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Ng KB, Guiu Hernandez E, Haszard J, Macrae P, Huckabee ML, Cakmak YO. Transcutaneous auricular vagus nerve stimulation alters cough sensitivity depending on stimulation parameters: potential implications for aspiration risk. Front Neurosci 2024; 18:1265894. [PMID: 38406583 PMCID: PMC10885700 DOI: 10.3389/fnins.2024.1265894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 01/03/2024] [Indexed: 02/27/2024] Open
Abstract
Background Transcutaneous auricular vagus nerve stimulation (taVNS) is considered a safe and promising tool for limb rehabilitation after stroke, but its effect on cough has never been studied. It is known that the ear and larynx share vagal afferent pathways, suggesting that stimulating the ear with taVNS might have effects on cough sensitivity. The specific stimulation parameters used can influence outcomes. Objective To investigate the effect of various stimulation parameters on change in cough sensitivity, compared to the reference parameter of 25 Hz stimulation at the left concha (most commonly-used parameter for stroke rehabilitation). Design, setting, and participants: Randomized, single-blind, active-controlled, eight-period cross-over design conducted March to August 2022 at a New Zealand research laboratory with 16 healthy participants. Interventions All participants underwent eight stimulation conditions which varied by stimulation side (right ear, left ear), zone (ear canal, concha), and frequency (25 Hz, 80 Hz). Main outcome measures: Change in natural and suppressed cough threshold (from baseline to after 10 min of stimulation) assessed using a citric acid cough reflex test. Results When compared to the reference parameter of 25 Hz stimulation at the left concha, there was a reduction in natural cough threshold of -0.16 mol/L for 80 Hz stimulation at the left canal (p = 0.004), indicating increased sensitivity. For the outcome measure of suppressed cough threshold, there was no significant effect of any of the stimulation conditions compared to the active reference. Conclusion Since stroke patients often have cough hyposensitivity with resulting high risk of silent aspiration, using 80 Hz taVNS at the left canal may be a better choice for future stroke rehabilitation studies than the commonly used 25 Hz taVNS at the left concha. Treatment parameters should be manipulated in future sham-controlled trials to maximize any potential treatment effect of taVNS in modulating cough sensitivity. Clinical trial registration ACTRN12623000128695.
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Affiliation(s)
- Karen B. Ng
- Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
- University of Canterbury Rose Centre for Stroke Recovery and Research, Christchurch, New Zealand
| | - Esther Guiu Hernandez
- University of Canterbury Rose Centre for Stroke Recovery and Research, Christchurch, New Zealand
| | - Jillian Haszard
- Division of Health Sciences, Biostatistics Centre, University of Otago, Dunedin, New Zealand
| | - Phoebe Macrae
- University of Canterbury Rose Centre for Stroke Recovery and Research, Christchurch, New Zealand
- School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand
| | - Maggie-Lee Huckabee
- University of Canterbury Rose Centre for Stroke Recovery and Research, Christchurch, New Zealand
- School of Psychology, Speech and Hearing, University of Canterbury, Christchurch, New Zealand
| | - Yusuf O. Cakmak
- Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand
- Point-of-Care Technologies Theme, Centre for Bioengineering, University of Otago, Dunedin, New Zealand
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Chung KF, McGarvey L, Song WJ, Chang AB, Lai K, Canning BJ, Birring SS, Smith JA, Mazzone SB. Cough hypersensitivity and chronic cough. Nat Rev Dis Primers 2022; 8:45. [PMID: 35773287 PMCID: PMC9244241 DOI: 10.1038/s41572-022-00370-w] [Citation(s) in RCA: 140] [Impact Index Per Article: 46.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/19/2022] [Indexed: 12/13/2022]
Abstract
Chronic cough is globally prevalent across all age groups. This disorder is challenging to treat because many pulmonary and extrapulmonary conditions can present with chronic cough, and cough can also be present without any identifiable underlying cause or be refractory to therapies that improve associated conditions. Most patients with chronic cough have cough hypersensitivity, which is characterized by increased neural responsivity to a range of stimuli that affect the airways and lungs, and other tissues innervated by common nerve supplies. Cough hypersensitivity presents as excessive coughing often in response to relatively innocuous stimuli, causing significant psychophysical morbidity and affecting patients' quality of life. Understanding of the mechanisms that contribute to cough hypersensitivity and excessive coughing in different patient populations and across the lifespan is advancing and has contributed to the development of new therapies for chronic cough in adults. Owing to differences in the pathology, the organs involved and individual patient factors, treatment of chronic cough is progressing towards a personalized approach, and, in the future, novel ways to endotype patients with cough may prove valuable in management.
