Impact of anemia on functional state of patients with chronic obstructive pulmonary disease

Alexandru Corlateanu1, Gloria Montanari2, Serghei Pylchenko1, Victor Botnaru1, Victoria Sircu1

1Department of Respiratory Medicine, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Moldova, 2Department of Respiratory Diseases, Department of  Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy

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Abstract

Background: The occurrence and prevalence of anemia in patients with chronic obstructive pulmonary disease (COPD) has been little studied. Recent studies prove that anemia in patients with COPD is highly prevalent and associated with increased mortality. Anemia is such a common and simple clinical finding that its real physiologic relevance in COPD can be frequently underestimated.

The aim of this study was to determine the prevalence of anemia in patients with COPD and to analyse the associations between hemoglobin levels and some clinical outcomes.

Methods: 158 consecutive patients with COPD were recruited into the study. Spirometry (FEV1, FVC, FEV1/FVC), hemoglobin levels, dyspnoea by MRC scale, exercise capacity by 6-minute walking distance (6MWD) test, the BODE index were evaluated. The comorbidities were assessed by Charlson Comorbidity Index (CCI).

Results: All patients were distributed according to the age in 2 groups: 80 elderly patients, mean age 72.2 ± 4.82 years and 78 younger patients, average age 56.8±3.94 years. Patients had the similar degree of bronchial obstruction, measured by FEV1,%: 42.3±12.82% versus 42.7±14.44% (p>0.05). Anemia was present in 25 (31%) elderly patients and in 22 (28%) young patients with COPD. Older patients with anemia had more comorbidities and higher BODE than nonanemic persons (CCI 3.16±1.18 versus 2.76 ±1.37, p<0.05 and BODE 7.3±1.5 versus 6.8±1.84, p<0,05). Mean MRC values were significantly higher (4.04±0.74 versus 3.73±0.59, p<0.05) and mean 6MWD was significantly shorter (181±69 m versus 221±85 m, p<0.05) in anemic in comparison with nonanemic elderly patients. The forward stepwise regression analysis shows that the level of hemoglobin is an important predictor of dyspnoea and an exercise capacity in elderly COPD patients which explains 21% of the MRC scale and 17% of the exercise capacity.

Conclusion: Anemia in COPD is an independent risk factor for worsening of dyspnoea and reducing functional capacity.


 

Introduction

Chronic obstructive pulmonary disease (COPD) is a major problem for public health worldwide and an important cause of morbidity and mortality at the global level. Its burden is expected to increase progressively in the next years (1).

The association of the COPD with anemia is widely discussed during the last years in literature (2, 3). It happens because COPD is a disease that was traditionally considered as an inductor of polycythemia (4, 5).

The connection between the anemia and important clinic parameters in patients with COPD is also characteristic for the other chronic conditions. Therefore, the strong association between the anemia and morbidity, increased mortality and decreased quality of life related to health are well studied in such pathologies like chronic kidney disease, cancer, congestive heart failure and HIV/AIDS infection (6, 7). Moreover, numerous studies have demonstrated the advantages of anemia correction in patients with these chronic pathologies that leads to the improvement of the functional state and physical activity tolerance, dyspnea decrease and amelioration of the quality of life (8, 9). Regarding COPD there were recently made just several minor studies, in which the role of anemia correction concerning the clinic parameters was examined (10).

 

Objectives

  • The evaluation of the anemia impact on the functional state in the older and young adult patients with COPD.
  • The determination of the predictors of dyspnea and physical activity tolerance in patients with COPD.

 

Methods

Totally, 158 patients were included in the study, 111 (70%) of which were males and 47 (30%) – females, aged between 44 and 80 years, the average age being 64,6 ± 8,9 years.

The positive diagnosis of COPD was established according to the GOLD classification, 2006 and ATS / ERS, 2004 (11, 12). The COPD diagnosis was based on the patient history of exposure to risk factors and presence of the obstructive syndrome, partially reversible or irreversible, with or without the presence of the symptoms. There were analyzed spirometry data, BODE index, physical activity tolerance and quality of life indices.

Statistical analysis: the correlation of the parameters was determined by Spearman correlation coefficient (R) appreciation. Multiple logistic regression (forward stepwise regression) has been also used for calculation.

