Four-year mortality and physical activity in Japanese patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical activity (PA) is associated with the risk of mortality in patients with chronic obstructive pulmonary disease (COPD); however, evidence is limited to the Japanese population. This study aimed to evaluate the effects of PA on long-term mortality in Japanese patients with COPD. METHODS: We conducted a prospective observational study in a cohort of Japanese patients with COPD and assessed mortality during a 4-year follow-up period. The Cox proportional hazards model was used to evaluate the association between PA and mortality. RESULTS: Among 309 patients (294 men; median age, 76 years), 287 completed follow-ups while 45 died. The all-cause mortality rate was 27.5% in patients with low PA and 4.1% in those with high PA. Adjusted hazard ratios for all-cause mortality were associated with high PA. CONCLUSIONS: Higher PA levels are associated with a better prognosis across different settings and patient characteristics, even in Japanese patients with COPD. TRIAL REGISTRATION: The study was registered in the UMIN Clinical Trials Registry (UMIN000032112).

Physical activity and outcomes in Japanese patients with chronic obstructive pulmonary disease: From the Ishinomaki COPD Network registry.

BACKGROUND: Low physical activity levels are associated with an increased risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD); however, evidence is limited in a population with a low frequency of exacerbations, such as the Japanese population. This study investigated the effects of physical activity on outcomes in Japanese patients with COPD. METHODS: We conducted a prospective observational study in a cohort of Japanese patients with COPD between April 2018 and July 2020. Characteristics, frequency of exacerbations, and mortality were assessed during the 1-year follow-up period. Logistic regression analysis evaluated the relationship between physical activity and outcomes. RESULTS: A total of 309 patients (294 males; median age, 75 years) with stable COPD were included, and 307 completed follow-up. Patients with lower levels of physical activity were older, and showed increased airflow obstruction, limited exercise capacity, increased dyspnea, depressive state, poor health status, muscle weakness, and more information needs for the disease. Patients with high levels of physical activity had a lower risk of exacerbation, including hospital admission, compared to those with low levels of activity (odds ratio [OR], 0.46; 95 % confidence interval [CI], 0.22-0.97; and OR, 0.21; 95 % CI, 0.09-0.50, respectively). High physical activity was associated with a reduced risk of all-cause mortality (OR, 0.07; 95 % CI, 0.01-0.55) and respiratory mortality (OR, 0.16; 95 % CI, 0.02-1.47). CONCLUSIONS: These findings showed that higher physical activity is associated with better clinical outcomes, even in a COPD population with a low frequency of exacerbations.

A case of metastatic endobronchial tumor from uterine leiomyosarcoma.

A 54-year-old woman presented with persistent productive cough, found to have an endobronchial tumor which obstructed the left upper lobe bronchus. Histopathological examination of a transbronchial biopsy of the endobronchial tumor suggested leiomyosarcoma. A positron emission tomography (PET)-CT revealed uterus tumor with moderate uptake of 18F-fluorodeoxyglucose, suggesting uterine malignancies. From the results of histological findings of the resected uterus and the biopsied bronchial specimen, she was diagnosed with uterine leiomyosarcoma and endobronchial metastasis. The systematic use of PET-CT could be useful for patients presenting with tumors that cause endobronchial metastasis of leiomyosarcomas.

Exhaled nitric oxide: A biomarker for chronic obstructive pulmonary disease.

The fractional concentration of exhaled nitric oxide (FeNO) is recognized as a biomarker of type 2 inflammation in asthma, which is related to airway eosinophilia. We conducted a prospective observational study in a cohort of Japanese patients with chronic obstructive pulmonary disease (COPD) to evaluate the relationship between FeNO and clinical features and patient outcomes over a 3-year period. Participants were categorized into two groups based on FeNO levels (high and low), and the clinical features and outcomes were compared between the groups. Patients with high FeNO levels showed features of asthma and eosinophilic inflammation compared to those with low levels. However, high FeNO levels were not associated with worse outcomes (exacerbations, hospital admissions, all-cause and disease-specific mortality) compared to low levels. These results provide evidence that baseline FeNO is related to eosinophilic inflammation; however, is not a predictor of future exacerbations or prognosis in patients with stable COPD.

Clinical Characteristics and Outcomes of Patients with Asthma-COPD Overlap in Japanese Patients with COPD.

