Smoking and COVID-19: A Scoping Review

Smoking affects a person’s overall health and damages nearly every organ of the body. Since smoking tobacco affects and damages the lungs, it increases the risk of respiratory infections and makes it easier for the coronavirus disease (COVID-19) to invade the lung tissue, causing more severe symptoms and increasing the risk of death. However, debates are still ongoing as to the effect of cigarette smoking on vulnerability to COVID-19. Some studies, where active smokers were underrepresented among patients with COVID-19, claimed that a “smoker’s paradox” may exist in COVID-19 and that smokers are protected from infection and severe complications of COVID-19. However, other studies reported the opposite trend. The objective of this study is to review the findings of epidemiological and in vitro studies about the association between smoking and the risk of contracting COVID-19, taking into account disease severity. Several epidemiological studies have found a higher smoking prevalence among COVID-19 infected patients. Also, studies had shown that people with respiratory diseases caused by tobacco use are at higher risk of developing severe COVID-19 symptoms. Studies have shown that in vitro, the acute exposure allows for more severe proximal airway epithelial disease from SARS-CoV-2 by reducing the mucosal innate immune response and the proliferation of airway basal stem cells and has implications for disease spread and severity in people exposed to cigarette smoke, with a more severe viral infection and cell death. Smoker patients with different comorbidities are at higher risk of contracting the COVID-19 virus and have a worse prognosis for the virus as well as for their comorbidities. Further investigations of the interaction between smoking and COVID-19 are warranted to accurately assess the risk of contracting COVID-19 among smokers, and the progression to mechanical ventilation or death in patients who suffer from it.

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A Systematic Review and Appraisal of Epidemiological Studies on Household Fuel Use and Its Health Effects Using Demographic and Health Surveys

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041411 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1411

Author(s):

Daniel B. Odo ◽

Ian A. Yang ◽

Luke D. Knibbs

Keyword(s):

Health Outcomes ◽

Exposure Assessment ◽

Health Effects ◽

Low Birthweight ◽

Respiratory Infections ◽

Epidemiological Studies ◽

The Body ◽

Demographic And Health Surveys ◽

Fuel Use ◽

Cooking Fuel

The domestic combustion of polluting fuels is associated with an estimated 3 million premature deaths each year and contributes to climate change. In many low- and middle-income countries (LMICs), valid and representative estimates of people exposed to household air pollution (HAP) are scarce. The Demographic and Health Survey (DHS) is an important and consistent source of data on household fuel use for cooking and has facilitated studies of health effects. However, the body of research based on DHS data has not been systematically identified, nor its strengths and limitations critically assessed as a whole. We aimed to systematically review epidemiological studies using DHS data that considered cooking fuel type as the main exposure, including the assessment of the extent and key drivers of bias. Following PRISMA guidelines, we searched PubMed, Web of Science, Scopus and the DHS publication portal. We assessed the quality and risk of bias (RoB) of studies using a novel tool. Of 2748 records remaining after removing duplicates, 63 were read in full. A total of 45 out of 63 studies were included in our review, spanning 11 different health outcomes and representing 50 unique analyses. In total, 41 of 45 (91%) studies analysed health outcomes in children <5 years of age, including respiratory infections (n = 17), death (all-cause) (n = 14), low birthweight (n = 5), stunting and anaemia (n = 5). Inconsistencies were observed between studies in how cooking fuels were classified into relatively high- and low-polluting. Overall, 36/50 (80%) studies reported statistically significant adverse associations between polluting fuels and health outcomes. In total, 18/50 (36%) of the analyses were scored as having moderate RoB, while 16/50 (32%) analyses were scored as having serious or critical RoB. Although HAP exposure assessment is not the main focus of the DHS, it is the main, often only, source of information in many LMICs. An appreciable proportion of studies using it to analyse the association between cooking fuel use and health have potential for high RoB, mostly related to confounder control, exposure assessment and misclassification, and outcome ascertainment. Based on our findings, we provide some suggestions for ways in which revising the information collected by the DHS could make it even more amenable to studies of household fuel use and health, and reduce the RoB, without being onerous to collect and analyse.

