COVID-19 and chronic rhinosinusitis: management and comorbidity – what have we learned?

References

• Hagemann J, Onorato GL, Jutel M, et al. Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA(2) LEN consensus. Allergy. 2021 Aug;76(8):2354–2366. doi: 10.1111/all.14815
   PubMed Web of Science ®Google Scholar
• Hagemann J, Zuberbier T, Walter Canonica G, et al. Reply to correspondence to ‘Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA2LEN consensus’. Allergy. 2022 Aug;77(8):2574–2575. doi: 10.1111/all.15330
   PubMed Web of Science ®Google Scholar
• Gane SB, Kelly C, Hopkins C. Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome? Rhinology. 2020 Jun 1;58(3):299–301. doi: 10.4193/Rhin20.114
   PubMed Web of Science ®Google Scholar
• Klimek L, Hagemann J, Alali A, et al. Telemedicine allows quantitative measuring of olfactory dysfunction in COVID-19. Allergy. 2021 Mar;76(3):868–870. doi: 10.1111/all.14467
   PubMed Web of Science ®Google Scholar
• Klimek L, Hagemann J, Doge J, et al. Olfactory and gustatory disorders in COVID-19. Allergo J Int. 2022;31(7):243–250. doi: 10.1007/s40629-022-00216-7
   PubMedGoogle Scholar
• Iacobucci G. Sixty seconds on … anosmia. BMJ. 2020 Mar 24;368:m1202. doi: 10.1136/bmj.m1202
   PubMedGoogle Scholar
• Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. London, England. doi: 10.1016/S0140-6736(20)30183-5
   PubMed Web of Science ®Google Scholar
• WHO. Coronavirus disease (COVID-19 pandemic). https://www.who.int/emergencies/diseases/novel-coronavirus-2019: WHO; 2020 [ 20.04.2020]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019
   Google Scholar
• Lüers J-C, Klußmann JP, Guntinas-Lichius O. Die Covid-19-Pandemie und das HNO-Fachgebiet: Worauf kommt es aktuell an? [The Covid-19 pandemic and otolaryngology: What it comes down to?]. Laryngorhinootologie. 2020;99(5):287–291. doi: 10.1055/a-1095-2344
   PubMedGoogle Scholar
• Chen Y, Liu Q, Guo D. Emerging coronaviruses: Genome structure, replication, and pathogenesis. J med virol. 2020;92(4):418–423. doi: 10.1002/jmv.25681
   PubMed Web of Science ®Google Scholar
• Zhang JJ, Dong X, Cao YY, et al. Clinical characteristics of 140 patients infected with SARS-CoV-2 in Wuhan, China. Allergy. 2020 Feb 19;75(7):1730–1741. doi: 10.1111/all.14238
   PubMed Web of Science ®Google Scholar
• Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054–1062. London, England. doi: 10.1016/S0140-6736(20)30566-3
   PubMed Web of Science ®Google Scholar
• Hastan D, Fokkens WJ, Bachert C, et al. Chronic rhinosinusitis in Europe–an underestimated disease. A GA(2)LEN study. Allergy. 2011 Sep;66(9):1216–1223. doi: 10.1111/j.1398-9995.2011.02646.x
   PubMed Web of Science ®Google Scholar
• Hirsch AG, Stewart WF, Sundaresan AS, et al. Nasal and sinus symptoms and chronic rhinosinusitis in a population-based sample. Allergy. 2017 Feb;72(2):274–281. doi: 10.1111/all.13042
   PubMed Web of Science ®Google Scholar
• Klimek L, Jutel M, Bousquet J, et al. Management of patients with chronic rhinosinusitis during the COVID-19 pandemic-An EAACI position paper. Allergy. 2021 Mar;76(3):677–688. doi: 10.1111/all.14629
   PubMed Web of Science ®Google Scholar
• Ostovar A, Fokkens WJ, Vahdat K, et al. Epidemiology of chronic rhinosinusitis in Bushehr, southwestern region of Iran: a GA2LEN study. Rhinology. 2019 Feb 1;57(1):43–48. doi: 10.4193/Rhin18.061
   PubMed Web of Science ®Google Scholar
