Changes in serum periostin levels in uncontrolled asthma in children (DADO phase 2 study)
Main Article Content
Keywords
asthma, biomarkers, children, eosinophils, periostin
Abstract
Objective: Asthma is an inflammatory airway condition and the most common chronic disease in children. However, there is a lack of biological markers for asthma, especially in children. This study aimed to analyze the changes in periostin levels in children with uncontrolled asthma after 12 months of optimized management. The secondary objectives were to evaluate the changes in symptoms, exacerbations, and other biomarkers after 12 months of follow-up.
Methods: This was an observational, prospective study of children aged 5 to 14 with uncontrolled asthma who visited the Hospital Materno Infantil of Badajoz’s Allergy Unit between September 2015 and June 2016. At the first visit and after a 12-month follow-up, lung function, asthma control test (ACT/cACT), quality of life by PAQLQ (Paediatric Asthma Quality of Life Questionnaire), blood eosinophils, total and specific IgE, and serum periostin levels were assessed. Periostin levels were also analyzed in a control group.
Results: After the 12-month follow-up, the percentage of symptoms, the proportion of patients with FEV1 <80%, and the levels of blood eosinophils decreased, whereas ACT and PAQLQ increased. Children with uncontrolled asthma showed high serum periostin concentrations on their first visit (901.48 ng/ml), which decreased after 12 months (67.93 ng/ml) (p<0.001). In the control group, periostin levels were 56.12 ng/ml. The sensitivity and specificity of periostin were 77.8% and 54.8%, respectively, for the diagnosis of controlled and uncontrolled asthma.
Conclusion: Our study showed that periostin levels in children with uncontrolled asthma decreased with the correct treatment after asthma control.
References
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3 Chipps BE, Haselkorn T, Rosén K, Mink DR, Trzaskoma BL, Luskin AT. Asthma exacerbations and triggers in children in tenor: impact on quality of life. J Allergy Clin Immunol Pract. 2018;6(1):169–76.e2. 10.1016/j.jaip.2017.05.027
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5 Matsumoto H. Serum periostin: a novel biomarker for asthma management. Allergol Int. 2014;63(2):153–60. 10.2332/allergolint.13-RAI-0678
6 Takayama G, Arima K, Kanaji T, Toda S, Tanaka H, Shoji S, McKenzie AN, et al. Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol. 2006;118(1):98–104. 10.1016/j.jaci.2006.02.046
7 Anderson HM, Lemanske RF Jr, Arron JR, Holweg CTJ, Rajamanickam V, Gangnon RE, Gern JE, et al. Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development. J Allergy Clin Immunol. 2017;139(3):790–796. 10.1016/j.jaci.2016.05.033
8 Lopez-Guisa JM, Powers C, File D, Cochrane E, Jimenez N, Debley JS. Airway epithelial cells from asthmatic children differentially express pro-remodeling factors. J Allergy Clin Immunol. 2012;129(4):990–7.e6. 10.1016/j.jaci.2011.11.035
9 Song JS, You JS, Jeong SI, Yang S, Hwang IT, Im YG, Baek HS, et al. Serum periostin levels correlate with airway hyper-responsiveness to methacholine and mannitol in children with asthma. Allergy. 2015 Jun;70(6):674–81. 10.1111/all.12599
10 Inoue Y, Izuhara K, Ohta S, Ono J, Shimojo N. No increase in the serum periostin level is detected in elementary school-age children with allergic diseases. Allergol Int. 2015 Jul;64(3):289–90. 10.1016/j.alit.2015.04.001
11 Habernau MA, Del Pozo AV, Rodríguez VFF, Bobadilla GP. Role of Periostin in Uncontrolled Asthma in Children (DADO study). J Investig Allergol Clin Immunol. 2017; 27(5):291–98. 10.18176/jiaci.0144
12 Plaza V, Alobid I, Alvarez C, Blanco M, Ferreira J, García G, Gómez-Outes A, et al. Spanish Asthma Management Guidelines (GEMA) VERSION 5.1. Highlights and Controversies. Arch Bronconeumol. 2022 Feb 58(2):150–58. English, Spanish. 10.1016/j.arbres.2021.05.010
13 Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, et al. International ERS/ATS guidelines on defining, evaluating, and treating severe asthma. Eur Respir J. 2014 Feb;43(2):343–73. 10.1183/09031936.00202013. Epub 2013 Dec Erratum In: Eur Respir J. 2014 Apr;43(4):1216. Dosage error in article text. Erratum in: Eur Respir J. 2018 Jul 27;52(1): Erratum in: Eur Respir J. 2022 Jun 9;59(6): PMid: 24337046.
