Impact of Aerobika® Oscillating Positive Expiratory Pressure (OPEP) in Improving Small Airway Disease and COPD Assessment Test (CAT) Score in Chronic Obstructive Pulmonary Disease (COPD)
Phase: NA
Conditions: COPD
Sponsor: National University of Malaysia

1 
THESIS PROPOSAL 
MASTERS OF INTERNAL MEDICINE 
UNIVERSITI KEBANGSAAN MALAYSIA 
Impact of Aerobika® Oscillating Positive Expiratory Pressure (OPEP) in Improving 
Small Airway Disease and COPD Assessment Test (CAT) Score in Chronic 
Obstructive  Pulmonary Disease (COPD)  . 
FF - 2021-175
Candidate: 
Dr. Siti Nurhanis binti Sahardin (P100643) 
Supervisor: 
Assoc. Prof. Dr. Mohamed Faisal Abdul Hamid 
Respiratory Unit, Department of Internal Medicine, UKMMC 
Co-supervisors: 
Assoc. Prof. Dr. Andrea Ban Yu-Lin 
Dr. Ng Boon Hau 
Dr. Nik Nuratiqah binti Nik Abeed 
Respiratory Unit, Department of Internal Medicine, UKMMC 
Statistic Advisor: 
Professor Dr. Syed Zulkifli Syed Zakaria 
Department of Paediatrics, UKMMC 
Co-Researchers: 
Rose Azzlinda Osman 
Sr. Scientific Officer, UKMMC 
Norita Idris 
Nur Amani Aris 
Azira Ahmad Kamil 
Respiratory Laboratory Technician, UKMMC 
Date : 21 February 2021

 
2 
TABLE OF CONTENTS 
CHAPTER 1: INTRODUCTION 
4 
1.1 
Research Background 
4 
1.2 
Problem Statement 
5 
1.3 
Research Question 
7 
1.4 
Hypothesis 
7 
CHAPTER 2: LITERATURE REVIEW 
8 
CHAPTER 3: RESEARCH OBJECTIVES 
13 
3.1 
Objectives 
13 
3.2 
Significance of Research 
13 
CHAPTER 4: RESEARCH METHODOLOGY 
14 
4.1 
Type of Study 
14 
4.2  
Study Design 
14 
4.3  
Study Protocol and Data Acquisition 
16 
4.4  
Operational Terms Definition 
17 
4.5 
Sample Size 
18 
4.6  
Data Collection Pathway 
19 
4.7  
Dummy Table 
20 
CHAPTER 5: RESEARCH ETHICS 
22 
CHAPTER 6: FINANCIAL PLANS 
23 
CHAPTER 7: RESEARCH INFORMATION 
24 

 
3 
CHAPTER 8: INFORMED CONSENT FORM 
32 
CHAPTER 9: DATA COLLECTION SHEET 
34 
CHAPTER 10: GANTT CHART 
36 
CHAPTER 11: APPENDICES 
37 
CHAPTER 12: REFERENCES 
45 
 
 
 
 
 

 
4 
CHAPTER 1 
INTRODUCTION 
 
1.1 
Research Background 
Chronic obstructive pulmonary disease (COPD) is a progressive chronic lung disease 
that makes breathing difficult with mucus buildup in the inflamed airway (1, 2) and lungs 
hyperinflation due to expiratory flow limitation.  Global Initiative for Chronic Obstructive 
Lung Disease (GOLD) defines COPD as a common, preventable and treatable disease (3) with 
significant morbidity and mortality, and incurs intensive expenditure of healthcare resources 
(4). This disease is currently the fourth leading cause of death in the world but is projected to 
be the 3rd leading cause of death by 2020. In 2012, global death from COPD accounted about 
6% which equal to more than 3 million deaths in world population (3). The mortality burden of 
COPD is expected to rise to 8.6% by 2030  (5). In Malaysia, the prevalence of moderate to 
severe COPD in Malaysia in 2010 is 4.7% which equals to 448,000 cases (5-7). 
COPD is attributed by long-term exposure to noxious particles and toxic gases (1). 
Tobacco smoking is the main cause of COPD globally (8). The Third National Health and 
Morbidity Survey (NHMS III) conducted in Malaysia in 2006 showed that the prevalence of 
male ever smokers was 57.6% and in female is 2.5% (9). Other than that, inhalation of organic 
or chemical dust and fumes, and biomass exposure also among the risk factors of COPD. 
Exposure to noxious particles will cause activation of inflammatory immune responses. 
However, continuous and repetitive exposure towards these noxious particles will lead to tissue 
remodelling in small airways causing smooth muscle hypertrophy and fibrosis causing major 
site of obstruction in COPD (10). 
COPD is characterized by a mixture of small airway disease and parenchymal lung 
tissue destruction causing emphysema which affecting gas transfer (11). Small airway is defined 
as airways of less than 2mm in internal diameter which lacks in cartilage, and have greater 
proportion of smooth muscles with fewer goblet cells in the epithelial layers (11). Approximately 
10-25% of total airways resistance in healthy lungs is due to the small airways, with their 
contribution to total airways resistance increasing substantially in COPD. As the small airways 
are located in the lung periphery, they are not easily evaluable, which can potentially interfere 

 
5 
with the diagnosis (especially at early stages), monitoring, detection of responses to clinical 
interventions, and prognostic evaluation in COPD (12).  
In COPD patients, the small airways represent the key sites of airflow obstruction, and 
small airway disease (SAD) is considered a functional hallmark of disease (13). The presence of 
SAD progressively increases with higher GOLD classifications and it is closely related to the 
high impact of disease measured by COPD Assessment Test (CAT) questionnaire. 
Distributions of SAD among COPD patients classified according to GOLD classification. In 
each of GOLD A, B, C and D class, the prevalence of SAD are 49%, 88%, 61%, and 96% 
respectively (Figure 1) (13). As presence of SAD is closely related to high impact of disease 
with CAT score ≥10 , they tend to have more symptoms  (13). 
 