• Shi JB, Fu QL, Zhang H, et al. Epidemiology of chronic rhinosinusitis: results from a cross-sectional survey in seven Chinese cities. Allergy. 2015 May;70(5):533–539. doi: 10.1111/all.12577
   PubMed Web of Science ®Google Scholar
• Vaira LA, Salzano G, Deiana G, et al. Anosmia and Ageusia: Common findings in COVID-19 patients. Laryngoscope. 2020;130(7):1787. doi: 10.1002/lary.28692
   PubMed Web of Science ®Google Scholar
• Soyka MB, Wawrzyniak P, Eiwegger T, et al. Defective epithelial barrier in chronic rhinosinusitis: the regulation of tight junctions by IFN-gamma and IL-4. J Allergy Clin Immunol. 2012 Nov;130(5):1087–1096 e10. doi: 10.1016/j.jaci.2012.05.052
   PubMed Web of Science ®Google Scholar
• Klimek L, Koennecke M, Hagemann J, et al. Immunology of chronic rhinosinusitis with nasal polyps as a basis for treatment with biologicals. HNO. 2019 Jan;67(1):15–26. doi: 10.1007/s00106-018-0557-7
   PubMed Web of Science ®Google Scholar
• Klimek L, Akdis CA, Jutel M, et al. Inhaled corticosteroids in early COVID-19-A tale of many facets. Allergy. 2021 Nov;76(11):3540–3542. doi: 10.1111/all.15041
   PubMed Web of Science ®Google Scholar
• Tomassen P, Vandeplas G, Van Zele T, et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J Allergy Clin Immunol. 2016 May;137(5):1449–1456 e4. doi: 10.1016/j.jaci.2015.12.1324
   PubMed Web of Science ®Google Scholar
• Tsetsos N, Goudakos JK, Daskalakis D, et al. Monoclonal antibodies for the treatment of chronic rhinosinusitis with nasal polyposis: a systematic review. Rhinology. 2018 Mar 1;56(1):11–21. doi: 10.4193/Rhin17.156
   PubMed Web of Science ®Google Scholar
• Klimek L, Förster-Ruhrmann U, Beule AG, et al. Indicating biologics for chronic rhinosinusitis with nasal polyps (CRSwNP). Allergo J Int. 2022;31(6):149–160. doi: 10.1007/s40629-022-00220-x
   Google Scholar
• Koennecke M, Klimek L, Mullol J, et al. Subtyping of polyposis nasi: phenotypes, endotypes and comorbidities. Allergo J Int. 2018;27(2):56–65. doi: 10.1007/s40629-017-0048-5
   PubMedGoogle Scholar
• Fokkens WJ, Lund VJ, Mullol J, et al. EPOS 2012: European position paper on rhinosinusitis and nasal polyps 2012. A summary for otorhinolaryngologists. Rhinology. 2012 Mar;50(1):1–12. doi: 10.4193/Rhino12.000
   PubMed Web of Science ®Google Scholar
• Liao B, Liu JX, Li ZY, et al. Multidimensional endotypes of chronic rhinosinusitis and their association with treatment outcomes. Allergy. 2018 Jul;73(7):1459–1469. doi: 10.1111/all.13411
   PubMed Web of Science ®Google Scholar
• Philpott CM, Erskine S, Hopkins C, et al. Prevalence of asthma, aspirin sensitivity and allergy in chronic rhinosinusitis: data from the UK National chronic rhinosinusitis epidemiology study. Respir Res. 2018 Jun 27;19(1):129. doi: 10.1186/s12931-018-0823-y
   PubMedGoogle Scholar
• Wu D, Bleier BS, Li L, et al. Clinical phenotypes of nasal polyps and comorbid asthma based on cluster analysis of disease history. J Allergy Clin Immunol Pract. 2018 Jul;6(4):1297–1305 e1. doi: 10.1016/j.jaip.2017.09.020
   PubMed Web of Science ®Google Scholar
• Khan A, Vandeplas G, Huynh TMT, et al. The Global Allergy and Asthma European Network (GALEN rhinosinusitis cohort: a large European cross-sectional study of chronic rhinosinusitis patients with and without nasal polyps. Rhinology. 2019 Feb 1;57(1):32–42. doi: 10.4193/Rhin17.255
   PubMed Web of Science ®Google Scholar
• Langdon C, Mullol J. Nasal polyps in patients with asthma: prevalence, impact, and management challenges. J Asthma Allergy. 2016;9:45–53. doi: 10.2147/JAA.S86251
