dr. isah, muhammad danasabe
TRANSCRIPT
SPIROMETRIC EVALUATION OF VENTILATORY FUNCTION OF ADULT MALE
CIGARETTE SMOKERS IN SOKOTO METROPOLIS
BY
Dr. ISAH, MUHAMMAD DANASABE
MB, BS (UDUS) 2002
A Dissertation submitted to the National Postgraduate Medical
College of Nigeria in part fulfillment of the requirement for the
Award of the fellowship of the College in Internal Medicine (PULMONOLOGY)
NOVEMBER 2015
DECLARATION
I hereby declare that the work described in this dissertation is original. I affirm that no part of
this work has been submitted to any other body or institution for the purpose of the award of
Fellowship or for publication.
Date………………………………………………… Sign…………………………………………………
Dr. ISAH MUHAMMAD DANASABE (MBBS, UDU SOKOTO)
CERTIFICATION I
We certify that Dr. Isah, Muhammad Danasabe of the Department of Medicine, Usmanu
Danfodiyo University Teaching Hospital, Sokoto produced this dissertation under our
supervision.
--------------------------------------------- -------------------------------------- Prof.
JU OKPAPI, FMCP Date
Consultant Physician
ABUTH, Zaria
--------------------------------------------- --------------------------------------
Prof. CH NJOKU, FWACP Date
Consultant Physician
UDUTH, Sokoto
CERTIFICATION II
This dissertation was carried out by Dr. Isah, Muhammad Danasabe of the Pulmonology unit,
Department of Medicine, Usmanu Danfodiyo University Teaching Hospital, Sokoto.
………………………………….. ……………………………………
Signature Date
Dr. Abdulmumini Yakubu
Head, Department of Medicine
UDUTH, Sokoto.
ACKNOWLEDGEMENT
Immense gratitude is due to Almighty God whose blessings and grace saw me through the
residency training programme till this moment.
I owe a debt of gratitude to my supervisors, Professors JU Okpapi and CH Njoku for their
support, mentorship, advice and guidance.
I am eternally grateful to Dr MA. Makusidi for his patience, understanding and constructive
criticisms.
I am appreciative of contributions by Professor AA Abba and Professor SA Isezuo and for their
guidance and valuable assistance
I am grateful to Dr. AA Sabir, Dr. AS Maiyaki, Dr. Y Abdulmumini, Dr. A Adeiza and a host of
other senior colleagues for their encouragement.
The co-operation I enjoyed from fellow residents in the Medicine departments of UDUTH,
Sokoto and ABUTH Zaria is well acknowledged.
Finally, I appreciate the patience, support and encouragement of my natal and conjugal family.
May Almighty God reward them abundantly.
LIST OF ABBREVIATIONS AND SYMBOLS
WHO - World Health Organization
UDUTH - Usmanu Danfodiyo University Teaching Hospital
FEV1 - Forced Expiratory Volume in one second
FVC - Forced Vital Capacity
PEF - Peak expiratory flow
FEF 25%-75% - Forced Expiratory flow between 25% and 75%
COPD - Chronic Obstructive Pulmonary Disease
NHANES -National Health and Nutrition Examination Survey
ATS - American Thoracic Society
ERS - European Respiratory Society
GOLD - Global Initiative for Obstructive Lung Disease
ACP - American College of Physicians
ACCP - American College of Chest Physicians
UMHS - University of Michigan Health System
CD - Cluster of Differentiation
IL - Interleukin
DNA - Deoxyribonucleic acid
mm - Millimeter
ECCS - European Community for Coal and Steel
TNF - Tumor Necrosis Factor
LLN - Lower Limit of Normal
SVC - Slow Vital Capacity
vs - Versus
Oc - Degree centigrade
km - Kilometer
BMI - Body Mass Index
SPSS -Statistical Package for Social Sciences
CDC - Centers for Disease Control and Prevention
kg - Kilogram
CI - Confidence Interval
LHS - Lung Health Study
PFT - Pulmonary Function Test
ABUTH -Ahmadu Bello University Teaching Hospital
TABLE OF CONTENT
TITLE PAGE……………………………………………………………………………………………………… I
DECLARATION...………………………………………………………………………………………………..II
CERTIFICATION I…………………….………………………………………………………………………...III
CERTIFICATION II ……………………………………………………………………………………………..IV
ACKNOWLEDGEMENT ………………………………………………………………………………………V
ABBREVIATIONS AND SYMBOLS……………………………………………………………………..VI
TABLE OF CONTENT …………………………………………………………………………………….VIII
ABSTRACT .............................................................................................................1
CHAPTER 1: INTRODUCTION……………………………………………………………………………….3
1.1: BACKGROUND
1.2: JUSTIFICATION
1.3: AIM AND OBJECTIVES
CHAPTER 2: LITERATURE REVIEW…………………………………………………………………....10
2.1: PREVALENCE OF TOBACCO SMOKING
2.2: BASIC PHYSIOLOGY
2.3: AETHIOPATHOGENESIS
2.4: PATHOPHYSIOLOGY
2.5: CLINICAL MANIFESTATION
2.6: DIAGNOSTIC EVALUATION
2.7: TREATMENT
CHAPTER 3: METHODOLOGY……………………………………………………………………………25
3.1: STUDY AREA
3.2: STUDY POPULATION
3.3: ETHICAL CONSIDERATION/CONSENT
3.4: STUDY DESIGN
3.5: SAMPLING TECHNIQUE
3.6: STUDY SUBJECTS
3.7: CONTROL
3.8: SAMPLE SIZE DETERMINATION
3.9: MATERIALS
3.10: STUDY PROCEDURE
3.11: DATA ANALYSIS
CHAPTER 4: RESULT (LIST OF TABLES AND FIGURES)………………………………………34
TABLE 1: CLINICAL AND SOCIODEMOGRAPHIC CHARACTERISITCS OF STUDY AND CONTROL SUBJECTS.
FIGURE 1: SUBJECTS BY AGE GROUP AND CIGARETTE SMOKING STATUS.
TABLE 2: ANTHROPOMETRIC PARAMETERS OF STUDY SUBJECTS AND CONTROLS.
TABLE 3: SMOKING CHARACTERISTICS OF STUDY SUBJECTS.
FIGURE 2: FREQUENCY OF CIGARETTE SMOKING INDEX AMONG AGE GROUP OF STUDY SUBJECTS.
TABLE 4: VENTILATORY FUNCTION TEST INDICES RESULT OF CIGARETTE SMOKERS AND NON SMOKERS
TABLE 5: VENTILATORY FUNCTION TEST INDICES RESULT OF CIGARETTE SMOKERS AND NON SMOKERS BY AGE
GROUP.
TABLE 6: VENTILATORY FUNCTION TEST STATUS OF CIGARETTE SMOKERS AND NON SMOKERS.
TABLE 7: CORRELATION MATRIX OF CLINICAL/SOCIODEMOGRAPHIC PARAMETERS AND CIGARETTE SMOKING
CHARACTERISTICS.
FIGURE 3: CORRELATION BETWEEN FEV1 AND PACK YEARS OF CIGARETTE SMOKING.
TABLE 8: MULTIPLE LINEAR REGRESSION ANALYSIS OF FEV1
CHAPTER 5- DISCUSSION…………………………………………………………………………………56
5.1: DISCUSSION
5.2: LIMITATION
5.3: CONCLUSION
5.4: RECOMMENDATION
REFERENCES…………………………………..…………………………………………………………………63
APPENDICES……………………………………………………………………………………………..……. 75
1: APPENDIX I (INFORMED CONSENT FORM)
2: APPENDIX II (QUESTIONNAIRE)
3: APPENDIX III (ETHICAL CLEARANCE LETTER)
4: APPENDIX IV (CLEMENT CLARKE ONE FLOW SPIROMETER, Version 1.3 Revision 0 (2002)
5: APPENDICES V-VIII (PICTURES OF PROCEDURE OF SPIROMETRY DURING DATA COLLECTION)
6: APPENDIX IX (HAUSA TRANSLATION OF STUDY QUESTIONNAIRE)
ABSTRACT
BACKGROUND
Cigarette smoking is a common social habit in Nigeria with extensive deleterious multisystemic
effects. Morbidity and mortality from cigarette related illnesses are preventable. However,
patients commonly presents to health facility for medical care when the cigarette smoking
related illnesses has advanced. Ventilatory dysfunction is one of the commonest cigarette
smoking related illnesses that affect the respiratory system and which can be easily detected
with spirometry.
AIM
The purpose of this study was to determine the impact of cigarette smoking on the ventilatory
function of adult male cigarette smokers compared with non smokers in Sokoto metropolis.
METHODS
This study was a population based cross-sectional study incorporating 200 subjects (150
cigarette smokers and 50 non smokers) that met inclusion criteria using snowball sampling
method. Subjects were drawn from local governments that constituted Sokoto metropolis
based on differential local government area population as a function of Sokoto metropolis
population and calculated sample size. Subsequently, subjects had a questionnaire partly
adapted from European Community Respiratory Health Survey administered to collect
demographic, clinical and cigarette smoking data. Ventilatory function test was carried out
using Clement Clarke (One flow) Spirometer, version 1.3 Revision 0. The highest value each of
ventilatory function index was chosen for analysis. Moreover, subject with ventilatory
dysfunction also had a post bronchodilator spirometry carried out in accordance with
American Thoracic Society guidelines. Results were compiled and statistically analyzed using
Statistical Package for Social Sciences, version 19.