 

Results

All the patients with COPD were divided in three groups according to the plasmatic level of the hemoglobin: 1 – patients with anemia (hemoglobin level below 130 g/l for both males and females); 2 – patients with polycythemia (hemoglobin level over 170 g/l for males and over 150 g/l for females); 3 – patients with normal level of hemoglobin.

Low level of hemoglobin was determined in 22 of 78 young adults (28%) with COPD and in 25 of 80 elderly patients (31%) with COPD.

The groups of young adult patients and older patients were divided according to the presence of anemia (table 1 and table 2). 

In the young adult patients group the average level of hemoglobin and number of erythrocytes in anemic and non-anemic patients was 118.9 ± 9.8 g/l and 4.2 ± 0.4 x 1012 and 147.8 ± 14.6 g/l and 4.9 ± 0.5 x 1012 respectively (p < 0,0001). It is important to mention that both groups of patients had the similar age (p > 0.05) and grade of airway obstruction (p > 0.05).

Young adult patients with anemia showed more severe dyspnea that was quantified according to the MRC breathlessness scale in comparison to the patients without anemia (3.8 ± 1.13 vs. 3.1 ± 0.65 points respectively, p < 0.05). Anemic patients showed more comorbidities: Charlson index was 2.36 ± 1.3 vs. 1.9 ± 1.2 in non-anemic patients (p < 0.05). Besides, the BODE index was higher in anemic patients (5.9 ± 2.04 vs. 5.0±2.3 points) (p < 0.05).

The exercise capacity quantified with the help of the 6-minute walk test was shorter in the patients with the low level of hemoglobin. The traversed distance in the 6-minute walk test was noticeably reduced in the anemic patients (226.3 ± 80.8 m vs. 266.8 ± 95.1 m in non-anemic patients) (p < 0.05).

 

Table 1 Young adult patients with COPD characteristics according to the anemia presence

 

Anemic patients

n=22

Non-anemic patients

n=56

p

Mean

SD

Mean

SD

Age, years

57.1

3.76

56.7

4.04

> 0.05

FEV1, l/s

1.4

0.5

1.4

0.53

> 0,05

FEV1, %

45.4

14.09

41.6

14.56

> 0.05

Erythrocytes, x1012

4.2

0.39

4.9

0.52

0.0001

Hb, g/l

118.9

9.77

147.8

14.58

0.0001

BMI, kg/m2

25.8

6.32

28.7

6.54

> 0.05

MRC, points

3.8

1.13

3.1

0.65

< 0.05

6MWT, m

226.3

80.79

266.8

95.16

< 0.05

BODE, points

5.9

2.04

5.0

2.3

< 0.05

Charlson index

2.36

1.3

1.86

1.21

< 0.05

 

The older patients with anemia showed a severe dyspnea level, so the MRC scale was 4.04 ± 0.74 vs. 3.73 ± 0.59 points in non-anemic patients (p = 0.04).

In the group of older patients with COPD, as well as in the group of young adult patients, the number of comorbidities and BODE index were increased in patients with anemia: Charlson index was 3.16 ± 1.18 vs. 2.76 ± 1.37 (p < 0.05) in non-anemic patients; index BODE was higher in anemic patients (7.3 ± 1.5 vs. 6.8 ± 1.8) (p < 0.05).

The traversed distance in the 6-minute walk test was shorter (181.4 ± 69.2 m vs. 220.8 ± 85.9 m) (p < 0.05). The level of dyspnea, evaluated by the MRC breathlessness scale was as well higher in anemic patients (4.04 ± 0.7 vs. 3.73 ± 0.6, p < 0.05).

The aim of the multiple regression (term used by Pearson, 1908) is to detect the relation between a dependent variable (the dyspnea level that is quantified by the MRC breathlessness scale) and a majority of independent variables (age, FEV1, level of hemoglobin, BMI, presence of comorbidities assessed by Charlson index and CDS index).

