EVALUATION OF VESTIBULOCOCHLEAR NERVE
AND OPTIC NERVE IN CHRONIC OBSTRUCTIVE
PULMONARY DISEASE BY USING EVOKED
POTENTIAL STUDY
Dissertation submitted to
THE TAMILNADU DR. M.G.R. MEDICAL UNIVERSITY
In partial fulfillment of the
Regulation for the award of the degree of
M.D. (PHYSIOLOGY)
BRANCH – V
THANJAVUR MEDICAL COLLEGE ,THANJAVUR
THE TAMIL NADU DR.M.G.R.MEDICAL UNIVERSITY
CHENNAI, INDIA
MAY - 2018
CERTIFICATE
This is to certify that this Dissertation entitled “Evaluation of
Vestibulocochlear Nerve and Optic Nerve in Chronic Obstructive Pulmonary
Disease by Using Evoked Potential Study” is a bonafied work done by
DR.K.Anitcheady, under my guidance and supervision in the Department of
Physiology, Thanjavur Medical College, Thanjavur during her Post Graduate course
from 2015 to 2018.
Dr.S.JeyakumarM.s,Mch(Vascular),D.N.B,F.R.C.S(Edin) Dr.R.Vinodha, M.D.,
The Dean, Professor and HoD,
Thanjavur Medical College, Thanjavur Medical College,
Thanjavur – 613004. Thanjavur – 613004.
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Dr.R.Vinodha, M.D.,
Professor and HOD,
Thanjavur Medical College,
Thanjavur – 613004.
DECLARATION
I solemnly declare that this Dissertation “Evaluation of
Vestibulocochlear Nerve and Optic Nerve in Chronic Obstructive
Pulmonary Disease by Using Evoked Potential Study”was done by me in the
Department of Physiology, Thanjavur Medical College and Hospital, Thanjavur
under the guidance and supervision of my professor Dr.R.VINODHA, M.D.,
Department of Physiology, Thanjavur Medical College, Thanjavur between 2015
and 2018.
This Dissertation is submitted to the TamilNaduDr.MGR Medical
University. Chennai in partial fulfillment of University requirements for the
award of M.D.Degree(Branch - V) in Physiology.
Dr.K.Anitcheady
Postgraduate Student,
Thanjavur Medical College ,
Thanjavur – 4.
ACKNOWLEDEMENT
I express my deep sense of gratitude to my beloved
Prof. Dr. R.Vinodha.MD, Professor of Physiology, my teacher and
my guide, who provided constant guidance and advice throughout
this study and without whose initiative and ethusiasm this study
would not have been completed.
I am extremely grateful to the Dean Thanjavur Medical
College for granting me permission to do this dissertation work in
Thanjauvr Medical College Hospital, Thanjavur.
CONTENTS
S.NO Title Page No
1 INTRODUCTION 1
2 AIM OF THE STUDY 5
3 REVIEW OF LITERATURE 6
4 MATERIALS AND METHODS 59
5 RESULTS 65
6 DISCUSSION 82
7 CONCLUSION 89
8 BIBILOGRAPHY
9 ANNEXURES
ABSTRACT
TOPIC:EVALUATION OF VESTIBULOCOCHLEAR NERVE AND
OPTIC NERVE INVOLVEMENT IN CHRONIC OBSTRUCTIVE
PULMONARY DISEASE BY USING EVOKED POTENTIAL STUDY.
The aim of the study is to evaluate the visual evoked potential (VEP) and
brainstem auditory evoked potential (BAEP) abnormalities in COPD patient and
its correlation with C-reactive protien (CRP) as a part of multi system disorder.
40 study group with chronic obstructive pulmonary diseases and 40
control group between the age group of 30-60 years were included in this study
based on criteria defined in the global initiative for chronic obstructive lung
disease (gold) 2004- guidelines.
Patients with chronic neuropathy without COPD diabetes mellitus,
chronic alcoholism, uremia, cystic fibrosis, sarcoidosis, leprosy, malignancy,
history of intake of neurotoxic drugs, hearing and visual impairment were
excluded.
Informed written consent from the study and control group were
obtained.
Result: There was significant prolongation of (P100) over the right eye in
COPD patients compared with controls. BAEP recording shows significant
prolongation of latency of wave I, II, III, IV and V over the left ear.
The indices of spirometry FVC, FEV FEV1/FVC, were significantly
decreased in COPD patients and CRP were significantly increased in COPD
patients when compared with control
Key words: VEP, BAEP, C-Reactive Protein, Chronic obstructive pulmonary
disease, Hypoxemia
1
INTRODUCTION
The term chronic obstructive pulmonary disease (COPD) was
introduced to bring together a variety of clinical syndromes associated
with destruction of and airflow obstruction. The terms chronic obstructive
airways disease(COAD) and chronic obstructive lung disease (COLD)
have been used as synonyms in different parts of the world and chronic
obstructive pulmonary diseases (COPD) has been defined by the Global
Initiative for chronic obstructive lung disease (GOLD) as “a disease stage
characterized by air flow limitation that is not fully reversible”
Chronic obstructive pulmonary diseases includes (i) emphysema
defined as the permanent abnormal distension of the air spaces distal to
the terminal bronchioles accompanies by destruction of their wall without
fibrosis.
(ii) chronic bronchitis defined on the presence of chronic
productive cough on most days for 3 months in each of two consecutive
years.
(iii) small air way disease in which small bronchioles are
narrowed.
Excluded from this definition is Bronchial Asthma , chronic
Bronchitis and emphysema were frequently coexist since they share
common etiological factors and after many years chronic bronchitis get
complicated by emphysema.
2
GOLD estimates suggested that chronic obstructive pulmonary
diseases, fourth most common cause of death world wide at present, will
be the third common cause of death world wide by 2020.
This disease is frequently seen in middle – aged subjects. Chronic
obstructive Pulmonary diseases affects male more frequently than
females because of smoking(1). It is equally prevalent in rural and urban
areas.
Increased smoking habits among younger people, increasing
urbanization, increasing automobiles and emergence of industries leading
to air pollution that has definite impact on the epidemiology of chronic
obstructive pulmonary diseases.(2)
Low birth weight, malnutrition recurrent respiratory infection in
childhood also predisposed of chronic obstructive pulmonary disease in
future.(3)
Spirometry is the most robust test of airflow limitation in patients
with chronic obstructive pulmonary diseases(4)
COPD is presently regarded as a multi – system disorder with
significant extra pulmonary manifestations in addition to its pulmonary
components. COPD patients displayed mild cerebral deficits, which are
related partially to pressure of arterial oxygen (Pao2) and to the degree of
pulmonary impairment.
3
COPD patients suffered deficits on neurophysiological functioning
suggesting of organic mental disturbances and the rate of
neuropsychological deficit increased from 27% in mild hypoxemia to
61% in severe hypoxemia. Progressive hypoxemia leads to an increase in
blood viscosity and pulmonary vascular resistance which result in cor -
Pulmonale and a decrease in cerebral perfusion.
When Pao2 falls below 60 mmHg tissue hypoxia occurs and this
cause systemic effects. Accordingly visual and auditory receptors are
sensitive and more affected by hypoxemia.(5)
An evoked potential is an electrical potential recorded from the
nervous system of a human or other animal following presentation of a
stimulus, as distinct from spontaneous potentials as detected by electro
encephalography, & electromyography, or other electro physical
recording method.
VEP is a series of signals representing the response of the visual
occipital cortex to visual stimulus including flash and pattern stimuli and
can be used as one of the objective non-invasive neurophysiological
parameters in the assessment of the functions of visual organs, visual
pathways and the optical CNS.(6)
P100 latency is the representative component of VEPs and the most
commonly used index for its high, steady amplitude and slight intra and
4
inter – individual variability of P100 latency of the VEP was defined as the
time from the stimulus onset to the main positive peak
Brainstem auditory evoked potentials (BAEP) are the potentials
recorded from the ear and vertex in response to a brief auditory
stimulation to assess the conduction through auditory pathway up to
midbrain(7)
The value of evoked potentials in assessing acute hypoxic state is
well established. However, its value in assessing the effect of chronic
hypoxic – hypercapnic states on mental function is not similarly well
defined and the results of different studies were inconsistent.
C - reactive protein (CRP) is an acute – phase protein synthesized
predominantly by hepatocytes in response to tissue damage or
inflammation. It reflects the total systemic burden of inflammation of
individuals and has been shown to be increased in COPD in stable
condition and during exacerbation.(8)
5
AIM AND OBJECTIVE OF THE STUDY
1. To assess the functional integrity of visual pathway by using visual
evoked potential (VEP) in COPD.
2. To assess the functional integrity of auditory pathway by using Brain
stem Auditory evoked potential (BAEP) in COPD
3. Pulmonary function Test (PFT) in COPD.
4. To correlate parameters of PFT with BAEP &VEP.
5. To correlate the level of C-Reactive protein(CRP) with PFT, VEP and
BAEP parameters.
6
REVIEW OF LITERATURE
Prior to 1979, patients with these conditions were often classified by
symptoms (chronic bronchitis, chronic asthma) by pathological
changes(emphysema) or by physiological correlates (pink puffers,blue
bloaters).Recognition that these entities overlapped and often coexisted
led to the term COPD.
Recently it has been realized that COPD is associated with a number
of co-morbidities, e.g. ischemic heart disease, hypertension, diabetes,
heart failure and cancer, suggesting that there is a generalized systemic
inflammatory process.
In 1956 the Medical Research Council in its journal used the term
chronic bronchitis to describe conditions with chronic cough with
expectoration of bronchial mucus hyper secretion. When other causes like
TB, PT Bronchiectasis were excluded.
In 1959 Higgins established the clear relationship between “smoking
and persistent cough and sputum production.
In 1960 gross and associates leads to the proteinase and antiproteinase
hypothesis in emphysema observed in ∝� antitrypsin deficiency.
COPD is a multisystem disorder that is frequently associated with
significant extra pulmonary manifestations. Peripheral neuropathy is
known to occurs as a systemic manifestation of COPD and the optic
nerve may also be affected due to the same manifestation Gupta et al.
7
Atisetal reported BAEP and VEP abnormalities. In late 1960 owen
and campell et al observed the pathological changes in airways due to
cigarette smoking.
In 1973 Bougly and colleagues published a series of papers on
prognosis factors in chronic obstructive pulmonary diseases and
prognosis values of lung function test in chronic obstructive pulmonary
diseases.
Fig.1 Front Chest Xray in Normal Patient & COPD
EPIDEMIOLOGY& AETIOLOGY
COPD is caused by long-term exposure to toxic particals and
gases. In developed countries, cigarette smoking accounts for over 90%
of cases. In developing country factors such as the inhalation of smoke
from biomass fuels used in heating and cooking in poorly ventilated
areas, are also implicated.(10)
8
However, only 10-20% of heavy smokers develop COPD,
indicating individual susceptibility. The development of COPD is
proportional to the number of cigarettes smoked per day; the risk of death
from COPD in patients smoking 30 cigarettes daily is 20 times that of
non-smoker. Autopsy studies have shown substantial numbers of
centriacinar emphysematous spaces in the lungs of 50% of smokers over
the age of 60 years independent of the diagnosis of significant respiratory
disease before death.
Climate and air pollution play a major role in urbanization, social
class and occupation may also play a part in aetiology, but these effects
are difficult to separate from that of smoking.The scocio-economic
burden of COPD is considerable.
PREVALENCE IN INDIA
Chronic obstructive pulmonary diseases is the second most
common lung disorder after pulmonary tuberculosis.(11)
Incidence are higher in males due to higher of smoking. It is a
disease of middle aged and elderly people, less common below the age of
35yrs.
Studies from North India, reported that the prevalence of chronic
bronchitis was as high as 16% in people above 40 yrs from rural areas.
9
Prevalence is more in North India than South India due to seasonal
variability, particularly extremes of climate in North India.
MORTALITY DUE TO CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
Chronic obstructive pulmonary disease (COPD) is a growing
global epidemic that is estimated to kill around three million people every
year. It is currently the fourth largest killer disease in the world and
expected to climb to the third position by the year 2030.
The number of deaths due to coronary heart disease, stroke and
other cardiovascular diseases have reduced substantially over the years,
whereas COPD is the only disease whose mortality rates have increased
substantially.
The WHO has estimated that mortality rate, due to COPD will
increase by around 60% in the southeast Asian region over the next two
decades. (12)
MORBIDITY DUE TO COPD:
COPD is a common and leading cause of worsening of quality of
life. The world health organization (WHO) has estimated that 600millions
people worldwide have COPD.
10
RISK FACTORS:
SMOKING
Pipe and cigar smokers have a higher mortality and morbidity
rates, COPD shows a dose response relationship with the number of pack-
years of tobacco consumed.
British Thoracic society guidelines suggest that most patients with
COPD have at least 20 pack year smoking history
An average cigarette smoker have high annual rate of decline
FEV1 of about 50ml; in non-smokers the decline in FEV1 begins at 30-
35yrs of age and this may occur earlier in smokers.(13)
Stopping cigarette smoking does not produce a substantial
improvement in FEV1 but the subsequent rate of decline is decreased.
Prolonged cigarette smoking and impaired respiratory epithelial
ciliary movement, inhibits the function of alveolar macrophages & leads
to hyperplasia and hypertrophy of mucus secreting glands. Cigarette
smoke also inhibits anti proteases and cause polymorphonuclear
leukocytes to release proteolytic enzymes. Smoking is associated with
increased airway responsiveness, which is associated with more rapid
progression in patients with COPD. Obstruction of small airway is the
earliest demonstrable mechanical defect in a smoker.
11
AIR POLLUTION
Incidence and mortality rates of both chronic bronchitis and
emphysema may be higher in industrialized urban areas. Exacerbation of
bronchitis are clearly related to periods of heavy pollution with sulfur
dioxide and particulate matter.
In developing countries like India traditional working fuels such as
wood, cow dung cake, etc along with poorly ventilated houses are
significant risk factors for chronic bronchitis
SOCIO ECONOMIC STATUS
Hrubec et al found a strong association between socio economic
status based on occupation and respiratory symptoms in a study of twins.