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Affiliation(s)
- Kian Fan Chung
- Experimental Studies Unit, National Heart & Lung Institute, Imperial College London, London, UK
- Department of Respiratory Medicine, Royal Brompton and Harefield Hospital, London, UK
| | - Lorcan McGarvey
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK
| | - Woo-Jung Song
- Department of Allergy and Clinical Immunology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Anne B Chang
- Australian Centre for Health Services Innovation, Queensland's University of Technology and Department of Respiratory and Sleep Medicine, Queensland Children's Hospital, Brisbane, Queensland, Australia
- Division of Child Health, Menzies School of Health Research, Darwin, Northern Territory, Australia
| | - Kefang Lai
- The First Affiliated Hospital of Guangzhou Medical University, National Center of Respiratory Medicine, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China
| | | | - Surinder S Birring
- Centre for Human & Applied Physiological Sciences, School of Basic & Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, London, UK
| | - Jaclyn A Smith
- Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, Manchester, UK
| | - Stuart B Mazzone
- Department of Anatomy and Physiology, University of Melbourne, Victoria, Australia.
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Yang S, Hincapie-Castillo JM, Ke X, Schelfhout J, Ding H, Sher MR, Zhou L, Chang CY, Wilson DL, Lo-Ciganic WH. Evaluation of Cough Medication Use Patterns in Ambulatory Care Settings in the United States: 2003-2018. J Clin Med 2022; 11:jcm11133671. [PMID: 35806956 PMCID: PMC9267927 DOI: 10.3390/jcm11133671] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/23/2022] [Accepted: 06/23/2022] [Indexed: 02/01/2023] Open
Abstract
Using 2003−2018 National Ambulatory Medical Care Survey data for office-based visits and 2003−2018 National Hospital Ambulatory Medical Care Survey data for emergency department (ED) visits, we conducted cross-sectional analyses to examine cough medication (CM) use trends in the United States (US) ambulatory care settings. We included adult (≥18 years) patient visits with respiratory-infection-related or non-infection-related cough as reason-for-visit or diagnosis without malignant cancer or benign respiratory tumor diagnoses. Using multivariable logistic regressions, we examined opioid antitussive, benzonatate, dextromethorphan-containing antitussive, and gabapentinoid use trends. From 2003−2005 to 2015−2018, opioid antitussive use decreased in office-based visits (8.8% to 6.4%, Ptrend = 0.03) but remained stable in ED visits (6.3% to 5.9%, Ptrend = 0.99). In both settings, hydrocodone-containing antitussive use declined over 50%. Benzonatate use more than tripled (office-based:1.6% to 4.8%; ED:1.5% to 8.0%; both Ptrend < 0.001). Dextromethorphan-containing antitussive use increased in ED visits (1.8% to 2.6%, Ptrend = 0.003) but stayed unchanged in office-based visits (3.8% to 2.7%; Ptrend = 0.60). Gabapentinoid use doubled in office-based visits (1.1% in 2006−2008 to 2.4% in 2015−2018, Ptrend < 0.001) but was negligible in ED visits. In US office-based and ED ambulatory care settings, hydrocodone-containing antitussive use substantially declined from 2003 to 2018, while benzonatate use more than tripled, and dextromethorphan-containing antitussive and gabapentinoid use remained low (<3%).