Purpose: Asthma-COPD overlap (ACO) has been reported as an association with a lower quality of life, frequent exacerbations, and higher mortality than those with COPD alone. However, clinical characteristics and outcomes of ACO remain controversial. Patients and Methods: We conducted a prospective observational study analyzing data of patients with stable COPD enrolled from the Ishinomaki COPD Network Registry. Patients with features of asthma who had a history of respiratory symptoms that vary over time and intensity, together with documented variable expiratory airflow limitation, were identified, and then defined as having ACO. The characteristics, frequency of exacerbations, and mortality during the 3-year follow-up were compared between patients with ACO and patients with COPD alone. Results: Among 387 patients with COPD, 41 (10.6%) were identified as having ACO. Patients with ACO tended to be younger, have higher BMI, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids. Inflammatory biomarkers including fractional exhaled nitric oxide, blood eosinophil count, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were significantly higher in patients with ACO than in those with COPD alone. Lung function, mMRC score, CAT score, and comorbidity index were not different between the groups. The annual rate of all exacerbations and severe exacerbations required hospital admission were not different between ACO and COPD alone (0.20 vs 0.14, 0.12 vs 0.10, events per person, respectively). Mortality was significantly higher in patients with COPD alone compared with those with ACO during the study period (P=0.037). Conclusion: The results of our study indicate that ACO is not associated with poor clinical features nor outcomes in an outpatient COPD cohort receiving appropriate treatment.

Clinical characteristics of Japanese patients with chronic obstructive pulmonary disease (COPD) with comorbid interstitial lung abnormalities: A cross-sectional study.

Smoking-related interstitial lung abnormalities are different from specific forms of fibrosing lung disease which might be associated with poor prognoses. Chronic obstructive pulmonary disease with comorbid interstitial lung abnormalities and that with pulmonary fibrosis are considered different diseases; however, they could share a common spectrum. We aimed to evaluate the clinical characteristics of Japanese patients with chronic obstructive pulmonary disease and comorbid interstitial lung abnormalities. In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. We evaluated the clinical characteristics of patients with chronic obstructive pulmonary disease with and without comorbid interstitial lung abnormalities by comparing the annualized rate of chronic obstructive pulmonary disease exacerbations per patient during the observational period. Among 463 patients with chronic obstructive pulmonary disease, 30 (6.5%) developed new interstitial lung abnormalities during the observational period. After 1-to-3 propensity score matching, we found that the annualized rate of chronic obstructive pulmonary disease exacerbations per patient during the observational period was 0.06 and 0.23 per year in the interstitial lung abnormality and control groups, respectively (P = 0.043). Our findings indicate slow progression of interstitial lung abnormality lesions in patients with pre-existing chronic obstructive pulmonary disease. Further, interstitial lung abnormality development did not significantly influence on chronic obstructive pulmonary disease exacerbation. We speculate that post-chronic obstructive pulmonary disease interstitial lung abnormalities might involve smoking-related interstitial fibrosis, which is different from specific forms of fibrosing lung disease associated with poor prognoses.

Herbal medicine-induced multiple pulmonary pseudotumors.

Japanese herbal medicines (HMs) cause adverse drug reactions (ADRs); however, solid nodule formation is uncommon. In this report, we aimed to show that ADRs with HM can mimic lung cancer. A 63-year-old man complained of back pain. His physician prescribed a traditional Japanese HM, Keishikajutsubuto, which alleviated his symptoms. After 4 weeks, a chest radiograph showed multiple lung nodules that were absent 6 months earlier; the patient did not have cough, fever, or dyspnea. Computed tomography (CT) showed multiple, bilateral lung nodules; however, blood tests and lung biopsy showed no abnormalities, ruling out interstitial pneumonia and lung cancer. Three months after the HM was discontinued, CT showed resolution of the lesions. Interstitial pneumonia was reported as a side effect of HM; however, no such side effect was reported for Keishikajutsubuto. When a patient presents with multiple lung nodules, a side effect of HM should be considered as a differential diagnosis.

Clinical characteristics and outcomes in Japanese patients with COPD according to the 2017 GOLD classification: the Ishinomaki COPD Network Registry.

