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1.
Front Immunol ; 13: 846605, 2022.
Article in English | MEDLINE | ID: covidwho-1798935

ABSTRACT

Cigarette smoking is reported in about one third of adults worldwide. A strong relationship between cigarette smoke exposure and chronic obstructive pulmonary disease (COPD) as well as lung cancer has been proven. However, about 15% of lung cancer cases, and between one fourth and one third of COPD cases, occur in never-smokers. The effects of cigarette smoke on the innate as well as the adaptive immune system have been widely investigated. It is assumed that certain immunologic features contribute to lung cancer and COPD development in the absence of smoking as the major risk factor. In this article, we review different immunological aspects of lung cancer and COPD with a special focus on non-smoking related risk factors.


Subject(s)
Cigarette Smoking , Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Adult , Causality , Cigarette Smoking/adverse effects , Humans , Lung Neoplasms/complications , Pulmonary Disease, Chronic Obstructive/etiology , Risk Factors , Tobacco
2.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
4.
Front Immunol ; 12: 648815, 2021.
Article in English | MEDLINE | ID: covidwho-1325521

ABSTRACT

Multiple lines of evidence have demonstrated that cigarette smoke or Chronic Obstructive Pulmonary Disease upregulates angiotensin-converting enzyme 2, the cellular receptor for the entry of the severe acute respiratory syndrome coronavirus 2, which predisposes individuals to develop severe Coronavirus disease 2019. The reason for this observation is unknown. We recently reported that the loss of function of Miz1 in the lung epithelium in mice leads to a spontaneous COPD-like phenotype, associated with upregulation of angiotensin-converting enzyme 2. We also reported that cigarette smoke exposure downregulates Miz1 in lung epithelial cells and in mice, and Miz1 is also downregulated in the lungs of COPD patients. Here, we provide further evidence that Miz1 directly binds to and represses the promoter of angiotensin-converting enzyme 2 in mouse and human lung epithelial cells. Our data provide a potential molecular mechanism for the upregulation of angiotensin-converting enzyme 2 observed in smokers and COPD patients, with implication in severe Coronavirus disease 2019.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Kruppel-Like Transcription Factors/metabolism , Receptors, Virus/genetics , Transcription, Genetic , Alveolar Epithelial Cells/metabolism , Angiotensin-Converting Enzyme 2/metabolism , Animals , BTB-POZ Domain , Cell Line , Cigarette Smoking/adverse effects , Kruppel-Like Transcription Factors/chemistry , Kruppel-Like Transcription Factors/genetics , Mice , Promoter Regions, Genetic , Protein Binding , Receptors, Virus/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Transcription, Genetic/drug effects , Tumor Necrosis Factors/pharmacology , Virus Internalization
5.
Int J Mol Sci ; 22(14)2021 Jul 16.
Article in English | MEDLINE | ID: covidwho-1323266

ABSTRACT

Smoking is a major risk factor for chronic obstructive pulmonary disease (COPD) and causes remodeling of the small airways. However, the exact smoke-induced effects on the different types of small airway epithelial cells (SAECs) are poorly understood. Here, using air-liquid interface (ALI) cultures, single-cell RNA-sequencing reveals previously unrecognized transcriptional heterogeneity within the small airway epithelium and cell type-specific effects upon acute and chronic cigarette smoke exposure. Smoke triggers detoxification and inflammatory responses and aberrantly activates and alters basal cell differentiation. This results in an increase of inflammatory basal-to-secretory cell intermediates and, particularly after chronic smoke exposure, a massive expansion of a rare inflammatory and squamous metaplasia associated KRT6A+ basal cell state and an altered secretory cell landscape. ALI cultures originating from healthy non-smokers and COPD smokers show similar responses to cigarette smoke exposure, although an increased pro-inflammatory profile is conserved in the latter. Taken together, the in vitro models provide high-resolution insights into the smoke-induced remodeling of the small airways resembling the pathological processes in COPD airways. The data may also help to better understand other lung diseases including COVID-19, as the data reflect the smoke-dependent variable induction of SARS-CoV-2 entry factors across SAEC populations.


