Table 3.

Prioritized List of Research Topics to Fill the Most Urgent Gaps in the Field of Chronic Obstructive Pulmonary Disease and Cardiovascular Disease

Priority	Research Topic	Number of Rounds	Degree of Agreement in Final Round	Summative Likert Score in Final Round
1	Conduct pragmatic clinical trials with patient-centered outcomes that collect both pulmonary and cardiac data elements. Specifically:  •Use pragmatic clinical trial designs to expedite the recruitment and retention of patients with COPD and cardiovascular disease, especially those with low health literacy and poor access to medications. •Ensure that pulmonary-related data (mMRC, CAT, spirometry) are reported in prospective trials focused on cardiovascular drugs, and cardiac-related data (biomarkers, echocardiographic studies) are reported in prospective trials focused on pulmonary drugs. •Integrate patient-centered outcomes into trials with the pairing of qualitative and quantitative methods to evaluate the impact of medications and interventions on patients’ symptoms. •Conduct real-world effectiveness trials of medications in the broad COPD population with concurrent cardiovascular disease, especially medications that decrease the burden of taking multiple inhalers and pills per day (i.e., polypuff, polypill). •Conduct stepped-wedge implementation trials in large health systems, to examine the benefit of newer medications, such as SGLT2i, in patients with COPD who have indications to receive this class of medication (type 2 diabetes, heart failure, chronic kidney disease).	1	95%	25
2	Determine the cost-effectiveness and other measures of benefit (NNT) of cardiac diagnostic tests (Cardiac Injury Score on ECG, biomarkers [natriuretic peptides, troponin], and echocardiography) in stable and exacerbated patients with COPD. Determine the cost-effectiveness and other measures of benefit (NNT) of spirometry with diffusion capacity to assess lung function among patients with cardiovascular disease.	1	82%	14
3	Refine our knowledge of phenotypes within the COPD population with the goal of understanding patients’ individualized risk of different cardiovascular diseases (i.e., which phenotype predisposes to heart failure, atherosclerotic cardiovascular disease, and atrial fibrillation). Determine the appropriate screening studies and treatments for the different phenotypes.	2	87%	13
4	Identify and further develop the key elements of pulmonary and cardiac rehabilitation programs that specifically help patients with both COPD and cardiovascular disease, potentially aiming for an integrated cardiopulmonary program.	2	83%	12
5	Improve knowledge translation by increasing clinicians’ adherence to guidelines on the primary and secondary prevention of cardiovascular disease in patients with COPD and raise awareness of COPD as a “risk-enhancing diagnosis,” which requires more stringent lipid and blood pressure management.	2	82%	9
6	Define the incidence, prevalence, characteristics, and prognosis of major cardiovascular diseases in patients with COPD using contemporary definitions, including heart failure subtypes (preserved and reduced ejection fraction), acute coronary syndrome subtypes (type 1 and 2 events) and various arrhythmias (both atrial and ventricular).	2	83%	8
7	Determine the best approach to leverage cardiovascular disease seen on lung cancer screening CT scans (coronary calcium, enlarged aorta, pulmonary artery, atherosclerosis, etc.).	2	71%	7
8	Develop and test simplified medication and inhaler regimens that are low cost and accessible to those with low literacy who have COPD and cardiovascular disease. Examine the impact of different pricing strategies of medications on patients’ behavior to be adherent with the goal of changing health policy to improve patients’ access.	2	77%	6
9	Elucidate the mechanisms underlying the relationships between COPD and cardiovascular disease, such as congestive heart failure, atherosclerotic cardiovascular disease, and atrial fibrillation, which are common and affect patients’ long-term trajectory, with the goal of finding targeted therapies that prevent or slow both diseases.	2	77%	5
10	Raise awareness among clinicians about the evidence-based risks of cardiovascular treatments on lung function (such as statins, β-blockers) and pulmonary treatments on cardiovascular function (such as inhaled steroids, β-agonists).	1	59%	0
11	Define the optimal roles of primary care physicians, hospitalists, pulmonologists, and cardiologists in treating patients with COPD and cardiovascular disease in both the outpatient and inpatient settings with the goal of prioritizing patients’ needs.	1	65%	−1
12	Leverage technology to improve various aspects of care for patients with COPD and cardiovascular disease, such as delivery of supplemental oxygen that is automatically titrated to oxygen saturation with movement and participation in telerehabilitation programs.	1	71%	−2
13	Conduct longitudinal studies following stable and exacerbated patients with cardiac rhythm monitors to examine the risk of undetected or recurrent AF and response to therapy (pharmacologic and ablation).	1	36%	−9
14	Determine the risks and benefits of conservative medical management versus advanced cardiac testing or catheterization in patients hospitalized with COPD who have elevated troponin.	1	53%	−11
15	Determine the impact of using active language to describe COPD exacerbation (e.g., “lung attack), given the significantly elevated cardiopulmonary risk over time and specifically in the postexacerbation period.	1	35%	−13
16	Examine how environmental triggers, such as air pollution, mediate the relationship between COPD and cardiovascular disease.	1	24%	−14
17	Evaluate the impact of performing spirometry in hospitalized patients with cardiopulmonary symptoms to differentiate between airflow obstruction and other common conditions that cause dyspnea, such as congestive heart failure.	1	24%	−15

Definition of abbreviations: AF = atrial fibrillation; CAT = COPD assessment test; COPD = chronic obstructive pulmonary disease; CT = computed tomography; ECG = electrocardiography; mMRC = Modified Medical Research Council Dyspnea Scale; NNT = number needed to treat; SGLT2i = sodium-glucose cotransporter-2 inhibitors.

Seventeen participants voted on all questions. Participants were allowed to vote strongly agree or agree on only 5 of 17 priorities to facilitate generating a prioritized list with a gradient. The degree of agreement is the percentage of respondents who voted strongly disagree/disagree or neutral/agree/strongly agree about whether the gap should be considered a top priority, which was defined as significant potential for advancing the field and ultimately improving the lives of patients with COPD and cardiovascular disease. The last column is the summative Likert score, from which the final round was calculated, where strongly disagree was assigned −2, disagree was assigned −1, neutral was assigned 0, agree was assigned +1, and strongly agree was assigned +2. The final list of priorities was then ordered by the final-round summative Likert score.