Figure 1: Distribution of patients with and without SAD according to the GOLD 
classification(13) 
 
1.2 
Problem Statement 
As mentioned before, in COPD patients, the small airways represent the key sites of 
airflow obstruction, and SAD is considered a functional hallmark of disease (13).  Spirometry is 
the most reproducible and objective measurement of airflow limitation (3). However, it is not 
sensitive to evaluate SAD. In the context of lung function evaluation, the impulse oscillometry 
system (IOS), a type of forced oscillation technique, was recently proposed as a better way of 
detecting SAD than standard spirometry. IOS provides measurement for both proximal and 
distal airway resistance. In COPD patients, IOS is also useful to detect early phases of disease, 

 
6 
other than useful to assess bronchodilator responsiveness and effect, as well as to define 
different subgroups of patients according to airflow obstruction. SAD measured by IOS 
increases progressively according to the severity of disease assessed by GOLD classifications 
in COPD (13).  
The earliest indication of small airways disease when evaluated by spirometry is the 
deceleration of airflow at the terminal portion of the flow-volume curve, which can be detected 
by measuring the mean expiratory flow between 25% and 75% of Forced Vital Capacity (FVC) 
(FEF25-75%). This parameter is calculated by dividing the expiratory volume by the time 
difference between these two points in the mid-range of the FVC manoeuvre (12). The use of 
FEF25-75%/FVC can act as a potential clinical tool for early detection of COPD (12). Thus, 
patients who present with low FEF25-75% values should be monitored closely, as they are 
susceptible to COPD, even though they may have normal lung function (14).  
IOS is a simple, non-invasive method requiring only passive patient cooperation 
without special manoeuvre for evaluation of lung function through the measurement of both 
airway resistance and airway reactance.(15)  The pressure-flow oscillations are applied at the 
mouth superimposed on the subject’s tidal breaths to measure respiratory system resistance and 
reactance at different oscillation frequencies. It uses sound waves to rapidly detect airway 
changes. When analysed, these pressure signals separately quantify the degree of obstruction 
in the central and peripheral airways (15). In IOS, it enables measurement of total respiratory 
resistance (R5) and proximal respiratory resistance (R20), with the R5-R20 difference 
reflecting small airway resistance (16, 17). Small airway disease is significance if R5-R20 > 0.71 
cmH2O/L/sec (17-20). 
Treatment of COPD requires combination of pharmacological and non-
pharmacological approaches. In non-pharmacological treatment, chest physiotherapy and 
pulmonary rehabilitation is the cornerstone of management of COPD patients. It can result in 
improvement of symptoms, increased exercise capacity, and improvement in lung functions 
(21). By early detection of SAD in COPD, it enables the physician to offer patients with a more 
targeted approach therapy, for example the use of small particle size inhalers or mechanical 
intervention for example oscillating positive expiratory device (OPEP), such as Aerobika®. 
 
 
 

 
7 
1.3  
Research Question 
Can Aerobika® OPEP device improve small airway disease and CAT score in COPD on top 
of standard therapy. 
 
1.4   
Hypothesis 
Aerobika® OPEP improves small airway parameters and CAT score on top of standard 
therapy. 
 

 
8 
CHAPTER 2 
LITERATURE REVIEW 
In healthy people,  mucociliary clearance and cough mechanisms are normally effective 
and efficient, but become overloaded if these systems malfunction and in the presence of 
excessive bronchial secretions. Chest physiotherapy is commonly used to improve the 
mobilization and removal of airway secretions in patients with respiratory dysfunction (22). 
Other non-pharmacological therapy such as active cycle of breathing technique (ACBT) , 
positive expiratory pressure (PEP), oscillating PEP (OPEP) devices, and intrapulmonary 
percussive ventilation (IPV) are also known helpful in airway clearance (23). Techniques may 
be used alone or in combination with others. 
OPEP device has been developed since 1970s , and it was first developed and described 
in Switzerland, as an adjunct or supplement to traditional airway clearance methods  (22, 23).  It 
has been utilized to promote the clearance of respiratory secretions in individuals with impaired 
ability to cough, particularly in chronic diseases. It is a hand-held, drug-free medical device 
that is designed to expand the airways, mobilize mucus, and help to expel mucus from the 
lungs. It has been shown to improve health-related quality of life and improve lung function in 
COPD patients (24).  
During inhalation of OPEP, it will provide a linear pathway through an inhalation valve. 
Upon exhalation, a one-way valve within the device mechanism opens and closes intermittently 
resulting in positive pressure that will hold airways open and sustaining expiratory flow, 
combines with airway vibrations or oscillations resonating at a frequency similar to the cilia 
which decrease the viscoelastic properties of the mucus (23, 25-27). This will thin and help to 
mobilise sputum, making it easier for removal by deep force exhalations or coughing 
(“huffing”) techniques (Figure 2) (23).There are few models of OPEP devices, for example 
Aerobika® (Trudell Medical International), Acapella® (Smiths Medical), Flutter® (Axcan 
Scandipharm), Lung Flute® (Medical Acoustics), and Quake® (Thayer Medical). 
The Aerobika® OPEP device has been reported to improve symptoms and quality of 
life outcomes for COPD patients with mucus hypersecretion. This compares the responder rates 
from two separate studies using the same device, one with the St George’s Respiratory 
Questionnaire (SGRQ) and the other with the CAT score. First study done by Svenningsen et. 

 
9 
al. in 2016 is a randomized cross-over study in 27 COPD patients for 3-4 weeks, used the 
SGRQ. In their study, the mean SGRQ value for the 14 COPD patients with chronic bronchitis 
significantly improved from 49 to 40 (p = 0.01, paired t-test) following OPEP therapy. SGRQ 
is a standardized self-administered airways disease-specific questionnaire that divided into 
three subscales: symptoms, activity, and impacts. Overall, SGRQ is interpreted as quality of 
life scores (25). Second study by Sugett J. is a clinical assessment of 37 COPD patients over an 
8-week period, used the CAT score. In this study, the mean CAT value for the 26 COPD 
patients with chronic bronchitis significantly improved from 19.7 to 17.4 (p = 0.01, paired t-
test) following OPEP therapy. Even though using different validated questionnaire 
instruments, the results from these two separate studies show good agreement, with nearly two 
thirds of COPD patients with chronic bronchitis exhibiting clinically significant improvements. 
In terms of responder rate analysis, Aerobika® OPEP showed significant improvement in 
symptoms and quality of life greater than the Minimum Clinically Important Difference 
(MCID), where it proved 64% improvement in SGRQ (MCID ≥ 4) and 62% improvement in 
CAT score (MCID ≥ 2). (28) MCID is the smallest change in score that patients perceive as 
beneficial or detrimental, and is useful to aid the clinical interpretation of health status data, 
particularly in response to intervention. The most reliable estimate of the MCID for SGRQ is 
4 points (29), whereas of the CAT score is 2 points. (30) 
It is postulated that OPEP will help to increase exercise capacity in COPD patients. In 
a study done by Nicolini and colleagues in 2018, patients involved in the study were given 
Lung Flute® OPEP. In their study, OPEP users demonstrated improvement in exercise capacity 
measured by using 6 minutes walking test (6MWT) compared to control group (p < 0.008 vs 
0.01). They also showed improvement in COPD symptoms compared to control group assessed 
by using CAT score (p < 0.004 vs p < 0.012),  and the Modified Medical Research Council 
(MMRC) Dyspnoea Scale (p < 0.002 vs p < 0.012). However, in their study, OPEP has not 
shown a reduction number of exacerbation in the involved patient. (31, 32) 
Improvement in exercise capacity is also proved by a study done by Svenningsen et. al 
in 2016 in sputum-producer patients. Patients fitted into sputum-producers criteria if they had 
coughed and brought up sputum “several days a week” (>2 days a week) or “almost every day” 
in the month prior to the study. Exercise capacity is assessed at baseline, and after Aerobika® 
OPEP usage at week 3 to 4, and also during final visit at week 6 to 8 using 6MWT. All 
participants were trained by a pulmonary function technologist to use the device four-times 