RESULTS
Equal proportion of subjects in the two groups were young (<40years), unmarried, with
Primary school level of Education, and employed (majorly civil servants and commercial
motorcyclist). Mean age of subjects (34.27±8.91) years and control (35.08±10.35) years was
not statistically significant, p=.592. Similarly, mean of anthropometric indices which are
weight, height, Body Mass Index of both subjects and control were also not statistically
significant, with p-value of .663, .084, and .099, respectively. The age distribution among
participants revealed 80% of study subjects and 68% of control to be below 40 years of age.
Mean (SD) of age at commencement of cigarette smoking was 16.9(4.2) years while the mean
pack year was 8.7(8.9). The mean daily cigarette consumption rose from 3.69 to 13.29
cigarette sticks with a tendency of study subjects becoming moderate to heavy smokers as
they age. Mean values of the component of ventilatory function test (FEV1, FVC, FEV1/FVC)
except FVC was low among study subjects compared with control. Furthermore, the mean of
FEV1/FVC of subjects (75.60±7.53) and control (82.48±6.11) was statistically significant
(P<0.001). There was a negative correlation (r=0.056) between pack years of cigarette smoking
and FEV1 (p=.004). Obstructive ventilatory defect was found among 4 study subjects (4%) and 2
control (4%).
CONCLUSION
Cigarette smoking is associated with decline in ventilatory function test indices (FEV1and
FEV1/FVC) in adult males. Decline in FEV1 is directly related to pack years of cigarette smoking.
Spirometry helps in detection of ventilatory dysfunction among cigarette smokers.
CHAPTER 1
INTRODUCTION
1.1: BACKGROUND
Tobacco smoking despite being a common social habit is associated with numerous
deleterious effects on body systems, and not limited to the respiratory system.1 It is a
preventable cause of disease and premature death. The World Health Organization (WHO) has
put the number of tobacco smokers at 1.1 billion persons worldwide most of whom are in
their reproductive age group.2 This is about one third of world population aged ≥ 15 years. It is
also reported by WHO that tobacco smoking and its related diseases killed about 100 million
people worldwide in the 20th century and in future the number is likely to rise.2 Estimates
show that by 2030, countries in the developing world are expected to have about 7 million
tobacco smoking related deaths annually going by the current trend of cigarette smoking.2 The
morbidity and mortality owing to tobacco smoking tend to be underestimated because it is
sometimes cited as contributory or aggravating factor rather than a primary cause of disease
and death.3 Subjects with significant cigarette smoking history also lose an average of 13.2
years of life because of tobacco smoking.4
Tobacco is derived from dried leaf of Nicotianna tabacum, a plant indigenous to America but
now grown in many parts of the world. Tobacco can be chewed, sniffed or smoked in the form
of a cigarette, cigar, stem pipe or bidi. Cigarette contains nicotine which is the main addictive
factor. However, cigarette not only contains nicotine and harmane but other complex mixture
of chemical additives.5 These chemicals which have been implicated in the deleterious
multisystemic effect on the human body include nickel, chromium, hydrogen cyanide, volatile
phenols and benzopyrene.5
Over time, after commencement of cigarette smoking, the body becomes accustomed to
absorbing nicotine regularly. Due to accentuation of body demands, more cigarettes are
required to obtain the same level of stimulation. Otherwise, the body becomes indebted and
cannot provide the usual level of stimulation. Furthermore, the stimulatory effect does not last
long even if a larger dose is taken in the form of either high nicotine yielding cigarettes or
higher number of cigarettes. This is largely due to down regulation of nicotine receptors. Thus,
excessive smoking becomes a vicious cycle leading to higher tobacco consumption, higher
dependence on nicotine and increased likelihood to develop tobacco related illnesses.6 The
level of exposure to cigarette smoke is also determined by the pattern of cigarette smoking;
with cigarette puffers being less exposed than deep inhalers.
Tobacco smoking affects the lungs and airway among other multisystemic involvement.
Clinical manifestations of tobacco smoking on the respiratory system include; cough with or
without expectoration, difficulty in breathing, noisy breathing and eventually decline in lung
function.7 The single most important risk factor for accelerated decline in lung function is
cigarette smoking.7 However, other risk factors which may act in concert with cigarette
smoking include airway hyper-responsiveness, air pollution and occupational exposure to
organic and inorganic dust.1,7 Inhalation of tobacco smoke has been shown to cause
bronchoconstriction in human and this response can become manifest as early as eight
seconds following exposure and could last for up to thirty minutes even without additional
exposure.1,8 There seems to be a linear relationship between amount of tobacco smoked
/duration of smoking and its effect on the respiratory system.9-11
There are four major physiologic components that ensure adequate respiration: - they are
ventilation, gas diffusion, blood flow and control of breathing. Any disorder that affects one or
more of these functional components could manifest with symptoms and signs of respiratory
system disease. Cigarette smoking could affect each of these major physiologic components of
respiration on the long run.
Spirometric evaluation of lung function dates back to the 17th century.12 Spirometry is a test
that examines the functional capacity of lungs and respiratory system. It measures airflow and
lung volumes during inspiratory and expiratory maneuvers from full expiration and inspiration,
respectively. Spirometry has been attested as one of the investigations of choice for detection
of both subclinical and clinical effects of tobacco smoking on the airway.7,13-15 Spirometry is an
easy, effective, objective, relatively safe and reproducible method of ventilatory function
measurement.7 Parameters measured during spirometry include Forced expiratory volume in
one second (FEV1), Forced vital capacity (FVC), Forced expiratory flow between twenty five
percent and seventy five percent of FVC (FEF 25%-75%), Peak expiratory flow (PEF) and ratio
of FEV1/FVC.7 Tobacco smokers usually progress slowly from normal spirometry to borderline
ventilatory function defect and then to unequivocal ventilatory function defect.16 These
changes are as a result of inflammation, immune response and scarring in the airway/lungs of
cigarette smokers exposed to its noxious particles and gases. These pathologic changes result
in increased resistance to airflow in the airways, altered lung compliance, progressive airflow
obstruction and air trapping.7 The onset of symptomatic phase of ventilatory function defect in
tobacco smokers is variable but often does not occur until FEV1 has fallen to fifty percent or
less of predicted normal or patient’s best.17 Intriguingly, not every cigarette smoker develop
ventilatory dysfunction even with significant exposure.7
Prevalence of low ventilatory function increases with age and are highest in current smokers,
intermediate in former smokers, and lowest in never smokers.7,11 Early identification of
tobacco smokers who are susceptible to airflow limitation or have already developed it could
lead to targeted smoking cessation.7,18 This by extension could limit tobacco smoking related
morbidity and mortality. Tobacco smoking cessation programme entails behavioral change
approach, nicotine replacement therapy and use of nicotine receptor agonist. These methods
could be used singly or in combination.
1.2: JUSTIFICATION
Cigarette smoking has enormous deleterious effects on the airway and other body systems
which are subclinical at early phases.17 Moreover, with the rising incidence of tobacco smoking
related illnesses especially Chronic Obstructive Pulmonary Disease (COPD) it will be prudent if
affected patients are detected early and managed.7 This is important because, currently there
is no treatment that can reverse the natural history of airflow limitation when at advanced
stage. Furthermore, early stage of airflow limitation is neither appreciated by the subject nor is
it readily recognized by the health care providers clinically. Symptomatic patients may also
adapt to their condition or neglect symptoms. When case finding is limited to symptomatic
smokers, there may be the risk of missing quite a significant number of subjects who are at risk
of developing airway obstruction. These call for ways through which tobacco smoking related
diseases can be detected early.
Spirometric screening among cigarette smokers is one way through which ventilatory function
defect could be detected early and cigarette smoking cessation advocated.19-23 All is not known
about susceptibility of the airway to the deleterious effect of cigarette smoking since not all
smokers become symptomatic. Studies on the effects of cigarette smoking during early
adulthood may help identify other factors that determine the susceptibility of individuals to
the hazardous effects of tobacco smoke.
A lung function test is recommended for subjects presenting with respiratory symptoms
and/or exposure to tobacco smoke or other risk factors.7 Data from the United States National
Health and Nutrition Examination Survey (NHANES) revealed that over 60% of American adult
with low pulmonary function were asymptomatic.24 Reports from American Thoracic Society
(ATS), European Respiratory Society (ERS), Global Initiative for Chronic Obstructive Lung
Disease (GOLD), American College of Physicians (ACP), American College of Chest Physicians
(ACCP) and University of Michigan Health System (UMHS) have all recommended spirometric
evaluation on all persons with significant tobacco exposure, even though ACCP, ACP, ERS, ATS
extended their recommendation to evaluate only persons that are symptomatic.25
Recent recommendations commissioned by the United States Agency for Health Research and
Quality and the USA Preventive Services Task Force found little if any justification for
conducting spirometry in primary care for the screening of COPD.18 However, these
conclusions were largely based on the cost and poor prognostic value of spirometry to predict
future respiratory impairment and not on the role spirometry plays in detection of ventilatory
defects.
There are few published studies that sought to evaluate ventilatory function among cigarette
smokers in Nigeria. In a study carried out among about 200 Nigerian firefighters (100 smokers
and 101 non smokers) in Lagos, prevalence of symptoms indicative of respiratory disorder was
similar in both cases and controls.26 The results of lung function were also similar among both
groups and all participants had airflow limitation. These may not be unexpected as the two
groups are exposed to smoke from biomass combustion in the course of their duty which is a
significant confounding factor.
