Use of a wearable device to compare subjective and objective fatigue in lung cancer patients and cancer-free controls.

PURPOSE: The study evaluates the use of heart rate variability (HRV), a measure of autonomic nervous system (ANS) modulation via wearable smart bands, to objectively assess cancer-related fatigue (CRF) levels. It aims to enhance understanding of fatigue by distinguishing between LF/HF ratios and LF/HF disorder ratios through HRV and photoplethysmography (PPG), identifying them as potential biomarkers. METHODS: Seventy-one lung cancer patients and 75 non-cancer controls wore smart bands for one week. Fatigue was assessed using Brief Fatigue Inventory, alongside sleep quality and daily interference. HRV parameters were analyzed to compare groups. RESULTS: Cancer patients showed higher fatigue and interference levels than controls (64.8% vs. 54.7%). Those with mild fatigue had elevated LF/HF disorder ratios during sleep (40% vs. 20%, P = 0.01), similar to those with moderate to severe fatigue (50% vs. 20%, P = 0.01), indicating more significant autonomic dysregulation. Notably, mild fatigue patients had higher mean LF/HF ratios than controls (1.9 ± 1.34 vs. 1.2 ± 0.6, P = 0.01), underscoring the potential of disorder ratios in signaling fatigue severity. CONCLUSIONS: Utilizing wearable smart bands for HRV-based analysis is feasible for objectively assess CRF levels in cancer patients, especially during sleep. By distinguishing between LF/HF ratios and LF/HF disorder ratios, our findings suggest that wearable technology and detailed HRV analysis offer promising avenues for real-time fatigue monitoring. This approach has the potential to significantly improve cancer care by providing new methods for managing and intervening in CRF, particularly with a focus on autonomic dysregulation as a crucial factor.

A dynamic approach to support outbreak management using reinforcement learning and semi-connected SEIQR models.

BACKGROUND: Containment measures slowed the spread of COVID-19 but led to a global economic crisis. We establish a reinforcement learning (RL) algorithm that balances disease control and economic activities. METHODS: To train the RL agent, we design an RL environment with 4 semi-connected regions to represent the COVID-19 epidemic in Tokyo, Osaka, Okinawa, and Hokkaido, Japan. Every region is governed by a Susceptible-Exposed-Infected-Quarantined-Removed (SEIQR) model and has a transport hub to connect with other regions. The allocation of the synthetic population and inter-regional traveling is determined by population-weighted density. The agent learns the best policy from interacting with the RL environment, which involves obtaining daily observations, performing actions on individual movement and screening, and receiving feedback from the reward function. After training, we implement the agent into RL environments describing the actual epidemic waves of the four regions to observe the agent's performance. RESULTS: For all epidemic waves covered by our study, the trained agent reduces the peak number of infectious cases and shortens the epidemics (from 165 to 35 cases and 148 to 131 days for the 5th wave). The agent is generally strict on screening but easy on movement, except for Okinawa, where the agent is easy on both actions. Action timing analyses indicate that restriction on movement is elevated when the number of exposed or infectious cases remains high or infectious cases increase rapidly, and stringency on screening is eased when the number of exposed or infectious cases drops quickly or to a regional low. For Okinawa, action on screening is tightened when the number of exposed or infectious cases increases rapidly. CONCLUSIONS: Our experiments exhibit the potential of the RL in assisting policy-making and how the semi-connected SEIQR models establish an interactive environment for imitating cross-regional human flows.

Cancer-related fatigue classification based on heart rate variability signals from wearables.

