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Abstract: Evidence suggests that people living in urban areas have an increased risk of lung cancer due to higher levels of air pollution in these areas. Benzo[a]pyrene (B[a]P) is currently used as the main indicator of carcinogenic polycyclic aromatic hydrocarbons (PAHs) in air pollution, but there is concern that B[a]P may not be the ideal surrogate of choice for PAH mixtures since higher potency PAHs have recently been identified which could potentially contribute more and variably to the overall carcinogenicity. Dibenzo[a, h]anthracene (DBA) and dibenzo[a, l]pyrene (DB[a, l]P) are estimated to have carcinogenic potencies 10 or more times greater than B[a]P but data on their presence and formation in the environment are limited. Several occupational and environmental PAH biomonitoring studies are reviewed here, with particular focus on the specific exposure groups, study design, sample tissue, in particular the use of nasal tissues, and biomarkers used in each study. Consideration of these data is then used to propose a novel biomonitoring approach to evaluate exposure, uptake and the role of high potency PAHs in air pollution-related lung cancer. This is based upon an occupational study examining specific DNA adducts for DBA and DB[a, l]P in nasal cells to evaluate the extent to which these high potency PAHs might contribute to the increased risk of developing lung cancer from air pollution. [Copyright &y& Elsevier]

Abstract: Environmental tobacco smoke (ETS), or second-hand smoke, is a widespread contaminant of indoor air in environments where smoking is not prohibited. It is a significant source of exposure to a large number of substances known to be hazardous to human health. Numerous expert panels have concluded that there is sufficient evidence to classify involuntary smoking (or passive smoking) as carcinogenic to humans. According to the recent evaluation by the International Agency for Research on Cancer, involuntary smoking causes lung cancer in never-smokers with an excess risk in the order of 20% for women and 30% for men. The present paper reviews studies on genotoxicity and related endpoints carried out on ETS since the mid-1980s. The evidence from in vitro studies demonstrates induction of DNA strand breaks, formation of DNA adducts, mutagenicity in bacterial assays and cytogenetic effects. In vivo experiments in rodents have shown that exposure to tobacco smoke, whole-body exposure to mainstream smoke (MS), sidestream smoke (SS), or their mixture, causes DNA single strand breaks, aromatic adducts and oxidative damage to DNA, chromosome aberrations and micronuclei. Genotoxicity of transplacental exposure to ETS has also been reported. Review of human biomarker studies conducted among non-smokers with involuntary exposure to tobacco smoke indicates presence of DNA adducts, urinary metabolites of carcinogens, urinary mutagenicity, SCEs and hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene mutations (in newborns exposed through involuntary smoking of the mother). Studies on human lung cancer from smokers and never-smokers involuntarily exposed to tobacco smoke suggest occurrence of similar kinds of genetic alterations in both groups. In conclusion, these overwhelming data are compatible with the current knowledge on the mechanisms of carcinogenesis of tobacco-related cancers, occurring not only in smokers but with a high biological plausibility also in involuntary smokers. [Copyright &y& Elsevier]

The US Environmental Protection Agency has recently performed the Research Triangle Park Particulate Matter Panel Study. This was a 1-year investigation of PM and related co-pollutants involving participants living within the RTP area of North Carolina. Primary goals were to characterize the relationships between ambient and residential PM measures to those obtained from personal exposure monitoring and estimate ambient source contributions to personal and indoor mass concentrations. A total of 38 participants living in 37 homes were involved in personal, residential indoor, residential outdoor and ambient PM2.5 exposure monitoring. Participants were 30 non-smoking hypertensive African-Americans living in a low-moderate SES neighborhood (SE Raleigh, NC) and a cohort of eight individuals having implanted cardiac defibrillators (Chapel Hill, NC). Residential and ambient monitoring of PM10 and PM10–2.5 (coarse by differential) was also performed. The volunteers were monitored for seven consecutive days during each of four seasons (summer 2000, fall 2000, winter 2001, spring 2001). Individual PM2.5 personal exposure concentrations ranged from 4 to 218 μg m−3 during the study. The highest personal exposures were determined to be the result of passive environmental tobacco exposures. Subsequently, ∼7% of the total number of personal exposure trials were excluded to minimize this pollutant''s effect upon the overall analysis. Results indicated that a pooled data set (seasons, cohorts, residences, participants) was appropriate for investigation of the basic mass concentration relationships. Daily personal PM2.5 mass concentrations were typically higher than their associated residential or ambient measurements (mean personal=23.0, indoor=19.1, outdoor=19.3, ambient=19.2 μg m−3). Mean personal PM2.5 exposures were observed to be only moderately correlated to ambient PM2.5 concentrations (r=0.39). [Copyright &y& Elsevier]

