The human lung tissue microbiota remains largely uncharacterized, although a number of studies based on airway samples suggest the existence of a viable human lung microbiota. Here we characterized ...the taxonomic and derived functional profiles of lung microbiota in 165 non-malignant lung tissue samples from cancer patients.
We show that the lung microbiota is distinct from the microbial communities in oral, nasal, stool, skin, and vagina, with Proteobacteria as the dominant phylum (60 %). Microbiota taxonomic alpha diversity increases with environmental exposures, such as air particulates, residence in low to high population density areas, and pack-years of tobacco smoking and decreases in subjects with history of chronic bronchitis. Genus Thermus is more abundant in tissue from advanced stage (IIIB, IV) patients, while Legionella is higher in patients who develop metastases. Moreover, the non-malignant lung tissues have higher microbiota alpha diversity than the paired tumors.
Our results provide insights into the human lung microbiota composition and function and their link to human lifestyle and clinical outcomes. Studies among subjects without lung cancer are needed to confirm our findings.
Abstract
Background
The shape of the exposure-response curve describing the effects of air pollution on population health has crucial regulatory implications, and it is important in assessing causal ...impacts of hypothetical policies of air pollution reduction.
Methods
After having reformulated the problem of assessing the short-term impact of air pollution on health within the potential outcome approach to causal inference, we developed a method based on the generalized propensity score (GPS) to estimate the average dose-response function (aDRF) and quantify attributable deaths under different counterfactual scenarios of air pollution reduction. We applied the proposed approach to assess the impact of airborne particles with a diameter less than or equal to 10
μ
m (PM
10
) on deaths from natural, cardiovascular and respiratory causes in the city of Milan, Italy (2003-2006).
Results
As opposed to what is commonly assumed, the estimated aDRFs were not linear, being steeper for low-moderate values of exposure. In the case of natural mortality, the curve became flatter for higher levels; this behavior was less pronounced for cause-specific mortality. The effect was larger in days characterized by higher temperature. According to the curves, we estimated that a hypothetical intervention able to set the daily exposure levels exceeding 40
μ
g/m
3
to exactly 40 would have avoided 1157 deaths (90%CI: 689, 1645) in the whole study period, 312 of which for respiratory causes and 771 for cardiovascular causes. These impacts were higher than those obtained previously from regression-based methods.
Conclusion
This novel method based on the GPS allowed estimating the average dose-response function and calculating attributable deaths, without requiring strong assumptions about the shape of the relationship. Its potential as a tool for investigating effect modification by temperature and its use in other environmental epidemiology contexts deserve further investigation.
Abstract Background The National Institute for Occupational Safety and Health (NIOSH), in 2011, developed the “ Total Worker Health ®” (TWH) as a holistic approach to protect and promote the workers’ ...safety, health, and well-being. After over ten years from the TWH development, the aim of the present systematic review is to provide a comprehensive overview of the worldwide TWH initiatives. Methods PubMed, Scopus and ISI Web of Science were searched for TWH studies published up to the 31 st of July 2023, and 43 investigations could be included. The review was registered on the International prospective register of systematic reviews PROSPERO with the reference number CRD42023416972. Results Issues that emerged as relevant for the TWH operationalization were the awareness about the TWH approach and fundamentals, the leadership commitment, and a participatory engagement of the workforce: these aspects all contributed to acceptable and effective setting oriented TWH plans, specifically tailored on the peculiarities of the workplace, including small enterprises and multiemployer worksites. Evaluation and continual improvement were reported as fundamental for the successful implementation of TWH initiatives. Limited resources for safety and health initiatives, in terms of time, people, and funds, together with difficulties in the identification of safety and health priorities and a poor participatory culture were recognized as obstacles to the TWH application. Training resulted the core component of the TWH leadership and workforce preparedness, with beneficial results in terms of safety culture and adoption of preventive measures. Conclusions Although interesting aspects emerged from our review, future longitudinal investigations should confirm the effectiveness, easy integration, and long-term sustainability of TWH models in different workplaces, in order to effectively support safe and health-enhancing works able to improve innovation and productivity.
SARS-CoV-2 symptoms are non-specific and can range from asymptomatic presentation to severe pneumonia. Asymptomatic subjects carrying SARS-CoV-2 often remain undiagnosed and it is still debated ...whether they develop immunoglobulins (Ig) and how long they persist. The aim of this study was to investigate the development and persistence of antibodies against SARS-CoV-2 in asymptomatic subjects infected by the virus. This follow-up study was performed on the 31 asymptomatic subjects who presented a positive nasal swab or serology against SARS-CoV-2 (Ig against Spike-RBD) in the first part of the UNICORN study (March 2020) aimed at attesting previous or current contacts with the virus in the personnel of the University of Milan. Eight weeks after the first Ig measure, these subjects were invited to donate a second blood sample for testing serum antibodies (IgM, IgG and total antibodies) and to fill-in a structured questionnaire. About 80% of asymptomatic subjects did not present circulating immunoglobulins against SARS-CoV-2 after 8 weeks from a positive nasal swab against the virus. Moreover, in more than 40% of these subjects, no Ig against SARS-CoV-2 were detected at any time. Finally, about two third of subjects with immunoglobulins at baseline did not present IgG against SARS-CoV-2 after 8 weeks. The majority of subjects who developed an asymptomatic SARS-CoV-2 infection do not present antibodies against the RBD-spike protein after 8 weeks of follow-up. These data should be taken into account for the interpretation of the serological evidences on SARS-CoV-2 that are emerging nowadays.