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Affiliation(s)
- Seonkyeong Yang
- Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA; (S.Y.); (C.-Y.C.); (D.L.W.)
| | - Juan M. Hincapie-Castillo
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;
| | - Xuehua Ke
- Center for Observational and Real-World Evidence (CORE), Merck & Co., Inc., Rahway, NJ 07065, USA; (X.K.); (J.S.); (H.D.)
| | - Jonathan Schelfhout
- Center for Observational and Real-World Evidence (CORE), Merck & Co., Inc., Rahway, NJ 07065, USA; (X.K.); (J.S.); (H.D.)
| | - Helen Ding
- Center for Observational and Real-World Evidence (CORE), Merck & Co., Inc., Rahway, NJ 07065, USA; (X.K.); (J.S.); (H.D.)
| | | | - Lili Zhou
- Global Patient Safety, BeiGene USA, Inc., San Mateo, CA 94403, USA;
| | - Ching-Yuan Chang
- Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA; (S.Y.); (C.-Y.C.); (D.L.W.)
| | - Debbie L. Wilson
- Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA; (S.Y.); (C.-Y.C.); (D.L.W.)
| | - Wei-Hsuan Lo-Ciganic
- Department of Pharmaceutical Outcomes & Policy, College of Pharmacy, University of Florida, Gainesville, FL 32611, USA; (S.Y.); (C.-Y.C.); (D.L.W.)
- Center for Drug Evaluation and Safety (CoDES), College of Pharmacy, University of Florida, Gainesville, FL 32610, USA
- Correspondence: ; Tel.: +1-352-273-6255
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May G, May MM. A Possible Treatment for Persistent Cough Status Post-pulmonary Carcinoid Tumor Resection. Cureus 2022; 14:e25499. [PMID: 35783886 PMCID: PMC9242652 DOI: 10.7759/cureus.25499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2022] [Indexed: 11/28/2022] Open
Abstract
Cough is a common symptom of many underlying pathologies; sometimes, the etiology is well understood and, therefore, treatment can be applied accordingly. However, when the underlying etiology of the cough is not well understood, a nonconventional approach can sometimes be promising. In this article, a cough of unknown etiology resistant to conventional treatments seems to be suppressed with the use of acupuncture techniques.
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Al-Biltagi M, Bediwy AS, Saeed NK. Cough as a neurological sign: What a clinician should know. World J Crit Care Med 2022; 11:115-128. [PMID: 36331984 PMCID: PMC9136724 DOI: 10.5492/wjccm.v11.i3.115] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 03/24/2022] [Accepted: 04/26/2022] [Indexed: 02/06/2023] Open
Abstract
Cough is a common respiratory complaint driving patients to seek medical advice. Besides being a fundamental respiratory sign, it is also a crucial neurological sign. There are three main types of coughs: Reflex cough (type I), voluntary cough (type II), and evoked cough (type III). Cough is a reflex predominantly mediated by control centers in the respiratory areas of the brainstem, modulated by the cerebral cortex. Cough reflex sensitivity could be increased in many neurological disorders such as brainstem space-occupying lesions, medullary lesions secondary to Chiari type I malformations, tics disorders such as Tourette's syndrome, somatic cough, cerebellar neurodegenerative diseases, and chronic vagal neuropathy due to allergic and non-allergic conditions. Meanwhile, cough sensitivity decreases in multiple sclerosis, brain hypoxia, cerebral hemispheric stroke with a brainstem shock, Parkinson's disease, dementia due to Lewy body disease, amyotrophic lateral sclerosis, and peripheral neuropathy as diabetic neuropathy, hereditary sensory and autonomic neuropathy type IV, vitamin B12, and folate deficiency. Arnold's nerve ear-cough reflex, syncopal cough, cough headache, opioids-associated cough, and cough-anal reflex are signs that could help diagnose underlying neurological conditions. Cough reflex testing is a quick, easy, and cheap test performed during the cranial nerve examination. In this article, we reviewed the role of cough in various neurological disorders that increase or decrease cough sensitivity.