Cigarette smoking is a common social habit in Sokoto metropolis. A recent study put
prevalence of cigarette smoking among in-school adolescents to be 8.3% and age of onset to
be 15-19 years.27
This study seeks to determine the effect of cigarette smoking on ventilatory function among
adult cigarette smokers in Sokoto metropolis. The result from this study is expected to further
highlight the need for spirometric screening among cigarette smokers for early detection of its
deleterious effect on the airway, particularly that it is a pioneer study from North Western,
Nigeria. This will further limit morbidity and mortality from cigarette smoking especially if
cessation programmes are made available and sustained. Previous data has shown that unless
there is continuous re-enforcement of spirometry in screening of cigarette smokers for
ventilatory function defect, the enthusiasm of smoking cessation fades.28
1.3: AIM AND OBJECTIVES
1.3.1: GENERAL
To assess the ventilatory function of adult male cigarette smokers
1.3.2: SPECIFIC
(1)- To determine spirometric indices (FEV1, FVC, FEV1/FVC) of adult male cigarette smokers.
(2)-To compare the ventilatory function of adult male cigarette smokers with that of age
matched adult male non cigarette smokers.
(3)-To assess the effect of duration and quantity of cigarette smoking on ventilatory function.
CHAPTER 2
LITERATURE REVIEW
2.1: PREVALENCE OF TOBACCO SMOKING
Tobacco smoking and tobacco related illnesses are universal health problems with significant
morbidity and mortality.1 It has become a major public health problem and a huge burden on
health care facilities all over the world.1 WHO has estimated the number of tobacco smokers
to be 1.1 billion worldwide.2 In the same vein, WHO report on global tobacco epidemic
country survey profile for Nigeria, has put current adult cigarette smoking prevalence at 6.1%
and 0.2% for males and females, respectively.2 Studies on prevalence of cigarette smoking in
Sokoto ranged between 4.6%-10.8% in different surveys.27,29-31 However, Desalu et al found a
prevalence of 31.9% in Northeastern Nigeria while Awopeju et al (Southwestern Nigeria),
Friday et al (Southeastern Nigeria, and Fawibe et al (Northcentral Nigeria) in their studies got a
prevalence of 17.9%, 6.4%, 5.7%, respectively.32-35 Cigarette smoking is reported to be
commoner among males in Nigeria and Sokoto in particular.2,27,29-36 This may largely be due to
social, economic, religious and cultural factors in Nigeria especially in Northern Nigeria where
there is promotion of seclusion for females and limiting their free mixing with adults of
opposite sex thereby hindering reportage of this social habit.36-38 Furthermore, the urban and
rural divide in prevalence of cigarette smoking is closing up.39 Estimates predict that by 2030,
developing world is expected to have about 7 million tobacco smoking related deaths annually
going by the current trend of cigarette smoking.2 United States National Health and Nutrition
Examination Survey (NHANES) revealed that a significant number of people who enrolled in
the survey had asymptomatic impaired pulmonary function.24 This invariably means that most
people with asymptomatic impaired pulmonary function may not be known by their physicians
owing to the problems of late identification of the disease as well as late patient presentation.
2.2: BASIC PHYSIOLOGY
The respiratory tract extends from the anterior nares down to the alveoli.40 Alveoli are
exposed to incoming air, in the process oxygen is transferred to the blood for onward
distribution to the tissues and at the same time enables removal of carbon dioxide from the
blood.40 For the atmospheric air to reach the alveoli and for the alveoli to participate in gas
exchange process, there must be a connecting air pathway. This pathway which is largely lined
by pseudostratified ciliated columnar epithelium consists of the trachea, main stem bronchi,
lobar bronchi and bronchioles in descending order.40 The airway epithelium is interspersed
with goblet cells. These in addition to the submucosal glands secrete mucus which helps in
trapping inhaled particles before they can reach and damage the airway/lung tissues. The
alveolus which consists of alveolar duct and alveolar sac is the main site for gas exchange. It is
lined mainly by type 1 pneumocytes and a few type 2 pneumocytes which produce surfactant
to reduce surface tension in alveolar sac.40 The pulmonary capillaries lie in close proximity to
the alveoli and the distance between its endothelium and alveolar epithelium constitute the
gas diffusion barrier.
2.3: PATHOGENESIS
Cigarette smoking is the most epidemiologically important risk factor for airflow limitation
worldwide.7 Worrisome is the availability and marketing of cheap, filter-less, high-tar and
high- metal containing cigarettes in developing countries including Nigeria.5,41-43 These will
likely worsen morbidity and mortality from tobacco related diseases. Other variables in favor
of cigarette smoking morbidity and mortality are depth of inhalation, number of puffs, time
spent smoking and number of cigarettes smoked.
Cigarette smoke must be inhaled for effective delivery to the pulmonary alveoli, where
absorption of nicotine and other cigarette additives take place. From the lungs, they are
absorbed into the alveolar capillary blood and carried to the heart and then to the brain and
other organs.
Nicotine and cigarette additives are a source of chemical injury to the lungs. Human body
induces an inflammatory response as a defense mechanism against these agents of chemical
injury.1,7 Attraction and influx of macrophages, polymorphonuclear cells, T lymphocytes
(predominantly cluster of differentiation 8+{CD8+}) and B lymphocytes to the site of
inflammation is associated with release of cytokines (tumor necrosis factor alpha{TNF α},
interleukin 6 and 8{IL6, IL8}), protease, elastase, matrix metalloproteinase and depletion of
glutathione.1,7 This cascade of events which is aimed at healing the injury leads to antiprotease
inactivation, deoxyribonucleic acid (DNA) damage of fibroblast /bronchial epithelial cells,
generation of free oxygen radicals and perpetuation of the inflammatory process.1,7 When the
triggering factor is removed, inflammation abates and healing may be associated with fibrosis
depending on the extent of lung injury.
2.4: PATHOPHYSIOLOGY
Pathologic changes following airway exposure to tobacco smoke are found in the central
airways, peripheral airways, lung parenchyma, and pulmonary vasculature.7
Major changes in the airway include 7:
(1) Infiltration of the surface epithelium by Inflammatory cells which include neutrophils,
macrophages, T lymphocytes (especially CD8+) which is driven by inflammatory mediators,
particularly cytokines, chemokines, and oxidants.
(2) Increase in the number of goblet cells and enlarged mucus-secreting submucosal glands
with associated mucus hypersecretion.
(3) Chronic inflammation leading to repeated cycles of injury and repair of the airway wall.
These result in structural remodeling of the airway wall, with increase collagen deposition and
scar tissue formation.7 Furthermore, these changes compromise and narrow the airway lumen
producing fixed airways obstruction. Pulmonary vascular changes include thickening of the
vessel wall intima which begins early.7 Other pulmonary vascular changes are increase in
smooth muscle and the infiltration of the vessel wall by inflammatory cells.7 The direct
corresponding physiologic changes following chronic inhalation of tobacco smoke include
mucus hypersecretion, ciliary dysfunction, airflow limitation, pulmonary hyperinflation and gas
exchange abnormalities.
2.5: CLINICAL MANIFESTATION
Cigarette smokers could manifest with respiratory symptoms and have ventilatory function
abnormalities.36 Passive exposure to cigarette smoke (second hand smoke or side stream
smoke) which has been defined as regular unintentional exposure to cigarette smoke at some
time of the day from a co-habitant who smokes cigarette may also contribute to the burden of
tobacco related respiratory symptoms and airflow limitation.44-45 Not all significant cigarette
smokers develop clinically significant airflow limitation.7 This has led to a concept of the
"susceptible smoker". However, the determinants of this susceptibility have not yet been
identified. This suggests that other factor(s) modify each individual's risk but are largely
unknown. The possibility that these factors might modify the effect of cigarette smoking on
lung function is a plausible explanation for differences in susceptibility. Onset of symptomatic
phase of airflow limitation in tobacco smokers is variable. However, studies have shown that it
does not occur until FEV1 has fallen to 50% or less of predicted normal or patient’s best.7,17
Study of patients with early onset airway obstruction from cigarette smoking in the
Netherlands found surprisingly little positive correlation between presence of symptoms and
regular cigarette smoking.46 Furthermore, mild and even moderate airway obstruction have
also been shown to occur without complaints or symptoms there by impeding early
diagnosis.46-47 Cigarette smokers commonly present with cough, difficulty in breathing, sputum
production, noisy breathing and other multisystemic clinical features remote from the
respiratory system.7
Pulmonary diseases that are usually associated with cigarette smoking include acute
bronchitis, chronic bronchitis, emphysema, bronchial carcinoma and spontaneous
pneumothorax.1,7 These diseases manifest with airflow limitation which could be in the form
of an obstructive lesion, restrictive lesion or a mixture of both.
Cigarette smoking could increase the risk of respiratory infection, resulting in a greater
disability from respiratory tract infections.1,48 Tuberculosis is perhaps the most important
smoking-associated infection. Smoking has a substantial effect on tuberculin skin test
reactivity, skin test conversion, and development of active tuberculosis.49 A case-control study
from India found a prevalence risk ratio of 2.9 and a mortality risk ratio of 4.2 to 4.5 (for rural
and urban residents, respectively) when ever-smokers were compared with never-smokers.50
Thus, smoking contributes substantially to the worldwide disease burden of tuberculosis.
