Female Lung Research Articles

P63.15 Clinical Analysis of 89 Female Patients With Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a kind of tumor with obvious heterogeneity. Accurate classification is a prerequisite of appropriate selection of treatment. Females differ from males in several demographic, hormone and clinical characteristics, which may lead to different prognosis in SCLC. Our study is aimed at summarizing the clinicopathological characteristics, management and prognosis of female small cell lung cancer and contributing to the promotion of precision treatment of SCLC.

Increased CD47 and MHC Class I Inhibitory Signals Expression in Senescent CD1 Primary Mouse Lung Fibroblasts.

Cellular senescence is more than a proliferative arrest in response to various stimuli. Senescent cells (SC) participate in several physiological processes, and their adequate removal is essential to maintain tissue and organism homeostasis. However, SC accumulation in aging and age-related diseases alters the tissue microenvironment leading to deterioration. The immune system clears the SC, but the specific scenarios and mechanisms related to recognizing and eliminating them are unknown. Hence, we aimed to evaluate the existence of three regulatory signals of phagocytic function, CD47, major histocompatibility complex class I (MHC-I), and calreticulin, present in the membrane of SC. Therefore, primary fibroblasts were isolated from CD1 female mice lungs, and stress-induced premature senescence (SIPS) was induced with hydrogen peroxide. Replicative senescence (RS) was used as a second senescent model. Our results revealed a considerable increment of CD47 and MHC-I in RS and SIPS fibroblasts. At the same time, no significant changes were found in calreticulin, suggesting that those signals might be associated with evading immune system recognition and thus averting senescent cells clearance.

The cancer survival index: Measuring progress in cancer survival to help evaluate cancer control efforts in Canada.

A comprehensive evaluation of progress in cancer survival for all cancer types combined has not previously been conducted for Canada. The cancer survival index (CSI) is superior to age standardization in measuring such progress. Data are from the population-based Canadian Cancer Registry, record-linked to the Canadian Vital Statistics Death database. CSI estimates for both sexes combined were calculated as the weighted sum of the sex- and cancer-specific age-standardized net survival estimates. Sex-specific CSI estimates were calculated separately using sex-specific cancer type weights. From the 1992-to-1994 period to the 2015-to-2017 period, the five-year CSI increased 8.6 percentage points to 63.7%. It increased by 8.9 percentage points to 61.8% among males, and by 8.2 percentage points to 65.8% among females. The contribution of a cancer and sex combination to change in the CSI over time is a function of its assigned weight and changes in its age-standardized net survival. Female breast was the most influential cancer and sex combination, contributing 10.1% to the overall increase, followed by prostate (8.2%) and female lung (7.3%). The increase in the index since the 2005-to-2007 period was most impacted by lung cancer among both females (11.1%) and males (9.4%). While prostate cancer survival increased over the entire study period, it has recently decreased, resulting in a counterproductive 8.1% contribution since the 2005-to-2007 period. Steady progress has been made in overall cancer survival in Canada since the early 1990s. Female breast cancer has contributed the most to this progress overall, but more recently female lung cancer has been the most influential.

1418Geographic disparities in temporal trends for the most prevalent cancer types in Argentina, 1996-2015

Abstract Background There are significant differences in cancer mortality burden along time and between regions, related to changes in individual and contextual conditions. We aimed to analyze the geographic pattern and temporal trend of cancer mortality in Argentina, simultaneously, by using mapping techniques. Methods Age-standardized mortality rates (ASMR, direct method) and average annual percent change (APC, joinpoint regression method) in 1996-2015 were estimated for breast, lung, prostate, colon, cervix, stomach and total cancer in Argentina. Mortality maps were constructed (provincial level, n = 24) for the 2013-2015 period, overlapping temporal trend information (1996-2015), using ascending or decreasing arrows for rising (positive) or decreasing (negative) APC, respectively; the arrow size was proportional to the APC magnitude. Results Both sexes show a similar geographical pattern in cancer ASMR characterized by higher rates in the central and southern Argentinian provinces, and lower rates in the northern provinces. However, men present higher rates than women (ASMRs between 85-158/100,000 deaths/year, and between 67-99/100,000, respectively). Most of tumour sites presented negative APC in most provinces, with geographical disparities on their magnitude. Nevertheless, lung cancer in women (mean APC=1.4%) and colon cancer (1.5% in men and 2.1% in women) showed increasing mortality trends. Conclusions Overall, cancer shows favorable mortality temporal trends, with heterogeneity between provinces in the APC magnitude. Maps suggest that geographical disparities may be linked to social inequalities. Key messages Geographical pattern in cancer ASMR was similar by sex, although with higher rates in men. Cancer sites show decreasing mortality trends, except female lung cancer and colon cancer.