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It’s Time for New Treatments in Pancreatic Cancer Pathology

Romanian Journal of Diabetes Nutrition and Metabolic Diseases ◽

10.2478/rjdnmd-2013-0009 ◽

2013 ◽

Vol 20 (1) ◽

pp. 69-75

Author(s):

Ramona Crişan ◽

Mihaela Aldea ◽

Gabriel Kacso

Keyword(s):

Pancreatic Cancer ◽

Clinical Trials ◽

Randomized Clinical Trials ◽

Epidemiological Studies ◽

Human Pancreatic Cancer ◽

Reference List ◽

Risk Of Death ◽

Pancreatic Cancer Cells ◽

Summary Relative Risk

Abstract Background and aims: The objective of this study was to conclude if there are enough scientific evidences to consider metformin as a potential treatment for pancreatic cancer. Material and Method: We performed a systematic search using PubMed and MedlinePlus up to September 2012. Reference list of relevant peer reviewed literature were hand searched. Ultimately 15 articles were included. Results: Epidemiological studies had revealed that therapy with metformin was associated with 21% reduced risk for all types of malignancies, 31% reduction in overall summary relative risk, the median survival was longer: 16.6 vs. 11.5 months and the risk of death has decreased with 33%. In vitro it was proven that low doses of metformin block the stimulation of DNA synthesis and the growth of human pancreatic cancer cells. Prospective randomized clinical trials to confirm these data were already launched. Conclusions: These results raise the possibility that metformin could improve the poor prognostic of patients suffering from pancreatic cancer. Other clinical trials should confirm this hypothesis.

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Vitamin D Modulation of the Innate Immune Response to Paediatric Respiratory Pathogens Associated with Acute Lower Respiratory Infections

Nutrients ◽

10.3390/nu13010276 ◽

2021 ◽

Vol 13 (1) ◽

pp. 276

Author(s):

Amy S. Bleakley ◽

Paul V. Licciardi ◽

Michael J. Binks

Keyword(s):

Vitamin D ◽

Immune Responses ◽

Immune Cell ◽

Respiratory Infections ◽

Cell Types ◽

Innate Immune ◽

Respiratory Pathogens ◽

Acute Lower Respiratory Infections ◽

Syncytial Virus

Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are Streptococcus pneumoniae, respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms “vitamin D” and “Streptococcus pneumoniae” or “Respiratory Syncytial Virus” or “Influenza”. A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.

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Development of an Affordable, Sustainable and Efficacious Plant-Based Immunomodulatory Food Ingredient Based on Bell Pepper or Carrot RG-I Pectic Polysaccharides

Nutrients ◽

10.3390/nu13030963 ◽

2021 ◽

Vol 13 (3) ◽

pp. 963

Author(s):

Sue McKay ◽

Paul Oranje ◽

Jari Helin ◽

Jean H. Koek ◽

Ellen Kreijveld ◽

...

Keyword(s):

Respiratory Infections ◽

Human Study ◽

Short Chain Fatty Acids ◽

Innate Immune ◽

Bell Pepper ◽

Immunostimulatory Activity ◽

Food Ingredient ◽

Pectic Polysaccharides

The prevalence of acute respiratory infections and their impact on quality of life underlies the need for efficacious solutions that are safe, sustainable and economically viable. Polysaccharides in several (traditional) plant extracts have been shown to be immunostimulatory, and some studies suggest beneficial effects against respiratory infections. The aim of this study was to (i) identify the active polysaccharide constituents from affordable and renewable crops (bell pepper and carrot) using activity-guided fractionation, (ii) evaluate in vitro effects on innate immune responses (phagocytosis and cytokine secretion), microbiota modulation and production of short chain fatty acids, followed by (iii) the evaluation of effects of a bell pepper extract enriched for the active component in a human proof of concept study. We identified rhamnogalacturonan-I (RG-I) as the nutricophore responsible for the immunostimulatory activity with substantial structural and functional equivalence between bell pepper (bp) and carrot (c). The in vitro studies showed that bpRG-I and cRG-I comprise similar immune- and microbiota modulatory potential and the human study demonstrated that bpRG-I was well tolerated and enhanced innate immune responsiveness in vivo. This is an important step towards testing the efficacy of RG-I from bpRG-I or cRG-I in an infection trial in humans.

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A novel, anatomy-similar in vitro model of 3D airway epithelial for anti-coronavirus drug discovery

10.1101/2021.03.03.433824 ◽

2021 ◽

Author(s):

Yaling Zhang ◽

Dingailu Ma ◽

Jitao David Zhang ◽

Xinan Liu ◽

Qihui Zhu ◽

...