Background: Cancer-related fatigue (CRF) is the most distressing side effect in cancer patients and affects the survival rate. However, most patients do not report their fatigue level. This study is aimed to develop an objective CRF assessment method based on heart rate variability (HRV). Methods: In this study, patients with lung cancer who received chemotherapy or target therapy were enrolled. Patients wore wearable devices with photoplethysmography that regularly recorded HRV parameters for seven consecutive days and completed the Brief Fatigue Inventory (BFI) questionnaire. The collected parameters were divided into the active and sleep phase parameters to allow tracking of fatigue variation. Statistical analysis was used to identify correlations between fatigue scores and HRV parameters. Findings: In this study, 60 patients with lung cancer were enrolled. The HRV parameters including the low-frequency/high-frequency (LF/HF) ratio and the LF/HF disorder ratio in the active phase and the sleep phase were extracted. A linear classifier with HRV-based cutoff points achieved correct classification rates of 73 and 88% for mild and moderate fatigue levels, respectively. Conclusion: Fatigue was effectively identified, and the data were effectively classified using a 24-h HRV device. This objective fatigue monitoring method may enable clinicians to effectively handle fatigue problems.

Measurement of Cancer-Related Fatigue Based on Heart Rate Variability: Observational Study.

BACKGROUND: Cancer-related fatigue is a serious side effect of cancer, and its treatment can disrupt the quality of life of patients. Clinically, the standard method for assessing cancer-related fatigue relies on subjective experience retrieved from patient self-reports, such as the Brief Fatigue Inventory (BFI). However, most patients do not self-report their fatigue levels. OBJECTIVE: In this study, we aim to develop an objective cancer-related fatigue assessment method to track and monitor fatigue in patients with cancer. METHODS: In total, 12 patients with lung cancer who were undergoing chemotherapy or targeted therapy were enrolled. We developed frequency-domain parameters of heart rate variability (HRV) and BFI based on a wearable-based HRV measurement system. All patients completed the BFI-Taiwan version questionnaire and wore the device for 7 consecutive days to record HRV parameters such as low frequency (LF), high frequency (HF), and LF-HF ratio (LF-HF). Statistical analysis was used to map the correlation between subjective fatigue and objective data. RESULTS: A moderate positive correlation was observed between the average LF-HF ratio and BFI in the sleep phase (ρ=0.86). The mapped BFI score derived by the BFI mapping method could approximate the BFI from the patient self-report. The mean absolute error rate between the subjective and objective BFI scores was 3%. CONCLUSIONS: LF-HF is highly correlated with the cancer-related fatigue experienced by patients with lung cancer undergoing chemotherapy or targeted therapy. Beyond revealing fatigue levels objectively, continuous HRV recordings through the photoplethysmography watch device and the defined parameters (LF-HF) can define the active phase and sleep phase in patients with lung cancer who undergo chemotherapy or targeted chemotherapy, allowing a deduction of their sleep patterns.

Antineutrophil Cytoplasmic Antibodies and Organ-Specific Manifestations in Eosinophilic Granulomatosis with Polyangiitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a rare and often severe systemic vasculitis associated with antineutrophil cytoplasmic antibodies (ANCAs). EGPA can affect multiple organ systems, but the relationships between ANCA status and the organ-specific manifestations of EGPA in previous reports were inconsistent. OBJECTIVE: To investigate the association of the ANCA status with organ-specific manifestations in EGPA. METHODS: We performed a systematic review of studies published before March 16, 2020, in the PubMed, Embase, Web of Science, and Cochrane Library databases. The primary outcome was the association of ANCA status with organ-specific involvements of EGPA. Odds ratios (ORs) and 95% CIs were calculated using a random-effects model. RESULTS: A total of 24 cross-sectional studies with 2527 patients with EGPA, including 921 ANCA-positive patients and 1606 ANCA-negative patients, were included in the meta-analysis. The significant results of pooled analyses revealed that compared with patients with EGPA with negative ANCA status, patients with EGPA with positive ANCA status had higher risks of peripheral neuropathy (OR, 1.701), renal involvement (OR, 5.097), and cutaneous purpura (OR, 1.746) and lower risks of pulmonary infiltrates (OR, 0.589) and cardiac involvement (OR, 0.427). The pooled analysis also revealed no significant association of ANCA status with asthma and involvements of the central nervous system, gastrointestinal tract, or skin. CONCLUSIONS: This study provides more evidence that patients with EGPA may exhibit different features of disease based on their ANCA status.