   PubMed Web of Science ®Google Scholar
• De Greve G, Hellings PW, Fokkens WJ, et al. Endotype-driven treatment in chronic upper airway diseases. Clin Transl Allergy. 2017;7(1):22. doi: 10.1186/s13601-017-0157-8
   PubMedGoogle Scholar
• Seys SF, Scheers H, Van den Brande P, et al. Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients. Respir Res. 2017 Feb 23;18(1):39. doi: 10.1186/s12931-017-0524-y
   PubMedGoogle Scholar
• Zhang Y, Derycke L, Holtappels G, et al. Th2 cytokines orchestrate the secretion of MUC5AC and MUC5B in IL-5-positive chronic rhinosinusitis with nasal polyps. Allergy. 2019 Jan;74(1):131–140. doi: 10.1111/all.13489
   PubMed Web of Science ®Google Scholar
• Green RH, Brightling CE, Woltmann G, et al. Analysis of induced sputum in adults with asthma: identification of subgroup with isolated sputum neutrophilia and poor response to inhaled corticosteroids. Thorax. 2002 Oct;57(10):875–879. doi: 10.1136/thorax.57.10.875
   PubMed Web of Science ®Google Scholar
• Chong LY, Head K, Hopkins C, et al. Intranasal steroids versus placebo or no intervention for chronic rhinosinusitis. Cochrane Database Syst Rev.2016 Apr 26 4. CD011996 4. 10.1002/14651858.CD011996.pub2
   Google Scholar
• Rudmik L, Soler ZM. Medical therapies for adult chronic sinusitis: A systematic review. JAMA. 2015 Sep 1;314(9):926–939. doi: 10.1001/jama.2015.7544
   PubMed Web of Science ®Google Scholar
• Klimek L, Bachert C. Current aspects of nasal glucocorticosteroid therapy. HNO. 2000 Jul;48(7):544–555. doi: 10.1007/s001060050614
   PubMed Web of Science ®Google Scholar
• Pundir V, Pundir J, Lancaster G, et al. Role of corticosteroids in functional endoscopic sinus surgery–a systematic review and meta-analysis. Rhinology. 2016 Mar;54(1):3–19. doi: 10.4193/Rhin15.079
   PubMed Web of Science ®Google Scholar
• Voorham J, Xu X, Price DB, et al. Healthcare resource utilization and costs associated with incremental systemic corticosteroid exposure in asthma. Allergy. 2019 Feb;74(2):273–283. doi: 10.1111/all.13556
   PubMed Web of Science ®Google Scholar
• Kirsche H, Klimek L. ASA-intolerance syndrome and persistent rhinosinusitis: Differential diagnosis and treatment. HNO. 2015 May;63(5):357–363. doi: 10.1007/s00106-015-0008-7
   PubMed Web of Science ®Google Scholar
• Klimek L, Pfaar O. Aspirin intolerance: does desensitization alter the course of the disease? Immunol Allergy Clin North Am. 2009 Nov;29(4):669–675. doi: 10.1016/j.iac.2009.07.008
   PubMed Web of Science ®Google Scholar
• Kowalski ML, Agache I, Bavbek S, et al. Diagnosis and management of NSAID-Exacerbated respiratory disease (N-ERD)-a EAACI position paper. Allergy. 2019 Jan;74(1):28–39. doi: 10.1111/all.13599
   PubMed Web of Science ®Google Scholar
• Hox V, Lourijsen E, Jordens A, et al. Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper. Clin Transl Allergy. 2020;10(1):1. doi: 10.1186/s13601-019-0303-6
   PubMed Web of Science ®Google Scholar
• Price DB, Trudo F, Voorham J, et al. Adverse outcomes from initiation of systemic corticosteroids for asthma: long-term observational study. J Asthma Allergy. 2018;11:193–204. DOI:10.2147/JAA.S176026
   PubMed Web of Science ®Google Scholar
• Gandhi NA, Pirozzi G, Graham NMH. Commonality of the IL-4/IL-13 pathway in atopic diseases. Expert Rev Clin Immunol. 2017 May;13(5):425–437. doi: 10.1080/1744666X.2017.1298443
   PubMed Web of Science ®Google Scholar
• Dupixent® 300 mg Injektionslösung in einer Fertigspritze, R.L.S. GmbH - Fachinformation, (2020).
