Enhanced COPD Management in Suspected Lung Cancer Patients - Improving Outcomes Through Timely Intervention
Phase: NA
Conditions: COPD (Chronic Obstructive Pulmonary Disease), Lung Cancer (Diagnosis), Lung Neoplasm Malignant, Lung Carcinoma, Pulmonary Neoplasms, Pulmonary Neoplasm, Pulmonary Cancers, Pulmonary Cancer, Pulmonary Carcinoma, COPD, COPD - Chronic Obstructive Pulmonary Disease, Airflow Obstruction, Chronic
Sponsor: Ditte Krag-Hansen

 
Enhanced COPD Management in 
Suspected Lung Cancer Patients - 
Improving Outcomes Through timely 
Intervention 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PhD student: 
Ditte Krag-Hansen, MD 
 
Principal supervisor: 
Morten Hornemann Borg, MD, PhD, Associate Professor, Chief consultant 
 
Co-supervisors: 
Anders Løkke, MD, PhD, Professor, Consultant 
Ingeborg Farver-Vestergaard, PsyD, PhD, Associate Professor
 
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1 

 
Study overview 
Identifying and treating COPD in patients undergoing lung cancer evaluation is crucial. Early 
intervention could lead to better management of both diseases, improving health status, reducing 
healthcare costs, and potentially increasing survival rates.  
 
This study aims to assess the impact of early diagnosis and optimal treatment of COPD on clinical 
outcomes in patients under evaluation for lung cancer. The study will combine information through 
an open-label RCT at the Lung Cancer Investigation Unit at Lillebaelt Hospital Vejle. 
 
The findings could inform clinical practice by emphasizing the importance of integrated care 
approaches for patients with coexisting COPD and lung cancer, ultimately leading to better health 
outcomes. 
 
Introduction 
Chronic Obstructive Pulmonary Disease (COPD) and lung cancer frequently coexist due to shared 
risk factors, most notably smoking, which is the leading cause of both conditions [1]. COPD, 
characterized by persistent airflow limitation and chronic inflammation of the airways [2, 3], is a 
major contributor to morbidity and mortality worldwide [4]. Similarly, lung cancer is one of the 
most common and deadliest cancers [5], with a significant overlap in the patient populations 
affected by COPD [6]. Studies suggest that individuals with COPD are at an increased risk of 
developing lung cancer [6], with rates estimated to be four to six times higher than in the general 
population [7]. This overlap is not merely coincidental but is thought to be influenced by chronic 
inflammation, oxidative stress, and impaired immune responses in the lungs of patients with 
COPD, which can promote carcinogenesis [6]. 
 
Despite the frequent coexistence of COPD and lung cancer [1, 6], patients are usually not 
investigated for COPD as usual care, therefore, COPD often remains underdiagnosed or is 
diagnosed late [8], particularly in patients being evaluated for lung cancer [9, 10]. Delayed 
diagnosis and untreated COPD can negatively affect a patient’s overall prognosis, complicating the 
management of lung cancer [10, 11]. At the same time, some patients with COPD are incorrectly 
diagnosed [12] and suboptimal treated [12, 13, 14] resulting in progressive deterioration of health 
status [15, 16]. Deterioration of health status including lung function is contributed by 
comorbidities in patients with COPD especially cardiovascular diseases [17, 18].   
Overall, patients with COPD tend to have poorer tolerance to lung cancer treatments, including 
surgery, chemotherapy, and radiotherapy, due to compromised lung function [6]. In contrast, early 
detection and optimal management of COPD, including pharmacotherapy, smoking cessation, and 
pulmonary rehabilitation, may improve lung function [19, 20], enhance treatment tolerance, and 
reduce complications during cancer therapy [6, 19, 20].  
 
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Given the high prevalence of both COPD and lung cancer in individuals with a history of smoking, 
identifying and treating COPD in patients undergoing lung cancer evaluation is crucial. Early 
intervention could lead to better management of both diseases, improving health status, reducing 
healthcare costs, and potentially increasing survival rates. This study aims to assess the impact of 
early diagnosis and optimal treatment of COPD on clinical outcomes in patients under evaluation 
for lung cancer. Specifically, it will explore how timely COPD management affects cancer treatment 
tolerability, postoperative recovery, hospitalization rates, and overall survival in this high-risk 
population. The findings could inform clinical practice by emphasizing the importance of integrated 
care approaches for patients with coexisting COPD and lung cancer, ultimately leading to better 
health outcomes.  
 