Keyword(s):

Innate Immune ◽

Airway Epithelial ◽

Dose Prediction ◽

Respiratory Airway ◽

Immune Signatures ◽

Human Dose ◽

Physiological Relevance ◽

Coronavirus Infection ◽

Vitro Model

SARS-CoV-2 and its induced COVID-19 remains as a global health calamity. Severe symptoms and high mortality, caused by cytokine storm and acute respiratory distress syndrome in the lower respiratory airway, are always associated with elderly individuals and those with comorbidities; whereas mild or moderate COVID-19 patients have limited upper respiratory flu-like symptoms. There is an urgent need to investigate SARS-CoV-2 and other coronaviruses replication and immune responses in human respiratory systems. The human reconstituted airway epithelial air-liquid interface (ALI) models are the most physiologically relevant model for the investigation of coronavirus infection and virus-triggered innate immune signatures. We established ALI models representing both the upper and the lower respiratory airway to characterize the coronavirus infection kinetics, tissue pathophysiology, and innate immune signatures from upper and lower respiratory tract perspective. Our data suggested these in vitro ALI models maintain high physiological relevance with human airway tissues. The coronavirus induced immune response observed in these upper and lower respiratory airway models are similar to what has been reported in COVID-19 patients. The antiviral efficacy results of a few promising anti-coronavirus drugs in these models were consistent with previous reports and could be valuable for the human dose prediction. Taken together, our study demonstrates the importance of 3D airway epithelial ALI model for the understanding of coronavirus pathogenesis and the discovery and development of anti-coronavirus drugs.

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The Air We Breathe: Air Pollution as a Prevalent Proinflammatory Stimulus Contributing to Neurodegeneration

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.647643 ◽

2021 ◽

Vol 15 ◽

Author(s):

Monika Jankowska-Kieltyka ◽

Adam Roman ◽

Irena Nalepa

Keyword(s):

Air Pollution ◽

Neurodegenerative Disease ◽

Air Pollutants ◽

Disease Onset ◽

Circulatory System ◽

Epidemiological Studies ◽

The Body ◽

The Central Nervous System

Air pollution is regarded as an important risk factor for many diseases that affect a large proportion of the human population. To date, accumulating reports have noted that particulate matter (PM) is closely associated with the course of cardiopulmonary disorders. As the incidence of Alzheimer’s disease (AD), Parkinson’s disease (PD), and autoimmune disorders have risen and as the world’s population is aging, there is an increasing interest in environmental health hazards, mainly air pollution, which has been slightly overlooked as one of many plausible detrimental stimuli contributing to neurodegenerative disease onset and progression. Epidemiological studies have indicated a noticeable association between exposure to PM and neurotoxicity, which has been gradually confirmed by in vivo and in vitro studies. After entering the body directly through the olfactory epithelium or indirectly by passing through the respiratory system into the circulatory system, air pollutants are subsequently able to reach the brain. Among the potential mechanisms underlying particle-induced detrimental effects in the periphery and the central nervous system (CNS), increased oxidative stress, inflammation, mitochondrial dysfunction, microglial activation, disturbance of protein homeostasis, and ultimately, neuronal death are often postulated and concomitantly coincide with the main pathomechanisms of neurodegenerative processes. Other complementary mechanisms by which PM could mediate neurotoxicity and contribute to neurodegeneration remain unconfirmed. Furthermore, the question of how strong and proven air pollutants are as substantial adverse factors for neurodegenerative disease etiologies remains unsolved. This review highlights research advances regarding the issue of PM with an emphasis on neurodegeneration markers, symptoms, and mechanisms by which air pollutants could mediate damage in the CNS. Poor air quality and insufficient knowledge regarding its toxicity justify conducting scientific investigations to understand the biological impact of PM in the context of various types of neurodegeneration.

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Innate Immune Signaling and Porphyromonas gingivalis-accelerated Atherosclerosis

Journal of Dental Research ◽

10.1177/154405910608500202 ◽

2006 ◽

Vol 85 (2) ◽

pp. 106-121 ◽

Cited By ~ 121

Author(s):

F.C. Gibson ◽

H. Yumoto ◽

Y. Takahashi ◽

H.-H. Chou ◽

C.A. Genco

Keyword(s):

