**6. In vivo studies of homocysteine in COPD patients**

Table 1 summarises the subject characteristics on patients in the three studies of lung function, COPD and homocysteine. All of the studies are relatively small but all involved a control arm of asymptomatic subjects. All are cross-sectional studies of COPD outpatients. The first study to link HCY and lung function in COPD was a Japanese study of Kai et al who measured lung function twice within a 1-year interval. In all studies postbronchodilator FEV1 was measured though it is not clear whether this was done for the controls in the Fimognari et al study. Reversibility was measured only in the Kai et al study. Table 1 shows that the Seemungal et al study enrolled slightly younger patients than both other studies with the Kai et al study enrolling only males. The CRP in both Seemungal et al and Fimognari et al studies was measured using immunometric assays.

The BMI in the Kai et al study was low at 20 kgm-2. Some of the controls, though asymptomatic, may have had abnormal lung function in the Kai et al and Seemungal et al studies as the Mean FEV1 was 76 to 83% but this is unlikely in the Fimognari et al study as the Mean FEV1was 104%. The Kai et al study had COPD patients with the more severe

homocysteine exists in the oxidised form in plasma. About 75% of total homocysteine is protein bound. Plasma HCY concentrations may be altered by several physiological factors:

Kai et al and Fimognari et al measured HCY by high performance liquid chromatography with fluorescence detection and Seemungal et al used a polarization immunoassay technique (Kai et al 2006, Figmonari 2011). Though the techniques were different their

Smoking is by consensus the most important risk factor in the development of COPD (GOLD 2010). Cigarette smoking causes elevation of plasma HCY (Bazzano et al 2003, Kai et al 2006) though the effect may be variable (Nygard 1998). Smoking is also a risk factor for the development of vascular disease and cessation of smoking contributes to cardiac risk reduction (Ford 2007). Several studies have linked and continue to link homocysteine with cardiovascular risk (Homocysteine Studies 2002, Givvimani 2011, and Tehlivets 2011). Since both cardiovascular disease and COPD share a common cause (Izquierdo et al, 2010) which itself causes hyperhomocysteinaemia, it is reasonable to expect that COPD should be

The first study to find a difference in homocysteine in COPD patients was reported by Andersson and colleagues (Andersson 2001). They examined the plasma from 19 patients with COPD and 29 healthy subjects. They found that total plasma homocysteine levels were higher in COPD than controls. But also that there was a decreased concentration of reduced glutathione and decreased reduced to total glutathione ration nine COPD. They speculated on a relationship between HCY as a surrogate marker of extracellular pro-oxidant activity

Table 1 summarises the subject characteristics on patients in the three studies of lung function, COPD and homocysteine. All of the studies are relatively small but all involved a control arm of asymptomatic subjects. All are cross-sectional studies of COPD outpatients. The first study to link HCY and lung function in COPD was a Japanese study of Kai et al who measured lung function twice within a 1-year interval. In all studies postbronchodilator FEV1 was measured though it is not clear whether this was done for the controls in the Fimognari et al study. Reversibility was measured only in the Kai et al study. Table 1 shows that the Seemungal et al study enrolled slightly younger patients than both other studies with the Kai et al study enrolling only males. The CRP in both Seemungal et al

The BMI in the Kai et al study was low at 20 kgm-2. Some of the controls, though asymptomatic, may have had abnormal lung function in the Kai et al and Seemungal et al studies as the Mean FEV1 was 76 to 83% but this is unlikely in the Fimognari et al study as the Mean FEV1was 104%. The Kai et al study had COPD patients with the more severe

age, gender and body mass.

associated with elevated HCY.

and plasma homocysteine.

results were similar and are compared below.

**4. Why study homocysteine in the COPD patient?** 

**5. Homocysteine and COPD and oxidative stress** 

**6. In vivo studies of homocysteine in COPD patients** 

and Fimognari et al studies was measured using immunometric assays.


\*Median Values only shown in paper.

Table 1. Comparison of Patient Characteristics in three Lung Function Studies in COPD (Data are expressed as means except where otherwise stated.)

COPD (Mean FEV1 38%) compared to Fimognari et al 53%. In the controls, the HCY levels appeared much lower in the Seemungal et al study than the others. The HCY levels in the COPD patients were identical in the Kai et al and Seemungal et al studies but higher in the Fimognari et al study though in the latter only medians are shown. Also, CRP levels were significantly lower in the Seemungal et al study than in the Fimognari et al Study.

The BMI in the Kai et al study was low at 20 kgm-2. Some of the controls, though asymptomatic, may have had abnormal lung function in the Kai et al and Seemungal et al studies as the FEV1 was 76 to 83% but this is unlikely in the Fimognari et al study as the FEV1 was 104%. The Kai et al study had COPD patients with the more severe COPD (FEV1 38%) compared to Fimognari et al 53%. In the controls, the HCY levels appeared much lower in the Seemungal et al study than the others. The HCY levels in the COPD patients were identical in the Kai et al and Seemungal et al studies but higher in the Fimognari et al study though in the latter only medians are shown. Also, CRP levels were significantly lower in the Seemungal et al study than in the Fimognari et al Study.

In conclusion there are differences in the patients between the three studies that make it difficult to actually compare *all* of the findings.
