{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T21:25:55Z","timestamp":1782854755881,"version":"3.54.5"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T00:00:00Z","timestamp":1742169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: Increased levels of nitric oxide (NO) are produced in various inflammatory diseases like allergic asthma. Fractional exhaled NO has been studied as a biomarker of type 2 inflammation in asthma, while the use of nasal NO (nNO) as a diagnostic tool for allergic rhinitis (AR) is less established. In the present study, we investigated nNO as a potential biomarker for differentiating AR from nonallergic rhinitis (NAR). Materials and methods: Medical students were invited to complete a questionnaire on rhinitis symptoms. Individuals who reported nasal symptoms were invited to participate in the clinical phase of the study, which included considering the patient\u2019s medical history, clinical examination, skin-prick tests (SPTs) for the 14 most relevant allergens in the region, and nNO measurement using the NIOX VERO portable nitric oxide analyzer. Informed consent was obtained at each stage of recruitment and clinical assessment. Results: Overall, 62 out of 122 volunteers recruited reported rhinitis symptoms and were investigated further with nNO measurements and SPTs. In total, 39 had SPT-confirmed AR, while 23 were classified as NAR subjects. Both nNO measurements and SPTs were performed on the same day, during the pollen season. The comparison of mean nNO concentrations (830 \u00b1 247 ppb and 851 \u00b1 373 in AR and NAR groups, respectively) showed no statistically significant difference. Conclusions: we concluded that nNO is not a reliable independent biomarker in the diagnosis of AR.<\/jats:p>","DOI":"10.3390\/medicina61030516","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T08:57:02Z","timestamp":1742201822000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Assessing Nasal Nitric Oxide in Allergic Rhinitis: A Controversial Biomarker"],"prefix":"10.3390","volume":"61","author":[{"given":"Natalia","family":"Louca","sequence":"first","affiliation":[{"name":"Medical School, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Damianou","sequence":"additional","affiliation":[{"name":"Medical School, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nektaria","family":"Kostea","sequence":"additional","affiliation":[{"name":"Medical School, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0511-5352","authenticated-orcid":false,"given":"Panayiotis","family":"Kouis","sequence":"additional","affiliation":[{"name":"Medical School, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8339-9285","authenticated-orcid":false,"given":"Panayiotis","family":"Yiallouros","sequence":"additional","affiliation":[{"name":"Medical School, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8935-278X","authenticated-orcid":false,"given":"Constantinos","family":"Pitsios","sequence":"additional","affiliation":[{"name":"Medical School, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Savour\u00e9, M., Bousquet, J., Jaakkola, J.J.K., Jaakkola, M.S., Jacquemin, B., and Nadif, R. (2022). Worldwide prevalence of rhinitis in adults: A review of definitions and temporal evolution. Clin. Transl. Allergy, 12.","DOI":"10.1002\/clt2.12130"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1111\/all.15679","article-title":"Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis","volume":"78","author":"Bousquet","year":"2023","journal-title":"Allergy"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/all.12573","article-title":"Phenotypes and endotypes of rhinitis and their impact on management: A PRACTALL report","volume":"70","author":"Papadopoulos","year":"2015","journal-title":"Allergy"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/S1081-1206(10)62612-9","article-title":"National guidelines needed to manage rhinitis and prevent complications","volume":"82","author":"Rachelefsky","year":"1999","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1093\/eurheartj\/ehr304","article-title":"Nitric oxide synthases: Regulation and function","volume":"33","author":"Forstermann","year":"2011","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/med.21599","article-title":"Inducible nitric oxide synthase: Regulation, structure, and inhibition","volume":"40","author":"Cinelli","year":"2019","journal-title":"Med. Res. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Marcos, M.C., and Cisneros Serrano, C. (2022). What is the added value of FeNO as T2 biomarker?. Front. Allergy, 3.","DOI":"10.3389\/falgy.2022.957106"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Kouis, P., Papatheodorou, S.I., and Yiallouros, P.K. (2015). Diagnostic accuracy of nasal nitric oxide for establishing diagnosis of primary ciliary dyskinesia: A meta-analysis. BMC Pulm. Med., 15.","DOI":"10.1186\/s12890-015-0147-3"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Beydon, N., Kouis, P., Marthin, J.K., Latzin, P., Colas, M., Davis, S.D., Haarman, E., Harris, A.L., Hogg, C., and Kilbride, E. (2023). Nasal nitric oxide measurement in children for the diagnosis of primary ciliary dyskinesia: European Respiratory Society technical standard. Eur. Respir. J., 61.","DOI":"10.1183\/13993003.02031-2022"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1177\/00034894221093890","article-title":"Nasal Nitric Oxide as a Biomarker in the Diagnosis and Treatment of Sinonasal Inflammatory Diseases: A Review of the Literature","volume":"132","author":"Benedict","year":"2022","journal-title":"Ann. Otol. Rhinol. Laryngol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/alr.23090","article-title":"International consensus statement on allergy and rhinology: Allergic Rhinitis\u20142023","volume":"13","author":"Wise","year":"2023","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"E213","DOI":"10.1002\/lary.24590","article-title":"Nasal nitric oxide is dependent on sinus obstruction in allergic rhinitis","volume":"124","author":"Suojalehto","year":"2014","journal-title":"Laryngoscope"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, C., Zheng, K., Liu, X., Zheng, M., Liu, Z., Wang, X., and Zhang, L. (2020). Use of Nasal Nitric Oxide in the Diagnosis of Allergic Rhinitis and Nonallergic Rhinitis in Patients with and without Sinus Inflammation. J. Allergy Clin. Immunol. Pract., 8.","DOI":"10.1016\/j.jaip.2019.12.017"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/S0954-6111(98)90308-0","article-title":"Effect of topical steroids on nasal nitric oxide production in children with perennial allergic rhinitis: A pilot study","volume":"92","author":"Baraldi","year":"1998","journal-title":"Respir. Med."