Our study showed that the circulating levels of hs-CRP were significantly elevated in patients with COPD compared with controls (4.8 vs. 0.8 mg/l) (t=11.574, p < 0.01). The main finding of our study is that CRP level in stable COPD patients has the strongest association with 6MWD and FEV1. We also found that CRP levels correlated independently with other important prognostic clinical variables: namely BMI and GOLD stage(spirometric classification). Some studies have demonstrated elevated levels of CRP and fibrinogen in patients with COPD [9, 10] and a meta-analysis by Gan et al. confirmed a significant increase in CRP levels in COPD patients compared with controls indicating a persistent systemic inflammation in subjects with COPD . Yende et al. reported a higher level of serum CRP in cases with an obstructive pattern in their spirometry (3.5 mg/l) in comparison to normal population (2.5 mg/l) (p < 0.0001) . In a study conducted by Broekhuizen et al., stable COPD patients had increased levels of inflammatory markers like CRP . F. Karadag, found out that serum CRP was significantly higher in stable COPD patients than in control subjects (p < 0.001) . This study confirms that circulating CRP levels are higher in stable COPD patients and may thus be regarded as a valid biomarker of low-grade systemic inflammation.
In our study, hs-CRP was found to be significantly higher in smokers as compared to quitters (r = 0.796; p < 0.01). Our work duplicates the previous finding of Juan P de Torres et al. regarding higher CRP levels in those COPD patients who are active smokers compared with those who are not [13, 14]. Unfortunately, this effect could not be confirmed in the control group because we only recruited non-smoking individuals to represent the “normal” population. However, the level of CRP in the ex-smoking COPD population remained significantly higher than in the non-smoking control group. In contrast to the above findings, Pinto-Plata et al., showed a significantly higher level of CRP in COPD patients (50.03 ± 1.51 mg/l) than in smoking (2.02 ± 1.04 mg/l) and non smoking control groups (2.24 ± 1.04 mg/l) (p < 0.001) .
The authors suggest that, although cigarette smoking has a role in promoting inflammatory process in COPD patients, it is not the leading cause of increased inflammatory markers. It should be noticed that only some cases develop inflammatory reaction following cigarette smoking, and this can be due to genetic differences.
In our study, CRP is inversely correlated with FEV1. In assessing the association between hs- CRP and lung function, Shaaban et al., looked at cross-sectional and longitudinal changes between CRP and FEV1 decline . Their analysis included 531 subjects demonstrating a negative association between FEV1 and CRP(p = 0.002) and higher CRPlevels over time were associated with a faster FEV1 decline. Similarly, a recent study found CRP levels associated with accelerated decline in FEV1 and mortality in patients with mild to moderate COPD, indicating that CRP measurements might enable identification of patients at a high risk of disease progression and mortality .
We observed that CRP levels are inversely correlated with 6MWD. Koechlin et al., found that CRP levels were inversely correlated with endurance time and Broekhuizen et al., also found that CRP increases in those patients with poor exercise capacity [11, 17]. The study by Pinto Plata and colleagues takes these findings one step further. They evaluated 88 patients with COPD and 71 controls and subjected them to extensive physiological testing and a detailed review of medications. Consistent with the results reported by Broekhuizen et al. they found that serum CRP levels were inversely related to the distanced achieved in the 6MWD independent of other factors such as age, sex and smoking history .
One of the important extrapulmonary manifestations of COPD is skeletal muscle dysfunction and wasting . With increasing severity of disease, patients with COPD lose muscle bulk, especially in their thighs and upper arms. Over time, these patients lose exercise endurance and complain of fatigue and dyspnea with only a minimal degree of exertion . These symptoms curtail their ability to exercise and compromise their cardiac fitness, which further limits their exercise tolerance, creating a vicious downward spiral that can eventually lead to generalized debility and immobility . Indeed, some authors postulate that the skeletal muscle dysfunction is a direct consequence of the systemic effects of the disease  whereas others propose that the “myopathy” is an independent process that contributes to the systemic inflammatory load of the disease . Whatever the mechanism, our results indicate that measuring CRP levels in stable conditions could indirectly reflect the exercise capacity of these patients, an important prognostic factor of the disease. Encouragingly, early interventions with exercise programmes may restore some of the lost health status related to muscle dysfunction and increase patients' exercise tolerance and stamina. Collectively, these studies have extended our concept of COPD beyond the pulmonary system, provided a solid clinical and epidemiological rationale for linking systemic inflammation with peripheral muscle dysfunction and raised the possibility of using anti-inflammatory treatment to mitigate systemic inflammation in the hope of improving health outcomes in these patients.
Interestingly, in our study, BMI is inversely correlated inversely with CRP. This contrasts with the study by Marie-Kathrin Breyer et al., who found that obese COPD patients (BMI ≥ 30 kg/m2) were 3.3 times more likely (95% CI, 1.5-7.0, p = 0.002) to have highly elevated CRP levels compared to normal weight (BMI 21-24.9 kg/m2) COPD patients, after taking clinically relevant confounders into account . In contrast, COPD patients with a low BMI (<21 kg/m2) were 2 times less likely (OR, 0.5; 95% CI, 0.3-0.9, p = 0.022) to have highly elevated CRP levels compared to normal-weight peers. Schols et al., observed high CRP level in a special subset of 16 COPD patients with high resting energy expenditure (REE) and low fat free mass (FFM) . More studies are needed to help resolve these controversial findings. It has been proposed that inflammatory cytokines could be secreted by adipocytes and by inflammatory cells present in adipose tissue . Further research is needed to elucidate the effect of different cytokines on body composition and vice versa.
Regarding the severity of disease based on GOLD criteria (spirometric classification), the mean serum CRP level was found to be significantly increased in severe cases. Pinto-Plata et al.  showed that there was no significant difference between the severity of disease and serum CRP level but de Torres and co-workers  indicated that serum CRP level significantly increased with the aggravation of disease. Therefore, although we expect the inflammatory process to be worse and the inflammatory markers to be increased by increasing the severity of disease, more studies are required in this regard.