Recent animal studies indicate that the adolescent brain is especially vulnerable to nicotine-induced alterations in synaptic function, echoing the increased susceptibility to nicotine dependence and withdrawal noted for adolescent smokers. We administered nicotine to adolescent rats via continuous minipump infusions from PN30 to PN47.5, using 6 mg/kg/day, a dose rate that replicates the plasma nicotine levels found in smokers, and examined the effects on cell signaling mediated through adenylyl cyclase (AC) and its response to catecholamines. Studies were conducted during nicotine administration (PN45) and in the posttreatment, withdrawal period (PN50, 60, 75). Adolescent nicotine augmented AC activity as evidenced by increased responsiveness to the direct AC stimulants, forskolin and Mn2+. The effects on AC were equally noted in brain regions enriched (striatum) or sparse (cerebellum) in cholinergic projections, implying that the effects are secondary to activation/repression of neural circuits, rather than representing direct effects on AC mediated by nicotinic cholinergic receptors. AC responses to dopaminergic and noradrenergic stimulants were also enhanced by nicotine exposure. However, in contrast to earlier work with serotonin-mediated responses, the effects on catecholaminergic stimulation were smaller and did not display the sex-dependence noted for serotonin. An alternate administration paradigm that maximizes episodic withdrawal (twice-daily nicotine injections) induced AC more rapidly at lower nicotine doses. Our results indicate that adolescent nicotine exposure elicits lasting alterations in synaptic signaling that intensify and persist during withdrawal. These findings support the concept that the adolescent brain is especially susceptible to persistent nicotine-induced alterations. [Copyright &y& Elsevier]

In the fetus, nicotine is a neuroteratogen that elicits cell damage and loss and subsequent abnormalities of synaptic function. We explored whether these effects extend into adolescence, the period when most people begin smoking. Beginning on postnatal day 30, rats were given a 1 week regimen of nicotine infusions or twice-daily injections, at doses (0.6, 2 and 6 mg/kg/day) set to achieve plasma levels found in occasional to regular smokers. We assessed indices of cell packing density and cell number (DNA concentration and content), cell size (total protein/DNA ratio) and neuritic projections (membrane/total protein) in the midbrain, hippocampus and cerebral cortex, three regions known to be vulnerable to developmental effects of nicotine. With either route of administration, nicotine evoked shortfalls in DNA concentration and content, compensatory elevations of total protein/DNA, and reductions in the membrane/total protein ratio. Nearly all of the effects were apparent even at the lowest dose of nicotine and remained fully evident 1 month posttreatment. Although both males and females showed significant alterations, in general the effects were larger in females. Our results indicate that in adolescence, even a brief period of continuous or intermittent nicotine exposure, elicits lasting alterations in biomarkers associated with cellular and neuritic damage. As the effects are detected at exposures that produce plasma concentrations one-tenth of those in regular smokers, the exquisite sensitivity of the adolescent brain to nicotine neurotoxicity may contribute to lasting neurobehavioral damage even in occasional smokers. [Copyright &y& Elsevier]

India is the second most populous country in the world with a population of nearly 1.3 billion, comprising 20% of the global population. There are an estimated 37.5 million cases of asthma in India, and recent studies have reported a rise in prevalence of allergic rhinitis and asthma. Overall, 40-50% of paediatric asthma cases in India are uncontrolled or severe. Treatment of allergic rhinitis and asthma is sub-optimal in a significant proportion of cases due to multiple factors relating to unaffordability to buy medications, low national gross domestic product, religious beliefs, myths and stigma regarding chronic ailment, illiteracy, lack of allergy specialists, and lack of access to allergen-specific immunotherapy for allergic rhinitis and biologics for severe asthma. High quality allergen extracts for skin tests and adrenaline auto-injectors are currently not available in India. Higher postgraduate specialist training programmes in Allergy and Immunology are also not available. Another major challenge for the vast majority of the Indian population is an unacceptably high level of exposure to particulate matter (PM) 2.5 generated from traffic pollution and use of fossil fuel and biomass fuel and burning of incense sticks and mosquito coils. This review provides an overview of the burden of allergic disorders in India. It appraises current evidence and justifies an urgent need for a strategic multipronged approach to enhance quality of care for allergic disorders. This may include creating an infrastructure for education and training of healthcare professionals and patients and involving regulatory authorities for making essential treatments accessible at subsidised prices. It calls for research into better phenotypic characterisation of allergic disorders, as evidence generated from high income western countries are not directly applicable to India, due to important confounders such as ethnicity, air pollution, high rates of parasitic infestation, and other infections., Competing Interests: MTKs department received educational grant from ALK Abello, MEDA, Thermo Fisher and other companies for annual PracticAllergy course in recent years. MTK received funds from ALK Abello to attend EAACI conference. Other authors have no conflict of interest to declare., (© 2020 Published by Elsevier Inc. on behalf of World Allergy Organization.)

