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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 1  |  Page : 297-304

Surfactant protein D in chronic obstructive pulmonary disease and type 2 diabetes mellitus


1 Department of Medical Biochemistry, Menoufia University, Shebin El-Kom, Menoufia Governorate, Egypt
2 Department of Chest, Menoufia University, Shebin El-Kom, Menoufia Governorate, Egypt

Date of Submission17-Dec-2015
Date of Acceptance07-Mar-2016
Date of Web Publication25-Jul-2017

Correspondence Address:
Mai A.H. Abou Elenin
Department of Medical Biochemistry, Menoufia University, Shebin El-Kom, Menoufia Governorate, 32511
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_525_15

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  Abstract 


Objective
The objective of this study was to evaluate the role of serum surfactant protein D (SP-D) in chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM).
Background
SP-D plays a critical role in innate host defense of the lung. SP-D binds bacterial, fungal, and viral pathogens, enhancing their opsonization and their killing by alveolar macrophages. COPD may be considered as a novel risk factor for T2DM via multiple pathophysiological alterations such as inflammation, oxidative stress, administration of glucocorticoids, insulin resistance, and weight gain. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations, and worsened COPD outcomes.
Patients and methods
This study was carried out on 87 patients classified into the following groups: group I, which included 35 patients with COPD without diabetes mellitus; group II, which included 18 patients with COPD and T2DM; group III, which included 19 patients with T2DM without COPD; and group IV, which included 15 age-matched and sex-matched healthy individuals. All individuals were subjected to full history taking, clinical examination, estimation of BMI, forced expiratory volume in 1 s% (FEV1%) predicted, forced vital capacity% (FVC%) predicted, and FEV1/FVC and laboratory investigations including estimation of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and serum SP-D, which was carried out using the enzyme-linked immunosorbent assay technique.
Results
There was a significant statistical difference regarding serum SP-D between studied groups. The highest level of it was in group I than in group II, more lower in group IV, and the lowest level was in group III. There was a significant positive correlation between SP-D and each of age and smoking index, whereas there was a significant negative correlation between SP-D and each of BMI, FBG, HbA1c, FEV1% predicted, FVC% predicted, and FEV1/FVC in studied participants. Age, BMI, and FEV1% predicted are good predictors of SP-D in studied patient groups. Age and smoking index are risk factors for COPD in group I and for COPD and diabetes mellitus in group II, and they are not risk factors for T2DM (group III).
Conclusion
SP-D was significantly higher in COPD either alone or with T2DM, and it was significantly lower in isolated T2DM. Although SPD did not increase significantly with increasing COPD severity in COPD groups I and II, it correlated negatively with spirometric parameters in all studied participants. There was a positive correlation between SP-D and each of age and smoking index, whereas there was a negative correlation between SP-D and each of BMI, FBG, HbA1c, FEV1% predicted, FVC% predicted, and FEV1/FVC. Factors that predicted serum level of SP-D were age, BMI, and FEV1%. Age and smoking index were risk factors for COPD and they were not risk factors for T2DM.

Keywords: chronic obstructive pulmonary disease, surfactant protein D, type 2 diabetes mellitus


How to cite this article:
Ghanayem NM, Abou Elnour ES, El Wahsh RA, El-Shazlya RM, Abou Elenin MA. Surfactant protein D in chronic obstructive pulmonary disease and type 2 diabetes mellitus. Menoufia Med J 2017;30:297-304

How to cite this URL:
Ghanayem NM, Abou Elnour ES, El Wahsh RA, El-Shazlya RM, Abou Elenin MA. Surfactant protein D in chronic obstructive pulmonary disease and type 2 diabetes mellitus. Menoufia Med J [serial online] 2017 [cited 2019 Apr 18];30:297-304. Available from: http://www.mmj.eg.net/text.asp?2017/30/1/297/211516




  Introduction Top


Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to severity in individual patients [1]. Type 2 diabetes mellitus (T2DM) has become a global health problem [2].

This type, previously referred to as non-insulin-dependent diabetes mellitus (DM) or adult-onset DM, includes individuals who have insulin resistance and usually have relative (rather than absolute) insulin deficiency. Most patients with this type of diabetes are obese, and obesity itself causes some degree of insulin resistance [3]. Diabetic microvascular complications are the major causes of morbidity and premature mortality in T2DM [4].

COPD may be considered as a novel risk factor for T2DM via multiple pathophysiological alterations such as inflammation, oxidative stress, administration of glucocorticosteroids, insulin resistance, and weight gain. On the other hand, diabetes may act as an independent factor, negatively affecting pulmonary structure and function. Diabetes is associated with an increased risk of pulmonary infections, disease exacerbations, and worsened COPD outcomes [5].

Pulmonary surfactant is a complex mixture of lipids (~90%) and proteins (~10%) that constitutes the mobile liquid phase covering the large surface area of the alveolar epithelium. It maintains minimal surface tension within the lungs in order to avoid lung collapse during respiration. Four surfactant proteins (SPs) – SP-A, SP-B, SP-C, and SP-D – are intimately associated with surfactant lipids in the lung [6].

SP-D has an important protective role in the immune system against inhaled microorganisms and allergens. It has a role in protection against viral, bacterial, and fungal infections, as well as apoptotic cells [7]. SP-D, a lung-derived innate immune protein, may be an important effector molecule in the pathogenesis of COPD [8].

Deficiencies in proteins of the innate immune system such as SP-D have been found to be associated with alterations of glucose metabolism. These deficiencies run in parallel with inflammation and impaired insulin action [9].

The aim of this study is to evaluate the role of serum SP-D in COPD and T2DM.


  Patients and Methods Top


Patients

This study was carried on 87 patients; there were 30 women and 57 men with age ranging from 51 to 75 years. The patients were attendants of Chest Department and outpatient clinics of Menoufia University Hospitals during the period from April 2014 to January 2015. This study was approved by the ethics committee of Faculty of Medicine, Menoufia University.

They were classified into four groups:

Group I included 35 patients with COPD without DM – seven women and 28 men with a mean age of 62.6 ± 6.5 years; group II included 18 patients with COPD and T2DM – eight women and 10 men with a mean age of 61.2 ± 7.2 years; group III included 19 patients with T2DM without COPD – eight women and 11 men with a mean age of 59.2 ± 4.4 years; and group IV included 15 age-matched and sex-matched healthy individuals – seven women and eight men with a mean age of 59.3 ± 5.4 years.

Inclusion criteria for patients with T2DM were BMI less than 40 kg/m 2, and absence of infection within the previous month and any other systemic diseases.

Exclusion criteria for the studied patient groups were acute exacerbation of COPD in COPD patients, respiratory failure, any other pulmonary diseases, and systemic diseases other than COPD and T2DM.

Methods

All individuals were subjected to full history taking, clinical examination, estimation of BMI, forced expiratory volume in 1 s% (FEV1%) predicted, forced vital capacity% (FVC%) predicted and FEV1/FVC and laboratory investigations including estimation of fasting blood glucose (FBG), glycated hemoglobin (HbA1c), and serum SP-D, which was carried out using enzyme-linked immunosorbent assay technique.

Samples collection

Five milliliters of venous blood was taken from each fasting patient (12 h) and divided as follows: 3 ml was put in a plain tube, left to clot for 30 min at room temperature, and then subjected to centrifugation for 10 min at 4000 rpm and the serum obtained was put in plain vacutainer tubes and stored at −20°C until the time of assay of SP-D; 1 ml was put immediately in an EDTA tube for HbA1c; and the remaining 1 ml was transferred into a plain tube for immediate estimation of FBG.

Assay methods

  1. Blood glucose was determined using enzymatic colorimetric method, using Spinreact kit (Spain) [10].

    The principle is as follows: glucose is oxidized by glucose oxidase to glucoronic acid and hydrogen peroxide. The formed hydrogen peroxide is detected by a chromogenic oxygen acceptor, phenol aminophenazone, in the presence of peroxidase.
  2. HbA1c was determined using CROMA HbA1c [11] using kits supplied by Boditech Med Inc. (Chuncheon, Gangwondo, Republic of Korea).