In so many studies it was observed that an inverse relation between
percapita income &obstructive lung disease.
OCCUPATION:
Chronic bronchitis is more prevalent in workers who engage in
occupation exposing them to either inorganic or organic dusts, or to
noxious gases. Surveys have found accelerated decline in lung function in
such workers (eg) workers in plastic plants to exposure to toluene
disorganate etc. Exposure to cadmium can increase the change of
development of emphysema and hence COPD.(14)
12
RECURRENT RESPIRATORY INFECTIONS:
Frequency of acute respiratory illness are higher in patients with
chronic bronchitis. Epidemiological studies however implicate recurrent
respiratory illness as one of the major factors associated with etiology as
well as progression of chronic airway obstruction.(15)
AIRWAY HYPER RESPONSIVENESS AND ATOPY:
Even though airway hyper responsiveness is a feature of asthma
many patient with COPD also share this feature but less than 15% of
reversibility of obstruction to bronchodilators.
GROWTH AND NUTRITION:
Studies have shown that nutrition may affect both the growth and
decline in ventilator function. There is also some evidence that severe
viral pneumonia early in life may lead to chronic obstruction particularly
in small airways.
GENETIC FACTORS:
∝� ANTITRYPSIN DEFICIENCY:
∝� antitrypsin (∝� AT) is a polymorphic glycoprotein responsible
for the majority of anti-protease activity in the serum, whose synthesis is
governed by a gene on 14q 32 chromosome. The most commonest
13
deficient allele termed ZZ (corpiZZphenotype I) results from a single
amino acid substitution 342 Glu-Lys. Which cause spontaneous
polymerization of the polypeptide, markedly impairing its release into,
circulation from the liver.
It is commonly seen among people from europeon descent 1:2000
to 1:7000 people, rate in people from African and Asian leniage. ∝� AT
deficiency accounts for 2% of observe cases of emphysema, patients
present with premature development of emphysema, chronic bronchitis.
The patient usually present with cough and dyspnea in the fourth decade.
Nearly 80% had a family history of lung disease with autosomal recessive
inheritance .
The average decline of FEV1 is 100-300ml/yr for smokers and 50
to 80ml/yr for ex-smoker of lifetime nonsmokers.
Pathologically panacinar emphysema predominates and
radiographically changes are most marked in lower lobes. Tobacco
smoking is an extremely important cofactor for development of disease in
∝� AT deficiency. These patients are also at increased risk of hepatic
cirrhosis.(16)
• Pathological changes characteristic of COPD are found in the
proximal airways, peripheral airways, lung parenchyma, and
pulmonary vasculature. These changes include chronic
14
inflammation, and structural changes resulting from repeated injury
and repair.
• Inhaled cigarette smoke and other noxious particles cause lung
inflammation, a normal response which appears to be amplified in
patients who develop COPD.
• There is a characteristic pattern in inflammation in the lungs of
COPD patients, with increased numbers of neutrophils (in the
airway lumen), macrophages(airway lumen, airway wall, and
parenchyma), and CD8+ lymphocytes (airway wall and
parenchyma). The pattern is different from that seen in asthma.
• Lung inflammation is further amplified by oxidative stress and an
excess of proteases in the lung.
• Physiological changes characteristic of the disease include mucus
hypersecretion, air-flow limitation and air trapping (leading to
hyperinflation) , gas exchange abnormalities, and corpulmonale.(17)
• Systemic features of COPD, particularly in patients with severe
disease, include cachexia, skeletal muscle wasting, increased risk
of cardiovascular disease, anemia, osteoporosis, and depression.
• Exacerbations represent a further amplification in the airways of
patients with COPD, and may be triggered by infection with
bacteria or viruses or by environmental pollutants.
15
OXIDATIVE STRESS:
Oxidative stress may be an important amplifying mechanism in
COPD. Biomarker of oxidative stress (e.g., hydrogen peroxide, 8-
isoprostane) are increased in the exhaled breath condensate, sputum, and
systemic circulation of COPD patients. Oxidative stress is further
increased in exacerbations. Oxidants are generated by cigarette smoke
and other inhaled particulates, and released from activated inflammatory
cells such as macrophages and neutrophils.
There may also be a reduction in endogenous antioxidants in
COPD patients. Oxidative stress has several adverse consequences in the
lungs, including activation of inflammatory genes, inactivation of
antiproteases, stimulation of mucus secretion, and stimulation of
increased plasma exudation. Many of these adverse effects are mediated
by peroxynitrite, which is formed via and interaction between protease-
non protease imbalance.
PROTEASE-ANTIPROTEASE IMBALANCE
There is compelling evidence for an imbalance in the lungs of
COPD patients between proteases that break down connective tissue
components and antiporteases that protect against this. Several proteases,
derived from inflammatory cells and epithelial cells, are increased in
COPD patients. There is increasing evidence that they may interact with
each other.(18)
16
Protease-mediated destruction of elastin, a major connective tissue
component in lung parenchyma and is an important feature of
emphysema.
SYSTEMIC FEATURES
It is increasingly recognized that COPD involves several systemic
features, particularly in patients with severe disease, and that these have a
major impact on survival and comorbid diseases. Cachexia is commonly
seen in patients with severe COPD. There may be a loss of skeletal
muscle mass and weakness as a result of increased apoptosis and /or
muscle disuse.
Patients with COPD also have increased likeliness of having
osteoporosis, depression and chronic anemia. Increased concentrations of
inflammatory mediators, including TNF- �, IL-6 and oxygen-derived free
radicals, may mediate some of these systemic effects. There is an increase
in the risk of cardiovascular diseases, which is correlated with and
increase in C-reactive protein (CRP).(19)
EXACERBATIONS
Exacerbations represent a further amplification of the inflammatory
response in the airways of COPD patients, and may be triggered by
infection with bacteria or viruses or by environmental pollutants. There is
17
a relative lack of information about the inflammatory mechanisms
involved in exacerbations of COPD. In mild and moderated exacerbations
there is an increase in neutrophils and in some studies also eosinophils in
sputum and the airway wall. This is associated with increased
concentrations of certain mediators, including TNF-�, LTB4 and IL-8,
and an increase in biomarkers of oxidative stress.
There is even less information about severe exacerbations,
although on study showed a marked increase in neutrophils in the airway
wall and increased expression of chemokines. During an exacerbation
there is increased hyperinflation and air trapping, with reduced expiratory
flow, thus accounting for the increased dyspnea. There is also worsening
of VA/Q abnormalities resulting in severe hypoxemia.(20)
PATHOLOGY:
Pathologic changes characteristic of COPD are found in the
proximal airways, peripheral airways, lung parenchyma and pulmonary
vasculature. The pathological changes include chronic inflammation with
increased numbers of specific inflammatory cell types in different parts of
the lung, and structural changes resulting from repeated injury and repair.
In general the inflammatory and structural changes in the airways
increase with disease severity and persist on smoking cessation.
18
Pathological changes in COPD.
Proximal airways (trachea, bronchi> 2 mm internal diameter)
Inflammatory cell: increased Macrophages, CD8+ (Cytotoxic) T
lymphocytes, few neutrophils or eosinophils
Structural changes: increased Goblet cells. Enlarged submucosal glands
(both leading to mucus hypersecretion), squamous metaplasia of
epithelium
Peripheral airways (bronchioles<2mm internal diameter)
Inflammatory cells: increased Macrophages, T Lymphocytes
(CD8+>CD4+), B lymphocytes, lymphoid follicles, fibroblasts, few
neutrophils or eosinophils
Structural changes: Airway wall thickening, Peribronchial fibrosis,
luminal inflammatory exudates, airway narrowing (obstructive
bronchiolitis) increased inflammatory response and exudates correlated
with disease severity
Lung parenchyma (respiratory bronchioles and alveoli)
Inflammatory cells: increased Macrophages, CD8+ T lymphocytes
Structural Changes: Alveolar wall destruction, apoptosis of epithelial
and endothelial cells.
• Centrilobular emphysema: dilatation and destruction of respiratory
bronchioles; most commonly seen in smokers
19
• Panacinar emphysema: destruction of alveolar sacs as well as
respiratory bronchioles; most commonly seen in alpha – 1 antitrypsin
deficiency
Pulmonary Vasculature
Inflammatory cells: increased Macrophages,T lymphocytes
Structural Changes: Thickening of intima, endothelial cell dysfunction,
smooth muscle cell proliferation leads to pulmonary hypertension.
Fig 2: Mechanisms of Small Airway Obstruction in COPD
Small airways are the major sites of airflow limitation. Small
airways show a variety of lesions narrowing their lumina, including
goblet cell hyperplasia, mucosal and submuosal inflammatory cell,
edema, peribronchial fibrosis, intra luminal mucus plugs and increased
smooth muscle.(21)
20
In large cartilaginous airways chronic bronchitis in associated with
hypertrophy of sub mucosal mucus producing glands.
Quantitation of this anatomic change is known as Reid Index is
based on thickness of submucosal glands to that of bronchial wall.
In patients with chronic bronchitis it is 0.44 ± 0.09 otherwise
normally 0.52 ± 0.08. emphysema begins as an increase in the number of
and sizes of alveolar fenestrate and results in eventual destruction of
alveolar septae and their attachments to terminal and respirator
bronchioles.
With centriacinar emphysema the distension and destruction are
mainly limited to the respiratory bronchioles with relatively less change
peripherally in the acinus.
Panacinar emphysema involves both central and peripheral
portions of acinus.
PATHOGENESIS OF EMPHYSEMA:
Chronic exposure to cigarette smoker, fumes and dust may lead to
inflammatory cell recruitment within terminal air space of the lungs.
These cells release elastolytic proteinases that damage the extracellular
matrix of the lung.
21
Inflammatory Cells in COPD
Neutrophils: increased in sputum of normal smokers. Further increase in
COPD and related to disease severity. Few neutrophils are seen in tissue.
They may be important in mucus hypersecretion and through release of
proteases.(22)
Macrophages: Greatly increased numbers are seen in airway lumen, lung
parenchyma, and bronchoalveolar lavage fluid. Derived from blood
monocytes that differentiate within lung tissue. Produce increased
inflammatory mediators and proteases in COPD patients in response to
cigarette smoke and may show defective phagocytosis.
T lymphocytes: Both CD4+ and CD8+ cells are increased in the airway
wall and lung parenchyma, with increased CD8+:CD4+ratio. Increased
CD8+T cells (Tc1)and Th1 cells which secrete interferon-� and express
the chemokine receptor CXCR3. CD8+ cells may be cytotoxic to alveolar
cells, contributing to their destruction.
B lymphocytes: increased in peripheral airways and within lymphoid
follicles, possibly as a response to chronic colonization and infection of
the airways.
Eosinophils: increased eosinophil proteins in sputum and increased
eosinohils in airway wall during exacerbations.
Epithelial cells: may be activated by cigarette smoke to produce
inflammatory mediators.
22
Inflammatory Mediators Involved in COPD
Chemotactic factors:
Lipid mediators : e.g., leukotriene B4(LTB4 )attracts neutrophils and T
lymphocytes
Chemokines :e.g interleukin–8 (IL-8)attracts neutrophils and monocytes
Proinflammatory cytokines: e.g., tumor necrosis factor –� (TNF- �),
IL-1�, and IL-6 amplify the inflammatory process and may contribute to
some of the systemic effects of COPD
Growth factors: e.g., transforming growth factor- (TGF-) may induce
fibrosis in small airways.
Fig:3 Pathogenesis of Emphysema
23
PATHOPHYSIOLOGY:
AIRFLOW LIMITATION:
The extent of inflammation, fibrosis, and luminal exudates in small
airways is correlated with the reduction in FEV1/FVC ratio, and probably
with the accelerated decline in FEVI characteristic of COPD. Airflow
limitation and increased airway resistance may be caused by loss of
elastic recoil during passive exhalation due to emphysema, by increased
collapsibility of small airways through loss of radial traction on airway or
to intrinsic narrowing of small airways
HYPERINFLATION :
The residual volume and the functional residual capacity (FRC) are
almost higher than normal. In addition prolongation of expiration is
associated with obstruction which would lead to dynamic increase in FRC
(dynamic hyperinflation)
Dynamic hyprerinflation contributes additionally to discomfort
associated with air flow obstruction by flattening the diaphragm fiber
length and a perpendicular insertion with the lower ribs.(23)
IMPAIRED GAS EXCHANGE:
Maldistribution of inspired air and blood flow is always present.
24
When the mismatching is severe, impairment of gas exchange is
reflected in the abnormalities of arterial blood gases.
Small airway narrowing causes a decrease in ventilation of their
distal alveolar acini. When the alveolar capillaries remain intact, this
results in mismatch of ventilation and perfusion leading to mild or
moderate hypoxemia.
COPD IS A DISEASE OF SYSTEMIC INFLAMMATION:
Chronic obstructive pulmonary disease has classically been
considered to be an intrathoracic condition characterized by poorly
reversible airway obstruction.
However COPD has been recently recognized as a multicomponent
disorder, associated with systemic inflammation and extra pulmonary
manifestations.
It has now been well documented that the inflammation that
develops in the patient, does not confine to the lungs, but spills into the
systemic circulation through the pulmonary vessels and predispose almost
every organ system in the body with particular predilection to the heart,
as the heart is the first organ that receives all the blood from the
pulmonary vasculature
There is always a persistant low grade systemic inflammatory
response present in part of COPD patients.
25
Various studies have shown enhanced levels of acute phase
proteins like C-Reactive Protein (CRP ) and pro inflammatory cytokines
such as TNF - ∝ and IL – 6 in many COPD patients.
Moreover, there has been a consistent strong association between
reduced lung function and systemic inflammation. Even increased
polymorphism have been shown in the inflammatory genes and there is
increasing interest in identifying a haplotype of inflammatory genes
which predisposes to systemic manifestation of COPD.
These inflammatory markers along with persistent hypoxia
increase the basal metabolism in the body leading to catabolic changes
such as reduced muscle mass, wasting of skeletal muscles and
diaphragmatic weakness.
