Metabolic syndrome in hospitalized patients with chronic obstructive pulmonary disease Evgeni Mekov1 , Yanina Slavova1 , Adelina Tsakova2 , Marianka Genova2 , Dimitar Kostadinov1 , Delcho Minchev1 and Dora Marinova1 1 Clinical Center for Pulmonary Diseases, Medical University—Sofia, Sofia, Bulgaria 2 Central Clinical Laboratory, Medical University—Sofia, Sofia, Bulgaria
ABSTRACT
Submitted 1 May 2015 Accepted 10 June 2015 Published 2 July 2015 Corresponding author Evgeni Mekov, dr [email protected] Academic editor Teresa Seccia Additional Information and Declarations can be found on page 13 DOI 10.7717/peerj.1068 Copyright 2015 Mekov et al. Distributed under Creative Commons CC-BY 4.0
Introduction. The metabolic syndrome (MS) affects 21–53% of patients with chronic obstructive pulmonary disease (COPD) with a higher prevalence in the early stages of COPD, with results being highly variable between studies. MS may also affect natural course of COPD—number of exacerbations, quality of life and lung function. Aim. To examine the prevalence of MS and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. Material and methods. 152 patients with COPD admitted for exacerbation were studied for presence of MS. All of them were also assessed for vitamin D status and diabetes mellitus type 2 (DM). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. Results. 25% of patients have MS. 23.1% of the male and 29.5% of the female patients have MS (p > 0.05). The prevalence of MS in this study is significantly lower when compared to a national representative study (44.6% in subjects over 45 years). 69.1% of all patients and 97.4% from MS patients have arterial hypertension. The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p = 0.002 and p = 0.001 respectively) and higher total CAT score (p = 0.017). Average BMI is 27.31. None of the patients have MS and BMI 102 cm in males, >88 cm in females; 2. Triglycerides >1.7 mmol/L (or on therapy); 3. HDL FEV1 ≥ 50% predicted); severe (50%>FEV1≥30% predicted); very severe (50 nmol/l 25–50 nmol/l FEV1≥30% FEV11.7 mmol/L (or on therapy)
69.1% (n = 105) 28.3% (n = 43) 29.6% (n = 45) 34.2% (n = 52) 15.8% (n = 24)
59.6% (n = 68) 8.8% (n = 10) 19.3% (n = 22) 23.7% (n = 27) 7.9% (n = 9)
Fasting glucose >5,5 mmol/L (or on therapy) HDL 0.05).
r2
Exacerbations and duration of hospital stay Our study found a significant difference between the number of total exacerbations according to the presence of MS (Table 4, p = 0.015). The number of severe exacerbation, moderate exacerbation and duration of hospital stay did not reach significance. Triglycerides and blood glucose levels in our study did not correlate with number of exacerbations. Linear regression showed presence of MS as risk factor for higher number of exacerbations (R = 0.207, r2 = 0.043, p = 0.010, B = 0.596, 95% CI [0.143–1.050]). From the MS components presence of arterial hypertension is strongest risk factor for exacerbation (R = 0.228, r2 = 0.052, p = 0.005, B = 0.615, 95% CI [0.192–1.038]).
Quality of life The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p = 0.002 and p = 0.001 respectively) and higher total CAT score (p = 0.017) (Table 5). However prevalence of MS is not significantly different between patients with less symptoms (CAT 0–9) and breathlessness (mMRC 0 or 1) compared to patients with more symptoms (CAT ≥ 10) and breathlessness (mMRC ≥ 2) (Table 1). Regression analyses also showed that MS is a risk factor for reduced quality of life, measured with total CAT score (R = 0.205, r2 = 0.042, p = 0.011, B = 3.711, 95% CI [0.859–6.562]). Presence of MS also impairs cough and sleep—first (R = 0.285, r2 = 0.081, p < 0.0005, B = 0.684, 95% CI [0.313–1.055]) and seventh (R = 0.268, r2 = 0.072, p = 0.001, B = 0.930, 95% CI [0.390–1.470]) CAT questions.