 
10 
daily with each session consisting of 10–20 blows into the device, followed by 2–3 “huff” 
coughs. Treatment sessions were documented at home by the patient using a daily diary. Post 
OPEP study, in sputum-producers only, it showed significant improvement  in 6MWT with p-
value of 0.04 compared to pre-OPEP group.  Their study also proved that the spirometry result 
(FVC value) in sputum-producer patients with OPEP showed significant improvement 
compared to off-OPEP group (6%  improvement in FVC, p = 0.02). (25, 32)  
Additionally, Aerobika® OPEP will help to reduce moderate to severe exacerbation. 
The risk of experiencing subsequent exacerbations is two to four times higher in COPD patients 
with a prior exacerbation compared to those without prior exacerbation. Therefore, prevention 
is an important treatment goal (33). In a study done by Burudpakdee and colleagues in 2017,  
significantly fewer patients provided with the Aerobika® OPEP device compared to matched 
controls experienced moderate-to-severe exacerbations (18.5% vs 25.7% respectively, p = 
0.014) or severe exacerbations (13.8% vs 19.0%, respectively, p = 0.046) in 30 days.(34)  
There is a study showed that Aerobika® is the most effective OPEP in reducing COPD 
re-exacerbations compared to other OPEP devices. In a study done by Tse et. al. in 2020 on 
comparison of impact between two-commonly used OPEP devices; Aerobika® and Acapella® 
in COPD or chronic bronchitis patients, patients using Aerobika® OPEP had a 31% reduction 
in COPD or chronic bronchitis related readmission within 30 days of the index hospitalization 
(12.0% vs. 17.4%; p = 0.001) compared to Acapella. This significant difference persisted over 
a 12-month duration, with a smaller proportion of Aerobika® patients having a severe 
exacerbation requiring hospitalization (39.6% vs. 45.3%; p = 0.013) and fewer hospitalizations 
per patient (mean, 0.75 vs. 0.90; p = 0.010). Aerobika® users also have significantly longer 
time to first severe exacerbation than Acapella users (log-rank p = 0.01). This suggests that 
Aerobika® OPEP device may be a beneficial add-on to usual care and that OPEP devices may 
vary in clinical effectiveness. (26) 
There is evidence for the cost-effectiveness of the Aerobika® device in the 
management of COPD, in terms of savings in direct medical costs associated with reduction in 
COPD exacerbations. By using real-world clinical evidence to evaluate the incremental 
performance of the Aerobika®, Khoudigian-Sinani et. al. in 2017 analysed data from published 
literature and national fee schedule to model the cost-effectiveness of Aerobika® OPEP in 
patients who had experienced an exacerbation in the previous months, or post-exacerbation 
care population. When the effect of Aerobika® device was assumed to last 30 days, use of the 

 
11 
device resulted in improved outcomes (six fewer exacerbations per 100 patients per year) lead 
to cost-savings, compared to no OPEP therapy (2). Similar analysis was done by Thanh and 
colleagues in 2019 which showed that the Aerobika® OPEP is a potential component of a 
treatment strategy for symptom control and reduce the risk of re-exacerbations in patients with 
COPD, with more effective and less costly economic outcome (24). Therefore, Aerobika® 
device is a treatment option that provides clinical benefit and results in direct medical cost 
savings in a post-exacerbation care COPD population in a long run. In real population, usage 
of OPEP device may be beneficial as it can reduce visits to the emergency department, reduced 
early rehospitalizations and lower the treatment cost by the means of reducing COPD 
exacerbation (26, 34, 35). 
On the other hand, there is only one study measures the outcome of sputum clearance 
in COPD patients with OPEP. Svenningsen and colleagues in a study done in 2016 proved that 
OPEP statistically and clinically significant helpful in improving sputum clearance in sputum-
producers COPD patient. Patient Evaluation Questionnaire (PEQ)-ease-bringing-up-sputum 
score (pre-OPEP 3.9 ± 0.8, post-OPEP 2.7 ± 1.1; p = 0.005) is used for evaluation, at which 
this context, a reduced PEQ score indicates improved sputum clearance (25, 32) . 
In COPD, sputum clearance might be expected to reduce airflow limitation  and allow 
occluded lung units to be recruited. It is postulated that usage of OPEP can improve small 
airway disease parameters using IOS. At the moment, there are no studies available on small 
airway disease parameters improvement after OPEP usage.  
In summary, this study would like to propose that non-pharmacological treatment for 
airway clearance is as important as pharmacological therapy. The aim of the study is to 
demonstrate that the usage of Aerobika® OPEP device among COPD patients may augment 
sputum clearance, improve small airway parameters by IOS as well as patient’s symptoms as 
measured by CAT score. In addition, it will also help to improve exercise quality as well as 
lung function in this group of people.  
 
 

 
12 
 
 
 
Figure 2: Oscillating positive expiratory pressure (OPEP) mode of action model (23). 
 
 
 
 
 
 
 
 
Figure 3: Aerobika® OPEP device 
 
 

 
13 
CHAPTER 3 
RESEARCH OBJECTIVES 
 
3.1 
Objectives 
 
3.1.1 Primary 
To demonstrate improvement of small airway parameter using IOS after introduction of 
Aerobika® OPEP in 3 and 6 months among COPD patients in UKMMC. 
 
3.1.2 Secondary 
I. 
To evaluate improvement of symptoms using CAT score after 3 and 6 months. 
II. 
To evaluate improvement of lung function (using spirometry) and exercise capacity 
(using 6MWT) after 3 and 6 months. 
III. 
To evaluate moderate and severe exacerbation rates after Aerobika® OPEP device 
usage in 3 and 6 months. 
 
3.2 
Significance of Research 
 
Aerobika® OPEP device is an alternative non-pharmacological therapy to improve patient’s 
symptoms, quality of life, reduce exacerbation and hospitalization, thus will reduce cost of 
treatment in a long run. 
 

 
14 
CHAPTER 4 
RESEARCH METHODOLOGY 
 
4.1 
Type of Study 
 
This is a single center, prospective, interventional study of COPD patients who are under 
follow up of Respiratory Unit Universiti Kebangsaan Malaysia Medical Center (UKMMC). 
All patients involved in the study will be given Aerobika® OPEP on top of standard care of 
COPD. 
 
4.2  
Study Design 
 
4.2.1 Period of Study 
The study will be conducted from June 2021 to November 2022 after receiving approval by 
the research ethics committee. 
 
4.2.2 Study Setting 
The study will be conducted in the Respiratory Unit, Department of Internal Medicine of 
Universiti Kebangsaan Malaysia Medical Centre (UKMMC). 
 
4.2.3 Sampling Population 
This study will include patients diagnosed with COPD GOLD 2-4 attending the respiratory 
outpatient clinic UKMMC from June 2021 until November 2022. Demographic and clinical 
data will be collected. Patient will be followed-up at 3 and 6 months after intervention. 
 
