Correlation between hyperinflation defined as an elevated RV/TLC ratio and body composition and cytokine profile in patients with chronic obstructive pulmonary disease

Renata Rubinsztajn, Tadeusz Przybyłowski, Marta Maskey-Warzęchowska, Magdalena Paplińska-Goryca, Krzysztof Karwat, Patrycja Nejman-Gryz, Ryszarda Chazan

Department of Internal Medicine, Pneumonology and Allergology, Warsaw Medical University, Poland

 

 

Correlation between hyperinflation defined as an elevated RV/TLC ratio and body composition and cytokine profile in patients with chronic obstructive pulmonary disease

Korelacje pomiędzy rozdęciem miąższu płucnego mierzonego wskaźnikiem RV%TLC i składem ciała oraz profilem cytokinowym u chorych na przewlekłą obturacyjną chorobę płuc

The authors declare no finacial disclosure

 

 

ABSTRACT

Introduction: Body composition is an important prognostic factor in patients with COPD. The decrease in fat free mass (FFM), muscle mass (MM) and increase in visceral fat is associated with an elevated secretion of cytokines which promote systemic inflammation.

The aim of the study was to evaluate body composition and the cytokine profile in patients with COPD in relation with the presence of hyperinflation.

Material and methods: The study group consisted of 149 patients (61F, 88M) with stable COPD in all stages of severity aged 68 ± 8.8 yrs. All the patients underwent spirometry and bodypletysmography with bronchial reversibility testing. Hyperinflation was defined as RV%TLC > 48% and > 126% predicted. Body composition was analyzed by bioimpedance. The following serum inflammatory markers were evaluated: C-reactive protein, IL-6, IL-8, TNF-α, CC16, adiponectin and resistin.

Results: Hyperinflation was found in 96 patients (group A) and it was more frequent in women than men (49/61 vs. 47/88, p < 0.001). BMI and age in this group were comparable to those in patients without hyperinflation (group B). Patients with hyperinflation have lover FFM, FFM index, MM and MM index and total body water and higher fat mass and fat mass index. We found significantly higher serum concentrations of inflammatory markers in group A: IL-6 – 6.4 ± 10.9 vs. 3.6 ± 4.2 pg/ml, resistin – 9.3 ± 4.2 vs. 7.6 ± 2.4 ng/ml, CRP 4.1 ± 2.3 vs. 2.9±2.1 mg/l, respectively.

Conclusions: Patients with hyperinflation have a lower FFMI, TBW and MMI and a higher proportion of fat tissue. Hyperinflation is associated with elevated concentrations of inflammatory markers what may be associated with more severe disease. Body compositions abnormality and higher activity of systemic inflammation could therefore be a negative prognostic factor in COPD patients.

Key words: COPD, RV%TLC, body composition, systemic inflammation

Pneumonol Alergol Pol 2015; 83: 120–125

 

STRESZCZENIE

Wstęp: Skład ciała jest ważnym czynnikiem prognostycznym u chorych na POChP. Spadek beztłuszczowej masy ciała (FFM), masy mięśni (MM) i wzrost masy trzewnej tkanki tłuszczowej jest związane ze wzrostem wydzielania cytokin odpowiedzialnych za systemowe zapalenie.

Celem pracy była ocena wpływu hiperinflacji układu oddechowego na stan odżywienia i profilu cytokin u chorych na POChP.

Materiał i metody: Grupa badana składała się z 149 chorych (61K, 88M), w stabilnym okresie POChP, którzy reprezentowali wszystkie stopnie ciężkości choroby, w wieku 68 ± 8,8 lat. Wszyscy chorzy mieli wykonaną spirometrię i pletyzmografię z próbą rozkurczową. Rozdęcie było definiowane, jako zwiększenie RV%TLC > 48% and > 126% wn. Skład ciała był mierzony metodą bioimpendancji. Wykonano pomiar następujących cytokin w surowicy: białko C-reaktywne (CRP), IL-6, IL-8, TNF-α, CC16, adiponektyna i rezystyna.

