Cluster Analysis Reveals Heterogeneity in Symptom Burden Among Patients With COPD

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Distinct patterns of symptom severity among patients with COPD sheds light on the heterogeneous nature of the patients’ experience.

New research published in ERJ Open Research reveals distinct patterns of symptom severity among patients with chronic obstructive pulmonary disease (COPD), shedding light on the heterogeneous nature of their experiences.

By identifying groups of patients with similar symptom burdens, the study authors provide insights that could enhance understanding of the disease’s impact and guide more targeted, multidimensional treatment approaches.

“This study highlights the substantial challenges faced by patients with COPD, including non-respiratory symptoms, and emphasizes the need to implement patient-centered care approaches to reduce symptom burdens and enhance clinical outcomes and patient HRQOL,” says Yvette C. Terrie, RPh, BS Pharm, consultant pharmacist. “In the study, examples of commonly experienced symptoms, such as dry mouth, fatigue, and challenges sleeping, may be disease-related but may also be a manifestation of an adverse drug effect.”

COPD is characterized by respiratory symptoms (eg, dyspnea, cough), sputum production and systemic manifestations (eg, fatigue, depressive feelings), and pain. These symptoms significantly impact patients’ QOL and functional performance.

Despite their substantial effect, these symptoms are often under-reported or overlooked. Existing research highlights the need for a comprehensive approach to COPD management, considering respiratory and non-respiratory symptoms. However, previous cluster analyses have not focused on a broad COPD population nor included non-COPD controls to understand symptom burden.

The study authors sought to assess the severity and burden of respiratory and non-respiratory symptoms in patients with COPD and non-COPD participants and to explore associations between symptom clusters and clinical characteristics in a cross-sectional analysis.

Participants with COPD were recruited from primary, secondary, and tertiary care settings in the southern Netherlands, while non-COPD participants were recruited from the same general practices as primary care patients, with strict criteria ensuring they had no history of significant respiratory or other health conditions. The study team assessed demographic and clinical characteristics and measured functional mobility with the Timed Up and Go test. They used the COPD Assessment Test to evaluate health status evaluated.

Symptom severity for 20 physical and psychological symptoms was measured using a visual analogue scale (VAS), with a cut-off of 30 mm and higher defining a symptom as present. Only participants with complete symptom assessments were included. K-means cluster analysis was conducted to identify patterns of symptom severity within the COPD group, with the optimal number of clusters determined using silhouette analysis to evaluate clustering validity.

A total of 836 individuals volunteered for the study, including 718 patients with COPD and 118 non-COPD participants. Of these, 180 patients with COPD from tertiary care and two participants without COPD participants were excluded due to incomplete symptom data.

Patients with missing data from tertiary care were generally older and had worse health status. Patients with COPD and non-COPD participants were similar in terms of gender and age, but patients with COPD had worse lung function, functional mobility, and health status. And a higher proportion experienced breathlessness-related activity limitations were former smokers and were care-dependent.

The analysis showed patients with COPD had higher median symptom scores compared to non-COPD participants for most symptoms, except for pain, dizziness, and micturition.

Dyspnea, fatigue, and muscle weakness were the most common symptoms among patients with COPD, while non-COPD participants predominantly reported insomnia and micturition issues, though with lower prevalence.

Symptom burden showed overlap among COPD patients from different care settings, highlighting the need for consistent care regardless of the setting.

“Due to their drug expertise, pharmacists can aid in optimizing drug therapy and be instrumental in medical management via screening for potential drug-drug interactions and contraindications, identifying possible adverse drug events, and making clinical recommendations to individualize patient therapy and adjustments to treatments and dosing when warranted to improve adherence rates and long-term clinical outcomes.  Additionally, many patients with COPD are also more likely to have other comorbidities such as CVD, diabetes, depression, and anxiety. As a result, complex drug regimens that warrant taking multiple medications each day may be overwhelming to some patients and contribute to nonadherence,” stresses Ms. Terrie.

Three distinct clusters of patients with COPD were identified based on symptom severity. Cluster 1 had the least symptom burden, cluster 2 had a moderate burden, and cluster 3 had the highest.

Dyspnea and fatigue were prevalent across all clusters, with cluster 3 reporting the highest symptom scores for most symptoms, except for dyspnea, fatigue, cough, muscle weakness, and edema, which were similar in clusters 2 and 3.

Participants in cluster 3 were more likely to be female and had worse health status, greater care dependency, and a history of myocardial infarction. Symptoms and clinical characteristics generally worsened from cluster 1 to cluster 3, indicating a need for targeted management strategies.

These findings stress the importance of routinely evaluating respiratory and non-respiratory symptoms in COPD management to improve patient outcomes.

“In addition to complex drug regimens, improper inhaler techniques can affect outcomes in patients with COPD. Pharmacists can be instrumental in educating patients about proper inhaler techniques and routinely assess patient techniques to ensure the correct delivery of prescribed therapy,” Ms. Terrie explains.

“A recent study revealed that an estimated 69% of patients hospitalized with COPD used inhaler devices incorrectly, with 66% of patients making critical errors during inhaler use, which meaningfully impacted the effectiveness of the medication and the patient’s response to therapy. The findings also highlight the disease and treatment burdens encountered by patients with COPD and the need to expand awareness among clinicians about identifying and addressing treatment challenges including proper inhaler technique to manage COPD effectively.”