},{"key":"ref_15","first-page":"58","article-title":"Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids","volume":"99","author":"Kharitonov","year":"1997","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S123","DOI":"10.33549\/physiolres.934393","article-title":"Exhaled and Nasal Nitric Oxide\u2014Impact for Allergic Rhinitis","volume":"69","author":"Antosova","year":"2020","journal-title":"Physiol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"(2005). ATS\/ERS Recommendations for Standardized Procedures for the Online and Offline Measurement of Exhaled Lower Respiratory Nitric Oxide and Nasal Nitric Oxide, 2005. Am. J. Respir. Crit. Care Med., 171, 912\u2013930.","DOI":"10.1164\/rccm.200406-710ST"},{"key":"ref_18","first-page":"86","article-title":"Seasonal non-allergic rhinitis (SNAR)\u2014A new disease entity? A clinical and immunological comparison between SNAR, seasonal allergic rhinitis and persistent non-allergic rhinitis","volume":"43","author":"Enbom","year":"2005","journal-title":"Rhinology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1111\/j.1398-9995.2008.01695.x","article-title":"Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response","volume":"63","author":"Campo","year":"2008","journal-title":"Allergy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1016\/0006-291X(91)91268-H","article-title":"Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans","volume":"181","author":"Gustafsson","year":"1991","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1183\/09031936.93.06091368","article-title":"Increased amount of nitric oxide in exhaled air of asthmatics","volume":"6","author":"Alving","year":"1993","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1034\/j.1398-9995.2002.23625.x","article-title":"Executive Summary of the Workshop Report 7\u201310 December 1999, Geneva, Switzerland","volume":"57","author":"Bousquet","year":"2002","journal-title":"Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.anai.2010.05.014","article-title":"Relationship between fractional exhaled nitric oxide and nasal nitric oxide in airways disease","volume":"105","author":"Williamson","year":"2010","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1111\/j.1365-2222.1997.tb00719.x","article-title":"Nasal nitric oxide is increased in allergic rhinitis","volume":"27","author":"Arnal","year":"1997","journal-title":"Clin. Exp. Allergy"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"228","DOI":"10.3342\/ceo.2012.5.4.228","article-title":"Nasal and Exhaled Nitric Oxide in Allergic Rhinitis","volume":"5","author":"Lee","year":"2012","journal-title":"Clin. Exp. Otorhinolaryngol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1017\/S0022215116009087","article-title":"Measuring nasal nitric oxide in allergic rhinitis patients","volume":"130","author":"Nesic","year":"2016","journal-title":"J. Laryngol. Otol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.anai.2020.07.003","article-title":"Clinical application of nasal nitric oxide measurement in allergic rhinitis","volume":"125","author":"Ambrosino","year":"2020","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1034\/j.1399-3003.1999.13b14.x","article-title":"Exhaled and nasal NO levels in allergic rhinitis: Relation to sensitization, pollen season and bronchial hyperresponsiveness","volume":"13","author":"Henriksen","year":"1999","journal-title":"Eur. Respir. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1034\/j.1398-9995.2003.00098.x","article-title":"Characterization of airway nitric oxide in allergic rhinitis: The effect of intranasal administration of L-NAME","volume":"58","author":"Palm","year":"2003","journal-title":"Allergy"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1046\/j.1365-2362.2001.00825.x","article-title":"Effect of nitric oxide inhibition on nasal airway resistance after nasal allergen challenge in allergic rhinitis","volume":"31","author":"Maniscalco","year":"2001","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kalpaklioglu, A.F., Baccioglu, A., and Yalim, S.A. (2021). Can nasal nitric oxide be a biomarker to differentiate allergic and non-allergic rhinitis?. Egypt. J. Otolaryngol., 37.","DOI":"10.1186\/s43163-021-00154-1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2500\/ajr.2006.20.2921","article-title":"Nasal Levels of Nitric Oxide as an Outcome Variable in Allergic Upper Respiratory Tract Disease: Influence of Atopy and Hayfever on nNO","volume":"20","author":"Moody","year":"2006","journal-title":"Am. J. Rhinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s10661-012-2540-1","article-title":"Analysis of airborne pollen fall in Nicosia (Cyprus)","volume":"185","author":"Gucel","year":"2012","journal-title":"Environ. Monit. Assess."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ge, C., Zhuang, H., Yo, H., and Zhang, C. (2025). Correlation between peripheral blood iNKT cell levels and exhaled NO in patients with allergic rhinitis. Hum Immunol, 2.","DOI":"10.1016\/j.humimm.2025.111255"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/3\/516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:54:51Z","timestamp":1760028891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/3\/516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,17]]},"references-count":34,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["medicina61030516"],"URL":"https:\/\/doi.org\/10.3390\/medicina61030516","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,17]]}}}