   Google Scholar
• Fokkens WJ. EPOS2020: a major step forward. Rhinology. 2020 Feb 1;58(1):1. doi: 10.4193/Rhin20.401
   Web of Science ®Google Scholar
• Fokkens WJ, Lund V, Bachert C, et al. EUFOREA consensus on biologics for CRSwNP with or without asthma. Allergy. 2019 Dec;74(12):2312–2319. doi: 10.1111/all.13875
   PubMed Web of Science ®Google Scholar
• Hopkins C, Surda P, Bast F, et al. Prevention of chronic rhinosinusitis. Rhinology. 2018 Dec 1;56(4):307–315. doi: 10.4193/Rhin17.027
   PubMed Web of Science ®Google Scholar
• Kilty SJ, Lasso A, Mfuna-Endam L, et al. Case-control study of endoscopic polypectomy in clinic (EPIC) versus endoscopic sinus surgery for chronic rhinosinusitis with polyps. Rhinology. 2018 Jun 1;56(2):155–157. doi: 10.4193/Rhin17.115
   PubMed Web of Science ®Google Scholar
• Rudmik L, Soler ZM, Hopkins C, et al. Defining appropriateness criteria for endoscopic sinus surgery during management of uncomplicated adult chronic rhinosinusitis: a RAND/UCLA appropriateness study. Rhinology. 2016 Jun;54(2):117–128. doi: 10.4193/Rhin16.023
   PubMed Web of Science ®Google Scholar
• Wang M, Bu X, Fang G, et al. Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps. Allergy. 2021;76(3):789–803. doi: 10.1111/all.14665
   PubMed Web of Science ®Google Scholar
• Bousquet J, Akdis C, Jutel M, et al. Intranasal corticosteroids in allergic rhinitis in COVID-19 infected patients: An ARIA-EAACI statement. Allergy. 2020;75(10):2440–2444. doi: 10.1111/all.14302
   PubMed Web of Science ®Google Scholar
• Hayward G, Thompson MJ, Perera R. et al. Corticosteroids for the common cold. Cochrane Database Syst Rev.2015 Oct 13 2015. CD008116 10. 10.1002/14651858.CD008116.pub3
   PubMedGoogle Scholar
• Fokkens WJ, Lund VJ, Hopkins C, et al. European position paper on rhinosinusitis and nasal polyps 2020. Rhinology. 2020 Feb 20;58(Suppl S29):1–464. doi: 10.4193/Rhin20.401
   Google Scholar
• Keith PK, Dymek A, Pfaar O, et al. Fluticasone furoate nasal spray reduces symptoms of uncomplicated acute rhinosinusitis: a randomised placebo-controlled study. Prim Care Respir J. 2012 Sep;21(3):267–275. doi: 10.4104/pcrj.2012.00039
   PubMedGoogle Scholar
• Meltzer EO, Bachert C, Staudinger H. Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo. J Allergy Clin Immunol. 2005 Dec;116(6):1289–1295. doi: 10.1016/j.jaci.2005.08.044
   PubMed Web of Science ®Google Scholar
• Förster-Ruhrmann L, Klimek U, Becker S, et al. Stellungnahme zur Anwendung von Glukokortikosteroiden bei entzündlichen Erkrankungen der oberen Atemwege. Laryngorhinootologie. 2020 May;99(5):280–281. doi: 10.1055/a-1148-3553
   PubMedGoogle Scholar
