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      WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation — Updates in COVID-19

      review-article
      , MD a , , , MD a , b , , MD, PhD c , d , e , f , , MD g , , MD h , i , j , , MD, FRCPCP k , , MD l , , MD, MSc R, CABHS m , , MD, FACAAI, FAAAAI n , , MD, DrPH o , , MD n , , MD, FACAAI p , , MD, FACS, ERS, PARS q , , MD, PhD r , s , t , u , , MD, FRCP v , , BMedSci, MBBS, FRACP, PhD w , , MD x , , MD, PhD y , , MD, PhD z , , MD, PhD aa , , MD, FCCP, D'ABSM ab , , MD, FCCP ac , , MD ad , , MD ae , , MD af , , MD ag , , MD ah , , MD ai , , MD, PhD f , aj , ak , , PhD al , , MD am , , MD, PhD an , , DO ao , , MD, PhD ap , , MD, PhD aq , , MD ar , , MD as , at , , MD au , , MD av , , MD, PhD aw
      The World Allergy Organization Journal
      World Allergy Organization
      Multifactorial cough, Cough phenotypes, Type 2 inflammation, COVID 19, Reflux-cough, Upper airway cough syndrome, Lower airway disease, Obstructive sleep apnea

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          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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          Most cited references222

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          Persistent Symptoms in Patients After Acute COVID-19

          This case series describes COVID-19 symptoms persisting a mean of 60 days after onset among Italian patients previously discharged from COVID-19 hospitalization.
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            An inflammatory cytokine signature predicts COVID-19 severity and survival

            Several studies have revealed that the hyper-inflammatory response induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of disease severity and death. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α and IL-1β in hospitalized patients with coronavirus disease 2019 (COVID-19) upon admission to the Mount Sinai Health System in New York. Patients (n = 1,484) were followed up to 41 d after admission (median, 8 d), and clinical information, laboratory test results and patient outcomes were collected. We found that high serum IL-6, IL-8 and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival (P < 0.0001, P = 0.0205 and P = 0.0140, respectively). Notably, when adjusting for disease severity, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. These findings were validated in a second cohort of patients (n = 231). We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of patients with COVID-19 to stratify prospective clinical trials, guide resource allocation and inform therapeutic options.
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              European Position Paper on Rhinosinusitis and Nasal Polyps 2020

              The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.
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                Author and article information

