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Leitzke M, Roach DT, Hesse S, Schönknecht P, Becker GA, Rullmann M, Sattler B, Sabri O. Long COVID - a critical disruption of cholinergic neurotransmission? Bioelectron Med 2025; 11:5. [PMID: 40011942 DOI: 10.1186/s42234-025-00167-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Accepted: 01/30/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Following the COVID-19 pandemic, there are many chronically ill Long COVID (LC) patients with different symptoms of varying degrees of severity. The pathological pathways of LC remain unclear until recently and make identification of path mechanisms and exploration of therapeutic options an urgent challenge. There is an apparent relationship between LC symptoms and impaired cholinergic neurotransmission. METHODS This paper reviews the current literature on the effects of blocked nicotinic acetylcholine receptors (nAChRs) on the main affected organ and cell systems and contrasts this with the unblocking effects of the alkaloid nicotine. In addition, mechanisms are presented that could explain the previously unexplained phenomenon of post-vaccination syndrome (PVS). The fact that not only SARS-CoV-2 but numerous other viruses can bind to nAChRs is discussed under the assumption that numerous other post-viral diseases and autoimmune diseases (ADs) may also be due to impaired cholinergic transmission. We also present a case report that demonstrates changes in cholinergic transmission, specifically, the availability of α4β2 nAChRs by using (-)-[18F]Flubatine whole-body positron emission tomography (PET) imaging of cholinergic dysfunction in a LC patient along with a significant neurological improvement before and after low-dose transcutaneous nicotine (LDTN) administration. Lastly, a descriptive analysis and evaluation were conducted on the results of a survey involving 231 users of LDTN. RESULTS A substantial body of research has emerged that offers a compelling explanation for the phenomenon of LC, suggesting that it can be plausibly explained because of impaired nAChR function in the human body. Following a ten-day course of transcutaneous nicotine administration, no enduring neuropathological manifestations were observed in the patient. This observation was accompanied by a significant increase in the number of free ligand binding sites (LBS) of nAChRs, as determined by (-)-[18F]Flubatine PET imaging. The analysis of the survey shows that the majority of patients (73.5%) report a significant improvement in the symptoms of their LC/MEF/CFS disease as a result of LDTN. CONCLUSIONS In conclusion, based on current knowledge, LDTN appears to be a promising and safe procedure to relieve LC symptoms with no expected long-term harm.
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Affiliation(s)
- Marco Leitzke
- Department of Nuclear Medicine, University of Leipzig Medical Centre, Leipzig, 04103, Germany.
- Department of Anesthesiology, Intensive Care Medicine, Pain- and Palliative Therapy Helios Clinics, Colditzer Straße 48, Leisnig, 04703, Germany.
| | - Donald Troy Roach
- School of Comillas University, Renegade Research, Madrid, 28015, Spain
| | - Swen Hesse
- Department of Nuclear Medicine, University of Leipzig Medical Centre, Leipzig, 04103, Germany
| | - Peter Schönknecht
- Department of Psychiatry and Neurology Altscherbitz, Schkeuditz, 04435, Germany
- Outpatient Department for Forensic-Psychiatric Research, University of Leipzig, Leipzig, 04103, Germany
| | - Georg-Alexander Becker
- Department of Nuclear Medicine, University of Leipzig Medical Centre, Leipzig, 04103, Germany
| | - Michael Rullmann
- Department of Nuclear Medicine, University of Leipzig Medical Centre, Leipzig, 04103, Germany
| | - Bernhardt Sattler
- Department of Nuclear Medicine, University of Leipzig Medical Centre, Leipzig, 04103, Germany
| | - Osama Sabri
- Department of Nuclear Medicine, University of Leipzig Medical Centre, Leipzig, 04103, Germany
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Kobayashi T, Dignass A, Roblin X, Takatori Y, Kaise T, Oortwijn A, Jamoul C, Hibi T. Filgotinib induction-study baseline characteristics of patients with ulcerative colitis who achieve sustained corticosteroid-free remission: post hoc analysis of the phase 2b/3 SELECTION study. Intest Res 2025; 23:65-75. [PMID: 39026439 PMCID: PMC11834366 DOI: 10.5217/ir.2024.00007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 04/04/2024] [Accepted: 04/15/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND/AIMS Obtaining and maintaining corticosteroid-free remission are important goals of treatment for ulcerative colitis (UC). Characteristics associated with achieving corticosteroid-free remission were assessed in filgotinib-treated patients in SELECTION, a 58-week, phase 2b/3 trial in moderately to severely active UC. METHODS This post hoc analysis used data from filgotinib-treated patients receiving corticosteroids at maintenance baseline in SELECTION. Univariate logistic regression was performed to assess induction baseline characteristics associated with 6 months of corticosteroid-free remission at week 58, defined as clinical remission without using corticosteroids for at least 6 months. RESULTS At maintenance baseline, 92 and 81 patients were receiving corticosteroids in the filgotinib 200 mg and filgotinib 100 mg groups, respectively. Age, body mass index, history of pancolitis, disease duration, fecal calprotectin levels, C-reactive protein levels, Mayo Clinic Score, concomitant corticosteroids, immunomodulators, and aminosalicylates had no statistically significant effect on the likelihood of achieving corticosteroid-free remission. Baseline characteristics associated with increased odds of corticosteroid-free remission were Mayo Clinic Endoscopic Subscore of 2 (vs. 3) in the filgotinib 200 mg and filgotinib 100 mg groups, and female (vs. male) sex, current (vs. former or never) smoking, and being biologic‑naive (vs. experienced) in the filgotinib 200 mg group. CONCLUSIONS Steroid tapering can be achieved in patients with UC receiving filgotinib 200 mg independently of baseline characteristics such as clinical activity and duration of illness. However, the likelihood of achieving corticosteroid-free remission was higher among patients who were biologic-naive, current smokers, had low endoscopic inflammatory burden and who were female.
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Affiliation(s)
- Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt am Main, Germany
| | - Xavier Roblin
- IBD Unit, University Hospital of Saint-Étienne, Saint-Étienne, France
| | | | | | | | | | - Toshifumi Hibi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
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Honap S, Zou G, Danese S, Peyrin-Biroulet L, Jairath V. Personalized (N-of-1) Clinical Trials for Inflammatory Bowel Disease: Opportunities and Challenges. Clin Gastroenterol Hepatol 2025; 23:14-23. [PMID: 39303799 DOI: 10.1016/j.cgh.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 08/03/2024] [Accepted: 08/07/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND & AIMS Heterogeneity of treatment effects in inflammatory bowel disease (IBD) means that many individuals or patient subgroups depart from the average for whom the outcomes from traditional randomized trials may not be applicable. The N-of-1 trial is a design in which a single patient is followed over time with the treatments being randomized from period to period with the intention of finding the most effective treatment for that patient. The aim was to investigate the utility of N-of-1 trials in IBD. METHODS To identify relevant articles for this scoping review, a MEDLINE literature search was conducted through the PubMed platform for articles published in the English language using the search terms "inflammatory bowel disease," "Crohn's disease," "ulcerative colitis," "N-of-1 trials," "single case designs," and "personalized trials." RESULTS N-of-1 trials have seen a resurgence across several medical disciplines, driven by a need for more personalized medicine and patient-centered health care; their use in IBD is scarce with only 3 trials identified. Studies involving multiple N-of-1 trials can generate robust evidence for each participant and average effect estimates. The N-of-1 trial may hold potential for studying patients with IBD that are excluded from or underrepresented by randomized trials, such as those with extraintestinal manifestations, pouchitis, and proctitis. Although methodologically sound and akin to the rigor of a randomized controlled trial, the crossover periods inherent to the study design can be perceived as burdensome by patients and researchers. CONCLUSIONS The N-of-1 trial design provides a patient-centered means of objectively determining individual response to therapy.
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Affiliation(s)
- Sailish Honap
- INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France; School of Immunology and Microbial Sciences, King's College, London, United Kingdom; Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, United Kingdom
| | - Guangyong Zou
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy
| | | | - Vipul Jairath
- Department of Epidemiology and Biostatistics, Western University, London, Ontario, Canada; Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University, London, Ontario, Canada; and; Lawson Health Research Institute, Western University, London, Ontario, Canada.
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Halder N, Yadav S, Lal G. Neuroimmune communication of the cholinergic system in gut inflammation and autoimmunity. Autoimmun Rev 2024; 23:103678. [PMID: 39500481 DOI: 10.1016/j.autrev.2024.103678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 11/01/2024] [Accepted: 11/01/2024] [Indexed: 11/08/2024]
Abstract
Neuroimmune communication in the body forms a bridge between two central regulatory systems of the body, i.e., nervous and immune systems. The cholinergic system is a crucial modulatory neurotransmitter in the central and peripheral nervous system. It includes the neurotransmitter acetylcholine (ACh), the enzyme required for the synthesis of ACh (choline acetyltransferase, ChAT), the enzyme required for its degradation (acetylcholinesterase, AChE), and cholinergic receptors (Nicotinic acetylcholine receptors and muscarinic acetylcholine receptors). The cholinergic system in neurons is well known for its role in cognitive function, sensory perception, motor control, learning, and memory processes. It has been shown that the non-neuronal cholinergic system (NNCS) is present in various tissues and immune cells and forms a neuroimmune communications system. In the present review, we discussed the NNCS on immune cells, its role in homeostasis and inflammatory reactions in the gut, and how it can be exploited in treating inflammatory responses.
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Affiliation(s)
- Namrita Halder
- Biotechnology Research and Innovation Council-National Centre for Cell Science (BRIC-NCCS), SPPU campus, Ganeshkhind, Pune, MH-411007, India
| | - Sourabh Yadav
- Biotechnology Research and Innovation Council-National Centre for Cell Science (BRIC-NCCS), SPPU campus, Ganeshkhind, Pune, MH-411007, India
| | - Girdhari Lal
- Biotechnology Research and Innovation Council-National Centre for Cell Science (BRIC-NCCS), SPPU campus, Ganeshkhind, Pune, MH-411007, India.
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Youssef A, Rehman AU, Elebasy M, Roper J, Sheikh SZ, Karhausen J, Yang W, Ulloa L. Vagal stimulation ameliorates murine colitis by regulating SUMOylation. Sci Transl Med 2024; 16:eadl2184. [PMID: 39565873 DOI: 10.1126/scitranslmed.adl2184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 06/21/2024] [Accepted: 10/31/2024] [Indexed: 11/22/2024]
Abstract
Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which are unknown, that shorten the lifespans of 7 million patients worldwide by nearly 10%. Here, we found that decreased autonomic parasympathetic tone resulted in increased IBD susceptibility and mortality in mouse models of disease. Conversely, vagal stimulation restored neuromodulation and ameliorated colitis by inhibiting the posttranslational modification SUMOylation through a mechanism independent of the canonical interleukin-10/α7 nicotinic cholinergic vagal pathway. Colonic biopsies from patients with IBDs and mouse models showed an increase in small ubiquitin-like modifier (SUMO)2 and SUMO3 during active disease. In global genetic knockout mouse models, the deletion of Sumo3 protected against development of colitis and delayed onset of disease, whereas deletion of Sumo1 halted the progression of colitis. Bone marrow transplants from Sumo1-knockout (KO) but not Sumo3-KO mice into wild-type mice conferred protection against development of colitis. Electric stimulation of the cervical vagus nerve before the induction of colitis inhibited SUMOylation and delayed the onset of colitis in Sumo1-KO mice and resulted in milder symptoms in Sumo3-KO mice. Treatment with TAK-981, a first-in-class inhibitor of the SUMO-activating enzyme, ameliorated disease in three murine models of IBD and reduced intestinal permeability and bacterial translocation in a severe model of the disease, suggesting the potential to reduce progression to sepsis. These results reveal a pathway of vagal neuromodulation that reprograms endogenous stress-adaptive responses through inhibition of SUMOylation and suggest SUMOylation as a therapeutic target for IBD.