Wyniki: Rozdęcie stwierdzono u 96 chorych (grupa A), było ono częstsze u kobiet niż mężczyzn (49/61 v. 47/88, p < 0,001). Indeks masy ciała i wiek były podobne do grupy chorych bez rozdęcia (grupa B). Grupa A miała niższe FFM i FFMI, MM i MMI i całkowitą masę wody oraz wyższą masę tłuszczową i indeks masy tłuszczowej. W grupie A stwierdzono istotnie statystycznie wyższe stężenie w surowicy markerów zapalenia: IL-6 — 6,4 ± 10,9 v. 3,6 ± 4,2 pg/ml, resistin — 9,3 ± 4,2 v. 7,6 ± 2,4 ng/ml, CRP 4,1 ± 2,3 v. 2,9 ± 2,1 mg/l.

Wnioski: Chorzy, u których stwierdza się rozdęcie płuc mają niższe FFMI, TBW, MMI i więcej tkanki tłuszczowej. U chorych z rozdęciem płuc stwierdza się podwyższone stężenie markerów stanu zapalnego w porównaniu z chorymi bez rozdęcia, co może świadczyć o bardziej zaawansowanym procesie chorobowym. Zarówno zaburzenia w składzie ciała jak i wyższa aktywność zapalenia systemowego w grupie chorych z rozdęciem płuc może wskazywać na ich gorsze rokowanie

Słowa kluczowe: POChP, RV%TLC, skład ciała, zapalenie

Pneumonol Alergol Pol 2015; 83: 120–125

 

Introduction

Chronic obstructive pulmonary disease is characterized by progressive airflow limitation which is a result an inflammatory response in the airways to noxious particles and gases [1]. Pathological changes that lead to airway obstruction may have the form of chronic bronchitis and/or pulmonary emphysema. In patients with predominant chronic bronchitis the inflammatory process involves mainly the small airways and bronchioles, resulting in peribronchiolar fibrosis, muscular hypertrophy and mucus hypersecretion. Whereas in patients with predominant emphysema, pronounced lung parenchyma destruction is observed; the loss of lung elasticity impairs emptying of the lungs during expiration leading to an increase in the end-expiratory lung volume [2]. This process intensifies with increasing airway obstruction e.g. during COPD exacerbation. Irrespective of the predominant nature of pathological changes, inflammatory cells cumulate in the airways, secreting various mediators responsible for the above mentioned process and structural changes [3]. Systemic inflammation results in the development of extrapulmonary manifestations, including alterations in body composition. In some patients cachexia occurs, in the majority, the loss of fat free mass (FFM) is observed along with the progression of the disease. Nutrition disorders are associated with increased secretion of inflammatory mediators (TNF-α, IL-6, IL-8, CRP) [4]. Low body mass index (BMI) is believed to be an independent risk factor of mortality in COPD [5]. Lung hyperinflation has an impact on numerous factors that are taken into account in the evaluation of the COPD patient including the sense of dyspnoea assessed by the Medical Research Council (MRC) scale, quality of life, FEV1 decline, energy balance and body composition disorders [6, 7].

The objective of the study was to evaluate the influence of lung hyperinflation on the nutrition status and cytokine profile in patients with COPD.

 

Material and methods

The study group included 149 patients with stable COPD (61 women and 88 men) aged 68 ± 8.8 years. COPD was diagnosed in accordance with the GOLD 2010 recommendations [8]. The criterion for stable COPD was lack of exacerbation for a period of at least 6 weeks prior to study inclusion.

The study group was divided into two subgroups: A — patients with hyperinflation, and B — patients without hyperinflation with predefined criteria as described below.

All patients underwent anthropometric measurements of height and body mass including: fat free mass (FFM, kg), muscle mass (MM, kg), total body water (TBW, kg), body fat content (BF, %). The measurements were performed under fasting condition in the morning. Body mass index (BMI), muscle mass (MMI) and fat free mass indices (FFMI) were calculated. Body composition was assessed using bioimpedance (Tanita T5896, TANITA Corporation of America, Inc, Arlington Heights, USA). Spirometry with bronchial reversibility testing (LungTest 1000, MES, Poland) according to the guidelines of the Polish Respiratory Society (Polskie Towarzystwo Chorób Płuc, PTChP) [9], bodyplethysmography (BodyBox, Medisoft, Sorinnes, Belgium and Vmax 6200 Autobox (SensorMedics, Yorba Linda, USA) were performed. Lung hyperinflation was defined as the residual volume/total lung capacity ratio (RV%TLC) > 48% and residual volume (RV) > 126% of predicted value [10]. The study was approved by the Bioethical Committee of the Warsaw Medical University (KB/207/2008).