Concomitant occurence of multiple autoantibodies against human cytochromes P450

Cytochromes P450 (CYPs) are a large superfamily of heme-containing enzymes that are essential for the metabolism of a variety of endogenous and xenobiotic compounds. The role and the possible diagnostic or prognostic value of the occurrence of anti-CYP autoantibodies (aAbs) in cancer patients are essentially unclear. Recently we reported the monitoring of aAbs against CYP4Z1 and CYP19A1 in breast cancer patients and healthy controls. In the present study, we extended this investigation by screening the sera of 47 lung cancer patients (17 female and 30 male; age range 49–84) and 119 healthy controls (60 female and 59 male; age range 21–72) for the presence of aAbs directed against CYP2D6, CYP4Z1, or CYP17A1, respectively. Determination of anti-CYP aAb levels was done using our previously established ELISA method. Most sera gave low signals while a small fraction showed stronger responses; however, there were no statistically significant differences between the different test groups. Also, there was no significant difference in aAb signals between the various subtypes of lung cancer. Unexpectedly, sera from two female lung cancer patients (age 67 (adenocarcinoma) and 70 (small cell carcinoma)) and from four healthy controls (one female and three male; age range 34–48) showed significantly elevated signals for more than one of the three CYPs tested. These findings corroborate earlier reports that anti-CYP aAbs occur with low frequency in the general population and, moreover, suggest that the simultaneous presence of multiple aAbs targeting different CYPs should be taken into consideration when evaluating anti-CYP aAbs as biomarkers.

Club Cells Are the Primary Target for Permethrin-Induced Mouse Lung Tumor Formation.

Permethrin has been shown to increase lung adenomas in female CD-1 mice, but not in male mice or Wistar rats. The proposed mode of action (MOA) for permethrin-induced female mouse lung tumor formation involves morphological changes in Club cells; increased Club cell proliferation; increased Club cell hyperplasia, and lung tumor formation. In this study, the treatment of female CD-1 mice with tumorigenic doses (2500 and 5000 ppm) of permethrin, but not with a nontumorigenic dose (20 ppm), for 14 and/or 28 days increased Club cell replicative DNA synthesis. Global gene expression analysis of female mouse lung samples demonstrated that permethrin treatment up-regulated 3 genes associated with cell proliferation, namely aldehyde dehydrogenase 3a1 (Aldh3a1), oxidative stress-induced growth inhibitor 1, and thioredoxin reductase 1. Treatment with 2500 and 5000 ppm, but not 20 ppm, permethrin for 7 days produced significant increases in mRNA levels of these 3 genes. Immunohistochemical analysis demonstrated that Club cell secretory protein, CYP2F2, and ALDH3A1 colocalized in Club cells; confirmed by flow cytometry analysis of lung cells employing KI67 as a cell proliferation marker. Overall, the present data extend the proposed MOA by demonstrating that Club cells are the primary initial target of permethrin administration in female mouse lungs. As humans are quantitatively much less sensitive to agents that increase Club cell proliferation and lung tumor formation in mice, it is most likely that permethrin could not produce lung tumors in humans. This conclusion is supported by available negative epidemiological data from several studies.

124I-Iodo-DPA-713 Positron Emission Tomography in a Hamster Model of SARS-CoV-2 Infection.

