Serum Free Radical Scavenging Capacity Profiles of Patients with Chronic Obstructive Pulmonary Disease.

Background: Oxidative stress is an important mechanism for the development and progression of chronic obstructive pulmonary disease (COPD). It may also contribute to systemic manifestation in patients with COPD. Reactive oxygen species (ROS) including free radicals play a crucial role in oxidative stress in COPD. The aims of this study were to determine serum scavenging capacity profile against multiple free radicals and to evaluate its correlation with pathophysiology, exacerbations, and prognosis in patients with COPD. Methods: Serum scavenging capacity profile against multiple free radicals comprising hydroxyl radical (•OH), superoxide radical (O2 -•), alkoxy radical (RO•), methyl radical (•CH3), alkylperoxyl radical (ROO•), and singlet oxygen (1O2) was assessed using the multiple free-radical scavenging method in 37 patients with COPD (mean age, 71 years; mean forced expiratory volume in 1 s, 55.2% predicted). The severity of emphysema was evaluated by Goddard classification on chest computed tomography. Exacerbations were recorded prospectively for 1 year and the overall mortality was assessed 5 years after the initial assessment. Results: •OH scavenging capacity was significantly decreased (p < 0.05) and O2 -• and •CH3 scavenging capacity tended to decrease in patients with COPD compared to that in healthy controls. On the other hand, ROO• scavenging capacity tended to increase. In addition, RO• scavenging capacity was associated with severity of emphysema (p < 0.05) and exacerbation frequency (p < 0.02). There was a difference in the profile of the scavenging capacity between survived and deceased patients with COPD for 5 years after initial assessment. Conclusion: Characteristic profile of free radical scavenging capacity can provide insight into the pathophysiology and prognosis of patients with COPD.

Mini Nutritional Assessment Short-Form as screening tool for osteoporosis in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVES: Osteoporosis is a common complication of chronic obstructive pulmonary dis-ease (COPD). It is impractical to measure bone mineral density (BMD) in all patients with COPD. This study aimed to investigate the relationship between Mini Nutritional Assessment Short-Form (MNA-SF), a simple nutritional status questionnaire, and osteoporosis, and to determine whether it can be used as a reliable screening tool for osteoporosis in patients with COPD. METHODS AND STUDY DESIGN: Thirty-seven patients with stable COPD were enrolled in this prospective cohort study. Patients with MNA-SF scores >11 were defined as well-nourished, and those with scores of ≤11 being at risk for malnutrition. Body composition, BMD, and undercarboxylated osteocalcin (ucOC), a bone metabolism marker, were measured using bioelectrical impedance, dual energy X-ray, and electrochemiluminescence immunoassay, respectively. RESULTS: Seventeen (45.9%) were classified as at risk for malnutrition, and 13 (35.1%) had osteoporosis. Patients at risk for malnutrition had significantly more osteoporosis and higher ucOC values than well-nourished patients (p=0.007, p=0.030, respectively). Patients with osteoporosis also had significantly lower body mass index (BMI) and fat-free mass index than those without osteoporosis (p= 0.007 and p=0.005, respectively), although FEV1 % pred was not significantly different. MNA-SF (cutoff value; 11) had better sensitivity to identify the presence of osteoporosis than BMI (cutoff value; 18.5 kg/m2) (sensitivity, 0.769; specificity, 0.708; sensitivity, 0.462; specificity, 0.875, respectively). CONCLUSIONS: MNA-SF was associated with osteoporosis and bone metabolism markers in patients with COPD. MNA-SF may be a useful screening tool for osteoporo-sis in patients with COPD.

Fractal dimension in CT low attenuation areas is predictive of long-term oxygen therapy initiation in COPD patients: Results from two observational cohort studies.

BACKGROUND: Some chronic obstructive pulmonary disease (COPD) patients develop hypoxemia with disease progression, with some even requiring long-term oxygen therapy (LTOT). Lung function, especially diffusing capacity, and the annual decline in PaO2, are reported to be predictive factors of chronic respiratory failure. However, the association between lung morphometry evaluated using computed tomography (CT) images and LTOT initiation is unknown. METHODS: We retrospectively evaluated the relationship between clinical indices, including pulmonary function, body mass index (BMI), and CT parameters, at baseline and LTOT initiation in two prospective COPD cohorts. In the Nara Medical University cohort (n = 76), the low attenuation area (LAA) and its fractal dimension (fractal D) were adapted as the indices for parenchymal destruction in CT images. The association between these CT measurements and LTOT initiation was replicated in the Kyoto University cohort (n = 130). RESULTS: In the Nara Medical University cohort, lower BMI (hazard ratio [HR]:0.70, p = 0.006), lower % diffusing capacity (%DLCO) (HR: 0.92, p = 0.006), lower %DLCO/VA (HR, 0.90, p = 0.008), higher RV/TLC (HR, 1.26, p = 0.012), higher LAA% (HR: 1.18, p = 0.001), and lower fractal D (HR: 3.27 × 10-8, p < 0.001) were associated with LTOT initiation. Multivariate analysis in the Kyoto University cohort confirmed that lower %DLCO and lower fractal D were independently associated with LTOT initiation, whereas LAA% was not. CONCLUSION: Fractal D, which is the index for morphometric complexity of LAA in CT analysis, is predictive of LTOT initiation in COPD patients.