Aim and objectives 
To assess the impact of early COPD diagnosis and optimal treatment on health status outcomes in 
patients undergoing lung cancer work-up and to evaluate the effect of early COPD diagnosis and 
optimal treatment on COPD-related health status in patients undergoing lung cancer work-up. 
Design and methods 
Effect of optimised COPD treatment alongside lung cancer workup: a randomized open-label trial 
 
Aim 
To evaluate the impact of tailored COPD consultations and optimised treatment on health status 
outcomes in patients undergoing evaluation for suspected lung cancer who also present with 
COPD.  
 
Trial design 
The study is a randomized, controlled, open label trial. Patients referred for diagnostic evaluation 
of suspected lung cancer, who exhibit obstructive airflow limitation, defined as FEV₁/FVC < 75 % or 
FEV₁ < 80 % on pulmonary function testing, will get redirected to participate in the trial alongside 
the lung cancer investigation. The participants who meet the criteria for COPD [21] will be 
randomized to receive either tailored COPD consultations alongside their lung cancer investigation 
or usual care (lung cancer investigation only) with an equal allocation ratio 1:1 using a 
computer-generated table of random numbers in REDcap. The study protocol is reported in 
accordance with SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) [22]. 
 
Setting 
The RCT will be conducted at the Lung Cancer Investigation Unit, Lillebaelt Hospital Vejle, which 
evaluates approximately 1,000 patients for suspected lung cancer and diagnoses approximately 
500 lung cancer cases each year. All patients referred for suspected lung cancer undergo routine 
spirometry. Patients diagnosed with lung cancer are referred for thoracic surgery at the 
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Department of Thoracic Surgery, Odense University Hospital, or for oncological treatment at the 
Department of Oncology, Lillebaelt Hospital Vejle. If lung cancer is ruled out, patients are either 
discharged or followed up with CT imaging as appropriate. 
 
Inclusion criteria 
●​ Age ≥ 18 years 
●​ Undergoing diagnostic evaluation for suspected lung cancer 
●​ Spirometry showing obstructive airflow limitation  (FEV₁/FVC < 75 %, FEV₁ < 80 % and no 
reversibility) at the first outpatient visit at the lung cancer evaluation 
 
Exclusion Criteria 
●​ Presence of significant comorbidities that may interfere with diagnostic procedures or 
spirometry  
●​ Pregnant or breastfeeding women. 
 
Intervention 
Eligible patients will be randomized 1:1 to either the intervention group or usual care (Figure 1). 
Participants in both arms will undergo standard diagnostic evaluation for suspected lung cancer in 
timely manner. In the intervention group, patients will additionally receive tailored COPD 
consultations at the COPD clinic of Lillebaelt Hospital Vejle during diagnostic work-up. These 
consultations will include assessment and treatment according to GOLD guidelines [21], including: 
●​ Pharmacological management 
●​ Smoking cessation support 
●​ Referral to pulmonary rehabilitation as appropriate  
●​ Referral for nutritional assessment and optimization when appropriate 
●​ Referral to cardiovascular evaluation when appropriate 
●​ Referral to sleep apnea evaluation when appropriate 
 
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Figure 1: Participant flow chart 
 
Data collection 
An overview of the data collection for this study can be found in Table 1. The primary outcome is 
the change in COPD Assessment Test (CAT score) over 6 months. CAT consists of a questionnaire 
with eight items with the possibility of scoring 0-40 on respiratory symptoms. Participants will be 
tested at baseline, and after a follow-up period of 3 and 6 months after enrollment of the study. 
The baseline visit and the 6 months follow-up will be a physical meeting whereas the 3 months 
follow-up will be a conversation through a phone call conducted by the PhD-student.  
 
The participants will be asked about new medication, the results of the lung cancer evaluation of 
treatment plans along with disease-related information. The information will be checked through 
the participant’s electronic medical journal if access at the baseline visit is granted. This 
information is important to further and better clarify COPD consultations effect on disease-related 
outcomes. Secondary outcomes will be disease-related information, change in BMI, change in 1 
min sit-to-stand test, the proKOL questionnaire, the HADS questionnaire and smoking cessation 
rates. Covariates include the participants characteristics (e.g. sex, age, risk factors, comorbidity).   
 