Further the systemic inflammation also increase oxidative stress in
various other organs.
Up to 70% of COPD have underlying osteoporosis. There has also
been a strong association between depression and COPD. There is
emerging evidence indicating insulin resistance in some COPD. Patients
due to systemic inflammation.(24)
COPD has also been related to increased cardiovascular morbidity
and diabetes mellitus.
26
FIG 4: Systemic Effects of COPD Inflammation
Hypoxemia results in peripheral nerve damage by harming the
vasonervosum. In the early stages of ischemia mechanisms to reduce
peripheral neuropathy are activated, but these become insufficient over
time and obvious neuropathy is inevitable in chronic hypoxemia.
It has been hypothesized that the abnormal brain stem auditory
potential and visual evoked potential findings are due to brain stem
hypoxia which increases with severity of COPD.
In addition to chronic hypoxemia and hyperapnia, other associated
factors in patients with COPD, including tobacco smoking, malnutrition,
and drugs used in COPD treatments like long acting inhaled B2 agonists,
inhaled anticholinergic agents, inhaled glucocorticoids &sustained release
of theophyline , may be possibly associated with neuropathy seen in
27
COPD patients. Factors contributing to the development of pulmonary
artery hypertension in COPD patients.
(i) ABNORMAL BLOOD GAS TENSIONS:
HYPOXEMIA:
In COPD there in a negative correlation between oxygen saturation
of the blood and pulmonary artery pressure. Hypoxemia is known to be a
potent arteriolar constrictor in the pulmonary circulation. As the severity
of disease progresses in COPD there is more arterial desaturation
correlation with an increase in pulmonaryartery pressure.
Exacerbation of COPD with hypoxemia are associated with acute
worsening of pulmonary hypertension.
Pulmonary artery pressure (P.pa) can also increase acutely during
the episodes of hypoxemia that occur during rapid eye movement of sleep
and it has been suggested that recurrent nocturnal pulmonary
hypertension can result in pathologic changes in pulmonary vessels and
fixed hypertension.(25)
HYPERCAPNEA:
In patients with COPD there in positive correlation between arterial
CO2 pressure (paco2) and pulmonary artery pressure. The mechanism
28
could be a change in lung mechanism due to hyperventilation induced by
hypercapnea or the potentiation of hypoxia pulmonary vaso constriction.
ACIDEMIA:
Hypoxia and acidemia act synergistically to produce pulmonary
vasoconstriction in patients with COPD. Thus for as given oxygen
saturation the mean pulmonary artery pressure is higher with increasing
arterial hydrogen concentration.
(ii) EFFECTS OF ABNORMAL PULMONARY MECHANICS
Changes in airway resistance may augment pulmonary vascular
resistance in pulmonary artery pressure, correlating with decrease in
FEV1.
(iii) EFFECTS OF INCREASED CARDIAC OUTPUT:
In patient with COPD (Vascular bed may be reduced) even small
increase in flow that occurs during exercise may increase pulmonary
artery pressure.
(iv) EFFECTS OF BLOOD VISCOSITY:
Polycythemia can develop secondary to chronic hypoxemia in
COPD patients, this contributes to blood viscosity which also adds up to
the pulmonary artery hypertension (PAH)
29
(v) ROLE OF PULMONARY ENDOTHELIUM:
There is increasing evidence that endothelial dysfunction is an
underlying factor in development of pulmonary artery hypertension. This
may result in reduction in nitric oxide synthesis or release in response to
hypoxemia.
Thus the putative role of nitric oxide in preventing an excessive
rise in pulmonary vascular tone, as a result of stimuli such as hypoxemia,
may be lost in COPD.
It has also been suggested that nitric oxide may have an inhibitory
effect on cell proliferation in the pulmonary vessel walls that therefore
has a role in preventing the vascular remodeling that occurs in hypoxic
COPD. Circulating levels of endothelin have been found to be increased
in patients who have emphysema and pulmonary hypertension.
PATHOLOGY:
Changes in pulmonary circulation occurs characteristically in the
peripheral arteries in patients with COPD. An early increase in intimal
thickness in small pulmonary arteries that occur due to accumulation of
smooth muscles that are laid down longitudinally along the length of the
vessel. Hypertrophy in muscular pulmonary vessels, has also been
reported in patients of COPD who develop sustained pulmonary arterial
hypertension.
30
Pulmonary thrombosis may also occur in patients with COPD that
may be secondary to peripheral airway inflammation.
Thus structural changes rather than simply hypoxia,
vasoconstriction is the major factor in the development of sustained
pulmonary hypertension in patients with COPD.(26)
CONSEQUENCES OF PULMONARY HYPERTENSION IN COPD
Chronic bronchitis and emphysema usually coexist
pathologically.Those patients with either predominant chronic bronchitis
or emphysema.
The blue and bloated type also known as type B or non fighters
was thought to characterize the bronchial type of disease.
These patients had hypoxemia, hypercapnea and secondary
polycythemia, they developed pulmonary hypertension relatively early in
the course of disease. Right ventricular hypertrophy or corpulmonale
ensure and repeated episodes of right heart failure occurred.(27)
In contrast the pink puffers variety also known as type A or fighter,
represent the emphysematous patients characterized by severe
breathlessness, but with preservation of blood gas values thus no
pulmonary hypertension, at least until the later stages of disease.
It was not known that the degree of mucous gland hypertrophy
indicative of chronic bronchitis was similar whatsoever the clinical
31
pattern and that more than 50% of patients with blue & bloated clinical
pattern had severe emphysema.
COR PULMONALE:
Corpulmonle is defined as right ventricular hypertrophy and
dilation secondary to pulmonary hypertension caused by disease of the
lung parenchyma and / or pulmonary vasculature, unrealated to both sides
of heart, the prevalence of corpulmonale is also higher in patients with
hypacapnia, hypoxemia and polycythemia.
OEDEMA
There is increasing evidence that the oedema which develops late
in the course of the disease in patients with COPD may not be entirely
due to right ventricular failure.
The key factor leading to changes in salt and water balance in
patients with COPD is the development of hypoxemia and hypercapnia.
The most consistent factor in renal function in patients with hypoxic
COPD, particularly those with oedema is a reduction in renal blood flow.
Hypercapnia reduces renal blood flow through catecholamine
release and via a neuraly mediated action. Arginine vasopressin(AVP)
levels may be in-appropriately high in patients with COPD. There is also
evidence of activation of rennin – angiotensin – aldosterone axis. Thus a
32
complex interaction between pulmonary haemodynamics and changes in
salt, water and hormonal. homeostatsis occurs in patients with hypoxia
and hypercapnic COPD leading to peripheral oedema.
CLINICAL FEATURES:
The characteristic symptoms of COPD are breathlessness on
exertion, mostly accompanied by wheeze and cough, which is often but
not invariably productive. Most patients have a smoking history of at
heart 20 pack years before symptoms develop, commonly in the fifth
decade.(28)
PHYSICAL SIGNS:
These are not specific to the disease and depend on degree of air
flow limitation and over inflation. In early disease the only abnormal
findings is wheeze on forced expiration and forced expiratory time
prolonged beyond 6 seconds with more advanced disease the breathing
pattern is characteristic with a prolonged expiratory phase.
Some patients adopting pursed lip breathing on expiration which
may reduce expiratory airway collapse. The use of accessory muscles of
respiration particularly sternomastoid is seen in advanced disease. These
patients adopt the position of leaning forward, supporting themselves
with their aims to fix the shoulder girdle and allowing the use of
33
pectoralis and latissimusdorsi muscle to increase chest wall movement
(the tripod position).
In later stages the chest is often barrel shaped, an increased anterior
posterior diameter, horizontal ribs, prominence of the sternal angle and
wide subcostal angle. An inspiratory tracheal tug may be detected. The
horizontal position of diaphragm also acts to pull on the lower ribs during
inspiration (Hoovers sign)
On percussion there is decreased cardiac and hepatic dullness
indicating overinflation.
Breath sounds may have a prolonged expiratory phase or may be
uniformly diminished.
RADIOLOGY:
Chest X-ray
There are no specific features on plain chest X-ray for chronic bronchitis.
⇒ The features casually described are for emphysema, bronchial wall
thickening seen as parallel line opacities on plain chest X-Ray has
been described in chronic bronchitis
Radiographic signs for emphysema are
• Low flattened diaphragm : the border of the diaphragm in the
midclavicular line below the seventh rib
34
• Height of patients lung being greater than 29.9cm
• An obtuse costophrenic angle
• Reduction in size and number of pulmonary vessels particularly in
periphery of lung.
• Heart shadow is vertical and narrow
• In lateral film increase in the retrosternal airspace.
COMPUTED TOMOGRAPHY
Has greater sensitivity and specificity than plain chest X-ray for
emphysema but is rarely necessary except for diagnosis for diagnosis of
bronchiectasis & evaluation of bullous lung disease.
GAS TRANSFER FOR CARBON MONOXIDE
Gas transfer for carbon monoxide values are below normal in many
patients with COPD
ARTERIAL BLOOD GAS ANALYSIS:
Measurement of arterial blood gas is essential in patients with
COPD to confirm the degree of hypoxemia and hypercapnia & in acute
exacerbation to determine the hydrogen ion concentration
Other tests : ∝�AT level
35
Clinical assessment : early systolic click
Electrocardiography : Tall peaked P waves in lead II, III & AVF
P Value > 2.5mm.Rt axis deviation
MANAGEMENT OF COPD
NON PHARMACOLOGICAL MEASURES
1. Smoking cessation
2. Basic information about COPD
3. Self management skills(29)
Pharmacological measures:
(i) Nicotine replacement therapy
(ii) Use of bupropion (abstinence)
(iii) Bronchodilators
GLUCOCORTICOSTEROIDS:
Inhaled glucocorticoids are appropriate for symptomatic COPD
patients with an FEV1 < 50% predicted (stage III & IV)
36
HOME OXYGEN THERAPY (HOT)
OTHER PHARMACOLOGIC TREATMENT:
⇒ ∝� Antitrypsin Augmentation therapy
ANTIBIOTICS: amoxicillin or cefixime (400mg once daily)
ANTIMUCOLYTIC AGENTS
DIURETIC THERAPY (OEDEMATOUS PATIENTS)
VACCINES: Influenza vaccines
SPIROMETRY
The most robust test of airflow limitation in patients with COPD.
Forced expiratory volume in one second (FEV1) is recommended as the
measurement of choice in COPD:
• FEV1 is reproducible & objective measurement
• It is simple and relatively quiet to measure and can be measured at all
stages of the disease.
• The expiratory maneuver records not only FEV1 but also FVC and
FEV1 / FVC ratio less than 70% is diagnostic of airway obstruction.
37
FLOW VOLUME LOOPS:
Expiratory flow at 75% or 50% of vital capacity have been used as
a measure of airflow limitation .
x-axis = volume in liters
y-axis = flow in liters/sec
ABC = inspiratory part of the loop (oval)
ACD = expiratory part of the loop (triangular)
ABCD=muscle dependent part of the loop
DA= effort (muscle)independent part of the loop
AC = vital capacity
CD= peak expiratory flow (PEFR)
Fig 5: Flow Volume Loops
TIMED VITAL CAPACITY (TVC) OR FORCED VITAL
CAPACITY (FVC)
FVC is the maximum volume of air which can be breathed out as
‘forcefully’ and ‘rapidly’ as possible following as maximum inspiration.
38
Thus TVC is exactly similar to VC except that there is a special stress on
rapid, forcible and complete exhalation.
COMPONENTS OF TVC (FVC):
(i) FEV1 (Forced Expiratory Volume in 1 sec), i.e., volume of FVC
expired in the first sec of exhalation. Normal: 80% of FVC.
(ii) FEV2 (Forced Expiratory Volume in 2 sec), i.e. volume of FVC
expired in the first two seconds of exhalation. Normal: 95% of
FVC.
(iii) FEV3 (Forced Expiratory Volume in 3 sec), i.e. volume of FVC
expired in the first three seconds of exhalation. Normal: 98-100%
of FVC.
Clinical Significance of TVC (FVC): To distinguish between
‘restrictive’ and ‘obstructive’ lung disorders.
REVERSIBILITY TO BRONCHODILATORS:
1. To help distinguish those patients with marked reversibility (at least
12% or 200ml of FEV1) who have underlying asthma.
2. To aid with future management.
3. The FEV1 after bronchodilator is the best predictor of survival.(30)
39
It is usually recommended that the response to bronchodilator be
assessed either using repeated doses from metered dose inhaler or in the
nebulized route.
VISUAL EVOKED POTENTIALS:
Introduction: the visual evoked potential (VEP) is primarily a
relatively large, positive polarity have generated in the occipital cortex in
response to visual stimulation. It measures the conduction time of
neuronal activity from the retinal to the occipital cortex and is used
clinically as a measures of the integrity and function of that pathway. The
optic nerve in the primary structure examined the VEP is of large enough
voltage that can be seen occasionally on a routine EEG as an occipital
wave within the first 150ms after a single photic stimulus of primary
interest is the latency of the positive wave at approximately 100ms after
stimulation called P100 peak is usually easy to recognize and measure(31)
VARIABLES INFLUENCING VEP
AGE
Age has been reported to influence the latency of P100 at a rate of
2.5 ms/decade after fifth decade This has been attributed to age-related
changes in both retina and the rostral part of visual system The amplitude
of VEP remains reasonably stable in the adult life. In the first decade, the
40
amplitude is higher and the mean amplitude is almost double of adult
value however, beyond 50 years, there is conflicting data. In infants and
young children, the P100 latency on large checks (30º) reaches the adult
value by 20 weeks whereas the latency on smaller checks takes 5-6 years
to reach the adult value. The maximum change occurs in the first year of
life
GENDER
The P100 latency is longer in adult males compared to females.
