High-flow nasal cannula for reducing hypoxemic events in patients undergoing bronchoscopy: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Patients undergoing bronchoscopic procedures may develop hypoxemia and severe complications. High-flow nasal cannula (HFNC) may prevent hypoxemic events during bronchoscopy. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of HFNC in these patients. METHODS: We conducted a search in PubMed, Embase, and the Cochrane Library for RCTs published before November 2021. Individual effect sizes were standardized, and a meta-analysis was performed to calculate the pooled effect size using random-effects models. The primary outcome was the incidence of hypoxemic events (oxygen saturation [SpO2] < 90%) during bronchoscopy. Secondary outcomes included the incidence of interrupted bronchoscopy due to desaturation, lowest SpO2 during bronchoscopy, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), end-tidal CO2 (EtCO2) at the end of bronchoscopy, and the incidence of intubation after the procedure. RESULTS: Five trials involving 257 patients were reviewed. The incidence of hypoxemic events was lower in the HFNC group than in the conventional oxygen therapy group (risk ratio, 0.25; 95% confidence interval [CI], 0.14-0.42). The lowest SpO2 during the procedure was significantly higher in the HFNC group than in the conventional oxygen therapy group (weighted mean difference [WMD], 7.12; 95% CI, 5.39-8.84). PaO2 at the end of the procedure was significantly higher in the HFNC group than in the conventional oxygen therapy group (WMD, 20.36; 95% CI, 0.30-40.42). The incidence of interrupted bronchoscopy due to desaturation, PaCO2 and EtCO2 at the end of the procedure, and the incidence of intubation after the procedure were not significantly different between groups. CONCLUSIONS: HFNC may reduce the incidence of hypoxemic events and improve oxygenation in patients undergoing bronchoscopy.

Association of short-term exposure to air pollution with depression in patients with sleep-related breathing disorders.

Air pollution is associated with sleep-related breathing disorders; however, the effects of air pollution on depression in patients with SRBDs remain unclear. A cross-sectional study was conducted to collect polysomnographic (PSG) data and Beck Depression Inventory-IA (BDI-IA) responses from 568 subjects with SRDBs in a sleep center in 2015 to 2017. Exposure to air pollution, including particulate matter with an aerodynamic diameter of ≤10 µm (PM10), particulate matter with an aerodynamic diameter of ≤2.5 µm (PM2.5), nitrogen (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3), in 1-month averages was collected. Associations of air pollution with the respiratory disturbance index (RDI), oxygen desaturation index (ODI), arousal index (ARI), sleep architecture, and BDI-IA were examined. We observed that interquartile range (IQR) increases in 1-month PM2.5, PM10, and NO2 levels were respectively associated with 4.1/hour (h) (95% confidence interval (CI): 1.7/h to 6.4/h), 3.7/h (95% CI: 1.4/h to 6.0/h) and 1.9/h (95% CI: 0.1/h to 3.7/h) increases in the ARI. For sleep architecture, IQR increases in 1-month PM2.5 and CO levels were respectively associated with a 6.2% (95% CI: 6.1% to 6.3%) increase in non-rapid eye movement sleep 1 (N1) and a 2.0% (95% CI: -3.8% to -0.1%) decrease in non-rapid eye movement sleep 2 (N2). For depression, an IQR change in the 1-month CO was associated a moderate/severe depressive status according to the BDI-IA (odds ratio, OR: 2.981, p < 0.05; 95% CI: 1.032 to 8.611). Short-term exposure to air pollution increased the risk of arousal and light sleep as well as depression in patients with SRBDs. The results suggest that SRBD patients could be a population at risk for depression due to short-term exposure to air pollution.

