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Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Is Elevated in Patients with Asthma and Airway Obstruction

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Summary

Neutrophilic airway inflammation is one of the features of severe asthma. Neutrophil gelatinase-associated lipocalin (NGAL), or lipocalin-2, is a glycoprotein associated with neutrophilic inflammation and can be detected in blood. Recently, blood NGAL levels have been reported to be elevated in chronic obstructive pulmonary disease. However, the clinical significance of serum NGAL levels in patients with asthma has not been elucidated. The aim of this study was to explore the association between serum NGAL level and clinical parameters in patients with asthma. Sixty-one non-smoking people with stable asthma were enrolled in this study. All patients underwent blood collection and pulmonary function tests. The associations between serum NGAL levels and clinical parameters were analyzed retrospectively. Serum NGAL levels in patients with asthma and obstructive ventilatory defect were higher than those in patients with asthma without obstructive ventilatory defect (76.4±51.4 ng/mL vs. 39.3±27.4 ng/mL, P=0.0019). Serum NGAL levels were correlated with forced expired flow at 50% of vital capacity %predicted and forced expired flow at 75% of vital capacity %predicted (r=−0.3373, P=0.0078 and r=−0.2900, P=0.0234, respectively). Results of a multiple regression analysis demonstrated that serum NGAL level was independently associated with obstructive ventilatory defect. Serum NGAL levels were elevated in patients with asthma and obstructive ventilatory defect. NGAL may be involved in airway remodeling possibly mediated by neutrophilic inflammation in asthma.

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References

  1. Murdoch JR, Lloyd CM. Chronic inflammation and asthma. Mutat Res, 2010,690(1–2):24–39

    Article  CAS  Google Scholar 

  2. Hammad H, Lambrecht BN. Barrier Epithelial Cells and the Control of Type 2 Immunity. Immunity, 2015,43(1): 29–40

    Article  CAS  Google Scholar 

  3. Bel EH. Clinical phenotypes of asthma. Curr Opin Pulm Med, 2004,10(1):44–50

    Article  Google Scholar 

  4. Simpson JL, Scott R, Boyle MJ, et al. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology, 2006,11(1):54–61

    Article  Google Scholar 

  5. Ricklefs I, Barkas I, Duvall MG, et al. ALX receptor ligands define a biochemical endotype for severe asthma. JCI Insight, 2017,2(14):e93534

    Article  Google Scholar 

  6. Shaw DE, Berry MA, Hargadon B, et al. Association between neutrophilic airway inflammation and airflow limitation in adults with asthma. Chest, 2007,132(6): 1871–1875

    Article  CAS  Google Scholar 

  7. Ordonez CL, Shaughnessy TE, Matthay MA, et al. Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance. Am J Respir Crit Care Med, 2000,161(4 Pt 1):1185–1890

    Article  CAS  Google Scholar 

  8. Berry M, Morgan A, Shaw DE, et al. Pathological features and inhaled corticosteroid response of eosinophilic and non-eosinophilic asthma. Thorax, 2007,62(12):1043–1049

    Article  Google Scholar 

  9. Ray A, Kolls JK. Neutrophilic Inflammation in Asthma and Association with Disease Severity. Trends Immunol, 2017,38(12):942–954

    Article  CAS  Google Scholar 

  10. Alam R, Good J, Rollins D, et al. Airway and serum biochemical correlates of refractory neutrophilic asthma. J Allergy Clin Immunol, 2017,140(4):1004–1014

    Article  CAS  Google Scholar 

  11. Ekberg-Jansson A, Andersson B, Bake B, et al. Neutrophil-associated activation markers in healthy smokers relates to a fall in DL(CO) and to emphysematous changes on high resolution CT. Respir Med, 2001,95(5):363–373

    Article  CAS  Google Scholar 

  12. Goetz DH, Holmes MA, Borregaard N, et al. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell, 2002,10(5):1033–1043

    Article  CAS  Google Scholar 

  13. Cockayne DA, Cheng DT, Waschki B, et al. Systemic biomarkers of neutrophilic inflammation, tissue injury and repair in COPD patients with differing levels of disease severity. PLoS One, 2012,7(6):e38629

    Article  CAS  Google Scholar 

  14. Otto GP, Hurtado-Oliveros J, Chung HY, et al. Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach. PLoS One, 2015,10(4):e0124429

    Article  Google Scholar 

  15. Ohlsson S, Wieslander J, Segelmark M. Increased circulating levels of proteinase 3 in patients with anti-neutrophilic cytoplasmic autoantibodies-associated systemic vasculitis in remission. Clin Exp Immunol, 2003,131(3):528–535

    Article  CAS  Google Scholar 

  16. Eagan TM, Damas JK, Ueland T, et al. Neutrophil gelatinase-associated lipocalin: a biomarker in COPD. Chest, 2010,138(4):888–895

    Article  Google Scholar 

  17. Asthma GIf. Global Strategy For Asthma Management And Prevention 2019

  18. Bolignano D, Lacquaniti A, Coppolino G, et al. Neutrophil Gelatinase-Associated Lipocalin as an Early Biomarker of Nephropathy in Diabetic Patients. Kidney Blood Press Res, 2009,32(2): 91–98

    Article  CAS  Google Scholar 

  19. Bchir S, Nasr HB, Bouchet S, et al. Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease. J Cell Mol Med, 2017, 21(7):1280–1291

    Article  CAS  Google Scholar 

  20. Kiljander T, Helin T, Venho K, et al. Prevalence of asthma-COPD overlap syndrome among primary care asthmatics with a smoking history: a cross-sectional study. NPJ Prim Care Respir Med, 2015,25:15047

    Article  Google Scholar 

  21. Sin DD, Miravitlles M, Mannino DM, et al. What is asthma-COPD overlap syndrome? Towards a consensus definition from a round table discussion. Eur Respir J, 2016,48(3):664–673

    Article  Google Scholar 

  22. Papaiwannou A, Zarogoulidis P, Porpodis K, et al. Asthma-chronic obstructive pulmonary disease overlap syndrome (ACOS): current literature review. J Thorac Dis, 2014,6Suppl 1:S146–151

    PubMed  PubMed Central  Google Scholar 

  23. Wang J, Lv H, Luo Z, et al. Plasma YKL-40 and NGAL are useful in distinguishing ACO from asthma and COPD. Respir Res, 2018,19(1):47

    Article  Google Scholar 

  24. Menezes AMB, Montes de Oca M, Perez-Padilla R, et al. Increased risk of exacerbation and hospitalization in subjects with an overlap phenotype: COPD-asthma. Chest, 2014,145(2):297–304

    Article  Google Scholar 

  25. Hardin M, Cho M, McDonald ML, et al. The clinical and genetic features of COPD-asthma overlap syndrome. Eur Respir J, 2014,44(2):341–350

    Article  CAS  Google Scholar 

  26. Owen-Woods C, Joulia R, Barkaway A, et al. Local Microvascular Leakage Promotes Trafficking of Activated Neutrophils to Remote Organs. J Clin Invest, 2020,130(5):2301–2318

    Article  CAS  Google Scholar 

  27. Hirota N, Martin JG. Mechanisms of airway remodeling. Chest, 2013,144(3):1026–1032

    Article  Google Scholar 

  28. Nauseef WM, Borregaard N. Neutrophils at work. Nat Immunol, 2014,15(7):602–611

    Article  CAS  Google Scholar 

  29. Wang Y, Jia M, Yan X, et al. Increased neutrophil gelatinase-associated lipocalin (NGAL) promotes airway remodelling in chronic obstructive pulmonary disease. Clin Sci (Lond), 2017,131(11):1147–1159

    Article  CAS  Google Scholar 

  30. Garay-Rojas E, Harper M, Hraba-Renevey S, et al. An apparent autocrine mechanism amplifies the dexamethasone-and retinoic acid-induced expression of mouse lipocalin-encoding gene 24p3. Gene, 1996, 170(2):173–180

    Article  CAS  Google Scholar 

  31. Kuwabara T, Mori K, Mukoyama M, et al. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons. Kidney Int, 2009,75(3):285–294

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Respiratory Medicine, Tokyo Medical University, Tokyo, 160-0023, Japan

    Junichiro Kawagoe, Yuta Kono, Yuki Togashi, Mayuko Ishiwari, Kazutoshi Toriyama, Chika Yajima, Hideaki Nakayama & Shinji Abe

  2. Department of Respiratory Medicine, Toranomon Hospital, Tokyo, 105-8470, Japan

    Satoshi Kasagi

  3. Department of Respiratory Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan

    Yasuhiro Setoguchi

Authors
  1. Junichiro Kawagoe
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  2. Yuta Kono
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  3. Yuki Togashi
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  4. Mayuko Ishiwari
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  5. Kazutoshi Toriyama
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  6. Chika Yajima
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  7. Hideaki Nakayama
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  8. Satoshi Kasagi
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  9. Shinji Abe
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  10. Yasuhiro Setoguchi
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Correspondence to Yuta Kono.

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The authors declare that they have no conflict of interest.

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Kawagoe, J., Kono, Y., Togashi, Y. et al. Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) Is Elevated in Patients with Asthma and Airway Obstruction. CURR MED SCI 41, 323–328 (2021). https://doi.org/10.1007/s11596-021-2350-1

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  • DOI: https://doi.org/10.1007/s11596-021-2350-1

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