INTRODUCTION

 

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality in industrialized and developing countries. As COPD is a progressive disease, the number of COPD patients with severe disease and chronic respiratory failure will increase in the coming years¹. It is becoming increasingly clear that COPD is characterized by systemic manifestations. These are not simply consequences of altered lung function but represent manifestations of systemic disease². Although the effect of chronic respiratory insufficiency on central nervous system is well known, its effect on the peripheral nervous system was addressed recently in some studies³. COPD is one of the most important diseases that affect quality of life of patients. Peripheral neuropathy and/or myopathy are known to complicate and worsening the prognosis and quality of life of COPD patients⁴. More recently, the GOLD guidelines have identified the goals of treatment for patients with COPD. These include improvement of exercise tolerance and emotional function (health-related quality of life), prevention of disease progression, and minimization of symptoms^5-7.

Aim of the study:

        The objective of this work is to evaluate the presence of peripheral neuropathy and/or myopathy that complicate COPD and their influence on the quality of life of patients with COPD.

 

METHODS

 

Study population:

        This study was carried out in Tanta University Hospital, Neurology and Chest departments. A group of 40 patients with COPD, as defined by the American Thoracic Society⁸, were recruited from the outpatient Chest clinic, and from the inpatient Chest Department. All patients were in a clinically stable condition and not suffering from a respiratory tract infection or an exacerbation of their disease at least 4 weeks prior to the study. The patients divided into two groups, group (A): 20 patients their mean age was 65±8.3 years (16 males and 4 females) were diagnosed as severe COPD patients. Group (B) with 20 patients with moderate COPD their mean age was 61±6.7 years (18 males and 2 females). Exclusion criteria were malignancy, cardiac failure, distal arteriopathy, recent surgery, severe endocrine, hepatic or renal disorders, and musculoskeletal disorders that lead to functional limitation, other causes of neuropathy as diabetes mellitus. A group (C) of 15 non-smokers healthy age and sex-matched volunteers were studied as a control group. Written informed consent was obtained from all subjects.

Methodology:

Pulmonary Function Tests (PFT):

All patients and control subjects underwent spirometry. Forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and FEV1/FVC ratio were measured to confirm the diagnosis of COPD and to assess the severity, classifying the patients into groups; severe (30%  ≤ FEV₁ < 50% predicted) group A, and moderate  (50% ≤ FEV₁ < 80% predicted) group B.

 

Arterial Blood Gases (ABG):

Arterial oxygen tension was measured, at room air, in a blood sample from the radial artery for all COPD patients and control subjects (Table 1).

 

Clinical COPD Questionnaire (CCQ):

The CCQ is short (10 items), easy to complete. Patients take approximately 2 minutes to complete the questionnaire, and assistance is generally not required⁷. Patients are asked to recall their experiences during the previous week (week version). They respond to each question using a 7-point scale from 0 = asymptomatic/no limitation to 6 = extremely symptomatic/totally limited. Adding all the scores together and dividing this sum by the number of questions calculate the overall clinical COPD control score and the scores of the domains. Thus, the overall clinical COPD control score as well as the score on each of the three domains varies between 0 (very good health status) to 6 (extremely poor health status)⁸.

 

Neurological and electrophysiological examinations:

All subjects were evaluated clinically by one of us who not informed about the patients clinical or laboratory findings. The other neurologist did the neurophysiologic examinations. The median, ulnar, common peroneal and posterior tibial nerves were evaluated for distal latencies, amplitudes and motor conduction velocities. The sensory distal latencies, amplitudes and conduction velocities of median, ulnar and sural nerves were examined. Needle EMG examinations of deltoid, biceps, abductor pollicis brevis, rectus femoris, anterior tibialis and extensor digitorum brevis muscles were obtained during rest, minimal and maximal contractions.

Statistical Analysis:

The data were expressed in mean±SD and statistical analysis was performed using SPSS program for windows version 8

 

RESULTS

 

The results of pulmonary functions tests and arterial blood gases are summarized in Table (1).

 

The Neurological and Neurophysiological Results;

We found 18 patients with COPD (45% of COPD groups) suffering from peripheral neuropathy and/or myopathy. Their neurological characteristics were as follow; on clinical examinations, we found 7 (17.5% of COPD groups) patients (4 in group A, and 3 in group B) with peripheral neuropathy mainly sensory affecting lower limb more than upper limbs. Three patients (7.5% of COPD groups) showed weakness in shoulder and pelvic girdle muscles and all of them were from group A.

On neurophysiologic examinations, we found 9 (22.5% of COPD groups) patients with peripheral neuropathy, 5 in group A and 4 in group B with subclinical neuropathy. The neuropathy was mixed sensory motor affecting lower limbs more than upper limbs (Table 2).  Needle EMG examination showed 5 (12.5% of COPD groups, 3 in group A and 2 in group B) patients with myopathic pattern. In comparison between COPD patients with neuropathy and/ or myopathy we found that, those patients were more hypoxic (PaO₂, 56±67) and hypercabnic (PaCO₂, 58±73) than COPD patients without neuropathy and/or myopathy (PaO₂ 59±84) and (PaCO₂ 53±47) with P ≤ 0.05.