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Affiliation(s)
- Ayman Youssef
- Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
- Autonomic Dysfunction Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Ata Ur Rehman
- Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Mohamed Elebasy
- Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Jatin Roper
- Department of Medicine, Division of Gastroenterology, Duke University, Durham, NC 27710, USA
| | - Shehzad Z Sheikh
- University of North Carolina, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, NC 27599, USA
| | - Jorn Karhausen
- Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
- Humanitas Research Hospital, Rozzano, MI 20089, Italy
| | - Wei Yang
- Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
| | - Luis Ulloa
- Center for Perioperative Organ Protection, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.2). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:769-858. [PMID: 38718808 DOI: 10.1055/a-2271-0994] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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Kumarapperuma H, Wang R, Little PJ, Kamato D. Mechanistic insight: Linking cardiovascular complications of inflammatory bowel disease. Trends Cardiovasc Med 2024; 34:203-211. [PMID: 36702388 DOI: 10.1016/j.tcm.2023.01.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 01/13/2023] [Accepted: 01/13/2023] [Indexed: 01/25/2023]
Abstract
Cardiovascular diseases (CVD) are the leading cause of mortality worldwide despite an aggressive reduction of traditional cardiovascular risk factors. Underlying inflammatory conditions such as inflammatory bowel disease (IBD) increase the risk of developing CVD. A broad understanding of the underlying pathophysiological processes between IBD and CVD is required to treat and prevent cardiovascular events in patients with IBD. This review highlights the commonality between IBD and CVD, including dysregulated immune response, genetics, environmental risk factors, altered gut microbiome, stress, endothelial dysfunction and abnormalities, to shed light on an essential area of modern medicine.
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Affiliation(s)
- Hirushi Kumarapperuma
- School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia
| | - Ran Wang
- Mater Research Institute, The University of Queensland, Translational Research Institute, Queensland 4102, Australia
| | - Peter J Little
- School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Department of Pharmacy, Xinhua College of Sun Yat-sen University, Tianhe District, Guangzhou 510520, China
| | - Danielle Kamato
- School of Pharmacy, Pharmacy Australia Centre of Excellence, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Discovery Biology, Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland 4111, Australia; School of Environment and Science, Griffith University, Nathan, Queensland 4111, Australia.
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Zanussi JT, Zhao J, Wei WQ, Karakoc G, Chung CP, Feng Q, Olsen NJ, Stein CM, Kawai VK. Clinical diagnoses associated with a positive antinuclear antibody test in patients with and without autoimmune disease. BMC Rheumatol 2023; 7:24. [PMID: 37550754 PMCID: PMC10405518 DOI: 10.1186/s41927-023-00349-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 07/27/2023] [Indexed: 08/09/2023] Open
Abstract
BACKGROUND Antinuclear antibodies (ANA) are antibodies present in several autoimmune disorders. However, a large proportion of the general population (20%) also have a positive test; very few of these individuals will develop an autoimmune disease, and the clinical impact of a positive ANA in them is not known. Thus, we test the hypothesis that ANA + test reflects a state of immune dysregulation that alters risk for some clinical disorders in individuals without an autoimmune disease. METHODS We performed high throughput association analyses in a case-control study using real world data from the de-identified electronic health record (EHR) system from Vanderbilt University Medical Center. The study population included individuals with an ANA titer ≥ 1:80 at any time (ANA +) and those with negative results (ANA-). The cohort was stratified into sub-cohorts of individuals with and without an autoimmune disease. A phenome-wide association study (PheWAS) adjusted by sex, year of birth, race, and length of follow-up was performed in the study cohort and in the sub-cohorts. As secondary analyses, only clinical diagnoses after ANA testing were included in the analyses. RESULTS The cohort included 70,043 individuals: 49,546 without and 20,497 with an autoimmune disease, 26,579 were ANA + and 43,464 ANA-. In the study cohort and the sub-cohort with autoimmune disease, ANA + was associated (P ≤ 5 × 10-5) with 88 and 136 clinical diagnoses respectively, including lupus (OR ≥ 5.4, P ≤ 7.8 × 10-202) and other autoimmune diseases and complications. In the sub-cohort without autoimmune diseases, ANA + was associated with increased risk of Raynaud's syndrome (OR ≥ 2.1) and alveolar/perialveolar-related pneumopathies (OR ≥ 1.4) and decreased risk of hepatitis C, tobacco use disorders, mood disorders, convulsions, fever of unknown origin, and substance abuse disorders (OR ≤ 0.8). Analyses including only diagnoses after ANA testing yielded similar results. CONCLUSION A positive ANA test, in addition to known associations with autoimmune diseases, Raynaud's phenomenon, and idiopathic fibrosing alveolitis related disorders, is associated with decreased prevalence of several non-autoimmune diseases.
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Affiliation(s)
- Jacy T Zanussi
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Juan Zhao
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Wei-Qi Wei
- Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, USA
- Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Gul Karakoc
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Cecilia P Chung
- Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA
- Division of Rheumatology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Tennessee Valley Healthcare System - Nashville Campus, Nashville, TN, USA
| | - QiPing Feng
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Nancy J Olsen
- Department of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - C Michael Stein
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Vivian K Kawai
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
- Vanderbilt Genetics Institute, Vanderbilt University School of Medicine, Nashville, TN, USA.
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Kucharzik T, Dignass A, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengiesser K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa (Version 6.1) – Februar 2023 – AWMF-Registriernummer: 021-009. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2023; 61:1046-1134. [PMID: 37579791 DOI: 10.1055/a-2060-0935] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Affiliation(s)
- T Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - A Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - R Atreya
- Medizinische Klinik 1 Gastroent., Pneumologie, Endokrin., Universitätsklinikum Erlangen, Erlangen, Deutschland
| | - B Bokemeyer
- Interdisziplinäres Crohn Colitis Centrum Minden - ICCCM, Minden, Deutschland
| | - P Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt, Deutschland
| | - K Herrlinger
- Innere Medizin I, Asklepios Klinik Nord, Hamburg, Deutschland
| | - K Kannengiesser
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Städtisches Klinikum Lüneburg, Lüneburg, Deutschland
| | - P Kienle
- Abteilung für Allgemein- und Viszeralchirurgie, Theresienkrankenhaus, Mannheim, Deutschland
| | - J Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Sozialstiftung Bamberg Klinikum am Bruderwald, Bamberg, Deutschland
| | - A Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | - S Schreiber
- Klinik für Innere Medizin I, Universitätsklinikum Schleswig Holstein, Kiel, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Jena, Jena, Deutschland
| | - J Stein
- Abteilung Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt, Deutschland
| | - A Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - N Teich
- Internistische Gemeinschaftspraxis, Leipzig, Deutschland
| | - B Siegmund
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité Campus Benjamin Franklin - Universitätsmedizin Berlin, Berlin, Deutschland
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Yalcin BM, Ustaoglu M, Kirac Y. The relationship between the severity of inflammatory bowel diseases and expirium air carbon monoxide levels. Int J Colorectal Dis 2023; 38:188. [PMID: 37428260 DOI: 10.1007/s00384-023-04468-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 07/11/2023]
Abstract
INTRODUCTION We investigated the relationship between expirium air carbon monoxide (E-CO) levels and disease severity in patients with ulcerative colitis (UC) and Crohn's disease (CD). METHODS After their first follow-ups, the E-CO levels of 162 patients with UC and 100 with CD were measured for four consecutive weeks. Blood samples were collected from all the patients, and their clinical severity was determined 1 month after their initial presentation. The clinical severity of CD was determined using the Harvey Bradshaw index (HBI), while the patients with UC completed the SEO clinical activity index (SEOI). The relationships between the disease severity and the means of these four E-CO readings were then compared. RESULTS The mean age of the participants was 42.28 ± 14.9 years, and 158 (60.3%) were men. In addition, 27.2% of the UC group and 44% of the CD group were smokers. The mean SEOI score was 145.7 ± 42.0 (min = 90, max = 227), and the mean HBI score was 5.75 ± 3.3 (min = 1, max = 15). Increased CO ppm (OR = -9.047 to 7.654 95% CI) and the number of cigarettes smoked per day (OR = -0.161 to 1.157 95% CI) emerged as independent risk factors for lower SEO scores in the linear regression models (p < 0.001), while the number of cigarettes smoked per day (OR = 0.271 to 1.182% 95 CI) was a risk factor for higher HBI scores (p = 0.022). CONCLUSION UC severity decreased with higher E-CO levels and the mean number of cigarettes smoked, while CD severity increased in line with the mean number of cigarettes smoked.
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Affiliation(s)
- Bektas Murat Yalcin
- Department of Family Medicine, Faculty of Medicine, Ondokuz Mayis University, Samsun, 55100, Turkey.
| | - Muge Ustaoglu
- Department of Family Medicine, Faculty of Medicine, Ondokuz Mayis University, Samsun, 55100, Turkey
| | - Yildiz Kirac
- Department of Gastroentrology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey
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11
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Salehi Z, Motlagh Ghoochani BFN, Hasani Nourian Y, Jamalkandi SA, Ghanei M. The controversial effect of smoking and nicotine in SARS-CoV-2 infection. ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2023; 19:49. [PMID: 37264452 PMCID: PMC10234254 DOI: 10.1186/s13223-023-00797-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 04/18/2023] [Indexed: 06/03/2023]
Abstract
The effects of nicotine and cigarette smoke in many diseases, notably COVID-19 infection, are being debated more frequently. The current basic data for COVID-19 is increasing and indicating the higher risk of COVID-19 infections in smokers due to the overexpression of corresponding host receptors to viral entry. However, current multi-national epidemiological reports indicate a lower incidence of COVID-19 disease in smokers. Current data indicates that smokers are more susceptible to some diseases and more protective of some other. Interestingly, nicotine is also reported to play a dual role, being both inflammatory and anti-inflammatory. In the present study, we tried to investigate the effect of pure nicotine on various cells involved in COVID-19 infection. We followed an organ-based systematic approach to decipher the effect of nicotine in damaged organs corresponding to COVID-19 pathogenesis (12 related diseases). Considering that the effects of nicotine and cigarette smoke are different from each other, it is necessary to be careful in generalizing the effects of nicotine and cigarette to each other in the conducted researches. The generalization and the undifferentiation of nicotine from smoke is a significant bias. Moreover, different doses of nicotine stimulate different effects (dose-dependent response). In addition to further assessing the role of nicotine in COVID-19 infection and any other cases, a clever assessment of underlying diseases should also be considered to achieve a guideline for health providers and a personalized approach to treatment.
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Affiliation(s)
- Zahra Salehi
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | | | - Yazdan Hasani Nourian
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Sadegh Azimzadeh Jamalkandi
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
| | - Mostafa Ghanei
- Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran.