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Affiliation(s)
- Mohammed Al-Biltagi
- Department of Pediatrics, University Medical Center, King Abdulla Medical City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31512, Al Gharbia, Egypt
- Department of Pediatrics, University Medical Center, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31512, Alghrabia, Egypt
- Department of Chest Disease, University Medical Center, King Abdullah Medical City, Arabian Gulf University, Manama 26671, Bahrain
- Department of Chest Diseases, University Medical Center, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Kingdom of Bahrain, Manama 26671, Bahrain
- Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Almuharraq, Bahrain
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Rouadi PW, Idriss SA, Bousquet J, Laidlaw TM, Azar CR, Al-Ahmad MS, Yañez A, Al-Nesf MAY, Nsouli TM, Bahna SL, Abou-Jaoude E, Zaitoun FH, Hadi UM, Hellings PW, Scadding GK, Smith PK, Morais-Almeida M, Gómez RM, Gonzalez Diaz SN, Klimek L, Juvelekian GS, Riachy MA, Canonica GW, Peden D, Wong GW, Sublett J, Bernstein JA, Wang L, Tanno LK, Chikhladze M, Levin M, Chang YS, Martin BL, Caraballo L, Custovic A, Ortega-Martell JA, Jensen-Jarolim E, Ebisawa M, Fiocchi A, Ansotegui IJ. WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19. World Allergy Organ J 2021; 14:100618. [PMID: 34963794 PMCID: PMC8666560 DOI: 10.1016/j.waojou.2021.100618] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 10/30/2021] [Accepted: 11/12/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.
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Affiliation(s)
- Philip W. Rouadi
- Department of Otolaryngology - Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon
| | - Samar A. Idriss
- Department of Otolaryngology - Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon
- Department of Audiology and Otoneurological Evaluation, Edouard Herriot Hospital, Lyon, France
| | - Jean Bousquet
- Hospital Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
- Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany
- Macvia France, Montpellier France
- Université Montpellier, France, Montpellier, France
| | - Tanya M. Laidlaw
- Department of Medicine, Harvard Medical School, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital Boston, MA, USA
| | - Cecilio R. Azar
- Department of Gastroenterology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon
- Department of Gastroenterology, Middle East Institute of Health (MEIH), Beirut, Lebanon
- Department of Gastroenterology, Clemenceau Medical Center (CMC), Beirut, Lebanon
| | - Mona S. Al-Ahmad
- Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait
| | - Anahi Yañez
- INAER - Investigaciones en Alergia y Enfermedades Respiratorias, Buenos Aires, Argentina
| | - Maryam Ali Y. Al-Nesf
- Allergy and Immunology Section, Department of Medicine, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
| | | | - Sami L. Bahna
- Allergy & Immunology Section, Louisiana State University Health Sciences Center, Shreveport, LA, USA
| | | | - Fares H. Zaitoun
- Department of Allergy Otolaryngology, LAU-RIZK Medical Center, Beirut, Lebanon
| | - Usamah M. Hadi
- Clinical Professor Department of Otolaryngology Head and Neck Surgery, American University of Beirut, Lebanon
| | - Peter W. Hellings
- KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Allergy and Clinical Immunology, Leuven, Belgium
- University Hospitals Leuven, Department of Otorhinolaryngology, Leuven, Belgium
- University Hospital Ghent, Department of Otorhinolaryngology, Laboratory of Upper Airways Research, Ghent, Belgium
- Academic Medical Center, University of Amsterdam, Department of Otorhinolaryngology, Amsterdam, the Netherlands
| | | | - Peter K. Smith
- Clinical Medicine Griffith University, Southport Qld, 4215, Australia
| | | | | | - Sandra N. Gonzalez Diaz
- Universidad Autónoma de Nuevo León, Hospital Universitario and Facultad de Medicina, Monterrey, NL, Mexico
| | - Ludger Klimek
- Center for Rhinology and Allergology, Wiesbaden, Germany
| | - Georges S. Juvelekian
- Department of Pulmonary, Critical Care and Sleep Medicine at Saint George Hospital University Medical Center, Beirut, Lebanon