Subject(s)
Airway Remodeling/drug effects , Alveolar Epithelial Cells/drug effects , Cigarette Smoking/adverse effects , Epithelial Cells/metabolism , Alveolar Epithelial Cells/metabolism , Alveolar Epithelial Cells/pathology , Cell Differentiation/drug effects , Cells, Cultured , Cigarette Smoking/metabolism , Epithelial Cells/drug effects , Humans , Neoplasms, Basal Cell/metabolism , Primary Cell Culture , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Respiratory Mucosa/metabolism , Respiratory Mucosa/pathology , Smoke , Smoking/adverse effects , Smoking/metabolism
6.
Int J Mol Sci ; 22(14)2021 Jul 18.
Article in English | MEDLINE | ID: covidwho-1314669

ABSTRACT

A large body of evidence shows the harmful effects of cigarette smoke to oral and systemic health. More recently, a link between smoking and susceptibility to coronavirus disease 2019 (COVID-19) was proposed. COVID-19 is due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses the receptor ACE2 and the protease TMPRSS2 for entry into host cells, thereby infecting cells of the respiratory tract and the oral cavity. Here, we examined the effects of cigarette smoke on the expression of SARS-CoV-2 receptors and infection in human gingival epithelial cells (GECs). We found that cigarette smoke condensates (CSC) upregulated ACE2 and TMPRSS2 expression in GECs, and that CSC activated aryl hydrocarbon receptor (AhR) signaling in the oral cells. ACE2 was known to mediate SARS-CoV-2 internalization, and we demonstrate that CSC treatment potentiated the internalization of SARS-CoV-2 pseudovirus in GECs in an AhR-dependent manner. AhR depletion using small interference RNA decreased SARS-CoV-2 pseudovirus internalization in CSC-treated GECs compared with control GECs. Our study reveals that cigarette smoke upregulates SARS-CoV-2 receptor expression and infection in oral cells. Understanding the mechanisms involved in SARS-CoV-2 infection in cells of the oral cavity may suggest therapeutic interventions for preventing viral infection and transmission.


Subject(s)
COVID-19/metabolism , COVID-19/virology , Cigarette Smoking/adverse effects , SARS-CoV-2/drug effects , Smoking/adverse effects , Virus Internalization/drug effects , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Cigarette Smoking/physiopathology , Disease Susceptibility , Epithelial Cells/metabolism , Epithelial Cells/virology , Gingiva/metabolism , Gingiva/virology , Humans , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Virus/metabolism , Respiratory Mucosa/metabolism , SARS-CoV-2/physiology , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Smoking/metabolism
7.
Proc Natl Acad Sci U S A ; 118(19)2021 05 11.
Article in English | MEDLINE | ID: covidwho-1214016

ABSTRACT

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.


Subject(s)
Lab-On-A-Chip Devices , Models, Biological , Pulmonary Alveoli/physiology , Alveolar Epithelial Cells , Antiviral Agents/pharmacology , Cigarette Smoking/adverse effects , Dimethylpolysiloxanes/chemistry , Gelatin/chemistry , Humans , Hydrogels/chemistry , Methacrylates/chemistry , Porosity , Pulmonary Alveoli/cytology , Pulmonary Alveoli/pathology , Respiration , Respiratory Mucosa/cytology , Respiratory Mucosa/physiology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity
8.
Afr J Prim Health Care Fam Med ; 13(1): e1-e3, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1089009