Pulmonary function test (PFT) Our study did not find differences in FVC, FEV1, FEV1/FVC, FEV6, FEV1/FEV6, PEF, FEF2575 and FEV3 according to the presence of MS. It should be noted that there is tendency for FVC and FEV1/FVC ratio. However, because of this there is significant difference in FEV3/FVC ratio (Table 6).
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Table 5 Mean CAT score on every question and in total according to presence of MS. MS
Mean CAT score
N
MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes
CAT1 1.95 CAT1 2.63 CAT2 1.92 CAT2 2.34 CAT3 2.54 CAT3 2.97 CAT4 3.52 CAT4 3.74 CAT5 1.23 CAT5 1.66 CAT6 1.54 CAT6 1.68 CAT7 1.28 CAT7 2.21 CAT8 2.62 CAT8 3.08 Total CAT 16.61 Total CAT 20.32
114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38
P value P=0.002 P = 0.063 P = 0.092 P = 0.361 P = 0.198 P = 0.695 P=0.001 P = 0.068 P = 0.017
Table 6 Mean PFT values. MS
Mean PFT value
N
No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes
FEV1 55.56% FEV1 54.68% FVC 80.46% FVC 72.45% FEV1/FVC 0.53 FEV1/FVC 0.57 FEV6 73.89% FEV6 68.63% FEV1/FEV6 0.57 FEV1/FEV6 0.61 PEF 55.62% PEF 56.66% FEF2575 38.89% FEF2575 40.95% FEV3 66.62% FEV3 63.89% FEV3/FVC 0.81 FEV3/FVC 0.85
114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38
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P value P = 0.811 P = 0.094 P = 0.091 P = 0.277 P = 0.107 P = 0.735 P = 0.316 P = 0.601 P =0.033
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Figure 1 Prevalence of MS in COPD patients.
Regression analyses also showed that MS is not a risk factor for reduced pulmonary function. However some of the components of MS are associated with reduced pulmonary function with highest impact of HDL on FVC (R = 0.183, r2 = 0.033, p = 0.024, B = −8.517, 95% CI [−15.904–−1.130]) and FEV1 (R = 0.251, r2 = 0.063, p = 0.001, B = −10.391, 95% CI [−16.865–−3.918]). Fasting glucose is associated with increased FEV1/FVC ratio (R = 0.186, r2 =0.035, p = 0.022, B = 1.238, 95% CI [0.183–2.294]) probably because of lowering FVC. There is no difference in prevalence of MS in patients with FEV1 50% or regarding GOLD stage (Table 1).
DISCUSSION This study found comparable but relatively low prevalence of MS compared to previous studies (Table 7) (Fig. 1). The prevalence of MS in our study is significantly lower when compared to the general Bulgarian population (44.6% in subjects over 45 years) (Borissova et al., 2007). The odds ratio for COPD patients admitted for exacerbation of having MS is 0.41 compared to general population (95% CI [0.28–0.61], p < 0.0005). Two Bulgarian studies examined the prevalence of MS in COPD patients. An epidemiological study conducted in Bulgaria in COPD patients reported a prevalence of 13.8%. These results differ significantly from the literature data probably because of the different criteria for metabolic syndrome (presence of DM, BMI >30 and blood pressure >140/90 mmHg) which makes data comparing irrelevant (Pavlov et al., 2010). A more recent study indicates that the prevalence of metabolic syndrome is 41.8% in patients with COPD . However, this study was not conducted using a random sample (exclusion criteria was presence of DM, people were aged 49–79 years for patients with COPD and
