Acute exacerbations of idiopathic pulmonary fibrosis are associated with high mortality and are of unknown cause. The effect of air pollution on exacerbations of interstitial lung disease is unknown. This study aims to define the association of air pollution exposure with acute exacerbation of idiopathic pulmonary fibrosis.
Patients with idiopathic pulmonary fibrosis and corresponding air pollution data were identified from a longitudinal cohort. Air pollution exposures were assigned to each patient for ozone, nitrogen dioxide, particulate matter, sulfur dioxide and carbon monoxide based on geo-coded residential addresses. Cox proportional hazards models were used to estimate the association of air pollution exposures and acute exacerbations.
Acute exacerbation was significantly associated with antecedent 6-week increases in mean level, maximum level and number of exceedances above accepted standards of ozone (hazard ratio (HR) 1.57, 95% CI 1.09–2.24; HR 1.42, 95% CI 1.11–1.82; and HR 1.51, 95% CI 1.17–1.94, respectively) and nitrogen dioxide (HR 1.41, 95% CI 1.04–1.91; HR 1.27, 95% CI 1.01–1.59; and HR 1.20, 95% CI 1.10–1.31, respectively).
Increased ozone and nitrogen dioxide exposure over the preceding 6 weeks was associated with an increased risk of acute exacerbation of idiopathic pulmonary fibrosis, suggesting that air pollution may contribute to the development of this clinically meaningful event.
Toxin-antitoxin (TA) systems are essential for bacterial persistence under stressful conditions. In particular, Mycobacterium tuberculosis express VapBC TA genes that encode the stable VapC toxin and the labile VapB antitoxin. Under normal conditions, these proteins interact to form a non-toxic TA complex, but the toxin is activated by release from the antitoxin in response to unfavorable conditions. Here, we present the crystal structure of the M. tuberculosis VapBC26 complex and show that the VapC26 toxin contains a pilus retraction protein (PilT) N-terminal (PIN) domain that is essential for ribonuclease activity and that, the VapB26 antitoxin folds into a ribbon-helix-helix DNA-binding motif at the N-terminus. The active site of VapC26 is sterically blocked by the flexible C-terminal region of VapB26. The C-terminal region of free VapB26 adopts an unfolded conformation but forms a helix upon binding to VapC26. The results of RNase activity assays show that Mg2+ and Mn2+ are essential for the ribonuclease activity of VapC26. As shown in the nuclear magnetic resonance spectra, several residues of VapB26 participate in the specific binding to the promoter region of the VapBC26 operon. In addition, toxin-mimicking peptides were designed that inhibit TA complex formation and thereby increase toxin activity, providing a novel approach to the development of new antibiotics.
Information on time spent in microenvironments has a critical role for personal exposure to environmental pollutants. Unlike several large-scale studies in Western countries, no comprehensive research on time-activity patterns for exposure assessment has been conducted in Korea. We investigated determinants of residential indoor and transportation times of individuals over 10-years old in the Korean population. The population-based study collected time-activity patterns of 31,634 Koreans for two consecutive days. The residential indoor and transportation times were collected for a weekday and a weekend day. The impact of sociodemographic factors on time-activity was assessed using multiple linear regression models. The residential indoor times were 14.23 h for the weekday and 16.13 h for the weekend and shorter than those in Western countries. The transportation times were 1.75 h for the weekday and 1.68 h for the weekend day. The most significant factors in residential indoor time were employment status, age, monthly income, and gender for the weekday and employment status and gender for the weekend day. The factors in transportation were gender, employment status, and monthly income for the weekday and gender, employment status, age, and marriage status for the weekend day. Determinants of the time-activity pattern need to be taken into account in exposure assessment, epidemiological analyses, and exposure simulations, as well as in the development of preventive strategies. As Korean population activity patterns are substantially different from those in Western countries such as USA, Germany, and UK, this information could be critical for exposure assessment in Korea and other Asian countries.
Time-activity data are traditionally collected by telephone interviews or through paper diaries, which are time consuming and costly. As a potential alternative that may greatly save staff time, a web survey to collect time-activity data was developed and tested in this study. We collected 24-h recall web diaries from 151 parents of young children mostly under 55 years of age (who also answered for their children) and 55 older adults (Z55 years of age) both on a weekday and a weekend day every 3 months during an 18-month period. The performance and reliability of the web surveys collected were evaluated, including the survey-completion rate, and the percentage of surveys with unreasonable time being reported as spent sleeping and with missing reports of being in transit between locations. We also compared the web-survey data with time-activity information we collected from the same subjects in telephone interviews and found that these data sources were fairly consistent with each other. However, we observed slightly more compliance issues for the web than the telephone survey, but most of these issues could be addressed and minimized by refining some questions or the survey interface. Our study suggests that it is critical to reduce participants' burden and improve survey interface design for optimal compliance and data quality. In conclusion, web surveys are a promising method to consider for time-activity data collection.
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