DIAGNOSIS OF COPD 1

Chapter 1: Objective
Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that makes it
difficult for people to breathe. It is a common respiratory condition that affects millions of
people globally. COPD is characterized by chronic bronchitis, emphysema, and sometimes
asthma.COPD is mainly caused by smoking. However, exposure to air pollutants, fumes, and
dust at work can also increase the risk of developing the disease. COPD develops slowly over
several years and typically affects people over the age of 40.

The initial symptoms of COPD are mild and can easily be overlooked. These symptoms
include coughing, wheezing, and shortness of breath, especially during physical exertion. As
the disease progresses, the symptoms become more severe and can severely impact a person's
quality of life. Some of the symptoms include fatigue, chest tightness, chronic cough, and
respiratory infections. “Common symptoms of COPD include feeling short of breath while
resting or when doing physical activity, cough, wheezing, fatigue,
and/or mucus production that does not go away[1] (RN, n.d.)” .

The diagnosis of COPD requires a lung function test called spirometry. This test measures
how well the lungs are functioning and how much air they can hold. Other tests, such as
blood tests and chest X-rays, can also be used to confirm the diagnosis of COPD.

There is no cure for COPD, but there are several treatments available to manage the
symptoms and prevent further damage. The treatment plan for COPD is usually
individualized and depends on the severity of the disease. Treatment includes medications,
oxygen therapy, pulmonary rehabilitation, and lifestyle changes.

Smoking cessation is the most important factor in managing COPD. It is essential to avoid
smoking and exposure to secondhand smoke to prevent further damage to the lungs. People
with COPD should also avoid air pollution, dust, and fumes, which can exacerbate the
condition.In conclusion, COPD is a chronic lung disease that requires long-term
management. Early diagnosis and treatment can help improve the quality of life for people
with COPD. Avoiding smoking and exposure to air pollutants is essential in preventing the
development of the disease. By working closely with a healthcare professional, people with
COPD can manage their symptoms and live a fulfilling life. “Worldwide, the most commonly
encountered risk factor for COPD is tobacco smoking[3] (Agusti, 2017)”.
The main objective of the diagnosis of Chronic Obstructive Pulmonary Disease (COPD) is to
accurately identify and assess the degree of lung damage in order to provide appropriate
treatment and management options. This involves the use of various diagnostic tests, such as
spirometry, pulmonary function tests, and chest X-rays, to measure lung function and detect
changes in lung structure. Early diagnosis can help improve the long-term outcomes and
quality of life for patients with COPD by enabling timely interventions, including smoking
cessation, medication therapy, and pulmonary rehabilitation .

1.1 Early Diagnosis of COPD

The early diagnosis of COPD involves a thorough medical history and physical
examination, including a spirometry test. This test measures the amount and speed of
air that a person can exhale, which can help identify any obstruction in the airways. In
addition, a chest X-ray or CT scan may be ordered to look for any structural
abnormalities in the lungs.
DIAGNOSIS OF COPD 2

If COPD is suspected, the doctor may also order blood tests to look for signs of
inflammation and check for other conditions that may worsen COPD symptoms, such
as heart disease. A sputum test may also be conducted to check for bacterial or viral
infections that can cause exacerbations of COPD. “Bronchiectasis (BE) might be
frequently present in COPD but masked by COPD symptoms.[11] (Kahnert, 2020)”

Early diagnosis is crucial to starting proper treatment, which includes smoking

cessation, medication, and pulmonary rehabilitation. Smoking cessation is the most
important step in managing COPD, as tobacco smoke is the primary cause of the
disease. Medications such as bronchodilators and corticosteroids can help improve
lung function and reduce inflammation. Pulmonary rehabilitation, which includes
exercise training and breathing techniques, can also help improve symptoms and
overall quality of life. “In COPD patients, clinical diagnosis and radiological signs of
BE showed only weak correlations.[12] (Jörres, 2020)”

In conclusion, early diagnosis of COPD is essential in the proper management of the

condition. It involves a comprehensive evaluation, including spirometry testing, chest
imaging, blood tests, and sputum analysis. With early diagnosis and proper treatment,
people with COPD can lead a fulfilling life.
The term chronic, in chronic obstructive pulmonary disease, means that it lasts for a
long time. “Symptoms of COPD sometimes improve when a person stops smoking,
takes medication regularly, and/or attends pulmonary rehabilitation[2] (RN B. F.,
n.d.)”

1.2 Morphometric measurement of COPD

Early diagnosis of COPD plays a crucial role in the successful management of the
disease. Various imaging techniques are used to diagnose COPD, including CT
Thorax scans, pulmonary function tests, and airway measurements using computer-
aided diagnostic (CAD) software.
Differnt types of morphometric measurements :
Radiologists use morphometric measurements to describe the quantitative evaluation
of anatomical structures or features seen in diagnostic pictures. Several morphometric
measurements are frequently employed in the context of chronic obstructive
pulmonary disease (COPD) to evaluate the severity and phenotypic traits of the
disease. The following are some essential morphometric measurements in COPD:
a) Airways measurement :
The measurement of the airway lumen's inner diameter.
Wall thickness: The thickness of the airway's wall as measured.
Airway lumen cross-sectional area is referred to as the lumenal area.
Percentage of the airway's wall area in relation to the overall cross-sectional area.
b)lung parenchyma measurement :
Quantification of the degree of lung tissue loss caused by emphysema.
The amount of lung attenuation (measured in Hounsfield Units) on computed
tomography (CT) images, which indicates the presence of emphysema or fibrosis, is
referred to as lung density.
c)vascular measurement:
Pulmonary vessel diameter: Measurement of the diameter of pulmonary blood
vessels.
DIAGNOSIS OF COPD 3

 Vessel wall thickness: Measurements of the thickness of vessel walls.