Background: Some studies have shown associations of maternal age at delivery with asthma and food allergy in offspring. However, the relationship between maternal age at delivery and allergic rhinitis is largely unclear. This study aimed to investigate the association between maternal age at delivery and allergic rhinitis in a population sample of Asian children, and to explore potential effect modifiers., Methods: A total of 1344 singleton-birth children (763 boys, 56.8%; mean age, 6.4 years) participating in the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren (LIGHTS) cohort were evaluated by a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire and interviewed by pediatricians. Allergic sensitization was determined by using Phadiatop Infant. Multiple logistic regression models with covariates adjustment were performed to investigate the association of maternal age at delivery with allergic rhinitis and allergic sensitization in offspring., Results: Among 1344 study children, 793 (59%) had physician-diagnosed allergic rhinitis. Advanced maternal age at delivery (≥40 years) was significantly associated with increased odds of allergic rhinitis (adjusted odds ratio [AOR] = 4.58, 95% confidence interval [CI]: 1.90-11.03) and allergic sensitization (AOR = 2.86, 95% CI: 1.13-7.22) in offspring. A sex-stratified analysis revealed that the association of advanced maternal age with allergic rhinitis was statistically significant only in female offspring (AOR = 7.02, 95% CI: 1.89-26.14). Stratified analyses by birth order or environmental tobacco smoke exposure during pregnancy did not reveal any significant differences., Conclusion: Advanced maternal age at delivery was associated with increased risk of allergic rhinitis in Asian children, probably more pronounced among girls., (© 2020 The Authors.)

Background: Food allergy (FA) is a common public health problem that affects both children and adults. Empirical knowledge of the burden of FA in Kuwait is limited. This study sought to estimate the prevalence of FA among schoolchildren in Kuwait and assess associations between FA and the coexistence and severity of asthma, rhinitis, and eczema., Methods: Schoolchildren aged 11-14 years (n = 3,864) were enrolled in a cross-sectional study. Parents completed questionnaires regarding their children's early life exposures and clinical history of FA and allergic diseases. Study-defined FA was ascertained by a convincing clinical history. Associations were assessed using Poisson regression with robust variance estimation, and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated., Results: The 12-month prevalence of study-defined FA was estimated to be 4.1% (154/3,738), with more girls being affected than boys (aPR = 1.44, 95% CI: 1.04-1.99). Egg (2.7%), fish (1.6%), shellfish (1.3%), peanut (1.3%), and tree nut (1.2%) were the most reported offending food allergens. Underweight and adiposity, cesarean section delivery, exposure to household dogs during infancy, and parental history of doctor-diagnosed FA were associated with an increased prevalence of study-defined FA. However, later birth order was associated with a reduced prevalence of study-defined FA. The prevalence of eczema only was higher in children with study-defined FA than in those without study-defined FA (aPR = 3.49, 95% CI: 2.37-5.14). In contrast, this association was not pronounced for children who had asthma only (aPR = 1.56, 95% CI: 0.94-2.57) or rhinitis only (aPR = 1.40, 95% CI: 0.86-2.28). Study-defined FA was associated with a 9.20-fold (95% CI: 4.50-18.78) higher prevalence of coexisting asthma, rhinitis, and eczema. Moreover, study-defined FA was associated with increased severity of symptoms of asthma, rhinitis, and eczema., Conclusions: FA affects a considerable proportion of schoolchildren in Kuwait, and the most reported offending food allergens are similar to those reported in Western countries. Study-defined FA was associated with the coexistence and increased severity of asthma, rhinitis, and eczema, indicating that FA may link the comanifestations of allergic diseases and contribute to their chronicity and severity.