2.6: DIAGNOSTIC EVALUATION
Spirometry is an important diagnostic modality for detection, monitoring and management of
various respiratory diseases and represents one of the important diagnostic tools for
measuring airflow limitation.7 It is fundamental to the diagnosis and assessment of many
airway diseases and is often the only necessary test.51 Nevertheless, this diagnostic test is
under-utilized at all levels of health care settings, especially in developing countries.51-54 A
spirometry test substantially improves diagnostic competence and case-finding of diseases like
COPD if applied in a pre-selected high risk population.13,55 Spirometry can also be used
preoperatively to determine the cardio-respiratory status of surgical patients, to measure lung
age, pre-employment evaluation and to aid in smoking cessation. However, underutilization of
spirometry, low test quality, and insufficient interpretation does contribute to the under-
diagnosis of ventilatory defects.56-57
Spirometry can be used in measuring volumes and ratios like FEV1, FVC, PEF, and FEV1/FVC
ratio. These measurements are commonly used with a reasonably high sensitivity and
specificity in detecting airflow limitation.1,7 FEV1 is the most widely accepted severity index of
airway obstruction probably because of its ease of measurement and reproducibility.58
Spirometry testing requires subject’s cooperation and sustained purposeful breathing
maneuver.
There are three stages of spirometry maneuver:
(1) Maximal inhalation.
(2) Maximal exhalation for at least one second (FEV1).
(3) Continued exhalation for several seconds to obtain FVC.
The current ERS and ATS goal for spirometry quality is at least three acceptable maneuvers the
best two of which are reproducible with largest 2 FEV1 matching within 0.15 litre.58-59 This is
referred to as grade B Spirometry maneuver quality. Others are Grade A -which is at least
three acceptable maneuver with FEV1 matching within 0.10 liter, Grade C-at least 2 acceptable
maneuver with FEV1 matching within 0.2 liter , Grade D only one acceptable maneuver with no
interpretation unless normal, Grade F- no acceptable maneuver with no interpretation. The
goal is to obtain an A or B grade even if it means performing additional acceptable FVC
maneuver(s).
Spirometry results for individuals are routinely compared with some set of standardized
reference values to determine how varied their results are from the predicted values. These
reference values are from previous reported normal values or linear regression equation
derived from healthy nonsmoking adults that are selected from a population and are
sufficiently representative of the individual(s) under study. Problems affecting production of
regression equations and standard reference values are discrepancies existing between
estimates of annual decline derived from cross sectional data sets as opposed to longitudinal
data sets. In addition, we also have problems of cohort effects caused by factors such as
environmental smoke exposure, status of subject nutrition and period effects caused by
changes in technique/ apparatus during the time studies are being performed.
Some notable reference equations for FEV1 include Knudson reference equation, European
community for coal and steel (ECCS) equation, Crapo reference equation, Morris reference
equation and Hakinson reference equation (National Health and Nutrition Examination Study
{NHANES} III).59-60 Spirometric reference values from NHANES III data set is being given
preference probably because it’s the reference equation that recruited the largest number of
study subjects, has wide age range of 8 to 80years and with multiethnic diversity among
subjects. 60
Although there is scarcity of comprehensive data on normal lung function test in Nigeria,
attempt has been made to have reference value for groups of people in different parts of the
country. Femi et al is credited with some pioneer studies on reference values of ventilatory
function indices in Nigeria.61 Furthermore, Ele in South Eastern Nigeria determined FEV1 and
FVC reference value for male adolescents and young adults of Ibo origin.62 His study reaffirmed
the strong correlation between anthropometric indices and spirometric measurement.
Curvilinear formulae for predicting peak expiratory flow rate was also derived by Njoku et al
and it was hoped that its use would give results that are in tandem with the observed normal
trend.63 Nku et al built on shortcomings of previous prediction equations by factoring more
anthropometric indices and producing equation not only for FEV1 and FVC but for PEFR.64 In
an overview of derived reference population equations for peak expiratory flow and by
extension components of spirometric evaluation in Nigeria, it was found that most fell short of
international standards.65 Problems bothering on wide acceptability of reference population
equations in Nigeria include 65:
(1) Limited number of study subjects.
(2) Focus on only a few component of ventilatory function test.
(3) Lack of inclusion of all the important parameters that affect lung function namely; age,
body weight and height in the formulation of prediction equations for lung function.
(4) None of the equations spans the ages from childhood through adolescent to the elderly.
(5) Most equations in current use are based on linear statistical models which are subject to
change.
6) Lack of expression of the lower limit of normal.
The natural course of ventilation function values and importantly FEV1 in healthy individuals is
marked by increase and decline at various points in human life. During childhood/adolescent
there is a gradual sustained rise in ventilatory function values; however, during adult life there
is a natural decline with a presiding intervening plateau during which there is little or no net
change in ventilation function.66 Discrepancy exist as to which age the above changes occur.
Studies by Brandli et al and van Pelt W et al showed FEV1 continues to rise up to the age of 25
years.67-68 Despite the discrepancy in evolution of pulmonary function, changes in FEV1 at any
given time is largely determined by:
(1)- The maximally attained level of lung function during early adulthood.
(2)- Onset of decline or alternatively duration of the plateau phase.
(3)- The rate of decline.
These factors act singly or in concert to determine one’s level of ventilatory function. Other
established predictors of one’s ventilatory function include height, gender, and race.7,65,69
Maternal cigarette smoking has been shown to negatively affect fetal respiratory system
growth and development and by extension compromises ventilatory function.8 Tracking of
lung function over time has better potential over a single test in determining which factor
predominates in influencing lung function and at what particular chronological age. However,
there are no published data demonstrating that when the results of the first Spirometry test
are normal in high risk patient, the measurement of annual changes in ventilatory functions is
better than a repeat of Spirometry test at 3-5 years interval.
There are various guidelines and criteria for diagnosis of airflow obstruction. These include
GOLD guideline, ERS criteria, and ATS criteria.7,58 GOLD recommends the use of a fixed ratio of
FEV1/FVC (post-bronchodilator) to define irreversible airflow obstruction, while using FEV1%
predicted to stage the severity of COPD.7 This criterion has significant patronage by clinicians
and researchers probably because it’s easier to use and has been in use for a long period.
However, GOLD recommendation on definition of irreversible airflow obstruction has been
challenged. Natural changes in ventilatory function with age are curvilinear with peak and
decline rather than being linear.66-68 Consequent to this, fixed ratio has been shown to over
diagnose airflow obstruction, especially in the elderly.70 Furthermore, since age-related
FEV1/FVC ratio decline varies among individuals, fixed ratio results in an apparent increase or
decrease in the prevalence of ventilatory function impairment associated with aging; or with
age-confounded factors such as cigarette smoking.
Another statistically acceptable approach for establishing lower limits for any spirometric
measurement is to define the lowest 5% of the reference population and result below this is
termed below the “lower limit of normal” (LLN). 58 Use of the LLN of the FEV1/FVC ratio rather
than the fixed ratio is the recommendation of ATS and ERS in an attempt to reduce the
number of false positives.58,70-71 It was also noted that a Slow Vital Capacity (SVC) maneuver
which is the maximum volume of air that can be exhaled or inspired in a slow/steady
maneuver may be more accurate than using FVC to diagnose airflow obstruction.71 However,
the two studies on which the LLN recommendation was made did not include post-
bronchodilator spirometry, which is a pre-requisite for the definition of airflow limitation that
is not fully reversible.70-71 The best method is probably the use of actual percentile curve which
although not in vogue in pulmonary medicine, has been used to great advantage in pediatrics
for growth monitoring over the years.72 These paediatric growth curves are standardized,
universally accepted and depict normal growth under optimal environmental conditions. It can
be used to assess children everywhere, regardless of ethnicity, socio-economic status and type
of feeding.
Air flow limitation is the hallmark of physiologic change in cigarette smokers. It is primarily
caused by fixed airway obstruction and the consequent increase in airway resistance. Airflow
obstruction that is not fully reversible is defined according to GOLD guidelines as, the presence
of a post bronchodilator FEV1 < 80% of the predicted value in combination with post
bronchodilator FEV1/FVC ratio of 0.70 or less of predicted.7
Using the ECCS regression equation, the normal average yearly decline in FVC from 25 years of
age is estimated to be about 29 ml/year for men and 25 ml/year for women.59 Longitudinal
studies have demonstrated about 7-30 ml/year larger decline in FEV1 among tobacco smokers
as compared to non-smokers.1,66,73-74
There is scarcity of longitudinal studies in Nigeria that have followed up subjects in a bid to
determine the normal decline in ventilatory function among its populace using spirometry.
Data estimating effect of cigarette smoking on ventilatory function are also scarce. However,
Muhammad et al in 2008 published a study that determined the effect of cigarette smoking on
pulmonary function and respiratory symptoms of firefighters (100 smokers and 101 non
smokers).26 Comparison of the results of lung functions which included PEF, FEV1, FVC and the
ratio FEV1/FVC were similar in both groups. All subjects had evidence of airflow limitation with
25 (25%) of the cigarette smoking firefighters having features of restrictive airways disease.
The prevalence of symptoms indicative of respiratory disorder was similar in both smokers and
non smokers: 70(70%) versus (vs.) 64 (63%) respectively. The overwhelming evidence of
airflow limitation and prevalence of symptoms was attributed to lack of use of respirator
device and not solely due to cigarette smoking. In a related study, Babatunde et al found
reduced lung function indices among cigarette smoking male undergraduate students in
comparison to their non cigarette smoking counterpart with direct relationship between
increasing duration/intensity of cigarette smoking and decline of lung function indices.75
2.7: TREATMENT
In promoting healthy lungs, cigarette smoking cessation should be the primary goal
irrespective of spirometry result in cigarette smokers. Cigarette smoking is a social behavioral
act that can be changed and the physician can play a crucial role in motivating a patient to
quit. The benefits of prevention and effective management of cigarette smoking are laudable
and mitigates its related morbidity and mortality.
