|Year : 2019 | Volume
| Issue : 1 | Page : 194-197
Study of serum YKL-40 level in patients with chronic obstructive pulmonary disease
Nourane Y Azab1, Ahmed A Khames1, Maha Yousif1, Ibrahim S El Madbouh2, Doaa S Fouda3
1 Department of Chest, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Biochemistry, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Al Mehalla Chest Hospital, Al Mehalla, Egypt
|Date of Submission||18-Jan-2017|
|Date of Acceptance||11-Mar-2017|
|Date of Web Publication||17-Apr-2019|
Doaa S Fouda
Source of Support: None, Conflict of Interest: None
The aim of the paper was to investigate the relationship between serum YKL-40 levels and severity of chronic obstructive pulmonary disease (COPD).
COPD is a major health problem with increasing morbidity and mortality throughout the world. A newly recognized biomarker, YKL-40, is a chitin-binding glycoprotein, and its serum level is elevated in inflammatory diseases. However, it has not been thoroughly investigated in COPD.
Patients and methods
A total of 30 patients with stable COPD and 10 healthy individuals as a control group were enrolled for estimation of modified Medical Research Counseling dyspnea scale, spirometry, and serum YKL-40 levels.
Serum YKL-40 level was increased significantly in patients with COPD compared with healthy controls. There was a positive correlation between serum YKL-40 level and each of modified Medical Research Counseling dyspnea scale severity and age, and a negative correlation with forced expiratory volume in the first second percent of predicted.
High serum YKL-40 levels were correlated with severity of COPD.
Keywords: biomarker, chronic obstructive pulmonary disease, glycoprotein, inflammation, spirometry, stable, YKL-40
|How to cite this article:|
Azab NY, Khames AA, Yousif M, El Madbouh IS, Fouda DS. Study of serum YKL-40 level in patients with chronic obstructive pulmonary disease. Menoufia Med J 2019;32:194-7
|How to cite this URL:|
Azab NY, Khames AA, Yousif M, El Madbouh IS, Fouda DS. Study of serum YKL-40 level in patients with chronic obstructive pulmonary disease. Menoufia Med J [serial online] 2019 [cited 2019 Aug 23];32:194-7. Available from: http://www.mmj.eg.net/text.asp?2019/32/1/194/256140
| Introduction|| |
Chronic obstructive pulmonary disease (COPD) is a major health problem with increasing morbidity and mortality throughout the world . It is characterized by a specific pattern of inflammation and is considered a systemic disease that involves pathology in several extra-pulmonary tissues . The glycoprotein YKL-40 consists of 383 amino acids with a molecular mass of 40 kDa and increases in systemic inflammations but does not get enoughly investigated in COPD. The aim of this work is to investigate the relationship between serum YKL-40 levels and severity of COPD.
| Patients and Methods|| |
This study was carried out in Al Mehalla Chest Hospital and in Chest and Medical Biochemistry Departments, Faculty of Medicine, Menoufia University, including 30 patients with COPD and 10 apparently healthy age-matched and sex-matched volunteers as a control group from July 2015 to December 2015. An informed consent was taken from all participants. Inclusion criteria of the patients were as follows: stable patients with COPD with different grades of severity. Exclusion criteria of the patients were as follows: history of acute exacerbation, hospitalization or administration of systemic glucocorticoids, immune-suppressive agents or any anti-inflammatory drugs in the last month , patients with liver cirrhosis, chronic renal failure, collagen disease , cancer , infection , obstructive sleep apnea, neuromuscular disease, decompensated cardiac failure , or diabetes mellitus . Each individuals underwent; history taking, general and local chest examination, routine laboratory investigations, chest radiography, oxygen saturation by pulse oximetry (at rest), estimation of modified Medical Research Council (mMRC) dyspnea scale , pulmonary function tests , and serum YKL-40 measurement by enzyme-linked immunosorbent assay method . The study was approved by the Ethical Committee of Faculty of Medicine Menoufia University and the patient gave an informed consent.
Measurement of pulmonary functions
All participants underwent (CHEST M.I., INC, Tokyo, Japan) spirometric testing at Pulmonary Function Test Unit at Al Mehalla Chest Hospital using a turbine spirometer (Chestgraph HI-105; Germany) based on a forced vital capacity maneuver before and 10 min after inhalation of 200 μg of salbutamol through a metered dose inhaler in which the participants were requested to exhale the maximum volume of air starting from a position of full inspiration and ending at a complete expiration. Those with post-bronchodilator change in forced expiratory volume in first second (FEV1%) of predicted more than 12% were excluded from the study. Spirometric parameters compatible with air flow obstruction were as follows: reduced FEV1/forced vital capacity less than 70% and FEV1 less than 80% of the reference value . At the time of spirometry, mMRC scale was estimated .