4.2.4 Inclusion Criteria 
I. 
Age 40 years or older 
II. 
COPD diagnosed according to the GOLD guidelines: GOLD 2 - GOLD 4 
III. 
Stable COPD patients with mucus hyperproduction: coughed and brought up sputum 
“several days a week” (>2 days a week) or “almost every day” in the month prior to the 
study (25) 
IV. 
Patients who can perform IOS 
V. 
Patients who can perform spirometry 

 
15 
VI. 
Patients who can perform 6MWT 
VII. 
Patients with small air disease as measured by IOS (R5-R20 > 0.71 cmH2O/L/sec) 
 
4.2.5 Exclusion Criteria 
I. 
COPD diagnosed according to the GOLD guidelines: GOLD 1 
II. 
Diagnosis of other chronic lung diseases: Asthma, Asthma-COPD Overlap, Interstitial 
Lung Disease, Bronchiectasis, Lung Cancer 
III. 
Patients with contraindication for spirometry: recent cardiac complications, major 
surgery (36), severe advanced respiratory disease, or those with cognitively or 
neurologically impairment (37) 
IV. 
Patients not recommended for OPEP: neuromuscular weakness, recent facial, oral or 
skull surgery or trauma, recent oesophageal surgery, active haemoptysis, acute 
sinusitis, untreated pneumothorax, known or suspected tympanic membrane rupture or 
other middle ear pathology, overt right-sided heart failure (23) 
V. 
Patients with contraindication for 6MWT (Table 1) 
VI. 
Patient unable or unwilling to give informed consent 
VII. 
Change of inhaler during study period (will be dropped out from study) 
 
Table 1: Absolute and relative contraindications for field walking tests (38) 

 
16 
 
4.3  
Study Protocol and Data Acquisition 
 
This is a prospective interventional study conducted on COPD patients (GOLD 2-4) 
under the Respiratory Unit, Department of Internal Medicine in UKMMC, who qualified both 
the inclusion and exclusion criteria. Beforehand, all potential subjects will undergo screening 
and survey to exclude any possible symptoms of COVID-19 disease. All eligible patients will 
be briefed about this study. 
 
Subsequently, consent will be obtained from those who are agree to participate, either 
from the patient him/herself or their next-of-kin. The process of briefing and obtaining consent 
will be only done once the patient is stable. These processes will not in any way interfering 
with clinical evaluation, investigation, treatment and intervention done to the patient by the 
attending doctor. All of the consented patients will be given Aerobika® OPEP.  
 
Prior to the initiation of Aerobika® OPEP device, baseline of IOS parameters, 
symptoms (using CAT score), lung function (using spirometry-FEV1 and FVC), exercise 
capacity (using 6MWT) and exacerbation episodes of the past 6 months will be done and 
recorded in data collection sheet. All recruited patients will receive OPEP and trained to use 
for 10 minutes, 2 times per day (32). Patients also will be emphasized that standard care for 
COPD management will be continued. An adherence sheet will also be provided to patients at 
which they can put crosses when they use the device as advised. They are encouraged to use 
Aerobika® immediately after using their inhalers in order to increase adherence of treatment. 
 
Patients will be given phone call 2 days after they received Aerobika® as a reminder 
and also to ensure they are using it in a correct way. At week 12 and week 24 of Aerobika® 
OPEP usage, their IOS parameters, symptoms (using CAT score), lung function (using 
spirometry-FEV1 and FVC), exercise capacity (using 6MWT) and exacerbation episodes will 
be reassessed. During clinic visit also, his/her standard management for COPD will be checked 
to ensure no change in the inhaler regime. Within the study period of 6 months, patient will be 
given follow-up phone calls every two to three weeks to ensure their adherence toward 
Aerobika®. 
 

 
17 
The entire clinical information will be retrieved from the medical department clerking 
chart and electronic health care record system of the studied patients. The follow-up data will 
be retrieved from the digital and written patient records to identify the frequency of 
exacerbation and any hospitalization. In cases where follow-up data are incomplete or missing, 
the patient or his/her next-of-kin will be called to obtain information on their condition, hospital 
admission, clinical and functional status. 
 
4.4  
Operational Terms Definition 
 
4.4.1 Chronic Obstructive Pulmonary Disease (COPD) 
Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable disease 
that is characterized by persistent respiratory symptoms and airflow limitation that is due to 
airway and/or alveolar abnormalities usually caused by significant exposure to noxious 
particles or gases (3) 
 
4.4.2 COPD Exacerbation 
COPD exacerbation is defined as: 
I. Mild COPD exacerbation was defined as worsening of symptoms that were self-
managed (by measures such as an increase in salbutamol use) and resolved without 
systemic corticosteroids or antibiotics 
II. Moderate exacerbation if treated with systemic steroids and/or antibiotics 
III. A severe exacerbation if hospitalisation is required for treatment of exacerbation or 
admission to emergency > 24 hours (39) 
 
4.4.3 COPD Staging based on GOLD 
 
GOLD STAGE 
SEVERITY 
FEV1 
 
Stage 1 
Mild 
FEV1 > 80% predicted 
 
Stage 2 
Moderate 
50% ≤ FEV1 < 80% predicted 
 
Stage 3 
Severe 
30% ≤ FEV1 < 50% predicted 
 
Stage 4 
Very severe 
FEV1 < 30% predicted. 
 
Table 2: Classification of Airflow Limitation Severity (Based on Post-Bronchodilator FEV1)(3) 

 
18 
 
 
4.5   Sample Size 
 
According to Cohen’s d formula, Cohen suggested that effect size of 0.2, 0.5 and 0.8 
as small, medium and large effect size respectively. Effect sizes are the most important 
outcome at which the researchers want to know whether an intervention or experimental 
manipulation has an effect greater than zero, or (when it is obvious an effect exists) how big 
the effect is (40). In our study, we aim to have a medium effect size with the usage of Aerobika®. 
An effect size of 0.5 is described as medium and is 'large enough to be visible to the naked eye' 
(41).  
By using online statistical calculator apps; Sample Size Calculator for Comparing 
Paired Differences, this study would require a sample size of 34 to achieve a power of 80% 
and a level of significance of 5% for detecting an effect size of 0.5 paired differences (Dhand, 
N. K., & Khatkar, M. S. (2014). Statulator: An online statistical calculator. Sample Size 
Calculator for Comparing Two Paired Means. http://statulator.com/SampleSize/ss2PM.html. 
 
Additional of 40% samples is recruited to avoid subject consent withdrawal, drop out, 
or missing data. Therefore, a total of minimum 48 patients will be recruited for this study. 
However, we aim to recruit 60 patients as we were sponsored 60 units of Aerobika® OPEP.  
 