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has spread throughout the world, with devastating effects of the virus as well as the repercussions of the resulting 'lockdowns'. South Africa went into a national lockdown in March 2020 to mitigate the impact of the virus. This included a ban on the sales of tobacco and electronic cigarette products. The ban has been a highly contentious issue in South Africa, discussed worldwide, which has drawn many criticisms. The prevalence rate of smoking in South Africa was around 21.5%, with the Western Cape province having a prevalence rate of 39%. We compared the number of chronic obstructive pulmonary disease (COPD) presentations at a large regional referral hospital in the Western Cape province from January to August 2019 with the same period in 2020. Electronic emergency centre data showed a reduction of 69.28% in COPD presentations. To control for some confounders for the same period, we also reviewed patients presenting with urinary tract infections, which showed only a 30.60% reduction. This notable reduction in COPD presentations reduced service pressure of emergency centre and most likely benefitted patients' health. Further research and policies are needed to ensure ongoing reduction in the prevalence of smoking.


Subject(s)
COVID-19 , Cigarette Smoking/adverse effects , Emergency Service, Hospital , Pandemics , Patient Acceptance of Health Care/statistics & numerical data , Pulmonary Disease, Chronic Obstructive/therapy , Tobacco Products/legislation & jurisprudence , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/virology , Cigarette Smoking/epidemiology , Cigarette Smoking/legislation & jurisprudence , Cigarette Smoking/prevention & control , Commerce/legislation & jurisprudence , Communicable Disease Control/methods , Humans , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/epidemiology , SARS-CoV-2 , South Africa/epidemiology , Symptom Flare Up , Tobacco Products/adverse effects , Tobacco Products/economics
9.
Acta Biomed ; 91(4): e2020148, 2020 10 21.
Article in English | MEDLINE | ID: covidwho-1059764

ABSTRACT

Coronavirus disease (COVID-19) is an infectious disease caused by the newly discovered coronavirus, Sars-Cov-2. This infection can cause mild to very severe respiratory and systemic illness mainly related with a cytokine storm. The epidemiology of COVID-19 is under continuous evolution, and studies are ongoing aiming at identifying the possible factors facilitating the diffusion of this infection. It is documented that air pollution and smoking are a leading cause of human morbidity and mortality globally, and can increase the risk of many diseases, including respiratory diseases. Overall, a linear relationship between exposure to atmospheric pollutants and diffusion of the Sars-Cov2 virus seems to exist. However, this correlation, cannot be regarded as a cause-effect relationship.  The available data show that air pollution is responsible for inflammation and hyper-activation of innate immunity that are associated with the worst outcomes of covid-19 but do not allow to conclude that atmospheric particulate is responsible for increased contagion. As to smoking, nicotine activation of nicotinic receptors leads to enhanced protease activation, apoptosis and inflammatory signaling through the same pathways (Renin-angiotensin system (RAS) and angiotensin-converting enzyme 2 (ACE2)) used by the virus increasing the inflammatory/destructive action of the virus itself. The increase in non-communicable diseases and of chronic inflammatory diseases is in line with environmental pollution, related climate changes, and with an augmented susceptibility to infectious diseases with increased contagiousness and morbidity. Restrictive measures to limit environmental pollution are needed worldwide as this represents a threat for human health.


Subject(s)
Air Pollution/adverse effects , COVID-19/epidemiology , COVID-19/transmission , Cigarette Smoking/adverse effects , Humans
10.
Laeknabladid ; 106(12): 574-579, 2020 Dec.
Article in Icelandic | MEDLINE | ID: covidwho-948771

