**9. Homocysteine and quality of life**

The St. Georges Respiratory Questionnaire (SGRQ) (Jones et al, 1992) assesses quality of life in three domains: symptoms, activities and impacts. Scores in three domains are combined to give weighted average called the total score (Jones et al, 1992). The SGRQ has been shown to be sensitive to different levels of health (Jones 1997). As a standardised questionnaire the SGRQ has the advantage of allowing direct comparison between different patient

Homocysteine is Elevated in COPD 29

decline in FEV1. Seemungal et al showed that HCY was related to COPD severity. Taken together these results suggest that HCY is involved in COPD pathogenesis. In 2001 Andersson et al showed that HCY was elevated in COPD and that patients with high HCY were more likely to have a low reduced GSH and low GSH:GSSG ratio (Andersson et al, 2001; Sibrian-Vazquez et al, 2010). Further there is evidence from a laboratory study that low levels of reduced glutathione are associated with emphysema in the rat (Hamlet et al, 2007). These studies suggest that HCY is involved in redox pathways in COPD and that a high HCY reflects an imbalance in the redox state favouring oxidative stress. However only cohort studies will allow us to determine which comes first the oxidative stress or the

The implications for management of COPD are not yet known. However, for now, COPD patients with an elevated HCY should be screened for cardiac disease and more closely monitored for evidence of a faster decline in lung function. Investigations into the role of

Homocysteine is a ubiquitous amino acid, elevation of which is associated with several diseases as diverse as thrombotic disorders and psoriasis. There is a strong link between cardiac disease and homocysteine levels. The cause and effects of HCY elevation in COPD are unknown but preliminary studies suggest that HCY is related to COPD pathogenesis and is likely to be associated with disorders in the redox pathway leading to oxidative stress in COPD. It is unknown whether HCY infiltrates the epithelium of the airway but HCY may

Andersson A, Ankerst J, Lindgren A, Larsson K, Hultberg B. (2001). Hyperhomocysteinemia

Andersson I, Grönberg A, Slinde F, Bosaeus I, Larsson S. (2007). Vitamin and mineral status

Antonio, CM, Nunes MC, Refsum H, Abraham AK. (1997). A novel pathway for the conversion of homocysteine to methionine in eukaryotes. *Biochem. J*. 328, 165±170 Austen SK, Coombes JS, Fassett RG. (2003). Homocysteine-lowering therapy in renal

Bazzano LA, He J, Muntner P, Vupputuri S, Whelton PK. (2003). Relationship between

Booth AA, Khalifah RG, Todd P, Hudson BG. (1997). In vitro kinetic studies of the formation

Amadori glycation pathways. *J. Biol. Chem*. 272, 5430±5437.

and changed plasma thiol redox status in chronic obstructive pulmonary disease.

in elderly patients with chronic obstructive pulmonary disease. *Clin Respir J*.

cigarette smoking and novel risk factors for cardiovascular disease in the United

of antigenic advanced glycation end products (AGEs). Novel inhibition of post-

antioxidants that may effectively lower HCY are ongoing (Zinellu et al 2008).

elevation in HCY.

**14. References** 

;1(1):23-9.

**12. Implications for management** 

**13. Concluding comments** 

well affect the endothelium of the lung.

*Clin Chem Lab Med*.;39(3):229-33.

disease. *Clin Nephrol*.;60(6):375-85.

States. *Ann. Intern. Med*. 138, 891–897.

populations and treatment groups and has been shown to be responsive when used for these comparisons (Jones et al, 1991; Jones & Lasserson, 1994). The Symptoms score assesses the degree of distress due to frequency and severity of respiratory symptoms, whilst the impacts component addresses psychosocial effects (Jones & Booth 1997).

Of the three studies, only the Seemungal et al study assessed quality of life via the St. Georges Respiratory Questionnaire (SGRQ) in the COPD subjects. All of the quality of life indices (total, symptoms, impacts and activities) were related to HCY levels with a minimum correlation of: symptoms score 0.295, impacts score 0.330 and total score 0.289. The activities score was the only component not related to HCY. The HCY scores were higher in patients with worse quality of life scores – consistent with the relationships found between FEV1 and HCY (Seemungal et al 2007). The SGRQ scores have been shown to be an important outcome measures in COPD and predict frequent exacerbations and hospitalisation (Seemungal et al, 1998; Wilkinson et al, 2004). Though few serum parameters have been shown to predict exacerbations apart from CRP (Dahl et al 2007), the relationship between HCY and SGRQ does raise intriguing possibilities. This is the only result so far available for HCY and life style in COPD, HCY has been related to life style determinants in cardiac disease (Nygard et al, 1998). Further the relationship of elevated CRP to ten year mortality in COPD (Dhal et al 2007) and of HCY to mortality in coronary artery disease (Nygard et al, 1997; Ford et al, 2007) raises the issue of whether HCY is also related to mortality in COPD which would only be revealed by long term studies of COPD.