Effects of pulmonary rehabilitation program on amyotrophic lateral sclerosis: A meta-analysis of randomized controlled trials.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) develop respiratory failure and progressive muscle weakness. The effects of pulmonary rehabilitation on the lung function of patients with ALS are unclear. OBJECTIVE: Through this meta-analysis of randomized controlled trials (RCTs), we evaluated the effects of pulmonary rehabilitation, such as type of treatment, on patients with ALS and compared the effectiveness of this treatment. METHODS: PubMed, EMBASE, Web of Science, and Cochrane databases were searched until December 2020. The methodological quality of each study was assessed using the updated Cochrane Risk of Bias tool (RoB 2.0). Data were analyzed using Review Manager version 5.4 (Cochrane Collaboration, Oxford, England), and the meta-analysis was performed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. RESULTS: Of 2168 articles, 10 trials were reviewed; among these trials, two focused on respiratory training and eight on physical exercise, three of which involved a combination of aerobic and resistance training. Our meta-analysis demonstrated no difference in the ALSFRS-R score and % FVC among patients with ALS. CONCLUSIONS: Respiratory training or physical exercise did not significantly affect the ALSFRS-R score and % FVC of patients with ALS. At 12 months after intervention, the ALSFRS-R score in the physical exercise group was higher than that in the usual care group. Further clinical trials are warranted to develop approaches for improving the lung function of patients with ALS.

High-Flow Nasal Cannula versus Noninvasive Positive Pressure Ventilation in Patients with Heart Failure after Extubation: An Observational Cohort Study.

Noninvasive positive pressure ventilation (NPPV) has been widely applied in patients with high-risk extubation failure, including heart failure. High-flow nasal cannula (HFNC) has been demonstrated to benefit patients with heart failure by reducing cardiac preload. This study aimed to compare the effectiveness of HFNC to NPPV for preventing extubation failure in patients with heart failure. This 3-year retrospective and single-center cohort study included patients with heart failure with left ventricular ejection fraction <50% who received prophylactic HFNC or NPPV after scheduled extubation from January 2015 to January 2018 from a medical center with four adult intensive care units. Demographics, comorbidities, diagnosis, and weaning status were collected. The primary outcome was treatment failure within 72 hours after extubation, which was defined as escalation to NPPV or reintubation in the HFNC group and was defined as requiring reintubation in the NPPV group. Secondary outcomes were reintubation within 72 hours, reintubation, duration of stay, and mortality during the intensive care unit and hospital stay. Of the 104 patients analyzed, characteristics of 58 patients in the HFNC group and 46 patients in the NPPV group were compared. The treatment failure within 72 hours in the two groups was not significantly different (25.9% vs 13%, p=0.106). Hypoxemic respiratory failure related treatment failure was significantly higher in the HFNC group. Prophylactic HFNC as first-line therapy had a comparable rate of reintubation within 72 hours to the prophylactic NPPV alone (17.2% vs 13%, p=0.556). Other secondary outcomes were similar between the two groups. Among patients with heart failure, HFNC was not inferior to NPPV for preventing extubation failure and reintubation. However, in case of an impending respiratory failure, selective patients may benefit from rescue NPPV.

The effects of threshold inspiratory muscle training in patients with obstructive sleep apnea: a randomized experimental study.

OBJECTIVES: Patients with obstructive sleep apnea (OSA) (an obstructed airway and intermittent hypoxia) negatively affect their respiratory muscles. We evaluated the effects of a 12-week threshold inspiratory muscle training (TIMT) program on OSA severity, daytime sleepiness, and pulmonary function in newly diagnosed OSA. METHODS: Sixteen patients with moderate-to-severe OSA were randomly assigned to a TIMT group and 6 to a control group. The home-based TIMT program was 30-45 min/day, 5 days/week, for 12 weeks using a TIMT training device. Their apnea-hypopnea index (AHI), Epworth sleepiness scale (ESS), and forced vital capacity (FVC) scores were evaluated pre- and post-treatment. Polysomnographic (PSG) analysis showed that 9 TIMT-group patients had positively responded (TIMT-responder group: post-treatment AHI < pre-treatment) and that 7 had not (TIMT non-responder group: post-treatment AHI > pre-treatment). RESULTS: Post-treatment AHI and ESS scores were significantly (both P < 0.05) lower 6% and 20.2%, respectively. A baseline AHI ≤ 29.0/h predicted TIMT-responder group patients (sensitivity 77.8%; specificity 85.7%). FVC was also significantly (P < 0.05) higher 7.2%. Baseline AHI and FEV6.0 were significant predictors of successful TIMT-responder group intervention. OSA severity and daytime sleepiness were also significantly attenuated. CONCLUSIONS: Home-based TIMT training is simple, efficacious, and cost-effective.