Fasting venous blood samples were collected for the assessment of systemic inflammation: CRP, IL-6, IL-8, TNF-α, CCL16, adiponectin and resistin were evaluated (ELISA, R&D Systems Quantikinine, (Minneapolis, Minnesota United State).

 

Statistical analysis

Statistical analysis was performed with Statistica for Windows (StatSoft, Inc. version 10. www.statsoft.com). The values of variables with normal distribution were presented as mean ± standard deviation, the variables non-normal distribution were presented as median and interquartile range. Distribution normality was assessed using the Shapiro-Wilk test. Depending on the nature of distribution of the examined variable, comparisons between the groups were made using Student’s t test or Wilcoxon test. To evaluate significance of correlation coefficient, Spearman correlation test was used. P < 0.05 was regarded statistically significant.

 

Results

Lung hyperinflation was found in 96 patients (49 women, 47 men). It was more frequent in the group of women — 49 (51%) vs. 47 (49%) p < 0.001. The age of patients from the two groups was comparable, the groups did not differ in BMI (27.5 ± 5.4 vs. 27.5 ± 4.8 kg/m2). Both groups differed in the results of lung function tests (Table 1). Patients with hyperinflation had a lower pre and post- bronchodilator FEV1. Pre-bronchodilator FVC was also lower, however there were no differences in post-bronchodilator FVC.

 

Table 1. Results of lung test in the studied groups

Hyperinflation (+)

Group A

Hyperinflation (−)

Group B

p

FEV1 (l)*

1.19± 0.42

1.88 ± 0.60

0.000

FEV1 (%pred)*

48.30 ± 14.71

69.10 ± 15.65

0.000

Increase of FEV1 (l)

0.16 ± 0.11

0.25 ± 0.18

0.0005

Increase of FEV1 (%pred)

6.41 ± 4.13

9.15 ± 6.30

0.0018

FVC (l)*

2.66 ± 0.76

3.55 ± 0.88

0.0000

FVC (%w.n.)*

FVC (%pred)

82.72 ± 15.17

99.58 ± 16.97

0.0000

Increase of FVC (l)

0.35 ± 0.26

0.32 ± 0.28

NS

Increase of FVC (%pred)

10.65 ± 7.38

9.17 ± 7.62

NS

TLC (l)*

7.1 ± 1.59

6.98 ± 1.36

NS

TLC (%w.n.)*

TLC (%pred)

128.92 ± 21.4

113.29 ± 17.29

0.0000

RV (l)*

4.30 ± 1.09

3.29 ± 0.71

0.0000

RV (%w.n.)*

RV (%pred)

195.54 ± 44.32

136.26 ± 23.45

0.0000

RV%TLC*

60.46 ± 6.27

47.44 ± 5.98

0.0000

RV%TLC (%w.n.)*

147.0 ± 15.0

114.0 ± 10.0

0.0000

*15 minutes after 400 µg salbutamol inhalation; FEV1 — forced expiratory volume in 1 second); FVC — forced vital capacity; RV — residual volume; TLC — total lung capacity

 

In patients with hyperinflation, lower fat free body mass and muscle mass were found, but a higher body fat and body water content measured in kilograms.

The analysis of body composition showed statistically significant differences between the study groups (Table 2).

 

Table 2. Body composition in patients with hyperinflations (group A) and without hyperinflations (group B)

Hyperinflation (+) group A

Hyperinflation (−) Group B

p

Total body water

(TBW. kg)

36.5 ± 8.0

40.9 ± 7.8

0.0006

Fat free mass

(FFM. kg)

49.4 ± 10.2

55.9 ± 10.7

0.0003

Fat free mass

18.2 ± 2.5

19.6 ± 2.46

0.002

Fat mass (kg)

32.5 ± 7.9

28.8 ± 8.1

0.008

Index

FFMI (kg/m2)

12.3 ± 3.6

10.3 ± 3.6

0.002

Muscle mass (kg)

47.6 ± 10.6

52.4 ± 10.3

0.0005

Index MMI (kg/m2)

17.5 ± 2.8

18.7 ± 2.4

0.001

Basal metabolic rate (kcal)

1472.6 ± 300.7

1646.0 ± 313.3

0.001

 