2) How did it come in to play .

With improvements in imaging technology and the need for more accurate and
impartial evaluations of disease features, morphometric measurements in radiology
have emerged. Traditional subjective evaluations focused on the visual interpretation
of radiological images, which was inaccurate and vulnerable to inter-observer
variability.
3) How they are used in diagnosis/phenotyping/severity of COPD in a
radiological manner?
In the radiological evaluation of COPD, morphometric data are essential for
diagnosis, phenotyping, and assessing the severity of the condition. The objective data
provided by radiological morphometric measurements can be combined with clinical
evaluations to increase the precision of the diagnosis of COPD, assist in phenotyping,
and gauge the severity of the condition. These assessments aid in the development of
tailored COPD medicines and a more individualised approach to patient management.

1.2.1 Objectives:

The objective of this study is to evaluate the morphometric measurements of airway

in smokers using the AWT-pi10 and FWHM principle in CAD software (Aview) in
correlation with CT Thorax scans images and pulmonary function tests (PFT), to
predict early diagnosis of COPD.

1.2.2 Methods:

This is a prospective observational study that will include smokers aged between 40-
60 years. The participants will undergo CT Thorax scans, PFT, and airway
measurements using Aview software. The AWT-pi10 and FWHM principle will be
used to measure the airway dimension. The airway wall thickness (AWT) will be
measured at the tenth generation of the bronchial tree, while full-width at half-
maximum (FWHM) will be used to assess airway narrowing. The correlation between
airway measurements, CT Thorax scans, and PFT will be analyzed. Depending on the
research goals, accessible imaging tools, and particular hypotheses being tested,
various studies may choose a different generation at which to assess airway wall
thickness (AWT). Although the 10th generation is frequently chosen as a benchmark
for AWT measurement, there are good arguments for also taking into account earlier
generations.
1) structural characteristics
2) Imaging resolution
3) Clinical Relevance
It's crucial to remember that the generation used for AWT measurement must make
sense within the context of the study or research. Depending on their unique
objectives and methodology, different studies may use a variety of measuring sites.
Researchers should explain why they chose particular generations of airways and
think about how these decisions may affect how their findings may be interpreted and
extrapolated.

1.2.3 Results:
DIAGNOSIS OF COPD 4

The results of this study will provide information on the usefulness of AWT-pi10 and
FWHM principle in CAD software for early diagnosis of COPD in smokers. It will
also provide insight into the correlation between airway measurements, CT Thorax
scans, and PFT. The study will help to identify potential biomarkers for early
detection of COPD.

1.2.4 Conclusion:

Early detection of COPD is essential for effective management of the disease. The use
of AWT-pi10 and FWHM principle in CAD software can help in the early diagnosis
of COPD in smokers. The study findings can be of great clinical significance in
predicting COPD prognosis and identifying high-risk individuals who may benefit
from early intervention.
DIAGNOSIS OF COPD 5

Chapter 2 : Diagnosis of COPD

2.1 Introduction

Chronic obstructive pulmonary disease, commonly known as COPD, is a chronic

respiratory disorder that affects millions of people worldwide. COPD is characterized
by a progressive decline in lung function, making it increasingly difficult for patients
to breathe. “Consider COPD in any patient that has dyspnea, chronic cough or
sputum production, and/or a history of exposures to risk factors[4] (Cihla, n.d.)”.
COPD is a major cause of morbidity and mortality worldwide and imposes a huge
burden on healthcare systems globally. Despite its significant impact, timely and
accurate diagnosis of COPD remains a challenge. Healthcare professionals use a
combination of clinical presentation, smoking history, and pulmonary function
tests to diagnose COPD and initiate appropriate treatment. Estimates of the prevalence
of clinically significant pulmonary vascular disease in patients with moderate to severe COPD
ranges from 25 to over 50%[21] (OA, 2010). Early diagnosis and management of COPD
can significantly improve patient outcomes and reduce the burden of disease. “The
most common respiratory symptoms include dyspnea, cough and/or sputum
production[5] (Agust, 2017)”.
2.1 Retrospective Analysis of the Impact of Smoking on Health: A Quantitative
and Qualitative Study
This thesis uses both quantitative and qualitative research methodologies to undertake
an extensive retrospective investigation of the consequences of smoking on health.
The goal of the study is to investigate the long-term effects of smoking on several
facets of physical and mental wellbeing, as reported by people who have smoked in
the past. This study will offer a comprehensive knowledge of the effects of smoking
from the perspective of former or current smokers by combining quantitative data
analysis and qualitative interviews.
Intoduction :
Smoking is a common practise that is known to significantly contribute to a number
of health problems. Even though the harmful effects of smoking have been thoroughly
researched, a retrospective analysis that combines quantitative and qualitative
methods can offer more depth into the viewpoints and experiences of smokers. By
examining both objective health markers and the subjective experiences provided by
smokers, this study tries to close this gap.
Methods :
Quantitative analysis :
A broad set of volunteers with a history of smoking will be chosen as a sample.
Data collection: Through self-report questionnaires or medical records,
comprehensive retrospective data on smoking behaviour, frequency, duration, and
associated health issues will be gathered.
Data analysis: A statistical analysis will be done to find links between smoking-
related factors and health outcomes such lung function, cardiovascular health, cancer
incidence, mental health problems, etc.
Qualitative analysis :
Interview selection: To learn more about the experiences of a subset of participants on
smoking and health, qualitative interviews will be conducted with them.
Semi-structured interviews: Extensive interviews with smokers about how smoking
affects their physical and mental health, social interactions, and quitting experiences
will be conducted.
DIAGNOSIS OF COPD 6