This has been attributed to larger head size and lower core body
temperature in males . In the age group below 19 years, P100 latency does
not vary with sex although a longer latency does not vary with sex
although a longer latency has been reported in girls. The mean
P100amplitude is greater in females compared to males. Although its basis
is unknown, hormornal differences have been suggested
EYE DOMINANCE
The P100 wave obtained by stimulating the dominant eye is shorter
and amplitude greater compared to the no dominant eye The amplitude of
transient VEPs from mid-occipital electrode ipsilateeral to hemi field
stimulation is greater in right hemi-field stimulation in right-handed
41
individuals. This has been attributed to the neuro anatomic asymmetries
of human striate cortex
EYE MOVEMENT
Eye movement reduces the amplitude of P100, but its latency is not
affected .the patients with nystagmus having a normal visual pathway
also have normal P100 latency.
VISUAL ACUITY
P100 latency remains normal in spite of pronounced diminution of
visual acuity. The latency of P100 is reported to be normal with visual
acuity as low as 20/120; however, the amplitude decreases with further
reduction of visual acuity.
DRUGS
Drugs producing papillary constriction such as pilocarpine can
increase P100 latency, which is attributed to decreases area of retinal
illumination. The mydriatics result in an opposite effect.
REPRODUCIBILITY AND VARIABILITY
During mental activity such as problem solving, the P100 latency
has been reported to decrease and the amplitude increase. An
42
unmotivated patient may alter the P100 latency or amplitude by closing
the eye, gazing off the screen, converging in front of target or even his
nose. These variables can often be detected by an observant technologist.
Simultaneous recording of Pattern electroretinogram (PERG) also helps
in documenting the fixation. An abnormal PERG raises the possibility of
improper fixation or retinal diseases; whereas a normal PERG suggests
adequate fixation. Whereas a normal PERG suggests adequate fixation.
Although the VEP waveforms are reproducible, they have an inherent
intraindividual variability. VEPs were repeated on three different
occasions within 1 week; P100 latency varied between 0 ms to 8 ms and
the inter-eye difference between 0ms and 6ms. In another study,
intraocular variability over a period of 6 months ranged up to 11 ms and
inter-eye variability up to 9ms. (32)
STEADY-STATE VEP
Steady –state VEPs are the response to visual stimuli given at a
rate of 3.5Hz or more. These responses overlap one another and appear as
somewhat sinusoidal oscillations, which persist during the period of
stimulation. Steady-state VEPs are also defined as repetitive evoked
potentials, which constitute discrete frequency components and remain
constant in amplitude and phase over an infinitely long period of time.
43
BASIS OF VEP ABNORMALITIES
The eyes are tested on at a time and each eye projects to the
occipital cortex through the optic chiasma. The unilateral VEP
abnormality therefore, obtained by full field monocular stimulation is
likely to be due to prechiasmal lesion. It the PSVEP is abnormal
bilaterally, it is not possible to locate the anatomical site of conduction
defect in the visual pathways. The VEP abnormalities may be:
1. Latency prolongation
2. Amplitude reduction
3. Combined latency and amplitude abnormalities
The commonest cause of prolonged P100 latency is demyelination in
the optic pathways where the amplitude of P100 remains normal. Sparing
of the P100 amplitude in demyelination was investigated in a study by
giving paired stimuli. The interstimulus interval if less than 40ms, the
second stimulus was abolished by the first. This may be responsible for
the preservation of P100 amplitude as well as its shape in partial optic
nerve demyelination, where the late arriving impulses through
demyelinated segments are inhibited. The latency and shape of P100
depend upon the surviving fastest conducting fibres. It has been
calculated that a demyelinating plaque of 10mm size would result in VEP
delay of 25ms Care must be taken in interpreting the delay of P100
latency. The amplitude of P100 has a wide interindividual variation
44
reducing its clinical utility. Intraocular amplitude ratio, therefore, has
been used for defining the abnormalities. Ischemic optic neuropathy
leading to axonal loss produces normal P100 latency and decreased
amplitude. The variables resulting in reduced retinal illumination such as
papillary size, refractive error, media opacities, and retinal diseases, etc.,
can lead to reduced amplitude. Optic nerve compression produces
segmental demyelination and axonal loss resulting in both latency and
amplitude abnormalities in VEP.
Shape abnormalities of P100 manifest with a W-shaped complex
(bifid pattern of P100) in which the two peaks are separated by 10-50ms.
This pattern is seen very rarely in normal individuals and its presence
usually suggests abnormality. The bifid P100 wave form may be attribute
to the following:
1. The upper visual field may contribute as negative polarity and
the lower as positive at inion. A summation of these tow
activates may result in W-shaped P100 waveform. This may be
excluded by recording the VEP by lower half visual field
stimulation
2. In patients with visual field defect, the “W” shape of VEP may
be due to shifting of transitional zone. This effect can be
eliminated by placing the recording electrodes laterally.
45
COMPONENTS OF ELECTRO DIAGNOSTIC EQUIPMENT
Electrodes (Active, Reference & Ground)
ELECTRODES
(i) There are types of electrodes: active, reference and ground. The
action potential is measured between active and reference
electrode whereas the ground electrode serves as a ‘zero’
voltage reference point.
(ii) They are made up of platinum, stainless steel, silver chloride,
chromium, nickel, silver and gold. Silver or gold electrodes
have the advantage of stable electrode polarization potentials
which result in noise-free recording.
(iii) In clinical practice, two varieties of electrodes are used: surface
and needle electrodes. In general, surface electrode is preferred,
Analog
display Stimulator
Amplifie Filter
Analogue
to digital
converter
(ADC)
Micro-
processo
Video
monitor
Audio
monitor
Memory
46
as using the needle electrodes have a greater chance of
infection.
(a) The surface electrodes are in the form of disc, cup or ring,
and are used in nerve conduction and motor evoked potential
recording. These electrodes are placed in position with the
help of electrode paste or jelly, which is gently rubbed on the
skin and then applied for proper contact.
(b) Needle electrode is commonly used for EMG study. They
consist of Teflon coated stainless steel wire which tapers to a
sharp tip.(33)
AMPLIFIER
A variable degree of amplification, up to 5x 105 folds is needed
before being displayed because of the following reasons:
(i) Biological signals are very small.
(ii) Intrinsic impedance of electrode. It varies with frequency and
electrode type used. The concentric needles have a higher
impedance.
(iii) Impedance of electrode-skin.
FILTER
It is a device that relatively allows a particular range of frequency
from a signal. It is required for eliminating the noise and useful for
47
bringing out the characteristics of the waveforms, i.e. Optimising the
recording.
(i) The low- frequency filters remove the slowly changing low-
frequency (up to 100HZ) components and allow the higher
frequencies to pass through. Therefore, it is also called as high pass
filter.
(ii) The high-frequency filters remove the rapidly changing high-
frequency components and allow the low frequency (up to 100Hz)
to pass through; therefore, it is also called low pass filters.
AVERAGER
(i) It extracts very small signals which are hidden or buried in large
noise; for example:
(a) Evoked potentials are buried in EEC noise; and
(b) Sensory nerve action potential (SNAP) in EMG noise
(ii) By averaging, the time-locked signals become prominent and
are stored in the memory of the equipment, while the noise
which is occurring randomly is cancelled out. Alternatively, the
noise can be time-locked and can be rejected subsequently.
DISPLAY
Two methods of waveform display are in use:
(i) Analogue oscilloscope display; and
48
(ii) Computer based digital video display
(i) Analogue Oscilloscope Display
Here the action potential signals are directly displayed on
cathode ray oscilloscope following amplification and filtering. It
can redisplay the waveform but certain details of waveform may
be lost.
(ii) Computer Based Digital Video Display
Here and analogue to digital converter (ADC) and digital
processing technique are used; therefore, the signals can be
redisplayed with greater sensitivity without any loss of
waveform accuracy.
STIMULATOR
It is required for nerve conduction and evoked potential studies.
Two types of stimulator are in use: Electrical and Magnetic.
(i) Electrical stimulators: It is of two types:
(a) Constant current stimulator: It delivers a constant current to
the subject over a wide range of stimulating electrode
impedance. Thus it is more stable and useful in repetitive nerve
stimulation and evoked potential studies.
(b) Constant voltage stimulator: It delivers a fixed voltage
between anode and cathode.
49
(ii) Magnetic stimulators: they are used for the non-invasive
stimulation of motor cortex, spinal cord and peripheral nerves.
SENSITIVITY (OR GAIN) AND SWEEP SPEED
The latency and duration of an action potential is influenced by
sensitivity (i.e. gain) and sweep speed (or time).
(i) On high sensitivity, there is the shortening of latency due to the
visualization of smaller deflection from the base line.
(ii) Increase in sweep speed results in the shortening of latency.
SIGNAL TRIGGER
It is useful for isolating and displaying the action potentials for
their quantitative analysis. It can be fixed and time-locked relative to the
start to sweep.
DELAY TIME
It continuously samples and stores into the memory ongoing action
potential activities. The action potential when exceeds the triggering
values, it is extracted from the memory and displayed.
50
LATENCY
• It is the time in msec from the stimulus artifact to the first negative
deflection of CMAP.
• It is a measure of conduction in the fastest conducting motor fibers.
• It includes neuro-muscular transmission time and propagation time
along the muscle membrane.(34)
AMPLITUDE
It is measured from baseline to the negative peak (base to peak) or
between negative and positive peaks (peak to peak).
Fig6: VEP in a normal individual
NORMAL VALUES FOR P100 V.E.P
(a) Latency : 100 msec.
(b) Amplitude : 10µV; and
(c) Duration : 60msec.
51
APPLICATION:
• Prolonged latency of P100 – demyelination of optic pathway
• Amplitude reduction of N75-P100 amplitude – Axonal loss
• Combined latency and amplitude defects : optic nerve compression
BRAIN STEM AUDITORY EVOKED POTENTIAL (BAEP)
It was in 1967 Sohmer and Feinmesser published the first known
reported recording cochlear potentials using surface electrodes in
humans. It was only in 1971 Jewett and Williston gave clear description
of these. Waves and interpreted that the later waves were generated at the
level of brain stem.
In 1977 selters and Brackmandescribed the importance of
prolonged interpeak latencies in patients with acoustic tumors. They also
postulated that this time delay was directly proportional to the size of the
tumor.
In 1975 it was Starr and Achor reported the effects of ABR
(auditory brain stem response) in patients with pathology of in the brain
stem.
Even though BERA provides information regarding auditory
function and sensitivity. It should not be considered as a substitute for
other methods of audiological evaluations. More over ideally it should be
viewed in conjunction with other audiological investigations.
52
This test involves recording of all forms of electrical response
generated at the level of brain. Stem in response to click/tone impulse by
placement of electrodes in the scalp. Stimulus is ideally provided by a
transducer placed in the insert earphone or head phone.
In auditory brain stem evoked response, the potentials are
generated by the brain stem. These recorded impulse contain a series of
peaks and troughs. The peaks are positive (vertex positive) and are
indicated by Roman Numerals I – VII.(35)
Normal BAEP, potential field distribution, waveform recognition,
and normal values
Classical BAEP consists of 5-8 vertex positive peaks, which are
labeled using Roman numerals. The initial five peaks are of clinical
interest. The succeeding peaks VI-VIII are quite variables and therefore
are not clinically useful. The through immediately following the peaks
are designated by the same numerical followed by a prime mark, e.g., the
trough of wave I is designated as I, the important features useful in the
recognition of different waveforms are as follows.
Wave I
Wave I is a prominent initial up – going peak in the ipsilateral ear-
recording channel. It appears 1.4 ms after the stimulus and is markedly
attenuated or absent from the contralateral ear-recording channel.
Employing a reference, wave I has a wide distribution of positivity and
53
negativity. The later is confined to the ipsilateral ear. Medial earlobe
recording provides higher amplitude of wave I compared to mastoid In a
difficult case, the amplitude of wave I can be improved by following
maneuvers:
1. Horizontal montage
2. Use of external canal needle electrode
3. Use of nasopharyngeal electrode
4. Increasing the stimulus intensity
5. Decreasing the stimulus rate
6. Alternating click polarity to reduce the stimulus artifact
Patients with central nervous systems problems only, should have a
preserved wave I since it originates from VII nerve. Conversely, the
patients with significant peripheral hearing impairment may have a very
poorly formed or absent wave I but relatively normal wave II-V. wave I
sometimes may have two separate components. The earlier component is
of higher amplitude especially during high intensity and high pitch
simulation. This component should be used for measurement. The later
component is of lower amplitude and is recorded at a more wide range of
stimulus intensity and pitch.
54
Wave II
Wave II is poorly defined in some adults and most neonates. It
sometimes appears as a small peak along the down – going slope of wave
I or in the up-going slope of wave III. It is more prominent in contra
lateral channel recording where it has a slightly prolonged latency
compared to ipsilateral. Absence of wave I on contralateral recording
may be helpful in differentiating wave I from wave II. Sometimes the
fusion of waves II and III results in M-shaped II-III complex.
Wave III
Wave III is usually a prominent peak, in the contralateral channel,
wave III often appears smaller and earlier than the ipsilateral ear because
its amplitude is similar at the vertex and contralarteral ear. This feature
may help in wave III recognition. Some normal subjects have a bifid
wave III, which is associated which is associated with a normal I-V IPL.
As with different configurations of wave IV and V, bifid wave III may be
related to the condensation or rarefaction clicks. In infants and some
adults, wave IV may normally be closer to III than to V and give and
appearance of bifid wave III. In contrast to wave IV and V, were II and
III tend to fuse in Ac-Cz recording , thus the latency of wave III
decreases and that of II increases. In some patients, a wave II-III complex
55
forms in the Ac-Cz derivation. This may help in the recognition of these
waves.
Wave IV and V
Wave I is the most prominent peak appearing 5.5ms after the
stimulus. It starts above the baseline and its trough is maximal below the
base line. On ispsilateral recording wave V fuses with IV resulting in a
wave IV-V complex. The wave IV and V may have the following
patterns.
1. Single peak which is completely fused as a tall wide pyramid, whose
base should be more than 1.5ms
2. Two peaks which are close but sill visibly separated
3. Wave IV may be on the up-going slope of wave V
4. Wave V may be on the down – going slope of wave IV]
5. Wave I and V tend to be separated on contralateral recording.
For recognizing wave V the following maneuvers are helpful:
1. On reducing the click intensity to as low as 10dB, wave V is the last
wave to persist in that area.