Ex Vivo Expansion and Drug Sensitivity Profiling of Circulating Tumor Cells from Patients with Small Cell Lung Cancer.

Small cell lung cancer (SCLC) represents one of the most aggressive malignancies among cancer types. Not only tumor sample availability is limited, but also the ability for tumor cells to rapidly acquire drug resistance are the rate-limiting bottlenecks for overall survival in current clinical settings. A liquid biopsy capable of capturing and enriching circulating tumor cells (CTCs), together with the possibility of drug screening, is a promising solution. Here, we illustrate the development of a highly efficient ex vivo CTC expansion system based on binary colloidal crystals substrate. Clinical samples were enrolled from 22 patients with SCLC in the study. The CTCs were enriched and expanded from the collected peripheral blood samples. Expanded cells were analyzed for protein expression and observed for drug sensitivity with the use of immunofluorescence and ATP titer evaluation, respectively. Successful CTC spheroid proliferation was established after 4 weeks within 82% of all the collected peripheral blood samples from enrolled patients. Upon immunofluorescence analysis, the enriched cells showed positive markers for EpCAM, TTF-1, synaptophysin and negative for CD45. Additionally, the expanded CTCs demonstrated marked heterogeneity in the expression of E-cadherin and N-cadherin. In a preliminary case series, the drug sensitivity of patient-derived CTC to cisplatin and etoposide was studied to see the correlation with the corresponding therapeutic outcome. In conclusion, our study demonstrates that it is possible to efficiently expand CTCs from SCLC within a clinically relevant time frame; the biomarker information generated from enriched CTCs can assist the selection of effective drugs and improve disease outcome.

Electrorheological Sensor Encapsulating Microsphere Media for Plague Diagnosis with Rapid Visualization.

Plague is a disease infected by an etiological agent, which is transmitted from fleas to a variety of wildlife rodents. Therefore, rapid diagnosis of plague on-site in the field is important. Polystyrene microspheres (SMs) of 2.2 µm diameter were synthesized by emulsion polymerization to adsorb magnetic nanoparticles (FNs), resulting in core-/shell-structured microspheres that generate a significant contrast in relative permittivities between SMs and FNs. Electrorheological displays (EDs) consisting of two indium tin oxide glasses with spacers were constructed to contain core-/shell-structured SM/FN (SM@FN) solutions for observing their transmittance change. The ED encapsulating dispersed SM@FN solution exhibited an opaque state because light was scattered significantly without the application of an alternating electric field (AEF). In the presence of an AEF, the particle chaining behavior results in enhancement of the transmittance of ED. At a specific frequency, the so-called characteristic frequency (Fc), the transmittance reaches a maximum. Fc could be used as an indicator to mark the shell materials. The antibody of Yersinia pestis (ab-Yp) was coated onto the SM@FN as a biosensing medium. The Fc of ab-Yp-modified microspheres shifted from 200 to 750 kHz with antigen coupling of Y. pestis antigen (ag-Yp). In the absence of fluorescence labeling, the large change in ED transmittance could be visualized during the Y. pestis detection. The limit of detection and the limit of quantification were ∼30 and ∼40 ng/µL, respectively, obtained within 30 s according to the highest transmittance of ED under the AEF at 750 kHz. Y. pestis detection was not affected by Escherichia coli and Staphylococcus aureus significantly. Compared with other common immunoassays, including the secondary immunochemical or enzyme-linked steps, this simple electrorheological sensor with high sensitivity and selectivity could be a candidate for on-site plague diagnosis.