Thematic analysis: To find recurring themes, new ones, and individual stories about
smoking and its effects, qualitative data will be transcribed and subjected to thematic
analysis.
Results :
Quantitative Results
The analysis of the quantitative data will provide light on the relationships between
smoking-related factors (such as frequency and duration) and various health
consequences.
Correlations between smoking and respiratory illnesses, cardiovascular diseases,
cancer incidence, mental health issues, and other pertinent health markers may be
discovered.
Qualitative Results
Qualitative interviews will reveal individual experiences and viewpoints around
smoking and health through thematic analysis.
The effects of smoking on social interactions, psychological health, hurdles to
quitting, and effective cessation techniques are just a few examples of possible
themes.
Conclusion:
This retrospective thesis seeks to offer a thorough understanding of the long-term
effects of smoking on physical and mental health by integrating quantitative and
qualitative methodologies. The results of this study can help shape public health
interventions, legislation, and support programmes aimed at smokers, promoting
better health outcomes and efforts to stop smoking.

2.2 Use computer aided software to measure Lung texture analysis

The most commonly used software for measuring AWT is CT software that allows
clinicians to measure various parameters such as AWT pi-10, FWHM, Low
Attenuation Area, Percentage Wall Area, and Lung Texture Analysis. Small airways
disease can be quantified through measurements reflecting morphology, quantification of
obstruction, and changes in airways walls.[20] (Gevenois, 2012)

In order to measure AWT using computer aided software, the clinician first needs to
upload an image of the lung. Once the image is uploaded, the software will
automatically segment the image and detect the AWT. expiratory CT is used for the
visualization of air trapping but also for the evaluation for bronchial wall collapse during
expiration[17] (WM, 1978)

The AWT values can then be measured using different parameters such as AWT pi-
10, FWHM, and Low Attenuation Area.

AWT pi-10 is the thickness of the airway where the inner diameter has fallen to
10% of its original size. FWHM is the full-width at half maximum of the airway
cross section and Low Attenuation Area refers to the voxels with an attenuation value
of -950 HU or less. Calculation of AWT Pi10: The average airway wall thickness of
10th generation airways is represented by AWT Pi10. The 10th generation of
peripheral airways, which is regarded as a representative section of the medium-sized
airways, is referred to as "Pi10" in this notation. The following stages are involved in
calculating AWT Pi10:
DIAGNOSIS OF COPD 7

In CT imaging, the airway tree can be divided into many generations based on the
branching pattern.
a) Identification of Airway Segments. Various segmentation techniques may be used
in different investigations, but they typically require either automated algorithms or
hand annotations.

b) Determining the Airway Wall limits: Each segmented airway's inner and outer
airway wall limits are noted. Computerised techniques that assess the grayscale
intensity of the CT images and recognise the transition can be used to do this.
c) Measurement of Airway Wall Thickness: For each identified airway segment, the
distance between the inner and outer margins of the airway wall is measured.
Perpendicular to the airway wall, this measurement is made typically several times
along the segment.

d) Calculating the average airway wall thickness values for each generation and
choosing the Pi10 values. The average wall thickness of the 10th generation of
airways is utilised to calculate AWT Pi10. Studies may use different methods for
selecting and averaging Pi10 values, hence it is important to make this apparent in the
research methodology.
Handling Outliers:
Imaging artefacts, measurement mistakes, or anatomical differences can all lead to
outliers in AWT Pi10 results. In order to guarantee the validity and correctness of the
data, outliers must be dealt with. A statistical method that finds results that
considerably deviate from the central tendency is often used to handle outliers.
Typical techniques for dealing with outliers include:

a) Statistical Criteria: Researchers may provide statistical criteria, such as identifying

outliers as numbers that deviate significantly from the mean or more from it. The
research population and imaging procedures should be used to identify these cutoff
values in advance.

b) Visual Inspection: CT images and AWT measures can be examined visually to spot
any glaring outliers, such as measurement blunders or picture artefacts. Manual
exclusion of blatant outliers is made possible via visual inspection.

Percentage Wall Area is another parameter that is often measured using

computer aided software. It measures the percentage of the airway wall
thickness compared to the total airway diameter. “The major limitation of
pulmonary function tests is in how they are interpreted [7] (AL-ASHKAR, 2003)”.
Pulmonary function tests (PFTs) have the following limitations: a) Variability: PFT
results can vary depending on the patient's effort, compliance, and method.
Measurements that are not accurate can result from insufficient patient effort during
the test.
DIAGNOSIS OF COPD 8

b) Lack of Regional Information: PFTs provide overall lung function measurements

but lack specific regional data. They don't provide particular information about the
structural alterations in the lungs or pinpoint specific abnormalities.

c) Limited Sensitivity: PFTs might not pick up on minor pulmonary function changes
or early-stage lung illnesses. They may not correctly reflect early disease progression
and are more useful in assessing intermediate to severe disease stages.

d) Limited Specificity: Spirometric measures alone cannot allow PFTs to differentiate

between various respiratory diseases. To make specific diagnosis, more testing and
examination are frequently necessary.

e) Non-Imaging Technique: PFTs do not directly see the lungs or the structures
around them. They mainly evaluate airflow, volume, and gas exchange to determine
lung function.
CT Scan with Computer-Aided Detection (CAD) Benefits
a) Visualisation of Lung Anatomy: High-resolution images from CT scans make it
possible to see the blood arteries, airways, and lung parenchyma in great detail. This
offers useful knowledge about illness patterns and structural anomalies.

