scholarly journals Mmp12 Is Upregulated by in utero Second-Hand Smoke Exposures and Is a Key Factor Contributing to Aggravated Lung Responses in Adult Emphysema, Asthma, and Lung Cancer Mouse Models

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexandra Noël ◽  
Zakia Perveen ◽  
Rui Xiao ◽  
Harriet Hammond ◽  
Viviana Le Donne ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Disease ◽  
Critical Role ◽  
In Utero ◽  
Air Pollutant ◽  
Second Hand Smoke ◽  
Disease Models ◽  
Chronic Obstructive ◽  
Adult Lung ◽  
Gene And Protein Expression

Matrix metalloproteinase-12 (Mmp12) is upregulated by cigarette smoke (CS) and plays a critical role in extracellular matrix remodeling, a key mechanism involved in physiological repair processes, and in the pathogenesis of emphysema, asthma, and lung cancer. While cigarette smoking is associated with the development of chronic obstructive pulmonary diseases (COPD) and lung cancer, in utero exposures to CS and second-hand smoke (SHS) are associated with asthma development in the offspring. SHS is an indoor air pollutant that causes known adverse health effects; however, the mechanisms by which in utero SHS exposures predispose to adult lung diseases, including COPD, asthma, and lung cancer, are poorly understood. In this study, we tested the hypothesis that in utero SHS exposure aggravates adult-induced emphysema, asthma, and lung cancer.Methods: Pregnant BALB/c mice were exposed from gestational days 6–19 to either 3 or 10mg/m3 of SHS or filtered air. At 10, 11, 16, or 17weeks of age, female offspring were treated with either saline for controls, elastase to induce emphysema, house-dust mite (HDM) to initiate asthma, or urethane to promote lung cancer. At sacrifice, specific disease-related lung responses including lung function, inflammation, gene, and protein expression were assessed.Results: In the elastase-induced emphysema model, in utero SHS-exposed mice had significantly enlarged airspaces and up-regulated expression of Mmp12 (10.3-fold compared to air-elastase controls). In the HDM-induced asthma model, in utero exposures to SHS produced eosinophilic lung inflammation and potentiated Mmp12 gene expression (5.7-fold compared to air-HDM controls). In the lung cancer model, in utero exposures to SHS significantly increased the number of intrapulmonary metastases at 58weeks of age and up-regulated Mmp12 (9.3-fold compared to air-urethane controls). In all lung disease models, Mmp12 upregulation was supported at the protein level.Conclusion: Our findings revealed that in utero SHS exposures exacerbate lung responses to adult-induced emphysema, asthma, and lung cancer. Our data show that MMP12 is up-regulated at the gene and protein levels in three distinct adult lung disease models following in utero SHS exposures, suggesting that MMP12 is central to in utero SHS-aggravated lung responses.

Chronic obstructive pulmonary disease and interstitial lung disease in patients with lung cancer

Respirology ◽  
2009 ◽  
Vol 14 (3) ◽  
pp. 377-383 ◽  
Author(s):  
Satoko MIZUNO ◽  
Yuichi TAKIGUCHI ◽  
Ayako FUJIKAWA ◽  
Ken MOTOORI ◽  
Yuji TADA ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

scholarly journals Pulmonary ventilation defects in older never-smokers

2014 ◽  
Vol 117 (3) ◽  
pp. 297-306 ◽  
Author(s):  
Khadija Sheikh ◽  
Gregory A. Paulin ◽  
Sarah Svenningsen ◽  
Miranda Kirby ◽  
Nigel A. M. Paterson ◽  
...  
Keyword(s):  
Pulmonary Function ◽  
Lung Disease ◽  
Obstructive Lung Disease ◽  
Pulmonary Function Tests ◽  
Pulmonary Ventilation ◽  
Forced Expiratory Volume ◽  
Airflow Limitation ◽  
Second Hand Smoke ◽  
Chronic Obstructive ◽  
Never Smokers