Behavioral interventions like aversion therapy and nicotine replacement strategies are the two
broad management strategies for sustained tobacco smoking cessation.
Cigarette smoking produces a progressive loss of airway function over time that is
characterized by an early onset of decline or accelerated decline of ventilatory function.73
Ventilatory function loss to cigarette smoking cannot be totally regained by cessation, but the
rate of decline slows after smoking cessation and tends towards that of nonsmokers.11,74
There is no substitute to primary prevention of cigarette smoking especially targeted at the
young. Prevention of tobacco use is fundamental to reduction in its related morbidity and
mortality. Effort in this regard should include public policies designed to discourage tobacco
use especially in public places, programmes promoting attitudinal change and providing
knowledge on dangers of tobacco use, personal social skill training and stress management.
CHAPTER 3
METHODOLOGY
3.1: STUDY AREA
Sokoto state has a population of 3,696,999 with Sokoto as its capital.76 It is made up of twenty-
three (23) local government areas(LGA); three (3) of which are metropolitan and has Sokoto as
its capital.76 Sokoto metropolis is formed by Sokoto north LGA, Sokoto south LGA and
Wamakko LGA with a population of 232,846, 194,914 and 179,619 respectively.76 Sokoto state
is located in North Western part of Nigeria between longitude 110 30” to 130 50” East and
latitude 40” to 60” North covering an area of 28,232.37 square kilometers (km).76 It shares
borders with Niger republic to the North, Kebbi state to the South and West and Zamfara state
to the East. It has an average annual temperature of 28.3 degree Celsius (°C) making it one of
the hottest cities in the country. The predominant occupation is farming with cereals and
onions commonly cultivated and livestock of different types are raised in the area. Industries
in Sokoto include tanning and leather crafts, pottery, rice milling, and cement factory.77
3.2: STUDY POPULATION:
Study population consists of adult male cigarette smokers and age matched non-cigarette
smokers as controls. The subjects were selected from residents of Sokoto north LG, Sokoto
south LG and Wamakko LG. Subjects involved in this study were chosen for their consistency
of smoking or non-smoking habit as assessed by a study questionnaire (appendix II) and having
met inclusion criteria. Due to non-reporting of tobacco smoking among females in the study
population, women were excluded. Once subjects were included in the study, none was
subsequently rejected except when they were unable to give the desired co-operation in the
experimental procedure.
3.3: ETHICAL CONSIDERATION/CONSENT
Approval from Ethics and Research Committee of UDUTH was obtained before
commencement of the study and informed consent was also obtained from each patient. All
information obtained were handled confidentially.
The whole cost of this research was borne by the Researcher.
3.4: STUDY DESIGN
The study is a comparative cross sectional study.
3.5: SAMPLING TECHNIQUE:
The study employed snowball sampling technique to enroll consenting consecutive subjects
and controls that fulfill the inclusion criteria. The choice of this sampling technique was to
enable recruitment of middle age to elderly subjects who are mostly indoors and get their
cigarette by proxy and subjects who smoke cigarette in hiding. Two cigarette selling points
were randomly chosen by balloting in each of the three LGA comprising Sokoto metropolis and
a volunteer resident in the each study area who has met inclusion criteria was chosen. The
volunteer who was the first study subject then helped identify potential subjects who are
cigarette smokers or non cigarette smokers while the Researcher assesses their eligibility and
inclusion as study subjects or control. As they are identified they were consecutively recruited.
3.6: STUDY SUBJECTS
3.6.1: INCLUSION CRITERIA
(a)- Subject aged 18-60 years.
(b)- Subjects who consented to the study.
(c)- Subjects who were current cigarette smoker.78
3.6.2: EXCLUSION CRITERIA
(a)- Subject who cannot tolerate/perform spirometry.
(b)- Subject with previous history of pulmonary surgery.
(c)- Subject with acute illness or any illness at the time of the study that could affect
ventilatory function test performance and result e.g. pneumonia, bronchial asthma and
bronchiectasis.
(d)- Subject with deformity of thoracic cage.
3.7: CONTROL
3.7.1: INCLUSION CRITERIA
(a)- Subject aged 18 - 60 years.
(b)- Subjects who consented to the study.
(c)- Subjects who were “never smoker”.78
3.7.2: EXCLUSION CRITERIA
(a)-Subject who cannot tolerate/perform spirometry.
(b)- Subject with acute illness or any illness at the time of the study that could affect
ventilatory function performance and result e.g pneumonia, bronchial asthma, and
bronchiectasis.
(c)- Subject who were current or former cigarette smoker.78
(d)- Subject who is a passive smoker
(e)- Subject with fixed chest cage deformity.
3.8: SAMPLE SIZE DETERMINATION
The minimum sample size for this study to allow for a meaningful statistically significant
analysis of result was obtained using the Fisher’s formular79:
n=Z2pq/d2
n= Sample size
p = Prevalence of current cigarette smoking among males in Nigeria is 9%.2 (9%=0.09)
Z= Standard normal deviate = 1.96 at a significance level of 0.05 and 95% confidence level
d = tolerable sampling error (level of precision) = 0.05
q = 1-p =1-0.09
q=0.91
n= (1.96)2 x 0.09 x 0.91/ (0.05)2
n=126
Assuming attrition rate of 10%, 10% of n=12.6. (This is to cover for respondents with
incomplete and improperly filled questionnaire, incomplete response from participants and
subjects unable to perform spirometry)
n=126+12.6 =138.6.
For purpose of this research, 150 subjects who were current cigarette smokers 78 were
enrolled and 50 apparently healthy age matched individuals who were “never smokers” 78
served as control in a ratio of 3:1.
The distribution of 150 study subjects and 50 control subjects across the 3 LGA constituting
Sokoto metropolis based on the differential LGA population and as a function of Sokoto
metropolis population, showed estimated sample ratio of study subject to control subject per
LGA to be 58:19 for Sokoto north LGA (population of 232,846) constituting 38.3% of subjects
and control, 48:16 for Sokoto south LGA (population of 194,914) constituting 32.1% subjects
and control and 44:15 for Wammako LGA (population of 179,619) constituting 29.6% of
subjects and control.
3.9: MATERIALS
1-Study questionnaire to be administered by the researcher (Appendix II)
2-Seca Freestanding Mobile Stadiometer (SCA217) STADIOMETER, PORTABLE, 8-81” for
measuring subject’s height
3-Hana mechanical Weighing scale, model BR9012 for measuring subject’s weight
4-Clement Clarke One flow Spirometer, Version 1.3 Revision 0, © CLEMENT CLARKE 2002 for
measurement of volumes and capacity (Appendix IV)
3.10: STUDY PROCEDURE
A questionnaire partly adapted from European Community Respiratory Health Survey
questionnaire80 (see appendix II) which has been pretested was administered by face to face
interview with the subjects by the researcher in Hausa or English language to record the
subject’s identification, demographic data, social history, duration of cigarette smoking,
quantity of cigarette smoked and clinical evaluation as it relates to airflow limitation. Smoking
status of subjects was determined based on Centers for Disease Control and Prevention
(CDC)78 categorization:
(a)-Current smoker- someone who at time of a study has smoked at least 100 cigarettes and
still smokes every day or some days,
(b)-Never smoker-someone who at the time of the study has not smoked up to 100 cigarettes
or has never smoked,
(c)-Former smoker-someone who at the time of study has smoked at least 100 cigarettes but
has currently quit smoking.
For the purpose of this study, study subjects were current cigarette smokers and control
subjects were never cigarette smokers.78 The pack year(s) of cigarette smoking for every study
subject which is product of number of cigarette pack(s) smoked per day and duration (in years)
of cigarette smoking was calculated.81 Smokers were further classified based on level of
exposure (smoking index criteria i.e product of number of cigarette/day and duration in years)
into81:
(a)-Light smokers with smoking index of 1-100,
(b)-Moderate smokers with smoking index of 101-300,
(c)-Heavy smokers with smoking index greater than 300.
The weight was taken to the nearest 0.1 kilogram (kg) with minimal clothing using a portable
weighing scale (Hana mechanical Weighing scale, model BR9012), placed on a hard flat
surface. The height was measured to the nearest 0.1 centimeter (cm) using a stadiometer
(Seca Freestanding Mobile Stadiometer). Standing height was measured without shoes or caps
and with the subject's back to a vertical backboard. Subject’s canthi and palpebra were
perpendicular to the horizontal with the patient facing forward. The occiput, buttock and both
back of heel placed together touching the vertical board. The body mass index (BMI) was
calculated using the formula: BMI = weight (kg) / height (meter square {m2}). All
anthropometric index measurements were done by the same observer (Researcher).
Spirometry was carried out using Clement Clarke One flow Spirometer, Version 1.3 Revision 0
(Appendix IV). Subjects were asked to abstain from smoking at least one hour prior to the
procedure (if this criterion is not met, subject is asked to either wait for an hour or postpone
till the next data collection day). The subjects were then asked to sit comfortably in a chair.