b) Quantitative Evaluation: CT scans can be used to quantitatively evaluate several

aspects of the lungs, including the size of the airways, the density of the lung tissue,
and the severity of emphysema. These measurements aid in a more accurate and
unbiased assessment of lung function and disease development.

c) Early Detection and Phenotyping: CT scans, particularly with cutting-edge imaging

methods and CAD systems, can spot subtle abnormalities and early indications of
lung illnesses. This supports phenotyping, early diagnosis, and individualised
treatment planning.
d) Comprehensive Evaluation: CT scans provide a comprehensive evaluation of the
lungs, allowing for the assessment of both functional and structural aspects. This can
aid in understanding the underlying mechanisms of disease and guide targeted
interventions.

e) Image-Guided Interventions: CT scans can assist in image-guided interventions

such as lung biopsies, bronchoscopic procedures, or surgical planning. The precise
anatomical information obtained from CT scans enhances the accuracy and safety of
these procedures.

It's important to note that while CT scans with CAD offer numerous advantages, they
also come with certain limitations such as radiation exposure, cost, and availability.
The choice of imaging modality depends on the specific clinical question, patient
characteristics, and resources available. “Currently available evidence and recent technical
advances allow quantification of airways disease and suggest that quantification of
emphysema extent and airways disease, both at CT, could match the definition of chronic
obstructive pulmonary disease phenotypes[18] (Hackx, 2012)”.

Lung Texture Analysis is a more advanced technique that uses CT images to measure
the texture of lung tissue. This technique can be used to detect changes in lung
tissue, such as fibrosis or emphysema. A computational method called lung texture
DIAGNOSIS OF COPD 9

analysis, commonly referred to as radiomics, derives quantitative information from

medical pictures, such as lung CT scans. It attempts to record minute patterns and
features of lung tissue that might not be visually obvious. With regard to the causes of
airflow limitation, CT can be used to quantify the two main contributions to COPD: emphysema,
and small airways disease (a narrowing of the airways)[19] (Bankier, 2012). The detection of
specific lung disorders like fibrosis or emphysema depends on the chosen analysis
methodologies and the characteristics of the dataset being analysed, even though lung
texture analysis can be useful for learning about changes in lung tissue.
1) Detection of Fibrosis
2) Detection of Emphysemia
Techniques for Quantification in Lung Texture Analysis:
To characterise lung tissue using lung texture analysis, numerous quantitative features
are extracted from CT scans. Lung volume reduction (LVR) and endoscopic lung volume
reduction (ELVR) are the current therapeutic options beside lung transplantation in cases of
severe emphysema[16] (Dis, 2018). Statistical metrics, shape descriptors, texture
descriptors, and spatial linkages are a few examples of these features. In lung texture
analysis, the following quantitative methods are frequently employed:

Analysis of the spatial distribution of gray-level intensities is done using the Gray-
Level Co-occurrence Matrix (GLCM).
The distribution of succeeding voxel runs is captured by the Gray-Level Run-Length
Matrix (GLRLM).
Laws' texture energy measures: Based on a set of predetermined filters, these
measures compute several types of texture energy.
Fractal analysis: Uses fractal dimensions to assess the complexity or irregularity of
lung structures.
Features based on histograms Determine the voxel intensities' distribution throughout
the various lung regions.
Based on the interactions between pixel intensities, local texture patterns are
described by local binary patterns (LBP).
The many facets of lung texture are intended to be quantified, and the numerical
measurements produced can be used “Pulmonary function tests (PFT’s) are
breathing tests to find out how well you move air in and out of your lungs and
how well oxygen enters your blood stream[6] (Fahy, n.d.)” .
Pulmonary function tests (PFTs) are essential in the diagnosis of COPD (chronic
obstructive pulmonary disease). PFTs frequently employ the following particular
assays to identify COPD:

FEV1 stands for forced expiratory volume in one second and measures how much air
is forcedly exhaled within the first second of a forced expiration. It displays the extent
of lung airflow restriction. Due to the enlarging of the airways and higher airflow
resistance in COPD, FEV1 is frequently decreased.

FEV1/FVC Ratio: The forced expiratory volume in one second (FEV1) and the forced
vital capacity (FVC), which is the total volume of air forcedly expelled following a
maximal inhalation, are being compared. Less than 0.70 in the FEV1/FVC ratio
suggests reduced airflow.
DIAGNOSIS OF COPD 10

The Diffusing Capacity of the Lung for Carbon Monoxide (DLCO or TLCO) test
measures how well the lungs can move gases, in particular carbon monoxide, from the
air we breathe into our bloodstream. Since lung tissue is being destroyed and gas
exchange is being hampered in COPD, DLCO frequently decreases.

Post-bronchodilator Readings: Following baseline PFT readings, bronchodilator drugs

(such as short-acting 2-agonists) are given, and the tests are repeated to determine
whether the airflow restriction is reversible. After bronchodilator treatment, a rise in
FEV1 of at least 12% and 200 mL from baseline is suggestive of reversible airflow
restriction, which may support the diagnosis of asthma-COPD overlap (ACO).

2.3 How those measurements are related to Lung Function Tests, FEV1 or FEV1/FVC?

FEV1 is the volume of air that a person can forcefully exhale in one second after
taking a deep breath. It is affected by the size of the airways, lung tissue elasticity,
and muscle strength. Age, height, and sex influence lung function by affecting lung
size and the strength of respiratory muscles.

FEV1/FVC ratio is a useful measurement in determining potential airflow obstruction.

