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Exploring biological risk factors of chronic obstructive pulmonary disease : old age and female sex

University of British Columbia

Chronic obstructive pulmonary disease (COPD) has various risk factors including old age and female sex; however, the biological reasoning behind these is not fully understood. COPD prevalence and mortality increase with age. COPD patients also seem to demonstrate pulmonary and systemic accelerated aging. When people age, repetitive sequences at their chromosomes ends, called telomeres, shorten. In COPD this may occur at an increased rate due to increased cell turnover or DNA damage, caused by inflammation and oxidative stress, and could contribute to lung function decline. Therefore, we measured telomere length in peripheral blood cells of COPD patients using qPCR and examined the relationship with lung function (FEV₁ % predicted, FVC % predicted and FEV₁/FVC) as well as inflammatory marker levels. We found that telomere length was positively related to FEV₁/FVC and negatively related to serum SP-D level, a lung specific marker of inflammation. This supports that COPD is a disease of accelerated aging and suggests that lung inflammation may be involved in the process. Females seem to be more susceptible to developing COPD than males. A major distinction between males and females is their sex hormone levels. The lung has sex hormone receptors and there are reports of experimental animal studies and observational human studies suggesting that sex hormones have an effect on the lung. Hence, in COPD patients we measured levels of the hormones estradiol, progesterone, testosterone, luteinizing hormone, follicle-stimulating hormone and sex hormone-binding globulin in their serum using ELISAs. The hormone levels of COPD patients fell within normal ranges and had expected relationships with age and BMI. We found a significant negative association between estradiol and FVC % predicted in males; an inverse relationship between progesterone and FVC % predicted in both sexes; and a positive relationship between LH concentration and FEV₁ % predicted in females. These data support that sex hormones affect lung function, though the mechanism by which they do so is unclear due to the scarcity of knowledge in the field. Telomeres and sex hormones seem to play a role in the risk factors of aging and female sex, respectively, and offer insight into COPD pathogenesis, though more research is needed.

Text

2010-04-22

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/24015

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/