PurposeMolecular imaging has provided unparalleled opportunities to monitor disease processes, although tools for evaluating infection remain limited. Coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mediated by lung injury that we sought to model. Activated macrophages/phagocytes have an important role in lung injury, which is responsible for subsequent respiratory failure and death. We performed pulmonary PET/CT with 124I-iodo-DPA-713, a low-molecular-weight pyrazolopyrimidine ligand selectively trapped by activated macrophages cells, to evaluate the local immune response in a hamster model of SARS-CoV-2 infection.ProceduresPulmonary 124I-iodo-DPA-713 PET/CT was performed in SARS-CoV-2-infected golden Syrian hamsters. CT images were quantified using a custom-built lung segmentation tool. Studies with DPA-713-IRDye680LT and a fluorescent analog of DPA-713 as well as histopathology and flow cytometry were performed on post-mortem tissues.ResultsInfected hamsters were imaged at the peak of inflammatory lung disease (7 days post-infection). Quantitative CT analysis was successful for all scans and demonstrated worse pulmonary disease in male versus female animals (P < 0.01). Increased 124I-iodo-DPA-713 PET activity co-localized with the pneumonic lesions. Additionally, higher pulmonary 124I-iodo-DPA-713 PET activity was noted in male versus female hamsters (P = 0.02). DPA-713-IRDye680LT also localized to the pneumonic lesions. Flow cytometry demonstrated a higher percentage of myeloid and CD11b + cells (macrophages, phagocytes) in male versus female lung tissues (P = 0.02).Conclusion124I-Iodo-DPA-713 accumulates within pneumonic lesions in a hamster model of SARS-CoV-2 infection. As a novel molecular imaging tool, 124I-Iodo-DPA-713 PET could serve as a noninvasive, clinically translatable approach to monitor SARS-CoV-2-associated pulmonary inflammation and expedite the development of novel therapeutics for COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11307-021-01638-5.

Age, period, and cohort effect of female lung cancer in China

Age, period, and cohort effect of female lung cancer in China

Lung Cancer Screening Study in Macao Smoking Individuals

背景与目的中国澳门肺癌发病率逐年上升，吸烟人群是肺癌的高发人群，本研究旨在了解中国澳门长期吸烟人群的肺癌发病情况及胸部低剂量计算机断层扫描(low-dose computed tomography, LDCT)肺结节特点。方法通过澳门中华医学会会员私家医生推荐及宣传招募中国澳门无症状长期吸烟人士，行胸部LDCT检查，分析肺癌、肺部结节检出率及影像学特点。结果符合纳入条件者291例，检出肺癌10例，检出率3.44%(95%CI: 2.78%-4.01%)，其中，肺腺癌5例，鳞癌、小细胞肺癌各2例，腺鳞癌1例。早期肺癌4例，占40%。212例检出肺结节，肺结节总检出率72.9%(95%CI: 67.8%-78.0%); 疑似肺癌结节44例，检出率15.1%(95%CI: 11.0%-19.2%)。单发结节51例，无肺癌检出; 多发结节161例，检出肺癌9例，两组肺癌检出率无统计学差异(P > 0.05)。 < 6 mm实性结节与 < 5 mm非实性结节组168例，未检出肺癌; ≥6 mm实性结节与≥5 mm非实性结节组44例，检出肺癌9例，两组比较有统计学差异(P < 0.05)。结论长期吸烟人群中肺癌检出率高，类型以腺癌为主，肺部结节发生率高，当实性结节≥6 mm或非实性结节≥5 mm时，肺癌检出率增高。建议在符合高危因素的男性吸烟人群中推行胸部LDCT筛查肺癌，女性肺癌筛查，应重新界定高危因素。

Cigarette Smoking Alters the Expression of Circulating microRNAs and Its Potential Diagnostic Value in Female Lung Cancer Patients.

