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Seasonal Antimicrobial Activity of the Airway: Post-Hoc Analysis of a Randomized Placebo-Controlled Double-Blind Trial.
Vargas Buonfiglio, LG, Vanegas Calderon, OG, Cano, M, Simmering, JE, Polgreen, PM, Zabner, J, Gerke, AK, Comellas, AP
Nutrients. 2020;(9)
Abstract
BACKGROUND It is widely unknown why respiratory infections follow a seasonal pattern. Variations in ultraviolet B (UVB) light during seasons affects cutaneous synthesis of vitamin D3. Serum vitamin D concentration influences the expression of airway surface liquid (ASL) antimicrobial peptides such as LL-37. OBJECTIVE We sought to determine the effect of seasons on serum vitamin D levels and ASL antimicrobial activity. METHODS Forty participants, 18-60 years old, were randomized 1:1 to receive 90 days of 1000 IU vitamin D3 or placebo. We collected ASL via bronchoscopy and measured serum 25(OH) vitamin D from participants before and after intervention across seasons. We measured ASL antimicrobial activity by challenging samples with bioluminescent Staphylococcus aureus and measured relative light units (RLUs) after four minutes. We also investigated the role of LL-37 using a monoclonal neutralizing antibody. RESULTS We found that participants, prior to any intervention, during summer-fall (n = 20) compared to winter-spring (n = 20) had (1) decreased live bacteria after challenge (5542 ± 175.2 vs. 6585 ± 279 RLU, p = 0.003) and (2) higher serum vitamin D (88.25 ± 24.25 vs. 67.5 ± 45.25 nmol/L, p = 0.026). Supplementation with vitamin D3 increased vitamin D levels and restored ASL antimicrobial activity only during the winter-spring. The increased ASL antimicrobial activity seen during the summer-fall was abrogated by adding the LL-37 neutralizing antibody. CONCLUSION ASL kills bacteria more effectively during the summer-fall compared to the winter-spring. Supplementation of vitamin D during winter-spring restores ASL antimicrobial activity by increasing the expression of antimicrobial peptides including LL-37.
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Personal level exposure and hazard potential of particulate matter during haze and non-haze periods in Singapore.
George, S, Chua, ML, ZheWei, DZ, Das, R, Bijin, VA, Connolly, JE, Lee, KP, Yung, CF, Teoh, OH, Thomas, B
Chemosphere. 2020;:125401
Abstract
Severe haze episodes originating from biomass burning are common in Southeast Asia. However, there is a paucity of data on the personal exposure and characteristics of Particulate Matter (PM) present in ambient air during haze and non-haze periods. Aims of this study were to monitor 24 h ambulatory exposure to PM among school children in Singapore; characterize haze and non-haze PM for their physicochemical properties, cytotoxicity and inflammatory potential, using bronchial epithelial cell culture model (BEAS-2B). Forty-six children had ambulatory PM exposure monitored using portable Aethalometer and their hourly activity recorded. The mean (±SE) PM exposure on a typical school day was 3343 (±174.4) ng/m3/min. Higher PM exposure was observed during haze periods and during commuting to and from the school. Characterization of PM collected showed a drastic increase in the proportion of ultrafine particle (UFP) in haze PM. These PM fraction showed higher level of sulphur, potassium and trace metals in comparison to those collected during non-haze periods. Dose dependent increases in abiotic reactive oxygen species generation, activation of NF-κB and cytotoxicity were observed for both haze and non-haze PM. Generally, haze PM induced significantly higher release of IL-6, IL-8 and TNFα by BEAS-2B cells in comparison to non-haze PM. In summary, this study provides experimental evidence for higher PM exposure during haze period which has the potential to elicit oxidative stress and pro-inflammatory cytokine release from airway epithelial cells.
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Asthma, Environment and Pollution: Where the Rubber Hits the Road.