ABSTRACT

INTRODUCTION: The COVID-19 pandemic has caused public health and economic turmoil across the globe. Severe COVID-19 disease most often presents with pneumonia and complications in acutely ill patients often stem from the lungs. The associations of lung disease, smoking and e-cigarette use with the incidence and severity of COVID-19 are unclear on a population level. METHODS: Data on 1761 patients from the Icelandic outpatient Landspitali COVID-19 Clinic were used. The prevalence of smoking, e-cigarette use and underlying lung diseases was calculated in the cohort, with stratification based on age groups and a clinical classification of symptom severity. It was tested whether these prevalences differed between age groups and classes of symptom severity. RESULTS: Most patients were in the age group between 35-54 years of age and a large majority had mild symptoms at diagnosis. The prevalence of smoking was 6% with the highest prevalence among 35-54 year olds. The prevalence of e-cigarette use was 4%. It was most prevalent in the age group between 18-34 years. There was no difference in the prevalence of smoking or e-cigarette use between classes of symptom severity. The prevalence of lung disease was 9%. It was higher among older patients and patients with more severe symptoms. CONCLUSION: The age distribution and prevalence of lung disease and their risk factors are described in the context of COVID-19 incidence and symptom severity in a whole-nation cohort of Icelanders. The cohort is younger and had less severe symptoms than in many previosly published studies of COVID-19. Interestingly, the prevalences of smoking and e-cigarette use were lower than in the Icelandic general population and they were not associated with symptom severity at diagnosis. To conclude, the results presented here indicate that underlying lung diseases are prevalent among people with severe COVID-19 symptoms but fail to demonstrate an association between cigarette smoking or e-cigarette smoking with COVID-19 severity.


Subject(s)
COVID-19/epidemiology , Cigarette Smoking/adverse effects , Lung Diseases/epidemiology , Vaping/adverse effects , Adult , Age Distribution , Age Factors , COVID-19/diagnosis , Cigarette Smoking/epidemiology , Female , Humans , Iceland/epidemiology , Lung Diseases/diagnosis , Male , Middle Aged , Prevalence , Risk Assessment , Risk Factors , Severity of Illness Index , Vaping/epidemiology
11.
J Adolesc Health ; 67(4): 519-523, 2020 10.
Article in English | MEDLINE | ID: covidwho-773592

ABSTRACT

PURPOSE: This study aimed to assess whether youth cigarette and electronic cigarette (e-cigarette) use are associated with coronavirus disease 2019 (COVID-19) symptoms, testing, and diagnosis. METHODS: An online national survey of adolescents and young adults (n = 4,351) aged 13-24 years was conducted in May 2020. Multivariable logistic regression assessed relationships among COVID-19-related symptoms, testing, and diagnosis and cigarettes only, e-cigarettes only and dual use, sociodemographic factors, obesity, and complying with shelter-in-place. RESULTS: COVID-19 diagnosis was five times more likely among ever-users of e-cigarettes only (95% confidence interval [CI]: 1.82-13.96), seven times more likely among ever-dual-users (95% CI: 1.98-24.55), and 6.8 times more likely among past 30-day dual-users (95% CI: 2.40-19.55). Testing was nine times more likely among past 30-day dual-users (95% CI: 5.43-15.47) and 2.6 times more likely among past 30-day e-cigarette only users (95% CI: 1.33-4.87). Symptoms were 4.7 times more likely among past 30-day dual-users (95% CI: 3.07-7.16). CONCLUSIONS: COVID-19 is associated with youth use of e-cigarettes only and dual use of e-cigarettes and cigarettes, suggesting the need for screening and education.


Subject(s)
Adolescent Behavior , Cigarette Smoking/adverse effects , Coronavirus Infections/etiology , Pneumonia, Viral/etiology , Vaping/adverse effects , Adolescent , Betacoronavirus , COVID-19 , Cigarette Smoking/epidemiology , Cross-Sectional Studies , Electronic Nicotine Delivery Systems , Female , Humans , Male , Pandemics , Risk Factors , SARS-CoV-2 , Surveys and Questionnaires , Vaping/epidemiology , Young Adult
12.
Food Funct ; 11(4): 3516-3526, 2020 Apr 30.
Article in English | MEDLINE | ID: covidwho-726012