Simple SummaryIn this study, we investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in lung cancer patients and healthy participants. Our findings support that cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.Cigarette smoking is a known risk factor for the development of lung cancer. We investigated whether circulating microRNA expression levels and their potential diagnostic value are affected by cigarette smoking in adenocarcinoma (AD) patients and healthy (H) participants. In total, 71 female AD patients and 91 H individuals were recruited, including 42 AD never-smokers (AD/CS−), 29 AD smokers (AD/CS+), 54 H never-smokers (H/CS−), and 37 H smokers (H/CS+). PCR array (754 microRNAs) and qPCR were performed on sera from the discovery and validation cohorts, respectively. The expression levels of miR-532-5p, miR-25-3p, and miR-133a-3p were significantly higher in adenocarcinoma patients than in healthy participants, independent of their smoking status. Multivariate analysis showed that levels of miR-133a-3p were independently associated with smoking. ROC analysis showed that only miR-532-5p discriminated AD patients from H controls (AUC: 0.745). However, when making comparisons according to cigarette smoking status, miR-532-5p discriminated AD/CS− patients from H/CS− controls with a higher AUC (AUC:0.762); miR-25-3p discriminated AD/CS+ patients from H/CS+ controls (AUC: 0.779), and miR-133a discriminated AD/CS+ patients from H/CS+ controls with the highest AUC of 0.935. Cancer and lung-cancer-enriched pathways were significantly associated with the three miRNAs; in addition, nicotinate/nicotinamide metabolism, inflammation, and pulmonary hypertension were associated with miR-133a-3p. Our findings highlight how cigarette smoking affects the reliable identification of circulating miRNAs as diagnostic biomarkers in lung cancer and suggest a smoking-dependent pathogenic role of miR-133a-3p in smokers.

Socioeconomic disparities in cancer incidence and mortality in England and the impact of age-at-diagnosis on cancer mortality.

BackgroundWe identify socioeconomic disparities by region in cancer morbidity and mortality in England for all-cancer and type-specific cancers, and use incidence data to quantify the impact of cancer diagnosis delays on cancer deaths between 2001–2016.Methods and findingsWe obtain population cancer morbidity and mortality rates at various age, year, gender, deprivation, and region levels based on a Bayesian approach. A significant increase in type-specific cancer deaths, which can also vary among regions, is shown as a result of delay in cancer diagnoses. Our analysis suggests increase of 7.75% (7.42% to 8.25%) in female lung cancer mortality in London, as an impact of 12-month delay in cancer diagnosis, and a 3.39% (3.29% to 3.48%) increase in male lung cancer mortality across all regions. The same delay can cause a 23.56% (23.09% to 24.30%) increase in male bowel cancer mortality. Furthermore, for all-cancer mortality, the highest increase in deprivation gap happened in the East Midlands, from 199 (186 to 212) in 2001, to 239 (224 to 252) in 2016 for males, and from 114 (107 to 121) to 163 (155 to 171) for females. Also, for female lung cancer, the deprivation gap has widened with the highest change in the North West, e.g. for incidence from 180 (172 to 188) to 272 (261 to 282), whereas it has narrowed for prostate cancer incidence with the biggest reduction in the South West from 165 (139 to 190) in 2001 to 95 (72 to 117) in 2016.ConclusionsThe analysis reveals considerable disparities in all-cancer and some type-specific cancers with respect to socioeconomic status. Furthermore, a significant increase in cancer deaths is shown as a result of delays in cancer diagnoses which can be linked to concerns about the effect of delay in cancer screening and diagnosis during the COVID-19 pandemic. Public health interventions at regional and deprivation level can contribute to prevention of cancer deaths.

Prognostic Characteristics of Operated Breast Cancer Patients with Second Primary Lung Cancer: A Retrospective Study.

Background and PurposeThe number of breast cancer patients with second primary lung cancer is increasing year by year. The aim of this study was to explore the prognostic characteristics of these multiple primary breast and lung cancer patients.MethodsOperated breast cancer patients with subsequent lung cancer who were admitted to our hospital from January, 2010 to August, 2020 were retrospectively analyzed. The univariate and multivariate Cox regression analyses were conducted to explore the prognostic risk factors of such patients. Meanwhile, the propensity score match (PSM) method was applied to compare the prognosis between lung cancer patients with and without the history of breast cancer.ResultsA total of 137 cases were included and most of them (94.9%) were asynchronous multiple primary carcinomas. The median interval between the diagnoses of breast cancer and lung cancer was 60 months (2–456 months), median age at the diagnosis of breast cancer was 49.5 (28–81) years old and median age at the diagnosis of lung cancer was 58 (31–84) years old. Univariate and multivariate Cox regression analysis indicated that poor differentiation [hazard ratio (HR)=6.372, 95% confidence interval (CI): 2.441–16.633, P<0.001] and pTNM stage III/IV (HR=5.830, 95% CI: 2.295–14.813, P<0.001) of lung cancer were independent prognostic risk factors for these patients. Before and after the PSM, the overall survival (OS) of lung cancer patients with breast cancer was significantly worse than that of single primary lung cancer patients (P<0.001, P=0.002).ConclusionDifferentiation status and pTNM stage were independent prognostic factors in operated breast cancer patients with second primary lung cancer. Meanwhile, the prognosis of this group of patients was worse than single primary lung cancer patients, which indicated that the medical history of breast cancer was also a prognostic risk factor of female lung cancer patients.