| | - Moussa A. Riachy
- Department of Pulmonary and Critical Care, Hôtel-Dieu de France University Hospital, Beirut, Lebanon
| | - Giorgio Walter Canonica
- Humanitas University & Personalized Medicine Asthma & Allergy Clinic-Humanitas Research Hospital-IRCCS-Milano Italy
| | - David Peden
- UNC Center for Environmental Medicine, Asthma, and Lung Biology, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics UNS School of Medicine, USA
| | - Gary W.K. Wong
- Department of Pediatrics, Chinese University of Hong Kong, Hong Kong, China
| | - James Sublett
- Department of Pediatrics, Section of Allergy and Immunology, University of Louisville School of Medicine, Shelbyville Rd, Louisville, KY, 9800, USA
| | - Jonathan A. Bernstein
- University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology/Allergy Section, Cincinnati, USA
| | - Lianglu Wang
- Department of Allergy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Precision Medicine for Diagnosis and Treatment of Allergic Disease, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Beijing, 100730, China
| | - Luciana K. Tanno
- Université Montpellier, France, Montpellier, France
- Desbrest Institute of Epidemiology and Public Health, UMR UA-11, INSERM University of Montpellier, Montpellier, France
- WHO Collaborating Centre on Scientific Classification Support, Montpellier, France
| | - Manana Chikhladze
- Medical Faculty at Akaki Tsereteli State University, National Institute of Allergy, Asthma & Clinical Immunology, KuTaisi, Tskaltubo, Georgia
| | - Michael Levin
- Division of Paediatric Allergology, Department of Paediatrics, University of Cape Town, South Africa
| | - Yoon-Seok Chang
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
| | - Bryan L. Martin
- Department of Otolaryngology, Division of Allergy & Immunology, The Ohio State University, Columbus, OH, USA
| | - Luis Caraballo
- Institute for Immunological Research, University of Cartagena. Cartagena de Indias, Colombia
| | - Adnan Custovic
- National Heart and Lund Institute, Imperial College London, UK
| | | | - Erika Jensen-Jarolim
- Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria
- The interuniversity Messerli Research Institute, Medical University Vienna and Univ, of Veterinary Medicine Vienna, Austria
| | - Motohiro Ebisawa
- Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan
| | - Alessandro Fiocchi
- Translational Pediatric Research Area, Allergic Diseases Research Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Holy See
| | - Ignacio J. Ansotegui
- Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Bilbao, Spain
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Abstract
Cough sensitivity can be described as the reaction intensity of the cough reflex to different stimuli which activate chemically and mechanically sensitive vagal afferent nerves innervating airways and lungs. Measurement of cough reflex sensitivity plays an important role in revealing the underlying mechanisms of cough and evaluating the effects of pharmacological interventions. Besides, different responses to cough suppression therapies indicate the existence of cough hypersensitivity. In consideration of these factors stated above, cough sensitivity should therefore be assessed with a variety of cough challenge tests. Based on the neuroanatomical characteristics of the cough reflex, chemical challenge tests have been developed to objectively assess cough sensitivity. In cough inhalation challenges, capsaicin and citric acid are commonly used as the tussive agents to induce cough, which are validated for describing a profile of cough sensitivity to chemical irritants. Recently, mechanical methodologies have also been tried to measure the mechanical sensitivity of the cough reflex. Methodological consideration and selection are necessary for the reasonable assessment of cough sensitivity while employing cough challenges in clinical trials. Thus, in this review, we will focus on describing various methodologies of cough sensitivity measurement and, detailing some factors influencing on the accuracy of outcomes in the experimentally induced cough.