Cohort studies in Europe, but not in North-America, showed an association between exposure to outdoor particulate matter with aerodynamic diameter ≤10 μm (PM10) and lung cancer risk. Only a ...case-control study on lung cancer and PM10 in South Korea has so far been performed. For the first time in Europe we analyzed quantitatively this association using a case-control study design in highly polluted areas in Italy.
The Environment And Genetics in Lung cancer Etiology (EAGLE) study, a population-based case-control study performed in the period 2002-2005 in the Lombardy Region, north-west Italy, enrolled 2099 cases and 2120 controls frequency-matched for area of residence, gender, and age. For this study we selected subjects with complete active and passive smoking history living in the same municipality since 1980 until study enrollment. Fine resolution annual PM10 estimates obtained by applying land use regression modeling to satellite data calibrated with fixed site monitor measurements were used. We assigned each subject the PM10 average estimates for year 2000 based on enrollment address. We used logistic regression models to calculate odds ratios (OR) and 95% confidence intervals (CI) adjusted for matching variables, education, smoking, and dietary and occupational variables.
We included 3473 subjects, 1665 cases (1318 men, 347 women) and 1808 controls (1368 men, 440 women), with PM10 individual levels ranging from 2.3 to 53.8 μg/m3 (mean: 46.3). We found increasing lung cancer risk with increasing PM10 category (P-value for trend: 0.04). The OR per 10 μg/m3 was 1.28 (95% CI: 0.95-1.72). The association appeared stronger for squamous cell carcinoma (OR 1.44, 95% CI: 0.90-2.29).
In a population living in highly polluted areas in Italy, our study added suggestive evidence of a positive association between PM10 exposure and lung cancer risk. This study emphasizes the need to strengthen policies to reduce airborne pollution.
Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer, which originates from the mesothelial cells of the pleura and is associated with asbestos exposure. In light of its aggressive ...nature, late diagnosis and dismal prognosis, there is an urgent need for identification of biomarkers in easily accessible samples (such as blood) for early diagnosis of MPM. In the last 10 years, epigenetic markers, such as DNA methylation and microRNAs (miRNAs), have gained popularity as possible early diagnostic and prognostic biomarkers in cancer research. The aim of this review is to provide a critical analysis of the current evidences on circulating epigenetic biomarkers for MPM and on their translational potential to the clinical practice for early diagnosis and for prognosis.
The "exposome" covers all disease determinants across a lifetime. Many exposome factors could induce epigenetic changes, especially in DNA methylation. Yet, the role of these modifications in disease ...development remains partly understood.
Although the possible relationship among the exposome factors, epigenetic modifications, and health/disease has been investigated extensively, all previous studies start from the assumption that epigenetic changes are always detrimental to (or represent an adverse effect on) the health of the affected individual. We hereby propose a new approach to investigate these modifications, and their possible relation with human health, in the context of the exposome.
Our hypothesis is based on the possibility that some environmentally-induced changes are plastic entities, responding physiologically to the environment to allow individual adaptation. Briefly, after evaluating the association between environmental exposure and the variation of a given biological parameter through regression models, we use the estimated regression function to predict values for each study subject. We then calculated the relative percent difference (PD) between the measured (i.e., observed) biological parameter and the predicted (i.e., expected) from the model. Notably, we have tested our hypothesis using two distinct models, specifically focusing on LINE-1 methylation and extracellular vesicles (EVs). We hypothesize that the greater the difference between the observed and the expected, the greater the inability of the subject to adapt to external stimuli.
Evidence about the role for reproductive and hormonal factors in the etiology of lung cancer in women is conflicting. To clarify this question, we examined 407 female cases and 499 female controls ...from the Environment And Genetics in Lung cancer Etiology population‐based case–control study. Subjects were interviewed in person using a computer‐assisted personal interview to assess demographics, education, smoking history, medical history, occupational history, reproductive and hormonal factors. Associations of interest were investigated using logistic regression models, adjusted for catchment area and age (matching variables), cigarette smoking (status, pack‐years and time since quitting). Additional confounding variables were investigated but did not substantially affect the results. We observed a reduced risk of lung cancer among women with later age at first live birth ≥31 years: odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.31–1.06, p‐trend = 0.05, later age at menopause (≥51 years: OR = 0.49, 95%CI = 0.31–0.79, p‐trend = 0.003) and longer reproductive periods (≥41 years: OR = 0.44, 95%CI = 0.25–0.79, p‐trend = 0.01). A reduced risk was also observed for hormone replacement therapy (OR = 0.63, 95%CI = 0.42–0.95, p = 0.03) and oral contraceptive use (OR = 0.67, 95%CI = 0.45–1.00, p = 0.05) but no trend with duration of use was detected. Menopausal status (both natural and induced) was associated with an augmented risk. No additional associations were identified for other reproductive variables. This study suggests that women who continue to produce estrogens have a lower lung cancer risk. Large studies with great number of never smoking women, biomarkers of estrogen and molecular classification of lung cancer are needed for a more comprehensive view of the association between reproductive factors and lung cancer risk.
What's new?
Despite numerous observational studies, the degree to which estrogens influence lung cancer risk in women has remained unclear. In an attempt to better understand this relationship, researchers here analyzed data from the Environment and Genetics in Lung Cancer Etiology (EAGLE) population‐based case‐control study in Italy. They report that women with later age at first live birth and at menopause, as well as women who had a longer reproductive period (time from menarche to menopause), benefited from reduced lung cancer risk. The analysis supports the hypothesis that women who continue to produce estrogens have a lower risk of lung cancer.
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