 

Table 2 Older patients with COPD characteristics according to the anemia presence

 

Anemic patients

n=25

Non-anemic patients

n=55

p

 

 

Mean

SD

Mean

SD

Age, years

73.5

5.59

71.69

4.36

> 0.05

FEV1, l/s

1.01

0.38

1.13

0.44

> 0.05

FEV1, %

42.29

13.05

42.35

12.84

> 0.05

Erythrocytes, x1012

4.01

0.54

4.9

0.59

0.000001

Hb, g/l

113.48

14.1

151.84

15.78

0.0001

BMI, kg/m2

26.87

5.28

26.76

6.28

> 0.05

MRC, points

4.04

0.74

3.73

0.59

0.04

6MWT, m

181.36

69,2

220.8

85.86

0.04

BODE, points

7.32

1.55

6.8

1.84

< 0.05

Charlson index

3.16

1.18

2.76

1.37

< 0.05

 

In order to identify the independent risk predictors in older patients for dyspnea worsening, the multiple logistic regression was applied. The statistic model chosen as independent risk factors for dyspnea in patients involved in the research the following: FEV1 and hemoglobin level. The determination coefficient R2 was 0.25 which means that the 25% of the dyspnea variability is explained by the FEV1 variability and hemoglobin level (table 3).

 

Table 3 Multiple regression results in older patients with COPD in the identification of the independent risk factors for dyspnea

 

Beta

SE

t (73)

p

Age

0.095

0.11

0.89

0.37

FEV1, %

-0.37

0.11

-3.4

0.001

Hemoglobin

-0.21

0.1

-2.04

0.04

BMI

-0.05

0.11

-0.43

0.66

Charlson index

0.01

0.11

0.09

0.92

CDS

0.20

0.11

1.8

0.06

 

 

Discussion

The first study that determined the prevalence of anemia and polycythemia in patients with COPD and the relation between the hemoglobin level and clinic evolution of COPD (the hemoglobin impact on the symptomatology, physical activity tolerance and mortality) was carried out by Cote and colleagues in 2007 (13). The anemia prevalence was 17% and this value is smaller in comparison to our data, what could be explained by the higher number of patients examined, 677 patients vs. 158 patients in our research. Meanwhile, like in our study the hemoglobin level was an independent risk factor and predictive for the dyspnea severity and reduced exercise capacity.

In another recent study Ranieri and colleagues reported on the high prevalence of anemia (in 48% of older hospitalized patients with COPD), that could be explained by the higher average patient’s age (81±7 years) and more abnormal functional state (Barthel index 71±31%) in comparison to our study.

In our research the anemia prevalence was significant in older patients with COPD (31%) and in middle-aged patients with COPD (28%). Anemia level was independently related to the high dyspnea level and reduced exercise capacity assessed by the 6-minute walk test.

In chronic diseases anemia is associated and with COPD because the inflammatory profile in COPD includes the mediators which can induce anemia (IL-1, TNF-α, IFN-Ɣ) and other important factors: malnutrition and smoking. In the future, the prospective studies are necessary for detection of anemia prevalence in COPD and its clinic impact. The advantages of hemoglobin correction are needed as well.

Schonhofer and colleagues (14) demonstrated that in 20 patients with severe COPD the anemia correction with blood transfusion reduces minute ventilation and work of breathing caused by COPD, supposing that the anemia correction could bring to dyspnea decrease and physical activity tolerance amelioration. Another study demonstrated that in 5 patients with severe anemia and COPD the adequate anemia correction increases chance to stop the invasive ventilation in these patients.

The pathophysiological mechanisms of the anemia in COPD are similar to the ones in the other chronic diseases. The mediators of the inflammatory response, such as IL-6, tumor necrosis factor-α, interferon-γ are potentially involved in the development of anemia in the chronic diseases, such as COPD (15). The increased levels of inflammatory cytokines reduce the red blood cells survivability, which demands the vigorous activity of the bone marrow. However, the bone marrow cannot respond adequately. This is caused by a relative erythropoietin resistance due to an attenuated ability of red blood cells progenitors to respond to erythropoietin. An attenuated mobilization of reticuloendothelial iron stores is an additional pathophysiologic factor (16).

The main limitation of our research can be considered an insufficient amount of the analyzed sample size. Our study didn’t have the objective to examine how the anemia treatment can affect the major clinic parameters in patients with COPD, but the obtained results reconfirm the hypothesis that the anemia in patients with COPD is associated with many serious consequences. In spite of the fact that anemia represents a possible systemic manifestation of COPD it could be also an associated phenomenon, that marks patients with severe disease. In addition, the hypothesis about the amelioration of the clinical parameters after anemia correction seems to be rational. However, this hypothesis needs to be verified in the further clinic studies.

 

Conclusion

In our research the anemia prevalence was 28% in the group of the young adult patients with COPD and 31% in older patients with COPD. Anemia in COPD is an independent risk factor for worsening of dyspnoea and reducing the functional capacity.

 

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