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July2007 Vol.44 Issue:      2 Table of Contents
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Neuropsychological Status and Health Related Quality of Life in Patients with Chronic Obstructive Pulmonary Disease

Mohamed A. Ahmed1, Khaled A. Mohamed1, Alaa Eldin M. Darweesh1, Safaa M. Wafy2, Hoda A. Makhlouf2

Departments of Neurology & Psychiatry1, Chest2, Assiut University



ABSTRACT

Background: A variety of neuropsychological factors may influence the quality of life of chronic obstructive pulmonary disease (COPD) patients beyond the extent of physical problems. This study aimed to investigate sub-clinical neuropsychological changes in patients with COPD; having different degrees of hypoxemia and their health related quality of life. Subjects and Methods: the study included 54 COPD patients compared with 40 normal healthy volunteers matched for age and sex as controls. COPD patients included 21patients without respiratory failure (RF) (38.9%) and 33 patients with RF (61.1%). All subjects underwent: study of Events Related Potentials (ERPs), Mini-Mental State Examination (MMSE), Kaufman Short Neuropsychological Assessment Procedure (K-SNAP) and Symptom Chick List-90-Revised (SCL-90-R). Patients were subjected to, spirometry, blood gases, conventional wakeful electroencephalography (EEG), and St. George Respiratory Questionnaire (SGRQ) examination. Results: Diffuse slowing in EEG reported in 54.5% of patients with RF and in 23.8% of patient without RF. There was a significant prolongation in P2L, N2L, and P3L in COPD patients without and with respiratory failure than controls; also, there was significant lower amplitude of P300 (P3A) in COPD patients with RF than the other groups. Both COPD patients without & with respiratory failure have mean total score and language score of MMSE significantly lower than the controls. The mean scores of Impairment Index on K-SNAP of COPD patients with and without RF were statistically significantly higher than the controls. Higher percentages of COPD patients with and without respiratory failure showed tendency to perform on the medium complex cognitive tasks better than the high complex cognitive tasks. COPD patients had significantly higher scores for many psychiatric symptoms than the controls and this was more remarkable among those with respiratory failure. Scores of all items of SCL-90-R were positively correlated to duration of COPD affection, severity of the disease and to different SGRQ components. COPD patients with RF have scores in all items of SGRQ significantly higher than those without RF. Conclusion: There were sub-clinical diffuse organic brain affection, associated with impairment of cognitive functions and many psychological troubles in COPD patients which were related to severity and duration of illness, which represent additional problems to physical effect of COPD, both reflecting more impairment in quality of life. So, early discovery and correction of these factors might help in improvement of quality of life of COPD patients.

(Egypt J. Neurol. Psychiat. Neurosurg., 2007, 44(2): 489-505)

 




INTRODUCTION

 

Chronic obstructive pulmonary disease (COPD) patients displayed mild cerebral deficits, which are related partially to pressure of arterial oxygen (PaO2) and to the degree of pulmonary impairment1. COPD patients suffered decrements in neuropsychological functioning suggesting of organic mental disturbance and the rate of neuropsychological deficits rose from 27% in mild hypoxemia to 61% in severe hypoxemia2. Also, cognitive impairment is known to affect a large number of COPD patients3 and its severity is directly related to age and duration of COPD4. Global ischemia leads to a variable degree of impairment of cognitive abilities5. Progressive hypoxemia leads to an increase in blood viscosity and pulmonary vascular resistance, which result in corpulmonale and a decrease in cerebral perfusion6,7. Because of the proposed link between cognitive functioning and oxygen transport, the study of cognitive functioning capabilities in older individuals with COPD is of particular interest8.

COPD is a major cause of psychiatric morbidity and it appears that a variety of psychological factors may influence the quality of life of these patients, over and above the extent of physical problems. During the illness, COPD patients may experience gross difficulties in their emotional functioning, sleep and rest, physical mobility, social interaction, activities of daily living, recreation, work and finance. It is generally accepted that patients with COPD frequently suffer from depression and anxiety9, and impairment in quality of life10.

Anxiety is common in individuals with obstructive lung diseases. Some studies report as many as 30% of individuals with COPD have it, as opposed to 3-5% of the general population9. Depression is a source of increased disability in COPD, and, as in other chronically ill patients populations, is often unrecognized and untreated. Nearly half of all patients experience some depressive symptoms which improved with multidisciplinary rehabilitation and at least one-fifth have had one or more major depressive episodes, frequently of long duration which may require specific pharmacotherapy11. 

In COPD, measures of health-related quality of life (HRQL) are nowadays frequently used as descriptive instruments or as outcome measures12. Since cure is still impossible for most COPD patients, a major goal of care is to improve HRQL13.

This study aimed to investigate objectively sub-clinical neuropsychological changes in patients with chronic obstructive pulmonary disease; having different degrees of hypoxemia and their health related quality of life. 