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin increases the activation of aryl hydrocarbon receptor and is associated with the aggressiveness of osteosarcoma MG-63 osteoblast-like cells.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor whose activity is modulated by xenobiotics and physiological ligands. Activation of the AhR by environmental xenobiotics may induce a conformational change in AhR and has been implicated in a variety of cellular processes, including inflammation and tumorigenesis. It is unknown whether the activation of AhR serves a role in modulating the progression of osteosarcoma. The osteosarcoma cell line MG-63, was treated with AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD treatment degrades AhR expression through activation of the AhR signaling pathway, however there were no survival differences observed in MG-63 cells. There were concomitant elevations of cyclooxygenase-2 and receptor activator of nuclear factor-κB ligand secretion from MG-63 cells upon TCDD treatment on a protein and mRNA level at 24 and 72 h. In addition, TCDD treatment also increases the production of prostaglandin E2 on MG-63 cells, and induces the expression of chemokine receptor CXCR4. However, CXCL12 production was not altered in MG-63 cells when stimulated with TCDD. The AhR antagonist CH-223191, blocks the effects on TCDD-induced RANKL, COX-2, PGE2 and CXCR4 changes. In conclusion, these findings suggest that AhR signal therapy should be further explored as a therapeutic option for the treatment of osteosarcoma.

Heat shock protein70 is implicated in modulating NF-κB activation in alveolar macrophages of patients with active pulmonary tuberculosis.

Heat shock proteins (HSPs) have been shown to modulate NF-κB activation. It is unknown whether HSP70 plays a role in modulating NF-κB-mediated pro-inflammatory cytokines released from alveolar macrophage (AM) of patients with active pulmonary tuberculosis (TB). Peripheral blood monocytes (PBMs) and AM were sampled from nineteen active TB patients and 14 healthy individuals. HSP70 expression was 3-fold higher in AMs of active TB patients than normal subjects, and declined after receiving 3-month anti-TB treatment. Overexpression of HSP70 by transfection with HSP70 plasmid decreased p-IκBα and p65 NF-κB activities. Inhibition of NF-κB activation using NF-κB or MAPK inhibitors increased HSP70 expression in AM of TB patients. Blocking p38- or ERK-MAPK decreased NF-κB and IκB activities, leading to up-regulated HSP70 expression. Overexpression of HSP70 alone or with p38 or ERK inhibitors decreased TNF-α (57%, 83% and 74%, respectively) and IL-6 (53%, 70%, and 67%, respectively) release from macrophages of TB patients. In conclusion, HSP70 modulates NF-κB activation in AM of TB patients, through inhibiting IκB-α phosphorylation or acting as a chaperon molecule to prevent NF-κB binding to the target genes by facilitating degradation. The upregulated HSP70 may suppress the release of pro-inflammatory cytokines during active PTB infection, and prevent overwhelming tissue damage.

Pulmonary rehabilitation coupled with negative pressure ventilation decreases decline in lung function, hospitalizations, and medical cost in COPD: A 5-year study.

Pulmonary rehabilitation (PR) brings benefits to patients with chronic obstructive pulmonary disease (COPD). Negative pressure ventilation (NPV) increases ventilation and decreases hyperinflation as well as breathing work in COPD. We evaluated the long-term effects of a hospital-based PR program coupled with NPV support in patients with COPD on clinical outcomes.One hundred twenty-nine patients with COPD were followed up for more than 5 years, with the NPV group (n = 63) receiving the support of NPV (20-30 cm H2O delivery pressure for 60 min) and unsupervised home exercise program of 20 to 30 min daily walk, while the control group (n = 6) only received unsupervised home exercise program. Pulmonary function tests and 6 min walk tests (6MWT) were performed every 3 to 6 months. Emergency room (ER) visits and hospitalization with medical costs were recorded.A significant time-by-group interaction in the yearly decline of forced expiratory volume in 1 s in the control group analyzed by mixed-model repeated-measure analysis was found (P = 0.048). The 6MWT distance of the NPV group was significantly increased during the first 4 years, with the interaction of time and group (P = 0.003), the time alone (P = 0.014), and the quadratic time (P < 0.001) being significant between the 2 groups. ER exacerbations and hospitalizations decreased by 66% (P < 0.0001) and 54% (P < 0.0001) in the NPV group, respectively. Patients on PR program coupled with NPV had a significant reduction of annual medical costs (P = 0.022).Our hospital-based multidisciplinary PR coupled with NPV reduced yearly decline of lung function, exacerbations, and hospitalization rates, and improved walking distance and medical costs in patients with COPD during a 5-year observation.

