IJCRR - 8(1), January, 2016
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CORRELATION OF DISEASE DURATION, SMOKING PACK YEARS AND FEV1% PREDICTED WITH BAEP PARAMETERS IN PATIENTS OF COPD
Author: Rupali Parlewar, Rubiya Shaikh
Abstract:COPD is a progressive disease associated with an amplified chronic inflammatory response to noxious particles or gases in the airways and lungs. It is characterized by airflow limitation that is not fully reversible. Long term exposure to lung irritants that damages the lungs and airways usually is the cause of COPD. Worldwide, the most commonly encountered risk factor for COPD is tobacco smoking. The early detection of auditory impairment can be possible by recording of BAEP in patients of COPD. Study includes 100 individual, all males with the age group of 40-60 yrs. were divided in two groups, study group (n=50) and controls (n=50). Study group includes patients of COPD, as per gold criteria and those had a duration of COPD for more than 5 years with stable course of disease. Controls are age & sex matched normal healthy adults. Spirometry was done in patients to confirm the diagnosis of COPD and the severity of airflow limitation. And BAEP recording was done. Latencies of wave I, II, III, IV, V and Interpeak latencies I-III, III-V, I-V of right ear had a statistically non-significant positive correlation with disease duration. There were increase in right ear latencies of wave I, II, III, IV, V and Interpeak latencies of I-III, III-V, I-V along with increase in smoking pack years indicating a positive correlation with p value < 0.05 showing a statistical significance. Also statistical significant (p value < 0.05) negative correlation between post-bronchodilator FEV1% predicted value and right ear latencies of wave I, II, III, IV, V &Interpeak latencies of I-III, III-V, I-V ; indicating prolongation of latencies of BAEP with reduction in FEV1% predicted. The progressive chronic hypoxemia leads to development of tissue hypoxia and decreases the cerebral perfusion; also it slows the nerve conduction in auditory pathways which causes prolongation of latency. The contents of tobacco smoke in addition to hypoxemia lead to hypoxia. Therefore smoking pack years and decreased FEV1% predicted value definitely have impact on BAEP.
Keywords: BAEP, Latencies, Interpeak latencies, FEV1 % predicted value, Smoking pack years, Disease duration, Hypoxia
Chronic Obstructive Pulmonary Disease (COPD), a common preventable and treatable disease, is characterised by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients (1). The term COPD is commonly used to refer the related conditions emphysema and chronic bronchitis (2).The recently published GOLD report (2014) used the term emphysema and chronic bronchitis for diagnosis of COPD, but they are not included in definition. Because chronic bronchitis defined as the presence of cough and sputum production for at least 3 months in each of 2 consecutive years, is not necessarily associated with airflow limitation. Emphysema, defined as destruction of the alveoli, is a pathological term that is sometimes (incorrectly) used clinically and describes only one of several structural abnormalities present in patients with COPD and can also be found in subjects with normal lung function (1). Long term exposure to lung irritants that damages the lungs and airways usually is the cause of COPD. Worldwide, the most commonly encountered risk factor for COPD is tobacco smoking(3,4,5). Studies show that approximately 80-90% of patients with COPD have been smoking and approximately 15% of all smokers will develop COPD (6). Non-smokers may also be at risk for developing COPD as a consequence of passive smoking, indoor and outdoor air pollution or occupational dusts and chemicals(7,8). COPD risk is related to the total burden of inhaled particles a person encounters over their lifetime (9).
1) Tobacco smoke includes cigarette, bidi, pipe, cigar and other types of tobacco smoking.
2) Indoor air pollution from the burning of biomass fuel used for cooking and heating in poorly vented dwellings, a risk factor that particularly affects women in developing countries (10).
3) Occupational dusts and chemicals are risk factors when the exposures to them are sufficiently intense and prolonged (7,11).
4) Outdoor air pollution also contributes to the lungs’ total burden of inhaled particles, although it appears to have a relatively small effect in causing COPD (1).
5) Genetic factors- The genetic risk factor that is best documented is a severe hereditary deficiency of alpha-1 antitrypsin (12).