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Affiliation(s)
- Yonglin Mai
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,Nanshan School of Medicine, Guangzhou Medical University, Guangzhou, China
| | - Liman Fang
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shuxin Zhong
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - S Dushinka Shaniya Helen de Silva
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.,International College of Education, Guangzhou Medical University, Guangzhou, China
| | - Ruchong Chen
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Kefang Lai
- State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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O’Hare C, Rahman T, Williams NT. Treatment of Chronic Refractory Cough in Adults: Focus on Neuromodulators and Other Therapeutic Modalities. J Pharm Technol 2020. [DOI: 10.1177/8755122520954866] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Objective: To evaluate the literature and educate health care professionals about the different management options for chronic refractory cough (CRC). Data Sources: Searches were performed through MEDLINE (1966 to July 2020) using OVID and EBSCOhost and EMBASE (1947 to July 2020) using OVID. Search terms included chronic cough, neurogenic cough, neuromodulators, chronic cough management, and chronic cough treatment. References of all relevant articles were further used to obtain additional articles. Study Selection and Data Extraction: This review includes articles in the English language and human trial literature. Twenty-three trials explored the use of oral neuromodulators in the management of CRC. Data Synthesis: CRC is a poorly understood disease that may have a complex neuropathic etiology. Oral neuromodulators, such as amitriptyline, baclofen, gabapentin, and pregabalin, continue to be the most commonly used agents for the management of CRC. Alternative pharmacological therapies such as botulinum toxin, anesthetic agents (benzonatate, lidocaine), and narcotic agents have efficacy data, and further research into effective doses and routes of administration is warranted. Alternative nonpharmacologic therapies more commonly used included speech pathology treatment. Conclusion: Several medication and alternative treatment interventions may be effective in managing CRC. Current studies used wide dosing and titration strategies, making it challenging to standardize therapy. No consistent method of assessing cough reflex was used between studies, as well as a lack of consistent randomization and small sample sizes. Additional research is needed to standardize treatment durations, optimum doses, and place in therapy of the available interventions in the management of CRC.
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Affiliation(s)
- Caroline O’Hare
- Southwestern Oklahoma State University, Weatherford, OK, USA
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陈 慧, 朱 刚, 张 欣. [Advances of the treatments and diagnosis for sensory laryngeal neuropathy]. LIN CHUANG ER BI YAN HOU TOU JING WAI KE ZA ZHI = JOURNAL OF CLINICAL OTORHINOLARYNGOLOGY, HEAD, AND NECK SURGERY 2020; 34:281-284. [PMID: 32791602 PMCID: PMC10127843 DOI: 10.13201/j.issn.2096-7993.2020.03.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Indexed: 04/30/2023]
Abstract
Sensory laryngeal neuropathy（SLN） is a kind of peripheral neuropathy presenting globus pharyngeus, chronic cough, increased mucus, dry throat, sore throat, frequent clearing of the throat, etc. When the sensory nerve of the larynx is affected by chemical, biological, mechanical or nutritional factors. Because of its nonspecific signs and symptoms, SLN is easy to be misdiagnosed as chronic pharyngitis or laryngopharyngeal reflux disease. SLN was came up to ENT physician in recent years and there are rare systematic reports currently, therefore, this review aims to summarize the etiology, clinical manifestations, diagnosis and treatment of SLN, to raise awareness of this disease among our colleagues.
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Affiliation(s)
- 慧红 陈
- 中南大学湘雅医院耳鼻咽喉头颈外科 耳鼻咽喉重大疾病湖南省重点实验室(长沙，410008)
| | | | - 欣 张
- 中南大学湘雅医院耳鼻咽喉头颈外科 耳鼻咽喉重大疾病湖南省重点实验室(长沙，410008)
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Driessen AK. Vagal Afferent Processing by the Paratrigeminal Nucleus. Front Physiol 2019; 10:1110. [PMID: 31555145 PMCID: PMC6722180 DOI: 10.3389/fphys.2019.01110] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 08/12/2019] [Indexed: 12/26/2022] Open
Abstract
The paratrigeminal nucleus is an obscure region in the dorsal lateral medulla, which has been best characterized as a collection of interstitial cells located in the dorsal tip of the spinal trigeminal tract. The paratrigeminal nucleus receives afferent input from the vagus, trigeminal, spinal, and glossopharyngeal nerves, which contribute to its long-known roles in the baroreceptor reflex and nociceptive processing. More recently, studies have shown that this region is also involved in the processing of airway-derived sensory information. Notably, these studies highlight an underappreciated complexity in the neuronal content and circuit connectivity of the paratrigeminal nucleus. However, much remains to be understood about how paratrigeminal processing of vagal afferents is altered in disease. The aim of the present review is to provide an update of the current understanding of vagal afferent processing in the paratrigeminal nucleus and to explore how dysregulation at this site may contribute to vagal sensory neural dysfunction during disease.