SUBJECTS AND METHODS

 

The present study was carried out on fifty-four COPD patients. They were selected from those consecutively attending the out patients clinic of Chest diseases department. They admitted to Chest diseases department of Assiut University Hospitals for investigation. The diagnosis of COPD was based on the definition provided by the American Thoracic Society6; a maximal forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) ratio of less than 0.7 and an FEV1 of less than 80 % of the predicted value. The mean age of the studied patients was 60.7±0.7 years. They were subdivided according to their arterial blood gasses into two groups: 1) Twenty-one patients without respiratory failure (38.9%) with mean age 62.5±1.2, 16 years (76.2%) of them were males and 5 (23.8%) were females. 2) Thirty-three patients with respiratory failure (61.1 %) (Pa O2 less than 60 mmHg), with mean age 64±1.1 years, 29 (87.9%) of them were males and 4 (12.1%) were females. In addition to forty apparently healthy age and sex matched volunteers as a control group.

Patients with previous cerebrovascular, or cardiovascular disease, focal neurological deficit, history of head trauma, patients with dementia, or major psychiatric disorders and intake of drugs that might affect the cognitive performance were excluded from the studied sample. Also, Patients with diabetes mellitus, uremia, hepatic or other metabolic and endocrine disturbances were excluded.

 

All COPD patients were subjected to:

1.      Chest, neurological and psychiatric history and examination.

2.      Chest X-ray to confirm the diagnosis of COPD and to exclude other associated condition as TB or pneumonia ... etc.

3.      Spirometry was used to determine forced expiratory volume in 1st second (FEV1), the forced vital capacity (FVC), and FEV1/FVC %. These parameters represent measurement of severity of COPD. Results were expressed in liters and liters/second and as percentage of normal value for gender, age, and height (percent predicted). Spirometry was assessed with Spirometer WIO Recorder Assembly; CAT No. 752609; SER 54065, A30; Sensor Medics Corporation; Yorba Linda, (A) and using standard protocols.

4.      Resting arterial blood gas analysis by blood gases analyzer including pH, arterial O2 tension (PaO2), arterial CO2 tension (PaCO2), HCO3 and O2 saturation. The apparatus is Lab850; CHIRON/ Diagnostics; Critical Care System.

5.      Conventional wakeful electroencephalogram (EEGs) using 10 channel Nihon Kohden equipment model (4217) employing scalp electrodes placed according to the international 10-20 system with bipolar and referential montages. Hyperventilation and photic stimulation were used as provocative tests.

6.      Event Related Potentials (ERPs) study using an auditory discrimination task paradigm by presenting a series of binaural 1,00Hz (standard) versus 2,00 Hz (target) tones at 70 dB with a 10 ms rise/fall and 40 ms plateau time. Tones were presented at a rate of 1.1/s with target tones occurring randomly with a 0.2 probability. Subjects were sitting with their eyes closed and were instructed to mentally count the number of the target, but not the frequent tones, and then asked to report the number of target tones counted at the end of each run. Evoked potentials were recorded from the scalp electrodes placed at CZ and PZ and were referred to linked ear. Filter sitting were 0.5 and 70 Hz, analysis time 1 second, sensitivity 20 μν and duration of stimulation 0.1 ms. To assess performance accuracy at the end of each session, the patient's count was compared with the actual number of target tones presented. Two or three trials were performed in order to demonstrate the consistency of the wave forms. Latencies and amplitudes of P200 and P300 were measured from stimulus artifact to the first and second major positive peaks with a range of 150- 250 and 250- 500ms, respectively for latencies and amplitudes were expressed in microvolt. Also, the first and second negative peaks (N100 and N200) preceding the previous positive peaks were measured. ERPs were done using a Nihon Kohden equipment model (7102).

7.      Evaluation of cognitive functions through Mini-Mental State Examination (MMSE)14 and Kaufman Short Neuropsychological Assessment Procedure (K-SNAP) (15).

8.      Assessment of psychiatric symptoms using the Arabic version of the Symptom Chick List-90-Revised (SCL-90-R)16.

9.      Assessment of the quality of life using the Arabic version of St. George Respiratory Questionnaire (SGRQ)17.

 

The control group was subjected to: Chest, neurological and psychiatric history and examination, evaluation of cognitive function and ERPs by the same protocol of the patients’ group. 

 

Instruments:

Mini-Mental State Examination (MMSE)14: It is a widely used instrument for monitoring cognitive impairment for research and clinical populations. The first of two sections asks questions about orientation, memory and attention. The second section tests the ability to name objects, follow verbal and written commands, write a sentence, and copy a complex polygon. It requires only 10 minutes to administer and score. It is well standardized, and reliability studies indicate that inter-rater reliability is 0.82 or better and test retest reliability is 0.89 or better.