Normal FEV1/FVC ratio values are generally above 70%, indicating that the majority
of air that can be forcibly exhaled is exhaled in the first second. However, this ratio
may be affected by lung volume, age, sex, height, and weight. People with lower
values of FEV1/FVC ratio could be at an increased risk of developing lung diseases.

Overall, the measurements of height, age, sex, and weight impact lung function tests
and can help in interpreting the results to assess for potential respiratory disease. A
recent publication reported bronchiectasis in 19.9% of lung-healthy individuals, compared to
35.1% of patients with severe COPD of the same age[13] (Tan, 2017)

2.4 In the Materials and Methodology, what are the variables, parameters, inclusion
and exclusion criteria to consider (e.g. GOLD Stage criteria)?

The variables, parameters, inclusion and exclusion criteria for early diagnosis of
COPD can vary depending on the specific study or diagnostic approach. However,
here are some general examples:
Variables:

Age
Gender
Smoking history (pack-years)
Occupational exposure to pollutants or dust
Respiratory symptoms (cough, sputum production, wheezing, shortness of breath)
Lung function parameters (FEV1, FVC, FEV1/FVC ratio, peak expiratory flow rate)
Parameters:

Spirometry (to measure lung function)

Chest X-ray or CT scan (to evaluate lung structure and rule out other lung diseases)
Blood tests (to check for signs of inflammation or infection)
Questionnaires (to assess symptoms and quality of life)
DIAGNOSIS OF COPD 11

A variety of questionnaires can be used to evaluate the symptoms and general health
of COPD sufferers. Questionnaires that are often used include:

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) offers a
questionnaire that evaluates how COPD affects a person's daily life, including
symptoms, activity restrictions, and general well-being. It includes inquiries on
breathlessness, sputum production, coughing, and how COPD affects daily activities.

CAT Score (COPD Assessment Test): GlaxoSmithKline (GSK) created the CAT
Score, a questionnaire that assesses the health and symptoms of people with COPD. It
consists of eight elements that measure symptoms such as cough, phlegm, tightness in
the chest, dyspnea, restrictions in one's ability to engage in certain activities,
confidence, and sleep quality.
SGRQ, or St. George's Respiratory Questionnaire: The SGRQ is a commonly used
questionnaire to evaluate the quality of life for people with respiratory conditions,
such as COPD. There are 50 items total, divided into three categories: symptoms,
activity restrictions, and effects on daily living. Higher scores on the SGRQ's overall
score and domain score indicate a disease's greater impact on quality of life.

The modified Medical Research Council (mMRC) Dyspnea Scale is a straightforward

instrument that measures how breathless people with COPD feel while going about
their regular lives. Higher scores on the scale, which ranges from 0 to 4, indicate
increased dyspnea and functional restrictions.

The COPD Assessment Test (CAT) is a different questionnaire designed to assess

how COPD affects a person's health and symptoms. It has eight questions that
evaluate symptoms, activity restrictions, and general wellbeing. A total score from 0
to 40 is provided by the CAT; higher values suggest a larger impact of COPD on
health status.

Depending on the individual research study or clinical practise scenario, a different

questionnaire may be used. Each questionnaire focuses on a distinct element of COPD
symptoms and health-related quality of life and has its own advantages. It is crucial to
choose a questionnaire that is in line with the objectives of the evaluation and the
particular requirements of the patient or research study.

Inclusion criteria:

Age range (e.g., 40-80 years)

Smokers or ex-smokers with a history of significant smoking exposure (e.g., >10
pack-years)
Presence of respiratory symptoms, such as chronic cough or shortness of breath
Abnormal spirometry results (e.g., FEV1/FVC ratio <0.70)

Exclusion criteria:

History of other lung diseases (e.g., asthma, cystic fibrosis, bronchiectasis)

Significant co-existing medical conditions that could affect lung function (e.g., heart
failure)
DIAGNOSIS OF COPD 12

Current or recent respiratory infections

Inability to perform spirometry or other required tests.

GOLD
Additionally, the Global Initiative for Chronic Obstructive Lung Disease (GOLD)
guidelines provide a useful framework for assessing the severity of COPD based on
spirometry results, symptoms, and exacerbation history. The GOLD criteria
categorize COPD into four stages (mild, moderate, severe, and very severe) based on
FEV1 and symptoms. The modified Medical Research Council dypnea scale (mMRC) was
used to define GOLD groups A-D [14] (Vogelmeier, 2017)

2.5 How are the groups classified?

The precise objectives and research questions of the study will determine the patient
separation criteria to be used in the methods section. Here are two potential strategies:

Based on their symptoms and history of exacerbations, people with COPD are divided
into four groups (A, B, C, and D) according to the GOLD classification. This
classification considers the exacerbation history as well as symptoms assessed by
questionnaires (such the CAT or mMRC). This method enables the distinction
between individuals with various levels of symptom severity and exacerbation risk. It
can be helpful for researching the effects of various treatment modalities or evaluating
the efficacy of therapies in particular GOLD groups. But it's crucial to remember that
the GOLD classification largely emphasises the severity and burden of COPD
symptoms

An alternative strategy is to divide patients into two groups, cases and controls. In this
method, patients with COPD (diagnosed using clinical and spirometric criteria) would
be the cases, and healthy persons would serve as the controls. To investigate the effect
of smoking on illness severity or outcomes, additional stratification within the cases
group based on smoking status (smokers vs. non-smokers) might be performed. By
comparing the traits, risks, and outcomes of COPD patients and non-COPD controls,
this method offers insights into the disease-specific determinants. When the goal is to
comprehend the characteristics and effects of COPD in comparison to a population
without the disease, it makes patient separation simpler and may be appropriate.