Krishnan, S, Panacherry, S
Indian journal of pediatrics. 2018;(10):893-898
Abstract
The detrimental effects of environmental pollution on one's health are undeniable and have been demonstrated time and time again. Breathing in pollutants in ambient air often has consequences throughout the body, including cardiovascular disease, effects on the reproductive system, and oncologic implications. In the respiratory system, chronic exposure yields a number of outcomes, including chronic obstructive pulmonary disease (COPD) and asthma exacerbations, increased rates of hospitalizations, and increased severity of acute illnesses. On a macro-level, this morbidity and mortality then leads to vast and far-reaching public health consequences the world over, including the loss of billions of dollars' worth of labor. This is especially applicable in developing countries, which often undergo rapid growth, industrialization and urbanization with a resultant increase in vehicular traffic, coal combustion, and fuel emissions as a whole. For this reason, environmental pollutants have been studied extensively, and countries around the globe have established laws that regulate ambient air levels of so-called criteria pollutants. This article will explore several of these criteria pollutants, including particulate matter, nitrogen dioxide, sulfur dioxide, and ozone, and their individual relationships to asthma pathophysiology. However, it is also emphasized that though each one of these toxins yields its own effects, the group of them often works together to have cumulative consequences. For these reasons and many more, it is important to remain aware and educated about these omnipresent environmental pollutants.
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Challenges and future direction of molecular research in air pollution-related lung cancers.
Shahadin, MS, Ab Mutalib, NS, Latif, MT, Greene, CM, Hassan, T
Lung cancer (Amsterdam, Netherlands). 2018;:69-75
Abstract
Hazardous air pollutants or chemical release into the environment by a variety of natural and/or anthropogenic activities may give adverse effects to human health. Air pollutants such as sulphur dioxide (SO2), nitrogen oxides (NOx), carbon monoxide (CO), heavy metals and particulate matter (PM) affect number of different human organs, especially the respiratory system. The International Agency for Research on Cancer (IARC) reported that ambient air pollution is a cause of lung cancer. Recently, the agency has classified outdoor air pollution as well as PM air pollution as Group 1 carcinogens. In addition, several epidemiological studies have shown a positive association between air pollutants to lung cancer risks and mortality. However, there are only a few studies examining the molecular effects of air pollution exposure specifically in lung cancer due to multiple challenges to mimic air pollution exposure in basic experimentation. Another major issue is the lack of adequate adjustments for exposure misclassification as air pollution may differ temporo-spatially and socioeconomically. Thus, the purpose of this paper is to review the current molecular understanding of air pollution-related lung cancer and potential future direction in this challenging yet important research field.
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5.
Drug Resistance and Gene Transfer Mechanisms in Respiratory/Oral Bacteria.
Jiang, S, Zeng, J, Zhou, X, Li, Y
Journal of dental research. 2018;(10):1092-1099
Abstract
Growing evidence suggests the existence of new antibiotic resistance mechanisms. Recent studies have revealed that quorum-quenching enzymes, such as MacQ, are involved in both antibiotic resistance and cell-cell communication. Furthermore, some small bacterial regulatory RNAs, classified into RNA attenuators and small RNAs, modulate the expression of resistance genes. For example, small RNA sprX, can shape bacterial resistance to glycopeptide antibiotics via specific downregulation of protein SpoVG. Moreover, some bacterial lipocalins capture antibiotics in the extracellular space, contributing to severe multidrug resistance. But this defense mechanism may be influenced by Agr-regulated toxins and liposoluble vitamins. Outer membrane porin proteins and efflux pumps can influence intracellular concentrations of antibiotics. Alterations in target enzymes or antibiotics prevent binding to targets, which act to confer high levels of resistance in respiratory/oral bacteria. As described recently, horizontal gene transfer, including conjugation, transduction and transformation, is common in respiratory/oral microflora. Many conjugative transposons and plasmids discovered to date encode antibiotic resistance proteins and can be transferred from donor bacteria to transient recipient bacteria. New classes of mobile genetic elements are also being identified. For example, nucleic acids that circulate in the bloodstream (circulating nucleic acids) can integrate into the host cell genome by up-regulation of DNA damage and repair pathways. With multidrug resistant bacteria on the rise, new drugs have been developed to combate bacterial antibiotic resistance, such as innate defense regulators, reactive oxygen species and microbial volatile compounds. This review summaries various aspects and mechanisms of antibiotic resistance in the respiratory/oral microbiota. A better understanding of these mechanisms will facilitate minimization of the emergence of antibiotic resistance.