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12
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Verhaeghe C, Talikka M, Sewer A, Sierro N, Auberson M, Peric D, Bornand D, Dulize R, Guedj E, Nef P, Tabruyn SP, Hoeng J, Peitsch MC, Lo Sasso G. Tobacco Alkaloid Assessment in a DSS-Induced Colitis Mouse Model with a Fully Humanized Immune System. Int J Mol Sci 2023; 24:ijms24076419. [PMID: 37047398 PMCID: PMC10095104 DOI: 10.3390/ijms24076419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/22/2023] [Accepted: 03/24/2023] [Indexed: 04/03/2023] Open
Abstract
Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms.
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13
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Leitzke M. Is the post-COVID-19 syndrome a severe impairment of acetylcholine-orchestrated neuromodulation that responds to nicotine administration? Bioelectron Med 2023; 9:2. [PMID: 36650574 PMCID: PMC9845100 DOI: 10.1186/s42234-023-00104-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2022] [Accepted: 12/30/2022] [Indexed: 01/19/2023] Open
Abstract
Following a SARS-CoV-2 infection, many individuals suffer from post-COVID-19 syndrome. It makes them unable to proceed with common everyday activities due to weakness, memory lapses, pain, dyspnea and other unspecific physical complaints. Several investigators could demonstrate that the SARS-CoV-2 related spike glycoprotein (SGP) attaches not only to ACE-2 receptors but also shows DNA sections highly affine to nicotinic acetylcholine receptors (nAChRs). The nAChR is the principal structure of cholinergic neuromodulation and is responsible for coordinated neuronal network interaction. Non-intrinsic viral nAChR attachment compromises integrative interneuronal communication substantially. This explains the cognitive, neuromuscular and mood impairment, as well as the vegetative symptoms, characterizing post-COVID-19 syndrome. The agonist ligand nicotine shows an up to 30-fold higher affinity to nACHRs than acetylcholine (ACh). We therefore hypothesize that this molecule could displace the virus from nAChR attachment and pave the way for unimpaired cholinergic signal transmission. Treating several individuals suffering from post-COVID-19 syndrome with a nicotine patch application, we witnessed improvements ranging from immediate and substantial to complete remission in a matter of days.
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Affiliation(s)
- Marco Leitzke
- Department of Anesthesiology, Helios Clinics, Colditzer Straße 48, 04703, Leisnig, Germany.
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14
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Mahmoudzadeh L, Abtahi Froushani SM, Ajami M, Mahmoudzadeh M. Effect of Nicotine on Immune System Function. Adv Pharm Bull 2023; 13:69-78. [PMID: 36721811 PMCID: PMC9871277 DOI: 10.34172/apb.2023.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 09/30/2021] [Accepted: 12/31/2021] [Indexed: 02/03/2023] Open
Abstract
As a parasympathetic alkaloid and the main substance in cigarette smoke, nicotine modulates the immune system, inhibits innate and acquired immunity and is used in treating many autoimmune diseases. It often stimulates the α7 receptor and causes an anti-inflammatory state in the body. This study is designed to evaluate the role of nicotine treatment on immune system. The results showed that nicotine affects many cells in immune system, alters the downstream intracellular mechanisms and changes lymphocytes polarization. This substance alters TLRs and STATs gene expression and thus changes in the innate immune system. All these events inhibit the secretion of pro-inflammatory cytokines and chemokines which increase angiogenesis and metastasis and exacerbates tumors due to increasing survival and cell growth. Nicotine can aggravate tumors in cancer patients, with many positive effects observed in the treating autoimmune disease, Nicotine treatment function in different conditions depends on factors such as concentration, how it is employed, treatment duration and other conditions such as body conditions affecting the immune system, hence, further studies and review of all conditions are required.
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Affiliation(s)
- leila Mahmoudzadeh
- Division of Immunology, Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | | | - Marjan Ajami
- Department of Food and Nutrition Policy and Planning Research, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mahmoudzadeh
- Nutrition Research Center and Department of Food Science and Technology, Faculty of Nutrition and Food Science, Tabriz University of Medical Sciences, Tabriz, Iran.,Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Corresponding Author: Maryam Mahmoudzadeh, Fax:+98 41 33363231,
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15
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Deng P, Yao P, Pei C, Li X, Wu J, Zhang S. Significance of diagnosis and prognosis for appendiceal orifice inflammation in ulcerative colitis: a real-world study. BMJ Open 2022; 12:e058973. [PMID: 36180123 PMCID: PMC9528594 DOI: 10.1136/bmjopen-2021-058973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVE Ulcerative colitis (UC) is a chronic inflammatory disease of the large intestine. At present, the significance of appendiceal orifice inflammation (AOI) in UC prognosis is still controversial. This prospective observational study investigated the importance of AOI in UC diagnosis and prognosis. Additionally, it compared the therapeutic efficacy of treatments in UC patients with or without AOI. DESIGN This study was a prospective, observational, single-centre, real-world study. Patients with AOI were included in the observation group, and patients without AOI were assigned to the control group. All patients were followed up for 1 year; the disease remission and treatment efficacy were re-examined by colonoscopy. In addition, the clinical, endoscopic and pathological features were collected before and after the treatment. RESULTS Patients with endoscopic diffuse inflammatory changes in the distal colorectum accompanied by AOI had a higher positive UC diagnosis rate than those without (96.5% vs 78.0%). Also, AOI had a specificity of 95.2% and a sensitivity of 28.3% for UC diagnosis. However, no difference in the modified Mayo score (p=0.881) or Baron grading was observed between the control and observation groups, indicating that AOI does not affect the treatment outcome of UC patients. CONCLUSION In this study, the observation of AOI improved the UC diagnostic accuracy in patients with diffuse lesions in the distal colorectum. Furthermore, the presence of AOI does not affect the treatment efficacies of UC. TRIAL REGISTRATION NUMBER ChiCTR1800017753.
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Affiliation(s)
- Peng Deng
- Department of Emergency Medicine, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Peng Yao
- Department of Emergency Medicine, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Chao Pei
- Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Xiao Li
- Department of Gastroenterology and Hepatology, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Junchao Wu
- Department of Gastroenterology and Hepatology, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Shu Zhang
- Department of Emergency Medicine, Sichuan University West China Hospital, Chengdu, Sichuan, China
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16
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Xu C, Nery PB, Wiefels C, Beanlands RS, Spence SD, Juneau D, Promislow S, Boczar K, deKemp RA, Birnie DH. Negative Association of Smoking History With Clinically Manifest Cardiac Sarcoidosis: A Case-Control Study. CJC Open 2022; 4:756-762. [PMID: 36148253 PMCID: PMC9486855 DOI: 10.1016/j.cjco.2022.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Accepted: 06/05/2022] [Indexed: 11/26/2022] Open
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17
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Wils P, Caron B, D’Amico F, Danese S, Peyrin-Biroulet L. Abdominal Pain in Inflammatory Bowel Diseases: A Clinical Challenge. J Clin Med 2022; 11:4269. [PMID: 35893357 PMCID: PMC9331632 DOI: 10.3390/jcm11154269] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/15/2022] [Accepted: 07/15/2022] [Indexed: 02/01/2023] Open
Abstract
Up to 60% of inflammatory bowel disease (IBD) patients experience abdominal pain in their lifetime regardless of disease activity. Pain negatively affects different areas of daily life and particularly impacts the quality of life of IBD patients. This review provides a comprehensive overview of the multifactorial etiology implicated in the chronic abdominal pain of IBD patients including peripheral sensitization by inflammation, coexistent irritable bowel syndrome, visceral hypersensitivity, alteration of the brain-gut axis, and the multiple factors contributing to pain persistence. Despite the optimal management of intestinal inflammation, chronic abdominal pain can persist, and pharmacological and non-pharmacological approaches are necessary. Integrating psychological support in care models in IBD could decrease disease burden and health care costs. Consequently, a multidisciplinary approach similar to that used for other chronic pain conditions should be recommended.
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Affiliation(s)
- Pauline Wils
- Department of Gastroenterology, Claude Huriez Hospital, University of Lille, F-59000 Lille, France
| | - Bénédicte Caron
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, F-54000 Nancy, France; (B.C.); (L.P.-B.)
- Department of Gastroenterology, University of Lorraine, Inserm, NGERE, F-54000 Nancy, France
| | - Ferdinando D’Amico
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.D.); (S.D.)
- Department of Biomedical Sciences, Humanitas University, 20090 Milan, Italy
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS Ospedale San Raffaele, 20132 Milan, Italy; (F.D.); (S.D.)
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, University of Lorraine, CHRU-Nancy, F-54000 Nancy, France; (B.C.); (L.P.-B.)
- Department of Gastroenterology, University of Lorraine, Inserm, NGERE, F-54000 Nancy, France
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18
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Edstorp J, Lampousi A, Carlsson S. Parental smoking, type 1 diabetes, and islet autoantibody positivity in the offspring: A systematic review and meta-analysis. Diabet Med 2022; 39:e14830. [PMID: 35290684 PMCID: PMC9311676 DOI: 10.1111/dme.14830] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 01/26/2022] [Accepted: 03/12/2022] [Indexed: 12/01/2022]
Abstract
AIMS Our aim was to synthesize current evidence on the association between parental smoking and incidence of type 1 diabetes and islet autoantibody positivity (IA) in the offspring by conducting a systematic review and meta-analysis. METHODS We searched Medline, Embase, and Cochrane Library until January 21, 2021, for human studies with parental tobacco use as exposure, type 1 diabetes or IA as outcome, and hazard, risk, or odds ratios as effect estimates. Summary relative risks (RR) and 95% confidence intervals (CI) were estimated with random-effects models. Heterogeneity was quantified with the I2 statistic, bias with the ROBINS-I tool, and the certainty of evidence with the GRADE tool. RESULTS We identified 535 records of which 23 were eligible including 25 927 cases of type 1 diabetes. Maternal smoking during pregnancy was associated with a reduced risk of type 1 diabetes (n = 22, RR 0.78, CI 0.71-0.86, I2 =69%). Including only studies with low to moderate risk of bias indicated similar results with less heterogeneity (n = 14, RR 0.73, CI 0.68-0.79, I2 = 44%). The certainty of evidence was graded as high. There was no clear association between type 1 diabetes and neither maternal (n = 6, RR 0.95, CI 0.78-1.14, I2 = 0%) nor paternal (n = 6, RR 0.90, 0.70-1.17, I2 = 68%) smoking during childhood. Furthermore, the association between maternal smoking during pregnancy and IA was weak (n = 4, RR 0.86, CI 0.44-1.65, I2 = 71%). CONCLUSIONS Maternal smoking during pregnancy may reduce the risk of type 1 diabetes in the offspring. Further studies are needed to elucidate potential mechanisms underlying this association. REGISTRATION Prospero CRD42021236717.
