Air pollution is a grave risk to human health that affects nearly everyone in the world and nearly every organ in the body. Fortunately, it is largely a preventable risk. Reducing pollution at its source can have a rapid and substantial impact on health. Within a few weeks, respiratory and irritation symptoms, such as shortness of breath, cough, phlegm, and sore throat, disappear; school absenteeism, clinic visits, hospitalizations, premature births, cardiovascular illness and death, and all-cause mortality decrease significantly. The interventions are cost-effective. Reducing factors causing air pollution and climate change have strong cobenefits. Although regions with high air pollution have the greatest potential for health benefits, health improvements continue to be associated with pollution decreases even below international standards. The large response to and short time needed for benefits of these interventions emphasize the urgency of improving global air quality and the importance of increasing efforts to reduce pollution at local levels.

Ozone is known to cause bronchial inflammation and airway hyper-responsiveness via oxidative injury and inflammation. While other ambient air pollutants such as particulate matter (PM) and NO2 showed decreasing trends of mean annual concentrations, ozone concentration did not decline recently in most countries worldwide. Short-term exposure to high concentration of ozone has been associated with increased mortality and cardiovascular and respiratory morbidity in many regions of the world. However, long-term effects of ozone were less investigated than short-term exposure due to the difficulty of modeling for ozone exposure and linking between individual exposure and health outcome data. Recently developed modeling of ozone exposure enabled investigation of long-term ozone effects on health outcomes. Recent findings suggested that long-term exposure to ozone is associated with an increased risk of cardiovascular and respiratory mortality. Longitudinal studies using large cohorts also revealed that long-term exposure to ozone was associated with a greater decline in lung function and progression of emphysema. Keeping standards for ozone as well as PM is needed to protect respiratory health of the general population and subjects with chronic respiratory diseases.

Background and Objectives.Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airflow limitation. Although airway inflammation and oxidative stress are known to be important in the pathogenesis of COPD, the mechanism underlying airflow obstruction is not fully understood. Gene expression profiling of lung tissue was performed to define the molecular pathways that are dysregulated in COPD.Methods.RNA was isolated from lung tissues obtained from 98 subjects with COPD and 91 control subjects with normal spirometry. The RNA samples were processed with RNA-seq using the HiSeq 2000 system. Genes expressed differentially between the two groups were identified using Student’st-test.Results.After filtering for genes with zero counts and noncoding genes, 16,676 genes were evaluated. A total of 2312 genes were differentially expressed between the lung tissues of COPD and control subjects (false discovery rate correctedq<0.01). The expression of genes related to oxidative phosphorylation and protein catabolism was reduced and genes related to chromatin modification were dysregulated in lung tissues of COPD subjects.Conclusions. Oxidative phosphorylation, protein degradation, and chromatin modification were the most dysregulated pathways in the lung tissues of COPD subjects. These findings may have clinical and mechanistic implications in COPD.

Ambient air pollution is associated with numerous adverse health outcomes, but the underlying mechanisms are not well understood; epigenetic effects including altered DNA methylation could play a role. To evaluate associations of long-term air pollution exposure with DNA methylation in blood, we conducted an epigenome-wide association study in a Korean chronic obstructive pulmonary disease cohort (N = 100 including 60 cases) using Illumina’s Infinium HumanMethylation450K Beadchip. Annual average concentrations of particulate matter ≤ 10 μm in diameter (PM10) and nitrogen dioxide (NO2) were estimated at participants’ residential addresses using exposure prediction models. We used robust linear regression to identify differentially methylated probes (DMPs) and two different approaches, DMRcate and comb-p, to identify differentially methylated regions (DMRs). After multiple testing correction (false discovery rate < 0.05), there were 12 DMPs and 27 DMRs associated with PM10 and 45 DMPs and 57 DMRs related to NO2. DMP cg06992688 (OTUB2) and several DMRs were associated with both exposures. Eleven DMPs in relation to NO2 confirmed previous findings in Europeans; the remainder were novel. Methylation levels of 39 DMPs were associated with expression levels of nearby genes in a separate dataset of 3075 individuals. Enriched networks were related to outcomes associated with air pollution including cardiovascular and respiratory diseases as well as inflammatory and immune responses. This study provides evidence that long-term ambient air pollution exposure impacts DNA methylation. The differential methylation signals can serve as potential air pollution biomarkers. These results may help better understand the influences of ambient air pollution on human health.

Background: Muscle wasting is associated with prognosis in patients with chronic obstructive pulmonary disease (COPD). The cross-sectional area of skeletal muscles on computed tomography (CT) could serve as a method to evaluate body composition. The present study aimed to determine the ability of CT-derived pectoralis muscle area (PMA) and pectoralis muscle density (PMD) to determine the severity of COPD and change in longitudinal pulmonary function in patients with COPD. Methods: A total of 293 participants were enrolled in this study, a whom 222 had undergone at least two spirometry measurements within 3 years after baseline data acquisition. PMA and PMD were measured from a single axial slice of chest CT above the aortic arch at baseline. The emphysema index and bronchial wall thickness were quantitatively assessed in all scans. The generalized linear model was used to determine the correlation between PMA and PMD measurements and pulmonary function. Results: PMA and PMD were significantly associated with baseline lung function and the severity of emphysema (P < 0.05). Patients with the lowest PMA and PMD exhibited significantly more severe airflow obstruction (β = − 0.06; 95% confidence interval: − 0.09 to − 0.03]. PMA was statistically associated with COPD assessment test (CAT) score (P = 0.033). However, PMD did not exhibit statistically significant correlation with either CAT scores or modified Medical Research Council scores (P > 0.05). Furthermore, neither PMA nor PMD were associated with changes in forced expiratory volume in 1 s over a 3-year periods. Conclusions: CT-derived features of the pectoralis muscle may be helpful in predicting disease severity in patients with COPD, but are not necessarily associated with longitudinal changes in lung function.

Exposure to cigarette smoking can increase the risk of cancers and cardiovascular and pulmonary diseases. However, the underlying mechanisms of how smoking contributes to disease risks are not completely understood. Epigenome-wide association studies (EWASs), mostly in non-Asian populations, have been conducted to identify smoking-associated methylation alterations at individual probes. There are few data on regional methylation changes in relation to smoking. Few data link differential methylation in blood to differential gene expression in lung tissue. We identified 108 significant (false discovery rate (FDR) < 0.05) differentially methylated probes (DMPs) and 87 significant differentially methylated regions (DMRs) (multiple-testing corrected p < 0.01) in current compared to never smokers from our EWAS of cotinine-validated smoking in blood DNA from a Korean chronic obstructive pulmonary disease cohort (n = 100 including 31 current, 30 former, and 39 never smokers) using Illumina HumanMethylation450 BeadChip. Of the 108 DMPs (FDR < 0.05), nine CpGs were statistically significant based on Bonferroni correction and 93 were novel including five that mapped to loci previously associated with smoking. Of the 87 DMRs, 66 were mapped to novel loci. Methylation correlated with urine cotinine levels in current smokers at six DMPs, with pack-years in current smokers at six DMPs, and with duration of smoking cessation in former smokers at eight DMPs. Of the 143 genes to which our significant DMPs or DMRs annotated, gene expression levels at 20 genes were associated with pack-years in lung tissue transcriptome data of smokers (Asan Biobank, n = 188). Our study of differential methylation in Koreans confirmed previous findings from non-Asian populations and revealed novel loci in relation to smoking. Smoking-related differential methylation in blood is associated with gene expression in lung tissue, an important target of adverse health effects of smoking, supporting the potential functional importance of methylation in smoking-related disease.