    The principle is as follows: CROMA HbA1c is based on the fluorescence immunoassay technology, specifically the competition immune-detection method. Whole blood is added to the mixture of hemolysis buffer and detection buffer, which results in hemolysis of red blood cells. The mixture containing HbA1c from the hemolyzed red blood cells and fluorescence-labeled HbA1c peptides from detection buffer is loaded onto the sample well of the cartridge. HbA1c from the blood competes with fluorescence-labeled HbA1c peptides for binding sites on HbA1c antibodies fixed on the nitrocellulose matrix. As a result, the higher concentration of HbA1c produces a lower fluorescence signal from HbA1c peptides. The signal is interpreted and the result displayed on CHROMA Reader in units of percentage.
  3. Human serum SP-D was quantitatively measured according to the manufacturer's protocol using a sandwich enzyme immunoassay technique using the Quantikine kit for Human SP-D Immunoassay [12] (catalog number DSFPD0, USA & Canada; R&D Systems Inc., Minneapolis, MN, USA).


The principle is as follows: this assay uses the quantitative sandwich enzyme immunoassay technique. A monoclonal antibody specific for SP-D has been precoated onto a microplate. Standards and samples are pipetted into the wells and any SP-D present is bound by the immobilized antibody. After washing away any unbound substances, an enzyme-linked monoclonal antibody specific for SP-D is added to the wells. After a wash to remove any unbound antibody-enzyme reagent, a substrate solution is added to the wells and color develops in proportion to the amount of SP-D bound in the initial step. The color development is stopped and the intensity of the color is measured.

Statistical analysis

The data collected were tabulated and analyzed by statistical package for the social science statistical package, version 20 (Armonk, New York, USA) on IBM-compatible computer.


  Results Top


The results of the present study are represented in [Table 1],[Table 2],[Table 3],[Table 4],[Table 5],[Table 6],[Table 7],[Table 8],[Table 9] and [Figure 1] and [Figure 2].
Table 1 Sociodemographic characteristics and lung functions parameters of studied groups

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Table 2 Statistical comparison among studied groups regarding biochemical parameters

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Table 3 95% confidence interval for the mean of serum log surfactant protein D according to smoking status

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Table 4 Statistical comparison among grades of chronic obstructive pulmonary disease severity of groups I and II regarding surfactant protein D

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Table 5 Correlation coefficient between surfactant protein D serum levels and all parameters among studied groups

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Table 6 Univariate regression analysis to predict circulating surfactant protein D in patients groups

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Table 7 Multivariate regression analysis to predict risk factors of each studied group

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Table 8 Cutoff value of surfactant protein D (ng/ml) in diagnosis of chronic obstructive pulmonary disease patients from controls

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Table 9 Cutoff value of surfactant protein D (ng/ml) in diagnosis of patients with type 2 diabetes mellitus from controls

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Figure 1: Receiver operating characteristic (ROC) curve of surfactant protein D (SP-D) for diagnosis of chronic obstructive pulmonary disease (COPD) patients from controls.

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Figure 2: Receiver operating characteristic (ROC) curve of surfactant protein D (SP-D) for diagnosis of patients with type 2 diabetes mellitus (DM) from controls.

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The results showed no statistically significant difference between the four studied groups as regards age and sex distribution. There was a significant statistical difference between groups I and II, I and III, I and IV, and II and III regarding BMI and between groups I and III, I and IV, II and III, and II and IV regarding smoking. There was a significant statistical difference between studied groups regarding lung function parameters, whereas a nonsignificant statistical difference existed between group I and group II in all lung function parameters and between groups III and IV regarding FEV1% predicted and FEV1/FVC [Table 1].

There was a significant statistical difference between studied groups regarding SP-D, FBG, and HbA1c, whereas a nonsignificant statistical difference existed regarding FBG and HbA1c between groups I and IV and II and III [Table 2]. Serum SP-D level was significantly higher among smokers than among nonsmokers [Table 3].

SP-D increased nonsignificantly with increasing grade of severity of COPD in groups I and II [Table 4]. There was a significant positive correlation between SP-D and each of age and smoking index in studied participants, whereas there was a significant negative correlation between SP-D and each of BMI, FBG, HbA1c, FEV1% predicted, FVC% predicted, and FEV1/FVC in studied participants [Table 5].

The results showed that factors that predicted serum level of SPD were age, BMI, and FEV1% [Table 6]. Age and smoking index were risk factors for COPD in group I and for COPD and DM in group II and they were not risk factors for T2DM (group III) [Table 7].

