**3. Measurements of homocysteine**

Human plasma contains both free homocysteine (HCY) and its oxidised form, homocystine (HCY-HCY), where two molecules are bound via a disulphide bond. About 99% of

Homocysteine is Elevated in COPD 25

Number Controls 23 25 29

Age Controls 66.4 64.8 70.6

% Males Controls 100 64 72.0

FEV1 (L) Controls 2.58 2.25 N/A

FEV1% Controls 83.3 76.1 104.5

FEV1/FVC% Controls 88.4 78.1 78.0

CRP (mg/L) Controls N/A 0.89 2.3

Table 1. Comparison of Patient Characteristics in three Lung Function Studies in COPD

significantly lower in the Seemungal et al study than in the Fimognari et al Study.

lower in the Seemungal et al study than in the Fimognari et al Study.

**7. Homocysteine, lung function and lung function decline** 

difficult to actually compare *all* of the findings.

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

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

In conclusion there are differences in the patients between the three studies that make it

The major manifestation of airflow obstruction in COPD is reduced maximum expiratory flow and slow forced emptying of the lungs (FEV1) and these features do not change

(Data are expressed as means except where otherwise stated.)

BMI (kgm-2)

HCY\*

(micro Mol/L)

\*Median Values only shown in paper.

Variable Kai 2006 Seemungal 2007 Fimognari 2009

COPD 24 29 42

COPD 70.7 69.1 71.3

COPD 100 79 85

Controls 24.2 27.4 28.1 COPD 20.0 24.0 26.5

Controls 9.8 8.2 11.5\* COPD 12.0 12.0 13.9\*

COPD 1.12 1.43 N/A

COPD 38.5 49.1 52.8

COPD 42.7 53.1 53.0

COPD N/A 2.05 5.5

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: age, gender and body mass.

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 results were similar and are compared below.