 

Clinical COPD Questionnaire (CCQ) results:

There was no significant difference in CCQ score between severe COPD patients and moderate COPD except in function symptoms score domain that showed significant difference between the two groups (P = 0.045) (Figure 1). The clinical COPD questionnaire scores showed significant difference between COPD patients with neuropathy and/or myopathy and patients without neuropathy and/or myopathy in symptoms, function domains and total scores (Figure 2).

 

Table 1. Pulmonary functions tests and arterial blood gases in the studied groups.

 

	Group A	Group B	Group C	P-value
FVC	76.3±8.2	84.4±11.3	94.00±7.44	0.001*
FEV1	44.5±3.6	58.1±4.6	103.40±8.18	0.001*
FEV/FVC	60.5±9.6	67.1±7.5	90.60±4.57	0.001*
PaO2	58±20	63±80	87±90	0.001*
PaCO2	56±90	48±11	37±50	0.001*

One way ANOVA

FEV₁ forced expiratory volume in one second, FVC forced vital capacity               

*Significant at p<0.01

Table 2. Neurophysiologic data of the studied groups.

 

	Group A Mean±SD	Group B Mean±SD	Group  C Mean±SD	P-value
Median nerve MNCV (M/S)	53.49±4.3	55.56±5.4	57.56±6.8	≥0.05
Ulnar nerve MNCV (M/S)	55.55±6.1	57.47±5.5	58.49±5.9	≥0.05
Common peroneal MNCV (M/S)	39.45±3.4	43.82±4.3	46.75±4.5	≤0.05
Posterior tibial MNCV (M/S)	40.43±4.6	44.56±5.4	47.67±4.4	≤0.05
Median nerve SNCV (M/S)	52.55±4.9	54.46±5.3	55.86±5                                                                                                   .6	≥0.05
Ulnar nerve SNCV (M/S)	52.88±4.6	53.66±4.8	54.78±5.3	≥0.05
Sural nerve distal latency (msec)	45.43±4.3	47.87±4.5	50.35±6.1	≤0.05

By one way ANOVA

 

 

Figure 1. CCQ= Clinical COPD Questionnaire, sym s=symptomatic score in severe COPD, sym m=symptomatic score in moderate COPD, fun s=function score in severe COPD, fun m=function score in moderate COPD, total s=total score in severe COPD, total m=total score in moderate COPD.

 

 

Figure 2. CCQ= Clinical COPD Questionnaire/M=peripheral neuropathy/myopathy, sym with=symptomatic score in COPD with P/M, sym out=symptomatic score in COPD without P/M, fun with=function score in COPD with P/M, fun out=function score in COPD without P/M, total with=total score in COPD with P/M, total out=total score in COPD without P/N.

DISCUSSION

 

Many studies have suggested the presence of peripheral neuropathy in patients with COPD^9,10.  In this study we found that the frequency of neuropathy 45%, symptomatic in 17.5% and subclinical neuropathy in 22.5% comparing to other studies (range between 44 and 87%)^11,12. This variation may depend on diagnostic criteria, non-uniformity between patients from different studies and electrophysiological study method.

The high incidence of neuropathy in COPD patients direct attention to increase our suspicion for neuropathy in COPD patients. The causes of neuropathy are thought to be multifactorial, metabolic, nutritional and toxic factors¹¹. The COPD patients with neuropathy were more hypoxic than patients without neuropathy. Hypoxia results in capillary endothelial hyperplasia and hypertrophy that predisposes to luminal occlusion¹². These changes were related to severity of hypoxia or its chronicity, need further investigations. On other hand, the frequency of myopathy was 20% (3 patients were symptomatic and 5 were subclinical), these figures may be higher than our expectation. Factors that can lead to myopathy may be malnutrition, hyperinflation, hypoxia and steroids¹³, but none of our patients received steroids in the last 6 months.

In comparison between COPD group with P/M and those without, we found that the former group was more hypoxic and hypercarbic than the last one. These changes may be a causal factors or resulting factors. Further investigations are needed to solve this viscous circle because peripheral neuropathy and myopathy worsening the pulmonary  functions¹⁴. 

Although spirometry is useful for assessing the effects of COPD on the lungs, it yields limited information relevant to health status or symptoms. According to CCQ the quality of life in COPD patients with neuropathy and /or myopathy was significantly more worsen in functional, symptoms and total scores domains than patients without neuropathy and/or myopathy. So neuropathy and myopathy add more burdens on health status and quality of life of the COPD patients.

Careful examination of patients with COPD for subclinical neuropathy and/or myopathy is needed for early interference, management these disorders and slowing progression of the disease if possible.

 

[Disclosure: Authors report no conflict of interest]

 

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