2. On increasing the rate of stimulation to as high as 100Hz, wave V
persists but the earlier waves disappear.
3. On Ai-Ac montage, wave V amplitude decreases.
56
Normal values of BAEP
Wave
(Latency ms)
Chiappa et al.
(1979)
Misra and Kalita
(n=30pts, 15-68
years)
I 1.7 ± 0.15 1.67±0.17
II 2.8 ± 0.17 2.78±0.21
III 3.9 ± 0.19 3.65±0.22
IV 5.1 ± 0.24 5.0±0.30
V 5.7±0.25 5.72±0.3
VI 7.3±0.29 7.2±0.48
I-III IPL 2.1±0.15 1.99±0.25
III-V IPL 1.9±0.18 2.08±0.30
I-V IPL 4.0±0.23 4.04±0.25
Fig 7:BAEP in a normal individual
The wave peaks have been postulated to arise from:
1. Cochlear nerves – Waves I and II
2. Cochlear nucleus – wave III
3. Superior olivary complex – wave IV
57
4. Nucleus of lateral lemniscus – wave V
5. Inferior colliculus – wave VI and VII
APPLICATION:
• It is an effective screening tool for evaluating cases of deafness due to
retrocochlear pathology i.e (Acoustic schwannoma). An abnormal
BERA is an indication for MRI scan.
• Used in screening newborns for deafness
• Used for intraoperative monitoring of central and peripheral nervous
system
• Monitoring patients in intensive care units
• Diagnosing suspected demyelinating disorders.(36)
C REACTIVE PROTEIN (CRP) :
Also known as pentraxin 1, is a non-glycosylated protein in
pentraxin family that also includes pentraxin 2/SAP and pentraxin
3/TSG-14. CRP is an acute phase reactant, a protein made by the liver
and released into the blood within a few hours after tissue injury, the start
of an infection, or other cause of inflammation.
A high level of CRP in the blood is a sign that there may be an
inflammatory process occurring in the body.(37)
58
MATERIALS AND METHODS
This case – control study was conducted at Thanjavur medical
college and hospital between February 2016-June 2017. It included 40
COPD patients recruited from chest outpatient clinic and 40 age and
matched as a control group. This study based on criteria defined in the
global initiative for chronic obstructive lung disease (gold) 2004
guidelines.
EXCLUSION CRITERIA: Patients with chronic neuropathy
without COPD, diabetes mellitus, chronic alcoholism, uremia, cystic
fibrosis, sarcoidosis, leprosy, malignancy, history of intake of neurotoxic
drugs, hearing and visual impairment.
Informed written consent from the study and control group
obtained
INCLUSION CRITERIA:cases were selected from COPD chest
outpatient clinic for regular follow. The patients were included only if
they had a stable course of disease with regular follow – up with no
hospitalization for COPD related illness during the preceding six months.
The diagnosis was based on the modified criteria defined in the Global
Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, and
had irreversible /partially reversible obstruction of airflow.
59
PULMONARY FUNCTION TEST: were performed using
computerized spirometer (INTEX 17) digital suga monitor model No:17
– 173SB, spiroexcel – MEDICAID. The following indices were recorded
FVC, FEV1&FEV1/FVC.
VEP and BAEP: Was carried out using digital four channel polygraph
intex monitor, MRI GNAINI – 15”/17’ INSTUMENT MODEL IT -
173SB.
PULMONARY FUNCTION TEST(PFT) :
Recorded using computerized spirometry. These days
computerized multifunctional spirometers are available which allow high-
quality made virtually breath. These spirometers display to high-
resolution graphic display as well as the predicted curves. The generated
reports may be seen on the display or can be printed. All pulmonary
function test parameters with actual. Predicted and percentage predicted
values, as well as normal range with the option of interpretation and lung
age can also be obtained. Moreover, all tests performed are presented
with both the selected test highlighted and the percentage variation from
best.
The subject is made to sit comfortable in a stool facing the
spirometer, nose is clipped and the mouthpiece is inserted between the
teeth and the lips.
60
The subject is then instructed to breathe in with maximum effort
form the end of resting expiration and subsequently to breathe out
completely with maximum effort. He is beforehand instructed not to
breathe in while he is breathing out. At least three such forced vital
capacity (FVC) curves are obtained and the maximum (best performance)
of three values is taken for calculation purposes, and other parameters
FEV1, FEV1/FVC etc. will be displayed with graphic display.
Fig 8: PFT demonstration
VEPs were recorded in a dark room 100cm away from the monitor.
A chess board pattern reversal method on a 12 inch screen. Stimulation
frequency at speed of 2Hz.
61
STIMULUS: the standard stimulus for VEPs is a checker board
pattern in which the squares alternate from black to white – the pattern
reversal VEP (PRVEP) Dark squarer become light and vice versa,
without a change in the overall. Luminance of the display. Typically, the
pattern is reversed 100 or 128 times at 1 to 2 Hz, and the results are then
averaged. Usually a repeat trial of averaged stimuli & also recorded.
PRVEPS require maintaining visual fixation on the center of the
pattern. The occipital cortex is particularly sensitive to the perception of
edge and a sharp bordered checkerboard produces a strong and
measurable response. PRVEPs are remarkably precise and constant for a
given subject echo has no clinical change and are very sensitive to
dysfunction in the visual conducting system.
Check size: 8º x 8º for the entire stimulus or video screen
Contrast: contrast is the difference in luminance (or brightness) of the
dark and light areas divide by the sum of their luminances.
Repetition frequency: the pattern reversal rate is usually two per second.
Averaging: Voltage signals are averaged over 100 trials, usually with a
duration of 500-ms each. VEPs have a relatively high signal to noise
ratio, and a larger number of trails is not required.
Filter: The Low – frequency filter is usually set at 1 Hz and the high
frequency filter at 100 – 300 Hz. (The shape of the standard P100 has a
frequency of approx 15 - 20Hz)
62
Fig 9: 10-20 Electrode placement system
VEP evaluation latency and amplitude P100 were assessed.
Sites where electrodes place were cleaned with 75% alcohol.
Electrodes were smeared with conductive paste, recording electrode was
positioned 1.5cm above the occipital bone reference on middle forehead,
ground electrode the vertex.
63
Fig10 : VEP demonstration
BRAIN AUDITORY EVOKED POTENTIAL (BAEP)
PROCEDURE:
1. Keep the instrument out of view of the subject, allow the subject to
sit comfortable on a chair in a fully relaxed state, the skin at the
point of the placement of electrodes is cleaned with ether or spirit.
2. Using electrode paste, the recording (active) electrodes are placed
on both the ears, ipsilateral or mastoid process as per 10-20
international system of EEG electrode placement the reference
electrode is placed at the vertex, i.e. at Cz; the ground electrode is
placed at Fz.
3. Give a brief click stimulus which is usually a square wave pulse of
0.1 msec duration. A click rate of 11-31 Hz is most commonly
used in clinical practice.
64
Were recorded in a quiet room at an intensity of 90dB, absolute
latencies of waves (I, II, III, IV& V) along with interpeak latencies
(IPLS) I-III, I-V & III-V.
Fig 11: BAEP demonstration
C – RP &BLOOD GLUCOSE: venous blood samplewere taken and
CRP were measured using semi automated analyzer - BIOSYSTEM 350
at siva clinical lab Thanjavur, by immunoturbido metric method (CRP)
and blood glucose by glucose oxidase method. (GOD)
PRINCIPLE OF CRP TEST:
The C-Reactive protein test is based on the principle of latex
agglutination. When latex particles complexed human anti-CRP are
mixed with a patients serum containing C-Reactive proteins, an visible
agglutination reaction will take place within 2 minutes. Normal C-
Reactive protein levels are below 3.0 mg/dl.
65
RESULT
Statistics were done using spss version 21 by student ‘t’ test
method. We included 80 subjects comprising 40 COPD patient and age
matched 40 healthy subjects.
TABLE: 1 CHARACTERISTIC OF COPD PATIENTS GROUP
AND HEALTHY CONTROL GROUP
PARAMETRES
COPD
(n=40)
Mean ± SD
CONTROL
(n=40)
Mean ± SD
P-VALUE
Age 43.68 ± 7.8 42.88 ± 7.7 0.648
FEV1 (% of Predicted ) 58.15 ± 28.3 94.82 ± 26.9 0.0001*
FVC (% of Predicted) 63.6 ± 24.1 91.5 ± 25.3 0.0001*
FEV1/FVC (%) 96.77 ± 20.1 106.89 ± 7.4 0.004*
CRP (mg/ml) 2.01 ± 0.4 1.69 ± 0.3 0.001*
*Significant when P ≤ 0.05
The indices of spirometry of COPD patients were significantly
decreased from control. And CRP were significantly increased from
control. The serum level of C-reactive protein in COPD patients were
significantly elevated (Table.1)
66
Diagram 1: ComparisionBetweenthe means of COPD and control of the
indices of – spirometry and CRP.
58.15
63.6
96.77
2.01
46
94.8291.5
99
1.69
16
0
10
20
30
40
50
60
70
80
90
100
FEV1 FVC FEV1/FVC CRP SMOKING
COPD
Ind
ices
o
fsp
iro
met
ry a
nd
CR
P
67
TABLE:2 BRAIN – STEM AUDITORY EVOKED POTENTIALS
(BAEP) VARIABLES IN COPD PATIENTS AND CONTROL
GROUP
LEFT EAR
LATENCIES
COPD
(n=40)
Mean ± SD
CONTROL
(n=40)
Mean ± SD
P VALUE
I (ms) 2.19 ± 1.7 1.29 ± 0.9 0.0041*
II (ms) 2.91 ± 0.7 2.38 ± 1.1 0.016*
III (ms) 4.25 ± 0.8 3.49 ± 0.5 0.000*
IV (ms) 5.6 ± 1.1 4.9 ± 0.8 0.001*
V (ms) 6.8 ± 1.3 6.1 ± 1.1 0.012*
INTERPEAK
LATENCIES
COPD
(n=40)
Mean ± SD
CONTROL
(n=40)
Mean ± SD
P VALUE
I – III (ms) 2.47 ± 0.6 2.49 ± 0.8 0.905
III – V (ms) 2.6 ± 0.9 2.58 ± 0.9 0.730
I – V (ms) 5.27 ± 1.5 5.05 ± 1.1 0.474
* Significant P value < 0.05
68
TABLE:3 BRAIN – STEM AUDITORY EVOKED POTENTIALS
(BAEP) VARIABLES IN COPD PATIENTS AND CONTROL
GROUP
RIGHT EAR
LATENCIES
COPD
(n=40)
Mean ± SD
CONTROL
(n=40)
Mean ± SD
P VALUE
I (ms) 1.67 ± 1.0 1.64 ± 3.2 0.956
II (ms) 2.78 ± 0.8 2.43 ± 1.4 0.189
III (ms) 4.01 ± 0.9 4.4 ± 7.0 0.670
IV (ms) 5.2 ± 1.0 5.8 ± 7.8 0.652
V (ms) 7.7 ± 6.6 6.6 ± 1.07 0.462
INTERPEAK
LATENCIES (IPLS)
COPD
(n=40)
CONTROL
(n=40) P VALUE
I – III (ms) 2.5± 0.7 2.39± 0.9 0.563
III – V (ms) 3.35± 4.1 2.39± 0.8 0.151
I – V (ms) 8.83± 10.2 6.8± 10.7 0.409
Significant when P ≤ 0.05
Over left ear, the latencies of wave I, II, III, IV and V were
increased in COPD patients (table 3) and it is statically not significant.
Over the right ear the latencies of waves I, II, III, IV and V were
increased in COPD patients not significant.
The interpeak latencies (IPL) of I-III, I-V and III-V were prolonged
in COPD on both left and right ears (Table 3)
69
Diagram 2 : Comparison Between The Means Of COPD Patients &
Control Group Of The Brain Stem Auditory Evoked Potential Of
Left Ear
2.19
2.91
4.25
5.6
6.8
1.29
2.38
3.49
4.9
6.1
0
1
2
3
4
5
6
7
8
9
10
I II III IV V
COPD CONTROL
Wav
e la
ten
cy
70
TABLE: 4 VISUAL EVOKED POTENTIALS (VEP) VARIABLES
INCOPD PATIENTS AND CONTROLS
LEFT EYE
COPD
(n=40)
Mean ± SD
CONTROL
(n=40)
Mean ± SD
P-VALUE
Latency P100 (ms) 106.89 ± 13.9 104.6 ± 14.4 0.921
Amplitude (mv) 8.79 ± 18.7 14.9 ± 30 0.272
RIGHT EYE
COPD
(n=40)
Mean ± SD
CONTROL
(n=40)
Mean ± SD
P-VALUE
Latency P100 (ms) 103.38 ± 16.2 93.38 ± 16.3 0.007*
Amplitude 10.6 ± 16.0 5.91 ± 5.1 0.080
*Significant when P ≤ 0.05
Over left eye, the latency (P100) and Amplitude were prolonged in
COPD patients. Over the right eye the latency (P100) were significantly
increased in COPD patients (P < 0.05) and amplitude of right eye not
significant.(table 4)
71
Diagram 3:Comparison Between The Means Of COPD Patients & Control
Group Of The Brain Stem Antibody Evoked Potential Of Right Ear
1.67
2.78
4.01
5.2
7.7
1.64
2.43
4.4
5.8
6.6
0
1
2
3
4
5
6
7
8
9
10
I II III IV V
COPD CONTROL
Wav
e la
tency
72
TABLE – 5 CORRELATION OF BRAIN STEM AUDITORY
EVOKED POTENTIAL (BAEP) VARIABLES RECORDED OVER
LEFT EAR WITH SPIROMETRY INDICES
LEFT EAR
LATENCIES
FEV1% of
pred
FVC% of
pred
FEV1/FVC%
pred
I r
p -0.118
0.469
0.015
0.925
-0.111
0.496
II r
p -0.183
0.259
-0.0234
0.147
-0.52
0.750
III r
p -0.62
0.705
-0.092
0.573
-0.075
0.646
IV r
p -0.097
0.553
-0.91
0.578
-1.02
0.531
V r
p -0.095
0.561
-0.41
0.803
-0.141
0.387
INTERPEAK LATENCIES(IPLs)
I – III r
p -0.044
0.789
-0.014
0.933
-1.68
0.300
III – V r
p -0.033
0.841
0.035
0.831
-0.084
0.605
I – V r
p - 0.55
0.738
0.029
0.858
-0.105
0.517
r - correlation value
Significant when P ≤ 0.05
BAER wave II, III, IV & V latency and I-III interpeak latency showed
negative correlation with FEV1, FVC and FEV1/FVC% of predicted
value and not significant over left ear in COPD patients.