Case-Control Approach :
An alternative strategy is to divide patients into two groups, cases and controls. In this
method, patients with COPD (diagnosed using clinical and spirometric criteria) would
be the cases, and healthy persons would serve as the controls. To investigate the effect
of smoking on illness severity or outcomes, additional stratification within the cases
group based on smoking status (smokers vs. non-smokers) might be performed. By
comparing the traits, risks, and outcomes of COPD patients and non-COPD controls,
this method offers insights into the disease-specific determinants. When the goal is to
comprehend the characteristics and effects of COPD in comparison to a population
without the disease, it makes patient separation simpler and may be appropriate.
Several elements, such as the research objectives, study design, statistical power
concerns, and the particular research topic under investigation, might affect the
appropriate and average population size for a study. It's crucial to keep in mind that
DIAGNOSIS OF COPD 13

there is no one solution that applies to all situations, and different research studies and
methodology may have varying population size needs.
The classification is done using two main parameters:

The degree of airflow limitation, as measured by the FEV1 (forced expiratory volume
in one second), which is a measure of how much air a person can exhale forcefully in
one second after taking a deep breath.

The frequency and severity of exacerbations (acute worsening of symptoms) in the

previous year. “The Global Initiative for Chronic Obstructive Lung Disease proposed
in 2011 a new system to classify chronic obstructive pulmonary disease (COPD)
patients into risk groups A-D, which considers symptoms and future
exacerbation risk to grade disease severity[8] (Zogg, 2014)” .

The classification is as follows:

Group A: Low risk, less symptoms: Patients in this group have an FEV1 greater than
or equal to 50% predicted and experience fewer symptoms. They have a low risk of
exacerbations (less than one per year).

Group B: Low risk, more symptoms: Patients in this group have an FEV1 greater than
or equal to 50% predicted and experience more symptoms. They have a low risk of
exacerbations (less than one per year).

Group C: High risk, less symptoms: Patients in this group have an FEV1 less than
50% predicted and experience fewer symptoms. They have a high risk of
exacerbations (more than one per year).

Group D: High risk, more symptoms: Patients in this group have an FEV1 less than
50% predicted and experience more symptoms. They have a high risk of
exacerbations (more than one per year).

The classification helps in deciding the treatment plan for COPD patients, as it takes
into account the severity of the disease and the risk of exacerbations.

2.6 What images are better to be taken from the CT Scan Thorax?

CT (computed tomography) scan of the thorax is a common imaging test used to

diagnose and evaluate various conditions affecting the chest area, including lung
diseases, heart problems, and infections. “COPD is a clinical diagnosis based on
symptoms with abnormal physiology Emphysema can be diagnosed on CT[9]
(Gross)”.

The optimal CT scan protocol for thorax imaging may vary depending on the specific
indication for the test, the patient's clinical history and symptoms, and the preferences
of the radiologist or healthcare provider interpreting the images. Imaging has been
integrated into standard clinical practice, and echocardiography is commonly used to screen
for pulmonary vascular disease in smokers.[22] (Rahaghi, 2014)
DIAGNOSIS OF COPD 14

However, generally, the following guidelines are recommended for CT scan thorax
imaging:
To uphold uniformity and fairness in research studies involving imaging data, the
selection of images and the creation of inclusion and exclusion criteria are crucial. To
guarantee consistency and reliability of the results, several factors are taken into
account when choosing images for analysis. Here are some considerations for image
selection in a study involving CT chest axial images:

Inclusion Criteria:

COPD Patients: The study may include patients diagnosed with COPD based on
clinical and spirometric criteria.
Image Quality: Images of sufficient quality are included to ensure accurate
interpretation and analysis. This typically involves evaluating factors such as
resolution, contrast, absence of motion artifacts, and proper image acquisition
techniques.

Inspiratory pictures: In COPD research, inspiratory CT chest axial pictures are

frequently employed. The dimensions of the airways and the properties of the lung
tissue are all detailed information provided by these images on lung structure. The full
extent of lung inflation is captured in inspiratory images, allowing for a better
evaluation of emphysematous changes, air trapping, and other structural
abnormalities.

Exclusion Standards:

Images of individuals with other important lung diseases or comorbidities may be

removed since they could throw off the study or affect how COPD-related alterations
are interpreted.
Motion Artefacts: To ensure proper assessment of lung structures, images with motion
artefacts, such as blurring brought on by patient movement during image acquisition,
may be eliminated.
Non-Standardized techniques: In order to preserve standardisation, images obtained
using non-standard imaging techniques may have an impact on the consistency or
quality of the images.
For a number of reasons, inspiratory-only CT chest axial images are frequently used
in COPD research. The National Lung Screening Trial (NLST) showed the benefit of low-
dose CT to reduce lung cancer mortality in at-risk individuals[24] (DR, 2011)

Lung anatomy Assessment: Inspiratory pictures offer a thorough look at the anatomy
of the lungs and can be used to evaluate emphysematous changes, the size of the
airways, and other anatomical characteristics important to COPD. Lung cancer, chronic
obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to
cause most deaths by 2050[23] (Xia, 2020). 
Avoiding Respiratory Variability: Since the lung usually inflates to a steady condition
during inspiration, respiratory motion artefacts have less of an impact on inspiratory
pictures. As a result, measurement reliability is increased and variability is decreased.
DIAGNOSIS OF COPD 15

Utilising inspiratory-only images ensures uniformity throughout the research

population and enables direct comparison of results between participants.
Researchers can maintain a fair and uniform choice of images, improving the
reliability and validity of the study findings, by applying standardised inclusion and
exclusion criteria, with a focus on image quality, the usage of inspirational images,
and the elimination of confounding factors.