The complete procedure was explained and demonstrated to the participants and all doubts if
any were clarified. Subjects were instructed to lift their chin, extend neck slightly and then
breathe in fully. Study participants also had their nostrils closed by a nose clip after which the
lips are sealed around the sterile mouth piece of the spirometer. Subject then forcefully blew
air out as fast and as completely as possible through the mouth. Best three readings (at least
ATS grade B)58 of the various lung volumes and flow data (FVC, FEV1, and FEV1/FVC) was
recorded. A post bronchodilator Spirometry was performed on subjects with ventilatory
function defect to quantify the degree of reversibility ten minutes after inhalation of 200μg of
salbutamol via a metered dose inhaler with the help of a spacer device. The criteria used to
define a significant bronchodilator response was based on ATS guidelines (≥ 12 % of baseline
and an absolute change of 200ml in FEV1).58 The United States third National Health and
Nutritional Survey (NHANES III) reference values was used to get the predicted values of
various lung volumes and flow data for each subject and control.82
Measurements of FEV1, FVC and FEV1/FVC were expressed as a percentage of predicted value
in order to control for the influence of age, weight and height. Spirometric data was
categorized as being consistent with normal (normal FEV1, FEV1/FVC ratio), an obstructive
pattern (reduced FEV1/FVC below LLN), restrictive pattern (reduced FEV1 and FVC with normal
or increased FEV1/FVC) and mixed pattern (Low, FEV1, Low FVC and Low FEV1/FVC ± low total
lung capacity).71 Spirometry was carried out in the mornings between 7:00 am to 11:00 am
throughout the data collection. All the data collected were analyzed.
3.11: DATA ANALYSIS
Data from the questionnaire were recorded and analyzed using Statistical Package for
Social Sciences version 19 (IBM SPSS version 19, SPSS Inc, Chicago, IL60606-6307, USA). Mean
± standard deviation was calculated for age, weight, height and BMI. Frequencies and
percentages were presented for smoking index. Independent sample t test was used to
compare significance for numerical variables at P<0.05. Pearson product moment Correlation
coefficient was used to examine relationship between pack years of cigarette smoking and
FEV1. Multiple linear regressions were carried out to determine the predictors of decline in
FEV1 from among independent variable like age, pack years, smoking index.
CHAPTER 4
RESULTS
Table 1: Clinical and sociodemographic characteristics of study subjects and control
Clinical/sociodemographic
parameters
Current Smokers
n (%)
Never smokers
n (%)
p value
Age ≤ 40 years
>40 years
Marital status Single
Married
Educational level Formal
Tertiary
Secondary
Primary
Informal
Occupation Employed
Civil servants
Commercial motorcyclist
Artisans/manual laborers
Unemployed
Respiratory symptom
Cough
120 (80%) 30 (20%)
127 (84.7)
23 (15.3)
141 (94.0)
30(20)
51(34)
60(40)
9 (6.0)
127 (84.7)
44(29.4)
60(40)
23(15.3)
23 (15.3)
2(1.3)
34 (68%) 16 (32%)
39 (78.0)
11 (22.0)
42 (84.0)
10(20)
12(24)
20(40)
8 (16.0)
38 (76.0)
15(30)
10(20)
13(26)
12 (24.0)
0(0)
0.592
0.147
0.110
0.552
0.099
A total of 200 subjects (150 current cigarette smokers and 50 never smokers) who met the
inclusion criteria participated in the study.
Married Subjects constituted 15.3% and 22% of cigarette smokers and non cigarette smokers,
respectively.
A total of 141(94.0%) study subjects and 42(34.0%) control had formal education. Those with
primary school level of education were the most predominant constituting 60(40.0%) cigarette
smokers and 20(40.0%) non cigarette smokers. Subjects with tertiary level of education
constituted 20% of cigarette smokers and 10% of non-cigarette smokers.
One hundred and twenty seven (84%) study subjects and 38(76%) control were employed.
Majority of study subjects were commercial motorcyclists (40% of study subjects and 20% of
control) and civil servants (29.4% of study subjects and 30% of control).
Two (1.3%) subjects of the total participants who were cigarette smokers had symptoms
referable to the respiratory system.
Figure 1: Subjects by age group and cigarette smoking status
The age range of subjects was 20-58 years. Majority of cigarette smokers 63(42%) were in the
age group 30-39 years. About 120(80.0%) study subjects and 34(68.0%) control were aged 40
years or below. The age groups 20-29 years and 30-39 years had 17(34%) participants each
among the control. The age group 50-60 years had the least number of participants constituting
11(7.3%) and 6(12%) of study subjects and controls, respectively.
Table 2: Anthropometric parameters of study subjects and controls.
Current smokers and non smokers did not differ in means of age, height, weight and BMI (Table
2). The mean (SD) of age was 34.27(8.91) in the study subjects and 35.08(10.35) among control
subjects.
Clinical
parameters
Current Smokers (n=150)
Mean (SD)
Never-smokers (n=50)
Mean (SD)
p value
Weight (kg)
Height(metre)
BMI (kg/m2)
70.74 (10.18)
1.6865 (0.08)
24.972 (3.87)
71.43 (8.07)
1.6628 (0.08)
26.008 (3.69)
.663
.084
.099
Table 3: Smoking characteristics of study subjects.
The mean age of cigarette smoking commencement was 16.90 (4.17) years. The mean pack
years and cigarette smoking index were 8.71 and 163.98, respectively. Daily cigarette stick
smoked increased from initial value of 3.69 to current value of 13.29. Other smoking
characteristics among study subjects were as displayed in Table 3.
CHARACTERISTICS
VALUE Mean±SD
Age at cigarette smoking onset (years) Initial daily cigarette number
Current daily cigarette number Pack years Smoking index Smoking duration (Years) Duration of abstinence(Years)
16.9±4.17
3.69±2.59
13.29±10.28
8.71±8.92 163.98±192.62
17.36±8.45
0.42±0.81
Figure 2: Frequency of cigarette smoking index among age group of study subjects
The distribution of cigarette smoking index is as depicted in Figure 2. Moderate smokers were
highest while heavy smokers were lowest constituting 46% and 12% of cigarette smokers
respectively. Majority of the light smokers 43(68.3%), moderate smokers 41(59.4%), and heavy
smokers 9(50%) were in the age group of 20-29 years, 30-39 years and 40-49 years respectively.
None of the study subject was below 20 years of age. There was no heavy smoker among age
group 20-29 years and no light smokers among age group 50-60 years. Figure 2 also shows
tendency to moderate or heavy smoking with age.
Table 4: Ventilatory function test result among cigarette smokers and non smokers
Comparison of mean values of ventilatory function test indices showed all except FVC to be
reduced in cigarette smokers compared non-cigarette smokers. From Table 4, the mean
FEV1/FVC of subjects (75.60±7.53) and control (82.48±6.11) was statistically significant with P <
0.001.
Spirometric
indices
Current Smokers
n=150 Mean (SD)
Never-smokers
n=50 Mean (SD)
p value
FEV1 (litre) FVC (litre) FEV1/FVC
2.89 (0.48)
3.71 (0.54)
75.60 (7.53)
2.96 (0.49)
3.58 (0.53)
82.48 (6.11)
.444
.166
<0.001
Table 5: Ventilatory function test result of cigarette smokers and non smokers by age group
The mean FEV1/FVC is higher among non cigarette smokers as compared with cigarette
smokers in all age groups. However, mean FEV1/FVC was statistically significant for the age
group 30-39 years and 40-49 years while FEV1 was statistically significant for the age group 20-
29 years.
Age Group
(years)
Spirometric
indices
Current Smokers
Mean (SD)
Never-smokers
Mean (SD)
p value
20-29
30-39
40-49
50-60
FEV1 (litre) FVC (litre) FEV1/FVC
FEV1 (litre) FVC(litre) FEV1/FVC
FEV1 (litre) FVC(litre) FEV1/FVC
FEV1 (litre) FVC(litre) FEV1/FVC
3.022 (0.37) 3.76 (0.48) 80.71 (7.35)
2.95 (0.48) 3.77 (0.55)
78.93 (6.42)
2.73 (0.48) 3.60 (0.56)
75.86 (6.05)
2.33 (0.51) 3.35 (0.59)
69.10 (9.59)
3.34 (0.41) 3.97 (0.40) 84.09(4.39)
3.02 (0.32) 3.64 (0.46) 83.48(5.48)
2.57 (0.30) 3.09 (0.34)
83.23 (4.38)
2.33 (0.26) 3.18 (0.44)
73.82 (8.38)
.004 .118 .079
.588
.378
.009
.331
.011
.001
.995
.545
.328
Table 6: Ventilatory Function Test result of cigarette smokers and non smokers
a- Fisher’s exact test
In this study, obstructive ventilatory defect was found in 8(4%) of all subjects. Two of the
subjects with obstructive ventilatory defect were non cigarette smokers and was not statistically
significant.
PFT status
Current Smokers
n=150 Number (%)
Never-smokers
n=50 Number (%)
Total
number
p value a
Obstructive
Normal
6 (4)
144(96)
2 (4)
48(96)
8 (4)
192(96)
0.51
0.46
Total
150 (100)
50 (100)
200 (100)
Table 7: Correlation matrix of clinical/sociodemographic parameters and cigarette smoking
characteristics. (Control variable: FEV1, FVC, FEV1/FVC)
Age (years)
Weight (kg)
Height (metre)
Pack years
Cigarette Smoking
index
Cigarette Smoking duration (years)
Age (year)
Correlation (r) 1.000 .142 .011 .586* .553* .856*
Significance (2-tailed)
.087 .896 .000 .000 .000
Weight (kg)
Correlation (r) .142 1.000 .212* .163* .170* .187*
Significance (2-tailed)
.087 .010 .049 .040 .024
Height (metre)
Correlation (r) .011 .212* 1.000 -.056 -.047 -.072
Significance (2-tailed)
.896 .010 .502 .576 .387
Pack years
Correlation (r) .586* .163* -.056 1.000 .956* .697*
Significance (2-tailed)
.000 .049 .502 .000 .000
Smoking index
Correlation (r) .553* .170* -.047 .956* 1.000 .646*
Significance (2-tailed)
.000 .040 .576 .000 .000
Smoking duration (years)
Correlation (r) .856* .187* -.072 .697* .646* 1.000
Significance (2-tailed)
.000 .024 .387 .000 .000
r= Correlation coefficient
*= Significant correlation
There were significant positive correlation between clinical/sociodemographic indices (age and
weight) and pack years, cigarette smoking index and cigarette smoking duration. The correlation
was most significant between age and Cigarette smoking duration (r=0.856).