Periodontal Disease ◽

Soft Tissues ◽

Periodontal Diseases ◽

Epidemiological Studies ◽

Innate Immune ◽

In Vivo Studies ◽

Atherosclerotic Cardiovascular Disease ◽

Systemic Complications ◽

Increased Risk

Periodontal diseases are a group of diseases that lead to erosion of the hard and soft tissues of the periodontium, which, in severe cases, can result in tooth loss. Anecdotal clinical observations have suggested that poor oral health may be associated with poor systemic health; however, only recently have appropriate epidemiological studies been initiated, with defined clinical endpoints of periodontal disease, to address the association of periodontal disease with increased risk for cardiovascular and cerebrovascular disease. Although conflicting reports exist, these epidemiological studies support this connection. Paralleling these epidemiological studies, emerging basic scientific studies also support that infection may represent a risk factor for atherosclerosis. With P. gingivalis as a model pathogen, in vitro studies support that this organism can activate host innate immune responses associated with atherosclerosis, and in vivo studies demonstrate that this organism can accelerate atheroma deposition in animal models. In this review, we focus primarily on the basic scientific studies performed to date which support that infection with bacteria, most notably P. gingivalis, accelerates atherosclerosis. Furthermore, we attempt to bring together these studies to provide an up-to-date framework of emerging theories into the mechanisms underlying periodontal disease and increased risk for atherosclerosis, as well as identify intervention strategies to reduce the incidence of periodontal disease in humans, in an attempt to decrease risk for systemic complications of periodontal disease such as atherosclerotic cardiovascular disease.

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Gastrointestinal epithelial innate immunity—regionalization and organoids as new model

Journal of Molecular Medicine ◽

10.1007/s00109-021-02043-9 ◽

2021 ◽

Vol 99 (4) ◽

pp. 517-530 ◽

Cited By ~ 1

Author(s):

Özge Kayisoglu ◽

Nicolas Schlegel ◽

Sina Bartfeld

Keyword(s):

Innate Immunity ◽

Inflammatory Responses ◽

The Body ◽

Innate Immune ◽

Cellular Interactions ◽

Human Gastrointestinal Tract ◽

Inflammatory Bowel ◽

Immune Sensing ◽

Innate Immune Sensing

AbstractThe human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body. It is equipped with a multitude of different innate immune sensors, such as Toll-like receptors, to mount inflammatory responses to microbes. Dysfunction of this intricate system results in inflammation-associated pathologies, such as inflammatory bowel disease. However, the complexity of the cellular interactions, their molecular basis and their development remains poorly understood. In recent years, stem cell–derived organoids have gained increasing attention as promising models for both development and a broad range of pathologies, including infectious diseases. In addition, organoids enable the study of epithelial innate immunity in vitro. In this review, we focus on the gastrointestinal epithelial barrier and its regional organization to discuss innate immune sensing and development.

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Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates

Human & Experimental Toxicology ◽

10.1177/0960327110388959 ◽

2010 ◽

Vol 30 (9) ◽

pp. 1119-1140 ◽

Cited By ~ 197

Author(s):

Somayyeh Karami-Mohajeri ◽

Mohammad Abdollahi

Keyword(s):

Oxidative Stress ◽

Metabolic Disorders ◽

Epidemiological Studies ◽

The Body ◽

Bibliographic Databases ◽

Ache Inhibitors ◽

Central Nervous Systems ◽

Enzymatic Pathways

Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963–2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.

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Antidiabetic drugs and the risk of cancer: beneficial, neutral, or detrimental?

Forum of Clinical Oncology ◽

10.2478/fco-2021-0014 ◽

2021 ◽

Vol 12 (1) ◽

pp. 74-81

Author(s):

Taoreed Adegoke Azeez ◽

Sharif Adeniyi Folorunso ◽

Chinedu Eguzozie ◽

Adeleke Adedapo Adegboyega

Keyword(s):

Diabetes Mellitus ◽

Clinical Trials ◽

Epidemiological Studies ◽

The Body ◽

Antidiabetic Drugs ◽

Pharmacological Agents ◽

Middle Income ◽

Beneficial Effects ◽

Risk Of Cancer

Abstract The prevalence of diabetes mellitus is rapidly rising, especially in low- and middle-income countries. Also, early-onset diabetes is on the rise, and millions of individuals have to be on antidiabetic medications for a prolonged period. Therefore, more people are getting exposed to the adverse effects of antidiabetic medications. Cancer is among the top ranking causes of death worldwide. Researches are still ongoing to understand the etiologies, precipitants, risk factors, correlates, and predictors of cancers. Diabetes mellitus is associated with various cancers, as extensively documented in the literature. There are conflicting reports about the association between antidiabetic drugs and cancer. This is even of crucial importance, considering that the prevalence of diabetes is rising. Insulin glargine is reported to be associated with cancers, but clinical trials have not confirmed this. Metformin is largely believed to be beneficial in oncologic practice. Glibenclamide is reported to reduce tumor growth. The association between pioglitazone and bladder cancer is still an area for further research. Meglitinides have also been associated with cancers. Incretin-based therapy and the α-glucosidase inhibitors appear to have beneficial effects on cancers. There is still a need for randomized multicentric clinical trials to further substantiate and clarify reports from epidemiological studies. Further in vitro studies will also be necessary to characterize the interaction of these pharmacological agents with other molecules in the body.

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