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Table 7 Prevalence of MS in patients with COPD. Authors
N
Studied population
Prevalence of MS
Akpinar et al., 2012 Funakoshi et al., 2010
133 7.189
Patients with COPD and controls Men aged 45–88 years
Kupeli et al., 2010 Lam et al., 2010 Marquis et al., 2005 Minas et al., 2011 Ozgen Alpaydin et al., 2013 Park et al., 2012
106 7.358 72 114 90 1.215
Hospitalized patients with COPD General population >50 years Patients with COPD and controls Men with COPD Patients with COPD and controls Patients with COPD and controls >40 years
Poulain et al., 2008 Watz et al., 2009
28 200
Patients with COPD Patients with COPD and chronic bronchitis
44.6% 16.8%, OR 0.72 (95% CI [0.51–1.02]) in GOLD I; 28.7%, OR 1.33 (95% CI [1.01–1.76]) in GOLD II–IV 27.3% 22.6%; OR 1.47 (95% CI [1.12–1.92]) 47% 21% 43% 33% vs. 22.2% for men; 48.5% vs. 29.6% for women OR 2.03 (95% CI [1.08–3.80]) Overweight—50%; Normal weight—0%. GOLD I—50%; GOLD II—53%; GOLD III—37%; GOLD IV—44%; Chronic bronchitis—53%
35–65 years for controls) (Stratev et al., 2012). Nonetheless it uses similar criteria for MS and when comparing the results our study finds lower prevalence of MS. The prevalence results could be explained with differences between the populations in different studies (physical activity, diet, lifestyle etc.). For example, Bulgaria is low-income country, which may impact diet preferences and treatment choices. Furthermore, patients in this study had been hospitalized due to exacerbation, which represents the most severe group of COPD patients. Having in mind that MS is more common in the early stages and decreases with COPD progression (Watz et al., 2009), COPD patients hospitalized for exacerbation may be considered as having advanced COPD. According to the NHANES III study, smokers are more likely to develop MS than nonsmokers in general population, and the risk increases with the number of pack-years even after adjusting for covariates (Park et al., 2003). Our study did not find significant differences in prevalence of MS according to smoking status and number of pack-years. These results could be explained with smoke being the biggest factor in developing COPD and effect of developing MS could be reduced. Moreover nicotine may be an appetite suppressant and lower the weight thus decreasing prevalence of metabolic syndrome (Chiolero et al., 2008). Third, hospitalized COPD patients are patients with predominantly advanced disease and prone to cachexia and wasting. Also, lifestyle changes (quiting smoking) in the presence of the two diseases should be considered which may change the prevalence of MS. Treatment with inhalatory corticosteroids (ICS) is not risk factor for MS similar to findings for DM (O’Byrne et al., 2012) and fasting glucose level are not influenced by ICS. COPD is a disease that affects mainly the lungs, but is characterized by systemic inflammation and a number of extrapulmonary manifestations. Only 1/3 of patients with COPD die due to respiratory failure. Main cause of death is lung cancer and cardiovascular complications (Calverley et al., 2007).