Human Adipose-Derived Mesenchymal Stem Cells Ameliorate Elastase-Induced Emphysema in Mice by Mesenchymal-Epithelial Transition.

PURPOSE: Chronic obstructive pulmonary disease (COPD) is a worldwide problem because of its high prevalence and mortality. However, there is no fundamental treatment to ameliorate their pathological change in COPD lung. Recently, adipose-derived mesenchymal stem cells (ADSCs) have attracted attention in the field of regenerative medicine to repair damaged organs. Moreover, their utility in treating respiratory diseases has been reported in some animal models. However, the detailed mechanism by which ADSCs improve chronic respiratory diseases, including COPD, remains to be elucidated. We examined whether human ADSCs (hADSCs) ameliorated elastase-induced emphysema and whether hADSCs differentiated into alveolar epithelial cells in a murine model of COPD. METHODS: Female SCID-beige mice (6 weeks old) were divided into the following four groups according to whether they received an intratracheal injection of phosphate-buffered saline or porcine pancreatic elastase, and whether they received an intravenous injection of saline or hADSCs 3 days after intratracheal injection; Control group, hADSC group, Elastase group, and Elastase-hADSC group. We evaluated the lung function, assessed histological changes, and compared gene expression between hADSCs isolated from the lung of Elastase-hADSC group and naïve hADSCs 28 days after saline or elastase administration. RESULTS: hADSCs improved the pathogenesis of COPD, including the mean linear intercept and forced expiratory volume, in an elastase-induced emphysema model in mice. Furthermore, hADSCs were observed in the lungs of elastase-treated mice at 25 days after administration. These cells expressed genes related to mesenchymal-epithelial transition and surface markers of alveolar epithelial cells, such as TTF-1, ß-catenin, and E-cadherin. CONCLUSION: hADSCs have the potential to improve the pathogenesis of COPD by differentiating into alveolar epithelial cells by mesenchymal-epithelial transition.

Resting Breathing Instability During Wakefulness as a Predictor of Clinical Outcome in COPD.

BACKGROUND: Dyspnea is a common symptom in patients with COPD. It causes physical inactivity and impaired health-related quality of life. Although optimal breathing methods alleviate dyspnea, it is unclear whether breathing instability has a clinical impact on patients with COPD. This study aimed to investigate whether resting breathing instability during wakefulness was associated with dyspnea assessed by the modified Medical Research Council (mMRC) dsypnea scale and whether breathing instability can be a novel predictor of clinical outcomes. METHODS: Forty-four subjects with stable COPD were enrolled (mean age, 71.0 y). Resting breathing was monitored for 15 min by using respiratory inductance plethysmography. Breathing instability was evaluated with the coefficient of variation for breath-by-breath respiratory duration and tidal volume ([Formula: see text]) by using an artifact-free respiratory signal for 5 min. Pulmonary function testing and blood gas analysis were performed (mean FEV1 percent of predicted, 68.5%). Questionnaires with regard to dyspnea and health-related quality of life were also completed. Exacerbations were recorded prospectively for 1 year after the initial assessment. RESULTS: The coefficients of variation for [Formula: see text] were significantly higher in the subjects with an mMRC dyspnea scale score ≥ 2 versus those with an mMRC dyspnea scale score < 2 (26.4 ± 7.4% vs 20.3 ± 6.4%, P = .006) . The coefficients of variation for respiratory duration and VT were not associated with age, body mass index, and pulmonary function variables. In multivariate analysis, FEV1 percent of predicted and coefficient of variation for [Formula: see text] remained significant predictors for an mMRC dyspnea scale score ≥ 2 (P = .004 and P = .01, respectively). Coefficient of variation values were also correlated with several health-related quality of life domains. The exacerbation frequency was associated with the coefficient of variation for [Formula: see text]. CONCLUSIONS: Resting breathing pattern during wakefulness is a novel assessment tool for severity of dyspnea, which can be one of the predictors for exacerbation in patients with COPD.