โรคปอดอุดกั้นเรื้อรังและสารต้านอนุมูลอิสระ
คำสำคัญ:
โรคปอดอุดกั้นเรื้อรัง, สารอนุมูลอิสระ, สารต้านอนุมูลอิสระบทคัดย่อ
บทนำ โรคปอดอุดกั้นเรื้อรัง มีอัตราการเสียชีวิตเป็นอันดับสามของโลก และยังไม่ทราบสาเหตุของการเกิดโรค
ที่แน่ชัด แต่พบว่าเกี่ยวข้องกับสารอนุมูลอิสระจากการสูบบุหรี่ มลพิษ หรือปฏิกิริยาทางชีวเคมีภายในร่างกาย
เหนี่ยวนำให้เกิดการอักเสบแบบเรื้อรังของหลอดลมและเกิดถุงลมโป่งพอง ซึ่งอาจพบการหลั่งเมือกมากผิดปกติ
ร่วมด้วย ซึ่งปัจจุบันยังไม่สามารถรักษาโรคนี้ได้หายขาดได้ แต่มีรายงานที่ระบุว่าการใช้สารต้านอนุมูลอิสระ
สามารถป้องกันและลดสารอนุมูลอิสระที่เป็นสาเหตุสำคัญของโรคนี้ได้
วัตถุประสงค์ ทบทวนสาเหตุของการเกิดและพัฒนาของโรค และความสัมพันธ์ของสารต้านอนุมูลอิสระในการ
ป้องกันและรักษาโรคปอดอุดกั้นเรื้อรัง
สรุป สารต้านอนุมูลอิสระเป็นแนวทางหนึ่งที่สามารถยับยั้งสารอนุมูลอิสระที่เป็นสาเหตุของการเกิดโรคได้ แต่
พบว่าสารต้านอนุมูลอิสระยังไม่สามารถรักษาโรคนี้ได้หายขาด อาจเพราะมีปริมาณไม่เพียงพอต่อการกำจัด
สารอนุมูลอิสระที่มีอยู่ในร่างกาย เนื่องจากการพัฒนาของโรคได้รับสารอนุมูลอิสระเป็นเวลานานจนกระตุ้นการ
อักเสบแบบเรื้อรัง เนื้อเยื่อในระบบทางเดินหายใจถูกทำลายจนยากที่จะซ่อมแซมหรือฟื้นฟู ดังนั้น จึงยังคงต้อง
ศึกษาเกี่ยวกับกลไกการเกิดโรคอย่างแท้จริง เพื่อการรักษาที่จำเพาะเจาะจงและฟื้นฟูร่างกายของผู้ป่วยให้กลับ
มาทำงานได้เหมือนเดิมมากที่สุด
References
1. Lozano R, Naghavi M, Foreman K, Lim S,
Shibuya K, Aboyans V, et al. Global and
regional mortality from 235 causes of
death for 20 age groups in 1990 and 2010:
a systematic analysis for the Global Burden
of Disease Study 2010. Lancet. 2012; 380:
2095-128.
2. Burney PG, Patel J, Newson R, Minelli C,
Naghavi M. Global and regional trends in
COPD mortality, 1990-2010. Eur Respir J.
2015; 45: 1239-47.
3. Vestbo J, Hurd SS, Agusti AG, Jones PW,
Vogelmeier C, Anzueto A, et al. Global
strategy for the diagnosis, management,
and prevention of chronic obstructive
pulmonary disease: GOLD executive
summary. Am J Respir Crit Care Med. 2013;
187: 347-65.
4. MacNee W. Pathogenesis of chronic
obstructive pulmonary disease. Proc Am
Thorac Soc. 2005; 2: 258-66; discussion
90-1.
5. Mitzner W. Emphysema--a disease of small
airways or lung parenchyma? N Engl J Med.
2011; 365: 1637-9.
6. Fletcher C, Peto R. The natural history of
chronic airflow obstruction. Br Med J. 1977;
1: 1645-8.
7. Buist AS, McBurnie MA, Vollmer WM,
Gillespie S, Burney P, Mannino DM, et al.
