The management of chronic obstructive pulmonary disease (COPD) has improved significantly due to advances in therapeutic agents, but it has also become apparent that there are issues that remain difficult to solve with the current treatment algorithm. COPD patients face a number of unmet needs concerning symptoms, exacerbations, and physical inactivity. There are various risk factors and triggers for these unmet needs, which can be roughly divided into two categories. One is the usual clinical characteristics for COPD patients, and the other is specific clinical characteristics in patients with comorbid conditions, such as asthma, cardiovascular disease, and bronchiectasis. These comorbidities, which are also associated with the diversity of COPD, can cause unmet needs resistance to usual care. However, treatable conditions that are not recognized as therapeutic targets may be latent in patients with COPD. We again realized that treatable traits should be assessed and treated as early as possible. In this article, we categorize potential therapeutic targets from the viewpoint of pulmonary and systemic comorbid conditions, and address recent data concerning the pathophysiological link with COPD and the impact of intervention on comorbid conditions in order to obtain evidence that could enable us to provide personalized COPD management.

Sedentary behavior and cognitive impairment have a direct impact on patients’ outcomes. An energy metabolic disorder may be involved in the overlap of these comorbid conditions (motoric cognitive risk (MCR)) in patients with chronic obstructive pulmonary disease (COPD). We aimed to explore the linkage between a proapoptotic protein, growth differentiation factor (GDF)-15, and MCR. Physical activity (PA), cognitive function (Japanese version of the Montreal Cognitive Assessment: MOCA-J), and the serum GDF-15 levels were assessed in healthy subjects (n = 14), asthmatics (n = 22), and COPD patients (n = 28). In the entire cohort, serum GDF-15 had negative correlations with exercise (Ex) (ρ = −0.43, p < 0.001) and MoCA-J (ρ = −0.44, p < 0.001), and Ex and MOCA-J showed a positive correlation (ρ = 0.52, p < 0.0001). Compared to healthy subjects and asthmatics, COPD patients showed the highest serum GDF-15 levels and had a significantly higher proportion of subjects with MCR (both sedentary lifestyle (EX < 1.5) and cognitive risk (MoCA-J ≤ 25)). Also, we found that serum GDF-15 has a screening potential (100% sensitivity) greater than aging (67% sensitivity) for detecting MCR in COPD patients. In conclusion, higher serum GDF-15 had interrelationships with a sedentary lifestyle and cognitive risk. This protein was not disease-specific but could be a screening biomarker to detect MCR related to poor health outcomes of COPD patients.

Background: As much as there are unmet needs for brief frailty assessment in patients with chronic obstructive pulmonary disease (COPD), the lack of a simplified and comprehensive dyspnea evaluation system that focuses on the patients’ perceptions of dyspnea and their COPD living disabilities remains a major challenge. We developed patient-reported outcome measures for dyspnea-related behavior and activity limitation (PROMs-D), which consisted of the Activity-limit Dyspnea Scale (ADS) and Self-Limit Dyspnea Scale (SDS), while investigated the usefulness of PROMs-D in identifying frailty. Methods: We administered PROMs-D and frailty status evaluations in 128 outpatients. Results: We classified 30 (23.4%), 50 (39.0%), and 48 (37.5%) patients as robust, prefrail, and frail, respectively. There was a positive correlation between SDS and ADS (ρ = 0.67, p < 0.001), and both ADS and SDS had high accuracies for detecting frailty (AUC, 0.82 and 0.78, respectively). Moreover, a PROMs-D score that consisted of the sum of ADS and SDS was more effective in stratifying frailty (cutoff value, 2; AUC, 0.85; sensitivity, 60%; specificity, 95%). Conclusions: PROMs-D could be used as the first step for frailty screening in patients with COPD, and we propose the importance of capturing the troublesome nature of living behaviors due to dyspnea in daily clinical practice.