73
TABLE–6: CORRELATION OF BRAIN STEM AUDITORY
EVOKED POTENTIAL (BAEP) VARIABLES RECORDED OVER
RIGHT EAR WITH SPIROMETRY INDICES
RIGHT EAR
LATENCIES
FEV1% of
pred
FVC% of
pred
FEV1/FVC%
pred
I r
p 0.015
0.925 -0.107
0.511
0.167
0.302
II r
p 0.254
0.114 0.150
0.356
0.202
0.212
III r
p 0.078
0.631 0.041
0.804
-0.015
0.929
IV r
p -0.001
0.995 -0.052
0.749
-0.021
0.898
V r
p 0.0167
0.302 0.133
0.415
0.114
0.485
INTERPEAK LATENCIES
I – III r
p 0.134
0.410
0.142
0.384
-0.067
0.681
III – V r
p 0.148
0.24
0.025
0.879
-0.033
0.838
I – V r
p 0.233
0.148
0.235
0.144
0.085
0.603
r - correlation value
Significant when P ≤ 0.05
BAER wave IV latency showed negative correlation with FEV1, FVC
and FEV1/FVC% of predicted value and not significant over right ear in
COPD patients.
74
TABLE – 7: CORRELATION OF VISUAL EVOKED POTENTIAL
(VEP) VARIABLES RECORDED OVER LEFT AND RIGHT EYE
WITH SPIROMETRY INDICES
LEFT EAR
LATENCIES
FEV1% of
pred
FVC% of
pred
FEV1/FVC%
pred
P100 (ms) r p 0.036
0.824
0.059
0.716
-0.001
0994
Amplitude (mv) r p -0.128
0.432
-0.074
0.651
-0.234
0.147
RIGHT EAR
LATENCIES
FEV1% of
pred
FVC% of
pred
FEV1/FVC%
pred
P100 (ms) Rp -0.096
0.557
-0.020
0.902
-0.063
0.695
Amplitude (mv) r p 0.038
0.814
0.009
0.956
0.042
0.799
r - correlation value
Significant when P ≤ 0.05
The correlation between the VEP variables and the characteristics
of COPD patients revealed that the latency P100 of Right ear were
correlated negatively with the spirometric indices and the amplitude of
Right ear were correlated positively and not significant with the
spirometric indices.
75
DIAGRAM 4:SCARTTERED PLOT DIAGRAM SHOWING
CORRELATION BETWEEN VEP VARIABLE OF LEFT EYE.
Negative correlation between <P100 latency and FEV1/ FVC index.
90
95
100
105
110
0 20 40 60 80 100 120
LP
10
0
FEV1/FVC
LP 100 Linear (LP 100)
76
DIAGRAM 5: SCARTTERED PLOT DIAGRAM SHOWING
CORRELATION BETWEEN VEP VARIABLE OF LEFT EYE.
Negative correlation between <P100 latency and FEV1 percent.
95
97
99
101
103
105
107
109
0 10 20 30 40 50 60 70 80 90 100
LP
10
0
FEV1 %
LP 100 Linear (LP 100)
77
TABLE 8: CORRELATION OF PFT VARIABLES WITH CRP IN
COPD PATIENTS
PARAMETERS CRP
% Predicted FVC r
p
0.187
0.248
% Predicted FEV1 r
p
0.062
0.703
% Predicted FEV1/FVC r
p
– 0.095
0.560
r - correlation value
Correlation of indices of spirometry (% predicted FVC, FEV1,
FEV1/FVC) with C- reactive protein, FEV1/FVC in COPD patients
showed negative correlation with CRP and statistically not significant.
78
TABLE – 9: CORRELATION OF BRAIN STEM AUDITORY
EVOKED POTENTIAL (BAEP) VARIABLES RECORDED OVER
LEFT AND RIGHT EAR WITH CRP
LEFT EAR
LATENCIES CRP
I r
p
-0.211
0.190
II r
p
-0.125
0.441
III r
p
0.054
0.739
IV r
p
0.214
0.185
V r
p
0.215
0.442
INTERPEAKLATENCIES
I – III r
p
0.327
0.040
III – V r
p
0.185
0.253
I – V r
p
0.275
0.086
RIGHT EAR
LATENCIES CRP
I r
p
– 0.142
0.383
II r
p
0.383
0.873
III r
p
0.089
0.584
IV r
p
0.241
0.133
V r
p
0.024
0.883
INTERPEAK LATENCIES
I – III r
p
0.239
0.138
III – V r
p
0.180
0.268
I – V r
p
0.000
1.000
r - correlation value
Significant when P ≤ 0.05
79
Correlation of brain – stem auditory evoked potentials (BAEP)
variables with C-reactive protein on both ears, BAEP wave III, IV and V
of left ear and BAEP wave I,II, III, IV and V of right ear shows positive
correlation with CRP on both ears, not significant but the interpeak
latency of left ear I-III shows significant positive correlation with
CRP.(table 9)
Interpeak latency I-III, III-V and I-V of left ear and interpeak
latency I-III, III-V, and I-V of right ear shows positive correlation with
CRP on both ears(table 9)
80
Diagram 6: Comparison Between The Means Of COPD Patients &
Control Group taking p(100) of both eyes(VEP)
104.6106.89
103.38
93.38
10
20
30
40
50
60
70
80
90
100
110
120
Left Eye Right Eye
COPD CONTROL
P1
00
L
aten
cy a
nd
A
pti
tud
e
81
TABLE – 10: CORRELATION OF VISUAL EVOKED
POTENTIAL (VEP) VARIABLES RECORDED OVER LEFT AND
RIGHT EYE WITH CRP.
LEFT EYE
LATENCY CRP
P100 (ms) r
p
0.303
0.057
Amplitude (mv) r
p
– 0.90
0.579
RIGHT EYE
LATENCY CRP
P100(ms) r
p
0.231
0.152
Amplitude (mv) r
p
0.015
0.927
r- correlation value
Significant when P ≤ 0.05
Correlation of visual evoked potential (VEP) variable with C-
reactive protein of both eyes.
VEP have latency (P100) shows positive correlation with CRP on
both eyes on the other hand. Wave amplitude of left eye shows negative
correlation with CRP but not significant.
82
DISCUSSION COPD is a multisystem disorder that is frequently associated with
significant extra pulmonary manifestations Gupta et al (38)
Although COPD affects the lung, it also produces significant
systemic consequences. The consequences can be detected clinically and
appear to be associated with the presence of systemic inflammatory
markers.
In our study we included stable COPD with no clinical evidence of
any neuropathy.
Our aim is to evaluate the brain stem auditory evoked potentials
and visual evoked potential abnormalities in stable COPD patient and its
correlation with C-reactive protein as a part of multisystem disorder
Indeed it is widely accepted that COPD patients with hypoxemia
have a higher mortality. Which is improved with oxygen therapy,
hypoxemia triggers oxidative stress and inflammation in COPD patients.
There is now sufficient evidence to support the presence of extra
pulmonary or systemic consequences of COPD that can be detected
clinically(39)
El- Kady et al found statically significant difference for all audio
logical measures between the control group and COPD.
The present study showed significant prolonged latency and
interpeak latencies with decrease in amplitude on both ears.
83
Sohma et al demonstrated depression of the auditory nerve brain
stem evoked response as well as vestibular and visual evoked potentials
during severe hypoxemia in cats.
In addition to chronic hypoxemia and hypercapnia, often associated
factors in patients with COPD, including tobacco, smoking malnutrition
and drugs used in COPD treatment like long acting inhaled B2 agonists,
inhaled anticholinergic agents, inhaled glucocorticords and sustained
release through of theophyline, may be possibly associated with
neuropathy seen in COPD patients.
Although COPD affects the lung, it also produces significant
systemic consequences. The consequences can be detected clinically and
appear to be associated with the presence of systemic inflammatory
markers.
Gan and co-workers were the first to note the importance of high
CRP levels in COPD patients. They showed that CRP is elevated in
patient who actively smoked. Brockhuizen et al found that CRP was a
marker of impaired energy metabolism, functional capacity and distress
in 102 severe COPD patients. It is widely accepted that CRP levels
relates to the presence of airflow obstruction. In the present study CRP
were significantly increased from control. The serum level of C-reactive
protein in COPD patients were significantly elevated, which is similar to
84
study done by Denise Rossato Silva et al, Marcelo Basso Gazzana et al
and Marli Maria Knorstet al.(40)
There is no sufficient evidence to support the presence of extra
pulmonary or systemic consequences of COPD that can be detected
clinically and that could also be measured by the determination of level of
increased systemic inflammatory markers. CRP is one of these markers
that could reflect the total systemic inflammation.
Friss et al detected prolongations in BAER wave V and interpeak
latency of III-V in preterm infants under hypercarbic state they speculated
that hypercarbia had a deleterious effect as neuronal function. IPL of
BAER III-V which represents the central portion of the auditory pathway
was significantly correlated with Paco2 and H2O3 and pH of the arterial
blood gas.
In the present study showed the latencies of wave I,II,III, IV and V
over left ear were prolonged in COPD patients and statistically
significant.
Over the right ear the latencies of wave I, II, III, IV and V
increased in COPD patients but not significant. The interpeak latencies
(IPL) of I-III, I-V and III-V were increased in COPD on both left and
right ears and not significant. The results of the present study agreed with
friss et al, shomer et al, Gupta et al (41)
85
Spirometry only gives us the pattern of lung function abnormality
(FEV1, FVC, FEV1/FVC), spirometry does not tell us if this patient has
asthma or COPD. The diagnosis will depend on the patients clinical
presentation and the spirometry merely provides collaborative evidence.
The results of the present study showed the indices of spirometry
(FEV1, FVC, FEV1/FVC) were significantly decreased from control. The
present study agreed with thunhou ong.et al.
In VEP significant increase in N -75 latency in COPD patients may
be attributed to synaptic delay or altered neuronal processing in optic
nerve which in accordance with the suggestion of singh et al. The P100
latency is the most consistent one having least variable peak when
compared with N75 and N145. Since, N145 wave is generated from extra-
striate visual cortex.(42)
The result of present study showed the latency (P100) of left eye
were increased in COPD patients and Amplitude decreased in COPD
patients. Over the right eye the latency (P100) were significantly increased
in COPD patients (P<0.05) but amplitude of right eye not significant, this
finding is similar to the recent studies with oze et al.(43)
Sezer et al also showed that P100 value was altered in COPD patient
and further hypothesized that the elevations in latencies were brought
about by the hypoxia, hypercapnea and acidosis resulting from COPD.
86
The finding of independency of factors viz. disease duration, smoking
and age on COPD corroborates with the observation of oze et al
In the present study showed in BAEP the latencies of wave I,II,III,
IV and V over left ear were prolonged in COPD patients and statistically
significant.
BAER wave IV latency showed negative correlation with
FEV1,FVC and FEV1/FVC % of predicted value and not significant over
right ear these results matched with that reported by Gupta et al and could
not find any correlation between BAEP parameters and indices of
pulmonary function test.
The present study the correlation between the VEP variables and
the spirometric indices revealed that the latency P100 of right ear were
correlated negatively with the spirometric indices and the amplitude of
right ear were correlated positively and not significant with the PFT,
However oze et al evaluated optic nerve involvement with severe COPD
and they observed VEP abnormalities which is similar to our study.
We could not find any correlation between the BAEP, VEP
parameters and pulmonary function test parameters, the poor correlation
in spite of significant BAEP, VEP abnormalities is probably due to the
narrow range of patients characteristic and pulmonary function
parameters in our patients as we included relatively stable patients during
the early course of COPD
87
Correlation of brain- stem auditory evoked potential (BAEP)
variables with C-reactive protein on both ears, BAEP wave III IV and V
of left ear and BAEP wave I, II, III, IV and V of right ear shows positive
correlation with Correlation with CRP on both ears, and not significant
but the interpeak latency of left ear I-III shows significant positive
correlation with CRP.
Interpeak latency I-III, III-V and I-V of left ear and interpeak
latency I-III, III-V and I-V of right ear shows positive correlation with
CRP on both ears. Which agrees with the study done by NesrienShalabi
et al Mohmed Abdel El salam et al, Fatma Abbas et al.(44)
Correlation of VEP variable with C-reactive protein over both eyes
VEP latency (P100) shows positive correlation with CRP over both eyes
on the other hand wave amplitude of left eye shows negative correlation
with CRP and not significant and is similar to study done be oze et al.
Correlation of indices of spirometry (% predicted FVC, FEV1,
FEV1/FVC) with C-reactive protein, FEV1/FVC in COPD patients
showed negative correlation with CRP and statistically not significant and
similar to study done by Oze et al.(45)
In our study BAER wave II, III, IV and V latencies and I-III
interpeak latency showed negative correlation with spirometric indices
and not significant over left ear in COPD patients.
88
In this study the COPD and control group were matched in age and
sex. CRP levels were significantly higher in COPD patients and indices
of spirometry (FEV/FVC) were decreased significantly in COPD patients.
In VEP the latency (P100) of left eye were increased in COPD patients and
Amplitude decreased in COPD patients. Over the right eye the latency
(P100) were significantly increased in COPD patients (P<0.05) and
amplitude of right eye not significant.
These data suggest that airways obstruction and long lasting COPD
resulting in hypoxemia, hypercapnia and respiratory acidosis which in
turn affect the ponto-medullary portion of the brain.