International variation in the prevalence
of COPD (the BOLD Study): a populationbased prevalence study. Lancet. 2007;
370: 741-50.
8. Hooper R, Burney P, Vollmer WM, McBurnie
MA, Gislason T, Tan WC, et al. Risk factors
for COPD spirometrically defined from the
lower limit of normal in the BOLD project.
Eur Respir J. 2012; 39: 1343-53.
9. Blanc PD, Eisner MD, Earnest G, Trupin
L, Balmes JR, Yelin EH, et al. Further
exploration of the links between
occupational exposure and chronic
obstructive pulmonary disease. J Occup
Environ Med. 2009; 51: 804-10.
10.Zhao J, Li M, Wang Z, Chen J, Zhao J, Xu Y,
et al. Role of PM2.5 in the development and
progression of COPD and its mechanisms.
Respir Res. 2019; 20: 120.
11. Maranetra KN, Chuaychoo B, Dejsomritrutai
W, Chierakul N, Nana A, Lertakyamanee
J, et al.The prevalence and incidence
of COPD among urban older persons of
Bangkok Metropolis. J Med Assoc Thai.
2002; 85: 1147-55.
12. Barnes PJ. Cellular and molecular
mechanisms of chronic obstructive
pulmonary disease. Clin Chest Med. 2014;
35: 71-86.
13. Takizawa H, Tanaka M, Takami K, Ohtoshi T,
Ito K, Satoh M, et al. Increased expression of
transforming growth factor-beta1 in small
airway epithelium from tobacco smokers
and patients with chronic obstructive
pulmonary disease (COPD). Am J Respir
Crit Care Med. 2001; 163: 1476-83.
14. Kirkham PA, Barnes PJ. Oxidative stress in
COPD. Chest. 2013; 144: 266-73.
15. Caramori G, Adcock IM, Casolari P, Ito K,
Jazrawi E, Tsaprouni L, et al. Unbalanced
oxidant-induced DNA damage and repair in
COPD: a link towards lung cancer. Thorax.
2011; 66: 521-7.
16. Rahman I. Antioxidant therapies in COPD.
Int J Chron Obstruct Pulmon Dis. 2006; 1:
15-29.
17. Sanguinetti CM. Oxidant/antioxidant
imbalance: role in the pathogenesis of
COPD. Respiration. 1992; 59 Suppl 1: 20-3.
18. Shishodia S, Potdar P, Gairola CG, Aggarwal
BB. Curcumin (diferuloylmethane) downregulates cigarette smoke-induced NFkappaB activation through inhibition
of IkappaBalpha kinase in human
lung epithelial cells: correlation with
suppression of COX-2, MMP-9 and cyclin
D1. Carcinogenesis. 2003; 24: 1269-79.
19. Biswas SK, McClure D, Jimenez LA, Megson
IL, Rahman I. Curcumin induces glutathione
biosynthesis and inhibits NF-kappaB
activation and interleukin-8 release in
alveolar epithelial cells: mechanism of
free radical scavenging activity. Antioxid
Redox Signal. 2005; 7: 32-41.
20. Barnes PJ, Burney PG, Silverman EK, Celli
BR, Vestbo J, Wedzicha JA, et al. Chronic
obstructive pulmonary disease. Nat Rev
Dis Primers. 2015; 1: 15076.
21. Chen H, Li Z, Dong L, Wu Y, Shen H, Chen
Z. Lipid metabolism in chronic obstructive
pulmonary disease. Int J Chron Obstruct
Pulmon Dis. 2019; 14: 1009-18.
22. Hogg JC. Pathophysiology of airflow
limitation in chronic obstructive pulmonary
disease. Lancet. 2004; 364: 709-21.
23. Stockley RA. Proteases and antiproteases.
Novartis Found Symp. 2001; 234: 189-99;
discussion 99-204.
24. Shujaat A, Minkin R, Eden E. Pulmonary
hypertension and chronic cor pulmonale
in COPD. Int J Chron Obstruct Pulmon Dis.