Table 3. Correlations between body mass compositions and lung test results

Parameters

R

p

FEV1 (l)/FEV1 (%w.n.) − FFMI

0.46/0.23

0.0000/0.0055

FEV1 (lLl)/FEV1 (%w.n.) − TBW

0.56/0.20

0.0000/0.014

FEV1 (l)/FEV1 (%w.n.) − MMI

0.45/0.21

0.0000/0.011

FVC (l) – FFMI (kg/m2)

0.41

0.0000

FVC (l) − TBW (kg)

0.61

0.0000

FVC (lL) – MMI (kg/m2)

0.40

0.0001/0.0001

TLC (%w.n.) − FFMI (kg/m2)

−0.42

0.0000

TLC (l)/TLC (%w.n.) − TBW (kg)

0.43/ −0.40

0.0000/0.0000

TLC (%w.n.) – MMI (kg/m2)

−0.44

0.00000

RV (%w.n.) – FFMI (kg/m2)

−0.40

0.000001

RV (%w.n.) – TBW (kg)

−0.32

0.0001

RV (%w.n.) – MMI (kg/m2)

−0.41

0.00000

RV%TLC – FFMI (kg/m2)

−0.34

0.000032

RV%TLC – TBW (kg)

−0.35

0.000025

RV%TLC – MMI (kg/m2)

−0.33

0.000075

All abbreviations in the text

 

The analysis of inflammatory markers showed statistically higher concentrations of serum IL-6, resistin and CRP in patients with lung hyperinflation. The serum concentrations of the selected inflammatory markers in both study groups are presented in Table 4.

 

Table 4. Serum concentrations of systemic inflammations markers

Group A

Group B

P

IL6 (pg/ml)

6.4 ± 10.9

3.6 ± 4.2

0.004

IL8 (pg/ml)

12.9 ± 19.5

14.5 ± 35.0

NS

Adiponectin (mg/ml)

1.2 ± 8.7

1.1 ± 6.82.8

NS

Resistin (ng/ml)

9.3 ± 4.2

7.6 ± 2.4

0.0081

TNF-α (pg/ml)

2.4 ± 2.6

2.1 ± 0.8

NS

CCL16 (ng/ml)

29.1 ± 16.7

31.6 ± 15.3

NS

CRP (mg/ml)

4.1 ± 2.3

2.9 ± 2.21

0.003

All abbreviations in the text

 

Table 5. Correlations between lung test results and systemic inflammations markers

Adiponectin/FEV1 (l)*

−0.3

< 0.0001

Adiponectin/FVC (l)*

−0.34

< 0.0001

Adiponectin/TLC (l)

−0.28

0.001

Adiponectin/RV%TLC*

0.24

0.004

Resistin/FEV1 (%w.n.)*

−0.2

0.015

TNF-α/RV (l)*

0.26

0.002

CCL16/RV%TLC*

0.38

< 0.001

 

In the whole group, statistically significant correlations between level of adiponectin, resistin, TNF-α and CCL16 protein and spirometric and plethysmographic indices were shown. Correlations with the degree of hyperinflation measured with RV%TLC were shown only for adiponectin and CCL16 protein.

 

