the Role of Fractional Exhaled Nitric Oxide (FeNO) and Inflammatory Biomarkers in Diagnosing Non-Chronic Cough in Pediatric Patients: A Cross-Sectional Study
-
Soheila Alyasin
,
Zahra Kanannejad
,
Seyed Hesamodin Nabavizadeh
,
Hossein Esmaeilzadeh
,
Erfan Sadeghi
,
Hafez Shojaadini
,
Ashkan Akbarzadeh
,
Nazanin Ayareh
,
Leila Johari
Abstract
Fractional exhaled nitric oxide (FeNO) has emerged as a potential biomarker for differentiating between various causes of non-chronic cough, particularly in conditions associated with airway inflammation, such as asthma. This study aimed to evaluate the diagnostic efficacy of FeNO in pediatric patients with non-chronic cough and its ability to differentiate between asthma exacerbations and respiratory tract infections.
Seventy-five pediatric patients aged 10-18 years with non-chronic cough were categorized into three groups: good control asthma (GCA, n=28), acute asthma exacerbation (AAE, n=26), and respiratory tract infection (RTI, n=21). Clinical assessments included FeNO measurement, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC) count, hemoglobin (HB), platelet count (PLT), and immunoglobulin E (IgE) levels. Univariate and multivariate multinomial logistic regression models were applied to assess the predictive value of these variables.
FeNO levels were significantly higher in the AAE group (46.58±22.66 ppb) compared to the GCA and RTI groups, indicating elevated eosinophilic airway inflammation in asthma exacerbations. CRP was a significant predictor of both AAE and RTI, with a one-unit increase in CRP increasing the odds of exacerbation or infection by 2.6-fold. Body max index (BMI) was inversely associated with the risk of RTI. Hemoglobin, platelet count, and IgE levels were significantly higher in the AAE group compared to the other groups, while WBC counts, though elevated, were not statistically significant.
FeNO associated with other inflammatory markers, including CRP and BMI, could enhance diagnostic accuracy and inform clinical decision-making in managing pediatric respiratory conditions. To confirm these results, future studies with larger sample sizes should be performed.
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7. Nakwan N, Ruklerd T, Perkleang T, Taptawee P. The levels and correlations of FeNO, blood eosinophils and lung function in well-controlled asthma. Advanc Resp Med. 2022;90(3):183-92.
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17. Mukae H, Kaneko T, Obase Y, Shinkai M, Katsunuma T, Takeyama K, et al. The Japanese respiratory society guidelines for the management of cough and sputum (digest edition). Resp Invest. 2021;59(3):270-90.
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21. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-12.
22. Jousilahti P, Salomaa V, Hakala K, Rasi V, Vahtera E, Palosuo T. The association of sensitive systemic inflammation markers with bronchial asthma. Ann Allergy Asthma Immunol. 2002;89(4):381-5.
23. Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med. 2007;175(7):661-6.
24. Shore SA, Fredberg JJ. Obesity, smooth muscle, and airway hyperresponsiveness. J Allergy Clin Immunol. 2005;115(5):925-7.
25. Peters U, Dixon AE, Forno E. Obesity and asthma. J Allergy Clin Immunol. 2018;141(4):1169-79.
26. Kang M, Sohn SJ, Shin MH. Association between Body Mass Index and Prevalence of Asthma in Korean Adults. Chonnam Med J. 2020;56(1):62-7.
27. Hjellvik V, Tverdal A, Furu K. Body mass index as predictor for asthma: a cohort study of 118,723 males and females. Eur Respir J. 2010;35(6):1235-42.
28. Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N, Enander I, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323(15):1033-9.
29. Kanannejad Z, Alyasin S, Esmaeilzadeh H, Nabavizadeh H, Amin R. Asthma and COVID-19 pandemic: focus on the eosinophil count and ACE2 expression. Eur Ann Allergy Clin Immunol. 2022;54(6):284-9.
30. Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax. 1998;53(2):91-5.
31. Aslan ES, Aydın H, Tekin YK, Keleş S, White KN, Hekim N. Association between iron metabolism and SARS-COV-2 infection, determined by ferritin, hephaestin and hypoxia-induced factor-1 alpha levels in COVID-19 patients. Mol Biol Rep. 2023;50(3):2471-8.
32. Beri D, Singh M, Rodriguez M, Barbu-Stevanovic M, Rasquinha G, Mendelson A, et al. Elucidating parasite and host-cell factors enabling Babesia infection in sickle red cells under hypoxic/hyperoxic conditions. Blood Advances. 2023;7(4):649-63.
33. Daniel Y, Hunt BJ, Retter A, Henderson K, Wilson S, Sharpe CC, Shattock MJ. Haemoglobin oxygen affinity in patients with severe COVID-19 infection. Br J Haematol. 2020 Aug;190(3):e126-e127.
34. Tahseen R, Parvez M, Kumar GS, Jahan P. A correlational study on neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in bronchial asthma. Advanc Human Biol. 2023;13(1):68-72.
35. Parihar V, Sengar GS, Beniwal M. To evaluate role of Neutrophil to lymphocyte ratio and Platelet to Lymphocyte ratio as diagnostic marker in children with acute exacerbation of bronchial asthma. Authorea Preprints. 2023.
36. Asseri AA. Distinguishing Childhood Asthma Exacerbations from Stable Asthma: The Utility of Inflammatory White Blood Cell Biomarkers. Diagnostics. 2024;14(15):1663.
37. Kubala S, Haque TT. Mast cells in allergic diseases. Front Media SA; 2023. p. 1248954.
38. Palacionyte J, Januskevicius A, Vasyle E, Rimkunas A, Bajoriuniene I, Vitkauskiene A, et al. Novel Serum Biomarkers for Patients with Allergic Asthma Phenotype. Biomedicines. 2024;12(1):232.
39. Osei-Bimpong A, Meek J, Lewis S. ESR or CRP? A comparison of their clinical utility. Hematology. 2007;12(4):353-7.
40. Girdhar A, Kumar V, Singh A, Menon B, Vijayan V. Systemic inflammation and its response to treatment in patients with asthma. Resp care. 2011;56(6):800-5.
2. Sato S, Saito J, Sato Y, Ishii T, Xintao W, Tanino Y, et al. Clinical usefulness of fractional exhaled nitric oxide for diagnosing prolonged cough. Respir Med. 2008;102(10):1452-9.
3. Nakajima T, Nagano T, Nishiuma T, Nakata K, Nishimura Y. Usefulness Analysis of Fraction of Exhaled Nitric Oxide for the Differential Diagnosis of Acute Cough. In vivo (Athens, Greece). 2022;36(1):446-9.
4. Bai H, Shi C, Yu S, Wen S, Sha B, Xu X, et al. A comparative study on the value of lower airway exhaled nitric oxide combined with small airway parameters for diagnosing cough-variant asthma. Ther Adv Respir Dis. 2023;17:17534666231181259.
5. Escamilla-Gil JM, Fernandez-Nieto M, Acevedo N. Understanding the cellular sources of the fractional exhaled nitric oxide (FeNO) and its role as a biomarker of type 2 inflammation in asthma. BioMed Res Int. 2022;2022(1):5753524.
6. Badar A, Salem AM, Bamosa AO, Qutub HO, Gupta RK, Siddiqui IA. Association between FeNO, total blood IgE, peripheral blood eosinophil and inflammatory cytokines in partly controlled asthma. J Asthma Allergy. 2020:533-43.
7. Nakwan N, Ruklerd T, Perkleang T, Taptawee P. The levels and correlations of FeNO, blood eosinophils and lung function in well-controlled asthma. Advanc Resp Med. 2022;90(3):183-92.
8. Sen P, Khatri SB, Tejwani V. Measuring exhaled nitric oxide when diagnosing and managing asthma. Cleve Clin J Med. 2023;90(6):363-70.
9. Canãz M, Erdenen F, Uzun H, Mũderrisoglu C, Aydin S. The relationship of inflammatory cytokines with asthma and obesity. Clin Invest Med. 2008;31(6):E373-E9.
10. Kuna M, Štefanović M, Ladika Davidović B, Mandušić N, Birkić Belanović I, Lugović-Mihić L. Chronic Urticaria Biomarkers IL-6, ESR and CRP in Correlation with Disease Severity and Patient Quality of Life—A Pilot Study. Biomedicines. 2023;11(8):2232.
11. Hoshino M, Ohtawa J, Akitsu K. Increased C-reactive protein is associated with airway wall thickness in steroid-naive asthma. Annals Allergy Asthma Immunol. 2014;113(1):37-41.
12. Jousilahti P, Salomaa V, Hakala K, Rasi V, Vahtera E, Palosuo T. The association of sensitive systemic inflammation markers with bronchial asthma. Annals Allergy Asthma Immunol. 2002;89(4):381-5.
13. Kumar A, Jat KR, Sankar J, Lakshmy R, Lodha R, Kabra S. Role of high-sensitivity C-reactive protein (hs-CRP) in assessment of asthma control in children. J Asthma. 2023;60(7):1466-73.
14. Ko AR, Kim YH, Sol IS, Kim MJ, Yoon SH, Kim KW, Kim KE. High-Sensitivity C-Reactive Protein Can Reflect Small Airway Obstruction in Childhood Asthma. Yonsei Med J. 2016 May;57(3):690-7.
15. Ali KM, Jamal N, Smail SW, Lauran M, Bystrom J, Janson C, et al. Biomarkers of type 2 and non-type 2 inflammation in asthma exacerbations: Biomarkers of inflammation in Asthma. Central Europ J Immunol. 2024;49(2):1-11.
16. Guida G, Bertolini F, Carriero V, Levra S, Sprio AE, Sciolla M, et al. Reliability of Total Serum IgE Levels to Define Type 2 High and Low Asthma Phenotypes. J Clin Med. 2023;12(17):5447.
17. Mukae H, Kaneko T, Obase Y, Shinkai M, Katsunuma T, Takeyama K, et al. The Japanese respiratory society guidelines for the management of cough and sputum (digest edition). Resp Invest. 2021;59(3):270-90.