Kaufman Short Neuropsychological Assessment Procedure (K-SNAP)15: It is a brief individually nationally normed measure of an adolescence or adult' ability to demonstrate intact mental function at 3 levels of cognitive complexity: A) Least complexity, attention – orientation, b) Medium complexity: simple memory and perception skills and C) Most complex: reasoning and planning abilities. It is intended for people aged 11 to over 85 years. The administration time of the test is about 30 minutes. The test was translated into Arabic language and measures of reliability, validity and standardization were done in a non-published work18. Test- retest reliability correlation coefficient was r = 0.73-0.81. 

Symptoms Chick Lis t- 90- Revised (SCL-90-R): it is a 90-item self-report symptom inventory developed to reflect the psychological symptom pattern of psychiatric and medical patients. Each item of the “90” is rated on a 5-point scale of distress (0-4), ranging from non-at-all at one pole to “extremely “at the other pole. Psychological symptoms include; somatization, obsessive compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism. Under usual circumstances, the SCL-90-R requires between 12-15 minutes to complete. On this scale, higher scores indicate a more severe symptom. Patients have score of 60 or more at any of these symptoms was considered at high risk and need psychiatric help.

St. George Respiratory Questionnaire (SGRQ)17: It is a standardized, disease-specific; self-administered health status instrument consisting of 50 items grouped under three components, namely, symptoms, activity, and impact.  The symptom component includes 8 items to assess the frequency of cough, sputum production, and dyspnea, and the duration and frequency of attacks of dyspnea or wheeze (problems caused by specific respiratory symptoms). The 16 items in the activity component identify physical activities that induce dyspnea or that are affected by dyspnea (restriction of activity by dyspnea). The 26 items in the impact component broadly assess the impact of the disease on different aspects of social and emotional functions, and on expectations for health (impact on everyday life caused by the disease). The response to each item is in the form of "true" or "false" answers for the activity and impact components. Component scores are calculated using empirically determined weights attached to each item, and a total score is calculated based on the responses to all items. The scores ranged from 0–100% of possible distress. A higher SGRQ score, either the total score or individual component score, represents a poorer quality of life. The mean completion times for the SGRQ have been reported to be 10 min., not including the time required for scoring.

Ethical aspects:

The Institutional Ethical Committee, faculty of Medicine Assiut University, approved the protocol of the study. Each patient and control gave an informed consent to participate in the study.

 

Statistical analysis:

Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS- version 11). All of the results are presented as mean ± SE and frequencies. Univariaite analysis using Chi-square and ANOVA tables were performed to test the significant differences between patients and controls. Comparisons were performed using the Mann-Whitney U test for continuous variables, while the x2 test was used for comparisons of proportions. Multivariate analysis was performed by multiple logistic regressions. A p value ≤0.05 was regarded as statistically significant. Parametric and nonparametric (Spearman) correlations were calculated to study the relationships between different variables. Pearson correlation was also used for comparing groups.

 

RESULTS

 

Clinical features of COPD patients:

Cough and expectoration were noted in all COPD patients. Among those without respiratory failure; dyspnea in 95.2 % and chest wheezes in 95.2 %, while patients with respiratory failure reported dyspnea in 97 % and chest wheezes in 87.9 %. The mean values of blood gases and spirometry of patients groups were presented in table (1).

 

Neurophysiological parameters:

Patients without respiratory failure showed diffuse slowing in 23.8%, while paroxysmal slowing and paroxysmal sharp activities occurred in 14.3%. Patients with respiratory failure had diffuse slowing in 54.5%, paroxysmal slowing in 21.2%, focal changes in 15.2 % and paroxysmal sharp activities in 3%. Significant higher percentages of COPD patients with RF have diffuse slowing (P = 0.02), paroxysmal slowing (P = 0.000) and focal changes (P = 0.02) (Table 2).

Regarding event related potentials; there were significant prolongation in P 200 latency (P2L), N2L, and P3L in COPD patients without and with respiratory failure when compared with those of healthy controls. Also, there was significant lower amplitude of P 300 (P3A) in patients with respiratory failure (P <0.01) compared to controls. However, there was no significant statistical difference in these parameters between both groups of COPD patients (P > 0.05 for each) (table 3). In total COPD patients significant negative correlation between FVC % and N2 latency (r = - 0.279, P = 0.04), i.e. as FVC% decrease N2 latency increases (fig. 2). In COPD patients without RF there were significant negative correlation among FEV1 % and FVC % and N200 latency (r = - 0.481, P = 0.02; r = - 0.491, P = 0.02) (fig. 3 & 4). However, in COPD patients with RF, there were no significant correlations among ERPs parameters and spirometric measurements.