Discussion

The obtained results have shown differences in body composition of COPD patients, depending on the presence lung hyperinflation defined as an elevated RV/TLC ratio. Guera et al., while comparing patients with emphysema and chronic bronchitis, observed malnutrition defined as BMI < 18 kg/m2 more frequently in patients with emphysema, compared to patients with chronic bronchitis and asthma, in whom BMI > 28 kg/m2 was more frequent [11]. Kurosaki et al. showed that in patients with pulmonary emphysema diagnosed at chest CT, the severity of emphysematous lesions correlated with muscle and fat mass [12]. Furthermore, in COPD patients, a larger area of abdominal fat measured at CT was shown in comparison with the control group. This area increased with the severity of COPD, and correlated positively with the degree of dyspnea. In patients with emphysema, a negative correlation of the degree of emphysema with waist circumference, fat free body mass, body fat mass and subcutaneous fat area was shown [13]. We did not find differences in BMI between the groups. Patients with lung hyperinflation had a lower fat free body mass, muscle mass and body water and a higher proportional body fat content. The mean FEV1% in the group was < 50% predicted and was statistically lower, compared to the group without hyperinflation, in addition, in the group with hyperinflation, improvement in FEV1 after administration of salbutamol was smaller. The reversibility test was negative in both groups. In the study group, a negative correlation between the degree of hyperinflation and total body water and FFMI and MMI was shown, what confirms the presence of body composition disorders, particularly in patients with emphysema. The disorders may be the effect of lower physical activity [14], higher energy expenditure and systemic inflammation. The degree of hyperinflation and the values of FEV1 are independent factors that influence mortality [15]. Patients with hyperinflation measured with IC/TLC ratio < 0.25, in the study by Casanova et al. had 3.15 times higher mortality risk than patients with IC/TLC > 0.25 [16]. What is the role of systemic inflammation in the process? Deterioration of functional parameters is related to increased inflammatory markers [3]. In the group with hyperinflation, patients with worse functional parameters had significantly higher serum levels of IL-6, resistin and CRP. The literature evaluates systemic inflammation in COPD in various aspects. Piehl-Aulin et al. showed an elevated level of high-sensitivity (hs)CRP in stable COPD patients, compared to the control group; in the same group, they observed an elevated concentration of IL-6 in patients in FEV1 < 50% predicted, and IL-8 in patients with a severe stage of the disease. However, the authors did not show an elevated concentration of TNF-α, compared to the control group, or correlation of its level with the severity of the disease [17]. In another study, an increased level of TNF-α and IL-8 in COPD patients, compared to healthy smokers was not shown [18]. Whereas Pinto-Plata demonstrated that TNF-α and IL-6 levels increase with COPD severity of [19]. Engström et al. showed a negative correlation between concentration of CCL16 protein and the degree of hyperinflation measured with RV/TLC, whereas in patients with FEV1%FVC < 0.7, a negative correlation between CRP and FEV1, FVC, RV/TLC and DLCO was found [19]. Fat tissue is also the source of active substances that participate in systemic inflammation [20, 21].

Adiponectin, which is secreted by fat tissue, has an anti-inflammatory effect. Its level decreases in obese patients and increases with the degree of COPD progression [22]. In the study group, the level of adiponectin did not depend on the degree of hyperinflation. Another factor that is secreted by fat tissue is resistin [23]. Its main role is to maintain carbohydrate homeostasis. It was shown that resistin is related to obesity, type 2 diabetes, atherosclerosis and chronic inflammation [24]. Literature presents inconsistent data on the level of resistin in patients with obstructive diseases. Some authors have shown that the level of resistin increases with the severity of the disease [25], however, others have not found differences in its concentration between COPD patients and the control group [26]. In our study group, the serum resistin in patients with hyperinflation was statistically higher, furthermore, resistin correlated weakly but significantly with FEV1 (% pred.), which indirectly proves its relation to systemic inflammation in COPD patients. It seems practical to assess body composition and systemic inflammation in COPD patients, particularly in those with predominant emphysema.

 

Conclusions

COPD patients with lung hyperinflation have had lower FFMI, TBW, MMI and more body fat.

In patients with lung hyperinflation, elevated levels of inflammatory markers was found, what may indicate a more advanced progression of the disease.

Body composition disorders and more active systemic inflammation in patients with lung hyperinflation may imply poor prognosis.

 

Conflict of interest

The authors declare no conflict of interest.

 

Address for correspondence: dr n. med. Renata Rubinsztajn, Klinika Ch. Wewnętrznych, Pneumonologii i Alergologii WUM, ul. Banacha 1a, 02–097 Warszawa, tel.: + 48 22 599 851, faks: + 48 22 599 15 60, e-mail: rrubinsztajn@wum.edu.pl

 

DOI: 10.5603/PiAP.2015.0019

Received: 14.09.2014

 

References:

  1. Śliwiński P, Górecka D, Jassem E, Pierzchała W. Zalecenia Polskiego Towarzystwa Chorób Płuc dotyczące rozpoznawania i leczenia przewlekłej obturacyjnej choroby płuc. Pneumonol Alergol Pol. 2014; 82: 227−263.

  2. Thomas M, Decramer M, O’Donnell DE. No room to breathe: the importance of lung hyperinflation in COPD. Prim Care Respirator J 2013; 22: 101−111.