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Affiliation(s)
- Alexandria K Driessen
- School of Biomedical Science, Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, Australia
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Shi G, Shen Q, Zhang C, Ma J, Mohammed A, Zhao H. Efficacy and Safety of Gabapentin in the Treatment of Chronic Cough: A Systematic Review. Tuberc Respir Dis (Seoul) 2018; 81:167-174. [PMID: 29926540 PMCID: PMC6030663 DOI: 10.4046/trd.2017.0089] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Revised: 10/06/2017] [Accepted: 11/13/2017] [Indexed: 12/18/2022] Open
Abstract
Despite recent clinical guidelines, the optimal therapeutic strategy for the management of refractory chronic cough is still a challenge. The present systematic review was designed to assess the evidence for efficacy and safety of gabapentin in the treatment of chronic cough. A systematic search of PubMed, Embase, Cochrane Library databases, and publications cited in bibliographies was performed. Articles were searched by two reviewers with a priori criteria for study selection. Seven relevant articles were identified, including two randomized controlled trials, one prospective case-series designed with consecutive patients, one retrospective case series of consecutive patients, one retrospective case series with unknown consecutive status, and two case reports comprising six and two patients, respectively. Improvements were detected in cough-specific quality of life (Leicester Cough Questionnaire score) and cough severity (visual analogue scale score) following gabapentin treatment in randomized controlled trials. The results of prospective case-series showed that the rate of overall improvement of cough and sensory neuropathy with gabapentin was 68%. Gabapentin treatment of patients with chronic cough showed superior efficacy and a good safety record compared with placebo or standard medications. Additional randomized and controlled trials are needed.
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Affiliation(s)
- Guanglin Shi
- Department of Respiratory Medicine, Nantong Pulmonary Hospital (The Sixth People's Hospital of Nantong), Nantong, China
| | - Qin Shen
- Medical School of Nantong University, Nantong, China
| | - Caixin Zhang
- Medical School of Nantong University, Nantong, China
| | - Jun Ma
- Department of Respiratory Medicine, Nantong Pulmonary Hospital (The Sixth People's Hospital of Nantong), Nantong, China
| | - Anaz Mohammed
- Medical School of Nantong University, Nantong, China
| | - Huan Zhao
- Department of Respiratory Medicine, Nantong Pulmonary Hospital (The Sixth People's Hospital of Nantong), Nantong, China.