The diagnostic accuracy of SP-D in the diagnosis of COPD patients from controls was 94%, with a sensitivity of 97.1%, specificity of 86.7%, positive predictive value of 94.4%, and negative predictive value of 92.9% at a cutoff point of 66.55 ng/ml [Table 8], whereas the diagnostic accuracy of SP-D in the diagnosis of patients with T2DM from controls was 69.7%, with a sensitivity of 77.8%, specificity of 60%, positive predictive value of 70%, and negative predictive value of 69.2% at a cutoff point of 48.85 ng/ml [Table 9].


  Discussion Top


SP-D is an important regulatory protein that may aid in controlling chronic inflammation, reducing oxidative radical formation, facilitating phagocytosis and agglutination, reducing cell death, and enhancing apoptotic and necrotic cell clearance [13].

SP-D is produced predominantly by type II pneumocytes; its expression is correlated with pulmonary function and is increased in stable COPD, with higher levels observed during acute exacerbation. Changes in SP-D level are associated with the improvement of COPD symptoms [14].

A reduced ability to sense and eradicate pathogens could thus cause frequent respiratory tract infections, reduced vital capacity, and chronic inflammation resulting in insulin resistance and T2DM [15].

This study assesses serum SP-D in COPD and T2DM.

In the present study, neither age nor sex was significantly different between patients and controls. This was in agreement with the studies of Makarevich et al. [16], Wang et al. [17], Jeon et al. [18], and Zahran et al. [19].

In the present study, there was a significant statistical difference between group I and controls regarding FEV1% predicted, FVC% predicted, and FEV1/FVC. These results were in agreement with those of Pride and Soriano [20] and Donaldson et al. [21], who found significantly lower values of FEV1 and FEV1% predicted in smokers with COPD than in controls.

In the present study, there was a significant statistical difference between group III and controls regarding FVC% predicted. This was in agreement with the study of Uz-Zaman et al. [22], Anandhalakshmi et al. [23], and Aparna [24], who found that FVC and FEV1 were significantly reduced in T2DM.

In the current study, there was a significant statistical difference between groups I and IV regarding SP-D. This was in agreement with the study of Lomas et al. [7] and Winkler et al. [25]. Alveolar damage in COPD causes leakage of SP-D from the pulmonary compartment into the systemic circulation, resulting in lowered broncoalveolar lavage fluid but higher serum SP-D levels [8].

In the current study, in group I and II there was a nonsignificant increase in serum SP-D level with an increase in the grade of severity of COPD. This was in agreement with the studies of Lomas et al. [7], Liu et al. [14], Winkler et al. [25], and Ozyurek et al. [26]. Liu et al. [14] stated that the serum SPD levels were not associated with COPD disease severity according to the GOLD guidelines.

In contrast to these findings, El-Deek et al. [27], Ju et al. [28], and Sin et al. [29] found that SP-D levels increased significantly and correlated with the degree of airway obstruction and grade of severity of COPD.

In the present study, serum SP-D level was significantly higher among smokers than among nonsmokers. This was in agreement with the study of Lomas et al. [7], Fernández-Real et al. [30], and also Winkler et al. [25], who stated that cigarette smoke is capable of disrupting SP-D's quaternary structure, which might play a role in an impaired immunological function and an increased translocation of SP-D from the lung into the circulation.

In the current study, there was a statistically significant difference between groups II and IV regarding FBG, HbA1c, and SP-D. This was in agreement with the study by Mishra et al. [31], who found a significant difference in FBG and HbA1c between controls and patients complaining of COPD and T2DM.

In the current study, there was a statistically significant difference between groups III and IV regarding FBG, HbA1c, and SP-D. This was in agreement with the studies of Pueyo et al. [32] and Fernández-Real et al. [30], who found that circulating SP-D concentrations were significantly decreased in T2DM when compared with nondiabetic individuals in both nonobese and obese individuals. There is a relationship between plasma insulinase activity and serum SP-D. SP-D is inactivated by neutrophil serine proteinases. Insulinase activity has been shown to be increased 14.5-fold in neutrophils from diabetic patients; a number of different peptides have been described to be degraded by insulinase, including insulin, insulin-like growth factor-I, and insulin-like growth factor-II. It is unknown whether SP-D could be cleaved by insulinase. In addition, some molecules with insulinase activity (protein disulfide isomerase) seem to control insulin degradation and the inflammatory process simultaneously [30].

In the present study, there was a significant positive correlation between SP-D and each of age and smoking index in studied participants, whereas there was a significant negative correlation between SP-D and each of BMI, FBG, HbA1c, FEV1% predicted, FVC% predicted, and FEV1/FVC in studied participants.