Figure 3: Correlation between FEV1 and pack years.
There was a negative correlation between pack years and FEV1(r=0.056) as depicted in figure 3.
Table 8: Multiple linear regression analysis of FEV1
Multiple linear regression analysis showed that age, weight and cigarette smoking duration are
better predictors of FEV1 decline. However, age was the most powerful predictor of FEV1
decline
(P value of 0.019).
Explanatory factor Standardized coefficient
Beta (T) p value
Age (years) Weight (kg) Height (metre) BMI (kg/m2) Pack years Cigarette Smoking duration
-.377
-.381
.556
.502
.047
-.046
-2.364
-.588
1.214
.726
.439
-.252
.019
.558
.227
.469
.662
.801
CHAPTER 5
DISCUSSION
5.1: DISCUSSION
Studies have documented tobacco smoking to be common among males.2,32,39 WHO has also
expressed concern over the increased involvement of teenagers in the habit of tobacco
smoking.2 The present study revealed 120(80%) of smokers were 40 years or below. This may
be due to early indulgence in cigarette smoking habit 27,29 and more patronage of cigarette
selling points (the data collection points for the current study)by adolescents, young adult over
middle aged and elderly who probably get cigarette by sending others on errand to get it on
their behalf. Similarly, Hammad et al also had a significant number (64%) of their study
subjects to be below 40 years.14 Moreover, even studies that were not population based and
where probability sampling technique were used revealed similar results.83
From the current study 127(84%) study subjects and 38(76%) control were employed. Civil
servants constituting 15 (30%) controls and 60 (40%) commercial motorcyclist among subjects
were the dominant occupation among participants in this study. These may not be
unconnected with the urban setting of data collection and the timing of data collection
(morning) when most civil servants were trying to get to their working places and commercial
motorcyclists are making brisk business due to high turnout of commuters. Even though
cigarette smoking is prevalent among Civil servants and Commercial motorcyclist84-87, these
groups of workers (civil servant and commercial motorcyclist) have not been found to have
significant risk for development of ventilatory dysfunction owing to their jobs. However,
commercial motorcyclist operating in an urban setting with significant low air quality could be
exposed to air pollution and its attendant respiratory effects.88 The study by Hammad et al14
recruited subjects that were all employed with predominant occupation been Labourer (48%),
Shopkeeper (24%) and Farmer (14%). However, there was no mention of how their occupation
could have impacted on their ventilatory function even though physical activity is known to
impact ventilatory function.17 In another study by Mousa et al, 65(12.7%) subjects recruited
had occupation that was risky for development of COPD but failed to give details of their
jobs.89
Subjects with significant history of cigarette smoking are usually symptomatic. However, this is
not invariable. Only 2(1.3%) study subjects were symptomatic and presented with cough in
this study. This is low when compared to other studies by Hammad et al 14 and Muhammad et
al 47 that had 75% and 78%, respectively of study subjects with cough. Although, cough was
still the predominant symptom in their studies other symptoms include sputum production
(>50%) and dyspnoea (>30%) in both studies. These differences might be due to low mean
pack years and smoking index of 8.71 and 163, respectively among study subjects in the
current study.
There was no significant difference in the mean of age and anthropometric indices among
cigarette smokers and non smokers indicating a proper matching in this study (Table 2). The
mean age of cigarette smokers and non smokers were 34.27 years and 35.08 years,
respectively. This is in agreement with a comparative spirometric study by Harkirat et al90
among 100 subjects (25 non cigarette smokers and 75 cigarette smokers) aimed at
determining relationship between cigarette smoking and pulmonary function and had mean
age of 37.16 years and 34.56 years among cigarette smokers and non smokers, respectively.
Study subjects in some other studies were much older.47,73,91-92 These variations may be due to
sampling technique, study design and population sampled.
In this study, available data suggest a decline in all ventilatory function test indices except for
FVC in cigarette smokers compared with non cigarette smokers, although only FEV1/FVC was
statistically affected (Table 3). This finding is comparable with that by Jaya et al in India where
all spirometric indices were higher in non cigarette smokers except FEV1/FVC.93 Toshio and co
worker73 and Nancy and co workers94 also showed no significant difference in the value of FVC
between cigarette smokers and non smokers. Furthermore, Toshio and co worker found that
cigarette smoking did not make significant contribution to FVC decline especially in those that
were asymptomatic.73 In contrast, studies by Sunita et al 91, Rubeena et al 92 ,Ritesh et al 95
suggested spirometric indices to be significantly higher in non cigarette smokers compared to
cigarette smokers.
Decline in ventilatory function test indices of cigarette smokers has been observed to be
related to number of cigarette smoked, duration of exposure and pattern of inhalation.6,96
Mussavir et al 9 in their study showed that asymptomatic cigarette smokers show significant
decline in spirometric abnormality after about 10 pack years or more of smoking while Xu and
co workers11 reported that consumption of 25 or more cigarette daily was the minimum
threshold for acceleration of FEV1 decline. However, all this is not invariable. Furthermore,
there is discrepancy as to the exact age at which natural decline in ventilatory function occurs
even though cigarette smoking expedites it. However, studies have suggested that peak
ventilatory function is reached at 20-29 years of age. 63,66-68 Toshio and co worker also found
no significant change in ventilatory function test indices before the age of 30 years among
cigarette smokers.73 The result of the study by Toshio and co worker73 , Mussavir et al9 and Xu
and co workers11 are in support of the pattern of ventilatory function test indices in this study
which may largely be attributable to the fact that significant numbers of the study subjects
were young (80%), largely asymptomatic (96%), light to moderate cigarette smokers (87%) and
with low mean pack years and cigarette smoking index of 8.71 and 163, respectively. The
predominantly young study subjects in the current study may also not be unconnected with
the sampling technique and the socio-cultural practice among study population where the
young go to buy cigarette to smoke while most middle aged and elderly send people on errand
to buy cigarette on their behalf.
In the same vein, it’s been observed that all subjects who smoke cigarette do not develop
ventilatory function changes in the same way. Probably genetics, physical training, nutritional
status and a host of other factors which are difficult to control for may play a role.17,97
In accordance with GOLD criteria for categorization of spirometric indices result,7 majority of
the subjects had no ventilatory dysfunction in the present study constituting 96% of both
cigarette smokers and non smokers. It is higher when compared with studies of Rubeena et al
92 and Sunita et al 91 that had a total of 77(77%) and 75(75%) of their study subjects having
normal spirometric ventilatory function, respectively. Obstructive ventilatory dysfunction was
also the predominant ventilatory dysfunction pattern found in the current study and studies of
Rubeena et al 92 and Sunita et al.91 The prevalence of undiagnosed ventilatory dysfunction
among study subjects from this study was 4% in both study subjects and control. Juan et al got
a lower prevalence of 2.3%.98 A higher prevalence of 12.6% and 5.7% was recorded by
Barthwal et al and Nabeel et al respectively.23,99 Toshio and co worker have attributed 6.3% of
ventilatory dysfunction among Japanese workers in their study to be low and probably due to
selection bias.73 The result of ventilatory function pattern in the current study that revealed
predominant normal ventilatory function and few obstructive ventilatory dysfunction may be
explained by the large number of young study subjects, having low mean pack years and
probably being in their early phase of airway changes. However, other more specific
pulmonary function test (body plethysmography, carbon monoxide diffusion capacity) could
be employed to improve detection of ventilatory dysfunction.100
A linear relationship is expected between FEV1 and pack years.11,89,101 This study corroborates
this fact with a negative correlation between pack years and FEV1 (r=0.056). Similar negative
correlation was observed by Paula et al and Sumangala et al.15,101 This however, is in contrast
with the study by David et al that found very low correlation (r= - 0.24) between pack years of
smoking and FEV1.102
The most important independent variable that determines PFT indices for normal healthy
individuals are age and height.69 Multiple linear regression from this study suggested age,
weight and smoking duration to be the better predictors of FEV1 decline at P<0.05. However, P
value was significant for only age (P value of 0.019). Paula and co workers in their study also
found age among other factors to be better explanatory factors for lowered FEV1 than pack
years.15
5.2: LIMITATIONS
1-No biochemical verification of subject’s self-reported cigarette smoking was done due to
cost of such toxicology test.
2- Differences in the amount of inhaled smoke per cigarette, or differences in unmeasured
exposure to environmental tobacco smoke outside the home were not measured.
3- Use of NHANES III reference values that may not strictly apply to our population.
5.3: CONCLUSION
This study has fulfilled the set objectives of assessing the ventilatory function of adult cigarette
smokers, to compare ventilatory function between cigarette smokers and non cigarette
smokers and to determine the effect of duration and quantity of cigarette smoke exposure on
ventilatory function. Almost all pulmonary function parameters were reduced in cigarette
smokers and the only type of ventilatory dysfunction found was the obstructive pattern.
Airflow obstruction was detected in 1 of every 25 subjects. However, further studies are
needed to determine the cost effectiveness of regular spirometric screening among cigarette
smokers especially those asymptomatic which was not evaluated in the current study.