PURPOSE: The GOLD report provides a framework for classifying COPD in a way that reflects its clinical impact and allows treatment recommendations. The GOLD 2017 proposes a new classification whereby patients are grouped as A-D according to their symptoms and history of exacerbations. However, the clinical characteristics and outcomes in these patients are not well documented. PATIENTS AND METHODS: In this prospective observational study, we analyzed data from the Ishinomaki COPD Network Registry. All patients with stable COPD were classified into the four groups defined by GOLD 2017. The patient demographics, clinical characteristics, number of exacerbations, and mortality rate during 1 year of follow-up were compared between the groups. RESULTS: Four hundred and one patients with stable COPD were identified. There were 240 patients (59.9%) in group A, 122 (30.4%) in group B, 16 (4.0%) in group C, and 23 (5.7%) in group D. Patients in groups B, C, and D had ORs of 2.95, 3.92, and 5.45, respectively, for risk of exacerbation relative to group A. Groups C and D experienced exacerbations more frequently, including exacerbations leading to hospital admission, than groups A and B (both P<0.001) during the 1-year follow-up period. Patients with a high risk of exacerbation (groups C and D) had a lower body mass index, showed more symptoms, used more respiratory medications, and had more severe airflow limitation than patients at low risk of exacerbation (groups A and B). Mortality was not different between the high-risk and low-risk groups. CONCLUSION: The results of our study provide evidence that the GOLD 2017 classification identifies patients with COPD at risk of exacerbations, including those requiring hospitalization, but has a poor ability to predict mortality.

Early Detection of Chronic Obstructive Pulmonary Disease in Primary Care.

Objective To evaluate the effectiveness of an early detection program for chronic obstructive pulmonary disease (COPD) in a primary care setting in Japan. Methods Participants of ≥40 years of age who regularly visited a general practitioner's clinic due to chronic disease were asked to complete a COPD screening questionnaire (COPD Population Screener; COPD-PS) and undergo simplified spirometry using a handheld spirometric device. Patients who showed possible COPD were referred to a respiratory specialist and underwent a detailed examination that included spirometry and chest radiography. Results A total of 111 patients with possible COPD were referred for close examination. Among these patients, 27 patients were newly diagnosed with COPD. The patients with COPD were older, had lower BMI values, and had a longer smoking history in comparison to non-COPD patients. COPD patients also had more comorbid conditions. A diagnosis of COPD was significantly associated with a high COPD-PS score (p<0.001) and the detection of possible airflow limitation evaluated by the handheld spirometric device (p<0.01). An ROC curve analysis demonstrated that 5 points was the best COPD-PS cut-off value for the diagnosis of COPD. The combination of both tools showed 40.7% of sensitivity and 96.4% of specificity. Conclusion The use of the COPD-PS plus a handheld spirometric device could facilitate the early detection of undiagnosed COPD in primary care.

Two Cases of Tsunami Dust Pneumonia: Organizing Pneumonia Caused by the Inhalation of Dried Tsunami Sludge after the 2011 Great East Japan Earthquake.

We report two cases of organizing pneumonia (OP) secondary to the inhalation of the dried tsunami sludge which formed during the 2011 Great East Japan Earthquake and the consequent tsunami. After the disaster, both of these patients had been engaged in the restoration work. About half a month later, they developed shortness of breath and pulmonary infiltrates. These patients were diagnosed with interstitial pneumonia. Their biopsy specimens revealed multifocal peribronchiolitis and OP. An electron probe microanalysis of these specimens demonstrated the presence of elements from the earth's crust in the inflammatory lesions. These two cases indicate that exposure to dried tsunami sludge can cause OP.

Inflammatory biomarkers in asthma-COPD overlap syndrome.

BACKGROUND: The clinical phenotypes and underlying mechanisms of asthma-COPD overlap syndrome (ACOS) remain elusive. This study aimed to investigate a comparison of COPD patients with and without ACOS, focusing on inflammatory biomarkers, in an outpatient COPD cohort. METHODS: We conducted a cross-sectional study analyzing prospectively collected data from the Ishinomaki COPD Network registry. All participants were diagnosed with COPD, confirmed by using spirometry, and were aged 40-90 years and former smokers. Patients with features of asthma including both variable respiratory symptoms and variable expiratory airflow limitation were identified and defined as having ACOS. Then, the inflammatory biomarkers such as fractional exhaled nitric oxide level, blood eosinophil count and percentage, total immunoglobulin E (IgE) level, and presence of antigen-specific IgE were evaluated. RESULTS: A total of 257 patients with COPD were identified, including 37 (14.4%) with ACOS. Patients with ACOS tended to be younger, have a shorter smoking history, and use more respiratory medications, especially inhaled corticosteroids and theophylline. Mean fractional exhaled nitric oxide level was significantly higher in those with ACOS than in those without ACOS (38.5 parts per billion [ppb] vs 20.3 ppb, P<0.001). Blood eosinophil count and percentage were significantly increased in those with ACOS (295/mm3 vs 212/mm3, P=0.032; 4.7% vs 3.2%, P=0.003, respectively). Total IgE level was also significantly higher, and presence of antigen-specific IgE was observed more frequently in patients with ACOS. Receiver operating characteristic curve analysis indicated that the sensitivity and specificity of these biomarkers were relatively low, but combinations of these biomarkers showed high specificity for ACOS diagnosis. CONCLUSION: These results provide evidence that these inflammatory biomarkers can be used to support the diagnosis of ACOS.