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease with few successful treatments, and is strongly associated with cigarette smoking (CS). Since the novel coronavirus has spread worldwide seriously, there is growing concern that patients who have chronic respiratory conditions like COPD can easily be infected and are more prone to having severe illness and even mortality because of lung dysfunction. Loquat leaves have long been used as an important material for both pharmaceutical and functional applications in the treatment of lung disease in Asia, especially in China and Japan. Total flavonoids (TF), the main active components derived from loquat leaves, showed remarkable anti-inflammatory and antioxidant activities. However, their protective activity against CS-induced COPD airway inflammation and oxidative stress and its underlying mechanism still remain not well-understood. The present study uses a CS-induced mouse model to estimate the morphological changes in lung tissue. The results demonstrated that TF suppressed the histological changes in the lungs of CS-challenged mice, as evidenced by reduced generation of pro-inflammatory cytokines including interleukin 6 (IL-6), IL-1ß, tumor necrosis factor α (TNF-α), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) and diminished the protein expression of transient receptor potential vanilloid 1 (TRPV1). Moreover, TF also inhibited phosphorylation of IKK, IκB and NFκB and increased p-Akt. Interestingly, TF could inhibit CS-induced oxidative stress in the lungs of COPD mice. TF treatment significantly inhibited the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). In addition, TF markedly downregulated TRPV1 and cytochrome P450 2E1 (CYP2E1) and upregulated the expression of SOD-2, while the p-JNK level was observed to be inhibited in COPD mice. Taken together, our findings showed that the protective effect and putative mechanism of the action of TF resulted in the inhibition of inflammation and oxidative stress through the regulation of TRPV1 and the related signal pathway in lung tissues. It suggested that TF derived from loquat leaves could be considered to be an alternative or a new functional material and used for the treatment of CS-induced COPD.


Subject(s)
Cigarette Smoking/adverse effects , Drugs, Chinese Herbal/administration & dosage , Eriobotrya/chemistry , Flavonoids/administration & dosage , Pulmonary Disease, Chronic Obstructive/drug therapy , TRPV Cation Channels/immunology , Animals , Cytochrome P-450 CYP2E1/genetics , Cytochrome P-450 CYP2E1/immunology , Humans , Interleukin-6/genetics , Interleukin-6/immunology , Male , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Plant Leaves/chemistry , Pulmonary Disease, Chronic Obstructive/etiology , Pulmonary Disease, Chronic Obstructive/immunology , Signal Transduction/drug effects , Smoke/adverse effects , Superoxide Dismutase/genetics , Superoxide Dismutase/immunology , TRPV Cation Channels/genetics
13.
J Clin Virol ; 126: 104338, 2020 05.
Article in English | MEDLINE | ID: covidwho-124784

ABSTRACT

BACKGROUND: The World Health Organization has highlighted the need for improved surveillance and understanding of the health burden imposed by non-influenza RNA respiratory viruses. Human coronaviruses (CoVs) are a major cause of respiratory and gastrointestinal tract infections with associated morbidity and mortality. OBJECTIVES: The objective of our study was to characterize the epidemiology of CoVs in our tertiary care centre, and identify clinical correlates of disease severity. STUDY DESIGN: A cross-sectional study was performed of 226 patients admitted with confirmed CoV respiratory tract infection between 2010 and 2016. Variables consistent with a severe disease burden were evaluated including symptoms, length of stay, intensive care unit (ICU) admission and mortality. RESULTS: CoVs represented 11.3% of all positive respiratory virus samples and OC43 was the most commonly identified CoV. The majority of infections were community-associated while 21.6% were considered nosocomial. The average length of stay was 11.8 days with 17.3% of patients requiring ICU admission and an all-cause mortality of 7%. In a multivariate model, female gender and smoking were associated with increased likelihood of admission to ICU or death. CONCLUSION: This study highlights the significant burden of CoVs and justifies the need for surveillance in the acute care setting.


Subject(s)
Cigarette Smoking/adverse effects , Coronavirus Infections/diagnosis , Coronavirus/physiology , Respiratory Tract Infections/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Cohort Studies , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cross-Sectional Studies , Female , Hospitalization , Humans , Intensive Care Units , Male , Middle Aged , Ontario/epidemiology , Prevalence , Prognosis , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/mortality , Respiratory Tract Infections/virology , Sex Factors , Young Adult
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