  3. Gan WQ, Man SF, Senthilselvan A, Sin DD. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax 2004; 59: 574−580.

  4. Raguso CA, Luthy C. Nutritional status in chronic obstructive pulmonary disease: role of hypoxia. Nutrition 2011; 27: 138−143.

  5. Landbo C, Prescott E, Lange P, Vestbo J, Almdal TP. Prognostic value of nutritional status in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160: 1856−1861.

  6. O’Donnell DE, Revill SM, Webb KA. Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 164: 770−777.

  7. Wilson DO, Rogers RM, Wright EC, Anthonisen NR. Body weight in chronic obstructive pulmonary disease. The National Institutes of Health Intermittent Positive-Pressure Breathing Trial. Am Rev Respir Dis 1989; 139: 1435−1438.

  8. Global Strategy for Diagnosis, Management, and Prevention of COPD, www.goldcopd.org. 2010.

  9. Tomalak W, Antczak A, Boros P. et al. Zalecenia Polskiego Towarzystwa Chorób Płuc dotyczące wykonywania badań spirometrycznych. Pneumonol Alergol Pol. 2006; 74 (Suppl. 1).

  10. Diez Herranz A. RV/TLC% ratio: alternative criteria of normality. Eur Resp J 1995; 8: 1812−1813.

  11. Guerra S, Sherrill DL, Bobadilla A, Martinez FD, Barbee RA. The relation of body mass index to asthma, chronic bronchitis, and emphysema. Chest 2002; 122: 1256−1263.

  12. Kurosaki H, Ishii T, Motohashi N, Motegi T, Yamada K, Kudoh S. et al. Extent of emphysema on HRCT affects loss of fat-free mass and fat mass in COPD. Inter Med 2009; 48: 41−48.

  13. Furutate R, Ishii T, Wakabayashi R. et al. Excessive visceral fat accumulation in advanced chronic obstructive pulmonary disease. Inter J Chron Obstruct Pulmon Dis 2011; 6: 423−430.

  14. Monteiro F, Camillo CA, Vitorasso R. et al. Obesity and physical activity in the daily life of patients with COPD. Lung 2012; 190: 403−410.

  15. Martinez FJ, Foster G, Curtis JL et al. Predictors of mortality in patients with emphysema and severe airflow obstruction. Am J Respir Crit Care Med 2006; 173: 1326−1334.

  16. Casanova C, Cote C, de Torres JP et al. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2005; 171: 591−597.

  17. Piehl-Aulin K, Jones I, Lindvall B, Magnuson A, Abdel-Halim SM. Increased serum inflammatory markers in the absence of clinical and skeletal muscle inflammation in patients with chronic obstructive pulmonary disease. Respiration 2009; 78: 191−196.

  18. Liu SF, Chin CH, Wang CC, Lin MC. Correlation between serum biomarkers and BODE index in patients with stable COPD. Respirology 2009; 14: 999−1004.

  19. Pinto-Plata V, Casanova C, Mullerova H. et al. Inflammatory and repair serum biomarker pattern: association to clinical outcomes in COPD. Respir Res 2012; 13: 71.

  20. Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004; 15: 2792−2800.

  21. Wernstedt Asterholm I, Tao C, Morley TS. et al. Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling. Cell Metab 2014; 20: 103−118.

  22. Garcia P., Sood A. Adiponectin in pulmonary disease and critically ill patients. Curr Med Chem 2012; 19: 5493−5500.

  23. Kim KH, Lee K, Moon YS, Sul HS. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 2001; 276: 11252−1156.

  24. Karbowska A, Boratynska M, Klinger M. Resistin: a pathogenic factor or a biomarker of metabolic disorders and inflammation? Postepy Hig Med Dosw (Online) 2009; 63: 485−491.

  25. Al Mutairi SS, Mojiminiyi OA, Shihab-Eldeen A., Al Rammah T., Abdella N. Putative roles of circulating resistin in patients with asthma, COPD and cigarette smokers. Dis Markers 2011; 31: 1−7.

  26. Breyer MK, Rutten EP, Vernooy JH. et al. Gender differences in the adipose secretome system in chronic obstructive pulmonary disease (COPD): a pivotal role of leptin. Respir Med 2011; 105: 1046−1053.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Czasopismo Pneumonologia i Alergologia Polska dostęne jest również w Ikamed - księgarnia medyczna

Wydawcą serwisu jest "Via Medica sp. z o.o." sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl