WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways

Philip W Rouadi¹, Samar A Idriss^{1

2}, Jean Bousquet^{3

4

5

6}, Tanya M Laidlaw⁷, Cecilio R Azar^{8

9

10}, Mona Sulaiman Al-Ahmad¹¹, Anahí Yáñez¹², Maryam Ali Y Al-Nesf¹³, Talal M Nsouli¹⁴, Sami L Bahna¹⁵, Eliane Abou-Jaoude¹⁴, Fares H Zaitoun¹⁶, Usamah M Hadi¹⁷, Peter W Hellings^{18

19

20

21}, Glenis K Scadding²², Peter K Smith²³, Mario Morais-Almeida²⁴, R Maximiliano Gómez²⁵, Sandra N González Díaz²⁶, Ludger Klimek²⁷, Georges S Juvelekian²⁸, Moussa A Riachy²⁹, Giorgio Walter Canonica³⁰, David Peden³¹, Gary W K Wong³², James Sublett³³, Jonathan A Bernstein³⁴, Lianglu Wang³⁵, Luciana Kase Tanno^{6

36

37}, Manana Chikhladze³⁸, Michael Levin³⁹, Yoon-Seok Chang⁴⁰, Bryan L Martin⁴¹, Luis Caraballo⁴², Adnan Custovic⁴³, José Antonio Ortega-Martell⁴⁴, Erika Jensen-Jarolim^{45

46}, Motohiro Ebisawa⁴⁷, Alessandro Fiocchi⁴⁸, Ignacio J Ansotegui⁴⁹

Affiliations

¹ Department of Otolaryngology - Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon.
² Department of Audiology and Otoneurological Evaluation, Edouard Herriot Hospital, Lyon, France.
³ Hospital Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany.
⁵ Macvia France, Montpellier France.
⁶ Université Montpellier, Montpellier, France.
⁷ Department of Medicine, Harvard Medical School, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital Boston, MA, USA.
⁸ Department of Gastroenterology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon.
⁹ Department of Gastroenterology, Middle East Institute of Health (MEIH), Beirut, Lebanon.
¹⁰ Department of Gastroenterology, Clemenceau Medical Center (CMC), Beirut, Lebanon.
¹¹ Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait.
¹² INAER - Investigaciones en Alergia y Enfermedades Respiratorias, Buenos Aires, Argentina.
¹³ Allergy and Immunology Section, Department of Medicine, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
¹⁴ International Cough Institute, Washington D.C, USA.
¹⁵ Allergy & Immunology Section, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
¹⁶ Department of Allergy Otolaryngology, LAU-RIZK Medical Center, Beirut, Lebanon.
¹⁷ Clinical Professor Department of Otolaryngology Head and Neck Surgery, American University of Beirut, Lebanon.
¹⁸ KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Allergy and Clinical Immunology, Leuven, Belgium.
¹⁹ University Hospitals Leuven, Department of Otorhinolaryngology, Leuven, Belgium.
²⁰ University Hospital Ghent, Department of Otorhinolaryngology, Laboratory of Upper Airways Research, Ghent, Belgium.
²¹ Academic Medical Center, University of Amsterdam, Department of Otorhinolaryngology, Amsterdam, the Netherlands.
²² Department of ENT, RNENT Hospital, London, UK.
²³ Clinical Medicine Griffith University, Southport Qld, 4215, Australia.
²⁴ Allergy Center, CUF Descobertas Hospital, Lisboa, Portugal.
²⁵ School of Health Sciences, Catholic University of Salta, Argentina.
²⁶ Universidad Autónoma de Nuevo León, Hospital Universitario and Facultad de Medicina, Monterrey, Nuevo León, Mexico.
²⁷ Center for Rhinology and Allergology, Wiesbaden, Germany.
²⁸ Department of Pulmonary, Critical Care and Sleep Medicine at Saint George Hospital University Medical Center, Beirut, Lebanon.
²⁹ Department of Pulmonary and Critical Care, Hôtel-Dieu de France University Hospital, Beirut, Lebanon.
³⁰ Humanitas University, Personalized Medicine Asthma & Allergy Clinic-Humanitas Research Hospital-IRCCS-Milano Italy.
³¹ UNC Center for Environmental Medicine, Asthma, and Lung Biology, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics UNS School of Medicine, USA.
³² Department of Pediatrics, Chinese University of Hong Kong, Hong Kong, China.
³³ Department of Pediatrics, Section of Allergy and Immunology, University of Louisville School of Medicine, 9800 Shelbyville Rd, Louisville, KY, USA.
³⁴ University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology/Allergy Section, Cincinnati.
³⁵ 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.
³⁶ Desbrest Institute of Epidemiology and Public Health, UMR UA-11, INSERM University of Montpellier, Montpellier, France.
³⁷ WHO Collaborating Centre on Scientific Classification Support, Montpellier, France.
³⁸ Medical Faculty at Akaki Tsereteli State University, National Institute of Allergy, Asthma & Clinical Immunology, KuTaisi, Tskaltubo, Georgia.
³⁹ Division of Paediatric Allergology, Department of Paediatrics, University of Cape Town, South Africa.
⁴⁰ Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
⁴¹ Department of Otolaryngology, Division of Allergy & Immunology, The Ohio State University, Columbus, OH, USA.
⁴² Institute for Immunological Research, University of Cartagena. Cartagena de Indias, Colombia.
⁴³ National Heart and Lund Institute, Imperial College London, UK.
⁴⁴ Health Science Institute, Autonomous University of Hidalgo, Mexico.
⁴⁵ Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria.
⁴⁶ The Interuniversity Messerli Research Institute, Medical University Vienna and Univ, of Veterinary Medicine Vienna, Austria.
⁴⁷ Clinical Research Center for Allergy and Rheumatology,National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
⁴⁸ Translational Pediatric Research Area, Allergic Diseases Research Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Holy See.
⁴⁹ Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Bilbao, Spain.

PMID: 34934475
PMCID: PMC8654622
DOI: 10.1016/j.waojou.2021.100617

Review

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways

Philip W Rouadi et al. World Allergy Organ J. 2021.

. 2021 Dec 4;14(12):100617.

doi: 10.1016/j.waojou.2021.100617. eCollection 2021 Dec.

Authors

Affiliations

¹ Department of Otolaryngology - Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon.
² Department of Audiology and Otoneurological Evaluation, Edouard Herriot Hospital, Lyon, France.
³ Hospital Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.
⁴ Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany.
⁵ Macvia France, Montpellier France.
⁶ Université Montpellier, Montpellier, France.
⁷ Department of Medicine, Harvard Medical School, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital Boston, MA, USA.
⁸ Department of Gastroenterology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon.
⁹ Department of Gastroenterology, Middle East Institute of Health (MEIH), Beirut, Lebanon.
¹⁰ Department of Gastroenterology, Clemenceau Medical Center (CMC), Beirut, Lebanon.
¹¹ Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait.
¹² INAER - Investigaciones en Alergia y Enfermedades Respiratorias, Buenos Aires, Argentina.
¹³ Allergy and Immunology Section, Department of Medicine, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
¹⁴ International Cough Institute, Washington D.C, USA.
¹⁵ Allergy & Immunology Section, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
¹⁶ Department of Allergy Otolaryngology, LAU-RIZK Medical Center, Beirut, Lebanon.
¹⁷ Clinical Professor Department of Otolaryngology Head and Neck Surgery, American University of Beirut, Lebanon.
¹⁸ KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Allergy and Clinical Immunology, Leuven, Belgium.
¹⁹ University Hospitals Leuven, Department of Otorhinolaryngology, Leuven, Belgium.
²⁰ University Hospital Ghent, Department of Otorhinolaryngology, Laboratory of Upper Airways Research, Ghent, Belgium.
²¹ Academic Medical Center, University of Amsterdam, Department of Otorhinolaryngology, Amsterdam, the Netherlands.
²² Department of ENT, RNENT Hospital, London, UK.
²³ Clinical Medicine Griffith University, Southport Qld, 4215, Australia.
²⁴ Allergy Center, CUF Descobertas Hospital, Lisboa, Portugal.
²⁵ School of Health Sciences, Catholic University of Salta, Argentina.
²⁶ Universidad Autónoma de Nuevo León, Hospital Universitario and Facultad de Medicina, Monterrey, Nuevo León, Mexico.
²⁷ Center for Rhinology and Allergology, Wiesbaden, Germany.
²⁸ Department of Pulmonary, Critical Care and Sleep Medicine at Saint George Hospital University Medical Center, Beirut, Lebanon.
²⁹ Department of Pulmonary and Critical Care, Hôtel-Dieu de France University Hospital, Beirut, Lebanon.
³⁰ Humanitas University, Personalized Medicine Asthma & Allergy Clinic-Humanitas Research Hospital-IRCCS-Milano Italy.
³¹ UNC Center for Environmental Medicine, Asthma, and Lung Biology, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics UNS School of Medicine, USA.
³² Department of Pediatrics, Chinese University of Hong Kong, Hong Kong, China.
³³ Department of Pediatrics, Section of Allergy and Immunology, University of Louisville School of Medicine, 9800 Shelbyville Rd, Louisville, KY, USA.
³⁴ University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology/Allergy Section, Cincinnati.
³⁵ 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.
³⁶ Desbrest Institute of Epidemiology and Public Health, UMR UA-11, INSERM University of Montpellier, Montpellier, France.
³⁷ WHO Collaborating Centre on Scientific Classification Support, Montpellier, France.
³⁸ Medical Faculty at Akaki Tsereteli State University, National Institute of Allergy, Asthma & Clinical Immunology, KuTaisi, Tskaltubo, Georgia.
³⁹ Division of Paediatric Allergology, Department of Paediatrics, University of Cape Town, South Africa.
⁴⁰ Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea.
⁴¹ Department of Otolaryngology, Division of Allergy & Immunology, The Ohio State University, Columbus, OH, USA.
⁴² Institute for Immunological Research, University of Cartagena. Cartagena de Indias, Colombia.
⁴³ National Heart and Lund Institute, Imperial College London, UK.
⁴⁴ Health Science Institute, Autonomous University of Hidalgo, Mexico.
⁴⁵ Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria.
⁴⁶ The Interuniversity Messerli Research Institute, Medical University Vienna and Univ, of Veterinary Medicine Vienna, Austria.
⁴⁷ Clinical Research Center for Allergy and Rheumatology,National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan.
⁴⁸ Translational Pediatric Research Area, Allergic Diseases Research Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Holy See.
⁴⁹ Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Bilbao, Spain.

PMID: 34934475
PMCID: PMC8654622
DOI: 10.1016/j.waojou.2021.100617

Abstract

Background: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear.

Objectives: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined.

Outcomes: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

Keywords: Chemoreceptors; Chronic cough; Mechanoreceptors; P2X3; Pathogenesis; TRP channel.

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Figures

**Fig. 1**
**Neuro-anatomical aspects and mechanistic concepts in modulation of chronic cough from animal and human models**, COPD (chronic obstructive pulmonary disease), n. (nerve), OSA (obstructive sleep apnea), TRP channels (Transient receptor potential channels)

See this image and copyright information in PMC

References

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WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways

Affiliations

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways

Authors

Affiliations

Abstract

Figures

References

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