COPD: balancing oxidants and antioxidants

Figures & data

Figure 1 Schematic depicting the cascade of events underlying the biological effects of cigarette smoking.

Note: With exposure to cigarette smoke, there is generation of oxidative stress followed by cell signaling, activation of transcription factors, and release of mediators. Abbreviations: COPD, chronic obstructive pulmonary disease; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2, nuclear factor erythroid 2-related factor 2.

Table 1 Clinical application of antioxidants summary table

Class of antioxidants	Examples	Clinical application (RCT or other)	Reference(s)
Thiols	N-acetylcysteine, carbocysteine	Decreased COPD exacerbation rate (RCT).	^Citation117,Citation118
Nrf2 activators	Sulforaphane	No RCTs yet. Ex vivo/in vitro study demonstrates improved glucocorticoid sensitivity in alveolar macrophages from COPD patients.	^Citation102
Food/plant-derived polyphenols	Curcumin, resveratrol	No RCTs yet. Oral curcumin in a mouse model of emphysema attenuated lung lavage neutrophils and mean linear intercept measurements.	^Citation123
Dietary modifications	Increased fruit and vegetable intake	Large population review studies demonstrated positive association with FEV1 with increased flavonoid intake (solid fruits) and decreased COPD-associated mortality risk in men. A single RCT over a 3-year period with increased fruit and vegetable intake demonstrated increased FEV1 (% predicted) and decreased exacerbation rate.	^Citation127–Citation129,Citation133
Vitamins	Vitamins C, E, and D	Important to address deficiencies. Insufficient data to suggest high-dose supplementation to temper respiratory pathology. Often used in combination with other nutrient supplements, herbs, or diet modifications.	^Citation126,Citation128,Citation142–Citation144

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; Nrf2, nuclear factor erythroid 2-related factor 2; RCT, randomized controlled trial.

Table 2 COPD and vitamin D reports

Year of publication	Article title or study goal	Population studied and type of study	Results of the study	Reference
2005	Relationship of serum 25-OH vitamin D and lung function.	Third National Health and Nutrition Examination Survey, 1988–1994, USA; observational cohort study.	Association between serum 25-OH vitamin D and FEV1 and FVC, but not the FEV1/FVC ratio. Also, no statistical association with chronic bronchitis or emphysema.	^Citation165
2009	Relationship of serum 25-OH vitamin D and URTI.	Third National Health and Nutrition Examination Survey, 1988–1994, USA; observational cohort study.	Serum 25-OH vitamin D was inversely associated with recent URTI. Participants with serum 25-OH vitamin D <10 ng/mL and a COPD diagnosis had much higher odds of recent URTI than participants with levels ≥30 ng/mL.	^Citation166
2011	Relationship of vitamin D status to adult lung function and COPD.	Hertfordshire Cohort Study, UK; observational cohort study.	Total vitamin D intake (diet and supplemental) was positively associated with FEV1, FEV1/FVC ratio and decreasing odds of COPD prevalence. However, serum 25-OH vitamin D was not associated with FEV1, but was positively associated with COPD prevalence.	^Citation167
2012	High doses of vitamin D to reduce COPD exacerbations – randomized trial.	Leuven, Belgium; randomized, single-center, double-blind, placebo-controlled trial.	Treatment: 100,000 IU of vitamin D or placebo every 4 weeks for 1 year. Among the total 182 patients studied, no significant differences were noted. However, those patients with severe vitamin D deficiency (ie, serum 25-OH vitamin D <10 ng/mL) at baseline who received the vitamin D supplementation had a significant decrease in their exacerbation rate.	^Citation146
2012	Relationship of vitamin D deficiency (serum 25-OH vitamin D ≤20 ng/mL) with smoking and lung function.	VA Normative Aging Study (only men in this cohort), Boston, MA, USA; observational cohort study.	In the overall cohort, there were no direct associations between vitamin D deficiency, smoking, and lung function. However, current smokers with vitamin D deficiency had corresponding lower lung function and more rapid decline of FEV1 per pack-year of smoking.	^Citation168
2014	No association of 25-OH vitamin D with COPD exacerbations	Dutch and Swiss primary care settings, 365 patients; prospective cohort study.	Serum 25-OH vitamin D categories: <10 ng/mL = severe deficiency; <20 ng/mL = deficiency; 20–29.99 ng/mL = insufficient; ≥30 ng/mL = sufficient. No significant associations, but a trend for lower risk of exacerbation was found in patients with sufficient levels. All patients with levels <30 ng/mL had equivalent risk of exacerbation.	^Citation169

Abbreviations: 25-OH, 25-hydroxyvitamin D; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume, in1 second; FVC, forced vital capacity; URTI, upper respiratory tract infection; VA, Department of Veterans Affairs.

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