2007; 2: 273-82.
25. Di Stefano A, Caramori G, Oates T, Capelli
A, Lusuardi M, Gnemmi I, et al. Increased
expression of nuclear factor-kappaB in
bronchial biopsies from smokers and
patients with COPD. Eur Respir J. 2002;
20: 556-63.
26. Renda T, Baraldo S, Pelaia G, Bazzan E,
Turato G, Papi A, et al. Increased activation
of p38 MAPK in COPD. Eur Respir J. 2008;
31: 62-9.
27. Barnes PJ. Immunology of asthma and
chronic obstructive pulmonary disease.
Nat Rev Immunol. 2008; 8: 183-92.
28. McAleer JP, Kolls JK. Directing traffic: IL-17
and IL-22 coordinate pulmonary immune
defense. Immunol Rev. 2014; 260: 129-44.
29. Taylor AE, Finney-Hayward TK, Quint JK,
Thomas CM, Tudhope SJ, Wedzicha JA, et
al. Defective macrophage phagocytosis of
bacteria in COPD. Eur Respir J. 2010; 35:
1039-47.
30. Donnelly LE, Barnes PJ. Defective
phagocytosis in airways disease. Chest.
2012; 141: 1055-62.
31. Ito K, Barnes PJ. COPD as a disease of
accelerated lung aging. Chest. 2009; 135:
173-80.
32. Mercado N, Ito K, Barnes PJ. Accelerated
ageing of the lung in COPD: new concepts.
Thorax. 2015; 70: 482-9.
33. Madeo F, Zimmermann A, Maiuri MC,
Kroemer G. Essential role for autophagy
in life span extension. J Clin Invest. 2015;
125: 85-93.
34. Mizumura K, Cloonan SM, Haspel JA,
Choi AMK. The emerging importance of
autophagy in pulmonary diseases. Chest.
2012; 142: 1289-99.
35. Church DF, Pryor WA. Free-radical chemistry
of cigarette smoke and its toxicological
implications. Environ Health Perspect.
1985; 64: 111-26.
36. Rajendrasozhan S, Yao H, Rahman I.
Current perspectives on role of chromatin
modifications and deacetylases in lung
inflammation in COPD. COPD. 2009; 6:
291-7.
37. Hoidal JR, Fox RB, LeMarbe PA, Perri R,
Repine JE. Altered oxidative metabolic
responses in vitro of alveolar macrophages
from asymptomatic cigarette smokers. Am
Rev Respir Dis. 1981; 123: 85-9.
38. Nauseef WM, Metcalf JA, Root RK. Role of
myeloperoxidase in the respiratory burst
of human neutrophils. Blood. 1983; 61:
483-92.
39. Selby C, Drost E, Wraith PK, MacNee W.
In vivo neutrophil sequestration within
lungs of humans is determined by in vitro
“filterability”. J Appl Physiol (1985). 1991;
71: 1996-2003.
40. MacNee W, Wiggs B, Belzberg AS, Hogg
JC. The effect of cigarette smoking on
neutrophil kinetics in human lungs. N Engl
J Med. 1989; 321: 924-8.
41. Shaykhiev R, Crystal RG. Early events in
the pathogenesis of chronic obstructive
pulmonary disease. Smoking-induced
reprogramming of airway epithelial basal
progenitor cells. Ann Am Thorac Soc. 2014;
11 Suppl 5: S252-8.
42. Schikowski T, Ranft U, Sugiri D, Vierkotter
A, Bruning T, Harth V, et al. Decline in
air pollution and change in prevalence
in respiratory symptoms and chronic
obstructive pulmonary disease in elderly
women. Respir Res. 2010; 11: 113.
43. Apte JS, Marshall JD, Cohen AJ, Brauer M.
Addressing Global Mortality from Ambient
PM2.5. Environ Sci Technol. 2015; 49:
8057-66.
44. Abu-Elmagd M, Alghamdi MA, Shamy
M, Khoder MI, Costa M, Assidi M, et al.