Hyperpolarized 3He MRI previously revealed spatially persistent ventilation defects in healthy, older compared with healthy, younger never-smokers. To understand better the physiological consequences and potential relevance of 3He MRI ventilation defects, we evaluated 3He-MRI ventilation-defect percent (VDP) and the effect of deep inspiration (DI) and salbutamol on VDP in older never-smokers. To identify the potential determinants of ventilation defects in these subjects, we evaluated dyspnea, pulmonary function, and cardiopulmonary exercise test (CPET) measurements, as well as occupational and second-hand smoke exposure. Fifty-two never-smokers (71 ± 6 yr) with no history of chronic respiratory disease were evaluated. During a single visit, pulmonary function tests, CPET, and 3He MRI were performed and the Burden of Obstructive Lung Disease questionnaire administered. For eight of 52 subjects, there was spirometry evidence of airflow limitation (Global Initiative for Chronic Obstructive Lung Disease-Unclassified, I, and II), and occupational exposure was reported in 13 of 52 subjects. In 13 of 52 (25%) subjects, there were no ventilation defects and in 39 of 52 (75%) subjects, ventilation defects were observed. For those subjects with ventilation defects, six of 39 showed a VDP response to DI/salbutamol. Ventilation heterogeneity and VDP were significantly greater, and forced expiratory volume in 1 s (FEV1)/forced vital capacity was significantly lower ( P < 0.05) for subjects with ventilation defects with a response to DI/salbutamol than subjects with ventilation defects without a response to DI/salbutamol and subjects without ventilation defects. In a step-wise, forward multivariate model, FEV1, inspiratory capacity, and airway resistance significantly predicted VDP ( R2 = 0.45, P < 0.001). In conclusion, most never-smokers had normal spirometry and peripheral ventilation defects not reversed by DI/salbutamol; such ventilation defects were likely related to irreversible airway narrowing/collapse but not to dyspnea and decreased exercise capacity.

scholarly journals Impact of coronavirus disease-2019 on chronic respiratory disease in South Korea: an NHIS COVID-19 database cohort study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tak Kyu Oh ◽  
In-Ae Song
Keyword(s):  
Lung Cancer ◽  
Cohort Study ◽  
South Korea ◽  
Hospital Mortality ◽  
Lung Disease ◽  
Chronic Obstructive ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
External Agents ◽  
The Impact

Abstract Background The impact of underlying chronic respiratory diseases (CRDs) on the risk and mortality of patients with coronavirus disease 2019 (COVID-19) remains controversial. We aimed to investigate the effects of CRDs on the risk of COVID-19 and mortality among the population in South Korea. Methods The NHIS-COVID-19 database in South Korea was used for data extraction for this population-based cohort study. Chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease (ILD), lung cancer, lung disease due to external agents, obstructive sleep apnea (OSA), and tuberculosis of the lungs (TB) were considered CRDs. The primary endpoint was a diagnosis of COVID-19 between January 1st and June 4th, 2020; the secondary endpoint was hospital mortality of patients with COVID-19. Multivariable logistic regression modeling was used for statistical analysis. Results The final analysis included 122,040 individuals, 7669 (6.3%) were confirmed as COVID-19 until 4 June 2020, and 251 patients with COVID-19 (3.2%) passed away during hospitalization. Among total 122,040 individuals, 36,365 individuals were diagnosed with CRD between 2015 and 2019: COPD (4488, 3.6%), asthma (33,858, 27.2%), ILD (421, 0.3%), lung cancer (769, 0.6%), lung disease due to external agents (437, 0.4%), OSA (550, 0.4%), and TB (608, 0.5%). Among the CRDs, patients either with ILD or OSA had 1.63-fold (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.17–2.26; P = 0.004) and 1.65-fold higher (OR 1.65, 95% CI 1.23–2.16; P < 0.001) incidence of COVID-19. In addition, among patients with COVID-19, the individuals with COPD and lung disease due to external agents had 1.56-fold (OR 1.56, 95% CI 1.06–2.2; P = 0.024) and 3.54-fold (OR 3.54, 95% CI 1.70–7.38; P < 0.001) higher risk of hospital mortality. Conclusions Patients with OSA and ILD might have an increased risk of COVID-19. In addition, COPD and chronic lung disease due to external agents might be associated with a higher risk of mortality among patients with COVID-19. Our results suggest that prevention and management strategies should be carefully performed.

