Skip to main content
Top
Published in: Clinical and Translational Allergy 1/2019

Open Access 01-12-2019 | IgE Antibodies | Research

Characterization of a subgroup of non-type 2 asthma with cow’s milk hypersensitivity in young subjects

Authors: N. Tsolakis, L. Nordvall, C. Janson, N. Rydell, A. Malinovschi, K. Alving

Published in: Clinical and Translational Allergy | Issue 1/2019

Login to get access

Abstract

Background

Asthma with atopy is often characterized by type 2 inflammation but less progress has been made in defining non-type 2 asthma. We have previously identified a subgroup of young non-atopic asthmatics with perceived food hypersensitivity and poor asthma control.

Objective

Our aim was to further characterize this subgroup of non-type 2 asthmatics, including the use of a broad panel of inflammation-related proteins.

Methods

Sex- and age-matched subjects (10–35 years old) were divided into three groups with regard to history of asthma and atopy: non-atopic asthmatics with perceived cow’s milk hypersensitivity but with IgE antibodies < 0.35 kUA/L (NAA; n = 24), non-atopic controls with IgE < 0.35 kUA/L (NAC; n = 24), and atopic asthmatics with IgE ≥ 0.35 kUA/L (AA; n = 29). Serum or plasma were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP), a multiplex immunoassay comprising 92 inflammation-related proteins (Proseek Inflammation), and an ELISA for human neutrophil lipocalin (S-HNL). Fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, C-reactive protein (CRP), airway responsiveness to methacholine (PD20), and asthma-related quality of life (mAQLQ) were also measured.

Results

NAA had lower FeNO (p < 0.001) and B-Eos count (p < 0.001), but scored worse on mAQLQ (p = 0.045) compared with AA. NAA displayed higher levels of matrix metalloproteinase-1 (MMP-1) compared with both NAC (p = 0.011) and AA (p = 0.001), and lower PD20 compared with NAC (p < 0.001). In NAA, S-HNL correlated negatively with PD20 (rho = − 0.048, p < 0.05) and CRP correlated negatively with mAQLQ (rho = − 0.439, p < 0.05).

Conclusion

In a subgroup of non-atopic young asthmatics with perceived cow’s milk hypersensitivity we observed poor asthma-related quality of life, airway hyperresponsiveness, and clinically relevant non-type 2 inflammation. MMP-1 was elevated in this group, which deserves further studies.
Appendix
Available only for authorised users
Literature
1.
go back to reference Fricker M, Heaney LG, Upham JW. Can biomarkers help us hit targets in difficult-to-treat asthma? Respirology. 2017;22(3):430–42.CrossRefPubMed Fricker M, Heaney LG, Upham JW. Can biomarkers help us hit targets in difficult-to-treat asthma? Respirology. 2017;22(3):430–42.CrossRefPubMed
2.
go back to reference Malinovschi A, et al. Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity. J Allergy Clin Immunol. 2016;138(5):1301–8.CrossRefPubMed Malinovschi A, et al. Simultaneously increased fraction of exhaled nitric oxide levels and blood eosinophil counts relate to increased asthma morbidity. J Allergy Clin Immunol. 2016;138(5):1301–8.CrossRefPubMed
3.
go back to reference Malinovschi A, et al. 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.CrossRefPubMed Malinovschi A, et al. 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.CrossRefPubMed
4.
go back to reference Tsolakis N, et al. Absence of serum IgE antibodies indicates non-type 2 disease in young asthmatics. Clin Exp Allergy. 2018;48(6):722–30.CrossRefPubMed Tsolakis N, et al. Absence of serum IgE antibodies indicates non-type 2 disease in young asthmatics. Clin Exp Allergy. 2018;48(6):722–30.CrossRefPubMed
5.
go back to reference de Nijs SB, Venekamp LN, Bel EH. Adult-onset asthma: is it really different? Eur Respir Rev. 2013;22(127):44–52.CrossRefPubMed de Nijs SB, Venekamp LN, Bel EH. Adult-onset asthma: is it really different? Eur Respir Rev. 2013;22(127):44–52.CrossRefPubMed
6.
go back to reference Johnson J, et al. Perceived food hypersensitivity relates to poor asthma control and quality of life in young non-atopic asthmatics. PLoS ONE. 2015;10(4):e0124675.CrossRefPubMedPubMedCentral Johnson J, et al. Perceived food hypersensitivity relates to poor asthma control and quality of life in young non-atopic asthmatics. PLoS ONE. 2015;10(4):e0124675.CrossRefPubMedPubMedCentral
7.
8.
go back to reference Simpson JL, et al. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax. 2007;62(3):211–8.CrossRefPubMed Simpson JL, et al. Innate immune activation in neutrophilic asthma and bronchiectasis. Thorax. 2007;62(3):211–8.CrossRefPubMed
9.
go back to reference Patelis A, et al. Aeroallergen and food IgE sensitization and local and systemic inflammation in asthma. Allergy. 2014;69(3):380–7.CrossRefPubMed Patelis A, et al. Aeroallergen and food IgE sensitization and local and systemic inflammation in asthma. Allergy. 2014;69(3):380–7.CrossRefPubMed
10.
go back to reference Heijkenskjold-Rentzhog C, et al. Alveolar and exhaled NO in relation to asthma characteristics-effects of correction for axial diffusion. Allergy. 2014;69(8):1102–11.CrossRefPubMed Heijkenskjold-Rentzhog C, et al. Alveolar and exhaled NO in relation to asthma characteristics-effects of correction for axial diffusion. Allergy. 2014;69(8):1102–11.CrossRefPubMed
11.
go back to reference Vidal C, et al. Evaluation of the phadiatop test in the diagnosis of allergic sensitization in a general adult population. J Investig Allergol Clin Immunol. 2005;15(2):124–30.PubMed Vidal C, et al. Evaluation of the phadiatop test in the diagnosis of allergic sensitization in a general adult population. J Investig Allergol Clin Immunol. 2005;15(2):124–30.PubMed
12.
go back to reference Assarsson E, et al. Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS ONE. 2014;9(4):e95192.CrossRefPubMedPubMedCentral Assarsson E, et al. Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS ONE. 2014;9(4):e95192.CrossRefPubMedPubMedCentral
13.
go back to reference Nathan RA, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113(1):59–65.CrossRefPubMed Nathan RA, et al. Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004;113(1):59–65.CrossRefPubMed
14.
go back to reference Juniper EF, et al. Development and validation of the mini asthma quality of life questionnaire. Eur Respir J. 1999;14(1):32–8.CrossRefPubMed Juniper EF, et al. Development and validation of the mini asthma quality of life questionnaire. Eur Respir J. 1999;14(1):32–8.CrossRefPubMed
15.
go back to reference Siroux V, et al. Quality-of-life and asthma-severity in general population asthmatics: results of the ECRHS II study. Allergy. 2008;63(5):547–54.CrossRefPubMed Siroux V, et al. Quality-of-life and asthma-severity in general population asthmatics: results of the ECRHS II study. Allergy. 2008;63(5):547–54.CrossRefPubMed
16.
go back to reference American Thoracic S, European Respiratory S. 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. 2005;171(8):912–30.CrossRef American Thoracic S, European Respiratory S. 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. 2005;171(8):912–30.CrossRef
17.
go back to reference Standardization of spirometry, 1994 update. American Thoracic Society. Am J Respir Crit Care Med. 1995;152(3):1107–36. Standardization of spirometry, 1994 update. American Thoracic Society. Am J Respir Crit Care Med. 1995;152(3):1107–36.
18.
go back to reference Hedenstrom H, Malmberg P, Agarwal K. Reference values for lung function tests in females. Regression equations with smoking variables. Bull Eur Physiopathol Respir. 1985;21(6):551–7.PubMed Hedenstrom H, Malmberg P, Agarwal K. Reference values for lung function tests in females. Regression equations with smoking variables. Bull Eur Physiopathol Respir. 1985;21(6):551–7.PubMed
19.
go back to reference Hedenstrom H, Malmberg P, Fridriksson HV. Reference values for lung function tests in men: regression equations with smoking variables. Ups J Med Sci. 1986;91(3):299–310.CrossRefPubMed Hedenstrom H, Malmberg P, Fridriksson HV. Reference values for lung function tests in men: regression equations with smoking variables. Ups J Med Sci. 1986;91(3):299–310.CrossRefPubMed
20.
go back to reference Solymar L, et al. Nitrogen single breath test, flow-volume curves and spirometry in healthy children, 7–18 years of age. Eur J Respir Dis. 1980;61(5):275–86.PubMed Solymar L, et al. Nitrogen single breath test, flow-volume curves and spirometry in healthy children, 7–18 years of age. Eur J Respir Dis. 1980;61(5):275–86.PubMed
21.
go back to reference Schulze J, et al. Methacholine challenge–comparison of an ATS protocol to a new rapid single concentration technique. Respir Med. 2009;103(12):1898–903.CrossRefPubMed Schulze J, et al. Methacholine challenge–comparison of an ATS protocol to a new rapid single concentration technique. Respir Med. 2009;103(12):1898–903.CrossRefPubMed
22.
go back to reference Benjamini Y, Hochberg Y. Controlling the face discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Ser B. 1995;57(1):289–300. Benjamini Y, Hochberg Y. Controlling the face discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc Ser B. 1995;57(1):289–300.
23.
go back to reference Fjaertoft G, et al. Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: a study of the kinetics. Acta Paediatr. 2005;94(6):661–6.CrossRefPubMed Fjaertoft G, et al. Human neutrophil lipocalin (HNL) as a diagnostic tool in children with acute infections: a study of the kinetics. Acta Paediatr. 2005;94(6):661–6.CrossRefPubMed
24.
go back to reference Venge P, et al. Human neutrophil lipocalin as a superior diagnostic means to distinguish between acute bacterial and viral infections. Clin Vaccine Immunol. 2015;22(9):1025–32.CrossRefPubMedPubMedCentral Venge P, et al. Human neutrophil lipocalin as a superior diagnostic means to distinguish between acute bacterial and viral infections. Clin Vaccine Immunol. 2015;22(9):1025–32.CrossRefPubMedPubMedCentral
25.
go back to reference Akçali SD, Kurt B, Uçar F, Erdemir E, Alay E. Human neutrophil gelatinase-associated lipocalin: a new biomarker in asthma-COPD overlap syndrome. Eur Respir J. 2016;48(60):PA5014. Akçali SD, Kurt B, Uçar F, Erdemir E, Alay E. Human neutrophil gelatinase-associated lipocalin: a new biomarker in asthma-COPD overlap syndrome. Eur Respir J. 2016;48(60):PA5014.
26.
go back to reference Monadi M, et al. Serum C-reactive protein in asthma and its ability in predicting asthma control, a case-control study. Caspian J Intern Med. 2016;7(1):37–42.PubMedPubMedCentral Monadi M, et al. Serum C-reactive protein in asthma and its ability in predicting asthma control, a case-control study. Caspian J Intern Med. 2016;7(1):37–42.PubMedPubMedCentral
27.
go back to reference Olafsdottir IS, et al. C reactive protein levels are increased in non-allergic but not allergic asthma: a multicentre epidemiological study. Thorax. 2005;60(6):451–4.CrossRefPubMedPubMedCentral Olafsdottir IS, et al. C reactive protein levels are increased in non-allergic but not allergic asthma: a multicentre epidemiological study. Thorax. 2005;60(6):451–4.CrossRefPubMedPubMedCentral
28.
go back to reference Keatings VM, et al. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155(2):542–8.CrossRefPubMed Keatings VM, et al. Effects of inhaled and oral glucocorticoids on inflammatory indices in asthma and COPD. Am J Respir Crit Care Med. 1997;155(2):542–8.CrossRefPubMed
29.
go back to reference Yalcin AD, Bisgin A, Gorczynski RM. IL-8, IL-10, TGF-beta, and GCSF levels were increased in severe persistent allergic asthma patients with the anti-IgE treatment. Mediators Inflamm. 2012;2012:720976.CrossRefPubMedPubMedCentral Yalcin AD, Bisgin A, Gorczynski RM. IL-8, IL-10, TGF-beta, and GCSF levels were increased in severe persistent allergic asthma patients with the anti-IgE treatment. Mediators Inflamm. 2012;2012:720976.CrossRefPubMedPubMedCentral
30.
go back to reference Jatakanon A, et al. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1532–9.CrossRefPubMed Jatakanon A, et al. Neutrophilic inflammation in severe persistent asthma. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1532–9.CrossRefPubMed
31.
32.
go back to reference Zhang X, et al. Divergent effect of mometasone on human eosinophil and neutrophil apoptosis. Life Sci. 2002;71(13):1523–34.CrossRefPubMed Zhang X, et al. Divergent effect of mometasone on human eosinophil and neutrophil apoptosis. Life Sci. 2002;71(13):1523–34.CrossRefPubMed
34.
go back to reference Ingram JL, Kraft M. Metalloproteinases as modulators of allergic asthma: therapeutic perspectives. DovePress. 2015;2015(2):61–74. Ingram JL, Kraft M. Metalloproteinases as modulators of allergic asthma: therapeutic perspectives. DovePress. 2015;2015(2):61–74.
35.
go back to reference Reel B, et al. Diverse patterns of cyclooxygenase-independent metalloproteinase gene regulation in human monocytes. Br J Pharmacol. 2011;163(8):1679–90.CrossRefPubMedPubMedCentral Reel B, et al. Diverse patterns of cyclooxygenase-independent metalloproteinase gene regulation in human monocytes. Br J Pharmacol. 2011;163(8):1679–90.CrossRefPubMedPubMedCentral
36.
go back to reference Medina C, Radomski MW. Role of matrix metalloproteinases in intestinal inflammation. J Pharmacol Exp Ther. 2006;318(3):933–8.CrossRefPubMed Medina C, Radomski MW. Role of matrix metalloproteinases in intestinal inflammation. J Pharmacol Exp Ther. 2006;318(3):933–8.CrossRefPubMed
37.
go back to reference Berntson L, Hedlund-Treutiger I, Alving K. Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2016;34(5):941–5.PubMed Berntson L, Hedlund-Treutiger I, Alving K. Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2016;34(5):941–5.PubMed
38.
go back to reference Rogers NK, et al. Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1) activity and increase airway smooth muscle contraction in asthma. PLoS ONE. 2014;9(2):e90565.CrossRefPubMedPubMedCentral Rogers NK, et al. Extra-cellular matrix proteins induce matrix metalloproteinase-1 (MMP-1) activity and increase airway smooth muscle contraction in asthma. PLoS ONE. 2014;9(2):e90565.CrossRefPubMedPubMedCentral
39.
go back to reference Ohta Y, et al. Dual modulation of airway smooth muscle contraction by Th2 cytokines via matrix metalloproteinase-1 production. J Immunol. 2008;180(6):4191–9.CrossRefPubMed Ohta Y, et al. Dual modulation of airway smooth muscle contraction by Th2 cytokines via matrix metalloproteinase-1 production. J Immunol. 2008;180(6):4191–9.CrossRefPubMed
40.
go back to reference Naveed SU, et al. Matrix metalloproteinase-1 activation contributes to airway smooth muscle growth and asthma severity. Am J Respir Crit Care Med. 2017;195(8):1000–9.CrossRefPubMedPubMedCentral Naveed SU, et al. Matrix metalloproteinase-1 activation contributes to airway smooth muscle growth and asthma severity. Am J Respir Crit Care Med. 2017;195(8):1000–9.CrossRefPubMedPubMedCentral
41.
go back to reference Fulkerson PC, Chemokines REM (2006) CXC|CXCL9 (MIG). Encyclopedia of Respiratory Medicine, p 398/402. Fulkerson PC, Chemokines REM (2006) CXC|CXCL9 (MIG). Encyclopedia of Respiratory Medicine, p 398/402.
42.
go back to reference Xie M, et al. IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling. J Allergy Clin Immunol. 2015;135(2):386–94.CrossRefPubMed Xie M, et al. IL-27 and type 2 immunity in asthmatic patients: association with severity, CXCL9, and signal transducer and activator of transcription signaling. J Allergy Clin Immunol. 2015;135(2):386–94.CrossRefPubMed
43.
44.
go back to reference Alving K, Malinovschi A. Basic aspects of nitric oxide. Eur Respir. 2010;49:1–31. Alving K, Malinovschi A. Basic aspects of nitric oxide. Eur Respir. 2010;49:1–31.
45.
go back to reference Salazar J, et al. C-reactive protein: an in-depth look into structure, function, and regulation. Int Sch Res Notices. 2014;2014:653045.PubMedPubMedCentral Salazar J, et al. C-reactive protein: an in-depth look into structure, function, and regulation. Int Sch Res Notices. 2014;2014:653045.PubMedPubMedCentral
46.
go back to reference Rutz S, Wang X, Ouyang W. The IL-20 subfamily of cytokines-from host defence to tissue homeostasis. Nat Rev Immunol. 2014;14(12):783–95.CrossRefPubMed Rutz S, Wang X, Ouyang W. The IL-20 subfamily of cytokines-from host defence to tissue homeostasis. Nat Rev Immunol. 2014;14(12):783–95.CrossRefPubMed
47.
go back to reference Gong W, et al. Interleukin-20 promotes airway remodeling in asthma. Inflammation. 2014;37(6):2099–105.CrossRefPubMed Gong W, et al. Interleukin-20 promotes airway remodeling in asthma. Inflammation. 2014;37(6):2099–105.CrossRefPubMed
Metadata
Title
Characterization of a subgroup of non-type 2 asthma with cow’s milk hypersensitivity in young subjects
Authors
N. Tsolakis
L. Nordvall
C. Janson
N. Rydell
A. Malinovschi
K. Alving
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Clinical and Translational Allergy / Issue 1/2019
Electronic ISSN: 2045-7022
DOI
https://doi.org/10.1186/s13601-019-0250-2

Other articles of this Issue 1/2019

Clinical and Translational Allergy 1/2019 Go to the issue