The clinical outcomes and predictive factors for in-hospital mortality in non-neutropenic patients with candidemia.

Recent epidemiologic studies have showed that candidemia is an important nosocomial infection in hospitalized patients. The majority of candidemia patients were non-neutropenic rather than neutropenic status. The aim of this study was to determine the clinical outcome of non-neutropenic patients with candidemia and to measure the contributing factors for mortality. A total of 163 non-neutropenic patients with candidemia during January 2010 to December 2013 were retrospectively enrolled. The patients' risk factors for mortality, clinical outcomes, treatment regimens, and Candida species were analyzed. The overall mortality was 54.6%. Candida albicans was the most frequent Candida species (n = 83; 50.9% of patients). Under multivariate analyses, hemodialysis (OR, 4.554; 95% CI, 1.464-14.164) and the use of amphotericin B deoxycholate (OR, 8.709; 95% CI, 1.587-47.805) were independent factors associated with mortality. In contrast, abdominal surgery (OR, 0.360; 95% CI, 0.158-0.816) was associated with a better outcome. The overall mortality is still high in non-neutropenic patients with candidemia. Hemodialysis and use of amphotericin B deoxycholate were independent factors associated with mortality, whereas prior abdominal surgery was associated with a better outcome.

Exercise-Induced Changes in Exhaled NO Differentiates Asthma With or Without Fixed Airway Obstruction From COPD With Dynamic Hyperinflation.

Asthmatic patients with fixed airway obstruction (FAO) and patients with chronic obstructive pulmonary disease (COPD) share similarities in terms of irreversible pulmonary function impairment. Exhaled nitric oxide (eNO) has been documented as a marker of airway inflammation in asthma, but not in COPD. To examine whether the basal eNO level and the change after exercise may differentiate asthmatics with FAO from COPD, 27 normal subjects, 60 stable asthmatics, and 62 stable COPD patients were studied. Asthmatics with FAO (n = 29) were defined as showing a postbronchodilator FEV1/forced vital capacity (FVC) ≤70% and FEV1 less than 80% predicted after inhaled salbutamol (400 µg). COPD with dynamic hyperinflation (n = 31) was defined as a decrease in inspiratory capacity (ΔIC%) after a 6 minute walk test (6MWT). Basal levels of eNO were significantly higher in asthmatics and COPD patients compared to normal subjects. The changes in eNO after 6MWT were negatively correlated with the percent change in IC (r = -0.380, n = 29, P = 0.042) in asthmatics with FAO. Their levels of basal eNO correlated with the maximum mid-expiratory flow (MMEF % predicted) before and after 6MWT. In COPD patients with air-trapping, the percent change of eNO was positively correlated to ΔIC% (rs = 0.404, n = 31, P = 0.024). We conclude that asthma with FAO may represent residual inflammation in the airways, while dynamic hyperinflation in COPD may retain NO in the distal airspace. eNO changes after 6MWT may differentiate the subgroups of asthma or COPD patients and will help toward delivery of individualized therapy for airflow obstruction.

Circulating angiopopietin-1 correlates with the clinical course of multiple organ dysfunction syndrome and mortality in patients with severe sepsis.