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The vast majority of patients with COPD have a vitamin D deficiency (Romme et al., 2013). Aside from its role in the metabolism of calcium and phosphorus, vitamin D is involved in the pathogenesis of multiple diseases, including MS, mainly because it affects the secretion and the function of insulin (Ju, Jeong & Kim, 2014). However, in our study vitamin D levels do not significantly differ in relation to presence of MS. Presence of MS is also not related to vitamin D status. There are no studies that examine the relationship between osteoporosis and MS in patients with COPD. However, both diseases share common risk factors such as smoking, lack of physical activity, and treatment with corticosteroids. Some of the components of the metabolic syndrome (arterial hypertension, elevated triglycerides, reduced HDL cholesterol) are risk factors for low bone density. Systemic inflammation in MS plays a role in the pathogenesis of osteoporosis (McFarlane, 2006). On the other hand, studies examining the relationship between MS and osteoporosis showed inconsistent results, probably due to the protective effect of obesity (Zhou et al., 2013). However, the number of fractures in our study does not significantly differ regarding the presence of MS. The presence of at least one fracture also does not differ significantly in relation to presence of MS. Most patients with DM have MS, but the opposite is not necessarily true (Ginsberg & Stalenhoef, 2003). The presence of MS in this study is associated with presence of DM, higher BMI and BAI. Hyperglycemia is associated with elevated glucose concentrations in tissues and bronchial aspirates where it may stimulate infection by enhancing bacterial growth and by promoting bacterial interaction with the airway epithelium (Brennan et al., 2007). Hyperglycemia also impairs both innate and adaptive immunity, suppressing the host response to infection. The presence of MS in patients with COPD increases the frequency of exacerbations (2.4 vs. 0.7) and their duration–(7.5 vs. 5.0 days) according to Kupeli et al. (2010), and 8 versus 5.5 days, according to Abdelghaffar et al. (2012). Our study found a significant difference between the number of total exacerbations according to the presence of MS. However, the number of severe exacerbation, moderate exacerbation and duration of hospital stay did not differ significantly. Triglycerides and blood glucose levels in our study did not correlate with number of exacerbations as reported by other authors (Kupeli et al., 2010). The presence of MS is associated with significantly worse cough and sleep and higher total CAT score. This confirms the data about reduced quality of life in patients with MS (Ford & Li, 2008). However, the prevalence of MS is not significantly different between patients with less symptoms (CAT 0–9) and breathlessness (mMRC 0 or 1) compared to patients with more symptoms (CAT ≥10) and breathlessness (mMRC ≥2). These mixed results may be explained with COPD having higher negative impact on quality of life than MS (physical limitation due to shortness of breath) as suggested for DM (Arne, Janson & Janson, 2009), and ameliorating the effect in patients having both diseases. COPD is characterized by airflow obstruction, which is not fully reversible. MS is associated with a reduction of lung volumes (Fimognari et al., 2007; Leone et al., 2009; Lin et al., 2006; Nakajima et al., 2008; Yeh et al., 2011). It should be noted that some studies
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found no association between lung function and the presence of MS (Yamamoto et al., 2014). MS in our study is not associated with worsen pulmonary function. There is also no difference in prevalence of MS in patients with FEV1 50% or regarding GOLD stage.
CONCLUSIONS This study finds a 25% prevalence of MS in COPD patients admitted for exacerbation, which is significantly lower than the general population. MS is more prevalent in females, but the gender difference is not statistically significant. In this study, most of the patients are former smokers, and the prevalence of MS does not differ regarding smoking status and treatment with ICS. The presence of MS is associated with the presence of DM, higher BMI and BAI, more exacerbations during the previous year and lower quality of life. MS is not associated with increased hospital stay and lower pulmonary function. This study finds comparable but relatively low prevalence of MS compared to previously published data (21–53%). As MS is more common in the early stages and decreases with COPD progression, the COPD patients admitted for exacerbation may be considered as having advanced COPD.
ADDITIONAL INFORMATION AND DECLARATIONS Funding This manuscript is part of a PhD project, which is partially funded by Medical University— Sofia, Sofia, Bulgaria (grant number 15-D/2014, project number 22-D/2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Grant Disclosures The following grant information was disclosed by the authors: Medical University—Sofia: 15-D/2014.
Competing Interests The authors declare there are no competing interests.
Author Contributions • Evgeni Mekov conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper. • Yanina Slavova conceived and designed the experiments, contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper. • Adelina Tsakova and Marianka Genova performed the experiments, contributed reagents/materials/analysis tools, reviewed drafts of the paper.
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• Dimitar Kostadinov and Delcho Minchev contributed reagents/materials/analysis tools, reviewed drafts of the paper. • Dora Marinova contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper.
Human Ethics The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers): Medical University-Sofia Research Ethics Commission approved the study (#2976/2014).
Data Deposition The following information was supplied regarding the deposition of related data: http://figshare.com/articles/MS in COPD/1439301.