Axial scans with a slice thickness of 1mm are preferred, as they provide high-
resolution images of the chest area and allow for better detection of small
abnormalities.

The thorax area should be imaged from the top of the lung apices to the bottom of the
costophrenic angles, including the entire lung parenchyma, mediastinum, and upper
abdomen.

The patient should be positioned supine (lying on their back) with their arms raised
above their head, and the scan should be performed during a single breath-hold to
minimize motion artifacts.

Intravenous contrast may be used to enhance the visualization of blood vessels,

tumors, or other abnormalities in the chest area. If the majority of your study's non-
contrast-enhanced CT (NECT) scans are used to assess COPD, there are particular
advantages and considerations with this imaging technique.

Non-contrast-enhanced CT scans can be very helpful in evaluating emphysema and

airway problems in COPD because they offer important information on the
anatomical properties of the lungs. NECT scans are frequently utilised in studies of
COPD for the following reasons:
Radiation Dose
Structural Assessment
Simplified Image Acquisition
Consistency in Image Analysis
It's crucial to keep in mind that NECT scans could be constrained in comparison to
contrast-enhanced CT scans. Contrast-enhanced scans may be better appropriate for
certain research issues or when evaluating illnesses beyond the purview of COPD
since they can give greater details about the pulmonary vasculature.

High picture quality, appropriate image acquisition procedures, and suitable training
for radiologists or researchers involved in image interpretation and analysis are
essential when employing NECT scans. Additionally, it's crucial to match the imaging
modality you choose with the precise research aims and the variables your study is
evaluating, taking into account both the potential benefits and limits of NECT
scans.However, in some cases, such as in patients with renal insufficiency, allergic
reactions to contrast agents, or certain types of lung disease, contrast may not be
recommended. “CT not routinely recommended except for detection of bronchiectasis
or lung cancer screening[10] (Cihla, Assessment of COPD Diagnosis and Initial)” .

Overall, a high-quality CT scan thorax can provide detailed images of the chest area,
which can aid in the diagnosis and treatment of various thoracic conditions. However,
DIAGNOSIS OF COPD 16

the specific imaging protocol should be tailored to the individual patient's needs and
clinical situation.

2.7 Do we need to include quantification of emphysema like the 15th percentile

method (Perc 15) ?

Quantification of emphysema, including the 15th percentile method (Perc 15), can be
a useful tool in the evaluation of patients with chronic obstructive pulmonary disease
(COPD) or other lung diseases that involve emphysema.

The Perc 15 method is a measurement of the percentage of lung voxels (3D

pixels) with an attenuation value below a certain threshold, typically -950
Hounsfield units (HU). The 25th percentile, sometimes referred to as the lower
quartile or first quartile, is typically referred to as "Perc 25". The value below which
25% of the data points fall is a statistical measure known as the significance level.
The following stages are involved in calculating Perc 25:

Data sorting: Sort the dataset from the smallest to the highest value in descending
order.

Find the Position: Find the 25th percentile's location in the sorted dataset. Position =
(25/100) * (n + 1), where 'n' is the total number of data points in the dataset, can be
used to do this.

Find the Value: In the sorted dataset, find the value at the calculated location. The
value at that place directly indicates the 25th percentile if the position is an integer. To
acquire the accurate value if the location is not an integer, you might need to
interpolate between the values before and after the position.

In interpolation, the value between two adjacent data points is predicted based on how
close together they are in the interval. One of the most used interpolation techniques
is linear interpolation, which computes the value using a weighted average of the
values in the vicinity.

It's vital to remember that depending on the software or statistical tool being utilised,
the precise calculation procedure may change. This threshold is used to distinguish
between normal lung tissue and emphysematous lung tissue, which has lower
attenuation values due to destruction of the alveolar walls.

Several studies have shown that the Perc 15 method can provide useful information
on the severity and distribution of emphysema, as well as the prognosis and
response to therapy in patients with COPD or other lung diseases. For example, a
higher Perc 15 value has been associated with a greater degree of lung function
impairment, more severe symptoms, and an increased risk of exacerbations.

However, the use of the Perc 15 method is not mandatory in all cases, and its
inclusion in the CT scan report may depend on the specific clinical context and the
preferences of the interpreting radiologist or healthcare provider. Other quantitative
DIAGNOSIS OF COPD 17

measures of emphysema, such as the emphysema index or the mean lung density,
may also be used in some cases.

Overall, the decision to include quantification of emphysema in the CT scan report

should be based on a careful assessment of the patient's clinical history, symptoms,
and imaging findings, as well as the available evidence and guidelines for the
evaluation and management of COPD or other lung diseases. “For tumors,
SUVpeak values did not vary with acquisition time. SUVmax displayed significant differences
between 1.5- and 5–10-min reconstruction times. SUV41% was the most time-dependent
parameter. For the liver, the SUVaverage was the sole parameter that did not vary over time.[15]
(Sher, 2016)”

2.8 What specific measurements should be taken from this specific study?

In general, the following measurements are commonly used in the diagnosis and
evaluation of COPD:

Spirometry: Spirometry is a pulmonary function test that measures lung function by

assessing the amount and rate of air flow during breathing. The two most important
spirometry measurements for diagnosing COPD are forced expiratory volume in one
second (FEV1) and forced vital capacity (FVC). The ratio of FEV1/FVC is used to
determine the severity of airflow limitation, which is a key feature of COPD.

Imaging: Imaging tests, such as chest X-rays or computed tomography (CT) scans,
may be used to evaluate lung structure and detect any abnormalities or signs of
COPD, such as emphysema or airway wall thickening.

