Takashi Motegi

Long-term effectiveness of an inpatient pulmonary rehabilitation program for elderly COPD patients: comparison between young-elderly and old-elderly groups.

Objective:  To evaluate the long‐term effects of pulmonary rehabilitation in elderly COPD patients, we monitored patients for 1 year after they completed a 2‐week inpatient pulmonary rehabilitation program. We also compared the effects of pulmonary rehabilitation on young‐elderly (age 65–74 years) and old‐elderly (age 75 years or over) COPD patients.

Excessive visceral fat accumulation in advanced chronic obstructive pulmonary disease

Background: Previous studies have suggested links between chronic obstructive pulmonary disease (COPD), cardiovascular disease, and abdominal obesity. Although abdominal visceral fat is thought to be associated with cardiovascular risk factors, the degree of visceral fat accumulation in patients with COPD has not been directly studied. The aim of this study was to investigate the abdominal visceral fat accumulation and the association between visceral fat and the severity and changes in emphysema in COPD patients. Methods: We performed clinical and laboratory tests, including pulmonary function, dyspnea score, and the six-minute walking test in COPD patients (n = 101) and control, which included subjects with a smoking history but without airflow obstruction (n = 62). We used computed tomography to evaluate the abdominal visceral fat area (VFA), subcutaneous fat area (SFA), and the extent of emphysema. Results: The COPD group had a larger VFA than the control group. The prevalence of non-obese subjects with an increased VFA was greater in the Global Initiative for Chronic Obstructive Lung Disease Stages III and IV than in the other stages of COPD. The extent of emphysema was inversely correlated with waist circumference and SFA. However, VFA did not decrease with the severity of emphysema. VFA was positively correlated with the degree of dyspnea. Conclusion: COPD patients have excessive visceral fat, which is retained in patients with more advanced stages of COPD or severe emphysema despite the absence of obesity.

A comparison of three multidimensional indices of COPD severity as predictors of future exacerbations

Background Prediction of future exacerbations of chronic obstructive pulmonary disease (COPD) is a major concern for long-term management of this disease. Aim To determine which of three multidimensional assessment systems (the body mass index, obstruction, dyspnea, and exercise capacity [BODE] index; dyspnea, obstruction, smoking, exacerbations [DOSE] index; or age, dyspnea, obstruction [ADO] index) is superior for predicting exacerbations. Methods This was a 2-year prospective cohort study of COPD patients. Pulmonary function tests, the 6-minute walk distance (6MWD), Modified Medical Respiratory Council (MMRC) dyspnea scores, chest computed-tomography measurements, and body composition were analyzed, and predictions of exacerbation by the three assessment systems were compared. Results Among 183 patients who completed the study, the mean annual exacerbation rate was 0.57 events per patient year, which correlated significantly with lower predicted forced expiratory volume in 1 second (FEV1) (P < 0.001), lower transfer coefficient of the lung for carbon monoxide (%DLco/VA) (P = 0.021), lesser 6MWD (P = 0.016), higher MMRC dyspnea score (P = 0.001), higher DOSE index (P < 0.001), higher BODE index (P = 0.001), higher ADO index (P = 0.001), and greater extent of emphysema (P = 0.002). For prediction of exacerbation, the areas under the curves were larger for the DOSE index than for the BODE and ADO indices (P < 0.001). Adjusted multiple logistic regression identified the DOSE index as a significant predictor of risk of COPD exacerbation. Conclusion In this study, the DOSE index was a better predictor of exacerbations of COPD when compared with the BODE and ADO indices.

Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. COPD exacerbation, or episodic worsening of symptoms, often results in hospitalization and increased mortality rates. Airway infections by new bacterial strains, such as nontypeable Haemophilus influenzae (NTHi), are a major cause of COPD exacerbation. NTHi express lipooligosaccharides that contain sialic acids, and may interact with Siglec-14, a sialic acid recognition protein on myeloid cells that serves as an activating signal transduction receptor. A null allele polymorphism in SIGLEC14 may attenuate the inflammatory responses to NTHi by eliminating Siglec-14 expression. We asked if the loss of Siglec-14 attenuates the inflammatory response by myeloid cells against NTHi, and if the SIGLEC14-null polymorphism has any effect on COPD exacerbation. We found that NTHi interacts with Siglec-14 to enhance proinflammatory cytokine production in a tissue culture model. Inhibitors of the Syk tyrosine kinase suppress this response. Loss of Siglec-14, due to SIGLEC14-null allele homozygosity, is associated with a reduced risk of COPD exacerbation in a Japanese patient population. Taken together, Siglec-14 and its downstream signaling pathway facilitate the “infection–inflammation–exacerbation” axis of COPD disease progression, and may represent promising targets for therapeutic intervention.

Efficient integrated education for older patients with chronic obstructive pulmonary disease using the Lung Information Needs Questionnaire.

Aim:  Education is a key issue for the long‐term management of chronic obstructive pulmonary disease in older patients. We tested the hypothesis that integrated care focusing on patient information needs for self‐management can improve patient information needs and health outcomes.

Presence of In-Home Caregiver and Health Outcomes of Older Adults with Chronic Obstructive Pulmonary Disease

OBJECTIVES: To determine whether the presence of in‐home caregivers is associated with changes in the health outcomes of older adults with chronic obstructive pulmonary disease (COPD).