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ABSTRACT
Submitted 1 May 2015 Accepted 10 June 2015 Published 2 July 2015 Corresponding author Evgeni Mekov, dr [email protected] Academic editor Teresa Seccia Additional Information and Declarations can be found on page 13 DOI 10.7717/peerj.1068 Copyright 2015 Mekov et al. Distributed under Creative Commons CC-BY 4.0
Introduction. The metabolic syndrome (MS) affects 21–53% of patients with chronic obstructive pulmonary disease (COPD) with a higher prevalence in the early stages of COPD, with results being highly variable between studies. MS may also affect natural course of COPD—number of exacerbations, quality of life and lung function. Aim. To examine the prevalence of MS and its correlation with comorbidities and COPD characteristics in patients with COPD admitted for exacerbation. Material and methods. 152 patients with COPD admitted for exacerbation were studied for presence of MS. All of them were also assessed for vitamin D status and diabetes mellitus type 2 (DM). Data were gathered for smoking status and exacerbations during the last year. All patients completed CAT (COPD assessment test) and mMRC (Modified Medical Research Council Dyspnea scale) questionnaires and underwent spirometry. Duration of current hospital stay was recorded. Results. 25% of patients have MS. 23.1% of the male and 29.5% of the female patients have MS (p > 0.05). The prevalence of MS in this study is significantly lower when compared to a national representative study (44.6% in subjects over 45 years). 69.1% of all patients and 97.4% from MS patients have arterial hypertension. The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p = 0.002 and p = 0.001 respectively) and higher total CAT score (p = 0.017). Average BMI is 27.31. None of the patients have MS and BMI 102 cm in males, >88 cm in females; 2. Triglycerides >1.7 mmol/L (or on therapy); 3. HDL FEV1 ≥ 50% predicted); severe (50%>FEV1≥30% predicted); very severe (50 nmol/l 25–50 nmol/l FEV1≥30% FEV11.7 mmol/L (or on therapy)
69.1% (n = 105) 28.3% (n = 43) 29.6% (n = 45) 34.2% (n = 52) 15.8% (n = 24)
59.6% (n = 68) 8.8% (n = 10) 19.3% (n = 22) 23.7% (n = 27) 7.9% (n = 9)
Fasting glucose >5,5 mmol/L (or on therapy) HDL 0.05).
r2
Exacerbations and duration of hospital stay Our study found a significant difference between the number of total exacerbations according to the presence of MS (Table 4, p = 0.015). The number of severe exacerbation, moderate exacerbation and duration of hospital stay did not reach significance. Triglycerides and blood glucose levels in our study did not correlate with number of exacerbations. Linear regression showed presence of MS as risk factor for higher number of exacerbations (R = 0.207, r2 = 0.043, p = 0.010, B = 0.596, 95% CI [0.143–1.050]). From the MS components presence of arterial hypertension is strongest risk factor for exacerbation (R = 0.228, r2 = 0.052, p = 0.005, B = 0.615, 95% CI [0.192–1.038]).
Quality of life The presence of MS is associated with significantly worse cough and sleep (1st and 7th CAT questions; p = 0.002 and p = 0.001 respectively) and higher total CAT score (p = 0.017) (Table 5). However prevalence of MS is not significantly different between patients with less symptoms (CAT 0–9) and breathlessness (mMRC 0 or 1) compared to patients with more symptoms (CAT ≥ 10) and breathlessness (mMRC ≥ 2) (Table 1). Regression analyses also showed that MS is a risk factor for reduced quality of life, measured with total CAT score (R = 0.205, r2 = 0.042, p = 0.011, B = 3.711, 95% CI [0.859–6.562]). Presence of MS also impairs cough and sleep—first (R = 0.285, r2 = 0.081, p < 0.0005, B = 0.684, 95% CI [0.313–1.055]) and seventh (R = 0.268, r2 = 0.072, p = 0.001, B = 0.930, 95% CI [0.390–1.470]) CAT questions.