Proteasome activity related with the daily physical activity of COPD patients.

BACKGROUND: COPD is a debilitating disease that affects patients' daily lives. One's daily physical activity (DPA) decreases due to multifactorial causes, and this decrease is correlated with a poor prognosis in COPD patients. Muscle wasting may at least be partly due to increased activity of the ubiquitin proteasome pathway and apoptosis. METHODS: This study investigated the relationships among DPA, circulating proteasome activity, and protein carbonyl in COPD patients and healthy subjects (HSs). This study included 57 participants (42 patients and 15 healthy subjects). Ambulatory DPA was measured using actigraphy, and oxygen saturation was measured with a pulse oximeter. RESULTS: COPD patients had lower DPA, lower 6 min walking distance (6MWD), lower delta saturation pulse oxygenation (SpO2) during the 6MWT, and lower delta SpO2 during DPA than HSs. COPD patients had higher proteasome activity and protein carbonyl than HSs. Circulating proteasome activity was significantly negatively correlated with DPA (r=-0.568, P<0.05) in COPD patients, whereas delta SpO2 during the 6MWT was significantly positively correlated with proteasome activity (r=0.685, P<0.05) in HSs. Protein carbonyl was significantly negatively correlated with the body mass index (r=-0.318, P<0.05), mid-arm circumference (r=0.350, P<0.05), calf circumference (r=0.322, P<0.05), forced expiratory volume in the first second (r=-0.441, P<0.01), and 6MWD (r=-0.313, P<0.05) in COPD patients. Our results showed no significant difference in inflammatory markers (interleukin-6 and tumor necrosis factor-α) or ubiquitin between the two groups. CONCLUSION: COPD patients had lower DPA levels and higher circulating proteasome activity than HSs, and a negative correlation of DPA with circulating proteasome activity.

Associations of autophagy with lung diffusion capacity and oxygen saturation in severe COPD: effects of particulate air pollution.

Although traffic exposure has been associated with the development of COPD, the role of particulate matter <10 µm in aerodynamic diameter (PM10) in the pathogenesis of COPD is not yet fully understood. We assessed the 1-year effect of exposure to PM10 on the pathogenesis of COPD in a retrospective cohort study. We recruited 53 subjects with COPD stages III and IV and 15 healthy controls in a hospital in Taiwan. We estimated the 1-year annual mean levels of PM10 at all residential addresses of the cohort participants. Changes in PM10 for the 1-year averages in quintiles were related to diffusion capacity of the lung for carbon monoxide levels (r=-0.914, P=0.029), changes in the pulse oxygen saturation (ΔSaO2; r=-0.973, P=0.005), receptor for advanced glycation end-products (r=-0.881, P=0.048), interleukin-6 (r=0.986, P=0.002), ubiquitin (r=0.940, P=0.017), and beclin 1 (r=0.923, P=0.025) in COPD. Next, we observed that ubiquitin was correlated with ΔSaO2 (r=-0.374, P=0.019). Beclin 1 was associated with diffusion capacity of the lung for carbon monoxide (r=-0.362, P=0.028), ΔSaO2 (r=-0.354, P=0.032), and receptor for advanced glycation end-products (r=-0.471, P=0.004). Autophagy may be an important regulator of the PM10-related pathogenesis of COPD, which could cause deterioration in the lung diffusion capacity and oxygen saturation.

Synthesis of Canthardin Sulfanilamides and Their Acid Anhydride Analogues via a Ring-Opening Reaction of Activated Aziridines and Their Associated Pharmacological Effects.