• Darveaux JI, Lemanske RF Jr. Infection-related asthma. J Allergy Clin Immunol Pract. 2014 Nov;2(6):658–663. doi: 10.1016/j.jaip.2014.09.011
   PubMed Web of Science ®Google Scholar
• Hewitt R, Farne H, Ritchie A, et al. The role of viral infections in exacerbations of chronic obstructive pulmonary disease and asthma. Ther Adv Respir Dis. 2016 Apr;10(2):158–174. doi: 10.1177/1753465815618113
   PubMed Web of Science ®Google Scholar
• Pfeifer M, Lommatzsch M, Korn S, et al. Stellungnahme - Asthma-Patienten und COVID-19: Lungenexperten raten: Therapie mit inhalierbaren Steroiden (ICS) unverändert fortführen. 2020. [accessed 2023 August 06]. https://dgaki.de/wp-content/uploads/2020/03/Statement-Asthma-und-COVID-19_F-002.pdf
   Google Scholar
• Abidi K, Khoudri I, Belayachi J, et al. Eosinopenia is a reliable marker of sepsis on admission to medical intensive care units. Crit Care. 2008;12(2):R59. doi: 10.1186/cc6883
   PubMed Web of Science ®Google Scholar
• Kulaylat AS, Buonomo EL, Scully KW, et al. Development and validation of a prediction model for mortality and adverse outcomes among patients with peripheral eosinopenia on admission for clostridium difficile infection. JAMA Surg. 2018 Dec 1;153(12):1127–1133. doi: 10.1001/jamasurg.2018.3174
   PubMed Web of Science ®Google Scholar
• Pouliquen IJ, Kornmann O, Barton SV, et al. Characterization of the relationship between dose and blood eosinophil response following subcutaneous administration of mepolizumab. Int J Clin Pharmacol Ther. 2015 Dec;53(12):1015–1027. doi: 10.5414/CP202446
   PubMed Web of Science ®Google Scholar
• Ghazi A, Trikha A, Calhoun WJ. Benralizumab–a humanized mAb to IL-5Ralpha with enhanced antibody-dependent cell-mediated cytotoxicity–a novel approach for the treatment of asthma. Expert Opin Biol Ther. 2012 Jan;12(1):113–118. doi: 10.1517/14712598.2012.642359
   PubMed Web of Science ®Google Scholar
• Bachert C, Han JK, Desrosiers MY, et al. Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: A randomized, placebo-controlled trial. J Allergy Clin Immunol. 2022;149(4):1309–1317 e12. doi: 10.1016/j.jaci.2021.08.030
   PubMed Web of Science ®Google Scholar
• Agache I, Beltran J, Akdis C, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020 May;75(5):1023–1042. doi: 10.1111/all.14221
   PubMed Web of Science ®Google Scholar
• Howarth P, Chupp G, Nelsen LM, et al. Severe eosinophilic asthma with nasal polyposis: A phenotype for improved sinonasal and asthma outcomes with mepolizumab therapy. J Allergy Clin Immunol. 2020 Jun;145(6):1713–1715. doi: 10.1016/j.jaci.2020.02.002
   PubMed Web of Science ®Google Scholar
• Dupilumab Core Company Data Sheet. 2019.
   Google Scholar
• CHMP EMA. Assessment report - Dupixent. 2017.