Pulmonary function test (PFT) Our study did not find differences in FVC, FEV1, FEV1/FVC, FEV6, FEV1/FEV6, PEF, FEF2575 and FEV3 according to the presence of MS. It should be noted that there is tendency for FVC and FEV1/FVC ratio. However, because of this there is significant difference in FEV3/FVC ratio (Table 6).
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Table 5 Mean CAT score on every question and in total according to presence of MS. MS
Mean CAT score
N
MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes MS—no MS—yes
CAT1 1.95 CAT1 2.63 CAT2 1.92 CAT2 2.34 CAT3 2.54 CAT3 2.97 CAT4 3.52 CAT4 3.74 CAT5 1.23 CAT5 1.66 CAT6 1.54 CAT6 1.68 CAT7 1.28 CAT7 2.21 CAT8 2.62 CAT8 3.08 Total CAT 16.61 Total CAT 20.32
114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38
P value P=0.002 P = 0.063 P = 0.092 P = 0.361 P = 0.198 P = 0.695 P=0.001 P = 0.068 P = 0.017
Table 6 Mean PFT values. MS
Mean PFT value
N
No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes No Yes
FEV1 55.56% FEV1 54.68% FVC 80.46% FVC 72.45% FEV1/FVC 0.53 FEV1/FVC 0.57 FEV6 73.89% FEV6 68.63% FEV1/FEV6 0.57 FEV1/FEV6 0.61 PEF 55.62% PEF 56.66% FEF2575 38.89% FEF2575 40.95% FEV3 66.62% FEV3 63.89% FEV3/FVC 0.81 FEV3/FVC 0.85
114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38 114 38
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P value P = 0.811 P = 0.094 P = 0.091 P = 0.277 P = 0.107 P = 0.735 P = 0.316 P = 0.601 P =0.033
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Figure 1 Prevalence of MS in COPD patients.
Regression analyses also showed that MS is not a risk factor for reduced pulmonary function. However some of the components of MS are associated with reduced pulmonary function with highest impact of HDL on FVC (R = 0.183, r2 = 0.033, p = 0.024, B = −8.517, 95% CI [−15.904–−1.130]) and FEV1 (R = 0.251, r2 = 0.063, p = 0.001, B = −10.391, 95% CI [−16.865–−3.918]). Fasting glucose is associated with increased FEV1/FVC ratio (R = 0.186, r2 =0.035, p = 0.022, B = 1.238, 95% CI [0.183–2.294]) probably because of lowering FVC. There is no difference in prevalence of MS in patients with FEV1 50% or regarding GOLD stage (Table 1).
DISCUSSION This study found comparable but relatively low prevalence of MS compared to previous studies (Table 7) (Fig. 1). The prevalence of MS in our study is significantly lower when compared to the general Bulgarian population (44.6% in subjects over 45 years) (Borissova et al., 2007). The odds ratio for COPD patients admitted for exacerbation of having MS is 0.41 compared to general population (95% CI [0.28–0.61], p < 0.0005). Two Bulgarian studies examined the prevalence of MS in COPD patients. An epidemiological study conducted in Bulgaria in COPD patients reported a prevalence of 13.8%. These results differ significantly from the literature data probably because of the different criteria for metabolic syndrome (presence of DM, BMI >30 and blood pressure >140/90 mmHg) which makes data comparing irrelevant (Pavlov et al., 2010). A more recent study indicates that the prevalence of metabolic syndrome is 41.8% in patients with COPD . However, this study was not conducted using a random sample (exclusion criteria was presence of DM, people were aged 49–79 years for patients with COPD and
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Table 7 Prevalence of MS in patients with COPD. Authors
N
Studied population
Prevalence of MS
Akpinar et al., 2012 Funakoshi et al., 2010
133 7.189
Patients with COPD and controls Men aged 45–88 years
Kupeli et al., 2010 Lam et al., 2010 Marquis et al., 2005 Minas et al., 2011 Ozgen Alpaydin et al., 2013 Park et al., 2012
106 7.358 72 114 90 1.215
Hospitalized patients with COPD General population >50 years Patients with COPD and controls Men with COPD Patients with COPD and controls Patients with COPD and controls >40 years
Poulain et al., 2008 Watz et al., 2009
28 200
Patients with COPD Patients with COPD and chronic bronchitis
44.6% 16.8%, OR 0.72 (95% CI [0.51–1.02]) in GOLD I; 28.7%, OR 1.33 (95% CI [1.01–1.76]) in GOLD II–IV 27.3% 22.6%; OR 1.47 (95% CI [1.12–1.92]) 47% 21% 43% 33% vs. 22.2% for men; 48.5% vs. 29.6% for women OR 2.03 (95% CI [1.08–3.80]) Overweight—50%; Normal weight—0%. GOLD I—50%; GOLD II—53%; GOLD III—37%; GOLD IV—44%; Chronic bronchitis—53%
