Papers of the Month
By Adeline Lopez
Air cleaners may improve COPD
Portable air cleaners may improve respiratory symptoms among former smokers with chronic obstructive pulmonary disease (COPD), according to an NIEHS-funded study. This is the first such environmental intervention to show potential health benefits of reduced indoor pollution among these individuals.
COPD is a progressive disease characterized by lung injury and inflammation, and there are limited treatment options. Smoking cessation can slow the advancement of COPD, but former smokers continue to be affected by the disease, which can be worsened by exposure to air pollutants such as particulate matter and nitrogen dioxide.
The team conducted a blinded, randomized controlled trial of 116 former smokers with moderate to severe COPD. Participants received active or sham portable HEPA air cleaners for their homes and were followed for six months.
The active HEPA filter group experienced reduced respiratory symptoms and fewer urgent health care visits compared with the sham group. They also had lower rates of systemic steroid, antibiotic, or rescue medication use. Active HEPA filter users performed better on the breathlessness, cough, and sputum scale, and had better functional respiratory capacity compared with the sham group.
According to the authors, interventions that improve indoor air quality represent a potentially novel approach for improving respiratory health in patients with COPD.
Citation: Hansel NN, Putcha N, Woo H, Peng R, Diette GB, Fawzy A, Wise RA, Romero K, Davis MF, Rule AM, Eakin MN, Breysse PN, McCormack MC, Koehler K. 2021. Randomized clinical trial of air cleaners to improve indoor air quality and COPD health: results of the CLEAN AIR STUDY. Am J Respir Crit Care Med; doi:10.1164/rccm.202103-0604OC. [Online 27 August 2021]
Tool quantifies differences in DNA repair among individuals
CometChip — a high-throughput tool developed with NIEHS funds to quantify DNA damage — can be used to measure differences among individuals in terms of their bodies’ capacity to repair such damage, according to a recent institute-supported study. That information may help to shed light on how much of a person’s disease risk is due to genetic versus environmental factors.
DNA damage can lead to mutations that drive diseases such as cancer, but damage levels and resulting genetic mutations can vary greatly among individuals due to differences in their genetics. Relatively few studies have evaluated variation in DNA repair capacity between individuals, and most of those involved small sample sizes.
Using CometChip, researchers explored DNA repair within individuals over time. They measured levels of DNA damage in cells collected from more than 50 people at multiple timepoints following oxidative damage and used Comet measurements in cultured cells as a control. Their analysis included more than 1,500 samples and more than 150,000 data points.
The team reported significant variability in DNA repair efficiency among individuals, with a 9.5-fold difference between the fastest and slowest repair rates. The researchers also observed differences in repair rates between visits for the same individual, indicating that DNA damage levels vary over time and may be affected by environmental factors.
According to the authors, CometChip may be useful for detecting differences in DNA repair capacity in large-scale clinical studies. They note that identifying people with reduced DNA repair capacity could inform personalized medical treatments.
Citation: Ngo LP, Kaushal S, Chaim IA, Mazzucato P, Ricciardi C, Samson LD, Nagel ZD, Engelward BP. 2021. CometChip analysis of human primary lymphocytes enables quantification of inter-individual differences in the kinetics of repair of oxidative DNA damage. Free Radic Biol Med 174:89–99.
Pancreatic cancer signatures point to early detection, new treatments
Researchers funded in part by NIEHS identified promising new targets for treatment and early diagnosis of pancreatic cancer after examining various aspects of tumor genes and proteins. The international team sought to reveal the underlying molecular changes that drive the development and progression of pancreatic ductal adenocarcinoma (PDAC), a highly aggressive condition with poor patient survival.
Using samples from 140 pancreatic cancers and more than 70 normal pancreatic tissues, they carried out genomic, RNA, and microRNA sequencing, combined with detailed analyses of protein modifications. The team verified mutations in several genes as major drivers of PDAC. Focusing on 222 proteins that were at least twice as abundant in cancerous cells than in normal cells, they identified 12 proteins that they say could aid early detection in blood samples.
They also found nearly 5,000 sites within these proteins with increased phosphate groups and more than 1,700 sites with increased carbohydrate chains. The team said several of these patterns offered clues for treatment, such as blocking the enzymes involved in specific protein modifications associated with PDAC.
Such integrated gene and protein sequencing can aid early detection of PDAC and help researchers identify novel therapeutic targets, according to the authors.
Citation: Cao L, Huang C, Cui Zhou D, Hu Y, Lih TM, Savage SR, Krug K, Clark DJ, Schnaubelt M, Chen L, da Veiga Leprevost F, Eguez RV, Yang W, Pan J, Wen B, Dou Y, Jiang W, Liao Y, Shi Z, Terekhanova NV, Cao S, Lu RJ, Li Y, Liu R, Zhu H, Ronning P, Wu Y, Wyczalkowski MA, Easwaran H, Danilova L, Mer AS, Yoo S, Wang JM, Liu W, Haibe-Kains B, Thiagarajan M, Jewell SD, Hostetter G, Newton CJ, Li QK, Roehrl MH, Fenyö D, Wang P, Nesvizhskii AI, Mani DR, Omenn GS, Boja ES, Mesri M, Robles AI, Rodriguez H, Bathe OF, Chan DW, Hruban RH, Ding L, Zhang B, Zhang H; Clinical Proteomic Tumor Analysis Consortium. 2021. Proteogenomic characterization of pancreatic ductal adenocarcinoma. Cell 184(19):5031–5052.e26.
Cord blood profile may predict preterm birth
In the most comprehensive analysis of cord serum to date, NIEHS-funded researchers identified elevated levels of several metals as key drivers of preterm birth risk. Preterm birth, which occurs before 37 weeks of pregnancy, is a risk factor for newborn mortality and adverse health effects in childhood and later in life.
Researchers analyzed levels of 56 chemicals in umbilical cord serum collected from 745 pregnant women enrolled in a birth cohort in Bangladesh between 2008 and 2011. Using advanced statistical techniques, they examined the effect of individual chemicals and mixtures of chemicals on preterm birth.
The team found titanium, arsenic, and barium were the most important predictors of preterm birth, with evidence of an interactive effect between arsenic and barium. They also constructed chemical risk scores to measure mixture effects and found that women with the highest scores were nearly four times more likely to experience preterm birth than women with the lowest scores.
According to the authors, these findings highlight the importance of considering chemical mixture effects in human health studies.
Citation: Huang H, Wei L, Chen X, Zhang R, Su L, Rahman M, Golam Mostofa M, Qamruzzaman Q, Zhao Y, Yu H, Wei Y, Christiani DC, Chen F. 2021. Cord serum elementomics profiling of 56 elements depicts risk of preterm birth: evidence from a prospective birth cohort in rural Bangladesh. Environ Int 156:10673.