89
CONCLUSION
• Smoking, airway obstruction and long lasting COPD leading to
hypoxemia, hypercapnia and respiratory acidosis which may affect the
ponto-medullary portion of the brain.
This study confirm that there were subclinical VEP and BAEP
impairment resulted from COPD illness, which were related to the
severity and disease duration.
• optic and auditory nerves are commonly affected in COPD which
represent an additional problem to physical effect of COPD , and of
course both will reflect more impairment in quality of life. So early
discovery and correction of these factors might decrease disabilities
and help in improvement of quality of life of COPD patients.
• The findings from this study indicate that impairment of VEP and
BAEP occurred in association with mild chronic respiratory
insufficiency. Therefore, the respiratory condition must be taken into
account when evaluating VEP and BAEP.
• We found that the levels of CRP in stable COPD were not different as
compared to control subjects. These results if confirmed in a larger
study, which also excludes patients with comorbidities related to
chronic inflammation, could contribute to a better understanding of
CRP concentrations in COPD patients.
BIBLIOGRAPHY
1. Sharma S.K.. “Chronic obstructive lung disease” API text book of medicine,
Siddarth N. Shah, 2003, 7th editionChapter 6, Pg. 297.
2. William MacNee “Chronic Bronchitis and emphysema”. Crofton and
Douglass Respiratory Diseases Chapter 616, edited by Antony Seaton,
Douglas Seaton, fifth edition, Blackwell Sciences, Volume – 1, 650.
3. Suzanne Hurd, Ph.D. “The impact of COPD on lung health world wide,
epidemiology and incidence:,Chest, 2000. Vol. 117 : 1S – 4S.”
4. Benjamin Burrows, Richard H.Earle. “Course and prognosis of chronic
obstructive lung disease”, The New England Journal of Medicine 1669, Vol.
280 – 8, Pg. 297 – 404.
5. Pfeifer G, Kunze K, Bruch M,: Polyneuropathy associated with chronic
hypoxemia: Prevalence in patients with chronic obstructive pulmonary
disease. J Neurol 1990;237 : 230 – 3.
6. Sezer M, Yaman M, and Oruc S, Visual evoked potential changes in chronic
obstructive pulmonary disease. Eur J Gen Med 2007; 4(3) : 115 – 118.
7. Gupta PP, Sood S, and Atreja A,: Evaluation of brainstem auditory evoked
potentials in stable patients with chronic obstructive pulmonary disease. Ann
Thorac med 2008; 4:128 – 34.
8. Man SF, cornett JE, Anthonisen NR, C-reactive protein and mortality in mild
to moderate chronic obstructive pulmonary disease. 2004.pp.249-66.
Age Sex
Wave
Latency
P100(ms)
Amptitude
(mv)
Wave
Latency
I
II III IVInter Peak
Latency VI -III III - V I - V
96.9 ± 3.6 7.8 ± 1.9 1.67 ± 0.17 2.78 ± 0.01 3.65 ± 0.22 5.6 ± 0.30 5.72 ± 0.3 1.99 ± 0.25 2.08 ± 0.30 4.04 ± 0.25
1 33 M63.5
115
4.72
8.32
1.35
1.35
2.3
2.3
3.3.
3.3
5.12
5.12
5.75
5.12
1.95
1.95
2.65
2.65
4.6
4.6
2 36 M106
100.5
0
0
1.08
1.82
2.08
1.85
322
2.98
4.12
4.38
6.68
3.38
2.14
1.86
2.46
2.38
4.6
4.32
3 33 M97
98
2.7
3.28
1.05
1.05
2
2
3.98
3.98
5.03
5.03
6.15
6.15
2.93
2.93
2.17
2.14
5.1
5.1
4 44 M95
97
3.28
2.7
1.05
1.08
2.08
1.48
4.58
3.28
6.2
4.5
7.72
5.38
3.53
2.2
3.34
2.3
6.87
4.5
5 45 M92.8
102
2.83
1.4
1.23
1.23
2.2
2.2
3.25
3.25
4.3
4.3
3.42
3.45
2.02
2.02
2.17
2.17
4.19
4.19
6 55 M92.5
102
2.83
14.77
1.18
1.23
2.82
2.22
3.8
4.2
4.35
5.48
5.18
6.6
2.62
2.97
1.28
2.4
3.9
5.37
7 51 M7.55
88.5
13
3
1.1
1.12
1.92
2
2.92
2.88
3.98
3.35
4.95
4.18
1.92
1.38
2.03
1.6
3.95
2.95
8 53 M90.5
11.2
3
3
1.42
0.35
2.38
11
3.65
2.28
4.82
4.82
5.72
7.85
2.23
1.9
2.27
4.87
4.8
6.77
9 33 M105
87
2.83
2.83
1.23
0.98
2.68
2.12
3.85
2.3
4.88
4.3
6.3
5.82
2.62
2.32
2.45
2.52
5.47
4.84
10 34 M95.8
73.5
10.6
6.7
1.9
0.05
2.72
1.88
3.8
2.7
5.08
3.8
6.1
4.35
1.68
1.65
2.52
1.64
4.2
6.3
11 44 M79
73.5
2.7
2.7
1.05
0.8
2.17
2.1
3.28
3.4
4.25
4.6
5.45
5.65
2.23
2.6
2.17
2.25
4.4
4.85
12 47 F70
73.5
12
12.7
1.15
0.82
2.02
1.88
3.7
2.95
6.55
3.8
7.38
4.82
2.55
2.13
3.65
1.87
6.23
4.01
13 46 M88
79
1.12
2
0.68
0.68
1.7
1.7
2.78
2.78
4.42
4.42
6.05
6.05
2.1
2.1
3.3
3.3
5.4
5.4
CONTROL
Sl.
No
VEP FINDINGS BAEP FINDINGS
Age Sex
Wave
Latency
P100(ms)
Amptitude
(mv)
Wave
Latency
I
II III IVInter Peak
Latency VI -III III - V I - V
Sl.
No
VEP FINDINGS BAEP FINDINGS
14 31 M86.8
74.8
15
1
1
1.2
1.92
2
2.92
2.58
3.98
3.35
4.95
4.18
1.92
1.38
2.03
1.6
3.95
2.98
15 33 M98
98
17.5
17.37
1.05
0.8
2.18
2.1
3.28
3.4
4.25
4.6
5.45
5.65
2.23
2.6
2.17
2.25
4.4
4.85
16 46 F103.5
103.5
6.94
6.94
1.08
0.75
1.92
1.55
2.98
2.78
5.08
3.82
6.98
49
1.9
1.9
4
4
5.9
5.9
17 44 M100.5
99
12.65
14.61
1
1.3
2
2.17
3.02
4.47
4.35
5.52
5.22
8.12
2.12
3.17
2.2
3.65
4.22
6.82
18 48 F107
97
9.43
10.21
6.78
0.82
1.7
1.88
2.68
2.8
4.05
4.25
6.72
5.52
1.9
1.9
4.04
2.7
3.94
4.7
19 49 M98
94
8.86
11.27
0.75
0.88
1.7
2.17
3.18
3.18
4.15
4.1
5.75
5.25
2.61
2.3
2.6
2.07
5.2
4.37
20 33 M102.5
101
18.7
19.42
0.55
0.65
2.3
2.5
3.08
4.7
7.05
5.15
8.05
5.92
6.5
4.05
0.53
1.22
6.5
5.27
21 37 M94.5
94.5
2.49
2.52
0.62
0.08
1.75
1.88
2.75
2.78
3.9
4.38
4.98
0.08
2.13
2.8
2.03
2.034.16
22 34 M100.5
99.5
8.05
7.71
1.18
1.08
2.2
2.08
4.4
3.22
5.72
5.05
7.88
7.88
2.2
2.14
3.48
4.63
6.7
6.77
23 51 F103.5
102
2.24
2.17
0.38
0.9
1.88
2.68
3.35
4.15
5.62
5.7
7.8
7.7
3
3.25
4.4
3.6
74
68.5
24 49 M102
107
8.55
7.3
0.98
1.3
2.9
2.62
4.28
4.88
5.78
5.7
7.2
6.82
3.3
3.55
2.92
1.74
6.22
3.32
25 47 M88
97
7.52
7.89
1.1
1.8
2.5
1.9
4
2.75
4.6
4.55
5.38
5.5
2.9
1.2
1.38
2.75
4.28
3.95
26 34 M104
104
7.01
1.1
1.98
2.2
2.78
2.9
3.4
48
4.05
6.3
5.03
6.85
1.42
2.63
1.63
2
3.08
4.63
27 36 M93.5
95.5
9.18
1.9
1.98
1.65
2.8
2.28
3.8
2.9
5.5
3.48
6.3
4.2
1.9
1.25
2.42
1.3
4.32
2.55
28 42 M100
100
5.8
8.7
0.95
1.58
2.45
2.58
2.88
4.15
3.72
4.88
6.42
5.6
1.93
5.75
3.54
1.45
5.47
4.02
29 44 F92.5
95.5
1.5
1.7
1.72
1.78
2.4
2.38
3.12
2.03
4.4
4.3
6
4.95
1.4
1.27
28
1.9
4.28
3.17
Age Sex
Wave
Latency
P100(ms)
Amptitude
(mv)
I II III IV V I-III III-V I-V
96.9 ± 3.6 7.8 ± 1.9 1.67 ±0.17 2.78±0.21 3.65±0.22 5.6±0.30 5.72±0.3 1.99±0.25 2.08±0.30 4.04±0.25
41 51 M44.5
44.5
2.5
2.5
1.1
1.1
2.3
2.3
3.22
3.22
3.95
3.95
4.72
4.72
2.12
2.12
1.5
1.5
3.62
3.62
42 55 M 99.5
94.5
2.19
2.19
0.62
1.7
1.38
3.42
2.15
4.58
2.8
5.65
3.85
8.98
1.53
2.88
1.7
4.4
3.23
7.28
43 56 M109.5
109.5
4.9
4.9
1.95
1.95
2.88
2.88
3.85
3.85
5.52
5.52
6.38
6.38
1.9
1.9
2.5
2.5
4.4
4.4
44 31 M 100.5
102
7.31
16.22
0.78
1.05
1.95
2.65
4.03
3.7
7.55
5.08
8.85
7.55
3.25
3.25
4.82
3.85
8.07
6.5
45 32 M116
101
4.57
6.2
2.83
2.83
3.65
3.65
5.28
5.28
6.32
6.32
8.48
8.48
2.9
2.9
3.2
3.2
6.1
6.1
46 31 M 111
99
7.7
3.1
1.42
0.38
2.58
1.1
3.65
2.28
4.82
4.22
5.92
7.15
2.23
1.9
2.27
4.87
4.5
6.77
47 53 M103
112.5
13.1
23.3
1.23
0.98
2.68
2.12
3.85
3.3
4.88
4.53
6.3
5.82
2.62
2.32
2.45
2.52
5.07
4.84
48 44 F103
103
6.14
6.16
1.9
1.05
2.72
1.88
3.58
2.7
5.08
3.5
6.1
4.35
1.68
1.65
2.52
1.65
42
33
49 47 M102
103.8 123
1.82
1.82
3.08
3.08
4.03
4.03
5.3
5.3
6.32
6.32
2.21
2.21
2.29
2.29
4.5
4.5
50 51 M104
103.5
4
12
298
1
4
2.55
5.85
3.52
6.9
5.12
7.8
6.7
2.87
2.52
1.98
3.18
4.82
5.7
51 53 F109
106.5
1.7
6.51
1.62
1.32
2.33
4.03
3.42
5.03
4.58
6
5.6
8.22
1.8
3.71
2.18
3.19
3.98
6.9
52 57 M103
103.5
4.67
6.01
1.4
0.3
2.65
1.75
4.7
3.75
6.88
6.28
5.9
8.3
3.3
3.43
2.15
4.55
5.48
7.98
COPD (STUDY GROUP)
Sl.
No
BAEP FINDINGS
Wave Latency Inter Peak Latency VEP FINDINGS
Age Sex
Wave
Latency
P100(ms)
Amptitude
(mv)
I II III IV V I-III III-V I-V
Sl.
No
BAEP FINDINGS
Wave Latency Inter Peak Latency VEP FINDINGS
53 41 M109.8
105
4.01
8.81
1.92
1.55
3.7
3.02
4.82
3.9
6.62
6.18
6.95
8.4
2.1
2.35
2.13
4.8
5.03
6.85
54 51 F104.5
104.5
7.86
7.86
1.27
1.88
3.05
2.68
4.75
5.83
7.08
6.05
9.65
7.05
3.48
3.48
4.9
2.02
8.38
8.47
55 32 M103.5
104.5
7.74
7.32
1.15
1.75
2.28
3.98
4.68
6.12
6.52
8.22
7.85
9.78
3.5
4.37
32
3.66
6.7
8.03
56 33 M102.5
98
4.93
4.01
4.03
4.03
5.32
5.32
6.1
6.1
7.55
7.55
8.38
8.38
2.07
2.07
2.28
2.28
4.35
43
57 34 M102.8
145
4.93
8.8
10.6
1.45
2.5
2.95
4.47
4.18
6.82
5.08
8.75
6.1
2.46
2
4.28
1.92
8.15
4.65
58 38 M104.5
99.5
7.64
1.9
1.32
1.9
2.08
3.02
3.78
3.9
4.75
3.32
6.4
6.7
2.46
2
2.62
28
5.8
4.8
59 57 F105.5
103
10.62
11.79
2.88
1.1
2.05
3.4
3.12
4.3
4.02
5.7
5.45
6.38
2.24
3.2
2.33
2.28
4.57
5.45
60 42 M103
102
6.17
5.54
1.08
2
2.58
2.88
4.08
3.35
5.5
4.12
5.85
6.2
3.03
1.35
1.8
2.85
4.83
42
61 41 M100
101
9.65
9.09
0.88
0.4
2.78
1.4
4.25
3.68
6.4
4.3
8.62
6.28
3.7
2.68
4.37
3.2
8.07
5.88
62 32 M103.5
108
7.64
6.36
1.25
1.45
2.9
2.92
4.4
4.15
5.82
5.95
7.32
7.48
3.15
2.7
2.92
3.33
6.07
6.03
63 41 M100
102
10.72
11.69
0.92
1
1.65
1.9
3.18
2.68
5.82
3.32
7.8
5.4
2.26
1.68
4.5
2.72
6.76
4.4
64 53 M103
103
7.88
7.58
2.4
1.88
3.9
3.72
5.18
4.55
6.55
5.6
7.88
7.7
2.67
2.67
3.15
3.15
8.82
8.82
65 48 F106
109
9.27
12.37
6.98
1.3
2.9
2.6
4.28
4.8
5.78
5.58
7.2
6.62
3.3
3.88
2.92
1.74
6.22
5.32
66 41 F 96 7.821.88
1.38
2.68
2.28
3.92
3.25
4.5
4.12
5.4
5.05
2.04
1.87
1.48
1.8
352
3.67
67 44 M102
100
8.3
15.61
1.82
6.98
2.88
2.48
3.22
3.32
4.18
4.53
4.9
5.85
1.4
2.34
1.68
2.53
3.08
4.87
Age Sex
Wave
Latency
P100(ms)
Amptitude
(mv)
I II III IV V I-III III-V I-V
Sl.
