Background Guidelines recommend that symptoms as well as lung function should be monitored for the management of patients with chronic obstructive pulmonary disease (COPD). time (p?0.001), but the OCD did not (p?=?0.097). Multiple regression analyses revealed that the changes in the OCD, mMRC, CRQ dyspnea and SGRQ activity were significantly correlated to changes in forced expiratory volume in one second (FEV1) (correlation of determination (r2)?=?0.05-0.19), diffusing capacity for carbon monoxide (r2?=?0.04-0.08) and psychological status evaluated by Hospital Anxiety and Depression Scale (r2?=?0.14-0.17), although these correlations were weak. Peak Borg score decreased rather significantly, but was unrelated to changes in clinical measurements. Conclusion Dyspnea worsened over time in patients with COPD. However, as different dyspnea measurements showed different evaluative characteristics, it is important to follow dyspnea using appropriate measurements. Progressive dyspnea was related not only to progressive airflow limitation, but also to various factors such as worsening of diffusing capacity or psychological status. Changes 239101-33-8 in peak dyspnea at the end of exercise may evaluate different aspects from other dyspnea measurements. Keywords: COPD, Dyspnea, Airflow limitation, Diffusing capacity, Exercise, Psychological status, Disease progression Background Dyspnea is the main symptom of which most patients with chronic obstructive pulmonary disease (COPD) complain. Guidelines recommend that symptoms as well as lung function should be monitored for the 239101-33-8 management of patients with COPD . Dyspnea is regarded as a potential marker of disease progression of COPD, because it worsens over time, predicts mortality, and responds to therapy . However, only a few 239101-33-8 observational studies have been performed to analyze the longitudinal changes in dyspnea [3-5]. It is still unknown how changes in dyspnea are related to changes in forced expiratory volume in one second (FEV1) and other clinical measurements; the gold standard measurement for following dyspnea has also not been established, as none of the available methods is optimal, having regard to their merits and limitations . In previous cross-sectional studies, we reported that three dyspnea measurements with activities of daily living such as the Oxygen Cost Diagram (OCD) , the modified Medical Research Council dyspnea scale (mMRC)  and the Baseline Dyspnea Index (BDI) , and the two dimensions of disease-specific health status questionnaires of the Chronic Respiratory Disease Questionnaire (CRQ)  and the St. Georges Respiratory Questionnaire (SGRQ)  performed equally well in assessing dyspnea of patients with COPD; however, the Borg scale  at the end of exercise evaluated different aspects of dyspnea FLNC . However, although unidimensional measurements such as OCD or MRC, which were 239101-33-8 initially developed to quantify dyspnea in a category or analog scale, have excellent discriminative properties, it is estimated that they would not be so useful as an evaluative instrument . Therefore, we hypothesized that, although different dyspnea measurements worsened over time, the associated changes would differ depending on the instruments used, and that changes in dyspnea are related to the changes in a variety of factors, such as FEV1. We previously recruited patients with COPD, and assessed multiple clinical measurements every 6 months over 5 years [5,15]. In the present study, we reviewed the data and compared longitudinal changes in different dyspnea measurements and the relevant contributory factors using multiple regression 239101-33-8 analyses. Methods Subjects We previously consecutively recruited 137 male outpatients with moderate to very severe COPD [5,15]. Inclusion criteria included: (1) smoking history.