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Anaerobic bacteria cultured from cystic fibrosis airways correlate to milder disease: a multisite study.
Muhlebach, MS, Hatch, JE, Einarsson, GG, McGrath, SJ, Gilipin, DF, Lavelle, G, Mirkovic, B, Murray, MA, McNally, P, Gotman, N, et al
The European respiratory journal. 2018;(1)
Abstract
Anaerobic and aerobic bacteria were quantitated in respiratory samples across three cystic fibrosis (CF) centres using extended culture methods. Subjects aged 1-69 years who were clinically stable provided sputum (n=200) or bronchoalveolar lavage (n=55). 18 anaerobic and 39 aerobic genera were cultured from 59% and 95% of samples, respectively; 16 out of 57 genera had a ≥5% prevalence across centres.Analyses of microbial communities using co-occurrence networks in sputum samples showed groupings of oral, including anaerobic, bacteria, whereas typical CF pathogens formed distinct entities. Pseudomonas was associated with worse nutrition and F508del genotype, whereas anaerobe prevalence was positively associated with pancreatic sufficiency, better nutrition and better lung function. A higher total anaerobe/total aerobe CFU ratio was associated with pancreatic sufficiency and better nutrition. Subjects grouped by factor analysis who had relative dominance of anaerobes over aerobes had milder disease compared with a Pseudomonas-dominated group with similar proportions of subjects that were homozygous for F508del.In summary, anaerobic bacteria occurred at an early age. In sputum-producing subjects anaerobic bacteria were associated with milder disease, suggesting that targeted eradication of anaerobes may not be warranted in sputum-producing CF subjects.
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The aetiology of diarrhoea, pneumonia and respiratory colonization of HIV-exposed infants randomized to breast- or formula-feeding.
Zash, RM, Shapiro, RL, Leidner, J, Wester, C, McAdam, AJ, Hodinka, RL, Thior, I, Moffat, C, Makhema, J, McIntosh, K, et al
Paediatrics and international child health. 2016;(3):189-97
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Abstract
BACKGROUND Diarrhoea and pneumonia are common causes of childhood death in sub-Saharan Africa but there are few studies describing specific pathogens. OBJECTIVES The study aimed to describe the pathogens associated with diarrhoea, pneumonia and oropharyngeal colonization in children born to HIV-infected women (HIV-exposed infants). METHODS The Mashi Study randomized 1200 HIV-infected women and their infants to breastfeed for 6 months with ZDV prophylaxis or formula-feed with 4 weeks of ZDV. Children were tested for HIV by PCR at 1, 4, 7, 9 and 12 months and by ELISA at 18 months. Pre-defined subsets of children were sampled during episodes of diarrhoea (n = 300) and pneumonia (n = 85). Stool was tested for bacterial pathogens, rotavirus and parasites. Children with pneumonia underwent bacterial blood culture, and testing of nasopharyngeal aspirates for viral pathogens by PCR. Oropharyngeal swabs were collected from a consecutive subset of 561 infants at the routine 3-month visit for bacterial culture. RESULTS The median age (range) at sampling was 181 days for diarrhoea (0-730) and 140 days for pneumonia (2-551). Pathogens were identified in 55 (18%) children with diarrhoea and 32 (38%) with pneumonia. No differences in pathogens by child HIV status (HIV-infected vs HIV-uninfected) or feeding strategy were identified. Campylobacter was the most common diarrhoeal pathogen (7%). Adenovirus (22%) and other viruses (19%) were the primary pathogens isolated during pneumonias. More formula-fed infants had oropharyngeal colonization by pathogenic Gram-negative bacteria (16.8% vs 6.2%, P = 0.003), which was associated with a non-significant increased risk of pneumonia (OR 2.2, 95% CI 0.8-5.7). CONCLUSION A trend toward oropharyngeal bacterial colonization was observed in formula-fed infants. Although viruses were most commonly detected during pneumonia, respiratory colonization by Gram-negative bacteria may have contributed to pneumonia in formula-fed infants.
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The effects of lutein on respiratory health across the life course: A systematic review.