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Affiliation(s)
- Jessica Edstorp
- Institute of Environmental MedicineKarolinska InstituteStockholmSweden
| | | | - Sofia Carlsson
- Institute of Environmental MedicineKarolinska InstituteStockholmSweden
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19
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Hua X, Lopes EW, Burke KE, Ananthakrishnan AN, Richter JM, Lo CH, Lochhead P, Chan AT, Khalili H. Smoking Behaviour Changes After Diagnosis of Inflammatory Bowel Disease and Risk of All-cause Mortality. J Crohns Colitis 2022; 16:1030-1038. [PMID: 35102373 PMCID: PMC9351977 DOI: 10.1093/ecco-jcc/jjac015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 11/30/2021] [Accepted: 01/25/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND AND AIMS We examined smoking behaviour changes after diagnoses of Crohn's disease [CD] and ulcerative colitis [UC] and evaluated their impact on mortality. METHODS Study population included incident CD or UC cases from three cohorts of the Nurses' Health Study [NHS], NHSII, and Health Professionals Follow-up Study. Smoking and other risk factors were prospectively assessed. Smoking behaviour changes were categorised as never, former [i.e., quit smoking before diagnosis], quitters [i.e., quit smoking after diagnosis], and current [i.e., continue smoking after diagnosis]. Follow-up for date and cause of death was completed through linkage to the National Death Index. Cox proportional hazard regression was used to estimate hazard ratios [HRs] and 95% confidence intervals [CIs]. RESULTS Among 909 eligible CD and UC cases, 45% were never smokers, 38% were past smokers, and 16% were active smokers at the time of diagnosis. Among active smokers, 70% of patients with CD and 44% of patients with UC continued to smoke after diagnosis. In patients with CD, compared with current smokers, the multivariable-adjusted HRs [95% CI] of death were 0.19 [0.10 to 0.38] for never smokers, 0.31 [0.16 to 0.57] for former smokers, and 0.41 [0.18 to 0.93] for quitters. Similarly for UC, compared with current smokers, we observed a reduced risk of mortality for never smokers [HR = 0.23, 95% CI 0.10 to 0.51], former smokers [HR = 0.23, 95% CI 0.11 to 0.48], and quitters [HR = 0.28, 95% CI 0.11 to 0.72]. CONCLUSIONS In three cohorts of health professionals, a substantial proportion of patients with new diagnosis of CD and UC and history of smoking continued to smoke after diagnosis. Smoking cessation around the time of diagnosis was associated with a significant reduction in mortality.
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Affiliation(s)
- Xinwei Hua
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Emily W Lopes
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kristin E Burke
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - James M Richter
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Chun-Han Lo
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Paul Lochhead
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Clinical and Translation Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA,Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
| | - Hamed Khalili
- Corresponding author: Hamed Khalili, MD, MPH, Digestive Healthcare Center, Crohn’s and Colitis Center, Massachusetts General Hospital, 165 Cambridge Street, 9th Floor, Boston, MA 02114, USA. Tel.: 617 726 7933; fax: 617 726 3080;
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20
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Serafini MA, Paz AH, Nunes NS. Cholinergic immunomodulation in inflammatory bowel diseases. Brain Behav Immun Health 2022; 19:100401. [PMID: 34977822 PMCID: PMC8683952 DOI: 10.1016/j.bbih.2021.100401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 11/29/2021] [Accepted: 12/04/2021] [Indexed: 12/28/2022] Open
Abstract
Inflammatory bowel diseases (IBD) are chronic intestinal disorders characterized by dysregulated immune responses to resident microbiota in genetically susceptible hosts. The activation of the cholinergic system has been proposed for the treatment of IBD patients according to its potential anti-inflammatory effect in vivo. The α-7-nicotinic-acetylcholine receptor (α7nAChR) is involved in the inhibition of inflammatory processes, modulating the production of cytokines, suppressing dendritic cells and macrophage activity, leading to the suppression of T cells. In this review, we address the most recent studies and clinical trials concerning cholinergic signaling and its therapeutic potential for inflammatory bowel diseases.
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Affiliation(s)
- Michele A. Serafini
- Biological Sciences, Physiology Graduate Program, Federal University of Rio Grande do Sul, 90050170, Porto Alegre, Brazil
- Cells, Tissue and Genes Laboratory, Experimental Research Center, Hospital de Clinicas de Porto Alegre, 90035903, Porto Alegre, Brazil
| | - Ana H. Paz
- Morphological Sciences Department, Basic Health Sciences Institute, Federal University of Rio Grande do Sul, 90050170, Porto Alegre, Brazil
- Cells, Tissue and Genes Laboratory, Experimental Research Center, Hospital de Clinicas de Porto Alegre, 90035903, Porto Alegre, Brazil
| | - Natalia S. Nunes
- Experimental Transplantation Immunotherapy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 20852, Bethesda, MD, USA
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21
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Kanauchi Y, Yamamoto T, Yoshida M, Zhang Y, Lee J, Hayashi S, Kadowaki M. Cholinergic anti-inflammatory pathway ameliorates murine experimental Th2-type colitis by suppressing the migration of plasmacytoid dendritic cells. Sci Rep 2022; 12:54. [PMID: 34997096 PMCID: PMC8742068 DOI: 10.1038/s41598-021-04154-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 12/07/2021] [Indexed: 12/20/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease. Several studies have demonstrated that α7 nicotinic acetylcholine receptors (α7nAChRs) exert anti-inflammatory effects on immune cells and nicotine suppress UC onset and relapse. Plasmacytoid dendritic cells (pDCs) reportedly accumulate in the colon of UC patients. Therefore, we investigated the pathophysiological roles of α7nAChRs on pDCs in the pathology of UC using oxazolone (OXZ)-induced Th2-type colitis with BALB/c mice. 2-deoxy-D-glucose, a central vagal stimulant suppressed OXZ colitis, and nicotine also ameliorated OXZ colitis with suppressing Th2 cytokines, which was reversed by α7nAChR antagonist methyllycaconitine. Additionally, α7nAChRs were expressed on pDCs, which were located very close to cholinergic nerve fibers in the colon of OXZ mice. Furthermore, nicotine suppressed CCL21-induced bone marrow-derived pDC migration due to Rac 1 inactivation, which was reversed by methyllycaconitine, a JAK2 inhibitor AG490 or caspase-3 inhibitor AZ-10417808. CCL21 was mainly expressed in the isolated lymphoid follicles (ILFs) of the colon during OXZ colitis. The therapeutic effect of cholinergic pathway on OXZ colitis probably through α7nAChRs on pDCs were attributed to the suppression of pDC migration toward the ILFs. Therefore, the activation of α7nAChRs has innovative therapeutic potential for the treatment of UC.
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Affiliation(s)
- Yuya Kanauchi
- Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Takeshi Yamamoto
- Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Minako Yoshida
- Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Yue Zhang
- Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Jaemin Lee
- Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Shusaku Hayashi
- Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan
| | - Makoto Kadowaki
- Division of Gastrointestinal Pathophysiology, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
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22
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Sinopoulou V, Gordon M, Dovey TM, Akobeng AK. Interventions for the management of abdominal pain in ulcerative colitis. Cochrane Database Syst Rev 2021; 7:CD013589. [PMID: 34291816 PMCID: PMC8407332 DOI: 10.1002/14651858.cd013589.pub2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Ulcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the colon. UC and Crohn's disease (CD) are the most common inflammatory bowel diseases (IBDs). However, UC tends to be more common than CD. It has no known cure but can be managed with medication and surgery. However, studies have shown that abdominal pain persists in up to one-third of people with UC in remission. Abdominal pain could be a symptom of relapse of the disease due to adverse effects of medication, surgical complications and strictures or adhesions secondary to UC. OBJECTIVES To assess the efficacy and safety of interventions for managing abdominal pain in people with ulcerative colitis. SEARCH METHODS We searched CENTRAL, MEDLINE and five other databases and clinical trials registries on 28 April 2021. We contacted authors of relevant studies and ongoing or unpublished trials that may be relevant to the review. We also searched references of trials and systematic reviews for any additional trials. SELECTION CRITERIA All published, unpublished and ongoing randomised trials that compared interventions for the management of abdominal pain with other active interventions or standard therapy, placebo or no therapy were included. People with both active and inactive disease were included. We excluded studies that did not report on any abdominal pain outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently conducted data extraction and 'Risk of bias' assessments. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs), respectively, with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS We included five studies (360 randomised participants). Studies considered mainly participants in an inactive state of the disease. No conclusions could be drawn about the efficacy of any of the interventions on pain frequency, pain intensity, and treatment success. The certainty of the evidence was very low for all comparisons because of imprecision due to sparse data, and risk of bias. One study compared a low FODMAPs diet (n=13) to a sham diet (n=13). The evidence is very uncertain about the effect of this treatment on pain frequency (MD -4.00, 95% CI -20.61 to 12.61) and intensity (MD -9.00, 95% CI -20.07 to 2.07). Treatment success was not reported. One study compared relaxation training (n=20) to wait-list (n=20). The evidence is very uncertain about the effect of this treatment on pain frequency at end of intervention (MD 2.60, 95% CI 1.14 to 4.06) and 6-month follow-up (MD 3.30, 95% CI 1.64 to 4.96). Similarly, the evidence is very uncertain about the effect of this treatment on pain intensity at end of intervention (MD -1.70, 95% CI -2.92 to -0.48) and 6-month follow-up (MD -2.30, 95% CI -3.70 to -0.90). Treatment success was not reported. One study compared yoga (n=30) to no intervention (n=30). The study defined treatment success as the presence or absence of pain; however, the data they provided was unclear. Pain frequency and intensity were not reported. One study compared a kefir diet (Lactobacillus bacteria, n=15) to no intervention (n=15). The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.17, 95% CI -0.91 to 0.57). Pain frequency and treatment success were not reported. One study compared a stellate ganglion block treatment (n=90) to sulfasalazine treatment (n=30). The study defined treatment success as "stomachache"; however, the data they provided was unclear. Pain frequency and intensity were not reported. Two studies reported withdrawals due to adverse events. One study reported withdrawals due to adverse events as zero. Two studies did not report this outcome. We cannot draw any conclusions about the effects of any of the interventions on withdrawals due to adverse events because of the very limited evidence. The reporting of secondary outcomes was inconsistent. Adverse events tended to be very low or zero. However, we can make no clear judgements about adverse events for any of the interventions, due to the low number of events. Anxiety was measured and reported at end of intervention in only one study (yoga versus no intervention), and depression was not measured in any of the studies. We can therefore draw no meaningful conclusions about these outcomes. AUTHORS' CONCLUSIONS We found very low-certainty evidence on the efficacy and safety of interventions for the management of abdominal pain in ulcerative colitis. Pervasive issues with very serious imprecision from small samples size and high risk of bias have led to very low-certainty outcomes, precluding conclusions. While few adverse events and no serious adverse events were reported, the certainty of these findings was again very low for all comparisons, so no conclusions can be drawn. There is a need for further research. We have identified eight ongoing studies in this review, so an update will be warranted. It is key that future research addresses the issues leading to reduced certainty of outcomes, specifically sample size and reporting that leads to high risk of bias. It is also important that if researchers are considering pain as a critical outcome, they should report clearly if participants were pain-free at baseline; in that case, data would be best presented as separate subgroups throughout their research.