Estimation of modified Medical Research Council dyspnea scale
Using the scale, we ask the patients to choose one of five statements to describe their breathlessness and they take a score from one to five as follow:
- Only get breathless with strenuous exercise
- Get short of breath when hurrying on the level or walking up a slight hill
- Walk slower than people of the same age on the level because of breathlessness or have to stop for breath, when walking at own place on the level
- Stop for breath after walking about 100 yards or after a few minutes on the level
- Too breathless to leave the house or breathless when dressing.
Estimation of oxygen saturation by pulse oximetry (at rest)
Arterial oxygen saturation was measured with pulse oximeter. The oximeter probe has two light-emitting diodes, one red and one infrared, located on one side of the probe. The probe was placed on the fingertip of the patients, and great care was taken to ensure that the test person's fingers were warm during the process. Measurements were performed when the patient was awake, had not exercised, and had been sitting for more than or equal to 10 min in the same position, and after an interval of more than or equal to 1.5 h since the last meal. It took 1–3 min for the measured value on the display to remain constant for more than 15 s .
Arterial blood gas analysis is more accurate; however, pulse oximetry is considered sufficiently accurate for most clinical purposes as it provides continuous, noninvasive monitoring of oxygen saturation of hemoglobin in arterial blood.
Measurement of serum YKL-40
Approximately 5 ml of venous blood sample was collected from each participant, let for 30 min to be coagulated, and then centrifuged for 10 min; the serum was taken and kept in refrigerator till analysis by enzyme-linked immunosorbent assay.
The correlations between the variables were examined by Pearson's and Spearman's correlation analyses. Continuous variables were determined as average ± SD, and categorical variables were determined as numbers and percentage. In the comparison of averages, Student's t-test and analysis of variance test were used for parametric variables, and the Mann–Whitney U-test and Kruskal–Wallis test were used for nonparametric variables. The value of P less than 0.05 was accepted as statistically significant .
| Results|| |
As shown in [Table 1], there was no significant statistical difference between patients with COPD and the controls regarding age, smoking, and pack-year index. SaO2 and FEV1% were highly significantly statistically lower in patients with COPD than the controls. Serum YKL-40 level was highly significantly statistically elevated in patients with COPD compared with the controls.
|Table 1: Demographic characteristics of patients with chronic obstructive pulmonary disease and the controls|
Click here to view
As shown in [Table 2], in contrast to the control group, there was a highly significant positive correlation between serum YKL-40 level in patients with COPD and their age.
As shown in [Table 3], there was a highly significant negative correlation between serum YKL-40 level in patients with COPD and their FEV1% of predicted, a negative but insignificant correlation between serum YKL-40 level in patients with COPD and their SaO2, and a significant positive correlation between serum YKL-40 level in patients with COPD and their mMRC dyspnea scale.
|Table 3: Correlation between serum YKL-40 level and forced expiratory volume in the first second of predicted, oxygen saturation, and modified Medical Research Council in patients group|
Click here to view
| Discussion|| |
Recent investigations studied the role of YKL-40 as a potential new marker in determining the severity and prognosis of many systemic diseases ,.
In the current study, serum YKL-40 level was significantly increased in patients with COPD (2242.03 ± 1844.8) than controls and was negatively correlated to their FEV1% of predicted [Table 1] and [Table 3]. Similarly, Aziz et al.  reported an inverse relationship between serum YKL-40 level and pulmonary function tests, and a negative correlation between FEV1% of predicted and YKL-40 level in patients with COPD. S'verine et al.  also reported significantly elevated levels of YKL-40 glycoprotein in the serum and bronchoalvelar lavage fluid and a greater number of YKL-40 expressing cells in bronchial biopsies of smokers with COPD, in relation to smokers without COPD and to never smoker healthy individuals. This may be because of the increased airway inflammation, alveolar destruction, and tissue remodeling occurring in patients with COPD.
In the current study, there was a highly significant positive correlation between serum YKL-40 level in patients with COPD and their age (P = 0.000233) but not in the controls [Table 2]. These results partially come in agreement with Aziz et al.  who reported that there was a significant positive correlation between the serum YKL-40 level and the age in both patients with COPD and controls. Johansen et al.  conducted a study of 8899 general population (not specific to patients with COPD) and demonstrated that serum YKL-40 level and age have a linear relationship. This result can be explained on the basis that YKL-40 is a glycoprotein that increases in systemic inflammation and tissue remodeling . By increasing age, many systems show different forms of inflammation and tissue remodeling leading to increased level of this glycoprotein.
In the current study, there was a highly significant difference regarding arterial oxygen saturation (SaO2) between patients with COPD (89.47 ± 2.81%) and controls (98 ± 1.17%) [Table 1]. There was also a negative but nonsignificant correlation between SaO2 and the serum YKL-40 level in patients with COPD [Table 3]. This comes in agreement with Douglas et al.  who declared that the more severe the COPD, the more worse the hypoxia and hypercapnea and stated that arterial blood gas analysis is helpful for gauging the severity of an exacerbation as well as in identifying those patients currently in need of oxygen therapy and those potentially requiring mechanical ventillatory support. Aziz et al.  reported a negative correlation between serum level of YKL-40 and arterial oxygen saturation. Tissue hypoxia and hypoxia-related mediators can also cause systemic inflammation in COPD as confirmed by Kent et al..