Cigarette smoking among apparently healthy adult leads to decline in ventilatory function and
is directly related to pack years. This study reaffirms the well-established correlation between
smoking and decline in FEV1.
5.4: RECOMMENDATIONS
The following are recommendations from this study
1-Cigarette smokers should undergo spirometry for early diagnosis of ventilatory dysfunction.
2-Subjects with abnormal spirometric result should be further investigated in a bid to establish
a diagnosis and institute treatment.
3- Irrespective of spirometric result cigarette smokers should be encouraged to quit.
4-Additional well designed, larger, multicenter studies are needed to determine clinical benefit
and cost effectiveness of spirometric screening of at risk population.
CHAPTER 6
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APPENDICES
1: APPENDIX 1 (Participant information and consent form)
STUDY TITLE: SPIROMETRIC EVALUATION OF VENTILLATORY FUNCTION OF ADULT MALE
CIGARETTE SMOKERS IN SOKOTO METROPOLIS.
I am Dr. ISAH, M.D and I am carrying out a study on breathing function of adult cigarette
smokers and non- smokers under the supervision of PROF. J U OKPAPI and PROF. C H NJOKU.
The purpose of my study is to investigate whether or not cigarette smoking has effect on
breathing ability.
I would like you to participate in this study because you have met criteria as a subject.
I would like you to play the following role as a subject in this study:
1-You will complete a questionnaire detailing your biodata, cigarette smoking history/other
forms of nicotine use and history of symptoms referable to your chest or breathing.
2-Your height, weight in minimal cloth and waist circumference would be measured.
3-You will perform breathing test which will entail breathing in and out through an instrument
after you have been taught how to.
Potential pain, discomfort or any bodily harm is not expected, but your co-operation and effort
during the breathing test would give a valuable result.
From this study you would be able to know the status of your breathing function and the
result would be communicated to you.
All information obtained from you would be treated with utmost confidentiality.
You have the right to withdraw your consent at any stage of the study, and your refusal to
further participate in this study at any stage will not in any way affect my relation with you.
You will not bear any expenses for this study.
The above has been well explained to me in................... (Language)
I willingly (voluntarily) accept to participate in this study. My declaration is willingly and upon
my honour.
I ………………………………………………………… do hereby consent to participate in the above study.
Signature / thumb print …………… Date …………………..
In the presence of Interpreter / Witness Full Name ……………………………………………
Signature/Thumb print………………….. Date …………………….
Name of investigator-Dr. Isah, Muhammad Danasabe
Phone number of investigator-08033925238
2: APPENDIX II (QUESTIONNAIRE)
SPIROMETRIC EVALUATION OF VENTILLATORY FUNCTION OF ADULT MALE CIGARETTE
SMOKERS IN SOKOTO METROPOLIS
1. Serial number: ………2. Subject initials: ……..3. Phone number: ………………….4. Age: ………
5. Marital status:- Single ( ) Married ( ) Divorce ( ) Widower ( )
6. Educational level:- a-None ( ) b- Quranic ( ) c- Primary ( ) d- Secondary ( ) e-Tertiary ()
7. Occupation: (PRESENT) ………………………… PREVIOUS…………………………….
8. Do you have any of the following symptoms below? Tick if Yes, if No move to 10
Cough ( ) Difficulty in breathing ( ) sputum production ( ) Chest pain ( ) Noisy breathing ( )
9. What is the Longest Duration of symptom(s)? ………………………………
10. Have you ever smoked cigarette? Yes ( ) No ( ).If Yes, go to 11 and if No move to 22
11. How old were you when you started smoking cigarette? ……… years.
12. How many stick of cigarette per day when you started smoking cigarette? ………………
13-Do you now smoke? Yes ( ) No ( ), If Yes go to 14, if No go to 15
14. How many sticks of cigarette do you now smoke per day? …………………………
15. What is the highest and lowest number of cigarette per day and its duration?
Highest no/duration…………………… Lowest no/duration………………………
16-Have you abstained or cut down on smoking? Yes ( ) No If Yes, why
1-………………………………. 2………………………… 3………………………………
17. What type of abstinence-partial () b-total ( ) c- partial + total ( )
18. What was the duration of abstinence? …………………………………….
19. How many sticks per day do you smoke during period of partial abstinence?........... .
20. Have you attempted quitting cigarette smoking? Yes ( ) No ( )
21. Do you wish to quit? Yes ( ) No ( )
22. Do you use any form of tobacco apart from cigarette? YES ( ) NO ( ) If yes,
type(s)……………………..
23. Do people regularly smoke around you at home or work? Yes ( ) No ( ) If Yes go to 24 if No
go to 25
24. How many hours are you exposed to other people’s tobacco smoke?.....................
25. Do you use recreational drugs? YES ( ) NO ( ) If yes, type(s) ……………………………………
26. Are you on any prescribed medication? Yes ( ) No ( ). If yes type(s)……………………
27. Do you engage in regular physical exercise? YES ( ) NO ( )
28. Weight (kg) ……. Height (m) …… BMI …….Waist circumference (cm) ……………………
29. Calculated 1-Pack years…………………………. 2- Smoking index ……………………
30. Spirometry a- FEV1 1st……………… 2nd…………… 3rd……………. post bronchodilator…………
b- FVC 1st………………. 2nd…………… 3rd……………. post bronchodilator…………
c- FEV1/FVC 1st…………… 2nd………… 3rd………… post bronchodilator…………
3-APPENDIX IV: ETHICAL CLEARANCE LETTER.
4-APPENDIX III (CLEMENT CLARKE ONE FLOW SPIROMETER (VERSION 1.3 Revision 0)
5-APPENDIX V (Picture of researcher holding Clement Clarke One Flow Spirometer)
6-APPENDIX VI: Researcher explaining how subject would perform adequate spirometry
proceadure.
7-APPENDIX VII: Subject blowing into the mouth piece of Spirometer while Researcher
monitors.
8-APPENDIX VIII: Subject blowing into the mouth piece of Spirometer.
9: APPENDIX IX (HAUSA TRANSLATION OF STUDY QUESTIONNAIRE)
BINCHIKEN YANAYIN NUMFASHI DA NAURAN SPIROMETER TSAKANIN MAZA MANYA MASU
SHAN SIGARI A BIRNIN SOKOTO.
1. namba: ………2. Harafin farkun suna: ……..3. namban waya: ………………….4. Shekaru: ………
5. Ma tsayin aure:- ba aure ( ) da aure ( ) rasa mata (saki) ( ) rasa mata (mutuwa) ( )
6. Yanayin neman ilimi:- a-ba bu ( ) b- ilimin Quranic ( ) c- ilimin Pramari ( ) d- ilimin Sekandari
( ) e-ilimin jami’a ( )
7. sana’a: (na yanzu) ………………………… (na da)…………………………….
8. Ka na da wayan nan alamun chiwo da aka nuna kasa? , in a, dagwala, in a’a je 10
Tari ( ) huka ( ) tudda majina ( ) ciwon kirji ( ) Nunfashi mai kara( )
9. Menene mafi tsawan lokaji da ka fara lura da alamun chiwo? ………………………………
10. ka tab a shan sigari ? a ( ) a’a ( ).in a, je 11 kuma in a’a je 22
11. Ka na shekara nawa ka fara shan sigari? Shekara ………….……
12. Karan sigari nawa kake shag a yini daka fara sha? ………………
13-ka na shan sigari yanzu? a ( ) a’a ( ), in a je 14, in a’a je 15
14- Karan sigari nawa kake shag a yini yanzu ? …………………………
15. menene mafi yawan da mafi karanchin Karan sigari kake shag a yini da kiyasin shekaru?
Mafi yawa/kiyasin shekaru…………………… Mafi karanchi/kiyasin shekaru……………………
16-ka taba dakatarda ko rage shan sigari? a ( ) a’a ( ). In a, menene dalili(ai)
1-………………………………. 2………………………… 3………………………………
17. wani irin dakatarwa ne? a-ragewa ( ) b- gaba daya( ) c- a+b ( )
18. menene tsawon lokaci da ka dakatar da shan sigari? …………………………………….
19. Lokacin da ka rage sha Karin sigari nawa ka ke sha?........... .
20. Ka taba kudddutta barin shan sigari? a ( ) a’a ( )
21. Yanzu ka na sun bari? a ( ) a’a ( )
22. Kana shan wani kama da sigari dab a sigarin taba ba? a ( ) a’a ( ). In a, menene?
……………………..
23. Akwai masu shan sigari zagaye da kai a gida ko wurin aiki? a ( ) a’a ( ) in a, je 24, in a’a je
25.
24.Menene tsawon lokaci da kake cikin masu shan sigari zagaye da kai a gida ko wurin
aiki?.....................
25. kana shan kwayoyi masu mahe da juya hankali? a( ) a’a ( ) in a, wani ko wasu iri
……………………………………
26. Akwai magunguna da likita ya kayyade maka yansu? a ( ) a’a ( ). In a, wani ko wasu iri
……………………
27. kana yawan motsa jiki? a ( ) a’a( )
28. weight (kg) ……. Height (m) …… BMI ……. Waist circumference (cm) ……………………
29. Calculated 1-Pack years…………………………. 2- Smoking index ……………………
30. Spirometry a- FEV1 1st……………… 2nd…………… 3rd……………. post bronchodilator…………
b- FVC 1st………………. 2nd…………… 3rd……………. post bronchodilator…………
c- FEV1/FVC 1st…………… 2nd………… 3rd………… post bronchodilator…………