Evaluation of the Effects of Airborne
Particulate Matter on Bone MarrowMesenchymal Stem Cells (BM-MSCs):
Cellular, Molecular and Systems Biological
Approaches. Int J Environ Res Public
Health. 2017; 14.
45. Fischer BM, Voynow JA, Ghio AJ. COPD:
balancing oxidants and antioxidants. Int
J Chron Obstruct Pulmon Dis. 2015; 10:
261-76.
46. Rahman I, Skwarska E, MacNee W.
Attenuation of oxidant/antioxidant
imbalance during treatment of
exacerbations of chronic obstructive
pulmonary disease. Thorax. 1997; 52:
565-8.
47. Torres-Ramos YD, Garcia-Guillen ML,
Olivares-Corichi IM, Hicks JJ. Correlation of
Plasma Protein Carbonyls and C-Reactive
Protein with GOLD Stage Progression in
COPD Patients. Open Respir Med J. 2009;
3: 61-6.
48. Vezina FA, Cantin AM. Antioxidants and
Chronic Obstructive Pulmonary Disease.
Chronic Obstr Pulm Dis. 2018; 5: 277-88.
49. Lomas DA, Lipson DA, Miller BE, Willits
L, Keene O, Barnacle H, et al. An oral
inhibitor of p38 MAP kinase reduces
plasma fibrinogen in patients with chronic
obstructive pulmonary disease. J Clin
Pharmacol. 2012; 52: 416-24
Shibuya K, Aboyans V, et al. Global and
regional mortality from 235 causes of
death for 20 age groups in 1990 and 2010:
a systematic analysis for the Global Burden
of Disease Study 2010. Lancet. 2012; 380:
2095-128.
2. Burney PG, Patel J, Newson R, Minelli C,
Naghavi M. Global and regional trends in
COPD mortality, 1990-2010. Eur Respir J.
2015; 45: 1239-47.
3. Vestbo J, Hurd SS, Agusti AG, Jones PW,
Vogelmeier C, Anzueto A, et al. Global
strategy for the diagnosis, management,
and prevention of chronic obstructive
pulmonary disease: GOLD executive
summary. Am J Respir Crit Care Med. 2013;
187: 347-65.
4. MacNee W. Pathogenesis of chronic
obstructive pulmonary disease. Proc Am
Thorac Soc. 2005; 2: 258-66; discussion
90-1.
5. Mitzner W. Emphysema--a disease of small
airways or lung parenchyma? N Engl J Med.
2011; 365: 1637-9.
6. Fletcher C, Peto R. The natural history of
chronic airflow obstruction. Br Med J. 1977;
1: 1645-8.
7. Buist AS, McBurnie MA, Vollmer WM,
Gillespie S, Burney P, Mannino DM, et al.
International variation in the prevalence
of COPD (the BOLD Study): a populationbased prevalence study. Lancet. 2007;
370: 741-50.
8. Hooper R, Burney P, Vollmer WM, McBurnie
MA, Gislason T, Tan WC, et al. Risk factors
for COPD spirometrically defined from the
lower limit of normal in the BOLD project.
Eur Respir J. 2012; 39: 1343-53.
9. Blanc PD, Eisner MD, Earnest G, Trupin
L, Balmes JR, Yelin EH, et al. Further
exploration of the links between
occupational exposure and chronic
obstructive pulmonary disease. J Occup
Environ Med. 2009; 51: 804-10.
10.Zhao J, Li M, Wang Z, Chen J, Zhao J, Xu Y,
et al. Role of PM2.5 in the development and
progression of COPD and its mechanisms.
Respir Res. 2019; 20: 120.
11. Maranetra KN, Chuaychoo B, Dejsomritrutai
W, Chierakul N, Nana A, Lertakyamanee
J, et al.The prevalence and incidence
of COPD among urban older persons of
Bangkok Metropolis. J Med Assoc Thai.
2002; 85: 1147-55.
12. Barnes PJ. Cellular and molecular
mechanisms of chronic obstructive
pulmonary disease. Clin Chest Med. 2014;
35: 71-86.