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5 
 
T1, baseline visit in 
lung cancer 
investigation unit 
T2, 3 months’ 
follow-up 
T3, 6 months’ 
follow-up 
Sociodemographic 
info 
X 
 
 
Body Mass Index 
(BMI) 
X 
 
X 

 
Tabel 1: Chart of data collection 
 
Sample size calculation 
The sample size calculation is based on the CAT score, aiming to detect a difference of 3 based on a 
standard deviation (SD) of 7.7, with a power of 80% and a significance level of 5%. The SD is 
calculated from a similar previous Danish study optimizing COPD treatment in patients with lung- 
or head and neck cancer [27]. Accounting for a 25% dropout rate, the sample size is calculated to 
be 280 participants. The estimated lung cancer rate of 50 % is not taken into account when 
calculating the sample size because lung cancer will be presented as subgroup analysis. 
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Spirometry and 
reversibility testing 
X 
 
 
Smoking history and 
status 
X 
X 
X 
ProKOL [23] to clarify 
treatment and 
rehabilitation needs 
(includes CAT [24]) 
X 
X 
X 
1 min sit-to-stand test 
[25] 
X 
 
X 
Disease-related 
information 
(exacerbations, 
mortality, 
hospitalisations, 
cancer treatment 
tolerability, 
postoperative 
recovery, overall 
survival) 
X 
X 
X 
Hospital Anxiety and 
Depression Scale 
(HADS) [26] 
X 
X 
X 
Cardiovascular 
investigation 
(coronary calcium 
scan) 
X 
 
 
Sleep apnea 
investigation 
X 
 
 

 
Statistical Analysis 
Patients will be categorized based on their assignment to either the usual care group or the 
intervention group. The randomisation will be stratified to ensure equal distribution of known or 
unknown COPD and the median of baseline CAT score. The median of baseline CAT score is 
perceived to be 12.7, found from similar studies [27, 28, 29, 30, 31, 32, 33, 34]. The randomisation 
group will be distributed in three strata according to the CAT score as mild (0-9), moderate (10-20) 
or high (21-40) symptom burden.  
 
Every participant in the intervention group will receive tailored COPD consultations by the 
PhD-student minimizing significant variation between the interventions. Baseline characteristics 
will be analyzed descriptively. In case of significant differences between the study groups on key 
characteristics, multivariate analyses will be performed adjusting for potential confounders such as 
sex, age and smoking status [27, 32]. Primary and secondary outcomes will be evaluated using 
appropriate statistical tests, including ANCOVA. The primary outcome is a CAT score difference 
from baseline to the 6 months’ follow-up for the intervention group compared to the control 
group. If the 6 months’ data is missing due to death, the 3 months’ data will be used to calculate a 
surrogate for the CAT score. As a secondary analysis, the test will be performed without the 
missing data. A sensitivity analysis will be performed on the difference of the two analysis 
methods. Subgroup analyses will be performed to explore differences in intervention effects 
among patients with known COPD and patients with newly diagnosed COPD. Additionally, 
subgroup analyses and adjusted analyses will be performed to account for the potential effects of 
lung cancer diagnosis on study outcomes as well as kaplan-meier analysis. All the statistics will be 
performed using Stata.  
 
Ethical Considerations 
The study protocol was approved by The Health Research Ethics Committee 2, Region of Southern 
Denmark (Project-ID S-20250091). The study will adhere to the Declaration of Helsinki [35].  
 
The eligible patients are recruited at the day of their first visit in the Lung Cancer Investigation 
Unit, Lillebaelt Hospital Vejle, after the usual consultation by a doctor and a nurse including lung 
function testing. Identification focuses on patients who may have diagnosed or potential COPD and 
are obtained by the clinical nurse who has performed the lung function testing. Initial contact are 
conducted by the PhD-student who are located at the Lung Cancer Investigation Unit. At this stage, 
the patient is briefly informed about the study, including its purpose to investigate the impact of 
early diagnosis and optimal treatment of COPD on clinical outcomes in patients undergoing lung 
cancer evaluation. Patients are asked whether they are interested in receiving further information 
about participation. Before consent is obtained, the PhD-student will perform thorough oral and 
written information in a consultation room in the Lung Cancer Investigation Unit. The information 
is given in a private and undisturbed setting to ensure confidentiality and allow sufficient time for 
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discussion. The patients are allowed to bring along their desired companions when the information 
is given. It is ensured that the information interview takes place without interruptions by 
conducting the conversation in a closed room and allocating adequate time for questions and 
reflection. Patients are encouraged to ask questions involving the companion if they wish. The oral 
and written information includes a description of the study design, as well as the potential benefits 
and risks associated with early COPD diagnosis and treatment, participant rights, and data handling 
procedures. Informed consent is obtained after the patient has confirmed their willingness to 
participate in the same setting as the first visit at the Lung Cancer Investigation Unit. The patients 
will provide written and informed consent prior to inclusion obtained by the PhD-student and 
receive usual care independent of the allocated group.  
 
The consent will include permission to collect  questionnaire content and allowance to store data 
from the study as described above. The consent allows the PhD-student, the sponsor and the 
sponsor’s representatives as well as any supervisory authority, direct access to obtain information 
from the patient’s medical records, etc., including electronic medical records, for the purpose of 
reviewing information about the trial subject’s health status that is necessary for the conduct of 
the research project, as well as for control purposes, including self-monitoring, quality control, and 
monitoring, which they are obliged to carry out. It is always possible to withdraw consent. 
 