The cantharidinimide derivatives, 5a-h, including sulfanilamides containing pyrimidyl, pyrazinyl, hydrogen, thiazolyl, and oxazolyl groups were synthesized. Modification of cantharidinimide by means of the reaction of activated aziridine ring opening led to the discovery of a novel class of antitumor compounds. The analogues 10i-k, 11l-n, 12o-p, and 16q-s were obtained from treating cantharidinimide 6 and analogues (7, 8, and 13) with activated aziridines, which produced a series of ring-opened products including normal and abnormal types. Some of these compounds showed cytotoxic effects in vitro against HL-60, Hep3B, MCF7, and MDA-MB-231 cancer cells. The most potent cytostatic compound, N-cantharidinimido-sulfamethazine (5a), exhibited anti-HL-60 and anti-Hep3B cell activities. Two compounds 5g and 5h displayed slight effects on the Hep3B cell line, while the other compounds produced no response in these four cell lines.

Proteoglycan 4 is a diagnostic biomarker for COPD.

INTRODUCTION: The measurement of C-reactive protein (CRP) to confirm the stability of COPD has been reported. However, CRP is a systemic inflammatory biomarker that is related to many other diseases. OBJECTIVE: The objective of this study is to discover a diagnostic biomarker for COPD. METHODS: Sixty-one subjects with COPD and 15 healthy controls (10 healthy non-smokers and 5 smokers) were recruited for a 1-year follow-up study. Data regarding the 1-year acute exacerbation frequency and changes in lung function were collected. CRP and the identified biomarkers were assessed in the validation COPD cohort patients and healthy subjects. Receiver operating characteristic values of CRP and the identified biomarkers were determined. A validation COPD cohort was used to reexamine the identified biomarker. Correlation of the biomarker with 1-year lung function decline was determined. RESULTS: Proteoglycan 4 (PRG4) was identified as a biomarker in COPD. The serum concentrations of PRG4 in COPD Global initiative for chronic Obstructive Lung Disease (GOLD) stages 1+2 and 3+4 were 10.29 ng/mL and 13.20 ng/mL, respectively; 4.99 ng/mL for healthy controls (P<0.05); and 4.49 ng/mL for healthy smokers (P<0.05). PRG4 was more sensitive and specific than CRP for confirming COPD severity and acute exacerbation frequency. There was no correlation between CRP and PRG4 levels, and PRG4 was negatively correlated with the 1-year change in predicted forced vital capacity percent (R (2)=0.91, P=0.013). CONCLUSION: PRG4 may be a biomarker for identification of severity in COPD. It was related to the 1-year forced vital capacity decline in COPD patients.

Low bone mineral density in COPD patients with osteoporosis is related to low daily physical activity and high COPD assessment test scores.

COPD patients have an increased prevalence of osteoporosis (OP) compared with healthy people. Physical inactivity in COPD patients is a crucial risk factor for OP; the COPD assessment test (CAT) is the newest assessment tool for the health status and daily activities of COPD patients. This study investigated the relationship among daily physical activity (DPA), CAT scores, and bone mineral density (BMD) in COPD patients with or without OP. This study included 30 participants. Ambulatory DPA was measured using actigraphy and oxygen saturation by using a pulse oximeter. BMD was measured using dual-energy X-ray absorptiometry. OP was defined as a T-score (standard deviations from a young, sex-specific reference mean BMD) less than or equal to -2.5 SD for the lumbar spine, total hip, and femoral neck. We quantified oxygen desaturation during DPA by using a desaturation index and recorded all DPA, except during sleep. COPD patients with OP had lower DPA and higher CAT scores than those of patients without OP. DPA was significantly positively correlated with (lumbar spine, total hip, and femoral neck) BMD (r=0.399, 0.602, 0.438, respectively, all P<0.05) and T-score (r=0.471, 0.531, 0.459, respectively, all P<0.05), whereas CAT scores were significantly negatively correlated with (total hip and femoral neck) BMD (r=-0.412, -0.552, respectively, P<0.05) and (lumbar spine, total hip, and femoral neck) T-score (r=-0.389, -0.429, -0.543, respectively, P<0.05). Low femoral neck BMD in COPD patients was related to high CAT scores. Our results show no significant difference in desaturation index, low SpO2, and inflammatory markers (IL-6, TNF-α, IL-8/CXCL8, CRP, and 8-isoprostane) between the two groups. Chest physicians should be aware that COPD patients with OP have low DPA and high CAT scores.

