Chronic obstructive pulmonary disease (COPD) is a disease of chronic, progressive airflow limitation with increasing prevalence globally. Cigarette smoke is a common cause of COPD. It contains >4000 chemicals out of which para-benzoquinone (p-BQ), a compound isolated recently is thought to be a major causative factor. This is produced from oxidation and disproportionation of para-benzosemiquinone, a pyro-product of cigarette smoke in the lungs. This p-BQ forms adduct with protein and cause oxidative damage leading to COPD. The research on animal model has shown that p-BQ is responsible for inducing emphysematous change in guinea pig lungs.
The p-BQ is neutralized by the formation of anti-p-BQ antibody in the system. However, for unknown reasons in some smokers, deficiency of the neutralizing antibody develops at or after the middle age and the unabated oxidative damage from the active p-BQ leads to the development of COPD. This fact has been supported by the observation of significantly lower anti-p-BQ antibody levels in smoker COPD patients compared to smoker non-COPD patients. Another substance that protects against p-BQ is ascorbic acid (Vitamin C), a well-known antioxidant. It is observed that pretreatment of the guinea pigs with Vitamin C can prevent the p-BQ induced emphysema. Since guinea pigs, such as human beings, are devoid of the enzymes to produce Vitamin C in their body and depend on dietary supplementation of the Vitamin, the prevention of p-BQ induced emphysema with Vitamin C raises the possibility of the same prospect in human beings too. The preventive dose of Vitamin C (30 mg Vitamin C/kg body weight) in guineapigs may be effective in human beings also. p BQ induced continued oxidative damage may be active in the progression of COPD in humans and the treatment with a high dose of Vitamin C may help the natural course of COPD.
We have, therefore, decided to test the role of long-term high dose Vitamin C (2 g/day, 500 mg four times orally) in a small cohort of our COPD patients (n = 26) who were randomized to receive either a standard COPD therapy or the same with add-on high dose Vitamin C. They were followed up longitudinally every 3 months for 6 months with spirometry and clinical examination with intermittent telephonic enquiry to ensure compliance. The basic demographic data of these patients are summarized in Table 1. It has been found that on longitudinal follow-up there is hardly any difference in lung function. However, at 6 months, there is a drop in exacerbation rate in patients receiving add-on Vitamin C. Exacerbation rates were found to be higher (odds ratio 5.26 [2.44–11.31], P value < 0.0001) in standard therapy alone.
The reduction in exacerbation rate appears to be a significant finding despite obvious limitations of the observation. The number of patients recruited is too small to make a definitive inference and the follow-up also needs to be for a longer duration. Since exacerbations are related to faster decline of lung function, poor functional capacity, health-related quality of life, and survival prospects, a reduction in exacerbation rate would mean a lot for COPD patients. This small observation demands attention from that point of view to be validated with further research work.
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1. López-Campos JL, Tan W, Soriano JB. Global burden of COPD Respirology. 2016;21:14–23
2. Chatterjee IB. Process for the isolation of a major harmful oxidant from cigarette smoke. CSIR assignee US Patent No 6,929, 012 2005
3. Ghosh A, Ganguly S, Dey N, Banerjee S, Das A, Chattopadhyay DJ, et al Causation of cigarette smoke-induced emphysema by p-benzoquinone and its prevention by vitamin C Am J Respir Cell Mol Biol. 2015;52:315–22
4. Banerjee S, Bhattacharyya P, Mitra S, Kundu S, Panda S, Chatterjee IB. Anti-p
-benzoquinone antibody level as a prospective biomarker to identify smokers at risk for COPD Int J Chron Obstruct Pulmon Dis. 2017;12:1847–56
5. Panda K, Chattopadhyay R, Chattopadhyay DJ, Chatterjee IB. Vitamin C prevents cigarette smoke-induced oxidative damage in vivo
Free Radic Biol Med. 2000;29:115–24