Burden of chronic obstructive pulmonary disease in the elderly population.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease and an important health care problem in older adults. The impact of age and specific geriatric issues on COPD in elderly patients has not been well established. METHODS: A cross-sectional study of elderly COPD patients was conducted in Japan by using a regional COPD registry database. We compared indices of disease severity (pulmonary function, exercise tolerance, quality of life, and frequency of exacerbations), presence of comorbidities, geriatric conditions (cognitive function, mental status, and activities of daily living [ADL]), and adherence to prescribed drug regimens between elderly and younger patients with COPD. RESULTS: In total, 279 patients with stable COPD (median age, 74 years) were identified; 86% of these patients were elderly (65 years of age or older). Elderly COPD patients, especially those who were 75 years of age or older, had significantly more cases of dyspnea, lower exercise tolerance, and poorer ADL and a higher incidence of severe exacerbations than younger patients (all P<0.05). In addition, the prevalence of comorbidities, including cardiovascular disease and cancer, was significantly higher in elderly COPD patients. Elderly COPD patients had specific geriatric conditions, including cognitive impairment. Adherence to inhaled drug regimens in elderly patients was as favorable as that in younger patients. CONCLUSIONS: Age and specific geriatric conditions have a great negative impact on COPD in elderly patients. Geriatric conditions should be addressed in the management of elderly COPD patients.

Impact of a large-scale natural disaster on patients with chronic obstructive pulmonary disease: the aftermath of the 2011 Great East Japan Earthquake.

BACKGROUND: A large-scale natural disaster may exacerbate chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD). The aftermath of a natural disaster can include poor access to medication, medical equipment, and medical supplies. Little is known about the impact on patients with COPD. METHODS: A retrospective cohort study was conducted at a regional medical center in Ishinomaki, the area affected most severely by the Great East Japan Earthquake in 2011. The study was performed 6 months after the disaster. The characteristics, clinical courses, and outcomes of COPD patients hospitalized after emergency visits during the study period were investigated and compared. RESULTS: One hundred patients (112 episodes) were identified. Within a few days after the disaster, patients undergoing oxygen therapy at home came to the hospital to receive oxygen. In the subacute phase (from the third to the fifth week), the number of hospitalizations due to COPD exacerbations was significantly increased compared to the numbers observed before the earthquake (p<0.05). On admission, COPD patients reported significantly reduced participation in the activities of daily living (ADLs) after as compared to before the disaster. The incidence of cases of exacerbated COPD normalized 6 weeks after the earthquake. CONCLUSIONS: The large-scale natural disaster that hit Japan in 2011 had a serious negative impact on the clinical outcomes of COPD patients in the disaster-affected area.

The impact of the 2011 Great East Japan Earthquake on hospitalisation for respiratory disease in a rapidly aging society: a retrospective descriptive and cross-sectional study at the disaster base hospital in Ishinomaki.

OBJECTIVE: To investigate the impact in an aging society of the 2011 Great East Japan earthquake on hospitalisation for respiratory disease at the disaster base hospital. DESIGN: Descriptive and cross-sectional study. SETTING: Emergency care in Japanese Red Cross Ishinomaki Hospital, a regional disaster base hospital in Miyagi, Japan. PARTICIPANTS: 322 emergency patients who were hospitalised for respiratory disease from 11 March to 9 May 2011, and 99 and 105 emergency patients who were hospitalised in the corresponding periods in 2009 and 2010, respectively. MAIN OUTCOME MEASURES: Description and comparison of patient characteristics and disease distribution in terms of age, time after the disaster and activities of daily living (ADL). RESULTS: 1769 patients were admitted to our hospital during the study period (compared to 850 in 2009 and 1030 in 2010), among whom 322 were hospitalised for respiratory disease (compared to 99 in 2009 and 105 in 2010). Pneumonia (n=190, 59.0%) was the most frequent cause of admission for pulmonary disease, followed by acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) (n=53, 16.5%), asthma attacks (n=27, 8.4%) and progression of lung cancer (n=22, 6.8%). Compared with the corresponding periods in 2009 and 2010, the increase in the absolute numbers of admissions was highest for pneumonia, followed by AE-COPD and asthma attacks. At hospitalisation, 195 patients were 'dependent' and 54 patients were 'partially dependent'. Respiratory admissions accompanied by deterioration of ADL after the disaster were more frequent in elderly and female patients. CONCLUSIONS: After the Great East Japan Earthquake, admissions for pneumonia and exacerbation of chronic respiratory disease in the elderly increased at the disaster base hospital.