These indicators are not diagnostic themselves, but the presence of multiple key indicators increases the probability of a diagnosis of COPD. Spirometry is required to make a clinical diagnosis of COPD; the presence of a post-bronchodilator FEV1 /FVC < 0.70confirms the presence of persistent airflow limitation and thus of COPD. Spirometry (meaning measuring of breath) is the most common of the pulmonary function tests measures how much air can breathe out (volume) and how fast can blow air out (flow)(13). COPD is often associated with clinical manifestations that include metabolic abnormalities, weight loss, muscle weakness and wasting, anxiety, depression(14), Osteoporosis, Cardiovascular diseases like Corpulmonale(15), Atherosclerosis, ischemic heart disease and stroke(16). Many of the systemic co-morbidities associated with COPD have been related to systemic inflammation (17). There is rapidly growing body of evidence indicating that the pulmonary disease observed in patients with COPD is also associated with systemic inflammation(18). COPD is associated with systemic inflammation, recognized as a risk factor for its systemic complications. Hypoxemia triggers oxidative stress and inflammation in COPD patients (19).
The existing medical literature suggests that 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 (20). There are some studies showing that auditory receptors are affected from hypoxia (21,22). The early detection of auditory impairment can be possible by recording of BAEP in patients of COPD. Brainstem auditory evoked potentials (BAEPs) are the potentials recorded from the ear and vertex in response to a brief auditory stimulation to assess the conduction through the auditory pathway up to the midbrain (23). BAEP is a far field recording of the synchronized response of a large number of neurons in auditory pathway. The use of the BAEP has been well documented both from a neurological and audio logical stand point (24).
BAEP is a simple, non-invasive procedure to detect early impairment of acoustic nerve and CNS pathway, even in the absence of specific symptoms. Therefore Correlation of disease duration, smoking pack years and FEV1 % predicted with BAEP parameters done in patients of COPD.
MATERIALS AND METHODS
The present study was conducted in the Department of Physiology and Department of Pulmonary Medicine in Grant Government Medical College and J.J Hospital, Mumbai. Before commencement of study, approval was taken from the Institutional Ethical Committee.
The study design involved 100 individuals which can be divided in two groups. Group I –Diagnosed patients of COPD as per GOLD criteria, after applying inclusion and exclusion criteria were accepted for study (n=50) Group II –Age and sex matched normal healthy adults (n=50). In addition, spirometry was done to confirm the diagnosis of COPD and the severity of airflow limitation was determined by GOLD gradation criteria (post-bronchodilator FEV1 /FVC ratio less than 70%, consistent with airflow limitation that is not fully reversible,GOLD criteria).
The evaluation was done in following stages -
1) A written informed consent was taken from all participants of this study.
2) A detailed history-taking and thorough clinical exami- nation was done.
3) Spirometric test was performed in both groups and diagnosis of COPD was confirmed in cases
4) BAEP recording was done. Among COPD patients, those had a duration of COPD for more than 5 years with stable course of disease, having a regular follow up for 1 year with no hospitalization for COPD related illness in preceding 6 months were included in study group. All COPD patients in study were males and had smoking history. They were having moderate to severe airflow limitation. The subjects who met the criteria were selected for the study. The study and control group were selected as per inclusion and exclusion criteria. Spirometry test was done in study group with the help of MEDGRAPHICS Body Plethysmographmachine.
Inclusion criteria for selection of COPD patient -
1. Males with age group of 40-60 years.
2. On spirometric test, patients having post-Bronchodilator FEV1 % predicted valueless than 80% with FEV1 / FVC ratio <0.70.
3. Patients with normal auditory function tests.
Inclusion criteria for controls
1. Normal healthy male individuals with age group of 40-60 years.
2. Subjects having no addiction (Non-smokers).
3. Subjects having normal hearing.
Exclusion criteria for both
1. Patients of COPD in acute exacerbation.
2. Subjects having any clinical neuropathy.
3. Subjects having hearing loss.
4. Subjects suffering from another acute/ chronic medical disorder like hypertension, diabetes mellitus, malignancy, leprosy, tuberculosis.
5. Subjects with history of addiction to alcohol, drug abuse.
6. Subjects with history of drug intake known to cause central neuropathy e.g. Reserpine, Phenytoin, Alphamethyldopa, Nitrofurantoin.
7. Subjects who had history of taking ototoxic drugs e.g. Gentamycin, Amikacin, Streptomycin, Kanamycin and Quinine.
Evoked Potential study(26) Pre-test preparation-
The skin was prepared by mild abrading and degreasing by Nu-Prep gel. Standard cup electrodes were used. The electrodes were placed on their respective sites using electrode paste as per 10-20 international system of electrode placement. The tests were carried out in a quiet room. EMGand EP digital neurophysiological system software, Neuro-MEPw version 3.0, 64.0 was used to conduct evoked potential tests.
Brain stem auditory evoked potential Recording -
All the techniques of recording, machine settings and instruments were maintained uniformly throughout the study. Patients were made to lie down comfortably on couch and were asked to close their eyes and relax. BAEPs are obtained using monaural (one ear at a time) stimulation.