This was in agreement with the studies of Shakoori et al. [8] and Sorensen et al. [33], who found a significant positive correlation between SP-D and age. Ozyurek et al. [26], El-Deek et al. [27], and Sorensen et al. [33] found a significant positive correlation between SP-D and smoking index, whereas Shakoori et al. [8], Sorensen et al. [33], and Zhao et al. [34] found a significant negative correlation between SP-D and BMI. Fernández-Real et al. [30] and Pueyo et al. [32] found a significant negative correlation between SP-D and each of FBG and HbA1c, whereas Ozyurek et al. [26], Ju et al. [28], El-Deek et al. [27], and Sin et al. [29] found a significant negative correlation between SP-D and FEV1% predicted; in contrast to this, Liu et al. [14] found that the serum or sputum SP-D levels did not significantly correlate with pulmonary function FEV1% predicted and FEV1/FVC.

In the current study, we found that age and smoking index are risk factors for COPD. The link between aging and the pathogenesis of COPD is strongly supported by numerous studies such as the study by Karrasch et al. [35], who reported that during aging pulmonary function progressively deteriorates and pulmonary inflammation increases, accompanied by structural changes, which are described as senile emphysema.

Environmental gases, such as cigarette smoke or other pollutants, may accelerate the aging of lung or worsen aging-related events in lung by defective resolution of inflammation – for example, by reducing antiaging molecules, such as histone deacetylases, and this consequently induces accelerated progression of COPD [36].

In addition, Lindberg et al. [37] found a high cumulative incidence of COPD after 10 years of smoking. This emphasizes the importance of early smoking cessation in the reduction of incidence of COPD. In contrast to this, the study of Shakoori et al. [8] did not show significant correlations of smoking with either serum SP-D levels or risk of COPD.

In the present study, we found that age, smoking index, and BMI are not risk factors for DM. In contrast to this, Hu et al. [38] found in a cross-sectional study that age, obesity, total cholesterol, triglycerides, living in rural areas, and diabetes family history are all risk factors for prediabetes and diabetes. In addition, they were surprised to see that smoking appeared to be a protecting factor against diabetes.

In the present study, the diagnostic accuracy of SP-D in diagnosis of COPD patients from controls was 94%, with a sensitivity of 97.1% and a specificity of 86.7% at a cutoff point of 66.55 ng/ml. These results come in line with those of Sin et al. [29], Ozyurek et al. [26], and Moreno et al. [13].

Sin et al. [29] reported that elevated serum SP-D is a good marker of reduced lung function, worsening health status (especially dyspnea), and other poor outcomes in patients with lung disease. Thus, serum SP-D is a promising biomarker for tracking disease progression and predicting clinical outcomes in COPD.

In the present work, the diagnostic accuracy of SP-D in diagnosis of patients with T2DM from controls was 69.7%, with a sensitivity of 77.8% and a specificity of 60% at a cutoff point of 48.85 ng/ml, so the diagnostic accuracy of SP-D was higher in diagnosis of COPD than in T2DM. These results are in agreement with those of Fernández-Real et al. [30].





SP-D was significantly higher in COPD either alone or with T2DM, and it was significantly lower in isolated T2DM. SP-D increased nonsignificantly with increasing grade of severity of COPD. There was a significant positive correlation between SP-D and each of age and smoking index, whereas there was a significant negative correlation between SP-D and each of BMI, FBG, HbA1c, FEV1% predicted, FVC% predicted, and FEV1/FVC. Age and smoking index were risk factors for COPD, and they were not risk factors for T2DM. The diagnostic accuracy of SP-D was higher in diagnosis of COPD than in T2DM.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Mansour OF, Bakr RM, Rabab A, El Wahsh RA, Zanfal AM. Osteoporosis in patients with chronic obstructive pulmonary disease. Menoufia Med J 2015; 28:521–524.  Back to cited text no. 1
  [Full text]  
2.
Ghanayem NM, Khamis SS, El-Shafie MK, El-Ghobashi YA, El-Shazly RM, Habib MS. The potential association of heat shock protein 70-2+1267A/G gene polymorphism with nephropathy in type II diabetic patients. Menoufia Med J 2014; 27:589–593.  Back to cited text no. 2
    
3.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2011; 33:62–69.  Back to cited text no. 3
    