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Affiliation(s)
| | - Morris Gordon
- School of Medicine, University of Central Lancashire, Preston, UK
| | - Terence M Dovey
- College of Health, Medicine and Life Sciences, Brunel University London, London, UK
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Dautzenberg B, Levi A, Adler M, Gaillard R. Transdermal nicotine in non-smokers: A systematic review to design COVID-19 clinical trials. Respir Med Res 2021; 80:100844. [PMID: 34153704 PMCID: PMC8183099 DOI: 10.1016/j.resmer.2021.100844] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2020] [Revised: 05/26/2021] [Accepted: 05/29/2021] [Indexed: 01/08/2023]
Abstract
Recent data show an interaction between COVID-19 and nicotine and indicate the need for an assessment of transdermal nicotine use in non-smokers. Assessments have been conducted into the short-term cognitive effects of nicotine and into diseases such as Parkinson's, Tourette syndrome, ADHD or ulcerative colitis. METHODS Analyses of nicotine administration protocols and safety were conducted after reviewing Medline and Science Direct databases performing a search using the words [transdermal nicotine] AND [non-smoker] AND selected diseases. RESULTS Among 298 articles identified, there were 35 reviewed publications reporting on 33 studies of non-smokers receiving transdermal nicotine for >48hours. In the 16 randomized trials, 7 crossover, 1 case/control and 9 open studies patients received an initial nicotine dose of between 2.5mg and 15mg/day. In 22 studies, daily doses increased by 2 to 7 steps in 3 to 96 days until the dose was between 5mg and 105mg/day. The target nicotine dose was 19.06±20.89mg/day. The 987 non-smokers (534 never-smokers, 326 ex-smokers and 127 classified as "non-smokers") received or did not receive nicotine. The most common side-effects were nausea and skin itching. Forty-three (7.1%) non-smokers stopped treatment because of an adverse event of nicotine. No hospitalization related to nicotine side-effects were reported. CONCLUSION Despite a relatively safe tolerance profile, transdermal nicotine therapy in non-smokers can only be used in clinical trials. There is a lack of formal assessment of the potential risk of developing a tobacco addiction. This review offers baseline data to set a transdermal nicotine protocol for non-smokers with a new purpose.
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Affiliation(s)
- B Dautzenberg
- APHP Sorbonne University, Pitié-Salpêtrière Hospital, 75013 Paris, France; Institut Arthur Vernes, Smoking Cessation Unit, 75006 Paris, France.
| | - A Levi
- Department of Psychiatry, Service Hospitalo-Universitaire, GHU Paris Psychiatrie & Neurosciences, 75014 Paris, France
| | - M Adler
- Smoking Cessation Unit, Hôpital Antoine, Béclère APHP, 92140 Clamart, France
| | - R Gaillard
- Department of Psychiatry, Service Hospitalo-Universitaire, GHU Paris Psychiatrie & Neurosciences, 75014 Paris, France; Université de Paris, 75006 Paris, France; Unité de Neuropathologie expérimentale, Département Santé Globale, Institut Pasteur, 75015 Paris, France
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24
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Ruiz Castro PA, Yepiskoposyan H, Gubian S, Calvino-Martin F, Kogel U, Renggli K, Peitsch MC, Hoeng J, Talikka M. Systems biology approach highlights mechanistic differences between Crohn's disease and ulcerative colitis. Sci Rep 2021; 11:11519. [PMID: 34075172 PMCID: PMC8169754 DOI: 10.1038/s41598-021-91124-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 05/21/2021] [Indexed: 12/11/2022] Open
Abstract
The molecular mechanisms of IBD have been the subject of intensive exploration. We, therefore, assembled the available information into a suite of causal biological network models, which offer comprehensive visualization of the processes underlying IBD. Scientific text was curated by using Biological Expression Language (BEL) and compiled with OpenBEL 3.0.0. Network properties were analysed by Cytoscape. Network perturbation amplitudes were computed to score the network models with transcriptomic data from public data repositories. The IBD network model suite consists of three independent models that represent signalling pathways that contribute to IBD. In the “intestinal permeability” model, programmed cell death factors were downregulated in CD and upregulated in UC. In the “inflammation” model, PPARG, IL6, and IFN-associated pathways were prominent regulatory factors in both diseases. In the “wound healing” model, factors promoting wound healing were upregulated in CD and downregulated in UC. Scoring of publicly available transcriptomic datasets onto these network models demonstrated that the IBD models capture the perturbation in each dataset accurately. The IBD network model suite can provide better mechanistic insights of the transcriptional changes in IBD and constitutes a valuable tool in personalized medicine to further understand individual drug responses in IBD.
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Affiliation(s)
- Pedro A Ruiz Castro
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland.
| | - Hasmik Yepiskoposyan
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland.
| | - Sylvain Gubian
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
| | - Florian Calvino-Martin
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
| | - Ulrike Kogel
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
| | - Kasper Renggli
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
| | - Manuel C Peitsch
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
| | - Julia Hoeng
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland
| | - Marja Talikka
- Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000, Neuchâtel, Switzerland.
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25
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26
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Possible Therapeutic Role of Cholinergic Agonists on COVID-19 related inflammatory response. JOURNAL OF BASIC AND CLINICAL HEALTH SCIENCES 2021. [DOI: 10.30621/jbachs.869857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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27
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Suarez-Roca H, Mamoun N, Sigurdson MI, Maixner W. Baroreceptor Modulation of the Cardiovascular System, Pain, Consciousness, and Cognition. Compr Physiol 2021; 11:1373-1423. [PMID: 33577130 DOI: 10.1002/cphy.c190038] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Baroreceptors are mechanosensitive elements of the peripheral nervous system that maintain cardiovascular homeostasis by coordinating the responses to external and internal environmental stressors. While it is well known that carotid and cardiopulmonary baroreceptors modulate sympathetic vasomotor and parasympathetic cardiac neural autonomic drive, to avoid excessive fluctuations in vascular tone and maintain intravascular volume, there is increasing recognition that baroreceptors also modulate a wide range of non-cardiovascular physiological responses via projections from the nucleus of the solitary tract to regions of the central nervous system, including the spinal cord. These projections regulate pain perception, sleep, consciousness, and cognition. In this article, we summarize the physiology of baroreceptor pathways and responses to baroreceptor activation with an emphasis on the mechanisms influencing cardiovascular function, pain perception, consciousness, and cognition. Understanding baroreceptor-mediated effects on cardiac and extra-cardiac autonomic activities will further our understanding of the pathophysiology of multiple common clinical conditions, such as chronic pain, disorders of consciousness (e.g., abnormalities in sleep-wake), and cognitive impairment, which may result in the identification and implementation of novel treatment modalities. © 2021 American Physiological Society. Compr Physiol 11:1373-1423, 2021.
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Affiliation(s)
- Heberto Suarez-Roca
- Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, North Carolina, USA
| | - Negmeldeen Mamoun
- Department of Anesthesiology, Division of Cardiothoracic Anesthesia and Critical Care Medicine, Duke University, Durham, North Carolina, USA
| | - Martin I Sigurdson
- Department of Anesthesiology and Critical Care Medicine, Landspitali, University Hospital, Faculty of Medicine, University of Iceland, Reykjavik, Iceland
| | - William Maixner
- Department of Anesthesiology, Center for Translational Pain Medicine, Duke University, Durham, North Carolina, USA
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28
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Qin Z, Xiang K, Su DF, Sun Y, Liu X. Activation of the Cholinergic Anti-Inflammatory Pathway as a Novel Therapeutic Strategy for COVID-19. Front Immunol 2021; 11:595342. [PMID: 33633726 PMCID: PMC7901247 DOI: 10.3389/fimmu.2020.595342] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 12/29/2020] [Indexed: 12/13/2022] Open
Abstract
The outbreak of coronavirus disease 2019 (COVID-19) underlined the urgent need for alleviating cytokine storm. We propose here that activating the cholinergic anti-inflammatory pathway (CAP) is a potential therapeutic strategy. However, there is currently no approved drugs targeting the regulatory pathway. It is evident that nicotine, anisodamine and some herb medicine, activate the CAP and exert anti-inflammation action in vitro and in vivo. As the vagus nerve affects both inflammation and specific immune response, we propose that vagus nerve stimulation by invasive or non-invasive devices and acupuncture at ST36, PC6, or GV20, are also feasible approaches to activate the CAP and control COVID-19. It is worth to investigate the efficacy and safety of the strategy in patients with COVID-19.
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Affiliation(s)
- Zhen Qin
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China.,Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, China
| | - Kefa Xiang
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Ding-Feng Su
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Yang Sun
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
| | - Xia Liu
- Department of Clinical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai, China
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29
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Kucharzik T, Dignass AU, Atreya R, Bokemeyer B, Esters P, Herrlinger K, Kannengießer K, Kienle P, Langhorst J, Lügering A, Schreiber S, Stallmach A, Stein J, Sturm A, Teich N, Siegmund B. Aktualisierte S3-Leitlinie Colitis ulcerosa – Living Guideline. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:e241-e326. [PMID: 33260237 DOI: 10.1055/a-1296-3444] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Torsten Kucharzik
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Axel U Dignass
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | - Raja Atreya
- Medizinische Klinik 1, Universitätsklinikum Erlangen, Deutschland
| | - Bernd Bokemeyer
- Gastroenterologische Gemeinschaftspraxis Minden, Deutschland
| | - Philip Esters
- Medizinische Klinik I, Agaplesion Markus Krankenhaus, Frankfurt am Main, Deutschland
| | | | - Klaus Kannengießer
- Klinik für Allgemeine Innere Medizin und Gastroenterologie, Klinikum Lüneburg, Lüneburg, Deutschland
| | - Peter Kienle
- Allgemein- und Viszeralchirurgie, Theresienkrankenhaus und Sankt Hedwig-Klinik GmbH, Mannheim, Deutschland
| | - Jost Langhorst
- Klinik für Integrative Medizin und Naturheilkunde, Klinikum am Bruderwald, Bamberg, Deutschland
| | - Andreas Lügering
- Medizinisches Versorgungszentrum Portal 10, Münster, Deutschland
| | | | - Andreas Stallmach
- Gastroenterologie, Hepatologie und Infektiologie, Friedrich Schiller Universität, Jena, Deutschland
| | - Jürgen Stein
- Innere Medizin mit Schwerpunkt Gastroenterologie, Krankenhaus Sachsenhausen, Frankfurt/Main, Deutschland
| | - Andreas Sturm
- Klinik für Innere Medizin mit Schwerpunkt Gastroenterologie, DRK Kliniken Berlin Westend, Berlin, Deutschland
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten, Leipzig, Deutschland
| | - Britta Siegmund
- Medizinische Klinik I, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Deutschland
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30
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Chen W, Shu Q, Fan J. Neural Regulation of Interactions Between Group 2 Innate Lymphoid Cells and Pulmonary Immune Cells. Front Immunol 2020; 11:576929. [PMID: 33193374 PMCID: PMC7658006 DOI: 10.3389/fimmu.2020.576929] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Accepted: 10/05/2020] [Indexed: 12/18/2022] Open
Abstract
Emerging evidence supports the involvement of nervous system in the regulation of immune responses. Group 2 innate lymphoid cells (ILC2), which function as a crucial bridge between innate and adaptive immunity, are present in large numbers in barrier tissues. Neuropeptides and neurotransmitters have been found to participate in the regulation of ILC2, adding a new dimension to neuroimmunity. However, a comprehensive and detailed overview of the mechanisms of neural regulation of ILC2, associated with previous findings and prospects for future research, is still lacking. In this review, we compile existing information that supports neurons as yet poorly understood regulators of ILC2 in the field of lung innate and adaptive immunity, focusing on neural regulation of the interaction between ILC2 and pulmonary immune cells.