13. Takizawa H, Tanaka M, Takami K, Ohtoshi T,
Ito K, Satoh M, et al. Increased expression of
transforming growth factor-beta1 in small
airway epithelium from tobacco smokers
and patients with chronic obstructive
pulmonary disease (COPD). Am J Respir
Crit Care Med. 2001; 163: 1476-83.
14. Kirkham PA, Barnes PJ. Oxidative stress in
COPD. Chest. 2013; 144: 266-73.
15. Caramori G, Adcock IM, Casolari P, Ito K,
Jazrawi E, Tsaprouni L, et al. Unbalanced
oxidant-induced DNA damage and repair in
COPD: a link towards lung cancer. Thorax.
2011; 66: 521-7.
16. Rahman I. Antioxidant therapies in COPD.
Int J Chron Obstruct Pulmon Dis. 2006; 1:
15-29.
17. Sanguinetti CM. Oxidant/antioxidant
imbalance: role in the pathogenesis of
COPD. Respiration. 1992; 59 Suppl 1: 20-3.
18. Shishodia S, Potdar P, Gairola CG, Aggarwal
BB. Curcumin (diferuloylmethane) downregulates cigarette smoke-induced NFkappaB activation through inhibition
of IkappaBalpha kinase in human
lung epithelial cells: correlation with
suppression of COX-2, MMP-9 and cyclin
D1. Carcinogenesis. 2003; 24: 1269-79.
19. Biswas SK, McClure D, Jimenez LA, Megson
IL, Rahman I. Curcumin induces glutathione
biosynthesis and inhibits NF-kappaB
activation and interleukin-8 release in
alveolar epithelial cells: mechanism of
free radical scavenging activity. Antioxid
Redox Signal. 2005; 7: 32-41.
20. Barnes PJ, Burney PG, Silverman EK, Celli
BR, Vestbo J, Wedzicha JA, et al. Chronic
obstructive pulmonary disease. Nat Rev
Dis Primers. 2015; 1: 15076.
21. Chen H, Li Z, Dong L, Wu Y, Shen H, Chen
Z. Lipid metabolism in chronic obstructive
pulmonary disease. Int J Chron Obstruct
Pulmon Dis. 2019; 14: 1009-18.
22. Hogg JC. Pathophysiology of airflow
limitation in chronic obstructive pulmonary
disease. Lancet. 2004; 364: 709-21.
23. Stockley RA. Proteases and antiproteases.
Novartis Found Symp. 2001; 234: 189-99;
discussion 99-204.
24. Shujaat A, Minkin R, Eden E. Pulmonary
hypertension and chronic cor pulmonale
in COPD. Int J Chron Obstruct Pulmon Dis.
2007; 2: 273-82.
25. Di Stefano A, Caramori G, Oates T, Capelli
A, Lusuardi M, Gnemmi I, et al. Increased
expression of nuclear factor-kappaB in
bronchial biopsies from smokers and
patients with COPD. Eur Respir J. 2002;
20: 556-63.
26. Renda T, Baraldo S, Pelaia G, Bazzan E,
Turato G, Papi A, et al. Increased activation
of p38 MAPK in COPD. Eur Respir J. 2008;
31: 62-9.
27. Barnes PJ. Immunology of asthma and
chronic obstructive pulmonary disease.
Nat Rev Immunol. 2008; 8: 183-92.
28. McAleer JP, Kolls JK. Directing traffic: IL-17
and IL-22 coordinate pulmonary immune
defense. Immunol Rev. 2014; 260: 129-44.
29. Taylor AE, Finney-Hayward TK, Quint JK,
Thomas CM, Tudhope SJ, Wedzicha JA, et
al. Defective macrophage phagocytosis of
bacteria in COPD. Eur Respir J. 2010; 35:
1039-47.
30. Donnelly LE, Barnes PJ. Defective
phagocytosis in airways disease. Chest.
2012; 141: 1055-62.
31. Ito K, Barnes PJ. COPD as a disease of
accelerated lung aging. Chest. 2009; 135:
173-80.