 

Mini-Mental State Examination subtest (MMSE):

In the current study, both COPD patients without and with respiratory failure have mean total and language scores of MMSE significantly lower than the controls (P< 0.01 for each in total and P< 0.001 for each in language scores).  We found no significant difference in scores of other items of MMSE among COPD patients (P>0.05 for each). Moreover, there were no significant differences in MMSE items of patients without when compared to patients with respiratory failure (table 4). In total COPD patients and COPD patients with RF there was a significant positive correlation between recall scores and FEV1 % (r = 0.286, P < 0.05, and r = 0.369, P < 0.05 respectively). There was no significant correlation among MMSE subtest or total scores and either all parameters of blood gases, age or duration of the disease (P>0.05 for each).

 

Kaufman Short Neuropsychological Assessment Procedure (K-SNAP):

The mean scores of Impairment Index on K-SNAP of COPD patients with respiratory failure (3.42±1.11) and without respiratory failure (3.95±1.1) were statistically significantly higher than the controls (2.5±0.5) (P = 0.000). However, mean scores of subitems of K-SNAP showed no significant differences among COPD patients (with and without respiratory failure) and controls. Also there were no significant differences between the two patient groups (Table 5).

According to K-SNAP manual, comparison between the scaled score significant difference helps determine whether the person display a significant difference in how he or she process information: sequentially versus simultaneously, auditorially versus visually, or via simple memory versus perception. Significant differences between Gestalt Closure and Number Recall may reflect differences in the person’s sequential versus simultaneous processing of information. The current study showed significant higher percentages of COPD patients with respiratory failure (100%) and without respiratory failure (90 %) have significant differences between Gestalt Closure and Number Recall than the controls (25%) (P = 0.006).

To compare tasks of medium complexity with tasks of high complexity tasks according to K-SNAP manual we compare the Four-Letter Word scaled score (medium complexity task) with scaled scores on Gestalt Closure, Number Recall, and Recall/ Closure Composite (high complexity tasks). The study showed that percentages of COPD patients with respiratory failure (54.5 %) and COPD without respiratory failure (52 %) significant higher than the controls (0.0 %) have significant score differences between Four-Letter Words / Gestalt Closure (P = 0.000). The same was found as regard Four-Letter Words/ Recall/ Closure Composite; 57.1 % of COPD patients without respiratory failure, 54.5 % of patients with respiratory failure and 12.5 % of controls (P = 0.004) (Table 6).

There were no significant correlation among all parameters of pulmonary function tests and subtests of K-SNAP among various groups (P>0.05 for each).

 

SCL-90-R:

COPD patients with and without respiratory failure reported mean scores of all items of SCL-90-R higher than the controls. Patients without respiratory failure recorded mean scores in depressive symptom significantly higher (p< 0.01) than the controls, while those with respiratory failure recorded mean scores in somatization, obsession, depression, paranoid ideation, psychoticism (p< 0.001 for each) and anxiety (P<0.01) significantly higher than the controls. No significant difference between the two patients’ groups (table 7). In patients without respiratory failure; hostility, somatization and phobia had highest frequency (47.6%, 42.9% and 38.1% respectively) followed by anxiety (23.8%), paranoid and psychoticism (14.3% for each of them).  In patients with respiratory failure; somatization, anxiety, hostility and phobia had highest frequency (48.5%, 39.4%, 33.3% and 33.3% respectively) followed by depression (15.2%), paranoid ideation (15.2%) and psychoticism (12.1%). No significant differences in psychiatric disorders between patients with and without respiratory failure (table 8). There were significant positive correlation between scores of all SCL-90-R items and duration of the disease (P = 0.02). Depression and anxiety symptoms showed negative correlations to values of FEV1and FVC (p = 0.01, 0.02 for each). Depression showed positive correlation to total, activity and impact SGRQ scores (P < 0.05), anxiety and sensitivity were positively correlated only to activity score (P < 0.05), while somatization was positively correlated only to impact score (P < 0.05).

 

SGRQ score

As regarded SGRQ scores, patients with RF have mean scores significantly higher than those without RF (P=<0.05) for the four SGRQ component scores (Fig. 1).  In total COPD patients, total, symptom and impact scores were positively correlated to duration of illness (P< 0.05). Impact score was negatively correlated to values of FEV1 and FVC (P< 0.05) while total score was negatively correlated to FEV1 value (P< 0.05) only. Impact score was negatively correlated to Pa O2 and O2 sat values (0.04, 0.05 respectively), while total score was negatively correlated only to Pa O2 (P = 0.04).

Table 1. Arterial blood gases and spirometric parameters among patients groups.