14 Dundas I, Chan EY, Bridge PD, McKenzie SA. Diagnostic accuracy of bronchodilator responsiveness in wheezy children. Thorax. 2005 Jan;60(1):13–6. 10.1136/thx.2004.029934. PMid: 15618576; PMCID: PMC1747153.
15 Pastorello EA. Skin test for diagnosis of IgE mediated allergy. Allergy 1993; 48:57–62. 10.1111/j.1398-9995.1993.tb04758.x
16 Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, et al. American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011 Sep 1;184(5):602–15. 10.1164/rccm.9120-11ST
17 Liu AH, Zeiger RS, Sorkness CA, Ostrom NK, Chipps BE, Rosa K, Watson ME, et al. The Childhood Asthma Control Test: retrospective determination and clinical validation of a cut point to identify children with poorly controlled asthma. J Allergy Clin Immunol. 2010 Aug;126(2):267–73, 273.e1. 10.1016/j.jaci.2010.05.031
18 Juniper EF, Guyatt GH, Feeny DH, Ferrie PJ, Griffith LE, Townsend M. Measuring quality of life in children with asthma. Qual Life Res. 1996 Feb;5(1):35–46. 10.1007/BF00435967
19 Ontsuka K, Kotobuki Y, Shiraishi H, Serada S, Ohta S, Tanemura A, Yang L, et al. Periostin, a matricellular protein, accelerates cutaneous wound repair by activating dermal fibroblasts. Exp Dermatol. 2012 May;21(5):331–36. 10.1111/j.1600-0625.2012.01454.x
20 Konradsen JR, Skantz E, Nordlund B, Lidegran M, James A, Ono J, Ohta S, et al. Predicting asthma morbidity in children using proposed markers of Th2-type inflammation. Pediatr Allergy Immunol. 2015 Dec;26(8):772–79. 10.1111/pai.12457
21 Inoue T, Akashi K, Watanabe M, Ikeda Y, Ashizuka S, Motoki T, Suzuki R, et al. Periostin as a biomarker for the diagnosis of pediatric asthma. Pediatr Allergy Immunol. 2016 Aug;27(5):521–26. 10.1111/pai.12575
22 Silkoff PE, Laviolette M, Singh D, FitzGerald JM, Kelsen S, Backer V, et al. ADEPT Investigators. Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study. Respir Res. 2016 Apr 23; 17:43. 10.1186/s12931-016-0360-5
23 Fleming L, Tsartsali L, Wilson N, Regamey N, Bush A. Sputum inflammatory phenotypes are not stable in children with asthma. Thorax. 2012 Aug;67(8):675–81. 10.1136/thoraxjnl-2011-201064
24 Nagasaki T, Matsumoto H, Izuhara K, KiHAC Respiratory Medicine Group. Utility of serum periostin in combination with exhaled nitric oxide in the management of asthma. Allergol Int. 2017 Jul;66(3):404–10. 10.1016/j.alit.2017.02.003
25 Heaney LG, Djukanovic R, Woodcock A, Walker S, Matthews JG, Pavord ID, Bradding P, et al. Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK). Thorax. 2016 Feb;71(2):187–89. 10.1136/thoraxjnl-2015-207326
26 Scichilone N, Crimi C, Benfante A, Battaglia S, Iemmolo M, Spatafora M, Crimi N. Higher serum levels of periostin and the risk of exacerbations in moderate asthmatics. Asthma Res Pract. 2016 Jan 4;2:1. 10.1186/s40733-015-0019-x
27 Kato G, Takahashi K, Izuhara K, Komiya K, Kimura S, Hayashi S. Markers that can Reflect Asthmatic Activity before and after Reduction of Inhaled Corticosteroids: A Pilot Study. Biomark Insights. 2013 Aug 4;8:97–105. 10.4137/BMI.S12537
28 Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Koth LL, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009 Sep 1;180(5):388–95. 10.1164/rccm.200903-0392OC. Epub 2009 May 29. Erratum In: Am J Respir Crit Care Med. 2009 Oct 15;180(8):796. PMid: 19483109; PMCID: PMC2742757.