To determine plasma concentrations of angiopoietin (Ang)-1, Ang-2, Tie-2, and vascular endothelial growth factor (VEGF) in patients with sepsis-induced multiple organ dysfunction syndrome (MODS) and determine their association with mortality.The study prospectively recruited 96 consecutive patients with severe sepsis in a l intensive care unit of a tertiary hospital. Plasma Ang-1, Ang-2, Tie-2, and VEGF levels and MODS were determined in patients on days 1, 3, and 7 of sepsis. Univariate and Cox proportional hazards analysis were performed to develop a prognostic model.Days 1, 3, and 7 plasma Ang-1 concentrations were persistently decreased in MODS patients than in non-MODS patients (day1: 4.0 ±â€Š0.5 vs 8.0 ±â€Š0.5 ng/mL, P < 0.0001; day 3, 3.2 ±â€Š0.6 vs 7.3 ±â€Š0.5 ng/mL, P < 0.0001, day 7, 2.8 ±â€Š0.6 vs 10.4 ±â€Š0.7 ng/mL, P < 0.0001). In patients with resolved MODS on day 7 of sepsis, Ang-1 levels were increased from day 1 (4.7 ±â€Š0.6 ng/mL vs 9.1 ±â€Š1.4 ng/mL, n = 43, P = 0.004). Plasma Ang-1 levels were lower in nonsurvivors than in survivors on days 1 (4.0 ±â€Š0.5 vs 7.1 ±â€Š0.5 ng/mL, P < 0.0001), 3 (3.8 ±â€Š0.6 vs 7.1 ±â€Š0.5 ng/mL, P < 0.0001), and 7 (4.7 ±â€Š0.7 vs 11.0 ±â€Š0.8 ng/mL, P < 0.0001) of severe sepsis. In contrast, plasma Ang-2 levels were higher in nonsurvivors than in survivors only on day 1 (15.8 ±â€Š2.0 vs 9.5 ±â€Š1.2 ng/mL, P = 0.035). VEGF and Tie-2 levels were not associated with MODS and mortality. Ang-1 level less than the median value was the only independent predictor of mortality (hazard ratio, 2.57; 95% CI 1.12-5.90, P = 0.025).Persistently decreased Ang-1 levels are associated with MODS and subsequently, mortality in patients with sepsis.

Total lesion glycolysis determined per RECIST 1.1 criteria predicts survival in EGFR mutation-negative patients with advanced lung adenocarcinoma.

OBJECTIVE: The aim of this retrospective study was to investigate the clinical impact of F-FDG PET in patients with advanced lung adenocarcinoma stratified according to the epidermal growth factor receptor (EGFR) mutation status. PATIENTS AND METHODS: A total of 56 patients with advanced lung adenocarcinoma were included in the study. Thirty-one patients (55%) were EGFR mutation-positive, whereas the remaining 25 (45%) participants tested negative for EGFR mutations. All of the patients underwent F-FDG PET/CT for pretreatment planning. The main outcome measure was overall survival (OS) at 24 months. The following F-FDG PET/CT-derived variables were tested for their associations with OS: main tumor SUVmax, main tumor total lesion glycolysis, and target lesions TLG determined per RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria (TLGRECIST). We also investigated the clinical characteristics in relation to OS and EGFR mutation status. RESULTS: In EGFR mutation-positive patients, neither the clinical characteristics nor F-FDG PET/CT-derived parameters were significantly associated with OS. In contrast, univariate analysis identified male sex, a positive history of smoking, and TLGRECIST greater than or equal to 412 g as adverse prognostic factors for OS in EGFR mutation-negative patients. After adjustment for potential confounders in multivariate analysis, TLGRECIST was the sole independent predictor of OS in this subgroup. CONCLUSIONS: TLG determined per RECIST 1.1 criteria is an independent predictor of OS in EGFR mutation-negative patients with advanced lung adenocarcinoma. Further studies are needed to investigate whether this parameter may be a promising tool for stratifying such patients for risk-adapted therapies.

Associated bone mineral density and obstructive sleep apnea in chronic obstructive pulmonary disease.

BACKGROUND: Osteoporosis is an important issue for patients with chronic obstructive pulmonary disease (COPD). Worse systemic inflammation and reduced exercise capacity have been reported in COPD patients with obstructive sleep apnea (OSA), implying that OSA may be an independent factor for osteoporosis in COPD patients. METHODS: A total of 66 patients with bone mineral density (BMD) and polysomnography results from a previous COPD cohort (January 2008 to January 2013) were retrospectively enrolled. Clinical characteristics such as medication, pulmonary function, BMD, and results of polysomnography were analyzed. RESULTS: The BMD in those with OSA was significantly lower than in those without OSA (-1.99±1.63 versus -1.27±1.14, P=0.045). In univariate analysis, body mass index, forced expiratory volume in 1 second, percentage of predicted value, incremental shuttle walk test, apnea-hypopnea index, and oxygen desaturation index (ODI) were significantly associated with BMD. After multivariate linear regression analysis, the ODI was still an independent factor for BMD. In addition, smaller total lung capacity is significantly associated with higher ODI and lower BMD, which implies that lower BMD might cause severer OSA via decreased total lung capacity. CONCLUSION: OSA may be an independent factor for BMD in patients with COPD, which implies a possible vicious cycle takes place in these patients.