 

Variable

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

Blood gases

  pH

  PaO2

  PaCO2

  HCO3

  O2 saturation

Pulmonary functions

  FEV1 L/sec

  FEV1 %

  FVC L/sec

  FVC %

  FEV1/FVC%

  PEF L/sec

  PEF%

  FEF25-75 L/sec

  FEF25-75 %

Mean ± SE

7.42 ± 0.04

72.10 ± 11.40

47.90 ± 11.45

30.07  ±7.22

94.39 ± 2.79

 

0.86 ± 0.39

38.29  ±16.78

1.26  ±0.50

43.52  ± 14.58

59.05  ±10.09

1.76  ±0.85

28.95  ±14.92

0.77  ±0.48

31.05 ± 22.90

Mean ± SE

7.41  ±0.05

44.55  ±9.28

54.60  ± 10.25

34.64  ±5.81

76.97 ± 12.89

 

0.66 ± 0.25

27.26 ± 8.95

1.24  ±0.50

34.99 ± 12.81

54.68 ± 9.13

1.49 ± 0.72

22.71 ± 8.79

0.42 ± 0.15

16.82 ± 5.47

 

Table 2. Patterns of EEG in studied groups.

 

EEG patterns

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

P value

No. (%)

No. (%)

Normal EEG

Diffuse slowing

Paroxysmal slowing

Paroxysmal sharp activities

Focal changes

9 (42.9)

5 (23.8)

3 (14.3)

3 (14.3)

1 (4.8)

9 (27.3)

18 (54.5)

7 (21.2)

1 (3)

5 (15.2)

0.01

0.00

0.01

0.02

0.02

 

Table 3. Event related potentials parameters of the studied sample.

 

ERPs parameters

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

Controls

(No.= 40)

P200 Latency (ms)

177.52 ± 44.45**

175.33 ± 37.57***

140 ± 35.60

N200 Latency (ms)

274  ±49.50*

288.45 ± 63.67**

249.20  ± 37.60

P300 Latency (ms)

382.71  ±70.53**

425.27  ±82.95***

349.30 ± 25.08

P300 Amplitude (µv)

6.15 ± 14.15

4.41 ± 2.30**

6.04 ± 1.81

N.B.: * (significant between patients and controls)

 

Table 4. Mean scores of MMSE subsets of studied groups.

 

MMSE

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

Controls

(No. = 40)

Orientation

Registration

Attention & calculation

Recall

Language

Total

7.95 ± 2.42

2.90 ± 0.30

2.48 ± 2.16

1.95 ± 1.02

6.76 ± 2.19***

21.95 ± 4.60**

8.18 ± 1.96

2.85 ± 0.57

2.58 ± 1.95

2.03 ± 1.29

6.76 ± 2.18***

22.61 ± 3.58**

8.75 ± 1.50

2.88 ± 0.34

2.75 ± 1.89

1.88 ± 1.18

8.75 ± 1.50

25.13 ± 3.26

N.B.: * (significant between patients and controls)

 

Table 5. Mean scores of K-SNAP items of the studied groups.

 

K-SNAP item

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

Controls

 

(No. = 40)

Mental state

Gestalt closure

Number recall

Four letter word

Gestalt/recall

G-Recall/4LW

Impairment Index

7.14 ± 2.44

4.67 ± 3.23

5.67 ± 2.30

0.48 ± 1.08

10.33 ± 5.19

10.95 ± 5.36

3.95± 1.1***

7.76 ± 2.02

4.97 ± 2.70

5.88 ± 2.43

0.48 ± 1.33

10.85 ± 4.30

11.33 ± 4.72

3.42 ± 1.11***

7.5 ± 2.86

5.37 ± 4.35

5.50 ± 1.96

0.38 ± 1.01

10.87 ± 3.70

11.25 ± 3.85

2.5 ± 0.5

N.B.: * (significant between patients and controls)

 

Table 6. Frequency of significant scaled score differences of K- SNAP items.

 

Variable

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

Controls

(No. = 40)

P value

Gestalt Closure/ Number Recall

19 (90 %)

33 (100 %)

10 (25 %)

0.006

Four-Letter Words/ Gestalt Closure

11 (52 %)

18 (54.5 %)

0 (0.0 %)

0.000

Four-Letter Words/ Number Recall

7 (33.3)

10 (30 %)

10 (25 %)

0.76

Four-Letter Words/ Recall-Closure Composite

12 (57.1 %)

18 (54.5 %)

5 (12.5 %)

0.004

 

 

Table 7. Mean scores of psychiatric symptoms of SCL-90-R in patients and controls.

 

SCL-90-R dimensions

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

Controls

(No. = 40)

Mean ±SE

Mean ±SE

Mean ±SE

Somatization

55.8±2.3

57.7±1.4***

51.4±1.8

Obsession

43.1±2.3

47.5±1.4***

40.8±1.5

Sensitivity

43.2±2.1

44.6±1.5

41.6±1.2

Depression

47.1±1.9**

48.5±1.6***

42.6±1.1

Anxiety

48.1±2.6

52.4±2.1**

46.2±1.7

Hostility

49.3±3.1

53±1.8

51.6±2.6

Phobia

52.6±1.7

54.8±2.0***

50.1±2.8

Paranoid ideation

45.7±2.6

48.2±1.8***

41.8±0.9

Psychoticism

45.7±2.1

47.3±1.5***

42.2±0.8

 

 

Table 8. Frequency of psychiatric disorders in COPD patients (cut-off point ≥60).