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Wei W, Liu R, ZhangTong Y, Qiu Z. The efficacy of specific neuromodulators on human refractory chronic cough: a systematic review and meta-analysis. J Thorac Dis 2016; 8:2942-2951. [PMID: 27867572 DOI: 10.21037/jtd.2016.10.51] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
BACKGROUND There have been several published reports on the use of orally administered, specific centrally acting medicines for the treatment of idiopathic cough; however, there is no extant systematic review of randomized controlled trials (RCTs) that evaluated their efficacy and safety for the treatment of idiopathic cough in human beings. METHODS We conducted a series of definitive systematic reviews and meta-analyses of RCTs. Claims data from the MEDLINE, EMBASE, LILACS, CBM, CNKI, VIP, Wan Fang, and Cochrane Library databases were used. We also reviewed articles and reference lists of relevant articles pertaining to human subjects published prior to March 26, 2016. No language restrictions were imposed. Two authors independently reviewed the titles and abstracts of the retrieved studies, which were matched using Review Manager 5.3 software. Disagreements were resolved by consensus. The outcome data were the number of subjects whose symptoms declined, measured by cough or Leicester Cough Questionnaire (LCQ) score. Random effect meta-analyses were used to pool the findings. Publication bias was assessed using funnel plots. RESULTS Three RCTs, regarding the medicines baclofen, amitriptyline, and gabapentin, were conducted involving 92 persons in total. Our reviews confirmed that baclofen, amitriptyline, and gabapentin show promise in the treatment of cough for select cases of refractory chronic cough. After-treatment relief of cough symptoms was significant (risk ratio =2.41; 95% CI: 1.15-5.04, n=84). Each of the medicines was well tolerated with minimal side effects. Methodological biases in the design and execution of cluster randomized trials might contribute to any selection bias in this review. CONCLUSIONS Baclofen, amitriptyline, and gabapentin may be effective 'non-specific' antitussives in clinical settings, although none of them are used in medical assessments or routinely included in the anatomic diagnostic protocol.
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Affiliation(s)
- Weili Wei
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Ruilin Liu
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Yangzi ZhangTong
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zhongmin Qiu
- Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
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Abstract
Vagal sensory neuropathy or vagal hypersensitivity has been implicated in the pathophysiology of chronic cough. Earlier reports have shown gabapentin to be effective in sensory laryngeal neuropathy and symptom conditions that have a proven neural origin. We present a case report of a patient with chronic refractory cough due to a soft tissue mass in the lung that caused compression of the mediastinal structures. The patient was successfully treated with gabapentin with reduction in the cough intensity, duration, and frequency.
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Affiliation(s)
- Shrikant Atreya
- Department of Palliative Care and Psycho-oncology, Tata Medical Center, Kolkata, West Bengal, India
| | - Gaurav Kumar
- Department of Palliative Care and Psycho-oncology, Tata Medical Center, Kolkata, West Bengal, India
| | - Soumitra Shankar Datta
- Department of Palliative Care and Psycho-oncology, Tata Medical Center, Kolkata, West Bengal, India
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Ferrè ER, Haggard P, Bottini G, Iannetti GD. Caloric vestibular stimulation modulates nociceptive evoked potentials. Exp Brain Res 2015; 233:3393-401. [PMID: 26282602 PMCID: PMC4868137 DOI: 10.1007/s00221-015-4412-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2014] [Accepted: 08/08/2015] [Indexed: 01/01/2023]
Abstract
Vestibular stimulation has been reported to alleviate central pain. Clinical and physiological studies confirm pervasive interactions between vestibular signals and somatosensory circuits, including nociception. However, the neural mechanisms underlying vestibular-induced analgesia remain unclear, and previous clinical studies cannot rule out explanations based on alternative, non-specific effects such as distraction or placebo. To investigate how vestibular inputs influence nociception, we combined caloric vestibular stimulation (CVS) with psychophysical and electrocortical responses elicited by nociceptive-specific laser stimulation in humans (laser-evoked potentials, LEPs). Cold water CVS applied to the left ear resulted in significantly lower subjective pain intensity for experimental laser pain to the left hand immediately after CVS, relative both to before CVS and to 1 h after CVS. This transient reduction in pain perception was associated with reduced amplitude of all LEP components, including the early N1 wave reflecting the first arrival of nociceptive input to primary somatosensory cortex. We conclude that cold left ear CVS elicits a modulation of both nociceptive processing and pain perception. The analgesic effect induced by CVS could be mediated either by subcortical gating of the ascending nociceptive input, or by direct modulation of the primary somatosensory cortex.
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Affiliation(s)
| | - Patrick Haggard
- Institute of Cognitive Neuroscience, University College London, London, UK
| | - Gabriella Bottini
- Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy
- Cognitive Neuropsychology Laboratory, Niguarda Ca' Granda Hospital, Milan, Italy
| | - Gian Domenico Iannetti
- Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK
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