35–65 years for controls) (Stratev et al., 2012). Nonetheless it uses similar criteria for MS and when comparing the results our study finds lower prevalence of MS. The prevalence results could be explained with differences between the populations in different studies (physical activity, diet, lifestyle etc.). For example, Bulgaria is low-income country, which may impact diet preferences and treatment choices. Furthermore, patients in this study had been hospitalized due to exacerbation, which represents the most severe group of COPD patients. Having in mind that MS is more common in the early stages and decreases with COPD progression (Watz et al., 2009), COPD patients hospitalized for exacerbation may be considered as having advanced COPD. According to the NHANES III study, smokers are more likely to develop MS than nonsmokers in general population, and the risk increases with the number of pack-years even after adjusting for covariates (Park et al., 2003). Our study did not find significant differences in prevalence of MS according to smoking status and number of pack-years. These results could be explained with smoke being the biggest factor in developing COPD and effect of developing MS could be reduced. Moreover nicotine may be an appetite suppressant and lower the weight thus decreasing prevalence of metabolic syndrome (Chiolero et al., 2008). Third, hospitalized COPD patients are patients with predominantly advanced disease and prone to cachexia and wasting. Also, lifestyle changes (quiting smoking) in the presence of the two diseases should be considered which may change the prevalence of MS. Treatment with inhalatory corticosteroids (ICS) is not risk factor for MS similar to findings for DM (O’Byrne et al., 2012) and fasting glucose level are not influenced by ICS. COPD is a disease that affects mainly the lungs, but is characterized by systemic inflammation and a number of extrapulmonary manifestations. Only 1/3 of patients with COPD die due to respiratory failure. Main cause of death is lung cancer and cardiovascular complications (Calverley et al., 2007).
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The vast majority of patients with COPD have a vitamin D deficiency (Romme et al., 2013). Aside from its role in the metabolism of calcium and phosphorus, vitamin D is involved in the pathogenesis of multiple diseases, including MS, mainly because it affects the secretion and the function of insulin (Ju, Jeong & Kim, 2014). However, in our study vitamin D levels do not significantly differ in relation to presence of MS. Presence of MS is also not related to vitamin D status. There are no studies that examine the relationship between osteoporosis and MS in patients with COPD. However, both diseases share common risk factors such as smoking, lack of physical activity, and treatment with corticosteroids. Some of the components of the metabolic syndrome (arterial hypertension, elevated triglycerides, reduced HDL cholesterol) are risk factors for low bone density. Systemic inflammation in MS plays a role in the pathogenesis of osteoporosis (McFarlane, 2006). On the other hand, studies examining the relationship between MS and osteoporosis showed inconsistent results, probably due to the protective effect of obesity (Zhou et al., 2013). However, the number of fractures in our study does not significantly differ regarding the presence of MS. The presence of at least one fracture also does not differ significantly in relation to presence of MS. Most patients with DM have MS, but the opposite is not necessarily true (Ginsberg & Stalenhoef, 2003). The presence of MS in this study is associated with presence of DM, higher BMI and BAI. Hyperglycemia is associated with elevated glucose concentrations in tissues and bronchial aspirates where it may stimulate infection by enhancing bacterial growth and by promoting bacterial interaction with the airway epithelium (Brennan et al., 2007). Hyperglycemia also impairs both innate and adaptive immunity, suppressing the host response to infection. The presence of MS in patients with COPD increases the frequency of