 

SCL-90-R dimensions

COPD patients without RF

(No. = 21)

COPD patients with RF

(No. = 33)

Controls

(No. = 40)

No. (%)

No. (%)

No. (%)

Somatization

9(42.9%)

16(48.5%)

8(20%)

Obsession

1(4.8%)

2(6.1%)

0

Sensitivity

1(4.8%)

2(6.1%)

0

Depression

2(9.5%)

5(15.2%)

0

Anxiety

5(23.8%)

13(39.4%)

8(20%)

Hostility

10(47.6%)

11(33.3%)

10(25%)

Phobia

8(38.1%)

11(33.3%)

8(20%)

Paranoid ideation

3(14.3%)

5(15.2%)

0

Psychoticism

3(14.3%)

4(12.1%)

0

 

 

Fig. (1): SGRQ Scales among studied groups.

 

 

 

r =-0.279, P<0.05

 

Fig. (2): Correlation between FVC% and N2L in total patients.

r = -0.481, P<0.05

 

Fig. (3): Correlation between FEV1% and N2L in COPD without RF.

 

 

r =-491, P<0.05

 

Fig. (4): Correlation between FVC% and N2L in COPD without RF.


DISCUSSION

 

Results from the present study disclose the presence of diffuse brain pathology in COPD patients whether there were respiratory failure or not as manifested by EEG abnormalities and ERPs parameters. In EEG high rates of diffuse slowing, paroxysmal slowing, paroxysmal sharp activities and focal changes were present in COPD patients.  Also, significant prolongation in P2L, N2L, and P3L were present in both groups of COPD patients. In addition to the significant lower amplitude of P3A in patients with respiratory failure. This was associated with cognitive impairment in the form of significant lower mean total and language scores of MMSE in COPD patients than the controls and higher mean score of Impairment Index on K-SNAP of COPD patients than the controls.

Our findings were consistent with Hialmarsen et al.19 as they reported that COPD patients were cognitively impaired as compared to age matched healthy controls using Mini-Mental State Examination (MMSE). Also Hatice et al.20 showed that total cognitive impairment even in stage 1 stabilized and mild hypoxaemic COPD patients compared with controls, this impairment was more severe in some subtest of short mental test. They found significant direct correlation between total cognitive score and vital capacity. Antonelli et al.21 reported a direct correlation between age and the duration of hypoxaemic hypercapnic respiratory failure and recall and other cognitive functions. Antonelli et al.22 showed that among the patients followed during a two years period, the cognitive decline was more accelerated in that having severe bronchial obstruction.

Grant et al.2 reported that there was moderate to severe neuropsychological test impairment suggestive of cerebral dysfunction in 42% of patients with COPD compared with 14 % of controls. Fix et al.1 revealed that mild cerebral deficits on several neuropsychological tests were significantly related to partial pressure of arterial oxygen (PaO2). Impairment of pulmonary functioning significantly correlated with the degree of alpha frequency slowing over the posterior cortical regions, and the slowest alpha frequencies occurred in those COPD patients with the lowest FEV1/FVC ratios23. The present results go parallel to the explanations of many authors as they reported that in COPD patients there was diffuse pathology due to chronic hypoxia and decreases cerebral perfusion rather than focal ischaemic effects. Cohen et al.24 reported that acute severe or extreme hypoxia have a normal EEG and does not cause neurologic deficits. Chaouat et al.25 and Plywaczewski et al.26 reported that patients with COPD experience oxygen deprivation for prolonged periods, especially during physical exercise, exacerbation of disease, and sleep which aggravates brain damage caused by cerebral hypoperfusion. Van Dijk et al.27 reported that COPD patients with lower arterial oxygen pressure are associated with periventricular white matter lesions. Hamilton et al.28 reported that chronic hypoxia due to chronic obstructive pulmonary disease (COPD) constitutes a stress to cerebral metabolic homeostasis.  Ortapamuk and Naldoken29 demonstrate that cerebral perfusion is significantly altered in COPD patients and hypoxemic patients showed more deterioration in cerebral perfusion and cognitive performance than non-hypoxemic patients.

