study improved lipid profile in exercising COPD group can be attributed to anti-inflammatory effects of exercise [24].

All the subjects included in our study belonged to moderate COPD group as per GOLD classification [8]. Lung functions were reduced in both groups though statistically reduction was less in those who were following self regime of exercise and thus were more physically active in comparison to other group and are expected to have lesser pro inflammatory cytokines (though we have not measured them) thus limiting inflammation and lung function decline. Inflammation is known to effect lung functions in COPD [25,26] and physical inactivity is linked to COPD [27]. Exercise has anti-inflammatory effects and also provides symptomatic improvement [28]. Thus possible explanations for our findings could be low levels of inflammation and lesser physical inactivity.

In conclusion on the basis of study the Oxidant Anti- Oxidant imbalance, lipid profile derangement and lung function decline is less in exercising COPD group as compared to those who were not exercising.

Limitation of the present study is that the subjects included were newly diagnosed cases not following any recommended or supervised exercises but were doing self-exercise regime. Thus a follow up study before and after enrolling subjects to pulmonary rehabilitation is required along with evaluation of pro and anti inflammatory cytokines.

Acknowledgement

Authors are thankful to participants of the study and also to the supporting staff.

References

1. WHO site http://www.who.int world bank / WHO global burden of disease study.
2. Buist AS, Vollmer VM, McBurnie MA. Worldwide burden of COPD in high and low income countries. Part I: The burden of obstructive lung disease (BOLD). Initiative Int J Tuber C Lung Dis 2008; 12: 703-708.
3. Burtis A Carl, Ashwood R Edward. Lipids, lipoproteins and apolipoproteins. In: Burtis A Carl, Ashwood R Edward editors, Tietz Textbook of Clinical Chemistry, 3rd edition. Philadelphia: WB Saunders Company 1993; 61-62.
4. Rahman I, MacNee W. Role of transcription factors in inflammatory lung diseases. Thorax 1998; 53:601-612.
5. Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J et al. ‘American Thoracic Society/ European Respiratory Society statement on pulmonary rehabilitation.’ Am J Respir Crit Care Med 2006; 173 (12): 1390-1413
6. Berry MJ, Rejeski J, Adair NE, Zaccaro D. Exercise rehabilitation and chronic obstructive pulmonary disease stage. Am J Respir Crit Care Med 1999; 160: 1248-1253.
7. Bloomer RJ, Fisher-Wellman, K. The role of exercise in minimizing postprandial oxidative stress in cigarette smokers. Nicotine Tob. Res 2009; 11, 3-11.
8. Global Strategy for the Diagnosis, Management and Prevention of COPD. Global Initiative for Chronic Obstructive Lung Disease (GOLD).www.goldcopd.org/uploads/users/files/GOLD_Spirometry_2010.pdf.
9. Aebi HE.Catalase in vitro.Meth Enzymol 1984; 105: 121-126.
10. Paglia DE, Valentine WN. Studies on the quantitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158-168.
11. McCord JM, Fridovich I. Superoxide dismutase an enzymic function for erythrocuprein Hemocuprein. J. Biol. Chem 1969; 244, 6049-6055.
12. Philpot J. Assay for MDA levels. Rad Res 1963: 3: 55-80.
13. Lowry OH, Rosebrough NJ, Farr AL. Protein measurement with the folin phenol reagent. J Biol Chem 1951; 193: 265–275.
14. Friedewald WT, Levy RI, Frederickson DS. Estimationof the concentration of low density lipoprotein cholesterol in plasma, without the use of the preparative centrifuge. Clin Chem. 1972;18:499–502.
15. Marti B, Suter E, Riesen WF, Tschopp A, Wanner HU, Gutzwiller F. Effects of long term self monitored exercise on the serum lipoprotein and apolipoprotein profile in middle aged men. Atherosclerosis1990; 81(1): 19-31.
16. Abdus Salam KG, Manan M, Ghazala et al .Comparision of lipid profile and apoprotein in sedentary workers and those involved in regular exercise. J Ayub Med Coll Abbottabad 2001; 18(4):16-20.
17. Remels AH, Gosker HR, van der Velden J, Langen RC, Schols AM: Systemic inflammation and skeletal muscle dysfunction in chronic obstructive pulmonary disease: state of the art and novel insights in regulation of muscle plasticity. Clin Chest Med 2007; 28: 537–552, vi
18. Meier B, Radeke HH, Selle S, Younes M, Sies H, Resch K, et al.Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem J 1989; 263: 539-545.
19. Van Helvoort HA, Heijdra YF, Thijs HM,Vina J, Wanten GJ, Dekhuijzen PN. Exercise induced systemic effects in muscle-wasted patients with COPD. Med Sci Sports Exerc 2006; 38: 1543-1552.
20. Bailey DM, Davie B, Young IS. Intermittent hypoxic training: implications for lipid peroxidation induced by acute normoxic exercise in active men. Clinical Science (London, England : 1979) 101, 465-475.
21. Barreiro E, Galdiz J B, Marinan M, Alvarez F J, Hussain SNA. Respiratory loading intensity and diaphragm oxidative stress: N-acetyl-cysteine effects . J Appl Physiol 2006; 100: 555-563.
22. Fernandez Real JM, Broch M, Vendrell J, Richart C, Ricart W. Interluekin-6 gene polymorphism and lipid abnormalities in healthy subjects. J Clin Endocrinol Metab 2000; 85: 1334-1339.
23. Panagiotakos DB, Pitsavos C, Chrysohoou C, Kavouras S, Stefanadis C.The associations between leisure-time physical activity and inflammatory and coagulation markers related to cardiovascular disease: the ATTICA Study. Preventive Medicine 2005; 40(4): 432-437.
24. Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA. The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol. 2011; 11: 607-615.
25. Dunnill MS, Massarella GR, Anderson JA. A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysema. Thorax 1969; 69: 39-42.
26. Matsuba K J L, Wright B R, Wiggs P D, Pare and Hogg J C. The changes in airways structure associated with reduced forced expiratory volume in one second. Eur Respir J 1989; 2: 834-839.
27. Nicholas S H , Michael I P. Does physical inactivity cause chronic obstructive pulmonary disease? Clinical Science 2010; 118, 565-572.
28. Garrod R, Ansley P, Canavan J, Jewell A: Exercise and the inflammatory response in chronic obstructive pulmonary disease (COPD) – does training confer anti-inflammatory properties in COPD? Med Hypotheses 2007; 68: 291–298.