The outcomes of this study will be evaluated on all patients by comparing all the 
parameters during baseline and at 3- and 6-months follow-up after using Aerobika®. There 
will be no non-interventional arm as the sample size will become bigger. During the COVID-
19 pandemic era, we would like to reduce the exposure towards those performing respiratory 
tests. The other limitations as well with larger sample size are budget and time constraint. 
 

 
19 
4.6  
Data Collection Pathway 
 
 
Week 0 (1st clinic visit): 
• 
Demographic data collected. 
• 
Baseline IOS, CAT score, spirometry, 6MWT 
• 
Distribution and training of Aerobika® 
Regular follow-up phone calls 
every 2 to 3 weeks for 
reminders and to ensure 
adherence to Aerobika® 
No. of patients recruited (n) 
Day 2: Phone call to ensure adherence 
Week 12 (1st follow-up clinic) 
• 
Reassessment of IOS, CAT Score, spirometry, 
6MWT 
• 
Evaluation about exacerbation 
Week 24 (2nd follow-up clinic) 
• 
Reassessment of IOS, CAT Score, spirometry, 
6MWT 
• 
Evaluation about exacerbation 
Data Analysis 
Number of patients 
excluded and reason(s) for 
exclusion 
All potential patients will undergo survey and 
screening to exclude possible COVID-19 symptoms. 
Eligible patients in HCTM are screened and consent 
obtained 

 
20 
 
4.7  
Dummy Table 
 
 
Table 1: Baseline demographic date 
 
 
 
 
Variables 
Study 
population 
(n= _) 
Stage 2 
Stage 3 
Stage 4 
p-value 
Age (mean +/- SD) 
 
 
 
 
 
Gender       
                    Male 
                    Female 
 
 
 
 
 
Ethnicity     
                    Malay 
                    Chinese 
                    Indian 
                    Others 
 
 
 
 
 
BMI (kg/m2) 
 
 
 
 
 
COPD Duration 
 
 
 
 
 
Education     
                      Primary 
                   Secondary 
                      Tertiary 
 
 
 
 
 
Smoking status 
                     Yes 
                     No 
 
 
 
 
 
Comorbidities 
 
 
 
 
 
 

 
21 
Table 2: IOS, CAT score, Spirometry, 6MWT and Exacerbation at Week 0, 12 and 24 for 
each COPD stage 
 
COPD stages:               
Stage 2 
Stage 3 
Stage 4 
Week:                           
0 
12 
24 
0 
12 
24 
0 
12 
24 
CAT Score 
 
 
 
 
 
 
 
 
 
6MWT 
 
 
 
 
 
 
 
 
 
Exacerbation 
 
 
 
 
 
 
 
 
 
 
FEV1 (L predicted) 
FEV1 (%predicted) 
FEV1/FVC (%) 
FEF 25-75 (L 
predicted) 
FEF 25-75 (% 
predicted) 
R20 (cm/H2O/L/sec) 
R5 (cm/H2O/L/sec) 
R5-R20 
(cm/H2O/L/sec) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
22 
CHAPTER 5 
RESEARCH ETHICS 
 
Approval from the Research and Ethics Committee of Universiti Kebangsaan Malaysia 
Medical Centre (UKMMC) will be sought in order to commence the study. All the collected 
information will be strictly confidential and only accessible by the research team members. All 
patients will be kept anonymous and coded into the data collection sheet.  
 
Participants will only be recruited in this study if informed consent was given, and will 
be allowed to withdraw from the study at any point. The research will be conducted according 
to standard of good clinical practice and the rights and safety of the participants are guaranteed 
throughout the study. 
 
 
 

 
23 
CHAPTER 6 
FINANCIAL PLANS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Items 
 
 
Justification 
 
Quantity 
 
Total (RM) 
 
VOTE 27000: Research Items 
 
 
Microguard Bacterial 
Filter 
 
Single use for every patient’s 
test 
 
RM 19.50 x 180 pcs 
 
RM 3 510.00 
 
 
Disposable 
Mouthpieces 
 
 
Single use for every patient’s 
test 
 
RM 4.50 x 180 pcs 
 
 
RM 810.00 
 
 
 
 
Calibration Gas 
 
 
Gas is used for operational 
standard for IOS and 
spirometry. 
 
 
 
RM 4.50 x 180 pcs 
 
 
 
RM 3 200.00 
 
 
Total 
 
RM 7 520.00 
 
 
VOTE 29000: Professional Service (Perkhidmatan Ikhtisas) 
 
 
Honorarium for 
Respiratory 
Laboratory 
Technicians 
 
 
Incentives for the involved 
respiratory unit technician 
who have expertise in 
handling the machines 
 
 
 
RM 15 x 180 patients 
 
 
RM 2 700.00 
 
 
Total 
 
RM 2 700.00 
 
GRAND TOTAL 
 
RM 10 220.00 

 
24 
 
CHAPTER 7 
RESEARCH INFORMATION 
 
 
INFORMATION SHEET 
(In reference for next-of-kin) 
 
 
 
 
 
 
Research Title: 
Impact of Aerobika® Oscillating Positive Expiratory Pressure (OPEP) in Improving Small 
Airway Disease and COPD Assessment Test (CAT) Score in Chronic Obstructive Pulmonary 
Disease (COPD)  
 
Researcher’s Name:  
Associate Professor Dr Mohamed Faisal Abdul Hamid / Dr Siti Nurhanis binti Sahardin 
 
Place of Conduct:  
Respiratory Unit, Department of Internal Medicine, Universiti Kebangsaan Malaysia Medical 
Centre (UKMMC). 
 
Introduction: 
COPD is a progressive airway disease, at which patients will have mucus hypersecretion and 
progressive severity of airflow limitation that cause difficulty in breathing and reduce in quality 
of life. This disease is also characterized by a mixture of small airway disease and parenchymal 

 
25 
lung tissue destruction causing emphysema which affecting gas transfer. Prevalence of small 
airway disease in COPD is higher with more advanced COPD stages.  
 
Aerobika® OPEP is a device to help for improvement in small airway disease in COPD patients 
measured by impulse oscillometry (IOS). IOS is a simple test at which patient has to breath 
normally through a device without any extra effort. It can also help with symptoms and sputum 
clearance as well. On the other hand, Aerobika® can improve patient’s lung function test, 
exercise capacity, and at the same time help to reduce exacerbation rate which in long run can 
reduce hospitalization and treatment cost. With the use of Aerobika® OPEP device, patient 
can actively take part in the management of COPD at home. This device can be used on a daily 
basis in the comfort of your home, without any additional risk. 
 
Purpose of Study: 
This study aims to demonstrate that the usage of Aerobika® OPEP can help to improve small 
airway diseases and symptoms in COPD (GOLD 2-4) patients. Other than that, it can help to 
improve quality of life as well as reduce exacerbation rate of COPD. 
 
Type of Intervention:  
On top of your current standard care for COPD, you will be given Aerobika® OPEP device 
once consented for this study. During first visit, we will assess your symptoms and small 
airway disease parameters, as well as lung function test, 6 Minutes Walking Test (6MWT) and 
exacerbation episodes. Subsequently, we will see you in clinic after 12 and 24 weeks for follow 
up to reassess back all the parameters to compare for any improvement after Aerobika® OPEP 
usage.  
 