Fibrocyte trafficking in patients with chronic obstructive asthma and during an acute asthma exacerbation.

BACKGROUND: Fibrocytes express several chemokine receptors (CCR7 and CXCR4) that regulate their recruitment and trafficking into tissue-damage sites in response to specific chemokine gradients (CCL19 and CXCL12). OBJECTIVE: We investigated whether these chemoattractants and S100A9, through the receptor for advanced glycation end-products (RAGE; ie, its receptor), are involved in fibrocyte trafficking in patients with chronic obstructive asthma (COA) and during an acute exacerbation (AE) in patients without airflow obstruction (Asthma AE group). METHODS: We collected peripheral blood from 14 asthmatic patients with normal pulmonary function, 14 patients with COA, 11 patients in the Asthma AE group, and 14 healthy subjects. Isolated circulating fibrocytes were used for migration assay. Expression of CCR7, CXCR4, S100A9, and RAGE in fibrocytes was measured by using flow cytometry. CCL19 and CXCL12 expression in bronchial tissues was determined by using immunohistochemistry and RT-PCR. RESULTS: There were higher numbers of circulating fibrocytes in patients in the Asthma AE group and patients with COA. The expression of CXCL12 in bronchial tissues and CXCR4 in circulating fibrocytes was higher in the Asthma AE group and, to a lesser extent, in patients with COA. The expression of CCL19 in bronchial tissues and CCR7 in fibrocytes was higher in patients with COA. CXCL12/CXCR4 and CCL19/CCR7 enhanced fibrocyte transmigration in the Asthma AE group and in patients with COA, respectively. The upregulated expression of S100A9 and RAGE in fibrocytes of patients in the Asthma AE group and those with COA contributes to the enhanced basal migratory motility of fibrocytes. CONCLUSION: The CXCR4/CXCL12 axis contributes to chemotaxis of fibrocytes in patients in the Asthma AE group, whereas the CCR7/CCL19 axis plays an important role in patients with COA. S100A9 enhances the basal migratory motility of fibrocytes from patients in the Asthma AE group and patients with COA.

Mobile-phone-based home exercise training program decreases systemic inflammation in COPD: a pilot study.

BACKGROUND: Moderate-intensity exercise training improves skeletal muscle aerobic capacity and increased oxidative enzyme activity, as well as exercise tolerance in COPD patients. METHODS: To investigate whether the home-based exercise training program can reduce inflammatory biomarkers in patients with COPD, twelve patients using mobile phone assistance and 14 with free walk were assessed by incremental shuttle walk test (ISWT), spirometry, strength of limb muscles, and serum C-reactive protein (CRP) and inflammatory cytokines. RESULTS: Patients in the mobile phone group improved their ISWT walking distance, with decrease in serum CRP after 2 months, and sustained at 6 months. Patients in the control group had no improvement. Serum IL-8 in the mobile phone group was significantly reduced at 2, 3 and 6 months after doing home exercise training compared to baseline. IL-6 and TNF-α were significantly elevated at 3 and 6 months in control group, while there were no changes in mobile phone group. The strength of limb muscles was significantly greater compared to baseline at 3 and 6 months in the mobile phone group. CONCLUSIONS: A mobile-phone-based system can provide an efficient home endurance exercise training program with improved exercise capacity, strength of limb muscles and a decrease in serum CRP and IL-8 in COPD patients. Decreased systemic inflammation may contribute to these clinical benefits. (Clinical trial registration No.: NCT01631019).