High incidence of stroke in young women with sleep apnea syndrome.

OBJECTIVE: Patients with sleep apnea syndrome (SAS) carry a higher stroke risk. The differential stroke risk between sex and among different age groups has not yet been specifically addressed in previous studies. METHODS: Using a universal insurance claims database, we identified a large cohort of SAS patients from 1997 to 2010 and assessed the sex- and age-specific stroke risk compared with a control cohort matched for age, sex, and index date. Cox regression analyses were performed to assess the hazard ratio (HR) of stroke and the corresponding 95% confidence interval (CI). Stroke-free probabilities were computed using the Kaplan-Meier method and differences between both cohorts were examined using the log-rank test. RESULTS: We identified 29,961 patients with SAS and a control cohort of 119,844 subjects without SAS. The overall incidence of stroke in the SAS cohort was 37% higher compared to the non-SAS cohort (54.6 per 10,000 individual-years vs 39.8 per 10,000 individual-years). After controlling for sex and comorbidities, the SAS cohort exhibited a 19% higher risk for stroke compared to the control cohort (adjusted HR, 1.19 [95% CI, 1.09-1.30]). Women with SAS ages 35 years or younger had the highest stroke risk compared to older age groups of the same sex and their risk for stroke was relatively higher compared to their male counterparts. CONCLUSION: Women aged 35 years or younger with SAS have a higher stroke risk.

Histological subtype and smoking status, but not gender, are associated with epidermal growth factor receptor mutations in non-small-cell lung cancer.

Mutations in epidermal growth factor receptor (EGFR) commonly occur in non-small-cell lung cancer (NSCLC) patients characterized by female gender, never-smoker status and adenocarcinoma histology. The aim of this study was to determine whether gender is a confounding factor for EGFR mutations in NSCLC. To elucidate the confounding effect, Pearson's χ2 test and logistic regression models were used to correlate these characteristics with EGFR mutations in 426 NSCLC patients treated at our institutes. Of those 426 NSCLC patients, 47% were females, 57% were non-smokers and 84% had adenocarcinomas. The multivariate logistic regression analysis demonstrated that never-smoker status [odds ratio (OR)=3.49, 95% confidence interval (CI): 1.99-6.13; P<0.001)] and adenocarcinoma (OR=9.43, 95% CI 3.62-24.56; P<0.001) were associated with EGFR mutations; however, gender was not (OR=1.25, 95% CI: 0.73-2.15; P=0.416). Furthermore, gender was not associated with EGFR mutation subtypes (OR=1.19, 95% CI: 0.56-2.50; P=0.650). The frequency of EGFR mutations among females and males was not different in non-smokers (64.8 vs. 55.8%, P=0.204) or ever-smokers (27.8 vs. 24.2%, P=0.775). Therefore, if the assessment for EGFR mutation status was limited to non-smoking females with adenocarcinoma, up to 40% of the patients harboring EGFR mutations would be precluded from the benefit of EGFR inhibitor therapy. Our results indicated that gender is a confounding factor for EGFR mutations in NSCLC and suggested that gender may not be associated with tumorigenesis in NSCLC-harboring EGFR mutations.

Comparison of domiciliary oxygen using liquid oxygen and concentrator in northern Taiwan.