32. Mercado N, Ito K, Barnes PJ. Accelerated
ageing of the lung in COPD: new concepts.
Thorax. 2015; 70: 482-9.
33. Madeo F, Zimmermann A, Maiuri MC,
Kroemer G. Essential role for autophagy
in life span extension. J Clin Invest. 2015;
125: 85-93.
34. Mizumura K, Cloonan SM, Haspel JA,
Choi AMK. The emerging importance of
autophagy in pulmonary diseases. Chest.
2012; 142: 1289-99.
35. Church DF, Pryor WA. Free-radical chemistry
of cigarette smoke and its toxicological
implications. Environ Health Perspect.
1985; 64: 111-26.
36. Rajendrasozhan S, Yao H, Rahman I.
Current perspectives on role of chromatin
modifications and deacetylases in lung
inflammation in COPD. COPD. 2009; 6:
291-7.
37. Hoidal JR, Fox RB, LeMarbe PA, Perri R,
Repine JE. Altered oxidative metabolic
responses in vitro of alveolar macrophages
from asymptomatic cigarette smokers. Am
Rev Respir Dis. 1981; 123: 85-9.
38. Nauseef WM, Metcalf JA, Root RK. Role of
myeloperoxidase in the respiratory burst
of human neutrophils. Blood. 1983; 61:
483-92.
39. Selby C, Drost E, Wraith PK, MacNee W.
In vivo neutrophil sequestration within
lungs of humans is determined by in vitro
“filterability”. J Appl Physiol (1985). 1991;
71: 1996-2003.
40. MacNee W, Wiggs B, Belzberg AS, Hogg
JC. The effect of cigarette smoking on
neutrophil kinetics in human lungs. N Engl
J Med. 1989; 321: 924-8.
41. Shaykhiev R, Crystal RG. Early events in
the pathogenesis of chronic obstructive
pulmonary disease. Smoking-induced
reprogramming of airway epithelial basal
progenitor cells. Ann Am Thorac Soc. 2014;
11 Suppl 5: S252-8.
42. Schikowski T, Ranft U, Sugiri D, Vierkotter
A, Bruning T, Harth V, et al. Decline in
air pollution and change in prevalence
in respiratory symptoms and chronic
obstructive pulmonary disease in elderly
women. Respir Res. 2010; 11: 113.
43. Apte JS, Marshall JD, Cohen AJ, Brauer M.
Addressing Global Mortality from Ambient
PM2.5. Environ Sci Technol. 2015; 49:
8057-66.
44. Abu-Elmagd M, Alghamdi MA, Shamy
M, Khoder MI, Costa M, Assidi M, et al.
Evaluation of the Effects of Airborne
Particulate Matter on Bone MarrowMesenchymal Stem Cells (BM-MSCs):
Cellular, Molecular and Systems Biological
Approaches. Int J Environ Res Public
Health. 2017; 14.
45. Fischer BM, Voynow JA, Ghio AJ. COPD:
balancing oxidants and antioxidants. Int
J Chron Obstruct Pulmon Dis. 2015; 10:
261-76.
46. Rahman I, Skwarska E, MacNee W.
Attenuation of oxidant/antioxidant
imbalance during treatment of
exacerbations of chronic obstructive
pulmonary disease. Thorax. 1997; 52:
565-8.
47. Torres-Ramos YD, Garcia-Guillen ML,
Olivares-Corichi IM, Hicks JJ. Correlation of
Plasma Protein Carbonyls and C-Reactive
Protein with GOLD Stage Progression in
COPD Patients. Open Respir Med J. 2009;
3: 61-6.
48. Vezina FA, Cantin AM. Antioxidants and
Chronic Obstructive Pulmonary Disease.
Chronic Obstr Pulm Dis. 2018; 5: 277-88.
49. Lomas DA, Lipson DA, Miller BE, Willits
L, Keene O, Barnacle H, et al. An oral
inhibitor of p38 MAP kinase reduces
plasma fibrinogen in patients with chronic
obstructive pulmonary disease. J Clin
Pharmacol. 2012; 52: 416-24
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