Background

Chronic obstructive pulmonary disease (COPD), the most pervasive chronic respiratory disease and the leading contributor to the global disease burden, increased in rank from 11 to 6th in disability-adjusted life years (DALYs) among all causes between 1990 and 2019 [1, 2]. In 2019, COPD caused 3.28 million deaths and 74.43 million DALYs, 78.77 and 75.78% of which were attributable to exposure risk factors, respectively. Additionally, the prevalence and disease burden of COPD varied by sex and socioeconomic status [2]. A previous study found that low-sociodemographic index (SDI)-regions had the greatest burdens of COPD, and risk factors such as smoking and environmental pollution had the highest contributions to COPD-related mortality and DALYs [2: Figure S1, there were almost no differences in the age-standardized SEVs between males and females. Air pollution (including ambient particulate matter and ozone) is an important risk factor for COPD. But cumulative evidences suggested that women appear to be more sensitive to the effects of air pollution and smoking, because of their smaller airways (which means proportionately greater exposure), higher expression of genes involved in cytochrome P450 regulation in female, and hormonally mediated differences in pollution metabolism, etc. [13,14,15] This does not seem to support the higher COPD burden on men. On the other hand, male patients with COPD have worse survival than female patients might explain the higher disease burden of COPD to some extent [16,17,18]. Possible support for this is based on phenotypic differences between men and women in COPD [13, 19]. Chronic bronchitis is more common in women and emphysema is more common in men, the latter showing a faster decline in lung function and higher mortality. Additionally, for non-optimal temperature (including low and high temperature), it has been associated with elevated mortality risk [20, 21]. The impact of high temperature might be the alteration of fluid and electrolytic balance in COPD patients [21]. Cold weather might increase airway inflammation (TNF -α, leukotrienes, prostaglandins, etc.) [22,23,24]. Nevertheless, little is known about whether their effects differ between sexes, which need to be further explored. Therefore, based on the available evidence, the differences in disease burden caused by temperature may also be mainly due to the poorer survival of men. But alternative explanations should not be excluded.

Smoking, a key driver of COPD progression and the only behavioral risk that is controllable, is a vitally important risk factor that should be considered. It has been reported that exposure to cigarette smoke causes the destruction of the extracellular matrix, a shortage in blood supply, and the death of epithelial cells in the lungs. [25, 26] Herein, a strong correlation between smoking and COPD was confirmed once again; although smoking had the second-lowest global exposure rate compared to other risk factors, the global PAF of age-standardized DALY attributable to smoking was far larger than those of other risk factors. In addition, unlike the PAFs of other risk factors, the PAF of DALYs attributable to smoking showed remarkable heterogeneity among teenagers, middle-aged and older people. This may reflect the chronic additive effects of smoking, which are far greater than those of other risk factors. Many strategies for the control of smoking, such as economic, cultural, media-based, and family functioning measures, have been suggested in previous studies [27,28,29,30]. As the age-standardized DALY rate attributable to smoking had the steepest decline in the slope in low- and low-middle-SDI regions between 2000 and 2009, we should explore additional practicable and valid ways to generalize smoking prevention measures. Notably, as COPD is a chronic disease, there is a certain lag from the implementation of control measures to the corresponding effect.

An extremely obvious negative correlation was observed between the PAF of age-standardized DALY attributable to household air pollution and the SDI. With the development of society, the age-standardized DALY, YLL, YLD, and death rates of COPD attributable to household air pollution showed a steady downward trend but were still higher in low- and low-middle-SDI regions than in other regions. In resource-limited settings, solid fuels such as wood and cow dung, which are easily accessible, are used as cooking fuel in less-developed countries [31]. Poor ventilation and longer exposure durations also contribute to the increased rates [32]. Therefore, the COPD burden due to household air pollution in low- and low-middle-SDI regions remains a significant concern and requires more attention.

Although the age-standardized DALY, YLL, YLD, and death rates of COPD attributable to ambient particulate matter were relatively stable at the global level, the age-standardized SEVs of and COPD burdens attributable to ambient particulate matter and ozone exposure presented undesirable increasing trends in the low- and low-middle-SDI regions, suggesting that a control strategy consisting of a series of specific measures should be designed. Public health policy- and decision-makers should prioritize the design and implementation of effective ad hoc policies to address ambient particulate matter and ozone pollution.

Unlike smoking, the attributable age-standardized DALY rate and SEV of which is similar between the high-middle-SDI region and high-SDI region, the attributable age-standardized DALY rate and SEV of secondhand smoke exposure were lower in the high-SDI region than in the high-middle-SDI region. Greater limitations regarding smoking in public places may explain this finding to some extent, which is supported by an increasing body of evidence [33,34,35,36]. In addition, the age-standardized DALY and death rates caused by exposure to occupational dust was generally higher in men than in women since men have higher exposure to hazardous. However, some regions or countries with significant increases in occupational particles exposure for women also need attention. Different regions may be associated with low temperatures or high temperatures. Interestingly, relatively consistent and obvious trends of COPD burdens attributable to low and high temperatures were observed over the entire study period (the burden attributable to exposure to high temperature increased, whereas the burden attributable to low temperature decreased). This result may be influenced by global warming.

Conclusions

In summary, we need individualized measures for different high-risk groups according to their different pattern of COPD burden attributable to risk factors (e.g., the most important risk factors vary for women in different SDI regions). The DALY and death rates of COPD attributable to each risk factor except household air pollution and low temperature were the highest in the low-middle-SDI region. Notably, the undesirable increases in the COPD burdens attributable to ambient particulate matter, ozone, and high-temperature exposure in the low-middle- and low-SDI regions urgently need more attention and the implementation of relevant policies. Additionally, the observation that COPD burden attributable to ambient particulate matter, ozone, and low and high-temperature exposure is greater in males than in females, which couldn't be explained by the difference in SEV. Biological differences between male and female in COPD and its risk factors need to be further researched.

Limitations

Although this GBD study fills a gap of distributions and trends of the disease burden of COPD attributable to each risk factor, several limitations should be noted. Common deficiencies, such as the use of data based on information derived from samples not necessarily representative of the whole country/territory under study, have been explained exhaustively in many previously published GBD studies [1, 2, 4, 37]. In addition, different diagnostic thresholds for airway obstruction (expiratory volume in one second/forced vital capacity < 0.70, or the lower limit of normal) may influence the diagnosis rate of COPD [38]. Moreover, the issue of confounding between air pollution and smoking, which has not been addressed, inevitably produces deviation.