                Contributors
                Journal
                World Allergy Organ J
                World Allergy Organ J
                The World Allergy Organization Journal
                World Allergy Organization
                1939-4551
                22 November 2021
                December 2021
                22 November 2021
                : 14
                : 12
                : 100618
                Affiliations
                [a ]Department of Otolaryngology - Head and Neck Surgery, Eye and Ear University Hospital, Beirut, Lebanon
                [b ]Department of Audiology and Otoneurological Evaluation, Edouard Herriot Hospital, Lyon, France
                [c ]Hospital Charité, Universitätsmedizin Berlin, Humboldt-Universität zu Berlin, Berlin, Germany
                [d ]Department of Dermatology and Allergy, Comprehensive Allergy Center, Berlin Institute of Health, Berlin, Germany
                [e ]Macvia France, Montpellier France
                [f ]Université Montpellier, France, Montpellier, France
                [g ]Department of Medicine, Harvard Medical School, Division of Allergy and Clinical Immunology, Brigham and Women's Hospital Boston, MA, USA
                [h ]Department of Gastroenterology, American University of Beirut Medical Center (AUBMC), Beirut, Lebanon
                [i ]Department of Gastroenterology, Middle East Institute of Health (MEIH), Beirut, Lebanon
                [j ]Department of Gastroenterology, Clemenceau Medical Center (CMC), Beirut, Lebanon
                [k ]Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait
                [l ]INAER - Investigaciones en Alergia y Enfermedades Respiratorias, Buenos Aires, Argentina
                [m ]Allergy and Immunology Section, Department of Medicine, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar
                [n ]International Cough Institute, Washington D.C, USA
                [o ]Allergy & Immunology Section, Louisiana State University Health Sciences Center, Shreveport, LA, USA
                [p ]Department of Allergy Otolaryngology, LAU-RIZK Medical Center, Beirut, Lebanon
                [q ]Clinical Professor Department of Otolaryngology Head and Neck Surgery, American University of Beirut, Lebanon
                [r ]KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Allergy and Clinical Immunology, Leuven, Belgium
                [s ]University Hospitals Leuven, Department of Otorhinolaryngology, Leuven, Belgium
                [t ]University Hospital Ghent, Department of Otorhinolaryngology, Laboratory of Upper Airways Research, Ghent, Belgium
                [u ]Academic Medical Center, University of Amsterdam, Department of Otorhinolaryngology, Amsterdam, the Netherlands
                [v ]Department of ENT, RNENT Hospital, London, UK
                [w ]Clinical Medicine Griffith University, Southport Qld, 4215, Australia
                [x ]Allergy Center, CUF Descobertas Hospital, Lisboa, Portugal
                [y ]School of Health Sciences, Catholic University of Salta, Argentina
                [z ]Universidad Autónoma de Nuevo León, Hospital Universitario and Facultad de Medicina, Monterrey, NL, Mexico
                [aa ]Center for Rhinology and Allergology, Wiesbaden, Germany
                [ab ]Department of Pulmonary, Critical Care and Sleep Medicine at Saint George Hospital University Medical Center, Beirut, Lebanon
                [ac ]Department of Pulmonary and Critical Care, Hôtel-Dieu de France University Hospital, Beirut, Lebanon
                [ad ]Humanitas University & Personalized Medicine Asthma & Allergy Clinic-Humanitas Research Hospital-IRCCS-Milano Italy
                [ae ]UNC Center for Environmental Medicine, Asthma, and Lung Biology, Division of Allergy, Immunology and Rheumatology, Department of Pediatrics UNS School of Medicine, USA
                [af ]Department of Pediatrics, Chinese University of Hong Kong, Hong Kong, China
                [ag ]Department of Pediatrics, Section of Allergy and Immunology, University of Louisville School of Medicine, Shelbyville Rd, Louisville, KY, 9800, USA
                [ah ]University of Cincinnati College of Medicine, Department of Internal Medicine, Division of Immunology/Allergy Section, Cincinnati, USA
                [ai ]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
                [aj ]Desbrest Institute of Epidemiology and Public Health, UMR UA-11, INSERM University of Montpellier, Montpellier, France
                [ak ]WHO Collaborating Centre on Scientific Classification Support, Montpellier, France
                [al ]Medical Faculty at Akaki Tsereteli State University, National Institute of Allergy, Asthma & Clinical Immunology, KuTaisi, Tskaltubo, Georgia
                [am ]Division of Paediatric Allergology, Department of Paediatrics, University of Cape Town, South Africa
                [an ]Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
                [ao ]Department of Otolaryngology, Division of Allergy & Immunology, The Ohio State University, Columbus, OH, USA
                [ap ]Institute for Immunological Research, University of Cartagena. Cartagena de Indias, Colombia
                [aq ]National Heart and Lund Institute, Imperial College London, UK
                [ar ]Health Science Institute, Autonomous University of Hidalgo, Mexico
                [as ]Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria
                [at ]The interuniversity Messerli Research Institute, Medical University Vienna and Univ, of Veterinary Medicine Vienna, Austria
                [au ]Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, Sagamihara, Japan
                [av ]Translational Pediatric Research Area, Allergic Diseases Research Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Holy See
                [aw ]Department of Allergy and Immunology, Hospital Quironsalud Bizkaia, Bilbao, Spain
                Author notes
                []Corresponding author. rouadipws@ 123456gmail.com
                Article
                S1939-4551(21)00112-5 100618
                10.1016/j.waojou.2021.100618
                8666560
                ed69110e-8ec1-4100-94f8-6d2dbcfc73f1
                © 2021 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 4 September 2021
                : 30 October 2021
                : 12 November 2021
                Categories
                Article

                Immunology
                multifactorial cough,cough phenotypes,type 2 inflammation,covid 19,reflux-cough,upper airway cough syndrome,lower airway disease,obstructive sleep apnea

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