Benefits of joining in this study: 
• You can know your degree of small airway disease parameters, exercise capacity as 
well as severity of airway limitation and it will be monitored closely. 
• Your medications will be reviewed accordingly to ensure effective standard care of 
treatment 
• Your symptoms will be monitored by a standard clinical questionnaire.  
• You will be monitored closely by the same doctor throughout the study. 
  

 
26 
Risk of joining in this study: 
• There is no risk or added cost for using Aerobika® or IOS. 
 
Participation in this study is entirely voluntary. It is your choice to participate (or allow patient 
to participate). Regardless of your choice, the standard quality of care and treatment remain the 
same. All data obtained will be recorded and will be used for analysis. 
Confidentiality: 
Information collected during this study will be kept confidential. Access to the data is only by 
the researcher team and the Research Ethics Committee of UKMMC. No specific reference to 
any individual will be reported in this study. Participants have the right to know the outcome 
of this study.  
 
Reimbursements: 
Participants do not have to pay for the lung function test, nor be paid for participating in this 
study. 
 
Right to Refuse or Withdraw: 
This study is of voluntary basis, patient or his/her next-of-kin have the right to withdraw from 
this study at any time of the study. The choice is yours and all your right will be respected. 
 
Who to contact: 
1) Dr Siti Nurhanis binti Sahardin (+60133086481). 
Respiratory Unit, Department of Internal Medicine, University Kebangsaan Malaysia 
Medical Centre, UKMMC. 
 
2) Associate Professor Dr Mohamed Faisal Abdul Hamid (+60391456108). 
Respiratory Unit, Department of Internal Medicine, University Kebangsaan Malaysia 
Medical Centre, UKMMC. 
 
 

27 
Figure: Aerobika® OPEP 

32 
CHAPTER 8 
INFORMED CONSENT FORM 
Research Title: 
Impact of Aerobika® Oscillating Positive Expiratory Pressure (OPEP) in Improving Small 
Airway Disease and COPD Assessment Test (CAT) Score in Chronic Obstructive Pulmonary 
Disease (COPD)  
Researcher’s Name:  
Associate Professor Dr Mohamed Faisal Abdul Hamid / Dr Siti Nurhanis binti Sahardin 
I, ………………………………………………………, IC No: …...…………………............., 
•
Have read all the information in the Patient Information Sheet and understand the aim
and purpose of this study.
•
Have been given enough time to think about it and all of my question have been
answered to my satisfaction.
•
Understand that I may freely choose to withdraw from this study at any time without
reason and without repercussions.
•
Understand that anonymity will be ensured in the final write up.
I understand all the above and voluntarily agree to take part in this research study, to follow 
the study procedures and to provide the necessary information as requested. 
………………………………….……..… 
 ……….......……………………………………. 
Signature/Thumbprint 
  Date 
………………………………….………..  
 ………....……………………………………… 
Witness Signature 
  Researcher Signature 
…………………………………………... 
  Siti Nurhanis binti Sahardin (880504-01-5504) 
Witness Name /IC no 
  Researcher Name/ IC no 
…………………………………………... 
 ………………………………………………… 
Date 
  Date 

34 
CHAPTER 9 
DATA COLLECTION SHEET 
Name.  
  : ………………………………………………………………..… 
Contact Number: ……………………………………………….……. 
Age 
  : …………………………………………………….. 
Gender 
  : …………………………………….………………. 
Ethnicity 
  : ……………………………………………….……. 
Background Medical Problem: 
•
Diabetes Mellitus
•
Hypertension
•
Ischaemic heart Disease
•
Heart Failure
•
Previous stroke
•
Dyslipidaemia
•
Others:
…………………………………………………………………………………………
…………………………………………………………………………………………. 
PATIENT’S STICKER 

 
35 
 
Weight: ………………….    Height: ……………………….   BMI: ……………………… 
 
First diagnosis of COPD: …………. MMRC Class: ………………. COPD stage: ……… 
 
Number of exacerbations in the past 6 months : …………………………..……….………  
 
Current COPD inhalers: …………………………………………..………………………..  
 
Inhaler technique: …………………………… 
 
Week:                          
0 
12 
24 
CAT Score 
 
 
 
6MWT 
 
 
 
Exacerbation 
 
 
 
 
FEV1 (L predicted) 
FEV1 (%predicted) 
FEV1/FVC (%) 
FEF 25-75 (L 
predicted) 
FEF 25-75 (% 
predicted) 
R20 (cm/H2O/L/sec) 
R5 (cm/H2O/L/sec) 
R5-R20 
(cm/H2O/L/sec) 
 
 
 
 
 
 
 
 
 
 

 
36 
CHAPTER 10 
GANTT CHART 
 
 
 
November 
2020-
January 
2021 
January 
2021 
January 
2021- June 
2021 
June 2021-
November  
2022 
November
2022-
January 
2023 
January 
2023-April 
2023 
April 
2023-May 
2023 
Literature 
review 
 
 
 
 
 
 
 
Proposal 
correction, 
submission 
and 
presentation 
 
 
 
 
 
 
 
Ethics 
Committee 
Approval 
 
 
 
 
 
 
 
Recruitment 
of study 
subjects 
 
 
 
 
 
 
 
Data entry 
and analysis 
 
 
 
 
 
 
 
Writing 
report and 
thesis 
submission 
 
 
 
 
 
 
 
Thesis 
presentation 
 
 
 
 
 
 
 

 
37 
CHAPTER 11 
APPENDICES 
 
Appendix A: 
Modified Medical Research Council (MMRC) Questionnaire for Categorizing COPD Severity. 
 
 
Severity 
Score 
Level of Breathlessness 
 
None 
0 
Only breathlessness with strenuous exercise 
 
Mild 
1 
Shortness of breath hurrying or walking up a slight 
hill 
 
Moderate 
2 
Walks slower than age group or has to stop for breath 
when walking on level ground at own pace 
 
Severe 
3 
Stops for breath after walking 100 meters or a few 
minutes on level ground 
 
Very severe 
4 
Breathless when dressing/undressing or too breathless 
to leave the house 
 
 
 
 
 
 
 
 

 
38 
Appendix B: 
UKMMC Medical COVID-19 Assessment Form 
 
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HOSPITAL CAASELOR TIJANJ<U MUHRIZ 
MEDICAL CQVID-19 ASSESSMENT FORM 
DATE 
""'--------------
IC NUMBER ___________ 
_ 
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RISK EXPOSUR_E _ 
CONTENT_-==-=---
1 Travefio or residence m known high nsk area 'Mthin the last ---
JJ ja~-- ---------~ 
2 Close contact with a pneumonia case of unknown cause 
linked to COV1D 19 duster within 14 days bef0<e onsel of 
illness 
3Contact with covio pa\Jents/PUI/Ouarantine 1ndivldual/ 
Tabl9b,~nskciuster 
___ 
_ 
CLINICAL SIGN AND SYMPTOMS 
,__ 
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2 Sore lhroa~t ____ 
_ 
_\ ___ _ 
~l!9h 1mostly dry) 
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_ 
Signatura ______ 
_ 
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M$1SOI001 :201S 
c..iMo .. Ot,t$~1k7 
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39 
Appendix C: 
COPD Assessment Test (CAT) Score 
 
 
 
The CAT is available and free to use globally (no charges will be associated with its use) in 
the situations described in the terms of use on the CAT website (42). 