The Neutrophil to Lymphocyte Ratio Is Related to Disease Severity and Exacerbation in Patients with Chronic Obstructive Pulmonary Disease

Objective Although chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation, the association between the neutrophil to lymphocyte ratio (NLR; an indicator of inflammation) and the clinical status of COPD has not been well studied. We hypothesized that the NLR is associated with disease severity and exacerbation in COPD patients. Methods We performed blood testing, pulmonary function testing, chest computed tomography, a body composition analysis, and a 6-minute walk test and applied the modified Medical Research Council (MMRC) dyspnea scale for 141 stable COPD patients. In addition, we calculated the body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index to evaluate the disease severity. Finally, we examined the association between the NLR and clinical parameters in stable COPD patients, and we further investigated changes in the NLR between exacerbation and the stable state. Results The NLR was positively correlated with the BODE index, extent of emphysema, and MMRC score (p<0.001 for all), while inversely correlated with airflow obstruction (p<0.001), body mass index (p<0.001), fat-free mass index (p=0.001), and the 6-minute walk distance (p<0.001). We obtained the NLR during exacerbation from 49 patients. The NLR was significantly higher at exacerbation compared to the stable state (p<0.001). Conclusion The NLR was associated with disease severity and exacerbation in COPD patients. Therefore, the usefulness of the NLR in COPD patients should be elucidated in clinical settings in future investigations.

α1,6-Fucosyltransferase (Fut8) is implicated in vulnerability to elastase-induced emphysema in mice and a possible non-invasive predictive marker for disease progression and exacerbations in chronic obstructive pulmonary disease (COPD)

Fut8 (α1,6-Fucosyltransferase) heterozygous knock-out (Fut8(+/-)) mice had an increased influx of inflammatory cells into the lungs, and this was associated with an up-regulation of matrix metalloproteinases, MMP-2 and MMP-9, after treatment with porcine pancreatic elastase (PPE), exhibiting an emphysema-prone phenotype as compared with wild type mice (Fut8(+/+)). The present data as well as our previous data on cigarette-smoke-induced emphysema [8] led us to hypothesize that reduced Fut8 levels leads to COPD with increased inflammatory response in humans and is associated with disease progression. To test this hypothesis, symptomatic current or ex-smokers with stable COPD or at risk outpatients were recruited. We investigated the association between serum Fut8 activity and disease severity, including the extent of emphysema (percentage of low-attenuation area; LAA%), airflow limitation, and the annual rate of decline in forced expiratory volume in 1 s (FEV(1)). Association with the exacerbation of COPD was also evaluated over a 3-year period. Serum Fut8 and MMP-9 activity were measured. Fut8 activity significantly increased with age among the at risk patients. In the case of COPD patients, however, the association was not clearly observed. A faster annual decline of FEV(1) was significantly associated with lower Fut8 activity. Patients with lower Fut8 activity experienced exacerbations more frequently. These data suggest that reduced Fut8 activity is associated with the progression of COPD and serum Fut8 activity is a non-invasive predictive biomarker candidate for progression and exacerbation of COPD.

Diagnostic Values For Club Cell Secretory Protein (CC16) in Serum of Patients of Combined Pulmonary Fibrosis and Emphysema

Abstract Combined pulmonary fibrosis and emphysema (CPFE) is an under-recognized syndrome for which the diagnostic use of serum biomarkers is an attractive possibility. We hypothesized that CC16 and/or TGF-β1 or combinations with other biomarkers are useful for diagnosing CPFE. Patients with respiratory symptoms and a smoking history, with or without chronic obstructive pulmonary disease, were divided into the following three groups according to findings of high-resolution computed tomography of the chest: controls without either emphysema or fibrosis, patients with emphysema alone, and patients compatible with the diagnosis of CPFE. Serum concentrations of CC16, TGF-β1, SP-D, and KL-6 were measured in patients whose condition was stable for at least 3 months. To investigate changes in biomarkers of lung fibrosis in patients with a life-long smoking history, additional measurements were performed on the patients with idiopathic pulmonary fibrosis (IPF) of smoking history. The mean age of the first three groups was 68.0 years, whereas that of the IPF group was 71.8 years, and the groups contained 36, 115, 27, and 10 individuals, respectively. The serum concentration of CC16 in the four groups was 5.67 ± 0.42, 5.66 ± 0.35, 9.38 ± 1.04 and 22.15 ± 4.64 ng/ml, respectively, indicating that those patients with lung fibrosis had a significantly higher concentration. The combined use of CC16, SP-D, and KL-6 provided supportive diagnosis in conjunction with radiological imaging in diagnosis of CPFE. We conclude that a combination of biomarkers including CC16 could provide useful information to screen and predict the possible diagnosis of CPFE.

Emphysema on imaging is associated with quality of life in elderly patients with chronic obstructive pulmonary disease.

Background:  Limited data are available on the association between the severity of emphysema or airway narrowing, and health‐related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD), which has been seen to be more prevalent among elderly subjects. The aim of this study was to examine the association between HRQOL, physical parameters and structural alterations in lung of COPD patients.