29 Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, Bradding P, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007 Dec;62(12):1043–9. 10.1136/thx.2006.073429
30 Tajiri T, Matsumoto H, Gon Y, Ito R, Hashimoto S, Izuhara K, Suzukawa M, et al. Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma. Allergy. 2016 Oct;71(10):1472–79. 10.1111/all.12922
31 Yavuz ST, Bagci S, Bolat A, Akin O, Ganschow R. Association of serum periostin levels with clinical features in children with asthma. Pediatr Allergy Immunol. 2021 Jul;32(5):937–44. 10.1111/pai.13444
32 Choudhary S, Kumar P, Banerjee M, Singh K, Goyal JP. Relationship of Serum Periostin with Asthma Control in Children: Single Center Experience. Indian Pediatr. 2023 Oct 15;60(10):822–25. Epub 2023 May 30. PMid: 37260069. 10.1007/s13312-023-3012-0
2 Urrutia I, Aguirre U, Sunyer J, Plana E, Muniozguren N, Martínez-Moratalla J, et al. Estudio de Salud Respiratoria de la Comunidad Europea. Cambios en la prevalencia de asma en la población española del Estudio de Salud Respiratoria de la Comunidad Europea (ECRHS-II) [Changes in the prevalence of asthma in the Spanish cohort of the European Community Respiratory Health Survey (ECRHS-II)]. Arch Bronconeumol. 2007;43(8):425–30. Spanish. https://doi.org/10.1016/s1579-2129(07)60098-6. Erratum In: Arch Bronconeumol. 2007 Oct;43(10):589.
3 Chipps BE, Haselkorn T, Rosén K, Mink DR, Trzaskoma BL, Luskin AT. Asthma exacerbations and triggers in children in tenor: impact on quality of life. J Allergy Clin Immunol Pract. 2018;6(1):169–76.e2. 10.1016/j.jaip.2017.05.027
4 Sánchez-García S, Habernau Mena A, Quirce S. Biomarkers in inflammometry pediatric asthma: utility in daily clinical practice. Eur Clin Respir J. 2017;4(1):1356160. 10.1080/20018525.2017.1356160
5 Matsumoto H. Serum periostin: a novel biomarker for asthma management. Allergol Int. 2014;63(2):153–60. 10.2332/allergolint.13-RAI-0678
6 Takayama G, Arima K, Kanaji T, Toda S, Tanaka H, Shoji S, McKenzie AN, et al. Periostin: a novel component of subepithelial fibrosis of bronchial asthma downstream of IL-4 and IL-13 signals. J Allergy Clin Immunol. 2006;118(1):98–104. 10.1016/j.jaci.2006.02.046
7 Anderson HM, Lemanske RF Jr, Arron JR, Holweg CTJ, Rajamanickam V, Gangnon RE, Gern JE, et al. Relationships among aeroallergen sensitization, peripheral blood eosinophils, and periostin in pediatric asthma development. J Allergy Clin Immunol. 2017;139(3):790–796. 10.1016/j.jaci.2016.05.033
8 Lopez-Guisa JM, Powers C, File D, Cochrane E, Jimenez N, Debley JS. Airway epithelial cells from asthmatic children differentially express pro-remodeling factors. J Allergy Clin Immunol. 2012;129(4):990–7.e6. 10.1016/j.jaci.2011.11.035
9 Song JS, You JS, Jeong SI, Yang S, Hwang IT, Im YG, Baek HS, et al. Serum periostin levels correlate with airway hyper-responsiveness to methacholine and mannitol in children with asthma. Allergy. 2015 Jun;70(6):674–81. 10.1111/all.12599