BACKGROUND/PURPOSE: Long-term oxygen therapy has become standard treatment for patients with chronic respiratory insufficiency. However, patterns of long-term home oxygen therapy have not been well studied in Taiwan. Oxygen concentrator systems are commonly used in Taiwan, but liquid oxygen delivery systems are portable and may provide advantages over the concentrator system. This study compared oxygen usage between patients from a liquid oxygen group (LOG) and an oxygen concentrator group (OCG). The authors also assessed the physiologic responses of patients with chronic obstructive pulmonary disease (COPD) to ambulatory oxygen use at home. METHODS: The study used a retrospective, cross-sectional, observational survey design. The LOG comprised 42 patients, and the OCG comprised 102 patients. We recruited participants in northern Taiwan from July 2009 to April 2010. The questionnaire instruments that were used to collect data consisted of three parts: demographic characteristics, devices used in respiratory care, and activity status with portable oxygen. Two-minute walking tests were performed on COPD patients in their homes. RESULTS: COPD was the most common diagnosis in our study, with more than 50% of patients who received oxygen long term in both groups having received this diagnosis. The LOG used oxygen for an average of 21.7 hours per day, whereas OCG averaged 15.2 hours per day (p<0.001). In the OCG, 92.2% of patients used a concentrator alone, whereas 23.8% of the LOG used liquid oxygen alone (p<0.001). The LOG patients were involved in significantly more outdoors activities (p=0.002) and reported traveling with oxygen more often (p<0.001) than the OCG patients. For patients with the same dyspnea level of COPD severity, those using liquid oxygen had a lower increase in pulse rate after the walking test, in comparison with the concentrator users. CONCLUSION: Patients in the LOG used oxygen for longer hours, went on more outings, and were more likely to travel with oxygen than patients in the OCG. Being ambulatory with liquid oxygen might enable patients with COPD to walk more effectively.

Characterization of the interactions between protein and carbon black.

A considerable amount of studies have been conducted to investigate the interactions of biological fluids with nanoparticle surfaces, which exhibit a high affinity for proteins and particles. However, the mechanisms underlying these interactions have not been elucidated, particularly as they relate to human health. Using bovine serum albumin (BSA) and mice bronchoalveolar lavage fluid (BALF) as models for protein-particle conjugates, we characterized the physicochemical modifications of carbon blacks (CB) with 23nm or 65nm in diameter after protein treatment. Adsorbed BALF-containing proteins were quantified and identified by pathways, biological analyses and protein classification. Significant modifications of the physicochemistry of CB were induced by the addition of BSA. Enzyme modulators and hydrolase predominately interacted with CB, with protein-to-CB interactions that were associated with the coagulation pathways. Additionally, our results revealed that an acute-phase response could be activated by these proteins. With regard to human health, the present study revealed that the CB can react with proteins (∼55kDa and 70kDa) after inhalation and may modify the functional structures of lung proteins, leading to the activation of acute-inflammatory responses in the lungs.

Distinct clinical outcomes of non-small cell lung cancer patients with epidermal growth factor receptor (EGFR) mutations treated with EGFR tyrosine kinase inhibitors: non-responders versus responders.

INTRODUCTION: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been associated with favorable progression free survival (PFS) in patients with non-small cell lung cancers (NSCLC) harboring EGFR mutations. However, a subset of this population doesn't respond to EGFR-TKI treatment. Therefore, the present study aimed to elucidate survival outcome in NSCLC EGFR-mutant patients who were treated with EGFR TKIs. METHODS: Among the 580 consecutive NSCLC patients who were treated at our facility between 2008 and 2012, a total of 124 treatment-naïve, advanced NSCLC, EGFR-mutant patients treated with EGFR TKIs were identified and grouped into non-responders and responders for analyses. RESULTS: Of 124 patients, 104 (84%) responded to treatment, and 20 (16%) did not; and the overall median PFS was 9.0 months. Notably, the PFS, overall survival (OS) and survival rates were significantly unfavorable in non-responders (1.8 vs. 10.3 months, hazard ratio (HR) = 29.2, 95% confidence interval (CI), 13.48-63.26, P<0.0001; 9.4 vs. 17.3 months, HR = 2.74, 95% CI, 1.52-4.94, P = 0.0008; and 58% vs. 82% in 6, 37% vs. 60% in 12, and 19 vs. 40% at 24 months, respectively). In multivariate analysis, treatment efficacy strongly affected PFS and OS, independent of covariates (HR = 47.22, 95% CI, 17.88-124.73, P<0.001 and HR = 2.74, 95% CI, 1.43-5.24, P = 0.002, respectively). However, none of the covariates except of the presence of EGFR exon 19 deletion in the tumors was significantly associated with better treatment efficacy. CONCLUSIONS: A subset of NSCLC EGFR-mutant patients displayed unfavorable survival despite EGFR TKI administration. This observation reinforces the urgent need for biomarkers effectively predicting the non-responders and for drug development overcoming primary resistance to EGFR TKIs. In addition, optimal therapeutic strategies to prolong the survival of non-responders need to be investigated.