Electrode placement - Active electrodes (Mi , Mc ) - over mastoid processes Reference electrode (Cz ) - at vertex Ground electrode (Fz ) - at forehead in midline Montage consisting of the following derivations was used for BAEP recordingChannel 1: Vertex - ipsilateral mastoid process (Cz - Mi ) Channel 2: Vertex - contralateral mastoid process (Cz -Mc ) The following machine setting was used throughout the study.
1) Stimulus - Monaural auditory stimulus in the form of clicks were delivered through TDH-39P headphone at a rate of 10 per second (10 Hz) with the alternating polarity. The click stimuli at an intensity 100 dB SPL was given to the stimulated ear (ipsilateral) and masking sound (white noise) of 60 dB SPL to non-stimulated, contralateral ear through the headphone. Stimulus duration was 0.1 milliseconds. Responses to 2000 click stimuli were averaged for 10 milliseconds.
2) Filter- Low and High band pass filter was set at 100 Hz and at 3000 Hz respectively.
3) Impedance - The electrode impedance was kept below 5 kΩ The signals picked up by these electrodes were filtered, averaged, amplified and displayed on the computer monitor. Two trials of recording were done and wave forms were super imposed to check for reproducibility. Parameter studied: BAEP waveforms from each ear with absolute latencies of I, II, III, IV, V waves and Inter peak latencies (IPLs) of I-III, III-V, I-V were considered for comparison among COPD patients and controls.
The results were expressed as mean and standard deviation for each variable, separately for right and left side. Unpaired (independent) t-test was used for intergroup comparisons in the healthy volunteers group and the COPD group, p-value of 0.05 or less has been considered as statistically significant. Correlation between disease duration, smoking pack years and FEV1 % predicted with BAEP and VEP parameters were done. All statistical analyses were carried out with the help of SPSS version 20.0 software.
In the present study, mean age group of COPD patients was 52.92 ± 3.93 years with disease duration of 10.82 ± 2.89. All were smokers with smoking pack year index 31.04 ± 6.6. On spirometric findings, all COPD patients were having post-bronchodilator FEV1 /FVC ratio less than 0.7, a GOLD diagnostic criteria of COPD. COPD patients were having moderate to severe airflow obstruction (grade 2 and 3) as per GOLD gradation of severity of airflow limitation with mean post-bronchodilator FEV1 % predicted value 47.73 ± 8.13. There were no clinical signs and symptoms of peripheral neuropathy in study group. Correlation of patient’s characteristics with BAEP and VEP parameters was given in table no. 1-5. Present study found that there was non-significant correlation between disease duration and BAEP parameters while there was significant correlation of BAEP parameters with smoking pack years and severity of airflow obstruction. Similar findings are present in some studies Vijay Kumar et al (27) (1996), Hafez et al (28) (2009), NesrienShalabietal(29) (2012). Vijay Kumar(27) (1996) studied BAEP in tobacco smokers and found latency of wave I and wave III were significantly prolonged. They concluded that abnormal BAEP findings were due to nicotine and toluene of smoke. Hafez et al(28) (2009) found positive correlation of BAEP & VEP with disease duration, smoking pack years & PaCO2 . Their study showed negative correlation with spirometric indices. NesrienShalabi(29) (2012) found latencies of wave I,III,V of BAEP had significant negative correlation with FEV1 , FEV1 / FVC and these latencies were positively correlated with smoking index. Gupta et al (30) (2008) in their study found 65% of COPD patients had abnormalities in one or more BAEP variables. They hypothesized that the abnormal BAEP findings are due to brainstem hypoxia which increases with the severity of COPD. As COPD patients in their study were heavy smokers, they had given the possibility of the contents of cigarette smoke leading to BAEP abnormalities. In addition to chronic hypoxemia and hypercapnia, other associated factors in patients with COPD, including tobacco smoking; malnutrition; and drugs used in COPD treatment, may be possibly associated with neuropathy seen in COPD patients.
The progressive chronic hypoxemia leads to development of tissue hypoxia and decreases the cerebral perfusion; also it slows the nerve conduction in auditory pathways which causes prolongation of latency. The contents of tobacco smoke in addition to hypoxemia lead to hypoxia. Therefore smoking pack years and decreased FEV1% predicted value definitely have impact on BAEP.
Authors acknowledge the immense help received from the scholars whose articles are cited and included in the references of this manuscript. Authors are also grateful to authors /editors /publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.
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