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Affiliation(s)
- Weiwei Chen
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.,The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Qiang Shu
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China
| | - Jie Fan
- Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.,Research and Development, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA, United States.,McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States
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31
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Kannichamy V, Antony I, Mishra V, Banerjee A, Gandhi AB, Kaleem I, Alexander J, Hisbulla M, Khan S. Transdermal Nicotine as a Treatment Option for Ulcerative Colitis: A Review. Cureus 2020; 12:e11096. [PMID: 33240692 PMCID: PMC7681756 DOI: 10.7759/cureus.11096] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Ulcerative colitis (UC) is primarily a disease of non-smokers or ex-smokers. Since there have been previous claims of the beneficial effects of transdermal nicotine, researchers studied its efficacy to include it in the treatment regimen: to prevent remissions and as maintenance therapy. This review aims to evaluate the efficacy of transdermal nicotine as a treatment option for mild to moderately active ulcerative colitis. We shortlisted 22 articles after a careful analysis and elimination process. These articles were reviewed and analyzed, and it was found that transdermal nicotine in combination with conventional therapy was more beneficial than individual treatment with either. Further controlled studies evaluating the appropriate dosage for remission and maintenance treatment needs to be done.
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Affiliation(s)
- Vishmita Kannichamy
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Ishan Antony
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Vinayak Mishra
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Amit Banerjee
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Arohi B Gandhi
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Ifrah Kaleem
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Josh Alexander
- General Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Mohamed Hisbulla
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences and Psychology, Fairfield, USA
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32
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Haupt-Jorgensen M, Buschard K. Can a gluten-free diet be partly protective for COVID-19 infection? APMIS 2020; 128:558-559. [PMID: 32854147 PMCID: PMC7461366 DOI: 10.1111/apm.13075] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 08/18/2020] [Indexed: 01/28/2023]
Affiliation(s)
| | - Karsten Buschard
- The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen, Denmark
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33
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A Systematic Review and Meta-Analysis of Hospitalised Current Smokers and COVID-19. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17207394. [PMID: 33050574 PMCID: PMC7601505 DOI: 10.3390/ijerph17207394] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Revised: 09/29/2020] [Accepted: 10/08/2020] [Indexed: 02/07/2023]
Abstract
SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It produces severe acute respiratory disease (COVID-19), which is fatal in many cases, characterised by the cytokine release syndrome (CRS). According to the World Health Organization, those who smoke are likely to be more vulnerable to infection. Here, in order to clarify the epidemiologic relationship between smoking and COVID-19, we present a systematic literature review until 28th April 2020 and a meta-analysis. We included 18 recent COVID-19 clinical and epidemiological studies based on smoking patient status from 720 initial studies in China, the USA, and Italy. The percentage of hospitalised current smokers was 7.7% (95% CI: 6.9-8.4) in China, 2.3% (95% CI: 1.7-2.9) in the USA and 7.6% (95% CI: 4.2-11.0) in Italy. These percentages were compared to the smoking prevalence of each country and statistically significant differences were found in them all (p < 0.0001). By means of the meta-analysis, we offer epidemiological evidence showing that smokers were statistically less likely to be hospitalised (OR = 0.18, 95% CI: 0.14-0.23, p < 0.01). In conclusion, the analysis of data from 18 studies shows a much lower percentage of hospitalised current smokers than expected. As more studies become available, this trend should be checked to obtain conclusive results and to explore, where appropriate, the underlying mechanism of the severe progression and adverse outcomes of COVID-19.
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34
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Ruiz Castro PA, Kogel U, Lo Sasso G, Phillips BW, Sewer A, Titz B, Garcia L, Kondylis A, Guedj E, Peric D, Bornand D, Dulize R, Merg C, Corciulo M, Ivanov NV, Peitsch MC, Hoeng J. Anatabine ameliorates intestinal inflammation and reduces the production of pro-inflammatory factors in a dextran sulfate sodium mouse model of colitis. JOURNAL OF INFLAMMATION-LONDON 2020; 17:29. [PMID: 32855621 PMCID: PMC7446176 DOI: 10.1186/s12950-020-00260-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 08/18/2020] [Indexed: 12/12/2022]
Abstract
Background Inflammatory bowel disease (IBD) is the collective term for chronic immune-mediated diseases of unknown, multifactorial etiology, arising from the interplay between genetic and environmental factors and including two main disease manifestations: ulcerative colitis (UC) and Crohn’s disease. In the last few decades, naturally occurring alkaloids have gained interest because of their substantial anti-inflammatory effects in several animal models of disease. Studies on mouse models of IBD have demonstrated the anti-inflammatory action of the main tobacco alkaloid, nicotine. In addition, anatabine, a minor tobacco alkaloid also present in peppers, tomato, and eggplant presents anti-inflammatory properties in vivo and in vitro. In this study, we aimed to evaluate the anti-inflammatory properties of nicotine and anatabine in a dextran sulfate sodium (DSS) mouse model of UC. Results Oral administration of anatabine, but not nicotine, reduced the clinical symptoms of DSS-induced colitis. The result of gene expression analysis suggested that anatabine had a restorative effect on global DSS-induced gene expression profiles, while nicotine only had limited effects. Accordingly, MAP findings revealed that anatabine reduced the colonic abundance of DSS-associated cytokines and increased IL-10 abundance. Conclusions Our results support the amelioration of inflammatory effects by anatabine in the DSS mouse model of UC, and suggest that anatabine constitutes a promising therapeutic agent for IBD treatment.
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Affiliation(s)
- Pedro A Ruiz Castro
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Ulrike Kogel
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Giuseppe Lo Sasso
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Blaine W Phillips
- Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, The Kendall #02-07, Science Park II, Singapore, 117406 Singapore
| | - Alain Sewer
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Bjorn Titz
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Llenalia Garcia
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Athanasios Kondylis
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Emmanuel Guedj
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Dariusz Peric
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - David Bornand
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Remi Dulize
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Celine Merg
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Maica Corciulo
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Nikolai V Ivanov
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Manuel C Peitsch
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
| | - Julia Hoeng
- Philip Morris International R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
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35
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Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications. Int J Mol Sci 2020; 21:ijms21165807. [PMID: 32823591 PMCID: PMC7461543 DOI: 10.3390/ijms21165807] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 08/10/2020] [Accepted: 08/11/2020] [Indexed: 12/12/2022] Open
Abstract
While SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) as the receptor for cell entry, it is important to examine other potential interactions between the virus and other cell receptors. Based on the clinical observation of low prevalence of smoking among hospitalized COVID-19 patients, we examined and identified a “toxin-like” amino acid (aa) sequence in the Receptor Binding Domain of the Spike Glycoprotein of SARS-CoV-2 (aa 375–390), which is homologous to a sequence of the Neurotoxin homolog NL1, one of the many snake venom toxins that are known to interact with nicotinic acetylcholine receptors (nAChRs). We present the 3D structural location of this “toxin-like” sequence on the Spike Glycoprotein and the superposition of the modelled structure of the Neurotoxin homolog NL1 and the SARS-CoV-2 Spike Glycoprotein. We also performed computational molecular modelling and docking experiments using 3D structures of the SARS-CoV-2 Spike Glycoprotein and the extracellular domain of the nAChR α9 subunit. We identified a main interaction between the aa 381–386 of the SARS-CoV-2 Spike Glycoprotein and the aa 189–192 of the extracellular domain of the nAChR α9 subunit, a region which forms the core of the “toxin-binding site” of the nAChRs. The mode of interaction is very similar to the interaction between the α9 nAChR and α-bungarotoxin. A similar interaction was observed between the pentameric α7 AChR chimera and SARS-CoV-2 Spike Glycoprotein. The findings raise the possibility that SARS-CoV-2 may interact with nAChRs, supporting the hypothesis of dysregulation of the nicotinic cholinergic system being implicated in the pathophysiology of COVID-19. Nicotine and other nicotinic cholinergic agonists may protect nAChRs and thus have therapeutic value in COVID-19 patients.
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Divergent Effect of Cigarette Smoke on Innate Immunity in Inflammatory Bowel Disease: A Nicotine-Infection Interaction. Int J Mol Sci 2020; 21:ijms21165801. [PMID: 32823518 PMCID: PMC7461043 DOI: 10.3390/ijms21165801] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/04/2020] [Accepted: 08/09/2020] [Indexed: 02/07/2023] Open
Abstract
Cigarette smoke (CS) has adverse effects in patients with Crohn’s disease (CD), an inflammatory bowel disease (IBD) that has been associated with microbial infection, immuno-dysregulation, and mucosal dysfunction. However, CS seems to provide relief and protection to patients with another IBD known as ulcerative colitis (UC). These two subsets are featured as M1- and M2-mediated responses, respectively. Nicotine is the most active, addictive, and studied ingredient in CS. The mechanism of how nicotine and/or other CS ingredients induce pro-inflammatory or anti-inflammatory phenotypes in IBD patients remains under investigation. Our most recent in vitro nicotine study provided significant insights toward understanding the contradictory effects of nicotine on IBD patients, and it elucidated the mechanistic role of α7nAChR in modulation of macrophages in tobacco smokers. Shifting the beneficial effect of nicotine to a harmful outcome in CD patients was linked to a nicotine-microbe interaction that supports a microbial etiology in CD pathogenesis. Among the most debated pathogens in CD etiology is Mycobacterium avium subspecies paratuberculosis (MAP). Other studies associated nicotine with upregulation of miR-124 expression in macrophages, which led to anti-inflammatory response. This review discusses published work on the role of nicotine in modulation of the innate immune response and subsequent signaling in macrophages in IBD subsets.
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Le Berre C, Loy L, Lönnfors S, Avedano L, Piovani D. Patients' perspectives on smoking and inflammatory bowel disease: An online survey in collaboration with European Federation of Crohn's and Ulcerative Colitis Associations. World J Gastroenterol 2020; 26:4343-4355. [PMID: 32848338 PMCID: PMC7422536 DOI: 10.3748/wjg.v26.i29.4343] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 05/25/2020] [Accepted: 07/21/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Smoking has detrimental effects on Crohn’s disease (CD) activity while data on ulcerative colitis (UC) are conflicting. Little is known about the use and impact of alternative smoking products in inflammatory bowel diseases (IBD).
AIM To understand the patients’ perceptions of the impact of smoking on their IBD and to assess differences between CD and UC patients.
METHODS The questionnaire was developed by Philip Morris Products SA in cooperation with European Federation of Crohn's and Ulcerative Colitis Associations. The final survey questionnaire consisted of 41 questions divided in 8 categories: (1) Subject screener; (2) Smoking history; (3) Background information; (4) IBD disease background; (5) Current disease status; (6) Current therapeutics and medications; and (7) Current nicotine/cigarettes use and awareness of the impacts of smoking on IBD. The questionnaire was submitted online from 4th November 2019 to 11th March 2020 through the European Federation of Crohn's and Ulcerative Colitis Associations website to IBD patients who were current smokers or had a history of smoking.
RESULTS In total 1050 IBD patients speaking nine languages participated to the survey. Among them, 807 (76.9%) patients declared to have ever smoked or consumed an alternative smoking product, with a higher proportion of current cigarette smokers among CD patients (CD: 63.1% vs UC: 54.1%, P = 0.012). About two-thirds of the participants declared to have ever stopped cigarette smoking and restarted (67.0%), with a significantly higher proportion among UC patients compared to CD patients (73.1% vs 62.0%, P = 0.001). We also found significant differences between CD and UC patients in the awareness of the health consequences of smoking in their disease and in the perceived impact of smoking on disease activity, for both cigarettes and alternative smoking products.