4.
Ghanayem NM, El-Shafie MK, Badr EA, Abou Elnour ES, Khamis SS, Abd El Gayed EM. Study of the heat shock protein 70-1 gene polymorphism and the risk of nephropathy in type II diabetic patients. Menoufia Med J 2014; 27:582–588.  Back to cited text no. 4
  [Full text]  
5.
Mirrakhimov A. Chronic obstructive pulmonary disease and glucose metabolism: a bitter sweet symphony. Cardiovasc Diabetol 2012; 11:1–26.  Back to cited text no. 5
    
6.
Kishore U, Greenhough T, Waters P, Shrive A, Ghai R, Kamran M, et al. Surfactant proteins SP-A and SP-D: structure, function and receptors. Mol Immunol 2006; 43:1293–1315.  Back to cited text no. 6
    
7.
Lomas D, Silverman E, Edwards L, Locantore N, Miller B. Serum surfactant protein D is steroid sensitive and associated with exacerbations of COPD. Eur Respir J 2009; 34:95–102.  Back to cited text no. 7
    
8.
Shakoori T, Sin D, Bokhari N, Ghafoor F, Shakoori A. SP-D polymorphisms and risk of COPD. Dis Markers 2012; 33:91–100.  Back to cited text no. 8
    
9.
Fernández-Real J, Pickup J. Innate immunity, insulin resistance and type 2 diabetes. Trends Endocrinol Metab 2008; 19:10–16.  Back to cited text no. 9
    
10.
Burtis E, Santos-Rosa M, Bienvenu J, Whicher J. Role of the clinical laboratory in diabetes mellitus. In: Bruit C; Ashwood E, editors. Tietz textbook of clinical chemistry. St Louis, MO: Mosby; 2006. pp. 837–903.  Back to cited text no. 10
    
11.
Brooks DE, Devine DV, Harris PC. A rapid, quantitative whole blood immunochromatographic platform for point-of-care testing. Clin Chem 1999; 45:1676–1678.  Back to cited text no. 11
    
12.
Matalon S, Shrestha K, Kirk M, Waldheuser S, McDonald B, Smith K, et al. Modification of surfactant protein D by reactive oxygen-nitrogen intermediates is accompanied by loss of aggregating activity in vitro and in vivo. FASEB J 2009; 23:1415–1430.  Back to cited text no. 12
    
13.
Moreno D, Garcia A, Lema D, de Sanctis J. Surfactant protein D in chronic obstructive pulmonary disease (COPD). Recent Pat Endocr Metab Immune Drug Discov 2014; 8:42–47.  Back to cited text no. 13
    
14.
Liu W, Ju C, Chen R, Liu Z. Role of serum and induced sputum surfactant protein D in predicting the response to treatment in chronic obstructive pulmonary disease. Exp Ther Med 2014; 8:1313–1317.  Back to cited text no. 14
    
15.
Fernà ndez-Real JM, Ricart W. Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 2003; 24:278–301.  Back to cited text no. 15
    
16.
Makarevich A, Valevich V, Pochtavtsev A. Evaluation of pulmonary hypertension in COPD patients with diabetes. Adv Med Sci 2007; 52:265–272.  Back to cited text no. 16
    
17.
Wang F, Liang Y, Zhang F, Wang J, Wei W, Tao Q, et al. Prevalence of diabetic retinopathy in rural China: the Handan Eye Study. Ophthalmology 2009; 116:461–467.  Back to cited text no. 17
    
18.
Jeon Y, Kim M, Huh J, Mok J, Song S, Kim S, et al. Cystatin C as an early biomarker of nephropathy in patients with type 2 diabetes. J Korean Med Sci 2011; 26:258–263.  Back to cited text no. 18
    
19.
Zahran A, Essa E, Abd Elazeem W. Study of serum tumor necrosis factor alpha and interleukin 6 in type 2 diabetic patients with albuminuria. Life Sci J 2012; 9:877–882.  Back to cited text no. 19
    
20.
Pride N, Soriano J. Chronic obstructive pulmonary disease in the United Kingdom: trends in mortality, morbidity, and smoking. Curr Opin Pulm Med 2002; 8:95–101.  Back to cited text no. 20
    
21.
Donaldson G, Seemungal T, Bhowmik A, Wedzicha J. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax 2002; 57:847–852.  Back to cited text no. 21
    