18. Smith AD, Cowan JO, Brassett KP, Filsell S, McLachlan C, Monti-Sheehan G, et al. Exhaled nitric oxide: a predictor of steroid response. Am J Respir Crit Care Med. 2005;172(4):453-9.
19. Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011;184(5):602-15.
20. Malinovschi A, Fonseca JA, Jacinto T, Alving K, Janson C. Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects. J Allergy Clin Immunol. 2013;132(4):821-7.e1-5.
21. Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111(12):1805-12.
22. Jousilahti P, Salomaa V, Hakala K, Rasi V, Vahtera E, Palosuo T. The association of sensitive systemic inflammation markers with bronchial asthma. Ann Allergy Asthma Immunol. 2002;89(4):381-5.
23. Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med. 2007;175(7):661-6.
24. Shore SA, Fredberg JJ. Obesity, smooth muscle, and airway hyperresponsiveness. J Allergy Clin Immunol. 2005;115(5):925-7.
25. Peters U, Dixon AE, Forno E. Obesity and asthma. J Allergy Clin Immunol. 2018;141(4):1169-79.
26. Kang M, Sohn SJ, Shin MH. Association between Body Mass Index and Prevalence of Asthma in Korean Adults. Chonnam Med J. 2020;56(1):62-7.
27. Hjellvik V, Tverdal A, Furu K. Body mass index as predictor for asthma: a cohort study of 118,723 males and females. Eur Respir J. 2010;35(6):1235-42.
28. Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N, Enander I, et al. Eosinophilic inflammation in asthma. N Engl J Med. 1990;323(15):1033-9.
29. Kanannejad Z, Alyasin S, Esmaeilzadeh H, Nabavizadeh H, Amin R. Asthma and COVID-19 pandemic: focus on the eosinophil count and ACE2 expression. Eur Ann Allergy Clin Immunol. 2022;54(6):284-9.
30. Jatakanon A, Lim S, Kharitonov SA, Chung KF, Barnes PJ. Correlation between exhaled nitric oxide, sputum eosinophils, and methacholine responsiveness in patients with mild asthma. Thorax. 1998;53(2):91-5.
31. Aslan ES, Aydın H, Tekin YK, Keleş S, White KN, Hekim N. Association between iron metabolism and SARS-COV-2 infection, determined by ferritin, hephaestin and hypoxia-induced factor-1 alpha levels in COVID-19 patients. Mol Biol Rep. 2023;50(3):2471-8.
32. Beri D, Singh M, Rodriguez M, Barbu-Stevanovic M, Rasquinha G, Mendelson A, et al. Elucidating parasite and host-cell factors enabling Babesia infection in sickle red cells under hypoxic/hyperoxic conditions. Blood Advances. 2023;7(4):649-63.
33. Daniel Y, Hunt BJ, Retter A, Henderson K, Wilson S, Sharpe CC, Shattock MJ. Haemoglobin oxygen affinity in patients with severe COVID-19 infection. Br J Haematol. 2020 Aug;190(3):e126-e127.
34. Tahseen R, Parvez M, Kumar GS, Jahan P. A correlational study on neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in bronchial asthma. Advanc Human Biol. 2023;13(1):68-72.
35. Parihar V, Sengar GS, Beniwal M. To evaluate role of Neutrophil to lymphocyte ratio and Platelet to Lymphocyte ratio as diagnostic marker in children with acute exacerbation of bronchial asthma. Authorea Preprints. 2023.
36. Asseri AA. Distinguishing Childhood Asthma Exacerbations from Stable Asthma: The Utility of Inflammatory White Blood Cell Biomarkers. Diagnostics. 2024;14(15):1663.
37. Kubala S, Haque TT. Mast cells in allergic diseases. Front Media SA; 2023. p. 1248954.
38. Palacionyte J, Januskevicius A, Vasyle E, Rimkunas A, Bajoriuniene I, Vitkauskiene A, et al. Novel Serum Biomarkers for Patients with Allergic Asthma Phenotype. Biomedicines. 2024;12(1):232.
39. Osei-Bimpong A, Meek J, Lewis S. ESR or CRP? A comparison of their clinical utility. Hematology. 2007;12(4):353-7.
40. Girdhar A, Kumar V, Singh A, Menon B, Vijayan V. Systemic inflammation and its response to treatment in patients with asthma. Resp care. 2011;56(6):800-5.
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| Asthma exacerbation Biomarkers FeNO test Non-chronic coughs Pediatrics Respiratory tract infection | ||
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How to Cite
1.
Alyasin S, Kanannejad Z, Nabavizadeh SH, Esmaeilzadeh H, Sadeghi E, Shojaadini H, Akbarzadeh A, Ayareh N, Johari L. the Role of Fractional Exhaled Nitric Oxide (FeNO) and Inflammatory Biomarkers in Diagnosing Non-Chronic Cough in Pediatric Patients: A Cross-Sectional Study. Iran J Allergy Asthma Immunol. 2025;:1-10.