scholarly journals Serum carcinoembryonic antigen elevation in benign lung diseases

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yi Yang ◽  
Mingfang Xu ◽  
Huan Huang ◽  
Xiaolin Jiang ◽  
Kan Gong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Disease ◽  
Carcinoembryonic Antigen ◽  
Lung Diseases ◽  
Circulatory System ◽  
Detection Methods ◽  
Chronic Obstructive ◽  
Endocrine Diseases ◽  
Serum Carcinoembryonic Antigen ◽  
Positive Rate

AbstractCarcinoembryonic antigen (CEA) is not only used to aid the diagnosis of lung cancer, but also help monitor recurrence and determine the prognosis of lung cancer as well as evaluate the therapeutic efficacy for lung cancer. However, studies have also shown that CEA is present at low levels in the serum of patients with benign lung diseases (BLD), which will interfere with the accurate judgment of the disease. Due to difference in sample size, detection methods, cutoff values and sources of BLD, the positive rate of CEA in BLD is different with different literature. Therefore, it is necessary to define CEA levels in patients of different BLD in a large sample study. 4796 patients with BLD were included in this study. The results showed that the CEA levels of 3.1% (149/4796) patients with BLD were elevated, with three cases exceeds 20 ng/mL (0.06%, 3/4796). The results from the literature showed that BLD had a mean positive rate of 5.99% (53/885) and only two cases had CEA above 20 ng/mL. The CEA elevations mainly distributed in chronic obstructive pulmonary disease (COPD), pneumonitis and interstitial lung disease and significantly correlated with age of patients (OR 2.69, 95% CI 1.94–3.73, p < 0.001). Pulmonary tuberculosis (7/1311, 0.53%) had the lowest positive rate of CEA elevations while pulmonary alveolar proteinosis (6/27, 22.22%) had the highest positive rate. The majority of patients with abnormally elevated CEA levels had multiple underlying diseases, mainly diseases of the circulatory system (42.28% [63/149]), endocrine diseases (26.85% [40/149]), and respiratory or heart failure (24.16% [36/149]. In endocrine diseases, 87.5% (35/40) of patients had diabetes. In conclusion, CEA is present at a low positive rate in the serum of patients with BLD, but few exceed 20 ng/mL. For lung disease patients, if CEA levels rise, we should carry out comprehensive analysis of types of lung diseases, age of patients, and comorbid diseases.

scholarly journals Mindfulness-Based Symptom and Stress Management Apps for Adults With Chronic Lung Disease: Systematic Search in App Stores (Preprint)

2018 ◽  
Author(s):  
Otis L Owens ◽  
Jenay M Beer ◽  
Ligia I Reyes ◽  
David G Gallerani ◽  
Amanda R Myhren-Bennett ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Disease ◽  
Chronic Lung Disease ◽  
Cultural Sensitivity ◽  
Participatory Design ◽  
Mobile Apps ◽  
Reading Level ◽  
Chronic Obstructive ◽  
Evidence Based ◽  
Plain Language