Arterial blood gas analysis: Arterial blood gas analysis is a test that measures the
oxygen and carbon dioxide levels in the blood, as well as the acidity (pH) of the
blood. This test may be used to assess the severity of COPD and determine the need
for oxygen therapy.

Physical examination: A physical examination, including listening to the patient's

lungs with a stethoscope, may reveal signs of COPD, such as wheezing or diminished
breath sounds.

Medical history: A patient's medical history, including any symptoms, smoking

history, occupational exposures, and family history, may provide important clues to
the diagnosis of COPD.

It's worth noting that the specific measurements used for the diagnosis of COPD may
vary depending on the diagnostic criteria used by different organizations or healthcare
providers. For example, the Global Initiative for Chronic Obstructive Lung Disease
(GOLD) guidelines recommend using spirometry to diagnose and stage COPD, while
other organizations may place more emphasis on imaging or other tests.
It is usual practise to use guidelines or suggestions offered by respected healthcare
organisations or systems in radiological studies pertaining to particular diseases or
ailments. To promote precision, uniformity, and high quality in radiological imaging
and interpretation, these organisations frequently develop standards and protocols.
DIAGNOSIS OF COPD 18

Here are a few well-known groups that offer recommendations for radiological
studies:

American College of Radiology (ACR)

European Society of Radiology (ESR)
Radiological Society of North America (RSNA)
National Institute for Health and Care Excellence (NICE)
Referencing policies or suggestions from these bodies when conducting a radiological
study can improve the precision and uniformity of the research technique. To ensure
adherence to current best practises and preserve the highest level of accuracy and
dependability in your study, it is critical to examine the most recent recommendations
pertinent to your unique research topic and healthcare system.

2.9 Which simple statistics to use to arrive to a conclusion (E.g p <0.05). The
reason for this study and its novel factor that can have future implications.

The specific statistical tests and methods used will depend on the type of data
collected, the research question being investigated, and the study design.

However, some commonly used statistical tests for medical research include:

t-test: Used to compare the means of two groups of continuous data, such as lung
function measurements in patients with and without COPD.

Chi-square test: Used to analyze categorical data, such as smoking status or the
presence/absence of specific symptoms in patients with COPD.

Logistic regression: Used to evaluate the relationship between one or more predictor
variables and a binary outcome, such as the presence or absence of COPD.

ANOVA: Used to compare the means of multiple groups of continuous data, such as
lung function measurements in patients with mild, moderate, or severe COPD.

To arrive at a conclusion, you would typically compare the statistical results to a

predetermined level of statistical significance, such as a p-value of less than 0.05,
which indicates that the probability of obtaining the observed results by chance is less
than 5%. If the p-value is below this threshold, the results are considered statistically
significant and support the hypothesis being tested.

It's important to note that statistical significance does not necessarily imply clinical
significance, and the findings of a study should be interpreted in the context of their
clinical relevance and potential implications for patient care.

References
Agust, A. (2017). GLOBAL INITIATIVE FOR CHRONIC.
DIAGNOSIS OF COPD 19

Agusti, A. (2017). GLOBAL INITIATIVE FOR CHRONIC.

AL-ASHKAR, F. (2003). Interpreting pulmonary function tests. CLEVELAND CLINIC
JOURNAL OF MEDICINE.
Cihla, A. N. (n.d.). Assessment of COPD Diagnosis and Initial. Consulting Pulmonologist
Appalachian Pulmonary Health Program.
Cihla, A. N. (n.d.). Diagnosis and Initial Assessment of COPD. Retrieved from wvctsi.org:
https://www.wvctsi.org/media/12908/diagnosis-and-initial-assessment-of-copd.pdf
Fahy, B. (n.d.). PATIENT EDUCATION | INFORMATION SERIES. Retrieved from
American Thoracic Society:
https://www.thoracic.org/patients/patient-resources/resources/pulmonary-function-
tests.pdf
Gross, T. J. (n.d.). Introduction to Chest CT: Basics, Pointers, and Pitfalls. lowa city.
RN, B. F. (n.d.). PATIENT EDUCATION | INFORMATION SERIES. Retrieved from
American Thoracic Society:
https://www.thoracic.org/patients/patient-resources/resources/copd-intro.pdf
RN, S. C. (n.d.). PATIENT EDUCATION | INFORMATION SERIES. Retrieved from
American Thoracic Society:
https://www.thoracic.org/patients/patient-resources/resources/copd-intro.pdf
Zogg, S. (2014). Differences in classification of COPD patients into risk groups A-D: a
cross-sectional study.

References
Agust, A. (2017). GLOBAL INITIATIVE FOR CHRONIC.
Agusti, A. (2017). GLOBAL INITIATIVE FOR CHRONIC.
AL-ASHKAR, F. (2003). Interpreting pulmonary function tests. CLEVELAND CLINIC JOURNAL
OF MEDICINE.
Bankier, A. A. (2012). Chronic Obstructive Pulmonary Disease: CT Quantification of Airways
Disease. Radiology.
Cihla, A. N. (n.d.). Assessment of COPD Diagnosis and Initial. Consulting Pulmonologist
Appalachian Pulmonary Health Program.
Cihla, A. N. (n.d.). Diagnosis and Initial Assessment of COPD. Retrieved from wvctsi.org:
https://www.wvctsi.org/media/12908/diagnosis-and-initial-assessment-of-copd.pdf
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DR, A. (2011). National Lung Screening Trial Research T. New Engl.
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Gevenois, P. A. (2012). Chronic Obstructive Pulmonary Disease: CT Quantification of Airways
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DIAGNOSIS OF COPD 20

RN, B. F. (n.d.). PATIENT EDUCATION | INFORMATION SERIES. Retrieved from American

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