The collection and storage of personal data will comply with the Data Protection Act and the 
GDPR. The results of the project will be treated confidentially. The results will be stored on a 
secure server controlled by the Region of Southern Denmark. The results will only be disclosed in 
pseudonymised (de-identified) form, where neither your name, date of birth, address, nor the like 
will be disclosed. The results from the project will be published in an anonymous form.  
 
This study's risk of harm are considered as time used by the patient to participate in the study, use 
of mental capacity in an already difficult situation and side-effects to the medical inhalators or 
medication for smoking cessation. The study will not introduce trial based medication, medical 
procedures or additional blood tests to the participants. The participants are informed to contact 
the PhD-student if any side-effects to the new medication appear. At the follow-up visits, the 
participants will be asked about side-effects and any inconvenience regarding the study 
participation. The second follow-up visit is physical, meaning a minor inconvenience for the 
participants. It is possible to schedule the second follow-up visit with the PhD-student at the same 
time as other visits to the hospital. Overall, the study is assessed to carry low risk, which is 
proportionate to the anticipated benefits in terms of improved disease understanding, better 
management, and potentially improved health outcomes and prognosis for participants. If any 
serious adverse events happens, the study will not proceed without a thorough investigation 
including a risk/benefit analysis.   
 
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Every patient will receive usual care regarding lung cancer evaluation. A possible cancer diagnosis 
or treatment will not be delayed by the intervention. The intervention will be a thorough 
evaluation to find the right parts of intervention for the individual. Therefore, the study trial 
appears as a quality improvement of usual care. The patients are entitled to compensation due to 
injuries from healthcare treatments or side effects to drugs due to the Danish Patient 
Compensation. 
Dissemination of Results 
The project protocol and conclusions of any kind will be published by www.clinicaltrials.gov. It 
must be stated that positive, negative, as well as inconclusive results will be published. Our 
strategy for dissemination of the results involves three levels:  
 
1) Local: The project group will inform local collaborators about the study and present the progress 
and preliminary results at local department- and interdisciplinary meetings. If the study shows 
positive results it may continue in clinical practice at the Lung Cancer Investigation Unit at 
Lillebaelt Hospital Vejle. 
 
2) National: The project group will present the study protocol and the results at national meetings 
of relevant scientific societies and, at meetings for relevant patient organizations and in 
mainstream media for the broad public.  
 
3) International: The project group aims to present the results at meetings in international 
scientific societies and at international conferences. Results will be published in peer-reviewed 
journals. Participants will receive a summary of the study findings. 
 
Impact 
This study aims to improve outcomes for patients with both COPD and lung cancer by focusing on 
early COPD diagnosis and treatment during lung cancer evaluation. The frequent coexistence of 
these conditions, driven by shared risk factors, most notably smoking, often results in late COPD 
diagnosis, complicating cancer treatment. Early intervention could improve lung function, enhance 
cancer treatment tolerance, reduce hospitalizations, and potentially increase survival. 
 
By addressing this gap, the study may lead to integrated care approaches that improve health 
status and reduce healthcare costs. Findings could inform clinical guidelines for managing COPD in 
lung cancer patients, highlighting the value of early diagnosis. The inclusion of cost-effectiveness 
analysis will also provide insights into the economic benefits of early COPD treatment, supporting 
better healthcare resource allocation. 
 
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The research has the potential to shift clinical practice by reinforcing the need for integrated 
management of COPD in patients with lung cancer, leading to better overall health outcomes. 
 
Timeline 
 
2025 
2026 
2027 
2028 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Preparation and 
Recruitment 
 
 
 
 
 
 
 
 
 
 
 
 
-​
Planning 
x 
 
 
 
 
 
 
 
 
 
 
 
-​
Initiation 
 
x 
 
 
 
 
 
 
 
 
 
 
-​
Recruitment 
 
 
x 
x 
 
 
 
 
 
 
 
 
Data Collection and 
Follow-up 
 
 
 
 
 
 
 
 
 
 
 
 
-​
Complete 
recruitment 
 
 
 
 
x 
x 
 
 
 
 
 
 
-​
Follow-up 
 
 
 
 
 
 
x 
x 
 
 
 
 
Analysis and 
Dissemination 
 
 
 
 
 
 
 
 
 
 
 
 
-​
Data analysis 
 
 
 
 
 
 
 
 
x 
x 
 
 
-​
Disseminatio
n 
 
 
 
 
 
 
 
 
 
 
x 
x 
Tabel 2: Timeline 
 
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