Serum protein oxidation by diesel exhaust particles: effects on oxidative stress and inflammatory response in vitro.

Considerable evidence shows a key role for protein modification in the adverse effects of chemicals; however, the interaction of diesel exhaust particles (DEP) with proteins and the resulting biological activity remains unclear. DEP and carbon black (CB) suspensions with and without bovine serum albumin (BSA) were used to elucidate the biological effects of air pollutants. The DEP and CB samples were then divided into suspensions and supernatants. Two important goals of the interaction of DEP with BSA were as follows: (1) understanding BSA modification by particles and (2) investigating the effects of particles bound with BSA and the corresponding supernatants on cellular oxidative stress and inflammation. We observed significant free amino groups production was caused by DEP. Using liquid chromatography-mass spectrometry (LC-MS), we observed that BSA was significantly oxidised by DEP in the supernatants and that the peptides ETYGDMADCCEK, MPCTEDYLSLILNR and TVMENFVAFVDK, derived BSA-DEP conjugates, were also oxidised. In A549 cells, DEP-BSA suspensions and the corresponding supernatants reduced 8-hydroxy-2'-deoxyguanosine (8-OHdG) production and increased interleukin-6 (IL-6) levels when compared to DEP solutions without BSA. Our findings suggest that oxidatively modified forms of BSA caused by DEP could lead to oxidative stress and the activation of inflammation.

Amelioration of superoxide dismutase on ventilator-induced lung injury by suppressing leukocyte in the lungs and systemic circulation.

Superoxide dismutase (SOD) is a free radical scavenger and a broad-spectrum antioxidant. Its anti-inflammatory and immunomodulatory effects have recently been noted. We studied the effects of this antioxidant on lung damage, oxidative stress, and inflammation in a model of ventilator-induced lung injury (VILI), using 8- to 12-wk-old Sprange-Dawley rats (n = 40). Animals were randomized and evenly divided into two experimental groups, low tidal volume (V(T)) ventilation (V(T) = 9 ml/kg) and high V(T) ventilation (V(T) = 28 ml/kg). Each group was evenly divided into two subgroups: ten animals were treated with superoxide dismutase (SOD; 10,000 U/kg i.v., 2 h prior to the ventilation) and the rests were treated with vehicle. Lung injury was evaluated by histological examination, and cells counts of red blood cells (RBC) and white blood cells (WBC) in the alveoli and the septal wall thickness in lung tissues and serum lactate dehydrogenase (LDH). The lung permeability was assessed by the wet-to-dry weight ratio (W/D), lung weight to body weight ratio (LW/BW) and protein concentration in broncholavage fluid (BALF). Levels of oxidative stress and lipid peroxidation in the lungs were evaluated by tissue malondialdehyde (MDA) and methylguanidine (MG) in BALF, respectively. SOD pretreatment significantly decreased WBC counts in systemic circulation and in alveoli, and effectively attenuated high V(T) ventilation induced lung injury by reducing hyaline membrane development, septal wall thickness, lung W/D and LW/BW and serum LDH in relation to those of the control. In addition, lung tissues MDA and MG in BALF were also notably reduced.

Role of TRPV1 and P2X receptors in the activation of lung vagal C-fiber afferents by inhaled cigarette smoke in rats.

Inhaled cigarette smoke (CS) triggers airway reflexes that are thought to result from the activation of lung vagal C-fiber afferents (LVCAs) via the action of reactive oxygen species in rats. We investigated the role of transient receptor potential vanilloid 1 (TRPV1) and P2X receptors in LVCA activation. Activities of LVCAs were recorded in anesthetized and artificially ventilated rats. Airway challenge of CS produced a concentration-dependent fiber stimulation. Pretreatment with dimethylthiourea [DMTU; a scavenger of hydroxyl radical (OH)], capsazepine (CPZ; a TRPV1 receptor antagonist) and iso-pyridoxalphosphate-6-azophenyl-2',5'-disulphonate (iso-PPADS; a P2X receptor antagonist) separately reduced the fiber responses by 64, 40 and 44%, respectively, whereas pretreatment with hexamethonium (a nicotinic acetylcholine receptor antagonist) failed to alter the response. A combination of CPZ and iso-PPADS exerted a greater inhibitory effect compared with the effect of either single pretreatment. However, a combination of DMTU, CPZ and iso-PPADS did not further reduce the fiber response compared with the combined effect of CPZ and iso-PPADS. It was concluded that both TRPV1 and P2X receptors, but not nicotinic acetylcholine receptors, participate in the stimulation of LVCAs by inhaled CS, possibly through the action of OH.