   Google Scholar
• Gleich GJ, Klion AD, Lee JJ, et al. The consequences of not having eosinophils. Allergy. 2013 Jul;68(7):829–835. doi: 10.1111/all.12169
   PubMed Web of Science ®Google Scholar
• Liu F, Xu A, Zhang Y, et al. Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression. Int J Infect Dis. 2020 Jun;95:183–191.
   PubMed Web of Science ®Google Scholar
• Zou L, Ruan F, Huang M, et al. SARS-CoV-2 Viral load in upper respiratory specimens of infected patients. N Engl J Med. 2020 Mar 19;382(12):1177–1179. doi: 10.1056/NEJMc2001737
   PubMed Web of Science ®Google Scholar
• Tran K, Cimon K, Severn M, et al. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review. PLoS One. 2012;7(4):e35797. doi: 10.1371/journal.pone.0035797
   PubMed Web of Science ®Google Scholar
• Van Gerven L, Hellings PW, Cox T, et al. Personal protection and delivery of rhinologic and endoscopic skull base procedures during the COVID-19 outbreak. Rhinology. 2020 Jun 1;58(3):289–294. doi: 10.4193/Rhin20.119
   PubMed Web of Science ®Google Scholar
• Prevention. CgCfDCa. 2020.
   Google Scholar
• Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCov infection from an asymptomatic contact in Germany. N Engl J Med. 2020 Mar 5;382(10):970–971. doi: 10.1056/NEJMc2001468
   PubMed Web of Science ®Google Scholar
• Leong SC, Mogre D, Andrews P, et al. Reducing the risks of endoscopic sinonasal surgery in the Covid-19 era. Clinical Otolaryngology: Official Journal Of ENT-UK; Official Journal Of Netherlands Society For Oto-Rhino-Laryngology & Cervico-Facial Surgery. 2021 Jul;46(4):809–815. doi: 10.1111/coa.13743
   PubMed Web of Science ®Google Scholar
• Jones HAS, Salib RJ, Harries PG. Reducing aerosolized particles and droplet spread in endoscopic sinus surgery during COVID-19. Laryngoscope. 2021 May;131(5):956–960. doi: 10.1002/lary.29065
   PubMed Web of Science ®Google Scholar
• Workman AD, Welling DB, Carter BS, et al. Endonasal instrumentation and aerosolization risk in the era of COVID-19: simulation, literature review, and proposed mitigation strategies. Int Forum Allergy Rhinol. 2020 Jul;10(7):798–805. doi: 10.1002/alr.22577
   PubMed Web of Science ®Google Scholar
• Klimek L, Novak N, Cabanillas B, et al. Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation. Allergy. 2021 Nov;76(11):3307–3313. doi: 10.1111/all.14794
   PubMed Web of Science ®Google Scholar
• Klimek L, Agache I, Cooke E, et al. COVID-19 vaccines-The way forward. Allergy. 2022 Jan;77(1):15–16. doi: 10.1111/all.14995
   PubMed Web of Science ®Google Scholar
• Klimek L, Jutel M, Akdis CA, et al. ARIA-EAACI statement on severe allergic reactions to COVID-19 vaccines - an EAACI-ARIA position paper. Allergy. 2021 Jun;76(6):1624–1628. doi: 10.1111/all.14726
   PubMed Web of Science ®Google Scholar
• Klimek L, Novak N, Hamelmann E, et al. Severe allergic reactions after COVID-19 vaccination with the Pfizer/BioNTech vaccine in Great Britain and USA: Position statement of the German allergy societies: medical Association of German Allergologists (AeDAGerman Society For Allergology And Clinical Immunology (DGAKI) And Society For Pediatric Allergology And Environmental Medicine (GPA). Allergo J Int. 2021;30(2):51–55. doi: 10.1007/s40629-020-00160-4
   PubMedGoogle Scholar
• Klimek L, Hagemann J, Alali A, et al. The toll of noninfected CRS patients to the COVID-19 pandemic. Rhinology. 2020 Oct 1;58(5):522–523. doi: 10.4193/Rhin20.250
   PubMed Web of Science ®Google Scholar