 
40 
Appendix D: 
6 Minutes Walking Test (6MWT) 
 
 
 
 
-·~-.~.,g··-.( 
f1:~--~r-
. .. . 
. 
. 
UNIT RESPIRATORI 
MAKMAL PEMERIKSAAN KLINIKAL 
JABATAN PERUBATAN 
PUSAT PERUBATAN UKM 
03-91455555 eltt: 5581/6108 
6 MINUTES WALKING TEST REPORT 
A. DEMOGR..!\PHJC DATA 
Patient name: ________ _ 
Age 
: _____ years old 
Patient ID 
Hefght: 
cm 
Gender 
:MOFO. 
Weight: 
leg 
8. BORG SCALE 
L lf(!f.1_~~~~--=f_:;.:- : ... ~~~.r.i;'~l,fm:;~;.:·:;. 
i 
0 
I 
Nothing al all 
' 
0.5 
I 
~ramQly \veak 
. 
1 
I 
Very week 
; 
2 
Weak (liglli) 
3 
Moderate 
; 
4 
Somewhal Strong 
5 
srrong (Heavy) 
' 
6 
I 
7 
I 
VerySlrong 
: 
8 
9 
10 
I 
Extremely Strong 
. 
l 
Maximal 
' 
C.TEST 
! 
Parameter 
Start of test 
End oftest 
l Fatigue 
(Borg scale) 
I 
' 
I Dyspnea 
{Borg scale) 
I 
11 S?02 \ % } 
I : Pulse rate ( % ) 
j · Blood Pressure 
D. RESULT 
Stopped or paused before 6 minutes? No D Yes O , reason: _____ _ 
Number of laps: ___ (6 meters) 
Total distance walked in 6 minutes: ___ meters 
E. TECHNICIAN COMMENT 
Name: 
Sign 
Date 
---------

 
41 
Appendix E: 
Adherence Sheet 
 
Name/Nama: ………………………………………………….   MRN: ……………………… 
Year/Tahun: ………………………………..  
 
      Month/Bulan: ……………… 
 
Please put cross (X) if you have used your Aerobika® for 10 minutes 
Sila tandakan pangkah (X) bila anda sudah menggunakan Aerobika® selama 10 minit 
 
Date 
8am 
4pm 
 
Date 
8am 
4pm 
1 
 
 
 
17 
 
 
2 
 
 
 
18 
 
 
3 
 
 
 
19 
 
 
4 
 
 
 
20 
 
 
5 
 
 
 
21 
 
 
6 
 
 
 
22 
 
 
7 
 
 
 
23 
 
 
8 
 
 
 
24 
 
 
9 
 
 
 
25 
 
 
10 
 
 
 
26 
 
 
11 
 
 
 
27 
 
 
12 
 
 
 
28 
 
 
13 
 
 
 
29 
 
 
14 
 
 
 
30 
 
 
15 
 
 
 
31 
 
 
16 
 
 
 
 
 
 
 

 
45 
 
CHAPTER 12 
REFERENCES 
 
1. 
Hogg JC, Chu F, Utokaparch S, Woods R, Elliott WM, Buzatu L, et al. The nature of 
small-airway obstruction in chronic obstructive pulmonary disease. N Engl J Med. 
2004;350(26):2645-53. 
2. 
Khoudigian-Sinani S, Kowal S, Suggett JA, Coppolo DP. Cost-effectiveness of the 
Aerobika* oscillating positive expiratory pressure device in the management of COPD 
exacerbations. Int J Chron Obstruct Pulmon Dis. 2017;12:3065-73. 
3. 
GOLD Global Strategy for the Diagnosis, Management, and Prevention of Chronic 
Obstructive Pulmonary Disease (2020 Report). 
4. 
Ko FW, Chan KP, Hui DS, Goddard JR, Shaw JG, Reid DW, et al. Acute exacerbation 
of COPD. Respirology. 2016;21(7):1152-65. 
5. 
Ur Rehman A, Hassali MAA, Muhammad SA, Shakeel S, Chin OS, Ali I, et al. 
Economic Burden of Chronic Obstructive Pulmonary Disease Patients in Malaysia: A 
Longitudinal Study. Pharmacoecon Open. 2020. 
6. 
COPD prevalence in 12 Asia-Pacific countries and regions: projections based on the 
COPD prevalence estimation model. Respirology. 2003;8(2):192-8. 
7. 
Ho T, Cusack RP, Chaudhary N, Satia I, Kurmi OP. Under- and over-diagnosis of 
COPD: a global perspective. Breathe (Sheff). 2019;15(1):24-35. 
8. 
Rabe KF, Watz H. Chronic obstructive pulmonary disease. The Lancet. 
2017;389(10082):1931-40. 
9. 
Malaysia Ministry of Health. National Health Morbidity Survey III. Institute of Public 
Health, Malaysia; 2006. 
10. 
van den Berge M, Ten Hacken NHT, Cohen J, Douma WR, Postma DS. Small airway 
disease in asthma and COPD: clinical implications. Chest. 2011;139(2):412-23. 
11. 
Stewart JI, Criner GJ. The small airways in chronic obstructive pulmonary disease: 
pathology and effects on disease progression and survival. Curr Opin Pulm Med. 
2013;19(2):109-15. 
12. 
Leitao Filho FS, Hang Chen H, Ngan DA, Tam A, Kirby M, Sin DD. Current methods 
to diagnose small airway disease in patients with COPD. Expert Rev Respir Med. 
2016;10(4):417-29. 