Pulmonary fat embolization as a diagnostic finding for heat exposure.

The aim of this study was to examine whether the detection of pulmonary fat embolization is valid as a significant indicator of heat exposure in forensic autopsies. In 54 cases where there was no evidence of fracture, burn or pancreatitis, 25 cases (46.3%) showed pulmonary fat embolization, the degree of which was pathohistologically classified as slight in all cases. Among the 25 cases where the pulmonary fat embolization was detected, the individual had died under a high ambient temperature in 14 cases (56%). Based on logistic regression analysis, pulmonary fat embolization was found to be associated with a high ambient temperature, but not associated with coronary arteriosclerosis, fatty infiltration in the liver, severe infectious diseases, intracranial hemorrhage or the detection of methamphetamine in the blood. Further investigations are necessary before these findings can be applied in forensic autopsy cases; however, it is likely that the detection of pulmonary fat embolization is valuable as one of the diagnostic findings indicating antemortem heat exposure.

Sudden death from ischaemic heart disease in a female patient with Sjögren syndrome: a case report.

Primary Sjögren syndrome (SjS) has a comparatively good prognosis except when it is complicated by non-Hodgkin's lymphoma. We performed an autopsy on a young female patient with primary SjS who had died suddenly during a meal, and we discuss the relationship between primary SjS and the cause of death. Eosinophilic change of the cardiomyocytes and severe arteriolosclerosis were observed within the myocardium. In the conduction system, lymphocyte infiltration was detected in the bundle of His, in addition to arteriosclerosis in the sinoatrial node and atrioventricular node arteries. The cause of death was diagnosed as ischaemic heart disease induced by arteriolosclerosis: its development can probably be attributed mostly to primary SjS. It should thus be kept in mind that primary SjS can occasionally result in the development of cardiovascular complications, such as ischaemic heart disease, as well as systemic lupus erythematosus or rheumatoid arthritis.

Gene expression on liver toxicity induced by administration of haloperidol in rats with severe fatty liver.

Sudden deaths are often encountered in schizophrenic patients prescribed with antipsychotic drugs, and fatty liver may be more prevalent among patients with schizophrenia. The aim of this study is to investigate the adverse effects of antipsychotic drugs on fatty liver. We administered haloperidol intraperitoneally to fatty liver rats and examined the mRNA expression in the liver. Basic expressions of cytochrome P450 (CYP)1A2, CYP2C11 and CYP3A2 decreased, and response of these CYPs to haloperidol was reduced in the fatty liver. Metabolism of haloperidol was also suppressed in the fatty liver rats. Moreover, hepatic injury by administration of haloperidol was shown pathohistologically and molecular-biologically in severe fatty liver. These results suggest that fatty liver increases susceptibility to adverse effects of haloperidol, possibly leading to life-threatening events. It should be noted by clinicians that excessive dose of antipsychotic drugs may be more harmful in patients with fatty liver.

Experimental pulmonary fat embolism induced by injection of triolein in rats.

The relationship between the volume of fat flowing in the bloodstream and the degree of pulmonary fat embolism has remained unclear. In this study, in order to examine whether the volume of fat particles in the bloodstream could be estimated from the degree of pulmonary fat embolism, 0.05, 0.1, 0.15, 0.2 and 0.25 ml of triolein were injected into male rats weighing 300-320 g, through the caudal vein. Consequently, it was noted that the severity of pulmonary fat embolism tended to gradually increase in proportion to the volume of injected triolein, with the severity of pulmonary fat embolism being significantly augmented by the injection of 0.2 and 0.25 ml of triolein, based on morphometric analysis. In application to human cases, about 60 ml of fat particles was estimated to flow into the bloodstream after the occurrence of a pelvic fracture. Moreover, the results of this study led to the hypothesis that the prognosis of pulmonary fat embolism is affected by the severity of preceding conditions which have caused fat embolism.