In the present study the high complexity cognitive tasks were affected more than the medium complex tasks in COPD patients. This finding was reported by others, Grant et al.2, reported that higher cognitive functions (abstracting ability, complex perceptual- motor integration) were most severely affected in hypoxemic COPD patients also, there was decrements in motor speed, strength and coordination which may be related to decreased availability of oxygen to the brain30. Antonelli et al.21 after discriminate analysis of cognitive test scores showed that 48.5 % of patients with COPD had a specific pattern of cognitive deterioration characterized by a dramatic impairment in verbal and verbal memory tasks also cognitive impairment was significantly and positively correlated with age and duration of hypoxic hypercapnia. Stuss et al.31 found that measures of immediate and delay recall, complex attention and speed of information processing correlated highly with arterial carbon dioxide partial pressure and oxygen partial pressure. Kozora et al.32 suggested that COPD patients with mild hypoxemia may perform normally in cognitive measures and oxygen therapy may partially account for preservation of cognitive functions in these patients. Using different neuropsychiatric tests in assessment of cognitive functions Liesker et al.33 concluded that even non – hypoxemic COPD patients showed significant impairments in cognitive performance with no effect in health related quality of life.

Chronic respiratory insufficiency influences the cognitive and somatosensory functions, and indicate that there is a selective vulnerability of evoked potentials to this condition with no significant difference in P 300 amplitude in patients and control as patients had no hypoxemia34. In COPD patients, Reeves et al. (35) reported that there was progressive impairment of the auditory P300 evoked potential latency occurs with increasing severity of COPD. This impairment is present even in patients with mild COPD, suggesting some degree of accompanying cognitive decline early in the course of COPD with worsening as the disease progress. Also they reported Auditory P 300 latency was significantly correlated with the EFV1/FVC ratio (r = -0.56), indicating that increasingly severe airflow impairment is associated with longer auditory P300 latency. Hatice et al.20 showed that there may be impairment in cognitive performance even in early stage stabilized COPD patients this is related with the disease and in Vital Capacity. Also they reported that, P300 latency was prolonged and amplitude was decreased but the differenced was not significant as the sample size was smaller and the patients had mild hypoxemia. 

Our results revealed that depression and anxiety had significantly higher scores in COPD patients. Depression had reported in 15.2% & 9.5% in patients with and without respiratory failure respectively, while anxiety had reported in 39.4% & 23.8% respectively.

Depression and anxiety were nearly the only psychiatric symptoms reported in COPD patients in other studies. Many studies have demonstrated high levels of anxiety and depression among patients with chronic obstructive pulmonary disease36,37,38. Some reported that depression (≤42%) and anxiety (≤50%) are too more prevalent in COPD patients than in the general population. Some studies39,40 reported that the prevalence of depression in COPD patients has been estimated to range from 25% to 74%. Others reported higher rates of anxiety symptoms in COPD patients ranging from 13% to 51%9,41,42.  Also, they found that anxiety has been related to FVC, chest symptoms and dyspnea. Yellowlees and colleagues43 found that rate of anxiety disorders in patients with COPD was 34%. McCathie44 found that patients with COPD had a poor physiological status, and was more anxious than depressed but the symptoms were not within the clinical range of depression or anxiety. Gutierrez-Lobos et al.45 reported that COPD patients had higher prevalence of depressive symptoms and greater impairment of airflow. Depression in COPD is associated with additional disability and a poorer quality of life.

We found that depression, anxiety and other psychiatric symptoms were more frequent in patients with respiratory failure than those without and with increased severity of COPD. Similarly, Van Ede et al and Van Manen et al.37,39 concluded that depressive symptoms are common in patients with COPD and those with severe COPD have a 2.5 times greater risk of developing depression than controls. Dowson et al.38 found that, clinically relevant anxiety, indicated by higher Hospital Anxiety and Depression Scale (HADS), was more common in patients with severe COPD. Also anxiety and total mood symptoms improved during inpatient rehabilitation. Similarly, Withers et al.46 reported that levels of anxiety and depression were high in a significant minority of this group of patients with severe COPD and were significantly improved by pulmonary rehabilitation.  

The present study revealed that depression, anxiety and other psychiatric symptoms were positively correlated to quality of life scores and to the duration of illness. Similarly, Beekman et al., and Kunik et al.36,47, reported that COPD patients who develop anxiety or depression face greater levels of decline, more functional limitations, lower self efficacy, and more serious life events than those with only breathing difficulties. Others showed that anxiety and depression play a larger role in determining patients' quality of life than the COPD severity48,49,50. Psychological distress compounds the negative symptoms of COPD and other respiratory illness, resulting in longer hospital stays, adverse medical outcome, and higher mortality rates. Greater severity of depression in patients with COPD has been associated with diminished health-related quality of life, diminished functional status, impaired coping, greater COPD symptoms, failure of treatment for COPD exacerbations and higher mortality risk39,51-56. Also, anxiety has a negative impact on the quality of life of COPD patients. It is associated with greater disability and impaired functional status, specifically in the areas of general health, physical roles, emotional roles, social functioning, bodily pain, mental health function, and vitality50,57-59.