This study reported that mMRC dyspnea scale showed a highly significant difference regarding patients with COPD (2.5 ± 0.94) and controls (1) [Table 1]. There was also a significant positive correlation between mMRC dyspnea scale and serum YKL-40 level in patients with COPD [Table 3] and [Figure 1].
|Figure 1: Correlation between serum YKL-40 level and modified Medical Research Council in patients' group.|
Click here to view
| Conclusion|| |
Serum YKL-40 level was significantly high in patients with COPD compared with controls. There was a significant positive correlation between the severity of COPD state and the serum level of YKL-40. There was a significant positive correlation between the mMRC dyspnea scale and the serum level of YKL-40. There was a linear relationship between the serum YKL-40 level and the age only in patients with COPD.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Anto JM, Vermeire P, Vestbo J, Sunnyer J. Epidemiology of chronic obstructive pulmonary disease. Eur Respir J 2001; 17
Agusti AG. Systemic effects of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005; 4
Shuhui L, Mok YK, Fred WS. Role of mammalian chitinases in asthma. Int Arch Allergy Immunol 2009; 149
Johansen JS. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull 2006; 53
Fusetti F, Pijning T, Kalk KH, Bos E, Dijkstra BW. Crystal structure and carbohydrate-binding properties of the human cartilage glycoprotein-39. J Biol Chem 2003; 278
Kronborg G, Østergaard C, Weis N, Nielsen H, Obel N, Pedersen SS, et al.
Serum level of YKL-40 is elevated in patients with Streptococcus pneumoniae
bacteremia and is associated with the outcome of the disease. Scand J Infect Dis 2002; 34
Zaky DSE, Mabrouk FM, Zaki ER, Hendy OM. The value of YKL-40 in ischemic heart disease patients. Egypt J Intern Med 2016; 28
Nøjgaard C, Høst NB, Christensen IJ, Poulsene SH, Egstrup K, Price PA, et al.
Serum levels of YKL-40 increases in patients with acute myocardial infarction. Coron Artery Dis 2008; 19
Rathcke CN, Persson F, Tarnow L, Rossing P, Vestergaard H. YKL-40, a marker of inflammation and endothelial dysfunction, is elevated in patients with type 1 diabetes and increases with levels of albuminuria. Diabetes Care 2009; 32
Bestall JC, Paul EA, Garrod R, Gernham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax 1999; 54
Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al
. Seris ATS/ERS Task Force: standardization of lung function testing. Eur Respir J 2005; 26
Ober C, Tan Z, Sun Y, Possick JD, Pan L, Nicolae R, et al.
Effect of variation in CHI3L1 on risk of asthma, and lung function. N Engl J Med 2008; 358
Pellegrino R, Viegi G, Brusasco V, Carpo RO, Burgos F, Casaburi R, et al.
Interpretative strategies for lung function tests. Eur Respir J 2005; 26
Tannheimer M, Thomas A, Gerngross H. Oxygen saturation course and altitude symptomatology during and expedition to broad peak (8047 m). Int J Sports Med 2002; 23
Kirkpatrick LA, Feeney BC. A simple guide to IBM SPSS statistics for version 20.0
. Student ed. Belmont, CA: Wadsworth, Cengage Learning; 2013.
Boot RG, van Achterberg TA, van Aken BE, Renkema GH, Jacobs MJ, Aerts JM, et al.
Strong induction of members of the chitinase family of proteins in atherosclerosis. Arterioscler Thromb Vasc Biol 1999; 19
Volk B, Johansen JS, Stoltenberg M, Garbarsch C, Price PA, Ostergaard M, et al.
Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Osteoarthritis Cartilage 2001; 9
Aziz G, Servet K, Halit C, Aynur K, Necati B, Asiye Y, et al.
High serum YKL-40 level in patients with COPD is related to hypoxemia and disease severity. Tohoku J Exp Med 2013; 229
S'verine L, Alexander K, Nassim A, Nassim A, Martine G, Jennifer R, et al.
YKL-40 is elevated with chronic obstructive pulmonary disease and activate alveolar macrophages. J Immunol 2008; 181
Johansen JS, Bojesen SE, Tybjaerg-Hansen A, Mylin AK, Price PA, Nordestgaard BG. Plasma YKL-40 and total and disease-specific mortality in the general population. Clin Chem 2010; 56
Douglas CM, Cynthia B, Sarah EG, Peter BB. Management of acute exacerbations of COPD: a summary and appraisal of published evidence. Chest 2001; 119
Kent BD, Mitchell PD, MeNicolas WT. Hypoxemia in patients with COPD: cases, effects, and disease progression. Int J Chron Obstruct Pulmon Dis 2011; 6
[Table 1], [Table 2], [Table 3]