CONCLUSION This survey found significant differences between CD and UC patients in both awareness and perception of the impact of smoking on their disease. Further efforts should be done to encourage smoking cessation for all IBD patients, including UC patients.
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Affiliation(s)
- Catherine Le Berre
- Institut des Maladies de l'Appareil Digestif, Nantes University Hospital, Nantes 44000, France
| | - Laura Loy
- IBD Center, Department of Gastroenterology, Humanitas Clinical and Research Institute, Rozzano, Milan 20089, Italy
| | - Sanna Lönnfors
- European Federation of Crohn's and Ulcerative Colitis Associations, Brussels B-1000, Belgium
| | - Luisa Avedano
- European Federation of Crohn's and Ulcerative Colitis Associations, Brussels B-1000, Belgium
| | - Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele MI, Milan 20090, Italy
- Humanitas Clinical and Research Center - IRCCS, Milan, Rozzano 20089, Italy
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Farsalinos K, Barbouni A, Niaura R. Systematic review of the prevalence of current smoking among hospitalized COVID-19 patients in China: could nicotine be a therapeutic option? Intern Emerg Med 2020; 15:845-852. [PMID: 32385628 PMCID: PMC7210099 DOI: 10.1007/s11739-020-02355-7] [Citation(s) in RCA: 193] [Impact Index Per Article: 38.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Accepted: 04/23/2020] [Indexed: 12/15/2022]
Abstract
The effects of smoking on Corona Virus Disease 2019 (COVID-19) are currently unknown. The purpose of this study was to systematically examine the prevalence of current smoking among hospitalized patients with COVID-19 in China, considering the high-population smoking prevalence in China (26.6%). A systematic review of the literature (PubMed) was performed on April 1. Thirteen studies examining the clinical characteristics of hospitalized COVID-19 patients in China and presenting data on the smoking status were found. The pooled prevalence of current smoking from all studies was calculated by random-effect meta-analysis. To address the possibility that some smokers had quit shortly before hospitalization and were classified as former smokers on admission to the hospital, we performed a secondary analysis in which all former smokers were classified as current smokers. A total of 5960 patients were included in the studies identified. The current smoking prevalence ranged from 1.4% (95% CI 0.0-3.4%) to 12.6% (95% CI 10.6-14.6%). An unusually low prevalence of current smoking was observed from the pooled analysis (6.5%, 95% CI 4.9-8.2%) as compared to population smoking prevalence in China. The secondary analysis, classifying former smokers as current smokers, found a pooled estimate of 7.3% (95% CI 5.7-8.9%). In conclusion, an unexpectedly low prevalence of current smoking was observed among patients with COVID-19 in China, which was approximately 1/4th the population smoking prevalence. Although the generalized advice to quit smoking as a measure to reduce health risk remains valid, the findings, together with the well-established immunomodulatory effects of nicotine, suggest that pharmaceutical nicotine should be considered as a potential treatment option in COVID-19.
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Affiliation(s)
- Konstantinos Farsalinos
- Department of Public and Community Health, School of Public Health, University of West Attica, Leoforos Alexandras 196A, 11521, Athens, Greece.
| | - Anastasia Barbouni
- Department of Public and Community Health, School of Public Health, University of West Attica, Leoforos Alexandras 196A, 11521, Athens, Greece
| | - Raymond Niaura
- Departments of Social and Behavioral Science and Epidemiology, College of Global Public Health, New York University, New York, USA
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Tai LC, Ahn CH, Nyein HYY, Ji W, Bariya M, Lin Y, Li L, Javey A. Nicotine Monitoring with a Wearable Sweat Band. ACS Sens 2020; 5:1831-1837. [PMID: 32429661 DOI: 10.1021/acssensors.0c00791] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
The tobacco epidemic is a public health threat that has taken a heavy toll of lives around the globe each year. Smoking affects both the smokers and those who are exposed to secondhand smoke, and careful tracking of exposure can be key to mitigating the potential hazards. For smokers, the variation of chemical compositions between commercial cigarettes has led to ambiguity in estimating the health risks, both for active smokers and others involuntarily exposed to tobacco smoke and byproducts. In this regard, sweat possesses an attractive opportunity to monitor smoke exposure due to sweat's abundance in biomolecules and its great accessibility. Here, we present a wearable sweat band to monitor nicotine, a prominent ingredient in cigarettes, as a viable way to quantitatively assess a wearer's exposure to smoking. Both smokers and normal subjects are tested to demonstrate the use of this device for smoke-related health monitoring. Our results exhibit confirmable and elevated nicotine levels in sweat for subjects inhaling cigarette smoke. This continuous and personalized sweat sensing device is leverage to monitor smoke pollution for a potentially broad population.
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Affiliation(s)
- Li-Chia Tai
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
- Berkeley Sensor and Actuator Center, University of California, Berkeley, California 94720, United States
- Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Christine Heera Ahn
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
| | - Hnin Yin Yin Nyein
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
- Berkeley Sensor and Actuator Center, University of California, Berkeley, California 94720, United States
- Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Wenbo Ji
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
- Berkeley Sensor and Actuator Center, University of California, Berkeley, California 94720, United States
- Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Mallika Bariya
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
- Berkeley Sensor and Actuator Center, University of California, Berkeley, California 94720, United States
- Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Yuanjing Lin
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
- Berkeley Sensor and Actuator Center, University of California, Berkeley, California 94720, United States
- Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Lu Li
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
- Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
| | - Ali Javey
- Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States
- Berkeley Sensor and Actuator Center, University of California, Berkeley, California 94720, United States
- Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States
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Abstract
Various lifestyle factors including physical activity and obesity, stress, sleep, and smoking may modify the risk of developing inflammatory bowel diseases (IBDs). In patients with established IBD, these lifestyle factors may significantly impact the natural history and clinical outcomes. Recreational exercise decreases the risk of flare and fatigue in patients with IBD. In contrast, obesity increases the risk of relapse and is associated with higher anxiety, depression, fatigue, and pain and higher health care utilization. Obesity also modifies pharmacokinetics of biologic agents unfavorably and is associated with a higher risk of treatment failure. Sleep disturbance is highly prevalent in patients with IBD, independent of disease activity, and increases the risk of relapse and chronic fatigue. Similarly, stress, particularly perceived stress rather than major life events, may trigger symptomatic flare in patients with IBD, although its impact on inflammation is unclear. Cigarette smoking is associated with unfavorable outcomes including the risk of corticosteroid dependence, surgery, and disease progression in patients with Crohn's disease; in contrast, smoking does not significantly impact outcomes in patients with ulcerative colitis, although some studies suggest that it may be associated with a lower risk of flare. The effect of alcohol and cannabis use in patients with IBD is inconsistent, with some studies suggesting that cannabis may decrease chronic pain in patients with IBD, without a significant effect of biological remission. Although these lifestyle factors are potentially modifiable, only a few interventional studies have been conducted. Trials of structured exercise and psychological therapy including mindfulness-based therapies such as meditation and yoga and gut-directed hypnotherapy have not consistently demonstrated benefit in clinical and/or endoscopic disease activity in IBD, although may improve overall quality of life.
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Vrablicova Z, Soltys K, Krajcovicova A, Stuchlikova K, Sturdik I, Koller T, Huorka M, Payer J, Killinger Z, Jackuliak P, Tkacik M, Stuchlik S, Sekac J, Hlavaty T. Impact of smoking cigarette on the mRNA expression of cytokines in mucosa of inflammatory bowel disease. Physiol Res 2020; 68:S183-S192. [PMID: 31842582 DOI: 10.33549/physiolres.934301] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
It is well known that smoking is the risk factor in the development and clinical course of Crohn s disease (CD), but on the other hand, smoking is a protective factor against ulcerative colitis (UC). The pathways that are influenced by smoking in CD and UC are poorly understood. The aim of our study was to analyse the influence of smoking on the mRNA expression of cytokines in mucosa in patients with CD and UC. We performed a cross-sectional study. The cohort consisted of 86 IBD patients (48 CD patients and 38 UC patients) and took place at the IBD Centre at the University Hospital Bratislava-Ružinov. We took the demographic and clinical data of each patient, including information about their smoking habits. We performed a colonoscopy on each patient and took biopsies from both inflamed and non-inflamed sigma (CD, UC) and terminal ileum (CD). mRNA was extracted from mucosal biopsy samples for each cytokine and was normalized to a housekeeping gene (GAPDH). Finally, we compared the mRNA expression of target cytokines in the mucosa of smokers and non-smokers in IBD patients. Smokers with Crohn s disease have a significantly higher mRNA expression of pro-inflammatory cytokine TNF ? (p=0.003) in inflamed mucosa in sigma compared with non-smokers. In smokers with ulcerative colitis, we observed significantly higher mRNA expression of anti-inflammatory cytokine IL 10 (p=0.022) in non-inflamed mucosa of sigma. Similarly, smokers with UC have a significantly decreased mRNA expression of cytokine TLR 2 (p=0.024) and CCR1 (p=0.049) in non-inflamed mucosa of sigma. Based on our results, smoking has a positive influence on cessation and the clinical course of UC due to the stimulation of anti-inflammatory cytokine IL 10 in mucosa. On the other hand, smokers with CD have a higher expression of pro-inflammatory cytokine TNF ?, which could be associated with a worsening of the disease and response to therapy.
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Affiliation(s)
- Z Vrablicova
- 5th Department of Internal Medicine, Sub-department of Gastroenterology and Hepatology, Faculty of Medicine, Comenius University Bratislava, University Hospital Bratislava, Slovak Republic
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Farsalinos K. Editorial: Nicotine and SARS-CoV-2: COVID-19 may be a disease of the nicotinic cholinergic system. Toxicol Rep 2020; 7:658-663. [PMID: 32355638 PMCID: PMC7192087 DOI: 10.1016/j.toxrep.2020.04.012] [Citation(s) in RCA: 158] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
- Konstantinos Farsalinos
- Laboratory of Mol. Biology and Immunology, Department of Pharmacy, University of Patras, Panepistimiopolis, 26500, Greece
- School of Public Health, Department of Public and Community Health, University of West Attica, 11521, Greece
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43
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Yeshi K, Ruscher R, Hunter L, Daly NL, Loukas A, Wangchuk P. Revisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural Products. J Clin Med 2020; 9:E1273. [PMID: 32354192 PMCID: PMC7288008 DOI: 10.3390/jcm9051273] [Citation(s) in RCA: 91] [Impact Index Per Article: 18.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/18/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic and life-long disease characterized by gastrointestinal tract inflammation. It is caused by the interplay of the host's genetic predisposition and immune responses, and various environmental factors. Despite many treatment options, there is no cure for IBD. The increasing incidence and prevalence of IBD and lack of effective long-term treatment options have resulted in a substantial economic burden to the healthcare system worldwide. Biologics targeting inflammatory cytokines initiated a shift from symptomatic control towards objective treatment goals such as mucosal healing. There are seven monoclonal antibody therapies excluding their biosimilars approved by the US Food and Drug Administration for induction and maintenance of clinical remission in IBD. Adverse side effects associated with almost all currently available drugs, especially biologics, is the main challenge in IBD management. Natural products have significant potential as therapeutic agents with an increasing role in health care. Given that natural products display great structural diversity and are relatively easy to modify chemically, they represent ideal scaffolds upon which to generate novel therapeutics. This review focuses on the pathology, currently available treatment options for IBD and associated challenges, and the roles played by natural products in health care. It discusses these natural products within the current biodiscovery research agenda, including the applications of drug discovery techniques and the search for next-generation drugs to treat a plethora of inflammatory diseases, with a major focus on IBD.
