In this study, we analyzed the relationships of exercise capacity and health status to mortality in patients with chronic obstructive pulmonary disease (COPD). We recruited 150 male outpatients with stable COPD with a mean postbronchodilator FEV1 at 47.4% of predicted. Their pulmonary function, progressive cycle ergometry, and health status using the Chronic Respiratory Disease Questionnaire, the St. George's Respiratory Questionnaire (SGRQ), and the Breathing Problems Questionnaire were measured at entry. Among 144 patients who were available for the 5-year follow-up, 31 had died. Univariate Cox proportional hazards analysis revealed that the SGRQ total score and the Breathing Problems Questionnaire were significantly correlated with mortality; however, with the Chronic Respiratory Disease Questionnaire, the total score was not significantly correlated. Multivariate Cox proportional hazards analysis revealed that the peak oxygen uptake and the SGRQ total score were both predictive of mortality, independent of FEV1 and age. Stepwise Cox proportional hazards analysis revealed that the peak oxygen uptake was the most significant predictor of mortality. We found that exercise capacity and health status were significantly correlated with mortality, although different health status measures had different abilities to predict mortality. These results will have a potentially great impact on the multidimensional evaluation of disease severity in COPD.
Background: Health status, dyspnea and psychological status are important clinical outcomes in chronic obstructive pulmonary disease (COPD). However, forced expiratory volume in one second (FEV1) measured by spirometry, the standard measurement of airflow limitation, has only a weak relationship with these outcomes in COPD. Recently, in addition to spirometry, impulse oscillometry (IOS) measuring lung resistance (R) and reactance (X) is increasingly being used to assess pulmonary functional impairment. Methods: We aimed to identify relationships between IOS measurements and patient-reported outcomes in 65 outpatients with stable COPD. We performed pulmonary function testing, IOS, high-resolution computed tomography (CT), and assessment of health status using the St. George's Respiratory Questionnaire (SGRQ), dyspnea using the Medical Research Council (MRC) scale and psychological status using the Hospital Anxiety and Depression Scale (HADS). We then investigated the relationships between these parameters. For the IOS measurements, we used lung resistance at 5 and 20 Hz (R5 and R20, respectively) and reactance at 5 Hz (X5). Because R5 and R20 are regarded as reflecting total and proximal airway resistance, respectively, the fall in resistance from R5 to R20 (R5-R20) was used as a surrogate for the resistance of peripheral airways. X5 was also considered to represent peripheral airway abnormalities. Results: R5-R20 and X5 were significantly correlated with the SGRQ and the MRC. These correlation coefficients were greater than when using other objective measurements of pulmonary function, R20 on the IOS and CT instead of R5-R20 and X5. Multiple regression analyses showed that R5-R20 or X5 most significantly accounted for the SGRQ and MRC scores. Conclusions: IOS measurements, especially indices of peripheral airway function, are significantly correlated with health status and dyspnea in patients with COPD. Therefore, in addition to its simplicity and non-invasiveness, IOS may be a useful clinical tool not only for detecting pulmonary functional impairment, but also to some extent at least estimating the patient's quality of daily life and well-being.
Matrix metalloproteinases (MMPs) are believed to be involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), and MMP-7 has been described as a useful biomarker for IPF. However, little is known regarding the significance of MMP-10 as a biomarker for IPF. This observational cohort study included 57 patients with IPF. Serum MMPs were comprehensively measured in all patients, and the relationships between these markers and both disease severity and prognosis were evaluated. Bronchoalveolar lavage fluid (BALF) MMP-7 and -10 levels were measured in 19 patients to investigate the correlation between these markers and their corresponding serum values. Immunohistochemical staining for MMP-10 was also performed in IPF lung tissue. Serum MMP-7 and -10 levels correlated significantly with both the percentage of predicted forced vital capacity (ρ = −0.31, p = 0.02 and ρ = −0.34, p < 0.01, respectively) and the percentage of predicted diffusing capacity of the lung for carbon monoxide (ρ = −0.32, p = 0.02 and ρ = −0.43, p < 0.01, respectively). BALF MMP-7 and -10 levels correlated with their corresponding serum concentrations. Only serum MMP-10 predicted clinical deterioration within 6 months and overall survival. In IPF lungs, the expression of MMP-10 was enhanced and localized to the alveolar epithelial cells, macrophages, and peripheral bronchiolar epithelial cells. MMP-10 may be a novel biomarker reflecting both disease severity and prognosis in patients with IPF.