Preventive use of noninvasive ventilation after extubation: a prospective, multicenter randomized controlled trial.

BACKGROUND: The effectiveness of noninvasive ventilation (NIV) after extubation in preventing post-extubation respiratory failure is still controversial. METHODS: We conducted a prospective, multicenter randomized controlled study involving patients on mechanical ventilation for > 48 hours who tolerated a 2-hour spontaneous breathing trial and were subsequently extubated. The patients were randomized to NIV or standard medical therapy. Re-intubation rate within 72 hours was the primary outcome measure. Multivariable logistic regression analysis was used to determine predictors for extubation failure. RESULTS: We randomized 406 patients to either NIV (no. = 202) or standard medical therapy (no. = 204). The 2 groups had similar baseline clinical characteristics. There were no differences in extubation failure (13.2% in control and 14.9% in NIV), intensive care unit or hospital mortality. Cardiac failure was a more common cause of extubation failure in control than in NIV. There was no difference in rapid shallow breathing index (RSBI) in extubation failure patients between control (80) and NIV (73). When using data from all patients, we found Acute Physiology and Chronic Health Evaluation (APACHE II) scores (odds ratio [OR] 1.13, 95% CI 1.07-1.20, P < .001), maximal inspiratory pressure (OR 1.04, 95% CI 1.00-1.08, P = .03), and RSBI (OR 1.03, 95% CI 1.02-1.05, P < .001) to be predictors of extubation failure. Abundant secretions were the most common reason (35.1%) for extubation failure identified by attending physicians. CONCLUSIONS: Preventive use of NIV after extubation in patients who passed spontaneous breathing trial did not show benefits in decreasing extubation failure rate or the mortality rate.

Physical training is beneficial to functional status and survival in patients with prolonged mechanical ventilation.

BACKGROUND/PURPOSE: Early physical training is necessary for severely deconditioned patients undergoing prolonged mechanical ventilation (PMV), because survivors often experience prolonged recovery. Long-term outcomes after physical training have not been measured; therefore, we investigated outcome during a 1-year period after physical training for the PMV patients. METHODS: We conducted a prospective randomized control trial in a respiratory care center. Thirty-four patients were randomly assigned to the rehabilitation group (n = 18) and the control group (n = 16). The rehabilitation group participated in supervised physical therapy training for 6 weeks, and continued in an unsupervised maintenance program for 6 more weeks. The functional independence measurement (FIM) was used to assess functional status. Survival status during the year after enrollment, the number of survivors discharged, and the number free from ventilator support were collected. These outcome parameters were assessed at entry, immediately after the 6 weeks physical therapy training period, after 6 weeks unsupervised maintenance exercise program, and 6 months and 12 months after study entry. RESULTS: The scores of total FIM, motor domain, cognitive domain, and some sub-items, except for the walking/wheelchair sub-item, increased significantly in the rehabilitation group at 6 months postenrollment, but remained unchanged for the control group. The eating, comprehension, expression, and social interaction subscales reached the 7-point complete independence level at 6 months in the rehabilitation group, but not in the control group. The 1-year survival rate for the rehabilitation group was 70%, which was significantly higher than that for the control group (25%), although the proportion of patients discharged and who were ventilator-free in the rehabilitation and control groups did not differ significantly. CONCLUSION: Six weeks physical therapy training plus 6 weeks unsupervised maintenance exercise enhanced functional levels and increased survival for the PMV patients compared with those with no such intervention. Early physical therapy interventions are needed for the PMV patients in respiratory care centers.