In the present study, patients with respiratory failure had significantly poor quality of life compared to those without respiratory failure. A similar results was reported by Incalzi who found 54.1% of COPD patients with partially reversible obstruction were recognized to have a distinctive health status profile characterized by a moderate to severe impairment of all components ('Symptoms', 'Activity', 'Impacts') of the SGRQ60.

In this study, the quality of life is markedly affected by duration of the disease, severity and respiratory insufficiency. Similarly; Hajiro61 found that, the scores for the total SGRQ and for the activity component were significantly higher for patients with severe COPD than for patients with moderate COPD and also significantly higher for moderate COPD patients than for mild COPD patients. Moreover, Peruzza62 demonstrated that a decrease in FEV1 is the factor most strictly related to the deterioration of QOL in COPD patients. Oxygen tension in arterial blood (PaO2) has been found to be significantly related to total SGRQ in patients with hypoxaemia63. Oxygen cost of breathing has been reported as a measure of energy utilization by the respiratory muscles64.

In conclusion, this study proved that there were sub-clinical diffuse organic brain affection that was associated with cognitive impairment and many psychological troubles resulted from COPD illness, which were related to the severity and duration of the illness and represent an additional problem to physical effect of COPD, both reflecting more impairment in quality of life. So, early discovery and correction of theses factors might decrease disabilities and help in improvement of quality of life of COPD patients.

 

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الملخـص العربى

 

الحالة العصبية و النفسية و جودة الحياة في مرضى السدة الرئوية المزمنة

 

من المعروف أن الكثير من المتغيرات النفسية والعصبية قد يؤثر على جودة الحياة لمرضى السدة الرئوية المزمنة زيادة على المشاكل الجسدية الناتجة من المرض وقد هدفت هذه الدراسة إلى فحص التغيرات العصبية والنفسية الغير ظاهرة إكلينيكياً وتقييم جودة الحياة لهؤلاء المرضى ممن لديهم درجات مختلفة من نقص الأوكسجين.

وقد اشتملت هذه الدراسة على 21 مريضا بالسدة الرئوية المزمنة الغير مصحوب بفشل في وظائف التنفس و 33 مريضا بالسدة الرئوية المزمنة  المصحوب بفشل في وظائف التنفس وذلك بالإضافة إلى 40 من الأفراد الأصحاء كعينة ضابطة.

وقد خضع المرضى والأصحاء إلى دراسة الجهد المستثار السمعى، اختبار الحالة العقلية المصغر، اختبـار كوفمان المصغر لتقييم الحالة العصبية والنفسية، اختبار قائمة الأعراض-90 المراجع وقد تم أيضاً إخضاع المرضى فقط لقياس وظائف التنفس وقياس غازات الدم ورسم مخ كهربائى واستبيان سان جورج لقياس جودة الحياة.

وقد أظهرت النتائج وجود تباطؤ منتشر فى موجات رسم المخ فى 54% من المرضى ممن لديهم فشل تنفسى و 23% ممن ليس لديهم فشل تنفسى وزيادة ذو دلالة إحصائية فى طول موجات الجهد المستثار السمعى فى كل المرضى مقارنة بالعينة الضابطة كما كانت سعة موجة  P300 أقل فى مرضى الفشل التنفسى من مثيلاتها فى باقى المجموعات. و كانت النتائج تشير إلى وجود اضطراب في الوظائف المعرفية في مرضى السدة الرئوية المزمنة المصحوب بفشل في وظائف التنفس و الغير مصحوب بفشل في وظائف التنفس أعلى منها في العينة الضابطة. كما أتضح أن مرضى السدة الرئوية المزمنة استطاعوا أداء المهام المعرفية متوسطة التعقيد بدرجة أفضل من أداء تلك العالية التعقيد. كما وجد أن هناك علاقة طردية بين اضطراب الوظائف المعرفية ووظائف التنفس, بمعنى انه كلما زاد اضطراب وظائف التنفس كلما زاد اضطراب الوظائف المعرفية عند هؤلاء المرضى. وقد كان المرضى يعانوا من كل الأعراض النفسية بدرجة أعلى من المجموعة الضابطة وقد كانت هذه الأعراض تتناسب طردياً مع فترة المرض وشدته وبنود اختبار سان جورج المختلفة. ونستخلص من تلك النتائج إنه توجد تأثيرات مخية عضوية غير واضحة إكلينيكياً مصحوبة بتدهور فى الوظائف المعرفية وكثير من الأعراض النفسية فى مرضى السدة الرئوية المزمنة تتزايد مع شدة المرض وطول فترته وكلاهم يعكس تدهوراً أكبر فى جودة الحياة، والاكتشاف المبكر ومحاولة إصلاح هذه العوامل ربما يساعد فى تحسين جودة الحياة لمرضى السدة الرئوية المزمنة.



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