Sex Differences in Pulmonary Eicosanoids and Specialized Pro-Resolving Mediators in Response to Ozone Exposure.

Ozone (O3) is a criteria air pollutant known to increase the morbidity and mortality of cardiopulmonary diseases. This occurs through a pulmonary inflammatory response characterized by increased recruitment of immune cells into the airspace, pro-inflammatory cytokines, and pro-inflammatory lipid mediators. Recent evidence has demonstrated sex-dependent differences in the O3-induced pulmonary inflammatory response. However, it is unknown if this dimorphic response is evident in pulmonary lipid mediator metabolism. We hypothesized that there are sex-dependent differences in lipid mediator production following acute O3 exposure. Male and female C57BL/6J mice were exposed to 1 part per million O3 for 3 h and were necropsied at 6 or 24 h following exposure. Lung lavage was collected for cell differential and total protein analysis, and lung tissue was collected for mRNA analysis, metabololipidomics, and immunohistochemistry. Compared with males, O3-exposed female mice had increases in airspace neutrophilia, neutrophil chemokine mRNA, pro-inflammatory eicosanoids such as prostaglandin E2, and specialized pro-resolving mediators (SPMs), such as resolvin D5 in lung tissue. Likewise, precursor fatty acids (arachidonic and docosahexaenoic acid; DHA) were increased in female lung tissue following O3 exposure compared with males. Experiments with ovariectomized females revealed that loss of ovarian hormones exacerbates pulmonary inflammation and injury. However, eicosanoid and SPM production were not altered by ovariectomy despite depleted pulmonary DHA concentrations. Taken together, these data indicate that O3 drives an increased pulmonary inflammatory and bioactive lipid mediator response in females. Furthermore, ovariectomy increases susceptibility to O3-induced pulmonary inflammation and injury, as well as decreases pulmonary DHA concentrations.

Risk of lung cancer among women in relation to lifetime history of tobacco smoking: a population-based case-control study in France (the WELCA study)

BackgroundThis study aims to provide new insights on the role of smoking patterns and cigarette dependence in female lung cancer, and to examine differences by histological subtype.MethodsWe conducted a population-based case-control study in the great Paris area among women including 716 incident cases diagnosed between 2014 and 2017 and 757 age-matched controls. Detailed data on smoking history was collected during in-person interviews to assess intensity and duration of tobacco smoking, time since cessation, smoking habits (depth of smoke inhalation, use of filter, type of tobacco, and type of cigarettes) and Fagerström test for cigarette dependence. The comprehensive smoking index (CSI), a score modelling the combined effects of intensity, duration and time since quitting smoking was determined for each subject. Multivariable logistic regression models were fitted to calculate odds ratios (ORs) and their confidence intervals (95%CI) of lung cancer associated with smoking variables.ResultsLung cancer risk increased linearly with intensity and duration of tobacco smoking while it decreased with time since cessation, to reach the risk in never-smokers after 20 years of abstinence. The combined effect of intensity and duration of tobacco smoking was more than multiplicative (p-interaction 0.012). The OR in the highest vs the lowest quartile of CSI was 12.64 (95%CI 8.50; 18.80) (p-trend < 0.001). The risk of small cell or squamous cell carcinomas increased with the CSI more sharply than the risk of adenocarcinomas. Deep smoke inhalation, dark vs blond tobacco, conventional vs light cigarettes, and unfiltered vs filtered cigarettes, as well as having mixed smoking habits, were found to be independent risk factors. Having high cigarette addiction behaviours also increased the risk after adjusting for CSI.ConclusionThis study provides additional insights on the effects of tobacco smoking patterns on lung cancer risk among women.

Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones

BackgroundPublished findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women.MethodsThe PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed.ResultsForty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87–0.98) and exogenous (OR: 0.86, 95% CI: 0.80–0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86–0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78–0.99) than in smoking women (OR: 0.98, 95% CI: 0.77–1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74–0.96).ConclusionsOur meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.

Palliative care as a predictor of healthcare resource use at end-of-life in adult Albertan lung cancer decedents between 2008-2015: A secondary data analysis.

e24009 Background: Early utilization of specialist palliative care (SPC) in cancer patients may reduce healthcare resource use, aggressive interventions, and costs at end-of-life. We evaluated the impact of SPC on healthcare resource utilization and aggressive interventions at end-of-life in patients who have died from lung cancer. Methods: Descriptive and multivariable logistic regression analyses were conducted on lung cancer decedents in the Calgary Zone, Alberta Health Services from 2008 to 2015. The primary exposure was timing of SPC (Early: receipt of SPC &gt; = 90 days before death; Late: &lt; 90 days before death; No SPC). The primary outcome was end-of-life healthcare resource use (defined as any of: hospital death, &gt; 1 emergency department visit, &gt; 1 hospital admission, &gt; 14 days of hospitalization, ≥1 intensive care unit admission, ≥1 new chemotherapy program (or any chemotherapy in the last 14 days of life) in the 30 days prior to death. Results: There were 3300 patients of which the majority (51.6%) of decedents were male. More female versus male lung cancer decedents (36.4% vs 28.7%) received early SPC. After adjusting for confounders, a strong association was found between early, late or no SPC and end-of-life healthcare resource use (ORno exposure 3.25 (95% CI 2.41-4.40) vs ORlate exposure 2.44 (95% CI 2.03-2.92) compared to those with early SPC; p &lt; 0.001). Males had 1.53 the odds of aggressive care at end-of-life compared to females (p &lt; 0.001). Stratified analysis by sex revealed a strong association between the absence of SPC utilization and end-of-life healthcare resource use. Young age ( &lt; 50 at death) was a strong driver of aggressive care at end-of-life in females versus males [OR 5.44 vs 2.53]. Conclusions: Early specialist palliative care was significantly associated with less end-of-life healthcare resource use in both male and female lung cancer decedents, with less early specialist palliative care use in males. Keywords: palliative care, early palliative care, cancer, end-of-life, healthcare resource use, lung cancer.

Forecasting of Lung Cancer Incident Cases at the Small-Area Level in Victoria, Australia.

Predicting lung cancer cases at the small-area level is helpful to quantify the lung cancer burden for health planning purposes at the local geographic level. Using Victorian Cancer Registry (2001–2018) data, this study aims to forecast lung cancer counts at the local government area (LGA) level over the next ten years (2019–2028) in Victoria, Australia. We used the Age-Period-Cohort approach to estimate the annual age-specific incidence and utilised Bayesian spatio-temporal models that account for non-linear temporal trends and area-level risk factors. Compared to 2001, lung cancer incidence increased by 28.82% from 1353 to 1743 cases for men and 78.79% from 759 to 1357 cases for women in 2018. Lung cancer counts are expected to reach 2515 cases for men and 1909 cases for women in 2028, with a corresponding 44% and 41% increase. The majority of LGAs are projected to have an increasing trend for both men and women by 2028. Unexplained area-level spatial variation substantially reduced after adjusting for the elderly population in the model. Male and female lung cancer cases are projected to rise at the state level and in each LGA in the next ten years. Population growth and an ageing population largely contributed to this rise.