22.
Uz-Zaman S, Banerjee J, Singhamahapatra A, Dey P, Roy A, Roy K, Roy K. Assessment of lung function by spirometry and diffusion study and effect of glycemic control on pulmonary function in type 2 diabetes mellitus patients of the Eastern India. J Clin Diagn Res 2014; 8:1–4.  Back to cited text no. 22
    
23.
Anandhalakshmi S, Manikandan S, Ganeshkumar P, Ramachandran C. Alveolar gas exchange and pulmonary functions in patients with type II diabetes mellitus. J Clin Diagn Res 2013; 7:1874–1877.  Back to cited text no. 23
    
24.
Aparna A. Pulmonary function tests in type 2 diabetics and non-diabetic people – a comparative study. J Clin Diagn Res 2013; 7:1606–1608.  Back to cited text no. 24
    
25.
Winkler C, Atochina-Vasserman E, Holz O, Beers M, Erpenbeck V, Krug N, et al. Comprehensive characterisation of pulmonary and serum surfactant protein D in COPD. Respir Res 2011; 12:1–11.  Back to cited text no. 25
    
26.
Ozyurek B, Ulasli S, Bozbas S, Bayraktar N, Akcay S. Value of serum and induced sputum surfactant protein-D in chronic obstructive pulmonary disease. Multidiscip Respir Med 2013; 8:1–7.  Back to cited text no. 26
    
27.
El-Deek S, Makhlouf H, Saleem T, Mandour M, Mohamed N. Surfactant protein D, soluble intercellular adhesion molecule-1 and high-sensitivity C-reactive protein as biomarkers of chronic obstructive pulmonary disease. Med Princ Pract 2013; 22:469–474.  Back to cited text no. 27
    
28.
Ju C, Liu W, Chen R. Serum surfactant protein D: biomarker of chronic obstructive pulmonary disease. Dis Markers 2012; 32:281–287.  Back to cited text no. 28
    
29.
Sin D, Leung R, Gan W, Paul Man S. Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study. BMC Pulm Med 2007; 7:1–7.  Back to cited text no. 29
    
30.
Fernà ndez-Real J, Valdés S, Manco M, Chico B, Botas P, Campo A, et al. Surfactant protein D, a marker of lung innate immunity, is positively associated with insulin sensitivity. Diabetes Care 2010; 33:847–853.  Back to cited text no. 30
    
31.
Mishra G, Dhamgaye T, Tayade B, Amol F, Amit S, Mulani D. Study of pulmonary function tests in diabetics with COPD or asthma. Appl Cardiopulm Pathophysiol 2012; 16:299–308.  Back to cited text no. 31
    
32.
Pueyo N, Ortega F, Mercader J, Moreno-Navarrete J, Sabater M, Bonà s S, et al. Common genetic variants of surfactant protein-D (SP-D) are associated with type 2 diabetes. PLOS ONE 2013; 8:1–10.  Back to cited text no. 32
    
33.
Sorensen G, Hjelmborg J, Kyvik K, Fenger M, Høj A, Bendixen C, et al. Genetic and environmental influences of surfactant protein D serum levels. Am J Physiol Lung Cell Mol Physiol 2006; 290:1010–1017.  Back to cited text no. 33
    
34.
Zhao X, Wu Y, Wei R, Cai H, Tornoes I, Han J, et al. Plasma surfactant protein D levels and the relation to body mass index in a Chinese population. Scand J Immunol 2007; 66:71–76.  Back to cited text no. 34
    
35.
Karrasch S, Holz O, Jorres R. Aging and induced senescence as factors in the pathogenesis of lung emphysema. Respir Med 2008; 102:1215–1230.  Back to cited text no. 35
    
36.
Ito K, Barnes P. COPD as a disease of accelerated lung aging. Chest 2009; 135:173–180.  Back to cited text no. 36
    
37.
Lindberg A, Jonsson A, Rönmark E, Lundgren R, Larsson L, Lundbäck B. Ten-year cumulative incidence of COPD and risk factors for incident disease in a symptomatic cohort. Chest 2005; 127:1544–1552.  Back to cited text no. 37
    
38.
Hu Y, Teng W, Liu L, Chen K, Liu L, Hua R, et al. Prevalence and risk factors of diabetes and diabetic retinopathy. PLoS One 2015; 10:1–11.  Back to cited text no. 38
    


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