BACKGROUND Up to 70% of lung cancer survivors are affected by chronic obstructive pulmonary disease (COPD), a common, debilitating, comorbid disease. Lung cancer and COPD are both characterized by symptoms such as breathlessness, fatigue, and psychological distress. These distressing chronic symptoms are exacerbated by stress and detract from an individual’s quality of life. OBJECTIVE The aim of this study was to identify and evaluate evidence-based, commercially available apps for promoting mindfulness-based strategies among adults with a COPD or lung cancer history (ie, chronic lung disease). METHODS For this review, an interdisciplinary research team used 19 keyword combinations in the search engines of Google and iOS app stores in May 2017. Evaluations were conducted on the apps’ (1) content, (2) usability heuristics, (3) grade-level readability, and (4) cultural sensitivity. RESULTS The search resulted in 768 apps (508 in iOS and 260 in Google stores). A total of 9 apps met the inclusion criteria and received further evaluation. Only 1 app had below an eighth-grade reading level; the ninth one did not have enough text to calculate a readability score. None of the 9 apps met the cultural sensitivity evaluation criteria. CONCLUSIONS This systematic review identified critical design flaws that may affect the ease of using the apps in this study. Few mobile apps promote mindfulness-based strategies among adults with chronic lung disease (ie, COPD or lung cancer or both), but those that exist, overall, do not meet the latest scientific evidence. Recommendations include more stringent regulation of health-related apps, use of evidence-based frameworks and participatory design processes, following evidence-based usability practices, use of culturally sensitive language and images, and ensuring that content is written in plain language.

Abstract 313: The Nuclear Liver X Receptor as a Potential Regulator of Interleukin 18 Binding Protein in the Lung

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Adelheid Kratzer ◽  
Jonas Salys ◽  
Zakaria Mouman ◽  
Martin Zamora ◽  
Laima Taraseviciene-Stewart
Keyword(s):  
Gene Expression ◽  
Cigarette Smoke ◽  
Target Gene ◽  
Binding Protein ◽  
Liver X Receptor ◽  
Second Hand Smoke ◽  
Chronic Obstructive ◽  
Interleukin 18 ◽  
Gene And Protein Expression

Background and Objectives: Second hand smoke (SHS) is a major risk factor for development of chronic obstructive pulmonary disease (COPD), including emphysema and chronic bronchitis in non-smokers. The role of liver X receptor (LXR) in the pathogenesis of COPD/emphysema is not well understood. Both LXR and LXR were found in the lung. The alpha isoform is involved in the regulation of lipid metabolism whereas the beta isoform is involved in the regulation of inflammation. Here we investigate the effects of cigarette smoke (CS) on LXR activation as well as target gene and protein regulation in vivo and in vitro . Methods: Sprague Dawley rats were exposed to SHS for 2 months. Lung tissue and bronchoalveolar lavage fluid (BALf) cells were examined for LXR gene expression and emphysema development (measured by mean linear intercept). Rat alveolar macrophages (AM) and rat pulmonary microvascular endothelial cells (RPMVEC) were treated with cigarette smoke extract (CSE), LPS or DMHCA, a steroidal LXR agonist) in vitro and changes in LXR and its target gene and protein expression were examined. Results: LXR gene expression was impaired and the expression of the LXR target gene, ATP binding cassette transporter A1 (ABCA1), was significantly downregulated in BALf cells from SHS-exposed rat lungs and in rat AM treated with CSE. Real-time PCR revealed significant downregulation of LXR and upregulation of LXR in BALf cells after 1 month of SHS exposure. Similar changes were also observed in CSE-treated RPMVEC. There was a significant increase in the pro-inflammatory interleukin 18 (IL18) levels in BALf cells of SHS-exposed rats, whereas the levels of IL18 binding protein (IL18bp), an endogenous inhibitor of IL18, remained unchanged. Interestingly, activation of LXR led to upregulation of IL18bp in AM and peritoneal macrophages where potential LXR response element (LXRE) sites were indentified, in silico , in the promoter region of IL18bp. Additionally, emphysematous changes and foamy macrophage accumulation were observed in lungs of LXR-deficient mice. Conclusions: These findings implicate IL18bp as a new LXR target gene involved in the anti-inflammatory signaling pathway. Our data suggest that LXR agonist treatment may be beneficial in the prevention and treatment of CS-induced emphysema.

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