 
46 
13. 
Crisafulli E, Pisi R, Aiello M, Vigna M, Tzani P, Torres A, et al. Prevalence of Small-
Airway Dysfunction among COPD Patients with Different GOLD Stages and Its Role in the 
Impact of Disease. Respiration. 2017;93(1):32-41. 
14. 
Kwon DS, Choi YJ, Kim TH, Byun MK, Cho JH, Kim HJ, et al. FEF25-75% Values 
in Patients with Normal Lung Function Can Predict the Development of Chronic Obstructive 
Pulmonary Disease. Int J Chron Obstruct Pulmon Dis. 2020;15:2913-21. 
15. 
Bickel S, Popler J, Lesnick B, Eid N. Impulse oscillometry: interpretation and practical 
applications. Chest. 2014;146(3):841-7. 
16. 
Piorunek T, Kostrzewska M, Stelmach-Mardas M, Mardas M, Michalak S, Gozdzik-
Spychalska J, et al. Small Airway Obstruction in Chronic Obstructive Pulmonary Disease: 
Potential Parameters for Early Detection. Adv Exp Med Biol. 2017;980:75-82. 
17. 
Brashier B, Salvi S. Measuring lung function using sound waves: role of the forced 
oscillation technique and impulse oscillometry system. Breathe. 2015;11(1):57-65. 
18. 
Su ZQ, Guan WJ, Li SY, Ding M, Chen Y, Jiang M, et al. Significances of spirometry 
and impulse oscillometry for detecting small airway disorders assessed with endobronchial 
optical coherence tomography in COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:3031-44. 
19. 
Lipworth BJ, Jabbal S. What can we learn about COPD from impulse oscillometry? 
Respir Med. 2018;139:106-9. 
20. 
Crim C, Celli B, Edwards LD, Wouters E, Coxson HO, Tal-Singer R, et al. Respiratory 
system impedance with impulse oscillometry in healthy and COPD subjects: ECLIPSE 
baseline results. Respir Med. 2011;105(7):1069-78. 
21. 
Rugbjerg M, Iepsen UW, Jorgensen KJ, Lange P. Effectiveness of pulmonary 
rehabilitation in COPD with mild symptoms: a systematic review with meta-analyses. Int J 
Chron Obstruct Pulmon Dis. 2015;10:791-801. 
22. 
Ni Y, Ding L, Yu Y, Dai R, Chen H, Shi G. Oscillatory positive expiratory pressure 
treatment in lower respiratory tract infection. Exp Ther Med. 2018;16(4):3241-8. 
23. 
Bourbeau J, McIvor RA, Devlin HM, Kaplan A. Oscillating positive expiratory 
pressure (OPEP) device therapy in Canadian respiratory disease management: Review, care 
gaps and suggestion for use. Canadian Journal of Respiratory, Critical Care, and Sleep 
Medicine. 2019;3(4):233-40. 
24. 
Thanh NX, Jacobs P, Suggett J, McIvor A, Kaplan A. Cost-Effectiveness of the 
Aerobika(R) Oscillating Positive Expiratory Pressure Device in the Management of Chronic 
Obstructive Pulmonary Disease Exacerbations in Canada. Can Respir J. 2019;2019:9176504. 

 
47 
25. 
Svenningsen S, Paulin GA, Sheikh K, Guo F, Hasany A, Kirby M, et al. Oscillatory 
Positive Expiratory Pressure in Chronic Obstructive Pulmonary Disease. COPD. 
2016;13(1):66-74. 
26. 
Tse J, Wada K, Wang Y, Coppolo D, Kushnarev V, Suggett J. Impact of Oscillating 
Positive Expiratory Pressure Device Use on Post-Discharge Hospitalizations: A Retrospective 
Cohort Study Comparing Patients with COPD or Chronic Bronchitis Using the Aerobika((R)) 
and Acapella((R)) Devices. Int J Chron Obstruct Pulmon Dis. 2020;15:2527-38. 
27. 
Barker R, Laverty AA, Hopkinson NS. Adjuncts for sputum clearance in COPD: 
clinical consensus versus actual use. BMJ Open Respir Res. 2017;4(1):e000226. 
28. 
Stockley RA. COPD10: Birmingham,United Kingdom, July 2016. Chronic Obstr Pulm 
Dis. 2017;4(3):225-46. 
29. 
Jones PW. St. George's Respiratory Questionnaire: MCID. COPD. 2005;2(1):75-9. 
30. 
Kon SSC, Canavan JL, Jones SE, Nolan CM, Clark AL, Dickson MJ, et al. Minimum 
clinically important difference for the COPD Assessment Test: a prospective analysis. The 
Lancet Respiratory Medicine. 2014;2(3):195-203. 
31. 
Nicolini A, Mascardi V, Grecchi B, Ferrari-Bravo M, Banfi P, Barlascini C. 
Comparison of effectiveness of temporary positive expiratory pressure versus oscillatory 
positive expiratory pressure in severe COPD patients. Clin Respir J. 2018;12(3):1274-82. 
32. 
Alghamdi SM, Barker RE, Alsulayyim ASS, Alasmari AM, Banya WAS, Polkey MI, 
et al. Use of oscillatory positive expiratory pressure (OPEP) devices to augment sputum 
clearance in COPD: a systematic review and meta-analysis. Thorax. 2020;75(10):855-63. 
33. 
Khakban A, Sin DD, FitzGerald JM, McManus BM, Ng R, Hollander Z, et al. The 
Projected Epidemic of Chronic Obstructive Pulmonary Disease Hospitalizations over the Next 
15 Years. A Population-based Perspective. Am J Respir Crit Care Med. 2017;195(3):287-91. 
34. 
Burudpakdee C, Seetasith A, Dunne P, Kauffman G, Carlin B, Coppolo D, et al. A 
Real-World Study of 30-Day Exacerbation Outcomes in Chronic Obstructive Pulmonary 
Disease (COPD) Patients Managed with Aerobika OPEP. Pulmonary Therapy. 2017;3(1):163-
71. 
35. 
Burudpakdee C, Near AM, Huang H, Coppolo D, Kushnarev V, Suggett J. A Real-
World Evidence Study Assessing the Impact of Adding the Aerobika Oscillating Positive 
Expiratory Pressure Device to Standard of Care Upon Healthcare Resource Utilization and 
Costs in Post-Operative Patients. Pulm Ther. 2018;4(1):87-101. 
36. 
Tiller NB, Simpson AJ. Effect of spirometry on intra-thoracic pressures. BMC Res 
Notes. 2018;11(1):110. 

 
48 
37. 
Sharshar RS, Mohamed AS. The utility of impulse oscillometry in asthma: A 
comparison of spirometry versus impulse oscillometry system. Egyptian Journal of Chest 
Diseases and Tuberculosis. 2017;66(2):207-9. 
38. 
Holland AE, Spruit MA, Singh SJ. How to carry out a field walking test in chronic 
respiratory disease. Breathe (Sheff). 2015;11(2):128-39. 
39. 
Sato M, Chubachi S, Sasaki M, Haraguchi M, Kameyama N, Tsutsumi A, et al. Impact 
of mild exacerbation on COPD symptoms in a Japanese cohort. Int J Chron Obstruct Pulmon 
Dis. 2016;11:1269-78. 
40. 
Lakens D. Calculating and reporting effect sizes to facilitate cumulative science: a 
practical primer for t-tests and ANOVAs. Front Psychol. 2013;4:863. 
41. 
Sullivan GM, Feinn R. Using Effect Size-or Why the P Value Is Not Enough. J Grad 
Med Educ. 2012;4(3):279-82. 
42. 
COPD Assessment Test: Healthcare Professional User Guide 
Expert guidance on frequently asked questions. (Issue 4: November 2018).