Melo van Lent, D, Leermakers, ETM, Darweesh, SKL, Moreira, EM, Tielemans, MJ, Muka, T, Vitezova, A, Chowdhury, R, Bramer, WM, Brusselle, GG, et al
Clinical nutrition ESPEN. 2016;:e1-e7
Abstract
BACKGROUND Lutein, a fat-soluble carotenoid present in green leafy vegetables and eggs, has strong antioxidant properties and could therefore be important for respiratory health. DESIGN We systematically reviewed the literature for articles that evaluated associations of lutein (intake, supplements or blood levels) with respiratory outcomes, published in Medline, Embase, Cochrane Central, PubMed, Web of Science and Google Scholar, up to August 2014. RESULTS We identified one Randomized Control Trial (RCT), two longitudinal, four prospective and six cross-sectional studies. The individual studies obtained a Quality Score ranging between 3 and 9. Six studies were performed in children, which examined bronchopulmonary dysplasia (BPD), asthma and wheezing. In adults, 7 studies investigated asthma, respiratory function and respiratory mortality. The RCT found a borderline significant effect of lutein/zeaxanthin supplementation in neonates on the risk of BPD (OR 0.43 (95% CI 0.15; 1.17). No association was found between lutein intake or levels and respiratory outcomes in children. A case-control study in adults showed lower lutein levels in asthma cases. Three studies, with a prospective or longitudinal study design, in adults found a small but a significant positive association between lutein intake or levels and respiratory function. No association was found in the other two studies. In relation to respiratory mortality, one longitudinal study showed that higher lutein blood levels were associated with a decreased mortality (HR 0.77 (95% CI 0.60; 0.99), per SD increase in lutein). CONCLUSION The published literature suggests a possible positive association between lutein and respiratory health. However, the literature is scarce and most studies are of observational nature.
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The in vitro generation of lung and airway progenitor cells from human pluripotent stem cells.
Huang, SX, Green, MD, de Carvalho, AT, Mumau, M, Chen, YW, D'Souza, SL, Snoeck, HW
Nature protocols. 2015;(3):413-25
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Abstract
Lung and airway epithelial cells generated in vitro from human pluripotent stem cells (hPSCs) have applications in regenerative medicine, modeling of lung disease, drug screening and studies of human lung development. Here we describe a strategy for directed differentiation of hPSCs into developmental lung progenitors, and their subsequent differentiation into predominantly distal lung epithelial cells. The protocol entails four stages that recapitulate lung development, and it takes ∼50 d. First, definitive endoderm (DE) is induced in the presence of high concentrations of activin A. Subsequently, lung-biased anterior foregut endoderm (AFE) is specified by sequential inhibition of bone morphogenetic protein (BMP), transforming growth factor-β (TGF-β) and Wnt signaling. AFE is then ventralized by applying Wnt, BMP, fibroblast growth factor (FGF) and retinoic acid (RA) signaling to obtain lung and airway progenitors. Finally, these are further differentiated into more mature epithelial cells types using Wnt, FGF, cAMP and glucocorticoid agonism. This protocol is conducted in defined conditions, it does not involve genetic manipulation of the cells and it results in cultures in which the majority of the cells express markers of various lung and airway epithelial cells, with a predominance of cells identifiable as functional type II alveolar epithelial cells.
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Taste receptors in innate immunity.
Lee, RJ, Cohen, NA
Cellular and molecular life sciences : CMLS. 2015;(2):217-36
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Abstract
Taste receptors were first identified on the tongue, where they initiate a signaling pathway that communicates information to the brain about the nutrient content or potential toxicity of ingested foods. However, recent research has shown that taste receptors are also expressed in a myriad of other tissues, from the airway and gastrointestinal epithelia to the pancreas and brain. The functions of many of these extraoral taste receptors remain unknown, but emerging evidence suggests that bitter and sweet taste receptors in the airway are important sentinels of innate immunity. This review discusses taste receptor signaling, focusing on the G-protein-coupled receptors that detect bitter, sweet, and savory tastes, followed by an overview of extraoral taste receptors and in-depth discussion of studies demonstrating the roles of taste receptors in airway innate immunity. Future research on extraoral taste receptors has significant potential for identification of novel immune mechanisms and insights into host-pathogen interactions.