10 Inoue Y, Izuhara K, Ohta S, Ono J, Shimojo N. No increase in the serum periostin level is detected in elementary school-age children with allergic diseases. Allergol Int. 2015 Jul;64(3):289–90. 10.1016/j.alit.2015.04.001
11 Habernau MA, Del Pozo AV, Rodríguez VFF, Bobadilla GP. Role of Periostin in Uncontrolled Asthma in Children (DADO study). J Investig Allergol Clin Immunol. 2017; 27(5):291–98. 10.18176/jiaci.0144
12 Plaza V, Alobid I, Alvarez C, Blanco M, Ferreira J, García G, Gómez-Outes A, et al. Spanish Asthma Management Guidelines (GEMA) VERSION 5.1. Highlights and Controversies. Arch Bronconeumol. 2022 Feb 58(2):150–58. English, Spanish. 10.1016/j.arbres.2021.05.010
13 Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, Adcock IM, et al. International ERS/ATS guidelines on defining, evaluating, and treating severe asthma. Eur Respir J. 2014 Feb;43(2):343–73. 10.1183/09031936.00202013. Epub 2013 Dec Erratum In: Eur Respir J. 2014 Apr;43(4):1216. Dosage error in article text. Erratum in: Eur Respir J. 2018 Jul 27;52(1): Erratum in: Eur Respir J. 2022 Jun 9;59(6): PMid: 24337046.
14 Dundas I, Chan EY, Bridge PD, McKenzie SA. Diagnostic accuracy of bronchodilator responsiveness in wheezy children. Thorax. 2005 Jan;60(1):13–6. 10.1136/thx.2004.029934. PMid: 15618576; PMCID: PMC1747153.
15 Pastorello EA. Skin test for diagnosis of IgE mediated allergy. Allergy 1993; 48:57–62. 10.1111/j.1398-9995.1993.tb04758.x
16 Dweik RA, Boggs PB, Erzurum SC, Irvin CG, Leigh MW, Lundberg JO, Olin AC, et al. American Thoracic Society Committee on Interpretation of Exhaled Nitric Oxide Levels (FENO) for Clinical Applications. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am J Respir Crit Care Med. 2011 Sep 1;184(5):602–15. 10.1164/rccm.9120-11ST
17 Liu AH, Zeiger RS, Sorkness CA, Ostrom NK, Chipps BE, Rosa K, Watson ME, et al. The Childhood Asthma Control Test: retrospective determination and clinical validation of a cut point to identify children with poorly controlled asthma. J Allergy Clin Immunol. 2010 Aug;126(2):267–73, 273.e1. 10.1016/j.jaci.2010.05.031
18 Juniper EF, Guyatt GH, Feeny DH, Ferrie PJ, Griffith LE, Townsend M. Measuring quality of life in children with asthma. Qual Life Res. 1996 Feb;5(1):35–46. 10.1007/BF00435967
19 Ontsuka K, Kotobuki Y, Shiraishi H, Serada S, Ohta S, Tanemura A, Yang L, et al. Periostin, a matricellular protein, accelerates cutaneous wound repair by activating dermal fibroblasts. Exp Dermatol. 2012 May;21(5):331–36. 10.1111/j.1600-0625.2012.01454.x
20 Konradsen JR, Skantz E, Nordlund B, Lidegran M, James A, Ono J, Ohta S, et al. Predicting asthma morbidity in children using proposed markers of Th2-type inflammation. Pediatr Allergy Immunol. 2015 Dec;26(8):772–79. 10.1111/pai.12457
21 Inoue T, Akashi K, Watanabe M, Ikeda Y, Ashizuka S, Motoki T, Suzuki R, et al. Periostin as a biomarker for the diagnosis of pediatric asthma. Pediatr Allergy Immunol. 2016 Aug;27(5):521–26. 10.1111/pai.12575
22 Silkoff PE, Laviolette M, Singh D, FitzGerald JM, Kelsen S, Backer V, et al. ADEPT Investigators. Longitudinal stability of asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) study. Respir Res. 2016 Apr 23; 17:43. 10.1186/s12931-016-0360-5
23 Fleming L, Tsartsali L, Wilson N, Regamey N, Bush A. Sputum inflammatory phenotypes are not stable in children with asthma. Thorax. 2012 Aug;67(8):675–81. 10.1136/thoraxjnl-2011-201064
24 Nagasaki T, Matsumoto H, Izuhara K, KiHAC Respiratory Medicine Group. Utility of serum periostin in combination with exhaled nitric oxide in the management of asthma. Allergol Int. 2017 Jul;66(3):404–10. 10.1016/j.alit.2017.02.003
25 Heaney LG, Djukanovic R, Woodcock A, Walker S, Matthews JG, Pavord ID, Bradding P, et al. Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK). Thorax. 2016 Feb;71(2):187–89. 10.1136/thoraxjnl-2015-207326
26 Scichilone N, Crimi C, Benfante A, Battaglia S, Iemmolo M, Spatafora M, Crimi N. Higher serum levels of periostin and the risk of exacerbations in moderate asthmatics. Asthma Res Pract. 2016 Jan 4;2:1. 10.1186/s40733-015-0019-x
27 Kato G, Takahashi K, Izuhara K, Komiya K, Kimura S, Hayashi S. Markers that can Reflect Asthmatic Activity before and after Reduction of Inhaled Corticosteroids: A Pilot Study. Biomark Insights. 2013 Aug 4;8:97–105. 10.4137/BMI.S12537
28 Woodruff PG, Modrek B, Choy DF, Jia G, Abbas AR, Ellwanger A, Koth LL, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med. 2009 Sep 1;180(5):388–95. 10.1164/rccm.200903-0392OC. Epub 2009 May 29. Erratum In: Am J Respir Crit Care Med. 2009 Oct 15;180(8):796. PMid: 19483109; PMCID: PMC2742757.
29 Berry M, Morgan A, Shaw DE, Parker D, Green R, Brightling C, Bradding P, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax. 2007 Dec;62(12):1043–9. 10.1136/thx.2006.073429
30 Tajiri T, Matsumoto H, Gon Y, Ito R, Hashimoto S, Izuhara K, Suzukawa M, et al. Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma. Allergy. 2016 Oct;71(10):1472–79. 10.1111/all.12922
31 Yavuz ST, Bagci S, Bolat A, Akin O, Ganschow R. Association of serum periostin levels with clinical features in children with asthma. Pediatr Allergy Immunol. 2021 Jul;32(5):937–44. 10.1111/pai.13444
32 Choudhary S, Kumar P, Banerjee M, Singh K, Goyal JP. Relationship of Serum Periostin with Asthma Control in Children: Single Center Experience. Indian Pediatr. 2023 Oct 15;60(10):822–25. Epub 2023 May 30. PMid: 37260069. 10.1007/s13312-023-3012-0
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Jan 1, 2025
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Habernau Mena, A., Gonzalo Garijo, M. A., Del Pozo Abejón, V., & Rodríguez Vidigal, F. F. (2025). Changes in serum periostin levels in uncontrolled asthma in children (DADO phase 2 study). Allergologia Et Immunopathologia, 53(1), 1-7. https://doi.org/10.15586/aei.v53i1.1134
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How to Cite
Habernau Mena, A., Gonzalo Garijo, M. A., Del Pozo Abejón, V., & Rodríguez Vidigal, F. F. (2025). Changes in serum periostin levels in uncontrolled asthma in children (DADO phase 2 study). Allergologia Et Immunopathologia, 53(1), 1-7. https://doi.org/10.15586/aei.v53i1.1134