exacerbations (2.4 vs. 0.7) and their duration–(7.5 vs. 5.0 days) according to Kupeli et al. (2010), and 8 versus 5.5 days, according to Abdelghaffar et al. (2012). Our study found a significant difference between the number of total exacerbations according to the presence of MS. However, the number of severe exacerbation, moderate exacerbation and duration of hospital stay did not differ significantly. Triglycerides and blood glucose levels in our study did not correlate with number of exacerbations as reported by other authors (Kupeli et al., 2010). The presence of MS is associated with significantly worse cough and sleep and higher total CAT score. This confirms the data about reduced quality of life in patients with MS (Ford & Li, 2008). However, the prevalence of MS is not significantly different between patients with less symptoms (CAT 0–9) and breathlessness (mMRC 0 or 1) compared to patients with more symptoms (CAT ≥10) and breathlessness (mMRC ≥2). These mixed results may be explained with COPD having higher negative impact on quality of life than MS (physical limitation due to shortness of breath) as suggested for DM (Arne, Janson & Janson, 2009), and ameliorating the effect in patients having both diseases. COPD is characterized by airflow obstruction, which is not fully reversible. MS is associated with a reduction of lung volumes (Fimognari et al., 2007; Leone et al., 2009; Lin et al., 2006; Nakajima et al., 2008; Yeh et al., 2011). It should be noted that some studies
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found no association between lung function and the presence of MS (Yamamoto et al., 2014). MS in our study is not associated with worsen pulmonary function. There is also no difference in prevalence of MS in patients with FEV1 50% or regarding GOLD stage.
CONCLUSIONS This study finds a 25% prevalence of MS in COPD patients admitted for exacerbation, which is significantly lower than the general population. MS is more prevalent in females, but the gender difference is not statistically significant. In this study, most of the patients are former smokers, and the prevalence of MS does not differ regarding smoking status and treatment with ICS. The presence of MS is associated with the presence of DM, higher BMI and BAI, more exacerbations during the previous year and lower quality of life. MS is not associated with increased hospital stay and lower pulmonary function. This study finds comparable but relatively low prevalence of MS compared to previously published data (21–53%). As MS is more common in the early stages and decreases with COPD progression, the COPD patients admitted for exacerbation may be considered as having advanced COPD.
ADDITIONAL INFORMATION AND DECLARATIONS Funding This manuscript is part of a PhD project, which is partially funded by Medical University— Sofia, Sofia, Bulgaria (grant number 15-D/2014, project number 22-D/2014). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Grant Disclosures The following grant information was disclosed by the authors: Medical University—Sofia: 15-D/2014.
Competing Interests The authors declare there are no competing interests.
Author Contributions • Evgeni Mekov conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper. • Yanina Slavova conceived and designed the experiments, contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper. • Adelina Tsakova and Marianka Genova performed the experiments, contributed reagents/materials/analysis tools, reviewed drafts of the paper.
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• Dimitar Kostadinov and Delcho Minchev contributed reagents/materials/analysis tools, reviewed drafts of the paper. • Dora Marinova contributed reagents/materials/analysis tools, wrote the paper, reviewed drafts of the paper.
Human Ethics The following information was supplied relating to ethical approvals (i.e., approving body and any reference numbers): Medical University-Sofia Research Ethics Commission approved the study (#2976/2014).
Data Deposition The following information was supplied regarding the deposition of related data: http://figshare.com/articles/MS in COPD/1439301.
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