No
BAEP FINDINGS
Wave Latency Inter Peak Latency VEP FINDINGS
68 45 M102
94
1.63
4
1.75
1.5
2.95
2.48
4
3.1
4.97
3.62
6
4.8
2.25
1.6
2
1.08
4.25
2.68
69 33 M101.5
89
7.86
1.54
1.18
1.12
24
1.85
3.48
3.62
4.58
4.95
5.2
5.45
2.3
2.5
1.72
1.83
4.02
4.33
70 33 M102.5
99.5
3.16
0.8
2.3
1.23
2.8
2
3.62
3.35
4.4
4.32
6.48
48
1.32
2.29
2.86
1.28
4.18
3.52
71 41 F97.5
93
5.35
72
2.3
1
3.32
2.1
4.28
2.8
5.03
4.88
5.82
6.02
1.98
1.8
1.59
3.22
3.52
5.02
72 47 F107
93
2.51
0.77
2.08
2.2
3.8
3.15
4.53
4.25
6.95
6.12
9.43
7.35
2.45
2.05
4.9
3.1
7.35
5.15
73 41 F107.8
110
4.04
0.39
1.25
1.45
2.9
2.9
4.4
4.15
5.82
5.95
7.32
7.48
3.15
2.7
2.92
3.33
6.07
6.03
74 43 M108
108
3.42
0.8
2.08
1.8
3.1
2.48
4.38
4.97
6.22
6.4
7.6
7.6
2.3
3.17
3.22
2.63
5.52
5.8
75 44 M111
104
4.85
0.93
1.9
1.2
2.8
2.37
4.88
3.7
6.58
5.55
7.82
6.68
2.98
2.45
2.94
2.98
5.92
5.43
Rt 43 M104
109
5.18
0.47
2.4
1.88
3.9
3.72
5.18
4.55
6.85
5.6
7.85
7.7
2.78
2.67
2.67
3.15
5.4
5.2
77 44 F106
106
3.63
2.72
1.68
1.25
2.5
3.38
5.22
4.38
6.8
5.9
7.1
6.03
3.54
3.05
1.88
1.6
5.42
4.65
78 47 F100
103
4.06
0.56
2.3
2.12
3.2
3
3.98
5.2
5.35
5.95
5.98
7.12
1.68
3.08
2
1.92
3.68
5
79 48 F113
97
4.34
8.54
2.92
1.98
3.32
1.95
5
2.78
5.78
4.42
6.7
4.75
2.08
1.7
1.7
1.97
3.78
3.6
80 49 M106.8
94
7.52
73
3.45
2.75
4.1
3.9
5.3
4.22
5.95
5.95
6.98
6.45
1.85
1.57
1.68
2.13
3.53
37
CRPBlood
GlucosePredicted Measured % Predicted Predicted Measured
%
PredictedPredicted Measured % Predicted
<6mg/L 80-120mg FVC FVC FVC FEV1 FEV1 FEV1 FEV1/FVC FEV1/FVC FEV1/FVC
41 51 M S 1.2 83 4.28 1.98 46 3.62 1.83 51 81.09 92.12 114
42 55 M S 2.3 117 3.04 1.55 51.1 2.63 1.46 56 83.21 94.19 113
43 56 M S 2.8 118 4.07 1.92 47 3.49 1.35 39 81.63 70.31 86
44 31 M N 2.7 121 3.93 4.17 106 3.44 3.94 115 85.49 44.48 118
45 32 M N 2.6 126 4.48 3.62 81 3.88 2.81 72 83.25 47.62 93
46 31 M N 2.8 121 4.61 4.48 97 4.01 1.02 25 83.79 22.77 27
47 53 M N 1.9 75 4.67 2.08 48 4.05 1.95 48 83.79 93.78 112
48 44 F N 1.3 83 4.7 2.39 51 4.08 1.41 35 83.97 59 70
49 47 M N 1.7 87 4.7 2.39 51 4.08 1.41 35 83.97 59 70
50 51 M S 2.2 89 4.23 1.7 40 3.6 0.89 24 82.71 52.35 63
51 53 F N 2.3 91 4.25 5.81 137 3.61 5.4 116 82.89 92.94 112
52 57 M N 3.1 75 4.49 3.09 69 3.85 2.88 78 82.53 93.2 113
53 41 M N 2.8 103 3.57 0.37 10 3.12 0.37 12 84.54 110 118
54 51 F N 2.3 107 4.7 2.39 51 4.08 1.41 35 83.97 59 70
55 32 M S 2.3 109 4.23 1.7 40 3.6 0.89 24 82.71 52.35 63
56 33 M S 1.9 111 2.92 2.66 91 2.52 2.33 92 83.02 87.59 106
57 34 M S 1.8 108 3.91 1.37 65 3.32 0.014 28 80.55 68.61 85
58 38 M S 2.1 98 3.96 4.01 101 3.48 3.7 106 82.89 92.77 111
59 57 F N 2.1 81 4.33 4.15 96 3.75 3.78 110 83.43 91.08 109
60 42 M N 2.3 73 3.75 1.74 46 3.28 1.25 35 84.54 71.84 88
COPD(STUDY GROUP)
Sl.No
BLOOD TEST SPIROMETRIC INDICES
AGE SexSmok
ing
CRPBlood
GlucosePredicted Measured % Predicted Predicted Measured
%
PredictedPredicted Measured % Predicted
<6mg/L 80-120mg FVC FVC FVC FEV1 FEV1 FEV1 FEV1/FVC FEV1/FVC FEV1/FVC
Sl.No
BLOOD TEST SPIROMETRIC INDICES
AGE SexSmok
ing
61 41 M N 2.4 84 3.75 1.74 46 3.28 1.25 25 84.54 71.84 85
62 32 M N 2 81 4.3 3.15 73 3.75 2.87 77 83.25 91.11 109
63 41 M S 1.9 83 3.75 2.58 69 3.35 2.22 66 83.43 86.05 103
64 53 M S 2.1 101 3.89 3.05 78 3.39 2.83 83 82.35 92.79 113
65 48 F N 1.7 121 3.01 1.74 58 2.6 1.17 45 82.07 67.24 82
66 41 F N 1.8 123 27 1.86 69 2.33 1.64 70 83.02 88.17 106
67 44 M N 1.9 123 3.4 1.55 46 2.97 1.41 47 84.92 90.77 107
68 45 M S 2 128 4.1 2.41 59 3.52 2.12 60 81.81 87.97 108
69 33 M S 1.7 129 4.36 3.25 75 3.81 2.77 73 83.61 85.23 102
70 33 M S 1.8 89 3.24 2.66 82 2.8 2.4 87 82.07 91.73 112
71 41 F N 1.9 98 3.85 1.74 48 3.37 1.16 34 84.92 66.67 79
72 47 F N 1.8 97 3.31 1.21 37 2.87 1.04 36 82.64 85.95 104
73 41 F S 2 96 3.31 1.82 55 2.87 1.58 55 82.64 86.81 103
74 43 M S 1.9 81 2.53 1.41 56 2.2 1.09 50 84.47 77.3 92
75 44 M S 1.7 83 4.3 3 70 3.75 2.97 79 83.25 99 119
76 43 M N 1.4 75 3.91 1.37 35 3.32 0.94 28 80.55 68.61 85
77 44 F N 2.1 81 2.92 2.66 91 2.52 2.33 92 83.02 87.59 100
78 47 F N 1 86 3.91 1.37 35 3.32 0.94 28 80.55 68.61 85
79 48 F N 1 87 4.3 3 70 3.75 2.97 79 83.25 99 119
80 49 M N 2 98 4.2 2.84 68 3.69 2.55 76 82.53 96.83 117
CRPBlood
GlucosePredicted Measured
%
PredictedPredicted Measured
%
PredictedPredicted Measured % Predicted
<6mg/L 80-120mg FVC FVC FVC FEV1 FEV1 FEV1 FEV1/FVC FEV1/FVC FEV1/FVC
1 33 M N 2.3 86 3.69 2.31 63 3.22 1.76 55 84.73 76.19 90
2 36 M N 1.2 73 3.93 4.17 106 3.44 3.94 115 85.49 94.48 111
3 33 M N 1.3 82 4.21 4.23 100 3.61 3.74 104 84.47 88.42 105
4 44 M N 1.1 61 2.96 3.13 106 2.71 2.97 101 84.47 94.89 112
5 45 M N 1.3 102 4.49 3.09 69 3.85 2.88 75 82.53 93.2 113
6 55 M N 1.2 101 4.49 3.09 69 3.85 2.88 78 82.53 93.2 113
7 51 M S 1.3 102 4.64 6.07 131 4.02 5.55 138 83.61 91.43 109
8 53 M N 1.8 101 4.3 3 70 3.78 2.97 79 83.75 99 119
9 33 M N 1.7 107 4.64 6.07 131 4.02 5.55 138 83.61 91.43 109
10 34 M N 1.6 86 4.35 3.25 81 3.86 2.86 82 82.35 88 107
11 44 M N 2.1 76 4.36 3.25 75 3.81 2.77 73 83.61 85.23 102
12 47 F N 2.9 71 4.33 3.35 77 3.78 3.06 81 83.43 91.34 109
13 46 M N 1.3 84 2.95 2.82 96 2.55 2.5 98 83.21 88.65 107
14 31 M N 1.7 113 4.64 6.07 131 4.02 5.55 138 83.61 91.43 109
15 33 M S 1.7 115 2.95 2.82 96 2.55 2.5 98 83.21 88.65 107
16 46 F N 1.9 116 4.36 3.28 78 3.81 2.77 73 83.61 85.23 102
17 44 M N 1.2 87 2.95 2.82 96 2.55 2.5 98 83.21 88.65 107
18 48 F N 2.1 88 3.29 2.66 81 2.88 2.59 90 85.68 97.37 114
19 49 M S 2.1 81 3.75 1.74 46 3.28 1.25 58 84.54 71.84 85
20 33 M N 1.1 98 4.64 6.07 131 4.02 5.55 135 83.61 91.43 109
CONTROL
Sl.
No
BLOOD TEST SPIROMETRIC INDICES
Age SexSmoki
ng
CRPBlood
GlucosePredicted Measured
%
PredictedPredicted Measured
%
PredictedPredicted Measured % Predicted
<6mg/L 80-120mg FVC FVC FVC FEV1 FEV1 FEV1 FEV1/FVC FEV1/FVC FEV1/FVC
Sl.
No
BLOOD TEST SPIROMETRIC INDICES
Age SexSmoki
ng
21 37 M N 1.9 101 4.64 6.07 131 4.02 5.55 135 83.61 91.43 109
22 34 M N 1.7 82 4.2 2.84 60 3.6 2.75 76 82.53 96.83 117
23 51 F N 1.8 87 4.64 6.07 131 4.02 5.55 138 83.61 91.43 109
24 49 M N 1.7 73 3.69 2.31 63 3.22 1.76 55 84.73 76.19 90
25 47 M S 2.1 41 4.21 4.23 100 3.61 3.74 104 84.47 88.42 108
26 34 M S 1.2 84 4.49 3.09 69 3.85 2.88 75 82.53 93.2 113
27 36 M N 1.3 62 4.49 3.09 69 3.85 2.88 78 82.53 93.2 113
28 42 M N 1.9 61 43 3 70 3.78 2.97 79 83.75 99 119
29 44 F N 1.7 75 4.64 6.07 131 4.02 5.55 138 83.61 91.43 109
30 47 F N 1.6 102 4.36 3.25 75 3.81 2.77 73 83.61 85.223 102
31 48 M N 1.7 112 4.32 3.25 81 3.86 2.86 82 82.35 88 107
32 33 F S 2.2 121 4.36 3.25 75 3.81 2.77 73 83.61 85.23 102
33 51 F N 1.9 124 4.64 6.07 131 4.02 5.55 138 83.61 91.43 109
34 57 F N 1.7 128 2.95 2.82 96 2.55 2.5 98 83.21 88.65 107
35 54 M N 1.7 111 4.36 3.28 78 3.81 2.77 73 83.61 85.23 102
36 51 M N 1.8 113 2.95 2.82 96 2.55 2.5 98 83.21 88.65 107
37 37 M S 1.6 98 3.69 2.31 63 3.22 1.76 55 84.73 76.19 90
38 32 M N 1.8 75 4.64 6.07 131 4.02 5.55 138 83.61 91.43 109
39 42 M N 1.7 86 2.95 2.82 96 2.55 2.5 98 83.21 88.65 107
40 51 M N 1.7 83 4.35 3.25 81 3.86 2.86 82 82.35 88 107
KEY TO MASTER CHART
VEP - Visual Evoked Potential
RT - Right
LT - Left
BAEP - Brainstem Auditory Evoked
Wave Latency - I, II, III, IV, V
Inter Peak Latency - I-III, III-V, I-V
PFT - Pulmonary Function Test
CRP - ‘C’ Reactive protein
FEV1 -
Forced expiratory volume in one
second
FVC - Forced Vital Capacity