Targeting androgen signaling in ILC2s protects from IL-33–driven lung inflammation, independently of KLRG1

Allergic asthma is more severe and frequent in women than in men. In male mice, androgens negatively control group 2 innate lymphoid cell (ILC2) development and function by yet unknown mechanisms. We sought to investigate the impact of androgen on ILC2 homeostasis and IL-33-mediated inflammation in female lungs. We evaluated the role of androgen receptor (AR) signaling and the contribution of the putative inhibitory receptor killer cell lectin-like receptor G1 (KLRG1). Subcutaneous pellets mimicking physiological levels of androgen were used to treat female mice together with mice expressing a reporter enzyme under the control of androgen response elements and mixed bone marrow chimeras to assess the cell-intrinsic role of AR activation within ILC2s. We generated KLRG1-deficient mice. We established that lung ILC2s express a functionally active AR that can be invivo targeted with exogenous androgens to negatively control ILC2 homeostasis, proliferation, and function. Androgen signaling upregulated KLRG1 on ILC2s, which inhibited their proliferation on E-cadherin interaction. Despite evidence that KLRG1 impaired the competitive fitness of lung ILC2s during inflammation, KLRG1 deficiency neither alters invivo ILC2 numbers and functions, nor did it lead to hyperactive ILC2s in either sexes. AR agonists can be used invivo to inhibit ILC2 homeostatic numbers and ILC2-dependent lung inflammation through cell-intrinsic AR activation. Although androgen signals in ILC2s to upregulate KLRG1, we demonstrate that KLRG1 is dispensable for androgen-mediated inhibition of pulmonary ILC2s.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Effects of Chlorpyrifos on Serine Hydrolase Activities, Lipid Mediators, and Immune Responses in Lungs of Neonatal and Adult Mice.

Chlorpyrifos (CPF) is an organophosphate (OP) pesticide that causes acute toxicity by inhibiting acetylcholinesterase (AChE) in the nervous system. However, endocannabinoid (eCB) metabolizing enzymes in brain of neonatal rats are more sensitive than AChE to inhibition by CPF, leading to increased levels of eCBs. Because eCBs are immunomodulatory molecules, we investigated the association between eCB metabolism, lipid mediators, and immune function in adult and neonatal mice exposed to CPF. We focused on lung effects because epidemiologic studies have linked pesticide exposures to respiratory diseases. CPF was hypothesized to disrupt lung eCB metabolism and alter lung immune responses to lipopolysaccharide (LPS), and these effects would be more pronounced in neonatal mice due to an immature immune system. We first assessed the biochemical effects of CPF in adult mice (≥8 weeks old) and neonatal mice after administering CPF (2.5 mg/kg, oral) or vehicle for 7 days. Tissues were harvested 4 h after the last CPF treatment and lung microsomes from both age groups demonstrated CPF-dependent inhibition of carboxylesterases (Ces), a family of xenobiotic and lipid metabolizing enzymes, whereas AChE activity was inhibited in adult lungs only. Activity-based protein profiling (ABPP)-mass spectrometry of lung microsomes identified 31 and 32 individual serine hydrolases in neonatal lung and adult lung, respectively. Of these, Ces1c/Ces1d/Ces1b isoforms were partially inactivated by CPF in neonatal lung, whereas Ces1c/Ces1b and Ces1c/BChE were partially inactivated in adult female and male lungs, respectively, suggesting age- and sex-related differences in their sensitivity to CPF. Monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH) activities in lung were unaffected by CPF. When LPS (1.25 mg/kg, i.p.) was administered following the 7-day CPF dosing period, little to no differences in lung immune responses (cytokines and immunophenotyping) were noted between the CPF and vehicle groups. However, a CPF-dependent increase in the amounts of dendritic cells and certain lipid mediators in female lung following LPS challenge was observed. Experiments in neonatal and adult Ces1d-/- mice yielded similar results as wild type mice (WT) following CPF treatment, except that CPF augmented LPS-induced Tnfa mRNA in adult Ces1d-/- mouse lungs. This effect was associated with decreased expression of Ces1c mRNA in Ces1d-/- mice versus WT mice in the setting of LPS exposure. We conclude that CPF exposure inactivates several Ces isoforms in mouse lung and, during an inflammatory response, increases certain lipid mediators in a female-dependent manner. However, it did not cause widespread altered lung immune effects in response to an LPS challenge.