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Affiliation(s)
- Karma Yeshi
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Roland Ruscher
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Luke Hunter
- School of Chemistry, University of New South Wales (UNSW), Sydney NSW 2052, Australia
| | - Norelle L. Daly
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Alex Loukas
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Phurpa Wangchuk
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
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Herland A, Maoz BM, Das D, Somayaji MR, Prantil-Baun R, Novak R, Cronce M, Huffstater T, Jeanty SSF, Ingram M, Chalkiadaki A, Benson Chou D, Marquez S, Delahanty A, Jalili-Firoozinezhad S, Milton Y, Sontheimer-Phelps A, Swenor B, Levy O, Parker KK, Przekwas A, Ingber DE. Quantitative prediction of human pharmacokinetic responses to drugs via fluidically coupled vascularized organ chips. Nat Biomed Eng 2020; 4:421-436. [PMID: 31988459 PMCID: PMC8011576 DOI: 10.1038/s41551-019-0498-9] [Citation(s) in RCA: 277] [Impact Index Per Article: 55.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 11/25/2019] [Indexed: 01/15/2023]
Abstract
Analyses of drug pharmacokinetics (PKs) and pharmacodynamics (PDs) performed in animals are often not predictive of drug PKs and PDs in humans, and in vitro PK and PD modelling does not provide quantitative PK parameters. Here, we show that physiological PK modelling of first-pass drug absorption, metabolism and excretion in humans-using computationally scaled data from multiple fluidically linked two-channel organ chips-predicts PK parameters for orally administered nicotine (using gut, liver and kidney chips) and for intravenously injected cisplatin (using coupled bone marrow, liver and kidney chips). The chips are linked through sequential robotic liquid transfers of a common blood substitute by their endothelium-lined channels (as reported by Novak et al. in an associated Article) and share an arteriovenous fluid-mixing reservoir. We also show that predictions of cisplatin PDs match previously reported patient data. The quantitative in-vitro-to-in-vivo translation of PK and PD parameters and the prediction of drug absorption, distribution, metabolism, excretion and toxicity through fluidically coupled organ chips may improve the design of drug-administration regimens for phase-I clinical trials.
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Affiliation(s)
- Anna Herland
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Division of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden
- AIMES, Department of Neuroscience, Karolinska Institute, Stockholm, Sweden
| | - Ben M Maoz
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
- Department of Biomedical Engineering, Tel Aviv University, Tel Aviv, Israel
- Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel
| | - Debarun Das
- CFD Research Corporation, Huntsville, AL, USA
| | | | - Rachelle Prantil-Baun
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Richard Novak
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Michael Cronce
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Tessa Huffstater
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Sauveur S F Jeanty
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Miles Ingram
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Angeliki Chalkiadaki
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - David Benson Chou
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Susan Marquez
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Aaron Delahanty
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Sasan Jalili-Firoozinezhad
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Department of Bioengineering and Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Portugal Graduate Program, Universidade de Lisboa, Lisbon, Portugal
| | - Yuka Milton
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Alexandra Sontheimer-Phelps
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Faculty of Biology, University of Freiburg, Freiburg, Germany
| | - Ben Swenor
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Oren Levy
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
| | - Kevin K Parker
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA
- Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, USA
| | | | - Donald E Ingber
- Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.
- Division of Micro and Nanosystems, KTH Royal Institute of Technology, Stockholm, Sweden.
- Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
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Penhasi A, Gomberg M, Shalev DE. A novel nicotine pectinate salt formulated in a specific time-controlled delivery system: A new approach for colon-targeted nicotine release. J Drug Deliv Sci Technol 2020. [DOI: 10.1016/j.jddst.2020.101583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Lamb CA, Kennedy NA, Raine T, Hendy PA, Smith PJ, Limdi JK, Hayee B, Lomer MCE, Parkes GC, Selinger C, Barrett KJ, Davies RJ, Bennett C, Gittens S, Dunlop MG, Faiz O, Fraser A, Garrick V, Johnston PD, Parkes M, Sanderson J, Terry H, Gaya DR, Iqbal TH, Taylor SA, Smith M, Brookes M, Hansen R, Hawthorne AB. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut 2019; 68:s1-s106. [PMID: 31562236 PMCID: PMC6872448 DOI: 10.1136/gutjnl-2019-318484] [Citation(s) in RCA: 1452] [Impact Index Per Article: 242.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 06/10/2019] [Accepted: 06/10/2019] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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Affiliation(s)
- Christopher Andrew Lamb
- Newcastle University, Newcastle upon Tyne, UK
- Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK
| | - Nicholas A Kennedy
- Royal Devon and Exeter NHS Foundation Trust, Exeter, UK
- University of Exeter, Exeter, UK
| | - Tim Raine
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Philip Anthony Hendy
- Chelsea and Westminster Hospital NHS Foundation Trust, London, UK
- Imperial College London, London, UK
| | - Philip J Smith
- Royal Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, UK
| | - Jimmy K Limdi
- The Pennine Acute Hospitals NHS Trust, Manchester, UK
- University of Manchester, Manchester, UK
| | - Bu'Hussain Hayee
- King's College Hospital NHS Foundation Trust, London, UK
- King's College London, London, UK
| | - Miranda C E Lomer
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Gareth C Parkes
- Barts Health NHS Trust, London, UK
- Barts and the London School of Medicine and Dentistry, London, UK
| | - Christian Selinger
- Leeds Teaching Hospitals NHS Trust, Leeds, UK
- University of Leeds, Leeds, UK
| | | | - R Justin Davies
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
- University of Cambridge, Cambridge, UK
| | - Cathy Bennett
- Systematic Research Ltd, Quorn, UK
- Royal College of Surgeons in Ireland (RCSI), Dublin, Ireland
| | | | - Malcolm G Dunlop
- University of Edinburgh, Edinburgh, UK
- Western General Hospital, Edinburgh, UK
| | - Omar Faiz
- Imperial College London, London, UK
- St Mark's Hospital, Harrow, UK
| | - Aileen Fraser
- University Hospitals Bristol NHS Foundation Trust, Bristol, UK
| | | | | | - Miles Parkes
- Cambridge University Hospitals NHS FoundationTrust, Cambridge, UK
| | - Jeremy Sanderson
- King's College London, London, UK
- Guy's and St Thomas' NHS Foundation Trust, London, UK
| | | | - Daniel R Gaya
- Glasgow Royal Infirmary, Glasgow, UK
- University of Glasgow, Glasgow, UK
| | - Tariq H Iqbal
- Queen Elizabeth Hospital Birmingham NHSFoundation Trust, Birmingham, UK
- University of Birmingham, Birmingham, UK
| | - Stuart A Taylor
- University College London, London, UK
- University College London Hospitals NHS Foundation Trust, London, UK
| | - Melissa Smith
- Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
- Brighton and Sussex Medical School, Brighton, UK
| | - Matthew Brookes
- Royal Wolverhampton NHS Trust, Wolverhampton, UK
- University of Wolverhampton, Wolverhampton, UK
| | - Richard Hansen
- Royal Hospital for Children Glasgow, Glasgow, UK
- University of Glasgow, Glasgow, UK
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Abstract
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
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48
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Willemze RA, Brinkman DJ, Welting O, van Hamersveld PHP, Verseijden C, Luyer MD, Wildenberg ME, Seppen J, de Jonge WJ. Acetylcholine-producing T cells augment innate immune-driven colitis but are redundant in T cell-driven colitis. Am J Physiol Gastrointest Liver Physiol 2019; 317:G557-G568. [PMID: 31322912 DOI: 10.1152/ajpgi.00067.2019] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Clinical trials suggest that vagus nerve stimulation presents an alternative approach to classical immune suppression in Crohn's disease. T cells capable of producing acetylcholine (ChAT+ T cells) in the spleen are essential mediators of the anti-inflammatory effect of vagus nerve stimulation. Besides the spleen, ChAT+ T cells are found abundantly in Peyer's patches of the small intestine. However, the role of ChAT+ T cells in colitis pathogenesis is unknown. Here, we made use of CD4creChATfl/fl mice (CD4ChAT-/- mice) lacking ChAT expression specifically in CD4+ T cells. Littermates (ChATfl/fl mice) served as controls. In acute dextran sulfate sodium (DSS)-induced colitis (7 days of 2% DSS in drinking water), CD4ChAT-/- mice showed attenuated colitis and lower intestinal inflammatory cytokine levels compared with ChATfl/fl mice. In contrast, in a resolution model of DSS-induced colitis (5 days of 2% DSS followed by 7 days without DSS), CD4ChAT-/- mice demonstrated a worsened colitis recovery and augmented colonic histological inflammation scores and inflammatory cytokine levels as compared with ChATfl/fl mice. In a transfer colitis model using CD4+CD45RBhigh T cells, T cells from CD4ChAT-/- mice induced a similar level of colitis compared with ChATfl/fl T cells. Together, our results indicate that ChAT+ T cells aggravate the acute innate immune response upon mucosal barrier disruption in an acute DSS-induced colitis model, whereas they are supporting the later resolution process of this innate immune-driven colitis. Surprisingly, ChAT expression in T cells seems redundant in the context of T cell-driven colitis.NEW & NOTEWORTHY By using different mouse models of experimental colitis, we provide evidence that in dextran sulfate sodium-induced colitis, ChAT+ T cells capable of producing acetylcholine worsen the acute immune response, whereas they support the later healing phase of this innate immune-driven colitis.
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Affiliation(s)
- Rose A Willemze
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands
| | - David J Brinkman
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands.,Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Olaf Welting
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands
| | - Patricia H P van Hamersveld
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands
| | - Caroline Verseijden
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands
| | - Misha D Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands
| | - Manon E Wildenberg
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands
| | - Jurgen Seppen
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands
| | - Wouter J de Jonge
- Amsterdam University Medical Center, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Meibergdreef, Amsterdam, The Netherlands.,Department of Surgery, University of Bonn, Bonn, Germany
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49
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Price LR, Martinez J. Biological effects of nicotine exposure: A narrative review of the scientific literature. F1000Res 2019; 8:1586. [PMID: 32595938 PMCID: PMC7308884 DOI: 10.12688/f1000research.20062.1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/20/2019] [Indexed: 09/07/2023] Open
Abstract
The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed. The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer. Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.
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Affiliation(s)
- Leonie R. Price
- Scientific and Regulatory Affairs, Japan Tobacco International, Genève, Genève, 1202, Switzerland
| | - Javier Martinez
- Scientific and Regulatory Affairs, Japan Tobacco International, Genève, Genève, 1202, Switzerland
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50
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Price LR, Martinez J. Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature. F1000Res 2019; 8:1586. [PMID: 32595938 PMCID: PMC7308884 DOI: 10.12688/f1000research.20062.2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/20/2019] [Indexed: 12/14/2022] Open
Abstract
The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed. The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer. Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.
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Affiliation(s)
- Leonie R. Price
- Scientific and Regulatory Affairs, Japan Tobacco International, Genève, Genève, 1202, Switzerland
| | - Javier Martinez
- Scientific and Regulatory Affairs, Japan Tobacco International, Genève, Genève, 1202, Switzerland
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